A challenging diagnostic and therapeutic case report: Ewing sarcoma / primitive neuroectodermal tumor of the bladder

 Corresponding author: Aboulaich Youness Copyright © 2025 Author(s) retain the copyright of this article. This article is published under the terms of the Creative Commons Attribution License 4.0. A challenging diagnostic and therapeutic case report: Ewing sarcoma / primitive neuroectodermal tumor of the bladder Aboulaich Youness 1, , Kharbach Youssef 2 and Khallouk Abdelhak 2 1 MD, Urology resident, Urology department, Tangier University Hospital, Faculty of Medicine and Pharmacy, Abdelmalek Essaâdi University, 90000 Tangier, Morocco. 2 MD, Urology professor, Urology department, Tangier University Hospital, Faculty of Medicine and Pharmacy, Abdelmalek Essaâdi University, 90000 Tangier, Morocco. World Journal of Advanced Research and Reviews, 2025, 26(01), 4193-4198 Publication history: Received on 21 March 2025; revised on 27 April 2025; accepted on 30 April 2025 Article DOI: https://doi.org/10.30574/wjarr.2025.26.1.1542 Abstract Background: Bladder ES/PNET is a rare entity with a few cases described in the literature. This article will focus on an atypical vesical presentation of this tumor. Summary: We report a case of Ewing's sarcoma arising in the bladder in a 37-year-old patient with type 2 diabetes who presented with clotting hematuria and irritative symptoms of the lower urinary tract. On clinical examination, a hard and mobile hypogastric mass was palpated. CT scan revealed an abdominopelvic mass with predominantly extravesical development. Cystoscopy showed apparent displacement of the vesical dome without clear lesions within it. Given this perplexing presentation, we performed mass excision with partial cystectomy. Anatomopathological, immunohistochemical, and molecular biology studies supported the diagnosis of Ewing's sarcoma of vesical origin. Unfortunately, the patient passed away one month later due to complications related to a digestive obstruction. Conclusion; The objective of our presentation was to describe an additional case that presented both diagnostic and therapeutic challenges, in order to stimulate further consideration and derive clear recommendations. Keywords: Case report; Bladder; ES/PNET; Exophytic 1. Introduction ES/PNET is a rare malignant primary tumor characterized by small round cells [1]. In the literature, only 22 cases of bladder ES/PNET have been documented [3-24]. Its preoperative diagnosis is still complicated due to the absence of specific imaging features. Definitive diagnosis relies on postoperative pathology, immunohistochemistry, and genetic analysis. Due to the minuscule number of reported cases, establishing clear guidelines for its management and treatment is challenging. Therefore, early diagnosis and treatment of ES/PNET patients are highly challenging. This article describes an unusual case of PNET in the bladder in an adult. 2. Case Presentation We present the case of a 37-year-old patient with a history of type II diabetes treated with oral antidiabetic agents. The patient presented with intermittent clotting hematuria for three months, accompanied by irritative symptoms of the lower urinary tract, including pollakiuria and urgency. On clinical examination, a hard abdominal mass was palpable in the hypogastric region. Abdominal CT scan revealed a necrotic abdominopelvic mass invading the vesical dome with World Journal of Advanced Research and Reviews, 2025, 26(01), 4193-4198 4194 irregular contours, showing heterogeneous enhancement after contrast administration. The mass measured 15 cm x 10 cm in transverse diameter and 14 cm in height, exerting a mass effect on the right iliac ureter and causing slight infiltration of the perivesical fat without visible iliac lymphadenopathy. Cystoscopy showed displacement of the vesical dome by the described mass, with a healthy mucosa. The patient underwent mass excision with partial cystectomy. Microscopic examination revealed a poorly differentiated malignant tumor proliferation composed of small round blue cells. Frequent mitotic figures and the presence of HomerWright rosettes in some regions were observed (Fig. 2a). Immunohistochemical analysis supported the diagnosis of Ewing's sarcoma, with focal positivity for anti-NSE, anti-synaptophysin, and anti-CD99 antibodies (Fig. 2b). However, anti-CD20, anti-CD3, anti-PS100, anti-desmin, anti-myogenin, anti-pancytokeratin, anti-ERG, and R MaB antibodies showed negative staining. The patient was referred to the oncology center for additional chemotherapy. Unfortunately, one month later, the patient passed away due to complications related to a digestive obstruction. Figure 1 Axial section of an abdominopelvic CT scan showing an exophytic development of PNET Figure 2 (a) Sheets of monomorphic small round cells with hyperchromatic nuclei and clear cytoplasm. (H&E, 400). (b) Histopathology section exhibiting strong membranous CD99 immunostaining (H&E, 350) World Journal of Advanced Research and Reviews, 2025, 26(01), 4193-4198 4195 3. Discussion A primitive neuroectodermal tumor (PNET) is a rare and malignant tumor belonging to the Ewing's family of tumors [1]. It was first described in 1918 [2]. These tumors pose both diagnostic and therapeutic challenges for clinicians and pathologists. The primary issue encountered with a bladder ES/PNET is the diagnostic problem due to its occurrence at an unusual age, the rarity of its localization in the bladder, and notably its atypical presentation as a predominantly exophytic tumor. Only 22 cases of bladder ES/PNET have been described in the literature (table 1). The youngest patient was 10 years old [11], the oldest was 81 years old [8], resulting in a mean age of 41.9 years, which is younger than that reported in urothelial carcinomas [25]. Table 1 Published cases of primitive neuroectodermal tumor (PNET) of the bladder to date. Author Year of publication Sex/age Tumor size (mm) Growth patern Treatment Banerjee et al. [3] 1997 M/21 80×60×40 Endophytic Cystectomy+chemotherapy Gousse et al. [4] 1997 F/15 30×20×20 Endophytic TURBT+ Partial cystectomy Mentzel et al. [5] 1998 M /21 140×100×100 Endophytic and exophytic TURBT + nephrostomy Desai. [6] 1998 F/38 120×70×35 Endophytic and exophytic Cystectomy Colecchia et al. [7] 2002 F/61 - Endophytic and exophytic - Krüger et al. [8] 2003 M/81 - Endophytic and exophytic TURBT + nephrostomy Lopez-Beltran et al. [9] 2006 F/21 90×80×60 Endophytic cystectomy+chemotherapy Ellinger et al. [10] 2006 M/72 - Endophytic and exophytic TURBT+ ileal conduit Osone et al. [11] 2007 M/10 10 Endophytic TURBT Al Meshaan et al. [12] 2009 F/67 30×25×10 Endophytic TURBT+ Partial cystectomy Busato et al. [13] 2011 F/52 33×15×22 Endophytic TURBT+ chemotherapy Okada et al. [14] 2011 M/65 50 Endophytic TURBT+ cystectomy+ chemotherapy Zheng et al. [15] 2011 M /74 - Endophytic and exophytic TURBT+ palliative surgery+ chemotherapy Rao et al. [16] 2011 F/14 150×120×75 Endophytic and exophytic Partial cystectomy Sueyoshi et al. [17] 2014 M/10 135×131×129 Endophytic and exophytic Double J tube + partial cystectomy+ chemotherapy Lam et al. [18] 2016 F/30 64×94×77 Endophytic TURBT+ chemotherapy+ cystectomy Vallonthaiel et al. [19] 2016 F/27 103×98×47 Endophytic TURBT+ chemotherapy Tonyalı et al. [20] 2016 F/38 40×26×25 Endophytic cystectomy + chemotherapy Zhang et al. [21] 2020 F/78 63×44 Endophytic TURBT Gao et al. [22] 2020 F/45 30 Endophytic TURBT + cystectomy + chemotherapy World Journal of Advanced Research and Reviews, 2025, 26(01), 4193-4198 4196 Liu et al. [23] 2020 M/64 60×50 Exophytic Partial cystectomy+ radiotherapy Jingyi et al. [24] 2023 F/19 55×36 Endophytic TURBT+ chemotherapy Present case 2025 M/37 150 × 100 × 140 Exophytic Partial cystectomy These tumors have a preference for the central nervous system in children and young adults, although they can occasionally develop in other locations such as the thoracic wall, head and neck, kidneys, adrenal glands, female genital tract, extremities, and scrotal sac [23]. The presence of a PNET in the bladder is extremely rare. The majority of the described cases (21/22) exhibit endophytic growth, while 8 of them are accompanied by exophytic growth. However, a tumor of purely exophytic development has only been reported in one case [23], and our case is the second. Cystoscopy confirmed this presentation by revealing a completely healthy vesical mucosa, which raises suspicions of an alternative diagnosis, such as a tumor originating from the digestive tract. Given the rarity of these tumors, it is difficult to consider them initially. A definitive diagnosis relies on anatomopathological study, immunohistochemistry, and molecular biology [1]. Apart from the diagnostic challenge, the second issue that arises is the treatment. Due to the limited number of patients with PNET, no recommendations can be established, and most knowledge about treatment has been derived from studies on the Ewing's sarcoma family and the reported cases in the literature. Seven patients underwent total cystectomy [3,6,9,14,18,20,22], five underwent partial cystectomy [4,12,16,17,23], and eight underwent only transurethral resection of the bladder [5,8,10,11,13,19,21,24]. Chemotherapy was associated in most cases, with a favorable response observed in some instances [19,24]. In our case, we performed a partial cystectomy with excision of the mass, and postoperative chemotherapy was planned. However, the patient's general condition rapidly deteriorated, preventing them from receiving the chemotherapy. Successful treatment necessitates a multimodal approach [3,9,20,22]. Most patients with apparently localized disease have occult metastases, thereby warranting additional therapy, such as chemotherapy [10]. Poor prognosis has been reported for those with existing metastases [12,13]. Abbreviations • ES/PNET: Ewing Sarcoma / Primitive Neuroectodermal Tumor of the Bladder • CT: computed tomography. 4. Conclusion In conclusion, clinicians and pathologists should be aware of this rare entity during diagnosis and management. Surgery supported by chemotherapy should be considered as an option, especially in advanced disease cases. With the description of new cases and long-term follow-up results, our knowledge and experience will continue to improve. Compliance with ethical standards Disclosure of conflict of interest The authors report no competing personal or financial interest related to this work. Statement of informed consent Written informed consent was obtained from the patient for publication of this case report and any accompanying images. World Journal of Advanced Research and Reviews, 2025, 26(01), 4193-4198 4197 References [1] Renard C, Ranchère-Vince D. Tumeurs de la famille Ewing/PNET : vers un nouveau paradigme? Annales de pathologie 2014, 12. [2] Stout AP. A tumor of the ulnar nerve. Proc NY Pathol Soc. 1918;12:2–12. [3] Banerjee SS, Eyden BP, McVey RJ, Bryden AA, Clarke NW. Primary peripheral primitive neuroectodermal tumour of urinary bladder. Histopathology 1997;30:486-90. [4] Gousse AE, Roth DR, Popek EJ, Cooley LD, Horowitz ME. Primary Ewing's sarcoma of the bladder associated with an elevated antinuclear antibody titer. J Urol 1997;158:2265-6. [5] Mentzel T, Flaschka J, Mentzel HJ, Eschholz G, Katenkamp D. Primary primitive neuroectodermal tumor of the urinary bladder. Clinicopathologic case report and differential small cell tumor diagnosis of this site. Pathologe 1998;19:154-8. [6] Desai S. Primary primitive neuroectodermal tumour of the urinary bladder. Histopathology 1998;32:477-8. [7] Colecchia M, Dagrada GP, Poliani PL, Pilotti S. Immunophenotypic and genotypic analysis of a case of primary peripheral primitive neuroectodermal tumour (pPNET) of the urinary bladder. Histopathology 2002;40:108-9. [8] Krüger S, Schmidt H, Kausch I, Böhle A, Holzhausen HJ, Johannisson R, Feller AC. Primitive neuroectodermal tumor (PNET) of the urinary bladder. Pathol Res Pract 2003;199:751-4. [9] Lopez-Beltran A, Pérez-Seoane C, Montironi R, Hernández-Iglesias T, Mackintosh C, de Alava E. Primary primitive neuroectodermal tumour of the urinary bladder: a clinico-pathological study emphasising immunohistochemical, ultrastructural and molecular analyses. J Clin Pathol 2006;59:775-8. [10] Ellinger J, Bastian PJ, Hauser S, Biermann K, Müller SC. Primitive neuroectodermal tumor: rare, highly aggressive differential diagnosis in urologic malignancies. Urology 2006;68:257-62. [11] Osone S, Hosoi H, Tanaka K, Tsuchiya K, Iehara T, Morimoto A, Hashida T, Yamashita M, Kawabata K, Nishijo K, Toguchida J, Hata J, Sugimoto T. A case of a ewing sarcoma family tumor in the urinary bladder after treatment for acute lymphoblastic leukemia. J Pediatr Hematol Oncol 2007;29:841-4. [12] Al Meshaan MK, Nayef M, Kwaider T, Otto W, Katchy KC. Peripheral primitive neuroectodermal tumor of the urinary bladder in an Arab woman with history of squamous cell carcinoma: a case report. J Med Case Rep 2009;3:6840. [13] Busato WF Jr, Almeida GL, Ogata DC. Primary primitive neuroectodermal tumor of the bladder: histologic and clinical features of 9 cases. Clin Genitourin Cancer 2011;9:63-7. [14] Okada Y, Kamata S, Akashi T, Kurata M, Nakamura T, Kihara K. Primitive neuroectodermal tumor/Ewing's sarcoma of the urinary bladder: a case report and its molecular diagnosis. Int J Clin Oncol 2011;16:435-8. [15] Zheng Y, Tan F, Wang L, Xu N, Mou H. Primary primitive neuroectodermal tumor of the urinary bladder: a case report and literature review. Med Oncol 2011;28:S388-91. [16] Rao RN, Sinha S, Babu S, Mehrotra R. Fine-needle aspiration cytology of primitive neuroectodermal tumor of the urinary bladder: a case report. Diagn Cytopathol 2011;39:924-6. [17] Sueyoshi R, Okawada M, Fujimura J, Saito M, Koga H, Lane GJ, Yamataka A. Successful complete resection of Ewing sarcoma arising from the bladder in a 10-year-old boy after chemotherapy. Pediatr Surg Int 2014;30:965-9. [18] Lam CJ, Shayegan B. Complete resection of a primitive neuroectodermal tumour arising in the bladder of a 31year-old female after neoadjuvant chemotherapy. Can Urol Assoc J 2016;10:E264-7. [19] Vallonthaiel AG, Kaur K, Jain D, Singh G, Tiwari D, Pramanik R, Singh P, Sharma MC. Ewing Sarcoma of Urinary Bladder Showing EWSR1 Rearrangement on FISH Analysis and Unique Response to Chemotherapy. Clin Genitourin Cancer 2016;14:e183-6. [20] Tonyalı Ş, Yazıcı S, Yeşilırmak A, Ergen A. The Ewing's Sarcoma Family of Tumors of Urinary Bladder: A Case Report and Review of the Literature. Balkan Med J 2016;33:462-6. [21] Zhang HZ, Wang SY, Shen XH. Ewing sarcoma of urinary bladder occurring simultaneously with high grade papillary urothelial carcinoma. Pathology 2020;52:612-5. World Journal of Advanced Research and Reviews, 2025, 26(01), 4193-4198 4198 [22] Gao L, Xie W, Li K, Huang G, Ji Y, Ou Y, Chen J. Primitive neuroectodermal tumor of urinary bladder: A case report and literature review. Medicine (Baltimore) 2020;99:e23032. [23] Liu B, Qi DJ, Zhang QF. Primary adult primitive neuroectodermal tumor of the bladder: A case report and literature review. Medicine (Baltimore) 2020;99:e21740. [24] Tan J, Liang J, Lu L. Ewing's sarcoma/primitive neuroectodermal tumor (ES/PNET) of the bladder in an adolescent: a case description. Quant Imaging Med Surg. 2023 Apr 1;13(4):2758-2762. [25] Rouprêt M, Babjuk M, Burger M, Capoun O, Cohen D, et al. European Association of Urology Guidelines on Upper Urinary Tract Urothelial Carcinoma: 2020 Update. Eur Urol. 2021 Jan;79(1):62-79.