Rosen's Breast Pathology, 4e

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Ductal Carcinoma In Situ

Ta b l e 1 1 . 1  Consensus Committee Recommendation for Nuclear Grading of DCIS

Low Nuclear Grade (NG1) • Monomorphic (monotonous) appearance • Size of duct epithelial nuclei or 1.5–2.0 normal red blood cell

• Chromatin diffuse, finely dispersed • “Occasional nucleoli and mitoses” • Cells usually polarized

High Nuclear Grade (NG3) • “Markedly pleomorphic”

• Size usually more than 2.5 duct epithelial nuclei • Chromatin vesicular with irregular distribution • “Prominent, often multiple nucleoli” • “Mitoses may be conspicuous”

Intermediate Nuclear Grade (NG2) • “Nuclei that are neither NG1 nor NG3”

Based on The Consensus Conference Committee. Consensus Conference on the classification of ductal carcinoma in situ. Cancer 1997;80:1798–1802.

assessment of ER and PR status in all DCIS cases 176 ; how- ever, since DCIS is often a lesion of microscopic dimension, little information was available about hormone receptor ex- pression until immunohistochemical methods became avail- able. Biochemical analysis employing homogenized tissue samples contained a substantial proportion of nonneoplastic tissue, and as a consequence, the majority of specimens of DCIS were reportedly receptor negative. In one study, the median level of ER in DCIS was 5 fmol/mg cytosol protein, significantly less than the median of 11 fmol/mg for infiltrat- ing duct carcinoma. 177 Barnes and Masood 178 described an immunohistochemi- cal study of ER in DCIS in 1990. Nuclear reactivity, usually heterogeneously distributed when present, was found in 75% of pure DCIS, in 73% of DCIS associated with invasive duct carcinoma, and in 100% of 36 examples of atypical duct hyperplasia. Nuclear ER reactivity was less frequent in com- edo DCIS than in other variants (Fig. 11.55). The same pat- tern of ER expression was usually found in the intraductal and in the infiltrating portions of carcinomas with both components. ER positivity was more frequent in tumors

Biomarkers in DCIS A variety of biologic markers have been studied in DCIS. Lari and Kuerer 175 performed a comprehensive review of 622 major studies that had reported on 25 traditional and emerg- ing biologic markers of DCIS and their associated recurrence risk. These studies appeared over a 10-year period beginning late 2000 and included 6,252 patients. The study included hormone receptors, proliferation markers, cell cycle regula- tion markers, among others. No prospective validation study was identified, and the various studies included in the review suffered from the usual limitations of variations in surgery, radiation, and endocrine therapy. Nonetheless, the review provides considerable information. For the three most com- mon biomarkers, the mean expression rates in DCIS were 68.7 for ER, 59.6% for PR, and 40.1% for HER2. Estrogen Receptor and Progesterone Receptor American Society of Clinical Oncology (ASCO) and College of American Pathology (CAP) currently endorse the routine

Ta b l e 1 1 . 2  Consensus Committee Recommendation for Reporting Necrosis in DCIS

Comedonecrosis “Central zone necrosis within a duct, usually exhibiting a linear pattern within ducts if sectioned longitudinally” Punctate “Nonzonal type necrosis (foci of necrosis that do not exhibit a linear pattern if longitudinally sectioned)”

Based on The Consensus Conference Committee. Consensus Conference on the classification of ductal carcinoma in situ. Cancer 1997;80:1798–1802.