Resident Program - Case of the Month
May 2021 – Presented by Dr. Jasper X. Zheng (Mentored by Dr. Chihong Heidi Zhou)
Mammary Analogue Secretory Carcinoma (MASC), also known as Secretory carcinoma, is a low-grade salivary carcinoma with analogous morphological and molecular features found in its counterpart, the secretory carcinoma of the breast.
Since its initial documentation in 2010, approximately 232 cases of MASC have been reported in literature . The most common site of occurrence is in parotid gland, followed by incidence of MASC development in the minor intraoral and submandibular glands . The usual age of presentation is around mid-forties with a slight preponderance for the male gender [1,2]. The most common clinical presentation of MASC is an indolent slow growing painless mass [1-3].
Macro and Microscopic features:
Grossly, MASC is typically a well-circumscribed and unencapsulated tumor with rubbery consistency, gray-white to brown cut surfaces, and a variable cystic component [2,3].
Histologically, MASC is predominantly an extraductal and unencapsulated neoplasm typically showing at least some infiltration. Occasionally, perineural invasion can be seen (Figure 4).
The MASC tumor is composed of lobules separated by fibrous septa. The lobules are composed of neoplastic cells that are epithelioid cuboidal to polygonal in appearance, with granular to vacuolated eosinophilic cytoplasm, and typically arranged in a microcystic, tubular or solid pattern [1-3, 6, 7]. The nuclei are ovoid with fine open chromatin and small distinct nucleoli [2,3].
The defining genetic feature of Mammary Analogue Secretory Carcinoma is the presence of ETV6-NTRK3 gene fusion as a result of chromosome 12 ETV6 gene fusion with NTRK3 gene on chromosome 15 [1-3]. Mammary Analogue Secretory Carcinoma is the only salivary tumor with this unique gene translocation.
Mammary Analogue Secretory Carcinoma is morphologically very similar to acinic cell carcinoma. The two entities can be distinguished by the identification of sparse to abundant intracellular basophilic granules supporting the diagnosis of acinic cell carcinoma . Acinic cell carcinoma usually exhibit diffuse positive DOG1 staining distinguishing it from MASC which has negative DOG1 staining . On the other hand, MASC exhibit strong S100, mammaglobin, GATA3, and STAT5a immunohistochemical staining. The detection of ETV6-NTRK3 gene fusion on FISH using ETV6 break-apart probes is a unique cytogenetic characteristic of Mammary Analogue Secretory Carcinoma that distinguish it from all other conventional salivary gland neoplasms [1-4].
Other possible differential diagnosis presented here in table format:
Distinguishing Cytological features
Distinguishing IHC staining
Mammary Analogue Secretory Carcinoma
|Granular to vacuolated eosinophilic cytoplasm||Mammaglobin, S100, GATA-3, and STAT5a has strong diffuse expression
DOG1 has Absent or weak membranous expression at tumor periphery
|ETV6-NTRK3 gene fusion|
Acinic Cell Carcinoma
|Basophilic cytoplasm with PAS+ zymogen granules||Negative for mammaglobin and S100
DOG 1 has Strong cytoplasmic and canalicular expression
|HTN3-MSANTD3 gene fusion|
Low-Grade Salivary Duct Carcinoma
|Cytoplasm with yellow lipofuscin-like pigment||Mammaglobin and S100 has strong diffuse expression
Negative for DOG 1
High-Grade Salivary Duct Carcinoma
|Abundant oncocytoid cytoplasm with distinct cell borders||Positive Mammaglobin and S100 expression
Negative for DOG 1
Androgen Receptor (AR) positivity > 90%
|HER 2 gene amplification|
Mucoepidermoid Carcinoma: 3 cell types: Intermediate, squamoid, and mucin-containing cells
|Intermediate squamoid mucin-containing cells||Focal nuclear expression of p63
Negative S100 expression
|CRTC1-MAML2 gene fusion|
Polymorphous Low-Grade Adenocarcinoma
|Monotonous pale nuclei with marked chromatin clearing
Rarely found in parotid gland
|Can have positive Mammaglobin and S100 expression||PRKD mutations and fusions|
- Goldblum, John R., et al. Rosai and Ackerman's Surgical Pathology. Elsevier, 2018.
- M., Fletcher Christopher D. Diagnostic Histopathology of Tumors. Elsevier, 2021.
- El-Naggar, A.K., et al. WHO Classification of Head and Neck Tumors. Lyon, France: International Agency for Research on Cancer; 2017.
- Khurram SA, Speight PM. Characterisation of DOG-1 expression in salivary gland tumours and comparison with myoepithelial markers. Head Neck Pathol. 2019;13:140–8.
- Griffith CC, Pai RK, Schneider F, Duvvuri U, Ferris RL, Johnson JT, Seethala RR. Salivary gland tumor fine-needle aspiration cytology: a proposal for a risk stratification classification. Am J Clin Pathol. 2015 Jun;143(6):839-53. doi: 10.1309/AJCPMII6OSD2HSJA. PMID: 25972326; PMCID: PMC5257286.
- Griffith CC, Stelow EB, Saqi A, et al. The cytological features of mammary analogue secretory carcinoma: a series of 6 molecularly confirmed cases. Cancer Cytopathol. 2013;121:234-241.
- Venkat S, Fitzpatrick S, Drew PA, Bhattacharyya I, Cohen DM, Islam MN. Secretory Carcinoma of the Oral Cavity: A Retrospective Case Series with Review of Literature. Head Neck Pathol. 2021 Mar 3. doi: 10.1007/s12105-021-01310-y. Epub ahead of print. PMID: 33660147.
- Jeffrey Krane, M.D., Ph.D., Sheets and clusters of bland polygonal epithelial cells, some containing mucin; others will have a finely eosinophilic granular cytoplasm., https://www.pathologyoutlines.com/topic/salivaryglandsmammary.html
- Jeffrey Krane, M.D., Ph.D., Nuclei are uniform, small, round, eccentrically located, with small nucleoli., https://www.pathologyoutlines.com/topic/salivaryglandsmammary.html
- Andreasen S, Varma S, Barasch N, Thompson LDR, Miettinen M, Rooper L, Stelow EB, Agander TK, Seethala RR, Chiosea SI, Homøe P, Wessel I, Larsen SR, Erentaite D, Bishop JA, Ulhøi BP, Kiss K, Melchior LC, Pollack JR, West RB. The HTN3-MSANTD3 Fusion Gene Defines a Subset of Acinic Cell Carcinoma of the Salivary Gland. Am J Surg Pathol. 2019 Apr;43(4):489-496. doi: 10.1097/PAS.0000000000001200. PMID: 30520817
- Todd M. Stevens, MD ; Vishwas Parekh, MD, Arch Pathol Lab Med (2016) 140 (9): 997–1001., https://doi.org/10.5858/arpa.2015-0075-RS