Acanthosis Nigricans – A Two-Sided Coin: Consider Metabolic Syndrome and Malignancies!

Authors

  • Uwe Wollina Academic Teaching Hospital DresdenDepartment of Dermatology and Allergology
  • Gesina Hansel Department of Dermatology and Allergology, Städtisches Klinikum Dresden, Academic Teaching Hospital
  • Torello Lotti University of Rome “G. Marconi”, Rome, Italy
  • Georgi Tchernev Onkoderma Policlinic for Dermatology and Dermatologic Surgery, Sofia, Bulgaria
  • Aleksandra Vojvodic Military Medical Academy of Belgrade, Serbia, and University of Rome Guglielmo Marconi Rome, Italy
  • Ivanka Temelkova Onkoderma Policlinic for Dermatology and Dermatologic Surgery, Sofia, Bulgaria

DOI:

https://doi.org/10.3889/oamjms.2019.258

Keywords:

Acanthosis nigricans, Metabolic syndrome, Malignancies, Paraneoplasia

Abstract

BACKGROUND: Acanthosis nigricans (AN) is acquired hyperpigmentation of the intertriginous body regions. Histologically, AN is characterised by a thickened stratum corneum and a variable amount of acanthosis. Although benign and rarely symptomatic, AN may be a red flag for underlying pathologies.

CASE PRESENTATION: We analysed our patients with AN and could differentiate three different patterns, that are illustrated by one case report each. The is the benign AN associated with metabolic syndrome including obesity. The second type is the paraneoplastic AN malignancy which is associated with a wider range of malignancies. This type may occur before, after or with the clinical appearance of the malignancy. The third type is relapsing AN after complete remission. We present a patient who had a malignant AN and was treated successfully for his cancer. Years later, however, AN relapsed. In that case in association with the appearance of skin tags. Cancer restaging excluded a tumour relapse. His BMI was 31.2 kg/m2, and the diagnosis of benign AN was confirmed.

CONCLUSIONS: The diagnosis of AN remains incomplete without screening for metabolic syndrome and/ or cancer. The combination of AN and skin tags is more often associated with metabolic syndrome. AN may be considered as a red flag for malignancies and the metabolic syndrome.

Downloads

Download data is not yet available.

Metrics

Metrics Loading ...

Plum Analytics Artifact Widget Block

Author Biographies

Uwe Wollina, Academic Teaching Hospital DresdenDepartment of Dermatology and Allergology

Head of Department of Dermatology and Allergology

Gesina Hansel, Department of Dermatology and Allergology, Städtisches Klinikum Dresden, Academic Teaching Hospital

Senior Advisor

Department of Dermatology and Allergology, Städtisches Klinikum Dresden, Academic Teaching Hospital

Torello Lotti, University of Rome “G. Marconi”, Rome, Italy

Professor of Dermatology

Department of Dermatology, University of Rome “G. Marconiâ€, Rome, Italy

 

Aleksandra Vojvodic, Military Medical Academy of Belgrade, Serbia, and University of Rome Guglielmo Marconi Rome, Italy

Professor of Dermatology

Military Medical Academy of Belgrade, Serbia, and University of Rome Guglielmo Marconi Rome, Italy

References

Schwartz RA. Acanthosis nigricans. J Am Acad Dermatol. 1994; 31(1):1-19. https://doi.org/10.1016/S0190-9622(94)70128-8

Sinha S, Schwartz RA. Juvenile acanthosis nigricans. J Am Acad Dermatol. 2007; 57(3):502-8. https://doi.org/10.1016/j.jaad.2006.08.016 PMid:17592743

Stuart CA, Gilkison CR, Smith MM, Bosma AM, Keenan BS, Nagamani M. Acanthosis nigricans as a risk factor for non-insulin dependent diabetes mellitus. Clin Pediatr (Phila). 1998; 37(2):73-9. https://doi.org/10.1177/000992289803700203 PMid:9492114

Hodak E, Gottlieb AB, Anzilotti M, Krueger JG. The insulin-like growth factor 1 receptor is expressed by epithelial cells with proliferative potential in human epidermis and skin appendages: correlation of increased expression with epidermal hyperplasia. J Invest Dermatol. 1996; 106(3):564-70. https://doi.org/10.1111/1523-1747.ep12344044 PMid:8648195

Lee JM, Okumura MJ, Davis MM, Herman WH, Gurney JG. Prevalence and determinants of insulin resistance among U.S. adolescents: a population-based study. Diabetes Care. 2006; 29(11):2427-32. https://doi.org/10.2337/dc06-0709 PMid:17065679

Muguet Guenot L, Aubert H, Isidor B, Toutain A, Mazereeuw-Hautier J, Collet C, Bourrat E, Denis Musquer M, Barbarot S; Groupe de Recherche de la Société Française de Dermatologie Pédiatrique. Acanthosis nigricans, hypochondroplasia, and FGFR3 mutations: Findings with five new patients, and a review of the literature. Pediatr Dermatol. 2019; 36(2):242-246. https://doi.org/10.1111/pde.13748 PMid:30762251

Mueller N, Sassa T, Morales-Gonzalez S, Schneider J, Salchow DJ, Seelow D, Knierim E, Stenzel W, Kihara A, Schuelke M. De novo mutation in ELOVL1 causes ichthyosis, acanthosis nigricans, hypomyelination, spastic paraplegia, high-frequency deafness and optic atrophy. J Med Genet. 2019; 56(3):164-175. https://doi.org/10.1136/jmedgenet-2018-105711 PMid:30487246

Ellis DL, Kafka SP, Chow JC, Nanney LB, Inman WH, McCadden ME, King LE Jr. Melanoma, growth factors, acanthosis nigricans, the sign of Leser-Trélat, and multiple acrochordons. A possible role for alpha-transforming growth factor in cutaneous paraneoplastic syndromes. N Engl J Med. 1987; 317(25):1582-7. https://doi.org/10.1056/NEJM198712173172506 PMid:2825016

Unal E, Guarneri C, Chokoeva AA, Wollina U, Tchernev G. Terra firma-forme dermatosis. Wien Med Wochenschr. 2017; 167(3-4):66-69. https://doi.org/10.1007/s10354-016-0519-1 PMid:27770322

Lim JH, Tey HL, Chong WS. Confluent and reticulated papillomatosis: diagnostic and treatment challenges. Clin Cosmet Investig Dermatol. 2016; 9:217-23. https://doi.org/10.2147/CCID.S92051 PMid:27601929 PMCid:PMC5003519

Lautenschlager S, Itin PH. Reticulate, patchy and mottled pigmentation of the neck. Acquired forms. Dermatology. 1998; 197(3):291-6. https://doi.org/10.1159/000018016 PMid:9812039

Samson SL, Garber AJ. Metabolic syndrome. Endocrinol Metab Clin North Am. 2014; 43(1):1-23. https://doi.org/10.1016/j.ecl.2013.09.009 PMid:24582089

Ogden CL, Carroll MD, Curtin LR, McDowell MA, Tabak CJ, Flegal KM. Prevalence of overweight and obesity in the United States, 1999-2004. JAMA. 2006; 295(13):1549-55. https://doi.org/10.1001/jama.295.13.1549 PMid:16595758

Ozlu E, Uzuncakmak TK, Takır M, Akdeniz N, Karadag AS. Comparison of cutaneous manifestations in diabetic and nondiabetic obese patients: A prospective, controlled study. North Clin Istanb. 2018; 5(2):114-119. https://doi.org/10.14744/nci.2017.68553 PMid:30374476 PMCid:PMC6191549

Palhares HMDC, Zaidan PC, Dib FCM, Silva APD, Resende DCS, Borges MF. Association between acanthosis nigricans and other cardiometabolic risk factors in children and adolescents with overweight and obesity. Rev Paul Pediatr. 2018;36(3):301-308. https://doi.org/10.1590/1984-0462/;2018;36;3;00017 PMid:30365811 PMCid:PMC6202888

KaradaÄŸ AS, You Y, Danarti R, Al-Khuzaei S, Chen W. Acanthosis nigricans and the metabolic syndrome. Clin Dermatol. 2018; 36(1):48-53. https://doi.org/10.1016/j.clindermatol.2017.09.008 PMid:29241752

Higgins SP, Freemark M, Prose NS. Acanthosis nigricans: a practical approach to evaluation and management. Dermatol Online J. 2008; 14(9):2.

Kazemi M, Pierson RA, Lujan ME, Chilibeck PD, McBreairty LE, Gordon JJ, Serrao SB, Zello GA, Chizen DR. Comprehensive Evaluation of Type 2 Diabetes and Cardiovascular Disease Risk Profiles in Reproductive-Age Women with Polycystic Ovary Syndrome: A Large Canadian Cohort. J Obstet Gynaecol Can. 2019; S1701-2163(18)30991-5. https://doi.org/10.1016/j.jogc.2018.11.026 PMid:30712903

Ramos-E-Silva M, Carvalho JC, Carneiro SC. Cutaneous paraneoplasia. Clin Dermatol. 2011; 29(5):541-7. https://doi.org/10.1016/j.clindermatol.2010.09.022 PMid:21855730

Krawczyk M, Mykała-Cieśla J, Kołodziej-Jaskuła A. Acanthosis nigricans as a paraneoplastic syndrome. Case reports and review of literature. Pol Arch Med Wewn. 2009; 119:180-183. https://doi.org/10.20452/pamw.642 PMid:19514649

Levine D, Miller S, Al-Dawsari N, Barak O, Gottlieb AB. Paraneoplastic dermatoses associated with gynecologic and breast malignancies. Obstet Gynecol Surv. 2010; 65(7):455-61. https://doi.org/10.1097/OGX.0b013e3181efb12a PMid:20723267

Scully C, Barrett WA, Gilkes J, Rees M, Sarner M, Southcott RJ. Oral acanthosis nigricans, the sign of Leser-Trélat and cholangiocarcinoma. Br J Dermatol. 2001; 145(3):506-7. https://doi.org/10.1046/j.1365-2133.2001.04393.x PMid:11531848

Ferraz de Campos FP, Narvaez MR, Reis PV, Gomes AC, Paraskevopoulos DK, Santana F, Fugita OE. Acanthosis Nigricans associated with clear-cell renal cell carcinoma. Autops Case Rep. 2016; 6(1):33-40. https://doi.org/10.4322/acr.2016.021 PMid:27284539 PMCid:PMC4880432

Deen J, Moloney T, Burdon-Jones D. Severe, Malignant Acanthosis Nigricans Associated with Adenocarcinoma of the Endometrium in a Young Obese Female. Case Rep Dermatol. 2017; 9(1):30-37. https://doi.org/10.1159/000456652 PMid:28413386 PMCid:PMC5346941

West L, Carlson M, Wallis L, Goff HW. The Sign of Leser-Trelát and Malignant Acanthosis Nigricans Associated With Fallopian Tube Carcinoma. Obstet Gynecol. 2018; 132(5):1116-1119. https://doi.org/10.1097/AOG.0000000000002920 PMid:30303917

Ziadi T, Alahyane A, El Fahssi M, Makhmari R, Elhjouji A, Baba H, Ould Jiddou C, Nafae I, Mejdane A, Bounaim A, Ait Ali A, Zentar A, Hommadi A, Sair K. [Adenocarcinoma of gallbladder revealed by acanthosis nigricans]. Gastroenterol Clin Biol. 2009; 33(10-11):986-8. https://doi.org/10.1016/j.gcb.2009.06.010 PMid:19765931

Yu Q, Li XL, Ji G, Wang Y, Gong Y, Xu H, Shi YL. Malignant acanthosis nigricans: an early diagnostic clue for gastric adenocarcinoma. World J Surg Oncol. 2017; 15(1):208. https://doi.org/10.1186/s12957-017-1274-5 PMid:29178944 PMCid:PMC5702104

Mignogna MD, Fortuna G, Falleti J, Leuci S. Gastric diffuse large B-cell lymphoma (DLBCL) exhibiting oral acanthosis nigricans and tripe palms. Dig Liver Dis. 2009; 41(10):766-8. https://doi.org/10.1016/j.dld.2009.02.049 PMid:19349220

Park KW, Lim DH, Lee SI. Malignant acanthosis nigricans in a patient with a gastrointestinal stromal tumor. Korean J Intern Med. 2013; 28(5):632-3. https://doi.org/10.3904/kjim.2013.28.5.632 PMid:24009466 PMCid:PMC3759776

Antonio JR, Trídico LA, Antonio CR. Malignant Acanthosis nigricans associated with early diagnosis of liver cancer. An Bras Dermatol. 2018; 93(4):616-617. https://doi.org/10.1590/abd1806-4841.20187560 PMid:30066784 PMCid:PMC6063124

Gunduz K, Coban M, Oztürk F, Ermertcan AT. Malignant acanthosis nigricans associated with ileocecal adenocarcinoma. Cutan Ocul Toxicol. 2013; 32(2):173-5. https://doi.org/10.3109/15569527.2012.713417 PMid:22916843

Patra S, Chakraborty PP, Barman H, Santra G. Acanthosis nigricans in insulinoma: before and after successful surgical enucleation. BMJ Case Rep. 2016; 2016:bcr2016218003. https://doi.org/10.1136/bcr-2016-218003 PMid:27836838 PMCid:PMC5128931

Owen CE. Cutaneous manifestations of lung cancer. Semin Oncol. 2016; 43(3):366-9. https://doi.org/10.1053/j.seminoncol.2016.02.025 PMid:27178690

Dainichi T, Moroi Y, Duan H, Urabe K, Koga T, Miyazono M, Sasaki T, Hashimoto T, Furue M. Paraneoplastic acanthosis nigricans and silent meningioma producing transforming growth factor-alpha. Eur J Dermatol. 2008; 18(6):721-2.

Cheng E, Roy DB, Magro CM. A case of acanthosis nigricans coexisting with mycosis fungoides. Dermatol Online J. 2015; 21(7).

Fahmy J, Halabi-Tawil M, Ram-Wolff C, Bagot M, Petit A. Paraneoplastic acanthosis nigricans: the first reported case associated with Sézary syndrome. Br J Dermatol. 2016; 174(1):233-4. https://doi.org/10.1111/bjd.14065 PMid:26264676

Singh SK, Rai T. A rare case of malignant acanthosis nigricans in a lady with ovarian cancer. Indian Dermatol Online J. 2013; 4(2):125-7. https://doi.org/10.4103/2229-5178.110640 PMid:23741672 PMCid:PMC3673379

McGinness J, Greer K. Malignant acanthosis nigricans and tripe palms associated with pancreatic adenocarcinoma. Cutis. 2006; 78(1):37-40.

Tammaro A, Giulianelli V, Parisella F, Persechino S. Bilaterally mammary acanthosis nigricans as paraneoplastic manifestation of prostate adenocarcinoma. G Ital Dermatol Venereol. 2016; 151(5):578-9.

Marschner ML, Reinhardt JF. Malignant acanthosis nigricans in rectal adenocarcinoma. Del Med J. 2011; 83(8):247-9.

Brantsch KD, Moehrle M. Acanthosis nigricans in a patient with sarcoma of unknown origin. J Am Acad Dermatol. 2010; 62(3):527-8. https://doi.org/10.1016/j.jaad.2009.02.010 PMid:20159329

Published

2019-05-13

How to Cite

1.
Wollina U, Hansel G, Lotti T, Tchernev G, Vojvodic A, Temelkova I. Acanthosis Nigricans – A Two-Sided Coin: Consider Metabolic Syndrome and Malignancies!. Open Access Maced J Med Sci [Internet]. 2019 May 13 [cited 2024 Apr. 20];7(18):3081-4. Available from: https://oamjms.eu/index.php/mjms/article/view/oamjms.2019.258

Most read articles by the same author(s)

<< < 3 4 5 6 7 8 9 10 11 12 > >>