Extra-skeletal Ewing sarcoma is a rare tumor, most commonly occurring in the paravertebral region, extremities, retroperitoneum, and very rarely in visceral locations. We present two primary visceral Ewing sarcomas confirmed at the molecular level: one located in the stomach and the other in the bladder. Both tumors demonstrated strong and diffuse membranous CD99 expression, accompanied by variable KIT immunoreactivity. Additionally, we provide a review of the literature on primary gastric and bladder ES, including an analysis of differential diagnoses for gastric and bladder tumors exhibiting CD99 and KIT expression.
JaveryOKrajewskiKO'ReganK, et al.A to Z of extraskeletal Ewing sarcoma family of tumors in adults: imaging features of primary disease, metastatic patterns, and treatment responses. AJR Am J Roentgenol. 2011;197(6):W1015-W1022. doi:https://doi.org/10.2214/AJR.11.6667
3.
BrasmeJFChalumeauMOberlinOValteau-CouanetDGasparN. Time to diagnosis of Ewing tumors in children and adolescents is not associated with metastasis or survival: a prospective multicenter study of 436 patients. J Clin Oncol. 2014;32(18):1935-1940. doi:https://doi.org/10.1200/JCO.2013.53.8058
4.
DoIAraujoESKalilRK, et al.Protein expression of KIT and gene mutation of c-kit and PDGFRs in Ewing sarcomas. Pathol Res Pract. 2007;203(3):127-134. doi:https://doi.org/10.1016/j.prp.2006.12.005
5.
ShidhamVBChivukulaMGuptaDRaoRNKomorowskiR. Immunohistochemical comparison of gastrointestinal stromal tumor and solitary fibrous tumor. Arch Pathol Lab Med.2002;126(10):1189-1192. https://doi.org/10.5858/2002-126-1189-ICOGST
6.
BridgeJA. editors Undifferentiated small round cell sarcomas of bone and soft tissue. In: WHO Classification of Tumours Editorial Board, editor. Soft tissue and bone tumours. International Agency for Research on Cancer; 2020. (WHO Classification of Tumours Series, 5th ed.; Vol. 3). pp. 321-333. Available from: https://publications.iarc.fr/588.
7.
OguraKElkriefABowmanAS, et al.Prospective clinical genomic profiling of ewing sarcoma: ERF and FGFR1 mutations as recurrent secondary alterations of potential biologic and therapeutic relevance. JCO Precis Oncol. 2022;6:e2200048. doi:https://doi.org/10.1200/PO.22.00048
8.
Llombart-BoschAMachadoINavarroS, et al.Histological heterogeneity of Ewing's sarcoma/PNET: an immunohistochemical analysis of 415 genetically confirmed cases with clinical support. Virchows Arch. 2009;455(5):397-411. doi: https://doi.org/10.1007/s00428-009-0842-7
9.
MachadoIYoshidaAMoralesMGN, et al.Review with novel markers facilitates precise categorization of 41 cases of diagnostically challenging, “undifferentiated small round cell tumors”. A clinicopathologic, immunophenotypic and molecular analysis. Ann Diagn Pathol. 2018;34:1-12. doi:https://doi.org/10.1016/j.anndiagpath.2017.11.011
10.
TokiSWakaiSSekimizuM, et al.PAX7 Immunohistochemical evaluation of Ewing sarcoma and other small round cell tumours. Histopathology. 2018;73(4):645-652. doi:https://doi.org/10.1111/his.13689
11.
WangWLPatelNRCarageaM, et al.Expression of ERG, an Ets family transcription factor, identifies ERG-rearranged Ewing sarcoma. Mod Pathol. 2012;25(10):1378-1383. doi:https://doi.org/10.1038/modpathol.2012.97
12.
FolpeALGoldblumJRRubinBP, et al.Morphologic and immunophenotypic diversity in Ewing family tumors: a study of 66 genetically confirmed cases. Am J Surg Pathol. 2005;29(8):1025-1033.
13.
MachadoITravesVCruzJLlombartBNavarroSLlombart-BoschA. Superficial small round-cell tumors with special reference to the Ewing's sarcoma family of tumors and the spectrum of differential diagnosis. Semin Diagn Pathol. 2013;30(1):85-94. doi:https://doi.org/10.1053/j.semdp.2012.01.007
14.
DelattreOZucmanJPlougastelB, et al.Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature. 1992;359(6391):162-165. doi:https://doi.org/10.1038/359162a0
15.
CzekallaRFuchsMStölzleA, et al.Peripheral primitive neuroectodermal tumor of the stomach in a 14-year-old boy: a case report. Eur J Gastroenterol Hepatol. 2004;16(12):1391-1400. doi:https://doi.org/10.1097/00042737-200412000-00026
16.
SoulardRClaudeVCamparoPDufauJPSaint-BlancardPGrosP. Primitive neuroectodermal tumor of the stomach. Arch Pathol Lab Med. 2005;129(1):107-110. doi:https://doi.org/10.5858/2005-129-107-PNTOTS
17.
RafailidisSBallasKPsarrasK, et al.Primary Ewing sarcoma of the stomach–a newly described entity. Eur Surg Res. 2009;42(1):17-20. doi:https://doi.org/10.1159/000166166
18.
InoueMWakaiTKoritaPV, et al.Gastric Ewing sarcoma/primitive neuroectodermal tumor: a case report. Oncol Lett. 2011;2(2):207-210. doi:https://doi.org/10.3892/ol.2011.246
19.
SongMJAnSLeeSSKimBSKimJ. Primitive neuroectodermal tumor of the stomach: a case report. Int J Surg Pathol. 2016;24(6):543-547. doi:https://doi.org/10.1177/1066896916639371
20.
KhuriSGilshteinHSayidaaSBisharaBKlugerY. Primary Ewing sarcoma/primitive neuroectodermal tumor of the stomach. Case Rep Oncol. 2016;9(3):666-671. doi:https://doi.org/10.1159/000449126
21.
ShuQLuoJNLiuXLJingMMouTGXieF. Extraskeletal Ewing sarcoma of the stomach: a rare case report. World J Clin Cases. 2023;11(1):201-209. doi:https://doi.org/10.12998/wjcc.v11.i1.201
ShiyanbolaONigdeliogluRDhallD, et al.Extraskeletal Ewing sarcoma of the gastrointestinal and hepatobiliary tract: deceptive immunophenotype commonly leads to misdiagnosis. Am J Surg Pathol. 2024;48(9):1185-1194. doi:https://doi.org/10.1097/PAS.0000000000002236
24.
KimHSKimSMinYDKeeKHHongR. Ewing's sarcoma of the stomach; rare case of ewing's sarcoma and suggestion of new treatment strategy. J Gastric Cancer. 2012;12(4):258-261. doi:https://doi.org/10.5230/jgc.2012.12.4.258
25.
GousseAERothDRPopekEJCooleyLDHorowitzME. Primary Ewing's sarcoma of the bladder associated with an elevated antinuclear antibody titer. J Urol. 1997;158(6):2265-2266. doi:https://doi.org/10.1016/s0022-5347(01)68231-4
26.
ColecchiaMDagradaGPPolianiPLPilottiS. Immunophenotypic and genotypic analysis of a case of primary peripheral primitive neuroectodermal tumour (pPNET) of the urinary bladder. Histopathology. 2002;40(1):108-109. doi:https://doi.org/10.1046/j.1365-2559.2002.1340e.x
27.
KrügerSSchmidtHKauschI, et al.Primitive neuroectodermal tumor (PNET) of the urinary bladder. Pathol Res Pract. 2003;199(11):751-754. doi:https://doi.org/10.1078/0344-0338-00492
28.
Lopez-BeltranAPérez-SeoaneCMontironiRHernández-IglesiasTMackintoshCde AlavaE. Primary primitive neuroectodermal tumour of the urinary bladder: a clinico-pathological study emphasising immunohistochemical, ultrastructural and molecular analyses. J Clin Pathol. 2006;59(7):775-778. doi:https://doi.org/10.1136/jcp.2005.029199
29.
OsoneSHosoiHTanakaK, et al.A case of a Ewing sarcoma family tumor in the urinary bladder after treatment for acute lymphoblastic leukemia. J Pediatr Hematol Oncol. 2007;29(12):841-844. doi:https://doi.org/10.1097/MPH.0b013e318158155b
30.
BusatoWFJrAlmeidaGLOgataDC. Primary primitive neuroectodermal tumor of the bladder: histologic and clinical features of 9 cases. Clin Genitourin Cancer. 2011;9(1):63-67. doi:https://doi.org/10.1016/j.clgc.2011.03.002
31.
OkadaYKamataSAkashiTKurataMNakamuraTKiharaK. Primitive neuroectodermal tumor/Ewing's sarcoma of the urinary bladder: a case report and its molecular diagnosis. Int J Clin Oncol. 2011;16(4):435-438. doi:https://doi.org/10.1007/s10147-010-0144-8
32.
SueyoshiROkawadaMFujimuraJ, et al.Successful complete resection of Ewing sarcoma arising from the bladder in a 10-year-old boy after chemotherapy. Pediatr Surg Int. 2014;30(9):965-969. doi:https://doi.org/10.1007/s00383-014-3573-z
33.
VallonthaielAGKaurKJainD, et al.Ewing sarcoma of urinary bladder showing EWSR1 rearrangement on FISH analysis and unique response to chemotherapy. Clin Genitourin Cancer. 2016;14(2):e183-e186. doi:https://doi.org/10.1016/j.clgc.2015.11.001
34.
LamCJShayeganB. Complete resection of a primitive neuroectodermal tumour arising in the bladder of a 31-year-old female after neoadjuvant chemotherapy. Can Urol Assoc J. 2016;10(7–8):E264-E267. doi:https://doi.org/10.5489/cuaj.3808
35.
TonyalıŞYazıcıSYeşilırmakAErgenA. The Ewing's sarcoma family of tumors of urinary bladder: a case report and review of the literature. Balkan Med J. 2016;33(4):462-466. doi:https://doi.org/10.5152/balkanmedj.2016.16533
36.
ZhangHZWangSYShenXH. Ewing sarcoma of urinary bladder occurring simultaneously with high grade papillary urothelial carcinoma. Pathology. 2020;52(5):612-615. doi:https://doi.org/10.1016/j.pathol.2020.05.004
37.
HoweASPearceJLianF,et al.A case of Ewing sarcoma of the bladder presenting in early infancy. J Pediatr Hematol Oncol. 2021;43(4):e478-e480. doi:https://doi.org/10.1097/MPH.0000000000002107
38.
ChenSDenizKSungYSZhangLDrySAntonescuCR. Ewing sarcoma with ERG gene rearrangements: a molecular study focusing on the prevalence of FUS-ERG and common pitfalls in detecting EWSR1-ERG fusions by FISH. Genes Chromosomes Cancer. 2016;55(4):340-349. doi:https://doi.org/10.1002/gcc.22336
39.
MiettinenMLasotaJ. KIT (CD117): a review on expression in normal and neoplastic tissues, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol. 2005;13(3):205-220. doi:https://doi.org/10.1097/01.pai.0000173054.83414.22
40.
GarciaJJKramerMJMackeyZBO'DonnellRJHorvaiAE. Utility of CD117 immunoreactivity in differentiating metastatic melanoma from clear cell sarcoma. Arch Pathol Lab Med. 2006;130(3):343-348. doi:https://doi.org/10.5858/2006-130-343-UOCIID
41.
Abou-GhanemNSaadEOliffIAGidronAFilipiukD. Isolated enteric myeloid sarcoma as a rare etiology of small bowel obstruction in a young female patient. Gastroenterology Res. 2022;15(1):39-46. doi:https://doi.org/10.14740/gr1481
42.
AldinucciDPolettoDNanniP, et al.Hodgkin and reed-sternberg cells express functional c-kit receptors and interact with primary fibroblasts from Hodgkin's disease-involved lymph nodes through soluble and membrane-bound stem cell factor. Br J Haematol. 2002;118(4):1055-1064. doi:https://doi.org/10.1046/j.1365-2141.2002.03732.x
43.
AtallahSMarcMSchernbergA, et al.Beyond surgical treatment in adenoid cystic carcinoma of the head and neck: a literature review. Cancer Manag Res. 2022;14:1879-1890. doi:https://doi.org/10.2147/CMAR.S355663
44.
MachadoILópez-SotoMVRubioLNavarroLLlombart-BoschA. Soft tissue myoepithelial carcinoma with rhabdoid-like features and EWSR1 rearrangement: fine needle aspiration cytology with histologic correlation. Diagn Cytopathol. 2015;43(5):421-426. doi:https://doi.org/10.1002/dc.23259
45.
GeraldWLLadanyiMde AlavaE, et al.Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants. J Clin Oncol. 1998;16(9):3028-3036. doi:https://doi.org/10.1200/JCO.1998.16.9.3028
46.
PelmusMGuillouLHosteinISierankowskiGLussanCCoindreJM. Monophasic fibrous and poorly differentiated synovial sarcoma: immunohistochemical reassessment of 60 t(X;18)(SYT-SSX)-positive cases. Am J Surg Pathol. 2002;26(11):1434-1440. doi:https://doi.org/10.1097/00000478-200211000-00005
47.
NaousR. TLE1 Positive clear cell sarcoma of the kidney: a case report and review of the literature. Case Rep Pathol. 2018;2018(16):3462096. doi:https://doi.org/10.1155/2018/3462096
48.
YoshidaAGotoKKodairaM, et al.CIC-rearranged Sarcomas: a study of 20 cases and comparisons with Ewing sarcomas. Am J Surg Pathol. 2016;40(3):313-323. doi:https://doi.org/10.1097/PAS.0000000000000570
49.
KaoYCOwoshoAASungYS, et al.BCOR-CCNB3 Fusion positive sarcomas: a clinicopathologic and molecular analysis of 36 cases with comparison to morphologic Spectrum and clinical behavior of other round cell sarcomas. Am J Surg Pathol. 2018;42(5):604-615. doi:https://doi.org/10.1097/PAS.0000000000000965
50.
ZhongHXuCChenXGuoXYangS. GLI1-altered Epithelioid soft tissue tumor: a newly described entity with a predilection for the tongue. Oral Surg Oral Med Oral Pathol Oral Radiol. 2022;134(1):e14-e22. doi:https://doi.org/10.1016/j.oooo.2021.10.007
51.
LuoWStevensTMStaffordPMiettinenMGatalicaZVranicS. NUTM1-Rearranged Neoplasms-A heterogeneous group of primitive tumors with expanding Spectrum of histology and molecular alterations-an updated review. Curr Oncol. 2021;28(6):4485-4503. doi:https://doi.org/10.3390/curroncol28060381
AgaimyADaumOMärklBLichtmanneggerIMichalMHartmannA. SWI/SNF Complex-deficient undifferentiated/rhabdoid carcinomas of the gastrointestinal tract: a series of 13 cases highlighting mutually exclusive loss of SMARCA4 and SMARCA2 and frequent co-inactivation of SMARCB1 and SMARCA2. Am J Surg Pathol. 2016;40(4):544-553. doi:https://doi.org/10.1097/PAS.000000000000055
