Introduction: Extraskeletal Ewing sarcoma (EES) is a rare subtype of Ewing Sarcoma. It is more common in older age group compared with Classic Ewing Sarcoma that is seen in pediatric patients. It usually presents in the upper extremities, hips, and pelvis. The breast is an unusual primary location for this tumor, and there are very few reported cases in the literature. In the Philippines, there have been no reported cases yet of EES primary to the breast in the pediatric age group. Case Description: This is a case of a right upper chest mass from a 13-year-old male noted with progression of size for the past 8 months associated with pain. A biopsy was done in the initial consult and yielded unremarkable results, hence management with unrecalled antibiotics and pain medications. Continuous worsening of symptoms led to consultation at our institution, wherein a non-tender, non-erythematous, non-movable, firm, 15 x 13 cm mass was noted at the right chest during his ER consult and subsequent admission. CT scan with contrast revealed a right chest wall mass (16.8 x 18.1 x 9.5 cm) with focal areas of intrathoracic extension and associated pleural thickening. The patient subsequently underwent an incision biopsy for further workup. Microscopically, sheets and cords of small round blue cells are seen with scant to ample amphophilic cytoplasm, increased nuclear to cytoplasmic ratio, coarse chromatin pattern, and inconspicuous nucleoli set in a background of fibrocollagenous stroma. About 5-10 mitoses are also seen per 10 high-power fields, some of which are atypical. Based on the patient’s medical history, radiographic findings and histomorphologic characteristics of the case, the primary working diagnosis for this case is a malignant small round blue cell neoplasm. Immunohistochemistry studies showed strong, diffuse, membranous, and cytoplasmic immunoreactivity to CD99, while the rest of the immunohistochemical stains (Desmin, Myogenin, Chromogranin, CD45, and SALL4) yielded negative results. Additionally, NKX2.2 was also performed which showed strong, diffuse, nuclear immunoreactivity to the neoplastic cells. The case is compatible with the diagnosis of Ewing Sarcoma. Subsequent molecular test on ESWR1 via Fluorescence in-situ hybridization (FISH) revealed an ESWR gene break apart, which further supports the diagnosis of Ewing Sarcoma. Six months after the biopsy, and having completed 3 cycles of chemotherapy, the patient subsequently underwent excision of the mass. The excised tumor was submitted for histopathologic evaluation, which showed good response (89% treatment effect, mainly composed of extensive necrosis). There is no involvement of the adjacent rib bone, and all surgical margins are negative for tumor; thus, this has been signed out as a case of Extraskeletal Ewing Sarcoma of the Breast. Discussion: Extraskeletal Ewing Sarcoma (EES) is a highly aggressive tumor seen among 12% of patients with Ewing Sarcoma (ES). It has a wide anatomic distribution.Typically, it is most common on the upper extremities, hips and pelvic area. It is also seen more among older age group, usually in the 4th decade of life in some of the reported cases, in comparison with classic ES. The breast is an unusual location for the tumor for both adult and pediatric patients. Most tumors of the breast commonly seen in the pediatric age group are metastatic processes, which include rhabdomyosarcoma and lymphoma. CD99 is an important and essential immunohistochemical stain (IHC) in the diagnosis of Ewing sarcoma; 95% of cases of ES has a diffuse, strong membranous expression. NKX2.2 is also useful in the diagnosis, as it is more specific with ES. S100, ERG and FL1 can also be used to support the diagnosis of ES. Molecular testing is also a requirement and helpful in the diagnosis of EES. The tumor is associated with FET-ETS fusion genes. EWSR1-FLI1 fusion is the most common genetic alteration with EES which resulted from translocation in the t(11;22)(q24;q12). Other mutation of the tumor include ESWR-ERG1. EES primary to the breast has a poorer prognosis despite multimodal treatments in comparison to EES located in different sites with a good prognosis. There have been nineteen (19) reported cases of EES primary to the breast. This accounts for less than 1% of overall cases for EES. Currently, there have been no reported cases of EES primary to the breast in the local setting. Conclusion Ewing sarcoma should still be considered as one of the main differential diagnoses for pediatric patients presenting with soft tissue mass in the breast as well as in other locations. Due to its aggressive clinical course, prompt diagnosis can help increase survivability, surveillance of recurrence, and metastasis.
Child ; Sarcoma, Ewing ; Mutation

Primary malignant bone tumors are extremely rare. Osteosarcoma, chondrosarcoma, Ewing's sarcoma, and myeloma are the most common malignancy in bone. Osteosarcoma and Ewing's sarcoma are common in children and adolescents, and the tumors are high lethality due to the high rate of pulmonary metastasis. While chondrosarcoma, myeloma, and chordoma are more common in middle aged and elderly people. Japanese Orthopaedic Association (JOA) published the secondary clinical practice guideline on the management of primary malignant bone tumors. We put an emphasis on explanation some important issue of this guideline for help Chinese musculoskeletal tumor professionals in clinical practice.
Humans ; Bone Neoplasms/surgery* ; Chondrosarcoma/therapy* ; Japan ; Orthopedics ; Osteosarcoma/pathology* ; Practice Guidelines as Topic ; Sarcoma, Ewing/therapy* ; Societies, Medical

Extraskeletal Ewing's sarcoma（EES） in the head and neck is extremely rare, with non-specific clinical manifestations, high malignancy, easy recurrence and metastasis, and poor prognosis. This paper reports a case of EES of the parapharyngeal skull base presenting with secretory otitis media as the initial symptom.The treatment consisted of surgery, chemotherapy and radiotherapy. No further metastasis or recurrence was observed during the two years and six months follow-up. Now we reviewed the relevant literatures and summarized the experience of diagnosis and treatment in EES.
Humans ; Otitis Media with Effusion/etiology* ; Sarcoma, Ewing/therapy* ; Skull Base ; Skull Base Neoplasms/therapy*

Osteosarcoma (OS), chondrosarcoma (CS), and Ewing sarcoma (ES) represent primary malignant bone tumors and pose significant challenges in oncology research and clinical management. Conventional research methods, such as two-dimensional (2D) cultured tumor cells and animal models, have limitations in recapitulating the complex tumor microenvironment (TME) and often fail to translate into effective clinical treatments. The advancement of three-dimensional (3D) culture technology has revolutionized the field by enabling the development of in vitro constructed bone tumor models that closely mimic the in vivo TME. These models provide powerful tools for investigating tumor biology, assessing therapeutic responses, and advancing personalized medicine. This comprehensive review summarizes the recent advancements in research on 3D tumor models constructed in vitro for OS, CS, and ES. We discuss the various techniques employed in model construction, their applications, and the challenges and future directions in this field. The integration of advanced technologies and the incorporation of additional cell types hold promise for the development of more sophisticated and physiologically relevant models. As research in this field continues to evolve, we anticipate that these models will play an increasingly crucial role in unraveling the complexities of malignant bone tumors and accelerating the development of novel therapeutic strategies.
Bone Neoplasms/pathology* ; Humans ; Osteosarcoma/pathology* ; Tumor Microenvironment ; Sarcoma, Ewing/pathology* ; Chondrosarcoma/pathology* ; Animals ; Cell Culture Techniques/methods* ; Cell Culture Techniques, Three Dimensional/methods* ; Cell Line, Tumor

OBJECTIVES: This study aimed to evaluate the diagnostic accuracy of Cyclin D1 as an adjunct immunomarker in CD99 positive small round cell neoplasms with primary consideration of PNET/EWS. MATERIALS AND METHODS: Tissue from 2017 to 2023 with a histopathologic diagnosis of CD99 positive small round blue cell tumors with primary consideration of Primitive Neuroectodermal Tumor (PNET)/Ewing Sarcoma were retrieved and Cyclin D1 immunohistochemical staining done. Diagnostic accuracy of Cyclin D1 immunostaining was determined by calculating the sensitivity, specificity, positive predictive value, and negative predictive value. RESULTS: Cyclin D1 immunohistochemical staining was performed in 19 specimens available, of which 13 yielded a positive result. Of these, 8 had a final histopathologic diagnosis of CD99 positive small round blue cell tumor with primary consideration of PNET/Ewing Sarcoma, resulting in sensitivity of 61.54%, specificity of 100%, positive predictive value of 100% and negative predictive value of 50.0%. The overall accuracy is 72.2%. CONCLUSION Cyclin D1 can be used as an adjunct immunomarker to aid in the diagnosis of CD99 positive round cell tumor with primary consideration of PNET/Ewing Sarcoma specifically in resource limited settings where molecular testing is not readily available. Given the high specificity of Cyclin D1 in such cases, it can be used to rule out other small round blue cell tumors that can also stain positive for CD99 such as Rhabdomyosarcoma. However, interpretation must be done in conjunction with the results of other immunohistochemical stains in order to increase its diagnostic accuracy.
Human ; Male,Female ; Cells ; Sarcoma, Ewing ; Sarcoma ; Neuroectodermal tumors, Primitive ; Cyclin D1

Ewing’s sarcoma is a rare cancerous tumor of bone or soft tissue that usually occurs mostly in young adults. The diagnosis of Ewing’s sarcoma in pregnancy, most especially the subtype extraskeletal Ewing’s Sarcoma, is very rare with only few cases published in the literature worldwide. We present a case of a primigravida diagnosed with extraskeletal Ewing’s sarcoma at 6 weeks age of gestation. Currently, because of the rarity of this condition, there is lack of a universal consensus on the recommended therapeutic approach. A multidisciplinary management involving the generalist obstetrician, perinatologist, medical oncologist, and neonatologist was initiated at the outset to provide timely balance between optimal maternal treatment and fetal well-being. The maternal and fetal condition was stable all throughout the course of the chemotherapy using doxorubicin during pregnancy. Close interdisciplinary coordination regarding the treatment plans across these subspecialists resulted in a successful pregnancy outcome.

OBJECTIVES: This study investigate the clinical and imaging features of Ewing sarcoma (ES) of the jaw. METHODS: Eight cases of pathologically diagnosed ES of the jaw from January 2010 to June 2022 were included in the study. Clinical and radiological features were retrospectively analyzed. RESULTS: Among the eight cases, the mean age at onset was 29.4 years, and the male to female ratio was 7∶1. The predilecting site was the posterior part of mandible, accounting for 75% of the cases. The lesions often exhibited early numbness of the lower lip and lymphadenopathy. The main radiographic manifestation of mandibular lesions was ill-defined radiolucency, mixed with fibrous or brush-like tumor matrix, and soft tissue mass. The maxillary ES lesions mainly presented as lytic bone destruction accompanied by adjacent soft tissue mass. Periosteal ossification was rarely seen. CONCLUSIONS The clinical and imaging characteristics of ES in the jaw are helpful for its diagnosis.
Male ; Humans ; Female ; Sarcoma, Ewing/pathology* ; Retrospective Studies ; Radiography ; Mandible/pathology* ; Lip ; Bone Neoplasms

Humans ; Sarcoma, Ewing/pathology* ; Pancreas/pathology*

Objective: To investigate the clinicopathological characteristics, pathological diagnosis of Ewing's sarcoma of the central nervous system. Methods: Six cases of Ewing's sarcoma of the central nervous system diagnosed at the First Affiliated Hospital of Nanjing Medical University, Nanjing, China from 2015 to 2022 were collected. The clinical manifestations, histological morphology, immunophenotype and molecular genetics of these cases were analyzed. The related literature was reviewed. Results: There were four males and two females, with a male to female ratio of 2∶1. The onset age was 17-40 years, with a median age of 23 years. All 6 tumors were located in the spinal cord (2 cases of cervical vertebra, 1 case of thoracic vertebra, 2 cases of lumbar vertebra, and 1 case of sacral vertebra). The patients' clinical manifestations were mostly lumbago, weakness and numbness of lower limbs/limbs. In 1 case, the tumor recurred and metastasized to the suprasellar region and the third ventricle. Microscopically, the tumor showed diffuse infiltrative growth. In some cases, the tumor was closely related to the spinal meninges. The tumor cells were arranged in sheet, lobular, thin-rope, and nest-like patterns. Homer-Wright rosette was visible. The tumor cells were small to medium in size, and most of them had scant cytoplasm. A few cells had clear cytoplasm. Some areas were rhabdoid. The tumor cell nuclei showed focal mild pleomorphism. The chromatin was uniform and delicate while the nucleoli were not obvious. Mitosis was commonly seen. The tumor was separated by fibrous connective tissue and may be accompanied by mucinous degeneration. Immunohistochemistry showed that all tumors were positive for CD99, NKX2.2, Fli1, ERG. ATRX, H3K27me3, INI1 and BRG1 were all retained. Immunohistochemical stains for EMA, GFAP and Olig2 were negative. The Ki-67 proliferation index was 30%-70%. EWSR1 break-apart FISH test was positive. Conclusions: Ewing's sarcoma is rare in the central nervous system and needs to be distinguished from a variety of neoplasms with primitive undifferentiated small cell morphology. Immunohistochemistry and molecular genetics may be required for a proper diagnosis.
Humans ; Male ; Female ; Young Adult ; Adult ; Adolescent ; Sarcoma, Ewing/pathology* ; Proto-Oncogene Protein c-fli-1 ; Immunohistochemistry ; Biomarkers, Tumor/genetics* ; Central Nervous System/pathology*

Humans ; Sarcoma, Ewing