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Uterine perivascular epithelioid cell tumors (PEComas) are rare neoplasms. PI3K/AKT/mTOR pathway upregulation is critical for their pathogenesis and is often associated with TSC1/TSC2 inactivation. Although first line mTOR inhibitors are an effective treatment, metastatic PEComas eventually progress. A 53-year-old woman presented a 4-month history of post-menopausal vaginal bleeding. Clinical and radiological examination detected a uterine mass and a single S1 bone lesion. The patient underwent a radical hysterectomy and bone biopsy. The anatomopathological evaluation concluded to an oligo-metastatic uterine PEComa. The tumor harbored a heterozygous deletion of 9q34 that contains the TSC1 gene. Concerning the primary lesion, the resection was complete and the single bone metastasis was treated with radiotherapy. Three months later, the patient presented bone, lung and subcutaneous metastatic progression. An everolimus and denosumab treatment was initiated. After 2 years of treatment, a clinically significant bone, lung and subcutaneous progression was detected. Following a literature review of the possible therapeutic options, we initiated a second line treatment by pazopanib. This treatment resulted in regression of the subcutaneous lesions and stability of lung and bone metastases. In this challenging, rare setting, our report suggests single agent, anti-angiogenic, tyrosine kinase inhibitor to be effective as second line treatment of metastatic uterine PEComa progressing on mTOR inhibitors.T-cell-mediated immune response is the prerequisite for T-cell-based immunotherapy. However, the limitation of T-cell infiltration in solid tumors restricted the therapeutic effect of T-cell-based immunotherapy. The present study screened the molecular and genetic features of The Cancer Genome Atlas (TCGA)-skin cutaneous melanoma (SKCM) cohort, revealing that T-cell infiltration negatively correlated with genome copy number alteration. The analysis of the TCGA-SKCM cohort indicated that the copy number of CDKN2A was significantly decreased in patients with low T-cell infiltration. The results were validated in the other two melanoma cohorts (DFCI, Science 2015, and TGEN, Genome Res 2017). Besides, the immunohistochemistry analysis of CDKN2A and CD8 expression in 5 melanoma in situ and 15 invasive melanoma patients also showed that CD8 expression was decreased in the patients with low CDKN2A expression and there was a positive correlation between CDKN2A and CD8 expression in these patients. Interestingly, the CDKN2A deletion group and the group with low expression of T-cell markers shared similar gene and pathway alteration as compared with the normal CDKN2A group and the group with high expression of T-cell markers, especially the chemokine pathway. Further mechanistic study indicated that CDKN2A enhanced T cell recruitment and chemokine expression possibly through modulating MAPK and NF-κB signaling pathways in a cell cycle-dependent manner. Finally, we also found that CDKN2A deletion negatively correlated with the expression of T-cell markers in many other cancer types. In conclusion, CDKN2A deletion could inhibit T cell infiltration by inhibiting chemokine expression in a cell cycle dependent manner.

Cutaneous melanoma (CM) is one of the most aggressive cancers with highly metastatic ability. To make things worse, there are limited effective therapies to treat advanced CM. Our study aimed to investigate new biomarkers for CM prognosis and establish a novel risk score system in CM.

Gene expression data of CM from Gene Expression Omnibus (GEO) datasets were downloaded and analyzed to identify differentially expressed genes (DEGs). TASIN-30 cost The overlapped DEGs were then verified for prognosis analysis by univariate and multivariate COX regression in The Cancer Genome Atlas (TCGA) datasets. Based on the gene signature of multiple survival associated DEGs, a risk score model was established, and its prognostic and predictive role was estimated through Kaplan-Meier (K-M) analysis and log-rank test. Furthermore, the correlations between prognosis related genes expression and immune infiltrates were analyzed

Tumor Immune Estimation Resource (TIMER) site.

A total of 103 DEGs were obtained based on GEO cohorts, and four genes were verified in TCGA datasets. Subsequently, four genes (

, and

) model was developed by univariate and multivariate Cox regression analyses. The K-M plots showed that the high-risk group was associated with shortened survival than that in the low-risk group (

< 0.0001). Multivariate analysis suggested that the model was an independent prognostic factor (high-risk vs. low-risk, HR= 2.06,

< 0.001). Meanwhile, the high-risk group was prone to have larger breslow depth (

< 0.001) and ulceration (

< 0.001).

The four-gene risk score model functions well in predicting the prognosis and treatment response in CM and will be useful for guiding therapeutic strategies for CM patients. Additional clinical trials are needed to verify our findings.

The four-gene risk score model functions well in predicting the prognosis and treatment response in CM and will be useful for guiding therapeutic strategies for CM patients. Additional clinical trials are needed to verify our findings.

Renal cell cancer may cause various paraneoplastic syndromes; however, paraneoplastic hypereosinophilia occurs exceedingly rare. Thus far, only two cases of clear cell renal cell carcinoma (CCRCC) associated with hypereosinophilia have been reported. In this paper, we present a case of paraneoplastic hypereosinophilia associated with renal cell carcinoma and a review of the reported cases of hypereosinophilia in solid tumors.

The review is based on an electronic literature search performed in the PubMed database in September 2020 with the following key terms eosinophilia & neoplasm; eosinophilia & cancer; eosinophilia & paraneoplastic syndrome. Papers were included based on screening the titles and/or abstracts. We also included the case of our patient in the analysis.

A 68-year-old Caucasian female patient with recurrent CCRCC was admitted to our Clinic for exacerbating dyspnea and chest and right upper abdominal pain, accompanied by confusion. Preliminary blood tests showed an increased white blood cell count of 40,770/μl, and an increased eosinophil count of 6,530/μl indicating eosinophilia.