Head and neck pathology Flashcards
70M, cheek lesion. PHx smoker
Dx:
Key features:
Warthin’s tumour (of parotid).
aka papillary cystadenoma lymphomatosum.
Well-circumscribed, papillary tumour.
MIcro: Double layer of oncocytic epithelial cells lining papillary/cystic structures + lymphoid component.
Name the three types of nasal papillomas
Inverted, oncocytic, exophytic
nasal lesion.
Dx?
Key features?
Sinonasal papilloma, inverted type
Predominantly endophytic non-destructive growth; ribbons/nests of hyperplastic, immature squamous epithelium; transmigrating intraepithelial neutrophilic inflammation.
Right nasal septum lesion
Dx?
Key features?
Sinonasal papilloma, oncocytic type
Essential: mixed exophytic and endophytic growth pattern; oncocytic cells with cuboidal to columnar morphology; intraepithelial microcysts with mucin and/or neutrophilic microabscesses.
nasal lesion.
Dx?
Key features?
Sinonasal papilloma, oncocytic type.
mixed exophytic and endophytic growth pattern; oncocytic cells with cuboidal to columnar morphology; intraepithelial microcysts with mucin and/or neutrophilic microabscesses.
left lower nasal septum lesion
Dx?
Key features?
Essential: proliferative, exophytic, and papillary growth; lined by a multilayered sinonasal-type epithelium; no high-grade squamous dysplasia; no inverted or destructive infiltrative growth.
Scattered intraepithelial neutrophils are common
mandibular biopsy
Dx?
Key features?
ameloblastoma, conventional
Essential: location in jaws; islands/strands of odontogenic epithelium bounded by cuboidal/columnar cells with palisaded, hyperchromatic nuclei; reverse polarity (less marked in plexiform pattern); loose central epithelium resembling stellate reticulum; no cytological atypia
Ameloblastoma of follicular pattern, with acanthomatous change in the la
Ameloblastoma (conventional), key features and subtypes
Key features: Essential: location in jaws; islands/strands of odontogenic epithelium bounded by cuboidal/columnar cells with palisaded, hyperchromatic nuclei; reverse polarity (less marked in plexiform pattern); loose central epithelium resembling stellate reticulum; no cytological atypia
Subtypes: Follicular, plexiform, acanthomatous, granular, basaloid, desmoplastic
pleomorphic adenoma
common mutation
70% of tumors show either PLAG1 or HMGA2 rearrangements
Left cheek excisional bx
Dx:
Key features:
IHC:
Dx: Pleomorphic adenoma.
The classical histologic features are seen, with a chondromyxoid matrix blending imperceptibly with the myoepithelial cells and showing small ducts in the background.
PA are well-delinated/encapsulated and composed of an admixture of epithelial, myoepithelial (bilayered ducts) and mesenchymal components (stroma). The stroma can be mucoid, myxoid, hyalinized, chondroid, osseous or lipomatous. The MEC can be spindled/oncocytic/basaloid/plasmacytoid etc..
IHC: PLAG1 and HMGA2 respectively, are emerging as sensitive, and specific IHC markers for pleomorphic adenoma.
Immunoexpression of S100 and SOX10 helps to differentiate oncocytic PA from other oncocytic tumours
28F rapidly growing gingival lesion
Dx?
Key features?
Giant cell epulis
Nonencapsulated aggregates of foreign body giant cells and fibroangiomatous stroma with hemorrhage, hemosiderin, acute and chronic inflammatory cells Alveolar bone often expanded in edentulous patients, leading to superficial bone loss with peripheral cuffing Variable mitotic activity
neck lesion
Dx
Key features
DDx:
Thyroglossal duct cyst
Essential: Perihyoidal location
Desirable: Midline lesion; respiratory or squamous lined cyst with associated thyroid follicular epithelium
Differential Diagnosis: The entities include epidermal inclusion cyst, dermoid cyst, branchial cleft cyst, bronchogenic cyst, cervical thymic cyst, and metastatic PTC, which can usually be separated based on anatomic site of involvement, imaging findings, and pertinent histologic features.
Medullary thyroid carcinoma
Essential and desireable dx features
IHC profile:
Essential: Primary non-follicular cell-derived thyroid tumour with morphologic and immunohistochemical features of neuroendocrine derivation including expression of calcitonin and/or CEA.
Desirable: Lack of expression of thyroglobulin
IHC: Calcitonin (+; 95%); CEA (+), SYN/Chromo/NSE/INSM1 (+); TTF1(+); Thyroglobulin (-; calcitonin-gene-related-peptide (+)
thyroid lesion
dx?
IHC
Medullary thyroid carcinoma
IHC: calcitonin(+); CEA(+); chromo/synapt/NSE/INSM1(+); variable/(-) PAX8; TTF1(+)
adenoid cystic carcinoma
architectural patterns:
What to look out for?
Common molecular event:
cribriform, tubular and solid
For solid, minimum 30% solid growth req’d
PNI!
Many have t(6;9) chromosomal translocation resulting in MYB::NFIB fusion
MYB::NFIB fusion in 50-70% MYBL1::NFIB fusion in up to 15% MYB or MYBL1 gene fusions are detected in > 90% of ACC Upregulation of MYB gene seen in fusion-negative cases
femal mouth lesion
Dx and features:
Key feature displayed in image
Polymorphous adenocarcinoma
Unencapsulated, although well circumscribed
Infiltrative growth
Incarcerated minor salivary glands
Significant perineural invasion
Striking variety of growth patterns
Eye of storm or whorled appearance
Concentric layering of cells around central nidus, creating targetoid tableau
Uniformly bland, round to polygonal or fusiform tumor cells
Slate blue-gray stroma usually only focal
Mitoses are infrequent
DDx: adenoid cystic ca: Nuclei are peg-shaped, carrot-shaped, or angular, with hyperchromasia; cribriform architecture more common; Ki67 usu higher in PAC
Image: Native minor mucous glands are surrounded , but not destroyed, by the neoplastic infiltrate. This encasement or entombment is quite characteristic of PAC. This does not represent mucinous differentiation in the neoplastic cells.
Below: The neoplastic cells are separated by a characteristic slate blue-gray stroma
palate lesion
dx:
Key histo features
ddx:
px:
polymorphous adenocarcnoma, low-grade subtype
typically involve minor salivary glands (60% palate)
Unencapsulated, infiltrative growth (incarcerate minor salivary glands), Striking variety of growth patterns
Eye of storm or whorled appearance Concentric layering of cells around central nidus, creating targetoid tableau
Slate blue-gray stroma usually only focal
Mitoses are infrequent
The neoplastic cells are separated by a characteristic slate blue-gray stroma . Reduplicated basement membrane material is also seen. The typical chondroid or myxochondroid stroma of pleomorphic adenoma is not seen in PAC.
Ddx: pleomorph adenoma, basal cell adenoma/carcinoma, adenoid cystic carcinoma (nuclei peg-shaped/carrot shaped;Ki67 usu higher)
Px: excellent long-term
cholesteatoma
key features
Keratinous material (keratin flakes; dead, anucleate keratin squames)
Stratified squamous epithelium with granular layer
Inflamed stroma with fibrous connective tissue
buccal lesion
dx
Key features
Irritation fibroma
Site: Most common along the bite line on the buccal mucosa (may be bilateral)
Also seen on the labial mucosa, tongue, palate and gingiva
Nonencapsulated nodular mass
Mass composed of fibrous connective tissue with collagen bundles interspersed with fibroblasts, blood vessels and scattered chronic inflammatory cells
Overlying surface of squamous epithelium
posterior nasal septum lesion
dx
key features
Respiratory epithelial adenomatoid hamartoma (REAH)
Proliferation (often polypoid) of medium sized glands lined by ciliated epithelium
Glands are surrounded by thick eosinophilic basement membranes
Lesion replaces background normal elements, often resulting in a decreased number of seromucinous glands
Features of chronic rhinosinusitis (chronic inflammation) and inflammatory sinonasal polyp
(edematous stroma admixed with chronic inflammation) may be seen in the background
Image: glands with cilia (green arrow) and thickened basement membrane
secretory ca (of parotid)
mutation?
IHC?
Harbours ETV6::NTRK3 or ETV6::RET fusion in most cases.
t(12;15) (p13;q25)
IHC: S100 and mammaglobbin (cyto +) (+)
cheek excision
dx?
Dx criteria
DDx and how to differentiated?
Key features demonstrated?
Molecular?
Secretory carcinoma
Essential: single cell type with vacuolated colloid-like secretory material; no zymogen cytoplasmic granules; IHC positivity for S100 protein, SOX10, and mammaglobin; lack of IHC staining for p40 and/or p63
Desirable: ETV6 or RET rearrangement demonstrated by FISH, RNA sequencing, or PCR
DDx: acinic cell carcinoma. In contrast to SC, acinic cell carcinomas demonstrate intense apical membranous staining for DOG1 around lumina and variable cytoplasmic positivity in most cases. Unlike acinic cell carcinoma, SC does not show true PAS-positive secretory zymogen cytoplasmic granules.
Approximately 90% of SC harbour a characteristic chromosomal rearrangement, t(12;15) (p13;q25) resulting in an ETV6::NTRK3 fusion
The tumour cells of SC have low-grade vesicular nuclei with finely granular chromatin and distinctive centrally located nucleoli, surrounded by pale pink granular or vacuolated cytoplasm.
Most common site of polymorphous adenocarcinoma?
Soft palate.
95% involves minor salivary glands
polymorphous adenocarcinoma
Molecular alteration?
Detection of PRKD1 p.Glu710Asp hotspot mutation or translocation of one of the PRKD1, PRKD2 or PRKD3 genes is highly specific for the diagnosis of PAC
soft palate lesion
Dx?
IHC?
Molecular?
Key features identified?
px?
Polymorphous adenocarcinoma
IHC: + for cytokeratins (e.g. CK7, in 100% of cases); + S100 protein (97% to 100%). Staining for p63 is reported in 78% to 100% of cases, whereas p40 is typically negative; this pattern is helpful in the differential diagnosis. Mammaglobin (+) (67% to 100%), CD117 (60%).
Molecular: Detection of PRKD1 p.Glu710Asp hotspot mutation or translocation of one of the PRKD1, PRKD2 or PRKD3 genes is highly specific for the diagnosis of PAC
The overall prognosis of PAC is excellent with a 10-year disease specific survival of 94 to 99%
Image: Various patterns, including tubules, trabeculae, microcysts, and cribriform architecture, are seen with a mucoid/myxoid background. The tumour is often arranged in a targetoid or streaming fashion in the periphery or around nerves.
polymorphous adenocarcinoma
subtypes + brief description
AC, the conventional subtype is typically an unencapsulated submucosal mass. The tumours are characterized by cytological uniformity, histological diversity, and an infiltrative growth pattern. Neoplastic cells are uniform in shape, with scant cytoplasm, bland oval nuclei, open chromatin, occasional small nucleoli and nuclear grooves.
PAC, cribriform subtype/cribriform adenocarcinoma of salivary gland (CASG). CASG is characterized by a multinodular growth pattern separated by fibrous septa, relatively uniform solid, cribriform and microcystic architecture, and optically clear nuclei. Glomeruloid and papillary structures, peripheral palisading and clefting is typically observed. CASG is associated with a propensity to base of tongue location, higher risk of lymph node metastasis, and higher frequency of PRKD gene rearrangement
base of tongue lesion
Dx?
Key features demonstrated
Polymorphous adenocarcinoma, cribriform subtype
Numerous patterns, with easily identified papillary structures and glomeruloid bodies. The nuclei show open chromatin. Fibrous connective tissue stroma is present.
adenoid cystic carcinoma vs polymorphous adenocarcinoma
localisation
Approximately 60% of AdCCs occur in the major and 30% in the minor salivary glands { 26476712 }. The parotid, submandibular, and minor glands of the palate are the predominant sites
vs
Over 95% of PAC involves minor salivary glands or seromucous glands of the upper aerodigestive tract with the palate being the most common site
adenoid cystic carcinoma
Key histo features
Growth patterns
High-grade features:
two main cell types, ductal and myoepithelial cells. The former cell type has eosinophilic cytoplasm and uniform round nuclei, and the latter has clear cytoplasm and hyperchromatic angular nuclei. Mitotic figures are infrequent. Perineural invasion is a hallmark of AdCC. Identification of both pseudocysts and true glandular lumina is usually required to make the diagnosis.
AdCC shows three growth patterns, tubular, cribriform, and solid.
High-grade features: Generally, AdCCs with >30% solid component pursue a more aggressive clinical course. In recent studies, the presence of any solid tumour component has been emphasized as an objective high-grade tumour marker
adenoid cystic carcinoma
Molecular
Demonstration of MYB/MYBL1 rearrangements or gene fusions by FISH or other methods can help establish a diagnosis of AdCC
adenoid cystic ca
IHC &
dx criteria
Pan-cytokeratin is strongly positive in ductal cells and weakly positive in myoepithelial cells. CK7 and KIT (CD117) are typically positive in ductal cells { 16140564 }, whereas p63, p40, calponin, and alpha-smooth muscle actin are positive in myoepithelial cells.
Essential: hyperchromatic, angulated nuclei, mixture of tubular, cribriform, and solid patterns associated with basophilic matrix and reduplicated basement membrane material.
Desirable: Perineural invasion; demonstration of MYB or MYBL1 rearrangements in selected cases
pleomorphic adenoma
Three components
Common gene rearrangement
- ductular structures
- myoepithelial cells (can be spndled, epithelioid, plasmacytoid, etc..), intimately adixe with stroma
- Mesenchymal-like tissue (often myxoid stroma, but can be chondroid, etc…)
- architecturally pleomorphic (cytologically blandd)
PLAG1-HMGA2 fusions very common
mucoepideroid carcinoma
Grading (AFIP)
PARAMETER
Intracystic component <20% +2
Neural invasion present +2
Necrosis present +3
Four or more mitoses per 10 HPF +3
Anaplasia +4
Low grade 0-4
Intermediate grade 5-6
High grade 7 or more
cheek lesion
dx:
Key histo features
IHC
Molecular
Secretory carcinoma
Low-grade neoplasm; indolent malignancy
Wide age range: 21-75 yrs
Histo: infiltrative tumor border, fibrous septae, ..tumor cells charactersitically ahve an eosinophilic, vacuolated (bubbly) cytoplasm with round nuclei and minimal atypia, Abundant bluish to deep pink intraluminal secretions are usually present. mitoses are rare
IHC: strongly S100 +, SOX10+, mammaglobin +; (-) p40/63, DOG1,
Molecular: Approximately 90% of SC harbour a characteristic chromosomal rearrangement, t(12;15) (p13;q25) resulting in an ETV6::NTRK3 fusion
65M rapidly growing cheek mass, facial paralysis
dx
Key features
IHC
px
salivary duct ca
Micro: Infiltrative lesion resembling DCIS with cribriform pattern is present (similar to breast ductal ca) +/- comedo-type necrosis. Invasive cells -> large cells with abundant eosinophilic cytoplasm and large, round nuclei with vesicula rchromatin and prominent nucleoli.
IHC: low/high CK, CEA, AR, HER2.
DDx: metastatic breast ca;
42M cheek mass
dx
aetiology
ddx
diagnostic molecular path:
Lymphoepithelial carcionoma
EBV
Key features: nests of large anaplastic carcinoma cells within a lymphoid stroma.
LEC must be distinguished from large cell undifferentiated carcinoma, and metastasis from nasopharynx
EBERish
rapidly growing cheek lesion
dx
key features
Subtypes:
IHC
Salivary duct carcinoma
Resembles mammary ductal carcinoma, most typically with apocrine (immuno)phenotype.
Display complex solid, cribriform, and papillary-cystic architecture with frequent comedonecrosis. Pleomorphic nuclei with coarse chromatin and prominent nucleoli, and abundant eosinophilic, typically apocrine cytoplasm { 25723113 ; 25871467 }. Lymphovascular and perineural invasion are common. A hyalinized nodule of a pre-existing PA may be present.
Subtypes: sarcomatoid; mucin–rich SDC; micropapillary SDC; basal-like; oncocytic; with rhabdoid features
IHC: AR is expressed in about 90% of SDCs, indicative of apocrine immunophenotype; Diffuse and strong immunoreactivity for ERBB2/HER2 (1/3 of cases). CK7 consistently (+), S100/SOX-10 (-).
chronic sialadenitis
Key features:
DDX:
Key features:
Varying degrees of acinar destruction, fibrosis and chronic inflammation, with lymphoid aggregates containing prominent germinal centers
Ducts may undergo squamous and mucous metaplasia
Lobular arrangement is maintained
May see microliths
DDx:
Mucoepidermoid carcinoma (infiltrative growth pattern/complex architecture)
IgG4 related sialadenitis (
Lymphoepithelial sialadenitis (LESA)
57M slow growing oral nodule
dx
Key features
common sites:
solitary circumscribed neuroma
Key features:
Well circumscribed, partially or completely encapsulated
Interlacing fascicles of plump spindle cells
Palisading is seen but may be subtle in areas
Nuclei are wavy and elongated
Not seen to arise from associated nerve
No mitotic activity is seen
Sites: 90% of tumors are found in head and neck
mucoepidermoid carcinoma
In one sentence, what is this entity? (histo features + molecular characteristic)
How do you grade this entity (WHO)?
Helpful IHC:
It is a malignant salivary gland neoplasm composed of mucous, intermediate and mucoepidermoid (squamous cells) showing variable cystic and solid components and ususally associated with MAML2 rearrangement.
Grading:
Histo feature + point value:
1) Cystic component < 25% 2
2) Neural invasion 2
3) Necrosis 3
4) 4 or more mitoses per 10hpf 3
5) anaplasia 4
Tumour grade:
Low grade (grade 1): 0-4
Intermediate grade (grade 2): 5-6
High grade (grade 3): 7 or more
IHC: p63/p40 (+); S100/SOX10 (-)
below: (low-grade MEC) Cystic spaces are partly lined by mucous cells. Other cell types include intermediate, squamoid and partly clear cells.
circumscribed nodule parotid
dx and describe entity in one statement
Key features:
IHC
Basal cell adenoma
BCA is a benign biphasic salivary gland neoplasm composed of basaloid and luminal cells, and often containing basement membrane material.
Key features:
Encapsulated or well circumscribed and show tubulotrabecular, cribriform, membranous or solid growth. The tumour shows peripheral palisading of dark cells with luminal paler cells and ducts. Nuclei are vesicular.
IHC: Epithelial and myoepithelial markers highlight the dual cell composition. Coexpression of nuclear β-catenin and LEF-1 is detected in BCAs.
oncocytic adenoma of thyroid
dx/definition
IHC
benign, non-invasive, encapsulated, follicular-cell-derived neoplasm composed of >75% oncocytic (Hürthle) cells.
If < 75% oncocytic cells, classified as follicular adenomas with oncocytic features
positive for PAX8 and TTF-1 and negative for calcitonin { 2428725 ; 10981870 ; 21552115 }. The cytoplasm and associated colloid of OA is positive for thyroglobulin { 10981870 }. There are no immunohistochemical stains that reliably distinguish OA from oncocytic carcinoma.
tongue lesion
dx
key features
common sites
Giatn cell fibroma
Key features:
Varying numbers of large, plump angular and stellate fibroblasts that may demonstrate multiple nuclei in the superficial connective tissue.
Proliferation of collagen bundles
Overlying surface epithelium with narrow and elongated epithelial rete ridges
Absence of inflammation
Most common location is the gingiva followed by the tongue, palate, buccal mucosa and lip
gingival lesion
dx
Key features
IHC
Odontogenic fibroma
Consists of variably cellular fibrocollagenous tissue with scattered, small, inactive odontogenic epithelium in strands, cords or nests
Calcification can be seen in association with odontogenic epithelium and when extensive could consider classification as ossifying variant of odontogenic fibroma
IHC: epithelium (+) for AE1/AE3, CK 14, CK19
DDx:
ameloblastic fibroma (below); desmoplastic fibroma;
gingival nodule
dx
Key features
Peripheral ossifying fibroma.
Features: spindle cell proliferation with calcificationor ossificaiton in gingial connective tissue (subepithelial stroma).
NB: dystrophic calcs OR lamellar bone OR woven bone is ESSENTIAL for dx.
Surface epithelium maybe ulcerated
mandible lesion
dx
key features
Odontogenic keratocyst
Mandible = most common site.
Normally incidentally discovered on XRs (can cuase local bone and soft tissue destruction).
Key features:
Uniform epithelial lining 6-8 cells thick lacking rete ridges. Epithelium characterised by palisaded hyperchromatic basal cell layer comprised of cuboidal to columnar cells. Luminal surface has “wavy”/corrugated parakeratotic epithelial cells.
tooth cyst
dx?
Key features?
Dx criteria
Radicular cyst.
Key features: lined by non-keratinized stratified squamous epithelium, that is proliferative with a characteristic arcading pattern. Hyaline (Rushton) bodies, mucous (goblet) cells or small areas of keratinization are not uncommon { 27957265 ; 25859536 }. The wall is composed of inflamed fibrous tissue, often with foamy histiocytes. Deposits of cholesterol crystals (clefts) with foreign body giant cells are often seen and may form luminal nodules.
Dx criteria: Essential: Non-vital tooth; cyst lined by non-keratinising epithelium.
Below: A cluster of hyaline (Rushton) bodies forms a small nodule in the epithelial lining, indicating an odontogenic cyst.
dentigerous cyst
dx criteria
ddx
Essential: well-defined radiolucency associated with the crown of an unerupted tooth; epithelium and cyst wall attached to the cementoenamel junction of unerupted tooth
Differential Diagnosis: Inflamed dentigerous cysts show hyperplasia and thickening of the lining epithelium and often foamy macrophages and cholesterol clefts associated with foreign body giant cells { 23278191 ; 30175860 }, and come to resemble radicular cysts histopathologically.
tooth cyst
dx?
Key features
Odontogenic keratocyst
The odontogenic keratocyst (OKC) is a developmental odontogenic cyst that is characterized histologically by a thin (corrugated) parakeratinzed stratified squamous epithelial lining (approximately 4-8 cells thick), typically w/o rete pegs, with palisaded and hyperchromatic basal cells and clinically by a tendency to recur after treatment.
Below: Cyst wall lined by uniform epithelium stratified squamous type without rete ridges but with hyperchromatic palisaded basal cell nuclei and characteristic corrugated surface parakeratin.
upper lip lesion
Dx
Key features
IHC
Canalicular adenoma (benign)
Essential: minor salivary gland location; monotonous, isomorphic syncytium of cuboidal to columnar cells anastomosing in a lattice of cords and canaliculi; no basal/myoepithelial layer
IHC: (+) pancytokeratin, CK7, S100 protein, SOX10, and CD117. (-) DOG1, desmin, and actins. There is a characteristic linear peripheral GFAP immunoreactivity.
Above photo: Low power demonstrates the interlacing canals and ribbons of neoplastic cuboidal-columnar cells separated by a loose, oedematous stroma.
Below: Adjacent ribbons of cells come together and form a knot (called “beading”), a feature quite characteristic of canalicular adenoma.
44M/F parotid mass
dx?
IHC:
DDx:
Below: well, circumscribed, encapsulated apperance
above image: Epitheloid and plasmacytoid myoepithelial cells.
DX: myoepithelioma
Essential: almost exclusive myoepithelial differentiation and absence of invasion
Desirable: tumour encapsulation (except in minor salivary glands)
IHC: positive for keratins, S100, SOX10, and myoepithelial markers such as p63, calponin, and SMA.
DDx: Differential Diagnosis: The tumour’s well-defined borders and lack of an invasive growth distinguish ME from myoepithelial carcinoma (MECA) { 25970687 ; 30789358 }. The characteristic basaloid biphasic pattern, peripheral palisading, and minimal to absent myxoid stroma of basal cell adenoma help to separate it from ME. Monomorphic histology and rare or absent ductal structures in ME differentiate it from pleomorphic adenoma { 19926180 ; 33231965 }. Differentiation from soft tissue ME may be difficult given overlapping histological features and the presence of PLAG1 gene rearrangements in both { 23630011 }.
Below: Salivary gland myoepithelioma, spindle cell with adipose metaplasia
33M jaw swelling/lesion mandible
dx?
Key features
Cemento-ossifying fibroma/ossifying fibroma
Key features:
Well defined lesion; may have thin fibrous capsule
Lesion consists of variable proportion of fibrous and mineralized tissue
Osteoblastic rimming of bone trabeculae is frequent
Stroma is fibroblastic with areas of hypercellularity and nuclear hyperchromasia
No significant atypia and mitoses are infrequent
Woven to lamellar bone, osteoid and dense acellular or paucicellular basophilic rounded cementum-like calcifications may all be present
cheek excision 60M
dx?
ddx?
Key features
Molecular
Mucoepidermoid carcinoma
Key features: multiple cell types (mucous, intermediate epidermoid/squamoid cells).
DDx: (with low-grade) mucocele, necrotizing sialometaplasia, sclerosing sialadenitis with mucous metaplasia, pleomorphic adenoma and Warthin tumour with oncocytic or squamous metaplasia, sclerosing polycystic adenoma, and secretory carcinoma.
Molecular: MAML2 rearrangement
cheek lesion 75F
dx?
Mucoepidermoid carcinoma with warthin-like pattern (lacks the well organised, double-layered oncocytic epithelium of that lesion)
Mucoepidermoid carcinoma
grading criteria
WHO
cystic component < 25% 2
Neural invasion 2
Necrosis 3
4 or more mitoses/10hpf 3
Anaplasia 4
Tumour grade:
Low (Gr 1): 0-4
Intermediate (Gr 2): 5-6
High (Gr 3): 7 or more
60M facial nerve paralysis
dx
key histo features
IHC
Molecular
Adenoid cystic carcinoma
Myoepithelial and ductal cells. Demonstration of true lumina and pseudocyts; PNI is hallmark.
IHC: epi cells pan-CK/CK7/CD117 (+); MEC S100 patchy, p63/p40 (+) (c.f. polymorphous carcinoma S100 S/D +; p63+, p40 -)
Molecular: MYB, MYBL1, or NFIB gene rearrangements are diagnostic of adenoid cystic carcinoma
Image:
Myoepithelial tumour cells with clear cytoplasm and angular nuclei surround multiple cyst-like areas (pseudocysts) that are contiguous with the stroma of the neoplasm (arrow). Small lumen surrounded by eosinophilic, cuboidal cells (asterisk) indicates a focus of true ductal differentiation.
57F cheek mass
dx:
IHC:
Molecular
acinic cell carcinoma
IHC: DOG1/SOX10+; no MEC differentiation -> (-) for p40/p63, S100 may stain intercalateducts; mammaglobin (-)
Molecular: NR4A3 rearrangement
65M cheek mass
Dx?
Essential and desireable dx criteria?
46F parotid mass
dx
Key features demonstrated
Confirmatory IHC
Molecular
Secretory carcinoma
SC has a prominent fibrosclerotic stroma and solid/microcystic structure. The tumor cells have bland vesicular round to oval nuclei, and distinctive centrally located nucleoli.
Single cell type with vacuolated colloid-like secretory material; no zymogen cytoplasmic granules;
IHC positivity for S100 protein, SOX10, and mammaglobin; lack of IHC staining for p40 and/or p63
Desirable: ETV6 or RET rearrangement demonstrated by FISH, RNA sequencing, or PCR
60M cheek lesion
dx
Key features
IHC
salivary duct carcinoma
Aggressive carcinoma resembling mammary ductal carcinoma, most typically with apocrine (immuno)phenotype.
Key features: frequent comedonecrosis. The cells have large pleomorphic nuclei with coarse chromatin and prominent nucleoli, and abundant eosinophilic, typically apocrine cytoplasm. Lymphovascular and perineural invasion are common.A hyalinized nodule of a pre-existing PA may be present. Rarely, SDC may be purely in situ.
IHC: AR(+, indicative or apocrine phenotype); mammaglobin (+),
slow growing right facial mass. 70M
dx
Key features
IHC
Epithelial-myoepithelial carcinoma
Essential: usually multinodular invasive growth; at least partly with a dual arrangement of inner ductal cells and outer prominent, and usually clear, myoepithelial cells
IHC: Ductal cells – CK7/EMA (+), occasionally S100; MEC: (var) CK (+); S100 (S), SMA, p63,p40, calponin (+)
Below image: demonstrating multinodular invasive growth.
2month infant facial swelling
dx
Key and desireable dx criteria
sialoblastoma
Essential: primitive, solid, organoid nests, basaloid epithelial cells with vesicular chromatin, and cuboidal to columnar ductal cells
Desirable: dividing fibrous stroma and peripheral palisading
base of tongue lesion
dx
Key and desireable dx features
Hyalinising clear cell carcinoma
Essential: nests, cords, and trabeculae of clear and/or eosinophilic cells in a hyalinized stroma
Desirable: EWSR1 fusion in selected cases
slow growing mass right cheek
dx
Key features demonstrated
IHC
Pleomorphic adenoma
Key features: The classical histologic features are seen, with a chondromyxoid matrix blending imperceptibly with the myoepithelial cells and showing small ducts in the background.
IHC:
50M submandibular mass
dx?
Pleomorphic adenoma with a prominent spindled cell myoepithelial component illustrated. Focal squamous metaplasia is present.
cheek mass
Basal cell adenoma
35M H/O solid organ transplant. Nasal congestion
dx
causes and how to differentiate
Invasive fungal rhinosinusitis
Fungal hyphae in mucosa, submucosa, vessels and bone
Zygomycetes: broad nonseptate hyphae branching at 90 degrees Aspergillus: slender septate hyphae branching at 45 degrees
mucocele
difference between extravasation mucocele vs mucus retention cyst
Retention mucoceles have an epithelial lining whereas extravasation mucoceles do not
52M deep cystic lesion cheek
Dx?
Key features?
IHC?
Molecular?
Px
Secretory carcinoma
Circumscribed/infiltrative margin; solid/cystic/ Pale eosinophilic colloid-like intraluminal secretions; secretions are periodic acid-Schiff (PAS) reagent positive and diastase resistant
Tumor cells have eosinophilic or vacuolated cytoplasm and monomorphic round vesicular nuclei with small but distinctive nucleoli
ICH: (+) CK7/GATA3/S100/SOX10/MUC4/Mammaglobin
Molecular: characterized by ETV6 gene rearrangement
PX: Generally low grade with indolent clinical behavior; however, local lymph node metastases may be seen in up to 22%
NB: acinic cell carcinoma GATA3-, PASD zyogen granules - ; MUC4-; DOG1+
MEC: p63+; mammaglobin/S100-
PAC usu minor salivary glands; p63+, GATA3-
SCUH
Essential and desireable dx criteria?
Frequent mutations?
Behaviour
Essential: a high-grade tumour with cytokeratin-positive tumour cells; no histological or immunohistochemical evidence of any specific line of differentiation; all histological mimics (see above) excluded.
Desirable: verification of IDH mutation status (in selected cases).
Dx of exclusion.
IDH2 hotspot mutations are identified in a significant subset of cases (33–85%) { 28084339 ; 28493366 ; 29683816 ; 31876581 }. IDH2 p.R172S is most common;
Aggressive.
salivary glands
List benign epithelial neoplasms
Pleomorphic adenoma
Basal cell adenoma
Warthin tumour
Oncocytoma
Salivary gland myoepithelioma
Canalicular adenoma
Cystadenoma of the salivary glands
Ductal papillomas
Sialadenoma papilliferum
Lymphadenoma
Sebaceous adenoma
Intercalated duct adenoma and hyperplasia
Striated duct adenoma
Sclerosing polycystic adenoma
Keratocystoma
salivary glands
List malignant epithelial lesions
Mucoepidermoid carcinoma
Adenoid cystic carcinoma
Acinic cell carcinoma
Secretory carcinoma
Microsecretory adenocarcinoma
Polymorphous adenocarcinoma
Hyalinizing clear cell carcinoma
Basal cell adenocarcinoma
Intraductal carcinoma
Salivary duct carcinoma
Myoepithelial carcinoma
Epithelial-myoepithelial carcinoma
Mucinous adenocarcinoma
Sclerosing microcystic adenocarcinoma
Carcinoma ex pleomorphic adenoma
Carcinosarcoma of the salivary glands
Sebaceous adenocarcinoma
Lymphoepithelial carcinoma
Squamous cell carcinoma
Sialoblastoma
Salivary gland carcinoma NOS
gene rearrangement in secretory ca
characterized by a specific rearrangement of the ETV6 or RET gene, and it harbours ETV6::NTRK3 or ETV6::RET fusion in most cases.
20M lesion attached to tooth root.
Dx:
Key features
demographic
cementoblastoma
Men and women less than 25 years old
Gross: Large mass of cementum on root of mandibular premolar or molar
Micro:
Large cementicles (globules) fused to form a mass within proliferative fibrovascular stroma
Trabeculae lined by plump osteoblasts
In below image: Expansile bone forming mass adherent to the root of the tooth (dotted line, with arrow).
molecular alteration + IHC in secretory ca vs salivary duct
secretory: e(12;15) translocation, ETV6-NTRK2 fusion.
Cs are positive for cytokeratin CK7, S100 protein, SOX10, vimentin, and mammaglobin, and negative for p63, p40, NR4A3, and DOG1
Salivary duct: Mammaglobin (+), AR(+); CK7(+), HER2 S/D 30%; s100/sox10 (-);
