Morphologic and immunohistochemical features of carcinoma involving microglandular adenosis of the breast following neoadjuvant chemotherapy

Abstract

Microglandular adenosis (MGA)-related lesions, including atypical MGA (AMGA) and carcinoma involving MGA (C-MGA), are characterized by epithelial atypia, negative hormone receptors and HER2 status, and can mimic invasive triple negative breast cancer (TNBC) in core needle biopsies (CNB) resulting in selection for treatment with neoadjuvant chemotherapy (NAC). We identified 12 cases of AMGA and/or C-MGA in post-NAC excision specimens (EXC) and analyzed their morphologic and immunohistochemical (IHC) features. All CNBs were initially diagnosed as containing TNBC. Upon re-review, TNBC was confirmed in 9 cases. In 3 CNBs AMGA and/or C-MGA had been interpreted as TNBC. AMGA was initially recognized in only 1 case but AMGA and/or C-MGA were present in an additional 9 CNBs. At EXC, no residual TNBC was present in 5 of 9 EXCs and all 12 cases showed residual AMGA and/or C-MGA. Similar to conventional MGA, AMGA and C-MGA were positive for S-100, laminin and collagen IV and negative for calponin and p63. Following NAC, these lesions retained their typical staining pattern despite acquiring treatment-related morphologic alterations, most notably of which were areas of single cell growth pattern seen in 8 EXCs. This study is the first to report the effects of NAC on AMGA and C-MGA. Our data showed no response of the AMGA and/or C-MGA following NAC in contrast to the high response rate of conventional TNBC. In particular, the infiltrative single cell pattern of post-NAC MGA-related lesions closely mimicked residual TNBC. The persistence of AMGA and C-MGA following NAC supports the notion that these lesions are distinct from conventional TNBC. Our findings also highlight the challenges in recognizing AMGA and C-MGA in CNBs which may lead to unwarranted treatment with NAC in the absence of conventional TNBC.

A case of extensively spreading acinic cell carcinoma of the breast with microglandular features

“…Recent reports indicate that atypical MGA and carcinoma involving MGA are less responsive to NAC than conventional TNBC. 18 There are several reports on the effect of NAC on ACC, suggesting that chemotherapy might be more effective for poorly differentiated as compared with well-differentiated ACC. 1,19 The findings in this case demonstrate that each component within a single tumor might respond differently to NAC.…”

“…In contrast, the MGA‐like well‐differentiated component was not accompanied by degenerative or necrotic tumor cells or fibrosis, suggesting that NAC had little effect on this part of the tumor. Recent reports indicate that atypical MGA and carcinoma involving MGA are less responsive to NAC than conventional TNBC 18 . There are several reports on the effect of NAC on ACC, suggesting that chemotherapy might be more effective for poorly differentiated as compared with well‐differentiated ACC 1,19 .…”

Papillary Breast Tumors: Continuing Controversies and Commentary on WHO's 2019 Criteria and Classification

“…This tenuous concept defies the observation that some mammary glandular lesions that are (almost certainly) benign also lack MECs at the perimeter of the glands, for example, some simple apocrine cysts, selected apocrine lesions, and microglandular adenosis. 12,13,39 Furthermore, this ambivalent concept does not lend itself to staging, at least in the extant TNM system, and the narrative of being "intermediate between carcinoma in situ and invasive carcinoma" is unlikely to be embraced by treating clinicians. To its credit, Breast Tumors regards both SPC and EPC as being noninvasive, at least those that bear low to intermediate grade nuclei.…”