Invasive lobular carcinoma harboring dual PIK3CA mutations and a CDH1 variant with prominent myxoid stroma: a case...

Invasive lobular carcinoma is defined by a characteristic discohesive growth pattern and is frequently associated with alterations in CDH1. The clinical interpretation of genomic findings in this tumor type, however, remains challenging. We describe a woman in her 50s with estrogen receptor-positive, HER2-negative invasive lobular carcinoma of the left breast, in whom comprehensive genomic profiling was performed. Histological examination of the primary tumor demonstrated classic lobular carcinoma accompanied by prominent myxoid stromal components surrounding tumor cells. After surgery, the patient received adjuvant endocrine therapy, followed by systemic chemotherapy at recurrence and subsequent treatment with abemaciclib and letrozole after the development of liver metastases, resulting in sustained disease stabilization. Genomic analysis identified two PIK3CA mutations (p.E542K and p.E726K) together with a truncating CDH1 variant (p.Q383*). The variant allele frequency of the CDH1 alteration was compatible with heterozygosity, raising the possibility of a germline event. Tumor mutational burden was low, and microsatellite instability was not detected. These molecular findings provided a rationale for consideration of PI3K pathway-directed therapy and prompted referral for genetic evaluation. This case illustrates the complexity of genomic interpretation in invasive lobular carcinoma and raises the possibility that stromal features, such as myxoid extracellular matrix, may contribute to tumor behavior and thus deserve further study.