Comprehensive Molecular Characterization of a Large Series of Calcified Chondroid Mesenchymal Neoplasms Widening Their Morphologic Spectrum.

Recently, FN1 fusions to receptor tyrosine kinase genes have been identified in soft tissue tumors with calcified chondroid matrix named calcifying chondroid mesenchymal neoplasms (CCMNs). We collected 33 cases of CCMN from the French network for soft tissue and bone tumors. We performed whole-exome RNA sequencing, expression analysis, and genome-wide DNA methylation profiling in 33, 30, and 20 cases of CCMN compared with a control group of tumors, including noncalcified tenosynovial giant cell tumor (TGCT). Among them, 15 cases showed morphologic overlap with soft tissue chondroma, 8 cases with tophaceous pseudogout, and 10 cases with chondroid TGCT. RNA-sequencing revealed a fusion of FN1 in 76% of cases (25/33) with different 5' partners, including most frequently FGFR2 (14 cases), TEK or FGFR1. Among CCMN associated with FGFR1 fusions, 2 cases had overexpression of FGF23 without tumor-induced osteomalacia. Four CCMN had PDGFRA::USP8 fusions; 3 of which had histologic features of TGCT and were located in the hip, foot, and temporomandibular joint (TMJ). All cases with FN1::TEK fusion were located at TMJ and had histologic features of TGCT with or without chondroid matrix. They formed a distinct cluster on unsupervised clustering analyses based on whole transcriptome and genome-wide methylome data. Our study confirms the high prevalence of FN1 fusions in CCMN. In addition, through transcriptome and methylome analyses, we have identified a novel subgroup of tumors located at the TMJ, exhibiting TGCT-like features and FN1::TEK fusions.

Angioleiomyoma: An Update with a 142-Case Series.

Angioleiomyomas are uncommon, noncancerous, smooth muscle tumors that primarily arise from blood vessels. Previous studies have yielded limited data due to the lack of interdisciplinary approaches or restricted patient pools. This study aims to provide a comprehensive analysis of angioleiomyomas, including the demographic, clinical, radiological, and histopathological features, with a large number of patients. Conducted as a retrospective investigation at a single center from January 2005 to June 2023, this study involved 142 patients. Relevant information was extracted from electronic medical records, covering clinical, radiological, histological, and demographic details. Angioleiomyomas mostly occurred at age 59 (1-87), predominately affect females (53%) and commonly arise in subcutaneous tissue (85%) and the lower limbs (76%). MRI findings revealed characteristic signals, with a high prevalence of the solid histologic type (65%), often displaying a reticular sign. Smooth muscle Actin was universally present (n = 95/95), while Desmin and Caldesmon showed positive expression in 83% (n = 71/85) and 98% (n = 92/94) of cases, respectively. This study presents an updated and comprehensive analysis of angioleiomyomas. Typically appearing as well-defined nodules in the extremities, these tumors can be effectively diagnosed using MRI, though histopathological analysis is generally essential for confirmation. Treatment primarily involves straightforward excision, with notable low complication and recurrence rates.

Enhanced accuracy and reduced delay in diagnosing bone tumors within an expert sarcoma network: A nationwide study.

INTRODUCTION: Primary bone tumors encompass a range of rare and diverse lesions. Pathological diagnosis poses significant challenges, with histological discrepancies extensively studied in soft tissue sarcomas but lacking specific investigation in bone lesions. This study aimed to determine the rate of major diagnostic discrepancies in primary bone tumors, assessing whether initial histological analysis within an expert referral center network reduces this rate and final diagnostic delay. Additionally, we examined the impact of mandatory systematic re-reading by expert pathologists on diagnostic variation and readjustment. METHODS: Our study cohort comprised patients with primary bone tumors, drawn from the national prospective French sarcoma network database. A total of 1075 patients were included from 2018 to 2019. RESULTS: The cohort exhibited a major discrepancy rate of 24%. Within the expert referral centers network, 49 cases (7%) showed major diagnostic discrepancies in the initial analysis, compared to 207 cases (57%) outside the network (p < 0.001). Regarding the final diagnostic delay, a mean of 2.8 weeks (±4.9) was observed within the network, contrasting with 6.5 weeks (±9.1) outside the network (p < 0.001). Systematic re-reading by an expert pathologist facilitated diagnosis readjustment in 75% of the 256 cases, with 68% of all diagnostic variations occurring preoperatively. CONCLUSION: Early management within the expert network significantly reduced major diagnostic discrepancies and shortened the diagnosis delay by approximately a month. Expert pathologist systematic re-readings were responsible for diagnosis readjustments in three-quarters of cases, with two-thirds of all diagnostic variations occurring preoperatively, thereby mitigating the consequences of mistreatment.