Salivary Neoplasms

Question 1

which salivary glands are mucinous vs. serous?

Answer 1

Parotid = serous
Sublingual = mucionous
Submandibular = seromucinous

Question 2

Mucocele

Answer 2

cyst like space with mucin and lined with mucocytes (macrophages digesting the mucin).
–> “plunging ranula” if descending into the neck.

Question 3

Sojren syndrome

Answer 3

ANY single field (10x) of >50 lymphocytes.

Question 4

Sialometaplasia

Answer 4

Caused by injury/radiation or a solitary lesion on the palate. See a lobular/duct like configuration (think: nests) of squamous cells. (Can have mucous cells still and intraluminal necrosis)

Question 5

List the two most common benign and malignant tumors

Answer 5

Pleomorphic adenoma > warthin’s tumor.

Mucoepidermoid>adenoid cystic.

Question 6

Overall treatment protocol for salivary neoplasms:

Answer 6

Resect BENIGN AND MALIGNANT.
If High grade: then neck dissection also for nodal mets.
(primary vs. mets, grade, and clean margins are most important in report).

Question 7

Pleomorphic adenoma

Answer 7

(benign): Two layer glands (epithelial inner, myoepithelial outer) in a myxoid to cartilaginous matrix (blue matrix). Myoepithelial cells can be sparse to solid and have spindled to plasmacytoid morphology.
Look for tyrosine crystals in the stroma.
Can recur/transform/metastasize: [a recurrent PA looks like buckshot nodules of blueish stroma].

Question 8

Features that are truly indicative of carcinoma (transformation) in pleomorphic adenoma:

Answer 8

NUCLEAR IRREGULARITIES: pleomorphism/enlargement/nucleoli.

NOT: metaplasia, mites or necrosis.

Question 9

Molecular signatures (x2) of pleomorphic adenoma:

Answer 9

PLAG and HMGA2 rearrangements.

[PLAG = Pleomorphic Adenoma Gene]

Question 10

Myoepithelioma

Answer 10

Benign: rare tumors made entirely of myoepithelial cells (can have a variety of morphologies:

Question 11

List myoepithelial markers:

Answer 11

SMA, GFAP, S100, calponis, p63, p40

Question 12

Myoeithelial carcinoma (incl. mutations x2)

Answer 12

Malignant: same as myoepithelial adenoma (only have myopia cells) but with INFILTRATIVE growth; usually in mutinous stroma.
Genetics: PLAG (if transformed from a pleomorphic adenoma) or EWSR (if clear cell morphology).

Question 13

Warthin tumor

Answer 13

Multifocal and bilateral in smokers.
Bilayered oncocytic cyst lining with lymphoid-rich stroma. (can have squamous/mucinous metaplasia). 1% rate of transformation.

Question 14

Oncocytoma

Answer 14

solid/trabecular architecture with only oncoyctes (no lymphoid stroma like in Warthin’s). Also, not to be confused with oncocytic metaplasia in elderly (which will be multifocal).

Question 15

Oncyoctic carcinoma

Answer 15

Malignant form of oncocytoma. Defined by INVASION. (Note: generally, invasion is a non-lobulated shape, does not have to be tiny nests of invasion). Cytologic atypia does NOT make it high grade; need mites/necrosis.

Question 16

Basal cell adenoma/carcinoma (including 2x mutations)

Answer 16

Epithelial and myoepithelial cells making large nests/lumens with peripheral palisading and pink hyalinized stroma (see eosinophilic globules).
Stains with beta catenin (usually).
Mutations: CTNNB1 and CYLD1 (brooke-spiegler syndrome).
Can transform to BC adenocarcinoma (invasion); usually with familial CYLD1 mutations.

Question 17

Canalicular adenoma

Answer 17

upper lip of older women.
multi cystic growth pattern where septa are 1-2 cells thick. Can see “beading” pattern, modules inside lumens. Stains for S100, and GAFP at the lumen/border only. No myoepithelial cells.

Question 18

Mucoepidermoid carcinoma (and 2x mutations)

Answer 18

3 cell types: squamous, intermediate, mucinous. Must see intracellular mucin (can use PAS-D to distinguish mucin vs. glycogen in SCC).
CRTC1-MAML2 rearrangements, or CRTC3.
There are many grading systems for MEC!

Question 19

Adenoid cystic carcinoma (AdCC)

(incl. mutations)

Answer 19

Frequently have nerve pain (likes nerves - perineurial invasion).
Aggressive: 90% dead in 10-15 years.
Ductal (outside) and myoepithelial (inner) cells in a variety of growth patterns (tubular is low grade, cribiform is intermediate, and solid is high grade).
MYB-NFIB translocation, or MYB activation.

Question 20

Polymorphous adenocarcinoma (PAC)

Answer 20

(do not confuse with “pleomorphic”).
Usually in the palate.
Looks like aden-cystic carcinoma but the nuclei are pale/vesicular (salt and peppery) rather than AdCC (dark and/or finely granular). Also, PAC has only one cell type (AdCC has two) - p40 is negative in PAC.

Cribiform variant has PRKD1/2/3 rearrangements.

Question 21

Acinic cell carcinoma

Answer 21

SHEETS of serous acinar cells.

HG if nuclear pleomorphism, mitoses, necrosis.

Question 22

(Mammary analogue) secretory carcinoma

Answer 22

ETV6-NRTK3 tyrosine kinase fusion protein.
Pale monotonous cells with a microcytic/papillary architecture and pale/dark intraluminal secretions. No zymogen granules. Can hobnail. S100 positive.

Question 23

Salivary duct carcinoma

Answer 23

(looks like HG ductal CA of breast).

large nests of peripheral cribiforming and central necrosis. AR+ and HER2+. Variety of growth patterns.

Question 24

Intraductal carcinoma

Answer 24

infiltrative and intraductal growth patterns. All nests be ringed by myoepithelial cells.

Question 25

Epithelial myoepithelial carcinoma

Answer 25

Rare neoplasm with bilayered tubules with single layer of epithelial cells inside and one to many layers of clear myoepithelial cells on the outside. Can have solid growth of myope cells also. HRAS mutation in 1/3rd.

Question 26

Clear cell carcinoma (and mutation)

Answer 26

Clear cells with wrinkled nuclei and fibrous septa of pink hyaline stroma. Pos for squamous markers (HMWK) and neg for my-epithelial markers.
Genes: EWSR-ATF1