Select Pathology of the Head & Neck

Key questions

1. Q1What is leukoplakia?

   A white patch or plaque that cannot be scraped off and cannot be characterized clinically or pathologically as any other disease — a diagnosis of exclusion.
2. Q2How often is leukoplakia premalignant, and who gets it?

   5–25% are premalignant; most U.S. leukoplakias are benign. Adults 40–70, often tobacco users.
3. Q3What does leukoplakia show under the microscope?

   Most show hyperkeratosis at first diagnosis (what makes it white); some show mild, moderate or severe dysplasia. Dysplasia grade does not reliably predict invasion, so biopsy.
4. Q4How do you work up a white oral patch?

   Try to scrape it off (candidiasis wipes off); if bilateral, think systemic disease (e.g., SLE); ask about chronic trauma such as cheek chewing (frictional hyperkeratosis); if it will not scrape off, biopsy.
5. Q5What is hairy leukoplakia?

   Fluffy, white, corrugated patches on the lateral border of the tongue caused by EBV, usually in immunocompromised patients (e.g., HIV); cannot be scraped off. Histology: hyperkeratosis and balloon cells containing EBV RNA.
6. Q6What is erythroplakia, and why is it worse than leukoplakia?

   A red, velvety patch in the oral cavity; less common than leukoplakia but almost always atypical — dysplasia, carcinoma in situ or minimally invasive carcinoma.
7. Q7What fraction of premalignant lesions become carcinoma?

   About 15% within 5 years.

Key questions

1. Q8Where does head and neck SCC arise?

   Oral cavity (under the tongue, floor of mouth, lower lip, soft palate), oropharynx (tonsils, base of tongue), nasal cavities and larynx. SCC is the majority of head and neck carcinomas.
2. Q9What are the classic risk factors?

   Chronic tobacco and alcohol use in middle-aged/older patients (synergistic). Others: betel quid and paan, actinic (sun) radiation and pipe smoking (lower lip).
3. Q10What is now the main cause of oropharyngeal SCC?

   High-risk HPV — about 90% of HPV-related oropharyngeal SCCs carry HPV-16 — in the tonsils and base of tongue.
4. Q11Which new group is getting oral tongue SCC?

   Patients under 40 with no known risk factors (non-smokers, HPV-negative).
5. Q12Which driver genes are altered?

   TP53, CDKN2A, PIK3CA; also NOTCH1 (loss of function) and FAT1 (tumor suppressor, cadherin family). HPV-negative tumors carry more somatic mutations.
6. Q13How does HPV cause cancer?

   Oncoproteins E6 and E7 inactivate the TP53 and RB pathways, respectively.
7. Q14Keratinizing vs non-keratinizing SCC under the microscope?

   Keratinizing (tobacco/alcohol): keratin pearls/whorls, irregular invasion, ulcerated firm lesion. Non-keratinizing (HPV): nests/sheets of basaloid cells without keratin pearls; p16 immunostain positive (nucleus + cytoplasm); HPV mRNA detectable.

Key questions

1. Q15What is field cancerization?

   Carcinogen exposure (tobacco/alcohol) damages the whole upper aerodigestive mucosa, so patients often have multiple primaries and metastases at presentation — and a high risk of a second primary.
2. Q16Where does classic SCC metastasize?

   Lymph nodes (cervical), lung and bone.
3. Q17Does tumor differentiation predict behavior?

   No — differentiation does not correlate with growth rate or overall behavior. Stage does.
4. Q18What are the survival numbers?

   Early stage: ~80% 5-year survival. Late stage: ~20%.
5. Q19How does HPV status change prognosis?

   HPV-16/18–associated SCC has a better prognosis than classic SCC (more radiosensitive, fewer distant metastases and second primaries).
6. Q20How is it treated?

   Surgical removal (can include floor of mouth/tongue), with radiation ± chemotherapy by stage.

Key questions

1. Q21What are the common causes of epistaxis?

   Digital trauma, dry nose/crusting and foreign bodies; also medications, allergies and inherited coagulopathies. Discrete lesions: pyogenic granuloma and angiofibroma.
2. Q22What is a pyogenic granuloma?

   A lobular capillary hemangioma — a benign vascular lesion, neither infectious nor granulomatous. A red, raised, friable papule that bleeds and ulcerates; common on gingiva and skin, can be in the nose; associated with pregnancy. Treat by removal or sclerosing injection.
3. Q23Who gets juvenile nasopharyngeal angiofibroma, and how does it present?

   Adolescent boys (7–19; rare after 25). Nasal obstruction (80–90%) and epistaxis (45–60%); also headache, facial swelling, unilateral rhinorrhea. Fills one side of the nasal cavity and deviates the septum.
4. Q24Where does angiofibroma arise, and what does it look like?

   Near the posterior attachment of the middle turbinate (posterolateral nasal wall/nasopharynx). Dense collagenous stroma with bland fibrosis and thin-walled vessels that cannot contract → brisk bleeding.
5. Q25What gene and associations does angiofibroma have?

   CTNNB1 (β-catenin) mutations; can occur with familial adenomatous polyposis. Hormonal theory (almost only males, hormone receptors on tumor); can be shrunk with estrogen/anti-androgens before surgery. Locally aggressive; intracranial extension and young age worsen prognosis.
6. Q26What is a sinonasal (Schneiderian) papilloma?

   A benign, almost always unilateral neoplasm of the respiratory mucosa of the nasal cavity and sinuses, in men 30–60; causes obstruction (sinusitis from blockage). Treat by complete excision.
7. Q27Compare the three sinonasal papilloma subtypes.

   Inverted (endophytic): most common, lateral wall/sinuses, EGFR mutations, 5–10(15)% malignant. Exophytic (filiform): septum, low-risk HPV, ~0% malignant. Oncocytic (cylindrical): lateral wall/sinus, eosinophilic mitochondria-rich cells with mucous cysts, KRAS, 14–19% malignant.
8. Q28Which malignancy arises from sinonasal papillomas, and when?

   Squamous cell carcinoma — at the first excision (usually focal, better prognosis) or months–years later with recurrences (worse prognosis).
9. Q29What characterizes nasopharyngeal carcinoma?

   Strong EBV association, geographic clustering (Southern China, Southeast Asia, Africa), close relationship to lymphoid tissue. Presents late with obstruction and epistaxis, often with neck-node metastases.
10. Q30Compare the nasopharyngeal carcinoma subtypes.

    Keratinizing: most common, large squamoid cells with ample cytoplasm. Non-keratinizing: smaller hyperchromatic cells in ribbons with intervening benign lymphocytes; EBV-linked; better prognosis (radiosensitive). Basaloid: rare, undifferentiated.

Key questions

1. Q31What is a laryngeal papilloma?

   A benign squamous neoplasm on the true vocal cords: exophytic, small (<1 cm), finger-like projections of orderly squamous epithelium over fibrovascular cores; may ulcerate and bleed.
2. Q32Adult vs juvenile laryngeal papillomas?

   Adults: usually solitary, rarely recur. Children: multiple (juvenile laryngeal/recurrent respiratory papillomatosis) from low-risk HPV 6/11 acquired at birth; recur often → many surgeries; often regress at puberty.
3. Q33What are the complications of juvenile papillomatosis?

   Airway obstruction; distal airway spread (can signal malignant transformation); rarely SCC with poor prognosis.
4. Q34How is papillomatosis treated and prevented?

   Surgery; some benefit from antivirals and chemotherapy; the HPV vaccine prevents it.
5. Q35Who gets laryngeal SCC, and what causes it?

   Men in their 7th decade; smoking in most cases, worsened by alcohol. Many arise from dysplasia; high-grade dysplasia carries the highest risk.
6. Q36Where does laryngeal SCC arise, and how does it present?

   Vocal cords, epiglottis, aryepiglottic folds or pyriform sinuses; hoarseness or dysphagia (cough). Plaque-like, ulcerated or fungating; variable differentiation.
7. Q37How is laryngeal SCC treated, and what predicts outcome?

   Stage predicts prognosis. Early: microinvasive procedures (mucosal stripping). Later: surgery with chemo and radiation.
8. Q38What else causes hoarseness from a vocal cord lesion?

   Singer's (vocal cord) nodules: bilateral, from voice overuse; hyperplastic epithelium over edematous submucosa; minimal cancer risk. Laryngeal polyps: often unilateral, older smokers.

Key questions

1. Q39Where do salivary tumors occur, and what predicts malignancy?

   65–80% arise in the parotid, and most parotid tumors are benign. The smaller the gland, the more likely malignant: ~40% submandibular, ~50% minor, 70–90% sublingual.
2. Q40What is a pleomorphic adenoma?

   The most common salivary tumor: a benign mixed tumor of epithelial (ductal), myoepithelial and mesenchymal (chondromyxoid) elements. Slow-growing, painless, mobile parotid mass; radiation raises risk; PLAG1 overexpression.
3. Q41Why do pleomorphic adenomas recur?

   They are well circumscribed but have an incomplete capsule with finger-like projections; enucleation leaves tumor behind (~25% recurrence), so complete excision with margin is needed. Rarely becomes carcinoma ex pleomorphic adenoma.
4. Q42What is a Warthin tumor?

   Papillary cystadenoma lymphomatosum: the second most common salivary tumor, benign, found almost only in the parotid; older men, smokers; 10% bilateral; low recurrence.
5. Q43Describe Warthin histology.

   Cystic, papillary spaces lined by a double layer of oncocytic epithelium (columnar luminal + cuboidal basal) packed with mitochondria (eosinophilic), over a dense lymphoid stroma with germinal centers.
6. Q44What is mucoepidermoid carcinoma?

   The most common primary malignant salivary tumor (also the most common in children). Mixed squamous, intermediate and mucus cells in sheets and microcysts; grade drives behavior. t(11;19) CRTC1::MAML2 fusion in ~half.
7. Q45How does mucoepidermoid grade affect outcome?

   Low grade: recurs but rarely metastasizes. Intermediate/high grade: recurs and metastasizes; ~50% 5-year survival.
8. Q46What is adenoid cystic carcinoma?

   A malignant tumor, ~50% in minor salivary glands (also parotid, lung, breast, sinuses): slow but relentless, with perineural invasion (pain, facial nerve palsy), "stubbornly recurrent" with late spread. Small dark basaloid cells in a cribriform ("Swiss cheese") pattern. MYB::NFIB → NOTCH1.