Case Of Sarcoma Research Articles

Detection of EWSR1 gene rearrangement by fluorescence in situ hybridization in bone and soft tissue tumors: clinical application evaluation and atypical signal analysis

Objective: To investigate the clinical application of EWSR1 gene rearrangement by fluorescence in situ hybridization (FISH) in bone and soft tissue tumors and to analyze the cases with atypical signal pattern. Methods: The cases detected for EWSR1 gene rearrangement by FISH in Beijing Jishuitan Hospital, Capital Medical University from 2014 to 2021 were collected, and the value of detecting EWSR1 gene rearrangement for diagnosing bone and soft tissue tumors was analyzed. The cases with atypical positive signals were further analyzed by next generation sequencing (NGS). Results: FISH using EWSR1 break-apart probe kit was successfully performed in 97% (205/211) of cases, 6 cases failed. Four of the 6 failures were due to improper decalcification, 1 case due to signal overlap caused by thick slices, and 1 case due to signal amplification and disorder. EWSR1 gene rearrangements were positive in 122 cases (122/205, 59%), atypical positive signal in 8 cases (8/205, 4%), and negative in 75 cases (75/205, 37%). In cases testing positive, the percentage of positive cells ranged from 34% to 98%, with 120 cases (120/122, 98%) showing a positive cell percentage greater than 50%. Among the 205 successfully tested cases, 156 cases were histologically diagnosed as Ewing's sarcoma, of which 110 were positive (110/156, 71%), 7 were atypical positive (7/156, 4%), and 39 were negative (39/156, 25%). Nine cases were histologically diagnosed as clear cell sarcoma of soft tissue, of which 6 were positive (6/9), 1 was atypical positive (1/9), and 2 were negative (2/9). Five cases were histologically diagnosed as extraskeletal myxoid chondrosarcoma, of which 2 were positive (2/5) and 3 were negative (3/5). Three cases were histologically diagnosed as angiomatoid fibrous histiocytoma, of which 2 were positive (2/3) and 1 was negative (1/3). Two cases were histologically diagnosed as myoepithelioma of soft tissue, of which 1 was positive (1/2) and 1 was negative (1/2). One case was histologically diagnosed as olfactory neuroblastoma with a positive result. The 29 other tumor cases including osteosarcoma, synovial sarcoma, and malignant melanoma and others were all negative. Basing on histology as the standard for diagnosis and considering atypical positive cases as negative, comparing with the 29 cases of other tumors as control group, the sensitivity for diagnosing Ewing's sarcoma through the detection of EWSR1 gene rearrangement was 71%, and the specificity was 100%; the sensitivity for diagnosing clear cell sarcoma of soft tissue was 67%, and the specificity was 100%; the sensitivity for diagnosing extraskeletal myxoid chondrosarcoma was 40%, and the specificity was 100%; the sensitivity for diagnosing angiomatoid fibrous histiocytoma was 67%, and the specificity was 100%; the sensitivity for diagnosing myoepithelioma of soft tissue was 50%, and the specificity was 100%; the sensitivity for diagnosing olfactory neuroblastoma was 100%, and the specificity was 100%. Four of 8 cases with atypical positive signals analyzed by NGS showed EWSR1 rearrangement, including EWSR1::FLI1 in one case of Ewing sarcoma, EWSR1::NFATC2 in one case of EWSR1::NFATC2-rearranged sarcoma, EWSR1::ATF1 in one case of clear cell sarcoma of soft tissue and EWSR1::NR4A3 in one case of extraskeletal myxoid chondrosarcoma. Conclusions: Detection of EWSR1 rearrangement by FISH is of utmost significance in the diagnosis of bone and soft tissue tumors. Cases with atypical positive signals should be further scrutinized, correlating with their histomorphology and verifying by NGS if necessary.

Myxoid Inflammatory Myofibroblastic Sarcoma: Clinicopathologic Analysis of 25 Cases of a Distinctive Sarcoma With Deceptively Bland Morphology and Aggressive Clinical Behavior.

The number of recognized sarcoma types harboring targetable molecular alterations continues to increase. Here we present 25 examples of a distinctive myofibroblastic tumor, provisionally termed "myxoid inflammatory myofibroblastic sarcoma," which might be related to inflammatory myofibroblastic tumor, and which occurred in 13 males (52%) and 12 females at a median age of 37 years (range: 7 to 79 years). Primary tumor sites were peritoneum (18 patients; 72%), paratesticular (2; 8%), chest wall (1), upper extremity (1), esophagus (1), retroperitoneum (1), and uterus (1). Nine peritoneal tumors (50%) were multifocal at presentation; all other tumors were unifocal. Tumors showed bland-to-mildly-atypical neoplastic myofibroblasts in a myxoid stroma, with prominent inflammatory infiltrates in 22 cases (88%). Most tumors showed delicate branching stromal vessels like those of myxoid liposarcoma, and most showed infiltrative growth through non-neoplastic tissue. Immunohistochemistry demonstrated expression of SMA (19/25 tumors; 76%), desmin (13/22; 59%), and CD30 (5/11; 45%), while ALK was expressed in 1 tumor (of 25; 4%) that was negative for ALK rearrangement. Sequencing of 11 tumors showed seven to harbor tyrosine kinase fusions (4 PDGFRB , 2 PML :: JAK1 , 1 SEC31A :: PDGFRA ). Two instead harbored hot spot KRAS mutations (G12V and Q61H), and 2 were negative for known driving alterations. Clinical follow-up was available for 18 patients (72%; median: 2.7 years; range: 4 mo-12.3 years). Nine patients (50%) were alive with no evidence of disease, 5 (28%) died of disease, and 4 (22%) were alive with disease. Seven patients (39%) experienced peritoneal relapse or distant metastasis. Two patients showed disease progression on conventional, nontargeted chemotherapy. The patient whose tumor harbored SEC31A :: PDGFRA was treated after multiple relapses with imatinib and sunitinib therapy, with progression-free periods of 5 and 2 years, respectively. Despite its bland appearance, myxoid inflammatory myofibroblastic sarcoma harbors a significant risk for disseminated disease, particularly when it occurs in the peritoneum. Targeted therapy could be considered for patients with disseminated disease.

Clinicopathological and molecular genetic analysis of 13 cases of primary retroperitoneal Ewing sarcoma

Retroperitoneal Ewing sarcomas (RES) are very rare and mostly described in case reports. The purpose of this study was to retrospectively analyze the clinicopathology, molecular characteristics, biological behavior, and therapeutic information of 13 cases of primary RES with immunohistochemical staining, fluorescence in situ hybridization, RT-PCR and NGS sequencing detection techniques. The thirteen patients included eight males and five females with a mean age of 34 years. Morphologically, the tumors were comprised of small round or epithelial-like cells with vacuolated cytoplasm (6/13,46 %) arranged in diffuse, nested (8/13,62 %) and perivascular (7/13,54 %) patterns. Unusual morphologic patterns, such as meningioma-like swirling structures and sieve-like structures were relatively novel findings. Immunohistochemical studies showed CD99 (12/13; 92 %), CD56 (11/13; 85 %), NKX2.2 (9/13; 69 %), PAX7 (10/11;91 %) and CD117(6/9;67 %) to be positive.12 cases (92 %) demonstrated EWSR1 rearrangement and 3 cases displayed EWSR1::FLI1 fusion by FISH. ERCC4 splice-site variant, a novel pathogenic variant, was discovered for the first time via RNA sequencing. With a median follow-up duration of 14 months (6 to 79 months), 8/13 (62 %) patients died, while 5/13(38 %) survived. Three cases recurred, and five patients developed metastasis to the liver (2 cases), lung (2 cases) and bone (1 case). RES is an aggressive, high-grade tumor, prone to multiple recurrences and metastases, with distinctive morphologic, immunohistochemical, and molecular genetic features. ERCC4 splicing mutation, which is a novel pathogenic variant discovered for the first time, with possible significance for understanding the disease, as well as the development of targeted drugs.

Primary epithelioid inflammatory myofibroblastic sarcoma of the brain with EML4::ALK fusion mimicking intra-axial glioma: a case report and brief literature review.

An aggressive subtype of inflammatory myofibroblastic tumor, epithelioid inflammatory myofibroblastic sarcoma occurs primarily inside the abdominal cavity, followed by a pulmonary localization. Most harbor anaplastic lymphoma kinase (ALK) gene rearrangements, with RANBP2 and RRBP1 among the well-documented fusion partners. We report the second case of primary epithelioid inflammatory myofibroblastic sarcoma of the brain, with a well-known EML4::ALK fusion. The case is notable for its intra-axial presentation that clinico-radiologically mimicked glioma.

Bone Sarcoma Survival in the US Military Health System: Comparison With the SEER Program.

Access to care is associated with cancer survival. The US Military Health System (MHS) provides universal health care to all beneficiaries. However, it is unknown whether survival among patients with bone sarcoma in a health system providing universal care is better than that in the general population. The aim of the study was to compare survival of patients with bone sarcoma in the US MHS with that of the US general population. The MHS data were obtained from the Department of Defense Automated Central Tumor Registry (ACTUR). The US general population data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) registry. Adult patients were defined as those aged 25 years or older with a histologically confirmed musculoskeletal bone sarcoma diagnosed from January 1, 1987, to December 31, 2013. Kaplan-Meier survival curves and multivariable Cox proportional hazards models were used to compare the overall survival of the two populations. The final analysis included 2,273 bone sarcoma cases from ACTUR and 9,092 bone sarcoma cases from SEER. ACTUR patients had significant lower 5-year all-cause death (hazard ratio = 0.72; 95% CI, 0.66 to 0.78) after adjustment for the potential confounders. ACTUR patients with bone sarcoma also exhibited significantly lower risk of all-cause death during the entire follow-up period than the SEER patients (hazard ratio = 0.75; 95% CI, 0.6 to 0.81). MHS beneficiaries with bone sarcoma may have longer survival than SEER patients. Our findings support the role of universal access to high-quality care in improving bone sarcoma outcomes.

An unusual case of primary splenic soft part alveolar sarcoma: case report and review of the literature with emphasis on the spectrum of TFE3-associated neoplasms

BackgroundAlveolar soft part sarcoma is a rare tumour of soft tissues, mostly localized in muscles or deep soft tissues of the extremities. In rare occasions, this tumour develops in deep tissues of the abdomen or pelvis.Case presentationIn this case report, we described the case of a 46 year old man who developed a primary splenic alveolar soft part sarcoma. The tumour displayed typical morphological alveolar aspect, as well as immunohistochemical profile notably TFE3 nuclear staining. Detection of ASPSCR1 Exon 7::TFE3 Exon 6 fusion transcript in molecular biology and TFE3 rearrangement in FISH confirmed the diagnosis.ConclusionWe described the first case of primary splenic alveolar soft part sarcoma, which questions once again the cell of origin of this rare tumour.

A case of primary cardiac intimal sarcoma with distant metastasis of the mandible

A case of primary cardiac intimal sarcoma with distant metastasis of the mandible

Complete resection of a giant intrapericardial cardiac synovial sarcoma

Synovial sarcoma of the heart is a rare tumor. Herein we would like to report a case of giant intrapericardial cardiac synovial sarcoma that originated from the right ventricle and grew outward near the diaphragm. After making adequate preoperative preparation, we performed the surgery as quickly as possible and resected the tumor completely. Based on the identification of the translocation on chromosome 18 rearrangement, the tumor can be diagnosed as a primary cardiac synovial sarcoma. Through this study, we aim to afford more information about cardiac synovial sarcomas as well as a reference for similar cases.

Analysis of 41 cases of non-metastatic Ewing's sarcoma in children

To summarize the clinical characteristics, treatment outcomes, and prognostic factors of children with non-metastatic Ewing's sarcoma (ES). A retrospective analysis was conducted on the clinical data of 41 children with non-metastatic ES diagnosed and treated at the Shanghai Children's Medical Center, Shanghai Jiao Tong University School of Medicine from January 2010 to December 2018. All patients underwent chemotherapy based on the RMS-2009 protocol of the center, and local treatment such as surgery and/or radiotherapy was performed according to risk grouping. The Kaplan-Meier method was used to calculate the overall survival (OS) and event-free survival (EFS) rates. Univariate prognostic analysis was performed using the log-rank test, and multivariate analysis was conducted with Cox regression. Of the 41 children, 21 were male and 20 were female. The median age at diagnosis was 7.7 years (range: 1.2-14.6 years). The median follow-up time for patients with event-free survival was 68.1 months (range: 8.1-151.7 months). As of the last follow-up, 33 patients were in complete remission, and the overall 5-year EFS and OS rates were (78±6)% and (82±6)%, respectively. Univariate analysis by the log-rank test showed that a tumor diameter ≥8 cm, time from diagnosis to start of local treatment ≥16 weeks, and incomplete surgical resection were associated with poor prognosis (P<0.05). Multivariate Cox regression analysis indicated that incomplete surgical resection (HR=8.381, 95%CI: 1.681-41.801, P=0.010) was an independent risk factor for poor prognosis in children with ES. Secondary tumors occurred in 2 cases. A comprehensive treatment strategy incorporating chemotherapy, surgery, and radiotherapy can improve the prognosis of children with ES. Poor prognosis is associated with an initial tumor diameter ≥8 cm, while complete surgical resection and early initiation of local treatment can improve outcomes.

Primary intracranial peripheral primitive neuroectodermal tumor: lessons from an exceptionally rare neoplasm. Illustrative case.

The primary intracranial peripheral primitive neuroectodermal tumor (pPNET) is a lesion subtype within the Ewing sarcoma family of tumors. pPNETs are extremely uncommon pathologies, accounting for 0.03% of intracranial tumors and 1% to 2% of Ewing sarcoma cases. Given its histological aspect similar to other highly proliferative malignant neuroectodermal neoplasms, pPNET merits extensive workup for accurate diagnosis and treatment. A 36-year-old male presented to the emergency department with a 1-year history of headaches in the right frontoparietal area, generalized tonic-clonic seizures, and a history of the resection of a tumor labeled as a meningioma 5 years before admission. He was neurologically intact. Brain magnetic resonance imaging revealed a heterogeneous focal lesion of 25 × 35 × 23 mm with a necrotic center and neoformative appearance in the right frontal cortex. The patient underwent multimodal treatment with gross-total resection, radiotherapy, and chemotherapy. Histopathological examination results supported the diagnosis of pPNET. At the 2-year follow-up, the patient had no new-onset symptoms, and brain imaging revealed absent signs of tumor recurrence. The present case describes an extraordinary pPNET case, initially confounded as a clear cell meningioma. Managing pPNET requires thorough investigation, careful differentiation from similar neuroectodermal lesions, and multimodal treatment to improve the patient's prognosis.

Two atypical cases of feline restrictive orbital myofibroblastic sarcoma (FROMS) initially presenting as oral masses

Two atypical cases of feline restrictive orbital myofibroblastic sarcoma (FROMS) initially presenting as oral masses

Primary breast sarcomas: A 13 case-series study treated in university hospital in central Tunisia over a 25-year period.

To retrospectively study the therapeutic modalities of primary breast sarcomas in view of the data of a local Tunisian experience. It is a monocentric, descriptive, retrospective study including 13 cases of primary breast sarcoma treated over a period of 25 years (1995-2020) in the oncological radiotherapy department of a university hospital in Sousse, Tunisia. In our study, 13 cases of non-metastatic breast sarcomas that has been identified, divided into ten cases of phyllodes sarcomas and three cases of non-phyllodes sarcomas.Surgically, all our patients had a mastectomy. Among them, seven underwent a lymph node procedure: five underwent axillary lymph node dissection, and two others had primary axillary lymph node biopsy. For the adjuvant treatment, all the patients included in our study received radiotherapy and seven received chemotherapy. Local recurrence occurred on the operative scar in one patient after completion of radiation therapy. Metastatic relapse was described in five patients. The time to onset of metastases varied between two months and five years. Nevertheless, a complete remission was noted in 6 patients with a follow-up varying from four years to 20 years. Two patients were lost to follow-up. Breast sarcomas remain a very rare entity of aggressive tumors.The therapeutic approach is poorly codified. For this reason, the therapeutic decision should always be discussed in a multidisciplinary assessment.

Abstract 4844: Epidemiology of bone and soft-tissue sarcomas: A two-decade analysis of the surveillance, epidemiology, and end results program

Abstract In the United States, ~15000 cases of bone and soft-tissue sarcomas are diagnosed annually, representing roughly 1% of all incident cancers. While several studies have analyzed independent predictors of outcomes for these sarcomas, small samples and confounding bias have limited their ability to establish reliable conclusions. The present analysis provides a comprehensive epidemiological description of patients with any of 16 distinct bone and soft-tissue sarcomas by querying the Surveillance, Epidemiology, and End Results database between 2000 and 2020. Incidence, prevalence, incidence-based mortality, survival rates, and case-fatality ratios were computed. Using patient age, sex, race, and ethnicity, as well as tumor size, grade, and stage as covariates, multivariable survival Cox proportional hazards regression analyses were performed to model hazard ratios (HRs) and identify independent predictors of worse prognosis. Only patients with myosarcoma and fibrous histiocytoma witnessed a decrease in the prevalence of their disease over time (both, p&amp;lt;0.05). The incidence of chondrosarcoma and synovial sarcoma increased in White and Asian patients but decreased in Black individuals (both, p&amp;lt;0.001), while their case-fatality rates remained constant and increased, respectively, regardless of race and ethnicity (all, p&amp;lt;0.05). Case-fatality rates only declined significantly for White and Non-Hispanic patients with solitary fibrous tumor (both, p&amp;lt;0.05). Aside from alveolar soft-part sarcoma and clear cell sarcoma, a 10-year increase in age of patients with bone and soft-tissue sarcomas resulted in 18% to 61% higher likelihood of death (all, p&amp;lt;0.05). For most malignancies, having a tumor size greater than 5 cm yielded a 37% to 189% higher likelihood of death. While incidence trends suggest improvements in diagnostic techniques and early tumor detection, survival and case-fatality trends indicate potential for advancement in treatment for most bone and soft-tissue sarcomas. Citation Format: Marc El Beaino, Rachel Baum, Katherine M. Connors, Karim Masrouha, Santiago A. Lozano-Calderon, Patrick P. Lin. Epidemiology of bone and soft-tissue sarcomas: A two-decade analysis of the surveillance, epidemiology, and end results program [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 4844.

Abstract 775: Underlying germline genetic architecture of pediatric sarcomas: Evaluating the role of common and rare variants in 4,160 patients

Abstract Some evidence suggests that pediatric sarcomas have both shared and distinct genetic profiles; however, large-scale efforts to characterize germline genetic susceptibility across these malignancies are limited by their rarity. We evaluated the role of common and rare variants in the genetic etiology of the more frequent pediatric sarcomas: osteosarcoma (OS); Ewing sarcoma (ES); and rhabdomyosarcoma (RMS), subcategorized into embryonal (ERMS) and alveolar (ARMS). METHODS: We evaluated 4,161 European-ancestry cases with genotype data (1,843 OS, 733 ES, 1,585 RMS, and ~61,000 cancer-free adult controls) and 2,474 cases with exome or genome sequencing (1,002 OS, 579 ES, 893 RMS, and 1,057 controls; jointly called with the same QC). Analyses included: 1) estimating disease heritability for both common SNPs (MAF&amp;gt;3%; genome-wide) and rare loss-of-function variants (MAF&amp;lt;1%; exome-wide); and 2) determining the frequency of rare predicted pathogenic (P) or likely pathogenic (LP; ACMG-AMP) variants in cancer susceptibility genes (CSG). RESULTS: For OS, we conducted a new GWAS and determined that common variants explained 2.7% (SE 1.1%) of disease heritability, while rare LOF variants explained 12.7% (SE 1.5%; compared to 0.4% for synonymous variants). A similar pattern was observed for ERMS, where rare LOF variants explained a greater proportion of disease heritability (RMS 8.6%, SE 1.2%; ERMS 12.6%, SE 1.7%; ARMS n/a due to small sample size) compared to common variants from our new GWAS (0.9%, SE 1.6%). Conversely, common variants explained a greater proportion of ES heritability (5.4%, SE 0.5%) and of ARMS heritability (15.5%, SE 6.4%). For 113 established CSGs, and for the 60 moderate-to-high penetrant autosomal dominant (AD) genes, OS and ERMS had significantly (Pexact&amp;lt;0.01) more rare P/LP variants overall compared to controls; whereas ARMS and ES had significantly fewer P/LP variants than ERMS and OS, similar to the controls. We confirmed previously reported AD genes, and identified new genes, with an enrichment of P/LP variants in ERMS and OS compared to controls. For both ARMS and ES, the only AD gene significantly enriched for P/LP variants was CHEK2. For all cases, patients with a P/LP variant were significantly younger and had significantly more poor outcomes (ie, metastasis, stage 4 disease, and/or death) than those without. For 49 autosomal recessive CSGs, heterozygous P/LP carrier frequencies were similar among all sarcomas (8-11%), and several specific genes had similar P/LP variant enrichment across sarcomas, and for ES and ARMS only, compared to controls. CONCLUSION: In the largest set of pediatric sarcoma cases assembled to date, genetic susceptibility was largely driven by rare P/LP AD gene variants in tumor types not characterized by canonical somatic fusions (OS and ERMS). In contrast, fusion-driven tumor types (ES and ARMS) were driven more by common variants. Citation Format: Lisa Mirabello, Laura E. Egolf, Bin Zhu, D. Matthew Gianferante, Kevin Wang, Shengchao Alfred Li, Mitchell J. Machiela, Logan G. Spector, Joshua D. Schiffman, Aniko Sabo, Alexander Renwick, Bailey Martin-Giacalone, Michael E. Scheurer, Sharon Plon, Douglas Hawkins, Rajkumar Venkatramani, Douglas Stewart, Lindsay M. Morton, Melissa M. Hudson, Gregory T. Armstrong, Smita Bhatia, Michael Dean, Katherine A. Janeway, Ana Patiño-Garcia, Fernando Lecanda, Massimo Serra, Claudia Hattinger, Katia Scotlandi, Adrienne M. Flanagan, Fernanda Amary, Irene L. Andrulis, Jay S. Wunder, Mandy L. Ballinger, David M. Thomas, Olivier Delattre, Aubrey K. Hubbard, Jia Liu, Wen Luo, Belynda D. Hicks, Meredith Yeager, Maryam Rafati, Wen-Yi Huang, Maria T. Landi, Adriana Lori, Ryan Diver, Sharon A. Savage, Stephen J. Chanock, Philip J. Lupo. Underlying germline genetic architecture of pediatric sarcomas: Evaluating the role of common and rare variants in 4,160 patients [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 775.

Synovial sarcoma of the dorsal aspect of the hand: a case report

BackgroundSynovial sarcoma is a rare soft tissue sarcoma, with incidences of 0.81/1,000,000 in children and 1.42/1,000,000 in adults. It is most commonly found in soft tissue and rarely in bone. It often has a slow growth pattern and a benign radiologic appearance.Case presentationThis study reports a case of metacarpal synovial sarcoma occurring in the hand-wrist of a 32-year-old Iranian man presented with the chief complaint of a lump on the dorsal ulnar side of his left hand and wrist. Initially, the first physician suspected the case to be a ganglion cyst. After two months of conservative treatment, the size of the lesion gradually increased. Magnetic resonance imaging (MRI) was performed and after an excisional biopsy and a postoperative histological analysis, the tumor was identified as a synovial sarcoma. The patient underwent a scheduled surgical procedure. Unfortunately, he had poor follow-ups and brought the pathologic results two months later when, the tumor had incredible growth, which makes this presentation rare.ConclusionsSince early diagnosis can lead to higher survival rates, this report increases doctors' awareness of this extremely malignant tumor that is rarely seen.

Initial local resection versus early referral for spermatic cord sarcoma: Any impact on treatment timelines and oncological outcomes?

ObjectivesSpermatic cord sarcomas are exceedingly rare, often misdiagnosed and subsequently improperly treated at local hospitals. This retrospective study looked at the oncological outcomes of spermatic cord sarcoma cases managed with curative intent resection at a tertiary referral sarcoma centre. We specifically studied how initial inadequate resections impact the oncologic outcomes compared to primary tumour resections at the reference centre. MethodsOne hundred eighteen consecutive patients affected by primary, localized spermatic cord sarcoma surgically managed at our reference centre from January 2001 through January 2021 were included. Primary endpoints were local relapse free (LRFS), distant metastasis free (DMFS) and overall survival (OS). These outcomes were evaluated with multi-nomial logistic regression and Cox proportional hazards regression models for a co-relation to known patient, tumour and treatment-related prognostic factors, including a prior inadequate resection and time from diagnosis to a complete oncologic resection as independent variables. Secondarily, we compared the above variables and treatment intervals among the subgroups of primary versus re-resection surgery. ResultsOver a median follow-up of 54 months (IQR 25–105), 12 patients (10.2%) developed local recurrence (LR) and 14 (11.6%) had distant metastasis (DM). 5-year local relapse (LRFS) and distant metastasis-free survival (DMFS) were 89.3% and 86.5%, respectively. Higher tumour grade and size were associated with a worse DMFS (p=<0.05). Likewise, marginal (R1) resection correlated with an inferior LRFS (p=< 0.05).Eighty-four patients (71.2%) had their initial diagnosis established on an inadequate surgical excision performed in a local hospital, followed by a re-excision at our centre (Re-resection group). During the same period, 34 (28.8%) were managed primarily with biopsy and treatment at our reference centre (Primary-resection group). The two groups had statistically significant differences in tumour size, histopathology, surgery duration, rate of postoperative complication and R0 resection (p < 0.005). Additionally, the difference in time intervals to achieve the treatment targets was statistically insignificant and did not correlate to the risk of recurrence as an independent variable. Residual disease was present in 51.2 % (n = 43) of the re-excision specimens. However, following a complete R0 resection, this did not correlate with a higher risk of recurrence (p = 0.481). ConclusionPrompt referral to a tertiary centre, where multidisciplinary evaluation and sound oncologic resections are the standard of treatment, can align the OS and DFS of patients receiving incomplete surgery elsewhere to those treated primarily in referral centres. The primary determinant of prognosis remains surgical margin, tumour size and grade.

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

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

Primary extraskeletal intradural Ewing sarcoma with acute hemorrhage: a case report and review of the literature

BackgroundSpinal cord tumors present a challenge in diagnosis and treatment due to their varied histopathological characteristics. While Ewing sarcoma is a rare malignant tumor typically originating from skeletal bone, cases of primary intradural extraskeletal Ewing sarcoma are exceptionally rare. The similarity of its presentation to other spinal tumors further complicates its identification and management.Case presentationWe report a case of a 58-year-old Palestinian male with intradural extraskeletal lumbar Ewing sarcoma. The patient initially presented with lower back pain and bilateral S1 radiculopathy, with more severe symptoms on the left side. Magnetic resonance imaging revealed a 7 cm oval-shaped mass with homogeneous contrast enhancement, obstructing the spinal canal from L3/L4 to L5/S1 levels. Initially, a myxopapillary ependymoma was suspected, but the patient’s sensory and motor functions suddenly deteriorated during hospitalization. Repeat magnetic resonance imaging indicated heterogeneous contrast enhancement, indicating acute intratumoral hemorrhage. Consequently, the patient underwent emergent L3–L5 laminotomy, with successful gross total resection of the tumor. Histopathological and immunohistochemical analyses confirmed the diagnosis of intradural extraskeletal Ewing sarcoma. Adjuvant therapy was administered to minimize the risk of local recurrence or distant metastasis. A systematic review of relevant literature, along with retrospective analysis of medical records, operative reports, radiological studies, and histopathological findings of similar cases, was also conducted.ConclusionsIntradural extraskeletal Ewing sarcoma is an infrequently encountered condition in adult patients, emphasizing the importance of considering it in the differential diagnosis of spinal tumors. Surgeons must possess a comprehensive understanding of this rare entity to ensure accurate staging and optimal management, particularly in the early stages when prompt intervention may improve prognosis.

Case Report: Granulocytic Sarcoma of the Parotid in Chronic Myeloid Leukemia: A Case Report and Literature review

Granulocytic sarcomas are infrequent, extramedullary malignant occurrences, generally seen with or secondary to acute myeloid leukemia (AML). Their association with chronic myeloid leukemia (CML) is rare and their appearance in parotid gland is sparsely reported in the literature, as per our literature search. In this report, we present an unusual and rare case of imatinib resistant BCR-ABL1 positive secondary granulocytic sarcoma to CML in chronic phase. The rarity of this clinical presentation presents a diagnostic dilemma, which required the pathologist and the clinician to combine a strong clinical suspicion with cytopathological features to diagnose this case, in order to ensure timely therapeutic modifications (shift from imatinib to second-generation tyrosine kinase inhibitor), considering the improvements in prognosis of imatinib resistant granulocytic sarcomas.

DDIT3-amplified or low-polysomic pleomorphic sarcomas without MDM2 amplification: Clinicopathological review and immunohistochemical profile of nine cases

Several high-grade pleomorphic sarcoma cases that cannot be classified into any existing established categories have been reported. These cases were provisionally classified into undifferentiated pleomorphic sarcoma (UPS). Some dedifferentiated liposarcoma (DDLS) cases may also have been classified into the UPS category due to the absence of MDM2 amplification or an atypical lipomatous tumor/well-differentiated liposarcoma component. We retrieved and reviewed 77 high-grade pleomorphic sarcoma cases, initially diagnosed as UPS in 66 cases and DDLS in 11 cases. Fluorescence in situ hybridization (FISH) analyses of DDIT3 and MDM2 were performed for available cases. Of the cases successfully subjected to DDIT3 FISH (n = 56), nine (7 UPS and 2 DDLS) showed DDIT3 amplification but no MDM2 amplification. Two UPS cases showed both telomeric (5′) and centromeric (3′) amplification of DDIT3 or low polysomy of chromosome 12, whereas 5 UPS and 2 DDLS cases showed 5′-predominant DDIT3 amplification. Histopathologically, all cases showed UPS-like proliferation of atypical pleomorphic tumor cells. Immunohistochemically, only one case showed focal nuclear positivity for DDIT3, supporting the previous finding that DDIT3 expression was not correlated with DDIT3 amplification. All three cases with focal MDM2 expression involved 5′-predominant amplification, two of which showed DDLS-like histological features. The majority of cases (7/9) showed decreased expression in p53 staining, suggesting that DDIT3 amplification regulates the expression of TP53 like MDM2. From a clinicopathological perspective, we hypothesize that DDIT3-amplified sarcoma, especially with 5′-predominant amplification, can be reclassified out of the UPS category.