A Cutaneous Facial Mass Identified as the New Entity Mammary Analogue - PowerPoint PPT Presentation

A Cutaneous Facial Mass Identified as the New Entity ‘Mammary Analogue Secretory Carcinoma’ of Probable Salivary Gland Origin Scott W. Binder, MD Professor and Senior Vice Chair Chief, Dermatopathology Geffen/UCLA Healthcare

Case Presentation A 50 year-old man presents with a 7 mm erythematous papule on the right face • Developed over a few months • Asymptomatic • No history of prior neoplasms including salivary gland tumors • Lesion located just lateral to nose

Clinical Impression “Rule out bug bite”

Histopathology 4

Histopathology 5

Histopathology 6

Histopathology 7

Histopathology 8

Histopathology 9

Differential Diagnoses • Acinic cell carcinoma • Apocrine or eccrine sweat duct tumor • Mammary analogue secretory carcinoma • Benign oncocytic neoplasms • Mucoepidermoid carcinoma • Metastasis from a visceral primary

Outside Special Stains S-100 EMA CK 7 CK 20 p63 Mucicarmine

Additional Immunohistochemistry Mammaglobin CEA CK 5/6 Thyroglobin TTF-1 PSA Ki67

Diagnosis • Mammary Analogue Secretory Carcinoma (MASC) • ? Primary salivary gland origin v. primary cutaneous tumor • Rule out metastasis

Background • MASC first described in 2010 by Skalova et al. • Morphologic overlap between acinic cell carcinoma and secretory carcinoma of the breast • Tumors affect all ages (range 14-77), slightly male-predominant

MASC • Presents as slowly growing mass, often near parotid gland • No evidence of primary cutaneous origin, as of yet • Most treated with non-radical excision +/-radiotherapy • Cases of lymph node metastases, local recurrences, low mortality Chiosea et al, Histopathology 2012

Histology of MASC • Unencapsulated, lobulated • Intercalated duct cells in tubular, microcystic, papillary patterns • L umina with ample “bubbly” secretions ( mucicarmine +) • Absence of serous acinar granules

Immunohistochemistry of MASC Staining • Usually positive • S100 • CK7 • Vimentin • Often positive • EMA • GCDFP • Mammaglobin • Negative • CK5/6, CK20 • P63, TTF-1, PSA, Thyroglobulin 17

Immunohistochemistry of most apocrine tumors • Cytokeratin 5/6+, p63+ • S100+/-, cytokeratin 7+ • Mammaglobin +/-, EMA+ (patchy, highlights ducts) • CEA+, GCDFP 15+/- 18

Key Differential Diagnoses of MASC Diagnosis Key Cytomorphologic Ancillary Testing Features Features Benign oncocytic Lack vacuolated cytoplasm, S-100 negative, anti- neoplasms (oncocytoma, more cohesive mitochondrial antibody oncocytic cystadenoma, positive Warthin tumor) Acinic cell carcinoma Usually lacks mucin PAS-D+ cytoplasmic granules, DOG-1 strongly positive, mammaglobin negative Mucoepidermoid Epidermoid differentiation p63 positive, S100 negative, carcinoma MAML2 translocation Metastatic carcinoma High grade nuclei, many Staining variable show necrosis 19

Fusion Gene • Almost all MASC had fusion gene ETV6-NTRK3 Normal Cells No ETV6 Split Signals Abnormal ETV6 split signals

Clinical Course • Patient had neoplasm completely excised by the ENT service • Work-up for primary underlying neoplasm is on-going and imaging studies are negative for primary salivary gland tumor

Summary • MASC is likely an under-recognized diagnosis and can present a diagnostic pitfall, easily being confused with a primary adnexal tumor given that it is a newly-described entity and too bland to be immediately interpreted as a metastasis or recurrence. The origin of this particular tumor is still uncertain, as no salivary gland primary has been detected in this patient. • Immunohistochemical stains for S100, CK7, p63, cytokeratin 5/6, mammaglobin, and identification of the ETV6-NTRK3 fusion gene would be required to completely evaluate tumors of this type • ? Primary cutaneous/subcutis MASC v. unusual primary apocrine sweat duct tumor (solid and cystic hidradenoma)

Cutaneous Metastases v. Adnexal Primary Carcinoma: A Practical Approach 23

Cutaneous Metastases • Clinical Considerations • Mean age at presentation is 62 • Most common primary tumors • Lung 30% • Melanoma 18% • G.I. Tract 14% • Breast 5% • Lymphoma 5% • In approximately 10% of cases, the primary is unknown • Histologic Types • Adenocarcinoma 40% • Melanoma 15% • Squamous carcinoma 15% • Other 30% 24

Cutaneous Metastases v. Primary Adnexal Carcinoma • Histopathologic Characteristics of Metastases • Tumor growth often concentrated in the deep dermis - “ bottom heavy ” appearance • Sparing of epidermis common • Ulceration and pagetoid spread rarely noted (colonic and melanoma) • Tumor necrosis sometimes present • Lymph/vascular invasion sometimes observed • High grade tumor cells with numerous mitoses 25

Cutaneous Metastases v. Primary Adnexal Carcinoma • Immunohistochemical Considerations • Battery may include • Cytokeratin 7 • Cytokeratin 20 • S-100 • MART-1/Melan-A/MITF or SOX-10 • PSA • TTF-1 • ER/PR/Her-2-neu • CDX-2 • Cytokeratin 5/6, p63* 26

Cutaneous Metastases v. Primary Adnexal Carcinoma • Recent studies have shown that CK5/6 and p63 may help distinguish primary adnexal neoplasms (CK5/6+/p63+) from most metastatic carcinomas (CK5/6-/p63-) • P63 especially helpful • D2-40 not been especially helpful in my lab 27

46 yo F with history of breast cancer x7 years 28

Histopathology 29

Histopathology 30

Histopathology 31

IHC Results CK7 32

IHC Results ER 33

IHC Results HER2/neu 34

IHC Results CK5/6 35

IHC Results P63 36

68 yo M w paranasal mass present x 1 yr – rapid recent growth 37

Histopathology 38

Histopathology 39

Histopathology 40

IHC Results CK5/6 41

IHC Results p63 42

Cutaneous Metastases v. Primary Adnexal Carcinoma • Impossible to reliably distinguish primary or metastatic eccrine/apocrine tumors from cutaneous metastases of breast carcinomas, especially apocrine or mucinous types • Immunohistochemical Staining of Breast v. Metastases • ER (estrogen receptor) • PR (progesterone receptor) • GCDFP-15 (gross cystic disease fluid protein) • CEA • Her-2-neu • None of these may reliably separate primary sweat duct tumors from breast metastases 43

Cutaneous Metastases v. Primary Adnexal Carcinoma • Aberrant staining of metastases • Technical • Antibody • Technique • Therapeutic effect – chemo and/or radiation/immune modulators • Tumor metastases may have different immuno phenotypes than the primary • Tumors don’t always read the books • Another tumor/primary is responsible for the aberrant staining 44

Cutaneous Metastases v. Primary Adnexal Carcinoma • Take Home • H&E considerations and clinical information most important for diagnostic purposes • Immunohistochemistry stains are useful ancillary studies, especially cytokeratin 5/6 and p63 but be careful as these may lead you astray • Be sure to eliminate the possibility of a basal cell carcinoma demonstrating unusual growth patterns • Always think of the possibility of a primary adnexal CA in the appropriate clinical and histologic context • Occasional inability to differentiate a primary adnexal CA from a visceral metastasis 45

References • Saliva A, Vanecek T, Sima R, Laco J, Weinreb I, Perez-Ordonez B, Starek I, Geierova M, Simpson RH, Passador-Santos F, Ryska A, Leivo I, Kinkor Z, Michal M. Mammary analogue secretory carcinoma of salivary glands, containing the ETV6-NTRK3 fusion gene: a hitherto undescribed salivary gland tumor entity. Am J Surg Pathol. 2010 May;34(5):599-608. • Griffith C, Seethala R, Chiosea SI. Mammary analogue secretory carcinoma: a new twist to the diagnostic dilemma of zymogen granule poor acinic cell carcinoma. Virchows Arch. 2011 Jul;459(1):117-8. • Fehr A, Löning T, Stenman G. Mammary analogue secretory carcinoma of the salivary glands with ETV6- NTRK3 gene fusion. Am J Surg Pathol. 2011 Oct;35(10):1600-2. • Rastatter JC, Jatana KR, Jennings LJ, Melin-Aldana H. Mammary analogue secretory carcinoma of the parotid gland in a pediatric patient. Otolaryngol Head Neck Surg. 2012 Mar;146(3):514-5. • Connor A, Perez-Ordoñez B, Shago M, Skálová A, Weinreb I. Mammary analog secretory carcinoma of salivary gland origin with the ETV6 gene rearrangement by FISH: expanded morphologic and immunohistochemical spectrum of a recently described entity. Am J Surg Pathol. 2012 Jan;36(1):27-34. • Chiosea SI, Griffith C, Assaad A, Seethala RR. Clinicopathological characterization of mammary analogue secretory carcinoma of salivary glands. Histopathology. 2012 Sep;61(3):387-94. • Griffith CC, Stelow EB, Saqi A, Khalbuss WE, Schneider F, Chiosea SI, Seethala RR. The cytological features of mammary analogue secretory carcinoma: a series of 6 molecularly confirmed cases. Cancer Cytopathol. 2013 May;121(5):234-41. • Bishop JA. Unmasking MASC: bringing to light the unique morphologic, immunohistochemical and genetic features of the newly recognized mammary analogue secretory carcinoma of salivary glands. Head Neck Pathol. 2013 Mar;7(1):35-9.