Introduction: Accessory breast tissue is a rare finding in the general population with an incidence of 1-2%. Ectopic mammary tissue may occur anywhere along the milk line, from the axilla to the groin. Thus, breast cancer present in the vulva may arise as a primary breast adenocarcinoma or distant metastasis. Differentiating the two can be clinically challenging but is critically important as it impacts prognosis and treatment. Using genomic and bioinformatic approaches, we re-evaluated a previously histopathologically diagnosed rare case of metachronous vulvar ectopic breast cancer.
Methods: Two biobanked breast tumor samples were obtained from a 43-year-old woman diagnosed with in situ breast cancer 17 months prior to her presentation and diagnosis with vulvar ectopic breast carcinoma. Whole exome (WES) and whole transcriptomic sequencing (RNAseq) were performed on all breast and vulvar tumor samples. Bioinformatics analysis was performed using the QIAGEN software suite (CLC Genomic Workbench, QCI-T) and Ingenuity Pathway Analysis (IPA). Sequence variants with >10 reads and 5% AF were selected for analysis.
Results: We performed detailed molecular characterization of breast and vulvar tumor samples. WES profiles revealed, respectively, 4904 and 166 somatic mutations from primary breast and vulva tumor tissues. Among these mutations, 60 mutations were shared between primary breast and vulva tumors. Given the length of the WES target (~54MB). We calculated the probability that the shared mutations could occur by chance alone. To estimate this likelihood, we made the assumption that all positions interrogated by WES could be mutated with equal probability. Under this assumption, it is highly unlikely that the 60 identical mutations identified in multiple samples would occur by chance alone (Fisher exact test - p <10100) Beyond these shared mutations, we identified a number of known breast cancer functional variants including variants in TP53, KMT2D, MET and an additional 32 likely pathogenic genes in the vulvar tumor that were not shared with the patient’s original breast tumor tissues. Similarly, we also identified a pathogenic variant in PRKAR1A and an additional 95 likely pathogenic variants in genes including ATRX, ATXN3, CTBP2, SCN2A only in the breast tumor.
Conclusion: This illustrative case provides an interesting resolution to a clinically difficult question: differentiating synchronous or metachronous breast carcinoma in the vulva. While unusual, answering this question correctly significantly impacts staging and treatment for that patient.
Citation Format: Sabina Swierczek, Deep Pandya, Jean-Noel Billaud, Boris Reva, Magdalena Swierczek, Matthew Reeves, Sara Farisello, Steven Sieber, Anya Laibangyang, Vaagn Andikyan, John A. Martignetti, Linus Chuang. Metastatic versus primary: Genomic analysis suggests a metastatic origin for breast cancer previously diagnosed as metachronous vulvar ectopic breast cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 70.
