Head and Neck Pathology Comprehensive Pathology

Anatomy and Developmental Anomalies of the Oral Cavity

• Anatomic Borders of the Oral Cavity:

  • Anterior: The vermilion border of the lips.

  • Posterior: A line extending from the junction of the hard and soft palate to the circumvallate papillae of the tongue.

  • Superior: The hard palate up to its junction with the soft palate.

  • Inferior: The anterior two-thirds of the tongue, ending at the line of the circumvallate papillae.

  • Lateral: The buccal mucosa of the cheeks.

• Facial Clefts:

  • These form if facial structures fail to fuse during the seventh week of embryonic life.

  • Cleft Upper Lip (Harelip): The most common facial cleft; it can be unilateral or bilateral and is frequently associated with cleft palate.

• Branchial Cleft Cyst:

  • Origin: Remnants of the branchial arches; most arise from the second branchial cleft.

  • Location: Lateral anterior neck or parotid gland, typically in young adults.

  • Content: Thin, watery fluid, and mucoid or gelatinous material; often appears turbid.

  • Lining: Usually stratified squamous epithelium, though foci of ciliated respiratory or pseudostratified columnar epithelium may occur.

  • Histology: Keratin-filled cysts often exhibit focal lymphoid aggregates below the lining epithelium.

Infections and Inflammatory Conditions of the Oral Cavity

• General Terminology:

  • Cheilitis: Inflammation of the lips.

  • Gingivitis: Inflammation of the gums.

  • Glossitis: Inflammation of the tongue.

  • Stomatitis: Inflammation of the oral mucosa.

• Aphthous Stomatitis (Canker Sores):

  • Characterized by painful, recurrent, small ulcers of the oral mucosa. They may be solitary or multiple. The cause is currently unknown.

• Ludwig Angina:

  • A rapidly spreading cellulitis originating in the submaxillary or sublingual space, often involving both. It is caused by bacteria from the normal oral flora.

• Candidiasis (Thrush/Moniliasis):

  • Caused by Candida albicans, which is normally present in the oral cavity, GI tract, and vagina. Pathogenicity occurs when the fungus penetrates tissues superficially. Common in diabetics and immunocompromised individuals.

• Herpes Simplex Virus Type 1 (HSV-1):

  • Causes herpes labialis (cold sores) and herpetic stomatitis.

  • Clinical Presentation: Vesicles rupture to form shallow, painful ulcers ranging from punctate size to $1\,cm$ in diameter.

  • Histology: "Ballooning degeneration" of epithelial cells and intranuclear viral inclusions (Cowdry type A).

• Viral-Related Proliferations:

  • Human Papillomavirus (HPV): Associated with sinonasal/Schneiderian papillomas. "High-risk" types ($16, 18, 31, 33, 35$) are strongly linked to oropharyngeal squamous cell carcinoma.

  • Epstein-Barr Virus (EBV/HHV-4): Linked to infectious mononucleosis, oral hairy leukoplakia, lymphoid malignancies, and specific epithelial malignancies (e.g., nasopharyngeal carcinoma, salivary gland undifferentiated carcinoma).

Benign and Preneoplastic Lesions

• Benign Oral Neoplasms:

  • Include pigmented nevi, fibromas, hemangiomas, lymphangiomas, and squamous papillomas.

  • Squamous Papilloma: Most common benign oral neoplasm; exophytic with branching fronds of squamous epithelium and fibrovascular cores. Historically associated with HPV types $6$ and $11$. Common sites: tongue, palate, buccal mucosa, tonsil, and uvula.

• Pyogenic Granuloma (Lobular Capillary Hemangioma):

  • Often called a "pregnancy tumor." It is neither infectious nor granulomatous.

  • Appearance: Elevated, soft, red/purple, lobulated, and often ulcerated; typically ranges from a few millimeters to a centimeter.

  • Histology: Submucosal lesion with cellular lobules of dilated vascular spaces surrounded by granulation tissue and chronic inflammatory infiltrate.

• Leukoplakia:

  • A descriptive clinical term for an asymptomatic white patch or plaque that cannot be scraped off. It is not a histologic diagnosis.

  • Risk: May represent hyperkeratosis, epithelial hyperplasia, or squamous carcinoma in situ. Some progress to invasive SCC.

• Erythroplakia:

  • The red equivalent of leukoplakia. It is less common but more likely to harbor moderate-to-severe dysplasia or carcinoma. "Speckled leukoplakia" contains both red and white areas.

• Mucocele:

  • A mucus-filled cystic lesion of the minor salivary glands, usually of the lower lip. Typically caused by trauma.

  • Histology: Granulation tissue lining a lumen filled with mucus and macrophages.

Malignant Tumors: Squamous Cell Carcinoma (SCC)

• General Characteristics: The most common malignant tumor of the oral mucosa. Frequently preceded by carcinoma in situ.

• Grading: Ranges from well-differentiated (Grade I, keratinizing) to undifferentiated/sarcomatoid.

• Metastasis: Primarily spreads to submandibular, superficial, and deep cervical lymph nodes. Over $50\%$ of patients who die from head/neck SCC have distant metastases (lungs, liver, bones).

• Prognostic Factors:

  • Depth of invasion.

  • Perineural invasion (tumor surrounding nerves).

  • Lymphovascular tumor emboli.

  • Pattern of infiltration: Single-cell infiltration is less favorable than a broad "pushing" border.

Specific Oral and Odontogenic Pathologies

• Tongue Diseases:

  • Macroglossia: Enlargement caused by lymphangioma, hemangioma (congenital), amyloidosis, or acromegaly (acquired). Seen in Down syndrome and Pompe disease.

  • Glossitis: Inflammation often linked to vitamin deficiencies (Pernicious anemia, Pellagra/B3, Riboflavin/B2, Pyridoxine/B6).

• Odontogenic Cysts:

  • Radicular (Apical Periodontal) Cyst: Most common; occurs at the tooth apex following pulp infection. May show cholesterol clefts, mucous cell metaplasia, or ciliated cells histologically.

  • Dentigerous Cyst: Associated with the crowns of unerupted teeth (e.g., mandibular $3^{rd}$ molars). Fluid accumulates between the crown and enamel epithelium. Risk of developing into ameloblastoma or SCC.

• Ameloblastoma:

  • Most common clinically significant odontogenic tumor. Slow-growing, locally invasive, and destructive.

  • Radiology: "Soap bubble" appearance.

  • Histology: Islands of odontogenic epithelium with central stellate reticulum-like areas and peripheral basal cells with a "picket fence" (palisading) appearance due to subnuclear vacuoles.

Nasal Cavity and Paranasal Sinuses

• Rhinitis:

  • Viral: Most common cause is the common cold (acute coryza). Leads to edema, nasal stuffiness, and rhinorrhea.

  • Allergic (Hay Fever): Plant-pollen or allergen sensitivity; can be seasonal or perennial.

• Nasal Polyps:

  • Smooth, pale, nonneoplastic mucosal masses.

  • Histology: Edematous mucoid stroma with mucous glands, plasma cells, lymphocytes, and many eosinophils.

• Sinusitis:

  • Acute: Duration < 3 weeks. Organisms: Haemophilus influenzae, Branhamella catarrhalis.

  • Chronic: Prolonged infection often involving anaerobic bacteria.

  • Complications: Mucocele (mucus accumulation), Pyocele (infected mucocele), Empyema (purulent exudate), Osteomyelitis (bone infection), Septic Thrombophlebitis (can spread to cavernous sinus), and intracranial abscesses.

• Inverted Papilloma:

  • Benign but locally aggressive tumor of the lateral nasal wall. Epithelial nests grow downward ("inverted") into the submucosa. Linked to HPV in some cases. Recurrence is high; $5\%$ progress to SCC.

Larynx and Salivary Glands

• Inflammatory Laryngeal Conditions:

  • Epiglottitis: Caused by H. influenzae type B. Pediatric emergency requiring potential tracheostomy due to inspiratory stridor and airway obstruction.

  • Croup: Laryngotracheobronchitis causing a "barking" cough and edema.

• Vocal Cord Nodule/Polyp: Reactive stromal process from voice abuse, smoking, or hypothyroidism. Early stages are myxoid/edematous; late stages are densely fibrotic.

• Laryngeal SCC:

  • Glottic ($2/3$): Limited to vocal cords; slow to metastasize; good prognosis.

  • Supraglottic ($1/3$): Involves false cords/epiglottis; nodal metastasis more common.

  • Transglottic/Infraglottic: Poorer prognosis; often require total laryngectomy.

• Benign Salivary Neoplasms:

  • Pleomorphic Adenoma (Mixed Tumor): Most common salivary tumor (especially parotid). Admixture of ductal/myoepithelial cells and chondromyxoid stroma.

  • Warthin Tumor: Benign parotid tumor. More common in men. Histology: Cystic spaces lined by oncocytes (eosinophilic epithelial cells) within dense lymphoid tissue with germinal centers.

• Malignant Salivary Neoplasms:

  • Mucoepidermoid Carcinoma: Admixture of mucocytes, epidermoid cells, and intermediate cells.

  • Adenoid Cystic Carcinoma: Slowly growing; invades perineural spaces (painful). Histology: Cribriform/sieve-like pattern with "cylindromatous" basement membrane material.

  • Acinic Cell Adenocarcinoma: Composed of basophilic cells filled with zymogen granules.

The Ear

• External Ear:

  • Keloids: Hyalinized collagen bundles after trauma/piercing.

  • Relapsing Polychondritis: Inflammation destroying cartilage (ears, nose, larynx).

  • Malignant Otitis Externa: Caused by Pseudomonas aeruginosa; common in elderly diabetics.

• Middle/Internal Ear:

  • Otosclerosis: Autosomal dominant; common cause of conductive hearing loss via bony ankylosis of the stapes footplate.

  • Schwannoma (Vestibular): Most common tumor of the inner ear. Histology: Biphasic (Antoni A and B areas) with Verocay bodies (nuclear palisading).

  • Meningioma: Attached to dura; can show psammoma bodies or meningothelial patterns; causes reactive hyperostotic bone changes.