Primary mammary small-cell carcinoma: A molecular analysis of 2 cases

Primary small-cell carcinoma of the breast is an exceedingly rare variant o f breast carcinoma whose genetic profile has not been previously investigat ed. We report the molecular features of 2 cases of small-cell carcinoma of the breast: 1 with an adjacent intraductal carcinoma, and 1 with prior pleo morphic lobular carcinoma in situ. Laser capture microdissection followed b y loss of heterozygosity (LOH) analysis revealed identical molecular altera tions at multiple chromosomal regions, including BRCA-1, BRCA-2, p53, and r etinoblastoma gene loci, in I case of small-cell carcinoma and its adjacent intraductal component. Additionally, LOH in I or both small-cell carcinoma s was detected at 3p, 4q31.2-qter, 8p21-24, 11q13 (MEN-1 locus), 11q23.3, 1 1q24.1-25, 16q24.1 (H-cadherin locus), and 17q25. The results of our molecu lar analysis suggest that genetic changes in mammary small-cell carcinoma r esembled those seen in both invasive ductal carcinomas and pulmonary small- cell carcinoma. Second, mammary small-cell carcinoma is clonally related to ductal carcinoma in situ and might represent an example of divergent diffe rentiation occurring in a multipotential neoplastic stem cell. HUM PATHOL 3 2: 753-757. Copyright (C) 2001 by W.B. Saunders Company.