H&N principles of staging evaluation and prognosis Flashcards
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?
Tumor, node, metastasis (TNM) staging system
Using the TNM staging system, how can you
differentiate a clinical stage from a pathologic stage?
● 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).
Which subsites share the following criteria (in
addition to subsite specific criteria) for T staging:
● T1: < 2 cm
● T2: > 2 cm, < 4 cmT3: > 4
● Lips and oral cavity
● 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)
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 management strategies. What does “very advanced local disease” generally represent?
Very advanced disease correlates with extension into
surrounding critical structures which are largely viewed as
unresectable or incurable.
What two head and neck subsites have a unique
nodal staging system compared with the majority
of subsites?
● Nasopharynx
● Thyroid
Tumor invasion of what subsites are considered by
some as unresectable?
● Nasopharynx ● Prevertebral fascia ● Base of skull ● Intracranial extension ● Mediastinum ● Subdermal lymphatics ● Carotid artery encasement (generally > 270 degrees)
Describe how the American Joint Committee on
Cancer reports the presence or absence of residual
tumor (R) following treatment.
● RX: Residual tumor cannot be assessed
● R0: No residual tumor
● R1: Microscopic residual tumor
● R2: Macroscopic residual tumor
How does the AJCC recommend reporting tumor
grade?
● GX: Grade cannot be assessed ● G1: Well differentiated ● G2: Moderately differentiated ● G3: Poorly differentiated ● G4: Undifferentiated
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?
Pain, cranial neuropathy, bleeding, unintentional weight
loss, lymphadenopathy, malaise, anorexia
What risk factors should be elicited when taking a
history on a patient with potential head and neck
cancer?
● 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 history of head and neck cancer
● Family history of cancer
● Poor dentition, chronic inflammation, or chronic irritation
● Immunosuppression
● Use of betel (quid or panna) (Asia)
* Major risk factors in developed countries
What risk factors are associated with advanced
head and neck cancer at presentation?
● Low income
● Black race
● Poorly differentiated tumors
● Patient neglect
Define the Eastern Cooperative Oncology Group
(ECOG) performance status system.
● 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
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?
Posterior nasal cavity, nasopharynx, fossa of Rosenmuller
and eustachian tube orifice
During fiberoptic or mirror laryngoscopy, what
maneuvers are critical for a complete oncologic
head and neck examination?
● 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
You perform an otoscopic examination on a
patient complaining of otalgia but note no obvious source of pain. Which nerve(s) might be impli-
cated in referred otalgia?
CN V3, IX (via Jacobson nerve), X (via Arnold nerve), and VII
(via the Ramsay Hunt branch of VII), as well as branches
from C2 and C3 through the great auricular nerve
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?
Fixation of the tumor
Note: fixation of nodal metastases should also be noted.
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?
Leukoplakia
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?
Erythroplakia
What common initial screening test evaluates for
pulmonary disease (metastases or primary lung
cancer)?
Chest radiograph. PET/CT is also often ordered now as the
initial screening test for distant metastases.
Which imaging modality is used most often in the
initial workup of head and neck cancer patients?
Contrast-enhanced CT
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?
With contrast (as patient’s allergies and renal status
permits). In the initial workup of differentiated thyroid
carcinoma, avoidance of iodinated contrast should be
considered.
What are frequently used as radiographic criteria
for a nodal malignancy on CT scan?
● Size > 1 cm
● Evidence of central necrosis (~100% specificity)
● Spherical shape (suggestive)
● Nodal grouping in the predicted drainage pathway, with
nodes > 1 cm
What is a key disadvantage of CT scans when evaluating an oral cavity or oropharyngeal neoplasm in a patient with tooth fillings?
Dental artifact often obscures anatomy/pathology.
In what situations is evaluation with MRI most
useful during the workup for head and neck
cancer?
● 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
When is a PET/CT scan indicated during the
treatment of a patient with head and neck cancer?
● 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
True or False. All head and neck tumors are PET
avid because of their high metabolic activity.
False. Several head and neck tumors have either variable/ inconsistent or no FDG-avidity. These include ● Well-differentiated thyroid cancer ● Medullary thyroid cancer ● Indolent lymphomas ● Neuroendocrine tumors ● Teratomas ● Soft tissue sarcomas
Why is it difficult to use a PET/CT scan to
determine the extent of a skull base tumor?
Brain metabolism is high, which can obscure skull-base
tumors, or tumors with intracranial invasion.
What might result in a false-positive result on a
PET/CT scan?
● Infection ● Normal physiologic activity ● Inflammation (e.g., after radiation, surgical resection or biopsy, aspiration) ● Osteoradnionecrosis ● Granulomatous disease ● Patient movement
What is one of the major limitations of PET/CT
scanning, which can result in a false-negative
scan?
It is unreliable for lesions < 1 cm in diameter (some scanners
can reportedly detect suspicious lymph nodes as small as
5 mm).
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?
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.
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?
Panorex
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?
FNA biopsy. CT-guided biopsy can also be considered.
When should an excisional lymph node biopsy be
considered?
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.
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?
Imaging
What is the most common pathologic type of
cancer in the head and neck (excluding salivary
and thyroid tumors)?
Squamous cell carcinoma (> 90%)
Which immunohistochemical marker is most
commonly associated with neural/cartilaginous tumors, melanoma, and Langerhans cell histiocy-
tosis?
S-100
Which immunohistochemical marker is associated
with carcinomas and papillomas?
Cytokeratin
Which immunohistochemical marker(s) is/are as-
sociated with melanoma?
● S-100
● HMB-45
● Melanoma-associated antigen recognized by T cells
(MART-1) (diagnostic)
Which immunohistochemical marker is associated
with neuroendocrine tumors (e.g., Merkel cell carcinoma, paraganglioma)?
● Neuron-specific enolase (NSE)
● Chromogranin
● Synaptophysin
Which immunohistochemical marker is most
commonly associated with lymphoma?
● Leukocyte common antigen (LCA/CD45)
● CD-20 → B-cell specificity
● CD-3 → T-cell specificity
Which tumors stain positive for vimentin on
immunohistochemistry? For desmin?
● Vimentin → sarcomas, lipomas, myomas
● Desmin → sarcomas, myomas
What subtypes of squamous cell carcinoma of the
head and neck have distinct clinical behaviors?
● Basaloid
● Verrucous (< 5%)
● Spindle cell
● Adenosquamous
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?
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.
Describe the histopathology for spindle cell
carcinoma.
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.
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?
● 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.
What is the management strategy of choice for
spindle cell carcinomas?
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.
How can adenosquamous carcinoma be distinguished from mucoepidermoid carcinoma?
Mucoepidermoid carcinoma does not include a mucosal
component. Adenosquamous carcinoma has a predominant mucosal squamous cell component and a deeper adenocarcinoma component.
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?
● Verrucous carcinoma
● Focal areas of high-grade squamous cell carcinoma
What is the preferred management for localized
verrucous carcinoma?
Complete surgical resection. Surgery was superior to
primary radiation in 5-year survival (89 vs. 58%).
What are the most common sites of metastasis for
head and neck squamous cell carcinoma?
● Lungs (66%)
● Bone (22%)
● Liver (10%)
● Less often skin, mediastinum, and bone marrow
Traditionally, what single prognostic factor has
been shown to decrease overall survival by as
much as 50%?
Regional nodal disease (N +)
When considering nodal disease, what factors have been considered negative prognostic features?
● 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
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?
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.
What tumor biomarkers can be used to help
determine prognosis in head and neck cancer?
● EGFR amplification and overexpression ● HPV status ● Loss of heterozygosity (suggests a loss of tumor suppressor gene function) ● Aneuploidy
When considering head and neck cancer as a
whole, what are the most important contributors
to overall cancer specific mortality?
● Locoregional recurrence (50 to 60%)
● Distant metastases (20 to 30%)
● Second primary disease (10 to 20%)
What comorbidities most commonly impact the
choice of therapeutic intervention in head and
neck cancer patients (therapeutic comorbidity)?
● 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)
What comorbidities have been found to negatively
impact prognosis in head and neck cancer
(prognostic comorbidity)?
● Recent myocardial infarction or ventricular arrhythmia
● Severe hypertension
● Severe hepatic disease
● Recent severe stroke
