Oral cavity and oropharynx

Question 1

Differential for this oral mucosal ulcer biopsy and how to resolve it.

Answer 1

1. Pemphigus vulgaris
2. Paraneoplastic pemphigus

Both can involve anti-desmoglein-3, however
paraneoplastic pemphigus tends to involve more than one antibody and the set almost always includes anti-envoplakin and anti-desmoplakin (it may also include anti-desmoglein-1, of pemphigus foliaceous). All of the above will stain in a “honeycomb” pattern on immunofluorescence.

Question 2

Answer 2

Oral hairy leukoplakia

This is an EBV-driven process which occurs in immunocompromised patients (80% of cases HIV associated in particular). Generally asymptomatic unless candidal superinfection occurs.

Grossly, a flat, white shaggy plaque usually on the lateral tongue.

Histologically, the epithelium is acanthotic with hyperkeratosis and parakeratosis. Perinuclear clearing with “balloon cells” is a characteristic feature. Viral replication may cause “nuclear beading.” Usually inflammation is only sparse.

Diagnosis relies on detection of EBV by EBER ISH. There is no propensity for malignant transformation, unlike the lichenoid processes.

Question 3

Answer 3

Mucous membrane pemphigoid

This disease is on a clinical spectrum with bullous pemphigoid and autoimmune epidermolysis bullosa. Both BP and MP can target BP180 or BP230, both AEB and MP can target type VII collagen. Laminin-332 appears to be the only unique target of MMP.

Since the mechanism is the same, the degree of clinical involvement of skin versus mucosal surfaces is what determines the diagnosis. Pathophysiologically, they are basically the same if the antibody spectrum is the same.

Question 4

Answer 4

Irritation fibroma

Most common oral mucosal mass. Usually just repetitive trauma related, however many may occur in Cowden syndrome and Tuberous sclerosis.

Nodular deposition of dense collagen with chronic inflammation and overlying thinned mucosa. Hyperkeratosis and ulceration may be seen. Fibroblasts should be spindled and indistinct.

Question 5

Answer 5

Giant cell fibroma

Histologically similar to irritation fibroma, with nodular dense collagen and chronic inflammation, but rather than indistinct spindled fibroblasts you have large, stellate myofibroblasts.

Tend to be unassociated with trauma and occur in younger patients. Likely to recur.

Question 6

Answer 6

Gingival fibromatosis

Generalized (but not always symmetric) enlargement of the gingiva.

Ddx: hereditary, drug-induced, related to poor oral hygiene, or idiopathic. Drugs include several antiepileptics (phenytoin, phenobarbital, topiramate, ethosuximide), antipsychotics (lamotrigine), and calcium channel blockers (nifedipine, amlodipine, verapamil, diltiazem). Main genetic cause is SOS1 gain-of-function.

Histologically characterized by dense eosinophilic to slightly basophilic fibrous tissue with associated mild chronic inflammation. The surface may have chronic inflammation or extreme elongation of the rete.