Impact of resection margin on outcome in soft-tissue sarcomas of the extremities treated with limb-sparing surgery and postoperative radiotherapy.

BACKGROUND: The standard curative treatments for extremity soft tissue sarcoma (ESTS) include surgical resection with negative margins and perioperative radiotherapy. However, the optimal resection margin remains controversial. This study aimed to evaluate the outcomes in ESTS between microscopically positive margin (R1) and microscopically negative margin (R0) according to the Union for International Cancer Control (UICC) (R + 1 mm) classification. METHODS: Medical records of patients with localized ESTS who underwent primary limb-sparing surgery and postoperative radiotherapy between 2004 and 2015 were retrospectively reviewed. Patients were followed for at least 5 years or till local or distant recurrence was diagnosed during follow-up. Outcomes were local and distal recurrences and survival. RESULTS: A total of 52 patients were included in this study, in which 17 underwent R0 resection and 35 underwent R1 resection. No significant differences were observed in rates of local recurrence (11.4% vs. 35.3%, p = 0.062) or distant recurrence (40.0% vs. 41.18%, p = 0.935) between R0 and R1 groups. Multivariate analysis showed that distant recurrences was associated with a Fédération Nationale des Centres de Lutte Contre le Cancer (FNCLCC) grade (Grade III vs. I, adjusted hazard ratio (aHR): 12.53, 95% confidence interval (CI): 2.67-58.88, p = 0.001) and tumor location (lower vs. upper extremity, aHR: 0.23, 95% CI: 0.07-0.7, p = 0.01). Kaplan-Meier plots showed no significant differences in local (p = 0.444) or distant recurrent-free survival (p = 0.161) between R0 and R1 groups. CONCLUSIONS: R1 margins, when complemented by radiotherapy, did not significantly alter outcomes of ESTS as R0 margins. Further studies with more histopathological types and larger cohorts are necessary to highlight the path forward.

Necroptosis-related lncRNA-based novel signature to predict the prognosis and immune landscape in soft tissue sarcomas.

BACKGROUND: Necroptosis-related long noncoding RNAs (lncRNAs) play crucial roles in cancer initiation and progression. Nevertheless, the role and mechanism of necroptosis-related lncRNAs in soft tissue sarcomas (STS) is so far unknown and needs to be explored further. METHODS: Clinical and genomic data were obtained from the UCSC Xena database. All STS patients' subclusters were performed by unsupervised consensus clustering method based on the prognosis-specific lncRNAs, and then assessed their survival advantage and immune infiltrates. In addition, we explored the pathways and biological processes in subclusters through gene set enrichment analysis. At last, we established the necroptosis-related lncRNA-based risk signature (NRLncSig) using the least absolute shrinkage and selection operator (LASSO) method, and explored the prediction performance and immune microenvironment of this signature in STS. RESULTS: A total of 911 normal soft tissue samples and 259 STS patients were included in current study. 39 prognosis-specific necroptosis-related lncRNAs were selected. Cluster 2 had a worse survival than the cluster 1 and characterized by different immune landscape in STS. A worse outcome in the high-risk group was observed by survival analysis and indicated an immunosuppressive microenvironment. The ROC curve analyses illustrated that the NRLncSig performing competitively in prediction of prognosis for STS patients. In addition, the nomogram presents excellent performance in predicting prognosis, which may be more beneficial towards STS patients' treatment. CONCLUSIONS: Our result indicated that the NRLncSig could be a good independent predictor of prognosis, and significantly connected with immune microenvironment, thereby providing new insights into the roles of necroptosis-related lncRNAs in STS.

Prognostic Factors Associated with Tumor Recurrence and Overall Survival in Soft Tissue Sarcomas of the Extremities in a Colombian Reference Cancer Center.

Introduction: Soft tissue sarcomas (STS) are low-incidence tumors whose clinical and histopathological factors are associated with adverse oncological outcomes. This study evaluated prognostic factors (PF) associated with tumor recurrence and overall survival (OS) in patients diagnosed with STS of the extremities, treated at the Instituto Nacional de Cancerología (INC), Bogotá, Colombia. Materials and Methods: An analytical observational study of a historical cohort was carried out, including patients diagnosed with STS and managed surgically in the Functional Unit for Breast and Soft Tissue Tumors of the INC from January 2008 to December 2018. Results: A total of 227 patients were included; 74.5% had tumors greater than 5 cm. Most patients (29.1%) were in stage IIIB at diagnosis. Age was associated with higher mortality (HR = 1.01; CI95%: 1-1.02; p = 0.048). Tumor persistence at admission to the INC (HR = 2.34; CI95%: 1.25-4.35; p = 0.007) and histologic grade III (HR = 5.36; CI95%: 2.29-12.56; p = <0.001) showed statistical significance in the multivariate analysis for recurrence of any type, as did the PFs associated with a higher risk of local recurrence (HR = 2.85; CI95%: 1.23-6.57; p = 0.014 and HR = 6.09; CI95%: 2.03-18.2; p = 0.001), respectively. Tumor size (HR = 1.03; CI95%: 1-1.06; p = 0.015) and histologic grade III (HR = 4.53; CI95%: 1.42-14.49; p = 0.011) were associated with a higher risk of distant recurrence. Conclusions: This cohort showed that in addition to histologic grade and tumor size, tumor persistence at the time of admission has an impact on disease recurrence, so STS should be managed by a multidisciplinary team with experience in this pathology in high-volume reference centers.

Superior scapular location: An overlooked albeit frequent finding in elastofibroma dorsi.

PURPOSE: To explore the frequency of superior scapular elastofibroma dorsi in a large patient series with elastofibroma dorsi. METHODS: 136 chest CTs from January 2016 to July 2022 reporting elastofibroma dorsi were retrospectively analyzed. Three radiologists assessed the number, size, and location of elastofibroma dorsi. Continuous variables underwent two-tailed t-tests with p < 0.05. Inter-observer agreement was assessed by using Cohen's Kappa values. RESULTS: In 136 patients (mean age, 75.9 +/- 9.8 years; 117 female), 330 elastofibroma dorsi were found. Six (4.4 %) patients had single, 87 (64 %) double, 22 (16.2 %) triple and 21 (15.4 %) quadruple lesions. All single and double lesions were in the inferior scapular regions. 43 (31.6 %) patients had superior scapular lesions in addition to inferior scapular elastofibroma dorsi. Inferior scapular elastofibroma dorsi was significantly larger than superior scapular elastofibroma dorsi. The probability of a right superior lesion was significantly higher in patients with a larger right inferior lesion. Inter-observer agreement was very good for experienced radiologist (κ = 94.1) and good for other radiologists (κ = 79.4 and κ = 78). CONCLUSION: In contrast to current belief, superior scapular elastofibroma dorsi accompanying the typical inferior scapular lesions is not uncommon and can even manifest bilaterally. To the best of our knowledge, this is the first case series reporting prevalence of quadruple elastofibroma dorsi.

Sporadic Malignant Triton Tumor of Shoulder: a Case Report.

Background: Malignant triton tumors (MTT) are subtype of malignant peripheral nerve sheath tumor (MPNST) which develop from Schwan cells of peripheral nerves or within neurofibromas, and shows rhabdomyoblastic differentiation. It is a rare soft tissue tumor with poor prognosis. Objective: We report a case of Malignant Triton Tumor (MTT) arising in the right shoulder in a 46 year old male patient presented to our Musculoskeletal Oncology Clinic at Royal Rehabilitation center at King Hussein Medical Center during June 2018. Case presentation: The patient was complaining of an 8 months long progressive right shoulder pain and swelling at the posterior lateral area of the shoulder. As accurate diagnosis is crucial in such case, investigations that included x-rays and magnetic resonance imaging (MRI) demonstrated an soft tissue tumor involving the right shoulder area leading to the differential diagnosis of aggressive soft tissue tumor which laid down the plan of an open incisional biopsy to be reported histopathological as a case of Malignant Triton Tumor which is a very rare and aggressive sarcoma originates from the peripheral nerve sheaths as it is subtype of malignant peripheral nerve sheath tumors after which excision of the entire tumor with safety margin was performed and referred for adjuvant chemotherapy. Conclusion: The treatment of choice is radical tumor excision with wide margins followed by chemotherapy and /or radiotherapy to improve the 5 years survival rates.

[Congenital spindle cell/sclerosing rhabdomyosarcoma: a clinicopathological analysis].

Objective: To investigate the clinicopathological features, immunophenotype and molecular genetic characteristics of congenital spindle cell/sclerosing rhabdomyosarcoma. Methods: Sixteen cases (including 10 consultation cases) of congenital spindle cell/sclerosing rhabdomyosarcoma diagnosed at the Beijing Children's Hospital, Capital Medical University, Beijing China, from April 2017 to January 2022 were collected. These cases were evaluated for clinical profiles, histomorphological features, immunophenotype and molecular characteristics. Results: Among the 16 patients, 9 were male and 7 were female. Five cases were present during maternal pregnancy and 11 cases were found immediately after birth. The tumors were located in the chest wall, low back, retroperitoneum, extremities or perineum. The tumors consisted of fasciculated spindle-shaped cells with localized mesenchymal sclerosis and vitreous metaplasia. Immunohistochemistry showed that the tumor cells expressed Desmin, Myogenin, MyoD1, SMA, CD56 and ALK to varying degrees, but not other markers such as CD34, CD99, pan-TRK, S-100 and BCOR. FISH analyses with NCOA2 (8q13) and VGLL2 (6q22) gene breakage probes revealed a breakage translocation in chromosome NCOA2 (8q13) in 4 cases (4/11). In the 6 cases subject to sequencing, a mutation at the p.L122R locus of MYOD1 gene was detected in 1 case (1/6). Two cases were examined by electron microscopy, which showed bundle-arranged myofilaments with some primitive myofilament formation. Five cases were resected with simple surgery, 2 cases were biopsied and followed up with observation only, and 9 cases were treated with surgery and adjuvant chemotherapy. Follow-up was available in 12 cases. At the end of the follow-up, 2 of the 12 patients developed local recurrences and 2 patients survived with disease. Conclusions: Congenital spindle cell/sclerosing rhabdomyosarcoma is a rare subtype of congenital rhabdomyosarcoma. It more commonly occurs in the chest, back and lower limbs of infants than other sites. NCOA2/VGLL2 gene fusion seems to be the most common genetic change. Its prognosis is better than other subtypes of rhabdomyosarcoma and those in adolescents and adults with the same subtype. Analysis and summary of its clinicopathological features can help differentiate it from other soft tissue tumors in infants and children and provide the information for appropriate treatments.

Fibroblast Growth Factor 23 is a Potential Prognostic Biomarker in Uterine Sarcoma.

BACKGROUND: Uterine sarcoma (US) is a highly malignant cancer with poor prognosis and high mortality in women. In this study, we evaluated the expression of human fibroblast growth factor 23 (FGF23) in different US subtypes and the relationship between survival and clinicopathological characteristics. METHODS: We conducted a comparative analysis of FGF23 gene expression in different pathological types of US. Utilizing a cohort from The Cancer Genome Atlas of 57 patients, a 50-patient microarray dataset (GSE119043) from the Gene Expression Omnibus and a Suining cohort of 44 patients, we analyzed gene expression profiles and corresponding clinicopathological information. Immunohistochemistry was used to examine the expression level of FGF23 in four US subtypes. Survival analysis was used to assess the relationship between FGF23 expression and prognosis in US patients. RESULTS: Compared with uterine normal smooth muscle and uterine leiomyoma, FGF23 expression was significantly upregulated in US and was differentially expressed in four US subtypes. Uterine carcinosarcoma exhibited the highest expression of FGF23 among the subtypes. Survival analysis revealed no correlation between FGF23 expression and either overall survival or progression-free survival in US (P > 0.05). Similar results were obtained from the validation cohorts. Univariate and multivariate analyses showed no significant correlation between FGF23 expression and the US prognosis. Tumor stage, CA125, and tumor recurrence were independent prognostic factors for survival of US patients. CONCLUSION: FGF23 was highly expressed in US and was promising as a novel potential biomarker for the diagnosis and prognosis of US.

Psammomatoid ossifying fibroma in the frontal sinus: An intriguing clinical encounter-A detailed case report.

BACKGROUND: Psammomatoid ossifying fibroma (POF) is a rare craniofacial neoplasm, primarily affecting the maxillofacial region, and typically observed in adolescents and young adults. This case report presents a unique occurrence of POF in a 50-year-old male, defying the conventional age range and exhibiting an unusual anatomical location within the frontal sinus. CASE: A 50-year-old male with a prior history of cecal adenocarcinoma and colectomy presented with left eye proptosis and new-onset headaches. Imaging revealed a well-defined calcified mass in the left frontal sinus, leading to a diagnosis of POF. Open surgical resection was performed to remove the tumor, and histopathological evaluation confirmed its diagnosis as psammomatoid ossifying fibroma. The patient exhibited no postoperative complications or signs of recurrence. CONCLUSION: This case underscores the diverse clinical presentations and diagnostic challenges associated with POF, emphasizing the importance of accurate diagnosis and multidisciplinary collaboration. Further research is needed to explore the genetic underpinnings and optimal management strategies for this intriguing condition.

Evaluation of the efficacy and safety of immunotherapy in sarcoma: a two-center study.

Background: Sarcoma is a highly heterogeneous malignancy with a poor prognosis. Although chemotherapy and targeted therapy have improved the prognosis to some extent, the efficacy remains unsatisfactory in some patients. The efficacy and safety of immunotherapy in sarcoma need further evaluation. Methods: We conducted a two-center study of sarcoma patients receiving PD-1 immunotherapy at Tianjin Medical University Cancer Institute and Hospital and Henan Provincial Cancer Hospital. The treatment regimens included PD-1 inhibitor monotherapy and combination therapy based on PD-1 inhibitors. The observed primary endpoints were median progression-free survival (mPFS) and median overall survival (mOS). Survival curves were compared using the Kaplan-Meier method. Results: A total of 43 patients were included from the two centers. The median follow-up time for all patients was 13 months (range, 1-48 months). In the group of 37 patients with advanced or unresectable sarcoma, the mPFS was 6 months (95%CI: 5-12 months), and the mOS was 16 months (95%CI: 10-28 months). The ORR was 10.8% (4/37), and the DCR was 18.9% (7/37). Subgroup analysis showed no significant differences in mPFS (p=0.11) and mOS (p=0.88) between patients with PD-L1 negative/positive expression. There were also no significant differences in mPFS (p=0.13) or mOS (p=0.72) between PD-1 inhibitor monotherapy and combination therapy. Additionally, there were no significant differences in mPFS (p=0.52) or mOS (p=0.49) between osteogenic sarcoma and soft tissue sarcoma. Furthermore, the results showed no significant differences in mPFS (p=0.66) or mOS (p=0.96) between PD-1 inhibitors combined with targeted therapy and PD-1 inhibitors combined with AI chemotherapy. Among the 6 patients receiving adjuvant therapy after surgery, the mPFS was 15 months (95%CI: 6-NA months), and the mOS was not reached. In terms of safety, most adverse events were mild (grade 1-2) and manageable. The most severe grade 4 adverse events were bone marrow suppression, which occurred in 4 patients but resolved after treatment. There was also one case of a grade 4 adverse event related to hypertension. Conclusion: Immunotherapy is an effective treatment modality for sarcoma with manageable safety. Further inclusion of more patients or prospective clinical trials is needed to validate these findings.

Synchronous carcinoma and sarcoma in a burn scar: a treatment conundrum.

Marjolijn's ulcer is a malignant ulcer in a burn scar. Types of malignancy are squamous cell carcinoma, basal cell carcinoma and malignant melanoma. Soft tissue sarcoma case reports indicate only one type of cancer. We present a patient in her 60s with a 10-year-old burn scar developing a biopsy-proven squamous cell carcinoma on the lateral aspect of the left thigh with metastatic superficial inguinal node. A wide excision and grafting of ulcer with ilioinguinal dissection done on left side. On the 12th postoperative day 2, subcutaneous swellings adjacent to the grafted area developed, on biopsy revealed to be pleomorphic sarcoma. PET CT scan revealed tumour deposits in the muscles of the left lower limb, liver and lung. There are no case reports of synchronous carcinoma and sarcoma in a burn scar. The case is reported for its rarity and the decision-making dilemma.

Abdominopelvic desmoplastic small round cell tumor with metastasis: A case report and literature review.

RATIONALE: Desmoplastic small round cell tumor (DSRCT) is a rare and rapidly metastasizing soft tissue sarcoma, distinguished by its unique cell morphology and pleomorphic differentiation. PATIENT CONCERNS: This report describes the case of an 18-year-old male diagnosed with abdominopelvic DSRCT exhibiting metastases to the peritoneum, liver, pleura, bone, and muscle. The patient primarily presented with symptoms of incomplete intestinal obstruction and an abdominal mass. DIAGNOSES: Colonoscopy revealed lumen stenosis caused by external compression mass. Contrast-enhanced computed tomography and 18F-fluorodeoxyglucose positron emission tomography/computed tomography revealed multiple lesions in the abdominopelvic cavity. A needle biopsy of an abdominal wall lesion established it as a malignant tumor, origin unknown. Immunohistochemical staining post-surgery showed positive results for Cytokeratin (CK), CK7, Desmin, Vimentin, Caudal type homeobox 2 (CDX2), and Ki-67. Fluorescence in situ hybridization analysis revealed an Ewing sarcoma breakpoint region 1/EWS RNA binding protein 1 (EWSR1) rearrangement, and next-generation sequencing identified an EWSR1-Wilms tumor protein 1 (WT1) gene fusion. INTERVENTIONS: The patient underwent laparoscopic exploratory surgery, which encompassed biopsy, ascites drainage, adhesion lysis, reinforcement of weakened sections of the small intestinal walls, and repositioning of twisted intestines. Postoperatively, the treatment protocol included fasting, rehydration, gastrointestinal decompression, and parenteral nutrition. However, the patient did not received chemotherapy. OUTCOMES: The patient declined further treatment and deceased in early November. LESSONS: This case highlights the nonspecific nature of DSRCT symptoms. In clinical practice, it is crucial to meticulously evaluate unexplained intestinal obstruction in young patients, considering DSRCT as a differential diagnosis to avoid delays in diagnosis.

Myoepithelial Carcinoma of Soft Tissue: Report of Two Cases.

CASE: A 40-year-old man was evaluated for a painful mass on his right calf, and a 36-year-old woman presented with a painless mass on her right foot. Final pathology revealed marked nuclear atypia and positivity for S100/SOX10 and AE1/AE3 confirming diagnoses of myoepithelial carcinoma. Both patients underwent surgical resection and are without evidence of local recurrence or metastatic disease at 1-year follow-up. CONCLUSION: Soft-tissue tumors presenting in the extremities warrant careful evaluation and timely histopathologic diagnosis. Myoepithelial carcinomas are rare, aggressive tumors with a propensity for local recurrence and metastasis. Treatment of these tumors should be discussed by a multidisciplinary tumor team.

Tumours of the foot: A 10 years retrospective analysis.

INTRODUCTION: The foot is a complex structure composed of several tissues, each of which can be the origin of the proliferation and development of the tumour. Most lesions about the foot are reactive or inflammatory, but some are true neoplasms. METHOD: This is a retrospective analysis of 4997 patient records treated in the Orthopaedic Oncology Unit of University Malaya Medical Centre, Malaysia, between 1 January 2010 to 31 December 2020. Demographic data of 195 patients with foot tumours were analysed out of 4997 neoplasm patients. RESULTS: There were 195 cases of foot tumours: 148 were benign, and 47 were malignant. 47 were bone tumours, 4 were metastases, and 144 were soft tissue tumours. Six patients succumbed to the disease, two cases of giant cell tumour (GCT) and one patient with synovial sarcoma had a recurrence. Treatment of foot tumours was wide resection in general. However, in metastasis cases, amputation was done. The majority of tumours were in the toes and dorsum of the foot. Soft tissue tumours of the foot occur in the elderly population in contrast to bone tumours, mainly in the second decade of life. The gender distribution was almost equal for foot tumours. Ganglion and Giant Cell Tumour of the bone are the commonest benign soft tissue and bone tumours. The most common malignant soft tissue and bone tumours are malignant melanoma and chondrosarcoma. The amputation rate is 5.64% the recurrence rate is 1.54%. Mortality rate is 3.08%. The MSTS score is 79%, and the TESS score is 76.23%. CONCLUSION: Foot tumours are relatively rare, mostly originating from soft tissue and exhibiting a benign nature. Nonetheless, a noteworthy proportion-approximately a quarter of these tumours-demonstrate malignancy. The surgical interventions undertaken in managing these tumours and associated functional outcomes generally yield acceptable results.

Right Thigh Mass Metastasis from Lung Cancer Mimicking Primary Soft Tissue Sarcoma: A Case Report.

BACKGROUND Soft tissue metastases (STMs) are less common than bone metastases and sometimes misdiagnosed as primary soft tissue malignancies. Skin, lungs, and breast are the most common primary lesions of STMs and rarely the presenting symptoms. We present an STM from lung adenocarcinoma that became a presenting symptom in nonsmoking woman. CASE REPORT A 47-year-old woman presented to our hospital with a painful mass in her right thigh and weight loss of 10 kg for 4 months. Femoral radiograph revealed a lesion suggestive of bone sarcoma. However, magnetic resonance imaging (MRI) showed it was more likely a primary soft tissue sarcoma. A small mediastinal mass was noticed on preoperative chest radiograph, and the patient denied any symptoms except the mass in the right thigh. Our clinicopathological conference team decided to perform a biopsy of mediastinal and right thigh masses. Histopathology examinations confirmed the right thigh mass as soft tissue metastasis from mediastinal mass, confirmed as lung adenocarcinoma. We treated the patient with palliative care with zoledronic acid and gefitinib. At the 6-month follow-up, the patient's symptoms significantly improved, and MRI showed a marked size reduction. CONCLUSIONS Diagnosis of STM can be difficult when presenting as the primary manifestation. Failure to identify promptly can lead to rapid disease progression and unfavorable prognosis. Failure to diagnose primary malignancy during biopsy occurs in approximately 28% of cases. This report has the potential to facilitate the avoidance of unnecessary procedures and highlight the importance of using a multidisciplinary approach in managing cases with malignancy.

Complications after limb salvage surgeries for musculoskeletal malignancies: 10-year experience of the main sarcoma center in Bulgaria.

INTRODUCTION: Limb salvage surgery is currently the most frequently used treatment option in Bulgaria for individuals with musculoskeletal malignancies. Clinical data about complications from these procedures is limited in the country, with only a few studies currently available.

Wound healing outcomes following treatment with synthetic hybrid-scale fiber matrix after resection of soft tissue tumors or infections.

BACKGROUND: Wide excision of soft tissue tumors or infections often results in large defects that can be challenging to manage. Advanced treatment modalities-including NPWT, skin grafts, and xenografts-can all be considered for post-resection wound management, but each has its limitations. An SHSFM, engineered to resemble human extracellular matrix, has demonstrated positive wound healing outcomes in prior studies. MATERIALS AND METHODS: Adult patients at a single institution who underwent resection of soft tissue tumor or infected tissue followed by treatment with SHSFM from 2020-2023 were retrospectively reviewed. RESULTS: Ten patients were included in the review after meeting the inclusion criteria. Overall, 7 of 10 wounds had documented complete closure, with 3 lost to follow-up. Average time to wound closure was 119 days. Patients either healed via secondary intention or were bridged to a split-thickness skin graft. The average VSS score was 3.3 when assessed. CONCLUSION: The current case series demonstrated that the SHSFM can support granulation tissue formation over exposed structures as a bridge to skin graft or can completely reepithelialize large wounds without skin grafting. The SHSFM offers a novel treatment option for post-resection surgical wounds.

A recurrent NTRK1 tyrosine kinase domain mutation pair is characteristic in a subset of dedifferentiated liposarcomas.

INTRODUCTION: Dedifferentiated liposarcoma (DDLPS) is a common form of liposarcoma with challenging treatment modalities. Pan-TRK immunopositivity can be often observed without NTRK gene fusion in soft tissue sarcomas with myogenic differentiation. Expression and the role of NTRK in DDLPS are under-studied. We sought to identify activating mutations of the NTRK genes. MATERIALS AND METHODS: 131 DDLPS patients were selected for pan-TRK immunohistochemistry and positive cases were analyzed by Sanger sequencing for NTRK1, NTRK2 and NTRK3 genes. Functional assays were performed using a lentiviral transduction system to study the effect of NTRK variants in fibroblast, immortalized fibroblast, and dedifferentiated liposarcoma cell lines. RESULTS: Out of the 131 DDLPS cases, 75 immunohistochemical staining positive cases, 46 were successfully Sanger sequenced. A recurrent somatic mutation pair in cis position (NGS) of the NTRK1 c.1810C>T (p.H604Y) and c.1838G>T (p.G613V) was identified in six cases (13%) that have never been reported in DDLPS. NTRK fusions were excluded in all six cases by FISH and NGS. The phospho-AKT immunopositivity among the six mutated cases suggested downstream activation of the NTRK signaling pathway. Functional assays showed no transforming effects, but resistance to first- and second-line TRK inhibitors of the p.G613V and p.H604Y variant. CONCLUSIONS: We detected (de novo/somatic) missense mutation variants in cis position of the NTRK1 gene in a subset of DDLPS indicating modifying mutations that may contribute to tumorigenesis in a subset of DDLPS. These variants beget resistance to TRK inhibitors indicating an interesting biomarker for other studies with TRK inhibitors.

Prostatic stromal tumour of uncertain malignant potential in a dog.

An 11-year-old male Miniature Dachshund dog was presented with dyschezia. Computed tomography examination 35 days after the initial visit revealed a prostate mass (4.0 × 3.5 × 2.7 cm) and prostatectomy and orchiectomy were performed 13 days later. Grossly, the prostate was rubbery and the cut surface of the mass was swollen. The mass was whitish and demarcated from the surrounding tissues. Microscopically, the mass had a capsulate consisting of atypical spindloid stromal cells arranged in a phyllode pattern and also in a fasciculated pattern admixed with acinar ductal cells. Atypical stromal cells contained round-to-oval finely hyperchromatic nuclei that had distinct nuclei and abundant eosinophilic cytoplasm. Immunohistochemically, the atypical stromal cells were positive for vimentin, CD34, desmin, α-smooth muscle actin, progesterone receptor and androgen receptor but negative for cytokeratin AE1/AE3, p63, c-Kit, DOG-1 and SOX10. On the basis of these findings, the tumour was diagnosed as a prostatic stromal tumour of uncertain malignant potential.

How to develop new systemic treatments in ultra-rare cancers with high unmet needs? The case of alveolar soft-part sarcoma.

Developing new drugs or generating evidence for existing drugs in new indications for ultra-rare cancers is complex and carries a high-risk of failure. This gets even harder in ultra-rare tumours, which have an annual incidence of 1 per 1,000,000 population or less. Here, we illustrate the problem of adequate evidence generation in ultra-rare tumours, using Alveolar Soft-Part Sarcomas (ASPS) - an ultra-rare sarcoma newly diagnosed in approximately 60 persons a year in the European Union - as an exemplar case showing challenges in development despite being potentially relevant for classes of agents. We discuss some possible approaches for addressing such challenges, especially focussing on constructive collaboration between academic groups, patients and advocates, drug manufacturers, and regulators to optimise drug development in ultra-rare cancers. This article, written by various European stakeholders, proposes a way forward to ultimately get better options for patients with ultra-rare cancers.

Establishment and characterization of NCC-ASPS2-C1: a novel patient-derived cell line of alveolar soft part sarcoma.

Alveolar soft part sarcoma (ASPS) is a rare mesenchymal tumor characterized by rearrangement of the ASPSCR1 and TFE3 genes and a histologically distinctive pseudoalveolar pattern. ASPS progresses slowly, but is prone to late metastasis. As ASPS is refractory to conventional chemotherapy, the only curative treatment is complete surgical resection. The prognosis of advanced and metastatic cases is poor, highlighting the need for preclinical research to develop appropriate treatment options. However, ASPS is extremely rare, accounting for < 1% of all soft tissue sarcomas, and only one patient-derived ASPS cell line is available from public cell banks worldwide for research. This study reports the establishment of a novel ASPS cell line derived from the primary tumor tissue of an ASPS patient, named NCC-ASPS2-C1. This cell line retains the ASPSCR1-TFE3 fusion gene, which is characteristic of ASPS. The characterization of this cell line revealed stable growth, spheroid formation, and invasive properties. By screening a drug library using NCC-ASPS2-C1, we identified several drugs that inhibited the proliferation of ASPS cells. In conclusion, the establishment of NCC-ASPS2-C1 provides a valuable resource for advancing ASPS research and developing novel treatments for this challenging disease.