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Current Breast Cancer Reports

, Volume 4, Issue 2, pp 96–101 | Cite as

The Diagnosis of Pleomorphic Lobular Carcinoma In Situ Warrants Complete Excision with Negative Margins

  • Lavinia P. MiddletonEmail author
Local-Regional Evaluation and Therapy (KK Hunt, Section Editor)

Abstract

Pleomorphic lobular carcinoma in situ (PLCIS) is a recently described variant of lobular carcinoma in situ. Although classic lobular carcinoma in situ (LCIS) is seen as a risk factor and non-obligate precursor for the development of invasive breast cancer, PLCIS is considered an even greater high-risk lesion. When patients are diagnosed with PLCIS on core biopsy, the recommendation is to perform an excisional biopsy of the affected area. Re-excision is not commonly recommended for patients with classic LCIS at or near a margin after breast conserving therapy, whereas excision with negative margins is recommended for patients with PLCIS. This review gives an overview of the biologic rationale for complete excision with negative margins for patients diagnosed with PLCIS, reviews historical data and clinical studies relevant to patients with PLCIS, and provides molecular rationale that supports treating patients with PLCIS more aggressively than patients with classic LCIS, and similar to intermediate-grade ductal carcinoma in situ (DCIS).

Keywords

Pleomorphic lobular carcinoma in situ Margin assessment Breast conserving therapy 

Notes

Disclosure

No conflicts of interest relevant to this article were reported.

References

Papers of particular interest, published recently, have been highlighted as: • Of importance

  1. 1.
    Dixon JM, Anderson TJ, Page DL, et al. Infiltrating lobular carcinoma of the breast. Histopathology. 1982;6:149–61.PubMedCrossRefGoogle Scholar
  2. 2.
    Frost AR, Tsangaris TN, Silverberg SG. Pleomorphic lobular carcinoma in situ. Pathol Case Rev. 1996;1:27–31.CrossRefGoogle Scholar
  3. 3.
    Georgian-Smith D, Lawton TJ. Calcifications of lobular carcinoma in situ of the breast: radiologic-pathologic correlation. Virchows Arch. 2001;176:1255–9.Google Scholar
  4. 4.
    Sapino A, Frigerio A, Peterse JL, Arisio R, Coluccia C, Bussolati G. Virchows Arch. 2000;436:421–30.PubMedCrossRefGoogle Scholar
  5. 5.
    Fadare O, Dadmanesh F, Alvarado-Cabrero I, et al. Lobular intraepithelial neoplasia [lobular carcinoma in situ] with comedo-type necrosis: a clinicopathologic study of 18 cases. Am J Surg Pathol. 2006;30:1445–53.PubMedCrossRefGoogle Scholar
  6. 6.
    Sneige N, Wang J, Baker BA, et al. Clinical, histopathologic, and biologic features of pleomorphic lobular (ductal-lobular) carcinoma in situ of the breast: a report of 24 cases. Mod Pathol. 2002;15:1044–50.PubMedCrossRefGoogle Scholar
  7. 7.
    Downs-Kelly E, Bell D, et al. Clinical implications of margin involvement by pleomorphic lobular carcinoma in situ. Arch Pathol Lab Med. 2011;135:737–43.PubMedGoogle Scholar
  8. 8.
    Foote FW, Stewart FW. Lobular carcinoma in situ: a rare form of mammary cancer. Am J Pathol. 1941;17:491–496.3.PubMedGoogle Scholar
  9. 9.
    Page DL, Schuyler PA, Dupont WD, et al. Atypical lobular hyperplasia as an unilateral predictor of breast cancer risk: a retrospective cohort study. Lancet. 2003;361:125–9.PubMedCrossRefGoogle Scholar
  10. 10.
    Fraser JL, Raza S, Chorny K, Connolly JL, Schnitt SJ. Columnar alteration with prominent apical snouts and secretions: a spectrum of changes frequently present in breast biopsies performed for microcalcifications. Am J Surg Pathol. 1998;22:1521–7.PubMedCrossRefGoogle Scholar
  11. 11.
    Carley AM, Chivukula M, Carter GJ, Karabakhtsian RG, Dabbs DJ. Frequency and clinical significance of simultaneous association of lobular neoplasia and columnar cell alterations in breast tissue specimens. Am J Clin Pathol. 2008;130:254–8.PubMedCrossRefGoogle Scholar
  12. 12.
    Middleton LP, Grant S, Stephens T, et al. Lobular carcinoma in situ diagnosed by core needle biopsy: when should it be excised? Mod Pathol. 2003;16:120–9.PubMedCrossRefGoogle Scholar
  13. 13.
    Liberman L, Sama M, Susnik B, et al. Lobular carcinoma in situ at percuteneous breast biopsy: surgical biopsy findings. AJR Am J Roentgenol. 1999;173:291–9.PubMedGoogle Scholar
  14. 14.
    Hwang H, Barke LD, Mendelson EB, Susnik B. Atypical lobular hyperplasia and classic lobular carcinoma in situ in core biopsy specimens: routine excision is not necessary. Mod Pathol. 2008;21:1208–16.PubMedCrossRefGoogle Scholar
  15. 15.
    Chivukula M, Haynik DM, Brufsky A, et al. Pleomorphic lobular carcinoma in situ (PLCIS) on breast core needle biopsies: clinical significance and immunoprofile. Am J Surg Pathol. 2008;32:1721–6.PubMedCrossRefGoogle Scholar
  16. 16.
    • Apple SK, Matin M, Olsen EP, Moatamed NA. Significance of lobular intraepithelial neoplasia at margins of breast conservation specimens: a report of 38 cases and literature review. Diagn Pathol. 2010;5:54. Review. This article discusses the significance of lobular carcinoma in situ at margins of resection and provides literature review.PubMedCrossRefGoogle Scholar
  17. 17.
    Jobsen JJ, Riemersma S, van der Palen J, et al. The impact of margin status in breast-conserving therapy for lobular carcinoma is age related. Eur J Surg Oncol. 2010;36:176–81.PubMedCrossRefGoogle Scholar
  18. 18.
    Ciocca RM, Li T, Freedman GM, Morrow M. Presence of lobular carcinoma in situ does not increase local recurrence in patients treated with breast-conserving therapy. Ann Surg Oncol. 2008;15:2263–71.PubMedCrossRefGoogle Scholar
  19. 19.
    Jolly S, Kestin LL, Goldstein NS, Vicini FA. The impact of lobular carcinoma in situ in association with invasive breast cancer on the rate of local recurrence in patients with early-stage breast cancer treated with breast-conserving therapy. Int J Radiat Oncol Biol Phys. 2006;66:365–71.PubMedCrossRefGoogle Scholar
  20. 20.
    Stolier AJ, Barre G, Bolton JS, et al. Breast conservation therapy for invasive lobular carcinoma: the impact of lobular carcinoma in situ in the surgical specimen on local recurrence and axillary node status. Am Surg. 2004;70:818–21.PubMedGoogle Scholar
  21. 21.
    Ben-David MA, Kleer CG, Paramagul C, et al. Is lobular carcinoma in situ as a component of breast carcinoma a risk factor for local failure after breast-conserving therapy? Results of a matched pair analysis. Cancer. 2006;106:28–34.PubMedCrossRefGoogle Scholar
  22. 22.
    Rosen PP, Kosloff C, Lieberman PH, et al. Lobular carcinoma in situ of the breast. Detailed analysis of 99 patients with average follow-up of 24 years. Am J Surg Pathol. 1978;2:225–51.PubMedCrossRefGoogle Scholar
  23. 23.
    Page DL, Kidd Jr TE, Dupont WD, et al. Lobular neoplasia of the breast: higher risk for subsequent invasive cancer predicted by more extensive disease. Hum Pathol. 1991;22:1232–9.PubMedCrossRefGoogle Scholar
  24. 24.
    World Health Organization Classification of Tumors. Pathology and Genetics of Tumours of Breast and Female Genital Organs. Edited by Tavassoli F, Devilee P. Lyon, France: IARC Press; 2003:37–38.Google Scholar
  25. 25.
    Hede K. Breast cancer testing scandal shines spotlight on black box of clinical laboratory testing. J Natl Cancer Inst. 2008;100:836–7. 844.PubMedCrossRefGoogle Scholar
  26. 26.
    Coradini D, Pellizzaro C, et al. Infiltrating ductal and lobular breast carcinomas are characterised by different interrelationships among markers related to angiogenesis and hormone dependence. Br J Cancer. 2002;87:1105–11.PubMedCrossRefGoogle Scholar
  27. 27.
    Middleton LP, Palacios DM, Bryant BR, et al. Pleomorphic lobular carcinoma: morphology, immunohistochemistry, and molecular analysis. Am J Surg Pathol. 2000;24:1650–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Porter PL, Garcia R, Moe R, et al. C-erbB-2 oncogene protein in in situ and invasive lobular breast neoplasia. Cancer. 1991;68:331–4.PubMedCrossRefGoogle Scholar
  29. 29.
    Frolik D, Caduff R, Varga Z. Pleomorphic lobular carcinoma of the breast: its cell kinetics, expression of oncogenes and tumour suppressor genes compared with invasive ductal carcinomas and classical infiltrating lobular carcinomas. Histopathology. 2001;39:503–13.PubMedCrossRefGoogle Scholar
  30. 30.
    Radhi JM. Immunohistochemical analysis of pleomorphic lobular carcinoma: higher expression of p53 and chromogranin and lower expression of ER and PgR. Histopathology. 2000;36:156–60.PubMedCrossRefGoogle Scholar
  31. 31.
    Berx G, Cleton-Jansen AM, Strumane K, et al. E-cadherin is inactivated in a majority of invasive human lobular breast cancers by truncation mutations throughout its extracellular domain. Oncogene. 1996;13:1919–25.PubMedGoogle Scholar
  32. 32.
    Acs G, Lawton TJ, et al. Differential expression of E-cadherin in lobular and ductal neoplasms of the breast and its biologic and diagnostic implications. Am J Clin Pathol. 2001;115:85–98.PubMedCrossRefGoogle Scholar
  33. 33.
    Dabbs DJ, Bhargava R, Chivukula M. Lobular versus ductal breast neoplasms: the diagnostic utility of p120 catenin. Am J Surg Pathol. 2007;31:427–37.PubMedCrossRefGoogle Scholar
  34. 34.
    • Chivukula M, Brufsky A, Carter G, et al. Molecular alterations in pleomorphic lobular carcinoma in situ (PLCIS) of the breast. Cancer Res. 2009;69(24 Supplement):5004. This article describes recent molecular alterations identified in pleomorphic DCIS.CrossRefGoogle Scholar
  35. 35.
    Reis-Filho JS, Simpson PT, Jones C, et al. Pleomorphic lobular carcinoma of the breast: role of comprehensive molecular pathology in characterization of an entity. J Pathol. 2005;207:1–13.PubMedCrossRefGoogle Scholar
  36. 36.
    Nishizaki T, Chew K, Chu L, et al. Genetic alterations in lobular breast cancer by comparative genomic hybridization. Int J Cancer. 1997;74(5):513–7.PubMedCrossRefGoogle Scholar
  37. 37.
    Hwang ES, Nyante SJ, Yi Chen Y, et al. Clonality of lobular carcinoma in situ and synchronous invasive lobular carcinoma. Cancer. 2004;100:2562–72.PubMedCrossRefGoogle Scholar
  38. 38.
    Simpson PT, Reis-Filho JS, Lambros MB, et al. Molecular profiling pleomorphic lobular carcinomas of the breast: evidence for a common molecular genetic pathway with classic lobular carcinomas. J Pathol. 2008;215:231–44.PubMedCrossRefGoogle Scholar
  39. 39.
    Gelsi-Boyer V, Orsetti B, Cervera N, et al. Comprehensive profiling of 8p11-12 amplification in breast cancer. Mol Cancer Res. 2005;3:655–67.PubMedCrossRefGoogle Scholar
  40. 40.
    Ormandy CJ, Musgrove EA, Hui R, et al. Cyclin D1, EMS1 and 11q13 amplification in breast cancer. Breast Cancer Res Treat. 2003;78:323–35.PubMedCrossRefGoogle Scholar
  41. 41.
    McCann AH, Kirley A, Carney DN, et al. Amplification of the MDM2 gene in human breast cancer and its association with MDM2 and p53 protein status. Br J Cancer. 1995;71:981–5.PubMedCrossRefGoogle Scholar
  42. 42.
    Bergamaschi A, Kim YH, Wang P, et al. Distinct patterns of DNA copy number alteration are associated with different clinicopathological features and gene-expression subtypes of breast cancer. Genes Chromosomes Cancer. 2006;45:1033–40.PubMedCrossRefGoogle Scholar
  43. 43.
    Fridlyand J, Snijders AM, Ylstra B, et al. Breast tumor copy number aberration phenotypes and genomic instability. BMC Cancer. 2006;6:96.PubMedCrossRefGoogle Scholar
  44. 44.
    Nordgard SH, Johansen FE, Alnaes GI, et al. Genome-wide analysis identifies 16q deletion associated with survival, molecular subtypes, mRNA expression, and germline haplotypes in breast cancer patients. Genes Chromosomes Cancer. 2008;47:680–96.PubMedCrossRefGoogle Scholar
  45. 45.
    Simpson PT, Reis-Filho JS, Gale T, Lakhani SR. Molecular evolution of breast cancer. J Pathol. 2005;205:248–54.PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  1. 1.Department of Pathology, Box 85The University of Texas MD Anderson Cancer CenterHoustonUSA

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