Lymphoma in Acquired Generalized Lipodystrophy

Overview

Journal Leuk Lymphoma

Specialties Hematology
Oncology

Date 2015 Apr 14

PMID 25864863

Citations 21

Authors

Rebecca J Brown

Jean L Chan

Elaine S Jaffe

Elaine Cochran

Alex M DePaoli

Jean-Francois Gautier

Cecile Goujard

Corinne Vigouroux

Phillip Gorden

Affiliations

Soon will be listed here.

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.

Citing Articles

Diagnosis, treatment and management of lipodystrophy: the physician perspective on the patient journey.

Patni N, Chard C, Araujo-Vilar D, Phillips H, Magee D, Akinci B Orphanet J Rare Dis. 2024; 19(1):263.

PMID: 38992753 PMC: 11241872. DOI: 10.1186/s13023-024-03245-3.

A Novel Subtype of Acquired Generalized Lipodystrophy Associated With Subcutaneous Panniculitis-Like T-cell Lymphoma.

Hoff F, Xing C, Garg A JCEM Case Rep. 2024; 2(5):luae069.

PMID: 38681964 PMC: 11055395. DOI: 10.1210/jcemcr/luae069.

Spontaneous Remission of Acquired Generalized Lipodystrophy Presenting in the Postpartum Period.

Bhatia R, Chennupathi P, Rosenstein E, Advani S JCEM Case Rep. 2024; 2(2):luae009.

PMID: 38314238 PMC: 10836637. DOI: 10.1210/jcemcr/luae009.

Obesity and Risk for Lymphoma: Possible Role of Leptin.

Jimenez-Cortegana C, Hontecillas-Prieto L, Garcia-Dominguez D, Zapata F, Palazon-Carrion N, Sanchez-Leon M Int J Mol Sci. 2022; 23(24).

PMID: 36555171 PMC: 9779026. DOI: 10.3390/ijms232415530.

Treatment Options for Lipodystrophy in Children.

Mainieri F, Tagi V, Chiarelli F Front Endocrinol (Lausanne). 2022; 13:879979.

PMID: 35600578 PMC: 9114741. DOI: 10.3389/fendo.2022.879979.

References

Garg A . Acquired and inherited lipodystrophies. N Engl J Med. 2004; 350(12):1220-34. DOI: 10.1056/NEJMra025261. View

Kedar A, Braylan R . Lymphohistiocytic anaplastic large cell lymphoma stage I: long-term survival after resection alone. Pediatr Hematol Oncol. 2000; 17(3):261-8. DOI: 10.1080/088800100276442. View

Oschlies I, Lisfeld J, Lamant L, Nakazawa A, DAmore E, Hansson U . ALK-positive anaplastic large cell lymphoma limited to the skin: clinical, histopathological and molecular analysis of 6 pediatric cases. A report from the ALCL99 study. Haematologica. 2012; 98(1):50-6. PMC: 3533659. DOI: 10.3324/haematol.2012.065664. View

Arioglu Oral E, Javor E, Ding L, Uzel G, Cochran E, Young J . Leptin replacement therapy modulates circulating lymphocyte subsets and cytokine responsiveness in severe lipodystrophy. J Clin Endocrinol Metab. 2005; 91(2):621-8. DOI: 10.1210/jc.2005-1220. View

Hall S, Gillespie J, Tenczynski T . Generalized lipodystrophy, scleroderma, and Hodgkin's disease. Arch Intern Med. 1978; 138(8):1303-4. View

Aslam A, Savage D, Coulson I . Acquired generalized lipodystrophy associated with peripheral T cell lymphoma with cutaneous infiltration. Int J Dermatol. 2013; 54(7):827-9. DOI: 10.1111/ijd.12185. View

Arioglu Oral E, Simha V, Ruiz E, Andewelt A, Premkumar A, Snell P . Leptin-replacement therapy for lipodystrophy. N Engl J Med. 2002; 346(8):570-8. DOI: 10.1056/NEJMoa012437. View

Smedby K, Askling J, Mariette X, Baecklund E . Autoimmune and inflammatory disorders and risk of malignant lymphomas--an update. J Intern Med. 2008; 264(6):514-27. DOI: 10.1111/j.1365-2796.2008.02029.x. View

Savage D, Semple R, Clatworthy M, Lyons P, Morgan B, Cochran E . Complement abnormalities in acquired lipodystrophy revisited. J Clin Endocrinol Metab. 2008; 94(1):10-6. DOI: 10.1210/jc.2008-1703. View

10.

Chan J, Lutz K, Cochran E, Huang W, Peters Y, Weyer C . Clinical effects of long-term metreleptin treatment in patients with lipodystrophy. Endocr Pract. 2011; 17(6):922-32. PMC: 3498767. DOI: 10.4158/EP11229.OR. View

11.

Misra A, Garg A . Clinical features and metabolic derangements in acquired generalized lipodystrophy: case reports and review of the literature. Medicine (Baltimore). 2003; 82(2):129-46. DOI: 10.1097/00005792-200303000-00007. View

12.

Yiannias J, DiCaudo D, Maskin E . Peripheral T-cell lymphoma presenting as lipoatrophy and nodules. Int J Dermatol. 2006; 45(12):1415-9. DOI: 10.1111/j.1365-4632.2006.02888.x. View

13.

Smedby K, Vajdic C, Falster M, Engels E, Martinez-Maza O, Turner J . Autoimmune disorders and risk of non-Hodgkin lymphoma subtypes: a pooled analysis within the InterLymph Consortium. Blood. 2008; 111(8):4029-38. PMC: 2288717. DOI: 10.1182/blood-2007-10-119974. View

14.

Bingham A, Mamyrova G, Rother K, Oral E, Cochran E, Premkumar A . Predictors of acquired lipodystrophy in juvenile-onset dermatomyositis and a gradient of severity. Medicine (Baltimore). 2008; 87(2):70-86. PMC: 2674585. DOI: 10.1097/MD.0b013e31816bc604. View

15.

Araujo-Vilar D, Sanchez-Iglesias S, Guillin-Amarelle C, Castro A, Lage M, Pazos M . Recombinant human leptin treatment in genetic lipodystrophic syndromes: the long-term Spanish experience. Endocrine. 2014; 49(1):139-47. PMC: 4412649. DOI: 10.1007/s12020-014-0450-4. View

16.

Chong A, Lupsa B, Cochran E, Gorden P . Efficacy of leptin therapy in the different forms of human lipodystrophy. Diabetologia. 2009; 53(1):27-35. DOI: 10.1007/s00125-009-1502-9. View

17.

Hubler A, Abendroth K, Keiner T, Stocker W, Kauf E, Hein G . Dysregulation of insulin-like growth factors in a case of generalized acquired lipoatrophic diabetes mellitus (Lawrence Syndrome) connected with autoantibodies against adipocyte membranes. Exp Clin Endocrinol Diabetes. 1998; 106(1):79-84. DOI: 10.1055/s-0029-1211955. View

18.

Haque W, Shimomura I, Matsuzawa Y, Garg A . Serum adiponectin and leptin levels in patients with lipodystrophies. J Clin Endocrinol Metab. 2002; 87(5):2395. DOI: 10.1210/jcem.87.5.8624. View

19.

Ebihara K, Kusakabe T, Hirata M, Masuzaki H, Miyanaga F, Kobayashi N . Efficacy and safety of leptin-replacement therapy and possible mechanisms of leptin actions in patients with generalized lipodystrophy. J Clin Endocrinol Metab. 2006; 92(2):532-41. DOI: 10.1210/jc.2006-1546. View

20.

Garg A . Clinical review#: Lipodystrophies: genetic and acquired body fat disorders. J Clin Endocrinol Metab. 2011; 96(11):3313-25. PMC: 7673254. DOI: 10.1210/jc.2011-1159. View