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The association of syringocystadenoma papilliferum (SCAP) with verrucous carcinoma (VC) of the skin in the same lesion is a rare, but well-documented event. Although human papillomaviruses (HPV) have been proposed to have an etiologic role in the development of the verrucous proliferations associated with SCAP, most of the immunohistochemical and molecular studies have failed to show the presence of their genomic material in these lesions. We report a series of four cases of SCAP associated with VC in anogenital lesions. In two of the cases, we demonstrated the presence of the BRAF V600E mutation by polymerase chain reaction and immunohistochemistry, both in the glandular and in the squamous component. No HPV-related histopathologic changes were found, nor could the presence of viral DNA be showed.

Background Carcinoma cuniculatum and verrucous carcinoma are both very well differentiated forms of squamous carcinoma and thus difficult to separate histologically from pseudocarcinomatous hyperplasia. The diagnosis of each often requires clinical-pathologic correlation. Methods We reviewed the literature on cases reported as carcinoma cuniculatum and compared these to the cases originally reported by Aird et al. In addition, we report an additional case of this entity that we encountered in our practice. Results In reviewing the literature it is evident that most authors consider carcinoma cuniculatum and verrucous carcinoma to be synonymous even though Aird's original two cases had no verrucous features. The lack of a clear conceptual distinction between these two entities may cause diagnostic confusion. Conclusion The purpose of this report is to record a case of carcinoma cuniculatum which the authors believe to be similar to those reported by Aird et al., to emphasize the differences between carcinoma cuniculatum and verrucous carcinoma, and to explain how the lack of a clear conceptual distinction between these two tumors can lead to further delay in an already difficult diagnosis.

Background: Verrucous carcinoma, a variant of squamous cell carcinoma, is distinct from squamous cell carcinoma in morphology and behavior. It preferentially occurs on the oropharyngeal mucosa, the urogenital mucosa, and the soles. In contrast to its malignant clinical picture, the tumor grows locally invasive but is histologically benign and metastasizes rarely. Methods: We report the uncommon occurrence of a large verrucous carcinoma on apparently uninvolved skin in the right axilla in a 47-year-old male. Results: Histologic examination reveals a cauliflower-like tumor consisting of deep invaginated epidermal proliferation with rabbit burrow-like, keratin-filled sinus formations; the basement membrane, however, remains intact. Immunohistology showed positivity for pancytokeratin (KL-1) and cytokeratin (CK) 18 and negativity for CK7, and assessment of the proliferative activity of the tumor cells revealed low percentage of Ki-67 expression. Furthermore, there were only scattered cells expressing p53 or bcl-2. Polymerase chain reaction excluded the presence of human papillomavirus. After complete excision, no signs of recurrence occurred over a follow-up period of three years. Conclusion: Verrucous carcinoma should be distinguished from typical squamous cell carcinoma. The clinicopathological features, differential diagnosis, and therapy are discussed here together with the molecular biologic aspects of the tumor.

Moesin, one of the ERM (ezrin; radixin; moesin) family members, is directly associated with the cytoplasmic domain of CD44, which is now thought to be related to the metastatic potential of tumor cells. Using immunohistochemistry we investigated the expression of moesin in normal epidermis and various kinds of epithelial skin tumors: squamous cell carcinoma, verrucous carcinoma, Bowen's disease, solar keratosis, keratoacanthoma, basal cell carcinoma, and extramammary Paget's disease. Normal skin showed positive epidermal staining for moesin with the exception of the stratum corneum. The expression of moesin varied with the type of skin tumor. In basal cell carcinoma, Bowen's disease, and extramammary Paget's disease, moesin expression was either faint or negative. In contrast to Bowen's disease, invasive squamous cell carcinoma showed more intense and heterogeneous staining of the cytoplasm and the cell membrane. Verrucous carcinoma was weakly positive, with a tendency for the moesin to be distributed in the cell membrane. The staining pattern of moesin varied among the different kinds of epithelial skin tumors, and its expression was generally similar to that of the standard form of CD44. These results suggest that moesin is closely inter-related with CD44 in epithelial skin cells as seen in other cellular systems, and that the variable pattern of moesin staining among the skin tumor cells could reflect expression disorders associated with the transformation.

Anogenital squamous cell carcinoma has been noted with increased frequency in HIV-seropositive patients. Verrucous carcinoma is a variant of squamous cell carcinoma that tends to be locally invasive and non-metastasizing. Although human papillomavirus (HPV) has been strongly implicated in other squamous neoplasms, it has been variably associated with verrucous carcinoma and has not been examined in these lesions in the HIV-positive population. The aim of this study was to examine the association of HPV with anal verrucous carcinoma in patients with the human immunodeficiency virus (HIV). HPV DNA in situ hybridization for HPV Types 6/11, 16/18, and 31/33/35 was performed on formalin-fixed, paraffin-embedded tissue from six cases of verrucous carcinoma and four cases of condyloma acuminatum in perianal specimens from HIV-seropositive patients. HPV DNA sequences were identified in five of six cases of verrucous carcinoma and in all cases of condyloma acuminatum. Of the five verrucous carcinomas that harbored detectable HPV DNA, four contained HPV 6/11 and two contained HPV 16/18. One contained both HPV 6/11 and HPV 16/18. All four cases of condyloma acuminatum were positive for HPV 6/11. One patient included in this series had three chronologically separate verrucous carcinomas. The initial lesion was negative for HPV DNA. Subsequent verrucous carcinomas were positive for HPV type 6/11 and type 16/18, respectively. The data presented support the concept that verrucous carcinoma in the HIV-seropositive population is associated with HPV, which may indeed play an important role in its pathogenesis.

An 85-year-old woman developed a tumor on her left thigh, thought to be a squamous cell carcinoma (SCC). Microscopy revealed irregularly shaped, bulbous and deep aggregates of pale/clear cells emanating from the surface and reaching the lowermost dermis. This asymmetric mass of keratinocytes showed focal necrosis and dyskeratosis but no frank anaplasia, mitoses or infiltrative pattern. The interface with the dermis was blunt but irregularly undersurfaced. A more characteristic pale cell acanthoma (PCA) was colliding with it and consisted of a superficial, more regularly psoriasiform proliferation with thin suprapapillary plates and erosion but no necrosis. While it has been known that PCA can be unusual polypoid, large or atypical no author has proposed that some of the latter variants could represent a malignancy, more akin to verrucous carcinoma than to conventional SCC, due to the paucity of overt anaplastic features and the underestimation of pushing invasion and low cytologic atypia as defining traits of malignancy. One case of SCC in situ with PCA has been recently acknowledged but this is not what we are reporting: We propose that voluminous, misshapen, asymmetric or deep “PCAs” may be low-grade carcinomas with pale cell differentiation and likely origin in a pre-existing PCA.

We report the case of a 67-year-old man with a granular, cauliflower-pink lesion on the skin of the thigh. Histopathological study showed a typical verrucous carcinoma associated with a syringadenoma papilliferum. To our knowledge this association has not been previously reported.

Five different cases of verrucous proliferative lesions of skin are described and discussed. One of each developed in a chronic ulcer on a heel, in a scar on a lower leg, and on the penis, and two appeared in the region of the buttock in relation to chronic inflammatory sinuses. All these lesions showed morphological and clinical features of verrucous carcinoma which are described. It has been concluded that the variously named verrucous lesions in the literature (epithelioma cuniculatum, florid papillomatosis, giant cutaneous papilloma and papillomatosis cutis carcinoides), as well as our five cases represent a verrucous carcinoma which is a particular type of squamous cell carcinoma. This tumor develops typically in moist areas which are frequently sites of chronic inflammation. Despite the favorable prognosis, it is a potentially invasive tumor.