Upper Airway & Head and Neck Pathology
From stuffy noses to p16: the upper airway's classic associations
Sinonasal inflammation: sinusitis, rhinitis and polyps
Sinus drainage. The frontal, maxillary and anterior ethmoid sinuses drain into the middle meatus through the ostiomeatal complex; the posterior ethmoid cells drain into the superior meatus, the sphenoid into the sphenoethmoidal recess, and the nasolacrimal duct into the inferior meatus. The maxillary ostium sits high on the sinus's medial wall, so drainage depends on cilia rather than gravity and fails quickly when mucosa swells. That is why the maxillary sinus is the one most often infected in adults, sometimes presenting as upper-tooth pain. Maxillary and ethmoid sinuses are present at birth, and ethmoid sinusitis predominates in young children; infection can cross the thin lamina papyracea into the orbit.
Acute rhinosinusitis. Most cases are viral (rhinovirus) and resolve within 7–10 days. Bacterial superinfection involves the same trio as otitis media: S. pneumoniae, nontypeable H. influenzae and Moraxella catarrhalis. Nontypeable H. influenzae lacks a capsule, so the Hib conjugate vaccine does not prevent it. Suspect bacteria when symptoms last more than 10 days without improvement, when high fever accompanies purulent discharge, or when symptoms worsen after initial improvement. Rare complications include orbital cellulitis, cavernous sinus thrombosis and brain abscess; in diabetic ketoacidosis or neutropenia, Mucor and Rhizopus cause invasive sinusitis with black eschar.
Allergic rhinitis. This is type I hypersensitivity. On re-exposure, allergen cross-links IgE on sensitized mast cells, which release histamine (sneezing, itching, clear rhinorrhea) and leukotrienes and recruit eosinophils (late-phase congestion). The turbinates are pale, boggy and bluish, and nasal smears show eosinophils. Allergic shiners, a transverse nasal crease from repeated "allergic salutes" and coexisting asthma or eczema complete the atopic picture.
Nasal polyps. Polyps are edematous, inflammatory outgrowths of sinonasal mucosa, typically bilateral and eosinophil-rich, that accompany chronic rhinosinusitis and asthma in adults. In a child they are unusual enough to prompt a sweat chloride test for cystic fibrosis. A unilateral nasal mass should be imaged to exclude a neoplasm.
Aspirin-exacerbated respiratory disease. Asthma, chronic rhinosinusitis with nasal polyps and respiratory reactions to aspirin or other COX-1 inhibitors form the Samter triad. Blocking COX-1 removes PGE2, which normally restrains mast cells and leukotriene synthesis, and shunts arachidonic acid into the 5-lipoxygenase pathway. The resulting surge of cysteinyl leukotrienes (LTC4, LTD4, LTE4) causes bronchospasm, congestion and rhinorrhea within hours of a dose. Management is NSAID avoidance, leukotriene modifiers (montelukast, zileuton) and, in selected patients, aspirin desensitization; selective COX-2 inhibitors are usually tolerated.
Epistaxis and nasopharyngeal tumors
| Feature | Anterior | Posterior |
|---|---|---|
| Frequency | About 90% | About 10%, but heavier |
| Source | Kiesselbach plexus on the anterior septum | Sphenopalatine artery (maxillary artery, external carotid) |
| Typical patient | Children and young adults; nose-picking, dry air, colds, intranasal steroids, cocaine | Older adults with hypertension or anticoagulation |
| Management | Lean forward, pinch the soft nose; vasoconstrictor, cautery, anterior packing | Posterior packing or balloon, embolization or arterial ligation |
Kiesselbach plexus. Branches of the anterior ethmoidal artery (from the ophthalmic, internal carotid system) meet branches of the sphenopalatine, greater palatine and superior labial arteries (external carotid system) on the anterior septum, where the mucosa is thin and exposed to drying and fingers. Recurrent epistaxis with telangiectasias on the lips, tongue and fingertips suggests hereditary hemorrhagic telangiectasia, an autosomal dominant disorder (ENG or ACVRL1) that also causes visceral arteriovenous malformations.
Juvenile nasopharyngeal angiofibroma. This benign but locally aggressive fibrovascular tumor arises near the sphenopalatine foramen almost exclusively in adolescent males and is thought to be androgen-sensitive. It causes nasal obstruction and profuse, recurrent, unilateral epistaxis. Its thin-walled vessels have little smooth muscle and bleed torrentially, so diagnosis rests on CT or MRI rather than biopsy, and treatment is preoperative embolization followed by resection.
Nasopharyngeal carcinoma. This carcinoma is strongly associated with EBV and is most common in southern Chinese and some African populations; salted fish containing nitrosamines adds risk. The usual histology is nonkeratinizing undifferentiated carcinoma: cytokeratin-positive tumor cells in a dense background of reactive lymphocytes (lymphoepithelioma). The first sign is often painless cervical lymphadenopathy. Other clues are epistaxis, nasal obstruction, cranial nerve palsies from skull-base invasion and unilateral serous otitis media in an adult, caused by tumor blocking the Eustachian tube. The tumor is radiosensitive and is treated with chemoradiation.
The larynx
Hoarseness. Any lesion that stops the true vocal cords from meeting evenly changes the voice.
| Feature | Vocal cord nodules | Recurrent respiratory papillomatosis | Laryngeal SCC |
|---|---|---|---|
| Cause | Voice overuse (singers, teachers, shouting children) | HPV 6 and 11; juvenile form acquired at birth from maternal genital infection | Tobacco and alcohol, synergistic |
| Appearance | Bilateral, symmetric, at the junction of the anterior and middle thirds | Multiple exophytic papillomas, often recurrent | Usually unilateral, irregular, ulcerated |
| Histology | Edematous, myxoid stroma under squamous epithelium | Squamous papillomas with fibrovascular cores and koilocytes | Keratinizing SCC arising from dysplasia |
| Malignant potential | None | Rare | Invasive cancer |
| Treatment | Voice therapy | Repeated surgical debulking | Radiation, surgery, chemoradiation |
Laryngeal carcinoma. Most laryngeal SCCs arise on the true cords (glottis). Hoarseness appears early and the glottis has sparse lymphatics, so these tumors are often found early and cured. Supraglottic tumors have rich lymphatic drainage and spread to cervical nodes sooner. Hoarseness that persists beyond a few weeks in a smoker warrants laryngoscopy. The low-risk HPV types 6 and 11 behind papillomatosis also cause anogenital warts (condylomata acuminata) and are covered by HPV vaccination.
Head and neck squamous cell carcinoma
Two pathways. More than 90% of head and neck cancers are squamous cell carcinomas. Classic tumors follow years of smoked or smokeless tobacco and alcohol, occur in older adults, involve the oral cavity, larynx and hypopharynx, and carry TP53 mutations. A rising share arise in the oropharynx (palatine tonsils and base of tongue) from HPV-16 in younger, often nonsmoking adults. In these tumors E6 degrades p53 and E7 inactivates Rb; loss of Rb feedback drives overexpression of p16, which serves as a surrogate marker. They often present as a cystic neck node from a small primary and have a markedly better prognosis. EBV is linked to nasopharyngeal rather than oropharyngeal carcinoma. EGFR is commonly overexpressed in head and neck SCC, and the anti-EGFR antibody cetuximab is used with radiation.
Precursor lesions. Leukoplakia is a white plaque that cannot be scraped off; erythroplakia is a red, velvety patch with a much higher risk of dysplasia or carcinoma. Both need biopsy, and dysplasia can progress to carcinoma in situ and then invasive SCC. Oral candidiasis, by contrast, scrapes off, and oral hairy leukoplakia (EBV, lateral tongue, HIV) is not premalignant.
Field cancerization: tobacco and alcohol bathe the whole upper aerodigestive mucosa, seeding many independent mutated clones, so a patient with one head and neck SCC is at high risk of synchronous or later second primaries in the head and neck, esophagus or lung. Smoking cessation and lifelong surveillance are essential.