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Surgical Pathology Criteria

Atypical Lobular Hyperplasia of the Breast


  • A proliferative lobular process that exhibits cytologic features of lobular carcinoma in situ but does not fulfil the requirements for extent of involvement

Alternate / historical names

  • Lobular neoplasia

Diagnostic Criteria

  • Same cytologic features as LCIS
    • May be classic or pleomorphic
      • 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


  • 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")

Differential Diagnosis

LCIS vs. Atypical Lobular Hyperplasia (ALH)

  • LCIS requires that all the acini in at least one lobular unit be completely filled and that half the acini in that unit must be expanded
  • If either of the above features is lacking, designate as ALH

Normal Breast Acini vs. Atypical Lobular Hyperplasia (ALH)

  • 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)
Cohesive Non-cohesive
May show moderate to marked pleomorphism Mild to moderate pleomorphism
No pagetoid involvement of ducts May show pagetoid pattern in ducts
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)


  • 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)


  • 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.
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