eMedicine Specialties > Dermatology > Viral Infections

Epidermodysplasia Verruciformis: Differential Diagnoses & Workup

Author: Grace F Kao, MD, Clinical Professor of Dermatopathology, Department of Dermatology, George Washington University Medical School; Director of Dermatopathology, Department of Pathology and Laboratory Medicine, Veterans Affairs Maryland Healthcare System
Contributor Information and Disclosures

Updated: Nov 13, 2007

Differential Diagnoses

Squamous Cell Carcinoma
Tinea Versicolor
Warts, Nongenital

Other Problems to Be Considered

Benign papillomas
Verruca plana

Workup

Laboratory Studies

  • HPVs can be detected by in situ hybridization using anti-HPV antibodies on formalin-fixed skin tissue specimens. Unfortunately, this viral typing is not readily available on a commercial basis. Typing can also be performed by polymerase chain reaction on fresh or frozen tissue specimens.
  • Defective cell-mediated immunity can be detected by the following studies:
    • Keratinocytes isolated from the premalignant lesions of patients with EV found to harbor HPV type 5 genomes show inhibition to natural cell-mediated cytotoxicity by normal peripheral blood mononuclear cells, whereas normal keratinocytes do not.
    • Patients with mixed HPV and HPV type 3 infection may demonstrate cutaneous anergy to locally applied contact sensitizers, such as dinitrochlorobenzene.
    • A normal number of antigen-presenting Langerhans cells are found in patients with EV. However, the possibility of a genetically determined defective function of these cells, leading to abnormal presentation and recognition of HPV antigens, has been considered.

Histologic Findings

Biopsy is performed for early detection of premalignant and malignant lesions and for the identification of EV-associated HPVs. The most characteristic findings are within the epidermis. The classic histologic manifestation of EV is a verruca plana–like lesion with mild hyperkeratosis and acanthosis, in which the keratinocytes contain perinuclear halos and blue-gray pallor. Perinuclear halos are a specific cytopathic effect, that is, the presence of clear cells in the granular and spinous layers with occasional enlarged, hyperchromatic, atypical nuclei, is present (see Media File 2 [left image]).

The nucleoplasm is clear, and keratohyalin granules of various sizes and shapes are present. The keratin layer is loose with a basket weave–like appearance. In premalignant tumors, the normal keratinocyte maturation is preserved. In contrast, in the malignant lesions, the normal surface maturation of keratinocytes is lost. HPV can be detected in the infected keratinocyte nuclei by in situ hybridization, particularly in the upper layers of the epidermis (see Media File 2 [right image]).

The premalignant lesions display features similar to actinic keratoses with prominent atypical, dyskeratotic cells. The cytopathic effects of viral warts are often missing, although large amounts of HPV DNA can be detected as is shown by using immunostains on a skin lesion (see Media File 3).

Invasive malignant tumors most commonly show squamous and occasionally adnexal differentiation. A well-differentiated squamous cell carcinoma seen in an EV-associated skin cancer is shown in Media File 4.

More on Epidermodysplasia Verruciformis

Overview: Epidermodysplasia Verruciformis
Differential Diagnoses & Workup: Epidermodysplasia Verruciformis
Treatment & Medication: Epidermodysplasia Verruciformis
Follow-up: Epidermodysplasia Verruciformis
Multimedia: Epidermodysplasia Verruciformis
References
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References

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Further Reading

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Keywords

EV, human papillomavirus, human papillomavirus infection, HPV, HPV infection, squamous cell carcinoma

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Contributor Information and Disclosures

Author

Grace F Kao, MD, Clinical Professor of Dermatopathology, Department of Dermatology, George Washington University Medical School; Director of Dermatopathology, Department of Pathology and Laboratory Medicine, Veterans Affairs Maryland Healthcare System
Grace F Kao, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, and International Society of Dermatopathology
Disclosure: Nothing to disclose.

Medical Editor

Kathryn Schwarzenberger, MD, Associate Professor of Medicine, Division of Dermatology, University of Vermont College of Medicine; Consulting Staff, Division of Dermatology, Fletcher Allen Health Care
Kathryn Schwarzenberger, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Contact Dermatitis Society, American Dermatological Association, Dermatology Foundation, Medical Dermatology Society, and Women's Dermatologic Society
Disclosure: Nothing to disclose.

Pharmacy Editor

Michael J Wells, MD, Associate Professor, Department of Dermatology, Texas Tech University Health Sciences Center
Michael J Wells, MD is a member of the following medical societies: Alpha Omega Alpha, American Academy of Dermatology, American Medical Association, and Texas Medical Association
Disclosure: Nothing to disclose.

Managing Editor

Lester F Libow, MD, Dermatopathologist, South Texas Dermatopathology Laboratory
Lester F Libow, MD is a member of the following medical societies: American Academy of Dermatology, American Society of Dermatopathology, European Academy of Dermatology and Venereology, International Society of Dermatology, Massachusetts Medical Society, New York Academy of Sciences, Phi Beta Kappa, Society for Investigative Dermatology, and Texas Medical Association
Disclosure: Nothing to disclose.

CME Editor

Joel M Gelfand, MD, MSCE, Medical Director, Clinical Studies Unit, Assistant Professor, Department of Dermatology, Associate Scholar, Center for Clinical Epidemiology and Biostatistics, University of Pennsylvania
Joel M Gelfand, MD, MSCE is a member of the following medical societies: Society for Investigative Dermatology
Disclosure: Nothing to disclose.

Chief Editor

Dirk M Elston, MD, Director, Department of Dermatology, Geisinger Medical Center
Dirk M Elston, MD is a member of the following medical societies: American Academy of Dermatology
Disclosure: Nothing to disclose.

 
 
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