Rosen's Breast Pathology, 4e

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Chapter 11

expression, and normal bcl-2 expression. Intermediate- grade DCIS tend to have mixed patterns of biologic marker expression. No single grading system for DCIS has been demon- strated to be notably superior for anticipating successful breast conservation, and none has gained universal accep- tance. A consensus conference convened in 1997 did not en- dorse any single system of classification, but recommended that a pathology report for DCIS provide information about the descriptive characteristics considered to be necessary in most grading schemes. 156 The three essential elements noted were nuclear grade, necrosis, and architectural pattern(s). Heterogeneity of nuclear grade is commonly encountered in DCIS; however, it is uncommon for high- and low-grade DCIS to be present in a single lesion. In the 1997 consen- sus report, nuclear grade was stratified in three categories (Table 11.1). The pathology report should reflect the high- est nuclear grade, but may indicate the relative proportions of grade when there is heterogeneity. Necrosis was defined as the “presence of ghost cells and karyorrhectic debris” (Table 11.2). Five architectural patterns were identified: comedo, cribriform, papillary, micropapillary, and solid. It was specified that comedo referred to “solid intraepithelial growth within the basement membrane with central (zonal) necrosis.” Such lesions are often but not invariably of high nuclear grade. Other elements recommended by the 1997 consensus re- port for inclusion in the diagnosis were lesion “size (extent, distribution)” and margin status. No particular methods for assessing size or margins were suggested. Interobserver variability is an important consideration in applying a grading system in clinical practice. This issue has been addressed in a limited number of studies, and the results suggest that architectural descriptions (e.g., cribri- form, micropapillary, and comedo) are less reproducible than nuclear grade and necrosis. 129,155–157 This probably re- flects the heterogeneity of architectural patterns that may be encountered in a single case, whereas nuclear grade tends to be consistent. The description of necrosis can also be a source of disagreement if quantification of necrosis is an ele- ment for classifying a lesion as the comedo type. 156 The usual

FIG. 11.46.  Concurrent cribriform intraductal and in situ lobular carcinoma. (Reproduced from Rosen PP. Coexis- tent lobular carcinoma in situ and DCIS in a single lob- ular-duct unit. Am J Surg Pathol 1980;4:241–246, with permission.)

necrosis, lesion size, and cell polarity. Most classifications have emphasized nuclear grade, necrosis, and architecture. Generally, three grades have been proposed: high, interme- diate, and low. There is a significant correlation between the grade of DCIS and a corresponding invasive compo- nent, if present, regardless of grading system. 155 The grad- ing categories also have significant associations with biologic characteristics of DCIS, especially lesions typically classified as high and low grade. High-grade lesions typically exhibit the following features: absence of ER and PR expressions, aneuploidy, high proliferative rate, periductal angiogen- esis, membrane reactivity for HER2, nuclear reactivity for p53, and abnormal bcl-2 expression. Conversely, low-grade DCIS are usually characterized by the following: presence of ERs and PRs, absence of aneuploidy, low proliferative rate, minimal periductal angiogenesis, absence of HER2 and p53

A

B

FIG. 11.47.  Lobular extension of DCIS. A,B: Solid DCIS extending into lobular glands.