Salivary tumors Flashcards
Why is it called pleomorphic adenoma?
Because the myoepithelial component can take on four different form (spindled, plasmacytic, epithelioid, or clear cell) and there may be a myxoid, cartilagenous, or bony stroma.
It is a biphasic tumor with myoepithelial and epithelial cells, so a clear epithelial component will always be present – it is the myoepithelials and stroma that are pleomorphic.
Two ways to have cancer arising from a pleomorphic adenoma
- It is actually a polymorphous adenocarcinoma, which is derived from similar precursors but has distinct cytogenetics. To identify this, examine the borders of the mass - polymorphous adenocarcinoma will have infiltrating borders.
- You can have a “carcinoma ex-pleomorphic adenoma” arising from the epithelial component. To identify this, look for epithelium with significant cytologic atypia.
Two tumor types that are adjacent to pleomorphic adenoma
Myoepithelioma: Myoepithelial proliferation with little stroma and no ductal component.
Basal cell adenoma: No stromal component and a pure population of basal cells.
Warthin tumor
2 layers of oncocytic epithelium surrounded by lymphoid stroma with germinal centers.
Done. 5 second, low-power diagnosis.
Mucoepidermoid carcinoma
Cystic or solid with a mixture of squamous cells, cuboidal epithelial cells, and mucinous cells – however, the mixture may be mostly squamous or mostly clear mucinous cells. That is why this tumor is OFTEN on the ddx for any salivary tumor.
They key to differentiating it in these cases is to find intracellular mucin – PAS +/- diastase or mucicarmine stain help with this.
Periphery should be infiltrative. May be low or high grade.
Most common malignant tumor of the salivary gland
Adenoid cystic carcinoma
THE PROTOTYPICAL CRIBRIFORM CARCINOMA
Composed of blue acinar-type cells with high N/C ratio and dense, angulated nuclei. Has myoepithelial cells and ductal cells.
Highly infiltrative, loves nerves.
Main ddx options for adenoid cystic carcinoma
Squamous cell carcinoma – If there are areas of keratinization, it is a cribriform squamous, not an ACC.
Cylindroma – another cribriform cancer of the skin adnexa which may arise in the same area (especially towards the ear).
What makes diagnosing acinic cell carcinoma tricky?
- It can look VERY similar to normal salivary gland, but WITHOUT identifiable ducts.
- It has pushing border infiltration rather than a more obvious invasive pattern
Secretory carcinoma
Also called “mammary analogue secretory carcinoma”, because it looks exactly like an equivalent ddx in the breast AND it expresses mammoglobin.
Can look a lot like adenoic cystic carcinoma, but has microcysts rather than cribriform pattern.
Hallmark IHC: S100+ and mammoglobin+
If it looks like DCIS, but you’re in the salivary gland, it is. . .
. . . salivary duct carcinoma
Which may also have cribriform architecture, mimicing adenoid cystic carcinoma.
Often has apocrine morphology.
Polymorphous adenocarcinoma occurs almost exclusively in. . .
. . . the intraoral minor salivary glands
You won’t find it in the parotid.
DDx for oncocytic lesions of the salivary gland
Warthin tumor
Oncocytoma
Oncocytic cystadenoma
Oncocytic acinic cell carcinoma
General approach to salivary neoplasms
Clusters of salivary neoplasms
Oncocytic adenoma/carcinoma (distinction made based on histologic behavior, Ki67 index).
A rare form of salivary gland lesion, often arising from the parotid gland.
To make this diagnosis, you must also do a mucicarmine stain to rule out an oncocytic mucoepidermoid carcinoma.
IHC: p63, EMA positive, S100 variable.
Negative for myoepithelial markers (GFAP, CEA).
Canalicular adenoma
Rare tumor, typically of the upper lip in an older female.
Monotypic tumor with thin cords (1-2 layers) of cells on a myxoid, vascular stroma – but NOT epithelial/myoepithelial. Diffusely S100+, GFAP+ at periphery/lumen.
No known malignant counterpart – this is benign.
PAS with Diastase
PAS stains both mucin and glycogen
However, adding diastase (basically amylase) will digest the glycogen, leaving behind only the stained mucin. Zymogen granules will also remain.
This stain is useful for differentiating squamous cell versus mucoepidermoid carcinoma with squamous differentiation.
Polymorphous adenocarcinoma
Most commonly arise from the palate. Good prognosis – PNI may be present, but rarely metastasizing (unless cribriform)
Single cell type with pale, oval, vesicular nuclei (like adenoid cystic carcinoma), but various architectural patterns: single file, whirling, lobular, papillary, cystic, cribriform, trabecular, ductal
Infiltrative growth pattern, often with perineural invasion. S100+, p40-.
-> Here, p40- is key to rule out pleomorphic adenoma and adenoid cystic carcinoma.
Genetics: PRKD1 mutation
Polymorphous adenocarcinoma - cribriform variant
Requires at least 30% cribriform architecture.
More aggressive than most polymorphous adenocarcinoma – frequent nodal metastases.
Mostly arises from the tongue or minor salivary glands. Papillary thryoid cancer-like (Orphan Annie) nuclei are a defining feature.
Genetics: PRKD1,2, or 3 rearrangements
Acinic Cell Carcinoma
80% arise in the parotid gland, 16% of cases with death or early metastasis
Resemble serous acinar cells, but grow in sheets without ducts or fat. May or may not have a lymphoid stroma. Cells have a granular cytoplasm with PAS+ and diastase-resistant granules. (Picture with normal parotid on left, tumor on right)
Generally low grade, but aggressive features include:
>2/10 mitoses, necrosis, LVI, PNI, pleomorphism, de-differentiation/high-grade transformation
Genetics: NR4A3, MSANTD3
Secretory carcinoma (salivary)
Analogue of the breast secretory carcinoma. Also carries the same translocation: ETV6::NTRK3. 70% arise from the parotid.
Generally low-grade, slow-growing, and painless. But, can undergo high-grade transformation.
Histology: Bland, monotonous cells in a microcystic architecture with intraluminal secretions. Lacks zymogen granules. Diffusely S100+ and mammoglobin+.
Salivary ductal carcinoma
Always high grade, resembles high-grade DCIS. Androgen receptor+, sometimes with Her2/NEU amplification, and can often be treated with androgen antagonists. Always ER/PR negative (positivity would suggest breast metastasis).
Like high-grade DCIS, large nests of apocrine-like cells with peripheral cribriforming and central necrosis.
May arise de-novo or out of a pleomorphic adenoma.
Intraductal carcinoma (salivary)
Resembles low-grade DCIS/ADH. This is NOT considered a variant of salivary ductal carcinoma. Excellent prognosis.
Bounded by a myoepithelial layer. Cribriform, papillary, or solid growth pattern. S100+.
Epithelial-Myoepithelial Carcinoma
Rare, but with striking histologic features. 14% metastasize, 10% death rate.
Bi-layered tubules with clear myoepithelial cells, sometimes with solid areas of myoepithelial cells punctuated by small, pink ducts.
Genetics: HRAS mutation in ~25-35%
Clear cell carcinoma (salivary)
Formerly “hyalinizing” CCC. Can have stromal hyaline, but doesn’t have to.
Monomorphous clear cells with wrinkled nuclei. Bands of (sometimes hyalinized) septae punctuating.
Positive stains: Keratin, HMWK, p40, p63
Negative stains: S100, GFAP, SMA, calponin
Genetics: EWSR-ATF1 translocation.
“Looks like a myoepithelial carcinoma, stains like a squamous cell carcinoma”
Salivary ductal carcinoma ex pleomorphic adenoma
The pleomorphic adenoma here is the loosely organized purple tumor with gray myxoid stroma on the right. The loosely organized ductal elements to the right are vacuolar and pleomorphic on high power.
Lymphoepithelial cyst
Cystic dilation of the salivary gland ducts, associated with HIV or autoinflammatory disease (ex, Sjogren’s, RA). Painless, unilocular mass within or adjacene to the salivary gland. Sporadic/rheum are usually unilateral, HIV frequently bilateral.
Lymphoid stroma (frequently with follicles), epithelially-lined unilocular cyst.
Rhinosporidiosis
Fungal infeciton of the nasal mucosa. Causes nasal discharge. Has a coccidoimycosis-like appearance on histology.
Low-grade polymorphous adenocarcinoma:
Looks like pleomorphic adenoma, but with clear invasion of the surrounding fatty tissue.
Mucoepidermoid carcinoma, epidermoid type
Adenocystic carcinoma
High-grade salivary ductal carcinoma
This was in the parotid gland based on surrounding serous salivary glands and a section of the facial nerve was present adjacent to the tumor. Be mindful and be wary of perineural invasion in parotid tumors!
Basal cell adenocarcinoma, well-differentiated
Cystic papillary acinic cell carcinoma
Chronic sialoadenitis
Note that there is a mucoid/myxoid stromal background similar to pleomorphic/polymorphous, however the salivary elements are arranged in well-formed ducts and acini and are well-differentiated.
The lymphoid infiltration with lymphoid follicle formation is a tip-off.
Remember:
Minor gland - Sjogren’s
Major gland - RA
Myoepithelioma, head and neck-type
May be spindle cell type or epithelioid type. Spindle cell types have some myxoid stroma as well.
Caused by translocations involving PLAG (NTF3-PLAG1, FBXO32-PLAG1 and GEM-PLAG1). “Soft tissue type” myoepitheliomas are clear cell morphology and caused by EWSR1 rearrangements. Rarely you can see these in the head and neck as well.
Note: Plasmacytoid myoepitheliomas may be negative or only variably positive for myoepithelial markers, so have a high suspicion.
Oral Hairy Leukoplakia
Characterized by acanthosis and parakeratosis. “Balloon cells” (cells with ballooning degeneration) are present in the spinous layer. Other viral cytopathic effect, including eosinophilic nuclear inclusions, is present.
Otherwise, there is little to no inflammation or dysplasia.
Caused by EBV, so order an EBER ISH to confirm.
Most often occurs on the lateral tongue in an immunocompromised individual (classic AIDS question).
Geographic tongue (aka benign migratory glossitis)
Grossly, appears as multiple, well-defined erythematous islands with raised white serpiginous borders that rapidly appear and migrate (shown).
Microscopically, the tongue has epithelium with hyperkeratosis, acanthosis, spongiosis, and Monro microabscesses (collections of PMNs). Acute and chronic inflammation will be present in the lamina propria.
This is an idiopathic inflammatory lesion on the tongue that is often asymptomatic. It usually occurs in females in the 10’s or 20’s.
Pyogenic granuloma
Grossly, appears as a bright red nodule, on the skin or mucosa.
Microscopically, displays mucosal ulceration with underlying mixed inflammatory cells. Vessels are arranged in a lobular pattern with dividing fibrous septae, and are often engorged with RBCs. Mitoses are pretty common, so the classic mistake is to call this an angiosarcoma or similar vascular neoplasm.
Importantly, this is a MISNOMER. There is no granuloma in pyogenic granuloma.
Caused by biting/trauma and poor oral hygiene (in the mouth). More frequent in the gingiva than the skin. Occurs more frequently in females (especially pregnant females), and usually in the 20’s-30’s.
IHC: SMA+, MSA+, CD31+, CD34+, Factor VIIIR antigen +
Epulis, aka congenital granular cell tumor
Clinically, occurs as a flesh-colored mass (which can be quite large and obstructive) on newborns, mostly on the alveolar ridge, then spontaneously regresses within the first year of life. Does not recur if completely excised. Predominantly occurs in females.
Histologically, shows atrophic squamous mucosa (the opposite of pseudoepitheliomatous hyperplasia!) overlying the tumor. The tumor is composed of polygonal cells with small nuclei, eosinophilic granular cytoplasm, and indistinct cell borders (similar to your regular granular cell tumor). A delicate meshwork of blood vessels flows through.
IHC: Vimentin +, acid phosphatase +, laminin +, Leu7+, NSE+, S100 NEGATIVE
Note that while the adult tumor is S100+, this one is S100 negative.
Hallmark features of adult granular cell tumor
- Pseudoepitheliomatous hyperplasia
- Pustulo-ovoid bodies of Milan (coarse granules which represent fused aggregates of phagolysosomes), shown
Proliferative verrucous leukoplakia
Clinically,
Most common in the gingiva, alveolar mucosa, and palate. Mostly seen in older females. Slow growing, and often becomes multifocal over time.
Microscopically starts as a localized, flat, hyperorthokeratosis. As it ages, it progresses to verrucous hyperorthokeratosis. Often has a lichenoid interface mucositis. This lesion is entirely exophytic and should not be endophytic – no downgrowth of the rete ridges.
Eventually, dysplasia develops and can progress to SCC or VC.
Verrucous squamous cell carcinoma
Important to recognize, as this behaves very differently to conventional SCC. It is analogous to a well-differentiated SCC, however it is only LOCALLY destructive and invasive with a pushing border, and it will not metastasize.
Diagnosis often requires comparison to normal to demonstrate the pushing border, and so it can be hard to diagnose on a small biopsy. It is good to consider this when you are clinically concerned for malignancy, but the biopsy looks benign.
Histologically, characterized by dramatic acanthosis and marked church spire keratinization without significant cytologic atypia. There is a proliferative basal cell layer only 1-2 cells thick, and rare mitoses are confined to this layer. There will be associated lymphocyic inflammation below the epithelium.
Spindle cell squamous cell carcinoma
70% present as a polypoid skin or mucosal mass. Often seen in those older than 50 years of age, more in men than women. Very aggressive neoplasm, with a life expectancy <2 years.
SCC variant with predominantly spindle cells or pleomorphic cells (so, sarcomatoid). Usually the spindle cells form a storiform pattern or short, interlacing fascicles.
Metastases have a highly variable morphology, which can be a diagnostic pitfall.
IHC: 50% keratin positive, variably expresses mesenchymal markers (actin, desmin)
Basaloid Squamous Cell Carcinoma
Uncommon and aggressive form of SCC – most are metastatic at the time of diagnosis. Nearly all of them occur in older male patients with a history of smoking or alcohol use.
Basaloid squamous cells in rounded nests with peripheral pallisading and admixed hyalinized stroma. Hyperchromatic appearance with high N:C ratio. Frequent mitoses and comedonecrosis.
This form of SCC is never associated with HPV.
Should be included in the differential for basaloid salivary neoplasms – this can look a LOT like adenoid cystic carcinoma.
IHC: SOX10+, diffuse p40/p63+, EMA+, CAM5.2+, CK34 beta E12+
Papillary squamous cell carcinoma
Rare variant. May infrequently be associated with HPV, but usually HPV independent.
Exophytic, papillary growth of squamous cells with thin fibrovascular cores. Papillae are entirely covered by severely dysplastic basaloid cells. At least 70% of the tumor must be papillary to make this diagnosis.
Lymphoepithelial carcinoma
Usually in older men, often metastatic at time of diagnosis. Often with a component of conventional SCC. Sometimes EBV-associated.
Composed of sheets and cords of polygonal, large, syncytial cells with eosinophilic cytoplasm and vesicular nucleoli, with scattered spindle cells and an abundant lymphoplastmacytic infiltrate.
IHC: p53 mutant, EBV +/-
Multifocal epithelial hyperplasia, aka Heck’s disease
Multifocal benign squamous proliferations of the oral cavity. Often located on the lips or buccal mucosa, presenting as multiple papules (shown). Common in children/adolescent girls.
Caused by HPV 13 or 32.
Histologically, mild hyperkeratosis, prominent acanthosis, normal cell maturation. “Mitosoid” figures are the pathognomonic hallmark (shown in boxes). May show rare koilocytes.
Squamous papilloma
Usually solitary papillary lesions, caused by HPV 6 and 11. Transmitted through sexual or non-sexual contact. Malignant transformation is extremely rare. If multiple, especially if young, consider recurrent respiratory papillosis instead.
Characterized by exophytic squamous proliferation with branching fibrovascular cores. Koilocytes may be present, but are not a required feature.
Squamous cell carcinoma, HPV positive
> 90% due to HPV16. Significantly better prognosis than conventional SCC. Strong predeliction for the oropharynx. Often presents at a high clinical stage, with an occult primary and lymph node metastases.
GRADING IS NOT APPLICABLE.
Histologically, non-keratinizing squamous cells with a high N:C ratio and basaloid look. Mitoses and apoptoses are common, and a thick lymphoid stroma is always present. There will be no recognizable in-situ component, as this is virally driven and not derived from a dysplastic field.
IHC: p16 block positive, HPV ISH positive, CK5/6 positive
Mycobacterial spindle cell pseudotumor
Almost exclusively seen in HIV. Presents as a firm mass arising from a lymph node.
Microscopically, composed of dense spindle cells arranged in a storiform pattern, effacing lymph node architecture. AFB reveals abundant M. avium-intracellulare.
IHC: CD68+, vimentin +, S100 +/-, desmin +/-, SMA +/-, CD31 neg, CD34 neg
Localization of the 10 major jaw lesions
Myoepithelioma
Most common in the 20’s-40’s, with equal sex distribution. Presents as a painless, slow growing mass.
Nearly 60% grow in the parotid, the remaining 40% in the hard/soft pallate.
Well-circumscribed tumor, with or without a capsule. Lacks any evidence of infiltrative borders, perineural of lymphovascular invasion, pleomorphism, or mitotic activity.
Background stroma is variale, and may have abundant myxoid, myxochondroid, or chondroid changes. Cells are myoepithelial cells that may be spindled, epithelioid, or plasmacytoid. Plasmacytoid forms will have round-to-oval hyperchromatic nuclei and abundant eosinophilic cytoplasm.
IHC: CK7+, calponin+, p40+, p63+, GFAP +, S100+, various actin +, PLAG1+/-
Molecular will lack PLAG1, but IHC for PLAG1 may be confusingly positive. Instead, EWSR1 fusions are the most common etiology, followed by FUS fusions.
This is a major differential diagnosis for pleomorphic adenoma, so just beware as you are working up pleos.
Sinonasal inflammatory polyp
Seen most commonly in allergic rhinosinusitis, usually in adults with rhinorrhea, nasal obstruction, or headaches.
Polyps originate from the lateral nasal wall or ethmoid recess. Despite appropriate surgical management, 50% of patients will have recurrence. This frequency is higher in those with asthma or aspirin intolerance.
Histologically, polyp lined by benign ciliated respiratory epithelium. The underlying stroma is edematous and has mixed chronic inflammatory cells (eos, lymphocytes, plasma cells), but should not have acute inflammation. Vessels may be ectatic within the lesion. No seromucinous glands are present within the polyp.
Secondary changes that may appear on polyps include squamous metaplasia, ulceration, fibrosis, infarction, granulation tissue, osseous or collagenous metaplasia, and amyloid-like deposition within the stroma.
Facial ducts and sinuses
Respiratory epithelioid adenomatoid hamartoma
Most commonly occurs in adults in the 6th decade of life, with no sex predilection. Patients usually present with 1 or more symptoms that may include nasal stuffiness, obstruction, right sinusitis, or epistaxis.
The main treatment is curative surgical resection.
Microscopically, composed of invaginated sinonasal glandular epithelium arising from the surface epithelium. Small-to-medium-sized glands with hyalinized intervening stroma and peripheral thick eosinophilic basement membranes are present. Glands are lined by respiratory epithelium, and may have squamous or osseous metaplasia and hyperplasia. Stroma may contain mixed chronic inflammatory cell infiltrate.
The major DDx are sinonasal hamartoma and adenocarcinoma.
IHC: Epithelium negative for CDX2 and CK20. Myoepithelial cells positive for p63 and S100.
Sinonasal seromucinous hamartoma
Submucosal proliferation of small glands or acini in tubules that grow in lobuiles or clusters, arranged in a haphazard configuration. Stroma may be dense and sclerotic to myxoid.
Importantly, myoepithelial/basal cells MAY BE ABSENT, however this is not an invasive lesion, and should not lead to a diagnosis of low-grade sinonasal adenocarcinoma. p63 will highlight only scattered abluminal cells in proliferating ducts (shown). No cytologic or architectural features of malignancy should otherwise be present.
Sinonasal/Schneiderian Papillomas
Nasal glial heterotopia
Most commonly seen in infancy, with an even sex distribution. Thought to be a congenital developmental defect in which the frontal lobe does not completely retract into the cranial cavity.
Further classified into subtypes by location:
* Extranasal: Most common. Lesion arises in the subcutaneous soft tissues of the nasal bridge, presents as a firm subcutaneous nodule.
* Intranasal: Lesion arises in the superior nasal cavity and presents as a polypoid mass which may cause obstruction.
* Mixed: Both components
Histologically, a glial fibrillary network within the sinonasal connective tissue. Neuroglial tissue can present in nests or sheets, may have a few gemistocytes. Rarely, choroid plexus, ependymal, or retinal pigmented cells may be seen. The overlying epidermis/mucosa is undisrupted. No meningeal layers or neurons should be present.
Major ddx is encephalocele, but this would show the presence of meningeal layers and possibly neurons.
IHC: GFAP and S100 to highlight glial cells. Trichrome can also be helpful, as it will stain glial tissue red while it will stain fibrous collagen blue.
Rhinoscleroma
A reactive pseudotumor to Klebsiella rhinoscleromatis.
Most commonly in the 10’s-20’s, female predominance, endemic in Egypt, India, Central America, Eastern Europe.
Klebsiella rhinoscleromatis is a non-motile, encapsulated, gram-negative bacillus. It can be cultured on MacConkey agar, and is susceptible to tetracyclines and fluoroquinolones.
Histologically, composed of expansile sheets of plasma cells (which may be Mott cells or have Russell bodies) and foamy histiocytes (Mikulicz cells) which will be filled with bacilli. Pseudoepitheliomatous hyperplasia may be present, and mucosal ulceration, submucosal cysts containing keratin, or vasculitis may be present. To stain organisms, Warthin Starry is most sensitive.
Progresses through clinical and histologic phases:
Catarrhal (rhinitic)
Proliferative (granulomatous)
Cicatrical (fibrosing/scaring)
Glomangiopericytoma
Rare sinonasal neoplasm most often found in elderly females. Presents as an obstructing mass (difficulty breathing, rhinorrhea).
Histologically, the surface is covered by benign respiratory epithelium. The submucosa contains a “patternless pattern” of spindled to epithelioid cells with ovoid nuclei, coarse chromatin, and amphophilic-to-eosinophilic cytoplasm without distinct borders. The spindled cells have a diffuse cellular or syncytial arrangement. There is a “Grenz” zone of clearing between the surface epithelium and stroma. Vessels are staghorn-like with perivascular hyalinization. Extravasated erythrocytes, eos, and mast cells are present.
Rarely associated with oncogenic osteomalacia (high serum AlkPhos and hypophosphatemia with normal PTH and calcium).
Prognosis is excellent. Recurrence in 33% of cases that have bone invasion or nuclear pleomorphism.
IHC: Nuclear beta catenin +, LEF1 +, SMA+, cyclin D1+, CD31 neg, CD34 neg, Factor VIIIR antigen neg
Molecular: Single nucleotide substitution in exon 3 of CTNNB1. Results in constitutively active beta catenin.
Nasopharyngeal angiofibroma
Rare, benign lesion that is most often seen in young-to-adolescent males. Patients present with chronic, recurrent epistaxis, obstruction, diplopia, tinnitus/deafness, or headaches. Most often seen in the posterolateral nasopharynx.
Histologically, characterized by a rich fibrocollagenous stroma with prominent vascularization with variably sized, slit-like blood vessels (somewhat resembling those of SFT) as well as a network of small, delicate capillaries that may be ectatic and contain attenuated-to-plump endothelial cells. Mast cells seen frequently throughout. Rare mitotic figures may be present.
The stroma may develop myxoid change following an embolization procedure, if performed. Don’t let this fool you into thinking it is myxoid liposarcoma, as this is another lesion with a delicate network of vessels (although in MLS they are even finer than angiofibroma).
Associated with FAP syndrome.
Prognosis is good with surgical management, but recurs in 25% of cases, usually in the first 2 years.
IHC: Stromal cells AR+, nuclear beta catenin +, SMA neg, desmin neg, CD34 neg
Sinonasal adenocarcinoma (non-intestinal type), low grade
No association with any exposures. Low-grade is most common in the ethmoid sinus with equal sex distribution (this has an excellent prognosis at 5 years, may recur in 25%, but rarely metastasizes).
Histologically, low-grade is composed of monotonous, bland cuboidal cells with round, basally located nuclei, eosinophilic cytoplasm, arranged in a cribriform pattern.
IHC: CK7+, S100+, SOX10+, DOG1+, CK20 neg, CDX2 neg, villin neg
Sinonasal adenocarcinoma (non-intestinal type), high grade
Typically seen in elderly males in their 50’s-60’s, no association with any exposures. High-grade is most common in the maxillary sinus with male predominance (poor prognosis, only 20% survival at 3 years, 33% with metastasis).
Histologically, high-grade is composed of epithelial cells with pleomorphic nuclei, prominent nucleoli, variable chromatin patterns, eosinophilic cytoplasm, and frequent mitoses and apoptoses. There is often a destructive growth pattern with invasion into nerves, vessels, lymphatics, and adjacent structures.
IHC: CK7+, S100+, CK20 neg, CDX2 neg, villin neg
Sinonasal adenocarcinoma (intestinal type)
Most common in adults in the 5th decade of life, usually in the ethmoid sinus or nasal cavity. Males usually have a history of exposure to wood-dust or leather-dust particulates. 10% have bilateral tumors. This cancer is locally aggressive, with a 60% 5 year survival rate and a high rate of recurrence. Metastasis is present in ~10% of cases.
Malignant epithelial cells have a variety of morphologies and configurations, but all are similar to those seen in the GI tract. Colonic-type with tubuloglandular architecture and “dirty necrosis” is most common. Papillary, solid, and mucinous (encompassing solid/glandular/signet ring/papillary mucinous) make up the rest.
IHC: CDX2+, CK20+, villin +, MUC2+, MUC4+
Sinonasal undifferentiated carcinoma
Rare carcinoma with male predominance and a wide age distribution. Has rapid onset of nasal symptoms , visual disturbance, and pain. Grows aggressively and occurs within multiple contiguous sites. Outcomes are poor.
Histologically, composed of monotonous polygonal epithelial cells with oval vesicular to hyperchromatic nuclei, inconspicuous to conspicuous eosinophilic nucleoli, and eosinophilic cytoplasm. Poorly defined borders. Malignant cells are arranged in various patterns (solid, trabecular, sheets, organoid, lobular, or ribbon-like). Necrosis and abundant mitoses are common. LVI and PNI are common.
This is a high grade, undifferentiated neoplasm, and is ultimately a diagnosis of exclusion. First, you have to exclude the more differentiated entities that can look like this (namely SCC, non-intestinal sinonasal adenocarcinoma, nasopharyngeal carcinoma), then you have to exclude the other undifferentiated entities (NUT carcinoma, SMARCB1 deficient, etc).
IHC: Positive for cytokeratin, negative for squamous markers, positive for IDH2 R172T (there is an antibody for this!)
Molecular: IDH2 R172 mutations are present in most cases
