Mammary Analogue Secretory Carcinoma of Salivary Glands

Abstract

Mammary analogue secretory carcinoma (MASC) is a recently described low-grade carcinoma with morphologic and genetic similarity, including ETV6-NTRK3 fusion, to secretory carcinoma of the breast. ETV6 is frequently involved in other epithelial and nonepithelial tumors, and many fusion partners of ETV6 have been reported. In the present study, 14 Japanese MASC cases were clinicopathologically and molecularly analyzed. The median age of the patients was 39 years, and the male:female ratio was 6:8. All cases showed histopathologic findings compatible with those previously described for MASC and harbored an ETV6 split as visualized by fluorescence in situ hybridization. Two cases showed thick fibrous septa and invasive features including vascular or perineural tumor involvement, findings that are rare in MASC. In addition, in these 2 cases, non-NTRK3 genes appeared to fuse with ETV6 (ETV6-X fusion). NTRK1 and NTRK2, both members of the NTRK family, were not involved. Of the 14 MASC cases, the ETV6-NTRK3 fusion transcript was positive in 6 cases, and the relative expression level of the ETV6-NTRK3 fusion transcript was variable, ranging from 1 to 5.8. Results of the present study of MASC suggest that (1) ETV6 occasionally fuses with unknown non-NTRK3 genes, (2) ETV6-X cases might have an invasive histology, (3) for molecular diagnosis of MASC, fluorescence in situ hybridization to detect ETV6 splits is the method of choice, and (4) the expression level of the ETV6-NTRK3 fusion transcript is considerably variable. These findings provide a novel insight into the oncogenesis, histopathology, diagnosis, treatment, and prognosis of this newly recognized carcinoma.

Utility of Immunohistochemistry and ETV6 (12p13) Gene Rearrangement in Identifying Secretory Carcinoma of Salivary Gland among Previously Diagnosed Cases of Acinic Cell Carcinoma

“…Skálová et al identified 5 SC cases with atypical junctions, exon 4 of ETV6 with exon 14 of NTRK3, and exon 5 of ETV6 with exon 14 of NTRK3 that have not been described in SC so far [16]. They also confirmed the observation of Ito et al that a subset of SC cases very likely harbors ETV6 fused with non-NTRK genes (ETV6-X fusion) [17]. Their study also suggested that cases with ETV6 gene fusing with genes other than NTRK3 or those cases displaying atypical exon junctions of ETV6-NTRK3 are associated with more aggressive/infiltrative histologic features of SC and less favorable clinical outcomes.…”

What hides behind the MASC: clinical response and acquired resistance to entrectinib after ETV6-NTRK3 identification in a mammary analogue secretory carcinoma (MASC)

“…Before its designation as a separate entity, MASCs were predominantly grouped with other low-grade salivary cancer histologies [most commonly acinic cell carcinoma (AciCC)]. In 2010, identification of the ETV6-NTRK3 translocation t(12:15)(p13;q25) confirmed these tumors to be a molecularly distinct disease; the histologic resemblance to secretory carcinoma of the breast (which also harbors this fusion gene) inspired the designation ‘mammary analogue secretory carcinoma’ [ 2 , 3 ]. Of note, while ETV6-NTRK3 represents the most common fusion in MASCs, some cases have been found to harbor rearrangements involving ETV6 and a non- NTRK3 partner [ 4 ].…”

Mutation analysis of the EGFR pathway genes, EGFR, RAS, PIK3CA, BRAF, and AKT1, in salivary gland adenoid cystic carcinoma

“…Using paraffin tumor sections, we performed interphase FISH analysis for the gene splits in MYB , MYBL1 , and NFIB , as well as gene fusions between these genes when the gene splits were present. FISH procedures have been described elsewhere [ 7 , 59 ] and the FISH probes that we used are shown in Supplementary Table 2 . The frequencies of gene abnormalities were determined by counting >100 tumor cells.…”