Decoding BCOR-ITD Sarcomas: Case Report of a Rare Pediatric Tumor With Challenges in Diagnosis.

Sarcomas characterized by BCOR gene alterations, are a distinct clinico-pathological group of high-grade tumors, that represent 5% of small round cell tumors without EWSR or FUS fusion. Diverse genetic alterations characterize this group, including BCOR-CCNB3 gene fusion being the most common alteration and less frequently internal tandem duplications (ITDs). We present a compelling case of a 3-year-old girl diagnosed with a high-grade nasoethmoidal sarcoma exhibiting BCOR-ITD. The diagnostic process illustrates the histological and immunophenotypic spectrum, requiring an extensive immunohistochemical panel and diverse molecular tests for accurate classification. Additionally, this case highlights the challenges in detecting BCOR-ITDs using different NGS panels, advocating for alternative molecular approaches. Our patient after 10 months since diagnosis is alive with progressive disease. This emphasizes the urgency for ongoing research to refine diagnostic methods and develop effective therapeutic strategies for these rare and aggressive tumors.

RAF1 gene fusions are recurrent driver events in infantile fibrosarcoma-like mesenchymal tumors.

Infantile fibrosarcomas (IFS) and congenital mesoblastic nephroma (CMN) are rare myofibroblastic tumors of infancy and early childhood commonly harboring the ETV6::NTRK3 gene fusion. IFS/CMN are considered as tumors with an 'intermediate prognosis' as they are locally aggressive, but rarely metastasize, and generally have a favorable outcome. A fraction of IFS/CMN-related neoplasms are negative for the ETV6::NTRK3 gene rearrangement and are characterized by other chimeric proteins promoting MAPK signaling upregulation. In a large proportion of these tumors, which are classified as IFS-like mesenchymal neoplasms, the contributing molecular events remain to be identified. Here, we report three distinct rearrangements involving RAF1 among eight ETV6::NTRK3 gene fusion-negative tumors with an original histological diagnosis of IFS/CMN. The three fusion proteins retain the entire catalytic domain of the kinase. Two chimeric products, GOLGA4::RAF1 and LRRFIP2::RAF1, had previously been reported as driver events in different cancers, whereas the third, CLIP1::RAF1, represents a novel fusion protein. We demonstrate that CLIP1::RAF1 acts as a bona fide oncoprotein promoting cell proliferation and migration through constitutive upregulation of MAPK signaling. We show that the CLIP1::RAF1 hyperactive behavior does not require RAS activation and is mediated by constitutive 14-3-3 protein-independent dimerization of the chimeric protein. As previously reported for the ETV6::NTRK3 fusion protein, CLIP1::RAF1 similarly upregulates PI3K-AKT signaling. Our findings document that RAF1 gene rearrangements represent a recurrent event in ETV6::NTRK3-negative IFS/CMN and provide a rationale for the use of inhibitors directed to suppress MAPK and PI3K-AKT signaling in these cancers. © 2024 The Pathological Society of Great Britain and Ireland.

Pediatric Plexiform Fibromyxoma: A Case Report.

The plexiform fibromyxoma is a rare mesenchymal tumor in adults that generally originates in the antrum of stomach, being its occurrence in pediatric patients exceptional. It was classified as a distinct entity by World Health Organization in 2010. No recurrences and metastases have been documented in many of the reported patients to date, being the surgical treatment curative. We report the case of a 3-month-old infant who presented to the emergency department with an episode of intestinal subocclusion requiring an emergent surgery. During the surgical intervention, a mass was identified in the jejunum, causing partial occlusion of its lumen. The surgical pathology report revealed an infiltrative tumor composed of spindle-shaped cells disposed in a stroma with a plexiform pattern alternating myxoid areas. These findings and the immunohistochemical characteristics of the neoplastic cells led to classify the tumor as a plexiform fibromyxoma. A description of the immunophenotype of this tumor is made and differential diagnosis with other gastrointestinal tumors is also discussed.

Papel de la inmunofluorescencia y el diagnóstico molecular en la caracterización de la discinesia ciliar primaria / Role of Immunofluorescence and Molecular Diagnosis in the Characterization of Primary Ciliary Dyskinesia

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