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Surgical Pathology Criteria
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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 may be a problem in pagetoid or complete involvement of ducts by LCIS, in solid low grade DCIS, or in lobular involvement by DCIS cells (cancerization of lobules)
DCIS LCIS
Cohesive Non-cohesive
May show moderate to marked pleomorphism Mild to moderate pleomorphism
No pagetoid involvement of ducts May show pagetoid pattern in ducts
May show irregular or partial involvement of acini Uniform involvment of acini
Frequent cribriform or micropapillary pattern No cribriform spaces or micropapillae
Frequently amphophilic cytoplasm Cytoplasm usually clear to eosinophilic
E-cadherin positive E-cadherin negative
Indeterminate cases will be encountered and should be treated as DCIS (excision with clear margins)

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)

Bibliography

  • Acs G, Lawton TJ, Rebbeck TR, LiVolsi VA, Zhang PJ. Differential expression of E-cadherin in lobular and ductal neoplasms of the breast and its biologic and diagnostic implications. Am J Clin Pathol. 2001 Jan;115(1):85-98.
  • Bentz JS, Yassa N, Clayton F. Pleomorphic lobular carcinoma of the breast: clinicopathologic features of 12 cases. Mod Pathol. 1998 Sep;11(9):814-22.
  • Bratthauer GL, Moinfar F, Stamatakos MD, Mezzetti TP, Shekitka KM, Man YG, Tavassoli FA. Combined E-cadherin and high molecular weight cytokeratin immunoprofile differentiates lobular, ductal, and hybrid mammary intraepithelial neoplasias. Hum Pathol. 2002 Jun;33(6):620-7.
  • Crisi GM, Mandavilli S, Cronin E, Ricci A Jr. Invasive mammary carcinoma after immediate and short-term follow-up for lobular neoplasia on core biopsy. Am J Surg Pathol. 2003 Mar;27(3):325-33.
  • Elsheikh TM, Silverman JF. Follow-up surgical excision is indicated when breast core needle biopsies show atypical lobular hyperplasia or lobular carcinoma in situ: a correlative study of 33 patients with review of the literature. Am J Surg Pathol. 2005 Apr;29(4):534-43.
  • 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. 1996 Oct 1;78(7):1403-16.
  • Goldstein NS, Bassi D, Watts JC, Layfield LJ, Yaziji H, Gown AM. E-cadherin reactivity of 95 noninvasive ductal and lobular lesions of the breast. Implications for the interpretation of problematic lesions. Am J Clin Pathol. 2001 Apr;115(4):534-42.
  • Jacobs TW, Connolly JL, Schnitt SJ. Nonmalignant lesions in breast core needle biopsies: to excise or not to excise? Am J Surg Pathol. 2002 Sep;26(9):1095-110.
  • Jacobs TW, Pliss N, Kouria G, Schnitt SJ. Carcinomas in situ of the breast with indeterminate features: role of E-cadherin staining in categorization. Am J Surg Pathol. 2001 Feb;25(2):229-36.
  • Lehr HA, Folpe A, Yaziji H, Kommoss F, Gown AM. Cytokeratin 8 immunostaining pattern and E-cadherin expression distinguish lobular from ductal breast carcinoma. Am J Clin Pathol. 2000 Aug;114(2):190-6.
  • Liberman L, Sama M, Susnik B, Rosen PP, LaTrenta LR, Morris EA, Abramson AF, Dershaw DD. Lobular carcinoma in situ at percutaneous breast biopsy: surgical biopsy findings. AJR Am J Roentgenol. 1999 Aug;173(2):291-9.
  • Maluf HM, Swanson PE, Koerner FC. Solid low-grade in situ carcinoma of the breast: role of associated lesions and E-cadherin in differential diagnosis. Am J Surg Pathol. 2001 Feb;25(2):237-44.
  • Middleton LP, Palacios DM, Bryant BR, Krebs P, Otis CN, Merino MJ. Pleomorphic lobular carcinoma: morphology, immunohistochemistry, and molecular analysis. Am J Surg Pathol. 2000 Dec;24(12):1650-6.
  • Ottesen GL, Graversen HP, Blichert-Toft M, Christensen IJ, Andersen JA. Carcinoma in situ of the female breast. 10 year follow-up results of a prospective nationwide study. Breast Cancer Res Treat. 2000 Aug;62(3):197-210.
  • 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. 2003 Jan 11;361(9352):125-9.
  • Schnitt SJ, Morrow M. Lobular carcinoma in situ: current concepts and controversies. Semin Diagn Pathol. 1999 Aug;16(3):209-23.
  • 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.
  • Sneige N, Wang J, Baker BA, Krishnamurthy S, Middleton LP. Clinical, histopathologic, and biologic features of pleomorphic lobular (ductal-lobular) carcinoma in situ of the breast: a report of 24 cases. Mod Pathol. 2002 Oct;15(10):1044-50.
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