Head and neck pathology

Question 1

70M, cheek lesion. PHx smoker

Dx:
Key features:

Answer 1

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.

Question 2

Name the three types of nasal papillomas

Answer 2

Inverted, oncocytic, exophytic

Question 3

nasal lesion.

Dx?
Key features?

Answer 3

Sinonasal papilloma, inverted type
Predominantly endophytic non-destructive growth; ribbons/nests of hyperplastic, immature squamous epithelium; transmigrating intraepithelial neutrophilic inflammation.

Question 4

Right nasal septum lesion

Dx?
Key features?

Answer 4

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.

Question 5

nasal lesion.

Dx?
Key features?

Answer 5

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.

Question 6

left lower nasal septum lesion

Dx?
Key features?

Answer 6

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

Question 7

mandibular biopsy

Dx?
Key features?

Answer 7

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

Question 8

Ameloblastoma (conventional), key features and subtypes

Answer 8

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

Question 9

pleomorphic adenoma

common mutation

Answer 9

70% of tumors show either PLAG1 or HMGA2 rearrangements

Question 10

Left cheek excisional bx

Dx:
Key features:
IHC:

Answer 10

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

Question 11

28F rapidly growing gingival lesion

Dx?
Key features?

Answer 11

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

Question 12

neck lesion

Dx
Key features
DDx:

Answer 12

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.

Question 13

Medullary thyroid carcinoma

Essential and desireable dx features
IHC profile:

Answer 13

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 (+)

Question 14

thyroid lesion

dx?
IHC

Answer 14

Medullary thyroid carcinoma
IHC: calcitonin(+); CEA(+); chromo/synapt/NSE/INSM1(+); variable/(-) PAX8; TTF1(+)

Question 15

adenoid cystic carcinoma

architectural patterns:
What to look out for?
Common molecular event:

Answer 15

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

Question 16

femal mouth lesion

Dx and features:
Key feature displayed in image

Answer 16

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

Question 17

palate lesion

dx:
Key histo features
ddx:
px:

Answer 17

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

Question 18

cholesteatoma

key features

Answer 18

Keratinous material (keratin flakes; dead, anucleate keratin squames)
Stratified squamous epithelium with granular layer
Inflamed stroma with fibrous connective tissue

Question 19

buccal lesion

dx

Key features

Answer 19

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

Question 20

posterior nasal septum lesion

dx

key features

Answer 20

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

Question 21

secretory ca (of parotid)

mutation?
IHC?

Answer 21

Harbours ETV6::NTRK3 or ETV6::RET fusion in most cases.
t(12;15) (p13;q25)
IHC: S100 and mammaglobbin (cyto +) (+)

Question 22

cheek excision

dx?
Dx criteria
DDx and how to differentiated?
Key features demonstrated?
Molecular?

Answer 22

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.

Question 23

Most common site of polymorphous adenocarcinoma?

Answer 23

Soft palate.
95% involves minor salivary glands

Question 24

polymorphous adenocarcinoma

Molecular alteration?

Answer 24

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

Question 25

# soft palate lesion Dx? IHC? Molecular? Key features identified? px?

Answer 25

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.

Question 26

# polymorphous adenocarcinoma subtypes + brief description

Answer 26

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

Question 27

# base of tongue lesion Dx? Key features demonstrated

Answer 27

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.

Question 28

# adenoid cystic carcinoma vs polymorphous adenocarcinoma localisation

Answer 28

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

Question 29

# adenoid cystic carcinoma Key histo features Growth patterns High-grade features:

Answer 29

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

Question 30

# adenoid cystic carcinoma Molecular

Answer 30

Demonstration of MYB/MYBL1 rearrangements or gene fusions by FISH or other methods can help establish a diagnosis of AdCC

Question 31

# adenoid cystic ca IHC & dx criteria

Answer 31

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

Question 32

# pleomorphic adenoma Three components Common gene rearrangement

Answer 32

1. ductular structures 2. myoepithelial cells (can be spndled, epithelioid, plasmacytoid, etc..), intimately adixe with stroma 3. Mesenchymal-like tissue (often myxoid stroma, but can be chondroid, etc...) 4. architecturally pleomorphic (cytologically blandd) PLAG1-HMGA2 fusions very common

Question 33

mucoepideroid carcinoma Grading (AFIP)

Answer 33

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

Question 34

# cheek lesion dx: Key histo features IHC Molecular

Answer 34

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

Question 35

# 65M rapidly growing cheek mass, facial paralysis dx Key features IHC px

Answer 35

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;

Question 36

42M cheek mass dx aetiology ddx diagnostic molecular path:

Answer 36

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

Question 37

# rapidly growing cheek lesion dx key features Subtypes: IHC

Answer 37

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 (-).

Question 38

# chronic sialadenitis Key features: DDX:

Answer 38

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)

Question 39

# 57M slow growing oral nodule dx Key features common sites:

Answer 39

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

Question 40

# mucoepidermoid carcinoma In one sentence, what is this entity? (histo features + molecular characteristic) How do you grade this entity (WHO)? Helpful IHC:

Answer 40

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.

Question 41

# circumscribed nodule parotid dx and describe entity in one statement Key features: IHC

Answer 41

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.

Question 42

# oncocytic adenoma of thyroid dx/definition IHC

Answer 42

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.

Question 43

# tongue lesion dx key features common sites

Answer 43

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

Question 44

# gingival lesion dx Key features IHC

Answer 44

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;

Question 45

# gingival nodule dx Key features

Answer 45

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

Question 46

# mandible lesion dx key features

Answer 46

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.

Question 47

# tooth cyst dx? Key features? Dx criteria

Answer 47

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.

Question 48

# dentigerous cyst dx criteria ddx

Answer 48

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.

Question 49

# tooth cyst dx? Key features

Answer 49

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.

Question 50

# upper lip lesion Dx Key features IHC

Answer 50

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.

Question 51

# 44M/F parotid mass dx? IHC: DDx: Below: well, circumscribed, encapsulated apperance

Answer 51

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

Question 52

33M jaw swelling/lesion mandible dx? Key features

Answer 52

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

Question 53

# cheek excision 60M dx? ddx? Key features Molecular

Answer 53

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

Question 54

# cheek lesion 75F dx?

Answer 54

Mucoepidermoid carcinoma with warthin-like pattern (lacks the well organised, double-layered oncocytic epithelium of that lesion)

Question 55

# Mucoepidermoid carcinoma grading criteria

Answer 55

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

Question 56

# 60M facial nerve paralysis dx key histo features IHC Molecular

Answer 56

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.

Question 57

# 57F cheek mass dx: IHC: Molecular

Answer 57

acinic cell carcinoma IHC: DOG1/SOX10+; no MEC differentiation -> (-) for p40/p63, S100 may stain intercalateducts; mammaglobin (-) Molecular: NR4A3 rearrangement

Question 58

# 65M cheek mass Dx? Essential and desireable dx criteria?

Question 59

# 46F parotid mass dx Key features demonstrated Confirmatory IHC Molecular

Answer 59

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

Question 60

# 60M cheek lesion dx Key features IHC

Answer 60

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 (+),

Question 61

# slow growing right facial mass. 70M dx Key features IHC

Answer 61

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.

Question 62

# 2month infant facial swelling dx Key and desireable dx criteria

Answer 62

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

Question 63

# base of tongue lesion dx Key and desireable dx features

Answer 63

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

Question 64

# slow growing mass right cheek dx Key features demonstrated IHC

Answer 64

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:

Question 65

# 50M submandibular mass dx?

Answer 65

Pleomorphic adenoma with a prominent spindled cell myoepithelial component illustrated. Focal squamous metaplasia is present.

Question 66

# cheek mass

Answer 66

Basal cell adenoma

Question 67

# 35M H/O solid organ transplant. Nasal congestion dx causes and how to differentiate

Answer 67

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

Question 68

# mucocele difference between extravasation mucocele vs mucus retention cyst

Answer 68

Retention mucoceles have an epithelial lining whereas extravasation mucoceles do not

Question 69

52M deep cystic lesion cheek Dx? Key features? IHC? Molecular? Px

Answer 69

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-

Question 70

SCUH Essential and desireable dx criteria? Frequent mutations? Behaviour

Answer 70

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.

Question 71

# salivary glands List benign epithelial neoplasms

Answer 71

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

Question 72

# salivary glands List malignant epithelial lesions

Answer 72

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

Question 73

gene rearrangement in secretory ca

Answer 73

characterized by a specific rearrangement of the ETV6 or RET gene, and it harbours ETV6::NTRK3 or ETV6::RET fusion in most cases.

Question 74

20M lesion attached to tooth root. Dx: Key features demographic

Answer 74

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).

Question 75

molecular alteration + IHC in secretory ca vs salivary duct

Answer 75

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 (-);