Lobular Carcinoma in Situ of the Breast

Definition

• A lesion composed of neoplastic lobular cells without stromal invasion

Alternate / historical names

• Lobular neoplasia

Diagnostic Criteria

• Uniform population of cells with round, sometimes eccentric nuclei
  • Two cytologic types (mixtures and intermediate forms may occur)
    • Classic
      • Small round nucleli
      • Fine chromatin, smooth nuclear contours
      • Nucleoli small, inconspicuous
      • Mitotic figures infrequent
      • Has been subdivided as:
        • Type A - small completely bland cells
        • Type B - slightly larger, slightly irregular, small nucleoli
    • Pleomorphic
      • Moderately large nuclei
      • Coarse chromatin
      • Promininent nucleoli
      • Mitotic figures not uncommon
      • Central necrosis may be seen
      • Requires confirmation of lobular nature with a negative E-cadherin stain
  • Lightly eosinophilic to vacuolated cytoplasm
    • Signet ring cells may be present
• Discohesive pattern
• Uniform cells (above) must fill all the acini in at least one lobular unit and half the acini must be expanded
  • Expansion of acini apparent at low magnification
  • Expanded acini typically balloon-like
• May form tiny acini but must not form cribriform spaces or micropapillae
• Pagetoid spread into ducts is common
  • May completely fill ducts
  • May involve sclerosing adenosis
• Lesions fulfilling some but not all required features of LCIS are considered 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 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 ("bag of marbles")

Differential Diagnosis

• Ductal vs. lobular carcinoma in situ
• Lobular carcinoma in situ vs. atypical lobular hyperplasia

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

Clinical

• Lobular carcinoma in situ is considered to be a marker of increased risk of invasive carcinoma it can be a precursor lesion
  • The increased risk applies to both breasts in most studies
    • Recent data suggest 2/3 of subsequent carcinomas are in the ipsilateral breast
  • In the past there has been no consensus about management of patients with LCIS in a core biopsy
    • A recent study provides data indicating that patients with LCIS in a core should have an excision
    • 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
      • If the LCIS is extensive
  • In an excisional biopsy:
    • We suggest excision with clear margins if florid/extensive, pleomorphic, extensively necrotic or predominantly signet ring
    • Otherwise, margins are not relevant if LCIS is the only lesion
      • Nevertheless, we generally report margin status to satisfy those who want the information

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 LCIS
• (Margins of excision are not relevant)

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