Oral cavity and oropharynx Flashcards
Differential for this oral mucosal ulcer biopsy and how to resolve it.
- Pemphigus vulgaris
- 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.
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.
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.
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.
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.
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.
NUT carcinoma
Undifferentiated tumor cells with pockets of “abrupt keratinization.” Necrosis is often present.
Caused by NUTM1 rearrangements.
IHC: All positive for NUT IHC. Most at least focally positive for CK5/6, p40, and p63.
Sinonasal undifferentiated carcinoma
Totally undifferentiated tumor cells.
An IDH2 mutated neoplasm with retained INI1 and negative for NUTM1 fusions. Frequently R172S or R172T.
70% are positive for IDH2 IHC.
50% are positive for CK7.
Pretty reliably AE1/AE3/CAM5.2 positive.
Has some morphologic and genetic overlap with sinonasal large cell neuroendocrine carcinoma.
Sinonasal Large Cell Neuroendocrine Carcinoma
May display IDH2 mutations similar to sinonasal undifferentiated carcinoma – these subtypes may exist on a spectrum.
IHC: neuroendocrine markers, dot-like panCK, some IDH2 positive.
Olfactory neuroblastoma
Occur at any age, peak incidence in 40’s-50’s, 3% of all sinonasal tract tumors.
Often lobular or polypoid. Histologic appearance determines grading. Tumor cells are usually small and uniform (about the size of lymphocytes), with scant cytoplasm surrounding round and regular nuclei with slightly hyperchromatic, delicate, punctate, salt-and-pepper nuclear chromatin.
Nucleoli are inconspicuous. The cells appear syncytial, often showing neuropil or neural tangles, which occasionally create Homer Wright pseudorosettes when the nuclei cuff or palisade around the fibrillar matrix.
As the tumor grade increases, tumor necrosis, increased mitoses, pleomorphism, and true Flexner–Wintersteiner rosettes may be seen (tight annular structures with lumen and possible secretions)
Intestinal-type sinonasal adenocarcinoma
CDX2, villin, SATB2 positive.
Driven by recurrent KRAS mutations.
High-grade non-intestinal type sinonasal adenocarcinoma
Variable molecular features.
CK7+, variably express SOX10/S100, DOG1, and neuroendocrine markers.
PAS+ (disatase resistant granules), mucin+, mucicarmine+
p40 focal/neg
CDX2-, STAB2-
Low-grade non-intestinal type sinonasal adenocarcinoma
Variable molecular features, but some CTNNB1 mutated, some BRAF V600E mutated.
CK7+, Variable expression of SOX10/S100 and DOG1
B-catenin nuclear positive (if CTNNB1 mutated), BRAF positive (if BRAF V600E mutated)
PAS+ (disatase resistant granules), mucin+, mucicarmine+
p40 focal/neg
CDX2-, STAB2-
Sinonasal renal cell-like adenocarcinoma
Obviously, the main DDx is true metastatic RCC, so you have to rule this out!
CAIX+ and CD10 diffuse, just like true RCC, BUT PAX8 negative and RCC negative.
