Detection of Merkel cell polyomavirus DNA in atypical fibroxanthoma in correlation to clinical features.

A clear etiopathogenetic concept for atypical fibroxanthoma (AFX) is not established yet. Nevertheless, AFX is known as a pleomorphic but indolent tumor primarily of the elderly and/or immunosuppressed patient occurring in severely sun- or radiation-damaged skin. These risk factors are almost identical to those of Merkel cell carcinoma (MCC), a highly malignant skin tumor being thought to be pathogenetically associated with the recently discovered Merkel cell polyomavirus (MCPyV). Because AFX and MCC share risk factors, the aim of this study was to evaluate presence of MCPyV DNA in 23 cases of AFX by PCR and direct DNA sequencing. Subsequently, we correlated clinical features with MCPyV DNA status in AFX. We detected MCPyV DNA in 4 of 23 AFX. All patients with MCPyV DNA-positive tumors were men. The mean age of patients with MCPyV DNA-positive AFX was 84.8 ± 8.7 years (vs. 75.2 ± 7.8 years of MCPyV DNA-negative AFX), the mean duration of tumor growth was 4.5 ± 2.3 months (vs. 5.1 ± 2.8 months) and the mean tumor diameter was 1.2 ± 0.3 cm (vs. 1.3 ± 0.7 cm). Ulceration was present in 75% of MCPyV DNA-positive tumors (vs. 65.2%). In conclusion, MCPyV DNA is present in 17% of AFX, in this cohort affecting predominantly male patients with higher age (>80 years). Clinical features seem to be independent of MCPyV DNA status. Although the role of MCPyV is unclear in this setting, it may act as a cofactor in the tumorigenesis of AFX in a subset of cases.

Follicular localization of dendritic cells in a xanthomatous inflammatory tumor of lung associated with human herpes virus-8 infection.

A 17-year-old man was treated with chemotherapy and radiation for nodular sclerosing Hodgkin lymphoma that presented as a left chest wall mass. Ten years later, a left upper lobe lung tumor was identified. The tumor resection demonstrated a 1.3-cm yellow lung nodule composed of epithelioid and spindled lipid-laden CD68+ and Factor XIIIa+ macrophages. Distinct follicular structures with dendritic cells positive for CD1a, fascin, and ALK-1 and largely devoid of intracytoplasmic lipid were a distinguishing feature of the lesion. Most of the xanthomatous macrophages expressed human herpes virus-8 antigen. The current World Health Organization classification of "inflammatory myofibroblastic tumors" is examined, and the association of a subset of "inflammatory pseudotumors" with immunodeficiency states and opportunistic infection is discussed.

A giant verruciform xanthoma.

BACKGROUND: Verruciform xanthoma (VX) is a rare, benign neoplasm arising predominantly in the oral cavity, but it has been reported to occur on the genital skin and mucosa as well. VX has also been described in association with epidermal nevi and squamous cell carcinoma. Because of the clinical and histologic similarities between VX and condyloma acuminata, and a recent report of HPV 6 in association with VX, we investigated the role of human papilloma virus (HPV) in the development of this entity. METHODS: In situ hybridization and a nested PCR approach utilizing degenerate primers were utilized to establish whether HPV infection could be playing a role in the development of the VX. RESULTS: In situ hybridization failed to identify HPV DNA. The highly sensitive nested PCR approach also failed to detect HPV DNA. CONCLUSIONS: The failure to detect HPV DNA, even by very sensitive methods, provides strong evidence that our case of VX is not an HPV-induced lesion. A review of other possible etiologies, including alternative infectious agents and genetic associations, are discussed.

Association of human papillomavirus type 6 with a verruciform xanthoma.

We report a case of verruciform xanthoma (VX) associated with human papillomavirus (HPV) in a 67-year-old male. The patient had a pale-reddish, granular and verrucous tumor on the right side of his scrotum for four years. Histopathologic examination showed typical features of VX. HPV was detected by immunohistochemistry, electron microscopy, and PCR examinations. Ultrastructural examination revealed virus-like particles of 40-50 nm in the nucleus of the upper epidermal keratinocytes. HPV type 6a DNA was detected in lesional tissue by polymerase chain reaction and sequence analysis. To the best of our knowledge, this is the first case report of VX associated with HPV.

Cutaneous verruciform xanthoma: a report of five cases investigating the etiology and nature of xanthomatous cells.

Verruciform xanthoma is a rare clinicopathologic entity of uncertain etiology that occurs primarily in the oral mucosa. Aggregates of foam cells in the submucosal stroma or papillary dermis in association with verrucous epithelial hyperplasia are the hallmark of this lesion. Extraoral (cutaneous) occurrence of verruciform xanthoma is much rarer and has been reported mostly in the genital skin. Five cases of extraoral cutaneous verruciform xanthoma (three from the scrotum, one from the penis, and one from the nose) and one histologic "simulant" (from skin of the nose) were studied. The lesions were solitary, raised, or polypoid with cup-shaped craters filled with parakeratotic cells that blended into keratinocytes of an acanthotic and papillomatous epidermis. There was a neutrophilic infiltrate of varying intensity between plump parakeratotic cells and keratinocytes, near the surface of the epidermis. Aggregates of foam cells were present in the papillary dermis, which was highly vascular. A plasma cell predominant infiltrate was seen at the base in a bandlike fashion. Despite the architectural resemblance of verruciform xanthoma to verrucous mucocutaneous lesions related to human papillomavirus infection, it was not detected by either immunohistochemistry, in situ hybridization, polymerase chain reaction, or Southern blot analysis in any case. The foam cells were weakly positive for cytokeratin and for Factor XIIIa but negative for S-100 protein. The KP1 and Mac 387 immunostain showed focal weak staining in foam cells. We postulate that a cascade of events pursue after initial keratinocytic damage attracting neutrophils, with subsequent phagocytosis of necrotic keratinocytic debris by dermal dendrocytes, eventually leading to the ultimate manifestation of the lesion as verruciform xanthoma. The etiologic agent remains elusive, but based on our findings, we conclude that verruciform xanthoma is most likely not a human papillomavirus-associated squamoproliferative lesion and that the foam cells, a histologic hallmark of the lesion, are most likely derived from dermal dendritic cells.

Characterization of verruciform xanthoma by in situ hybridization and immunohistochemistry.

Verruciform xanthoma (VX) is a rare, benign lesion, mainly found in the oral mucosa. Histologically and ultrastructurally, the lesion is characteristic and well defined. However, the etiology of the lesion remains unclear. The purpose of the present study was to elaborate upon the pathogenesis of VX by evaluation of an additional series of oral examples for human papillomaviruses (HPV), using immunohistochemistry and in situ hybridization, and to further characterize the cellular components of VX immunohistochemically. Twelve specimens diagnosed as VX were retrospectively collected. One of the twelve specimens was positive for HPV types 6/11 by in situ hybridization. None of the twelve specimens demonstrated the presence of HPV antigen by immunohistochemistry. By immunohistochemical studies, the predominant cells in the inflammatory infiltrate were T cells. The foam cells were of monocyte/macrophage lineage. S-100-positive (Langerhans) cells were occasionally found in the suprabasal layer of the epithelium. HLA-DR-positive keratinocytes were noted at the intense inflammatory sites. Taken together, these findings suggest that an immune response may play a role, at least in part, in VX pathogenesis.

Verruciform xanthoma: an immunocytochemical study.

Verruciform xanthoma is a rare lesion that occurs predominantly on the oral mucosae, but also on other mucosal sites and on the skin. We report an immunocytochemical analysis of the xanthoma cells in three cases of verruciform xanthoma (two vulval and one scrotal), and also attempt to identify human papilloma virus (HPV) as a possible trigger for the production of these lesions. We employed a panel of seven histiocytic markers (CD68 [KP1], KiM1P, HAM 56, lysozyme, vimentin, peanut agglutinin and factor X111a) and two others to identify HPV involvement (CAMVIR-1 and bovine papilloma virus-1 [BPV-1]). Results showed the xanthoma cells to be positive for CD68, KiM1P, HAM 56 and vimentin, with less consistent labelling for peanut agglutinin and lysozyme. CAMVIR-1 and BPV-1 were negative in all three cases. These findings support the view that the xanthoma cells are derived from a monocyte macrophage lineage and fail to demonstrate HPV as the cause.