Rare Sarcoma Research Articles

Genomic Profiling of Intimal Sarcoma Reveals Molecular Subtypes with Distinct Tumor Microenvironments and Therapeutic Implications

Intimal sarcoma is a rare and aggressive soft-tissue sarcoma with limited treatment options. We explored genomic profiles of intimal sarcoma to uncover therapeutic implications. We analyzed tumor tissues from patients with intimal sarcoma who visited the Seoul National University Hospital (SNUH) using whole-exome, whole-transcriptome, and clinical next-generation sequencing (NGS), integrated with intimal sarcoma NGS data from two public cohorts. We examined expression characteristics and tumor-infiltrating lymphocytes (TILs) according to molecular subtypes. Our study included 42 samples in total. Thirty-three patients showing copy number variation (CNV) enrichment with frequent CDK4/MDM2 amplifications were classified as the CNV-high (CNV-H) subtype. Five patients showing predominant MLH1 mutations or homozygous deletions were classified as the microsatellite instability-high-like (MSI-H-like) subtype. Hallmark pathways up-regulated in the CNV-H subtype included Wnt β-catenin and Hedgehog signaling. In the MSI-H-like subtype, interferon-γ response, tumor necrosis factor-α signaling via nuclear factor-κB, interferon-α response, inflammatory response, and interleukin-6-Jak-Stat3 signaling were up-regulated. CNV-H subtype samples predominantly showed an immune-desert phenotype, whereas MSI-H-like subtype samples predominantly showed an immune-inflamed phenotype. Two MSI-H-like subtype patients received pembrolizumab and experienced tumor shrinkage. We identified two intimal sarcoma molecular subtypes. Compared with CNV-H, MSI-H-like is enriched in pathways associated with tumor immune responses and TILs. Further efforts and clinical trials to better define these molecular subtypes are warranted to open new avenues for personalized treatment approaches and improve patient outcomes.

Subcapital Femoral Neck Fracture in a Professionally Active Patient Undergoing Palliative Treatment for Endothelial Cell-Derived Epithelioid Haemangioendothelioma (EHE)

Background and Clinical Significance: Femoral neck fracture frequently occurs in the elderly population but may also present in patients diagnosed with primary cancer or bone metastases. A pathological, oligosymptomatic fracture associated with epithelioid haemangioendothelioma (EHE), a rare endothelial cell-derived sarcoma, is uncommon. Case Presentation: A 44-year-old patient underwent biopsy procedures three times (2010, 2012, 2013) for a focal lesion of the left ischium, none confirming its malignant nature. The last biopsy revealed a neoplastic tissue with features of discrete dysplasia. The lesion did not undergo medical follow-up for seven consecutive years. In August 2020, the patient presented with right lower limb pain. A CT scan, PET/CT scan, and biopsy confirmed EHE with spindle/sarcomatous features. In November 2020, chemotherapy (5xADIC) started (PET/CT confirmed a partial response). After its completion in July 2021, bone progression occurred and sirolimus-based therapy was started. After 3 months, a small liver metastasis was visualized on PET/CT, which did not result in the termination of treatment. In December 2021, pamidronate-based antiresorptive therapy was started. Liver metastasis remained stable in follow-up CT scans. Due to pelvic and spinal lesions, the patient was assisted by elbow crutches and underwent radiotherapy, remaining professionally active. The patient did not report any trauma, but in August 2023, a subsequent CT scan revealed a subcapital fracture of the left femoral neck in the fusion phase. Due to pelvic changes and the stable nature of the fracture, surgical treatment was abandoned. Conclusions: An oligosymptomatic femoral neck fracture, not requiring medical intervention is considered a rare complication of bone cancer.

Retrospective analysis of the clinical outcomes of paraspinal soft-tissue sarcoma

Background ContextDue to the rarity and heterogeneity, paraspinal soft-tissue sarcomas represent a unique and challenging clinical entity for musculoskeletal oncologist. Reports on the treatment of paraspinal soft-tissue sarcoma are limited and the best treatment modality for this rare sarcoma type has not yet been well defined. PurposeTo introduce a modified classification of paraspinal sarcoma, review the outcome of patients treating in our center and determine the effective treatment for paraspinal soft-tissue sarcoma. Study Design/SettingRetrospective review of prospectively collected data. Patient SampleThe study included patients with paraspinal soft-tissue sarcomas in our center. Outcome MeasuresClinical outcomes, complications and survival. MethodsTwenty-five patients with paraspinal soft-tissue sarcomas treating at our center from April 2017 to December 2023 were retrieved from the hospital database. The treatment of these patients included surgery, chemotherapy, radiation, targeted therapy and immunological therapy according to respective tumor type. Patient demographics, tumor characteristics, treatment history, clinical outcomes and survival were collected from electronical medical records. ResultsAccording to the modified classification of paraspinal sarcoma, Type 1 tumors were diagnosed in 15 cases, Type 2 in 4, Type 3 in 5 and Type 4 in 1. All the patients received surgery. No patients in the study received intralesional resection, wide or marginal margins were achieved. Eleven patients received post-operative radiotherapy. The median follow-up duration in this study was 27 months (range 8-67 months). Three patients suffered from wound infection post-operatively and were successfully treated by debridement and antibiotics. Three patients had muscular weakness after surgery and gained improved muscular strength with rehabilitation. There was no implant failure complication. Three recurrence cases were recorded. Four patients died of brain or lung metastasis. Five patients survived with the disease and the remaining 16 patients were alive with disease free. ConclusionsCorrect pathological diagnosis before treatment is vital, and the modified classification can guide the surgical strategy for paraspinal soft-tissue sarcoma. Paraspinal soft-tissue sarcoma is best treated by comprehensive treatment approach with surgery as the main method, which can yield good outcomes.

Giant Abdominal Synovial Sarcoma: A Case Report

We report in this article the case of a 29-year-old man with no prior medical history who was diagnosed with a giant abdominal synovial sarcoma, treated with initial chemotherapy in preparation for surgery. This article presents a rare sarcoma entity with poor prognosis in young patients requiring early management

Navigating the Diagnostic Maze: A Case Report of Uncommon Cardiac Metastasis in Childhood Ewing Sarcoma

AbstractEwing sarcoma is a bone cancer affecting children and young adult males. It usually presents as a single bone tumor, but it can also occur in multiple locations. Nevertheless, Ewing sarcoma is an extremely aggressive tumor capable of metastasizing to other parts of the body, such as the lungs, bones, liver, and lymph nodes. Cardiac metastases are rare, indicating a poor prognosis, as they suggest that the cancer has become more advanced and challenging to treat.This case report describes a 9-year-old boy who presented with complaints of fever and multiple swellings in the calvaria, periorbital region, clavicle, and left thigh. Laboratory investigations revealed a high erythrocyte sedimentation rate, elevated absolute neutrophil count, high phosphate and calcium levels, and low magnesium levels. Computed tomography imaging revealed the presence of multifocal osseous expansile lytic lesions, multiple pulmonary metastases, and extensive soft tissue involvement of the heart. Based on these findings, possible differential diagnoses of Langerhans cell histiocytosis, lymphoma, and Ewing sarcoma were considered. Further histopathological examination and immunohistochemistry confirmed a final diagnosis of metastatic Ewing sarcoma.The most common metastasis sites for Ewing sarcoma are the lungs, with rare occurrences in the central nervous system, and metastasis to the heart is uncommon. We present here a rare undiagnosed Ewing sarcoma with cardiac metastasis, in addition to pulmonary and multifocal osseous metastasis. This case is unique because multifocal osseous involvement is rare and further lung and heart involvement is even rarer in Ewing sarcoma.

HDAC Inhibitors Induce HLA Class I Molecules through the SOX10-IRF1 Axis in Clear Cell Sarcoma Cells.

Although immune checkpoint inhibitors (ICIs) are an effective treatment for clear cell sarcoma (CCS), a rare melanocytic sarcoma with a poor prognosis, their efficacies are still limited. Therefore, a novel therapeutic strategy is required to improve the efficacy of ICIs. We previously reported that histone deacetylase (HDAC) inhibitors increased melanoma immunogenicity through the SOX10-IRF1 pathway and may improve the efficacy of ICIs for melanoma. We herein demonstrated that the inhibition of HDAC induced the expression of HLA class I molecules through IRF1 in CCS cells, similar to melanoma. The suppression of SOX10 by small interfering RNA (siRNA) induced the expression of HLA class I molecules. In addition, the isoform-specific inhibition of HDAC1/3 induced the expression of another IRF1 downstream molecule, PD-L1 in CCS cells in concert with the suppression of SOX10. Furthermore, the knockdown of IRF1 impaired the induction of PD-L1 expression in CCS cells. Therefore, the inhibition of HDAC1/3 has potential as a novel strategy to increase immunogenicity and as combination therapy with ICIs for CCS and melanoma.

Ultrasound Spot Diagnosis of Common Benign Subcutaneous Masses and Pseudomasses: What the Radiologist Needs to Know.

Common benign subcutaneous benign masses and pseudomasses represent a wide spectrum of masses among which lipomas and epidermal cysts account for a vast majority of the lesions encountered in routine practice. Other types of tumors originate from various components of the skin, such as the pilous tract, nerves, veins, arteries, or eccrine glands. In some instances, pseudomasses may be distinguished from tumoral masses using specific signs. When the diagnosis of a subcutaneous lesion lacks specificity for benignity with ultrasound, radiologists should ensure proper management of the patient to rule out the possibility of a rare but possible sarcoma of the subcutaneous layer.

The Capicua C1 Domain Is Required for Full Activity of the CIC::DUX4 Fusion Oncoprotein.

We show in mammalian settings that the capicua C1 functional domain is a supercharger for CIC::DUX4, a poorly studied fusion oncoprotein which drives a rare sarcoma with dismal outcomes.

Congenital Dermatofibrosarcoma Presenting as an Atrophic Plaque

Dermatofibrosarcoma protuberans (DFSP) is a rare sarcoma that most commonly occurs on the trunk of adult patients. However, DFSP can present congenitally, and this rarity may lead to misdiagnosis or late diagnosis. The authors present a case of a congenital DFSP that was not diagnosed until the patient was 17 years old. Her tumour was successfully treated with Mohs micrographic surgery. It is important to have DFSP on the differential for atrophic plaques or violaceous to red-brown nodules, even at a young age.

A rare expediting killer-primary thyroid gland sarcoma

Primary thyroid malignancies can be classified into differentiated type (follicular, papillary, medullary, and anaplastic) and un-differentiated type or non-epithelial malignancies, particularly lymphomas and sarcomas. The reported frequency of primary thyroid sarcoma (PTS) cases ranges from 0.01% to 1.5%. Based on this fact, we present a case report of rare primary thyroid sarcoma (PTS) in Hospital Sibu, Sarawak. Our patient is a 78-year-old lady with multiple co-morbidities and her clinical deterioration is so rapid that its progression mimics thyroid anaplastic carcinoma which is commonly seen in female elderly as well. To diagnose such uncommon thyroid malignancy, the histopathology of the tumour needs to be conducted with immunohistochemical staining. Radiographic imaging such as computed tomography or magnetic resonance imaging of whole body is required for staging purpose and to look for metastasis. We analyze the clinical presentations of PTS and discuss its treatment and prognosis. The treatment of PTS must be assessed individually on case-by-case basis as currently there is no general consensus on treating this cancer.

Immunologic and Targeted Molecular Therapies for Chordomas: A Narrative Review.

Chordomas are rare sarcomas arising from notochordal tissue and occur most commonly in the spine. The standard of care for chordomas without evidence of metastatic disease generally consists of en bloc resection followed by adjuvant radiotherapy. However, long-term (20-year) survival rates are approximately 30%. Chordomas are generally considered as chemo resistant. Therefore, systemic therapies have rarely been employed. Novel immunotherapies, including antibody therapy and tumor vaccines, have shown promise in early trials, leading to extended progression-free survival and symptom relief. However, the outcomes of larger trials using these vectors are heterogeneous. The aim of this review is to summarize novel chordoma treatments in immune-targeted therapies. The current merits, trial outcomes, and toxicities of these novel immune and targeted therapies, including those targeting vascular endothelial growth factor receptor (VEGFR) targets and the epidermal growth factor receptor (EGFR), will be discussed.

Primary osseous leiomyosarcoma of humerus misinterpreted as aneurysmal bone cyst: A case report and literature review.

Primary leiomyosarcoma of the bone (LMSB) is a rare aggressive sarcoma with limited treatment options. Histopathologic and immunohistochemical features are similar to their more common uterine and soft tissue counterparts. However, its broader spectrum of histopathologic features and rarity make diagnostic challenges. We present a case of LMSB in a 20-year-old female who presented with left shoulder aching pain for 3 months. An osteolytic intramedullary lesion was found in the left proximal humeral epi-metaphysis. Initial open biopsy showed a giant cell tumor of bone with aneurysmal bone cyst (ABC)-like changes. However, an open biopsy followed by extended curettage showed LMSB with ABC-like changes. Wide excision of the lesion and bipolar hemiarthroplasty followed by concomitant chemoradiation therapy was conducted. The mass was completely removed without significant problems. Complete mass excision and symptomatic improvements were achieved, and no subsequent relapses were observed. The authors encountered a rare case of LMSB. Most occurrences are in the lower extremity and trunk, respectively. ABC-like changes in bone tumors can lead to misdiagnosis. In this case, the ABC-like changes developed from the underlying LMSB as a secondary alteration. A careful examination of the underlying bone tumor is crucial to avoid misdiagnosing it as ABC or exhibiting ABC-like changes. Moreover, there has been no case report of LMSB with secondary ABC-like changes in bone.

Recurrent Dermatofibrosarcoma Protuberans with Fibrosarcomatous Transformation: A Case Report

Background: Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma with a propensity for local recurrence but a low risk of distant metastasis. Fibrosarcomatous transformation (FS-DFSP) is a rare but aggressive variant associated with increased metastatic potential. Case presentation: We present the case of a 39-year-old male with recurrent DFSP involving the scalp, mandible, and humerus, complicated by fibrosarcomatous transformation and distant metastases to the lungs and bones. The patient underwent multiple excisions, radiation therapy, and systemic treatments including chemotherapy and imatinib, but ultimately experienced disease progression. Conclusion: This case highlights the challenges in managing recurrent DFSP with fibrosarcomatous transformation. The rarity of this entity necessitates a high index of suspicion for early diagnosis and aggressive multidisciplinary management to improve patient outcomes. Further research is needed to identify effective treatment strategies for this aggressive variant of DFSP.

Clinical, imaging and pathological features of extraskeletal myxoid chondrosarcoma.

To evaluate clinical and radiological features of extraskeletal myxoid chondrosarcomas (EMC). Our pathology database was queried for cases of EMCs. Tumor location, size, imaging appearance, presence of metastases, disease recurrence, and clinical outcome were documented. Imaging studies were evaluated in consensus by a musculoskeletal radiologist and an orthopedic oncologist. Thirty subjects met the inclusion criteria (mean age 52.7 ± 16.2years; 19 male, 11 female), 17 (56.7%) of which had pre-operative imaging. Tumors occurred most often in the lower extremities (20/30; 66.7%). All cases presented as a soft-tissue mass without mineralization on XR or CT. On MRI, tumors were typically hyperintense on T2-weighted sequences (14/14; 100%) and had a chondroid matrix appearance (12/14; 85.7%). Tumor invasion was observed in 11 out of 16 (68.9%) patients and necrosis in 2 out of 11 subjects (18.2%). All subjects had their tumors examined by pathology, and 20 (66.7%) subjects also had descriptive information in addition to the diagnosis (tumor invasion, mitotic rate, and necrosis) noted in the pathology reports. The mean duration of follow-up was 9.4 ± 7.5 (1.0 - 29.6) years. At the last follow-up, 14 out of 28 (50%) subjects were disease-free, 6 out of 28 had persistent metastatic disease and 8 out of 28 had died. EMC is a rare sarcoma that commonly presents as lower extremity soft tissue mass with chondroid appearance on MRI. Unlike conventional chondrosarcomas, EMC do not demonstrate mineralization on XR or CT.

EP264 - Dermatofibrosarcoma protuberance of the perianal region

Abstract Introduction Dermatofibrosarcoma protuberans (DFSP) is a rare low-grade sarcoma affecting dermis and subcutaneous fat. Typically presents as slow-growing lump on the trunk, extremities or head and neck.(1) It can be locally aggressive with a high recurrence rate.(2) Only 6 reported cases of DFSP in peri-anal region. Case Description A 26-year-old male presented with slow-growing peri-anal lump for over a year with intermittent localised pain and episodes of bleeding. No other symptoms or trauma to peri-anal area noted. No relevant medical or surgical history. Examination revealed an irreducible two-by-five by one-centimetre semi-pedunculated perianal lump extending from the seven o’clock to eleven o’clock position. It was firm and tethered to the skin. Case Description Flexible sigmoidoscopy was normal. Excision biopsy histology reported diffuse infiltration of spindle cells with storiform pattern of growth without clear margins. Immunohistochemistry analysis expressed CD34 with minimal focal expression of SMA and variable Ki-67 proliferation indexed up to 15-20% in most active areas. SOX10, S100, desmin, factor XIIIA, MNF116 and CD31 were negative. Diagnosis was DFSP. Local lower gastrointestinal multi-disciplinary arranged urgent imaging and referral to tertiary centre. Magnetic resonance imaging of the pelvis identified no definite underlying localised restricted diffusion or solid enhancing nodule. Wide local excision at tertiary centre with histopathology confirmed clear margins. Conclusion Patient is under follow-up locally and at the tertiary. Urgency and a singular episode of stool incontinence was reported at two-weeks follow-up which subsequently normalised. He is currently under 3-6 monthly reviews with repeat MRI prior to next appointment. Patient has returned to normal activities.

Salvage tracheal surgery for symptomatic tracheal lesion, a rare primary pulmonary myxoid sarcoma: case report

Salvage tracheal surgery for symptomatic tracheal lesion, a rare primary pulmonary myxoid sarcoma: case report

Cellular and molecular landscape of primary dermatofibrosarcoma protuberans: Insights from single-cell RNA sequencing analysis.

Dermatofibrosarcoma protuberans (DFSP) is a rare cutaneous sarcoma characterized by the COL1A1-PDGFB fusion gene. This study utilized single-cell RNA sequencing to dissect the cellular and molecular landscape of primary DFSP. Distinct DFSP cell clusters, exhibiting fibroblast-like traits, revealed variations in pathways associated with proliferation, inflammation and metabolism. Differential gene expression analysis during the differentiation from tumour stem cells to DFSP cells unveiled SMOC2, DCN and TGFBR3 as potential regulators of tumour invasion and immune infiltration through VEGF/TGF-β signalling modulation. Cellular communication analysis highlighted interactions within DFSP cell clusters and with endothelial cells, implicating molecules such as NAMPT, ANGPT2 and PTN in pathogenesis and treatment resistance. These findings offer insights into DFSP intratumour heterogeneity, elucidate molecular mechanisms underlying tumour behaviour, and suggest potential therapeutic targets.

Undifferentiated Round Cell Sarcoma With CRTC1::SS18 Fusion: Expanding Clinicopathologic Features of a Rare Translocation Sarcoma With Prominent Desmoplastic Stroma

Undifferentiated round cell sarcomas (URCS) represent a diverse group of tumors, including conventional Ewing sarcoma, round cell sarcoma with EWSR1/FUS–non-ETS fusions, CIC-rearranged sarcoma, and sarcoma with BCOR alterations. Since 2018, 3 cases of URCS with a novel CRTC1::SS18 gene fusion have been reported in the literature. Herein, we report 3 additional cases of CRTC1::SS18 sarcoma, thereby doubling the number of described cases and expanding the clinicopathologic features of this rare translocation sarcoma. Together with the previously reported cases, we show that the male-to-female ratio is 1:2 with a median age of 34 years (range, 12-42 years). Tumors occurred primarily in intramuscular locations involving the lower extremity. Histologically, all tumors contained uniform round-to-epithelioid cells with a moderate amount of eosinophilic cytoplasm growing in sheets and nests with prominent desmoplastic stroma reminiscent of desmoplastic small round cell tumor. Immunohistochemical results were nonspecific, demonstrating variable expression of CD99 (patchy), ALK, GATA3, and cyclin D1. RNA sequencing revealed CRTC1::SS18 gene fusions in all cases, involving exons 1 to 2 of CRTC1 (the 5′ partner gene) on chromosome 19 and either exon 2 or exon 4 of SS18 (the 3′ partner gene) on chromosome 18. The clinical course was variable. Although 1 previously reported case demonstrated aggressive behavior with a fatal outcome, 2 others had a relatively indolent course with gradual growth for 6 to 7 years prior to resection. Two cases developed metastatic disease, including 1 case with bilateral lung metastasis and 1 with locoregional spread to a lymph node. By analyzing the clinicopathologic features, we aimed to improve recognition of this rare translocation sarcoma to better understand its biologic potential, optimize patient management, and expand the current classification of URCS.

Combined Application of Cold Physical Plasma and Chemotherapeutics against Chondrosarcoma Cells.

Chondrosarcoma (CS) is a rare malignant bone sarcoma that primarily affects cartilage cells in the femur and pelvis. While most subtypes exhibit slow growth with a very good prognosis, some aggressive subtypes have a poorer overall survival. CS is known for its resistance to chemotherapy and radiotherapy, leaving surgery as the sole effective therapeutic option. Cold physical plasma (CPP) has been explored in vitro as a potential therapy, demonstrating positive anti-tumor effects on CS cells. This study investigated the synergistic effects of combining CPP with cytostatics on CS cells. The chemotherapeutic agents cisplatin, doxorubicin, and vincristine were applied to two CS cell lines (CAL-78 and SW1353). After determining their IC20 and IC50, they were combined with CPP in both cell lines to assess their impact on the cell proliferation, viability, metabolism, and apoptosis. This combined approach significantly reduced the cell proliferation and viability while increasing the apoptosis signals compared to cytostatic therapy alone. The combination of CPP and chemotherapeutic drugs shows promise in targeting chemoresistant CS cells, potentially improving the prognosis for patients in clinical settings.

Clear cell sarcoma metastasizing to the pancreas

In this editorial based on a case report, we delve into a seldom-seen occurrence of clear cell sarcoma featuring pancreatic metastasis in a 47-year-old male patient. Recognized for its typical tendency to metastasize to the lungs, bones, and brain, clear cell sarcoma rarely extends its reach to the pancreas. Despite the initial absence of discernible abnormalities during the patient's physical examination, the manifestation of abdominal pain prompted further investigation. Subsequent abdominal computed tomography brought to light the presence of a pancreatic tumor, culminating in the definitive diagnosis of clear cell sarcoma with pancreatic metastasis. The successful management of this atypical presentation involved a series of surgical interventions, including distal pancreatectomy and splenectomy. This report not only sheds light on the infrequent manifestation of clear cell sarcoma within the pancreas but also underscores the pivotal role of vigilant postoperative follow-up in addressing this rare sarcoma. The emphasis on postoperative care serves as a crucial aspect of the broader narrative, acknowledging the need for ongoing monitoring and management to ensure a comprehensive and successful treatment trajectory for patients with this unique presentation of clear cell sarcoma.