Mammary Analog Secretory Carcinoma (MASC) of the oral mucosa with proven ETV6- NTRK3 fusion gene as the gold standard for diagnosis – A case series and literature review

Abstract

Abstract Introduction/Objective Mammary Analog Secretory Carcinoma (MASC) is a rare type of cancer that occurs in the salivary glands. It is named after its similarity in appearance and behavior to secretory carcinoma of the breast. The incidence of MASC is estimated at 0.3%, with less tha 500 cases reported. The diagnosis of MASC is based on a combination of clinical, radiographic, and histopathologic features. Prognosis is generally good, with a low risk of recurrence and metastasis; its differential diagnosis includes: acinic cell carcinoma, adenocarcinoma (primary or metastatic), mucoepidermoid carcinoma, and low-grade cribriform cystadenocarcinoma. MASC is characterized by ETV6-NTRK3 fusion gene, a translocation between the ETV6 gene on chromosome 12 and the NTRK3 gene on chromosome 15, leading to the fusion of these two genes and the production of a chimeric protein. FISH testing can detect the presence of the ETV6-NTRK3 fusion gene. The detection of the ETV6-NTRK3 fusion gene is highly specific for MASC and can aid in the diagnosis and management of this tumor. In addition, the presence of this gene fusion can have implications for targeted therapy, as drugs that target the NTRK3 gene may be effective in the treatment of MASC. Methods/Case Report This review aims to compare the characteristics of MASC in cases we diagnosed since 2015. Results (if a Case Study enter NA) Cases Case 1 (2015) 68yo Female Right Lower Lip, Biopsy Positive: S100, PAS with and without diastase and mammaglobin Negative: Mucicarmine ETV6 + Case 2 (2016) 54yo Female Right Buccal Mucosa, Biopsy Positive: S100, Mammaglobin Weakly positive: p63 ETV6 + Case 3 (2016) 42yo Male Right Buccal Mucosa, Biopsy Positive: S100, Ck7, Ck5/6, Vimentin Weakly positive: GFAP, p63 Negative: SMA, MSA, Calponin ETV6 + Case 4 (2018) 60yo Female Left Soft Palate, Biopsy Positive: CK7 Weakly positive: GATA-3 Negative: CK20, TTF-1, CDX-2, Napsin A ETV6 + Case 5 (2019) 57yo Female Right Palatal Mucosa, Biopsy Positive: S100, Ck7, Ck5/6, Vimentin Negative: p63, GFAP, Calponin, SMA ETV6 + Conclusion MASC is a very rare salivary gland tumor and the gold standard for its diagnosis is FISH for ETV6 gene rearrangement. All our cases showed ETV6- NTRK3 fusion gene, while 80% (4/5) of the patients were females. S100, mammaglobin and PAS were positive in all tested cases, consistent with previous reports. The histopathological diagnosis of MASC on a biopsy can be challenging; although immunohistochemical stains and morphology may be helpful hints, FISH testing should be considered when MASC is suspected.