Original Article

Breast implant-associated, ALK-negative, T-cell, anaplastic, large-cell lymphoma: Establishment and characterization of a model cell line (TLBR-1) for this newly emerging clinical entity†

  1. Melissa G. Lechner BA1,
  2. Stephen Lade MD2,
  3. Daniel J. Liebertz MD1,
  4. H. Miles Prince MD2,
  5. Garry S. Brody MD3,
  6. Howard R. Webster MD4,
  7. Alan L. Epstein MD, PhD1,‡,*

Article first published online: 8 NOV 2010

DOI: 10.1002/cncr.25654

Issue

Cancer

Cancer

Volume 117, Issue 7, pages 1478–1489, 1 April 2011

Additional Information

How to Cite

Lechner, M. G., Lade, S., Liebertz, D. J., Prince, H. M., Brody, G. S., Webster, H. R. and Epstein, A. L. (2011), Breast implant-associated, ALK-negative, T-cell, anaplastic, large-cell lymphoma: Establishment and characterization of a model cell line (TLBR-1) for this newly emerging clinical entity. Cancer, 117: 1478–1489. doi: 10.1002/cncr.25654

Author Information

  1. 1

    Pathology Department, USC Keck School of Medicine, Los Angeles, California

  2. 2

    Division of Hematology and Medical Oncology, Peter MacCallum Cancer Center, University of Melbourne, Victoria, Australia

  3. 3

    Plastic Surgery Department, University of Southern California Keck School of Medicine, Los Angeles, California

  4. 4

    ARC Plastic Surgery, University of Melbourne, Victoria, Australia

  1. ‡

    Fax: (323) 442-3049

*Pathology Department, Hoffman Medical Research Building Room 205, USC Keck School of Medicine, Los Angeles, CA 90033

  1. †

    M.G.L. characterized the TLBR-1 cell line, analyzed the data, and wrote the article. S.L., H.M.P., and H.R.W. provided clinical care and management of the patient, performed clinical studies on the original biopsy specimen, and wrote the case report. D.J.L. assisted with polymerase chain reaction (PCR) and qRT-PCR analyses and prepared the figures. G.S.B. identified the patient and arranged for transport of the biopsy specimen. A.L.E. established the cell line and supervised the studies. All authors reviewed the manuscript.

Publication History

  1. Issue published online: 18 MAR 2011
  2. Article first published online: 8 NOV 2010
  3. Manuscript Accepted: 9 AUG 2010
  4. Manuscript Revised: 22 JUN 2010
  5. Manuscript Received: 22 MAR 2010

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Keywords:

  • anaplastic large-cell lymphoma;
  • breast implant;
  • primary breast lymphoma;
  • human cell line;
  • Notch1

Recent evidence suggests an increased incidence of anaplastic large-cell kinase (ALK)-negative, T-cell, non-Hodgkin Lymphoma arising in association with salt-withdrawal textured breast implants. TLBR-1, a novel T-cell, anaplastic, large-cell lymphoma, has been established and characterized from a surgical biopsy and represents an important tool for studying this newly recognized disease entity.

Abstract

BACKGROUND:

Primary lymphomas of the breast are very rare (0.2-1.5% of breast malignancies) and the vast majority (95%) are of B-cell origin. Recently, 40 cases of clinically indolent anaplastic large-cell kinase (ALK)-negative, T-cell, anaplastic, non-Hodgkin lymphomas (T-ALCL) have been reported worldwide.

METHODS:

A tumor biopsy specimen from a patient in this series was obtained for characterization. By using a human stromal feeder layer and IL-2, a novel cell line, TLBR-1, was established from this biopsy and investigated by using cytogenetics and various biomolecular methods.

RESULTS:

Immunoperoxidase staining of the tumor biopsy showed a CD30/CD8/CD4 coexpressing T-cell population that was epithelial membrane antigen (EMA)+ and perforin+. Multiplex polymerase chain reaction (PCR) of TCRγ genes showed monoclonality that suggested a T-cell origin, yet pan-T markers CD2/5/7, anaplastic large-cell kinase (ALK)-1, pancytokeratins, CD20, CD56, and Epstein-Barr virus (EBV) by in situ hybridization (ISH) were negative. TLBR-1 is IL-2 dependent, has a relatively long doubling time (55 hours), and displays different cellular shapes in culture. Cytogenetic analysis of tumor and TLBR-1 cells confirmed a highly anaplastic cell population with a modal number of 47 chromosomes lacking t(2;5). PCR screens for EBV and human T-lymphotropic virus types 1 and 2 (HTLV-1/2) were negative. Fluorescence-activated cell-sorting (FACS) analysis showed strong positivity for CD4/8, CD30, CD71, and CD26 expression, and antigen presentation (HLA-DR+CD80+CD86+), IL-2 signaling (CD25+CD122+), and NK (CD56+) markers, and Western blots demonstrated strong Notch1 expression. Severe combined immunodeficiency (SCID) mouse TLBR-1 heterotransplants recapitulated the histology and marker characteristics of the original tumor.

CONCLUSIONS:

TLBR-1, a novel ALK-negative, T-cell, anaplastic, large-cell lymphoma, closely resembles the original biopsy and represents an important tool for studying this newly recognized disease entity. Cancer 2011. © 2010 American Cancer Society.

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