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Myxoinflammatory fibroblastic sarcoma is a rare soft tissue tumor with most occurring in the distal extremities of adult patients. It has a high rate of local recurrence and a low rate of metastasis. Because it may appear benign on clinical examination, and because the microscopic features are generally underrecognized, it is often inadequately treated and misdiagnosed. In this review, based upon experience and that of the literature, the intent is to highlight salient clinicopathologic features, detail the broad microscopic spectrum including high-grade aggressive variants, review the molecular features, and discuss its relation to hemosiderotic fibrolipomatous tumor.

Lymphatic metastasis is the most common pattern of bladder cancer (BCa) metastasis and has an extremely poor prognosis. Emerging evidence shows that ubiquitination plays crucial roles in various processes of tumors, including tumorigenesis and progression. However, the molecular mechanisms underlying the roles of ubiquitination in the lymphatic metastasis of BCa are largely unknown. In the present study, through bioinformatics analysis and validation in tissue samples, we found that the ubiquitin-conjugating E2 enzyme UBE2S was positively correlated with the lymphatic metastasis status, high tumor stage, histological grade, and poor prognosis of BCa patients. Functional assays showed that UBE2S promoted BCa cell migration and invasion in vitro, as well as lymphatic metastasis in vivo. Mechanistically, UBE2S interacted with tripartite motif containing 21 ( TRIM21 ) and jointly induced the ubiquitination of lipoma preferred partner ( LPP ) via K11-linked polyubiquitination but not K48- or K63-linked polyubiquitination. Moreover, LPP silencing rescued the anti-metastatic phenotypes and inhibited the epithelial-mesenchymal transition of BCa cells after UBE2S knockdown. Finally, targeting UBE2S with cephalomannine distinctly inhibited the progression of BCa in cell lines and human BCa-derived organoids in vitro, as well as in a lymphatic metastasis model in vivo, without significant toxicity. In conclusion, our study reveals that UBE2S , by interacting with TRIM21 , degrades LPP through K11-linked ubiquitination to promote the lymphatic metastasis of BCa, suggesting that UBE2S represents a potent and promising therapeutic target for metastatic BCa.

Spindle cell/pleomorphic lipomas (SCLs), cellular angiofibromas (CAFs) and mammary-type myofibroblastomas (MFBs) are rare benign mesenchymal tumors with monoallelic 13q14 deletion. They are predicted to have a common pathogenic mechanism due to shared similar histological and immunohistochemical features; however, pathological consequences of monoallelic 13q14 deletion remain unknown. We previously reported a CAF case with monoallelic 13q14 deletion in which the tumor expressed decreased levels of FOXO1 and RB1, both of which were encoded in 13q14, and increased reactive oxygen species (ROS) levels. We further demonstrated the activation of p38 mitogen-activated protein kinase (p38 MAPK) pathway induced by oxidative stress. We hypothesized that SCLs, CAFs and MFBs would share common molecular signatures involving FOXO1, ROS and p38 MAPK and that their expression patterns were different from those tumors without monoallelic 13q14 deletion such as solitary fibrous tumors (SFTs). We compared the expression levels of FOXO1, RB1, ROS markers and several signal transduction factors between SCLs and SFTs. SCLs expressed decreased levels of FOXO1 and RB1, whereas SFTs showed no change. Both tumor types exhibited increased markers of ROS; however, nuclear localization of phosphorylated p38 was significantly more frequent in SCLs than that in SFTs, suggesting p38 MAPK activation by oxidative stress. SFTs showed lower p38 MAPK activity and higher β-catenin expression, implying that oxidative stress was caused by increased cellular proliferation stress. Finally, CAFs and MFBs showed changes similar to those observed in SCLs. Overall, tumors with monoallelic 13q14 deletion showed shared molecular signatures that might be associated with pathogenesis.

Solitary fibrous tumor (SFT) is a mesenchymal tumor characterized by ovoid cells, branching blood vessels, stromal hyalinization, and CD34 immunoreactivity. Studies have shown loss of 13q in a group of morphologically similar entities, including cellular angiofibroma, mammary-type myofibroblastoma, and spindle cell lipoma. The histologic and immunophenotypic overlap between SFT and the latter group of tumors suggests that these tumors may be genetically linked. We tested a group of 40 SFTs to assess for loss of RB1 (13q14) by fluorescence in situ hybridization (FISH). All 38 SFTs with evaluable signals failed to show loss of RB1 (13q14) by FISH. All cases of cellular angiofibroma (1/1), spindle cell lipoma (6/6), and mammary-type myofibroblastoma (4/4), which were used as a control group, showed monoallelic or biallelic loss of RB1. The absence of RB1 loss in SFTs suggests that they are not related to cellular angiofibroma, mammary-type myofibroblastoma, or spindle cell lipoma.

The distinction between true anaphylaxis and conditions that mimic it can be challenging. We present the unique case of a 23-year-old woman treated for recurrent episodes of anaphylaxis over the course of 11 years and the subsequent discovery of an unlikely condition. We also discuss our approach in managing cases where an anaphylactic mimic is suspected.

Sclerosing lipogranuloma (SLG) is a rare disease that occurs in the male genital region. We report here three cases of SLG, including two of Y-shaped lesions in the penile base forming an intrascrotal mass, as well as a patient with a mass in the epidydimal region. All three lesions histologically exhibited formation of multiple granulomas consisting of multinucleated giant cells and epithelioid cells, in the fibroadipose tissue or around the epidydimis, in association with eosinophil infiltration. Membranocystic changes were found within the cytoplasm of multinucleated cells. In the two patients with scrotal lesions, membranocystic changes were positive for diastase-PAS reaction and on Sudan black B staining in dewaxed sections. CD68 staining was strongly positive in multinucleated giant cells and epithelioid cells. Most of the lymphocytes infiltrating the lesions were T cells associated with some S-100-positive dendritic cells. T-cell mediated immune reaction appears to be important in the histogenesis of SLG. The histogenesis is generally considered to be a foreign-body reaction to degenerated or damaged fatty tissue or lipids, but no apparent causative factors can be identified in some reported cases. All three patients in the present study had a good clinical course after biopsy or surgical excision. We thus report three cases of SLG including an unusual case in the epidydimal region, with some considerations regarding the histogenesis of SLG.

The high mobility group I, Y, and I-C proteins are low-molecular-weight, nonhistone chromosomal proteins that play a general role modulating gene expression during development and the immune response. Consistent with their role in early development, all three proteins are expressed at high levels during embryogenesis, and their expression is markedly diminished in differentiated cells. Exceptions to the general repression of these genes in adult tissues involve (1) A burst of synthesis of the HMG I protein during the immune response (during lymphocyte activation and preceding cytokine/adhesion molecule gene expression), (2) A constitutive expression of the HMG I and Y proteins in photoreceptor cells, and (3) Derepression of HMG I, Y, and often I-C expression in neoplastic cells. Work from several laboratories has now uncovered how these proteins participate in gene activation: (1) By altering the chromatin structure around an inducible gene-and thus influencing accessibility of the locus to regulatory proteins-(2) By facilitating the loading of transcription factors onto the promoters, and (3) By bridging adjacent transcription factors on a promoter via protein/protein interactions. Despite the similar structures and biochemical properties of the three proteins, the work has also provided clues to a division of labor between these proteins. HMG I and Y have demonstrable roles in enhanceosome formation, whereas HMG I-C has a specific role in adipogenesis. C-terminal truncations of HMG I-C and wild-type HMG Y appear to function in a manner analogous to oncogenes, as assessed by cellular transforation assays and transgenic mice. Future work should clearly define the similarities and differences in the biological roles of the three proteins, and should evolve to include attempts at pharmaceutical intervention in disease, based upon structural information concerning HMG I interactions with DNA and with regulatory proteins.