Glycogen-rich clear cell carcinoma of the breast (GRCCC) is an uncommon variant of invasive breast cancer with abundant tumor-cell glycogen and thought to have poor outcome. There are conflicting reports on the prognosis of GRCCC and its pathologic/diagnostic criteria. Some features overlap with carcinomas having hepatoid features. We hypothesize that immunomarkers of hepatic differentiation may help distinguish GRCCC from more common breast cancers.
As approved by the institutional research ethics board, cases diagnosed as “glycogen-rich clear cell carcinoma” or “invasive carcinoma with clear cell features” were identified from lab archives. A control cohort of non-GRCCC cases was also identified. All diagnoses were confirmed by pathologist review. Tumor grade, size, and ER/PgR/HER2 status were recorded. Freshly cut 4-μm sections from FFPE tumor blocks were mounted on charged slides and immunostained with Hep Par 1, alpha-fetoprotein (AFP) and GATA3 using standard clinical protocols. Stains were reviewed by 2 pathologists (MCC, JMW).
Eight cases had "clear cell features", and 5/8 met all WHO morphologic criteria for GRCCC (high-grade nuclei, polygonal cells, PAS-positive granules/globules). All GRCCCs had weak to moderate ER staining in 33- 66% of cells, were negative for PgR and HER2, and were positive for Hep Par 1 with a diffuse, strong granular cytoplasmic pattern. GRCCCs were also positive for GATA3 and negative for AFP. The remaining 3 cases “with clear cell features” had grade 2 nuclei, were GATA3-positive, had >90% strong positivity for ER and PgR, and were negative for HER2, Hep Par1 and AFP. The control cohort included 16 “luminal-like” (ER+/HER2 -), 21 HER2+, and 24 triple-negative tumors (total N = 61). GATA3 was positive in 51/61 (84%) of tumors. All tumors in the control cohort were negative for Hep Par 1 and AFP.
True GRCCC of the breast is likely a distinct high-grade tumor with strong granular-cytoplasmic Hep Par 1 staining. GRCCCs tend to be PgR and HER2-negative, and demonstrate weak-to-moderate ER positivity. Criteria for GRCCC should be applied strictly to exclude other tumors with “clear cell features”. Further work is warranted to establish the prognostic significance of this diagnosis.
Martin C. Chang.
Has not received any funding.
All authors have declared no conflicts of interest.