Breast Consultants - Services For Pathologists

Atypical Lobular Hyperplasia(ALH), and Focal Lobular Carcinoma in Situ (LCIS): (Download PDF Version)

David L. Page, M.D. and Colleagues, Breast Pathology Consultants

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 the 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 welldeveloped ALH). Atypical lobular hyperplasia (ALH) is the diagnostic term most frequently used [4-6] to denote most lesions in this series. The cancer risk implications of ALH have been verified in formal follow-up studies[7-10].

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(Page et al., 1991), 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 presence of ALH in lobular units(Page et al., 1988). 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 populationi
is not reliable as a predictor for an individual woman.

The co-existence of pattterns of lobular neoplasia with extensive distension, filling, and distortion of true 2 ducts may necessitate the application of the clinical implications of ductal carcinoma in situ, despite a dominance of the type of cytology seen in lobular neoplasia(Fisher et al., 1996).

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(Marshall et al., 1997; Page et al., 1985). 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 benefitted most from the prevention/intervention of tamoxifen had these lesions of ALH and related to ALH, (termed 'atypical hyperplasia' in pathology reports from biopsies)(Fisher et al., 1998).

Follow-up studies with uniform diagnostic criteria for atypical lobular hyperplasia, recognizing few cases of “LCIS” Also the NSABP studies terming cases “LCIS” only and representing some more extensive cases( Fisher et al, times 2).

References

1.. Foote FWJ, Stewart FW. Lobular Carcinoma in Situ. a rare form of mammary cancer. Am J. Path. 1941; 17:491-
496.

2. 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.

3. 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.

4. 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.

5. 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.

6. Schnitt SJ, Connolly JL, Tavassoli FA, et al.Interobserver reproducibility in the diagnosis of ductal proliferative breast lesions using standardized criteria. Am J Surg Pathol 1992; 16:1133-1143.

7. London SJ, Connolly JL, Schnitt SJ, Colditz GA. A prospective study of benign breast disease and risk of breast cancer. Jama 1992; 267:941-944.

8. 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.

9. 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.

10. 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.

11. Fisher, B., Costantino, J.P., Wickerham, D.L., Redmond, C.K., Kavanah, M., Cronin, W.M., Vogel, V., Robidoux, A.,
Dimitrov, N., Atkins, J., Daly, M., Wieand, S., Tan-Chiu, E., Ford, L. and Wolmark, N., Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study . J Natl Cancer Inst, 90: 1371-88,1998.

12. Fisher, E.R., Costantino, J., Fisher, B., Palekar, A.S., Paik, S.M., Suarez, C.M. and Wolmark, N., Pathologic findings
from the National Surgical Adjuvant Breast Project (NSABP) protocol B-17 - Five-year observations concerning lobular carcinoma in situ. Cancer, 78: 1403-1416,1996.

13. Page, D.L., Anderson, T.J. and Rogers, L.W., Epithelial hyperplasia. In: D.L. Page and T.J. Anderson (eds.), pp. 120-
156, Churchill Livingstone, Edinburgh (1987).

14. Byrne C, Connolly JL, Colditz GA, Schnitt SJ. Biopsy confirmed benign breast disease, postmenopausal use of exogenous female hormones, and breast carcinoma risk. Cancer 89 (10): 2046-52, 2000.

15. Dupont WD, Page DL. Breast cancer risk associated with proliferative disease, age at first birth, and a family history of breast cancer. Am J Epidemiol 125 (5): 769-79, 1987.

16. Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative breast disease. N Engl J Med 312 (3): 146-51, 1985.

17. Dupont WD, Page DL, Parl FF, Plummer WD, Jr., Schuyler PA, Kasami M, Jensen RA. Estrogen replacement therapy in women with a history of proliferative breast disease. Cancer 85 (6): 1277-83, 1999.

18. Fisher ER, Costantino J, Fisher B, Palekar AS, Paik SM, Suarez CM, Wolmark N. Pathologic findings from the National Surgical Adjuvant Breast Project (NSABP) Protocol B-17. Five-year observations concerning lobular carcinoma in situ. Cancer 78 (7): 1403-16, 1996.

19. Fisher ER, Land SR, Fisher B, Mamounas E, Gilarski L, Wolmark N. Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project: twelve-year observations concerning lobular carcinoma in situ. Cancer 100 (2): 238-44, 2004.

20. Jacobs TW, Byrne C, Colditz G, Connolly JL, Schnitt SJ. Pathologic features of breast cancers in women with previous benign breast disease. Am J Clin Pathol 115 (3): 362-9, 2001.

21. London SJ, Connolly JL, Schnitt SJ, Colditz GA. A prospective study of benign breast disease and the risk of breast cancer. Jama 267 (7): 941-4, 1992.

22. Marshall LM, Hunter DJ, Connolly JL, Schnitt SJ, Byrne C, London SJ, Colditz GA. Risk of breast cancer associated with atypical hyperplasia of lobular and ductal types. Cancer Epidemiol Biomarkers Prev 6 (5): 297-301, 1997.

23. Middleton LP, Grant S, Stephens T, Stelling CB, Sneige N, Sahin AA. Lobular carcinoma in situ diagnosed by core needle biopsy: when should it be excised? Mod Pathol 16 (2): 120-9, 2003.

24. Page DL, Dupont WD. Premalignant conditions and markers of elevated risk in the breast and their management. Surg Clin North Am 70 (4): 831-51, 1990.

25. 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 19 (2): 201-7, 1988.

26. Page DL, Dupont WD, Rogers LW, Rados MS. Atypical hyperplastic lesions of the female breast. A long-term follow-up study. Cancer 55 (11): 2698-708, 1985.

27. 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 22 (12): 1232-9, 1991.

28. Page DL, Schuyler PA, Dupont WD, Jensen RA, Plummer WD, Jr., Simpson JF. Atypical lobular hyperplasia as a unilateral predictor of breast cancer risk: a retrospective cohort study. Lancet 361 (9352): 125-9, 2003.

29. Schnitt SJ. Benign breast disease and breast cancer risk: morphology and beyond. Am J Surg Pathol 27 (6): 836-41, 2003.

30. Schnitt SJ. Benign breast disease and breast cancer risk: potential role for antiestrogens. Clin Cancer Res 7 (12 Suppl): 4419s-4422s; discussion 4411s-4412s, 2001.

31. Simpson JF, Page DL. Status of breast cancer prognostication based on histopathologic data. Am J Clin Pathol 102 (4 Suppl 1): S3-8, 1994.

32. Sneige N, Lim SC, Whitman GJ, Krishnamurthy S, Sahin AA, Smith TL, Stelling CB. Atypical ductal hyperplasia diagnosis by directional vacuum-assisted stereotactic biopsy of breast microcalcifications. Considerations for surgical excision. Am J Clin Pathol 119 (2): 248-53, 2003.

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