Rosen's Breast Pathology, 4e

357

Ductal Carcinoma In Situ

Marked periductal fibrosis can, on occasion, be associated with extensive obliteration of DCIS, a process referred to as “healing” by Muir and Aitkenhead 130 (Fig. 11.33). The resid- ual ductal structures typically consist of round-to-oval scars composed of circumferential layers of collagen and elastic tissue. The center of the duct may contain a few residual car- cinoma cells, fragments of calcification, or histiocytes. End- stage scars of periductal mastitis may not be distinguishable from those of obliterated comedocarcinoma. After a study of 425 breasts, Davies 131 concluded that “. . . ductal hyper- elastosis, obliteration, and fibrous plaques are not limited to breasts that are the seat of carcinoma. Indeed, the prevalence of these three lesions in major ducts that are unaffected by microscopic changes does not differ significantly in ‘normal’ and carcinomatous breasts.” At the other extreme, perhaps also representing the result of host response to the tumor or its products, one can encounter a severe inflammatory reaction that may lead to a mistaken diagnosis of mastitis, because DCIS is masked by the inflammation. CD10 is a cell-surface metalloproteinase that is expressed in a variety of normal cell types, including mammary myo- epithelial cells and lymphoid precursor cells. Stromal CD10 expression has been associated with biologically aggressive carcinomas. In an immunohistochemically analyzed tissue microarray study, no CD10 immunoreactivity was found in the stromal cells of the normal breast; however, CD10 re- activity was detected in the stroma in about 10% of DCIS cases and 50% of invasive carcinoma cases. 132 In this study, CD10 expression correlated significantly with tumor size, stage, grade, nodal involvement, and distant metastases, and was also related to cytoplasmic β-catenin expression in the invasive carcinoma cells. Secreted protein acid rich in cysteine (SPARC) is a mul- tifunctional glycoprotein that acts through several signaling pathways to regulate extracellular matrix as well as tissue re- modeling. It is possible that SPARC and CD10 play an inte- gral role in the development of invasive carcinoma. 133 Solid DCIS is formed by neoplastic cells that fill most or all of the duct space (Fig. 11.34). Microlumens and papillary structures are absent, but calcifications may be present. Ne- crosis is not a conspicuous feature of solid DCIS, but small foci may be present in affected ducts (Fig. 11.35). Patients with comedocarcinoma often have coexistent foci of solid DCIS. In contrast to solid intraductal hyperplasia, the po- lygonal cells are typically of a single type with low to moder- ate nuclear grade. The cytoplasm has a spectrum of cytologic appearances, including clear, granular, amphophilic and eosinophilic, and apocrine. Myoepithelial cells are variably present at the periphery of ducts involved by solid DCIS. LCIS, particularly of the florid type, can be mistaken for DCIS; indeed, one description recently proposed for florid LCIS was “solid-type DCIS that lacked E-cadherin expres- sion.” 134 Additional immunostains that can be helpful in dis- tinguishing LCIS from DCIS include p120, β-catenin, and high molecular weight cytokeratins. 135 Papillary DCIS is distinguished by the presence of a fibro- vascular stromal architecture supporting one or more of the foregoing structural patterns (see Chapter 14).

E FIG. 11.31.  (Continued)

correlation between the apoptotic index and p53 expression in intraductal and invasive carcinoma, leading the authors to speculate that p53 played a role in the regulation of apopto- sis and the development of necrosis in DCIS. Further evidence that altered control of apoptosis may contribute to necrosis in DCIS comes from studies of bcl-2 expression . The bcl-2 gene located on chromosome 18 plays an important role in regulating growth by inhibiting apop- tosis. Bcl-2 expression is inversely related to differentiation as well as to the expression of the estrogen receptor (ER), p53, and HER2 proteins in DCIS. 128 DCIS with biologic fea- tures that are most often associated with necrosis are char- acterized by downregulation of apoptosis inhibiting bcl-2 (Fig. 11.32). Sneige et al. 129 correlated the frequency of central necro- sis in DCIS with nuclear grade. Central necrosis was much more frequent in lesions with poorly differentiated nuclear grade (80%) than in those with intermediate (35%) or low (22%) nuclear grade.

FIG. 11.32.  DCIS, bcl-2 expression. Cytoplasmic and membranous immunoreactivity for bcl-2 is present in DCIS cells. Note cytoplasmic staining in periductal lymphocytes.