Salivary carcinomas Flashcards
Hallmark fusions of mucoepidermoid carcinoma
MECT1-MAML2
or
CRTC3-MAML2
Hallmark fusions of adenoid cystic carcinoma
MYB-NFIB
Rarely other MYB or NFIB rearrangements
Fusions in myoepithelial carcinoma
TGFBR3-PLAG
(but only present in a minority of cases)
Hallmark fusion of hyalinizing clear cell carcinoma
EWSR1-ATF1
Hallmark fusion of mamary-analogue secretory carcinoma
ETV6-NTRK3
Hallmark molecular features of polymorphous adenocarcinoma
PRKD1 E710D (75% of cases)
or
PRKD1/3 rearrangements (10% of cases)
Molecular features of salivary ductal carcinoma
Much more varied than most salivary carcinomas
May include variants in:
ERBB2
PIK3CA
HRAS
Also rarely involves fusions, including:
EML4-ALK
NCOA4-RET
ETV6-NTRK3*
*Note that this fusion is also seen in mamary analogue secretory carcinoma
MECT1-MAML2 in mucoepidermoid carcinoma
Present in:
70-80% of low-grade mucoepidermoid carcinomas
65-70% of intermediate grade
50% of high grade
CRTC3-MAML2 fusion in mucoepidermoid carcinoma
Present in only 5% of cases
Often seen in younger patients
Alternative adenoid cystic carcinoma fusions
MYB-RASD51B
MYB-TGFBR3
MYBL1-NFIB
Additional (non-defining) molecular features of adenoid cystic carcinoma
NOTCH1 mutations (10% of primary, 33% of recurrent/refractory) - poor prognostic indicator
FGFR1
PIK3CA
4q12 gain is a feature that predicts good response to targeted therapy with the TKI axitinib.
Targeted therapy for mammary analogue secretory carcinoma
1st line NTRK inhibitor: entrectinib
2nd line (after G623R acquisition): larotrectinib
DDx for an ETV6-NTRK3 fusion
In the head and neck, it is most likely a mammary analogue secretory carcinoma, BUT it COULD be a salivary ductal carcinoma.
You need morphology/IHC for definitive diagnosis.
DDx for an EWSR1-ATF1 fusion
In the head and neck, it could be either a (hyalinizing) clear cell carcinoma OR a myoepithelial carcinoma.
Morphology and IHC are necessary to confirm the diagnosis.
Molecular features of myoepithelial carcinoma
May contain several possible fusions:
* EWSR1 gene rearrangements, most often EWSR1-ATF1, but also others including EWSR1-POU5F1
* TGFBR3-PLAG1
* MSN-ALK
If myoepithelial carcinoma-ex pleomorphic adenoma, may harbor PLAG1 or HMGA2 rearrangements.
-> Caveat: The FGFR1-PLAG1 translocation may appear in de novo myoepithelial carcinoma
-> Second caveat: The TGFBR3-PLAG1 translocation is specific for myoepithelial carcinoma and has not been documented in pleomorphic adenoma.
What is “cribriform adenocarcinoma of the tongue and minor salivary gland”?
A morphologic variant of polymorphous adenocarcinoma which typically arises at the base of the tongue.
Has a distinct papillary glomeruloid and cribriform architecture with more pronounced clear nuclei and a greater propensity for lymph node metastasis.
More “malignant” than typical polymorphous adenocarcinoma, carries a worse prognosis.
