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Noninvasive malignancies

A variety of abnormalities can be identified in the cells lining the terminal duct lobular units short of an invasive malignant appearance penetrating the basement membrane (Figures 5.1,5.2,5.3,5.4,5.5). These include usual type hyperplasia, atypical hyperplasia, and noninvasive (in situ) carcinoma. Ductal and lobular patterns of atypical hyperplasia and in situ cancer can be recognized from the histological pattern of disease and cell type. Ductal carcinoma in situ is the most common form of noninvasive carcinoma (making up 4% of symptomatic and 25% of screen-detected 'cancers'). It is characterized by distortion, distention, and complete involvement by a homogenous and neoplastic population of cells in adjacent ducts and lobular units. By contrast, lobular carcinoma in situ is rare (<1% of screen-detected 'cancers') and exhibits relatively uniform expansion of the whole lobule by regular cells with regular, round or oval nuclei. While each involved lobular unit has a uniform cellular population, the pattern and even cytology may, and often does, vary between units with some intervening units being minimally involved or uninvolved. Some patients present with combined features that should be regarded as having clinical features of both processes.


Photomicrograph on left (A) shows a duct space filled with a mixture of atypical epithelial cells with admixed myoepithelial cells. The lesion does not meet the criteria for a diagnosis of DCIS and the designation 'ADH' is appropriate. Photomicrograph on right (B) shows a duct space replaced by a pure population of malignant ductal epithelial cells (DCIS) of intermediate grade.


High-grade DCIS (A), The CK 5/6 stain (B) picks out the intact myoepithelial layer around the periphery of the duct, while the in situ carcinoma cells that fill the duct show no staining. This stain helps to confirm that the tumour is not invasive. Compare with Fig. 7.5B where the lack of staining around the tubules of a tubular carcinoma helps to confirm its invasive nature.


Photomicrograph (A) shows duct space partly filled with a population of lobular epithelial cells - ALH. Associated microcalcification is common in these lesions. Photomicrograph (B) shows a similar pattern, but the lobules are now completely filled and expanded by atypical lobular epithelial cells - LCIS. It is recognized that the distinction between ALH and LCIS is not easy and a preferred blanket term for the proliferation is 'in situ lobular neoplasia'.


Magnification view mammogram of an area of suspicious microcalcification due to ductal carcinoma in situ.


Graph of recurrence-free survival of 1010 women treated with or without radiotherapy to the breast, following wide excision of ductal carcinoma in situ (with no disease at margins) in the EORTC 10853 trial. Risk of recurrence is almost halved by radiotherapy (hazard ratio 0.53, p<0.0001) but the absolute benefit may be small, particularly for some groups. O, observed number of events; N, number of patients; LE, local excision; RT, radiotherapy. (Adapted from Bijker N, et al. [2006]. J Clin Oncol 24:3381-87.)


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