American Journal of Medical Case Reports
ISSN (Print): 2374-2151 ISSN (Online): 2374-216X Website: Editor-in-chief: Samy, I. McFarlane
Open Access
Journal Browser
American Journal of Medical Case Reports. 2014, 2(9), 187-193
DOI: 10.12691/ajmcr-2-9-7
Open AccessCase Report

Epidermodysplasia Verruciformis Associated with Astrocytoma, Mantle Lymphoma and Hepatitis B Virus Infection

Mahmoud Ibrahim Yousef Elbadry1, and Ahmed Othman Ahmed Emam1

1Department of Internal Medicine, Sohag Faculty of Medicine, Sohag University, Sohag, Egypt

Pub. Date: September 22, 2014

Cite this paper:
Mahmoud Ibrahim Yousef Elbadry and Ahmed Othman Ahmed Emam. Epidermodysplasia Verruciformis Associated with Astrocytoma, Mantle Lymphoma and Hepatitis B Virus Infection. American Journal of Medical Case Reports. 2014; 2(9):187-193. doi: 10.12691/ajmcr-2-9-7


Epidermodysplasia verruciformis (EV) is a lifelong, rare autosomal recessive genetic hereditary skin disorder characterized by a unique susceptibility to human papilloma virus, associated with a high risk of malignant transformation. The disseminated verrucous lesions and pityriasis versicolor-like lesions persist from early childhood and can transform into a cutaneous malignancy in a fourth of patients. No definitive treatment against Epidermodysplasia verruciformis has been found yet. Extracutaneous cancers reported in Epidermodysplasia verruciformis are intestinal adenocarcinoma, plasmablastic lymphoma and leiomyosarcoma. Mantle cell lymphoma is uncommon under the age of 40 years and rare in patients under the age of 30 years. Here we are reporting a 19 year male patient with Epidermodysplasia verruciformis, astrocytoma and pulmonary tuberculosis who presented with symptoms of weight loss, indigestion and burning epigastric pain four months duration, Upper GIT endoscopy showed a gastric mass with active peptic ulcers. Biopsy revealed Mantle cell lymphoma. We investigated further and found to have immunodeficiency and hepatitis B virus infection. EV patients should receive regular follow-up for possible cutaneous or extracutaneous malignancy.

Epidermodysplasia verruciformis Astrocytoma Lymphoma Mantle-Cell Human papillomavirus DNA Tests Hepatitis B virus

Creative CommonsThis work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit


[1]  RamozN, Rueda LA, Bouadjar B, Montoya LS, Orth G, Favre M.Mutations in two adjacent novel genes are associated with epidermodysplasia verruciformis. Nature Genetics 2002; 32 (4): 579-81.
[2]  Cobb MW. Human papillomavirus infection. J Am Acad Dermatol. 1990; 22: 547.
[3]  Lazarczyk M, Pons C, Mendoza JA, Cassonnet P, Jacob Y, Favre M. Regulation of cellular zinc balance as a potential mechanism of EVER-mediated protection against pathogenesis by cutaneous oncogenic human papillomaviruses. The Journal of Experimental Medicine 2008; 205 (1): 35-42.
[4]  Orth G. Epidermodysplasia verruciformis: a model for understanding the oncogenicity of human papillomaviruses. Ciba Foundation Symposium 1986 ; 120: 157-74.
[5]  Antonsson A, Forslund O, Ekberg H, Sterner G, Hansson BG. The ubiquity and impressive genomic diversity of human skin papillomaviruses suggest a commensalic nature of these viruses. Journal of Virology 2000; 74 (24): 11636-41.
[6]  Gül U, Kiliç A, Gönül M, Cakmak SK, Bayis SS. Clinical aspects of epidermodysplasia verruciformis and review of the literature. International Journal of Dermatology 2007; 46 (10): 1069-72.
[7]  Lewandowsky F, Lutz W. Ein Fall einer bisher nicht beschriebenen Hauterkrankung (Epidermodysplasia verruciformis). Arch Dermatol Syphilol 1922; 141 193-203.
[8]  Glinsky W, Obalek S, Jablonska S, et al. T-cell defect in patients with epidermodysplasia verruciformis due to HPV types 3 and 5. Dermatologica 1981; 162: 141-147.
[9]  Jablonska S, Dabrowski J, Jakubowicz. Epidermodysplasia verruciformis as a model in studies on the role of papova virus in oncogenesis. Cancer Res 1972; 583-589.
[10]  Fischer MS. Knipke ML. Systemic alteration induced in mice by ultraviolet light irradiation and its relationship to ultraviolet carcinogenesis. Proc Natl Acad Scl USA 1977; 74: 1688-1692.
[11]  Hammer H, Hammer L, Lamber B. et al. Epidermodysplasia verruciformis. A case report including electron microscopy and DNA repair; investigation on dermatosis associated with multiple skin cancers. Acta Med Scand 1976; 200: 441-445.
[12]  Mitsuishi T, Kawana S, Kato T, Kawashima M. Human papillomavirus infection in actinic keratosis and bowen's disease: comparative study with expression of cell-cycle regulatory proteins p21 (Waf1/Cip1), p53, PCNA, Ki-67, and Bcl-2 in positive and negative lesions. Hum Pathol. 2003; 34 (9): 886-92.
[13]  Stetsenko GY, McFarlane RJ, Chien AJ, et al. Subungual Bowen disease in a patient with epidermodysplasia verruciformis presenting clinically as longitudinal melanonychia. Am J Dermatopathol. 2008; 30 (6): 582-5.
[14]  Sehgal VN, Luthra A, Bajaj P. Epidermodysplasia verruciformis: 14 members of a pedigree with intriguing squamous cell carcinoma. Int J Dermatol 2002; 41: 500-3.
[15]  Musshoff K. Clinical staging classification of non-Hodgkin’s lymphomas (author’s transl). Strahlentherapie 1977; 153: 218-221. German.
[16]  Rohatiner A, d’Amore F, Coiffier B et al. Report on a workshop convened to discuss the pathological and staging classifications of gastrointestinal tract lymphoma. Ann Oncol 1994; 5: 397-400.
[17]  de Oliveira WR, Festa Neto C, Rady PL, Tyring SK: Clinical aspects of epidermodysplasia verruciformis. J Eur Acad Dermatol Venereol 2003; 17: 394-398.
[18]  Androphy EJ, Dvoretzky I, Lowy DR. X-linked inheritance of epidermodysplasia verruciformis. Genetic and virologic studies of a kindred. Arch Dermatol. 1985; 121 (7): 864-8.
[19]  Gober MD, Rady PL, He Q, Tucker SB, Tyring SK, Gaspari AA. Novel homozygous frameshift mutation of EVER1 gene in an epidermodysplasia verruciformis patient. J Invest Dermatol. 2007; 127 (4): 817-20.
[20]  Lutzner MA. Epidermodysplasia verruciformis. An autosomal recessive disease characterized by viral warts and skin cancer. A model for viral oncogenesis. Bull Cancer 1978; 65: 169-182.
[21]  Jablonska S, Orth G, Jarzabek-Chorzelska M et al.Twenty-one years of follow-up studies of familial epidermodysplasia verruciformis. Dermatologica 1979; 158: 309-327.
[22]  Gewirtzman A, Bartlett B, Tyring S: Epidermodysplasia verruciformis and human papilloma virus. Curr Opin Infect Dis 2008; 21: 141-146.
[23]  Hu W, Nuovo G, Willen M, Somach S: Epidermodysplasia verruciformis in two half brothers with HIV infection. J Cutan Med Surg 2004; 8: 357-360.
[24]  Berger TG, Sawchuk WS, Leonardi C, et al.: Epidermodysplasia verruciformis-associated papillomavirus infection complicating human immunodeficiency virus disease. Br J Dermatol 1991; 124: 79-83.
[25]  Haas N, Fuchs PG, Hermes B, Henz BM: Remission of epidermodysplasia verruciformis-like skin eruption after highly active antiretroviral therapy in a human immunodeficiency virus-positive patient. Br J Dermatol 2001; 145: 669-670.
[26]  Kunishige JH, Hymes SR, Madkan V, et al.: Epidermodysplasia verruciformis in the setting of graft-versus-host disease. J Am Acad Dermatol 2007; 57: S78-80.
[27]  Blessing K, McLaren KM, Benton EC, et al.: Histopathology of skin lesions in renal allograft recipients--an assessment of viral features and dysplasia. Histopathology 1989; 14: 129-139.
[28]  Yutsudo M, Kanda R, Tanigaki T, et al.: Human papillomavirus type 38 isolated from patients with epidermodysplasia verruciformis. Intervirology 1986; 26: 104-108.
[29]  Gross G, Ellinger K, Roussaki A, et al.: Epidermodysplasia verruciformis in a patient with Hodgkin's disease: characterization of a new papillomavirus type and interferon treatment. J Invest Dermatol 1988; 91: 43-48.
[30]  Kreuter A, Hochdorfer B, Brockmeyer NH, et al.: A human papillomavirus-associated disease with disseminated warts, depressed cell-mediated immunity, primary lymphedema, and anogenital dysplasia: WILD syndrome. Arch Dermatol 2008; 144: 366-372.
[31]  Vu J, Wallace GR, Singh R, et al.: Common variable immunodeficiency syndrome associated with epidermodysplasia verruciformis. Am J Clin Dermatol 2007; 8: 307-310.
[32]  Wang YT, Geng B, Yoo KY, et al. Cutaneous granulomas and epidermodysplasia verruciformis in early onset combined immunodeficiency syndrome. Am J Dermatopathol. 2014; 36 (2): 179-83.
[33]  Iraji F, Faghihi G: Epidermodysplasia verruciformis: association with isolated IgM deficiency and response to treatment with acitretin. Clin Exp Dermatol 2000; 25: 41-43.
[34]  Gul U, Soylu S, Yavuzer R: Epidermodysplasia verruciformis associated with isolated IgM deficiency. Indian J Dermatol Venereol Leprol 2007; 73: 420-422.
[35]  Ishiji T, Kawase M, Honda M, et al. Distinctive distribution of human papillomavirus type 16 and type 20 DNA in the tonsillar and the skin carcinomas of a patient with epidermodysplasia verruciformis. Br J Dermatol 2000; 143: 1005-10.
[36]  Aoyama H, Seki S, Abo T, Usuba Y, Tomita Y, Tagami H. Epidermodysplasia verruciformis accompanied by familial large granular lymphocytosis and a decrease in T lymphocytes. Acta Derm Venereol 1993; 73: 52-54.
[37]  Yinnon AM, Rudensky B, Sagi E, et al. Invasive cryptococcosis in a family with epidermodysplasia verruciformis and idiopathic CD4 cell depletion. Clin Infect Dis 1997; 25: 1252-3
[38]  Tobin E, Rohwedder A, Holland SM, Carlson JA. Recurrent ‘sterile’ verrucous cyst abscesses and epidermodysplasia verruciformis-like eruption associated with idiopathic CD4 lymphopenia. Br J Dermatol 2003; 149: 627-633.
[39]  Majewski S, Skopinska-Rozewska E, Jablonska S, Wasik M, Misiewicz J, Orth G. Partial defects of cell-mediated immunity in patients with epidermodysplasia verruciformis. J Am Acad Dermatol 1986; 15: 966-73
[40]  Stray-Pedersen A, Jouanguy E, Crequer A, et al.Compound Heterozygous CORO1A Mutations in Siblings with a Mucocutaneous-Immunodeficiency Syndrome of Epidermodysplasia Verruciformis-HPV, Molluscum Contagiosum and Granulomatous Tuberculoid Leprosy. J Clin Immunol. 2014; 30.
[41]  Luiz Euribel Prestes-Carneiro, Gisele Alborghetti Nai, Márcia G. Silva, et al. Clinical presentation of tuberculoid leprosy in an epidermodysplasia verruciformis patient. J Infect Dev Ctries 2012; 6 (6): 526-530.
[42]  Jacyk WK and Lechner W. Epidermodysplasia verruciformis in lepromatous leprosy: Report of 2 cases. Dermatologica 1984; 168: 202-205.
[43]  Zantour B, Knani J, Boudawara N, et al.Familial idiopathic pulmonary fibrosis associated with autoimmune polyendocrinopathy and epidermodysplasia verruciformis. Rev Pneumol Clin. 2010; 66 (2): 127-31.
[44]  Haftek M, Jablonska S, Orth G. Specific cell-mediated immunity in patients with epidermodysplasia veruciformis and plane warts. Dermatologica 1985; 170: 213-220.
[45]  Orth G, Jablonska S, Jarzabek-Chorzelska M, et al. Characteristics of the lesions and risk of malignant conversion associated with the type of the human papillomavirus involved in epidermodysplasia verruciformis. Cancer Res 1979; 39: 1074-1082.
[46]  Toyoda H, Ido M, Nakanishi K, Nakano T, Kamiya H, Matsumine A, et al. Multiple cutaneous squamous cell carcinomas in a patient with interferon gamma receptor 2 (IFN gamma R2) deficiency. J Med Genet. 2010; 47 (9): 631-4.
[47]  de Oliveira WR, He Q, Rady PL, et al.: HPV typing in Brazilian patients with epidermodysplasia verruciformis: high prevalence of EV-HPV 25. J Cutan Med Surg 2004; 8: 110-115.
[48]  Kao G, et al. Cutaneous carcinogenesis: Etiologic Factors-Viruses. In: Miller S, Mahoney M, eds. Cutaneous Oncology: Pathophysiology, Diagnosis, and Treatment. London, England: Blackwell Science; 1997: 148-157.
[49]  Morrison C, Eliezri Y, Magro C, Nuovo GJ. The histologic spectrum of epidermodysplasia verruciformis in transplant and AIDS patients. J Cutan Pathol. Sep 2002; 29 (8): 480-9.
[50]  Berthelot C, Dickerson MC, Rady P, et al. Treatment of a patient with epidermodysplasia verruciformis carrying a novel EVER2 mutation with imiquimod. J Am Acad Dermatol. May 2007; 56 (5): 882-6.
[51]  Majewski S, Jablonska S. Human papillomavirus-associated tumors of the skin and mucosa. J Am Acad Dermatol 1997; 36: 659-685; quiz 686-688.
[52]  Shayanfar N, Babaheidarian P, Rahmani H, et al. Epidermodysplasia verruciformis associated with plasmablastic lymphoma and hepatitis B virus infection. Acta Dermatovenerol Croat. 2012; 20 (4): 267-71.
[53]  Boran P, Tokuc G, Ozberk M, Buyukbabani N, Dogan O. Epidermodysplasia verruciformis associated with natural killer/T cell lymphoma. J Pediatr. 2010; 156 (2): 340-340.
[54]  Youssef M, Denguezli M, Ghariani N, Belajouza C, Nouira R. Epidermodysplasia verruciformis associated with intestinal lymphoma: a model of viral oncogenicity. Pediatr Dermatol. 2007; 24 (5): 511-3.
[55]  Slawsky LD, Gilson RT, Hockely AJ et al. Epidermodysplasia verruciformis associated with severe immunodeficiency, lymphoma, and disseminated molluscum contagiosum. J Am Acad Dermatol 1992; 27: 448-450.
[56]  Feltkamp MC, Broer R, di Summa FM, et al. Seroreactivity to epidermodysplasia verruciformis-related human papillomavirus types is associated with nonmelanoma skin cancer. Cancer Res 2003; 63: 2695-700.
[57]  zur HH. Papillomaviruses causing cancer: evasion from host-cell control in early events in carcinogenesis. J Natl Cancer Inst 2000; 92: 690-698.
[58]  Yang JT, Liu CZ, Domer P, Iannaccone P. Expression of lymphomagenic oncogenes in T-cell lymphomas of HPV 16 transgenic mice. Cancer Detect Prev 1998; 22: 405-15.
[59]  Levine AM. Lymphoma complicating immunodeficiency dis-orders. Ann Oncol 1994; 5: Suppl 2: 29-35.
[60]  Majewski S, Jablonska S. Why epidermodysplasia verruciformis-a rare genetic disease-has raised such great interest. Int J Dermatol 2004; 43: 309-311.
[61]  Orth G. Host defenses against human papilloma viruses: lessons from epidermodysplasia verruciformis. Curr Top Microbiol Immunol 2008; 321: 59-83.
[62]  Özlem Boybeyi, Zuhal Akçören, Berna Oğuz, Canan Akyüz, Özden Sanal, Sibel Ergin, Sibel Ersoy-Evans, F. Cahit Tanyel. Multifocal leiomyosarcomatosis in a 6-year-old child with epidermodysplasia verruciformis and immune defect. Volume 44, Issue 7, 2009, Pages e5-e8.
[63]  Oliveira WR, Ferreira GN, Rady PL, Festa C, Tyring SK. Epidermodysplasia verruciformis associated with myelodysplastic syndrome: an intriguing association. J Cutan Med Surg. 2009; 13 (6): 317-20.
[64]  Eguiguren JM, Ribeiro RC, Pui CH, Hancock ML, Pratt CB, Head DR, Crist WM. Secondary non-Hodgkin's lymphoma after treatment for childhood cancer. Leukemia. 1991 ; 5 (10): 908-11.
[65]  van Voorst Vader PC, Orth G, Dutronquay V, Driessen LH, Eggink HF, Kallenberg CG, et al. Epidermodysplasia verruciformis. Skin carcinoma containing human papillomavirus type 5 DNA sequences and primary hepatocellular carcinoma associated with chronic hepatitis B virus infection in a patient. Acta Derm Venereol 1986; 66: 231-6.
[66]  Tanner JE, Alfieri C. The Epstein-Barr virus and post transplant lymphoproliferative disease: interplay of immunosuppression, EBV, and the immune system in disease pathogenesis. Transpl Infect Dis 2001; 3: 60-69.