Soft tissue sarcomas (STS) are an uncommon and biologically heterogeneous group of tumors arising from mesenchymal cells. The incidence is estimated at five cases per 100,000 people per year. Retroperitoneal sarcomas (RPS) account for 10–15% of all STS, and their management depends on their anatomical characteristics and histotype. Due to their very low incidence, it is recommended that RPS be treated in reference centers and evaluated by an experienced multidisciplinary team (MDT). In Spain, the Spanish Group for Research in Sarcomas (GEIS) brings together experts from various specialties to promote research on sarcomas and improve treatment results. This paper summarizes the GEIS recommendations for the diagnosis, treatment, and follow-up of patients with RPS.

(1) Background: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in the first two decades of life. One third of cases appear in the head and neck, with 60% of these being embryonal type. RMS is extremely rare in adults, comprising only 1% of adult malignancies, and of those, only 3.3% are rhabdomyosarcomas. (2) Case report: A 46 y.o. male presented with a 1 cm exophytic pediculated painless lesion on the dorsum of his tongue, with progressive growth for 3 months. An excisional biopsy revealed an “embryonal rhabdomyosarcoma with fusocellular areas, with negative rearrangement for gen FOXO1A, negative MDM2 (only focal positivity), and positive INI-1”. Subsequent contrast-enhanced MRI concluded the presence of a lesion with imprecise margins in the right half-tongue, 15 × 8 × 7 mm (longitudinal × transverse × craniocaudal), compatible with a sarcoma. The patient underwent a partial centrolingual glossectomy followed by reconstruction with a buccinator muscle local flap. After surgery, he received chemotherapy with eight cycles of VAC (vincristine, actinomycin, and cyclophosphamide) protocol. The patient is now disease free after 42 months, with good tongue function. (3) Discussion and conclusions: Embryonal RMS is an extremely rare sarcoma in adults, and the location in the tongue is even more exceptional (only two more similar cases are reported in the literature). The prognosis in adults is significantly poorer than in children. A complete margin-free resection with an adequate chemotherapy protocol is the treatment of choice in cases such as these.

Angiofibroma is a non-encapsulated, highly vascular tumor that usually originates in the nasopharynx. Laryngeal cases of extranasopharyngeal angiofibroma (ENA) are a very rare pathology, especially in children. Only eight ENA laryngeal cases have been described in the literature, and only one of them is a pediatric case. In this report we present an 11-year-old child with epiglottic ENA resected with transoral endoscopic ultrasonic surgery (TOUSS) with review of the literature. Because of reccurrence after five months he underwent re-excision with CO2 laser. Recurrences in ENA are infrequent, but as demonstrated in our case, close endoscopic follow-up is mandatory in this location. Endoscopic hemostatic procedures like TOUSS and CO2 laser ensure bloodless surgery for the management of this type of vascular laryngeal tumors.

Malignant gastrointestinal neuroectodermal tumor (MGNET) and clear cell sarcoma (CCS) of soft tissue represent related, extremely rare, malignant mesenchymal neoplasms. Both entities are genetically characterized by the same molecular alterations, EWSR1::CREB1 fusions. Malignant gastrointestinal neuroectodermal tumor has significant morphological overlap with CCS, although it tends to lack overt features of melanocytic differentiation. Recently, rare MGNET cases were reported in extragastrointestinal sites. The diagnosis represents a major challenge and significantly impacts therapeutic planning. In this study, we reported the clinicopathologic features of a molecularly confirmed MGNET of the neck and provided a review of the pertinent literature.

Gastrointestinal stromal tumor (GIST) is the most common gastrointestinal mesenchymal tumor, driven by tyrosine–protein kinase (KIT) and platelet-derived growth factor receptor A (PDGFRA) mutations. Specific variants, such as KIT exon 11 deletions, carry prognostic and therapeutic implications, whereas wild-type variants derive limited benefit from tyrosine kinase inhibitors. Given the limited reproducibility of established clinicopathologic risk models, deep learning (DL) applied to whole-slide images (WSI) emerged as a promising tool for molecular classification and prognostic assessment. We analyzed 8398 GIST cases from 21 centers in seven countries, including 7,238 with molecular data and 2,638 with clinical follow-up. DL models were trained on WSIs to predict mutations, treatment sensitivity, and recurrence-free survival (RFS). DL predicted mutational status in GIST from WSIs, with area under the curve of 0.87 for KIT and 0.96 for PDGFRA, and high performance was observed for subtypes, including KIT exon 11 del–inss 557 to 558 (0.67) and PDGFRA exon 18 D842V (0.93). For therapeutic categories, performance reached 0.84 for avapritinib sensitivity and 0.81 for imatinib sensitivity. DL models predicted RFS, with hazard ratios of 8.44 in the overall cohort and 4.74 in patients receiving adjuvant therapy. Prognostic performance was comparable with pathology-based scores, with highest discrimination in the overall cohort and in patients without adjuvant therapy. DL applied to WSIs enables prediction of molecular alterations, treatment sensitivity, and RFS in GIST, performing comparably with established risk scores across international cohorts, providing a baseline for future multimodal predictors. Significance: Deep learning on histology predicts KIT and PDGFRA mutations and stratifies recurrence-free survival in a large international cohort of gastrointestinal stromal tumors from multiple centers.