Atypical Lobular Hyperplasia and Atypical Ductal Hyperplasia Involving a Fibroadenoma Jean F Simpson, MD Department of Pathology, Vanderbilt University Medical Canter Nashville, TN

Case History A 41 year old woman underwent an ultrasound guided biopsy for a mass. The resulting diagnosis was discordant with the ultrasound impression, and an excision was performed. Figure 1 Click to view with ImageScope Click to view with a Web-Based Viewer Microscopic appearance The excisional biopsy specimen shows a circumscribed fibroglandular lesion. Within the epithelial component, there is a proliferation of monomorphic cells that fill acinar structures. The individual cells have round, regular nuclei with inconspicuous nucleoli, and homogenous pale cytoplasm, and occasional intracytoplasmic lumina. In these areas there are no well-developed cell borders; the cells grow in a dyshesive manner. Other areas contain a monomorphic population of cells that are arranged with distinct cell borders, and focally rigid architectural configurations. Final Diagnosis: Atypical lobular hyperplasia and atypical ductal hyperplasia involving a fibroadenoma 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 premalignancy 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 lobulocentric distortion by characteristic cells that varied from marked [2] (lobular carcinoma in situ) to minimal [3] – (minimally atypical lobular hyperplasia, not recognizing a risk as high as well developed ALH). Atypical lobular hyperplasia (ALH) is the diagnostic term most frequently used [4, 5] to 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 distention 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 4 times to 7 times that of the general population is not reliable as a predictor for an individual woman. The distinction of atypical ductal hyperplasia and low grade ductal carcinoma in situ is based on the extent of the lesion. Both of these entities are characterized by a uniform, monomorphic population of cells. In this example, the ADH is limited in its extent; none of the few involved spaces is completely populated by the same uniform cells. The atypical hyperplasia (both ALH and ADH) were confined to the fibroadenoma in this case; surrounding breast parenchyma was devoid of atypical hyperplasia. When atypical hyperplasia is confined to a fibroadenoma, the risk implications are less than when AH is present in the more characteristic setting of a lobular unit. 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, Simpson JF, Rogers LW. Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease. Hum Pathol 1991; 22:1232-9. 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: 19:201-7. Fitzgibbons PL , Henson DE , Hutter RVP, Canc Comm Coll Am P. 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; 55:2698-708. 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. Carter, et. al. "No Elevation in Long-Term Breast Carcinoma Risk for Women with Fibroadenomas that Contain Atypical Hyperplasia." Cancer; 2001; 92: 30-6.