HER2 Immunohistochemistry in Invasive Micropapillary Breast Carcinoma: Complete Assessment of an Incomplete Pattern

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.

To perform a detailed assessment of HER2 IHC staining patterns in IMPC.

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.

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.

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.