HER2 Immunohistochemistry in Invasive Micropapillary Breast Carcinoma

Context.-Invasive micropapillary carcinoma (IMPC) is a rare variant of breast carcinoma, composed of avascular morula-like tumor clusters surrounded by stromal spaces, which can affect the HER2 immunohistochemical (IHC) staining pattern. The 2013 American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) HER2 testing guideline suggests moderate to intense but incomplete (basolateral) staining be considered equivocal. Objectives.-To perform a detailed assessment of HER2 IHC staining patterns in IMPC. Design.-Hematoxylin-eosin and HER2 IHC slides were retrospectively reviewed to assess the morphology and HER2 IHC characteristics of IMPC. The 2018 ASCO/CAP guideline was applied. Results.-The cohort consisted of 187 IMPCs from 181 patients with median age of 58 years. Homogeneous (-90%) micropapillary component was found in 40% (75 of 187) of cases. Receptor profile was as follows: 75% (140 of 187) ER+ HER2(-), 19% (37 of 187) ER+ HER2(+), 4% (7 of 187) ER- HER2(+), and 2% (3 of 187) ER- HER2(-). Of 26 cases with HER2 IHC 3(+), 65% (17 of 26) showed a basolateral staining pattern with strong intensity. HER2 fluorescence in situ hybridization (FISH) showed amplification in 26% (17 of 66) of HER2 IHC equivocal cases: 76% (13 of 17) showed basolateral staining pattern and 24% (4 of 17) complete staining, with weak to moderate (2), moderate (14), or moderate to strong (1) intensity. Conclusions.-The most frequent staining pattern was basolateral, seen in 49% of cases, including 65% HER2 IHC positive and 76% HER2 IHC equivocal/FISH amplified. If a basolateral pattern and weak to moderate staining is observed in IMPC, alternative testing should be performed to confirm the HER2 status.

Automated summary

This study conducted a detailed assessment of HER2 immunohistochemical staining patterns in 187 cases of invasive micropapillary carcinoma (IMPC), finding that the most common staining pattern was basolateral, with many cases being HER2 IHC positive or equivocal/FISH amplified. If a basolateral pattern and weak to moderate staining is observed in IMPC, alternative testing should be done to confirm the HER2 status.