Clinical, Histopathologic, and Biologic Features of Pleomorphic Lobular (Ductal-Lobular) Carcinoma In Situ of the Breast: A Report of 24 Cases

Abstract

We reviewed 10 cases of pleomorphic lobular (ductal lobular) carcinoma in situ (PL/DLCIS) of the breast and compared them with 14 cases of pleomorphic lobular carcinoma in situ (PLCIS) found in association with invasive pleomorphic lobular carcinoma. The histologic features; immunohistochemical staining for estrogen receptors (ERs), p53, Ki67, E-cadherin, and gross cystic disease fluid protein-15 (GCDFP-15); and results of fluorescence in situ hybridization for HER-2/neu gene amplification were evaluated in all 24 cases. Histologically, PL/DLCIS cells were similar to those of PLCIS with invasion in that they were discohesive and medium to large in size with moderate to marked nuclear pleomorphism, small to prominent nucleoli, and moderate to abundant eosinophilic or vacuolated cytoplasm. In both groups, central necrosis was present in a small number of cases, and classic LCIS coexisted with the in situ lesion in less than half of the cases; in situ carcinomas were positive for ERs in 23 (100%) of 23 cases, p53 in 6 (25%) of 24 cases, and GCDFP-15 in 14 (74%) of 19 cases. The percentage of Ki67-positive tumor nuclei indicated moderate to high (more than 20%) proliferative activity in 8 (47%) of 17 cases. Immunostaining for E-cadherin was negative in all 24 cases. HER-2/neu gene amplification was observed in 1 (4%) of 23 cases. In cases with associated invasion, PLCIS had cytologic features and immunostaining patterns similar to those of the invasive pleomorphic component. Seven of the 10 patients who had PL/DLCIS without invasion underwent lumpectomy or simple mastectomy. Six of these patients had no evidence of disease in follow-up periods ranging from 4 to 32 months; the seventh patient developed recurrent disease 12 months after undergoing lumpectomy. We conclude that the cytologic features and biomarker expression profile of PL/DLCIS are similar to those of PLCIS with invasion but somewhat different from those of classic LCIS and ductal carcinoma in situ. Long-term follow-up studies are needed to further define the natural history of PL/DLCIS and its optimal management.

Stable ‘portrait’ of breast tumors during progression: data from biology, pathology and genetics

“…In another report, KI-67 expression was found in only 5% of low-grade but in 70% of high-grade DCIS. For P53, the respective percentages were 5% and 50% (Krishnamurthy & Sneige 2002). Regarding cyclins, while cyclin E has been associated with high-grade tumors, the inverse was observed for cyclin D1 (Loden et al 2002).…”

“…(see also Sneige et al 2002) and are very similar, based on their expression of biological markers and their pattern of genetic alterations. For instance, a frequent hypermethylation of the five cancerrelated genes RASSF1A, HIN1, RARB, CCND2 and TWIST, has been observed in in situ as well as in invasive lobular cancers (Fackler et al 2003).…”

Atypical lobular hyperplasia and classic lobular carcinoma in situ in core biopsy specimens: routine excision is not necessary

“…Necrosis and microcalcifications may be present. 6 Mixed carcinoma in situ. Proliferation of neoplastic ductal and lobular cells within the same ductule/acini, with heterogeneous expression of E-cadherin.…”

“…[3][4][5] These variants include pleomorphic lobular carcinoma in situ characterized by discohesive pleomorphic cells with abundant cytoplasm. 6 Rosen described 'florid' lobular carcinoma in situ characterized by 'tumor cells that fill and expand the duct lumen' that 'may develop central necrosis and calcifications'. 7 Sapino et al 8 and Fadare et al 9 also have defined in situ lesions with morphologic features of lobular neoplasia but with necrosis as lobular carcinoma in situ.…”

“…Not only do both pleomorphic lobular carcinoma in situ and lobular carcinoma in situ with necrosis show different morphology, they can also exhibit a more aggressive biologic marker profile compared to classic lobular carcinoma in situ. 6,[8][9][10][11][12] Microinvasive lobular carcinoma has been associated with pleomorphic lobular carcinoma in situ or lobular carcinoma in situ with necrosis, 6,8,9,13 although in routine practice, microinvasive carcinomas have also been observed in association with classic lobular carcinoma in situ. Lobular carcinoma in situ with nonclassic features has also been found to be more frequently associated with adjacent invasive carcinoma, especially invasive lobular carcinoma.…”