PVNS of the knee simulating lipoma arborescens on MR imaging

AbstractA case of pigmented villonodular synovitis of the knee, simulating lipoma arborescens, is presented. The MR imaging findings are correlated with histology with emphasis to the presence of fatty tissue in the lesion that could lead to misdiagnosis

Leiomyosarcoma as a Second Metachronous Malignant Neoplasm Following Colon Adenocarcinoma. A Case Report and Review of the Literature

Long-term cancer survivors are at increased risk for the development of second primary malignancies. This is usually associated with common genetic and etiologic factors and the treatment modality used for the primary cancer. In this paper we describe the case of a patient who developed a leiomyosarcoma in his left arm 5 years after he had a colon adenocarcinoma resected. Both primary tumours were treated successfully with surgical resection alone. The literature regarding second primary neoplasms, specifically focused on sarcomas, is briefly reviewed

Whole exome sequencing identifies APCDD1 and HDAC5 genes as potentially cancer predisposing in familial colorectal cancer

Germline mutations in predisposition genes account for only 20% of all familial colorectal cancers (CRC) and the remaining genetic burden may be due to rare high- to moderate-penetrance germline variants that are not explored. With the aim of identifying such potential cancer-predisposing variants, we performed whole exome sequencing on three CRC cases and three unaffected members of a Polish family and identified two novel heterozygous variants: a coding variant in APC downregulated 1 gene (APCDD1, p.R299H) and a non-coding variant in the 5' untranslated region (UTR) of histone deacetylase 5 gene (HDAC5). Sanger sequencing confirmed the variants segregating with the disease and Taqman assays revealed 8 additional APCDD1 variants in a cohort of 1705 familial CRC patients and no further HDAC5 variants. Proliferation assays indicated an insignificant proliferative impact for the APCDD1 variant. Luciferase reporter assays using the HDAC5 variant resulted in an enhanced promoter activity. Targeting of transcription factor binding sites of SNAI-2 and TCF4 interrupted by the HDAC5 variant showed a significant impact of TCF4 on promoter activity of mutated HDAC5. Our findings contribute not only to the identification of unrecognized genetic causes of familial CRC but also underline the importance of 5'UTR variants affecting transcriptional regulation and the pathogenesis of complex disorders.This article is based upon work from COST Action CA17118, supported by COST (European Cooperation in Science and Technology) and Transcan ERA-NET funding from the German Federal Ministry of Education and Research (BMBF). K.H. was supported from the EU Horizon 2020 program, grant No. 856620

Isolated primary schwannoma arising on the colon: report of two cases and review of the literature

Primary schwannoma of the large intestine is an extremely rare neoplasm. Here, we report two cases of colonic schwannoma confirmed pathologically after laparoscopic resection. A 52-year-old female and a 59-year-old female were referred by their general practitioners to our coloproctologic clinic for further evaluation and management of colonic submucosal masses. Colonoscopies performed in our institution revealed round submucosal tumors with a smooth and intact mucosa in the mid-ascending and descending colon, respectively. Computed tomography (CT) scans showed an enhancing soft tissue mass measuring 2 × 2 cm in the right colon and well-defined soft tissue nodule measuring 1.5 × 1.7 cm in the proximal descending colon, respectively. We performed laparoscopic right hemicolectomy and segmental left colectomy under the preoperative impression of gastrointestinal stromal tumors. Two cases were both diagnosed to be benign schwannoma of the colon after immunohistochemical stains (S-100 (+), smooth muscle actin (-), CD117 (-), and CD34 (-))

Primary osteosarcoma of the urinary bladder treated with external radiotherapy in a patient with a history of transitional cell carcinoma: a case report

<p>Abstract</p> <p>Introduction</p> <p>Primary osteosarcoma is one of the rare tumors affecting the urinary bladder. The occurrence of osteosarcoma in a patient with a long history of transitional cell carcinoma of the bladder is even more uncommon.</p> <p>Case presentation</p> <p>We present the case of a 74-year-old Greek man who was diagnosed with osteosarcoma 10 years after he had been diagnosed with transitional cell carcinoma of the bladder from which he had been free from recurrences for the past three years. Our patient was treated for the osteosarcoma with transurethral resection of bladder tumor and external beam radiation therapy. He died eight months after the diagnosis, suffering poor quality of life in the last months.</p> <p>Conclusion</p> <p>Osteosarcoma of the bladder has a dismal prognosis. External beam radiation therapy as an adjunct to transurethral resection of bladder tumor not only provides no benefit to patients with primary osteosarcoma of urinary bladder, but also may be associated with poor quality of life.</p

Whole-exome sequencing identifies a novel germline variant in PTK7 gene in familial colorectal cancer

Colorectal cancer (CRC) is the third most frequently diagnosed malignancy worldwide. Only 5% of all CRC cases are due to germline mutations in known predisposition genes, and the remaining genetic burden still has to be discovered. In this study, we performed whole-exome sequencing on six members of a Polish family diagnosed with CRC and identified a novel germline variant in the protein tyrosine kinase 7 (inactive) gene (PTK7, ENST00000230419, V354M). Targeted screening of the variant in 1705 familial CRC cases and 1674 healthy elderly individuals identified the variant in an additional familial CRC case. Introduction of this variant in HT-29 cells resulted in increased cell proliferation, migration, and invasion; it also caused down-regulation of CREB, p21 and p53 mRNA and protein levels, and increased AKT phosphorylation. These changes indicated inhibition of apoptosis pathways and activation of AKT signaling. Our study confirmed the oncogenic function of PTK7 and supported its role in genetic predisposition of familial CRC

Structure-guided mechanisms behind the metabolism of 2,4,6- trinitrotoluene by glutathione transferases U25 and U24 that lead to alternate product distribution

The explosive xenobiotic 2,4,6-trinitrotoluene (TNT) is a major worldwide environmental pollutant and its persistence in the environment presents health and environmental concerns. The chemical structure of TNT dictates that biological detoxification pathways follow predominantly reductive transformation of the nitro groups, and as a result, TNT is notoriously recalcitrant to mineralization in the environment. Plant-based technologies to remediate this toxic pollutant rely on a solid understanding of the biochemical detoxification pathways involved. Towards this, two Arabidopsis Tau class glutathione transferases, GSTU24 and GSTU25, have been identified that catalyze the formation of three TNT-glutathionylated conjugates. These two GSTs share 79 % identity yet only GSTU25 catalyzes the substitution of a nitro group for sulfur to form 2-glutathionyl-4,6-dinitrotoluene. The production of this compound is of interest because substitution of a nitro group could lead to destabilization of the aromatic ring, enabling subsequent biodegradation. To identify target amino acids within GSTU25 that might be involved in the formation of 2-glutathionyl-4,6-dinitrotoluene, the structure for GSTU25 was determined, in complex with oxidized glutathione, and used to inform site-directed mutagenesis studies. Replacement of five amino acids in GSTU24 established a conjugate profile and activity similar to that found in GSTU25. These findings contribute to the development of plant-based remediation strategies for the detoxification of TNT in the environment