Spindle Cell Melanoma Harboring a Nodule of Epitheloid Cell Melanoma Component: A Study of a Diagnostically Challenging Case

Background: Melanoma is a very heterogeneous human neoplasm. In addition to four major (conventional) histologic subtypes a number of uncommon variants do exist. Objective: An unusual case of a spindle cell melanoma (SCM) containing a demarcated nodule of conventional epitheliod cell melanoma component is described. Material and Methods: A 71-year-old man manifested with a protuberated ulcerated skin tumor arising on the right forearm. The resected biopsy was analyzed immunohistochemically with a variety of anti-human antibodies. Results: The tumor consisted of a highly cellular mass of spindle-shaped cells without any significant intratu-moral fibrosis. In addition, a nodule of epithelioid cell tumor component was present within the lesion. The spindle cell component showed a disperse reactivity for S100 protein and was negative for other melanocytic markers. It exhibited a very high mitotic activity and proliferation Ki-67 index. No melanin pigment was detected. In contrast, the epithelioid cell component was strongly positive for S100 protein, Melan-A/MART-1, HMB-45, and PNL-2. The mitotic and proliferation indices were much less pronounced and melanin deposits were visible. A diagnosis of a non-desmoplastic SCM harboring a nodule of epithelioid cell melanoma component was established. Conclusion: SCM often posses a diagnostic dilemma because its histomorphology is atypical and its immunohistochemical profile may differ from other subtypes of melanomas. The present paper points out this uncommon histopathological entity that may sometimes be encountered in dermatopathological practice and that requires more complex diagnostic approach.

Humanization of Tumor Stroma by Tissue Engineering as a Tool to Improve Squamous Cell Carcinoma Xenograft

The role of stroma is fundamental in the development and behavior of epithelial tumors. In this regard, limited growth of squamous cell carcinomas (SCC) or cell-lines derived from them has been achieved in immunodeficient mice. Moreover, lack of faithful recapitulation of the original human neoplasia complexity is often observed in xenografted tumors. Here, we used tissue engineering techniques to recreate a humanized tumor stroma for SCCs grafted in host mice, by combining CAF (cancer associated fibroblasts)-like cells with a biocompatible scaffold. The stroma was either co-injected with epithelial cell lines derived from aggressive SCC or implanted 15 days before the injection of the tumoral cells, to allow its vascularization and maturation. None of the mice injected with the cell lines without stroma were able to develop a SCC. In contrast, tumors were able to grow when SCC cells were injected into previously established humanized stroma. Histologically, all of the regenerated tumors were moderately differentiated SCC with a well-developed stroma, resembling that found in the original human neoplasm. Persistence of human stromal cells was also confirmed by immunohistochemistry. In summary, we provide a proof of concept that humanized tumor stroma, generated by tissue engineering, can facilitate the development of epithelial tumors in immunodeficient mice.

Neuroendocrine Differentiation in Sporadic CRC and Hereditary Nonpolyosis Colorectal Cancer

Extent neuroendocrine differentiation can be encountered in many human neoplasm derived from different organs and systems using immunohistochemistry and ultrastructural techniques. The tumor cells' behaviors resemble those of neurons and neuroendocrine cells. The presence of neuroendocrine differentiation reputedly appears to be associated with a poorer prognosis than the adenocarcinoma counterparts in sporadic human neoplasm. In this review the neuroendocrine carcinoma and the adenocarcinoma with neuroendocrine differentiation of colon and rectum both in sporadic colorectal carcinoma and the hereditary nonpolyposis colorectal cancer, the relationship of neuroendocrine differentiation and some possible molecular pathways in tumorogenesis of colorectal cancer will be discussed. Possible treatment strategy will also be addressed.