title: Lymphoma in acquired generalized lipodystrophy.
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.
authors: a Diabetes, Endocrinology and Obesity Branch (DEOB), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) , Bethesda , MD , USA.
authors: Rebecca J
authors: RJ
authors: Brown
authors: b Bristol Myers Squibb , San Diego , CA , USA.
authors: Jean L
authors: JL
authors: Chan
authors: c Hematopathology Section, Laboratory of Pathology, Center for Cancer Research, National Cancer Institute (NCI), National Institutes of Health (NIH) , Bethesda , MD , USA.
authors: Elaine S
authors: ES
authors: Jaffe
authors: a Diabetes, Endocrinology and Obesity Branch (DEOB), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) , Bethesda , MD , USA.
authors: Elaine
authors: E
authors: Cochran
authors: d William Sansum Diabetes Center , Santa Barbara , CA , USA.
authors: Alex M
authors: AM
authors: DePaoli
authors: e Department of Diabetes and Endocrinology , Assistance Publique - Hôpitaux de Paris, DHU FIRE, Lariboisière Hospital, University Paris-Diderot Paris-7 , Paris , France.
authors: Jean-Francois
authors: JF
authors: Gautier
authors: f APHP, Hôpital Bicêtre; Inserm CESP U1018; Faculté de Médecine Paris-Sud; Le Kremlin Bicêtre , Paris , France.
authors: Cecile
authors: C
authors: Goujard
authors: g Inserm, UMR_S938, Centre de Recherche Saint-Antoine, Faculté de Médecine Pierre et Marie Curie , F-75012 Paris , France.|h Sorbonne Universités, UPMC Univ Paris 6, UMR S938, F-75005 , Paris , France.|i ICAN, Institute of Cardiometabolism and Nutrition , F-75013 , Paris , France.|j AP-HP, Hôpital Saint-Antoine, Laboratoire Commun de Biologie et Génétique Moléculaires , F-75012 , Paris , France.
authors: Corinne
authors: C
authors: Vigouroux
authors: a Diabetes, Endocrinology and Obesity Branch (DEOB), National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK), National Institutes of Health (NIH) , Bethesda , MD , USA.
authors: Phillip
authors: P
authors: Gorden
mesh_terms: D000293:Adolescent; D000328:Adult; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015551:Autoimmunity; D015415:Biomarkers; D002675:Child, Preschool; D017809:Fatal Outcome; D005260:Female; D006801:Humans; D020738:Leptin / Q000009:adverse effects / Q000031:analogs & derivatives / Q000627:therapeutic use; D008060:Lipodystrophy / Q000150:complications* / Q000188:drug therapy / Q000276:immunology*; D016411:Lymphoma, T-Cell, Peripheral / Q000175:diagnosis / Q000188:drug therapy / Q000209:etiology* / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D016896:Treatment Outcome
chemical_list: D000970:Antineoplastic Agents; D015415:Biomarkers; D020738:Leptin; C415771:metreleptin
keywords: Acquired generalized lipodystrophy; T-cell lymphoma; leptin; metreleptin; mycosis fungoides