3. Malignant Epithelial Lesions Flashcards
1
Q
What are the Risk Factors for OSSC?
A
- 80% associated with tobacco, with or without alcohol
- 20-25% show no identifiable RFs, increasing incidence in:
- Young Adults , especially females on Lateral Tongue
- Older Women on Gingiva
2
Q
What is the Clinical Differential Diagnosis for Oral SCC? (6)
A
-
Non-Specific Ulcer:
- Traumatic Granuloma
-
Specific Infections:
- TB
- Deep Fungal Infection
- Syphilis
-
Immune-Mediated Conditions:
- Wegener’s Granulomatosis
- Chron’s Ds
3
Q
What are the best indicators of prognosis, and what guides tx, in Oral SCC?
A
Staging
- Tumor Size
- Extent of Metastatic Spread
The TNM System, except for nodal involvement
4
Q
What is the most important prognostic factor in Oropharyngeal CA?
A
HPV status, rather than stage
5
Q
Why do HPV+ tumors respond better to chemo?
A
Lack p53 mutations and field cancerization
- 60% reduction in risk of death
- 30% greater 5 yr survival than HPV - tumors
6
Q
What gives the best locoregional control and disease-free survival for advanced stages: 3, 4a, 4b-no distant mets OSCC?
A
Post-operative concurrent chemoradiation therapy
7
Q
What is the tx for OSCC with Distant Mets?
A
Single/multi-agent Chemotx
Not going to radiate it becuase it is throughout the entire body!
8
Q
What drugs are using in OSCC Chemotherapy?
A
- Cisplatin or Carboplatin
- 5-fluorouracil
- Taxanes (paclitaxel, docetaxel)
9
Q
What OSCC Radiation, targets the tumor site and mimimizes damage to surrounding tissue?
A
Intesity-Modulated Radiation Therapy (IMRT)
10
Q
What OSCC Radiation involves the placement of tiny radioactive seeds, used for small intraoral tumors or with IMRT to increase dosage?
A
Brachytherapy
11
Q
What is the Clinical appearance of OSCC?
A
- Irregular shape, mixture of red and white
- Ulcerated center with elevated rolled border, that is much firmer (indurated) than surrounding tissues
- Early lesions are Aysmptomatic (don’t hurt)
- Pain is a late feature
12
Q
What occurs with bone involvement in OSCC?
A
- “Moth-Eaten” Ragged RL
- Osteomyelitis
- Pathologic Fracture
- Bone Loss
- Faster than perio bone loss
13
Q
How does SCC of the Lip develop?
A
- Sun induced, not tobacco induced
- In the setting of Actinic Cheilitis; changes in months
14
Q
What is the clinical appearance of SCC of the Lip?
A
- 90% Lower Lip
- Crusted, non-tender, indurated ulceration
- < 1cm when discovered
- Slow-growing, well-differentiated lesion = better prognosis
15
Q
What is the most common site of involvement for OSCC (>50%)?
A
Lateroventral Tongue
(mostly posterior)
16
Q
In what population is SCC of the Tongue typically seen in?
A
-
Younger people (< 40 yrs old)
- Almost always at this site
- Majority have a history of tobacco and alcohol abuse
17
Q
What OSCC is most likely to develop from preexisting white/red lesion?
A
SCC of the FOM
18
Q
What is SCC of the FOM often associated with?
A
2nd Primary Malignancy
Ask the pt if they have a history of oral cancer
19
Q
What is the incidence for SCC of the FOM?
A
- Almost equals Lateral Tongue as a common site for OSCC (~35%)
- Majority have a history of of tobacco and alcohol abuse
20
Q
In what population is the prevelance of Oral Cancer the highest in?
A
Adult Disease
- White Men > 65 yrs
- Middle Aged Black Men
21
Q
In what population is SCC of the Gingiva/Alveolar Mucosa most prevelant in?
A
- Women (2:1)
- Those w/o identifiable RFs
22
Q
What is the clinical appearance of SCC of the Gingiva/Alveolar Mucosa?
A
- Epithelium will have a speckled (red and white), pebbly, granular surface
23
Q
What can SCC of the Gingiva/Alveolar Mucosa mimic?
A
Benign Reactive Lesions of Gums
-
Pyogenic Granulomas
- Can appear big and red, ~ inflammation
-
Perio Ds
- Smooth surfaced, and pink
- Bone loss will occur faster than in PD
- Biopsy if PD doesn’t respond to tx after a month
24
Q
Where do most SCC of the Palate arise?
A
Lateral Soft Palate - Oropharyngeal
Hard to tell if it arised in the max sinus and invaded down
25
Where do most Oropharyngeal Carcinomas arise from?
70% from **Tonsillar Region**
26
What are the Symptoms associated with Oropharyngeal Carcinoma (SCC of Palate)?
* **Persistant Sore Throat**
* Dysphagia (difficulty swallowing)
* Odynophagia (pain on swallowing)
* **Dull/Sharp Pain Referred to Ear**
## Footnote
*Pt may think they have a toothache so ask about these symptoms*
27
In what population does SCC of the Buccal Mucosa occur?
* Very common in **India** due to **betel quid** use
* Not very common site for OSCC in the western world
28
What can SCC of the Buccal Mucosa be confused for?
* **Aphtous Ulcer**, but it will be:
* Firm
* Persistant \> 2 weeks
29
What is the Histology of OSCC? (3)
* **Invasive cords/nests** of malignant squamous epithelial cells **arising from**, but not connected to, **dysplastic surface epithelium**
* Varying degrees of **Keratin Production** (keratin pearls) and **Dyskeratosis**
* **Desmoplasia** = tumor induced fibrosis
* Why the lesions feel firm
30
What Histology do the Tumor Cells of OSCC show? (3)
* Increased nuclear:cytoplasmic
* Cellular and nuclear pleomorphism
* Mitotic activity
31
What determins the stage in OSCC?
**TNM System**
* **T** = Tumor Size
* **N** = Nodal Involvement
* **M** = Metastasis (distant spread)
32
What is the Prognosis for OSCC? (3)
**Poor**
* **~2/3 of pts present in Stage III or IV**
* LN spread = Stage III (minimum)
* **~3-5% improved 5 yr survival** over the last decade, but still **1 of the worst prognoses of any major cancer**
* Even with tx: significant disfiguarment, disability, pain
33
What is the Follow-Up Needed for pts with OSCC? (4)
* Necessary for **Life of the Patient**
* **Field Effect** = Must **check Entire Mouth**
* Most **recurrences** will occur within the **first 2 years**
* May require biopsy of multiple areas
34
What population is Verrucous Carcinoma common in?
* **Elderly Males**
* With Historical **Smokeless Tobacco (Snuff)** Association
35
What may give rise to Verrucous Carcinoma of OSCC?
Proliferative Verrucous Leukoplakia (PVL)
36
In the **Grading** of OSCC, what microscopic features correlate with **increased risk for nodal metastasis**?
**Tumor Thickness** or **Depth of Invasion**
37
In the **Grading** of OSCC, what feature is associated with a **worse prognosis**?
**Extracapsular Spread** in a Lymph Node
38
What is the Location, Clinical Appearance, and Growth Pattern of Verrucous Carcinoma? How is this different from OSCC?
* **Diffuse** white or red and white **plaque**
* *****OSCC has an ulcerated center with an indurated rolled border*
* **Low-Risk Sites:** Hard Palate, Alveolar and Buccal Mucosa
* *OSCC is in High Risk Sites*
* **Grows Laterally**, invading with a **"pushing margin"**, but doesn't infiltrate or show mets
* *OSCC infiltrates and can mets*
39
How does Verrucous Carcinoma appear microscopically? How is this different from OSCC?
Appears very **bland/benign**, with **no features of dysplasia** and **no** **cytologic atypia**
* *OSCC arises from a dysplastic surface epithelium, with features of cytologic atypia:*
* *Increased Nuclear:Cytoplasm, Pleomorphism, and Mitotic acitivity*
40
What is the diagnosis of Verrucous Carcinoma based off of?
* Overall **Architecture** of the Tumor
* How it **Invades "pushing margin"**
## Footnote
*Not based on individual cell appearance because they look pretty normal*
41
What is the Histology of Verrucous Carcinoma?
* **Thick, abundant keratin production**, and a papillary or **verrucous surface**
* **Parakeratin Plugs** = parakeratin fills in the clefts between the surface projections (dark pink)
* **Wide, elongated rete ridges** that invade by **pushing into CT**
* Often intense chronic inflammatory infiltrate in the CT *(same as OSCC)*
42
What is the Treatment for Verrucous Carcinoma?
* **Surgical Excision**
* **Not as aggressive** as what is needed for OSCC, because it grows laterally.
* 90% ds free 5yrs after surgery
43
What is Carcinoma of the Maxillary Sinus?
SCC that arise in the Sinus
44
What is the Etiology for Carcinoma of the Maxillary Sinus?
* **Unknown** cause for most
* **Weak tobacoo link**
* Some may have **HPV**
* 1 type shows strong assoc to occupational exposure to **wood/leather dust**
45
What is the Clinical Appearance of Carcinoma of the Maxillary Sinus?
* Mostly aymptomatic until tumor fills and perforates the sinus
* Symptoms depend on direction of tumor growth
* _Lateral:_ p**ainful facial swelling**
* _Medial:_ chronic **unilateral nasal obstruction/bleeding**
* _Inferior:_ **palatal mass/ulceration**
* _Superior:_ **eyeball protrusion**
46
What is the radiographic appearance of Carcinoma of the Maxillary Sinus?
* Loose Teeth
* Moth-eaten Bone
* **Cloudy Sinus on PANX**
47
In what population is Nasopharyngeal Carcinoma more common?
* 20-55x more common in **Southern China**
* **Middle-Aged Males** (3:1), but can be any age
48
What is the etiology/pathogenesis of Nasopharyngeal Carcinoma?
* Primary tumor may be small and arise from **Waldeyer's Ring**
* Assoc with **EBV infection**, although etiology is multifactorial
49
What are the symptoms of Nasopharyngeal Carcinoma?
* Epistaxis
* Obstruction of 1 side of nose
50
What are the 2 possible histologies of Nasopharyngeal Carcinoma?
* **SCC** with or without keratin production
* Undifferentiated Type - lesional cells blend with stromal lymphocytes = **Lymphoepithelioma**
51
What is the treatment for localized Nasopharyngeal Carcinoma?
Radiation
52
What is the treatment for Metastatic Nasopharyngeal Carcinoma?
Radiation with concomitant Chemotx
53
What does BCC arise from?
* Basal cells of epidermis, OR
* Germ cells of hair follicles
54
What is the most common skin cancer?
BCC (80%)
55
What population of pts are affected by BCC?
* \> 40 yrs
* Fair complexion
* History of chronic sun exposure
56
What is the molecular pathogenesis of BCC?
* Dysregulation of **hedgehog signaling pathway**
* **TP53 mutations** in 50%
57
Where is BCC located on the skin?
Middle 3rd of face
58
What is the most common subtype of BCC?
**Nodulo-Ulcerative** (45-60%)
Located in the head and neck region
59
What subtype of BCC is found on the trunk?
Superficial BCC (15-35%)
60
What is the characteristics of Sclerosing (morpheaform) BCC?
* **Mimics scar tissue**, but:
* No previous history of trauma
* Continues to grow
* In the Head and Neck Region
61
What is the clinical appearance of BCC?
* **Umbilicated** (depressed) **papule** that may show **central ulceration**, with a **rolled pearly white border**
* May see **telangiectastic vessels**
* **Lacks adnexal skin structures (no hair)**
* **"Rodent Ulcer"**
* Untx lesions continue to enlarge slowly, with ulceration and destruction of underlying structures
62
What is the Histology of BCC?
* Basaloid cells that appear to "drop off" of the basal cell layer of the epidermis
* _Nodulo-Ulcerative BCC:_
* Characteristic **large lobules of tumor cells**
63
What is the prognosis for BCC?
* **Excellent**
* **\> 95% of pts cured after 1st tx**
* More aggressive lesions require _Mohs' surgery_:
* Larger, recurrent, or in embryonic planes of fusion
64
Why is Follow-Up of BCC important?
* Same concept as the Field Effect in the mouth from smoke
* **44%** chance of **2nd BCC**
* **6%** chance of **SCC within 3 yrs**
65
What is the etiology of Cutaneous SCC?
* Pre-exisiting AK
* Chronic sun (UV light) exposure
66
Where is Cutaneous SCC typically found?
* Face
* Helix of Ear
* Dorsum of Hands
* Arms
67
What is the treatment and prognosis for Cutaneous SCC?
* **Surgical Excision**
* Actinically-induced SCC are **well-differentiated and grow slowly**
* Prognosis is **Very Good**, if ID early
68
In what population is Cutaneous Melanoma predominate in?
* Slight **Male** predominance
* **Fair-skinned**
* **40-70 yrs old**
69
What is the most frequent site for Cutaneous Melanoma in men?
Back
70
What is the most frequent site for Cutaneous Melanoma on women?
lower extremity
71
What are the Risk Factors for Cutaneous Melanoma? (6)
1. History of increased # of sunburns
2. Indoor occupation, with outdoor recreation
3. Family history of melanoma
4. Personal history of melanoma
5. Dysplastic or Congenital Nevus
6. \> 100 Common Nevi
72
What is the most common mutation associated with Cutaneous Melanoma, and what other 2 are sometime seen?
**BRAF mutation**
* CDKN2A mutation
* CDK4 mutation
73
What mutation is associated with Mucosal Melanomas?
KIT mutations
74
What population does Cutaneous H/N Melanoma occur in?
* **Sun-exposed skin** of **older adults**, mainly **mid-face region**
75
What does Cutaneous H/N Melanoma develop from?
* A premalignant precursor called **Lentigo Maligna** (**Hutchinson Freckle**)
* **Melanoma in-situ**
76
What is the clinical appearance of Cutaneous H/N Melanoma?
* **Slowly expanding** (radial growth phase = 15 yrs)
* **Variegated macule** with **irregular borders**
77
What is the treatment for Cutaneous H/N Melanoma?
Surgical Excision with 1-2cm margins
78
What is the treatment for Aggressive or Recurrent Cutaneous H/N Melanoma?
Radiation or Immunotherapy (IFN-a, checkpoint inhibitors)
79
What is the treatment for Metastic Cutaneous H/N Melanoma?
**BRAF Inhibitor** (vemurafenib) and **T-Cell Promotor** (ipilimumab)
80
What is the single most important prognostic indicator for Cutaneous H/N Melanoma?
Breslow Tumor Thickness
81
What is the prognosis for Cutaneous H/N Melanoma, and what factors increase the prognosis?
* 92% 5 yr survival
* **3-5% develop a 2nd melanoma** = follow-up
* _Better Prognosis for:_
* Females
* Younger
* Not High Risk Areas (BANS)
* No Ulceration
82
What is the most common melanoma variant in the oral cavity?
Acral Lentiginous
83
Where are Oral (Mucosal) Melanomas found?
70-80% on **hard palate, maxillary alveolus**
84
What is the Clinical Appearance of Oral (Mucosal) Melanomas?
* _Early Lesions:_
* brown/black/blue macules with irregular borders
* A minority are colorless
* _Late Lesions:_
* Nodular
* May ulcerate
85
What does bone involvement in Oral (Mucosal) Melanomas appear as?
Ragged RL
86
What is the histological appearance of Oral (Mucosal) Melanomas?
* Invasive cells are **spindle-shaped, pleomorphic melanocytes** making **brown pigment**
* ****They are invading up into the lamina propria
87
In what type of melanoma is invasion of blood vessels and lymphatics more common, Oral or Cutaneous?
Oral Melanoma
88
What is the prognosis for Oral (Mucosal) Melanomas?
* **Much worse** once **depth \> 0.5mm**
* **10-25%** 5 yr survival
* Much worse than the 92% for cutaneous melanoma
* **Pts usually die due to mets rather than local extension**
89
What are components of Melanoma Staging?
* Breslow Thickness
* Clark Level
90
What does Breslow thickness measure?
From the granular cell layer to depth of invasion (mm)
91
What does Clark Level indicate in Melanomas?
**Anatomic extension of the tumor**
* I - epithelium
* II - penetrating papillary dermis
* III - filling papillary dermis
* IV - invasion of reticular dermis
* V - invasion of subcutaneous fat
