Τρίτη 21 Απριλίου 2020

Apocrine Variant of Pleomorphic Lobular Carcinoma In Situ: Further Clinical, Histopathologic, Immunohistochemical, and Molecular Characterization of an Emerging Entity

Apocrine Variant of Pleomorphic Lobular Carcinoma In Situ: Further Clinical, Histopathologic, Immunohistochemical, and Molecular Characterization of an Emerging Entity:

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To date, the apocrine variant of lobular carcinoma in situ (AP-LCIS) has been cursorily described as a subtype of lobular carcinoma in situ (LCIS). We retrospectively reviewed 34 cases of AP-LCIS (including 23 associated with invasive lobular carcinoma) to fully characterize it. AP-LCIS typically presented with screen-detected calcifications in older women (mean age: 65 y) and was characterized by distended terminal duct lobular units with relatively large “pleomorphic” cells, central necrosis, and calcifications. AP-LCIS cells exhibited abundant eosinophilic occasionally granular cytoplasm, hyperchromatic nuclei, and prominent nucleoli. Synchronous classic and/or florid LCIS was identified in 24/34 (70%) AP-LCIS, and in 9/11 (82%) pure AP-LCIS. Most (68%) cases of AP-LCIS were estrogen receptor–positive (50% strongly), 35% were progesterone receptor–positive, 26% were human epidermal growth factor 2–positive, 18% demonstrated high-proliferation rate (Ki67: >15%), and 90% were androgen receptor–positive. Aurora kinase A, immunoreactive in 38% of AP-LCIS cases, was not significantly associated with recurrence, development of invasion, or nodal positivity (P>0.05). Compared with conventional (nonapocrine) pleomorphic lobular carcinoma in situ (P-LCIS), aurora kinase A was expressed in a significantly greater proportion of P-LCIS (100%). AP-LCIS and P-LCIS did not otherwise differ in clinicopathologic features. Next-generation sequencing utilizing the Oncomine Comprehensive Panel v2, performed on 27 AP-LCIS cases, showed no specific molecular findings. In a mean follow-up of 57 months, 2 (of 11, 18%) pure AP-LCIS cases recurred (2 both in situ and invasive) and none metastasized or proved fatal. AP-LCIS should be regarded as another high-grade LCIS similar to P-LCIS in many respects, and pending additional studies should be managed similarly.

This work was presented, in part, at the 109th Annual Meeting of the United States and Canadian Academy of Pathology in March 2020 in Los Angeles, CA.

Conflicts of Interest and Source of Funding: supported by the Translational Research Program at Weill Cornell Medical Center Pathology and Laboratory Medicine. The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.

Correspondence: Elaine Zhong, MD, Department of Pathology, Weill Cornell Medicine, 525 East 68th Street, Starr 1036, New York, NY 10065 (e-mail: ewz7001@nyp.org).

Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved.


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