Faculty Bibliography

Salivary gland secretory carcinoma, also termed mammary analogue secretory carcinoma (MASC), is a recently described salivary gland neoplasm with characteristic histomorphologic findings similar to those of secretory carcinoma of the breast and harboring recurrent ETV6-NTRK3 fusions. Recent findings have expanded the molecular profile of salivary gland secretory carcinoma to include multiple novel ETV6 fusion partners, including RET, MET, and MAML3. Here, we report a case of cystic MASC with cribriform and papillary histology harboring two gene fusions, ETV6-RET and EGFR-SEPT14, identified by targeted RNA sequencing. The presence of the rearrangements was confirmed by FISH, RT-PCR, and Sanger sequencing. This is the first EGFR-SEPT14 fusion reported in secretory carcinoma as a single event or in association with an ETV6 rearrangement. This finding adds to the expanding molecular profile of this tumor entity, and may translate into novel treatment strategies.

Amyloidosis is characterized by extracellular deposition of insoluble protein fibrils in a beta-pleated sheet configuration. Breast amyloidosis is a rare entity which has previously been reported to present with localized involvement, or as a late manifestation of systemic amyloidosis. However, descriptions of the clinicopathologic features of localized breast amyloidosis remain limited. A retrospective search for breast amyloidosis diagnosed at our institution yielded 10 cases of breast amyloidosis. All patients were female, with a mean age of 69. Median follow-up for survival or progression was 13 months. Indications for breast or axilla biopsy included mammographic calcifications, mass, and axillary lymphadenopathy. Amyloid showed positive staining with Congo red in all cases, and amyloid typing revealed light chain lambda in 3 cases, amyloid transthyretin in 2 cases, light chain kappa in 1 case, and iatrogenic insulin-derived amyloidosis in 1 case. Amyloid occurred within axillary lymph nodes and alongside both benign and neoplastic breast tissue, including atypical ductal hyperplasia, lobular carcinoma in situ and ductal carcinoma in situ. Most cases were associated with predisposing clinical conditions, including autoimmune disease in 4 cases, B cell lymphomas in 2 cases, and diabetes mellitus treated with insulin in 1 case. In contrast to previously published case series, no patient had clinical evidence of systemic amyloidosis. Amyloidosis of the breast should be considered in the differential diagnosis of all mammographic calcifications and masses of the breast or axilla. When recognized correctly on biopsy, the diagnosis of amyloidosis can not only prevent further unnecessary surgical interventions due to radiology-pathology discordance, but initiate the necessary amyloidosis work-up. Although rare, an awareness of the clinicopathologic characteristics of this easily overlooked entity is of great importance for every practicing pathologist reviewing breast biopsies.

Multifocal breast cancer (MFBC), ductal type, has been hypothesized to arise by one of two mechanisms: either through intramammary/intralymphatic spread from a single index tumor (MBC-1), or as multiple independent tumors with each focus carrying its corresponding ductal carcinoma in-situ (MBC-2). In order to improve our understanding of MFBC pathogenesis, we employed laser capture microdissection coupled with whole-exome sequencing to study clonal origin in MFBC. We selected three cases of MBC-1 (C1 to C3) and MBC-2 (C4 to C6) and analyzed three foci from each case. MBC-1 cases were histologically similar and showed a strong predilection for satellite foci, vascular invasion and nodal metastasis when compared to MBC-2. Our bioinformatics approach provided strong evidence for clonal relationships in MBC-1, as demonstrated by distinct clusters of genes conserved across all tumor foci. Conversely, no gene clusters were shared across all the foci in MBC-2, suggesting multiple independent tumors. These findings provide further support for the two distinct pathogenetic mechanisms in MFBC.