Small Round Cell Tumor Research Articles

EWSR1::WT1 Fusions in Neoplasms Other Than Conventional Desmoplastic Small Round Cell Tumor: Three Tumors Occurring Outside the Female Genital Tract

Desmoplastic small round cell tumor (DSRCT) is a high-grade, primitive round cell sarcoma classically associated with prominent desmoplastic stroma, coexpression of keratin and desmin, and a characteristic EWSR1::WT1 gene fusion. DSRCT typically arises in the abdominopelvic cavity of young males with diffuse peritoneal spread and poor overall survival. Although originally considered to be pathognomonic for DSRCT, EWSR1::WT1 gene fusions have recently been detected in rare tumors lacking the characteristic morphologic and immunohistochemical features of DSRCT. Here, we report 3 additional cases of neoplasms other than conventional DSCRCT with EWSR1::WT1 gene fusions that occurred outside the female genital tract. Two occurred in the abdominopelvic cavities of a 27-year-old man and a 12-year-old girl, whereas the third arose in the axillary soft tissue of an 85-year-old man. All cases lacked prominent desmoplastic stroma and were instead solid and cystic with peripheral fibrous pseudocapsules and occasional intervening fibrous septa. Necrosis was either absent (1/3) or rare (2/3), and mitotic activity was low (<1 to 3 per 10 hpf). In immunohistochemical studies, there was expression of smooth muscle actin (3/3) and desmin (3/3), rare to focal reactivity for EMA (2/3), and variable expression of CK AE1/AE3 (1/3). Myogenin and MyoD1 were negative, and C-terminus-specific WT1 was positive in both cases tested (2/2). All 3 tumors followed a more indolent clinical course with 2 cases demonstrating no evidence of disease at 20 and 44 months after resection. The patient from case 3 died of other causes at 14 months with no evidence of recurrence. DNA methylation profiling showed that the 3 cases clustered with DSRCT; however, they demonstrated fewer copy number variations with 2 cases having a flat profile (0% copy number variation). Differential methylation analysis with hierarchical clustering further showed variation between the 3 cases and conventional DSRCT. Although further study is needed, our results, in addition to previous reports, suggest that EWSR1::WT1 gene fusions occur in rare and seemingly distinctive tumors other than conventional DSRCT with indolent behavior. Proper classification of these unusual soft tissue tumors with EWSR1::WT1 gene fusions requires direct correlation with tumor morphology and clinical behavior, which is essential to avoid overtreatment with aggressive chemotherapy.

CXCR4-directed PET/CT with [68 Ga]Ga-pentixafor in solid tumors—a comprehensive analysis of imaging findings and comparison with histopathology

BackgroundC-X-C motif chemokine receptor 4 (CXCR4) is overexpressed in various solid cancers and can be targeted by CXCR4-directed molecular imaging. We aimed to characterize the in-vivo CXCR4 expression in patients affected with solid tumors, along with a comparison to ex-vivo findings.MethodsA total 142 patients with 23 different histologically proven solid tumors were imaged with CXCR4-directed PET/CT using [68 Ga]Ga-pentixafor (total number of scans, 152). A semi-quantitative analysis of the CXCR4-positive tumor burden including maximum standardized uptake values (SUVmax) and target-to-background ratios (TBR) using blood pool was conducted. In addition, we performed histopathological staining to determine the immuno-reactive score (IRS) from patients’ tumor tissue and investigated possible correlations with SUVmax (by providing Spearman’s rho ρ). Based on imaging, we also assessed the eligibility for CXCR4-targeted radioligand therapy or non-radioactive CXCR4 inhibitory treatment (defined as more than five CXCR4-avid target lesions [TL] with SUVmax above 10).ResultsOne hundred three of 152 (67.8%) scans showed discernible uptake above blood pool (TBR > 1) in 462 lesions (52 primary tumors and 410 metastases). Median TBR was 4.4 (1.05–24.98), thereby indicating high image contrast. The highest SUVmax was observed in ovarian cancer, followed by small cell lung cancer, desmoplastic small round cell tumor, and adrenocortical carcinoma. When comparing radiotracer accumulation between primary tumors and metastases for the entire cohort, comparable SUVmax was recorded (P > 0.999), except for pulmonal findings (P = 0.013), indicative for uniform CXCR4 expression among TL. For higher IRS, a weak, but statistically significant correlation with increased SUVmax was observed (ρ = 0.328; P = 0.018). In 42/103 (40.8%) scans, more than five TL were recorded, with 12/42 (28.6%) exhibiting SUVmax above 10, suggesting eligibility for CXCR4-targeted treatment in this subcohort.ConclusionsIn a whole-body tumor read-out, a substantial portion of prevalent solid tumors demonstrated increased and uniform [68 Ga]Ga-pentixafor uptake, along with high image contrast. We also observed a respective link between in- and ex-vivo CXCR4 expression, suggesting high specificity of the PET agent. Last, a fraction of patients with [68 Ga]Ga-pentixafor-positive tumor burden were rendered potentially suitable for CXCR4-directed therapy.

Huge and Hemorrhagic Primary Undifferentiated Small Round Cell Tumor of the Orbit: A Case Report

Small round cell sarcomas are defined by malignant, round, small, relatively undifferentiated cells. When a tumor is poorly differentiated, identification of the diagnostic and morphological features is difficult and therefore, no definitive diagnosis may be possible [1].

A case of askin’s tumor presenting as acute paraplegia

Askin tumor is an uncommon malignant neoplasm of a neuroectodermic origin that arises from the soft tissues of the thoracopulmonary wall. Defined histologically by malignant small round cell tumor and immunohistochemistry positive for CD99. The lack of clinical guides that establish a standardized management contributes to its poor prognosis and short overall survival.

Biliary hemorrhage caused by a malignant small round cell tumor in the common bile duct: A case report

Type 2 diabetes mellitus (T2DM), which is distinguished by increased glucose levels in the bloodstream, is a metabolic disease with a rapidly increasing incidence worldwide. Nevertheless, the etiology and characteristics of the mechanism of T2DM remain unclear. Recently, abundant evidence has indicated that the intestinal microbiota is crucially involved in the initiation and progression of T2DM. The gut microbiome, the largest microecosystem, engages in material and energy metabolism in the human body. In this review, we concentrated on the correlation between the gut flora and T2DM. Meanwhile, we summarized the pathogenesis involving the intestinal flora in T2DM, as well as therapeutic approaches aimed at modulating the gut microbiota for the management of T2DM. Through the analysis presented here, we draw attention to further exploration of these research directions.

Primary intra-axial Ewing sarcoma of the central nervous system: report of a rare case with literature review

BackgroundPrimary intra-axial Ewing sarcoma (EWS) is extremely rare and a highly aggressive small blue round cell tumor in the central nervous system (CNS). We reported a case of primary intra-axial CNS-EWS in a 30-year-old male and presented an extensive literature review of CNS-EWS cases.Case presentationA 30-year-old male had been diagnosed with a grade 2 astrocytoma in the left frontal lobe a year ago and had received chemotherapy and radiotherapy. He presented with a right-sided mass, which was revealed to be a 6 cm contrast-enhancing lesion with heterogeneous hemorrhagic areas in the right frontal lobe. The patient underwent emergent craniotomy for surgical excision. Histologically, the tumor was composed of high-grade, small, blue, round cells forming trabecular islands and rosettes which were separated by fibrovascular tissues. In immunohistochemical (IHC) examination, the tumor cells were positive for CD99 and FLI-1. Fluorescence in situ hybridization analysis revealed the presence of EWSR1 gene rearrangement. The histopathological, IHC, and molecular findings were consistent with a diagnosis of EWS. Further imaging did not show evidence of another primary site. The patient was followed up without further therapy and succumbed to the disease three months after the diagnosis.ConclusionEWS is very rare but an aggressive neoplasm in the CNS. Chemoradiotherapy may promote secondary cancers but it is unclear whether the development of EWS was associated with chemoradiotherapy that our case had received for astrocytoma. EWS should be considered when diagnosing a CNS tumor that shows small, blue, round cell tumor morphology. A combination of IHC and molecular tests is required for accurate diagnosis to ensure that all patients receive the most appropriate treatment to optimize outcomes.

1936P Targeted therapy of desmoplastic small round cell tumor guided by multilayered molecular profiling

1936P Targeted therapy of desmoplastic small round cell tumor guided by multilayered molecular profiling

The Role of Whole Abdomen and Pelvis Radiation Therapy in Desmoplastic Small Round Cell Tumor

Desmoplastic small round cell tumor (DSRCT) is a rare entity that typically presents in adolescent and young adult men with widespread abdominopelvic disease. The benefit of whole abdomen and pelvis radiation therapy (WAPRT) after chemotherapy and maximal surgical resection is unknown. Our objective was to evaluate the oncologic benefit and toxicity of WAPRT in this rare and aggressive disease. We conducteda retrospective review of patients with DSRCT treated at our institution primarily between 2018-2021. The cumulative incidence (CI) of intra-abdominopelvic failure was compared among those who received WAPRT after chemotherapy and surgery vs those who received chemotherapy and surgery alone without WAPRT utilizing Gray's method. Progression-free survival (PFS) and overall survival (OS) were also compared among patients who did and did not receive WAPRT using the Kaplan-Meier method from the date of surgery. Toxicity was graded per CTCAE v5.0 criteria. Twenty-eight patients were included (median age 17.5 years; range 6-38 years; 78% male, 22% female). All patients received chemotherapy with VDC/IE, all but one underwent extensive tumor resection, and all but two received HIPEC at time of resection. Nineteen patients (median age 13 years) received WAPRT after surgery, while 9 patients (median age 24 years) were treated with systemic therapy and surgery alone. Patients who received WAPRT were generally treated to 30 Gy in 20 fractions utilizing intensity-modulated radiation therapy (IMRT), with a boost to gross disease to a total dose of 45-50 Gy in 9 patients. Median follow up was 20 months. The CI of intra-abdominopelvic failure at 12 and 24 months was 16% and 50% with WAPRT vs 74% and 87% without WAPRT (p = 0.003), with a median time from surgery to intra-abdominopelvic failure of 15 months after WAPRT vs 5 months without. PFS was also improved with WAP-RT (94% and 83% at 12 and 24 months) vs without WAPRT (67% and 0% at 12 and 24 months), p = 0.001. Among those who received WAPRT, patients who received a boost to gross disease had similar intra-abdominopelvic control as those who had no gross disease to boost and received WAPRT only (CI at 24 months 50% without boost vs 48% with, p = 0.95). OS did not differ between those who did and did not receive WAPRT (OS at 24 months, 88% vs 83%, p = 0.89). Most toxicities after WAPRT were mild, including grade 1-2 fatigue, nausea, and vomiting, with the exception of one patient who developed veno-occlusive disease. Although limited by selection bias and short follow up, our study shows durable intra-abdominopelvic control and an improvement in PFS after WAPRT with IMRT, without an effect on OS. Additional larger, prospective investigations evaluating the value and toxicity of WAPRT for DSRCT are warranted.

Malignant Small Round Cell Tumor: A Rare Aggressive Malignancy-Case Report

Background: Malignant Small round Cell Tumor (MSRCT) is very rare group of tumors. Malignant cells have similar histologic appearance making it difficult to distinguish one from another, and poses a diagnostic challenge with needs for a multimodal approach. Immunohistochemistry and immunophenotyping by flow cytometry, reverse transcriptase polymer chain reaction (RT-PCR) and fluorescence in situ hybridization are needed to confirm. The appropriate and best treatment in early stages of MSRCT is early surgical excision with chemoradiotherapy based on patient specification. Inspite of all these, tumors have poor prognosis and chance of recurrence are high. Method: Case study of a 27-year-old male who presented with a non-productive cough for 4 weeks, with feverish feeling with weight loss and shortness of breath and a new onset precordial chest pain non radiating and worse on exertion. On examination his vitals were: BP 121/91 mm of hg, pulse rate 114bpm, temperature 36.3 degrees Celsius, respiratory rate 24/per min, SPO2 96%.On examination, Elevated Jugular Venous Pressure, hyperactive precordium, displaced apex beat to 6th intercostal space anterior axillary line, muffled heart sounds and bilateral lower limb edema. Respiratory exam was unremarkable. Sputum gene expert was negative for mycobacterium tuberculosis and covid 19 rapid test was negative. Chest X Ray showed cardiomegaly and a transthoracic echocardiography revealed moderate-large pericardial effusion, with mild collapse of right atrium in diastole. Pericardiocentesis done showed hemorrhagic effusion with lymphocytes cell component, patient was initiated on treatment for TB pericarditis empirically. Three months later a chest CT scan done revealed extensive mediastinal/pericardial mass with lung nodules. An ultrasound guided mediastinal/Pericardial biopsy was done, revealed a poorly differentiated small round cell carcinoma. Results: Patient expired 14 weeks from the initial onset of symptoms while awaiting immunohistochemistry studies for specific diagnosis of the tumor and oncology review. Discussion: This demonstrates the complexity of establishing differential diagnosis of MSRCT in a resource limited setting with subsequent delay in treatment initiation, heralds poor prognosis. This also confirms difficulties in establishing differential diagnosis in poorly differentiated tumor.

Desmoplastic small round cell tumor with ovarian involvement on [18F]-FDG PET/CT

Desmoplastic small round cell tumor with ovarian involvement on [18F]-FDG PET/CT

Mesenchymal tumours of the pleura: review and update.

Primary mesenchymal tumours of the pleura are uncommon and can be diagnostically challenging due to their overlapping histopathologic and immunophenotypic features. Herein we discuss selected mesenchymal tumours of the pleura, including solitary fibrous tumour, calcifying fibrous tumour, desmoid fibromatosis, synovial sarcoma, schwannoma, malignant peripheral nerve sheath tumour, inflammatory myofibroblastic tumour, follicular dendritic cell sarcoma, epithelioid hemangioendothelioma, and desmoplastic small round cell tumour. We review their clinicopathologic characteristics, along with an update on the relevant immunohistochemical and molecular features.

Desmoplastic Small Round Cell Tumor: Study of Cytomorphologic and Immunophenotypical Features in Eight Cases, One with Usual Rhabdoid Morphology

Desmoplastic Small Round Cell Tumor: Study of Cytomorphologic and Immunophenotypical Features in Eight Cases, One with Usual Rhabdoid Morphology

Analysis of 55 Adult Cases Surgically Treated for Pontocerebellar Angle Tumors

Objective: Pontocerebellar angle (PCA) tumors, although typically of benign nature, are of significant clinical and pathological importance. The aim of this study is to investigate the clinical and pathological characteristics of PCA tumors, as well as surgical outcomes, which hold a significant place in clinical practice. Methods: 55 adult patients who underwent surgery for PCA tumors at the Department of Neurosurgery, Dicle University Faculty of Medicine, between 2013 and 2023 were included in the study. The clinical and pathological records of these patients were retrospectively reviewed. Results: The age of the patients (17 male, 38 female) ranged from 18 to 75 years. According to pathological diagnosis, 23 cases were diagnosed as meningioma, 19 as schwannoma, 6 as epidermoid tumors, 2 as metastases, 1 as hemangioblastoma, 1 as hemangioma, 1 as medulloblastoma, 1 as neuroblastoma, and 1 as small round cell tumor. Gross total resection was achieved in all cases. Overall, 47.3% of the patients had one or more postoperative complications. Postoperative permanent facial palsy developed in 6 patients. The overall mortality rate was 9%. Conclusion: PCA tumors constitute a significant group among intracranial tumors. Surgical treatment is an important option for the management of these tumors. Primary goal of the surgery is gross total resection which is feasible in today. Though postoperative complications are common, majority of them is temporary.

Burkitt lymphoma masquerading as nasopharyngeal angiofibroma

Primary nasopharyngeal (NP) lymphoma is a very rare tumor. Burkitt lymphoma is a subtype of non-Hodgkin’s B cell lymphoma. It is rare in the Waldeyer’s ring (3-5%). It is a highly aggressive, highly chemo sensitive lymphoma seen predominantly in childhood. Presenting a unique case of an 11 year old, male child presented to us with the chief complaints of bilateral nasal obstruction since 1 month, 6-7 episodes of nasal bleed since 1 week. Radiologically, a large soft tissue density mass lesion was seen in the region of nasopharynx, extending into the para/retro pharyngeal space. Excisional biopsy of the mass lesion histopathologic evaluation was suggestive of small round blue cell tumor, later confirmed to be Burkitt lymphoma after a bone marrow biopsy. Nasopharyngeal NHL should be kept in mind as a differential diagnosis, apart from inflammatory adenoid hypertrophy and benign tumors such as JNA while evaluating a nasopharyngeal mass in children. Nasopharyngeal NHL are highly chemo sensitive, therefore, an early diagnosis can aid timely commencement of chemotherapy and prevent progression and complications of the disease.

Desmoplastic small round cell tumor of the liver: diagnosing a rare case on liver biopsy

Desmoplastic small round-cell tumors (DSRCT) frequently develop in the retroperitoneum, pelvis, omentum, and mesentery. Here, we present an unusual case of primary DSRCT in the liver. The patient was an 11-year-old boy with multiple solid masses in the liver parenchyma. The tumor in the needle biopsy had a histology revealing a small round cell morphology and desmoplasia. It shows the immunohistochemical features of DSRCT and documentation of EWSR1-WT1 fusion.A potential diagnostic pitfall is exerted when evaluating liver biopsy, in which DSRCT is a great mimicker and may be easily confused with more common liver malignancies of childhood, such as hepatoblastoma, calcifying nested stromal-epithelial tumor, undifferentiated embryonal sarcoma, and other small round cell tumors, as well as the fibrolamellar variant of hepatocellular carcinoma. This distinction is critical because an accurate therapeutic approach requires a correct diagnosis.

Desmoplastic small round cell tumor of the pleura with brain metastasis: A case report and literature review

Introduction: Desmoplastic small round cell tumor (DSRCT) is a rare and aggressive mesenchymal neoplasm characterized by a chromosomal translocation involving the EWSR1 and WT1 genes. It typically arises in intra-abdominal tissues (i.e., mesentery, omentum, pelvic organs), and commonly spreads to regional lymph nodes, lungs, or liver, while central nervous system (CNS) metastasis is rare. Case Report: We present a unique case of DSRCT originating from the pleura in a young female, which was metastatic to intrathoracic and mediastinal tissue at diagnosis and later spread to the brain. The initial tumor samples exhibited characteristic histopathological features, including small round cells with minimal cytoplasm and indistinct borders embedded in a fibroblastic stroma. Notably, the brain metastasis demonstrated distinct histological characteristics, lacking the desmoplastic stroma observed in previous biopsies. Conclusion: This case underscores the diagnostic challenges associated with DSRCT, emphasizes the significance of early recognition and appropriate histological evaluation, and contributes to the limited literature on the histological features and metastatic behavior of this rare tumor.

B-cell Follicular Lymphoid Hyperplasia (Pseudolymphoma) of the Oral Cavity: A Diagnostic Quandary.

Pseudolymphoma is a reactive process involving lymphadenopathy, polyclonal proliferation of B or T-cells, simulating oral lymphoma. With its incidence being very rare, only four cases have been reported in oral cavity with the detailed immunocytochemical examination, which can be due to this entity's unawareness, underdiagnosis or overdiagnosis. It is prerogative to perform immunocytochemical investigations to prevent overdiagnosis as lymphoma, which can be debilitating to the patient. Wherein the treatment of pseudolymphoma initially includes topical or intralesional corticosteroid, antibiotics to surgical and radiotherapy based on its etiology. Herein, we discuss B-cell follicular lymphoid hyperplasia previously diagnosed as small round cell tumor.

Adamantinoma-like Ewing Sarcoma (ALES) May Harbor FUS Rearrangements : A Potential Diagnostic Pitfall.

Adamantinoma-like Ewing sarcoma (ALES) is a rare malignancy currently considered a variant of Ewing sarcoma with most known cases harboring EWSR1 rearrangements. Herein we present a series of 6 cases of EWSR1 -negative ALES. The tumors arose in the sinonasal tract (n=3), major salivary glands (submandibular gland=1; parotid=1), and anterior mediastinum (n=1) in patients ranging from 25 to 79 years of age. Most tumors were basaloid in appearance, growing in large nests separated by interlobular fibrosis without overt squamous pearls. However, 1 case closely resembled a well-differentiated neuroendocrine tumor with uniformly round nuclei, eosinophilic cytoplasm, and trabecular architecture. All cases were diffusely positive for pan-cytokeratin, p40 or p63, and CD99. A subset of cases showed diffuse reactivity for synaptophysin, including 1 sinonasal tumor which also demonstrated sustentacular S100 protein expression. Molecular testing showed FUS rearrangements in all cases. Gene partners included known ETS family members FEV (n=2) and FLI1 (n=1). Our results expand the molecular diagnostic considerations for ALES to include FUS rearrangements. We also show that ALES may harbor FUS :: FLI1 fusion, which has not been previously reported in the Ewing family of tumors. Furthermore, ALES may show unusual histologic and immunophenotypic features that can overlap with olfactory carcinoma including S100-positive sustentacular cells. ALES should be considered in the diagnostic differential of small round cell tumors and tumors with neuroendocrine differentiation with immunohistochemical workup to include p40 and CD99/NKX2.2.

Childhood pilomatrixoma mimicking malignant small round blue cell tumor with positivity for CD99: Potential pitfall in cytology.

Pilomatrixoma is a relatively rare benign skin appendageal tumor, often presenting in the pediatric age group as a nodular lesion and most commonly involving the head and neck, making it amenable to primary fine needle aspiration (FNA) diagnosis. We report the clinical and histopathological findings of two cases of pilomatrixoma in children, both of which were initially misdiagnosed as small round blue cell tumors due to high cellularity and misinterpretation of the proliferating basaloid cells. Histopathology revealed basal cell proliferation and mitoses indicating that they were progressive, early lesions. The first case showed membranous positivity for CD99 which prompted a diagnosis of Ewing sarcoma. Awareness of the morphological spectrum including positivity for CD99 and careful evaluation of cell block histology could have averted the misdiagnosis. Pilomatrixoma should be included as an important differential diagnosis when faced with primitive-appearing cells on FNA, especially in children with mass lesions in the head and neck region.

Unmasking the great imitators-noninfectious conditions masquerading as spinal tuberculosis in a developing country: A single-center case series analysis

The diagnosis of spinal tuberculosis often relies on clinical, radiological, and laboratory findings, particularly in resource-constrained settings. However, numerous noninfectious conditions exhibit similar clinical and radiological features to spinal tuberculosis, leading to potential misdiagnosis in the absence of microbiological or histopathological confirmation. This study aims to present a case series from a developing country, highlighting noninfectious conditions that mimic spinal tuberculosis. A retrospective analysis was conducted on hospital records and imaging of patients diagnosed with spinal tuberculosis, lacking microbiological or histopathological evidence, and unresponsive to empirical antitubercular treatment. Patients displaying noninfectious conditions resembling spinal tuberculosis upon further investigation were included. Clinical and radiological findings of these patients were thoroughly analyzed. Among a total of 23 patients observed over a 6-year period (2015-2020), various noninfectious conditions were identified as mimickers of spinal tuberculosis. These conditions included vertebral body haemangioma, ankylosing spondylitis (with or without Andersson lesion), rheumatoid pannus, osteoid osteoma, cystic hygroma, multiple myeloma, vertebral metastasis, malignant small round-cell tumor, pancreatic pseudocyst, esophageal duplication cyst, Modic changes in degenerative disc disease, Paget's disease, and psoas hematoma. Noninfectious spinal conditions can masquerade as spinal tuberculosis, underscoring the importance of obtaining a definitive tissue diagnosis before initiating antitubercular treatment. Particular attention should be given to features such as central lesions and the absence of soft tissue involvement in suspected cases of spinal tuberculosis, warranting a careful reconsideration of the diagnosis.