Rare Tumor Type Research Articles

Surgical resection of retinoblastoma-associated bladder leiomyosarcoma during pregnancy: a case report

BackgroundManagement of a bladder tumor during pregnancy is an uncommon clinical situation. Leiomyosarcoma of the urinary bladder is a rare histological type of bladder tumor and a rare secondary cancer in survivors of retinoblastoma (RB). However, there has been no report of RB-associated bladder leiomyosarcoma during pregnancy.Case presentationA 37-year-old pregnant woman with a medical history of RB in infancy presented with gross hematuria at the 17th week of gestation. Cystoscopy revealed a 40-mm papillary tumor on the left lateral wall of the urinary bladder. At the 25th week of gestation, she underwent transurethral resection of the bladder tumor, and the pathological diagnosis was bladder leiomyosarcoma with loss of RB1 expression. At the 31st week of gestation, she gave birth by caesarean section. One month after the delivery (to allow for involution of the uterus), she underwent partial cystectomy, and the specimen contained no residual leiomyosarcoma tissue.ConclusionsWe have reported a case of RB-associated bladder leiomyosarcoma that was successfully treated during and after pregnancy.

An unexpected intrabdominal discovery: a mesenteric desmoid tumor with small bowel obstruction. Case report and literature review

This case report describes a 54-year-old man who presented with abdominal discomfort, nausea, early satiety, and constipation. A CT scan revealed a large mass infiltrating the mesentery and close to bowel loops, raising suspicion of intestinal sub-occlusion. Urgent surgery was performed, resulting in a segmental jejunum resection to remove the identified mesenteric mass. Histological examination revealed a diagnosis of desmoid fibromatosis which is a rare type of soft tissue tumor with borderline malignancy that can cause bowel obstruction when it develops intra-abdominally. It is often associated with genetic predispositions and risk factors such as previous surgery and pregnancy. The case highlights the importance of considering a patient's surgical history when encountering desmoid fibromatosis to determine the most appropriate treatment approach.

Comprehensive study of clinical features, prognostic factors, and survival in patients with pancreatic solid pseudopapillary neoplasms based on the 2019 WHO classification.

Pancreatic solid pseudopapillary neoplasms (pSPNs) are a rare tumor type with a limited understanding of their clinical characteristics and survival outcomes. We aimed to investigate potential prognostic factors among the existing clinical features in patients diagnosed with pSPN. For this study, we utilized data from the Surveillance Epidemiology and End Results (SEER) database, specifically selecting patients with a histology type of pSPN from the years 2000 to 2019. Subsequently, we conducted both univariate and multivariate Cox regression analyses in a systematic manner to identify potential prognostic factors associated with overall survival (OS) and cancer-specific survival (CSS) in the selected group of patients. To assess the disparity in OS and CSS among different clinical features and treatments, Kaplan-Meier curves were generated. Furthermore, utilizing the results obtained from the multivariate analysis, we developed a nomogram predictive model to effectively forecast the prognosis of patients diagnosed with pSPN. Calibration plots were presented to demonstrate the predictive accuracy and reliability of the nomogram predictive model. The study comprised a total of 433 participants, with 85.7% of the patients diagnosed with pSPN being female and the remaining 14.3% being male. The Kaplan-Meier curves indicated that patients with pSPN who underwent primary tumor resection (PTR) and those who were younger than 70years old had significantly improved OS and CSS compared to those who did not undergo PTR or were aged 70years or older, respectively (P < 0.001). Male patients diagnosed with pSPN exhibited poor OS compared to female pSPN patients (P = 0.015). The multivariate Cox regression analysis indicated that age (OS: HR = 1.055, 95% CI = 1.027-1.084, P < 0.001. CSS: HR = 1.054, 95% CI = 1.019-1.091, P = 0.002) and PTR (OS: HR = 6.074, 95% CI = 1.922-19.194, P = 0.002. CSS: HR = 4.912, 95% CI = 1.188-20.312, P = 0.028) were independent prognostic factors for both OS and CSS. Moreover, tumor size (≥ 5 vs < 5cm CSS: HR = 4.788, 95% CI = 1.012-22.661, P = 0.048) was an independent prognostic factor for CSS. The independent prognostic factors identified through the multivariate Cox regression analysis were utilized to construct a nomogram model for predicting both OS and CSS in patients with pSPN. The accuracy of the nomogram model was visually testified by the calibration plot with acceptable predictive performance. Although the majority of patients diagnosed with pSPN are females, it was observed that male patients tend to have poorer OS compared to their female counterparts. The independent prognostic factors identified in the study were age and PTR, which were associated with both OS and CSS. Tumor size was an independent prognostic factor for CSS. Patients who underwent PTR exhibited improved OS and CSS outcomes. The developed nomogram and corresponding reference table provided promising prognostic predictions for pSPN outcoms, serving as a valuable resource for clinicians and patients alike.

The characteristics of invasive cardiac lipoma: case report and literature review.

Invasive cardiac lipoma is a rare type of primary cardiac tumor that is composed of adipose tissue but infiltrating the adjacent structures. It is a benign tumor that can cause significant morbidity and mortality due to its size and location within the heart. We describe a giant invasive intracardiac lipoma across atrial wall extending to the ascending aorta and the superior vena cava. This review will provide an overview of invasive cardiac lipoma, including its clinical presentation, diagnosis, and management.

Diagnostic experience of intravenous leiomyomatosis with emphasis on conventional ultrasonography imaging: a single-center study.

Intravenous leiomyomatosis (IVL) is a rare and aggressive tumor type that has the potential to extend into the inferior vena cava (IVC) and is susceptible to be misdiagnosed and neglected. Despite its clinical significance, there is a paucity of research that has focused on the specific manifestations of IVL on ultrasonography. Therefore, this study aims to systematically analyze the specific ultrasound features of IVL and augment its diagnostic accuracy. Prospective inclusion was granted to patients admitted to our hospital between December 2016 and March 2021 for an IVC-occupying lesion. Multi-modal ultrasonography, encompassing gray-scale and color Doppler, was conducted. Lesions were categorized as IVL or non-IVL based on pathological or follow-up data. Two ultrasound sonographers with over 5 years of experience read and recorded ultrasound data for all lesions, which were subsequently comparatively analyzed to identify specific signs of IVL. A total of 284 patients diagnosed with IVC-occupying lesions were included in the study. The lesion types comprised of IVL (n=67, 23.6%), IVC thrombus (n=135, 47.5%), tumor thrombus of renal carcinoma involving the IVC (n=35, 12.4%), tumor thrombus of liver carcinoma involving the IVC (n=24, 8.5%), leiomyosarcoma of the IVC (n=14, 4.9%), and tumor thrombus of adrenocortical adenocarcinoma (n=9, 4.1%). The presence of "sieve hole" and "multi-track" signs was observed in 20 IVL lesions under the grey-scale modality, while both signs were absent in the non-IVL group (P<0.01). The study found no statistically significant differences in the presentation of "sieve hole" and "multi-track" signs under the grey-scale and color Doppler modalities in cases of intravascular lithotripsy (IVL) (P>0.05). Using these two signs as diagnostic criteria for IVL, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), miss rate, misdiagnosis rate, and accuracy were determined to be 29.9%, 100%, 100%, 82.2%, 70.1%, 0, and 83.5%, respectively (AUC ROC=0.649; 95%CI: 0.537-0.761). IVL exhibits distinct ultrasound presentations, including "sieve hole" and "multi-track" signs, which demonstrate high specificity and accuracy as diagnostic indicators. Furthermore, these signs are corroborated by pathological evidence and effectively distinguish IVL from other lesions occupying the IVC.

An Effective Primary Treatment Using Radiotherapy in Patients with Eyelid Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a rare type of neuroendocrine tumor. Palpebral localization represents 2.5% of MCCs. Surgery is not always possible due to the localization or comorbidities of elderly patients. We hypothesized that radiotherapy (RT) alone could be a curative treatment in patients contraindicated for oncological surgery. We performed a retrospective monocentric study of patients with localized eyelid MCC treated with curative intent using curative radiotherapy. Overall, 11 patients with histologically confirmed eyelid MCC were treated with curative radiotherapy. The median age was 77 years old (range: 53-94). Curative RT was decided mainly due to difficult localization and significant co-morbidities. The median lesion dose was 57 Gy (range: 47-70). Most patients had adjuvant lymph nodes irradiation with a median dose of 50 Gy (n = 9; 82%). The median follow-up was 62 months (6-152 months). None of the seven deaths were MCC-related. None of our patients relapsed during follow-up. Side effects related to radiotherapy were mild (no grade ≥ 2) and rare (n = 3, 21%). Our data suggest that curative radiotherapy is an effective and safe treatment for Merkel cell carcinoma of the eyelid and periocular region. Radiotherapy alone allows limiting the aesthetic and functional sequelae in elderly and comorbid patients who are contraindicated for oncological surgery.

Extracranial Facial Nerve Schwannoma-Histological Surprise or Therapeutic Planning?

Schwannomas (neurilemomas) are benign, slow-growing, encapsulated, white, yellow, or pink tumors originating in Schwann cells in the sheaths of cranial nerves or myelinated peripheral nerves. Facial nerve schwannomas (FNS) can form anywhere along the course of the nerve, from the pontocerebellar angle to the terminal branches of the facial nerve. In this article, we propose a review of the specialized literature regarding the diagnostic and therapeutic management of schwannomas of the extracranial segment of the facial nerve, also presenting our experience in this type of rare neurogenic tumor. The clinical exam reveals pretragial swelling or retromandibular swelling, the extrinsic compression of the lateral oropharyngeal wall like a parapharyngeal tumor. The function of the facial nerve is generally preserved due to the eccentric growth of the tumor pushing on the nerve fibers, and the incidence of peripheral facial paralysis in FNSs is described in 20-27% of cases. Magnetic Resonance Imaging (MRI) examination is the gold standard and describes a mass with iso signal to muscle on T1 and hyper signal to muscle on T2 and a characteristic "darts sign." The most practical differential diagnoses are pleomorphic adenoma of the parotid gland and glossopharyngeal schwannoma. The surgical approach to FNSs requires an experienced surgeon, and radical ablation by extracapsular dissection with preservation of the facial nerve is the gold standard for the cure. The patient's informed consent is important regarding the diagnosis of schwannoma and the possibility of facial nerve resection with reconstruction. Frozen section intraoperative examination is necessary to rule out malignancy or when sectioning of the facial nerve fibers is necessary. Alternative therapeutic strategies are imaging monitoring or stereotactic radiosurgery. The main factors which are considered during the management are the extension of the tumor, the presence or not of facial palsy, the experience of the surgeon, and the patient's options.

Mesenteric Cyst of Mesothelial Origin in Young Women: Literature Review and Case Report

Introduction: The mesenteric cyst is a rare type of abdominal tumor in the adult and pediatric population1, the mesothelial cysts are more frequent in young women 2,3, there are mainly 3 forms of clinical presentation4. The asymptomatic clinical presentation is the most frequent and is diagnosed incidentally in complementary tests or surgeries5. Clinical case: A 38-year-old woman diagnosed with a mesocolon-dependent mesenteric cyst of mesothelial origin at the splenic angle level, the triphasic abdominopelvic CT scan reported an 11x11 cm cyst with a volume of 403 cc, the biopsy reported a simple mesothelial cyst. Complete removal of the tumor was performed using a laparoscopic approach. Conclusion: The treatment of choice for tumors of the mesentery is the complete removal of the tumor, the mere aspiration of its contents or partial resection is doomed to recurrence 6.

Primary intracranial sarcomas: a clinicopathological investigation.

The purpose of this study is to present a series of primary intracranial sarcomas (PIS), a rare type of tumor of the central nervous system, in order to improve our understanding of the disease. These tumors are heterogeneous and prone to recurrence after resection, exhibiting a high mortality rate. As PIS has yet to be understood and studied on a large scale, it is vital for further evaluation and research. Our study included 14 cases of PIS. The patients' clinical, pathological, and imaging features were retrospectively analyzed. Additionally, targeted DNA next-generation sequencing (NGS) was applied for the 481-gene panel to detect gene mutations. The average age for PIS patients was 31.4 years. Headache (7, 50.0%) was the most common symptom leading to the hospital visit. Twelve cases had PIS located in the supratentorial area and two in the cerebellopontine angle region. The maximum tumor diameter ranged from 19.0mm to 130.0mm, with an average diameter of 50.3mm. Pathological types of tumors were heterogeneous, with chondrosarcoma being the most common, followed by fibrosarcoma. Eight of the 10 PIS cases that underwent MRI scanning showed gadolinium enhancement; 7 of these cases were heterogeneous, and 1 of them was garland-like. Targeted sequencing was performed in two cases and identified mutations in genes such as NRAS, PIK3CA, BAP1, KDR, BLM, PBRM1, TOP2A, DUSP2, and CNV deletions of SMARCB1. Additionally, the SH3BP5::RAF1 fusion gene was also detected. Of the 14 patients, 9 underwent a gross total resection (GTR), and 5 chose subtotal resection. Patients who underwent GTR displayed a trend toward superior survival. Among the 11 patients with available follow-up information, one had developed lung metastases, three had died, and eight were alive. PIS is extremely rare compared to extracranial soft sarcomas. The most common histological type of intracranial sarcoma (IS) is chondrosarcoma. Patients who underwent GTR of these lesions showed improved survival rates. Recent advancements in NGS aided in the identification of diagnostic and therapeutic PIS-relevant targets.

Validation of miRNAs as diagnostic and prognostic biomarkers, and possible therapeutic targets in medullary thyroid cancers.

Medullary thyroid cancer (MTC) is a rare type of neuroendocrine tumor that produces a hormone called calcitonin (CT). Thyroidectomy is the preferred treatment for MTC, as chemotherapy has been shown to have limited effectiveness. Targeted therapy approaches are currently being used for patients with advanced, metastatic MTC. Several studies have identified microRNAs, including miR-21, as playing a role in the development of MTC. Programmed cell death 4 (PDCD4) is a tumor suppressor gene that is an important target of miR-21. Our previous research has shown that high levels of miR-21 are associated with low PDCD4 nuclear scores and high CT levels. The aim of this study was to investigate the potential of this pathway as a novel therapeutic target for MTC. We used a specific process to silence miR-21 in two human MTC cell lines. We studied the effect of this anti-miRNA process alone and in combination with cabozantinib and vandetanib, two drugs used in targeted therapy for MTC. We analyzed the effect of miR-21 silencing on cell viability, PDCD4 and CT expression, phosphorylation pathways, cell migration, cell cycle, and apoptosis. Silencing miR-21 alone resulted in a reduction of cell viability and an increase in PDCD4 levels at both mRNA and protein levels. It also led to a reduction in CT expression at both mRNA and secretion levels. When combined with cabozantinib and vandetanib, miR-21 silencing did not affect cell cycle or migration but was able to enhance apoptosis. Silencing miR-21, although not showing synergistic activity with TKIs (tyrosine kinase inhibitors), represents a potential alternative worth exploring as a therapeutic target for MTC.

5‑aminiolevulinic acid induces a radiodynamic effect with enhanced delayed reactive oxygen species production under hypoxic conditions in lymphoma cells: An invitro study.

Primary central nervous system lymphoma (PCNSL) is a rare and aggressive type of intracranial tumor. However, PCNSL is radiosensitive; thus, whole-brain radiotherapy (WBRT) is often selected as an alternative consolidation therapy. WBRT-related delayed neurotoxicity can affect the quality of life of the elderly. 5-aminolevulinic acid (ALA) is a natural precursor of heme and has been widely used as a live molecular fluorescence marker in brain tumor surgery. Experimental studies have demonstrated that combination therapy with 5-ALA and ionizing irradiation (IR), denoted radiodynamic therapy (RDT), resulted in tumor suppression in cancer, including glioma, melanoma, colorectal cancer, prostate cancer, breast cancer and lung cancer; however, to the best of our knowledge, this method has not been investigated in lymphoma. The present study aimed to investigate the radiodynamic effect of 5-ALA on lymphoma cells in vitro. The synthesis of 5-ALA-induced protoporphyrin IX (PpIX) was assessed under normal and hypoxic conditions in lymphoma cells (Raji, HKBML and TK). Subsequently, the radiodynamic effect of 5-ALA was evaluated using a colony formation assay and reactive oxygen species (ROS) production after RDT was examined using flow cytometry. Finally, the mitochondrial density in the lymphoma cells was evaluated. Lymphoma cells exhibited a high accumulation of 5-ALA-induced PpIX in the flow cytometric analysis, and a decrease in the surviving fraction under IR in cells with 5-ALA treatment compared with cells not treated with 5-ALA in the colony formation assay under normal and hypoxic conditions. Although ROS production 12 h after IR was increased compared with that immediately after IR (0 h), pretreatment with 5-ALA enhanced the delayed ROS production in each lymphoma cell line under normoxic conditions. Raji and TK cells exhibited an increase in ROS production 12 h after IR compared with that at 0 h in the 5-ALA-untreated cells under hypoxic conditions. Raji, HKBML and TK cells exhibited an increase in ROS production 12 h after IR compared with that at 0 h in the 5-ALA-treated cells, while TK cells exhibited enhancement of ROS production 12 h after IR in 5-ALA-treated cells compared with 5-ALA-untreated cells under hypoxic conditions. Other studies have demonstrated that impaired mitochondria damaged by IR produce ROS via the metabolic process, then damage the rest of the surrounding normal mitochondria, consequently propagating oxidative stress within tumor cells and leading to cell death. Thus, we hypothesized that the propagating oxidative stress after IR was associated with mitochondrial density in tumor cells. Namely, high accumulation of 5-ALA-indcued PpIX may promote ROS production in mitochondria of tumor cells after IR, and suppress the cell surviving fraction via the propagation of oxidative stress. In the colony formation assay, Raji cell colony formation was suppressed by RDT with 5-ALA. Simultaneously, the mitochondrial density in the Raji cells was higher than that in other cell lines. Pretreatment with 5-ALA enhanced delayed ROS production after IR in lymphoma cells under normoxic conditions. Under hypoxic conditions, only TK cells exhibited enhancement of ROS production 12 h after IR in the 5-ALA-treated group compared with the 5-ALA-untreated group. Although further studies evaluating the effect of hypoxic conditions in lymphoma cells are needed, the results suggested that RDT with 5-ALA could suppress colony formation under normal and hypoxic conditions in lymphoma cells. Therefore, RDT with 5-ALA is a potential treatment option for PCNSL.

Giant cell tumor of clivus: a rare case report and review of literature

Clival giant cell tumors (GCTs) are an extremely rare type of tumor, with only 13 cases reported to date. Despite being histologically considered benign, these tumors can be locally aggressive and have a high rate of local recurrence, as well as the potential for distant metastasis. Due to their rarity and the difficulty of treating them due to their critical location, the ideal treatment protocol for managing clival GCTs remains controversial. The present report describes a 22-year-old female who experienced ptosis on her right eye and visual disturbance for one month. Magnetic resonance imaging (MRI) revealed a large, heterogenous, lobulated mass lesion arising from the clivus, extending anteriorly and compressing the optic chiasm and optic tract, with both parasellar extension and extension into the sphenoid sinus. An endoscopic endonasal trans-sphenoidal procedure was performed to excise the lesion. Post-operative MRI revealed residual disease, so a revision surgery was done using a combined microscopic and endoscopic procedure. Following surgery, the patient was given Denosumab for one year as well as has been symptom-free for the past 18 months of follow-up. This report contributes to the limited literature on the GCTs involving the clivus.

Pure testicular choriocarcinoma with gastrointestinal metastasis and paraneoplastic symptoms: a case report

BackgroundPure testicular choriocarcinoma is a rare type of non-seminomatous germ cell tumor extremely poor prognostic with the tendency to bleed at the metastatic site. At the time of the diagnosis, 70% of patients have metastatic lesions. Depending on the site of the metastasis, symptoms vary. Gastrointestinal involvement is seen in less than 5% of cases, mostly in the duodenum.Case presentationWe present a 47 years old male with testicular choriocarcinoma involving the jejunum, lung, liver, and kidney presenting with acute abdominal pain, melena, and dyspnea with some paraneoplastic symptoms. The patient had increased, severe and constant pain in the right lower quadrant for the previous four days. Additionally, he was complaining of nausea, vomiting, anorexia, and a history of melena for the last 10 days. Dyspnea on exertion, hemoptysis, and dry cough were the symptoms he was suffering from, for almost one year. The patient’s general appearance was pale, ill, and thin with 10 kg of weight loss during the last some months. The computed tomography (CT) scan reported multiple metastatic lesions in both liver lobes and the left kidney. Pathologic study of the samples of small bowel lesions showed metastatic choriocarcinoma. Following the patient had been referred to an oncologist to start the chemotherapy regime. Finally, the patient has expired after 40 days of his first admission.ConclusionsTesticular choriocarcinoma is a rare but fatal malignancy among young men. Gastrointestinal metastases are infrequent involvement represented by melena and acute abdominal pain, obstruction, and mass. Physicians should consider it as a differential diagnosis for acute abdomen and gastrointestinal bleeding causation.

Demographic and socioeconomic factors in poorly differentiated Sertoli-Leydig cell tumors: A National Cancer Database analysis.

e17568 Background: Poorly differentiated Sertoli-Leydig cell tumor (PD-SLCT) is a rare and aggressive type of ovarian cancer. This cancer has a 5-year cancer-specific survival rate of 43.9% with a chance of early relapse of approximately 2-3 years following initial diagnosis. Given the rarity of the cancer, potential risk factors could offer providers and patients more information about the epidemiology. The National Cancer Database (NCDB) was analyzed to study the demographic factors in patients diagnosed with PD-SLCT. Methods: Cases of PD-SLCT (N = 405) in the NCDB from 2004 – 2020 were determined via histology (ICD-O-3 code = 8631). A retrospective cohort analysis using demographic factors such as race, age, sex, insurance status, urban/rural, facility type, and Charleson-Deyo score were analyzed by descriptive statistics and incidence trends were interpreted in regression analysis. Results: A total of 405 patients with a diagnosis of PD-SLCT were identified in the database with a steady incidence of patients diagnosed per year (mean = 23.8 per year, R2 = 0.1). The average age of diagnosis was 41.7 years (SD = 20.1, range = 8 – 90 years). The majority of patients were non-Hispanic (82.5%) and White (69.4 %). More patients were in the top quartile of income earners (30.8.%) and were privately insured (56.8%) relative to those who were uninsured or insured by Medicare/Medicaid (43.2%). A greater percentage of patients with PD-SLCT were treated at a non-academic program (54.0%) compared to an academic/research program (46.0%). More patients lived in metropolitan counties with a population greater than 1 million (59.8%) versus less populated metropolitan communities or urban communities (40.2%). Most individuals (84.2%) had Charlson-Deyo comorbidity scores of 0. Conclusions: This novel study of the NCDB addresses a significant knowledge gap on patients with PD-SLCT, as it provides demographic insight into this rare type of tumor and the patients who are diagnosed with it. Most PD-SLCT patients tend to be in the premenopausal age, as previously described in literature. Most patients are White and non-Hispanic. This is the first time the socioeconomic factors of PD-SLCT patients have been described in the literature: patients are more likely to be in the top income quartile, live in densely populated metropolitan areas, and be treated in a non-academic program. Further research is needed to better understand the impact of these factors on the diagnosis of, treatments utilized, and overall survival of patients with PD-SLCT to ensure that all patients receive the best possible care, regardless of their background.

Infrastructure for rare cancer in the Netherlands: Towards a comprehensive platform for early detection and diagnosis of rare cancers (FORCE).

TPS1612 Background: One in five patients with cancer has a rare type of tumor. For these patients, randomized controlled trials are often infeasible and, compared to patients with a more common tumor, their prognosis is poor due to late or incorrect diagnosis and fewer available treatment options. Moreover, most patients with rare cancer do not benefit yet from recent developments in ultrasensitive profiling of circulating cell-free DNA (USccfDNA). In some more common cancers, USccfDNA has improved early primary detection, detection of minimal residual disease (MRD), and early recurrence. The information needed to apply USccfDNA in most rare cancers is lacking, which delays innovation of personalized treatments and deprives these patients of a chance for a better outcome. FORCE aims to improve treatment outcomes for patients with rare cancers by systematically collecting their clinical data, tumor tissue and peripheral blood components. Methods: Retrospectively and prospectively collected data are used to build a data warehouse that provides comprehensive insight into the long-term biology of a rare cancer. The data warehouse is visualized as a train. The locomotive represents the infrastructure, which uses web-based tools for FAIR, comprehensive, multidisciplinary, data collection, workflow support and storage. The built-in “Call-me-in” module enables anyone who has been diagnosed with a rare tumor to collaborate and contribute their data to FORCE under strict privacy regulations. Each train carriage represents the data concerning a coherent set of rare tumor types, reflecting the ten domains defined by European Reference Network (ERN) Rare Adult Solid Cancers (EURACAN). Neuroendocrine neoplasms (NEN, EURACAN domain 4) is the first carriage joined to the FORCE infrastructure and serves as a use-case for the FORCE infrastructure. Currently, the first patients are being included in the prospective multicenter clinical biobank that makes optimal use of existing (data) infrastructure. A legal joint data registry agreement has been developed to enable a shared clinical biobank with a federated structure, and facilitate sharing of data and samples among participating institutes. FORCE-NEN has also developed a governance structure for the carriage and its relation to the central FORCE infrastructure. Both documents will serve as an adaptable template for other carriages. FORCE is now available for further international collaboration. We established a unique infrastructure in the Netherlands that combines the collection of clinical data, tumor and peripheral blood components of patients with a rare tumor, starting with NEN. The FORCE infrastructure will enable studies to optimize early primary detection, detection of minimal residual disease (MRD), and early recurrence by USccfDNA assays and facilitate future clinical trials.

Comprehensive analysis of molecular characteristics, TMB, and MSI in Chinese patients with neuroendocrine neoplasms.

e16236 Background: Neuroendocrine neoplasms (NENs) is a heterogeneous and rare tumor type. To date, most genomic profiling studies on NENs have mainly focused on pancreatic NENs (PanNENs), less is known about nonpancreatic NENs (NP-NENs). We explored the molecular characteristics, tumor mutational burdens (TMB) and microsatellite instability (MSI) in Chinese NENs patients based on different primary lesions to discover genomic profiles. Methods: We retrospectively analyzed molecular characteristics, TMB and MSI in 155 Chinese NENs patients from laboratory of Simcere Diagnosis (Nanjing, China) during 2019 to 2022. Tissue and plasma samples were profiled using the 551-gene panel next-generation sequencing (NGS). Results: The median age of 155 patients was 61 years old (range, 22-85 years old), the male to female ratio was 1.63:1. 118 cases with known primary lesions could be divided into PanNENs(n=22) and NP-NENs (n=96). There were no differences in age and ratio of PanNENs and NP-NENs. The most common SNV and indel mutations were TP53(23%), DAXX (22.7%), MEN1 (18.2%), KRAS (18.2%), ATM (13.6%), SMAD4 (13.6%) and TSC2 (13.6%) in PanNENs, in which CDK4/6 amplifications were often detected (31.8%, 27.3%). Gene fusions rarely occurred in this cohort. For NP-NENs, we identified TP53 (58.3%), MUC16 (29.2%), RB1(31.3%), LRP1B (22.9%), SMARCA4 (10.4%), SPTA1 (10.4%) and FAT3 (10.4%) as the most common SNV and indel mutations, with MYC (26%) and CDK4 (15.6%) amplifications. CCNE1 high-level amplification was especially common in digestive system NENs. Multiple gene fusions were found in NP-NENs. 13/155 (8.4%) patients carried pathogenic/likely pathogenic germline mutations in MUTYH(n=3), MSH3 (n=2), FANCG (n=2), RAD51D (n=1), CDH1 (n=1), ERCC3 (n=1), ATM (n=1), MEN1 (n=1), RECQL4 (n=1), most of them were associated with DNA damage repair (DDR) pathway. 92.3% (12/13) patients were NP-NENs with only one PanNENs harboring MUTYH germline mutation. 155 NEN patients could be evaluated for TMB, 24 (15.5%) patients had TMB≥10Muts/Mb, 7% (10/24) were lung-derived NENs. TMB was significantly higher in NP-NENs compared to PanNENs (4.26 muts/Mb vs. 2.13muts/Mb, P&lt;0.01). 138 patients could be evaluated for MSI status, only one NEN whose primary site was liver was MSI-H, the others were all MSS. Conclusions: Our data showed that PanNENs and NP-NENs had different mechanisms of tumorigenesis: DAXX and MEN1 alterations commonly identified in PanNENs primarily mediate DDR and PI3K-mTOR pathway. Frequent TP53, RB1 and CCNE1 aberrations in NP-NENs were associated with CDK signaling pathway. TMB was low in almost all NENs exclude lung-derived NENs. It revealed distinct drivers in different subtypes, potentially being used as relevant therapeutic targets.

Racial and ethnic differences in thymic epithelial tumors: A single-institution retrospective analysis.

e20649 Background: Thymic epithelial tumors (TETs) are a rare, heterogeneous group of malignancies that arise from the thymus. While the etiology of TETs remains unknown, variation in incidence rates amongst racial/ethnic groups has raised the possibility of germline predispositions. Unfortunately, due to the rarity of this disease, there is a limited understanding of the impact of race/ethnicity on tumor characteristics and treatment outcomes for TET patients. We sought to characterize patient/tumor data and investigate treatment outcomes based on race and ethnicity. Methods: We conducted a single-institution, retrospective database analysis of TET patients evaluated at the IUSCCC from 1979 – 2021 from which clinical annotations were available for 477 thymoma and 164 thymic carcinoma (TC) patients. We identified 112 thymoma and 35 TC patients who were deemed to have sufficient data for evaluation of racial/ethnic characteristics. Demographic/clinical variables and therapeutic interventions, including treatment outcomes, were analyzed. Data was compiled and analyzed using descriptive statistics and the Kaplan Meier method for survival analysis via GraphPad Prism software. Results: Of the 112 thymoma patients, 29 thymoma patients presented with de novo metastatic disease at the time of diagnosis. The median age at the time of diagnosis of all patients revealed a statistically significant difference between White and Black TET patients (53.0 v. 42.0 years, *p = 0.0195). There was a trend towards significance when median age of diagnosis between White and Asian TET patients was compared (53.0 v. 48.0 years, p = 0.0633, NS). Advanced histologic subtypes, include B3 and TC, appeared predominantly in Asian and Black patients at 77.7% and 56.3%, respectively, compared to White patients (44.9%), though the finding was not statistically significant. No statistically significant differences between racial/ethnic groups regarding progression free survival for unresectable or metastatic disease were observed, regardless of histology. There was a non-significant difference in recurrence free survival for resectable thymoma in White (30.0 months) and Asian/Pacific Islander (47.0 months) patients compared to Black patients (24.0 months). Conclusions: Overall, this analysis suggests differences in the median age of diagnosis for patients with thymic malignancies based on race, raising the possibility of inherent biologic differences driving oncogenesis and symptoms at the time of presentation. While no statistically significant differences in treatment outcomes were found based on race and ethnicity, Black patients appeared to experience shorter times to recurrence after definitive surgery. Further studies to understand the mechanistic differences driving tumorigenesis and potential disparities in treatment outcomes are greatly needed in this rare tumor type.

The impact of hispanic ethnicity in presentation and outcomes of patients with synovial sarcoma.

e18682 Background: Synovial sarcomas (SS) harbor a specific, balanced, reciprocal translocation t(X;18) leading to the oncogenic SS18-SSX fusion. It accounts for 5-10% of all soft tissue sarcomas, and there is a lack of information regarding the impact of race and ethnicity on its presentation and outcomes. Florida is currently not included in the SEER database, and it is the US's ninth-most diverse population, with a diversity index of 64.1% and with the sixth-highest Hispanic population among all states. Sylvester Comprehensive Cancer Center (SCCC) and Memorial Healthcare System (MHS) are two large oncology centers in South Florida that provide care for this rare type of tumor. We aimed to identify the impact of Hispanic ethnicity in SS. Methods: We retrospectively reviewed all patients with a confirmed diagnosis of SS between January 2003 and January 2022 in SCCC and MHS. All data were retrieved from electronic medical records. SPSS Statistics was utilized, Fisher exact test and log-rank test were used for analysis. A two-sided p &lt; 0.05 was considered statistically significant. Results: A total of 73 patients had a pathologically confirmed diagnosis of SS, with information regarding ethnicity, during the time period evaluated, 45.3% were Hispanic, and 54.7% were non-Hispanic. The Hispanic group was comprised mainly of female patients (66%) with a median age of diagnosis of 44 years old, these findings were similar in the non-Hispanic group, where 55% were women, and the median age at diagnosis was 42 years old. Fewer patients identified themselves as Black within the Hispanic group (3%) compared to the non-Hispanic (22%) (p = 0.016). The most common site of primary disease was the extremity in both groups (Hispanic 63% vs non-Hispanic 75%) (p = 0.384). Most tumors were diagnosed with a size bigger than 5cm (Hispanic 57% vs non-Hispanic 65%) (p = 0.577) and with pathology reporting a monophasic SS (Hispanic 45% vs non-Hispanic 50%) vs biphasic or poorly differentiated (p = 0.061). Non-Hispanics had more poorly differentiated tumors (Hispanic 3% vs non-Hispanic 17.5%) (p = 0.054). Hispanic patients did have fewer cases of metastatic disease at diagnosis (Hispanic 9% vs non-Hispanic 32%) (p = 0.023). The median overall survival (mOS) among Hispanic patients was not reached in our study, and mOS among the non-Hispanic patients was 5 years (p = 0.099). Conclusions: In our study, the patients more commonly presented with large tumors ( &gt; 5cm) in the extremity and monophasic histology, regardless of their ethnicity. Non-Hispanic patients more often had poorly differentiated tumors, metastatic disease at diagnosis, and a trend toward worse mOS. This study had limited power due to the limited number of patients, and further studies are needed to identify the presence of disease-related differences in these populations.

Expanding the spectrum of neoplasms harboring EWSR1:CREM fusion as detected by a real-world clinical genomics platform.

e15061 Background: Malignancies with various well-defined phenotypes and prognoses have been shown to possess gene fusions between Ewing Sarcoma Breakpoint Region 1 ( EWSR1) and one of the CREB family genes, specifically CREB1 and ATF1. However, less is known about neoplasms that harbor EWSR1:CREM rearrangements, which are thought to result in constitutive activation of CREM and subsequent dysregulation of oncogenes, such as BCL-2 family genes, EGFR1, and cyclins. EWSR1:CREM fusion has been identified in rare cases of angiomatoid fibrous histiocytoma, clear cell sarcoma, hyalinizing clear cell carcinoma of the head and neck, and intracranial myxoid mesenchymal tumor. Our study represents the largest to date and seeks to expand and further define the diversity of tumor subtypes that possess EWSR1:CREM fusions. Methods: Detection of EWSR1:CREM rearrangements by whole transcriptome sequencing was performed for &gt; 240,000 neoplasms submitted to Caris Life Sciences (Phoenix, AZ). Histological review of the identified tumors was performed by two board-certified pathologists (MGE, AER). Treatment and outcome information were collected, where available. Results: An EWSR1:CREM fusion was detected in 18 cases, which included one intracranial myxoid mesenchymal tumor, one mesothelioma, four hyalinizing clear cell carcinomas of the head and neck, two clear cell sarcomas, two small round and spindle cell sarcomas, and eight histologically malignant tumors having an epithelioid morphology. While the latter were in keeping with a disease entity recently reported in the medical literature (epithelioid neoplasm with predilection for mesothelial-lined cavities), several of these cases demonstrated unexpected neuroendocrine differentiation and were found at unusual sites, including the kidney, uterus, and cervical spine. Moreover, three cases had the features of squamous cell carcinoma. Surgical resection was performed in all patients, and pazopanib was utilized in two round and spindle cell sarcoma cases. This medication was shown radiographically to produce a partial response at 19 months and stable disease at 26 months, respectively, in heavily pretreated patients. Conclusions: By detecting an EWSR1:CREM rearrangement, molecular testing may aid in the diagnosis of a variety of rare tumor types, including a poorly understood malignant epithelioid neoplasm that arises in a variety of anatomic sites including mesothelial-lined cavities. Tumors harboring this fusion may ultimately be susceptible to treatment with tyrosine kinase inhibitor targeted therapy.

MANAGEMENT OF AN IMMATURE TERATOMA IN A YOUNG WOMAN DESIRING PREGNANCY : A CASE REPORT

Immature teratoma is a rare type of germ cell tumor that primarily affects young women and can present with diverse symptoms. We present a case of a 20-year-old female with a large abdominopelvic mass diagnosed as an immature teratoma. The patients chronic abdominopelvic pain and weight loss posed diagnostic challenges, but comprehensive diagnostic workup facilitated timely diagnosis and management. Radical surgery is the primary treatment option for immature teratomas, but alternative treatments such as chemotherapy may be appropriate in selected cases, particularly in young women with a desire to preserve fertility. A patient-centered approach is crucial for optimal outcomes. Further research is needed to determine the optimal chemotherapy regimen and duration of treatment for immature teratomas.