Fusions involving NTRK1, NTRK2, and NTRK3 are oncogenic drivers occurring in a spectrum of mesenchymal neoplasms ranging from benign to highly malignant tumors. To gain further insights into the staining profile with the pan-TRK assay, we analyzed a large number of soft tissue sarcomas and correlated our findings with molecular testing. Additionally, we expand the spectrum of NTRK-fusion tumors by reporting a mesenchymal lesion in the lung as well as a mesenchymal skin lesion in the spectrum of benign fibrous histiocytoma with NTRK-fusion. We retrospectively reviewed soft tissue sarcomas diagnosed at the Diagnostic and Research Institute of Pathology, Medical University of Graz, between 1999 and 2019, and cases from the consultation files of one of the authors (BLA). In total, 494 cases were analyzed immunohistochemically with pan-TRK antibody (clone EPR17341, RTU, Roche/Ventana) and positive cases (defined as any cytoplasmic/nuclear staining in more than 1% of tumor cells) underwent next-generation sequencing (NGS). Immunohistochemical staining was observed in 16 (3.2%) cases. Eleven cases with focal weak and moderate cytoplasmic/membranous or focal moderate to strong nuclear staining did not harbor an NTRK-fusion (three synovial sarcomas, three leiomyosarcomas, two extraskeletal myxoid chondrosarcomas, and one each: dedifferentiated liposarcoma, pleomorphic liposarcoma, and myxofibrosarcoma). Four cases showed strong diffuse nuclear and/or cytoplasmatic staining, and one case showed diffuse, but weak cytoplasmic staining. All these cases demonstrated an NTRK-fusion (LMNA-NTRK1, IRF2BP2-NTRK1, TMB3-NTRK1, ETV6-NTRK3, RBPMS-NTRK3). Pan-TRK assay (clone EPR17341, RTU, Roche, Ventana) immunohistochemistry serves as a reliable diagnostic marker that can also be expressed in non-NTRK-rearranged mesenchymal neoplasms. It can be used as a surrogate marker for identification of NTRK fusion, nevertheless, an RNA-based NGS for detection of the specific fusion should be performed to confirm the rearrangement, if patients are undergoing targeted therapy. Additionally, we identified NTRKfusion-positive, primary mesenchymal tumors of the lung and the skin.

Hallux rigidus is degenerative arthritis of the first metatarsophalangeal joint characterized by pain and stiffness in the joint with limitation of motion and functional impairment. Recently, bone grafts have been introduced in orthopedic procedures, namely osteosynthesis and arthrodesis. Allografts can induce bone formation, provide support for vascular and bone ingrowth and have a low risk of immunological rejection. A 52-year-old female patient with hallux rigidus underwent arthrodesis of the first metatarsophalangeal joint using Shark Screw® made of allogenic cortical bone. Corrective surgery was performed after 10 weeks, and a 5 × 3 mm large part of the Shark Screw® with the surrounding patient’s bone was removed. A histological evaluation revealed a vascularized graft with the newly formed compact lamellar bone fitting exactly to the cortical graft. The bone surface was lined by plump osteoblasts with osteoid production, and osteocytes were present in the lacunae. The arthrodesis of the first metatarsophalangeal joint using an allogenic cortical bone graft results in fast, primary bone healing without immunological rejection. This case suggests that the cortical allograft is a good and safe treatment option with an excellent graft incorporation into the host bone. However, as the literature evaluating the histology of different bone grafts is scarce, further high-level evidence studies with adequate sample sizes are needed to confirm our findings.

ZusammenfassungChordome sind maligne Knochentumoren, die mit einer jährlichen Inzidenz von 0,08 pro 100.000 Personen auftreten. Sie zeigen eine notochordale Differenzierung mit einer nukleären Expression von Brachyury (TBXT). Hauptlokalisation ist das axiale Skelett vom Clivus bis zum Sakrum und dem Os coccygis. Chordome wachsen langsam und lange nur lokal destruierend. Sie werden daher oft erst spät diagnostiziert. Putative Vorläuferläsionen sind Chordareste und der benigne notochordale Zelltumor. Dabei handelt es sich um zumeist mikroskopisch kleine, intraossäre Läsionen. Bei Chordomen werden unterschiedliche histologische Subtypen differenziert, welche sich prognostisch unterscheiden. Wiederkehrende genetische Veränderungen als Tumorauslöser sind nicht bekannt. Brachyury scheint eine noch nicht im Detail geklärte Schlüsselfunktion in der Entstehung von Chordomen zu besitzen. Die chirurgische En-bloc-Resektion mit negativen Resektionsrändern ist die einzige kurative Behandlungsoption. Die Hochdosisbestrahlung, speziell mit Protonen und Carbonionen, ist eine therapeutische Alternative in inoperablen Fällen. Medikamentöse Therapien sind für Chordome derzeit nicht zugelassen. Erste klinische Studien zu neuen Therapiemodalitäten laufen.

Background In the diagnosis of bone and soft-tissue sarcomas, the continuous advancement of various imaging modalities has improved the detection of small lesions, surgical planning, assessment of chemotherapeutic effects, and, importantly, guidance for surgery or biopsy. Method This review was composed based on a PubMed literature search for the terms “bone sarcoma,” “bone cancer” and “soft tissue sarcoma,” “imaging,” “magnetic resonance imaging”, “computed tomography”, “ultrasound”, “radiography”, and “radiomics” covering the publication period 2005–2020. Results and Conclusion As discussed in this review, radiography, ultrasound, CT, and MRI all play key roles in the imaging evaluation of bone and soft-tissue sarcomas. In daily practice, advanced MRI techniques complement standard MRI but remain underused, as they are considered time-consuming, technically challenging, and not reliable enough to replace biopsy and histology. PET/MRI and radiomics have shown promise regarding the imaging of sarcomas in the future. Key Points:  Citation Format

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