Salivary Tumor IHC

Question 1

Pleomorphic adenoma

Answer 1

Basal cells: pan-keratin, p63, SMA, actin, calponin, vimentin, S100

Luminal cells: pan-keratin, CK7, EMA, cKit/CD117, maspin

Question 2

Basal cell adenoma

Answer 2

Basal cells: SMA, p63, actin, beta catenin
Luminal cells: cKit/CD117, maspin

Question 3

Oncocytoma

Answer 3

Pan-cytokeratin, EMA positive

Negative stains: S-100, HMB-45, synaptophysin, mucin

*Note: May have clear cell morphology, in which case you are obligated to differentiate it from myoepithelial lesions and metastatic clear cell RCC

Question 4

Myoepithelioma

Answer 4

Cytokeratins, actin, p63, h-caldesmon, calponin, SMA-heavy chain, maspin

• Note: May have plasmacytoid or spindled morphology

Question 5

Mucoepidermoid carcinoma

Answer 5

Cytokeratin, p63, p40, CK7, EMA, mucin positive

Negative stains: CK20, vimentin, actin

Prognosis/Treatment: HER2

t(11;19), MECT1-MAML2

Question 6

Acinic cell carcinoma

Answer 6

Cytokeratin, EMA, PAS, PAS-D, DOG1, NR4A3 positive

Negative stains: Mucin, p63, calponin, calponin, S100

Note: NR4A3 highly specific

t(4;9), leading to NR4A3 upregulation

Question 7

Adenoid cystic carcinoma

Answer 7

Basal cells: SMA, actin p63, CD43, calponin, S100

Luminal cells: cKit/CD117, EMA, CK7, mapsin

MYB-NFIB fusion

Question 8

Polymorphous low-grade adenocarcinoma

Answer 8

Cytokeratin, EMA, S-100, SOX10, p63 (variable)

Negative stains: actin, calponin

Note: Unlike pleomorphic adenoma, lacks a basal cell layer. This feature and poor architectural circumscription are the key features to differentiation.

PRKD1 E710D

Question 9

Epithelial-myoepithelial carcinoma

Answer 9

Basal cells: SMA, actin, p63, PAS, S100, DOG1 (membranous pattern), SMMHC

Luminal cells: cKit/CD117,EMA, mapsin, DOG1 (apical pattern)

Negative: Androgen receptor

HRAS , rarely deletions in SMARCB1, rarely mutations in FBXW7 or p53, also PLAG1 or HMGA2 (may highlight residual PA in carcinoma ex-PA)

Question 10

Clear Cell Carcinoma, NOS
aka, Hyalinizing Clear Cell Carcinoma

Answer 10

Cytokeratin, EMA, PAS, CEA (variable), p40, p16 (variable, >70% in some cases)

Negative stains: SMA, demsin, mucin, S-100, PAS-D

> 80% with EWSR1::ATF1 fusion , EWSR1::CREM fusion also described

Question 11

Salivary Ductal Carcinoma

Answer 11

Cytokeratin, AR, EMA, CEA, GATA3, PSA, GCDFP-15, 35βE12 positive

Negative stains: ER, PR, myoepithelial markers

Prognostic: AR, HER2

May contain a variety of molecular alterations, including amplifications in PIK3CA, HRAS, ERBB2, BRAF, and FGFR3, rearrangements involving PLAG1 or HMGA2 (suggesting origination from pleomorphic adenoma), and tumor suppressor losses, including TP53, CDKN2A, PTEN, and ATM.

Question 12

Carcinoma Ex Pleomorphic Adenoma

Answer 12

High-grade salivary neoplasm arising from pre-existing pleomorphic adenoma

Histology and IHC will depend on which carcinoma arises, but it is ALWAYS high-grade.

Question 13

Stains to differentiate pleomorphic adenoma and polymorphous adenocarcinoma

Answer 13

Pref. pos in Pleomorphic adenoma: calponin, PLAG1, p40, GFAP, CK19

Pref. pos in Polymorphous adenocarcinoma: Ki67, p53, mammoglobin

Question 14

Myoepithelial carcinoma

Answer 14

S100, calponin, SMA, GFAP, p40, p63, SOX10, PLAG1

Negative for other melanocytic markers, HMB45 and Melan A

Molecular: PLAG or HMGA2 rearrangement (if PA origin), EWSR rearrangement (if clear cell morphology)

Question 15

Secretory Carcinoma

Answer 15

S100, mammoglobin, GATA3, CK7, SOX10, Pan-TRK

Negative: p40, p63, calponin

Molecular: ETV6::NTRK3

Question 16

Biphenotypic sinonasal sarcoma

Answer 16

Sarcoma composed of spindle cells with plump nuclei and prominent, hemangiopericytoma-like stromal vasculature, frequently enveloping epithelial structures.

S100, SMA, and PAX3 strongly positive.

CD34 negative.

Characteristically has a PAX3-MAML3 translocation.

Question 17

Sinonasal glomangiopericytoma

Answer 17

Submucosal syncytial proliferation of bland spindle cells arranged in a vaguely fascicular to storiform pattern. Numerous vessels with staghorn appearance and perivascular hyalinization are seen.

Diffusely SMA positive and nuclear beta catenin positive.

S100 is importantly negative, distinguishing this tumor from biphenotypic sinonasal sarcoma. CD34 is also negative.

Molecular is characterized by CTNNB1 (beta catenin) aberrations.

Question 18

Hyalinizing trabecular tumor

Answer 18

TTF-1, thyroglobulin, galectin-3, and importantly a unique membranous Ki-67 positivity.