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 Table of Contents  
CASE REPORT
Year : 2016  |  Volume : 19  |  Issue : 1  |  Page : 68-70

Squamous cell carcinoma in a patient with epidermodysplasia verruciformis


1 Department of Medicine, Nnamdi Azikiwe University, Nnewi, Anambra State, Nigeria
2 Department of Medicine, Nnamdi Azikiwe University Teaching Hospital, Nnewi, Anambra State, Nigeria

Date of Web Publication17-Dec-2015

Correspondence Address:
Ogochukwu Ifeanyi Ezejiofor
Department of Medicine, Nnamdi Azikiwe University, Nnewi Campus, Nnewi, Anambra State
Nigeria
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DOI: 10.4103/1119-0388.172072

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  Abstract 

Epidermodysplasia verruciformis (EV) is a rare autosomal recessive disease, characterized by early onset and lifelong occurrence of multiple flat warts. Infections with various serotypes of human papillomavirus (HPV) have been implicated. Defects in cell-mediated immunity have also been implicated in causing persistent viral infections and with continual exposure of such lesions to ultraviolet light transforms them to squamous cell carcinoma. This case report exemplifies such an association and advocates the need for early sun protective measures in individuals who suffer this disorder to prevent malignant transformation.

Keywords: Epidermodysplasia verruciformis, human papillomavirus, squamous cell carcinoma


How to cite this article:
Ezejiofor OI, Ozoh GA. Squamous cell carcinoma in a patient with epidermodysplasia verruciformis. Trop J Med Res 2016;19:68-70

How to cite this URL:
Ezejiofor OI, Ozoh GA. Squamous cell carcinoma in a patient with epidermodysplasia verruciformis. Trop J Med Res [serial online] 2016 [cited 2019 Sep 15];19:68-70. Available from: http://www.tjmrjournal.org/text.asp?2016/19/1/68/172072


  Introduction Top


Epidermodysplasia verruciformis (EV) is a rare autosomal recessive disease, characterized by early onset and lifelong occurrence of multiple flat warts, pityriasis-like macular lesions, and skin cancer in sun-exposed areas. There is a predisposition to widespread human papillomavirus (HPV) infection and development of cutaneous squamous cell carcinoma.[1],[2] Other modes of inheritance exist for this rare disorder such as sporadic, sex-linked, and autosomal dominant modes. Malignant tumors, especially squamous cell carcinoma, develop in up to 30-60% of these patients who are aged 20-40 years in the sun-exposed areas. This malignant transformation is, however, common in people with skin types 1 and 2 and less common in Africans, suggesting a protective effect of skin pigmentation.


  Case Report Top


A 25-year-old male, a student of a higher institution, presented to the dermatology outpatient clinic with complaint of hypopigmented scaly patches and some plaques on his forehead that were initially noticed by his mother about 23 years ago, at the age of 2 years. Since the onset, these patches have been progressively extending to involve the whole of his face, neck, upper extremities, trunk, and even his lower extremities to an extent [Figure 1], [Figure 2], [Figure 3]. They were neither itchy nor painful, and no other family member or contacts had similar lesions. He had presented to different health facilities where some medications were given, but to no avail. About 1 year ago, the lesion on the forehead developed a painless ulceration, prompting his presentation to our clinic for further evaluation. We made an assessment of EV with squamous cell transformation and proceeded to take an incisional biopsy from a nonulcerated lesion and an excisional biopsy of the ulcerated one.
Figure 1: Hypopigmented patches and plaques involving the scalp, face, and neck

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Figure 2: An ulcerated forehead lesion with biopsy-confirmed squamous cell carcinoma

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Figure 3: Similar hypopigmented patches and plaques on the neck and chest wall

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The histology report of the nonulcerated lesion showed an epidermal lesion, characterized by low-spike papillomatosis, hyperkeratosis, parakeratosis, slight acanthosis, prominent keratohyalin granules, and clusters of keratinocytes that were swollen, irregularly shaped, and with abundant slightly basophilic cytoplasms. Some of the keratinocytes exhibited pyknotic nuclei while some exhibited empty nuclei. No malignancy was seen, and the overall features were those of EV. The summary of the excisional biopsy report was that of moderately differentiated invasive squamous cell carcinoma.


  Discussion Top


Patients with EV are usually infected with multiple types of HPV. The condition presents in childhood and continues throughout life. Skin lesions include flat wart-like lesions of the dorsal hands, the extremities, the face, and the neck. These are flatter than typical flat warts, and may be quite abundant and confluent.

Over 30 different types of EV-HPV have been identified. These include HPV types 4, 5a, 5b, 8, 9, 12, 14, 15, 17, 19-25, 36-38, 47, and 50. However, HPV-5, HPV-8, and HPV-47 are found in more than 90% of patients, which transform into squamous cell carcinoma. The predisposition to infection by all these HPV types have been linked to a defective cell-mediated immunity, with mutations in EVER 1 and EVER 2 genes located in the chromosome 17q25.[3],[4] EVER 1 and EVER 2 genes have been hypothesized to either control HPV infection or play a role in the immune response to infection; however, approximately 25% of patients with EV lack EVER 1 and EVER 2 mutation and the abnormality in this category of patients is yet to be defined. Azzimonti et al.[5] reported a profound cluster of differentiation 8 (CD8+) T cell lymphopenia in a patient with clinical diagnosis of EV who lacked EVER 1 and EVER 2 mutation.

The mechanism involved in the malignant transformation in EV is not clear, but viral DNA has been identified in an EV-induced malignancy, suggesting a link between the virus and the transformation. Carcinogenic cofactors such as ultraviolet B and x-rays are probably important. This is likely so because squamous cell cancers are seen in areas exposed to sunlight and have also been noted in HPV-associated nasal papillomas. Also, the very high oncogenic strains of HPV such as 5, 8, and 47 selectively express the E6 and E7 portions of the viral genome, which code major oncoproteins responsible for the oncogenic potential of HPV. These E6/E7 regions cause cell immortalization or failure of programed cell death, resulting in transformation of the normal human keratinocytes into malignant cells.[6] The patients with EV and malignancy also have low production of interleukin-10 genotypes than those without malignancy.[7] Both E6 and E7 promote cell growth through many factors, one being neutralizing antioncogenic products such as tumor protein p53 (p53) and retinoblastoma protein (pRb), which are important for intracellular defense against neoplasm.

In EV, there is also an inability of programed cell death elimination of damaged DNA, and this is very important in malignant transformation. Therefore, in patients with EV, a decrease in the repair of UV-damaged DNA with oncogenic viral infection is important in the susceptibility to somatic mutation and malignant mutation.[8],[9],[10],[11]

Apart from surgical intervention for skin cancer, treatment for EV is largely preventive. Strict sun avoidance and protection with appropriate clothing and sunscreen should be started as soon as the disease is diagnosed to prevent malignancy in patients of all skin types.


  Conclusion Top


EV is a rare disorder, characterized by sustained infection with various strains of HPV. Defective cell-mediated immunity is implicated as the likely culprit, and transformation to squamous cell carcinoma can occur following unrestrained exposure to ultraviolet light.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Androphy EJ, Dvoretzy I, Lowy DR. X-linked inheritance of epidermodysplasia verruciformis. Genetic and virologic studies of a kindred. Arch Dermatol 1985;121:864-8.  Back to cited text no. 1
    
2.
Gober MD, Rady PL, He Q, Tucker SB, Tyring SK, Gaspari AA. Novel homozygous frameshift mutation of EVER 1 gene in an epidermodysplasia verruciformis patient. J Invest Dermatol 2007;127:817-20.  Back to cited text no. 2
    
3.
Toyoda H, Ido M, Nakanishi K, Nakano T, Kamiya H, Matsumine A, et al. Multiple cutaneous squamous cell carcinoma in a patient with interferon gamma receptor 2 (IFN gamma R2) deficiency. J Med Genet 2010;47:631-4.  Back to cited text no. 3
    
4.
Sun XK, Chen JF, Xu AE. A homozygous nonsense mutation in the EVER 2 gene leads to epidermodysplasia verruciformis. Clin Exp Dermatol 2005;30:573-4.  Back to cited text no. 4
    
5.
Azzimonti B, Mondini M, De Andrea M, Gioia D, Dianzani U, Mesturini R, et al. CD8+ T-cell lymphocytopeania and lack of EVER mutations in a patient with clinically and virologically typical epidermodysplasia verruciformis. Arch Dermatol 2005;141:1323-5.  Back to cited text no. 5
[PUBMED]    
6.
Kao G. Cutaneous carcinogenesis: Etiologic factors-viruses. In: Miller S, Mahoney M, editors. Cutaneous Oncology: Pathophysiology, Diagnosis, and Treatment. London, England: Blackwell Science; 1997. p. 148-57.  Back to cited text no. 6
    
7.
de Oliveira WR, Rady PL, Grady J, Hughes TK, Festa Neto C, Rivitti EA, et al. Polymorphism of interleukin 10 gene promoter in patients from Brazil with epidermodysplasia verruciformis. J Am Acad Dermatol 2003;49:639-43.  Back to cited text no. 7
    
8.
Vu J, Wallace GR, Singh R, Diwan H, Prieto V, Rady P, et al. Common Variable immunodeficiency syndrome associated with epidermodysplasia verruciformis. Am J Clin Dermatol 2007;8:307-10.  Back to cited text no. 8
    
9.
Morrison C, Eliezri Y, Magro C, Nuovo GJ. The histologic spectrum of epidermodyspasia verruciformis in transplant and AIDS patients. J Cutan Pathol 2002;29:480-9.  Back to cited text no. 9
    
10.
Berthelot C, Dickerson MC, Rady P, He Q, Niroomand F, Tyring SK, et al. Treatment of a patient with epidermodysplasia verruciformis carrying a novel EVER 2 mutation with imiquimod. J Am Acad Dermatol 2007;56:882-6.  Back to cited text no. 10
    
11.
Kunishige JH, Hymes SR, Madkan V, Wyatt AJ, Uptmore D, Lazar AJ, et al. Epidermodysplasia verruciformis in the setting of graft-versus-host disease. J Am Acad Dermatol 2007;57 Suppl:S78-80.  Back to cited text no. 11
    


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  [Figure 1], [Figure 2], [Figure 3]



 

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