EWSR1::WT1 Fusions in Neoplasms Other Than Conventional Desmoplastic Small Round Cell Tumor: Three Tumors Occurring Outside the Female Genital Tract.

Desmoplastic small round cell tumor (DSRCT) is a high-grade, primitive round cell sarcoma classically associated with prominent desmoplastic stroma, coexpression of keratin and desmin, and a characteristic EWSR1::WT1 gene fusion. DSRCT typically arises in the abdominopelvic cavity of young males with diffuse peritoneal spread and poor overall survival. Although originally considered to be pathognomonic for DSRCT, EWSR1::WT1 gene fusions have recently been detected in rare tumors lacking the characteristic morphologic and immunohistochemical features of DSRCT. Here, we report 3 additional cases of neoplasms other than conventional DSCRCT with EWSR1::WT1 gene fusions that occurred outside the female genital tract. Two occurred in the abdominopelvic cavities of a 27-year-old man and a 12-year-old girl, whereas the third arose in the axillary soft tissue of an 85-year-old man. All cases lacked prominent desmoplastic stroma and were instead solid and cystic with peripheral fibrous pseudocapsules and occasional intervening fibrous septa. Necrosis was either absent (1/3) or rare (2/3), and mitotic activity was low (<1 to 3 per 10 hpf). In immunohistochemical studies, there was expression of smooth muscle actin (3/3) and desmin (3/3), rare to focal reactivity for EMA (2/3), and variable expression of CK AE1/AE3 (1/3). Myogenin and MyoD1 were negative, and C-terminus-specific WT1 was positive in both cases tested (2/2). All 3 tumors followed a more indolent clinical course with 2 cases demonstrating no evidence of disease at 20 and 44 months after resection. The patient from case 3 died of other causes at 14 months with no evidence of recurrence. DNA methylation profiling showed that the 3 cases clustered with DSRCT; however, they demonstrated fewer copy number variations with 2 cases having a flat profile (0% copy number variation). Differential methylation analysis with hierarchical clustering further showed variation between the 3 cases and conventional DSRCT. Although further study is needed, our results, in addition to previous reports, suggest that EWSR1::WT1 gene fusions occur in rare and seemingly distinctive tumors other than conventional DSRCT with indolent behavior. Proper classification of these unusual soft tissue tumors with EWSR1::WT1 gene fusions requires direct correlation with tumor morphology and clinical behavior, which is essential to avoid overtreatment with aggressive chemotherapy.

Primary Soft-Tissue Lymphomas: MRI Features Help Discriminate From Other Soft-Tissue Tumors.

OBJECTIVES: MRI presentation of extra-nodal soft-tissue lymphomas (STLs) is scarcely reported and lacks of comparison with other soft-tissue tumors (STTs) including sarcomas (STS). Yet, suggesting this diagnosis on MRI would considerably reduce diagnostic intervals. Our aim was to investigate if conventional MRI could discriminate STLs from other STTs. METHODS: MRIs of STL patients were compared with those of patients addressed to a sarcoma reference center for the diagnosis of a STT. MRI characteristics depicting the tumor (size, signal, habitats, shape, surrounding tissues) were reported. Uni- and multivariate associations with STL diagnosis were evaluated in the entire cohort, and in the subgroups of benign and malignant STTs patients. Diagnostic performances of MRI features combinations were tested. RESULTS: We included 39 patients with STLs (median age: 69 years) and 368 patients with other STTs (122 benign STTs and 246 STS; median age: 58 years). Six MRI features were independent predictors of STL compared to all other STTs: intermediate SI on T1-WI, homogeneous enhancement (without necrotic areas), no blood signal, no fibrotic signal, no peritumoral enhancement and lack of abnormal intra- and peritumoral vasculature (p-value range: <0.0001-0.0163). Their simultaneous presence had a sensitivity of 0.88 (0.71-0.96) and a specificity of 0.88 (0.84-0.91). Other relevant MRI features were: no fat signal to discriminate against STS (p = 0.0409), the infiltrative growth pattern and the vessel and nerve encasement to discriminate against benign STTs (p = 0.0016 and 0.0011, respectively). CONCLUSION: Our research demonstrates that conventional MRI can help discriminating STLs from other STTs. Indeed, radiologists can help suggesting the possible diagnosis of STL, which could speed-up the subsequent proper histopathological analysis in light of MRI findings.

Abnormal vascularization of soft-tissue sarcomas on conventional MRI: Diagnostic and prognostic values.

PURPOSE: To assess the prevalence of abnormal vessels inside and surrounding soft-tissue sarcomas (STS) on conventional MRIs so as to evaluate their correlations with particular histotypes, histological grades, and prognosis. METHOD: This single-center retrospective study included 157 adult patients (median age: 61) with histologically-proven non-metastatic STS. All had pre-treatment conventional contrast-enhanced MRI. Two radiologists reported: presence of abnormal flow-voids, number and distribution (peri-tumoral and/or intra-tumoral), percentage of tumor circumference it covered, maximal diameter. The radiological findings were correlated with histopathology. Associations were evaluated with Chi-2 or t-tests. Survival analysis (for metastasis-free survival (MFS) and overall survival (OS)) included log-rank tests and multivariate Cox-model. RESULTS: Twenty-nine of 157 (18.5%) STS showed abnormal flow-voids that were peri-tumoral (9/157, 5.7%), intra-tumoral (5/157, 3.2%) or both intra- and peri-tumoral (15/157, 9.6%). Ten STS had more than 5 flow-voids, all being grade II-III, namely: 4 undifferentiated sarcomas, 2 solitary fibrous tumors, 1 alveolar soft-part sarcoma (ASPS), 2 leiomyosarcomas and 1 pleomorphic liposarcoma. The distribution of flow-voids was associated with survivals in the univariate analysis: patients with abnormal peritumoral flow-voids (APTFV) showed poorer OS and MFS (p = 0.039 and 0.014, respectively). These associations did not remain significant in multivariate analysis. Radio-pathological correlations revealed large tortuous tumoral neo-vessels with intra-vascular thrombi of tumor cells in ASPS and in one case of undifferentiated sarcoma displaying enrichment in genes involved in neo-angiogenesis at transcriptional level. CONCLUSIONS: APTFV on conventional MRIs may be associated with a higher risk of metastatic relapse and poorer OS in STS patients.

Alveolar soft-part sarcoma: can MRI help discriminating from other soft-tissue tumors? A study of the French sarcoma group.

OBJECTIVES: To investigate the imaging features of alveolar soft-part sarcomas (ASPS) on pre-treatment MRI in order to identify relevant criteria to distinguish ASPS from other soft-tissue tumors. METHODS: A series of 25 patients (mean age, 18.5 years old) with histologically proven ASPS from five French comprehensive cancer centers was compared to a control cohort of 292 patients with various histologically proven benign and malignant soft-tissue tumors representative of the 10-year long activity of one center. All had a baseline MRI with contrast-agent administration. Two radiologists independently reviewed the MRIs. Features assessing location, size, signal, architecture, periphery, and vascularization were reported. Their association with the histological diagnosis of ASPS was evaluated with chi-square or Fisher's test. Their prevalence, sensitivity, specificity, odds ratio, and reproducibility were calculated. RESULTS: Eight MRI features were significantly associated with ASPS: deep location (p < 0.001), high signal intensities on T1-weighted imaging (p < 0.001), central area of necrosis (p = 0.001), absence of fibrotic component (p = 0.003), infiltrative growth pattern (p = 0.003), absence of tail sign (p = 0.001), presence of intra- and peritumoral flow-voids (p < 0.001), and number of flow-voids ≥ 5 (p < 0.001). Twenty out of the 25 (80%) ASPS showed at least 7 of these 8 features compared to only four out of 292 (1.4%) tumors of the control cohort (1 benign vascular tumor, 1 solitary fibrous tumor, 2 high-grade soft-tissue sarcomas). The five ASPS with less than 7 out of 8 features measured less than 40 mm. CONCLUSION: The striking histological uniformity of ASPS translates into imaging. However, ASPS may be misdiagnosed as benign tumors or pseudo-tumors, notably intramuscular benign vascular tumors or vascular malformations. KEY POINTS: • ASPS are rare aggressive mesenchymal tumors displaying recurrent MRI features highly reminiscent of the diagnosis. • Deep-seated tumors presenting with mainly high signal intensity on T1-weighted imaging, an absence of fibrotic component, ill-defined margins without aponeurotic extension, and more than five central and peripheral flow-voids are very likely to be ASPS. • ASPS may be misdiagnosed as intramuscular benign vascular tumor or vascular malformation, which occur in the same age group.