Epidermodysplasia verruciformis (EV) is a viral-mediated disorder which occurs as an inherited condition. These lesions are flattened skin-colored to reddish hyperpigmented papules. They have a wide distribution and may number from a few to more than 50.
Epidemiology Disease Associations Pathogenesis Histopathological Features and Variants Prognosis Treatment Commonly Used Terms Internet Links
EPIDEMIOLOGY CHARACTERIZATION AGE RANGE-MEDIAN 25-58 years
Mean 39 years
DISEASE ASSOCIATIONS CHARACTERIZATION Immunocompromised states Organ transplantation
Epidermodysplasia verruciformis associated with neurofibromatosis type 1: coincidental association or model for understanding the underlying mechanism of the disease?
Alpsoy E, Ciftcioglu MA, Keser I, De Villiers EM, Zouboulis CC.
Department of Dermatology, Akdeniz University School of Medicine, 07070 Antalya, Turkey.
Br J Dermatol 2002 Mar;146(3):503-7 Abstract quote
We describe a 25-year-old man with epidermodysplasia verruciformis (EV) associated with neurofibromatosis type 1 (NF1).
The lesions, persisting for more than 15 years, consisted of widespread planar warts on the backs of the hands and wrists, and reddish-brown macules on the trunk, neck and face. During the last 5 years, our patient developed several epithelial tumours, namely solar keratoses, plaques of Bowen's disease and squamous cell carcinomas (SCCs). He also presented with NF1 lesions with neurofibromas, cafe-au-lait macules, axillary freckling and Lisch nodules. He had left tibial bowing.
Polymerase chain reaction analysis of the skin lesions demonstrated the presence of human papillomavirus (HPV) 15 in a flat wart, HPV 20 in a plaque of Bowen's disease, and HPV 15 and HPV 20 in an SCC lesion. Both EV and NF1 show an inherited predisposition to malignancy but the molecular mechanism underlying tumour development is not fully understood.
The appearance of both diseases in our patient may be a coincidental association but may also contribute to the identification of loci for susceptibility to NF1 and EV on chromosome 17.
- 'HPV vulvitis' revisited: frequent and persistent detection of novel epidermodysplasia verruciformis-associated HPV genotypes.
Division of Dermatology and Dermatopathology, Department of Pathology, Albany Medical College, Albany, NY 12208, USA.
- J Cutan Pathol. 2008 Mar;35(3):259-72. Abstract quote
BACKGROUND: 'Human papillomavirus (HPV) vulvitis' is a disputed entity where most studies examining for genital-mucosal (GM) HPV have been negative.
METHODS: Using degenerate and type specific primers for cutaneous (CU), GM and epidermodysplasia verruciformis (EV) HPV types, the prevalence of specific HPV types was investigated in biopsy specimens from 19 women with 'HPV vulvitis', seven with asymptomatic vulvar squamous papillomatosis (ASxVSP), and controls of vulvar fibroepithelial polyps (FEP) (15), vulvar condyloma (10) and normal vulva (NV) (10).
RESULTS: HPV DNA/EV HPV/GM HPV/CU HPV were detected in 84/74/47/5% of vulvitis patients, 78/71/0/28% of ASxVSP, 47/20/20/7% of FEP, 10/10%/0/0 of NV and 100/0/100/10% of condyloma. Fourteen putatively novel HPV genotypes were detected in vulvitis and ASxVSP patients, but not in controls. The two most frequent novel EV HPV, Alb-4 and DL285, were detected in 9/19 (47%) and 5/19 (26%) of vulvitis cases and were persistently identified in serial biopsies. HPV co-infection and Alb-4 infection occurred significantly more frequently in vulvitis patients, particularly those complaining of 'burning' (62/62% vs. 17/7%, p < or = 0.004). Koilocytosis was identified significantly more frequently in vulvitis compared with non-condyloma controls (81% vs. 40%, p = 0.0001), and its presence correlated with detection of HPV DNA (r = 0.3, p = 0.002).
CONCLUSION: The high frequency of novel EV HPV in HPV vulvitis and correlation of clinicopathologic findings with HPV DNA suggests that HPV vulvitis may indeed exist.
PATHOGENESIS CHARACTERIZATION Inherited disorder Autosomal recessive in most cases
Rare cases of X-linked recessive and autosomal dominant transmission
Human papilloma virus Most cass are HPV 5 and 8
Do epidermodysplasia verruciformis human papillomaviruses contribute to malignant and benign epidermal proliferations?
Majewski S, Jablonska S.
Department of Dermatology and Venereology, Warsaw School of Medicine, Koszykowa 82A, 02-008 Warsaw, Poland.
Arch Dermatol 2002 May;138(5):649-54 Abstract quote
The aim of this review is to present new data on epidermodysplasia verruciformis (EV) and EV human papillomaviruses (HPVs), regarded previously as specific to the disease. Recently introduced highly sensitive molecular methods for virologic studies allow detection of EV HPVs in non-EV populations.
In this article, we present the most recent findings on EV and EV HPVs, which shed new light on a possible contribution of EV viruses to malignant and benign epidermal proliferation. We discuss the significance of EV HPV DNA detection in premalignant cutaneous lesions and nonmelanoma skin cancers; however, direct evidence for the causative role of EV HPV is still not available. In psoriasis, a high frequency of EV HPV-5 and other EV HPVs in the skin and the presence of specific HPV-5 antibodies strongly suggest expression of EV HPV proteins in this extensive epidermal proliferation.
Epidermodysplasia verruciformis HPV-5 may also be transiently expressed in epidermal repair processes, whereas in psoriasis there is a continuous epidermal proliferation that could result in persistent viral expression.
A potential contribution of EV HPVs to the pathogenesis of psoriasis is also supported by the recently disclosed co-localization of susceptibility loci for psoriasis and EV in the same region of chromosome arm 17qter; however, specific genes for both conditions are still not identified.
Polymorphisms of the interleukin 10 gene promoter in patients from Brazil with epidermodysplasia verruciformis.
de Oliveira WR, Rady PL, Grady J, Hughes TK, Festa Neto C, Rivitti EA, Tyring SK.
Department of Dermatology, University of Sao Paulo, Brazil.
J Am Acad Dermatol. 2003 Oct;49(4):639-43. Abstract quote
BACKGROUND: Epidermodysplasia verruciformis (EV) is a rare genetic disorder characterized by development of lesions associated with human papillomavirus in early childhood and malignant transformation in approximately half of individuals during adulthood. The persistence of human papillomavirus infection in EV is thought to be a result of an immunogenetic defect, which determines the generation of several cytokines capable of down-regulating cell-mediated immunity.
OBJECTIVE: We sought to study the prevalence of interleukin 10 (IL-10) promoter polymorphisms in skin biopsy specimens of patients with EV compared with DNA samples from healthy individuals.Patients and methods DNA samples extracted from normal skin of 22 patients from Brazil with EV and blood samples from 27 healthy Brazilian individuals were studied for IL-10 promoter polymorphisms using restriction fragment length polymorphism analysis.
RESULTS: The patients with EV showed an increased rate of low-production genotypes of IL-10 compared with control subjects (P =.003). Patients with EV and skin cancer were more likely to have low-production IL-10 genotypes than patients with benign forms of EV.
CONCLUSION: IL-10 genotypes associated with low levels of IL-10 production may have an important role in the pathogenesis of EV, including the susceptibility for development of skin cancer in patients with EV.
HISTOLOGICAL TYPES CHARACTERIZATION General Moderate acanthosis and hyperkeratosis with characteristic enlargement of the keratinocytes with blue-gray pallor, occasional perinuclear halos, and irregular granular zone VARIANTS May have wide variation in histology similar to the spectrum of changes of HPV in the genital tract
The Histologic Spectrum of Epidermodysplasia Verruciformis
Gerard J. Nuovo, M.D.; Mona Ishag, M.D.
From the Department of Pathology, Ohio State University Medical Center, Columbus, Ohio, U.S.A.
Am J Surg Pathol 2000;24:1400-1406 Abstract quote
The classic histologic presentation of epidermodysplasia verruciformis is a verruca plana-type lesion with minimal hyperkeratosis and acanthotic areas where the cells contain perinuclear halos and blue–gray pallor. Whereas these lesions have a high malignant potential, it is important to elucidate the histologic spectrum of this entity and to differentiate it from its mimics.
Fifteen skin biopsies from people with multiple cutaneous warts clinically suspicious for epidermodysplasia verruciformis were analyzed both histologically and for human papillomavirus (HPV) deoxyribonucleic acid (DNA) by in situ hybridization. Ten of the lesions contained HPV DNA, either type 5 (n = 6), type 8 (n = 3), or type 51 (n = 1). Only three of these lesions showed typical verruca plana. The histologic marker of HPV DNA in the other seven viral-positive cases was rare perinuclear halos in association with an irregular granular layer. The other five cases, which were also negative for viral DNA after polymerase chain reaction in situ hybridization, rarely demonstrated the abrupt variation in keratohyaline granules and concomitant perinuclear halos.
The authors conclude that there is a wide spectrum of histologic changes in epidermodysplasia verruciformis and that viral testing in conjunction with the histologic and clinical findings can differentiate this premalignant entity from its mimics.
The histologic spectrum of epidermodysplasia verruciformis in transplant and AIDS patients.
Morrison C, Eliezri Y, Magro C, Nuovo GJ.
Department of Pathology, Ohio State University Medical Center, Center for Dermatologic Surgery, New York, NY, USA.
J Cutan Pathol 2002 Sep;29(8):480-9 Abstract quote
BACKGROUND: The purpose of this study was to correlate the histologic findings of skin lesions clinically suspicious for epidermodysplasia verruciformis with the viral findings in patients with organ transplants or AIDS.
METHODS: Thirty-seven skin biopsies from 17 patients (six with AIDS and 11 with transplants) were studied as a non-randomized, controlled, unblinded case series by in situ hybridization for HPV DNA.
RESULTS: Nineteen (51%) of these biopsies were HPV-positive by in situ hybridization either for HPV type 5 (five cases), type 8 (10 cases), type 16 (four cases) or HPV 31 (one case, with one case of dual infection). Only eight of the 19 HPV-positive tissues (42%) showed the classic histologic features of verruca planae. The more common histologic feature significantly associated with HPV detection was a focally thickened and disrupted granular layer (13/19 [68%] vs. 8/18 [44%], p < 0.04). Dysplasia was evident in 12/19 HPV-positive tissues (63%), which was significantly greater than in patients with congenital epidermodysplasia verruciformis (20%).
CONCLUSIONS: Oncogenic HPV types are detected in about one-half of skin biopsies from immunocompromised patients with a clinical presentation suspicious for epidermodysplasia verruciformis. Many of these lesions lack the histologic features of verruca planae, a focally thickened granular layer is a marker for viral detection, and the risk for dysplasia in such lesions is much higher than in epidermodysplasia verruciformis not associated with acquired immunosuppression.
- J Cutan Pathol. 2007 Jan;34(1):44-8. Abstract quote
Foci of histological changes of epidermodysplasia verruciformis (EV) were noted in five benign skin lesions. These skin lesions included an intradermal nevus, a pigmented seborrheic keratosis, an isolated papule on the forearm, a perianal lesion, and an acantholytic acanthoma. Because the changes resembled true EV so strongly despite the absence of clinical EV in these patients, we searched for EV-human papilloma virus (HPV) types in these skin lesions.
Polymerase chain reaction (PCR) analysis on the formalin-fixed, paraffin-embedded blocks was performed. As a positive control, we included tissue from two HIV-positive patients with clinical EV proven by biopsy. Studies were also performed on five other archived biopsies that did not show changes of EV on multiple tissue sections.
A nested PCR method detected EV-HPV types in three of the five benign skin lesions showing EV changes as well as in the positive controls. EV changes and EV-HPV can be found incidentally on biopsy in the absence of clinical EV; when such changes are the major histopathological finding in an isolated skin lesion, the lesion should be termed an EV acanthoma.
PROGNOSIS AND TREATMENT CHARACTERIZATION PROGNOSIS Squamous cell carcinoma develops in 30-50% of cases TREATMENT
Treatment of epidermodysplasia verruciformis with a combination of acitretin and interferon alfa-2a
Rana Anadolu, MD, etal
J Am Acad Dermatol 2001;45:296-9 Abstract quote
Epidermodysplasia verruciformis (EV) is an autosomal recessive disease characterized by the lifelong eruption of disseminated verrucae-like lesions. Numerous treatment modalities have been used to treat EV without benefit. Recently, retinoid and interferon therapies have been found to be of value in the treatment of EV. We present a case of EV that was treated with a combination of acitretin and interferon alfa-2a.
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Last Updated March 12, 2008
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