Polyomavirus-induced pilomatricomas in mice: from viral inoculation to tumour development.

Polyomavirus has been used extensively to study tumour induction in mice. Although most neoplasms are well characterized, those arising from hair follicles have been referred to by different names during the last four decades. The purpose of this research was to contribute to a more accurate histological characterization of these tumours as well as to study the viral progression from the onset of infection to the development of neoplasms. Polyomavirus A2 was inoculated into newborn C3H/BiDa mice, and at different time-points (from 5 to 70 days post-inoculation) the mice were sacrificed and studied using histological, immunocytochemical, ultrastructural and virological methods. The fully developed hair follicle tumours consisted of a proliferation of matrix cells that evolved into 'shadow' cells with empty nuclei and finally into amorphous keratin; the tumours were therefore diagnosed as pilomatricomas. Viral VP-1 was observed only in fully differentiated cells and not in proliferating-cell-nuclear-antigen (PCNA)-positive cells in the same tumour. In conclusion, Polyomavirus first replicated in the skin, and then disseminated through the blood and reached the outer sheath of the hair follicles and finally infected matrix cells, leading to the development of pilomatricomas from which infectious virus was isolated.

Detection of polyomavirus major capsid antigen (VP-1) in human pilomatricomas.

The family Polyomaviridae is composed of small, non-enveloped, double-stranded DNA viruses widely used to study cell transformation in vitro and tumor induction in vivo. The development of pilomatricomas in mice experimentally infected with polyomavirus led us to detect the viral major capsid protein VP-1 in human pilomatricomas. This tumor, even uncommon, is one of the most frequent benign hair follicle tumors in humans and is composed of proliferating matrix cells that undergo keratinization, and form cystic neoplasms. The detection of VP-1 was performed using the peroxidase-antiperoxidase technique in paraffin-embedded slides with a specific primary serum. Adjacent slides treated with normal rabbit serum as a primary were employed as internal control. Positive and negative controls were also employed as well as slides of lesions caused by human papillomavirus to rule out any unspecific cross-reactivity. In 4 out of 10 cases polyomavirus VP-1 was clearly detected in nuclei of human pilomatricomas proliferating cells, in a patchy pattern of distribution. The controls confirmed the specificity of the immunocytochemical procedure. These results could indicate either an eventual infection of the virus in already developed tumors or alternatively, a direct involvement of polyomavirus in the pathogenesis of some pilomatricomas. The recent discovery of a new human polyomavirus associated with Merkel cell carcinomas has been a strong contribution to better understand the pathogenesis of some human uncommon skin cancers. Hopefully the results reported in this work will encourage further research on the role of polyomavirus in other human skin neoplasms.