Molecular Pathology - Salivary Gland

Question 1

What genetic abnormalities are seen in mucoepidermoid carcinoma, and what is their prognostic significance?

Answer 1

t(11;19): CRTC1`-MAML2. 40-80% of cases, favorable.

t(11;15): CRTC3-MAML2. 5% of cases, favorable.

CDKN2A deletions are unfavorable even when concurrent with above.

Question 2

What genetic abnormalities are seen in adenoid cystic carcinoma? What is their significance?

Answer 2

t(6;9): MYB-NFIB. Seen in 30-85% of cases*, not prognostic.

1p36.33-p35.3 losses: Unclear significance.

*Almost all ACCs have overexpression of MYB mRNA/protein, including transfusion-negative cases. Some have t(8;9).

Question 3

What genetic abnormalities are seen in salivary duct carcinoma, and what is their significance?

Answer 3

amp(17q21.1): ERBB2 amplification. 40% of cases, can be targeted for anti-Her2 therapy.

3q26.32: PIK3CA mutations. 20% of cases, unclear significance.

TP53, PTEN, H-RAS mutations. May decrease efficacy of HER2 blockade.

Question 4

What genetic abnormality is seen in mammary analog secretory carcinoma?

What other lesion is it most analogous to?

Answer 4

t(12;15): ETV6-NTRK3

Shares morphologic and molecular features of secretory carcinoma of breast.

Question 5

What lesion is salivary duct carcinoma most similar to, both morphologically and molecularly?

Answer 5

Breast carcinoma with luminal AR-positive, apocrine phenotype.

Question 6

What genetic abnormality is seen in polymorphous low-grade adenocarcinoma?

In cribriform adenocarcinoma of minor salivary glands?

Answer 6

PRKD-1 gene mutations

Chromosomal rearrangements of PRKD genes (-1, -2, -3)

Question 7

What genetic abnormalities are seen in pleomorphic adenoma and carcinoma ex pleomorphic adenoma?

Answer 7

8q12 rearrangements: PLAG1. 25-30% of cases.

12q13-15 rearrangements: HMGA2. 10-15% of cases.

Carcinoma ex pleomorphic adenoma can have both of above, plus additional alterations (MDM2, MYC, HER2)

Question 8

What genetic abnormality is seen in hyalinizing clear cell carcinoma?

What lesion is it most analogous to?

Answer 8

t(12;22): EWSR1-ATF. Almost all cases! But be careful with nonspecific EWSR rearrangements.

Clear cell odontogenic carcinoma

Question 9

What genetic abnormality is seen in basal cell adenoma and adenocarcinoma?

With what other lesion is it morphologically and molecularly similar?

Answer 9

LOH at 16q12-13: CYLD.

(less significant: CTTNB1, LEF-1)

Dermal eccrine cylindromas

Question 10

What genetic abnormalities are seen in epithelial-myoepithelial carcinoma?

In myoepithelial carcinoma?

Answer 10

HRAS codon 61 mutations

EWSR1 rearrangements