Angiomatoid fibrous histiocytoma is a soft tissue neoplasm of low malignant potential, typically occurring in the superficial soft tissues of the extremities in children and young adults. Occurrence outside somatic soft tissues is most uncommon. This report describes eight such cases, involving the lung (three cases), mediastinum (one case), vulva (two cases), retroperitoneum (one case) and ovary (one case), with the latter three locations being hitherto unreported sites of occurrence. Patients had a median age of 48 years, and presented with symptoms related to the mass lesion (five cases) or were incidentally found to harbor a tumor (three cases). Besides the typical histological features such as an outer shell of lymphoid tissue, multinodular aggregates of dendritic-like tumor cells, blood-filled spaces and abundant admixed plasma cells, unusual features were found focally in some cases, including clear cells, rhabdomyoblast-like cells, pulmonary edema-like pattern and tumor cell cords lying in a myxoid stroma. Immunoreactivity for the epithelial membrane antigen, desmin, smooth-muscle actin, CD68 and CD99 was found in 100, 63, 43, 100 and 100% of cases, respectively. Molecular studies provided support for the diagnosis in all seven tested cases-EWS gene translocation in six cases (partner gene being CREB1 in three and ATF1 in two in which information was available) and FUS gene translocation in one case. Comparison of the reported cases of extrasomatic angiomatoid fibrous histiocytoma with their somatic soft tissue counterparts showed a number of differences: higher mean age, slight male predominance (particularly for bone lesions), larger tumors, higher frequency of systemic symptoms, higher recurrence rate, myxoid change being more common and a much higher frequency of EWS/ATF1 gene fusion.

Phosphaturic mesenchymal tumors typically cause paraneoplastic osteomalacia, chiefly as a result of FGF23 secretion. In a prior study, we identified FN1-FGFR1 fusion in 9 of 15 phosphaturic mesenchymal tumors. In this study, a total of 66 phosphaturic mesenchymal tumors and 7 tumors resembling phosphaturic mesenchymal tumor but without known phosphaturia were studied. A novel FN1-FGF1 fusion gene was identified in two cases without FN1-FGFR1 fusion by RNA sequencing and cross-validated with direct sequencing and western blot. Fluorescence in situ hybridization analyses revealed FN1-FGFR1 fusion in 16 of 39 (41%) phosphaturic mesenchymal tumors and identified an additional case with FN1-FGF1 fusion. The two fusion genes were mutually exclusive. Combined with previous data, the overall prevalence of FN1-FGFR1 and FN1-FGF1 fusions was 42% (21/50) and 6% (3/50), respectively. FGFR1 immunohistochemistry was positive in 82% (45/55) of phosphaturic mesenchymal tumors regardless of fusion status. By contrast, 121 cases of potential morphologic mimics (belonging to 13 tumor types) rarely expressed FGFR1, the main exceptions being solitary

Peripheral blood indices of systemic inflammation such as the neutrophil-lymphocyte ratio (NLR) have been shown to be prognostic in various cancers. We aim to investigate the clinical significance of these indices in patients with soft tissue sarcoma (STS). Seven hundred and twelve patients with available blood counts at diagnosis and/or metastatic relapse were retrospectively examined. An optimal cutoff for NLR-high (>2.5) in predicting overall survival (OS) was determined using receiver operating curve analyses. Survival analyses were performed using the Kaplan-Meier method and multivariate Cox proportional models. Our results show that NLR was significantly higher in patients with distant metastasis at diagnosis (n = 183) compared to those without (n = 529) (median: 4.36 vs 2.85, p < 0.0001). Progression of localized disease at diagnosis to metastatic relapse within the same patients was associated with an interval increase in NLR (median: 3.21 vs 3.74, p = 0.0003). In multivariate analysis, NLR-high was the only consistent factor independently associated with both worse OS (HR 1.53, 95% CI 1.10–2.13, p = 0.0112) and relapse-free survival (HR 1.41, 95% CI 1.08–1.85, p = 0.0125) in localized disease, as well as OS (HR 1.82, 95% CI 1.16–2.85, p = 0.0087) in metastatic/unresectable disease. In conclusion, high NLR is an independent marker of poor prognosis among patients with STS.

Associations of sarcoma with inherited cancer syndromes implicate genetic predisposition in sarcoma development. However, due to the apparently sporadic nature of sarcomas, little attention has been paid to the role genetic susceptibility in sporadic sarcoma. To address this, we performed targeted-genomic sequencing to investigate the prevalence of germline mutations in known cancer-associated genes within an Asian cohort of sporadic sarcoma patients younger than 50 years old. We observed 13.6% (n = 9) amongst 66 patients harbour at least one predicted pathogenic germline mutation in 10 cancer-associated genes including ATM, BRCA2, ERCC4, FANCC, FANCE, FANCI, MSH6, POLE, SDHA and TP53. The most frequently affected genes are involved in the DNA damage repair pathway, with a germline mutation prevalence of 10.6%. Our findings suggests that genetic predisposition plays a larger role than expected in our Asian cohort of sporadic sarcoma, therefore clinicians should be aware of the possibility that young sarcoma patients may be carriers of inherited mutations in cancer genes and should be considered for genetic testing, regardless of family history. The prevalence of germline mutations in DNA damage repair genes imply that therapeutic strategies exploiting the vulnerabilities resulting from impaired DNA repair may be promising areas for translational research.

Brain metastasis in sarcoma is rare, usually coexists with significant systemic disease and is associated with a grave prognosis. Use of chemotherapy and an aggressive treatment approach in well-selected patients may be associated with improved survival. Prospective studies are needed to confirm these findings.

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Pulmonary sclerosing pneumocytoma is a rare tumour with 23 cases reported to have metastasis to lymph nodes, but to date, only 6 had involved mediastinal nodal stations. Our patient was a 40-year-old Asian female with a 2.5 cm nodule in her right lower lobe. Positron-emission tomography suggested no nodal disease; but after resection, the intra-lobular, hilar and subcarinal nodes were all found to be involved. As prognosis of this rare disease is uncertain, we aim to report our findings against available literature and similar cases.

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