A rare case of Primary Small Cell Neuroendocrine Carcinoma of the Renal Pelvis: Case Report and Literature Review

A rare case of Primary Small Cell Neuroendocrine Carcinoma of the Renal Pelvis: Case Report and Literature Review | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report A rare case of Primary Small Cell Neuroendocrine Carcinoma of the Renal Pelvis: Case Report and Literature Review WeiZhou Pan, PengNan Hu, Hua Mi This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-5635353/v1 This work is licensed under a CC BY 4.0 License Status: Posted Version 1 posted You are reading this latest preprint version Abstract Background Neuroendocrine neoplasms (NENs) constitute a rare and highly aggressive category of malignant tumors that arise from cells within human tissues and exhibit diverse neural and endocrine functionalities. These tumors predominantly occur in the gastrointestinal tract, pancreas, lungs, and various other organs. However, primary small cell neuroendocrine carcinoma (SCNEC) of the urinary tract is relatively uncommon in clinical settings. Case Presentation: We present a case of primary small cell neuroendocrine carcinoma (SCNEC) of the ureter. The patient was admitted for the management of hematuria and abdominal pain, with a significant past medical history of multiple kidney stone surgeries. Following a comprehensive medical evaluation and a diagnostic ureteral biopsy, the patient was definitively diagnosed with SCNEC. The patient subsequently underwent surgical intervention and was administered a comprehensive treatment regimen consisting of chemotherapy augmented with tislelizumab. Regrettably, the patient died from disease progression one month postfollow-up. Conclusions Small cell neuroendocrine carcinoma (SCNEC) of the urinary system represents an exceptionally rare and aggressive malignant tumor, but its precise etiology and pathogenesis remain elusive. On the basis of the current body of research, we hypothesize that the emergence of these tumors may be linked to repeated cellular injury and regenerative processes. Through meticulous analysis of the presented case, we emphasis that, in clinical practice, suspected SCNEC patients should promptly undergo pathological biopsy to confirm the diagnosis, thereby ensuring timely and accurate patient management. For patients with sufficient physiological reserve to undergo surgery, we advocate for an aggressive surgical approach aimed at curative resection or debulking, in conjunction with a multidisciplinary treatment regimen encompassing chemotherapy and immunotherapy, with the aim of prolonging patient survival. Small cell neuroendocrine carcinoma Urinary tract tumors Chemotherapy Immunotherapy Case report Figures Figure 1 Figure 2 Background Neuroendocrine neoplasms (NENs) constitute an exceptionally rare class of malignant tumors with prohibitively high mortality rates,with an annual incidence of approximately 2.5–5.0 cases per 100,000 individuals 1 . These tumors originate from cells within human tissues that exhibit diverse neural and endocrine functionalities, predominantly affecting the intestines, pancreas, lungs, and other organs or tissues, with the urinary tract being a less frequent site of origin. NENs are categorized on the basis of their degree of differentiation into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Further subclassification of NECs into small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC) is based on the morphological characteristics of the tumor cells 2 . Primary SCNEC is exceedingly uncommon in the clinic, demonstrating highly aggressive biological behavior and frequently being diagnosed at an advanced stage, with the majority of patients experiencing a poor prognosis and succumbing to the disease within a year 3 . Within the urinary system, SCNEC most commonly manifests in the bladder and prostate, with renal pelvis involvement being a rare occurrence. In this study, we present a case of primary SCNEC of the renal pelvis and conduct a literature review, aiming to gain deeper insight into the clinical manifestations, diagnosis, and management of SCNEC through the analysis of this case. Furthermore, we endeavor to provide reliable clinical evidence to facilitate the formulation of subsequent standardized diagnostic and therapeutic protocols. Case Presentation A 52-year-old male patient was admitted for treatment on February 2, 2024, presenting with persistent hematuria for over a month and left-sided abdominal pain for half a month. The patient's medical history included multiple surgeries for stone removal, specifically bilateral nephrolithotomy and left ureterolithotomy. Physical examination revealed a firm left abdominal mass, approximately 5x10 cm in size, and positive flank pain upon percussion of the right kidney area. Abdominal ultrasound revealed the following findings: (1) a solid hypoechoic mass in the left renal pelvis, suspected to be renal pelvic carcinoma; (2) multiple hypoechoic masses adjacent to the abdominal aorta, considered metastatic lymph nodes; and (3) multiple stones in the right kidney with associated hydronephrosis. The results of the abdominal CT scan (Fig. 1 ) further confirmed the following: (1) a space-occupying lesion in the left kidney, suspected to be a malignant tumor involving the right adrenal gland (possibly renal pelvic carcinoma), with multiple metastatic foci at both renal hilums and severe hydronephrosis in the left kidney; (2) a retroperitoneal mass in the right kidney, suspected to be a metastatic tumor with possible hemorrhage; and (3) tumor thrombus formation in the inferior vena cava and left renal vein. Laboratory tests revealed occult blood in the urine (3 cells/µL), urinary tract infection, positive urine leukocytes (3 cells/µL), impaired renal function with a serum creatinine level of 159 µmol/L (normal range: 50–98 µmol/L), and a few atypical cells in the urine, which were suspected to be cancer cells. On the basis of the patient's medical history, physical examination, and auxiliary diagnostic results, the final diagnosis was a malignant tumor of the left renal pelvis, clinical stage cT4N2M1 IV. Given that the imaging findings suggest the presence of a tumor thrombus in the vena cava, surgical treatment was deemed inappropriate at this time. Instead, a percutaneous biopsy was performed to confirm the pathological type prior to formulating a subsequent treatment plan. The pathological results after the biopsy (Fig. 2 ) were as follows: CK (-), vimentin (-), Syn (+), CD56 (+), CgA (-), S-100 (-), CK7 (-), CK20 (-), P63 (-), TTF-1 (-), CD3 (-), CD10 (+), GATA3 (-), PSA (-), PAX-8 (-), Melan A (-), Desmin (-), SMA (-), myogenin (-), Ki-67 (+ 80%), and CK8/18 (+). The tumor exhibited characteristics consistent with those of small cell neuroendocrine carcinoma, with immunohistochemical testing showing the expression of several tumor markers. Given the patient's complex condition and advanced stage of malignancy, following consultation with the oncology department, it was decided to transfer the patient to the oncology department for chemotherapy combined with immunotherapy. The specific treatment regimens were as follows: intravenous infusion of 100 mg/m² etoposide on days 1–3, intravenous infusion of carboplantin AUC5 on day 1, and intravenous infusion of 200 mg of tislelizumab on day 3, which was repeated every three weeks. However, after completing the first cycle of comprehensive treatment, the patient was discharged and subsequently passed away during follow-up one month later. Discussion Neuroendocrine neoplasms (NENs) constitute a heterogeneous assortment of tumors arising from peptide-producing neurons and neuroendocrine cells. These tumors are ubiquitously distributed throughout the body, with the gastrointestinal tract (74%) and respiratory system (25%) being the most prevalent sites, whereas primary tumors in the genitourinary system are exceedingly uncommon (less than 1%) 2 , 4 . The occurrence of NENs is not confined to any particular age or sex;however,the majority of diagnoses occur between the ages of 40 and 60 years. While NENs are reported globally, specific regions, including the United States, Japan, and Nordic countries, present relatively elevated incidence rates 5 – 8 . Contemporary research data, both domestic and international, suggest a persistent increase in the incidence of NENs. Notably, in the United States, epidemiological studies have demonstrated a 6.4-fold increase in the incidence of NENs from 1973–2012, reaching a rate of 6.98 cases per 100,000 person-years 8 – 10 . In 2017, the International Agency for Research on Cancer (IARC) established a classification system for NENs on the basis of their degree of differentiation, distinguishing between well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Within the NEC category, further subclassification is made into small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC) on the on the basis of morphological attributes of the tumor cells 2 , 11 . The etiology and pathogenesis of small cell neuroendocrine carcinoma (SCNEC) of the urinary tract remain elusive, with debate surrounding the cellular origin of these tumors. The majority of theories propose that SCNEC arises from pluripotent stem cells differentiating into neuroendocrine cells, whereas alternative hypotheses suggest an origin from neuroendocrine cells within metaplastic or dysplastic epithelial lesions of the kidney. Studies have revealed a close association between urothelial cell dysfunction, repair processes, and the development of urothelial tumors. Factors such as local growth factor-stimulated repair, imbalances in epithelial-mesenchymal signaling feedback regulation, and epigenetic dysregulation of urothelial regeneration may contribute to malignant transformation 12 – 15 . The patient presented in this case had undergone multiple procedures for the removal of kidney and ureteral stones, with the recurrent damage and regeneration of the urothelium aligning with the aforementioned risk factors. We hypothesize that these factors may be involved in tumorigenesis, although further validation is needed. Patients with urinary SCNEC typically exhibit nonspecific clinical symptoms and imaging findings. Common manifestations include abdominal masses;abdominal, back, or flank pain;hematuria;and fever 16 . These symptoms overlap with those of other urinary system disorders, often leading to diagnostic oversights or misdiagnoses. Furthermore, a subset of SCNEC patients may present with paraneoplastic syndromes 17 , 18 , such as skin flushing, rash, and excessive thirst, which may indicate advanced disease stages and necessitate prompt attention. Radiologically diferentiating between renal SCNEC and renal cell carcinoma is challenging, and there are currently no effective or highly specific diagnostic tools 4 . Consequently, SCNEC is frequently misidentified as renal cell carcinoma or renal angiomyolipoma rupture, indicating the need for increased awareness of SCNEC in patients presenting with nonspecific symptoms such as hematuria and pain. Comprehensive and meticulous evaluations are imperative to ensure accurate diagnosis and mitigate the risks of misdiagnosis and missed diagnosis. The nonspecific clinical manifestations and signs of small cell neuroendocrine carcinoma (SCNEC) present diagnostic challenges and complexities. Pathological biopsy remains the definitive diagnostic gold standard for SCNEC. The pathognomonic features of SCNEC include small, round to oval tumor cells resembling lymphocytes. Additionally, some SCNEC cells exhibit a spindle-shaped morphology with scant cytoplasm, fine granular or hyperchromatic nuclei with inconspicuous nucleoli, and readily identifiable mitotic figures. These cells are often diffusely distributed or arranged in nests within the tissue and are frequently accompanied by necrosis 2 , 10 . Immunohistochemical analysis revealed that SCNEC expresses specific neuroendocrine markers, with sensitivity rates of NSE (90%), NF (83.3%), and Syn (45.5%) 19 . This characteristic is attributed to the secretory capacity of neuroendocrine neoplasms (NENs) for specific peptide hormones,such as chromogranin A (CgA), neuron-specific enolase (NSE), and pancreatic polypeptide 20 . As a subset of NENs, the diagnosis of SCNEC relies on immunohistochemical indicators, including CgA, Syn, and CD56. In the case reported herein, the patient's immunohistochemical results were positive for Syn and CD56, further confirming the diagnosis. Notably, the level of NSE, a marker of neural maturation, is elevated in body fluids and is closely correlated with the proliferation of malignant tumor cells. Therefore, NSE has significant value in the diagnosis, staging, and treatment planning of neuroendocrine tumors 21 , 22 . During the follow-up of this patient, a marked increase in the patient's NSE level, specifically 351.50 ng/mL (normal range: 15.7–17.0 ng/mL), provided a robust basis for confirming the diagnosis, formulating the treatment plan, and assessing the efficacy of chemotherapy. SCNEC demonstrates substantial invasiveness and a propensity for distant metastasis, with lymphatic spread being the most prevalent route of metastasis. At diagnosis, numerous patients present with lymph node or distant metastasis of the primary lesion, which aligns with conclusions documented in the literature 23 , 24 . In the present case, the patient presented with metastasis to the right adrenal gland and para-aortic lymph nodes at initial diagnosis. Furthermore, hematogenous metastasis is another frequent metastatic mode in advanced cases, predominantly affecting the lungs and liver. In addition to these pathways, SCNEC may disseminate through direct infiltration and peritoneal metastasis. Collectively, the diverse metastatic pathways exhibited by SCNEC are pivotal factors contributing to its rapid disease progression and unfavorable prognosis. Given the complexity and increased invasiveness of SCNEC, early diagnosis and prompt treatment are paramount. Clinicians must maintain a high index of suspicion and conduct thorough medical histories, physical examinations, and necessary imaging studies, including CT and MRI, to comprehensively evaluate the patient's disease status. SCNEC is a rare condition for which definitive treatment guidelines are currently lacking. For early-stage SCNEC, radical surgery is the recommended primary intervention, often followed by adjuvant chemotherapy, radiotherapy, or a combination of immunotherapies. In advanced cases where radical surgery is not feasible, comprehensive treatment strategies, such as chemotherapy, are employed to increase median overall survival 2 , 25 . Given the morphological and biological similarities between SCNEC and small cell lung carcinoma (SCLC) ,clinical treatment protocols often mirror those for SCLC. Specifically, platinum-based chemotherapy regimens have shown promising potential as adjuvant treatment for SCNEC, improving patient prognosis and survival rates 26 . A 2009 clinical trial involving 18 patients with operable small cell urothelial carcinoma (partially comprising small cell carcinoma components) demonstrated that a neoadjuvant chemotherapy regimen of four cycles of ifosfamide, doxorubicin, etoposide, and cisplatin resulted in a median survival period of 58 months, with 78% of patients experiencing a reduction in pathological stage 27 . Similar outcomes, including tumor stage reduction and increased survival rates, were reported in a retrospective study of 95 cT4aN0M0 bladder neuroendocrine carcinoma patients 28 . Despite its high degree of malignancy, SCNEC can be successfully treated in some cases. For example, B. Masood et al. reported a patient with bladder small cell neuroendocrine carcinoma who underwent radical cystectomy after four cycles of neoadjuvant chemotherapy with cisplatin and etoposide. The patient showed no recurrence, progression, or metastasis during the 13-month postoperative follow-up period 29 . However, it is crucial to note that this patient's TNM stage was cT4N2M1, corresponding to clinical stage IV, and the patient was in the late stages of the disease with poor overall health and was unable to tolerate radical or debulking surgery. The patient's treatment was limited to chemotherapy combined with immunotherapy to prolong life, but unfortunately, the patient succumbed to disease progression only one month after comprehensive treatment was initiated. In the selection of treatment strategies for SCNEC, in addition to the aforementioned chemotherapy and immunotherapy, targeted therapy has emerged as a promising option. Recent research on targeted drugs for neuroendocrine tumors has achieved certain advancements, such as radioligand therapy (RLT) and peptide receptor radionuclide therapy (PRRT), which target somatostatin receptors 30 . These treatment modalities effectively inhibit the growth and dissemination of tumor cells by targeting specific molecular markers. Conclusion Small cell neuroendocrine carcinoma (SCNEC) of the urinary system represents an exceedingly rare malignancy, but its precise etiology and pathogenesis remain elusive. On the basis of contemporary research findings, we postulate that the emergence of these tumors may be linked to repetitive cellular damage and regenerative processes. A thorough analysis of this particular case led us to strongly recommend that, in clinical practice, upon encountering a patient with suspected SCNEC, prompt arrangement of a pathological biopsy is imperative to confirm the diagnosis, thereby ensuring both timeliness and accuracy. For patients with sufficient physiological reserve to undergo surgery, we advocate an aggressive surgical approach aimed at curative resection or debulking, complemented by a comprehensive treatment strategy encompassing chemotherapy and immunotherapy, to maximize patient survival. Abbreviations NENs Neuroendocrine neoplasms NETs Neuroendocrine tumors NECs Neuroendocrine carcinomas SCNEC Small cell neuroendocrine carcinoma LCNEC Large cell neuroendocrine carcinoma SCLC Small cell lung carcinoma Declarations Acknowledgements The authors sincerely thank the patient for her consent for the publication of this case report. Conflicts of interest The authors have no conflicts of interest to declare. Author Contributions (I) Conception and design: WeiZhou Pan and PengNan Hu; (II) Administrative support: Hua Mi; (III) Provision of study materials or patients: WeiZhou Pan and PengNan Hu; (IV) Collection and assembly of data: WeiZhou Pan and PengNan Hu; (V)Manuscript writing: All authors; (VI) Final approval of manuscript: All authors. Funding This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors Data availability No datasets were generated or analysed during the current study Ethics approval and consent to participate The study was approved by the First Affiliated Hospital of Guangxi Medical University ethics board (No. 2024--E659--01),and informed consent was obtained from all individual participants.The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013). Consent for publication Written informed consent was obtained from the patient for publication of this case report. Competing interests The authors declare no competing interests. Clinical Trial No. Not applicable Conflicts of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. All procedures performed in this study were in accordance with the ethical standards of the Helsinki Declaration (as revised in 2013). 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Primary small cell neuroendocrine carcinoma of the kidney: morphological, immunohistochemical, ultrastructural, and cytogenetic study of a case and review of the literature. Endocr Pathol . 2009;20(1):24-34. doi:10.1007/s12022-008-9054-y Zhang S. Pulmonary neuroendocrine tumors: study of 266 cases focusing on clinicopathological characteristics, immunophenotype, and prognosis. J Cancer Res Clin Oncol . Published online 2023. Isgrò MA, Bottoni P, Scatena R. Neuron-Specific Enolase as a Biomarker: Biochemical and Clinical Aspects. Adv Exp Med Biol . 2015;867:125-143. doi:10.1007/978-94-017-7215-0_9 Kaiser E, Kuzmits R, Pregant P, Burghuber O, Worofka W. Clinical biochemistry of neuron specific enolase. Clin Chim Acta Int J Clin Chem . 1989;183(1):13-31. doi:10.1016/0009-8981(89)90268-4 Hashimoto Y, Ito T, Gotoh A, et al. Clinical characteristics, prognostic factors, and outcomes of patients with essential thrombocythemia in Japan: the JSH-MPN-R18 study. Int J Hematol . 2022;115(2):208-221. doi:10.1007/s12185-021-03253-0 Zhong W, Lin R, Zhang L, et al. Clinicopathologic characteristics, therapy and outcomes of patients with primary ureteral small cell carcinoma: a case series and systematic review of the literature. OncoTargets Ther . 2017;Volume 10:4105-4111. doi:10.2147/OTT.S138769 Shahab N. Extrapulmonary small cell carcinoma of the bladder. Semin Oncol . 2007;34(1):15-21. doi:10.1053/j.seminoncol.2006.10.025 Mascaux C, Paesmans M, Berghmans T, et al. A systematic review of the role of etoposide and cisplatin in the chemotherapy of small cell lung cancer with methodology assessment and meta-analysis . Lung Cancer . 2000;30(1):23-36. doi:10.1016/S0169-5002(00)00127-6 Siefker-Radtke AO, Kamat AM, Grossman HB, et al. Phase II Clinical Trial of Neoadjuvant Alternating Doublet Chemotherapy With Ifosfamide/Doxorubicin and Etoposide/Cisplatin in Small-Cell Urothelial Cancer. J Clin Oncol . 2009;27(16):2592-2597. doi:10.1200/JCO.2008.19.0256 Lynch SP, Shen Y, Kamat A, et al. Neoadjuvant chemotherapy in small cell urothelial cancer improves pathologic downstaging and long-term outcomes: results from a retrospective study at the MD Anderson Cancer Center. Eur Urol . 2013;64(2):307-313. doi:10.1016/j.eururo.2012.04.020 Masood B, Iqbal N, Iqbal W, Masood Y, Akbar MK, Mamoon N. Small-cell neuroendocrine carcinoma of the urinary bladder: A case report. Int J Health Sci . 2020;14(2):53-55. Cives M, Strosberg J. Radionuclide Therapy for Neuroendocrine Tumors. Curr Oncol Rep . 2017;19(2):9. doi:10.1007/s11912-017-0567-8 Additional Declarations No competing interests reported. Cite Share Download PDF Status: Posted Version 1 posted You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-5635353","acceptedTermsAndConditions":true,"allowDirectSubmit":true,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":391477434,"identity":"089755e1-6a52-43af-bcb0-aff934fc76b0","order_by":0,"name":"WeiZhou Pan","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"WeiZhou","middleName":"","lastName":"Pan","suffix":""},{"id":391477435,"identity":"a6722ebd-4f8b-40e2-9581-1619531dfe96","order_by":1,"name":"PengNan Hu","email":"","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":false,"prefix":"","firstName":"PengNan","middleName":"","lastName":"Hu","suffix":""},{"id":391477436,"identity":"11f001ad-2127-41e5-8081-d38a0ec2fc94","order_by":2,"name":"Hua Mi","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxUlEQVRIiWNgGAWjYDACZh4gUSHBw8/e2PjwA/FaztjISPYcbjaWIM4aoBbGtjQbgxvpbQI8xGjQbec9JvGD7TCPwc2HbQwSDHZyug0EtJgd5kuT7OE5zCN5O7HtQQFDsrHZAYJaeMwkeCQO8/DdTmw3kGA4kLiNGC2SfwwO8zDcPNgmwUOsFmmehDQegRuMxGsxtpY5YMMj2ZMIDGQDYvxy/ozhzbf/JOz52Y8/fPihwk6OoBY0YECa8lEwCkbBKBgFOAAAJ8Q/MEc1/3gAAAAASUVORK5CYII=","orcid":"","institution":"The First Affiliated Hospital of Guangxi Medical University","correspondingAuthor":true,"prefix":"","firstName":"Hua","middleName":"","lastName":"Mi","suffix":""}],"badges":[],"createdAt":"2024-12-13 04:23:24","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-5635353/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-5635353/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":72288295,"identity":"d59e962d-e8bc-4da0-81b1-0b9cdde29067","added_by":"auto","created_at":"2024-12-24 17:16:14","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":208918,"visible":true,"origin":"","legend":"\u003cp\u003eOn the enhanced scan of a small cell neuroendocrine carcinoma of the left renal pelvis, the tumor revealed the inferior vena cava and left renal vein as a venous tumor thrombus (blue) and multiple enlarged lymph nodes and soft tissue masses in the left hilum and abdominal aorta (green).\u003c/p\u003e","description":"","filename":"Fig.1.png","url":"https://assets-eu.researchsquare.com/files/rs-5635353/v1/8856686cd8bac66f2ab5d339.png"},{"id":72292050,"identity":"ddd791f3-c14a-437f-be61-b87b071ed806","added_by":"auto","created_at":"2024-12-24 17:32:14","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":120540,"visible":true,"origin":"","legend":"\u003cp\u003ePartial puncture of neuroendocrine carcinoma:Syn (+), CD56 (+), CgA (-), and Ki-67 (+ 80%).\u003c/p\u003e","description":"","filename":"Fig.2.png","url":"https://assets-eu.researchsquare.com/files/rs-5635353/v1/fb8ccad5520be8c1c5531ec8.png"},{"id":72293123,"identity":"1fbbac25-e1b1-4408-824a-ce4326154645","added_by":"auto","created_at":"2024-12-24 18:08:22","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":698926,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-5635353/v1/e0142053-df0f-4155-a6ca-225abeb23796.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"A rare case of Primary Small Cell Neuroendocrine Carcinoma of the Renal Pelvis: Case Report and Literature Review","fulltext":[{"header":"Background","content":"\u003cp\u003eNeuroendocrine neoplasms (NENs) constitute an exceptionally rare class of malignant tumors with prohibitively high mortality rates,with an annual incidence of approximately 2.5\u0026ndash;5.0 cases per 100,000 individuals\u003csup\u003e\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e\u003c/sup\u003e. These tumors originate from cells within human tissues that exhibit diverse neural and endocrine functionalities, predominantly affecting the intestines, pancreas, lungs, and other organs or tissues, with the urinary tract being a less frequent site of origin. NENs are categorized on the basis of their degree of differentiation into well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Further subclassification of NECs into small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC) is based on the morphological characteristics of the tumor cells\u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003ePrimary SCNEC is exceedingly uncommon in the clinic, demonstrating highly aggressive biological behavior and frequently being diagnosed at an advanced stage, with the majority of patients experiencing a poor prognosis and succumbing to the disease within a year \u003csup\u003e\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e\u003c/sup\u003e. Within the urinary system, SCNEC most commonly manifests in the bladder and prostate, with renal pelvis involvement being a rare occurrence. In this study, we present a case of primary SCNEC of the renal pelvis and conduct a literature review, aiming to gain deeper insight into the clinical manifestations, diagnosis, and management of SCNEC through the analysis of this case. Furthermore, we endeavor to provide reliable clinical evidence to facilitate the formulation of subsequent standardized diagnostic and therapeutic protocols.\u003c/p\u003e"},{"header":"Case Presentation","content":"\u003cp\u003eA 52-year-old male patient was admitted for treatment on February 2, 2024, presenting with persistent hematuria for over a month and left-sided abdominal pain for half a month. The patient's medical history included multiple surgeries for stone removal, specifically bilateral nephrolithotomy and left ureterolithotomy. Physical examination revealed a firm left abdominal mass, approximately 5x10 cm in size, and positive flank pain upon percussion of the right kidney area.\u003c/p\u003e \u003cp\u003eAbdominal ultrasound revealed the following findings: (1) a solid hypoechoic mass in the left renal pelvis, suspected to be renal pelvic carcinoma; (2) multiple hypoechoic masses adjacent to the abdominal aorta, considered metastatic lymph nodes; and (3) multiple stones in the right kidney with associated hydronephrosis. The results of the abdominal CT scan (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) further confirmed the following: (1) a space-occupying lesion in the left kidney, suspected to be a malignant tumor involving the right adrenal gland (possibly renal pelvic carcinoma), with multiple metastatic foci at both renal hilums and severe hydronephrosis in the left kidney; (2) a retroperitoneal mass in the right kidney, suspected to be a metastatic tumor with possible hemorrhage; and (3) tumor thrombus formation in the inferior vena cava and left renal vein. Laboratory tests revealed occult blood in the urine (3 cells/\u0026micro;L), urinary tract infection, positive urine leukocytes (3 cells/\u0026micro;L), impaired renal function with a serum creatinine level of 159 \u0026micro;mol/L (normal range: 50\u0026ndash;98 \u0026micro;mol/L), and a few atypical cells in the urine, which were suspected to be cancer cells.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e \u003cp\u003eOn the basis of the patient's medical history, physical examination, and auxiliary diagnostic results, the final diagnosis was a malignant tumor of the left renal pelvis, clinical stage cT4N2M1 IV. Given that the imaging findings suggest the presence of a tumor thrombus in the vena cava, surgical treatment was deemed inappropriate at this time. Instead, a percutaneous biopsy was performed to confirm the pathological type prior to formulating a subsequent treatment plan. The pathological results after the biopsy (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e) were as follows: CK (-), vimentin (-), Syn (+), CD56 (+), CgA (-), S-100 (-), CK7 (-), CK20 (-), P63 (-), TTF-1 (-), CD3 (-), CD10 (+), GATA3 (-), PSA (-), PAX-8 (-), Melan A (-), Desmin (-), SMA (-), myogenin (-), Ki-67 (+\u0026thinsp;80%), and CK8/18 (+). The tumor exhibited characteristics consistent with those of small cell neuroendocrine carcinoma, with immunohistochemical testing showing the expression of several tumor markers. Given the patient's complex condition and advanced stage of malignancy, following consultation with the oncology department, it was decided to transfer the patient to the oncology department for chemotherapy combined with immunotherapy. The specific treatment regimens were as follows: intravenous infusion of 100 mg/m\u0026sup2; etoposide on days 1\u0026ndash;3, intravenous infusion of carboplantin AUC5 on day 1, and intravenous infusion of 200 mg of tislelizumab on day 3, which was repeated every three weeks. However, after completing the first cycle of comprehensive treatment, the patient was discharged and subsequently passed away during follow-up one month later.\u003c/p\u003e \u003cp\u003e \u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eNeuroendocrine neoplasms (NENs) constitute a heterogeneous assortment of tumors arising from peptide-producing neurons and neuroendocrine cells. These tumors are ubiquitously distributed throughout the body, with the gastrointestinal tract (74%) and respiratory system (25%) being the most prevalent sites, whereas primary tumors in the genitourinary system are exceedingly uncommon (less than 1%) \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. The occurrence of NENs is not confined to any particular age or sex;however,the majority of diagnoses occur between the ages of 40 and 60 years. While NENs are reported globally, specific regions, including the United States, Japan, and Nordic countries, present relatively elevated incidence rates\u003csup\u003e\u003cspan additionalcitationids=\"CR6 CR7\" citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u003c/sup\u003e. Contemporary research data, both domestic and international, suggest a persistent increase in the incidence of NENs. Notably, in the United States, epidemiological studies have demonstrated a 6.4-fold increase in the incidence of NENs from 1973\u0026ndash;2012, reaching a rate of 6.98 cases per 100,000 person-years \u003csup\u003e\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eIn 2017, the International Agency for Research on Cancer (IARC) established a classification system for NENs on the basis of their degree of differentiation, distinguishing between well-differentiated neuroendocrine tumors (NETs) and poorly differentiated neuroendocrine carcinomas (NECs). Within the NEC category, further subclassification is made into small cell neuroendocrine carcinoma (SCNEC) and large cell neuroendocrine carcinoma (LCNEC) on the on the basis of morphological attributes of the tumor cells \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e\u003c/sup\u003e.\u003c/p\u003e \u003cp\u003eThe etiology and pathogenesis of small cell neuroendocrine carcinoma (SCNEC) of the urinary tract remain elusive, with debate surrounding the cellular origin of these tumors. The majority of theories propose that SCNEC arises from pluripotent stem cells differentiating into neuroendocrine cells, whereas alternative hypotheses suggest an origin from neuroendocrine cells within metaplastic or dysplastic epithelial lesions of the kidney. Studies have revealed a close association between urothelial cell dysfunction, repair processes, and the development of urothelial tumors. Factors such as local growth factor-stimulated repair, imbalances in epithelial-mesenchymal signaling feedback regulation, and epigenetic dysregulation of urothelial regeneration may contribute to malignant transformation \u003csup\u003e\u003cspan additionalcitationids=\"CR13 CR14\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e\u003c/sup\u003e. The patient presented in this case had undergone multiple procedures for the removal of kidney and ureteral stones, with the recurrent damage and regeneration of the urothelium aligning with the aforementioned risk factors. We hypothesize that these factors may be involved in tumorigenesis, although further validation is needed.\u003c/p\u003e \u003cp\u003ePatients with urinary SCNEC typically exhibit nonspecific clinical symptoms and imaging findings. Common manifestations include abdominal masses;abdominal, back, or flank pain;hematuria;and fever \u003csup\u003e\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e\u003c/sup\u003e. These symptoms overlap with those of other urinary system disorders, often leading to diagnostic oversights or misdiagnoses. Furthermore, a subset of SCNEC patients may present with paraneoplastic syndromes \u003csup\u003e\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e,\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e\u003c/sup\u003e, such as skin flushing, rash, and excessive thirst, which may indicate advanced disease stages and necessitate prompt attention. Radiologically diferentiating between renal SCNEC and renal cell carcinoma is challenging, and there are currently no effective or highly specific diagnostic tools\u003csup\u003e\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e\u003c/sup\u003e. Consequently, SCNEC is frequently misidentified as renal cell carcinoma or renal angiomyolipoma rupture, indicating the need for increased awareness of SCNEC in patients presenting with nonspecific symptoms such as hematuria and pain. Comprehensive and meticulous evaluations are imperative to ensure accurate diagnosis and mitigate the risks of misdiagnosis and missed diagnosis.\u003c/p\u003e \u003cp\u003eThe nonspecific clinical manifestations and signs of small cell neuroendocrine carcinoma (SCNEC) present diagnostic challenges and complexities. Pathological biopsy remains the definitive diagnostic gold standard for SCNEC. The pathognomonic features of SCNEC include small, round to oval tumor cells resembling lymphocytes. Additionally, some SCNEC cells exhibit a spindle-shaped morphology with scant cytoplasm, fine granular or hyperchromatic nuclei with inconspicuous nucleoli, and readily identifiable mitotic figures. These cells are often diffusely distributed or arranged in nests within the tissue and are frequently accompanied by necrosis \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e\u003c/sup\u003e. Immunohistochemical analysis revealed that SCNEC expresses specific neuroendocrine markers, with sensitivity rates of NSE (90%), NF (83.3%), and Syn (45.5%) \u003csup\u003e\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e\u003c/sup\u003e. This characteristic is attributed to the secretory capacity of neuroendocrine neoplasms (NENs) for specific peptide hormones,such as chromogranin A (CgA), neuron-specific enolase (NSE), and pancreatic polypeptide \u003csup\u003e\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e\u003c/sup\u003e. As a subset of NENs, the diagnosis of SCNEC relies on immunohistochemical indicators, including CgA, Syn, and CD56. In the case reported herein, the patient's immunohistochemical results were positive for Syn and CD56, further confirming the diagnosis. Notably, the level of NSE, a marker of neural maturation, is elevated in body fluids and is closely correlated with the proliferation of malignant tumor cells. Therefore, NSE has significant value in the diagnosis, staging, and treatment planning of neuroendocrine tumors \u003csup\u003e\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e,\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e\u003c/sup\u003e. During the follow-up of this patient, a marked increase in the patient's NSE level, specifically 351.50 ng/mL (normal range: 15.7\u0026ndash;17.0 ng/mL), provided a robust basis for confirming the diagnosis, formulating the treatment plan, and assessing the efficacy of chemotherapy.\u003c/p\u003e \u003cp\u003eSCNEC demonstrates substantial invasiveness and a propensity for distant metastasis, with lymphatic spread being the most prevalent route of metastasis. At diagnosis, numerous patients present with lymph node or distant metastasis of the primary lesion, which aligns with conclusions documented in the literature \u003csup\u003e\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e,\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e\u003c/sup\u003e. In the present case, the patient presented with metastasis to the right adrenal gland and para-aortic lymph nodes at initial diagnosis. Furthermore, hematogenous metastasis is another frequent metastatic mode in advanced cases, predominantly affecting the lungs and liver. In addition to these pathways, SCNEC may disseminate through direct infiltration and peritoneal metastasis. Collectively, the diverse metastatic pathways exhibited by SCNEC are pivotal factors contributing to its rapid disease progression and unfavorable prognosis. Given the complexity and increased invasiveness of SCNEC, early diagnosis and prompt treatment are paramount. Clinicians must maintain a high index of suspicion and conduct thorough medical histories, physical examinations, and necessary imaging studies, including CT and MRI, to comprehensively evaluate the patient's disease status.\u003c/p\u003e \u003cp\u003eSCNEC is a rare condition for which definitive treatment guidelines are currently lacking. For early-stage SCNEC, radical surgery is the recommended primary intervention, often followed by adjuvant chemotherapy, radiotherapy, or a combination of immunotherapies. In advanced cases where radical surgery is not feasible, comprehensive treatment strategies, such as chemotherapy, are employed to increase median overall survival \u003csup\u003e\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e,\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e\u003c/sup\u003e. Given the morphological and biological similarities between SCNEC and small cell lung carcinoma (SCLC) ,clinical treatment protocols often mirror those for SCLC. Specifically, platinum-based chemotherapy regimens have shown promising potential as adjuvant treatment for SCNEC, improving patient prognosis and survival rates\u003csup\u003e\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e\u003c/sup\u003e. A 2009 clinical trial involving 18 patients with operable small cell urothelial carcinoma (partially comprising small cell carcinoma components) demonstrated that a neoadjuvant chemotherapy regimen of four cycles of ifosfamide, doxorubicin, etoposide, and cisplatin resulted in a median survival period of 58 months, with 78% of patients experiencing a reduction in pathological stage \u003csup\u003e\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e\u003c/sup\u003e. Similar outcomes, including tumor stage reduction and increased survival rates, were reported in a retrospective study of 95 cT4aN0M0 bladder neuroendocrine carcinoma patients\u003csup\u003e\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e\u003c/sup\u003e. Despite its high degree of malignancy, SCNEC can be successfully treated in some cases. For example, B. Masood et al. reported a patient with bladder small cell neuroendocrine carcinoma who underwent radical cystectomy after four cycles of neoadjuvant chemotherapy with cisplatin and etoposide. The patient showed no recurrence, progression, or metastasis during the 13-month postoperative follow-up period\u003csup\u003e\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e\u003c/sup\u003e. However, it is crucial to note that this patient's TNM stage was cT4N2M1, corresponding to clinical stage IV, and the patient was in the late stages of the disease with poor overall health and was unable to tolerate radical or debulking surgery. The patient's treatment was limited to chemotherapy combined with immunotherapy to prolong life, but unfortunately, the patient succumbed to disease progression only one month after comprehensive treatment was initiated. In the selection of treatment strategies for SCNEC, in addition to the aforementioned chemotherapy and immunotherapy, targeted therapy has emerged as a promising option. Recent research on targeted drugs for neuroendocrine tumors has achieved certain advancements, such as radioligand therapy (RLT) and peptide receptor radionuclide therapy (PRRT), which target somatostatin receptors\u003csup\u003e\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e\u003c/sup\u003e. These treatment modalities effectively inhibit the growth and dissemination of tumor cells by targeting specific molecular markers.\u003c/p\u003e"},{"header":"Conclusion","content":"\u003cp\u003eSmall cell neuroendocrine carcinoma (SCNEC) of the urinary system represents an exceedingly rare malignancy, but its precise etiology and pathogenesis remain elusive. On the basis of contemporary research findings, we postulate that the emergence of these tumors may be linked to repetitive cellular damage and regenerative processes. A thorough analysis of this particular case led us to strongly recommend that, in clinical practice, upon encountering a patient with suspected SCNEC, prompt arrangement of a pathological biopsy is imperative to confirm the diagnosis, thereby ensuring both timeliness and accuracy. For patients with sufficient physiological reserve to undergo surgery, we advocate an aggressive surgical approach aimed at curative resection or debulking, complemented by a comprehensive treatment strategy encompassing chemotherapy and immunotherapy, to maximize patient survival.\u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eNENs \u0026nbsp;Neuroendocrine neoplasms\u003c/p\u003e\n\u003cp\u003eNETs \u0026nbsp;Neuroendocrine tumors\u003c/p\u003e\n\u003cp\u003eNECs \u0026nbsp;Neuroendocrine carcinomas\u003c/p\u003e\n\u003cp\u003eSCNEC \u0026nbsp;Small cell neuroendocrine carcinoma\u003c/p\u003e\n\u003cp\u003eLCNEC \u0026nbsp;Large cell neuroendocrine carcinoma\u003c/p\u003e\n\u003cp\u003eSCLC \u0026nbsp;Small cell lung carcinoma\u0026nbsp;\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eAcknowledgements\u003c/strong\u003e The authors sincerely thank the patient for her consent for the publication of this case report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConflicts of interest\u0026nbsp;\u003c/strong\u003eThe authors have no conflicts of interest to declare.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor Contributions\u0026nbsp;\u003c/strong\u003e(I) Conception and design: WeiZhou Pan and PengNan Hu; (II) Administrative support: Hua Mi; (III) Provision of study materials or patients: WeiZhou Pan and PengNan Hu; (IV) Collection and assembly of data: WeiZhou Pan and PengNan Hu; (V)Manuscript writing: All authors; (VI) Final approval of manuscript: All authors.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding\u003c/strong\u003e This study received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eData availability\u003c/strong\u003e No datasets were generated or analysed during the current study\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate\u003c/strong\u003e The study was approved by the First Affiliated Hospital of Guangxi Medical University ethics board (No. 2024--E659--01),and informed consent was obtained from all individual participants.The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki (as revised in 2013).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication\u003c/strong\u003e Written informed consent was obtained from the patient for publication of this case report.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests\u003c/strong\u003e The authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eClinical Trial No.\u003c/strong\u003e Not applicable\u003c/p\u003e\u003cp\u003eConflicts of Interest: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.\u003c/p\u003e\n\u003cp\u003eEthical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. Written informed consent was obtained from the patient for the publication of this case report and accompanying images. All procedures performed in this study were in accordance with the ethical standards of the Helsinki Declaration (as revised in 2013). The study was approved by the First Affiliated Hospital of Guangxi Medical University ethics board (No. 2024-E659-01).\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eAl-Ahmadie H, Iyer G. Updates on the Genetics and Molecular Subtypes of Urothelial Carcinoma and Select Variants. Published online 2019.\u003c/li\u003e\n\u003cli\u003eRindi G, Mete O, Uccella S, et al. Overview of the 2022 WHO Classification of Neuroendocrine Neoplasms. \u003cem\u003eEndocr Pathol\u003c/em\u003e. 2022;33(1):115-154. doi:10.1007/s12022-022-09708-2\u003c/li\u003e\n\u003cli\u003eQing D, Peng L, Cen F, Huang X, Wei Q, Lu H. 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Radionuclide Therapy for Neuroendocrine Tumors. \u003cem\u003eCurr Oncol Rep\u003c/em\u003e. 2017;19(2):9. doi:10.1007/s11912-017-0567-8\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"Small cell neuroendocrine carcinoma, Urinary tract tumors, Chemotherapy, Immunotherapy, Case report","lastPublishedDoi":"10.21203/rs.3.rs-5635353/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-5635353/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cb\u003eBackground\u003c/b\u003e\u003c/p\u003e \u003cp\u003eNeuroendocrine neoplasms (NENs) constitute a rare and highly aggressive category of malignant tumors that arise from cells within human tissues and exhibit diverse neural and endocrine functionalities. These tumors predominantly occur in the gastrointestinal tract, pancreas, lungs, and various other organs. However, primary small cell neuroendocrine carcinoma (SCNEC) of the urinary tract is relatively uncommon in clinical settings.\u003c/p\u003e\u003cp\u003e\u003cb\u003eCase Presentation:\u003c/b\u003e\u003c/p\u003e \u003cp\u003eWe present a case of primary small cell neuroendocrine carcinoma (SCNEC) of the ureter. The patient was admitted for the management of hematuria and abdominal pain, with a significant past medical history of multiple kidney stone surgeries. Following a comprehensive medical evaluation and a diagnostic ureteral biopsy, the patient was definitively diagnosed with SCNEC. The patient subsequently underwent surgical intervention and was administered a comprehensive treatment regimen consisting of chemotherapy augmented with tislelizumab. Regrettably, the patient died from disease progression one month postfollow-up.\u003c/p\u003e\u003cp\u003e\u003cb\u003eConclusions\u003c/b\u003e\u003c/p\u003e \u003cp\u003eSmall cell neuroendocrine carcinoma (SCNEC) of the urinary system represents an exceptionally rare and aggressive malignant tumor, but its precise etiology and pathogenesis remain elusive. On the basis of the current body of research, we hypothesize that the emergence of these tumors may be linked to repeated cellular injury and regenerative processes. Through meticulous analysis of the presented case, we emphasis that, in clinical practice, suspected SCNEC patients should promptly undergo pathological biopsy to confirm the diagnosis, thereby ensuring timely and accurate patient management. For patients with sufficient physiological reserve to undergo surgery, we advocate for an aggressive surgical approach aimed at curative resection or debulking, in conjunction with a multidisciplinary treatment regimen encompassing chemotherapy and immunotherapy, with the aim of prolonging patient survival.\u003c/p\u003e","manuscriptTitle":"A rare case of Primary Small Cell Neuroendocrine Carcinoma of the Renal Pelvis: Case Report and Literature Review","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2024-12-24 17:16:09","doi":"10.21203/rs.3.rs-5635353/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"444ded39-d327-4636-8a27-5c40daa9f533","owner":[],"postedDate":"December 24th, 2024","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[],"tags":[],"updatedAt":"2024-12-24T18:08:07+00:00","versionOfRecord":[],"versionCreatedAt":"2024-12-24 17:16:09","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-5635353","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-5635353","identity":"rs-5635353","version":["v1"]},"buildId":"qtupq5eGEP_6zYnWcrvyt","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}