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Salivary glands

Epithelial / myoepithelial tumors

Salivary duct carcinoma


Reviewer: Adriana Handra-Luca, M.D. (see Reviewers page)
Revised: 29 January 2013, last major update September 2012
Copyright: (c) 2003-2013, PathologyOutlines.com, Inc.

See colloid / mucin rich, low grade below

General
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● Uncommon tumor resembling invasive and in situ ductal carcinoma of breast, either high grade (papillary/micropapillary [Am J Surg Pathol 2004;28:319], sarcomatoid, colloid) or low grade (cribriform) (Arch Pathol Lab Med 2009;133:1763)
● First described in 1968 by Kleinsasser (Arch Klin Exp Ohren Nasen Kehlkopfheilkd 1968;192:100)

Clinical features
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● 0.2-2% of salivary gland tumors, 10% of salivary gland malignancies
● Usually elderly (most 50+ years, range 22-91 years), 75% males, may cause facial palsy
● Usually parotid gland (may be bilateral), also submandibular gland, minor salivary glands
● May arise in pleomorphic adenoma, polymorphous low grade adenocarcinoma, Warthin tumor, or de novo
● May be associated with osteoclast type giant cell tumor, IgG4 related chronic sclerosing sialadenitis (Hum Pathol 2009;40:881)
● May be hybrid tumor / synchronous with adenoid cystic carcinoma, epithelial-myoepithelial carcinoma, pleomorphic adenoma, squamous cell carcinoma (head and neck), Warthin tumor (Arch Pathol Lab Med 2011;135:1088)
● High grade tumors are aggressive with tumor infiltration into soft tissue, and frequent recurrence (60%)
● Metastases to regional lymph nodes and distant sites (bone, bowel, CNS, gingiva, inguinal lymph node, liver, lung, skin, uterus, vagina)
● Disease specific survival at 2 years is 75%, at 5 years is 55%

Poor prognostic factors
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● > 3 cm, metastases, small intraductal component, ER beta-, p53+,. HER2+, MMP9+, chromosome 7 polysomy

Treatment
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● Excision with regional lymph node sampling, radiation and chemotherapy
● Possibly prostate cancer-like hormonal therapy, docetaxel, paclitaxel, trasuzumab

Gross description
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● White-tan mass with solid or cystic cut surface or necrosis; firm, ill defined, infiltration of adjacent parenchyma
● Up to 7 cm (mean 3.5 cm)

Micro description
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● Resembles invasive ductal carcinoma of breast, either high grade (papillary/micropapillary, sarcomatoid [Hum Pathol 2000;31:208], colloid) or low grade (cribriform)
● Cells have eosinophilic cytoplasm, marked nuclear pleomorphism, vesicular nuclei, prominent nucleoli, squamoid
● May have anaplastic keratin+ cells, spindle, multinucleated, oseosarcomatous, rhabdoid or squamoid cells; no goblet cells, no apocrine cells
● Frequent perineurial and vascular invasion, fibrous and hyalinized stroma; numerous mitotic figures
● May have dystrophic calcification or necrosis (comedo-necrosis sometimes), neutrophil tumor cell cannibalism, cystic change, neuroendocrine features
● May be in situ only (Am J Surg Pathol 2004;28:266)
● May be associated with squamous cell carcinoma, bilateral chronic sialadenitis

Micro images
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Various images


Figure 1: cribriform pattern, 2: oncocyte-like cells, 3: infiltrating in cords, 4: perineurial invasion


Various patterns


H&E, CK7 and CK20


H&E and PPAR gamma expression

Cytology description
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● Necrosis, large polygonal cells, cribriform groups, oncocytic appearance

Positive stains
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● CK 5/6, CK7, CK8/18, CK19, CK20, EMA, CEA, B72.3; high Ki67, PCNA
● Also androgen receptor (>90%), PPAR gamma (80%, Mod Pathol 2003;16:1218), GCDFP-15 (especially intraductal component), PSA (60%, Am J Surg Pathol 2000;24:579), HER2 (50%), PAP (20%)
● Also BER-EP4, proline, glutamic acid, leucin-rich protein-1, ER beta, EGFR, COX2, E-cadherin (Am J Surg Pathol 2007;31:1645)
● Also Topo II alpha, alpha lactalbumin, p16, PELP, CD147, MMP9, MMP13, MCM2 (Hum Pathol 2005;36:670)
● Also MUC1, MUC2, MUC4, MUC6, MNAR, BUB1B, MAD2l1, Casp10, TGFalpha, laminin, collagen IV, TAG72/B72.3
● Also Lewis Y, cathepsin D, p16, pRb, CD44v6, CD44s(focal), high geminin index
● Overexpression of MMPII, cyclinD1, CDK4, mdm2, E2F1, p53

Negative stains
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● Calponin, smooth muscle actin, muscle specific actin, CK14 (in situ growth pattern), amylase, DOG1 (Mod Pathol 2012;25:919), MMP1 (nuclear), bcl2

Electron microscopy description
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● Interlobular or excretory duct origin (2 cell types: electron-lucent cytoplasm with scant organelles and second type with numerous mitochondria)

Molecular / cytogenetics description
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● Diploid or aneuploid, 6q alterations more frequently and 17p/17q less frequently than breast invasive ductal carcinoma
● Also chromosome 7 polysomy, 12q amplification, 9p LOH, methylation of MGMT, DAPK, RASSF1

Differential diagnosis
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Adenocarcinoma NOS: androgen receptor+
Metastatic carcinoma breast carcinoma is ER+, CEA-
● Eccrine sweat gland carcinoma: GCDFP15-
Mucoepidermoid carcinoma: particularly high grade mucoepidermoid carcinoma, which is androgen receptor+, has epidermoid and mucous cells
● Oncocytic adenocarcinoma: no prominent comedonecrosis or papillary growth, phosphotungstic acid+
Polymorphous low grade adenocarcinoma
Squamous cell carcinoma: similar appearance on cytology
● Terminal duct adenocarcinoma: more indolent


Colloid carcinoma (mucin rich) variant of salivary duct carcinoma

General
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● Very rare variant with large extracellular mucin lake (50% or less of tumor), containing clusters and single tumor cells
● May represent extreme variation of extracellular mucin expression
● Prognosis similar to classic type
● Usually major salivary glands, men

Treatment
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● Resection, radiotherapy

Micro images
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Figure C

Positive stains
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● CK7, EMA, androgen receptors, GCDFP-15, CEA, MUC2, MUC5B, MUC6 (Am J Surg Pathol 2003;27:1070), variable HER2 overexpression

Negative stains
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● CK20, S100, myoepithelial markers, ER, PR, MUC5AC, MUC7

Differential diagnosis
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Metastases
● Mucinous/colloid carcinoma of breast: better prognosis
Mucoepidermoid carcinoma: AR negative, intermediate and clear cells


Low grade salivary duct carcinoma

General
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● Rare tumor composed of cysts lined by small, multilayered, bland ductal cells with fine chromatin and small nucleoli
● Also called low grade intraductal carcinoma, low-grade cribriform cystadenocarcinoma, intraductal carcinoma, intraductal carcinoma with microinvasion
● First reported in 1996 (Cancer 1996;78:958)

Clinical features
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● Usually parotid gland
● Median age 64 years
● Excellent prognosis; no recurrence if complete resection

Treatment
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● Surgery, rarely radiotherapy

Gross description
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● Unencapsulated

Micro description
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● Must sample entire tumor to determine extent of invasion, rule out high grade foci
● Single to multiple dominant cysts accompanied by adjacent intraductal proliferation
● Cysts lined by small, multilayered, bland ductal cells with fine chromatin and small nucleoli
● Smaller ductal structures have variable proliferating ductal epithelium with cribriform, micropapillary or solid patterns resembling ADH or low grade DCIS of breast (Am J Surg Pathol 2004;28:1040)
● Attenuated myoepithelial cell layer, sclerotic stroma with secondary changes (inflammation, hemorrage, calcification)
● May have indistinct cytoplasm membranes, apocrine-type cytoplasmic microvacuoles, lipofuscin-like pigment
● May be entirely intraductal, have definite stromal invasion, transition between low grade and high grade areas
● May have adenosquamous carcinoma-like features
● Rarely goblet cells or oncocytoid cells
● No/rare mitotic figures or necrosis

Micro images
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Arising in intraparotid lymph node


Resembling ADH of breast

Positive stains
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● S100, calponin (myoepithelial cells lining cystic spaces), CK14, p63, GCDFP-15 (Am J Surg Pathol 2006;30:1014)
● Also MUC1, MUC2, MUC4, MUC6, CK19, AR, ER, PR

Negative stains
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● CK20, p53

Differential diagnosis
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Cystadenocarcinoma: no resemblance to breast ADH or DCIS, usually widely invasive
Acinic cell carcinoma-papillocystic variant: smaller vacuoles, S100-, zymogen granules by EM

End of Salivary glands > Epithelial / myoepithelial tumors > Salivary duct carcinoma


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