Invasive lobular carcinoma with extracellular mucin (ILCEM): clinicopathologic and molecular characterization of a rare entity.

Autor: Soong TR; Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA., Dillon DA; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Rice-Stitt TL; Department of Pathology, Massachusetts General Hospital, Boston, MA, USA., Wieczorek TJ; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.; Department of Pathology, Brigham and Women's Faulkner Hospital, Boston, MA, USA., Baker GM; Harvard Medical School, Boston, MA, USA.; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA., Darvishian F; Department of Pathology, New York University Langone Medical Center, New York, NY, USA., Collins LC; Harvard Medical School, Boston, MA, USA.; Department of Pathology, Beth Israel Deaconess Medical Center, Boston, MA, USA., Lester SC; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Schnitt SJ; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA.; Harvard Medical School, Boston, MA, USA., Harrison BT; Department of Pathology, Brigham and Women's Hospital, Boston, MA, USA. bharrison3@bwh.harvard.edu.; Harvard Medical School, Boston, MA, USA. bharrison3@bwh.harvard.edu.
Jazyk: angličtina
Zdroj: Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc [Mod Pathol] 2022 Oct; Vol. 35 (10), pp. 1370-1382. Date of Electronic Publication: 2022 Apr 27.
DOI: 10.1038/s41379-022-01084-w
Abstrakt: Invasive lobular carcinoma with extracellular mucin (ILCEM) is a rare histologic subtype of breast cancer. Little is known about the pathologic or genomic signatures that distinguish ILCEM from classic invasive lobular carcinoma (ILC) or mucinous carcinoma. We studied 17 breast cancers with lobular morphology and extracellular mucin. Thirteen tumors with sufficient tissue for DNA extraction were analyzed by a next generation sequencing (NGS) assay that interrogates 447 genes for mutations and copy number variations (CNVs). Median patient age was 66 yrs (range: 31-77 yrs). Sixteen patients presented with masses, 7 of which were >2 cm. Seven patients had lymph node metastases. The cases of ILCEM were moderately (n = 13) or poorly differentiated (n = 4), frequently exhibiting variant morphology that has not been previously described or emphasized, including grade 3 nuclei (n = 11), diffuse signet ring cells (n = 10), solid growth (n = 4), tumor necrosis (n = 3) or apocrine features (n = 2). All tumors showed absent or reduced membranous E-cadherin expression. Concurrent lobular carcinoma in situ (LCIS) was seen in 11/17 cases, 1 of which was a striking example of signet ring cell LCIS with extracellular mucin. Receptor profiles were ER+/HER2- (n = 15) and ER+/HER2+ (n = 2). With a median follow-up of 83.5 months (range: 3-171 months) in 12 patients with available information, 8 patients had recurrences resulting in 4 cancer-related deaths. The most common CNVs were 16q loss (n = 11) and 1q gain (n = 9). CDH1 gene-level alterations were detected in all but one case, including frameshift (n = 7), nonsense (n = 2), and donor splice site (n = 1) mutations and indels (n = 2). Recurrent mutations were also seen in PIK3CA (n = 3), POLQ (n = 3), TP53 (n = 3), ERBB3 (n = 3), ERBB2 (n = 2), and RUNX1 (n = 2). Genes with recurrent amplifications included GATA3 (n = 4), FOXA1 (n = 3), CCND1 (n = 2). Our data highlights ILCEM as a distinct variant of ILC that often presents with higher-grade and variant morphologic features and is associated with an aggressive clinical course. NGS data support an overall lobular-type molecular profile and reveal potentially targetable alterations in a subset of cases with recurrence.
(© 2022. The Author(s), under exclusive licence to United States & Canadian Academy of Pathology.)
Databáze: MEDLINE