Atypical Lobular Hyperplasia and Focal Lobular Carcinoma In Situ Dr. Jean F. Simpson

A 55 year old woman had suspicious microcalcifications detected on a screening mammogram. She underwent a core needle biopsy. The submitted slide is from the subsequent segmental mastectomy. Slide 1 Click to view with ImageScope Click to view with a Web-Based Viewer Microscopic Appearance The section is from the segmental mastectomy that was prompted by the needle biopsy. There is a proliferation of monomorphic cells filling, expanding, and distending terminal ducts and lobular units. Individual cells have round, regular nuclei with inconspicuous nucleoli, and homogenous pale cytoplasm, and occasional intracytoplasmic lumina. There are no well-developed cell borders; the cells grow in a dyshesive manner. These same cells undermine the normal luminal epithelium in some areas ('Pagetoid spread'). Final Diagnosis Atypical lobular hyperplasia and focal lobular carcinoma in situ Discussion and Clinical Implications We use the term 'lobular neoplasia' to indicate the full range of in situ changes with characteristic cells initially diagnosed as LCIS in 1941. Lobular neoplastic breast disease in women has been considered a special type of pre-malignancy since 1941 [1] in a paper that also described the related pattern of 'infiltrating lobular carcinoma'. During the 20-30 years following description of lobular carcinoma in situ (LCIS), the term 'lobular neoplasia' (LN) has been used for a spectrum of lobulo-centric distortion by characteristic cells that varied from marked [2] (lobular carcinoma in situ) to minimal [3] – (minimally atypical lobular hyperplasia, not recognising a risk as high as well developed ALH). Atypical lobular hyperplasia (ALH) is the diagnostic term most frequently used [4, 5]t o denote most lesions in this series. The cancer risk implications of ALH have been verified in formal follow-up studies. [6, 7, 8, 9] Cancer risk assessment is quantitatively elevated if the advanced patterns of lobular carcinoma in situ are present – this demands extensive distortion, filling and distension of a lobular unit, [2] and is usually seen in a background of many lobular units with diagnostic ALH. Another pattern that adds somewhat to risk is the involvement of true ducts with cells of ALH in the present of ALH in lobular units. [3] However, this finding is restricted to a single study, and the implication of raising subsequent risk of cancer from a range of four times to seven times that of the general population is not reliable as a predictor for an individual woman. Patient age is always a strong consideration in understanding clinical management. This is particularly true for ALH in which the implications of cancer risk fall after the menopause. [7, 9] With the current appropriate interest in breast cancer prevention, these lesions have taken on an even greater clinical importance. It is likely that many of the patients in the National Surgical Adjuvant Breast Project's prevention trial that benefited most from the prevention/intervention of tamoxifen had these lesions of ALH and related ALH, (termed 'atypical hyperplasia' in pathology reports from biopsies). References Foote FWJ, Stewart FW. Lobular Carcinoma in Situ. A rare form of mammary cancer. Am J Path 1941; 17: 491-496. Page DL, Kidd TE Jr, Dupont WD et al. Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease. Hum Pathol 1991; 22: 1232-1239. Page DL, Dupont WD, Rogers LW. Ductal involvement by cells of atypical lobular hyperplasia in the breast: a long-term follow-up study of cancer risk. Hum Pathol 1988: 19: 201-207. Fitzgibbons PL, Henson DE, Hutter RVP et al. Benign breast changes and the risk for subsequent breast cancer-An update of the 1985 consensus statement. Arch Pathol Lab Med 1998; 122: 1053-1055. Fitzgibbons PL. Atypical Lobular Hyperplasia: A study of pathologists' responses in the College of American Pathologists performance improvement programs in 3 surgical pathology. Arch Pathol Lab Med 2000; 124: 463-464. London SJ, Connoly JL, Schnitt SJ, Colditz GA. A prospective study of benign breast disease and risk of breast cancer. JAMA 1992; 267: 941-944. Page DL, Dupont WD, Rogers LW, Rados MS. Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer 1985; 55: 2698-2708. McDivitt RW, Stevens JA, Lee NC et al. Histologic types of benign breast disease and the risk for breast cancer. Cancer 1992; 69: 1408-1414. Marshall LM, Hunter DJ, Connolly JL et al. Risk of breast cancer associated with atypical hyperplasia of lobular and ductal types. Cancer Epidemiol Biomarkers Prev 1997; 6: 297-301.