Investigation of Histologic Correlates of Human Papillomavirus Infection in Penile Lesions Equivocal for Condyloma
UP Le, A Matthews, D Cook, L Greene, MF Evans, CSC Adamson, V Rajendran, Z Peng, T Ashikaga, K Cooper. University of Vermont and Fletcher Allen Health Care, Burlington
Background: Human papillomavirus (HPV) is considered the most common sexually transmitted disease in the developed world. Histologic distinction between condyloma acuminatum (CA) and seborrheic keratosis (SK) on penile skin is challenging when definitive viral-induced cytopathic changes are not present. Difficulty in classifying penile lesions equivocal for CA relates to lack of clear histologic criteria distinguishing warts from SK.
Design: SNOMED search through CoPath was used to identify penile specimens evaluated at FAHC between 1989-2006 with the following diagnoses: verruca vulgaris, CA, SK, or squamous papilloma. Each case was reviewed by three pathologists who assessed the following histologic features: architecture, character of stratum corneum and granular layer, and presence of immature parakeratosis (PK), coarse granules, koilocytes, dyskeratosis, melanin, horn pseudocysts, and inflammation. PCR was used to detect HPV in formalin-fixed, paraffin-embedded tissue blocks. PCR results were used to correlate viral presence with assessed histologic parameters.
Results: Out of 77 cases, there were 55 (71%) low risk HPV (LRHPV), 19 (25%) high risk HPV (HRHPV), and 3 (4%) negative for HPV by PCR. Histologic features most often seen in LRHPV lesions included rounded papillomatosis (62%), compact orthokeratosis (OK) with focal PK (44%), mild inflammation (64%), normal granular layer thickness (44%) with no evidence of coarse granules (64%), immature PK (73%), koilocytes (73%), increase in melanin (55%), and horn pseudocysts (58%). HRHPV lesions demonstrated generally similar histology but tended to show a slight preference for flat acanthosis (47%), OK (47%), and increased melanin along the basal layer (37%). Our predictions of viral presence based on histology revealed no false positives but did show 64% and 68% of false negative cases for LR and HRHPV, respectively.
Conclusions: The presence of koilocytes is a feature pathologists rely heavily upon in making a diagnosis of CA. The majority of our cases, morphologically equivocal for CA, were found to possess either LR or HRHPV by PCR. The standard morphologic criteria (given the present PCR data) are not predictive of HPV associated changes. It still remains a question whether HPV is a driver or mere passenger in the appearance of these penile lesions and expansion of this study using in situ hybridization and immunohistochemical stains to correlate with PCR data is ongoing.
Wednesday, March 24, 2010 1:00 PM
Poster Session VI # 92, Wednesday Afternoon