Acquired reactive digital fibroma: a clinicopathologic report of 5 cases of a new entity.

BACKGROUND: Fibroblastic proliferations in the dermis comprise a heterogeneous group of disorders that can pose diagnostic challenges. OBJECTIVE: We sought to study the clinicopathologic features of this tumor. METHODS: We reviewed the clinicopathologic features of 5 unusual mesenchymal tumors of the digits that, to our knowledge, correspond to an entity not previously described. RESULTS: The patients were 5 men. All cases were located in the digits and were associated with history of trauma. Histopathologically, the neoplasms were located mainly in the reticular dermis. The tumors consisted of solitary nodules composed of fascicles of benign-appearing spindle cells devoid of cytologic atypia. The spindle cells formed short fascicles arranged in a haphazard manner. On immunohistochemistry, the tumor cells expressed vimentin and in 2 cases, CD34. The tumor cells were negative for smooth muscle actin (SMA), desmin, h-caldesmon, epithelial membrane antigen (EMA), S100, CD68, CD99, and beta-catenin. LIMITATIONS: Only 5 cases were studied. CONCLUSIONS: Awareness of this entity is of importance to avoid misdiagnosis with other conditions. Based on the immunohistochemical pattern, we believe that these tumors are fibroblastic in origin. The peculiar gross appearance and location of the lesions is clinically quite distinctive and may lead to confusion with other neoplastic and reactive processes.

Development of a novel gene silencer pyrrole-imidazole polyamide targeting human connective tissue growth factor.

Pyrrole-imidazole (PI) polyamide can bind to specific sequences in the minor groove of double-helical DNA and inhibit transcription of the genes. We designed and synthesized a PI polyamide to target the human connective tissue growth factor (hCTGF) promoter region adjacent to the Smads binding site. Among coupling activators that yield PI polyamides, 1-[bis(dimethylamino)methylene]-5-chloro-1H-benzotriazolium 3-oxide hexafluorophosphate (HCTU) was most effective in total yields of PI polyamides. A gel shift assay showed that a PI polyamide designed specifically for hCTGF (PI polyamide to hCTGF) bound the appropriate double-stranded oligonucleotide. A fluorescein isothiocyanate (FITC)-conjugated PI polyamide to CTGF permeated cell membranes and accumulated in the nuclei of cultured human mesangial cells (HMCs) and remained there for 48 h. The PI polyamide to hCTGF significantly decreased phorbol 12-myristate acetate (PMA)- or transforming growth factor-ß1 (TGF-ß1)-stimulated luciferase activity of the hCTGF promoter in cultured HMCs. The PI polyamide to hCTGF significantly decreased PMA- or TGF-ß1-stimulated expression of hCTGF mRNA in a dose-dependent manner. The PI polyamide to hCTGF significantly decreased PMA- or TGF-ß1-stimulated levels of hCTGF protein in HMCs. These results indicate that the developed synthetic PI polyamide to hCTGF could be a novel gene silencer for fibrotic diseases.

Enhanced UVfemale1 tumor growth in CBF1 mice infected with Schistosoma mansoni due to modulation of Th1-like responses.

Effects of Schistosoma mansoni infection on anti-tumor immunity were examined in CBF1 mice with ultraviolet-induced UVfemale1 fibrosarcoma cells. Although many laboratory established tumor cells had rejection mechanisms independent of CD4(+) T cells, we confirmed that CD4(+) cells had significant roles in rejection of UVfemale1 cells in the syngeneic CBF1 mice. When we prepared two CBF1 mouse groups, S. mansoni-infected and schistosome-free, the former group showed up-regulation of Th2-like response to UVfemale1 cells, whereas the latter group mice showed rather type 1-dominant patterns. Cytotoxic activity against UVfemale1 cells tested in vitro, which was attributed to CD8(+) cells, was significantly weaker in S. mansoni-infected mice compared with infection-free mice. In tumor challenge experiments in vivo, we observed that rapid and complete rejection of UVfemale1 cells required the presence of CD8(+) T cells. Under only CD4-depleted situation, survival of tumor cells in schistosome-free mice was prolonged up to 1 month or more. Under the presence of both CD4(+) and CD8(+) cells, S. mansoni infected mice rejected the challenged UVfemale1 cells as was seen in normal mice. However, when CD8(+) cells were depleted from S. mansoni-infected mice, inoculated UVfemale1 cells grew more rapidly than in infection-free mice. Our results suggest that functionally polarized cytokine patterns in schistosome-infected hosts promote rapid tumor growth.

Telomerase activity, Ki-67, cyclin D1 and A expression, and apoptosis in solitary fibrous tumors: additional features of a predictable course?

Solitary fibrous tumors (SFTs) are infrequent soft tissue neoplasms which are usually benign and surgically curable. However, their behavior is not always predictable, although several clinical and pathological criteria of malignancy have been established. In many cancers, including some soft tissue tumors, telomerase activity (TA) has been shown to be a new reliable pathological marker of malignancy. Overexpression of some cyclins is associated with higher degrees of malignancy and predictive of the clinical course. In this study, we evaluated TA, mitotic and apoptotic indices (MI, AI), and the expression of Ki-67, cyclins D1 and A in five typical and two clinicopathologically atypical SFTs, the latter two of which had also recurred. High TA was demonstrated in the two atypical cases, which also showed a higher labeling index to Ki-67, as well as higher cyclin D1 and A expression, and either none or very few apoptoses. We suggest that TA, Ki-67, cyclin expression, and AI be evaluated in SFTs as possible adjunctive pathological criteria of behavior.

Doege-Potter syndrome: hypoglycemia associated with malignant solitary fibrous tumor.

We report a case of recurrent solitary fibrous tumor with associated hypoglycemia, the "Doege-Potter syndrome." These are rare tumors with a 12-13% rate of malignancy. The syndrome of hypoglycemia is seen in less than 5% of the cases, and the associated tumors are large with a high mitotic rate. The cause of hypoglycemia is related to insulin-like growth factors produced by these tumors. Resection in many cases is curable with resolution of the hypoglycemia. We discuss the different signs and symptoms and literature evidence of treatment options and follow-up.

Solitary fibrous tumor of the vagina.

The solitary fibrous tumor (SFT) is a rare tumor that most commonly arises in the pleura. Recent evidence has indicated that this tumor originates from mesenchymal, probably fibroblastic, cells and is not restricted to the pleura. However, its occurrence in the female genital tract is extremely rare. We report a case of primary SFT that originated from the vagina in a 34-year-old female. It was a pedunculated polypoid tumor and occurred at the site of scar tissue, caused by laceration during her last labor 7 years previously. Histologically, the tumor was predominantly composed of a random proliferation of spindle cells, intimately admixed with collagen. Immunohistochemically, the cells were strongly positive for CD34, vimentin and bcl-2, but were negative for S-100 protein, neuron-specific enolase, smooth muscle actin, desmin, CD68, cytokeratins and epithelial membrane antigen. To the best of our knowledge, this is the first reported case of a primary vaginal SFT in the English literature. Our report suggests to include SFT in the differential diagnosis of a spindle cell neoplasm originating from the vagina.