A proliferative lobular process that exhibits cytologic features of lobular carcinoma in situ but does not fulfil the requirements for extent of involvement
Classic: uniform, small, round, discohesive cells, has been subdivided as:
Type A - small completely bland cells
Type B - slightly larger, slightly irregular, small nucleoli
Pleomorphic: larger, sometimes irregular nuclei, often with prominent nucleoli
May exhibit pagetoid spread into ducts
No lobular unit completely fulfils the extent of involvement required for LCIS
No lobular units show complete filling of all the acini, OR
Even if all filled, fewer than half of the acini in the lobule expanded
There is no category of non-atypical lobular hyperplasia
Richard L Kempson MD
Department of Pathology
Stanford University School of Medicine
Stanford CA 94305-5342
Original posting:: May 1, 2006
Supplemental studies
Immunohistology
E-cadherin is typically negative in normal and neoplastic lobular cells
It appears to be a sensitive marker of ductal differentiation vs lobular differentiation; but its utility in borderline lesions is currently uncertain
In pagetoid spread of LCIS or ALH into ducts, an E-caherin negative population will be seen disrupting the positively stained normal ductal cells
Cytokeratin 8 (detected by CAM5.2) may stain both ductal and lobular processes but accentuates the discohesive pattern in LCIS and ALH ("bag of marbles")
ALH requires at least one of the following features:
At least one acinus must be filled by characteristic lobular cells, OR
Characteristic lobular cells must be present beneath normal acinar cells in several acini of a lobule
There is no category of (non-atypical) lobular hyperplasia
Ductal vs. Lobular differentiation may be a problem in pagetoid or complete involvement of ducts by ALH or in lobular involvement by DCIS cells (cancerization of lobules)
Frequent intraductal cribriform or micropapillary pattern
No cribriform spaces or micropapillae
E-cadherin positive
E-cadherin negative
Indeterminate cases should be treated as DCIS (excision with clear margins)
Clinical
Atypical lobular hyperplasia is a marker of increased risk of carcinoma to both breasts but it is uncertain whether it is also a preinvasive lesion
The most recent evidence suggests ALH in a core biopsy is an indication for excision particularly if it is extensive
We particularly consider its presence in a core biopsy to be an indication for excisional biopsy in the following situations:
If there is discordance between the mammographic and pathologic findings
If another lesion such as atypical ductal hyperplasia is present
If the lobular nature of the cells is at all equivocal
In an excisional biopsy, margins are not relevant if it is the only lesion unless the process is extensive
Relative risk for development of invasive breast carcinoma
No increased risk
Non-proliferative fibrocystic change
Fibroadenoma
Solitary papilloma
Slightly increased risk (1.5 to 2 times)
Proliferative fibrocystic change
Usual ductal hyperplasia
Sclerosing adenosis (florid)
Radial scar
Complex fibroadenoma (approximately 3 times risk)
Moderately increased risk (4 to 5 times)
Atypical ductal hyperplasia (no family history)
Atypical lobular hyperplasia
High risk (8 to 10 times)
Ductal carcinoma in situ, low grade
Lobular carcinoma in situ
Atypical ductal hyperplasia, if history of carcinoma in primary relatives
Very high risk (precise level not known)
Ductal carcinoma in situ, high grade
Grading / Staging / Report
Grading is not applicable
Staging is not applicable
The surgical pathology report should contain or address the following:
Type of resection or biopsy and location
Results of any supplementary studies performed
Extent of ALH
(Margins of excision are not relevant)
Bibliography
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. 1997 May;6(5):297-301.
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 Feb;19(2):201-7.
Simpson PT, Gale T, Fulford LG, Reis-Filho JS, Lakhani SR. The diagnosis and management of pre-invasive breast disease: pathology of atypical lobular hyperplasia and lobular carcinoma in situ. Breast Cancer Res. 2003;5(5):258-62.
