7 H&N Oncology

Question 1

1 What are the five basic phases of the cell cycle, and what occurs during each phase?

Answer 1

• Quiescent phase (G0): Resting state
• Gap 1 (G1): Preparation for cell division; increase in transcription/translation and ~ doubling of macromole cules
• Synthesis phase (S): Replication of chromosomes
• Gap 2 (G2): Continued cellular growth
• Mitosis phase (M): Chromosomes are separated, and two daughter cells result

Question 2

2 What is the term given to cells in permanent cell cycle arrest?

Answer 2

Senescent

Question 3

3 What are the key checkpoints within the cell cycle?

Answer 3

• G1/S checkpoint (“restriction point”): Prevent entry S-phase, rate-limiting step
• Intra-S phase checkpoint: Halt progression of S-phase if damaged DNA is detected
• G2/M checkpoint: Prevent entry into M phase
• M checkpoint: Ensure correct replication of DNA and avoid mitotic exit if errors exist

Question 4

4 If a lesion (i.e., partially replicated DNA, strand breaks, or other errors) is identified at a check point, what processes can be activated?

Answer 4

• Recruitment of DNA repair effector complexes
• Temporary cell-cycle arrest, which can lead to senescence or apoptosis, depending on the cell and the lesion

Question 5

5 What key tumor suppressor protein controls progression through the G1/S checkpoint (restriction point) and the G2/M checkpoint?

Answer 5

p53 (activates p21 → inhibits cyclin and cyclin-dependent kinase (Cdk) complexes)

Question 6

6 What two key classes of molecules regulate a cell’s progress through the cell cycle?

Answer 6

• Cdks: Catalytic subunit; require cyclin for activation; result in phosphorylation (activates/inactivates molecules necessary for progression through the cell cycle)
• Cyclins: Regulatory subunit that activates Cdk molecules when bound to form a heterodimer

Question 7

7 Although more than 15 Cdks have been identified, four have key biologic functions within the cell cycle. What are they, and what do they do?

Answer 7

• Cdk 1: Controls G2 phase and M phase (prophase) → Cyclin A dependent
• Cdk 2: Controls G1 to S transition and S phase → cyclin E (and A) dependent
• Cdk 4: G0 to G1 transition → cyclin D dependent
• Cdk 6: G0 to G1 transition → cyclin D dependent

Question 8

8 Specific families of activators and inhibitors regulate functional activities of the Cdk complexes. Identify the primary activators and inhibitors.

Answer 8

• Activators: Cdk-activating kinase (CAK) and Cdc-25
• Inhibitors: Cdk inhibitors (CKI) → Inhibitor of kinase 4 (INK4a), Cdk Interacting protein/kinase inhibitory protein (Cip/Kip)

Question 9

9 What type of gene helps to control cell growth or progression through the cell cycle?

Answer 9

Tumor suppressor gene (also called antioncogenes)

Question 10

10 What type of gene promotes cell growth and progression through the cell cycle?

Answer 10

Proto-oncogenes. Once a proto-oncogene is mutated, it is known as an oncogene

Question 11

11 The classic retinoblastoma tumor suppressor protein (pRb) functions to inhibit what key transcription factors, effectively preventing formation of cell cycle–related proteins and arresting the cell in G0 phase?

Answer 11

E2F factors

Question 12

12 Phosphorylation of pRb by what important cyclin Cdk complex(es) results in dissociation of pRb from E2F and subsequent entrance into the cell cycle?

Answer 12

Cyclin D-Cdk4 and cyclin D-Cdk6

Question 13

13 Release of E2F from pRb inhibition results in the transcription of multiple genes necessary for the function of the cell cycle. Transcription of what key cyclin protein results in activation of Cdk2, progression from G1 to S phase, additional pRb inactivation, and p27 degradation?

Answer 13

Cyclin E

Question 14

14 What genes are considered members of the Cip/ Kip family of tumor suppressor genes, and in what phase of the cell cycle do they inhibit cyclin-Cdk complexes?

Answer 14

• p21, p27, and p57
• G1 phase

Question 15

15 DNA damage results in activation of what key tumor suppressor gene and proapoptotic factor, which in turn activates p21 (a Cip/Kip Cdk complex inhibitor) and results in arrest of the cell cycle in G1 phase?

Answer 15

p53

Question 16

16 Transforming growth factor-β is a growth inhibitor, which results in activation of which INK4 tumor suppressor gene causing subsequent cell-cycle arrest in G1 phase?

Answer 16

p27

Question 17

17 What genes are considered members of the INK4a family of tumor-suppressor genes, and in what phase of the cell cycle do they inhibit cyclin-Cdk complexes?

Answer 17

• p16 and p19
• G1 phase

Question 18

18 Name the tumor suppressor gene that is a member of the INK4a family that prevents p53 degradation and therefore results in cell-cycle arrest at the G1-checkpoint.

Answer 18

p19

Question 19

19 Name the tumor suppressor gene that is a member of the INK4a family that inhibits cyclin D Cdk4/6 complexes and therefore results cell cycle arrest during the G1 phase.

Answer 19

p16

Question 20

20 What important enzymes function to dephosphorylate the targets of cyclin-Cdk complexes, such as pRb?

Answer 20

PP1 and PP2A (phosphatases)

Question 21

21 To promote an orderly progression through the cell cycle, cyclin-Cdk complexes must be degraded to allow the next phase of the cell cycle to progress uninterrupted. For example, S-phase complexes cannot be active during M phase and so forth. What important enzymatic process selecively targets these complexes for degradation?

Answer 21

Ubiquitin-dependent protein degradation (ubiquitylation)

Question 22

22 The phases G1, S, and G2 are collectively referred to as what?

Answer 22

Interphase

Question 23

23 What are the five stages of mitosis (M phase)?

Answer 23

• Prophase: Preparatory; cyclin A-Cdk1 active; condensation of chromatin, polarization of centrosomes, and initiation of mitotic spindle formation
• Prometaphase: Nuclear envelope breaks down, mitotic spindle microtubules attach to chromosomes
• Metaphase: Alignment of chromosomes at metaphase plate
• Anaphase: Separation of sister chromatids
• Telophase: Cytoplasmic division (cytokinesis) into two daughter cells; chromatid decondensation (expansion)

Question 24

24 Describe the “two-hit” hypothesis (Knudson, 1971) for carcinogenesis.

Answer 24

Loss of two alleles for a tumor-suppressor gene is necessary to result in loss of function and tumorigenesis. This hypothesis is not applicable to proto-oncogenes and dominant negative tumor suppressor genes (e.g., p53)

Question 25

25 In an effort to understand carcinogenesis, Fearon and Vogelstein (Cell, 1990) presented a model of tumor progression that involved which three hypotheses?

Answer 25

* Inactivation of tumor suppressor genes or activation of proto-oncogenes results in the formation of cancer. * A series of defined genetic events lead to the development of cancer. * This linear progression may vary, but ultimately it is the accumulation of genetic events that results in the development of a malignant phenotype.

Question 26

26 What is the estimated average of time required for the accumulation of enough genetic alterations to produce traditional head and neck squamous cell carcinoma (Renan, 1993)?

Answer 26

20 to 25 years

Question 27

27 Carcinogenesis models describe a linear progression from precancerous lesions to overtly malignant tumors. Describe the steps involved for each of the following models: 1. Genetic progression model for head and neck cancer 2. Multistep carcinogenesis

Answer 27

1. Hyperplasia → dysplasia (mild, moderate, severe) → carcinoma in situ → invasive carcinoma 2. Initiation → promotion → progression

Question 28

28 In upper aerodigestive tract tumors, what term describes the histopathologic changes seen in mucosa surrounding invasive carcinoma and result in an increased incidence of second primary tumors?

Answer 28

Field cancerization (Slaughter, 1953)

Question 29

29 What hypotheses focusing on the clonal abnormality required for tumor growth have been put forth to explain field cancerization?

Answer 29

* Abnormal, and genetically unique, clones form independently at multiple sites due to exposure to similar environmental carcinogens. * A single tumoral clone forms and subsequently migrates via lateral movement through the mucosa (shown in several studies to be accurate).

Question 30

30 What are the two predominant environmental carcinogens that have been associated with head and neck cancer, show a dose response, and can function synergistically?

Answer 30

* Tobacco * Alcohol

Question 31

31 Why might alcohol, in particular, function as a synergistic carcinogen with other environmental carcinogens?

Answer 31

It may decrease the effectiveness of both local and systemic detoxification enzymes (e.g., cytochrome P450 system).

Question 32

32 Does cessation of smoking and alcohol consumption reduce the risk of head and neck cancer development? If so, how long does it take for the risk to reach the level of never-smokers?

Answer 32

Yes. Some studies have shown 20 years or longer.

Question 33

33 How does diet impact the development of cancer of the upper aerodigestive tract?

Answer 33

A high intake of **fruits and vegetables** and low intake of **red meat** or processed meats has been associated with a decreased risk of head and neck cancer (INHANCE Consortium, 2012)

Question 34

34 Describe the cell-cycle dysregulation that is commonly seen in patients with environmentally related head and neck cancer. (Posner, Goldman’s Cecil Medicine, 24th ed., Chp196)

Answer 34

* Loss of **p16** (normally inhibits cyclin D) * Upregulation of **cyclin D** * Loss of **p53** (normally inhibits cell cycle progression and promotes apoptosis) * Upregulation of **EGFR** (enhances mitogenic signaling) * Upregulation of **COX-2** (increased angiogenesis, de creased apoptosis) * Increased **chromosomal instability (**increased aneuploidy)

Question 35

35 What genetic conditions are related to an increased risk of head and neck cancer?

Answer 35

* Fanconi anemia (AR; DNA repair gene mutation) * Cowden syndrome (AD: PTEN hematoma tumor syndrome; PTEN is a tumor suppressor gene) * Mutations in the cytochrome P450 enzymes (CYP1A1 mutations in Asian populations)

Question 36

36 What circular, double-stranded DNA virus commonly infects the basal layer of cutaneous of mucosal squamous epithelium and is spread by sexual contact?

Answer 36

Human papilloma virus (HPV)

Question 37

37 What two HPV strains are considered “low-risk” for the development of cancer and are frequently associated with papillomas and warts?

Answer 37

HPV 6 and 11

Question 38

38 What two HPV strains are considered “high-risk” for the development of cancer and have been associated with cervical, anogenital, and head and neck (predominantly oropharyngeal) carcinomas?

Answer 38

**HPV 16\* and 18** \*90% of HPV(+) head and neck carcinomas

Question 39

39 The HPV DNA encodes nine open reading frames (genes) on a single strand of its double-stranded circular DNA. Seven of these are considered early phase genes (E), and two are considered late phase genes (L). What are the general functions of the E and L genes, respectively?

Answer 39

* E genes: Regulate the transcription viral DNA * L genes: Encode capsid proteins involved in viral spread

Question 40

40 Name the two viral onco-proteins in HPV-related tumorigenesis, and identify the two genes, that control the transcription of these viral proteins.

Answer 40

* E6/E7: Onco-genes * E1/E2: Transcriptional regulators

Question 41

41 When HPV DNA integrates into host DNA, the process can result in deletion or loss of function of the E1 and E2 viral genes. This in turn results in what?

Answer 41

Loss of regulation of E6 and E7and subsequent increased transcription of these viral genes

Question 42

42 What HPV protein functions to inhibit the function of p53 by targeting it for ubiquitin-dependent degradation? What is the result?

Answer 42

* E6 * Progression through G1 checkpoint and inhibition of apoptosis

Question 43

43 What HPV protein phosphorylates pRb and thus targets it for ubiquitin-dependent degradation? What is the primary result?

Answer 43

* E7 * Release of pRb inhibition of E2F, activation of cell cycle related transcription, progression through the G1 checkpoint

Question 44

44 In addition to E2F-related transcription, the degradation of p53 results in over expression of what important protein? What impact does this have on cell-cycle progression?

Answer 44

* **p16** * Normally **inhibits Cdk4/6**, but with the loss of p53 and pRb, does not meaningfully result in cell cycle control. Can be used as a biomarker of HPV activity.

Question 45

45 In addition to HPV, what viruses have been associated with head and neck cancer?

Answer 45

* EBV: Nasopharyngeal carcinoma * HIV: Increased risk of head and neck cancers * Merkel cell polyomavirus: Merkel cell carcinoma * Human T-lymphotrophic virus (HTLV-1): Human T-Cell lymphoma/leukemia * Kaposi sarcoma associated herpesvirus (KSHV): Kaposi sarcoma

Question 46

46 Whereas the epidermal growth factor receptor (EGFR) is normally expressed in the epithelium of several organ systems (dermis, gastrointestinal tract, kidney), it has been found to be dysfunctional in what percentage of head and neck (squamous cell) cancers?

Answer 46

80 to 90%

Question 47

47 EGFR is a transmembrane glycoprotein that, when activated by binding an extracellular ligand, results in dimerization, tyrosine kinase activation, and a complex downstream pathway that ultimately results in what major outcomes?

Answer 47

* Cellular growth and proliferation * Apoptosis * Angiogenesis * Invasion * Metastasis

Question 48

48 How does EGFR expression relate to prognosis in head and neck squamous cell carcinoma?

Answer 48

Increased expression and amplification are related to decreased recurrence-free survival and cancer-specific survival rates.

Question 49

49 What strategies have been used to target aberrant signaling in head and neck squamous cell carcinoma based on a better understanding of EGFR signaling?

Answer 49

* Tyrosine kinase inhibitors (**geftinib**) * Monoclonal antibodies inhibiting dimerization (**cetuximab**) * Antisense oligodeoxynucleotide or small interfering mRNA inhibition of mRNA expression

Question 50

50 What immune cell is primarily responsible for identifying normal cells that have been altered by viral or tumor activity? What is the general function of these cells in patients with head and neck cancer?

Answer 50

* T cells * Decreased: T cells demonstrate increased apoptosis, decreased recruitment from the thymus, and poor proliferation. * Overall immunosuppression

Question 51

51 What important normal immune system function is designed to prevent the recognition of “self” through processes such as anergy, suppression, and ignorance, which makes stimulating the immune system to target self-derived tumor cells challenging?

Answer 51

Tolerance

Question 52

52 What cell-based therapeutic model has been studied in head and neck cancer with promising (although early) results that focuses on using the immune system to target cancer cells specifically?

Answer 52

Immunotherapy focused on manipulation of the following: * Cell signaling (i.e., cytokines such as interleukin-2) * Vaccination (i.e., Gardasil, whole-cell vaccines, dendritic cell vaccines, etc.) * T cells, dendritic cells, or antibodies

Question 53

53 What type of therapy has the potential to prevent head and neck cancer from occurring, recurring, or progressing?

Answer 53

Chemoprevention

Question 54

54 What prominent chemopreventive agents have been studied for use in patients with head and neck cancer?

Answer 54

* Retinoids and vitamin A (betacarotene) * COX-2 inhibitors * Aspirin * Selenium * Vitamin D * Interpheron-α2a * α-tocopherol (Vitamin E) Many others are being studied. There is great controversy surrounding most of these agents as studies have demonstrated conflicting results.

Question 55

55 What chemopreventive effects are retinoids purported to have on head and neck cancer?

Answer 55

They can retard progression of premalignant oral lesions (leukoplakia and erythroplakia) and have also been associated with lower rates of second primary tumors. Subsequent studies have called these results into question.

Question 56

56 True or False. The risk of head and neck cancer increases in the setting of vitamin A toxicity.

Answer 56

False. The risk increases with vitamin A deficiency.

Question 57

57 What inflammatory mediator is elevated in head and neck cancer cells?

Answer 57

**Prostaglandins** as a result of the upregulation of COX-1 and -2

Question 58

58 What oncologic staging system was devised in 1959 by the American Joint Committee on Cancer (AJCC) to describe the extent of the primary tumor, involvement of regional lymph nodes, and metastases to distant sites in an effort to form a cohesive system providing the clinician with an important tool to predict prognosis, counsel the patient, chose an intervention, and perform more consistent clinical research?

Answer 58

Tumor, node, metastasis (TNM) staging system

Question 59

59 Using the TNM staging system, how can you differentiate a clinical stage from a pathologic stage?

Answer 59

* Clinical stage is designated with a “c” and is based on physical examination or imaging (e.g., cT, cN, or cM). * Pathologic stage is designated with a “p” and is based on pathologic analysis of a specimen (e.g., pT, pN, pM)

Question 60

60 Which subsites share the following criteria (in addition to subsite specific criteria) for T staging: * T1: \< 2 cm * T2: \> 2 cm, \< 4 cm * T3: \> 4 cm

Answer 60

* Lips and oral cavity (need depth of invasion) * Oropharynx * Hypopharynx (plus additional criteria) * Major salivary gland (plus additional criteria) * Well-differentiated thyroid cancer and medullary thyroid cancer (plus additional division of T1a, T1b)

Question 61

61 In the 7th edition of the AJCC, the terms resectable and unresectable were changed to mean "moderately advanced local disease (T4a)" and "very advanced local disease (T4b)" in an effort to predict better the prognosis using current ma nagement strategies. What does “very advanced local disease” generally represent?

Answer 61

Very advanced disease correlates with extension into surrounding critical structures which are largely viewed as unresectable or incurable.

Question 62

62 The following head and neck subsites share what clinical nodal (N) staging system? * Oral cavity * Oropharynx (HPV-neg) * Hypopharynx * Larynx * Nasal cavity and paranasal sinuses * Major salivary glands

Answer 62

**NX** lymph nodes (LNs) cannot be assessed **N0** no regional LN metastasis **N1** single ipsilateral LN ≤3 cm and ENE(-) **N2a** single ipsilateral LN \>3 cm and ≤6 cm and ENE(-) **N2b** multiple ipsilateral LNs ≤6 cm and ENE(-) **N2c** bilateral or contralateral LNs ≤6 cm and ENE(-) **N3a** any LN \>6 cm and ENE(-) **N3b** any LN and ENE(+) \*skin involvement or soft tissue invasion with deep tethering to underlying muscle or adjacent structures, or clinical signs of nerve involvement, is classified as clinical ENE

Question 63

63 What two head and neck subsites have a unique nodal staging system compared with the majority of subsites?

Answer 63

* Nasopharynx * Thyroid

Question 64

65 Tumor invasion of what subsites are considered by some as unresectable?

Answer 64

* Nasopharynx * Prevertebral fascia * Base of skull * Intracranial extension * Mediastinum * Subdermal lymphatics * Carotid artery encasement (generally \> 270 degrees)

Question 65

66 Describe how the American Joint Committee on Cancer reports the presence or absence of residual tumor (R) following treatment.

Answer 65

* RX: Residual tumor cannot be assessed * R0: No residual tumor * R1: Microscopic residual tumor * R2: Macroscopic residual tumor

Question 66

67 How does the AJCC recommend reporting tumor grade?

Answer 66

* GX: Grade cannot be assessed * G1: Well differentiated * G2: Moderately differentiated * G3: Poorly differentiated * G4: Undifferentiated

Question 67

68 Patients with head and neck cancer will have symptoms related to the location and extent of their tumor that are often subsite specific. What “red flag” signs or symptoms should be reviewed with all patients who have concerns for head and neck cancer?

Answer 67

Pain, cranial neuropathy, bleeding, unintentional weight loss, lymphadenopathy, malaise, anorexia

Question 68

69 What risk factors should be elicited when taking a history on a patient with potential head and neck cancer?

Answer 68

* **Tobacco\*** (smoked and smokeless) and **alcohol\*** exposure * Viral infection (EBV and **HPV\***) * Radiation exposure * Diet low in fruits and vegetables and high in red meats and processed meats * Occupational risk factors such as woodworking, textile exposure, and nickel refining * Sun exposure * Personal or family history of head and neck cancer * Poor dentition, chronic inflammation, or chronic irritation * Immunosuppression * Use of betel (quid or panna) (Asia) \* Major risk factors in developed countries

Question 69

70 What risk factors are associated with advanced head and neck cancer at presentation?

Answer 69

* Low income * Black race * Poorly differentiated tumors * Patient neglect

Question 70

71 Define the Eastern Cooperative Oncology Group (ECOG) performance status system.

Answer 70

* Grade 0: Fully active, able to carry on all predisease performance without restriction * Grade 1: Restricted in physically strenuous activity but ambulatory and able to carry out work of a light or sedentary nature * Grade 2: Ambulatory and capable of all self-care but unable to carry out any work activities. Up and about \> 50% of waking hours * Grade 3: Capable of only limited self-care; confined to bed more than 50% of waking hours. * Grade 4: Completely disabled; cannot carry out any self care. Totally confined to bed or chair. * Grade 5: Deceased

Question 71

72 During a head and neck examination in an adult patient, you note unilateral serous otitis media. On flexible endoscopic examination, to what anatomical region(s) should you pay particular attention?

Answer 71

* Posterior nasal cavity * Nasopharynx * Fossa of Rosenmuller * Eustachian tube orifice

Question 72

73 During fiberoptic or mirror laryngoscopy, what maneuvers are critical for a complete oncologic head and neck examination?

Answer 72

* Phonation → assess vocal cord mobility * Tongue protrusion → full view of the epiglottis and vallecula * Puff out cheeks → full view of pyriform sinuses and postcricoid region

Question 73

74 You perform an otoscopic examination on a patient complaining of otalgia but note no obvious source of pain. Which nerve(s) might be implicated in referred otalgia?

Answer 73

* CN V3 * CN IX (via Jacobson nerve) * CN X (via Arnold nerve) * CN VII (via the Ramsay Hunt branch of VII) * Branches from C2 and C3 through the great auricular nerve

Question 74

75 On evaluation of a primary head and neck tumor, in addition to the location and size of the tumor, what information can be gained from palpation that is critical to the workup?

Answer 74

Fixation of the tumor Note: fixation of nodal metastases should also be noted.

Question 75

76 What premalignant lesion can present as a thickened white patch that can’t be scraped off on physical exam of the upper aerodigestive tract mucosa that can progress to invasive carcinoma in up to 30% of patients over a variable number of years?

Answer 75

Leukoplakia

Question 76

77 What premalignant mucosal lesion can appear as a flat red patch with a malignant potential of up to 60% over a variable number of years?

Answer 76

Erythroplakia

Question 77

78 What common initial screening test evaluates for pulmonary disease (metastases or primary lung cancer)?

Answer 77

Chest radiograph. PET/CT is also often ordered now as the initial screening test for distant metastases.

Question 78

79 Which imaging modality is used most often in the initial workup of head and neck cancer patients?

Answer 78

Contrast-enhanced CT

Question 79

80 CT scan of the head and neck is often ordered as a first-line imaging modality to evaluate the size, extent, and location of the primary tumor; status of the vasculature; and nodal disease. Should this scan be ordered with or without contrast?

Answer 79

**With contrast** (as patient’s allergies and renal status permits). In the initial workup of _differentiated thyroid carcinoma_, consider without contrast.

Question 80

81 What are frequently used as radiographic criteria for a nodal malignancy on CT scan?

Answer 80

* Size \> 1 cm * Evidence of central necrosis (~100% specificity) * Spherical shape (suggestive) * Nodal grouping in the predicted drainage pathway, with nodes \> 1 cm

Question 81

82 What is a key disadvantage of CT scans when evaluating an oral cavity or oropharyngeal neoplasm in a patient with tooth fillings?

Answer 81

Dental artifact often obscures anatomy/pathology.

Question 82

83 In what situations is evaluation with MRI most useful during the workup for head and neck cancer?

Answer 82

* Soft tissue tumor (e.g., base of tongue, infratemporal fossa, parapharyngeal space, parotid) * Intracranial extension or skull base involvement * Paranasal sinus disease (e.g., inspissated secretions vs. tumor) * Nasopharyngeal tumors * Temporal bone * Assessment of perineural invasion

Question 83

84 When is a PET/CT scan indicated during the treatment of a patient with head and neck cancer?

Answer 83

* Evaluation of equivocal disease * Workup of an unknown primary tumor (can identify up to a third of primary tumors) * Evaluate nodal disease (studies argue against its use in the cN0 neck) * Evaluate for distant metastases (may see a high number of false-positives but has a very high negative predictive value) * Surveillance after treatment

Question 84

85 True or False. All head and neck tumors are PET avid because of their high metabolic activity.

Answer 84

False. Several have either variable/inconsistent or no FDG-avidity. * Well-differentiated thyroid cancer * Medullary thyroid cancer * Indolent lymphomas * Neuroendocrine tumors * Teratomas * Soft tissue sarcomas

Question 85

86 Why is it difficult to use a PET/CT scan to determine the extent of a skull base tumor?

Answer 85

Brain metabolism is high, which can obscure skull-base tumors, or tumors with intracranial invasion.

Question 86

87 What might result in a false-positive result on a PET/CT scan?

Answer 86

* Infection * Normal physiologic activity * Inflammation (e.g., after radiation, surgical resection or biopsy, aspiration) * Osteoradnionecrosis * Granulomatous disease * Patient movement

Question 87

88 What is one of the major limitations of PET/CT scanning, which can result in a false-negative scan?

Answer 87

It is unreliable for lesions **\< 1 cm in diameter** (some scanners can reportedly detect suspicious lymph nodes as small as 5 mm).

Question 88

89 What is the sensitivity of PET scan for detecting squamous cell carcinoma recurrence less than 1 month after completion of radiation therapy? More than 1 month afterward?

Answer 88

**55%, 95%** Key issue: Waiting **3 months** after completion of radiation minimizes false-positives resulting from inflammation and continued tumor regression. Patients should be clinically assessed for tumor progression during or after therapy, and patients with progression or bulky (N3) disease may require restaging and salvage sooner.

Question 89

90 In addition to a CT scan, what imaging modality can be helpful for preoperative planning in a patient with a tumor invading the mandible that will require mandibulectomy or in a patient undergoing radiation therapy?

Answer 89

Panorex

Question 90

91 Although ultrasound is not often used for the workup of nodal or primary head and neck cancer (other than thyroid disease), it is often used to assist in what important diagnostic procedure?

Answer 90

FNA biopsy. CT-guided biopsy can also be considered.

Question 91

92 When should an excisional lymph node biopsy be considered?

Answer 91

It is not indicated for most head and neck cancers (e.g.,, squamous cell carcinoma). If there is concern for **hematoproliferative malignancy**, excisional biopsies are often necessary to provide adequate tissue for evaluation

Question 92

93 Incisional biopsies are routinely performed in the office setting for accessible tumors, such as oral cavity or oropharyngeal, to obtain a tissue diagnosis. Some clinicians recommend delaying this until after what key step in the workup?

Answer 92

Imaging

Question 93

94 What is the most common pathologic type of cancer in the head and neck (excluding salivary and thyroid tumors)?

Answer 93

Squamous cell carcinoma (\> 90%)

Question 94

95 Which immunohistochemical marker is most commonly associated with neural/cartilaginous tumors, melanoma, and Langerhans cell histiocytosis?

Answer 94

S-100

Question 95

96 Which immunohistochemical marker is associated with carcinomas and papillomas?

Answer 95

Cytokeratin

Question 96

97 Which immunohistochemical marker(s) is/are as sociated with melanoma?

Answer 96

* S-100 * HMB-45 * Melanoma-associated antigen recognized by T cells (MART-1) (diagnostic)

Question 97

98 Which immunohistochemical marker is associated with neuroendocrine tumors (e.g., Merkel cell carcinoma, paraganglioma)?

Answer 97

* Neuron-specific enolase (NSE) * Chromogranin * Synaptophysin

Question 98

99 Which immunohistochemical marker is most commonly associated with lymphoma?

Answer 98

* Leukocyte common antigen (LCA/CD45) * CD-20 → B-cell specificity * CD-3 → T-cell specificity

Question 99

100 Which tumors stain positive for vimentin on immunohistochemistry? For desmin?

Answer 99

* **Vimentin** → sarcomas, lipomas, myomas * **Desmin** → sarcomas, myomas

Question 100

101 Describe the World Health Organization (WHO) classification of mild, moderate, and severe dysplasia.

Answer 100

* Mild: nuclear atypia and architectural abnormalities of epithelial maturation confined to the basal third of the epithelium * Moderate: abnormalities extend to the middle third of the epithelium * Severe: abnormalities extend into the superficial third of the epithelium * Carcinoma in-situ: full-thickness abnormalities without invasion beyond the basement membrane

Question 101

102 What subtypes of squamous cell carcinoma of the head and neck have distinct clinical behaviors?

Answer 101

* Basaloid * Verrucous (\< 5%) * Spindle cell * Adenosquamous

Question 102

103 What subtype of squamous cell carcinoma is commonly seen in HPV-positive oropharyngeal tumors (tonsil and base of tongue) and are more likely to present at an advanced stage owing to early nodal and distant metastases?

Answer 102

**Basaloid carcinoma.** Note: Despite the early regional metastases, these tumors are fairly sensitive to treatment and therefore have a better prognosis than conventional squamous cell carcinoma.

Question 103

104 Describe the histopathology for spindle cell carcinoma.

Answer 103

**Spindle cell carcinoma** is also called **carcinosarcoma** or **pseudosarcoma** because it includes a squamous cell lesion on the surface and a more notable underlying malignant spindle cell component. Currently, it is thought that the tumor arises from epithelial cells and then undergoes _mesenchymal differentiation_.

Question 104

105 Why are spindle cell carcinomas, which are a subtype of squamous cell carcinoma, most commonly found in the oral cavity and larynx, also known as sarcomatoid, carcinosarcoma, or pseudosarcoma?

Answer 104

* Contains a superficial squamous cell lesion and a deeper malignant spindle cell component. * Stain positive for both **cytokeratin** (epithelial cells) and **vimentin** (mesenchymal cells). * Arises from epithelial cells and then undergoes mesenchymal differentiation

Question 105

106 What is the management strategy of choice for spindle cell carcinomas?

Answer 105

The strategy is controversial because of the limited numbers of case reports in the literature. Most recommend **surgery**. There is controversy about the radiosensitivity of the tumor.

Question 106

107 How can adenosquamous carcinoma be distinguished from mucoepidermoid carcinoma?

Answer 106

Mucoepidermoid carcinoma does not include a mucosal component. Adenosquamous carcinoma has a predom inant mucosal squamous cell component and a deeper adenocarcinoma component.

Question 107

108 What squamous cell carcinoma subtype manifests as a slow-growing, velvety, exophytic, and warty mass in elderly patients, and what pathologic feature determines their prognosis?

Answer 107

* Verrucous carcinoma * Focal areas of high-grade squamous cell carcinoma

Question 108

109 What is the preferred management for localized verrucous carcinoma?

Answer 108

Complete surgical resection. Surgery was superior to primary radiation in 5-year survival (89 vs. 58%).

Question 109

110 What are the most common sites of distant metastasis for head and neck squamous cell carcinoma?

Answer 109

* Lungs (66%) * Bone (22%) * Liver (10%) * Less often skin, mediastinum, and bone marrow

Question 110

111 Traditionally, what single prognostic factor has been shown to decrease overall survival by as much as 50%?

Answer 110

Regional nodal disease (N +)

Question 111

112 When considering nodal disease, what factors have been considered negative prognostic features?

Answer 111

* Presence of nodal disease (decreases survival by as much as 50%) * Increasing nodal size * Extracapsular spread * Bilateral neck disease * Matted lymph nodes * Disease in levels IV and V * “Skipped” levels * Invasion of local structures by nodal disease * Confluence of primary disease and nodal disease * Total number of involved lymph nodes

Question 112

113 During the radiologic workup for a patient with head and neck cancer, in addition to the information needed to provide a TNM stage, what specific radiologic feature regarding the primary tumor size has been identified as negative prognosticator?

Answer 112

**Gross tumor volume** (poorer locoregional control and overall survival). Note: Standardized uptake values (SUVs) for PET/CT scans have been investigated but results are inconclusive.

Question 113

114 What tumor biomarkers can be used to help determine prognosis in head and neck cancer?

Answer 113

* EGFR amplification and overexpression * HPV status * Loss of heterozygosity (suggests a loss of tumor suppressor gene function) * Aneuploidy

Question 114

115 When considering head and neck cancer as a whole, what are the most important contributors to overall cancer specific mortality?

Answer 114

* Locoregional recurrence (50 to 60%) * Distant metastases (20 to 30%) * Second primary disease (10 to 20%)

Question 115

116 What comorbidities most commonly impact the choice of therapeutic intervention in head and neck cancer patients (therapeutic comorbidity)?

Answer 115

* Severe lung disease and poor pulmonary function (e.g., not a candidate for a supraglottic laryngectomy) * Renal failure, hearing loss, neurologic disorder (e.g., choice of chemotherapeutic agents or therapy) * Severe atherosclerotic disease (e.g., may not be a candidate for free tissue transfer reconstruction)

Question 116

117 What comorbidities have been found to negatively impact prognosis in head and neck cancer (prognostic comorbidity)?

Answer 116

* Recent myocardial infarction or ventricular arrhythmia * Severe hypertension * Severe hepatic disease * Recent severe stroke

Question 117

118 What defines the ratio of therapy resulting in therapeutic effect to the amount that results in toxicity or mortality?

Answer 117

Therapeutic ratio or index

Question 118

119 What type of treatment regimen uses only surgery or radiation therapy for curative intent?

Answer 118

Single-modality treatment. Any approach using more than one treatment modality is considered multimodality or combined modality.

Question 119

120 What treatment approach uses chemotherapy and/or radiation therapy before definitive therapy?

Answer 119

Neoadjuvant/Induction therapy

Question 120

121 What treatment approach uses chemotherapy and radiation therapy together as the primary treatment modality?

Answer 120

Concurrent (concomitant) therapy

Question 121

122 What treatment approach uses radiation therapy with or without chemotherapy after primary surgical management?

Answer 121

Adjuvant therapy

Question 122

123 What treatment approach uses surgery, chemotherapy, and/or radiation for patients with recurrent or metastatic disease without the intent to cure? With the intent to cure?

Answer 122

* Palliative therapy * Salvage therapy

Question 123

124 Define the three types of clinical trials.

Answer 123

* Phase I: Defines the maximum tolerated dose or safety of a drug or invasive medical device * Phase II: Includes more patients than phase I; assesses the efficacy and side effects or toxicity associated with the intervention of interest * Phase III: Randomized prospective trial comparing the intervention of interest with the standard of care; at termination, can be considered for Food and Drug Administration approval for the intervention of interest

Question 124

125 What tumors are considered by the National Comprehensive Cancer Network (NCCN, 2011) to be very advanced and therefore managed with a unique algorithm regardless of tumor subsite?

Answer 124

T4b, any N, M0 or unresectable nodal disease

Question 125

126 The NCCN (2011) recommends either a clinical trial or standard therapy for patients diagnosed with very advanced head and neck cancer. How is standard therapy individualized, and what does it include?

Answer 125

ECOG performance status (PS): * PS 0–1: Concurrent chemoradiation therapy with cisplatin or induction chemotherapy followed by radiation or chemoradiation therapy * PS 2: Definitive radiation therapy or concurrent chemo radiation therapy * PS 3: Radiation therapy vs. single-agent chemotherapy vs. best supportive care Note: With improvement in surgical management recon structive techniques, some authorities suggest that surgical management should be considered for some T4b tumors.

Question 126

127 Patients with recurrent or persistent head and neck cancer after primary management are considered by the NCCN (2011) to have very advanced head and neck cancer. For patients who do not have distant metastases, what are the treatment options?

Answer 126

* Locoregional recurrence without prior radiation therapy * Resectable: Surgery ± adjuvant therapy (for adverse risk features) vs. primary chemoradiation therapy * Unresectable: individualized based on performance status to nonsurgical treatment * Locoregional recurrence or second primary with a history of prior radiation therapy * Resectable: Surgery ± reirradiation ± chemotherapy * Unresectable: Reirradiation ± chemotherapy vs. pallia tive care

Question 127

128 What is the standard therapy recommended by the NCCN (2011) for metastatic head and neck cancer? Based on ECOG performance status (PS):

Answer 127

* PS 0–1: Combination or single agent chemotherapy → best supportive care * PS 2: Single-agent chemotherapy or best supportive care → best supportive care * PS 3: Best supportive care

Question 128

129 What percentage of patients with locally advanced head and neck squamous cell carcinoma die from recurrent locoregional disease within five years of initial treatment?

Answer 128

30 to 50%

Question 129

130 What is the median length of survival for a patient diagnosed with locally advanced or metastatic head and neck squamous cell carcinoma?

Answer 129

6 to 9 months

Question 130

131 What are the primary goals of palliative therapy?

Answer 130

* Improve quality of life * Prolong life

Question 131

132 What prognostic factors predict poor outcome for patients with incurable head and neck squamous cell carcinoma?

Answer 131

* Poor performance status * Extensive tumor burden * Malnutrition * Prior history of extensive definitive therapeutic intervention * Rapid recurrence or progression

Question 132

133 What is the general surveillance schedule for history of physical examination and imaging as recommended by the NCCN (2011) for head and neck cancer?

Answer 132

History and physical examination * Year 1: Every 1 to 3 months * Year 2: Every 2 to 4 months * Year 3 to 5: Every 4 to 6 months * \> 5 years: Every 6 to 12 months Imaging * Within 6 months of treatment end for T3–4 or N2–3 cancers of the oropharynx, hypopharynx, glottic larynx, supraglottic larynx, and nasopharynx * Additional imaging based on concerning signs and symptoms

Question 133

134 When should you evaluate a patient’s thyroid stimulating hormone (TSH) level after completion of treatment for head and neck cancer?

Answer 133

If the neck was irradiated, check a TSH **every 6 to 12 months.**

Question 134

135 What are the three functional outcomes that are most commonly assessed for head and neck cancer?

Answer 134

* Airway * Speech * Swallowing

Question 135

136 What focuses on a patient’s perception of the impact of illness before, during, and after treat ment?

Answer 135

Health-related quality of life

Question 136

137 What domains are generally included in health related quality of life?

Answer 136

* Physical/somatic * Functional * Social * Psychological/emotional

Question 137

138 What are the three major categories that should be considered when determining candidacy for surgical intervention for head and neck cancer patients?

Answer 137

* Physiologic: Cardiorespiratory fitness, coagulation status, immune status, and weight loss (\> 10% body weight considered poor prognosticator for surgical intervention) * Anatomical: Surgical access to the subsite of interest (e.g., trismus in oropharyngeal cancer, brittle cervical spine or large osteophytes in laryngeal cancer) * Oncologic: Ability to achieve surgical margins, acceptable morbidity with complete resection

Question 138

139 When considering surgical management of a primary head and neck tumor, what is a critical component of successful management?

Answer 138

Ability to achieve negative margins

Question 139

140 For upper aerodigestive tract tumors, what is the minimum width of tissue that must be taken to achieve a negative margin?

Answer 139

Controversial. The presence of invasive carcinoma in the margin specimen is the only factor that indicates a positive margin. In many subsites, width cutoffs have been abandoned for narrow margin analysis resulting from the proximity of critical adjacent structures.

Question 140

141 True or False. En bloc tumor resection is the only oncologically sound method for surgical manage ment of a primary head and neck tumor

Answer 140

False. Narrow-margin analysis, “bread-loafing,” or tumor mapping with frozen pathologic analysis of margins does not compromise oncologic outcomes (Hinni, 2013)

Question 141

142 When a tumor invades a sensory or motor nerve, what is the recommended surgical approach?

Answer 141

**Dissect** proximally and distally along the nerve, take margins at either end and with the goal of obtaining negative margins on frozen section analysis.

Question 142

143 In a patient with biopsy-proven squamous cell carcinoma metastases to the cervical lymph nodes, what are the most likely site and subsite of origin?

Answer 142

Unknown primary: * Site: Upper aerodigestive tract * Subsite: Oropharynx

Question 143

144 Why is it clinically important, from both a prognostic and management standpoint, to identify the site of origin for an unknown primary tumor?

Answer 143

Failure to identify the site of origin results in * Significant decrease in 5-year overall survival (50%) * Need for wide-field radiation therapy with an increase in associated morbidity

Question 144

145 What imaging modality can be helpful in identifying the unknown primary in as many as 30% of TX head and neck cancer patients?

Answer 144

PET/CT scan

Question 145

146 Describe the surgical approach for a patient with an unknown primary tumor.

Answer 145

* Manual palpation of the upper aerodigestive tract * Visual inspection using naked-eye evaluation, rigid endoscopy, laryngoscopy and microscopy * Directed biopsies and frozen-section analysis. If negative, proceed. * Palatine and lingual tonsillectomy with frozen-section pathology ipsilateral to the cervical adenopathy. If nega tive, proceed. * Contralateral palatine and lingual tonsillectomy with frozen-section pathology. If negative, proceed. * Nasopharyngeal biopsies with frozen-section pathology. If negative, proceed. * Neck dissection and permanent serial sectioning of the biopsy specimens Note: If tumor is identified at any step, complete resection is advised. (Karni, 2011; Nagel, 2013).

Question 146

147 Why might tumor cells exposed to an increased concentration of growth factors, nutrients, and oxygen be more susceptible to radiation and hemotherapy?

Answer 146

**A larger number will transition from G0 to G1** and enter the cell cycle, during which their DNA is more susceptible to antineoplastic therapy.

Question 147

148 At what point during the cell cycle are cells most radiosensitive? Radioresistant?

Answer 147

* Radiosensitive: M phase and G2 * Radioresistant: S phase Note: The two most important checkpoints in relation to radiation damage are G1 and G2.

Question 148

149 Does the proliferation rate of a tumor determine its radiosensitivity?

Answer 148

Controversial. Both proliferating and nonproliferating tissues can be radiosensitive, but the effects in nonproliferating or slowly proliferating tissues are often delayed. Radiosensitivity is unique to each tumor.

Question 149

150 How does radiation result in cell killing?

Answer 149

Radiation therapy produces intracellular ionization → breaks chemical bonds, creates free radicals → DNA damage → cell death. Double-strand breaks are the most important and deadly injury imposed by radiation.

Question 150

151 What generally determines the maximum dose of radiation that can safely be delivered to a tissue?

Answer 150

Ability of adjacent normal tissue to withstand the radiation and effectively repair damage

Question 151

152 Although radiation can result in rapid cell death (apoptosis), some cells do not die until they attempt mitosis, and others continue to divide several times before cell death. What is this delayed cell killing called?

Answer 151

Mitotic cell death. This is why tumors do not shrink immediately after radiation and may take weeks to demonstrate the full effects of radiation treatment (simplified explanation).

Question 152

153 Describe the basic principles involved in clinical radiobiology, which is often described as the four Rs of radiotherapy.

Answer 152

* Repair: Sublethal damage between fractions * Redistribution: Into radiosensitive phases of the cell cycle * Repopulation: With increased time between fractions * Reoxygenation: Response to ionizing radiation is increased 1.5–3x in well-oxygenated cells; fractionation allows for increased oxygen delivery to previously hypoxic cells.

Question 153

154 What is the unit used to describe the absorbed radiation dose?

Answer 153

* Gray (Gy) = 1 Joule of energy per kilogram of material * 1 Gy = 100 centigray (cGy) = 100 rads (old unit) Note: The energy of radiation delivered determines the depth of tissue penetration.

Question 154

155 What are the two general forms of ionizing radiation?

Answer 154

* Particulate: Kinetic energy is carried by a particle that has a resting mass, such as electrons, protons, or neutrons. * Electromagnetic: Massless, chargeless packets of energy (photon) that move through space at the speed of light, including X-rays and gamma rays

Question 155

156 What are the three main radiotherapeutic modalities used clinically in head and neck cancer?

Answer 155

* Electrons: Produced by a linear accelerator; travel shorter distances within tissue * Photons/X-ray: Produced by linear accelerator; travel further within tissue; most widely used (e.g., intensity modulated radiation therapy, or IMRT) * Protons: Produced by a cyclotron; charged particles; pronounced peak of energy deposition with little dose deposited beyond it (Bragg peak) Note: Can use a mix of photons and electrons

Question 156

157 What device accelerates electrons to a high level of energy and then allows them to (1) exit the machine as an electron or (2) collide with a specific target that results in the emission of photons (both of which can be used for treatment)?

Answer 156

Linear accelerator

Question 157

158 In what type of radiation treatment is the radiation source located outside the patient?

Answer 157

External-beam radiation therapy (EBRT)

Question 158

159 What radiation strategy attempts to match the target volume (defined by high-resolution imag ing, such as CT or MRI) with a high dose of radiation while limiting the amount of radiation given to adjacent normal tissue?

Answer 158

Conformal therapy (three-dimensional conformal radiation therapy) Note: IMRT is preferentially used to accomplish these goals in the head and neck.

Question 159

160 What type of radiation therapy dynamically alters the intensity of radiation across a field during treatment delivery?

Answer 159

IMRT

Question 160

161 What type of radiation therapy delivers a full dose of radiation in a single (or very few) fraction(s) using photons generated by a cobalt-60 source or by a linear accelerator?

Answer 160

**Stereotactic radiation therapy**, referred to as **stereotactic radiosurgery** for intracranial and skull base applications

Question 161

162 What type of radiation therapy makes use of radionuclides that decay within specific anatomical subsites, resulting in very specific targeting?

Answer 161

Targeted radionuclide therapy (e.g., thyroid cancer and iodine-131)

Question 162

163 Which form of radiation energy is better able to deposit most of its energy at a specific target, minimizing the dose to surrounding tissues based on the Bragg peak?

Answer 162

Protons

Question 163

164 You are planning to treat a patient with a superficial head and neck cancer using photon radiation. To ensure that sufficient dose is deposited superficially, you create a material with a similar density to skin to place over the tumor. What is this called?

Answer 163

Bolus

Question 164

165 What type of fractionation schedule uses radiation given in multiple daily doses without changing the overall treatment time compared with traditional daily radiotherapy, and why does this potentially result in decreased late morbidity despite a higher total dose?

Answer 164

Hyperfractionation. Normal tissue is more sensitive to the size of each individual dose. Therefore, if you decrease the size of each individual dose while increasing the total dose given over the entire course, there should be increase tumor cell killing and decreased impact on normal tissues.

Question 165

166 What type of fractionation schedule relies on multiple daily treatments using larger doses of radiation and a shorter overall treatment time compared with standard daily radiation therapy?

Answer 165

Accelerated fractionation

Question 166

167 What are the three primary radiosensitizing strategies currently available?

Answer 166

* Decreasing hypoxemia (due to increased interstitial pressure within the tumor or comorbid anemia): Hyperbaric oxygen therapy\*, inhaled carbogen, hypoxic cell sensitizers (nimorazole, tirapazamine), recombinant human erythropoietin\*\* * Concomitant chemotherapy: Additive (kills micrometa stasis, toxicity profiles do not overlap) vs. synergistic effect (increased cytotoxic activity) * Targeted therapy: Goal is to decrease side effects and improve radiation efficacy; monoclonal antibody against EGFR (cetuximab). \* No change in 5-year outcomes \*\*Worse locoregional control and overall survival

Question 167

168 What are the five basic steps involved in radiation treatment?

Answer 167

1. Simulation 2. Treatment planning (defining target volumes, imaging, dose, schedule) 3. Verification 4. Dose delivery 5. Quality assurance

Question 168

169 Imaging the patient to delineate targets and treatment volumes is done using CT or MRI. Is this typically done before or after the patient is immobilized?

Answer 168

After. It allows for better accuracy of treatment.

Question 169

170 When planning radiation targets, what three volumes must be considered?

Answer 169

* Gross tumor volume: Delineates tumor boundaries * Clinical target volume: Identifies regions at high risk for harboring microscopic disease * Planning target volume: Includes a “margin” to allow and fraction to fraction variability in patient positioning

Question 170

171 What types of tissues are at risk for acute radiation related toxicity? Delayed toxicity?

Answer 170

* Acute: Rapidly dividing cells; skin, mucous membranes, bone marrow, tumor cells. Related to total treatment time, dose per fraction, total dose, time between treatments * Delayed: More slowly dividing cells; neural and connective tissue. Related to total dose and dose per fraction

Question 171

172 Acute radiation toxicity occurs over days to weeks following treatment. What are some of the most common toxicities associated with treatment of the head and neck?

Answer 171

* Mucositis * Dermatitis * Xerostomia * Hoarseness * Odynophagia * Dysphagia * Weight loss

Question 172

173 Delayed or late radiation toxicity occurs months to years after treatment. What are the most common toxicities?

Answer 172

* Xerostomia * Dental caries/decay * Osteoradionecrosis, chondronecrosis * Fibrosis * Hypothyroidism * Neurologic damage

Question 173

174 Compared with two- or three-dimensional conformal techniques, intensity-modulated radiation therapy may spare what organs within the head and neck?

Answer 173

* Salivary glands * Pharyngeal musculature * Otic structures * Optic structures * Temporomandibular joints (TMJs) * Brain

Question 174

175 In an effort to reduce the incidence of osteoradionecrosis, when should decayed and nonrestorable teeth be extracted in relation to radiation therapy?

Answer 174

_Before_ radiation

Question 175

176 What are the theoretical advantages to preoperative radiation therapy?

Answer 175

* Reduction of unresectable tumors to the point of resectability * Reduces the extent of necessary surgery * Microscopic disease is usually more radiosensitive pre operatively because it has a better blood supply. * Cells disseminated during the course of surgery may be less viable after radiation therapy. * Requisite treatment volumes are smaller preoperatively than postoperatively.

Question 176

177 What are the theoretical advantages to postoperative radiation therapy?

Answer 176

* Surgery is easier before radiation * Surgery allows for definition of the extent of tumor. * Fewer wound-related complications * Dosing can be adjusted depending on residual tumor after surgery.

Question 177

178 What type of fractionation regimen has been shown to result in better local control and overall survival compared with conventionally fractionated radiation therapy?

Answer 177

Hyperfractionated Note: With concurrent chemoradiation therapy, there is no benefit. This is a complex issue.

Question 178

179 What is the role of chemotherapy in the treatment of head and neck cancers?

Answer 178

* For patients undergoing treatment with curative intent, chemotherapy is used concurrent with radiation therapy to improve locoregional control of disease, either as definitive chemoradiation therapy or as chemoradiation therapy after complete surgical resection (adjuvant therapy). Induction chemotherapy (multidrug regimen given before definitive chemoradiation) is another accepted use of chemotherapy for head and neck cancer. * For patients with recurrent or metastatic disease not amenable to curative therapy, chemotherapy is used as a palliative treatment to help control disease and improve cancer-related symptoms.

Question 179

180 True or False. Head and neck squamous cell carcinoma is unusually sensitive to chemotherapy for a solid tumor

Answer 179

True

Question 180

181 For squamous cell carcinoma of the head and neck, chemotherapy (5-fluorouracil [5-FU]) and cisplatin) has been demonstrated to result in overall response rates up to 90%. What percentage of patients will have complete responses, and what percentage of these complete responses can be considered a cure?

Answer 180

* Complete response: 20 to 50% * Cure: ~ 0%; chemotherapy cannot be used with curative intent.

Question 181

182 Studies have shown that patients who have not been treated with prior surgery and/or radiation respond to chemotherapy almost twice as often as patients who had. What might explain this?

Answer 181

* Better performance status before treatment * Intact blood supply to the tumor * Prior radiation may select for clonal populations of chemo-resistant cells

Question 182

183 What class of chemotherapeutic agents target DNA and cause cross-linking, double-strand breaks, or substitutions, thereby interfering with DNA replication and ultimately causing mutation and/or cell death?

Answer 182

Alkylating agents

Question 183

184 What inorganic platinum chemotherapeutic agent results in DNA cross-links, denaturation of strands, covalent bonds with DNA bases, and DNA intrastrand cross-links?

Answer 183

Cisplatin

Question 184

185 What common side effects are associated with cisplatin administration?

Answer 184

1. Nephrotoxicity 2. Ototoxicity 3. Neurotixicity 4. Nausea/vomiting 5. Electrolyte disturbances 6. Myelotoxicity

Question 185

186 Name the second-generation platinum agent that binds with DNA to create interstrand and intrastrand cross-links and protein-DNA cross-links that ultimately result in interruption of the cell cycle and apoptosis

Answer 185

Carboplatin

Question 186

187 What class of chemotherapeutic agents inhibits accurate DNA replication by imitating naturally occurring metabolites imperative to DNA replication? What are some examples?

Answer 186

Antimetabolites 1. Methotrexate: Binds to **dihydrofolate reductase**, which is necessary for de novo synthesis of thymidine and purine synthesis 2. 5-FU: Irreversibly binds to **thymidylate synthetase**, blocking conversion of uridine to thymidine, thereby preventing DNA synthesis

Question 187

188 Cultured Streptomyces spp. produce compounds that function as antibiotic chemotherapeutic agents. What agent in this class results in (1) intercalation between base pairs; (2) forms com plexes with iron, thus reducing oxygen to super oxide and hydroxyl radicals which result in DNA strand breaks; (3) DNA cross-linking, alkylation, and oxygen radicals?

Answer 187

Antitumor antibiotics ● Doxorubicin ● Bleomycin ● Mitomycin

Question 188

189 What class of chemotherapeutic agents binds to free tubulin dimers and therefore results in disruption of microtubule polymerization or de polymerization and ultimate disruption of the cell cycle? What are some examples?

Answer 188

Alkaloids ● Vincristine: Binds irreversibly to microtubules and spindle proteins in S phase and interferes with the mitotic spindle → arrest in metaphase ● Vinblastine: Binds to tubulin and inhibits microtubule formation, disrupts mitotic spindle → arrest in M phase

Question 189

190 What class of chemotherapeutic agents causes stabilization of microtubules, thereby inhibiting the normal cell cycle by preventing microtubule disassembly and arrest at the G2/M phase and apoptosis? What are some examples?

Answer 189

Taxanes ● Docetaxel ● Paclitaxel

Question 190

191 What chimeric monoclonal antibody targeting EGFR, which is overexpressed in head and neck squamous cell carcinoma, has proven to be effective for this pathology?

Answer 190

Cetuximab

Question 191

192 What recombinant humanized monoclonal anti body targets EGFR and is currently being inves tigated in head and neck cancer?

Answer 191

Bevacizumab

Question 192

193 What are the potential pros and cons of induction or chemotherapy followed by definitive treatment in head and neck squamous cell carcinoma?

Answer 192

Pros: ● Decrease the size of the tumor prior to definitive management ● Increase the response to locoregional definitive manage ment (both radiation and surgery may be more effective for smaller tumors) ● Theoretically decreases the risk for distant metastases ● Assess tumor response to chemotherapy (also a surro gate marker for radiosensitivity) Cons: ● Difficulty identifying tumor extent ● Inability to tolerate definitive management due to toxicities ● Increased cost and complexity of treatment ● Decreased compliance with treatment

Question 193

194 Phase II trials demonstrated considerable promise for the use of an induction/neoadjuvant approach to head and neck squamous cell carcinoma. What were the results of subsequent phase III trials?

Answer 193

Controversial. Initial phase III studies demonstrated no survival advantage. However, more recent phase III trials, including agents such as docetaxel, cisplatin, and 5-FU, demonstrated both a progression-free survival and overall survival advantage (European Organization for Research and Treatment of Cancer [EORTC] 24971; TAX 324).

Question 194

195 The Head and Neck Contracts Program, run by the National Cancer Institute, and the Head and Neck Intergroup Study 0034 both demonstrated that adjuvant chemotherapy after primary surgery or radiation has the potential to reduce what key oncologic outcome measure?

Answer 194

● Distant metastases ● Did not impact overall survival ● Can be considered “maintenance” chemotherapy

Question 195

196 What are some of the attributes that define high risk disease in head and neck cancer patients that benefits from adjuvant chemotherapy?

Answer 195

● Positive surgical margins ● Extracapsular extension ● T3/T4 primary disease ● Higher nodal stage ● Perineural invasion ● Angiolymphatic invasion ● Involvement of level IV or V lymph nodes

Question 196

197 What is the rationale for using chemotherapy and radiation therapy together to treat head and neck squamous cell carcinoma?

Answer 196

Each modality functions independently from the other, but together they result in synergistic chemotherapeutic radiosensitization.

Question 197

198 Phase III trials have demonstrated improved dis ease-free survival for patients undergoing adjuvant chemoradiation therapy for high-risk disease. What factors conferred a high-risk status for these studies?

Answer 197

● Positive surgical margins ● Extracapsular extension

Question 198

199 Which agents have shown a survival advantage for concurrent chemotherapy as single agents?

Answer 198

● Cisplatin (low-dose daily; high-dose every 3 weeks) ● Carboplatin ● 5-FU

Question 199

200 Aggressive, multiagent chemotherapy has been added to radiation therapy for head and neck cancer and has resulted in a locoregional control rate in some studies of \> 90%. In this cohort of patients, what is the most likely oncologic failure?

Answer 199

Distant metastases. May suggest a role for induction chemotherapy. Note: Controversy is ongoing as to whether the benefit of multiagent chemotherapy outweighs the risks. Therefore, single-agent chemoradiation therapy remains the standard of care for this approach.

Question 200

201 What clinical outcome has driven research into definitive chemoradiation strategies for head and neck cancer? Name two studies that provided evidence to uspport this approach.

Answer 200

Organ preservation Department of Veterans Affairs Laryngeal Cancer Study Intergroup Radiation Oncology Group (RTOG) 91–11

Question 201

202 How are the lymph node levels divided in the neck? (▶ Fig. 7.1)

Answer 201

They are separated into levels based on anatomic or surgical and radiographic criteria. The following are the most commonly involved groups: ● Level I (IA/IB) ○ IA: Submental triangle ○ IB: Submandibular triangle ● Level II (IIA/IIB) ○ IIA: Upper jugular chain ○ IIB: Submuscular recess ● Level III: Middle jugular chain ● Level IV: Lower jugular chain ● Level V (VA/VB): Posterior triangle ○ VA: Spinal accessory chain ○ VB: Supraclavicular and transverse cervical chain ● Level VI: Anterior jugular chain

Question 202

203 In addition to the six nodal levels, there are additional, unclassified nodal groups that are important in the surgical management of the neck. What are these, and where are they found?

Answer 202

● Suboccipital nodes: Deep to the insertion of the trapezius muscle ● Retroauricular nodes: Superficial postauricular region ● Parotid nodes: Can be superficial to, within or deep to the parotid gland ● Retropharyngeal nodes: Between the prevertebral fascia and the pharyngeal constrictor muscles ● Facial nodes: Superficial and deep to the facial artery and vein

Question 203

204 What lymph node levels in the neck are unpaired?

Answer 203

Level IA. Level VI is often considered to have a right and a left but may also be considered as a single compartment.

Question 204

205 How is level IB distinguished from level IIA surgically and radiographically?

Answer 204

Posterior edge of the submandibular gland

Question 205

206 How is the lateral border of level IIA defined radiographically?

Answer 205

Posterior border of the internal jugular vein

Question 206

207 What anatomical structure divides lymph node level II into IIA and IIB surgically?

Answer 206

Spinal accessory nerve (CN XI)

Question 207

208 How are the superior and inferior boundaries of level IIA surgically defined?

Answer 207

● Superior: Skull base ● Inferior: Carotid bifurcation

Question 208

209 What are the radiographic and surgical landmarks that separate neck levels II and III?

Answer 208

Inferior border of the hyoid bone (radiographic) and carotid bifurcation (surgical)

Question 209

210 What are the superior and inferior borders of level III radiographically?

Answer 209

● Superior: Horizontal plane from the inferior border of the hyoid bone ● Inferior: Horizontal plane from the inferior border of the cricoid cartilage

Question 210

211 What are the radiographic and surgical landmarks that separate neck levels III and IV?

Answer 210

Inferior border of the cricoid cartilage (radiographic) and the omohyoid muscle (surgical)

Question 211

212 What anatomical structure divides lymph node level V into VA and VB?

Answer 211

A horizontal plane from the inferior border of the cricoid cartilage Note: Level VA includes the spinal accessory nodes, VB includes the transverse cervical nodes and supraclavicular nodes. Just inferior to the clavicle lies the sentinel node or Virchow node.

Question 212

213 What are the surgical landmarks that define level VI (central compartment) lymphatics?

Answer 212

Hyoid bone superiorly, suprasternal notch inferiorly, and common carotid arteries laterally

Question 213

214 Level VI lymph nodes are at greatest risk for metastasis from which primary locations?

Answer 213

● Glottic and subglottic larynx ● Pyriform sinus ● Cervical esophagus ● Thyroid gland

Question 214

215 What are the major divisions of cervical fascia in the neck?

Answer 214

● Superficial cervical fascia ● Deep cervical fascia: Superficial (investing), middle (visceral), and deep layers

Question 215

216 What layer of cervical fascia covers the superficial surface of the platysma muscle and is continuous with the superficial muscular aponeurotic system (SMAS) superiorly in the face and fascia overlying the chest, shoulder, and axilla?

Answer 215

Superficial cervical fascia

Question 216

217 Which layer of cervical fascia arises from the vertebral spinous processes, wraps around the SCM and trapezius muscles, covers the mylohyoid muscle and anterior bellies of the digastric muscle, attaches to the hyoid bone, forms the floor of the submandibular and posterior triangle, wraps around the submandibular gland and parotid glands, and splits at the mandible into the internal layer, which lies over the medial surface of the medial pterygoid muscle and inserts onto the skull base, while the outer layer passes over the masseter muscle and inserts onto the zygomatic arch?

Answer 216

Superficial (investing) layer of the deep cervical fascia

Question 217

218 What are the two subdivisions of the middle layer of the deep cervical fascia?

Answer 217

● Muscular division: Surrounds infrahyoid strap muscles, attached superiorly to the hyoid bone and thyroid cartilage and inferiorly to the sternum ● Visceral division: Surrounds the thyroid, trachea, and esophagus and extends into the mediastinum to connect with the fibrous pericardium. Superiorly, the fascia may blend with the buccopharyngeal fascia (controversial).

Question 218

219 Name the fascial layers that line the inner (pha ryngeal) and outer (cervical) surface of the pha ryngeal constrictor muscles.

Answer 218

● Inner: Pharyngobasilar fascia ● Outer: Buccopharyngeal fascia

Question 219

220 What are the two named divisions of the deep layer of the deep cervical fascia?

Answer 219

● Prevertebral fascia: Fused to the transverse processes of the vertebral bodies with extension medially to cover the prevertebral musculature and vertebral bodies. Continues posteriorly to cover the extensor muscles and insert onto the vertebral spinous processes ● Alar fascia: Located between the prevertebral fascia and the visceral division of the middle layer of the deep cervical fascia

Question 220

221 What layer(s) of cervical fascia form the carotid sheath?

Answer 220

The superficial (investing), middle (visceral), and deep layers of the deep cervical fascia

Question 221

222 What is enveloped by the superficial (investing) layer of the deep cervical fascia?

Answer 221

● Two muscles (SCM and trapezius) ● Two glands (parotid and submandibular gland) ● Two spaces (Posterior triangle, suprasternal space of Burns)

Question 222

223 What is the vascular supply and innervation of the platysma muscle?

Answer 222

● Innervation: Cervical branch of the facial nerve (CN VII) ● Arterial supply: Submental branch of the facial artery and suprascapular artery

Question 223

224 The SCM extends from the mastoid process of the temporal bone to the clavicle and manubrium, where it inserts as two separate heads (medial/ sternal and lateral/clavicular) forming the lesser supraclavicular fossa. What is the innervation and blood supply to this muscle?

Answer 223

● Innervation: Spinal accessory nerve (CN XI), ventral rami of C2–4 ● Arterial supply: ○ Occipital and posterior auricular arteries ○ Superior thyroid artery ○ Suprascapular artery

Question 224

225 Describe the innervation and arterial supply to the anterior and posterior bellies of the digastric muscle.

Answer 224

● Innervation ○ Anterior: mylohyoid branch of the inferior alveolar nerve (CN V3) ○ Posterior: facial nerve (CN VII) ● Arterial supply ○ Anterior: submental branch of the facial artery ○ Posterior: posterior auricular and occipital arteries

Question 225

226 Name the four paired infrahyoid strap muscles in order from superficial to deep.

Answer 225

● Superficial: sternohyoid and omohyoid ● Deep: sternothyroid and thryohyoid

Question 226

227 What is the predominant innervation and vascular supply to the infrahyoid strap musculature?

Answer 226

● Innervation: Ansa cervicalis (C1–3) ● Arterial supply: Superior thyroid artery and lingual artery

Question 227

228 What muscle can be found in the lateral neck extending from the transverse processes of C3 through C6 to the first rib, passing just posterior to the phrenic nerve, just anterior to the subclavian artery, and just medial to the brachial plexus?

Answer 227

Anterior scalene muscle

Question 228

229 What spinal nerves provide sensory innervation to the cervical skin?

Answer 228

Ventral rami of C2–4 from the cervical plexus * Lesser occipital nerve (C2): Posterior scalp and ear * Great auricular nerve (C2, C3): Anterior branch → skin over parotid gland; posterior branch → mastoid area, lower ear and lobule * Transverse cutaneous nerve (C2, C3): Ascending/de scending branches → anterolateral neck skin * Supraclavicular nerve (C3, C4): Medial, intermediate and lateral (posterior) branches → supraclavicular skin from second rib to shoulder

Question 229

230 What anatomical location describes the point where the cutaneous nerves of the cervical plexus exit posterior to the sterncleidomastoid muscle, and what is the relationship between this point d the spinal accessory nerve (CN XI)?

Answer 229

Erb’s point The spinal accessory nerve (CN XI) passes approximately 1 cm superior and deep to the sternocleidomastoid muscle and Erb’s point.

Question 230

231 What are the muscular branches that constitute the cervical plexus?

Answer 230

● Phrenic nerve (C3–5) ● Inferior branch of ansa cervicalis (C1–3) ● Segmental branches including cervical branches of the spinal accessory nerve (C1–4)

Question 231

232 What structure travels deep to the deep cervical fascia and superficial to the anterior scalene and can be found when dissecting levels III and IV?

Answer 231

Phrenic nerve (C3–5)

Question 232

233 The submandibular duct passes between what two nerves?

Answer 232

Lingual nerve and hypoglossal nerve

Question 233

234 The sympathetic trunk travels deep and medial to the carotid sheath and is just superficial to the prevertebral fascia and what muscle?

Answer 233

Longus colli

Question 234

235 What structure branches off the vagus nerve (CN X) at approximately T1–2, wraps around the subclavian artery from anterior to posterior, ascends in the neck along the tracheoesophageal groove, generally posterior to the inferior thyroid artery, and enters the larynx at a 30- to 45-degree angle by passing under the inferior constrictor muscle and through the cricothyroid joint space?

Answer 234

Right recurrent laryngeal nerve

Question 235

236 The left recurrent laryngeal nerve wraps around the aortic arch before passing superiorly in the neck in the tracheoesophageal groove to enter the larynx at a 0- to 30-degree angle by passing under the inferior constrictor muscle and through what laryngeal space?

Answer 235

Cricothyroid

Question 236

237 Describe the classic relationship between the inferior thyroid artery and the recurrent laryngeal nerve.

Answer 236

● 50%: Nerve passes deep to artery. ● 25%: Nerve passes between arterial branches. ● 25%: Nerve passes anterior to artery. Note: This relationship is extremely variable and may not represent a reliable landmark for identifying the nerve.

Question 237

238 What is the incidence of a right nonrecurrent inferior/recurrent laryngeal nerve?

Answer 237

0.5 to 1%

Question 238

239 What anomaly is associated with a right aberrant retroesophageal subclavian artery? Situs inversus?

Answer 238

● Right nonrecurrent inferior/recurrent laryngeal nerve ● Left nonrecurrent inferior/recurrent laryngeal nerve

Question 239

240 What structure is formed by the anastomoses of the posterior (dorsal) recurrent laryngeal nerve fibers and the posterior (dorsal) fibers of the internal branch of the superior laryngeal nerve, and what is its function?

Answer 239

Galen anastomosis (aka ramus anastomaticus)

Question 240

241 What artery branches from the aortic arch, passes over the trachea from left to right and branches into the right common carotid artery and right subclavian artery?

Answer 240

Innominate (brachiocephalic) artery

Question 241

242 What are the major divisions of the right subclavian artery?

Answer 241

● First part: Right, from innominate artery just posterior to the sternoclavicular joint to the medial border of the anterior scalene muscle; may rise 2 cm above the clavicle. Left, from aortic arch at T3–4 to the medial border of the anterior scalene muscle ● Second part: Highest point, spans the width of the anterior scalene muscle. ● Third part: Lateral border of anterior scalene muscle to outer border of the first rib → axillary artery

Question 242

243 What artery branches off the first part of the subclavian artery, ascends in the neck by passing through the foramina of the transverse processes of C1–C6, and enters the foramen magnum and joins with its paired contralateral vessel to form the basilar artery?

Answer 242

Vertebral artery

Question 243

244 What are the three arteries that arise from the first part of the subclavian artery?

Answer 243

● Vertebral artery ● Thyrocervical trunk ● Inferior thoracic artery

Question 244

245 Name the branches of the thyrocervical trunk that branch off the first part of the subclavian artery at approximately the medial border of the anterior scalene muscle?

Answer 244

● Inferior thyroid artery ● Suprascapular artery ● Superficial/transverse cervical artery

Question 245

246 On the left, the costocervical trunk arises from the first part of the subclavian artery, and on the right it arises from the second part. To what vessels does it give rise?

Answer 245

* Deep cervical artery * Superior intercostal artery

Question 246

247 What structures are contained within the carotid sheath?

Answer 246

* Carotid arteries: Medial * Internal jugular vein: Lateral * Vagus nerve: Posterior

Question 247

248 At what vertebral level(s) is the carotid bifurcation in the majority of people?

Answer 247

C3–4 (~ at the level of the superior border of the thyroid cartilage)

Question 248

249 What bony skull base structure runs between the internal and external carotid arteries?

Answer 248

Styloid process

Question 249

250 What are the branches of the external carotid artery, and to what named branches do these arteries give rise? (▶ Fig. 7.2)

Answer 249

1. Superior thyroid artery → infrahyoid, superior laryngeal, cricothyroid and sternocleidomastoid arteries 2. Ascending pharyngeal artery → pharyngeal, inferior tympanic, and meningeal arteries 3. Lingual artery → suprahyoid, dorsal lingual, and sub lingual arteries 4. Facial artery → ascending palatine, tonsillar, submental and glandular arteries 5. Occipital artery → Upper and lower branches to the sternocleidomastoid muscle 6. Posterior auricular artery → stylomastoid artery 7. Internal maxillary artery → see below 8. Superficial temporal artery → frontal and parietal branch

Question 250

251 What artery arises at the level of the greater cornu of the hyoid bone from the external carotid, runs deep to the posterior belly of the digastric muscle and stylohyoid muscle, turns at the middle constrictor to follow the posterior boundary of the submandibular gland and medial border of the medial pterygoid muscle, and then winds around the mandible at the level of the facial notch?

Answer 250

Facial artery

Question 251

252 What artery, or branch of this artery, often transverses level IIB in the neck and “tethers” the hypoglossal nerve in level IIA?

Answer 251

Occipital artery

Question 252

253 What are the three parts of the internal maxillary artery?

Answer 252

* First part/mandibular portion: Arises between the ramus of the mandible and the sphenodmandibular ligament, passes the posterior to the lateral pterygoid muscle * Second part/pterygoid portion: Within the lateral pterygoid muscle * Third part/pterygopalatine portion: Pterygopalatine fossa

Question 253

254 What are the branches of the first part (mandibular portion) of the internal maxillary artery?

Answer 253

* Deep auricular artery * Anterior tympanic artery * Middle meningeal artery * Accessory meningeal artery * Inferior alveolar artery * Mylohyoid artery

Question 254

255 What are the branches of the second part (pterygoid part) of the internal maxillary artery?

Answer 254

1. Anterior deep temporal artery 2. Posterior deep temporal arteries 3. Pterygoid branches 4. Masseteric artery 5. Buccinator/buccal artery

Question 255

256 What are the branches of the third part (pterygopalatine part) of the internal maxillary artery?

Answer 255

1. Posterior superior alveolar artery 2. Infraorbital artery 3. Sphenopalatine artery 4. Artery of the pterygoid (vidian) canal 5. Pharyngeal artery

Question 256

257 What sensory organ(s) is located at the bifurcation of the common carotid artery, and what is the innervation?

Answer 256

* Carotid sinus → internal carotid artery, baroreceptor, glossopharyngeal nerve (IX), vagus nerve (X), sympathetics * Carotid body → posterior or between the carotid bifurcation, chemoreceptor, same innervation

Question 257

258 What veins give rise to the external jugular vein, what structures does it drain, and where does it drain into?

Answer 257

* Retromandibular vein and postauricular vein * Scalp and face * Subclavian vein

Question 258

259 What superficial veins drain the anterior neck by emptying into the external jugular vein or the subclavian vein and are at risk during thyroidectomy and tracheostomy?

Answer 258

Anterior jugular veins

Question 259

260 What structures exit the skull base through the jugular foramen with the internal jugular vein?

Answer 259

Glossopharyngeal nerve (IX), vagus nerve (X), accessory nerve (XI), inferior petrosal sinus, and internal jugular vein

Question 260

261 The internal jugular vein drains most of the head and neck into what venous structure?

Answer 260

Subclavian vein → brachiocephalic vein

Question 261

262 What structure most commonly passes from the superior mediastinum, through the thoracic inlet on the left into level IV, passing anterior to the phrenic nerve and anterior scalene muscle, posterior to the carotid sheath, and most commonly terminates at the confluence of the left subclavian vein and internal jugular vein?

Answer 261

Thoracic duct

Question 262

263 What is the incidence of right-sided thoracic duct in the neck? Bilateral?

Answer 262

* Right-sided only: 4% * Bilateral thoracic ducts: 12 to 15%

Question 263

264 Malignancies involving the neck primarily arise as metastatic lesions (most commonly from the upper aerodigestive tract). What percentage of neck malignancies will arise primarily in the neck, and what are the most common sites of origin?

Answer 263

15%. Thyroid, salivary gland, and lymphoma

Question 264

265 What percentage of neck masses in pediatric patients are benign?

Answer 264

\> 90%, most commonly inflammatory

Question 265

266 Approximately what percentage of neck masses in adult patients are neoplastic?

Answer 265

~ 80%

Question 266

267 What is the most common head and neck malignancy in the _pediatric_ population and the second most common head and neck malignancy in the _adult_ population after squamous cell carcinoma?

Answer 266

Lymphoma

Question 267

268 What are common sites of origin for locoregional metastatic disease to cervical lymph nodes?

Answer 267

1. Upper aerodigestive tract 2. Head and neck skin 3. Major and minor salivary glands 4. Thyroid gland

Question 268

269 What are the most common sites of origin for distant metastatic disease to cervical lymph nodes?

Answer 268

1. Lung 2. Thoracic esophagus 3. Ovary 4. Prostate 5. Kidney

Question 269

270 What is the most likely site of origin for squamous cell carcinoma metastatic to cervical lymph nodes with an unknown primary?

Answer 269

Oropharynx (tonsil and tongue base)

Question 270

271 What are the most common symptoms associated with nodal metastases to the neck?

Answer 270

1. Palpable neck mass 2. Symptoms resulting from compression (e.g., dysphagia, dysphonia) 3. Symptoms resulting from invasion (e.g., recurrent lar yngeal nerve paralysis, accessory neuropathy, pain)

Question 271

272 What is the most common anterior neck mass diagnosed on physical examination?

Answer 271

Thyroid nodule

Question 272

273 What are important features of lymphadenopathy that can be detected on a careful physical examination?

Answer 272

* Location * Mobility on palpation and with swallowing * Potential deep involved structures * Firm (i.e., not rubbery) * Involvement of the skin

Question 273

274 True or False. Nodal cervical metastases from locoregional tumors are generally extremely painful.

Answer 273

False

Question 274

275 When malignant lymphadenopathy is immobile and invasion or adherence of the nodal disease to underlying structures is suspected, what is the neck referred to as, and what implications does this have on management?

Answer 274

Fixed. It may be unresectable.

Question 275

276 What is the best diagnostic test for determining the cause of a neck mass without a known primary tumor?

Answer 275

FNA biopsy

Question 276

277 What diagnostic test is indicated if an FNA biopsy is performed on a suspicious cervical lymph node with an unknown primary and the pathology demonstrates lymphoid cells?

Answer 276

Excisional lymph node biopsy, most commonly in the operating room

Question 277

278 Although there has been a significant amount of research into the application of sentinel lymph node biopsy for head and neck cancer, currently the literature supports its routine use for what types of cancer?

Answer 277

Cutaneous malignancies (especially **melanoma**). May also be used for known oral cavity cancer in patients with cN0 neck disease.

Question 278

279 What are the general steps involved with per forming a sentinel lymph node biopsy?

Answer 278

1. Primary tumor injected with technetium-99 sulfur colloid in the rads suite. 2. Lymphoscintigraphy is performed, and the sentinel node is identified. 3. Patient is brought to the operating room (generally within 4 hours). 4. Use the gamma probe to confirm the location of the sentinel node and design surgical incision. 5. Slowly inject ~ 0.3 mL of isosulfan blue intradermally (not subq). This should result in a lacelike pattern under the skin. This should be done at least 10 minutes before any local anesthetic is injected if any is injected at all. 6. Expose the tissue suspected of harboring the sentinel lymph node. 7. Using the gamma probe (pointing away from the primary site if possible to avoid shine-through), identify the area containing the node. Visual confirmation of a blue node is supportive but not required if the gamma probe is suggestive. 8. Excise the node and perform a 10-second gamma count in the dissection field to confirm that the sentinel node(s) was (were) removed. 9. With the node placed away from the primary site and sentinel biopsy site, perform a confirmatory gamma count for 10 seconds to ensure you have removed the correct node. 10. Excise the primary with appropriate margins. This may be done first if the primary is in close proximity to the sentinel lymph nodes. 11. Depending on the pathology report results, the wound can be closed or a formal neck dissection is performed. Note: It is not unusual for multiple lymph nodes to be identified. If the dissection bed after sentinel node excision contains \> 10% of the gamma count detected before the node was removed, further exploration for remaining nodes is warranted.

Question 279

280 In patients with common carotid artery or internal carotid artery invasion with tumor, which test should be employed before surgical resection of the involved carotid artery?

Answer 279

Carotid artery balloon occlusion test

Question 280

281 What imaging modality is most commonly used for the initial workup of an adult neck masses?

Answer 280

CT with contrast

Question 281

282 What imaging modality is best for evaluation of perineural spread associated with neck masses?

Answer 281

MRI

Question 282

283 What imaging modality is best used to determine distant metastatic spread of disease and as an adjunct in patients with an unknown primary tumor?

Answer 282

PET/CT

Question 283

284 What is the AJCC node (N) staging system for head and neck cancer (including salivary gland; excluding nasopharynx and thyroid)?

Answer 283

* NX: LNs cannot be assessed * N0: no regional LN met * N1: single ipsi LN ≤3 cm ENE(-) * N2a: single ipsi LN \>3 ≤6 cm ENE(-) * N2b: multiple ipsi LNs ≤6 cm ENE(-) * N2c: bilat or contralat LNs ≤6 cm ENE(-) * N3a: any LN \>6 cm and ENE(-) * N3b: any LN and ENE(+)

Question 284

285 What is the AJCC clinical lymph node (N) staging system for nasopharyngeal cancer?

Answer 284

* Differet from most other H&N cancer N staging * NX: LN cannot be assessed * N0: no regional LN met * N1: ≤6 cm above the caudal border of cricoid cartilage * Unilateral met in cervical LNs * Unilt or bilat mets in RPLN * N2: bilat met in cervical LNs ≤6 cm above the caudal border of cricoid cartilage * N3: * Unilat or bilat met in cervical LNs \>6 cm * Extension below the cuadal border of cricoid cartilage

Question 285

286 What is the AJCC lymph node (N) staging system for soft tissue sarcomas?

Answer 285

* Nx: Regional lymph nodes cannot be assessed. * N0: No regional lymph node metastases. * N1: Regional lymph node metastases

Question 286

287 What is the AJCC lymph node (N) staging system for thyroid cancer?

Answer 286

* NX: Regional lymph nodes cannot be assessed * N0: No evidence of regional lymph node metastasis * N0a\*: 1+ cytologic or histologically confirmed benign lymph nodes * N0b\*: No radiologic or clinical evidence of locoregional lymph node metastasis * N1\*: Metastasis to regional nodes * N1a\*: Metastasis to **level VI or VII (pretracheal, paratracheal, prelaryngeal / Delphian or upper mediastinal)** lymph nodes; this can be unilateral or bilateral disease * N1b\*: Metastasis to unilateral, bilateral or contralateral **lateral neck lymph nodes (levels I, II, III, IV or V)** or **retropharyngeal** lymph nodes \* All categories may be subdivided: (s) solitary tumor and (m) multifocal tumor (the largest tumor determines the classification)

Question 287

288 For a patient with squamous cell carcinoma of the head and neck, the presence of nodal disease traditionally results what 5-year overall survival?

Answer 287

50%

Question 288

289 In well-differentiated thyroid cancer, for what patient population does the presence of nodal metastases not influence their overall stage or prognosis?

Answer 288

Patients younger than 45 years

Question 289

290 What pathologic nodal features have been associated with poor prognosis in head and neck cancer?

Answer 289

* Extracapsular spread (may not be true for HPV positive tumors) * Involvement of levels IV and V * Skipped nodal levels * Number of involved nodes * Size of involved nodes * Bilateral nodal disease * Matted lymph nodes

Question 290

291 What is the difference between a therapeutic and an elective neck dissection?

Answer 290

* **Elective:** Performed in a **clinically N0 neck** owing to high risk (\> 20%) for occult metastases * **Therapeutic:** Performed in a **clinically N(+) neck**

Question 291

292 What type of neck dissection is delayed after primary chemoradiation therapy?

Answer 291

Staged neck dissection

Question 292

293 What type of neck dissection is performed for recurrent disease after primary therapeutic intervention?

Answer 292

Salvage neck dissection

Question 293

294 What is removed in a radical neck dissection?

Answer 293

* Lymph node levels I–V * SCM muscle * Spinal accessory nerve * Internal jugular vein

Question 294

295 What are the three types of a modified radical neck dissection?

Answer 294

All three include dissection of levels I–V. Each type varies from a radical neck dissection by preserving the sterno cleidomastoid (SCM), internal jugular vein (IJV) and/or spinal accessory nerve (SAN): * Type I: Preserves SAN * Type II: Preserves SAN + IJV * Type III (complete): Preserves SAN + IJV + SCM

Question 295

296 The NCCN (2011) recommends using the term comprehensive neck dissection instead of radical or modified radical. How does the NCCN define a comprehensive neck dissection?

Answer 295

Resection of nodal levels I–V, _regardless_ of preservation of SCM muscle, spinal accessory nerve, or IJV

Question 296

297 In a select neck dissection, the surgeon will remove the lymphatic basins at highest risk for disease, which may vary according to the tumor, subsite, and individual patient. What is the most accurate way to refer to a select neck dissection?

Answer 296

**Select neck dissection, levels X–X** (detailing which levels were removed). However, the most common select neck dissections have associated terminology with which it is important to be familiar (see below).

Question 297

298 In what type of neck dissection are levels I–III dissected, preserving the nonlymphatic structures of the neck?

Answer 297

**Supraomohyoid neck dissection.** Select neck dissection (levels I–III)

Question 298

299 In what type of neck dissection are levels I–IV dissected, preserving the non-ymphatic structures of the neck?

Answer 298

**Lateral neck dissection.** Select neck dissection (levels I–IV)

Question 299

300 In what type of neck dissection are levels II–V dissected, preserving the nonlymphatic structures of the neck?

Answer 299

**Posterolateral neck dissection.** Select neck dissection (levels II–IV)

Question 300

301 In what type of neck dissection is level VI dissected, preserving the nonlymphatic structures of the neck?

Answer 300

**Anterior/central neck dissection.** Select neck dissection (level VI)

Question 301

302 In what type of neck dissection are lymph node basins in addition to the more common I–V dissected?

Answer 301

* Extended neck dissection. This can include a radical neck dissection, modified neck dissection, or select neck dissection. * May designate using the type of dissection followed by the levels and additional lymph nodes dissected in parenthesis.

Question 302

303 What type of neck dissection is generally recommended for oral cavity cancer?

Answer 302

**Select neck dissection (level I-III)** at minimum, with **level IV for oral tongue cancers**. Bilateral dissection should be considered for those with **floor of mouth**, **ventral tongue**, or **midline tongue** involvement in those undergoing elective ipsilateral neck dissection with no plans for postoperative radiation therapy

Question 303

304 What type of neck dissection is generally recommended for oropharyngeal cancer?

Answer 303

**Select neck dissection (level II-IV).** Bilateral dissection should be considered for base of tongue tumors, posterior oropharyngeal tumors, and those that cross midline. Dissection of retropharyngeal nodes should be considered. Routinely dissecting level IIB in cN0 necks is controversial.

Question 304

305 What type of neck dissection is generally recommended for hypopharyngeal and laryngeal cancer?

Answer 304

Select neck dissection (level II–IV) and occasionally VI

Question 305

306 In what type of neck dissection does the surgeon attempt to identify the first-echelon lymph node or nodes draining a particular subsite in an effort to determine whether the cancer has metastasized locally?

Answer 305

Sentinel lymph node biopsy

Question 306

307 A meta-analysis of the **EORTC (no. 22931)** and **RTOG (no. 9501)** showed a benefit to postoperative concurrent chemoradiation in patients with locally advanced oral cavity, oropharynx, larynx, and hypopharynx squamous cell carcinoma when what risk factors were present?

Answer 306

Positive surgical margins and/or extracapsular spread

Question 307

308 What branches of the vagus nerve are at highest risk for injury during neck dissection for head and neck cancer?

Answer 307

Recurrent laryngeal nerve and superior laryngeal nerve and its branches

Question 308

309 After a select neck dissection (levels IA, IB, IIA, IIB, III), you note weakness in your patient’s ipsilateral **depressor anguli oris** and **depressor labii inferioris** and resultant asymmetry during smiling. What structure was likely injured?

Answer 308

Marginal mandibular branch of CN VII

Question 309

310 Describe the surgical techniques that can be used to decrease the risk of injury to the marginal mandibular nerve during neck dissection.

Answer 309

* Place incisions 3 to 4 cm (or two fingerbreadths) below the mandible. * **Ligate the common facial vein _under the superficial layer of the deep cervical fascia_ with a long tie.** Lift this with the skin flap (this may limit oncologic dissection). * Elevate plane between the submandibular gland and superficial layer of the deep cervical fascia (this may limit oncologic dissection). * Identify marginal mandibular nerve as it branches from the cervical branch of the facial nerve.

Question 310

311 What is the reported rate of marginal mandibular nerve injury after neck dissection (particularly level IB and occasionally level IIA), and what is the most common postoperative House-Brackmann score associated with neural injury?

Answer 310

* Immediate: ~ 20%. * Permanent: \< 5% * House-Brackmann grade II–III/VI

Question 311

312 What sequelae results from resection of the spinal accessary nerve?

Answer 311

**Shoulder syndrome:** Denervation of the trapezius muscleresulting in destabilization of the scapula and inability to abduct the shoulder \> 30 degrees, pain and shoulder girdle deformity. Injury from dissection around spinal accessory nerve in levels IIB and VA may also result in shoulder syndrome.

Question 312

313 What nerve can be injured during dissection in level IV, which can result in paralysis of the ipsilateral hemidiaphragm?

Answer 312

Phrenic nerve

Question 313

314 What factors increase the risk of postoperative wound infection or breakdown after neck dissection?

Answer 313

* Previous radiation therapy * Pharyngocutaneous or pharyngocervical fistula with salivary contamination * Chylous fistula * Hematoma * “Tight” wound closure with compromised vascular function * Comorbidities: Immunocompromised, malnourished, peripheral vascular disease, poorly controlled diabetes, and so forth

Question 314

315 When planning a neck incision, why should you place any “T-limb” at 90 degrees to the main incision?

Answer 314

To maximize vascular supply and minimize skin flap necrosis

Question 315

316 How should carotid artery exposure after neck dissection be dealt handled?

Answer 315

Coverage with vascularized tissue, preferably a **myocutaneous flap** (e.g., pectoralis major flap)

Question 316

317 What are the risk factors for carotid blowout, which include rupture of any component of the carotid system, after management of head and neck cancer?

Answer 316

* Radiation therapy (≥ 70 Gray to the neck; accelerated fractionation schedule) * Neck dissection (radical = 8x increased risk) * Wound infection, breakdown, pharyngocutaneous fistula with salivary contamination * Mobile foreign material (wet to dry dressing) * Tumor involvement of the vessel * Malnutrition

Question 317

318 What are the incidence and mortality rates associated with carotid blowout after management of the neck?

Answer 317

* Incidence: \< 4% (occurs months to years after intervention/diagnosis) * Mortality: 3 to 50%

Question 318

319 Why might patients receiving endovascular management for an acute carotid blowout fare better (less neurologic sequelae) than those undergoing emergent surgical intervention?

Answer 318

Patients going to surgery are more likely to have acute hemorrhage, common carotid rupture, and hemodynamic instability.

Question 319

320 What sequelae can result from sacrifice of both internal jugular veins?

Answer 319

**Facial and cerebral edema**, increased intracranial pressure, altered mental status, syndrome of inappropriate antidiuretic hormone secretion, abducens palsy, and blindness have all been associated.

Question 320

321 What is the prevalence of a persistent chylous fistula after neck dissection in area IV?

Answer 320

1 to 3%. Most are in the left neck, but 25% have been reported in the right neck.

Question 321

322 What is the normal volume of chyle that passes through the lymphatic duct per day, and what does it contain?

Answer 321

2–4 L/day. Fat (chylomicrons, long-chain fats), protein, electrolytes, and lymphocytes

Question 322

323 What are the possible sequelae of a persistent chyle leak?

Answer 322

Hypovolemia, electrolyte disturbances, hypoalbuminemia, coagulopathy, immunosuppression, infection (sepsis, wound infection), peripheral edema, possible chylothorax (50% mortality if left untreated), mortality (now 0.25% with treatment)

Question 323

324 Suspected chylous fluid can be tested for what components to confirm that it is in fact chyle?

Answer 323

* Chylomicrons * Triglycerides (\> 5 g/L) * Sudan III stain positive

Question 324

325 What steps can initially be used to treat persistent chyle leaks less than 500 mL per day (low-output) after neck dissection?

Answer 324

* **Low-fat, medium-chain fatty acid–only diet** * Suction wound drainage * **Pressure dressing** * Consult dietician or nutritionist and follow laboratory results closely. If not successful, consider total parenteral nutrition (TPN). Some recommend for output \< 500 mL/day x 5 days or longer.

Question 325

326 In a patient with a high-output chyle leak after neck dissection, despite maximal medical therapy or in the presence of complications, what treatment is recommended?

Answer 325

**Neck exploration and ligation of the thoracic duct.** Other surgical options should also be considered (thoracoscopic or laparoscopic approach).

Question 326

327 What laboratory test should be checked **yearly** in patients treated with neck radiation therapy?

Answer 326

Thyroid function tests (TSH)

Question 327

328 What is the difference in impact on quality of life between a radical neck dissection and a modified radical neck dissection?

Answer 327

Radical neck dissection results in significantly **worse shoulder function** and a trend toward increased pain. No difference in subjective appearance, activity, recreation, chewing, swallowing, or speech occurs.

Question 328

329 What are the boundaries of the oral cavity?

Answer 328

* Anterior: Vermilion border of the lip * Posterior/superior: Hard and soft palate junction * Posterior/inferior: Circumvallate papillae * Lateral: Anterior tonsillar pillars and glossotonsillar folds

Question 329

330 What are the anatomical subsites that constitute the oral cavity?

Answer 329

* **Lips:** Upper and lower, from vermilion border to buccal mucosa * **Buccal mucosa:** Mucosa lining cheeks and posterior lip from maxillary and mandibular vestibular folds to the pterygomandibular raphe (or anterior tonsillar pillars) * **Retromolar trigone:** See below * **Alveolar ridges** * **Upper (maxillary):** Horizontal hard palate to maxillary vestibule and superior pterygopalatine arch posteriorly * **Lower (mandibular):** Transition to floor of mouth to mandibular vestibule to ascending mandibular ramus posteriorly * **Hard palate:** Soft palate to upper (maxillary) alveolar ridge * **Floor of mouth:** Lower alveolar ridge to oral tongue and anterior tonsillar pillar, divided by the lingual frenulum anteriorly * **Oral tongue:** Anterior two thirds, from circumvallate papillae to tip

Question 330

331 What are the anatomical boundaries of the retromolar trigone?

Answer 330

Mucosa over the **ascending mandibular ramus**: * Superior: **Maxillary tuberosity** * Anterior: Posterior aspect of the second mandibular molar * Lateral: Buccal mucosa * Medial: Anterior tonsillar pillar

Question 331

332 Primary oral cavity tumors of which two subsites have the highest risk for bony invasion?

Answer 331

* Alveolar ridges * Retromolar trigone

Question 332

333 Describe the course of the Stensen duct (parotid duct) from the gland to the oral cavity.

Answer 332

Anterior parotid gland → superficial to the masseter muscle and buccal fat pad → **90-degree turn to pierce the buccinator muscle** → between the oral mucosa and buccinators muscle → papilla in buccal mucosa across from the second maxillary molar

Question 333

334 Describe the course of the Wharton duct (submandibular duct) from the gland to the floor of the mouth and its relationship to the lingual nerve along its course.

Answer 333

Anterior “deep lobe” of the submandibular gland → between the lingual and hypoglossal nerves over the hyoglossus muscle → anterior and superior ascent between the genioglossus and sublingual glands → over the lingual nerve → sublingual papilla just lateral to the lingual frenulum.

Question 334

335 What is the arterial supply to the oral cavity?

Answer 334

External carotid artery 1. Lingual artery → oral tongue 2. Greater palatine artery→ hard palate 3. Superior alveolar arteries (anterior, middle, and posterior) → gingival of the maxilla, alveolar ridge, teeth, buccal mucosa 4. Transverse facial artery (superficial temporal artery) → buccal mucosa 5. Facial artery → lips (labial arteries) 6. Buccal artery (maxillary a) → buccal mucosa 7. Inferior alveolar artery → mandible, mandibular teeth 8. Ascending pharyngeal artery + lesser palatine arteries → retromolar trigone, posterior floor of mouth 9. Submental (facial artery) and sublingual (lingual artery) arteries → floor of mouth

Question 335

336 Describe the venous drainage of the oral cavity.

Answer 335

All sites drain ultimately to the jugular system. The hard palate drains first through the **pterygoid plexus.**

Question 336

337 What is the relationship between the lingual artery and vein, hypoglossal nerve, and the hyoglossus and mylohyoid muscles?

Answer 336

From superficial to deep (or lateral to medial): * Mylohyoid muscle * Hypoglossal nerve and lingual vein * Hyoglossus muscle * Lingual artery * Genioglossus

Question 337

338 What nerves provide sensation to the upper and lower lips?

Answer 337

* Upper lip: Infraorbital nerve (CN V2) * Lower lip: Mental nerve (CN V3)

Question 338

339 What is the sensory innervation of the retromolar trigone?

Answer 338

* Lesser palatine nerves * Glossopharyngeal nerve (CN IX)

Question 339

340 What is the sensory innervation of the tongue?

Answer 339

* Anterior two-thirds * General sensory: **Lingual nerve** (CNV3) * Special sensory: **Chorda tympani nerve** via the **lingual nerve** (CNV3) * Posterior third * General and special sensory: **Glossopharyngeal nerve** (CN IX)

Question 340

341 What provides the sensory innervation of the floor of mouth?

Answer 340

Lingual nerve (CN V3) ## Footnote *The Lingual nerve Took a curve Around the Hyoglossus. "Well I'll be f\*#ked!" Said Wharton's Duct, "The bastard's gone and crossed us!"*

Question 341

342 What provides sensory innervation to the hard palate?

Answer 341

Nasopalatine nerve (CN V2) via the incisive canal

Question 342

343 What are the four intrinsic and four extrinsic tongue muscles?

Answer 342

All muscles are paired and separated in the midline by the lingual septum: * Intrinsic tongue musculature: Change the shape of the tongue * Superior longitudinal * Inferior longitudinal * Transverse * Vertical muscles * Extrinsic tongue musculature * Genioglossus * Hyoglossus * Palatoglossus * Styloglossus

Question 343

344 Which tongue muscle is not innervated by the hypoglossal nerve (CN XII), and by what is it innervated?

Answer 343

**Palatoglossus** is innervated by the pharyngeal branch of the vagus nerve (CNX).

Question 344

345 What space is defined medially by the buccinators muscle and its fascia, the mandible inferiorly, the zygomatic arch superiorly, the risorius, zygomaticus major, and levator labii superioris muscles laterally, the orbicularis oris muscle anteriorly, and the anterior border of the masseter muscle and the parotid gland posteriorly?

Answer 344

Buccal space

Question 345

346 What space is defined (1) by the layers of the deep cervical fascia as they split around the mandible and come back together at the ventral and dorsal borders of the mandibular ramus, thus enclosing the lateral pterygoid muscle; and (2) by the fascia surrounding the medial pterygoid, masseter and temporalis muscles?

Answer 345

Masticator space

Question 346

347 Which lymph node areas usually drain the oral cavity?

Answer 346

Levels I, II, and III. Drainage pathways to level IV have also been described.

Question 347

348 What lymph node basins drain the lips?

Answer 347

* Submandibular lymph nodes (level IB) → upper and lower lip * Submental lymph nodes (level IA) → lower lip, primarily midline lesions * Other: preauricular, parotid, perifacial → upper lip

Question 348

349 What is the typical lymphatic drainage of the oral tongue?

Answer 348

* Tip → submental lymph nodes (level IA) * Ventral tongue → submental and submandibular lymph nodes (level IA and IB) * Lateral tongue → submandibular (level IB), jugulodigastric nodes (level IIA), directly to levels III and IV Note: **Laterality of lymphatic drainage of the oral tongue** due to the lack of lymphatic anastomoses across the fibrous lingual septum **is unique** from the base of tongue.

Question 349

350 What lymph node basin(s) is primarily responsible for draining the retromolar trigone?

Answer 349

Upper jugular nodes (level IIA)

Question 350

351 What is the lymphatic drainage for the floor of mouth?

Answer 350

* Anterior → Level IA and IB (often bilateral) * Posterior → Level IIA (ipsilateral)

Question 351

352 What lymphatic basins preferentially drain the buccal mucosa?

Answer 351

Levels IA and IB

Question 352

353 Which lymph nodes preferentially drain the hard palate?

Answer 352

Levels I and II

Question 353

354 What environmental risk factors act synergistically in the formation of oral cavity squamous cell carcinoma and are the most common risk factors in the Western world?

Answer 353

Tobacco and alcohol

Question 354

355 In addition to tobacco and alcohol use, what risk factors place a patient at higher risk for developing oral cavity cancer?

Answer 354

* Betel nut chewing * Chewing tobacco or other oral tobacco * Chronic periodontal disease or irritation * History of head and neck radiation * History of head and neck cancer * Immunodeficiency * Sun exposure (lip) * Other: Plummer-Vinson syndrome, chronic syphilis

Question 355

356 Is HPV infection considered a major risk factor in the development of oral cavity carcinoma?

Answer 355

No. Although it is a risk factor, it is not considered a major risk factor, and its role in carcinogenesis in the oral cavity is unclear.

Question 356

357 What is the most common malignancy of the oral cavity?

Answer 356

Squamous cell carcinoma (~95%) Note: For the hard palate, tumors most commonly arise in the minor salivary glands.

Question 357

358 What are the most common squamous cell carcinoma subtypes found within the oral cavity?

Answer 357

1. Sarcomatoid carcinoma 2. Basaloid carcinoma 3. Verrucous carcinoma

Question 358

359 What are the most common malignancies of the oral cavity, _excluding_ squamous cell carcinoma?

Answer 358

* Lymphoma * Minor salivary gland tumors: Adenoid cystic carcinoma, mucoepidermoid carcinoma, polymorphous low-grade adenocarcinoma, adenocarcinoma * Sarcoma: Osteosarcoma, chondrosarcoma, malignant fibrous histiosarcoma, rhabdomyosarcoma, liposarcoma, Kaposi sarcoma * Melanoma: Malignant mucosal melanoma

Question 359

360 What common premalignant lesions are associated with an increased risk of developing an oral cavity squamous cell carcinoma?

Answer 359

* **Leukoplakia:** White plaque, cannot be wiped off; lower risk of malignant conversion (\< 30%) * **Erythroplakia:** Red plaque, not associated with obvious cause; higher risk of malignant conversion (\< 60%) * **Lichen planus:** Lacy white pattern on mucosa or atrophic lesions (red and smooth) or erosive lesions (depressed margins, covered with fibrinous exudate), more common in women (40s), \< 1% 10-year conversion rate * **Submucosal fibrosis:** Thickened and fibrotic buccal mucosa and deeper structures; associated with betel quid chewing, poor oral hygiene

Question 360

361 What premalignant lesion can be mistaken for verrucous carcinoma but is differentiated on pathology because it does not invade the lamina propria?

Answer 360

Verrucous hyperplasia. Most commonly occurs on the buccal mucosa of men in their fourth decade of life.

Question 361

362 What benign lesion manifests as a butterfly shaped ulceration commonly found at the hard–soft palate junction and is associated with pressure injuries?

Answer 361

Necrotizing sialometaplasia

Question 362

363 What benign lesion is commonly found in mucosal or salivary tissue and may resemble squamous cell carcinoma?

Answer 362

Pseudoepitheliomatous hyperplasia

Question 363

364 What are common benign exostoses that appear as firm submucosal masses on the anterior lingual mandible and midline hard palate?

Answer 363

**Torus mandibularis** and **torus palatini**, respectively

Question 364

365 What are the most common initial signs and symptoms associated with oral cavity cancer?

Answer 364

Bleeding, pain, halitosis, dysphagia, and dysarthria

Question 365

366 What is the most common site of oral verrucous carcinoma?

Answer 365

Buccal mucosa

Question 366

367 What is the most common location of oral tongue squamous cell carcinoma?

Answer 366

Posterolateral oral tongue

Question 367

368 What is the most common location of buccal mucosa squamous cell carcinoma?

Answer 367

Adjacent to the third mandibular molar

Question 368

369 When does the NCCN (2013) recommend PET/CT scan in the workup of patients with oral cavity cancer?

Answer 368

Consider for stage III–IV disease

Question 369

370 Name four common features of patients with early stage (stage I or II) oral cavity cancer. (▶ Table 7.4)

Answer 369

* Primary tumor \< 4 cm (T1–2) * No evidence of invasion into adjacent structures * No evidence of cervical metastases (N0) * No distant metastases (M0)

Question 370

371 How is a T4a oral cavity tumor defined?

Answer 370

Moderately advanced local disease: * Lip: through cortical bone or involves inferior alveolar nerve, floor of mouth, or skin of face * Oral cavity: invades adjacent structures only, eg, through cortical bone of mandible/maxilla or involves maxillary sinus or skin of face

Question 371

372 True or False. Superficial erosion bone or tooth socket alone meets the criteria for staging a tumor as T4a.

Answer 371

False

Question 372

373 How are T4b oral cavity tumors defined?

Answer 372

Very advanced local disease: Tumor invades masticator space, pterygoid plates, or skull base, and/or encases the internal carotid artery.

Question 373

374 What pathologic factors directly relate to prognosis in oral cavity cancer?

Answer 373

* Tumor thickness (\> 5 mm = increased risk of occult nodal disease, decreased recurrence free and overall survival rates) * Differentiation * Angiolymphatic invasion

Question 374

375 Which has a worse prognosis: upper or lower lip cancer?

Answer 374

**Upper lip cancer** tends to be more aggressive and to have early metastatic potential.

Question 375

376 What are the adverse risk features considered by the NCCN (2020) in their algorithm for oral cavity cancer management?

Answer 375

* Extranodal extension * Positive margins * Close margins * pT3 or pT4 primary * pN2 or pN3 nodal disease * Nodal disease in lev IV or V * PNI * LVI

Question 376

377 What treatment strategy recommended by the NCCN (2013) for early stage (stage I and II) oral cavity cancer?

Answer 376

* Surgical resection ± neck dissection as indicated by tumor thickness and location (preferred): * No adverse risk factors→ Surveillance * **One positive node** without adverse risk features→ Optional adjuvant radiation * Extracapsular spread and/or **positive margin**→ Chemoradiation (preferred) versus reexcision versus radiation therapy * Other adverse risk features→ Radiation therapy versus chemoradiation therapy. * Radiation therapy ± brachytherapy

Question 377

378 For patients with advanced stage disease (T1– 3 N1–3; T3 N0; T4a, any N), excluding T4b or unresectable nodal disease, what is the primary treatment strategy recommended by the NCCN (2013)?

Answer 377

* Surgical resection with ipsilateral or bilateral neck dissection (N2c or high risk to contralateral neck) * No adverse features: Radiation therapy (optional) * Extracapsular spread and/or positive margin: Chemoradiation therapy (preferred) vs reexcision versus radiation therapy * Other risk features: Radiation therapy versus chemoradiation therapy * Multimodality clinical trials

Question 378

379 How can the mandible be managed if an oral cavity cancer appears to invade the periosteum, cortex, or medullary space, either intraoperatively or on preoperative workup?

Answer 378

* **Marginal or rim mandibulectomy:** Periosteum or superficial cortical invasion * **Segmental mandibulectomy:** More than superficial cortical invasion, medullary invasion, invasion from perineural spread via the mandibular or mental foramen, hypoplastic/atrophic/edentulous mandible making rim mandibulectomy unsafe, invasion of periodontal ligament or tooth socket

Question 379

380 When performing osteotomy for mandibulotomy, which is preferable: straight or stepwise osteotomy? Median or paramedian placement?

Answer 379

* **Stepwise** mandibulotomy: Provides better alignment and stability * **Paramedian**: Minimizes trauma to the genioglossus, geniohyoid, and digastric muscles

Question 380

381 Describe the extent of neck dissection recom mended by the NCCN (2013) for oral cavity cancer based on clinical nodal staging.

Answer 380

* No neck dissection: It can be considered for T1N0 lower lip cancer, T1–T2N0 **oral tongue with \< 2 mm of invasion**, T1–T2N0 upper alveolar ridge and hard palate tumors. For lesions 2- to 4-mm thick, elective neck dissection is used when appropriate (patient reliability, other risk factors, and so forth). * N0: Select neck dissection. Supraomohyoid (levels I–III) recommended for oral cavity tumors \> 4 mm; level IIB dissection is controversial; can consider preserving for early stage disease. Consider suprahyoid dissection (levels IA and IB) for T2 lower-lip tumors. * N1–N2c: Select or comprehensive neck dissection as indicated * N3: Comprehensive neck dissection

Question 381

382 What regimen is recommended by the NCCN (2020) for **definitive** radiation therapy for oral cavity cancer with gross lymphadenopathy?

Answer 381

* Conventional fractionation: 66–70 Gy, Monday through Friday for 6-7 weeks * Concomitant boost accelerated: 72 Gy for 6 weeks (boost given during a second daily fraction for the last 12 days of treatment) * Hyperfractionation: 81.6 Gy x 7 weeks given twice daily Monday through Friday. * Low to intermediate risk: Sites of suspected subclinical spread * 44-50 Gy (2.0 Gy/fx) to 54-63 Gy (1.6-1.8 Gy/fx)

Question 382

383 What radiation dose is typically given to uninvolved nodal levels at risk for occult disease in oral cavity cancer undergoing definitive radiation?

Answer 382

44 to 64 Gy

Question 383

384 When should adjuvant radiation or chemoradiation begin after surgical resection for oral cavity cancer?

Answer 383

**Six weeks or less (often around 3 to 4 weeks).** Ideally **_all_** treatment will be completed within 12 weeks from diagnosis. Given 6 weeks of typical adjuvant therapy, this gives 6 weeks from diagnosis to initiation of adjuvant therapy.

Question 384

385 What is the recommended adjuvant radiation recommended for oral cavity cancer?

Answer 384

* Primary site: 60 to 66 Gy, daily Monday through Friday for 6 weeks * N(+) levels: 60 to 66 Gy * N(-) levels = sites of subclinical spread: 44 to 50 Gy

Question 385

386 What chemotherapeutic regimen is recommended when adjuvant chemoradiation therapy is planned for oral cavity cancer?

Answer 385

Concurrent cisplatin (100 mg/m2 every 3 weeks)

Question 386

387 What is the reconstruction of choice for lower-lip defects smaller than one-third the length of the lip, between one-third and two-thirds, greater than two-thirds? (▶ Fig. 7.3)

Answer 386

* Less than **1/3**: Primary closure * **1/3 to 2/3**: Abbe-Estlander flap * More than **2/3**: Karapandzic flap, Webster-Bernard flap, or radial forearm free flap with palmaris longus tendon

Question 387

388 What local flap using the facial artery can be used to close intraoral defects?

Answer 387

Facial artery musculomucosal (FAMM) flap

Question 388

389 In a patient with a floor of mouth or oral tongue tumor, resection followed by primary closure of a large defect can result in what long-term complication?

Answer 388

Tethered tongue

Question 389

390 What reconstructive options are best used to avoid trismus in defects of the buccal mucosa larger than 3 cm in diameter?

Answer 389

Skin graft or free tissue transfer

Question 390

391 What is the reconstruction of choice for patients with segmental resection of the anterior mandible?

Answer 390

Free tissue transfer with vascularized bone (i.e., fibula free flap)

Question 391

392 What is the reconstruction of choice for patients who have greater than 50% of the oral tongue resected?

Answer 391

Fasciocutaneous free flap, radial forearm free flap

Question 392

393 What reconstruction options are best in patients with segmental mandibulectomy who are not candidates for free tissue transfer?

Answer 392

Soft tissue pedicled flap with or without a reconstruction bar. Reconstruction bars should be used with caution without underlying bone. They are prone to **fracture**, **exposure**, and **infection**.

Question 393

394 What is an adequate nonsurgical method for rehabilitation of speech and swallow function after resection of a hard palate or maxillary alveolar ridge tumor with resultant oronasal or oroantral fistula?

Answer 393

Prosthetic obturator

Question 394

395 What head and neck subsite is defined by the posterior pharyngeal wall, lateral pharyngeal constrictors, superiorly by the hard palate, inferiorly by the vallecula and hyoid bone, and anteriorly by the circumvallate papilla and palatoglossal muscles?

Answer 394

Oropharynx

Question 395

396 What are the anatomical subsites of the orophar ynx, and how are they defined?

Answer 395

* **Tonsil\*:** Bordered by the anterior and posterior tonsillar pillars, glossotonsillar sulcus, confluence of the soft palate and tonsillar pillars, and superior pharyngeal constrictor muscle * **Base of tongue\*:** Circumvallate papillae anteriorly, glossotonsillar sulci laterally, hyoid bone/floor of the vallecula inferiorly * Soft palate: Hard palate anteriorly, palatopharyngeus muscle and uvula posteriorly, superior constrictor muscle laterally, confluence of the anterior and posterior tonsillar pillars inferiorly and nasopharynx superiorly * Posterior oropharyngeal wall: Level of the hyoid bone/ floor of vallecula inferiorly, soft palate superiorly, poste rior tonsillar pillars and piriform sinuses laterally * Valleculae ## Footnote **\* Most commonly involved subsites**

Question 396

397 What anatomical site is considered a part of the oropharynx and is defined as the space anterior to the lingual/oropharyngeal surface of the epiglottis, posterior to the base of tongue, medial to the glossoepiglottic fold and piriform sinus, and super ficial to the hyoepiglottic ligament (which denotes the superior extent of the pre-epiglottic space)?

Answer 396

Vallecula

Question 397

398 Lymphatic tissue of the nasopharynx and oro pharynx, including the pharyngeal tonsil, palatine tonsil, and lingual tonsil, constitute what impor tant complex?

Answer 397

Waldeyer ring

Question 398

399 What anatomical structures enter the pharynx between the superior and middle pharyngeal constrictor muscles, just inferior to the tonsil?

Answer 398

Stylopharyngeus muscle, styloglossus muscle, stylohyoid ligament, glossopharyngeal nerve (CN IX).

Question 399

400 What important fascial layer separates the tonsillar region from the parapharyngeal space?

Answer 399

Buccopharyngeal fascia.

Question 400

401 Name the layers of the posterior pharyngeal wall.

Answer 400

Mucosa → superior pharyngeal constrictor muscle → buccopharyngeal fascia → retropharyngeal space (contains lateral fat pads and retropharyngeal nodes) → alar fascia → prevertebral fascia → prevertebral muscles (laterally)/ anterior longitudinal ligament (medially) → vertebral bodies

Question 401

402 Name the muscular components of the soft palate and their innervation.

Answer 401

* Superior pharyngeal constrictor muscle (CN IX, X) * Palatopharyngeus muscle (CN X) * Palatoglossus muscle (CN X) * Tensor veli palatini muscle (CN V3) * Levator veli palatini muscle (CN X) * Uvular muscle (CN X)

Question 402

403 Describe the arterial supply to each oropharyngeal subsite.

Answer 402

External carotid system: * Tonsil: Tonsillar branch of the ascending pharyngeal artery, descending palatine artery, tonsillar branch of the facial artery,\* dorsal lingual artery, and ascending palatine artery * Base of tongue: Lingual artery\* and its branches (supra hyoid branch, dorsal lingual artery, and arteria profunda linguae) * Soft palate: Lesser palatine artery,\* ascending pharyngeal artery, tonsillar branches from the dorsal lingual artery, ascending palatine artery * Posterior pharyngeal wall: Ascending pharyngeal artery\* \* Denotes primary arterial supply.

Question 403

404 Describe the location of the internal carotid artery in relationship to the tonsil.

Answer 403

* Posterolateral to the lateral oropharyngeal wall * Separated from tonsil by superior constrictor and buccopharyngeal fascia * On average, it is 1.4 cm from the tonsillar fossa in a 1- year-old and 2.5 cm in an adult.

Question 404

405 Describe the venous outflow from the oropharynx.

Answer 404

Drains to the jugular venous system: * Tonsil: Tonsillar and pharyngeal plexus, lingual and facial veins * Base of tongue: Lingual and retromandibular veins * Soft palate: pharyngeal and pterygoid plexus, external palatine vein * Posterior pharyngeal wall: pharyngeal venous plexus

Question 405

406 What nerve is at risk during base of tongue surgery if resection of the hyoglossus muscle to the level of the hyoid bone is required? (▶ Fig. 7.4)

Answer 405

Hypoglossal nerve (CN XII)

Question 406

407 Which nerves supply the pharyngeal plexus?

Answer 406

* Vagus nerve (CN X), * Glossopharyngeal nerve (CN IX) * Sympathetic fibers from the superior cervical ganglion

Question 407

408 Which lymph node basins are common sites of spread of oropharyngeal carcinoma? (▶ Fig. 7.5; ▶Fig. 7.6)

Answer 407

Levels II, III, and IV most commonly

Question 408

409 In addition to levels II, III, and IV, what other lymph node group is at risk with tonsil, soft palate, and posterior pharyngeal wall cancer?

Answer 408

Retropharyngeal nodes

Question 409

410 Why do tumors of the base of tongue have a high risk of bilateral nodal disease?

Answer 409

Precollecting lymphatic channels on each side cross the midline to drain to the contralateral side (up to 30% at presentation). Level II is at highest risk for bilateral disease.

Question 410

411 Describe the three lymphatic systems associated with the soft palate.

Answer 410

* Medial → middle one-third of the jugular chain (level III) * Lateral → retropharyngeal lymph nodes * Anterior → hard palate → submental and submandibular nodes (levels IA and IB) Note: Uvular lymphatics drain primarily to level IIA

Question 411

412 Describe the lymphatic drainage of the posterior pharyngeal wall.

Answer 411

Retropharyngeal nodes (up to 44%), levels II and III

Question 412

413 What are the two most important risk factors associated with the development of oropharyngeal squamous cell carcinoma?

Answer 412

HPV infection and tobacco smoking. Traditional risk factors for head and neck squamous cell carcinoma are still relevant (see Oncology section)

Question 413

414 Which HPV subtypes are associated with an increased risk of oropharyngeal squamous cell carcinoma?

Answer 413

HPV 16 (predominant), 18, 31, and 33

Question 414

415 What is the most common malignancy of the oropharynx?

Answer 414

Squamous cell carcinoma

Question 415

416 What rare malignancy arising in the oropharynx (most commonly in the tonsil and base of tongue) is a poorly differentiated squamous cell carcinoma or undifferentiated carcinoma associated with a reactive lymphoplasmacytic infiltration?

Answer 415

Lymphoepithelial carcinoma

Question 416

417 What is the most common type of lymphoma found in the oropharynx?

Answer 416

Non-Hodgkin lymphoma. **Diffuse large B-cell lymphomas** are the most common subtype.

Question 417

418 What percentage of extranodal head and neck lymphomas are found in the Waldeyer ring?

Answer 417

36%

Question 418

419 What locally aggressive oral and cutaneous vascular malignancy can be found in the oropharynx (primarily soft palate) in AIDS patients?

Answer 418

Kaposi sarcoma

Question 419

420 What are the two most common salivary gland malignancies that arise in the oropharynx?

Answer 419

They arise from **minor salivary glands** most commonly in the soft palate, tonsil, and base of tongue: * Adenoid cystic carcinoma (cylindromatous or cribriform) * Mucoepidermoid carcinoma

Question 420

421 What malignant tumor can rarely arise from melanocytes in the mucosa of the oropharynx?

Answer 420

Malignant mucosal melanoma

Question 421

422 What are common initial symptoms of oropharyngeal malignancy?

Answer 421

Odynophagia, referred otalgia, dysphagia, speech distortion, globus, bleeding, painless neck mass

Question 422

423 Why might patients with oropharyngeal cancer often be initially diagnosed with stage III or IV disease?

Answer 422

Vague symptoms that are often experienced in benign disease processes

Question 423

424 If a patient with oropharyngeal cancer develops severe trismus, what might this indicate?

Answer 423

Invasion into the **masseteric space** with involvement of the pterygoid musculature

Question 424

425 A patient has a palpable mass centered in the right base of the tongue. On tongue protrusion, you note hemitongue atrophy and fasciculations on the right. Which nerve is likely involved by the tumor?

Answer 424

Hypoglossal nerve

Question 425

426 What adjuvant physical examination tool should be used when there is concern for an oropharyngeal malignancy?

Answer 425

Flexible endoscopy; evaluate for tumor extension, status of the larynx, etc. Mirror should be considered if flexible endoscopy is not available or as an adjunct to flexible endoscopy.

Question 426

427 In addition to direct visualization of the anatomy, what important physical examination maneuver should be performed in patients with possible oropharyngeal cancer?

Answer 426

Digital **palpation** for submucosal disease, friability, and mobility. **Palpation** of the neck is also imperative.

Question 427

428 What structure(s) are potentially involved if a patient presents with an immobile oropharyngeal tumor?

Answer 427

* Medial pterygoid muscle * Mandible * Maxillary tuberosity * Hyoid bone (lesser is II; greater is III) * Parapharyngeal structures

Question 428

429 Tumors in which oropharyngeal subsite is most commonly diagnosed by visual inspection at earlier stages?

Answer 428

Soft palate. They generally occur on the anterior oropharyngeal surface of soft palate.

Question 429

430 What patient specific/anatomical factors identified on physical examination may indicate that a patient with an oropharyngeal tumor is a poor candidate for a transoral procedure?

Answer 429

* Severe trismus due to tumor invasion or fibrosis * Narrow mandibular arch * Crowded oral cavity, making displacement of the soft tissues challenging * Long incisor teeth * High body mass index * Retrognathic * High Mallampati score * Mandibular tori

Question 430

431 What tumor specific factors can be identified on physical examination, which would suggest that a patient is a good candidate for transoral surgery?

Answer 430

* Exophytic * Mobile * Proximal oropharynx * No evidence of involvement of deep structures such as the mandible, pterygoid musculature, maxillary tuber osity, hyoid bone, or parapharyngeal structures * Predicted resection \< 50% of the base of tongue or \< 75% of the soft palate

Question 431

432 Describe the tumor specific contraindications to transoral tumor resection for an oropharyngeal tumor.

Answer 431

* Invasion of the skull base * Invasion or encasement of the great vessels * Invasion of the mandible * Confluent primary tumor and neck metastasis * Tumor extension potentially necessitating an R1 or R2 resection.

Question 432

433 How is T4a of HPV-neg oropharyngeal cancer defined? (▶ Ta ble 7.5)

Answer 432

**Moderately advanced local disease**. Invasion through larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible (mucosal extension to lingual surface of epiglottis from priamry tumors of the base of tongue and vallecula does not constitute invasion of larynx)

Question 433

434 How is T4b HPV-neg oropharyngeal cancer defined?

Answer 433

**Very advanced local disease.** Invasion through laterla pterygoid plates, lateral nasopharynx, skull base or encases carotid artery

Question 434

435 With regard to tongue-base tumors, does mucosal extension of a tumor to the lingual surface of the epiglottis constitute invasion of the larynx and T4a status?

Answer 434

No

Question 435

436 True or False. Nodal metastases to level VII (superior mediastinal lymph nodes: between the common carotid arteries laterally, superior border of manubrium, and innominate artery) are not considered distant metastases.

Answer 435

True

Question 436

437 Currently, there is no widely accepted staging system that takes into account HPV status of an oropharyngeal tumor. However, the NCCN (2013) does recommend HPV testing to better define prognosis. What test is currently recommended?

Answer 436

Immunohistochemical staining for **p16** Note: The best test to diagnose HPV status is controversial.

Question 437

438 What prognostic role does HPV positivity play in oropharyngeal squamous cell carcinoma?

Answer 437

Improved disease-free survival and overall survival when compared with HPV-negative oropharyngeal squamous cell carcinoma

Question 438

439 What are the adverse features identified by the NCCN (2020) for oropharyngeal cancer?

Answer 438

* Extracapsular nodal spread * Positive margins * pT3 or pT4 primary * N2 or N3 nodal disease * Nodal disease in levels IV or V * Perineural invasion * Vascular invasion * Lymphatic invasion

Question 439

440 What treatment modalities does the NCCN (2020) recommend for patients with HPV+ T1–2, N0 oropharyngeal cancer?

Answer 439

* Definitive RT * Resection of primary +/- ipsi or bilat neck * ENE +/- pos margin: CRT or RT * Pos margin: RE-resection, CRT, RT * Other risk features, RT o rCRT * Adverse features: ENE, pos margins, close margins, pT3 or pT4 primary, one positive node \>3 cm or multiple positive nodes, nodal dz in lev IV or V, PNI, vascular invasion, lymphatic invasion

Question 440

441 What treatment modalities does the NCCN (2020) recommend for patients with T1-3, N3 or T4, N0-3or opharyngeal cancer?

Answer 440

* Concurrent chemoradiation therapy with cisplatin (cat egory 1, preferred) * Surgical resection of the primary ± ipsilateral or bilateral neck dissection as indicated; additional intervention based on adverse features: * None → None * Extracapsular spread and or positive margin → Chemoradiation therapy * Other risk feature → radiation therapy ± concomitant chemotherapy * Induction chemotherapy (cat 3) + radiation therapy ± concomitant chemotherapy * Multimodality clinical trials

Question 441

443 For all stages of oropharyngeal cancer, if there is residual disease with radiation therapy ± concomitant chemotherapy, what intervention is recom mended?

Answer 441

Salvage surgery

Question 442

444 What radiation technique or modality is recommended for management of oropharyngeal tumors?

Answer 442

Intensity modulated radiation therapy (IMRT)

Question 443

445 What does the NCCN (2013) recommend for definitive radiation therapy for oropharyngeal cancer?

Answer 443

* Conventional fractionation: 66 to 74 Gy, daily Monday through Friday for 7 weeks * Altered fractionation: * Accelerated: 66 to 74 Gy to gross disease, 44 to 64 Gy to occult disease; six fractions/week * Concurrent boost accelerated: 72 Gy, daily + twice daily for last 12 treatments, for 6 weeks * Hyperfractionation: 81.6 Gy, twice daily, Monday through Friday, for 7 weeks

Question 444

446 When considering concurrent chemoradiation therapy, what amount of energy does the NCCN (2020) recommend for planning target volume?

Answer 444

* PTV * High risk: typically 70 Gy (2.0 Gy/fx) * Low to interm: 44-50 Gy (2.0 Gy/fx) to 54-63 Gy (1.6-1.8 Gy/fx)

Question 445

447 What does the NCCN (2013) recommend for adjuvant radiation therapy after primary surgical intervention for oropharyngeal cancer?

Answer 445

Conventional fractionation * 60 to 66 Gy to the primary and gross nodal disease * 44 to 64 Gy to occult nodal disease for 6 weeks

Question 446

448 What is the recommended radiation target volume of the neck in patients with oropharyngeal squamous cell carcinoma and ipsilateral N2a or N2b disease?

Answer 446

Levels IB-V and retropharyngeal lymph nodes

Question 447

449 What chemotherapy regimen is recommended for concurrent chemoradiation therapy in oropharyngeal squamous cell carcinoma?

Answer 447

Cisplatin: 100 mg/m2 every 3 weeks x three doses

Question 448

450 What surgical approach can be used for most early and some advanced oropharyngeal malignancies?

Answer 448

Transoral approach, including laser microsurgery or robotic surgery

Question 449

451 What surgical approach can be used for more extensive inferiorly located oropharyngeal tumors not amendable to transoral approaches and does not require mandibulotomy?

Answer 449

* Lateral pharyngotomy * Transhyoid pharyngotomy * Lingual release and pull-through technique

Question 450

452 What surgical approach can be used for the most advanced oropharyngeal lesions often requiring reconstruction?

Answer 450

Mandibulotomy with mandibular swing

Question 451

453 Similar to the management recommendations for oral cavity cancers, what options are available for surgical management of oropharyngeal tumors that invade the mandible?

Answer 451

* Periosteal or superficial cortical invasion only: Rim mandibulectomy * Medullary invasion: Segmental mandibulectomy See oral cavity malignancy for additional discussion of mandibulectomy indications.

Question 452

454 How should retropharyngeal lymph nodes be addressed in patients with advanced oropharyn geal squamous cell carcinoma?

Answer 452

Retropharyngeal lymph node dissection and/or radiation therapy

Question 453

455 When performing transoral lateral oropharyngectomy or base-of-tongue resection, in addition to clipping named vessels in the operative field with two or three clips and meticulous hemostasis, what additional procedures should be considered to decrease the risk of postoperative hemorrhage?

Answer 453

Ligation of vessels at risk for bleeding into the oropharynx (lingual, facial, and superior laryngeal arteries; some authorities consider tying off the external carotid system). This can be done during concomitant neck dissection or as a separate procedure.

Question 454

456 What is the most common method used for reconstruction of oropharyngeal defects after transoral procedures?

Answer 454

None: The wound is allowed to heal by secondary intention.

Question 455

457 If a patient undergoes transoral tumor extirpation for a primary base-of-tongue or tonsil tumor at the same time as a neck dissection, and the decision is made to allow the wound to heal by second intention, what should be carefully ruled out before closure of the neck?

Answer 455

Orocervical fistula

Question 456

458 What is the best reconstructive option for large oropharyngeal defects involving the tonsillar fossa, pharyngeal wall, and tongue base?

Answer 456

Fasciocutaneous free flap (radial forearm free flap is used most commonly)

Question 457

459 What are the most important goals of tongue base reconstruction?

Answer 457

* Maintenance of the airway with prevention of aspiration * Preservation of swallowing * Preservation of speech

Question 458

460 When considering a pectoralis major myocutaneous flap or a fasciocutaneous free flap for reconstruction of the oropharynx, which reconstructive option provides the best functional outcome with respect to swallowing?

Answer 458

Free flap reconstruction (decreased percutaneous endoscopic gastrostomy tube dependence)

Question 459

461 Although multiple reconstructive options are available for soft palate reconstruction, including primary closure, local mucosal flaps, and free tissue transfer, what additional option should be considered for smaller defects, and what healing process may contribute to decreased velopharyngeal insufficiency over time?

Answer 459

* Healing by second intention * Cicatricial scarring

Question 460

462 What might result if a large portion of the soft palate is resected and not reconstructed after surgery for oropharyngeal tumors?

Answer 460

Velopharyngeal insufficiency with nasopharyngeal reflux and hypernasal speech

Question 461

463 What are the anatomical boundaries of the hypopharynx?

Answer 461

* Superior: Hyoid bone/floor of vallecula, pharyngoepiglottic folds * Inferior: Plane at the lower border of the cricoid cartilage; esophageal introitus or cricopharyngeus muscle * Posteior: Junction of the pyriform sinuses in the post cricoid region * Anterior: Level of the superior surface of the hyoid bone/ floor of the vallecula to the inferior border of the cricoid cartilage and from the apex of one piriform sinus to the other

Question 462

464 Which paired subsite of the hypopharynx extends from the pharyngoepiglottic fold to the upper end of the esophagus or lower border of the cricoid cartilage and is referred to as an inverted pyramid (**base** at **pharyngoepiglottic fold**, **apex** at **level of cricoid**)?

Answer 462

Pyriform sinus

Question 463

465 What subsite of the hypopharynx extends from the level of the superior surface of the hyoid bone or floor of the vallecula to the inferior border of the cricoid cartilage and from the apex of one piriform sinus to the other?

Answer 463

Posterior hypopharyngeal wall

Question 464

466 What subsite of the hypopharynx extends from the anterior hypopharyngeal wall from below the posterior arytenoid cartilage to the inferior border of the cricoid cartilage?

Answer 464

Postcricoid area

Question 465

467 What subsite forms a transition point between the supraglottis and hypopharynx, is considered a part of the supraglottis, and often results in aggressive disease when involved by tumors?

Answer 465

“Marginal area”: Lateral wall of the aryepiglottic folds

Question 466

468 What is the distribution of hypopharyngeal tumors arising in the three subsites?

Answer 466

Varies geographically. In the United States: **Pyriform sinus (up to 86%)** \> posterior pharyngeal wall (10 to 23%) \> postcricoid area (less than 5%). In Egypt: **Postcricoid area (50.1%)** \> pyriform sinus (26.5%) \> posterior pharyngeal wall (23.4%)

Question 467

469 Between the area of transition of the inferior pharyngeal constrictor muscle and the cricopharyngeus muscle is a potential area of weakness and spread of posterior hypopharyngeal wall tumors beyond the hypopharynx. What is the name of this area?

Answer 467

Killian triangle

Question 468

470 What is the arterial supply to the hypopharynx?

Answer 468

External carotid artery: * **Superior laryngeal artery\*** * Branches of the lingual artery * Branches of the ascending pharyngeal artery \*Denotes primary blood supply; venous drainage is through the pharyngeal plexus, adjacent named veins, and jugular system.

Question 469

471 Describe the sensory and motor innervation of the hypopharynx.

Answer 469

* Sensory: Glossopharyngeal (IX) and vagus (X) nerves via the pharyngeal plexus; additionally, sympathetics from the pharyngeal plexus may also contribute. * Motor: Vagus (X) nerve via pharyngeal plexus

Question 470

472 Which aerodigestive tract primary site has the highest prevalence of cervical nodal metastasis?

Answer 470

Hypopharynx (approximately 70%)

Question 471

473 What is the primary lymphatic drainage of the hypopharynx?

Answer 471

Primarily drain to levels II–IV, also level VI (especially with inferior hypopharyngeal and postcricoid disease). Other nodal basins at risk include retropharyngeal nodes.

Question 472

474 What risk factors are associated with hypopharyngeal carcinoma?

Answer 472

* Tobacco smoking * Alcohol use * Chewing tobacco * Male sex * Fifth to seventh decade of life * Plummer-Vinson syndrome or Patterson-Brown-Kelly syndrome * Black race

Question 473

475 What syndrome with the triad of hypopharyngeal/esophageal webs, glossitis, and iron deficiency anemia can cause an increased risk of cervical esophageal and hypopharyngeal cancer, especially in nonsmoking women from the United States, Wales, or Sweden in their third to fifth decade of life?

Answer 473

Plummer-Vinson syndrome

Question 474

476 Tumors in which hypopharyngeal subsite(s) are associated with Plummer-Vinson syndrome?

Answer 474

Postcricoid region

Question 475

477 Approximately what percentage of hypopharyngeal tumors are squamous cell carcinoma?

Answer 475

95%

Question 476

478 Describe three of the most common nonepithelial tumors that form within the _hypopharynx_.

Answer 476

* Adenocarcinoma * Lymphoma * Sarcoma

Question 477

479 Where do adenocarcinomas of the hypopharynx arise?

Answer 477

Minor salivary glands or ectopic gastric mucosa

Question 478

480 What pathologic growth characteristics of hypopharyngeal cancer can make assessment of the primary tumor challenging?

Answer 478

* Submucosal spread * Skip lesions * Multifocal disease

Question 479

481 What is the risk of finding a second primary tumor in a patient with hypopharyngeal cancer?

Answer 479

Up to 18%

Question 480

482 What are the most common initial symptoms in patients with hypopharyngeal cancer?

Answer 480

* All stages: Dysphagia, neck mass, sore throat * Early stage (I/II): Gastroesophageal reflux, sore throat, dysphagia * Advanced stage (III/IV): Neck mass, shortness of breath, dysphagia, odynophagia, referred otalgia, hemoptysis, gastroesophageal reflux, hoarseness

Question 481

483 Approximately what percentage of hypopharyngeal tumors manifest at advanced stage (stage III– IV)?

Answer 481

70 to 75%

Question 482

484 Explain why patients with hypopharyngeal tumors, particularly those located in the pyriform sinus, develop referred otalgia.

Answer 482

Sensory fibers from the **superior laryngeal nerve** (particularly the _internal branch_) and **Arnold nerve** both synapse within the jugular ganglion.

Question 483

485 Why is in-office flexible endoscopy imperative in any patient with suspected hypopharyngeal cancer?

Answer 483

It is essential to evaluate the larynx to assess the presence of laryngeal invasion, cricoarytenoid joint fixation, and/or recurrent laryngeal nerve involvement.

Question 484

486 During flexible endoscopy, what maneuver can allow improved visualization of the pyriform sinuses and postcricoid space?

Answer 484

Asking the patient to **puff out the cheeks** or **perform a Valsalva** maneuver

Question 485

487 What signs are suggestive of hypopharyngeal cancer on flexible endoscopy?

Answer 485

* Mucosal fullness * Ulceration * Pooling of secretions * Hyperkeratotic lesions * Erythematous or friable lesions

Question 486

488 Aside from pathologic staging, what diagnostic imaging modalities are most commonly used for the workup of hypopharyngeal cancer, and what advantages do they provide for this subsite in particular?

Answer 486

* MRI: **Staging accuracy is 85%**; better at detecting submucosal spread * CT with contrast: Best for assessing **cartilage and bone invasion** * PET/CT: Recommended for stage III/IV disease; 10% of patients have distant metastatic disease; identification of an unknown primary; primary staging Note: At minimum, a chest X-ray is recommended to evaluate pulmonary metastases.

Question 487

489 During the workup for hypopharyngeal cancer, what test is occasionally ordered to work up second primaries in the esophagus?

Answer 487

Barium swallow (not an imaging modality of choice)

Question 488

490 What additional test should be ordered for any patient with hypopharyngeal cancer if the treatment plan includes partial laryngeal surgery or conservative hypopharyngectomy?

Answer 488

Pulmonary function tests

Question 489

491 Describe T1–3 hypopharyngeal tumor staging according to the AJCC, 7th edition. (▶ Table 7.6)

Answer 489

* T1: Limited to one subsite of hypopharynx and/or ≤ 2 cm * T2: One or more subsites of hypopharynx or an adjacent site or measures \> 2 cm and \< 4 cm without fixation of the hemilarynx * T3: \> 4 cm or with fixation of the hemilarynx or extension to the esophagus

Question 490

492 Describe the criteria for a T4a hypopharyngeal tumor.

Answer 490

**Moderately advanced local disease:** Invades thyroid/cricoid cartilage, hyoid bone, thyroid gland, or central compartment soft tissue (prelaryngeal strap muscles and subcutaneous fat)

Question 491

493 Describe the criteria for a T4b hypopharyngeal tumor

Answer 491

**Very advanced local disease:** Invades prevertebral fascia, encases carotid artery, or involves mediastinal structures

Question 492

494 Which head and neck aerodigestive tract primary site has the lowest 5-year survival rate?

Answer 492

Hypopharynx (20 to 47%)

Question 493

495 What is the most common cause of mortality in patients with hypopharyngeal cancer?

Answer 493

* Locoregional recurrence * Distant metastases (bone, lungs, liver) * Second primary tumors * Comorbid disease

Question 494

496 What clinical factors are associated with poor prognosis in hypopharyngeal cancer?

Answer 494

* Increasing age * Male sex * Black ethnicity * Poor performance status (ECOG or Karnofsky) * Traditional risk factors for head and neck cancer

Question 495

497 What tumor specific factors are associated with improved prognosis in hypopharyngeal cancer?

Answer 495

* Primary tumor located on the aryepiglottic fold or medial wall of the pyriform sinus * Low T or N stage, early overall stage * Smaller primary tumor volume

Question 496

498 Describe the adverse features highlighted by the NCCN ( 2013) for hypopharyngeal cancer.

Answer 496

* Extracapsular nodal spread * Positive surgical margins * pT3 or pT4 * pN2 or pN3 nodal disease * Perineural invasion * Vascular invasion * Lymphatic invasion

Question 497

499 What primary treatment modalities does the NCCN (2020) recommend for the management of most T1N0 and select T2N0 (not requiring total laryngectomy) tumors?

Answer 497

* Definitive radiation therapy * Partial laryngopharyngectomy (open or endoscopic) with ipsilateral or bilateral neck dissection as indicated * No adverse features → surveillance * Extracapsular spread ± positive margin → CRT * Positive margins → re-excision, XRT, CRT (T2) * Other risk features → radiation therapy ± chemotherapy * Multimodality clinic trial

Question 498

500 What primary treatment modalities does the NCCN (2013) recommend for the management of selected T2N0 (those requiring total laryngectomy), T1N + , T2–3 any N (if total laryngectomy is required)?

Answer 498

* Induction chemotherapy * Complete response → radiation therapy ± chemotherapy * Partial response → chemoradiation therapy * \< partial response → surgery * No adverse features → radiation therapy * Extracapsular spread ± positive margin → chemoradiation therapy * Other risk features → radiation therapy ± chemotherapy * Laryngopharyngectomy + neck dissection (includes level VI) * No adverse features → surveillance * Extracapsular spread ± positive margin → chemoradiation therapy * Other risk features → radiation therapy ± chemotherapy * Concurrent chemoradiation therapy (cisplatin) * Multimodality clinical trial

Question 499

501 What are the options available for managing T4a (any N) hypopharyngeal tumors according to the NCCN (2013)?

Answer 499

* Surgery + neck dissection (preferred) → adjuvant radia tion therapy ± chemotherapy * Induction chemotherapy * Complete response → radiation therapy ± chemo therapy * Partial response → chemoradiation therapy * \< Partial response → surgical salvage + neck dissection as indicated → radiation therapy ± chemotherapy ● * Concurrent chemoradiation therapy * Multimodality clinical trial

Question 500

502 What levels should be addressed in an elective neck dissection for hypopharyngeal cancer?

Answer 500

Select neck dissection **levels II–IV** with inclusion of level VI in pyriform apex tumors and retropharyngeal lymph nodes in pharyngeal wall tumors

Question 501

503 For patients undergoing surgical treatment for **hypopharyngeal squamous cell carcinoma**, what is the recommended extent of therapeutic neck dissection of the clinically N + ipsilateral neck?

Answer 501

Comprehensive neck dissection including **levels I-V** and inclusion of **level VI with pyriform apex tumors** and retropharyngeal lymph nodes with pharyngeal wall tumors

Question 502

504 What are the most common surgical approaches used for the management of hypopharyngeal tumors?

Answer 502

* Laryngeal conservation approach (T1, T2, and some T3 tumors): * Partial pharyngectomy: Lateral pharyngotomy, partial pharyngectomy via lateral pharyngeal approach, anterior transhyoid pharyngotomy * Partial laryngopharyngectomy * Supracricoid hemilaryngectomy * Transoral laser microsurgery * Total laryngectomy with partial/total pharyngectomy (T3, T4) * Total pharyngo-laryngo-esophagectomy (T4)

Question 503

505 An open partial pharyngectomy can be considered in patients with T1 or T2 hypopharyngeal tumors of the pyriform sinus. What are the contraindications to this procedure?

Answer 503

* Tumor extension to more than one wall of the pyriform sinus * Involvement of the pyriform apex * Involvement of the larynx including the medial wall of the pyriform sinus

Question 504

506 An open partial laryngopharyngectomy combines a classic hemilaryngectomy with a partial pharyngectomy and is used for what specific hypopharyngeal tumors?

Answer 504

Medial wall pyriform sinus tumors

Question 505

507 What are the advantages of transoral laser microsurgery and endoscopic resection of hypopharyngeal tumors when compared with open approaches?

Answer 505

* No tracheostomy * No reconstruction * Preservation of the suprahyoid musculature improving postoperative swallowing * Earlier return to an oral diet * Shorter hospital stay

Question 506

508 What is the surgical treatment of choice for **most T3 and T4 hypopharyngeal squamous cell carcinomas**?

Answer 506

Total laryngectomy with partial or total pharyngectomy with neck dissection as indicated by clinical nodal disease

Question 507

509 What are the contraindications for conservation laryngeal surgery in patients with hypopharyngeal malignancy?

Answer 507

* Thyroid or cricoid cartilage invasion * Pyriform apex involvement * Postcricoid region involvement * Impaired vocal cord mobility

Question 508

510 What is the recommended definitive radiation therapy for primary hypopharyngeal cancer and gross lymphadenopathy according to the NCCN (2013)?

Answer 508

* Conventional fractionation: 66 to 74 Gy, daily (Monday through Friday) for 7 weeks * Altered fractionation: * Accelerated: 6 fractions/week, 66 to 74 Gy to gross disease, 44 to 64 Gy to subclinical disease * Concomitant boost accelerated radiation therapy: 72 Gy/6 weeks with a boost given as a second daily dose for the last 12 days of treatment * Hyperfractionation: 81.6 Gy, twice daily (Monday through Friday) for 6 weeks

Question 509

511 What dose of radiation is generally recommended for subclinical hypopharyngeal nodal disease when given as definitive management?

Answer 509

44 to 64 Gy

Question 510

512 What dose of radiation is recommended for hypopharyngeal cancer when given as primary concomitant chemoradiation?

Answer 510

Conventional fractionation: * Gross disease: ≥ 70 Gy * Subclinical disease: 44 to 64 Gy

Question 511

513 What does the NCCN (2013) recommend for adjuvant radiation therapy after primary surgical intervention for hypopharyngeal cancer?

Answer 511

Conventional fractionation: * 60 to 66 Gy to the primary and gross nodal disease * 44 to 64 Gy to occult nodal disease for 6 weeks

Question 512

514 What chemotherapy regimen is recommended for concurrent chemoradiation therapy in hypopharyngeal squamous cell carcinoma?

Answer 512

Cisplatin: 100 mg/m² every 3 weeks in three doses

Question 513

515 What chemotherapy regimen is recommended for induction chemotherapy in patients with hypopharyngeal cancer?

Answer 513

Cisplatin and 5-FU (up to three cycles)

Question 514

516 What is the reconstruction of choice after an open conservation procedure for an early stage hypopharyngeal tumor?

Answer 514

Primary closure. Exception is for endoscopic tumor resection → healing by secondary intention

Question 515

517 What are the reconstructive options for circumferential defects of the hypopharynx?

Answer 515

* Tubed fasciocutaneous free flap * Gastric transposition (gastric "pull-up") * Colonic transposition * Jejunal free flap

Question 516

518 In terms of function, what are the differences between chemoradiation (organ sparing) therapy and surgery with adjuvant radiation therapy for hypopharyngeal cancer?

Answer 516

Although data are sparse, there are no studies that have shown a clear advantage in terms of function for one treatment algorithm over the other. Eating, aesthetics, and speech are comparable in most studies.

Question 517

519 What factors correlate with higher complication rate in patients with hypopharyngeal cancer treated with laser excision?

Answer 517

* Surgeon inexperience * Tumor size * Diagnosis of diabetes mellitus

Question 518

520 What are the most common complications associated with CO2 laser excision of hypopharyngeal carcinoma?

Answer 518

* Hemorrhage (8% in one series) * Pneumonia (6%) * Fistula (1%) * Less commonly local infection and dyspnea

Question 519

521 What anatomical structures form the superior and inferior limits of the cervical esophagus?

Answer 519

* Superior: Cricopharyngeus muscle * Inferior: Thoracic inlet (sternal notch)

Question 520

522 What are the layers of the cervical esophagus?

Answer 520

* Squamous epithelium * Submucosa * Inner circular muscle layer * Outer longitudinal muscle layer * Adventitia Note: There is no distinct serosal layer.

Question 521

523 Which section of the esophagus contains striated muscle? Smooth muscle?

Answer 521

* Upper one-third: Striated * Middle one-third: Mixed * Distal one-third: Smooth

Question 522

524 What structure(s) make up the upper esophageal sphincter?

Answer 522

* Posterior surface of thyroid and cricoid cartilage * Hyoid bone * Cricopharyngeus muscle * Inferior constrictor muscle (thyropharyngeus muscle) * Cervical esophageal muscles Extends 3 to 4 cm in total.

Question 523

525 True or False. The upper esophageal sphincter is tonically contracting.

Answer 523

True. Tonically contracting resulting from discharges from the vagus nerve (X)

Question 524

526 What potential space lies posterior to the cervical esophagus and communicates superiorly with the retropharyngeal space and inferiorly with the posterior mediastinum?

Answer 524

Retroesophageal space

Question 525

527 Describe the arterial supply to the esophagus.

Answer 525

Segmental blood supply: * Upper esophageal sphincter and cervical esophagus: Inferior thyroid artery * Thoracic esophagus: Aortic esophageal arteries, terminal bronchial arteries * Distal esophagus and lower esophageal sphincter: left gastric artery, branch of the left phrenic artery

Question 526

528 Describe the venous drainage of the cervical esophagus.

Answer 526

Segmental drainage: submucosal plexus → superior vena cava

Question 527

529 Describe the innervation of the esophagus.

Answer 527

* Sensory: Vagus (X), glossopharyngeal (IX), and spinal afferent nerves * Motor: Vagus (X) nerve, parasympathetic and sympathetic nerves * Intrinsic innervation: * Auerbach plexus: Between the inner circular and outer longitudinal muscle layers * Meissner plexus: Submucosa

Question 528

530 What lymph node basins drain the cervical esophagus?

Answer 528

Primarily levels II–IV. Also drains to level VI, retroesophageal, retropharyngeal, and superior mediastinal nodes (level VII).

Question 529

531 What are the risk factors for cervical esophageal squamous cell carcinoma?

Answer 529

* Tobacco * Alcohol * Gastroesophageal reflux * Plummer-Vinson syndrome

Question 530

532 What is the most common type of cervical esophageal cancer?

Answer 530

Squamous cell carcinoma (approximately 80%)

Question 531

533 What is the most common type of distal esophageal cancer?

Answer 531

Adenocarcinoma. Increasing incidence related to gastro esophageal reflux disease

Question 532

534 What are common initial symptoms in patients with cervical esophageal cancer?

Answer 532

Progressive dysphagia (solids, then solids and liquids) and weight loss. Other symptoms include hematemesis, pain, hoarseness or cough.

Question 533

535 What are the typical nasopharyngoscopy findings in patients with cervical esophageal cancer?

Answer 533

**Negative findings** unless esophagoscopy is performed or tumor extends to the hypopharynx.

Question 534

536 According to the AJCC, 7th edition, the cervical esophagus begins at approximately what distance from the incisors?

Answer 534

15 cm to less than 20 cm

Question 535

537 What imaging modality is most accurate at identifying the extent of cervical esophageal cancer and its relationship with adjacent soft tissues?

Answer 535

MRI

Question 536

538 What procedure is generally required for direct visualization, biopsy, and staging of an esophageal tumor?

Answer 536

EGD

Question 537

539 What procedure or diagnostic test is the most sensitive for T and N staging for esophageal cancer?

Answer 537

Endoscopic ultrasonography

Question 538

540 What is the new T staging system for cervical esophageal squamous cell carcinoma according to the AJCC 7th edition?

Answer 538

(▶ Table 7.7)

Question 539

541 What is the N staging system for cervical esophageal squamous cell carcinoma according to the AJCC 7th edition?

Answer 539

(▶ Table 7.8)

Question 540

542 Describe the staging system used to classify esophageal cancer based on the TNM stage.

Answer 540

* Stage IA: T1N0 * Stage IA: T2N0 * Stage IIA: T3N0 * Stage IIB: T1-T2N1 * Stage IIIA: T4aN0, T3N1, T1–2N2 * Stage IIIB: T3N2 * Stage IIIC: T4aN1–2, T4bAnyN, AnyTN3 * Stage IV: M1

Question 541

543 What tumor characteristics have been recently added to the AJCC, 7th edition, staging of esophageal cancer?

Answer 541

* Histologic type (squamous cell carcinoma versus adeno carcinoma) * Histologic grade (1–3) * Tumor location (upper, middle, or lower esophagus)

Question 542

544 Although cervical esophageal and hypopharyngeal squamous cell carcinomas are commonly grouped together, what is an important difference in staging at presentation?

Answer 542

Hypopharyngeal squamous cell carcinoma has a higher incidence of advanced T and N stages at presentation compared with cervical esophageal squamous cell carcinoma.

Question 543

545 True or False. Comparing stages, esophageal squamous cell carcinoma, and adenocarcinoma have similar survival rates

Answer 543

True

Question 544

546 What imaging modality may play a role in predicting prognosis in esophageal cancer, and what is the unit of measurement that is used to predict prognosis?

Answer 544

PET scans. Standardized uptake values (SUV). This has not borne out in other head and neck cancer thus far, despite intense evaluation.

Question 545

547 What overexpression or gene amplification of what molecular marker has been associated with poor outcome in esophageal cancer?

Answer 545

Human epidermal growth factor receptor (HER-2)

Question 546

548 What treatment modalities are recommended for esophageal cancer based on stage?

Answer 546

* Stage I: Endoscopic resection vs surgical resection * Stage II–III: Chemoradiation followed by surgery * Stage IV: Chemotherapy or best supportive care Note: Increasing stage is associated with poorer prognosis.

Question 547

549 What surgical technique is used for primary cervical esophageal tumors or hypopharyngeal tumors with involvement of the cervical esophagus?

Answer 547

Total pharyngo-laryngo-esophagectomy and total pharyngolaryngectomy with cervical esophagectomy

Question 548

550 What are the reconstructive options after surgery for cervical esophageal cancer when resection includes the esophagus below the thoracic inlet?

Answer 548

* Gastric transposition (gastric "pull-up") * Colonic transposition

Question 549

551 What are some of the disadvantages of the gastric transposition (gastric "pull-up") reconstruction for pharyngeal and esophageal defects?

Answer 549

* High incidence of morbidity and mortality * Inability to close some defects with oropharyngeal or nasopharyngeal extension * Frequent pulmonary complications * Risk of hypoparathyroidism * Gastric dumping syndrome * Gastric outlet obstruction * Regurgitation

Question 550

552 What are the reconstructive options after surgery for cervical esophageal cancer when resection does not include the esophagus below the thoracic inlet?

Answer 550

* Gastric transposition (gastric "pull-up") * Colonic transposition * Jejunal vascularized free flap * Tubed fasciocutaneus vascularized free flap

Question 551

553 What is the major functional disadvantage for patients undergoing jejunal free flap reconstruction for pharyngeal defects?

Answer 551

Poor speech and swallowing function. See also dysphagia and donor-site morbidity. Relatively low rate of stenosis.

Question 552

554 Describe the boundaries of the larynx according to the AJCC.

Answer 552

* Superior: Oropharynx; tip and lateral borders of the epiglottis * Inferior: Trachea; plane passing through the inferior limit of the cricoid cartilage * Posterior/lateral: Hypopharynx; laryngeal surface of the aryepiglottic folds, arytenoid region, interarytenoid space, mucous membrane covering the posterior surface of the cricoid cartilage * Anterior: Anterior/lingual surface of the suprahyoid epiglottis, thyrohyoid membrane, anterior commissure, thyroid cartilage, cricothyroid membrane, anterior arch of the thyroid cartilage

Question 553

555 What are the subsites of the larynx according to the AJCC?

Answer 553

* Supraglottis: Lingual and laryngeal surfaces of the epiglottis, laryngeal surface of aryepiglottic folds, arytenoids, false vocal folds; divided from glottis by a horizontal plane passing through the lateral margin of the ventricle at its junction with the superior surface of the vocal cord. * Glottis: Superior and inferior surface of the true vocal fold, anterior and posterior commissure; extends **1 cm below** the plane dividing supraglottis and glottis; lateral margin defined by the junction of the lateral aspect of the ventricle at its junction with the superior surface of the true vocal fold. * Subglottis: inferior margin of the glottis to inferior border of the cricoid cartilage.

Question 554

556 What subsite of the larynx arises from the **buccopharyngeal primordium** (third or fourth branchial arches) and therefore derives its arterial supply from the superior laryngeal arteries and lymphatic drainage is to levels II and III?

Answer 554

Supraglottis

Question 555

557 What subsites of the larynx arise from the **tracheobronchial primordium** (sixth branchial arch) and therefore derives its arterial supply from the inferior laryngeal arteries and lymphatic drainage is to levels IV and VI?

Answer 555

Glottis and subglottis

Question 556

558 What branchial arch structures give rise to the hyoid bone?

Answer 556

* Second branchial arch: **Lesser horn and upper portion** of the hyoid bone * Third branchial arch: **Greater horn and lower portion** of the hyoid bone

Question 557

559 What are the five subsites of the supraglottis?

Answer 557

1. Suprahyoid epiglottis 2. Infrahyoid epiglottis 3. Aryepiglottic fold (laryngeal surface) 4. False vocal fold (also called the ventricular bands) 5. Arytenoid

Question 558

560 What are the subsites of the glottis?

Answer 558

True vocal folds (superior and inferior surface), including the anterior and posterior commissures

Question 559

561 What are the subsites of the subglottis?

Answer 559

None

Question 560

562 What is the normal histology of the supraglottis?

Answer 560

* **_Pseudo_**stratified columnar respiratory epithelium. The lateral surface of the aryepiglottic folds and epiglottis are stratified squamous epithelium. Numerous mucous gland

Question 561

563 What is the normal histologic structure of the glottis, proceeding medial to lateral through the true vocal fold?

Answer 561

* Stratified squamous epithelium * Superficial lamina propria (Reinke space) * Vocal ligament (intermediate and deep lamina propria) * Thyroarytenoid muscle * Paraglottic fat * Thyroid cartilage

Question 562

564 What is the normal histology of the subglottis?

Answer 562

**_Pseudo_**stratified columnar epithelium

Question 563

565 What are the natural barriers to spread of laryngeal cancer? (▶ Table 7.9)

Answer 563

* Quadrangular membrane * **Conus elasticus\*** * **Thyrohyoid membrane\* (aperture for superior laryngeal neurovascular bundle allows spread)** * Laryngeal cartilages * Hyoepiglottic ligament * Anterior commissure tendon * Cricothyroid membrane \*Most commonly considered

Question 564

566 What sheet of fibroelastic tissue stretches from the epiglottis to the arytenoid and corniculate cartilages, contributes to the aryepiglottic fold superiorly, and defines the free margin of the false cord inferiorly?

Answer 564

Quadrangular membrane

Question 565

567 What sheet of fibroelastic tissue stretches from the vocal ligament to the superior margin of the cricoid laterally and inferior margin of the thyroid cartilage anteriorly (where it forms the cricothyroid membrane)?

Answer 565

Conus elasticus

Question 566

568 What 1 × 10-mm fibrous tissue band connects the vocal ligaments to the midline of the thyroid cartilage, is associated with a lack of perichondrium at the insertion point, and serves as a strong barrier to spread of laryngeal cancer (Kirchner, 1987)?

Answer 566

Anterior commissure tendon (the **Broyles ligament**)

Question 567

569 Broyles ligament, or the anterior commissure tendon, is often sited as a pathway for spread of laryngeal cancer through the thyroid cartilage. However, studies have shown that this structure actually serves as a strong barrier to spread in the absence of what tumor characteristics?

Answer 567

Significant supraglottic (petiole, pre-epiglottic space) or subglottic extension (ossified thyroid cartilage, lymphatics, cricothyroid membrane)

Question 568

570 Name the funnel-shaped space formed by the thyrohyoid membrane and thyroid cartilage anteriorly; the epiglottis posteriorly; the hyoepiglottic ligament, vallecula, and hyoid bone superiorly; and the thyroepiglottic ligament inferiorly. The space communicates laterally with the paraglottic space and acts as an avenue for tumor spread.

Answer 568

Pre-epiglottic space.

Question 569

571 Name the paired spaces that are defined by the thyroid cartilage laterally, the conus elasticus inferomedially, the ventricle medially, the quadrangular membrane superomedially, and the pyriform sinus mucosa posteriorly. It is an avenue for spread of laryngeal cancer and communicates anteriorly with the pre-epiglottic space.

Answer 569

Paraglottic space

Question 570

572 What important feature of the infrahyoid epiglottic cartilage allows easy tumor growth into the pre-epiglottic space?

Answer 570

Fenestrations

Question 571

573 Transglottic tumors by definition cross the ventricle and involve the supraglottis and glottis and may involve the subglottis. Define the theoretical methods by which a laryngeal tumor can become transglottic.

Answer 571

* Directly crossing the ventricle * Crossing at the anterior commissure * Via the paraglottic space (all three subsites of the larynx are accessible) * Spread along the arytenoid cartilage to the posterior ventricle

Question 572

574 Why do lateralized supraglottic tumors drain bilaterally?

Answer 572

The supraglottis is **formed embryologically from a single structure** (i.e., no midline fusion), and therefore its lymphatics cross midline, allowing for bilateral spread of disease.

Question 573

575 What is the inferior limit of the supraglottic lymphatic system within the larynx?

Answer 573

Inferior false vocal fold (barrier is the quadrangular membrane)

Question 574

576 What nodal levels are most commonly involved by supraglottic tumors?

Answer 574

Levels II, III, and IV. Bilateral disease is common, especially with midline tumors.

Question 575

577 What is the pathway for nodal spread from a supraglottic tumor to level II?

Answer 575

Along the superior laryngeal neurovascular bundle

Question 576

578 What supraglottic subsite presents a high risk for aggressive behavior and early nodal metastases?

Answer 576

The "marginal zone": suprahyoid epiglottis and superior aspect of the aryepiglottic folds

Question 577

579 What is the rate of occult nodal disease in supraglottic malignancies (considering all stages)?

Answer 577

Up to 40%. Increases with increasing T stage (10% T1 to 57% T4)

Question 578

580 Why do lateralized glottic tumors drain unilaterally?

Answer 578

They are formed embryologically by paired structures that fuse in the midline. Lymphatics within this subsite are minimal and do not communicate across midline.

Question 579

581 What is the risk of occult nodal metastases in glottic carcinoma?

Answer 579

18%. Increases with T stage

Question 580

582 What nodal levels are at risk for disease in glottic carcinoma?

Answer 580

Levels II, III, IV, and VI (prelaryngeal, pretracheal, and paratracheal nodes)

Question 581

583 What nodal levels are at highest risk for disease in subglottic carcinoma?

Answer 581

Level VI. Commonly present with contralateral or bilateral disease and mediastinal lymphadenopathy below level VII (distant metastases)

Question 582

584 What patient demographic is at highest risk for laryngeal cancer?

Answer 582

* Males (3.8:1) * Associated with tobacco exposure * Age younger than 40 years

Question 583

585 What are the strongest risk factors for laryngeal carcinoma?

Answer 583

* Tobacco smoking (packs per day and years of use) * Alcohol use (amount consumed and duration of use)

Question 584

586 What is the role of laryngopharyngeal reflux in laryngeal cancer?

Answer 584

Controversial. It is unclear whether it is an independent or associated risk factor.

Question 585

587 What percentage of laryngeal cancers have been associated with high-risk HPV (HPV 16 \> HPV 18)?

Answer 585

~ 25%. Clinical significance is unclear.

Question 586

588 What are four primary premalignant laryngeal lesions as defined by the WHO?

Answer 586

* Hyperplasia * Keratosis * Dysplasia: Mild, moderate, severe * Carcinoma in situ

Question 587

589 What significance does laryngeal leukoplakia have?

Answer 587

Leukoplakia means "white plaque" and without a biopsy gives no information relevant to management.

Question 588

590 What is the approximate rate of dysplasia in _laryngeal_ leukoplakia?

Answer 588

40%

Question 589

591 What is the approximate rate of malignant transformation of mild dysplasia? Severe dysplasia or carcinoma in situ?

Answer 589

* 11% * 30% Note: It may take up to 10 years for malignant conversion (average 3 years).

Question 590

592 What percentage of laryngeal tumors are squamous cell carcinomas?

Answer 590

85 to 95%

Question 591

593 According to WHO, what are the possible subtypes of squamous cell carcinoma found in the larynx?

Answer 591

* Verrucous * Spindle cell carcinoma (also called sarcomatoid carcinoma, carcinosarcoma, pseudosarcoma) * Adenoid (acantholytic) Basaloid squamous cell carcinoma * Clear cell carcinoma * Adenosquamous carcinoma * Giant cell carcinoma * Lymphoepithelial carcinoma

Question 592

594 What laryngeal lesion is characterized by proliferation of the squamous mucosa, elongated rete ridges that appear worrisome for carcinoma and show no evidence of cytologic abnormalities consistent with malignancy?

Answer 592

**Pseudoepitheliomatous hyperplasia.** It can be associated with infection (e.g., tuberculosis, syphilis, blastomycosis), trauma, granular cell tumor, and chronic irritation. It is easily mistaken for squamous cell carcinoma and requires proper orientation of specimens and periodic-acid Schiff stain.

Question 593

595 What pathology in the larynx is associated with trauma and infarction of salivary gland tissue (ducts and acini of seromucinous glands), is often misdiagnosed as squamous cell carcinoma or mucoepidermoid carcinoma, and requires immunohistochemistry for diagnosis?

Answer 593

Necrotizing sialometaplasia

Question 594

596 What subtype of squamous cell carcinoma results in largely exophytic growth, pushing margins, does not metastasize, is associated with HPV-16 and -18, and has an indolent course?

Answer 594

Verrucous carcinoma. It is the second most common site in the head and neck (to oral cavity).

Question 595

597 What epithelial laryngeal cancer contains both basaloid and squamous components (biphasic), cystic spaces, results in frequent regional and distant metastases, occurs most commonly in the supraglottis, and has a worse prognosis than standard squamous cell carcinoma?

Answer 595

Basaloid squamous cell carcinoma

Question 596

598 What epithelial laryngeal cancer contains malignant squamous epithelium on its surface associated with a deeper malignant spindle cell carcinoma (biphasic), is associated with tobacco and alcohol use, results in common regional metastases, and is relatively radioresistant?

Answer 596

Spindle cell carcinoma

Question 597

599 What is the most common location for adenosquamous carcinoma, a biphasic tumor arising from the basal layer of the epithelium and demonstrating behavior more aggressive than conventional squamous cell carcinoma, in the upper aerodigestive tract?

Answer 597

Larynx

Question 598

600 What is the key pathologic difference between laryngeal verrucous carcinoma and papillary squamous cell carcinoma, which demonstrates exophytic papillary growth with cores of fibrovascular stroma?

Answer 598

Significantly abnormal cytology

Question 599

601 According to the WHO, what are the possible subtypes of malignant salivary gland tumors found in the larynx, which make up less than 1% of all laryngeal tumors?

Answer 599

* Mucoepidermoid carcinoma * Adenoid cystic carcinoma * Adenocarcinoma * Acinic cell carcinoma * Carcinoma ex-pleomorphic adenoma * Epithelial-myoepithelial cell carcinoma * Salivary duct carcinoma

Question 600

602 What are the cells of origin for supraglottic adenocarcinoma?

Answer 600

Minor salivary glands

Question 601

603 Are salivary gland carcinomas of the larynx more common in men or women?

Answer 601

**Men (2:1).** However, **adenoid cystic carcinoma** has no gender bias.

Question 602

604 What are the two most common laryngeal malignant salivary gland cancers?

Answer 602

**Mucoepidermoid carcinoma and adenoid cystic carcinoma,** constituting one-third of malignant laryngeal salivary gland tumors

Question 603

605 What laryngeal tumor is composed of squamous, mucin-secreting, and intermediate-type cells and likely forms in the intercalated ducts of seromucinous glands?

Answer 603

Mucoepidermoid carcinoma

Question 604

606 What percentage of supraglottic cancers arising from minor salivary glands will be mucoepidermoid carcinoma on pathological analysis?

Answer 604

35%. They are less common than adenoid cystic (46%), more common than adenocarcinoma (12%).

Question 605

607 Adenoid cystic carcinoma is defined by uniform basaloid cells that grow in what three distinct patterns?

Answer 605

* Cribriform * Tubular * Solid

Question 606

608 According to the WHO, what are the possible subtypes of neuroendocrine tumors found in the larynx, which are the second most common tumors of the larynx next to squamous cell carcinoma?

Answer 606

* Atypical carcinoid tumor (54%) * Small cell carcinoma (28%) * Malignant paraganglioma (12%) * (Typical) carcinoid tumor (7%)

Question 607

609 What is the relative occurrence of supraglottic neuroendocrine tumors in men and women?

Answer 607

F\>M (3:1)

Question 608

610 What is the 5-year survival rate for laryngeal neuroendocrine carcinoma?

Answer 608

Although it is one of the most common extrapulmonary sites for neuroendocrine carcinoma, laryngeal neuroendocrine carcinoma is _extremely rare_. It is also most often lethal, with **2- and 5-year survival rates of 16% and 5%**, respectively.

Question 609

611 What subsite of the larynx is most commonly involved by both typical and atypical carcinoid tumors, which present as submucosal and polypoid masses?

Answer 609

Supraglottis

Question 610

612 To what unusual locations do atypical carcinoids commonly metastasize?

Answer 610

Skin and subcutaneous tissue

Question 611

613 What percentage of patients with laryngeal small cell carcinoma will develop distant metastases?

Answer 611

90%

Question 612

614 According to the WHO, what are the possible subtypes of **malignant soft tissue tumors found in the larynx**?

Answer 612

* Fibrosarcoma * Malignant fibrous histiocytoma * Liposarcoma * Leiomyosarcoma * Rhabdomyosarcoma * Angiosarcoma * Kaposi sarcoma * Malignant hemangiopericytoma * Malignant nerve sheath tumor * Alveolar soft part sarcoma * Synovial sarcoma * Ewing sarcoma

Question 613

615 According to the WHO, what are the possible subtypes of malignant bone and cartilage tumors in the larynx?

Answer 613

* Chondrosarcoma (most common) * Osteosarcoma

Question 614

616 What laryngeal tumors arise from ossified hyaline cartilage, most commonly from the cricoid cartilage?

Answer 614

Chondrosarcomas

Question 615

617 What is the distant metastasis rate in laryngeal chondrosarcoma?

Answer 615

8.5%

Question 616

618 According to the WHO, what are the possible subtypes of **malignant hematolymphoid tumors found in the larynx**?

Answer 616

* Extramedullary plasmacytoma (most common) * Lymphoma

Question 617

619 According to the WHO, what tumors most commonly metastasize from a distant site to the larynx?

Answer 617

* Kidney * Skin (melanoma) * Breast * Lung * Prostate * Gastrointestinal tract

Question 618

620 What is the most common site of second primaries in patients with larynx cancer?

Answer 618

**Lung.** Consider a pulmonary lesion a second primary tumor until proven otherwise.

Question 619

621 What are the clinical risk factors that may increase the likelihood of **stomal recurrence**?

Answer 619

* Primary subglottic tumor * Glottic tumor invading subglottis by \> 1 cm * T4 glottic primary tumor

Question 620

622 What are the proposed causes of stomal recurrence after total laryngectomy for laryngeal cancer?

Answer 620

* Positive tracheal margin * Paratracheal nodal metastases * Thyroid gland invasion * Seeding of the stoma at initial operati (CHECK BOOK)

Question 621

623 What is the most common initial symptom associated with supraglottic carcinoma?

Answer 621

Dysphagia. It can also manifest with dysphonia, odynophagia, otalgia, stridor, dyspnea, hemoptysis, and neck mass.

Question 622

624 What is the most common initial symptom associated with early versus late glottic carcinoma?

Answer 622

* Early disease: Dysphonia * Advanced disease: Stridor, dyspnea

Question 623

625 What are the most common initial symptoms associated with subglottic carcinoma?

Answer 623

Dyspnea and stridor

Question 624

626 Patients with what symptoms may require urgent or emergent management of their laryngeal tumor?

Answer 624

Dyspnea and stridor

Question 625

627 On endoscopy, which of the following lesions may be suspicious for a laryngeal carcinoma: ulceration, sessile lesion, polypoid lesion, submucosal fullness, or exophytic friable mass?

Answer 625

All should suggest possible malignant process.

Question 626

628 What laryngoscopy adjunct should be used in the clinic to evaluate a patient in whom you are concerned about a laryngeal malignancy?

Answer 626

Flexible fiberoptic laryngoscopy and/or video stroboscopy

Question 627

629 To evaluate a patient with laryngeal carcinoma for posterior invasion of the prevertebral fascia, you grasp the larynx and rock it back and forth. Inability to rock the larynx and lack of what sound/tactile feedback suggest invasion?

Answer 627

**Laryngeal crepitus** (movement of laryngopharyngeal framework across the prevertebral and vertebral structures)

Question 628

630 What is the most commonly used imaging modality for the initial workup of laryngeal cancer?

Answer 628

CT neck with contrast using fine cuts through the larynx (~ 1 mm)

Question 629

631 Which offers better evaluation of **cartilage invasion**: CT or MRI?

Answer 629

MRI

Question 630

632 When using MRI for the evaluation of a patient with laryngeal cancer, what modality or sequences would be most useful to determine invasion of the preepiglottic and/or paraglottic spaces?

Answer 630

T1-weighted gadolinium enhanced MRI with fat suppression. High negative predictive value. False-positive results are caused by inflammation.

Question 631

633 During direct endoscopic examination of the upper aerodigestive tract in the operating room for laryngeal cancer, what maneuver should be performed if there is concern for fixation of the larynx or immobility of a vocal cord?

Answer 631

Palpation of the laryngeal structures

Question 632

634 Describe microflap excision for laryngeal biopsy.

Answer 632

Microflap surgery requires dissection of the **superficial lamina propria** as opposed to excision. This allows for _sparing of the vocal ligament_ and affords _a better postoperative mucosal wave_.

Question 633

635 Why is detection of recurrence after radiation more difficult in laryngeal cancer?

Answer 633

Persistent edema and fibrosis are common post-treatment sequelae that obscure visualization of (often submucosal) tumor growth

Question 634

636 Although deep biopsies are often necessary to diagnose a recurrent laryngeal tumor after radiation therapy, what adverse outcomes are associated with biopsy in this setting?

Answer 634

Increased risk of infection, perichondritis, and chondroradionecrosis

Question 635

637 Describe the “T” staging system for epithelial supraglottic malignancies according to the AJCC. (▶ Fig. 7.7)

Answer 635

* T1: Tumor limited to one supraglottic subsite, normal vocal cord mobility. * T2: Tumor invasion of more than one subsite of the supraglottis or glottis or region outside the supraglottis (e.g., mucosa of base of tongue, vallecula, medial wall of pyriform sinus) without fixation of the larynx * T3: Tumor limited to the larynx with vocal cord fixation and/or invades any of the following: postcricoid area, pre epiglottic tissues, paraglottic space, and/or minor thyroid cartilage erosion (e.g., inner cortex). * T4a: Moderately advanced local disease: tumor invades through the thyroid cartilage and/or invades tissue beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscles of the tongue, strap muscles, thyroid, or esophagus). * T4b: Very advanced local disease: Tumor invades pre vertebral space, encases carotid artery, or invades mediastinal structures.

Question 636

638 What differentiates T2 from T3 supraglottic tumors?

Answer 636

T2 tumors do not invade the perilaryngeal spaces; T3 tumors present with vocal cord fixation.

Question 637

639 What differentiates T1 from T2 supraglottic tumors?

Answer 637

* T1 tumors are limited to one subsite with normal vocal cord mobility. * T2 tumors may involve multiple supraglottic subsites or adjacent regions (tongue base, glottis)

Question 638

640 Describe the “T” staging system for epithelial glottic malignancies according to the AJCC).

Answer 638

* T1: Tumor is limited to the vocal cord(s); may involve anterior or posterior commissure; normal vocal cord mobility. * T1a: Tumor is limited to one vocal cord. * T1b: Tumor involves both vocal cords. * T2: Tumor extends to supraglottis and/or subglottis or with impaired vocal cord mobility (some authors divide T2 into T2a and T2b; see below). * T3: Tumor is limited to the larynx with vocal cord fixation and/or invades the paraglottic space, and/or minor thyroid cartilage erosion (e.g., inner cortex). * T4a: Moderately advanced local disease: Tumor invades through the thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of neck including deep extrinsic muscle of the tongue, strap muscles, thyroid or esophagus). * T4b: Very advanced local disease: Tumor invades pre vertebral space, encases carotid artery, or invades mediastinal structures.

Question 639

641 Although the AJCC, (7th edition) does not differ entiate T2 into T2a and T2b, some authorities do. How are these stages defined?

Answer 639

Tumor extends to the supraglottis and/or subglottis: * T2a: Without impaired vocal cord mobility * T2b: With impaired vocal cord mobility

Question 640

642 What is the rate of nodal metastases in T1 glottic carcinoma?

Answer 640

5%

Question 641

643 What differentiates T3 from T4 glottic tumors?

Answer 641

T3 tumors are confined to the larynx, whereas T4 have spread extralaryngeally (into strap musculature, thyroid gland, trachea, esophagus).

Question 642

644 Describe the “T” staging system for **epithelial subglottic** malignancies according to the AJCC.

Answer 642

* T1: Tumor is limited to the subglottics. * T2: Tumor extends to vocal cord(s) with normal or impaired mobility. * T3: Tumor is limited to the larynx with vocal cord fixation. * T4a: Moderately advanced local disease. Tumor invades cricoid or thyroid cartilage and/or invades tissues beyond the larynx (e.g., trachea, soft tissues of the neck including deep extrinsic muscles of the tongue, strap muscles, thyroid or esophagus) * T4b: Very advanced local disease: Tumor invades pre vertebral space, encases carotid artery, or invades mediastinal structures.

Question 643

645 Describe the **stages of stomal recurrence after total laryngectomy** for laryngeal cancer (Sisson, 1989).

Answer 643

* Stage I: Superior to the stoma, at 9 to 3 o’clock position. Normal swallowing and esophagoscopy * Stage II: Above or below the stoma, 9 to 3 o’clock. Most have dysphagia and esophageal invasion. * Stage III: Below the stoma, at 9 to 3 o’clock. Esophagus is always involved. High risk of upper mediastinal disease * Stage IV: Lateral extension of the tumor under the clavicle, dysphagia, and esophageal invasion

Question 644

646 What is the overall 5-year survival rate for laryngeal cancer, and what subsite has the best overall survival?

Answer 644

* 64% * Glottic (79%) \> supraglottic (47%) \> subglottic (30 to 50%)

Question 645

647 During the initial workup of a patient with laryngeal cancer, **you identify cartilage invasion**. How does this impact prognosis and management?

Answer 645

* Upstages tumor (T3 or T4a) * Poorer response to radiation therapy * Decreased local control rates * Higher risk of chondroradionecrosis

Question 646

648 What is the incidence of distant metastasis in glottic carcinoma?

Answer 646

4%

Question 647

649 What are the most important clinical prognostic factors in order of importance?

Answer 647

* Clinical stage (most important to least: M \> N \> T) * Location of the primary (best to worst: glottic \> supraglottic \> subglottic)

Question 648

650 Why does involvement of the anterior commissure decrease prognosis (local control rates) for both surgery and radiation therapy?

Answer 648

Inadequate recognition of deep extension

Question 649

651 What factors increase the risk of peristomal recurrence after laryngectomy for laryngeal cancer?

Answer 649

* T3 or T4 tumors * Subglottic tumor extension

Question 650

652 What histologic characteristics decrease local control and overall survival?

Answer 650

* Extracapsular spread\* * Positive surgical margins\* * Histologic subtype * Histologic grade (well, moderate, poor) * Pattern of invasion (pushing vs infiltrative) * Perineural invasion\* * Vascular embolus (invasion)\* \*Considered adverse features impacting management decisions by the NCCN (2013)

Question 651

653 In addition to primary oncologic management, what behavioral modifications should be recommended to maximize treatment benefit and decrease the risk of recurrence for premalignant and malignant laryngeal cancer?

Answer 651

* Tobacco and alcohol cessation * Reflux control

Question 652

654 What is the wavelength and chromophore of the CO2 laser?

Answer 652

* Wavelength: 10,600 nm * Chromophore: water

Question 653

655 What is the wavelength and chromophore of the potassium-titalyl-phosphate (KTP) laser?

Answer 653

* Wavelength: 532 nm * Chromophore: Oxyhemoglobin

Question 654

656 What treatment modality makes use of photoreactive chemicals (5-aminolevulinic acid, Photo frin, hematoporphyrin, foscan), which are preferentially absorbed by premalignant or malignant cells and then subsequently activated by light of a specific frequency?

Answer 654

Photodynamic therapy

Question 655

657 What is the treatment of choice for premalignant laryngeal lesions?

Answer 655

* Complete excision with pathologic analysis (microflap, vocal cord stripping; higher risk for poor voice outcomes, laser resection) * Close follow-up * Can consider laser ablation (pulsed dye laser or KTP) once pathologic diagnosis is established

Question 656

658 What are the management options for carcinoma in situ?

Answer 656

Complete surgical excision or radiation therapy. Note: Recurrence is higher after surgical excision than after radiation therapy, but local control is equivalent with repeat excision.

Question 657

659 For a patient with significant airway obstruction from a laryngeal tumor, should you perform an emergent laryngectomy or tracheostomy?

Answer 657

**High tracheostomy.** No evidence has been established that tracheostomy increases the risk of peristomal recurrence, and emergent laryngectomy does not allow time for complete workup and counseling.

Question 658

660 In the Veterans Affairs’ (VA) laryngeal cancer study, what groups were compared?

Answer 658

* Induction chemotherapy and radiation for responders and surgery followed by postoperative radiation therapy for responders * Surgery and postoperative radiation

Question 659

661 What were the laryngeal preservation rates and overall survival figures in the VA laryngeal cancer study?

Answer 659

For patients with advanced resectable laryngeal cancer (stage III or IV, excluding T1N1), **induction chemotherapy and radiation allow for laryngeal preservation in 64% of patients** and a similar 2-year overall survival (68%) compared with total laryngectomy and postoperative radiation therapy

Question 660

662 What proportion of patients in the VA laryngeal cancer study preoperatively had mobile vocal cords? Cartilage invasion?

Answer 660

44% and 9%, respectively

Question 661

663 In the RTOG 91–11 organ preservation in advanced laryngeal cancer study, what groups were compared?

Answer 661

* Concurrent cisplatin and XRT * Induction cisplatin/5-FU followed by XRT for complete and partial responders or surgery and adjuvant XRT for non responders * Radiation alone

Question 662

664 What was the laryngeal preservation rate for concurrent chemoradiation, induction chemotherapy/radiation, and radiation alone in RTOG 91–11?

Answer 662

* CRT: 88% * Induction chemotherapy/radiation + radiotherapy: 75% * Radiotherapy alone: 70%

Question 663

665 What was the grade 3/4 mucositis rate for concurrent chemoradiation, induction chemotherapy/radiation, and radiation alone in RTOG 91–11?

Answer 663

* CRT: 43% * Induction chemotherapy + radiotherapy: 24% * Radiotherapy: 24%

Question 664

666 What patients with advanced laryngeal cancer were excluded from RTOG 91–11?

Answer 664

Patients were excluded if they were not eligible for total laryngectomy with curative intent, **T1 primary tumors**, and **large-volume T4 disease (transcartilaginous or \> 1-cm tongue base invasion)**.

Question 665

667 What are the contraindications to transoral resection of laryngeal carcinoma?

Answer 665

* Tongue base involvement * Subglottic extension (\> 5 mm) * Pyriform sinus or postcricoid extension * Cartilage invasion Note: Restricted vocal cord mobility and extension onto the arytenoid are relative contraindications.

Question 666

668 What factors are critical to transoral resection of laryngeal carcinoma?

Answer 666

Adequate exposure, accurate assessment of tumor extension, complete resection

Question 667

669 Name the open conservation laryngeal procedure in which **one vocal cord or one and a portion of the other vocal cord are removed in continuity with the adjacent paraglottic space and overlying thyroid cartilage**

Answer 667

**Vertical partial laryngectomy.** The vertical height of the larynx is maintained by the retained contralateral thyroid ala.

Question 668

670 What contraindicates vertical partial laryngectomy?

Answer 668

* Cricoid cartilage involvement (1-cm subglottic extension anteriorly and 5 mm posteriorly) * Thyroid cartilage involvement (often the case for trans glottic tumors because mucosal spread from the supraglottis to glottis across the ventricle brings tumor into close proximity to the inner thyroid perichondrium) * Poor pulmonary function

Question 669

671 Name the operation and its subtypes in which the **entire superior portion of the thyroid cartilage is removed** along with the underlying laryngeal structures, **reducing the vertical height of the larynx** by the subsequent reconstruction.

Answer 669

**Horizontal partial laryngectomy**: * Supraglottic * Extended supraglottic * Supracricoid (with cricohyoidopexy or cricohyoiodoepiglottopexy)

Question 670

672 What is the embryologic rationale behind horizontal hemilaryngectomy?

Answer 670

An embryologic boundary exists between the false and true vocal folds, resulting in independent lymphatic drainage from each. Therefore, in select (T1/T2) supraglottic tumors that do not extend into neighboring structures, horizontal supraglottic hemilaryngectomy may be considered an oncologically sound resection strategy.

Question 671

673 What are the contraindications for supracricoid horizontal partial laryngectomy?

Answer 671

* Arytenoid fixation * Cricoid/thyroid cartilage involvement * Hyoid involvement * Significant pre-epiglottic space disease * Poor pulmonary function

Question 672

674 What patient factors are critical to conservation laryngeal operations?

Answer 672

**Excellent cardiopulmonary reserve** and motivation to retain larynx

Question 673

675 What tumor factors contraindicate conservation laryngeal surgery?

Answer 673

* Cartilage invasion * Extralaryngeal spread * Interarytenoid involvement * Postcricoid spread * Invasion to pyriform apex

Question 674

676 What factors reduce the efficacy of radiation in laryngeal cancer?

Answer 674

* Cartilage invasion * T4 stage * Extralaryngeal spread

Question 675

677 What site(s) are most commonly involved by distant metastases from the larynx?

Answer 675

Lung and mediastinum (not including level VII)

Question 676

678 What subsite of the larynx has the highest risk for distant metastasis?

Answer 676

Supraglottis (up to 15%)

Question 677

679 What factors increase the risk of distant metastasis for laryngeal cancer?

Answer 677

History of nodal metastasis

Question 678

680 What is the management of choice for supraglottic carcinoma not requiring a total laryngectomy (mostly cT1–2, N0) according to the NCCN (2011)?

Answer 678

* Endoscopic resection → neck dissection * Open partial supraglottic laryngectomy → neck dissection * Definitive radiation therapy

Question 679

681 For patients undergoing primary surgical management of cT1–2N0 supraglottic carcinoma not requiring a total laryngectomy, what are the adjuvant treatment recommendations according to the NCCN (2011)?

Answer 679

* N0 → observation * One positive node, no adverse features → consider radiation therapy * N+ , positive margin → re-excision, XRT, or CRT * N+ , extracapsular spread → CRT or XRT alone

Question 680

682 What is the treatment of choice for cT1–2 N+ and select cT3 N1 supraglottic carcinomas not requiring a total laryngectomy according to the NCCN (2011)?

Answer 680

* Concurrent chemoradiation therapy with cisplatin (preferred) → additional therapy dictated by response to therapy * Definitive radiation therapy → additional therapy dictated by response to therapy * Partial supraglottic laryngectomy and neck dissection(s) → adjuvant therapy as dictated by pathologic findings * Induction chemotherapy

Question 681

683 What is the treatment of choice for a cT3N0 supraglottic carcinoma requiring a total laryngectomy according to the NCCN (2011)?

Answer 681

* Concurrent chemoradiation therapy with cisplatin (pre ferred) * Laryngectomy, ipsilateral thyroidectomy, with ipsilateral or bilateral neck dissection * Radiation therapy (if not a candidate for concurrent chemotherapy) * Induction chemotherapy

Question 682

684 For patients undergoing primary surgical management of cT3N0 supraglottic carcinoma, what are the adjuvant treatment recommendations according to the NCCN (2011)?

Answer 682

* N0 or 1 positive node without adverse features → consider radiation therapy * Extracapsular spread or positive margin → chemoradiation * Other risk features → radiation therapy with or without chemotherapy

Question 683

685 What is the management of choice for a cT3N2–3 supraglottic carcinoma requiring a total laryngectomy according to the NCCN (2011)?

Answer 683

* Concurrent chemoradiation therapy with cisplatin (pre ferred) → surgical salvage based on response to therapy * Laryngectomy, ipsilateral thyroidectomy with neck dissection(s) → radiation therapy → chemotherapy based on the presence of pathologic adverse features * Induction chemotherapy followed by chemoradiation therapy

Question 684

686 What is the management of choice for a cT4a N0-3 supraglottic carcinoma requiring according to the NCCN (2011)?

Answer 684

* Laryngectomy, ipsilateral thyroidectomy, with ipsilateral or bilateral neck dissection: * N0, no risk features → radiation therapy * Extracapsular spread and/or positive margin → chemoradiation therapy * Other risk features → radiation therapy → chemotherapy Note: For those who decline surgery, concurrent chemoradiation therapy, enrollment in a clinical trial, or induction chemotherapy followed by primary chemoradiation therapy can be considered.

Question 685

687 For patients undergoing primary induction chemotherapy for supraglottic carcinoma, what are the treatment recommendations based on response to induction according to the NCCN (2011)?

Answer 685

* Primary site: Complete response → radiation therapy with or without chemotherapy * Primary site: Partial response → chemoradiation therapy → if partial response → salvage surgery * Primary site \< partial response → surgery → radiation therapy with or without chemotherapy based on presence of pathological adverse features

Question 686

688 What dose of definitive radiation therapy is recommended by the NCCN (2011) for patients with T1–2 N0 supraglottic squamous cell carcino ma?

Answer 686

≥ 66 Gy

Question 687

689 What dose of definitive radiation therapy is recommended by the NCCN (2011) for patients with T2–3 N0–1 supraglottic squamous cell carci noma?

Answer 687

* Primary and cN+ ≥ 70 Gy, conventional fractionation (Monday through Friday for 7 weeks), high-risk nodal basins 44 to 64 Gy * Accelerated fractionation: 66 to 74 Gy to gross disease, 44 to 64 Gy to high-risk regions for 6 weeks * Concomitant boost accelerated radiation therapy: 72 Gy/ 6 weeks, second daily dose for the last 12 days Hyperfractionation: 81.6 Gy for 7 week

Question 688

690 What dose of radiation therapy is recommended by the NCCN (2011) for patients undergoing concomitant chemoradiation therapy for supraglottic squamous cell carcinoma?

Answer 688

70 Gy for 7 weeks, conventional fractionation

Question 689

691 What dose of radiation therapy is recommended by the NCCN (2011) for patients undergoing **postoperative** radiation therapy for supraglottic squamous cell carcinoma?

Answer 689

* Primary 60 to 66 Gy, conventional fractionation (Monday through Friday for 7 weeks), high-risk nodal basins 44 to 64 Gy * N+ neck: 60 to 66 Gy * N0, high-risk neck: 44 to 64 Gy

Question 690

692 What chemotherapeutic agent and dose are recommended by the NCCN (2011) for patients undergoing concomitant chemoradiation therapy for supraglottic squamous cell carcinoma?

Answer 690

Cisplatin 100 mg/m² every 3 weeks during radiation

Question 691

693 What levels of the neck should be addressed during an elective neck dissection for an N0 supraglottic cancer according to the NCCN (2011)?

Answer 691

Level II-IV, level VI when appropriate

Question 692

694 What is the initial local control achieved by radiation alone for T1 and T2 supraglottic carcinoma?

Answer 692

92 to 100%

Question 693

695 What percentage of patients who undergo supracricoid partial laryngectomy with cricohyoidopexy for supraglottic cancer will never achieve decannulation?

Answer 693

1.5%

Question 694

696 Which of the following has more influence on survival in supraglottic malignancies: histology of tumor (squamous vs. nonsquamous) or T/N staging?

Answer 694

T and N staging

Question 695

697 What is the management of choice for glottic carcinoma not requiring a total laryngectomy according to the NCCN (2011)?

Answer 695

* Radiation therapy * Partial laryngectomy/open or endoscopic resection as indicated * N0 → observe

Question 696

698 What is the management of choice for T3 glottic carcinoma requiring total laryngectomy (N0–1) according to the NCCN (2011)?

Answer 696

* Concurrent chemoradiation therapy with cisplatin (preferred) * Radiation (if not a candidate for surgery) * Surgery

Question 697

699 If a patient with T3 glottic cancer requiring a total laryngectomy (N0–1) undergoes concurrent chemoradiation therapy with cisplatin or primary radiation therapy alone, what are the recommended management steps based on the patient’s response to therapy at the primary site?

Answer 697

* Complete response (N0 at initial staging) → observe * Complete response (N+ at initial staging) or Residual nodal disease → neck dissection (CHECK BOOK) * Complete clinical response in neck → evaluation → if N+ → neck dissection, if N0 → observe * Residual tumor at the primary site → salvage surgery + neck dissection as indicated

Question 698

700 If a patient with T3 glottic cancer requiring a total laryngectomy (N0–1) elects to undergo primary surgical intervention, what are the recommended management steps based on the patient’s nodal status?

Answer 698

* N0 → Laryngectomy with ipsilateral thyroidectomy * N1 → Laryngectomy with ipsilateral thyroidectomy, ipsilateral or bilateral neck dissection * No adverse features → observe * Extracapsular spread or positive margins → chemoradiation therapy * Other risk features → radiation therapy → chemotherapy

Question 699

701 What is the treatment of choice for T3 glottic carcinoma requiring total laryngectomy (N2–3) according to the NCCN (2011)?

Answer 699

* Concurrent chemoradiation therapy with cisplatin (preferred) * Laryngectomy with ipsilateral thyroidectomy and ipsi lateral or bilateral neck dissection * Induction chemotherapy

Question 700

702 If a patient with T3N2–3 glottic carcinoma requiring a total laryngectomy undergoes con current chemoradiation therapy with cisplatin, what are the treatment options based on response to therapy?

Answer 700

● Primary site: complete response ● Residual tumor in neck → neck dissection ● Complete clinical response in neck → evaluation → if N0, observe, if N + then neck dissection ● Primary site: residual tumor ● Salvage surgery + neck dissection as indicated

Question 701

703 If a patient with T3N2–3 glottic carcinoma requiring a total laryngectomy undergoes primary surgical treatment, what are the treatment op tions based on pathologic analysis?

Answer 701

● No adverse features → observe ● Extracapsular spread and/or positive margins → chemo radiation therapy ● Other risk features → radiation therapy → chemotherapy

Question 702

704 If a patient with T3N2–3 glottic carcinoma requiring a total laryngectomy undergoes induc tion chemotherapy, what are the treatment options based on clinical response of the primary site?

Answer 702

● Complete response → definitive radiation therapy or chemoradiation therapy ● N + → neck dissection ● N0 → evaluation, if N + → neck dissection ● Partial response → chemoradiation therapy ● Complete response → observe ● Residual disease → Salvage surgery ● \< Partial/no response → surgery ● No adverse features → radiation therapy ● Extracapsular spread and/or positive margin →chemo radiation therapy ● Other risk features → radiation therapy → chemotherapy

Question 703

705 What is the treatment of choice for T4aN0 glottic carcinoma according to the NCCN (2011)?

Answer 703

Laryngectomy with ipsilateral thyroidectomy → unilateral/ bilateral neck dissection → chemoradiation therapy

Question 704

706 What is the treatment of choice for T4aN1 glottic carcinoma according to the NCCN (2011)?

Answer 704

Laryngectomy with ipsilateral thyroidectomy and ipsilateral neck dissection → contralateral neck dissection → chemo radiation therapy

Question 705

707 What is the treatment of choice for T4aN2–3 glottic carcinoma according to the NCCN (2011)?

Answer 705

Laryngectomy with ipsilateral thyroidectomy and ipsilateral or bilateral neck dissection → chemoradiation therapy

Question 706

708 What is the definitive radiation therapy for T1N0 glottic carcinoma recommended by the NCCN (2011)?

Answer 706

63 to 66 Gy, conventional fractionation

Question 707

709 What is the definitive radiation therapy for T1–2 glottic carcinoma recommended by the NCCN (2011)?

Answer 707

\> 66 Gy, conventional fractionation

Question 708

710 What is the definitive radiation therapy for \> T2N + glottic carcinoma recommended by the NCCN (2011)?

Answer 708

66 to 74 Gy, conventional fractionation (accelerated frac tionation schedules may be considered)Nodal levels at risk for disease: 44 to 64 Gy

Question 709

711 What is the radiation dose for primary concurrent chemoradiation therapy for glottic carcinoma recommended by the NCCN (2011)?

Answer 709

● Primary and N + disease: ≥ 70 Gy ● Nodal levels at high risk: 44 to 64 Gy

Question 710

712 What is the radiation dose for adjuvant radiation therapy for glottic carcinoma recommended by the NCCN (2011)?

Answer 710

● Primary: 60 to 66 Gy ● N + : 60 to 66 Gy ● N0: 44 to 64 Gy

Question 711

713 What is the chemotherapeutic agent and dose of choice for chemoradiation therapy for glottic carcinoma recommended by the NCCN (2013)?

Answer 711

Cisplatin 100 mg/m2 every 3 weeks (generally for three cycles)

Question 712

714 Describe vestibulotomy as a component of trans oral laser resection of glottic carcinoma.

Answer 712

Vestibulotomy refers to removing those portions of the false cord that overlie the tumor. It affords lateral exposure and may facilitate postoperative surveillance.

Question 713

715 What is the initial treatment of an airway fire?

Answer 713

First remove the endotracheal tube because it is providing the fuel (oxygen) for the fire. Irrigate with water, reintubate, and perform bronchoscopy to survey the injury.

Question 714

716 What is the point of entrance into the larynx during laryngofissure?

Answer 714

The larynx is divided in the midline, with entry at the anterior commissure.

Question 715

717 What are the benefits of transoral approach for cordectomy?

Answer 715

Avoidance of initial tracheostomy and external scar. The main disadvantage, of course, is poorer access.

Question 716

718 What are the indications for cordectomy via transoral access or laryngofissure?

Answer 716

● Cordectomy can be considered for T1 tumors limited to the middle third of the vocal fold. ● Contraindications include extension of tumor to vocal process or anterior commissure, subglottis, ventricle, or false cord.

Question 717

719 What is the standard treatment for subglottic carcinoma?

Answer 717

Total laryngectomy with paratracheal node dissection followed by radiation therapy (including the mediastinum) ± chemotherapy

Question 718

720 For carcinoma with unilateral subglottic extension, what additional surgery should be considered during total laryngectomy?

Answer 718

Ipsilateral thyroid lobectomy and paratracheal node dis section

Question 719

721 What are the surgical options for primary sub glottic squamous cell carcinoma?

Answer 719

When treated surgically, all require total laryngectomy with paratracheal node dissection

Question 720

722 What proportion of patients for whom radiation for advanced larynx cancer fails would be suitable candidates for salvage surgery?

Answer 720

Two-thirds

Question 721

723 What are some of the common indications for salvage surgery after nonoperative primary ma nagement of laryngeal cancer?

Answer 721

● Residual or recurrent locoregional disease ● Chondroradionecrosis ● Severe aspiration ● Laryngeal stenosis ● Pharyngoesophageal stenosis

Question 722

724 What are the contraindications to partial laryn gectomy in the salvage situation for patients with recurrent laryngeal cancer (Biller et al, 1970)?

Answer 722

● Subglottic extension \> 5 mm ● Cartilage invasion ● Contralateral vocal cord invasion ● Arytenoid cartilage invasion (other than vocal process) ● Vocal cord fixation ● Recurrence not associated with the primary lesion

Question 723

725 What complications are frequently associated with management of stomal recurrences?

Answer 723

● Vascular injury ● Hypocalcaemia ● Mediastinitis ● Fistula

Question 724

726 What laryngeal reconstructive technique used for supracricoid partial laryngectomy preserves the epiglottis?

Answer 724

Cricohyoidoepiglottopexy

Question 725

727 What laryngeal reconstructive technique is used after horizontal partial laryngectomy and requires resection of the epiglottis?

Answer 725

Cricohyoidopexy

Question 726

728 In a patient undergoing laryngopharyngectomy with primary closure, what additional procedure should be performed to decrease postoperative dysphagia?

Answer 726

Cricopharyngeal myotomy

Question 727

729 What type of stitch is most frequently used for closure of laryngopharyngectomy?

Answer 727

Running modified Connell stitch, followed by one or two layers of interrupted 3–0 Vicryl to imbricate overlying layers. Flood the mouth to ensure closure is water tight.

Question 728

730 What are the benefits of the artificial larynx for speech after total laryngectomy?

Answer 728

Inexpensive, relatively easy to learn, provides loud voice

Question 729

731 After laryngectomy, what type of speech is being used if a patient injects (swallows) air into the esophagus, which acts as a reservoir for the expelled air used for voicing?

Answer 729

Esophageal speech. This produces a characteristic belching sound. Patients are usually limited to soft volume and short duration of utterance.

Question 730

732 Name the one-way valve placed across the wall between the trachea and esophagus that allows exhaled air to pass through the neopharynx for voicing.

Answer 730

Tracheoesophageal prosthesis

Question 731

733 Describe primary tracheoesophageal puncture (pri mary TEP).

Answer 731

Before closing the pharyngeal defect, a hemostat is passed into the esophagus to the posterior tracheal wall, where a blade is used to create a small fistula. A catheter is placed through this to maintain patency until a prosthesis is fitted.

Question 732

734 Describe the esophageal insufflation test in evaluating candidates for secondary TEP.

Answer 732

A catheter is placed transnasally into the esophagus, air is insufflated, and the patient is asked to count.

Question 733

735 Describe two anatomical relative contraindications to TEP voice rehabilitation

Answer 733

● Microstomia (\< 1 cm) ● Pharyngeal stricture

Question 734

736 Why is a cricopharyngeal myotomy critical to total laryngectomy voice rehabilitation?

Answer 734

Cricopharyngeal muscle spasm diverts air passing through the TEP into the distal esophagus (instead of through the mouth), which prevents acquisition of alaryngeal speech

Question 735

737 What is the most common reason for TEP valve failure?

Answer 735

Candida fungal colonization

Question 736

738 What is the definitive treatment for aspiration through the TEP site in the setting of a properly functioning TEP valve?

Answer 736

A SCM flap or pectoralis major myofascial flap interposition (between the trachealis and esophagus) to reconstruct the party wall

Question 737

739 How should a dislodged TEP temporary catheter be triaged?

Answer 737

Urgently. If not replaced within 24 hours, the fistula is likely to close, and the TEP would require surgical revisi

Question 738

740 When factors imply that a patient has a functional larynx?

Answer 738

● Intelligible voice ● Able to take in adequate calories by mouth with no/ minimal aspiration ● Avoidance of a stoma

Question 739

741 What tumor factors most notably influence voice outcomes after surgery or radiation therapy?

Answer 739

Tumor extent and depth of invasion

Question 740

742 What patient factors affect the functional out come of total laryngectomy?

Answer 740

● Motivation for alaryngeal speech ● Ability to communicate by writing ● Manual dexterity for using voice prostheses ● Family and social support

Question 741

743 What are the functional effects after total laryn gectomy?

Answer 741

● Loss of normal speech (not aphonia) ● Inability to develop positive airway pressure (straining, coughing) ● Loss of nasal airflow (anosmia, air filtration) ● Presence of stoma (water precautions, body image)

Question 742

744 True or False. Aggressive tumor surveillance with imaging and examinations improves the detection of asymptomatic recurrences and second primar ies and therefore improves oncologic outcomes after primary management of laryngeal cancer.

Answer 742

False

Question 743

745 What are the early complications of conservation laryngectomy?

Answer 743

● Tracheotomy tube obstruction ● Hemorrhage ● Aspiration pneumonia ● Subcutaneous emphysema

Question 744

746 What is the long-term incidence of hypothyroid ism in patients treated primarily with radiation for laryngeal cancer?

Answer 744

70%

Question 745

747 What is the appropriate sequence of actions in the event of an airway fire?

Answer 745

Extubation, then removal of supplemental oxygen and instillation of saline into the airway, then reintubation

Question 746

748 What are the main risk factors for developing a pharyngocutaneous fistula after laryngectomy? Comment: Does history of neck radiation need to be included in the risk factors for fistula formation (or at least should we specify in patients who are not undergoing salvage)?

Answer 746

● Postoperative hemoglobin \< 12.5 ● Congestive heart failure ● Extended laryngectomy ● History of head and neck radiation

Question 747

749 What is the best initial treatment for pharyngo cutaneous fistula?

Answer 747

● Debridement ● Wound dressing with antiseptic packing material ● Nothing taken orally (NPO) ● Antibiotics (if infected) ● Consideration of hyperbaric oxygen therapy if initial measures are not successful

Question 748

750 What complications are associated with tracheot omy placement during total laryngectomy?

Answer 748

● Pneumothorax ● Hemorrhage via tracheoinnominate fistula ● Subcutaneous emphysema.

Question 749

751 What medical therapy would be most effective for a patient with persistent gastric inflation when attempting to use a transesophageal prosthesis?

Answer 749

Botulinum toxin injections to the cricopharyngeus muscle

Question 750

752 What are the boundaries that define the naso pharynx? (▶ Fig. 7.8)

Answer 750

● Superior: Sphenoid bone ● Anterior: Choana ● Posterior: Clivus, C1 and C2 vertebrae ● Inferior: Soft palate ● Lateral: Torus tubarius, Rosenmuller fossa

Question 751

753 What skull base foramen defines the lateral roof of the nasopharynx?

Answer 751

Foramen lacerum

Question 752

754 What space lies just posterior to the eustachian tube orifice and levator veli palatine muscle, at the junction of the lateral and posterior nasopharyn geal walls, inferior to the foramen lacerum and carotid canal within the sphenoid bone, medial to the foramen lacerum and spinosum, and superior to the upper border of the superior constrictor muscle?

Answer 752

Fossa of Rosenmuller

Question 753

755 What space will be violated if a nasopharyngeal tumor extends laterally through the buccopha ryngeal fascia? If it extends laterally through the anterior surface of the lateral pterygoid muscle?

Answer 753

● Parapharyngeal space ● Masticator space

Question 754

756 What is the relationship between internal carotid artery and the fossa of Rosenmüller?

Answer 754

Internal carotid artery lies immediately posterolateral to this space.

Question 755

757 What functional structure, located on the poste rior nasopharyngeal wall, is formed by the move ment of the superior constrictor muscle and palatopharyngeus muscle?

Answer 755

Passavant ridge

Question 756

758 What is the blood supply to the nasopharynx?

Answer 756

● Ascending pharyngeal artery (external carotid artery) ● Sphenopalatine artery (internal maxillary artery) ● Vidian artery (internal maxillary artery)

Question 757

759 What is the venous drainage of the nasopharynx?

Answer 757

Pharyngeal plexus → jugular system

Question 758

760 Sensation from the nasopharynx is conveyed by which nerve(s)?

Answer 758

● Glossopharyngeal nerve (CN IX) ● Cranial nerve V2

Question 759

761 What are the three subsites of the nasopharynx?

Answer 759

● Lateral wall ● Posterior wall ● Soft palate

Question 760

762 Where do most nasopharyngeal carcinomas originate?

Answer 760

Fossa of Rosenmüller

Question 761

763 What is the most common site of distant metastases from nasopharyngeal carcinomas?

Answer 761

Bone

Question 762

764 What nodal levels are at highest risk for metastases from a nasopharyngeal carcinoma? (▶ Fig. 7.9)

Answer 762

Retropharyngeal nodes and level II and VA. Bilateral disease is common.

Question 763

765 What percentage of patients with nasopharyngeal carcinoma will develop nodal disease diagnosed either on physical examination or with imaging?

Answer 763

80%

Question 764

766 What are the nodes of Rouviere?

Answer 764

Lateral retropharyngeal lymph nodes

Question 765

767 What are the primary risk factors associated with nasopharyngeal carcinoma?

Answer 765

● EBV ● Genetics (including ethnicity and gender) ● High intake of preserve foods (nitrosamines)

Question 766

768 People of what ethnicity are most commonly affected by nasopharyngeal carcinoma?

Answer 766

Chinese. It is endemic in Southern China and Southeast Asia.

Question 767

769 What food confers an increased risk for nasopha ryngeal carcinoma?

Answer 767

Salted fish. Thought to be related to the volatile nitros amines released in steam while cooking salt-cured foods and early exposure to these foods in childhood

Question 768

770 What genetic factors have been associated with nasopharyngeal carcinoma?

Answer 768

● Family history (especially first-degree relatives) ● Haplotype human leukocyte antigen (HLA) alleles ● Genetic polymorphisms in CYP2A6 (nitrosamine metab olizing gene) ● Male sex 3:1 ratio

Question 769

771 Describe the basic structure of the herpes virus that represents a major risk factor for developing nasopharyngeal carcinoma.

Answer 769

Epstein-Barr virus (EBV): ● Nuclear core early antigens (Ea) ● Double-stranded DNA ● Viral capsid antigen (VCA) ● Lytic membrane proteins (LMP): LMP-1, -2, -3 ● EBV nuclear antigens (EBNA): 1–6 ● EBV encoded ribonucleic acids (EBER)

Question 770

772 What is the primary mode of transmission of EBV infection?

Answer 770

Saliva

Question 771

773 In which nasopharyngeal cell type is EBV infection a risk factor for the development of malignancy?

Answer 771

Pseudostratified columnar respiratory epithelium. It is carried for life by the infected person

Question 772

774 What is the most common nasopharyngeal malignancy?

Answer 772

Nasopharyngeal carcinoma

Question 773

775 How does the WHO classify nasopharyngeal carcinoma?

Answer 773

● Type 1 (I): Squamous cell carcinoma ● Type 2a (II): Keratinizing undifferentiated carcinoma ● Type 2b (III): Nonkeratinizing undifferentiated carcinoma

Question 774

776 In lymphoepitheliomas, does the lymphoid infil trate give prognostic information?

Answer 774

No

Question 775

777 In lymphoepitheliomas, what characterizes a Regaud pattern?

Answer 775

Tumor cells growing in well-defined aggregates admixed with a lymphoid infiltrate

Question 776

778 What is the most common clinical manifestation for nasopharyngeal carcinoma?

Answer 776

Lymphadenopathy (60%)

Question 777

779 In addition to cervical lymphadenopathy, what initial symptoms are common in nasopharyngeal carcinoma?

Answer 777

● Blood tinged/stained saliva/sputum; more common than epistaxis ● Conductive hearing loss, serous otitis media ● Epistaxis ● Nasal obstruction ● Tinnitus ● Cranial nerve palsy

Question 778

780 A patient with nasopharyngeal carcinoma has headache and cranial nerve deficits. What do these symptoms most likely indicate?

Answer 778

Intracranial extension

Question 779

781 What syndrome is defined by tumor invasion of the base of skull with involvement of CN III–VI resulting in facial pain and diplopia?

Answer 779

Petrosphenoidal syndrome

Question 780

782 What notochord remnant presents as a benign cystic nasopharyngeal mass?

Answer 780

Thornwaldt cyst

Question 781

783 A patient has an ulcerative nasopharyngeal mass, bulky unilateral adenopathy, V1/V2 numbness, and ophthalmoplegia. This process has most likely invaded what structure?

Answer 781

Cavernous sinus

Question 782

784 A middle-aged immigrant from the Guangdong province in Southern China presents with a unilateral middle ear effusion. What is the most important diagnostic maneuver?

Answer 782

Nasopharyngoscopy

Question 783

785 A patient with locally advanced nasopharyngeal cancer complains of ipsilateral dry eye. Which nerve is most likely affected?

Answer 783

Vidian nerve

Question 784

786 A patient with locally advanced nasopharyngeal cancer has a unilateral true vocal-fold paralysis, winged scapula, and uvular deviation. What is the name of this syndrome?

Answer 784

Vernet syndrome

Question 785

787 A patient with locally advanced nasopharyngeal cancer has an ipsilateral constricted pupil and ptosis. What structure has been invaded?

Answer 785

Cervical sympathetic trunk

Question 786

788 What blood test predicts survival in EBV-related nasopharyngeal carcinoma?

Answer 786

Polymerase chain reaction (PCR) of EBV DNA

Question 787

789 What serologic test allows for screening and monitoring response to therapy in EBV-related nasopharyngeal carcinoma?

Answer 787

Anti-EBV viral capsid antigen (VCA) and early antigen (EA) immunoglobulin A (IgA)

Question 788

790 What characterizes WHO type 1 nasopharyngeal carcinoma?

Answer 788

Keratinization

Question 789

791 Which of the WHO subtypes for nasopharyngeal carcinoma is nonkeratinizing and undifferentiated?

Answer 789

WHO type 3

Question 790

792 How do WHO type 3 tumors tend to fail treat ment?

Answer 790

Distant metastases

Question 791

793 Where do WHO type 1 tumors tend to fail treatment?

Answer 791

Locoregional recurrence is most common.

Question 792

794 How often does nasopharyngeal carcinoma in volve the skull base at the time of diagnosis?

Answer 792

35%

Question 793

795 A nasopharyngeal malignancy extends into the nasal cavity but not the parapharynx. What is the AJCC T stage?

Answer 793

T1

Question 794

796 A nasopharyngeal malignancy extends into the sphenoid sinus. What is the AJCC T stage?

Answer 794

T3

Question 795

797 A nasopharyngeal malignancy causes a lateral rectus palsy. What is the AJCC T stage?

Answer 795

T4

Question 796

798 A patient with nasopharyngeal carcinoma has a palpable 2-cm supraclavicular fossa lymph node. What is the AJCC N stage?

Answer 796

T3b

Question 797

799 A patient with nasopharyngeal carcinoma has 3- cm bilateral retropharyngeal lymph nodes evident on MRI. What is the AJCC N stage?

Answer 797

N1

Question 798

800 Which is more important prognostically in naso pharyngeal carcinoma: low nodes or bilateral nodes?

Answer 798

Low (supraclavicular fossa) nodes

Question 799

801 How is the supraclavicular fossa defined for N staging nasopharyngeal carcinoma?

Answer 799

A triangle is bound by three points: the superior margin of the medial end of the clavicle, the superior margin of the lateral end of the clavicle, and the point where the neck meets the shoulder.

Question 800

802 A patient with nasopharyngeal carcinoma has a 5- cm ipsilateral level II lymph node. What is the AJCC N stage?

Answer 800

N1

Question 801

803 What is the least common WHO subtype of nasopharyngeal cancer in the Far East?

Answer 801

WHO type 1

Question 802

804 Compared with its incidence in the Far East, is WHO type 1 nasopharyngeal carcinoma more or less common in North America?

Answer 802

More

Question 803

805 What features of the primary tumor in nasopha rygenal carcinoma predict poor outcomes?

Answer 803

Cranial neuropathy, bone erosion, and extensive para pharyngeal space involvement

Question 804

806 Does upper cranial neuropathy give a worse prognosis than lower cranial neuropathy in nasopharyngeal carcinoma?

Answer 804

No

Question 805

807 What is the strongest predictor of regional failure in nasopharyngeal carcinoma?

Answer 805

Nodal stage

Question 806

808 What predicts a worse prognosis in nasopharyn geal cancer: prestyloid or poststyloid parapha ryngeal extension?

Answer 806

Prestyloid

Question 807

809 What is the strongest predictor of overall survival in nasopharyngeal carcinoma?

Answer 807

M stage

Question 808

810 What is the best treatment for stage III–IV nasopharyngeal carcinoma?

Answer 808

Concurrent chemoradiation therapy

Question 809

811 What is the best treatment for stage I nasopha ryngeal carcinoma?

Answer 809

External-beam radiation to the primary and bilateral necks

Question 810

812 What doses are used to treat the nasopharynx in nasopharyngeal carcinoma?

Answer 810

~ 70 Gy

Question 811

813 What is the best surgical treatment for regionally recurrent nasopharyngeal carcinoma?

Answer 811

Modified radical neck dissection

Question 812

814 Local recurrence of nasopharyngeal carcinoma involving the lateral nasopharyngeal wall, with extension across the midline, is best suited for what salvage surgical approach?

Answer 812

Anterolateral, or maxillary swing, approach

Question 813

815 What is the most sensitive imaging test for detecting nasopharyngeal carcinoma recurrence?

Answer 813

PET scan

Question 814

816 What are treatment options for locally recurrent or residual nasopharyngeal carcinoma?

Answer 814

Nasopharyngeal carcinoma is unique in the head and neck in that reirradiation shortly after treatment is often used for residual or recurrent disease. Other options include stereotactic radiation therapy, brachytherapy, photody namic therapy, endoscopic or open resection, chemo therapy, or combined regimens.

Question 815

817 What are common acute side effects of external beam radiation for nasopharyngeal carcinoma?

Answer 815

Mucositis, xerostomia, cutaneous erythema, malaise

Question 816

818 A patient is having seizures 4 years after primary radiation therapy for nasopharyngeal carcinoma. What is the likely cause?

Answer 816

Temporal lobe necrosis

Question 817

819 Fatigue and amenorrhea 6 years after radiation therapy are likely due to what late complication?

Answer 817

Hypopituitarism

Question 818

820 A patient develops hearing loss with normal immittance after treatment for nasopharyngeal carcinoma. What is the most common audiologic pattern?

Answer 818

Downsloping sensorineural hearing loss

Question 819

821 A patient develops hypernasal speech after an anterior approach surgical salvage of locally recurrent nasopharyngeal carcinoma. What is the most likely cause?

Answer 819

Palatal fistula

Question 820

822 What feature of tumor recurrence contraindicates nasopharyngectomy?

Answer 820

Cranial neuropathy

Question 821

823 The sphenopalatine artery enters the nasal cavity through the sphenopalatine foramen, which is located where?

Answer 821

Lateral nasal wall just posterior to the end of the middle turbinate

Question 822

824 Which nerve originates in the pterygopalatine fossa and innervates the hard palate?

Answer 822

Greater palatine

Question 823

825 The name of what line from the medial canthus to the angle of the mandible carries significant prognostic value in sinonasal malignancies? (▶ Fig. 7.10)

Answer 823

Öhngren line. It is largely of historical significance when plain X-rays were used to evaluate sinonasal malignancy.

Question 824

826 What are the anatomical boundaries of the pterygopalatine fossa?

Answer 824

The pterygopalatine fossa is a pyramidal space beneath the orbit that is bounded anteriorly by the posterior wall of the maxillary sinus and posteriorly by the pterygoid plates.

Question 825

827 Which nerves and what important vessel run through the pterygopalatine fossa?

Answer 825

Sphenopalatine, lesser and greater palatine nerves, Vidian; internal maxillary artery

Question 826

828 What is the most common site of sinonasal malignancy?

Answer 826

Maxillary sinus

Question 827

829 Tumors in which paranasal sinus are associated with the highest rate of neurological sequelae?

Answer 827

Sphenoid sinus

Question 828

830 What is the most common lymph node basin involved by metastatic sinonasal malignancy?

Answer 828

Upper jugulodigastric

Question 829

831 Which environmental risk factor is associated with adenocarcinoma of the ethmoid sinus?

Answer 829

Wood dust (wood workers)

Question 830

832 Nickel exposure greatly increases which type of sinonasal cancer?

Answer 830

Squamous cell carcinoma

Question 831

833 Inverted papilloma is associated with malignant transformation to what type of cancer?

Answer 831

Squamous cell carcinoma

Question 832

834 What is the most common sinonasal malignancy?

Answer 832

Squamous cell carcinoma

Question 833

835 Which histologic type of sinonasal malignancy is associated with exposure to wood dust?

Answer 833

Intestinal-type adenocarcinoma

Question 834

836 What is the second most common sinonasal malignancy?

Answer 834

Adenoid cystic carcinoma

Question 835

837 What histologic type of sinonasal adenoid cystic carcinoma is the most common and has the best prognosis?

Answer 835

Cribriform

Question 836

838 What rare sinonasal tumor is thought to arise from the mucoserous glands of the sinonasal cavity and stains positive with mucicarmine?

Answer 836

Mucoepidermoid carcinoma

Question 837

839 What is the most common location of sinonasal mucosal melanoma?

Answer 837

Lateral nasal wall including turbinates

Question 838

840 Esthesioneuroblastoma arises from what location?

Answer 838

Olfactory mucosa along the cribriform plate

Question 839

841 Which sinonasal tumor has the following histo pathologic features: S100-positive sustentacular cells, Homer-Wright rosettes, and Flexner-Winter steiner rosettes?

Answer 839

Esthesioneuroblastoma

Question 840

842 What sinonasal tumors can be considered small, round blue cell tumors?

Answer 840

Sinonasal undifferentiated carcinoma, small cell carcinoma, esthesioneuroblastoma, poorly differentiated and nonker atinizing squamous cell carcinoma, neuroendocrine carci noma, plasmacytoma, lymphoma, mucosal melanoma, Ewing sarcoma, rhabdomyosarcoma, synovial sarcoma, desmoplastic small round blue cell tumor

Question 841

843 What are common histopathologic features of sinonasal small cell carcinoma?

Answer 841

Small cells with scant cytoplasm and round hyperchromatic nuclei with absent or poorly visualized nucleoli. Cells grow in clusters and commonly display extensive necrosis and hemorrhage.

Question 842

844 What is the most common pediatric malignant sinonasal tumor?

Answer 842

Rhabdomyosarcoma

Question 843

845 Alveolar type rhabdomyosarcoma is associated with what chromosomal translocation?

Answer 843

t(2;13)(q35;q14), PAX3-FKHR gene fusion

Question 844

846 Hemangiopericytomas arise from what cell types?

Answer 844

Extracapillary pericytes (of Zimmerman)

Question 845

847 What are typical clinical features of sinonasal hemangiopericytomas?

Answer 845

Soft, slow-growing tumors typically arising in the nasal cavity that occasionally metastasize. The most common presentation is nasal obstruction and epistaxis

Question 846

848 In what anatomical site are sinonasal angiosarco mas most frequently found?

Answer 846

Nasal cavity

Question 847

849 Which type of tumor is the most common to metastasize to the nose and paranasal sinuses?

Answer 847

Renal cell carcinoma

Question 848

850 What is the most common sinonasal lymphoma in Western populations?

Answer 848

Diffuse large B-cell lymphoma

Question 849

851 What is the most common sinonasal lymphoma in Asian populations?

Answer 849

Natural kill (NK)/T-cell lymphoma

Question 850

852 What is the name of the syndrome in a patient who has epistaxis, diplopia, decreased visual acuity, and numbness above the eye?

Answer 850

Orbital apex syndrome

Question 851

853 What is the name of the constellation of symp toms that includes ophthalmoplegia, periorbital numbness, ptosis, proptosis, and fixed dilated pupil?

Answer 851

Superior orbital fissure syndrome

Question 852

854 A patient has unilateral nasal obstruction, eye proptosis, and decreased sensation of his cheek. Which cranial nerve is affected?

Answer 852

V2 (infraorbital nerve)

Question 853

855 Which imaging modalities are most useful in sinonasal malignancies?

Answer 853

MRI and CT scan

Question 854

856 How is CT superior to MRI in evaluation of paranasal sinus masses?

Answer 854

Better bone detail. Better evaluation of skull base and lamina papyracea erosion

Question 855

857 How is MRI superior to CT in the evaluation of paranasal sinus masses?

Answer 855

● Better soft tissue detail ● Differentiates tumor from inspissated secretions ● Better evaluation of dural invasion ● Differentiates brain invasion from brain edema ● Better assessment of perineural invasion

Question 856

858 TNM staging for sinonasal cancer includes what three primary anatomic sites?

Answer 856

Maxillary sinus, ethmoid sinus, and nasal cavity

Question 857

859 A squamous cell carcinoma localized to which two sinonasal sites is automatically stage T4?

Answer 857

Frontal and sphenoid sinuses

Question 858

860 What is unique about the AJCC staging of head and neck mucosal melanoma?

Answer 858

All lesions are considered T3 or T4, reflecting the aggressive behavior.

Question 859

861 What is the Kadish staging system for esthesio neuroblastoma?

Answer 859

(▶ Table 7.10)

Question 860

862 The Hyams grading system of esthesioneuroblas toma has proven to provide significant prognostic information and includes what histologic features?

Answer 860

● Lobular architecture ● Neurofibrillary background ● Rosettes ● Nuclear pleomorphism ● Mitosis ● Necrosis ● Calcification

Question 861

863 Which sinonasal sarcoma has the best prognosis?

Answer 861

Chondrosarcoma

Question 862

864 Which sinonasal malignancy has the worst prog nosis?

Answer 862

Mucosal melanoma

Question 863

865 Which sinonasal malignancy has the best prog nosis?

Answer 863

Minor salivary gland tumors

Question 864

866 Invasion of which structure by a sinonasal malig nancy has the worst prognosis?

Answer 864

Brain; 5-year survival is 26% in the largest series.

Question 865

867 Which pathologic finding in sinonasal malignancy has the worst prognosis?

Answer 865

Positive margins are associated with a 24% 5-year survival.

Question 866

868 What is the treatment of choice for advanced esthesioneuroblastoma?

Answer 866

Multimodality treatment including surgical resection and radiation therapy with or without chemotherapy

Question 867

869 What is the treatment of choice for most sinonasal undifferentiated carcinomas?

Answer 867

Multimodality treatment including surgical resection and radiation therapy with or without chemotherapy

Question 868

870 What is the treatment of choice for sinonasal diffuse large B-cell lymphoma?

Answer 868

Chemoradiation therapy (R-CHOP and IFRT)

Question 869

871 What long-term complication can occur after resection of a frontal sinus tumor with osteoplastic flap and frontal sinus obliteration?

Answer 869

Frontal sinus mucocele

Question 870

872 What is the surgical procedure best used to treat a sinonasal malignancy that has invaded through the cribriform plate?

Answer 870

Anterior craniofacial resection

Question 871

873 What is the surgical procedure best used to treat a sinonasal tumor limited to the medial wall of the maxillary sinus?

Answer 871

Inferior medial maxillectomy

Question 872

874 What is a common postoperative complication of medial maxillectomy?

Answer 872

Epiphora and/or recurrent dacryocystitis from division of the nasolacrimal duct

Question 873

875 What locoregional flaps are commonly used to close large anterior skull-base defects after ante rior craniofacial resection?

Answer 873

Vascularized pericranium and nasoseptal mucosa flaps

Question 874

876 What free tissue flap is best for reconstruction of large anterior skull base defects after craniofacial resection?

Answer 874

Rectus abdominis

Question 875

877 What free tissue flaps are best used for recon struction of total maxillectomy defects?

Answer 875

Osteocutaneous free flaps for bone stock to reconstruct the orbital floor, orbital rim, and/or alveolar ridge

Question 876

878 What are the two most common head and neck locations for osteosarcoma?

Answer 876

Mandible and maxilla

Question 877

879 Hemangiopericytomas arise most commonly from what head and neck site?

Answer 877

The sinonasal cavity

Question 878

880 What is the most common head and neck site of origin of leiomyosarcoma?

Answer 878

The oral cavity

Question 879

881 What is the most common head and neck site for chondrosarcoma?

Answer 879

The sinonasal cavity

Question 880

882 What hereditary syndrome is caused by a mutation in the p53 tumor suppressor gene resulting in a greatly increased risk of sarcomas as well as other cancers?

Answer 880

Li-Fraumeni syndrome

Question 881

883 What condition is associated with half of all neurogenic sarcomas (malignant peripheral nerve sheath tumor)?

Answer 881

Neurofibromatosis type 1

Question 882

884 What percentage of patients with head and neck fibrosarcomas report a history of prior radiation exposure?

Answer 882

10%

Question 883

885 What are the four histologic subtypes of rhabdo myosarcoma?

Answer 883

● Embryonal ● Alveolar ● Anaplastic (previously pleomorphic) ● Mixed

Question 884

886 What histologic subtypes of rhabdomyosarcoma have the worst prognosis?

Answer 884

Alveolar and anaplastic

Question 885

887 What is the most common head and neck sarcoma in children?

Answer 885

Rhabdomyosarcoma

Question 886

888 Head and neck rhabdomyosarcoma can be divided into three sites that have staging and prognostic value; what are they?

Answer 886

● Orbit ● Nonparameningeal ● Parameningeal

Question 887

889 What is the primary treatment for rhabdomyo sarcoma?

Answer 887

Chemotherapy is the mainstay of treatment. It is typically used with radiation as an induction agent and then concurrently. Typically, vincristine is the main agent used with two other agents. These regimens have been established by the Intergroup Rhabdomyosarcoma Studies (IRS) now renamed the Children’s Oncology Group (COG)

Question 888

890 What soft tissue sarcoma has the highest response rate to adjuvant radiation therapy?

Answer 888

Liposarcoma

Question 889

891 Synovial sarcoma is thought to be most likely derived from what cell type?

Answer 889

Pluripotent mesenchymal cells

Question 890

892 What are the most common head and neck sites of origin for synovial sarcoma?

Answer 890

Hypopharynx and retropharynx

Question 891

893 What recent chromosomal translocation has been identified in patients with epithelioid heman gioendothelioma?

Answer 891

t(1;3)(p36;q25)

Question 892

894 What prognostic factor is included in the AJCC staging system for sarcomas in addition to the traditional TNM staging factors?

Answer 892

Histologic grade (G1–G3)

Question 893

895 What is the T-staging system of soft tissue sarcomas according to the AJCC?

Answer 893

● Tx: Primary tumor cannot be assessed ● T0: No evidence of primary tumor ● T1: Tumor \< 5 cm in greatest dimension (T1a, superficial; T1b, deep); ● T2: tumor \> 5 cm in greatest dimension (T2a, superficial; T2b, deep)

Question 894

896 What prognostic factor at the time of surgical excision of head and neck osteosarcoma plays the most significant role in local control and survival rates?

Answer 894

Surgical margin status

Question 895

897 What is the primary treatment modality for osteosarcoma of the head or neck?

Answer 895

Surgery

Question 896

898 What is the treatment modality of choice for dermatofibrosarcoma protuberans?

Answer 896

Surgical resection

Question 897

899 What is the classic initial symptom of angiosarco ma?

Answer 897

Unexplained bruising of the forehead or scalp, which may progress in a rapid fashion in an elderly patient.

Question 898

900 What features are associated with most strongly associated with prognosis in angiosarcoma?

Answer 898

Size, grade, and depth. Tumors \< 5 cm and superficial tumors have significantly better survival than tumors \> 5 cm or deeply invasive tumors. High-grade tumors have also been associated with worse prognosis.

Question 899

901 What percentage of angiosarcomas will occur in the head and neck region?

Answer 899

50%

Question 900

902 What is the standard treatment for scalp angio sarcoma?

Answer 900

Wide local excision with postoperative radiation therapy

Question 901

903 What areas of the head and neck are most likely to be involved with dermatofibrosarcoma protuber ans?

Answer 901

Scalp and supraclavicular fossa

Question 902

904 What is the long-term prognosis for patients with dermatofibrosarcoma protuberans?

Answer 902

If it is adequately managed, dermatofibrosarcoma protu berans commonly recurs locally, but it seldom metastasizes. Long-term survival is therefore excellent.

Question 903

905 What modifications should be considered to Mohs surgery in the case of dermatofibrosarcoma, and why?

Answer 903

Because of the infiltrating growth pattern exhibited by dermatofibrosarcoma protuberans, some have advocated a "modified Mohs" procedure with paraffin sections as opposed to frozen sections, alternatively taking an extra border of tissue from around the tumor.

Question 904

906 What options are available for treatment of unresectable or recurrent dermatofibrosarcoma protuberans or in patients who are not surgical candidates?

Answer 904

Imatinib, a tyrosine kinase inhibitor, has been shown to induce partial or complete remission in dermatofibrosar coma protuberans.

Question 905

907 What are the relative recurrence rates for derma tofibrosarcoma protuberans treated with Mohs surgery and wide local excision respectively?

Answer 905

1.6% versus 20% (favoring Mohs) in a large meta-analysis

Question 906

908 Describe the common history and findings in patients with atypical fibroxanthoma.

Answer 906

A rapidly enlarging, red, ulcerated lesion within the field of prior radiation treatment.

Question 907

909 What is the treatment of choice for atypical fibroxanthoma?

Answer 907

Simple excision with clear margins, often by Mohs surgery. Nodal metastasis is rare

Question 908

910 How commonly does malignant fibrous histiocy toma recur?

Answer 908

Recurrence is common in malignant fibrous histiocytoma and even more so in patients previously exposed to radiation. Local metastasis is uncommon, whereas distant metastasis is more frequent.

Question 909

911 Pleomorphic undifferentiated sarcoma is formally known as what?

Answer 909

Malignant fibrous histiocytoma

Question 910

912 To what site does pleomorphic undifferentiated sarcoma most often metastasize?

Answer 910

Lungs

Question 911

913 What are common histologic features of pleo morphic undifferentiated sarcoma (malignant fi brous histiocytoma)?

Answer 911

A storiform pattern of pleomorphic and bizarre cells with foamy cytoplasm, marked atypia, and numerous mitotic figures in a collagenous background

Question 912

914 What are the risk factors for Kaposi sarcoma?

Answer 912

All Kaposi sarcomas are caused by HHV-8, but the groups most at risk for the disease are patients with AIDS and those who are on immunosuppression medications. Patients with AIDS are 20,000 times more likely to have Kaposi sarcoma than the general population and 300 times more likely than renal transplantation patients.

Question 913

915 Where are the most common locations for extranodal lymphoma in the head and neck?

Answer 913

Waldeyer ring. Nasopharynx \> tonsil \> tongue base

Question 914

916 What structures in the head and neck can be involved with lymphoma?

Answer 914

Essentially any; paranasal sinuses, salivary glands, thyroid, lymph nodes, Waldeyer ring, larynx, and the orbit are all possible sites.

Question 915

917 In addition to the lymph nodes, what anatomical sites should be considered for involvement in a patient with extranodal tonsillar non-Hodgkin lymphoma?

Answer 915

About 20% of patients with tonsillar non-Hodgkin lympho ma have gastrointestinal tract involvement.

Question 916

918 What percentage of patients with extranodal lymphoma will have associated nodal disease?

Answer 916

50%

Question 917

919 Between Hodgkin lymphoma and non-Hodgkin lymphoma, which is more likely to involve extra nodal disease at diagnosis?

Answer 917

Non-Hodgkin lymphoma (30% extranodal presentation) more than Hodgkin lymphoma (5%)

Question 918

920 What is the primary risk factor for parotid mucosa associated lymphoid tissue (MALT) lymphoma?

Answer 918

Sjögren syndrome

Question 919

921 What is the primary risk factor for thyroid MALT lymphoma?

Answer 919

Hashimoto thyroiditis

Question 920

922 What is the second most common malignancy in the head and neck?

Answer 920

Lymphoma; it makes up 15 to 20% of all head and neck cancers.

Question 921

923 What are the indolent non-Hodgkin lymphomas?

Answer 921

Follicular, B-cell chronic lymphocytic lymphoma, marginal B-cell, lymphoplasmacytic (Waldenstrom macroglobuline mia)

Question 922

924 What are the aggressive non-Hodgkin lymphomas?

Answer 922

Diffuse large B-cell, peripheral T-cell, mantle cell

Question 923

925 What are the highly aggressive non-Hodgkin lymphomas?

Answer 923

Burkitt, precursor T- and B-cell lymphoblastic

Question 924

926 Describe the endemic form of Burkitt lymphoma.

Answer 924

A form of non-Hodgkin lymphoma that arises from EBV genomic integration and t(8;14) translocation that con stitutively activates c-myc, causing mandible tumors among children of central Africa.

Question 925

927 What are common markers for B-cell lymphoma?

Answer 925

CD20, CD22, and CD79a are strongly positive in most B-cell lymphomas

Question 926

928 What is the typical histopathology of Hodgkin disease?

Answer 926

Reed-Sternberg cells, which contain two large nuclear lobes with pale chromatin and distinct eosinophilic nucleoli

Question 927

929 Describe tumor lysis syndrome.

Answer 927

The development of hypocalcemia, hyperkalemia, hyper uricemia, hyperphosphatemia, and acute renal failure in the days after initiation of chemotherapy for aggressive lymphoma. Death from cardiac arrhythmias can result.

Question 928

930 What are B-symptoms as they pertain to lympho ma?

Answer 928

Fever \> 38°C, \> 10% weight loss in 6 months, night sweats

Question 929

931 Are B-symptoms more common with Hodgkin lymphoma or non-Hodgkin lymphoma?

Answer 929

Hodgkin lymphoma

Question 930

932 How common are B-symptoms in patients with extranodal non-Hodgkin lymphoma?

Answer 930

Approximately 20% of patients with extranodal non Hodgkin lymphoma have B symptoms

Question 931

933 What are the findings for lymphoma on T1- and T2-weighted MRI with and without gadolinium enhancement?

Answer 931

T1-low signal intensity and T2-low to high signal intensity. Gadolinium uptake is variable but usually demonstrates low enhancement.

Question 932

934 How is FNA limited in diagnosing lymphoma?

Answer 932

FNA results yield cytology, which does not provide infor mation on nodal architecture (follicular vs. diffuse).

Question 933

935 Describe the Ann Arbor staging system for lymphoma.

Answer 933

● Stage I: single lymph node region or single extralym phatic organ ● Stage II: Two or more lymph node regions or extra lymphatic organs on one side of the diaphragm ● Stage III: Involvement on both sides of the diaphragm ● Stage IV: Diffuse or disseminated involvement of 1 or more extralymphatic organs with or without node involvement

Question 934

936 What is the mechanism of action of rituximab?

Answer 934

A monoclonal antibody against CD20, which is a B-cell marker

Question 935

937 What agents are included in CHOP therapy?

Answer 935

● Cyclophosphamide (Cytoxan) ● Hydroxydaunorubicin (doxorubicin) ● Oncovin (vincristine) ● Prednisone

Question 936

938 What is the primary treatment modality for localized (stage I or II) low-grade lymphoma?

Answer 936

Radiation therapy, to which chemotherapy is often added in more advanced disease.

Question 937

939 What is the primary role of surgery for head and neck non-Hodgkin lymphoma?

Answer 937

Surgery is useful for establishing diagnosis. Further treat ment is better served with radiation and chemotherapy.