Myxoinflammatory Fibroblastic Sarcoma, Nodular-Necrotizing Variant With Two YAP1::MAML2 Fusions and TRIM24::BRAF Fusion.

Myxoinflammatory fibroblastic sarcoma (MIFS) is a rare malignant soft tissue neoplasm typically found in the distal extremities of middle-aged adults. Histologically, MIFS presents with a myxoid stroma, a mixed inflammatory infiltrate, epithelioid/spindle cells resembling virocytes, pseudolipoblasts, and emperipolesis. Genetic alterations commonly include TGFBR3-MGEA5 rearrangements and VGLL3 amplifications.

An epithelioid hemangioendothelioma with a novel RREB1::TFE3 gene fusion.

Epithelioid hemangioendothelioma (EHE) is a rare vascular tumor of intermediate malignant potential. Most cases are characterized by a WWTR1::CAMTA1 gene fusion, with YAP1::TFE3 being the second most common. We present a case of EHE in a 78-year-old woman with an RREB1::TFE3 gene fusion, which, to our knowledge, has not previously been described.

Conference on challenges in sarcoma (CCS) 2024: Expert opinions on non-evidence-based management aspects.

Background: Soft tissue sarcomas (STS) and other mesenchymal tumours belong to rare, heterogeneous neoplasms with over 150 subtypes that pose significant challenges in diagnosis and clinical decision making. While guidelines address evidence-based diagnostic and therapeutic procedures, clinical situations and scenarios without evidence remain controversial in daily practice. The 2024 Conference on Challenges in Sarcoma (CCS2024) aimed to narrow these gaps with the support of an international and multidisciplinary panel of sarcoma experts.

Preoperative Ultrahypofractionated Radiation Therapy for Soft Tissue Sarcomas: Low Rate of Wound Complications.

Purpose: Normofractionated preoperative radiation therapy (nRT) with 50 Gy applied in 25 fractions represents the most widely used radiation therapy (RT) regimen in combined local treatment of soft tissue sarcomas (STSs). STSs are characterized by a low ratio of 4 to 5 Gy, which may translate into a higher sensitivity for hypofractionation. Increasing data from cohorts and phase 2 trials on ultrahypofractionated RT (uhRT) regimens are available.

Real-World-Time Data and RCT Synergy: Advancing Personalized Medicine and Sarcoma Care through Digital Innovation.

This manuscript examines the synergistic potential of prospective real-world/time data/evidence (RWTD/E) and randomized controlled trials (RCTs) to enrich healthcare research and operational insights, with a particular focus on its impact within the sarcoma field. Through exploring RWTD/E's capability to provide real-world/time, granular patient data, it offers an enriched perspective on healthcare outcomes and delivery, notably in the complex arena of sarcoma care. Highlighting the complementarity between RWTD/E's expansive real-world/time scope and the structured environment of RCTs, this paper showcases their combined strength, which can help to foster advancements in personalized medicine and population health management, exemplified through the lens of sarcoma treatment.

Xanthogranulomatous epithelial tumor: a novel entity of uncertain biologic potential.

Xanthogranulomatous epithelial tumor (XGET) is an extremely rare and recently described mesenchymal neoplasm characterized by a distinctive histological appearance and clinical presentation. This case report describes a unique case of XGET in a 66-year-old female patient who presented with a 5 cm mass in the dorsal distal left thigh. The clinical, radiological, and pathological findings, as well as the management and follow-up, are discussed.

The Sarcoma-Specific Instrument to Longitudinally Assess Health-Related Outcomes of the Routine Care Cycle.

Patient-based health related quality of life (HRQoL) measurements are associated with an improvement in quality of care and outcomes. For a complex disease such as sarcoma, there is no disease-specific questionnaire available which covers all clinically relevant dimensions. Herein, we report on the development of an electronically implemented, sarcoma-specific instrument to assess health-related outcomes, which encompasses a combination of generic questionnaires tailored to the respective disease and treatment status covering the entire longitudinal care cycle.

Quality of Sarcoma Care: Longitudinal Real-Time Assessment and Evidence Analytics of Quality Indicators.

Sarcomas represent a large group of rare to very rare diseases, requiring complex management with a transdisciplinary approach. Overall progress has been hampered because of discipline, institution and network fragmentation, and there is no global data harmonization or quality standards. To report on and improve quality, a common definition of quality indicators (QIs) of sarcoma care as well as the capacity to assess longitudinal real-time data is required.

Determining HER2 Status by Artificial Intelligence: An Investigation of Primary, Metastatic, and HER2 Low Breast Tumors.

The expression of human epidermal growth factor receptor 2 (HER2) protein or gene transcripts is critical for therapeutic decision making in breast cancer. We examined the performance of a digitalized and artificial intelligence (AI)-assisted workflow for HER2 status determination in accordance with the American Society of Clinical Oncology (ASCO)/College of Pathologists (CAP) guidelines. Our preliminary cohort consisted of 495 primary breast carcinomas, and our study cohort included 67 primary breast carcinomas and 30 metastatic deposits, which were evaluated for HER2 status by immunohistochemistry (IHC) and in situ hybridization (ISH).

Metastatic mesenchymal chondrosarcoma showing a sustained response to cabozantinib: A case report.

Mesenchymal chondrosarcoma is a rare and aggressive sarcoma subtype with high risk for distant metastases and poor prognosis. Currently NCCN- and ESMO-Guidelines recommend using Ewing sarcoma protocols as standard treatment. Nevertheless, in localized disease overall 5-year survival rates are below 50% whereas in metastatic spread median progression-free survival rates of only 5 months can be expected.

Biopsy Ratio of Suspected to Confirmed Sarcoma Diagnosis.

The ratio of malignancy in suspicious soft tissue and bone neoplasms (RMST) has not been often addressed in the literature. However, this value is important to understand whether biopsies are performed too often, or not often enough, and may therefore serve as a quality indicator of work-up for a multidisciplinary team (MDT). A prerequisite for the RMST of an MDT is the assessment of absolute real-world data to avoid bias and to allow comparison among other MDTs.

Development of a value-based healthcare delivery model for sarcoma patients.

The urgent need to restructure healthcare delivery to address rising costs has been recognised. Value-based health care aims to deliver high and rising value for the patient by addressing unmet needs and controlling costs. Sarcoma is a rare disease and its care is therefore usually not organised as an institutional discipline.

YAP1-TFE3-fused hemangioendothelioma: a multi-institutional clinicopathologic study of 24 genetically-confirmed cases.

YAP1-TFE3-fused hemangioendothelioma is an extremely rare malignant vascular tumor. We present the largest multi-institutional clinicopathologic study of YAP1-TFE3-fused hemangioendothelioma to date. The 24 cases of YAP1-TFE3-fused hemangioendothelioma showed a female predominance (17 female, 7 male) across a wide age range (20-78 years old, median 44).

Optimized workflow for digitalized FISH analysis in pathology.

Background: Effective workflow management in a diagnostic pathology laboratory is critical to achieve rapid turnover while maintaining high quality. Fluorescence in situ hybridization analysis (FISH) is the preferred technique for detecting single chromosomal aberrations in diagnostic surgical pathology.

Material And Methods: FISH analysis applying a rapid hybridization protocol and using an automated whole-slide fluorescence scanning device (3DHISTECH, Sysmex, Switzerland) were implemented in our workflow.

Radiological and histological findings in ancient salt mummies from the salt mine of Douzlākh, Iran.

Computed tomography studies and histological analyses were performed on the mummified remains found in the Chehrābād salt mine in northwestern Iran. The ancient salt mummies are dated to the Achaemenid (550-330 BC) and Sassanid (3rd-7th century AD) time period and died in mining incidents. The aim of the study was to describe the radiological and histological findings of several ancient Iranian salt mummies with special interest in pathological and postmortem changes.

Immunohistochemical detection of PAX-FOXO1 fusion proteins in alveolar rhabdomyosarcoma using breakpoint specific monoclonal antibodies.

Alveolar Rhabdomyosarcoma (ARMS) is an aggressive pediatric cancer with about 80% of cases characterized by either a t(1;13)(p36;q14) or t(2;13)(q35;q14), which results in the formation of the fusion oncogenes PAX7-FOXO1 and PAX3-FOXO1, respectively. Since patients with fusion-positive ARMS (FP-RMS) have a poor prognosis and are treated with an aggressive therapeutic regimen, correct classification is of clinical importance. Detection of the translocation by different molecular methods is used for diagnostics, including fluorescence in situ hybridization and RT-PCR or NGS based approaches.

Incidence, mortality, and survival trends of soft tissue and bone sarcoma in Switzerland between 1996 and 2015.

Background: Research on soft-tissue sarcoma (STS) and bone sarcoma (BS) is increasingly in the focus of physicians and pharmaceutical companies. Expanding knowledge has improved the management of sarcoma and possibly survival. Here we provide the first population-based data on time trends of incidence, mortality, and survival of STS and BS diagnosed in Switzerland between 1996 and 2015.

New Insights into Tumor Heterogeneity: A Case of Solid-Oncocytic Epithelial-Myoepithelial Carcinoma of the Parotid Gland Harboring a HRAS and Heterogeneous Terminating ARID1A Mutation.

Epithelial-myoepithelial carcinoma (EMC) can be a challenging diagnosis due to a lack of obvious invasion and bland cytology. We report an unusual case of a low-grade EMC with prominent fibrous stroma, an extensive solid-oncocytic differentiation and limited areas of morphological clearly identifiable characteristic biphasic (tubular) differentiation, clear cells and PAS-positive secretions/calcifications. Both areas were investigated by next generation sequencing (Oncomine comprehensive assay) and revealed a typical concordant HRAS p.

Gemcitabine Synergizes with Immune Checkpoint Inhibitors and Overcomes Resistance in a Preclinical Model and Mesothelioma Patients.

Purpose: Combination of immune checkpoint inhibitors with chemotherapy is under investigation for cancer treatment.

Experimental Design: We studied the rationale of such a combination for treating mesothelioma, a disease with limited treatment options.

Results: The combination of gemcitabine and immune checkpoint inhibitors outperformed immunotherapy alone with regard to tumor control and survival in a preclinical mesothelioma model; however, the addition of dexamethasone to gemcitabine and immune checkpoint inhibitors nullified the synergistic clinical response.

RANK ligand blockade with denosumab in combination with sorafenib in chemorefractory osteosarcoma: a possible step forward?

Background: There is no established systemic treatment option for unresectable osteosarcoma progressing after standard chemotherapy. A recently published clinical trial has demonstrated some activity of sorafenib in this situation. Preclinical research suggests a role for the inhibition of the receptor activator of nuclear factor-ĸB ligand (RANKL), but no clinical data have been reported so far.

Response of an aggressive periosteal aneurysmal bone cyst (ABC) of the radius to denosumab therapy.

Aneurysmal bone cyst (ABC), once considered a reactive lesion, has been proven to be a neoplasia characterized by rearrangements of the USP6-gene. Aggressive local growth and recurrences are common and therapeutic options may be limited due to the vicinity of crucial structures. We describe a case of a locally aggressive, multinucleated giant cell-containing lesion of the forearm of a 21-year old woman, treated with denosumab for recurrent, surgically uncontrollable disease.