Carcinoma cuniculatum in course of etanercept: blocking autoimmunity but propagation of carcinogenesis?

Carcinoma cuniculatum (CC) or verrucous squamous cell carcinoma is a rare variant of squamous cell carcinoma with low incidence of metastasis. It mainly affects men during the fifth-sixth decade of life, arising mostly on the weight-bearing surface of the foot, but it can also be found in other body areas. The favorable effects on the psoriatic, rheumatoid, juvenile polyarthritis as well as the ankylosing spondylitis after the application of Tumour Necrosis Factor (TNF)-alpha inhibitors, like etanercept, presume the availability of similarity between the etiopathogenetic mechanisms which are responsible for the generation of the inflammatory cascade. According to the latest studies, the sensitivity of the patients to TNF-alpha inhibitors could be genetically determined and may also be due to certain genetic polymorphisms of the NLP3 and CARD8 zones of the inflammasome. The blocking of the inflammatory reaction within the borderlines of the psoriatic arthritis could also be accepted as something of a double edged sword. There is a growing volume of literary data which informs us of the clinical manifestation, not only of skin, but also of other types of tumors after the application of TNF-alpha inhibitors. This inevitably generates the hypothesis that within a certain group of patients the TNF-alpha inhibitors have some additional, and currently obscure, effects on presumably key regulatory proteins of the so-called extrinsic apoptotic pathway. Other proteins of the human inflammasome could be also implicated in the regulation of the programmed cell death and the carcinogenesis - there are speculations, that the adapter protein, ASC/TMS1, could be one of these. The present study describes the case of a patient who developed a rare form of skin tumor - epithelioma cuniculatum - whilst undergoing etanercept therapy for psoriatic arthritis. Under discussion are the possible critical connections in the complex regulatory networks of the inflammatory processes, the programmed cell death (apoptosis) and the carcinogenesis which, in the near or distant future, could become the objects of a targeted therapy.

Morphologic and biologic studies on ten cases of verrucous carcinoma of the vulva supporting the theory of a discrete clinico-pathologic entity.

Ten cases of verrucous carcinoma (VC) of the vulva diagnosed from January 1989 to December 1996 were studied. Patient age ranged from 50 to 83 years. The following examinations were performed on buffered formalin-fixed material: 1). in situ DNA hybridization, probes HPV 6/11, 16/18, 31/35/51; and 2). a series of immunohistochemical stainings to demonstrate wild and mutant types of the p53 protein, cytokeratin expression and pattern distribution (AE1 and AE3), and proliferating pattern (MIB 1). In situ DNA hybridization analysis for human papillomavirus 6/11, 16/18, 31/35/51 was negative in all cases. Wild and mutant types of p53 protein transcribed from related oncosuppressor gene were not detected. Keratins AE1 and AE3 showed a peculiar distribution pattern, that is, AE1 was uniformly positive in the surface and intermediate layers, while it was almost negative in the basal layer which-on the contrary-was mainly positive to AE3 keratins. MIB-1 highlighted 10-40% of proliferating cells; however, in all cases, 70-80% of MIB-1 positivity was found in the basal layer of the neoplastic epithelium. These results seem to show the morphofunctional and growth characteristics of neoplastic epithelium, thus stressing that VC should be considered as a discrete entity in vulvar tumors.

Clinical implications of natural killer cytotoxicity in patients with squamous cell carcinoma of the penis.

Impairment of natural cytotoxicity mediated by natural killer (NK) cells may play a role in the pathogenesis of penile carcinoma. The aim of this study was to examine the NK activity profile and its prognostic significance in patients with squamous cell carcinoma of the penis. The NK activity was measured in peripheral blood mononuclear cells (PBMCs) from 39 patients diagnosed histologically as having invasive squamous cell penile carcinoma and 4 patients with verrucous carcinoma of the penis. Of 39 patients with invasive squamous cell carcinoma, 4 had undergone previous penile amputation. According to the prognosis, the patients with invasive squamous cell carcinoma were divided into two groups: with metastasis and without metastasis. The patients were evaluated in relation to clinicopathologic variables using univariate analyses. NK cell activity was significantly decreased in all patients with penile carcinoma when compared with the control groups (p < 0.0001). There was no statistically significant difference between the groups with and without metastasis. We conclude that there is a decrease in NK activity in PBMCs from patients with penile carcinoma and that the presence of advanced disease or metastatic involvement is not responsible for this reduction.

Carcinoma verrugoso de Ackerman: revisión de la literatura y presentación de un caso / Ackerman's verrucous carcinoma: review of the literature and report of a case

El carcinoma verrugoso o tumor de Ackerman es considerado una variedad especial del carcinoma espinocelular bien diferenciado que se caracteriza por su bajo grado de malignidad, comportamiento clínico específico y un pronóstico favorable. Este tumor, asociado desde siempre con el consumo de tabaco masticable, higiene bucal deficiente y prótesis mal adpatadas, se ha visto relacionado últimamente con la infección por el virus de papiloma humano. Presentamos un caso de carcinoma verrugoso en mucosa de cavidad bucal con historia de prótesis mal adaptadas y consumo de tabaco masticado en una mujer blanca de 60 años. Puesto que el diagnóstico de esta lesión suele ser confundido, el examen clínico e histopatológico del carcinoma verrugoso son indispensables, ya que de ellos depende la identificación del tumor y posterior planificación del tratamiento

Verrucous carcinoma of the face with a massive neutrophil infiltrate. Analysis of leucocyte chemotactic activity in the tumour extract.

An unusual case of verrucous carcinoma of the face with a massive infiltration of neutrophils was found in a 60-year-old Japanese man who presented with a scaly, crusty tumour studded with pustules of 3 years duration on the left cheek. Histological examination showed a proliferation of deceptively benign-looking epidermal cells with an intact basement membrane, accompanied by a dermal infiltration of neutrophils and mononuclear cells and formation of microabscesses containing multinucleate giant cells, suggesting deep fungal infection or blastomycosis-like pyoderma. The lesion, however, was unresponsive to antifungal or antibacterial treatments and ultimately attained a considerable size in the following months. Based on the findings of repeat biopsy conducted 4 months later indicating further deeper invasion, a diagnosis of verrucous carcinoma of the face was made, and a total excision of the tumour and left cervical lymph node dissection were finally carried out. It can be speculated that aberrant production of leucocyte chemotactic cytokines such as interleukin-8 by dysplastic keratinocytes, subsequent neutrophil infiltration/serum permeation, generation of leucotactic anaphylatoxin C5a from serum through complement activation and of lipid chemotactic factors (leukotriene B4 and 12-hydroxy-eicosatetraenoic acid) by infiltrating leucocytes and/or dysplastic keratinocytes provoked the characteristic accumulation of neutrophils in the verrucous carcinoma of this case.