An unusual mixed form of ductal carcinoma in situ (DCIS) of the breast is described, which exhibits a biphenotypic morphology encompassing a range of differential diagnostic DCIS subtypes. In adddition, immunophenotypic and ultrastructural studies demonstrate neuroendocrine and apocrine diVerentiation, raising questions regarding appropriate classification and biological behaviour. In two cases, coexistence of this mixed form of DCIS with lobular carcinoma in situ (LCIS) in the same duct lobular units is an additional unusual feature that might, at least in some cases, indicate a closer relation between them. (J Clin Pathol 2001;54:70-73) Keywords: lobular carcinoma in situ; ductal carcinoma in situ; apocrine diVerentiation Apocrine diVerentiation is common in invasive breast cancer 1 and it is usually recognised by tumour cells containing granular pink cytoplasm. Less commonly, however, the cytoplasm is foamy or clear. In these circumstances, apocrine diVerentiation is defined by immunohistochemical and ultrastructural characteristics.2 Although apocrine diVerentiation is not rare in ductal carcinoma in situ (DCIS), 3 its manifestation with a predominantly clear cell morphology is unusual. Similarly, neuroendocrine diVerentiation has more recently been characterised by combined morphological, immunohistological, and ultrastructural characteristics, firmly establishing the existence of endocrine diVerentiation in DCIS. 4 As a further illustratration of the heterogeneity possible in preinvasive breast neoplasia, we describe three unusual cases of DCIS showing dimorphic apocrine and neuroendocrine differentiation, two of which showed coexisting lobular carcinoma in situ (LCIS).
Materials and methodsTissues were fixed in 10% buVered formalin, routinely processed, and stained with haematoxylin and eosin. For immunohistochemistry, representative sections were selected and, using the avidin biotin technique, staining was performed for the following: E-cadherin (R&D systems, Oxon, UK), S100 protein (Dako, Cambridgeshire, UK), chromogranin (Dako), synaptophysin (Dako), the oestrogen receptor (Novocastra, Newcastle, UK), the progesterone receptor (Novocastra), gross cystic disease fluid protein (GCDFP-15; Signet, Dedham, Massachusetts, USA), epithelial membrane antigen (EMA; Dako), smooth muscle actin (SMA; Dako), neurone specific enolase (NSE; Dako), MIB1 (Immunotec, Marseilles, France). For electron microscopy, five selected pieces of tissue from case 1 were dewaxed and reprocessed after postfixation in osmium. Sections (1 µm thick) were cut and stained with toluidine blue. Ultrathin sections were cut and stained with uranyl acetate and lead citrate, one of which was from a spindle cell area.
Case histories and pathology
CASE 1A 45 year old woman had suspicious microcalcification on mammography. An excision biopsy measuring 4.0 × 3.0 × 1.0 cm was performed after needle localisation. Several additional margin shavings from the biopsy cavity were also removed. This was followed by a subcutaneous mastectomy six...