Recurrent lymphangiomyomatosis after transplantation: Genetic analyses reveal a metastatic mechanism

Magdalena Karbowniczek, Aristotelis Astrinidis, Binaifer R. Balsara, Joseph R. Testa, James H. Lium, Thomas V. Colby, Francis X. McCormack, Elizabeth Petri Henske

Research output: Contribution to journalArticle

185 Scopus citations

Abstract

Lymphangiomyomatosis (LAM) is characterized by the proliferation of abnormal smooth muscle cells and cystic degeneration of the lung. LAM affects almost exclusively young women. Although lung transplantation provides effective therapy for end-stage LAM, there are reports of LAM recurrence after lung transplantation. Whether these recurrent LAM cells arise from the patient or the lung transplant donor is an area of controversy. We used microsatellite marker fingerprinting and TSC2 gene mutational analysis to study a patient with recurrent LAM after single-lung transplantation. The DNA microsatellite marker pattern indicated the presence of patient-derived LAM cells in the allograft. A somatic one base pair deletion in exon 18 of the TSC2 gene was identified in pulmonary and lymph node LAM cells before transplantation. The same mutation was in the recurrent LAM, demonstrating that the recurrent LAM was derived from the patient. Fluorescence in situ hybridization revealed that cells immunoreactive with the monoclonal antibody HMB-45 did not contain a Y chromosome. These data indicate that histologically benign LAM cells can migrate or metastasize in vivo to the transplanted lung. In addition, the patient had no evidence of a renal angiomyolipoma at autopsy and therefore demonstrated for the first time that somatic TSC2 mutations cause LAM in patients without angiomyolipomas.

Original languageEnglish (US)
Pages (from-to)976-982
Number of pages7
JournalAmerican journal of respiratory and critical care medicine
Volume167
Issue number7
DOIs
StatePublished - Apr 1 2003

Keywords

  • Hamartin
  • Lung transplantation
  • Lymphangiomyomatosis
  • Tuberin
  • Tuberous sclerosis complex

ASJC Scopus subject areas

  • Pulmonary and Respiratory Medicine
  • Critical Care and Intensive Care Medicine

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  • Cite this

    Karbowniczek, M., Astrinidis, A., Balsara, B. R., Testa, J. R., Lium, J. H., Colby, T. V., McCormack, F. X., & Henske, E. P. (2003). Recurrent lymphangiomyomatosis after transplantation: Genetic analyses reveal a metastatic mechanism. American journal of respiratory and critical care medicine, 167(7), 976-982. https://doi.org/10.1164/rccm.200208-969OC