Abstract
Acquired generalized lipodystrophy (AGL) is a rare disease thought to result from autoimmune destruction of adipose tissue. Peripheral T-cell lymphoma (PTCL) has been reported in two AGL patients. We report five additional cases of lymphoma in AGL, and analyze the role of underlying autoimmunity and recombinant human leptin (metreleptin) replacement in lymphoma development. Three patients developed lymphoma during metreleptin treatment (two PTCL and one ALK-positive anaplastic large cell lymphoma), and two developed lymphomas (mycosis fungoides and Burkitt lymphoma) without metreleptin. AGL is associated with high risk for lymphoma, especially PTCL. Autoimmunity likely contributes to this risk. Lymphoma developed with or without metreleptin, suggesting metreleptin does not directly cause lymphoma development; a theoretical role of metreleptin in lymphoma progression remains possible. For most patients with AGL and severe metabolic complications, the proven benefits of metreleptin on metabolic disease will likely outweigh theoretical risks of metreleptin in lymphoma development or progression.
Acknowledgements
Alan Wayne (NIH) Ruchika Goel (NIH), Nirali N. Shah (NIH), and Stephanie Massaro (Yale University) provided clinical care for Case 3. For case 5, Baz Baz (AP-HP) provided clinical care, Nicolas Boissel (AP-HP) gave information on lymphoma diagnosis, and Olivier Lascols (AP-HP) performed genetic tests. Wyndham Wilson provided insight in the pathophysiology of lymphoma.
Funding
This work was supported by the intramural research programs of the National Institute of Diabetes and Digestive and Kidney Diseases (RJB, EC, PG) and the National Cancer Institute (ESJ), and by Assistance Publique-Hôpitaux de Paris and Inserm (JFG, CG and CV).
Role of the funding source: The authors are solely responsible for the study design, the collection, analysis, and interpretation of data, the writing of the manuscript, and the decision to submit for publication.
Potential conflict of interest:
Disclosure forms provided by the authors are available with the full text of this article at www.informahealthcare.com/lal. Dr Brown has nothing to disclose. Dr Chan reports being an employee of and holding stock in Bristol Myers Squibb, outside the submitted work. Dr Jaffe has nothing to disclose. Ms Cochran has nothing to disclose. Dr DePaoli reports a patent null issued. Dr Vigouroux reports personal fees from AstraZeneca outside the submitted work. Dr Goujard has nothing to disclose. Dr Gorden has nothing to disclose.