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Understanding the histogenesis of a HRAS‐PIK3R1 co‐driven metastatic metaplastic breast carcinoma associated with squamous metaplasia of lactiferous ducts
Author(s) -
FebresAldana Christopher A.,
Alvarez Moreno Juan C.,
Rivera Melissa,
Kaplan Stuart,
Paramo Juan,
Poppiti Robert
Publication year - 2020
Publication title -
pathology international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.73
H-Index - 74
eISSN - 1440-1827
pISSN - 1320-5463
DOI - 10.1111/pin.12887
Subject(s) - metaplastic carcinoma , pathology , cancer research , hras , biology , breast cancer , medicine , cancer , kras , colorectal cancer
Metaplastic breast carcinoma (MBC) represents a heterogeneous group of aggressive primary breast cancers that can show differentiation into carcinomatous and sarcomatous elements. Due to its rapid growth, this malignancy can replace precursor lesions, which remain unknown in most cases. Herein, we describe a MBC presenting as a deceptive post‐biopsy hematoma. Histopathological and immunohistochemical evaluation of the primary tumor revealed a squamous cell carcinoma arising in a background of squamous metaplasia of lactiferous ducts (SMOLD). In the absence of ductal carcinoma in situ , we consider SMOLD as a nonobligatory precursor of MBC. The tumor showed ‘dedifferentiation’ into spindle, mucin‐producing, osteoclast‐like giant cell and fibromatosis‐like carcinoma. Next‐generation sequencing revealed the driver mutations HRAS Q61R and PIK3R1 c.1738_1745+2del in addition to MYH11 S638L and amplification of ERCC5 and FGF14 , which were potential contributors to tumor phenotype. Tumor dedifferentiation was probably facilitated by epithelial‐to‐mesenchymal transition (EMT) with aberrant expression of platelet and endothelial adhesion molecule‐1, leading to early metastasis via hematogenous route rather than lymphatic. The co‐occurrence of phosphoinositide 3‐kinase and mitogen‐activated protein kinase pathway abnormalities along with EMT could mediate divergent growth in breast cancer.