Clinicopathological and Molecular Features of Glycogen-Rich Breast Carcinoma

Since its description by Hull and colleagues in 1981, several case series have described the clinicopathological features of glycogen-rich breast carcinoma (GRC); however, no detailed genetic study has been performed. We identified 10 patients with GRC; all were female (ages: 32 to 74 y; median: 51). Tumor size ranged from 0.7 to 3.8 cm (median: 1.45). All except one GRC showed relatively well-defined borders, and all were composed predominantly of nests containing clear cells with glycogen accumulation in cytoplasm confirmed by Periodic Acid-Schiff/Periodic Acid-Schiff- Diastase (PAS/PAS-D)staining. Using Nottingham grading, four were grade 2 and six were grade 3. Seven showed associated ductal carcinoma in situ (DCIS) with glycogen-rich features. Lymph node macrometastasis was seen in 2=two. Six were hormone receptor (HR) +/ human epidermal growth factor receptor 2 (HER2)-, 2 HR low +/ HER2- and 2 triple-negative. Follow-up (available for 9/10) ranged from 9 to 186 months (median: 38). All patients were alive; two patients had distant metastasis, one patient had local recurrence and six had no evidence of disease. DNA sequencing suggested two molecular subgroups: GATA3-mutant GRCs (5/10) with frequent RPKSB1 copy number gain (4/5) and TP53-mutant GRCs (4/10). GATA3-mutant GRCs were mixed grade 2/3, all were HR+ without distant metastasis while TP53-mutant GRCs were all grade 3, showed low +/- HR, and 3/4 patients showed distant metastasis/local recurrence. p53 immunohistochemistry showed mutant-pattern staining in three TP53-mutant GRCs tested as opposed to wild-type pattern in five GATA3-mutant GRCs. Molecular studies or p53 immunohistochemistry as a surrogate could be helpful to identify the TP53-mutant subgroup for closer follow-up and/or more aggressive treatment.