Treatment and survival of non-metastatic small cell carcinoma of the bladder from multiple centers in China.

Small cell carcinoma of the bladder (SCCB) is a rare, highly malignant neuroendocrine tumor. This study attempted to analyze tumor characteristics, treatments and clinical outcomes in China. We conducted a retrospective analysis of patients diagnosed with non-metastatic SCCB at multi-institutions between January 2007 and January 2022. The Kaplan-Meier method was used to calculate survival. A total of 20 patients were included. 10 had localized disease (T1-2N0), and 10 had locally advanced disease (≥ T3 or N+). 13 received local treatment (partial cystectomy or transurethral resection of the bladder tumor) and 7 received radical treatment (radical cystectomy or radiotherapy). A total of 18 patients (90%) received chemotherapy (CT), either neoadjuvant CT (n = 5) or adjuvant CT (n = 13). The median OS for the receiving local treatment was 65.3 months (95% CI 0 to 138 months) and the corresponding 1-year, 2-year, and 3-year OS was 77%, 54%, and 54%, respectively. The median OS for the receiving radical treatment was not reached and the corresponding 1-year, 2-year, and 3-year OS was 100%, 100%, and 75%, respectively. The median PFS for receiving local treatment was 13.8 months (95% CI 9.3 to 18.3 months) and the corresponding 1-year, 2-year, and 3-year PFS was 46%, 31%, and 31%, respectively. The median PFS for the receiving radical treatment was not reached and the corresponding 1-year, 2-year, and 3-year PFS was 83%, 56%, and 56%, respectively. This study reported the largest cohort of non-metastatic SCCB among Chinese population. Given its metastatic potential, CT remained an essential part of the treatment. The survival outcomes of radical cystectomy and RT in non-metastatic SCCB were encouraging.

Small-cell carcinoma in the head and neck region: A propensity score-matched analysis of the effect of surgery.

BACKGROUND: Head and neck small-cell carcinoma (HNSmCC) is a rare and aggressive cancer with a high tendency for distant metastasis. It is treated with multimodal treatment involving chemotherapy. Occasionally, surgery is performed for the management of locoregional HNSmCC. However, the benefits of surgery in this context have not yet been elucidated. Therefore, in this study, we aimed to investigate whether surgery could improve the survival of patients with HNSmCC. PATIENTS AND METHODS: We obtained data from patients with locoregional HNSmCC treated with chemoradiation therapy (CRT) from the Surveillance, Epidemiology, and End Results database. Patients who did and did not undergo surgery were matched using propensity scores. The overall survival (OS) and disease-specific survival (DSS) rates were estimated using the Kaplan-Meier method and tested using the log-rank test. Hazard ratios (HRs) were calculated using the Cox proportional hazard model. RESULTS: The 5-year OS rates of the patients who did and did not undergo surgery were 57.2% and 50.6%, respectively (P = 0.689); the corresponding 5-year DSS rates were 61.0% and 57.5% (P = 0.769). The adjusted HRs for surgery were 0.85 (95% confidence interval [CI]: 0.54-1.33) for OS and 0.87 (95% CI: 0.51-1.49) for DSS. CONCLUSION: The addition of surgery to CRT did not improve the survival of patients with locoregional HNSmCC.

The Use of Lurbinectedin for the Treatment of Small Cell and Neuroendocrine Carcinoma of the Prostate.

INTRODUCTION: Lurbinectedin is FDA approved for treatment of metastatic small cell lung cancer (SCLC) following progression on or after platinum-based chemotherapy. Prostatic small cell or neuroendocrine carcinoma (SC/NEPC) behaves like SCLC; however, no safety or efficacy data for lurbinectedin in SC/NEPC exists. PATIENTS AND METHODS: All SC/NEPC patients treated with lurbinectedin across 4 academic oncology centers were identified. Baseline patient data and lurbinectedin outcomes including radiographic responses (complete response [CR], partial response [PR], stable disease [SD], progressive disease [PD]), progression free survival (PFS), overall survival (OS), and treatment-related adverse events (trAEs) were described. Clinical benefit rate (CBR) included CR, PR, or SD on imaging. Descriptive statistics were performed. RESULTS: At first lurbinectedin dose, all 18 patients had metastatic disease. Median age was 63.5 (Range: 53-84), number of prior systemic therapies was 4 (Range: 2-7), and lurbinectedin cycles completed was 5 (Range: 1-10). ADT was administered during lurbinectedin treatment in 9/18 patients. CBR was 9/16 (56%). The most common trAEs were fatigue and anemia. Median OS and PFS were 6.01 (0.23-16.69) and 3.35 (0.16-7.79) months. CONCLUSIONS: Lurbinectedin showed modest but significant clinical benefit in some patients with SC/NEPC and demonstrated an acceptable toxicity profile with no hospitalizations from trAEs. SC/NEPC is an aggressive disease with a poor prognosis for which more treatment options are needed. Evidence for subsequent treatments after platinum-based chemotherapy is lacking. Lurbinectedin is an active treatment option for SC/NEPC; however, larger confirmatory studies are needed.

Small cell colorectal cancer: a rare tumour with an aggressive course.

A relatively healthy male patient in his 60s presented with chest pain and shortness of breath in addition to a history of significant weight loss over the preceding months. He was admitted to the hospital and investigated with a CT pulmonary angiogram, which did not demonstrate a pulmonary embolus, but he subsequently went on to have an ultrasound and CT scan because of abnormal findings. His CT demonstrated some thickening of the mid-transverse colon, and, in addition, large volume liver metastases described as innumerable and probably replacing most of the liver.Initially, his liver function tests were only mildly deranged at the presentation. Flexible sigmoidoscopy was performed, and a transverse colonic malignancy was identified and biopsied, which demonstrated an extrapulmonary small cell carcinoma (EPSCC). He was admitted for urgent chemotherapy for newly diagnosed metastatic small-cell colonic cancer; he developed tumour lysis syndrome following his first dose of chemotherapy. He continued to decline following this and died soon after his admission. Metastatic small-cell colonic cancer is a rare diagnosis which is challenging to manage due to the lack of trial evidence to drive treatment strategies. The management largely follows the pulmonary small cell cancer pathway. We, therefore, present a colonic EPSCC case outlining the diagnostic and treatment strategies for this disease.

[A Case of Small Cell Carcinoma of the Urethra].

We report a case of small cell carcinoma of the urethra with inguinal lymph node metastases. A 50- year-old female patient presented with gross hematuria. Cystoscopy and computed tomography (CT) revealed a tumor surrounding the urethra and an inguinal lymphadenopathy. Biopsy of the urethral tumor demonstrated small cell carcinoma. Four courses of chemotherapy with etoposide and cisplatin, followed by 66 Gy of irradiation achieved complete remission. Unfortunately, 14 months later, positroemission-CT scan revealed recurrence of inguinal lymph node metastases. Although seven courses of chemotherapy with nogitecan were carried out, a new metastatic bone tumor developed. Amrubicin was administered as a third-line treatment, but was canceled after one course because of side effects. The patient died at 39 months after diagnosis. Small cell carcinoma of urethra with metastases has extremely poor prognosis, as is demonstrated by this case.

Small cell carcinoma esophagus-A tertiary cancer center experience of a rare variant.

BACKGROUND: Esophageal cancer is quite prevalent worldwide and usually carries a poor prognosis. Histologically, although squamous cell carcinoma and adenocarcinoma predominate, small cell carcinoma (SmCC) cases have been reported. Overall, there is a paucity of literature regarding this variant. In this article, we aim to highlight this uncommon entity of carcinoma esophagus and share our experience of SmCC patients seen over a decade at our institute. METHOD: Records of patients with SmCC histology from 2010 to 2020 were assessed. Patients' demographic characteristics, clinical characteristics, treatment received, and outcomes were taken into consideration. Results were analyzed statistically using SPSS version 22. RESULTS: Fourteen patients (nine males and five females) with a median age of 57 years (range: 35 - 72 years) were analyzed. The majority of the patients 10/14 (71.4%) received palliative radiotherapy of either 30Gy/10 fractions or 35Gy/15 fractions. Only 1/14 (7.14%) patients received neoadjuvant chemotherapy and concurrent chemoradiation (CCRT). Overall, partial response was noted in all 11 patients (78.6%) who received treatment. The average median survival was 5 months (range: 1-11 months). CONCLUSION: Although the small sample size of the study prevents us from drawing a firm conclusion, we propose national and international collaborative prospective studies for framing definitive oncologic management strategies for this rare histological variant of esophageal cancer.

Differential NEUROD1, ASCL1, and POU2F3 Expression Defines Molecular Subsets of Bladder Small Cell/Neuroendocrine Carcinoma With Prognostic Implications.

Small cell carcinomas (SMC) of the lung are now molecularly classified based on the expression of transcriptional regulators (NEUROD1, ASCL1, POU2F3, and YAP1) and DLL3, which has emerged as an investigational therapeutic target. PLCG2 has been shown to identify a distinct subpopulation of lung SMC with stem cell-like and prometastasis features and poor prognosis. We analyzed the expression of these novel neuroendocrine markers and their association with traditional neuroendocrine markers and patient outcomes in a cohort of bladder neuroendocrine carcinoma (NEC) consisting of 103 SMC and 19 large cell NEC (LCNEC) assembled in tissue microarrays. Coexpression patterns were assessed and integrated with detailed clinical annotation including overall (OS) and recurrence-free survival (RFS) and response to neoadjuvant/adjuvant chemotherapy. We identified 5 distinct molecular subtypes in bladder SMC based on the expression of ASCL1, NEUROD1, and POU2F3: ASCL1+/NEUROD1- (n = 33; 34%), ASCL1- /NEUROD1+ (n = 21; 21%), ASCL1+/NEUROD1+ (n = 17; 17%), POU2F3+ (n = 22, 22%), and ASCL1- /NEUROD1- /POU2F3- (n = 5, 5%). POU2F3+ tumors were mutually exclusive with those expressing ASCL1 and NEUROD1 and exhibited lower expression of traditional neuroendocrine markers. PLCG2 expression was noted in 33 tumors (32%) and was highly correlated with POU2F3 expression (P < .001). DLL3 expression was high in both SMC (n = 72, 82%) and LCNEC (n = 11, 85%). YAP1 expression was enriched in nonneuroendocrine components and negatively correlated with all neuroendocrine markers. In patients without metastatic disease who underwent radical cystectomy, PLCG2+ or POU2F3+ tumors had shorter RFS and OS (P < .05), but their expression was not associated with metastasis status or response to neoadjuvant/adjuvant chemotherapy. In conclusion, the NEC of the bladder can be divided into distinct molecular subtypes based on the expression of ASCL1, NEUROD1, and POU2F3. POU2F3-expressing tumors represent an ASCL1/NEUROD1-negative subset of bladder NEC characterized by lower expression of traditional neuroendocrine markers. Marker expression patterns were similar in SMC and LCNEC. Expression of PLCG2 and POU2F3 was associated with shorter RFS and OS. DLL3 was expressed at high levels in both SMC and LCNEC of the bladder, nominating it as a potential therapeutic target.

EBV-positive small cell neuroendocrine carcinoma of nasopharynx as a probably unique subtype of neuroendocrine carcinoma: a clinicopathologic study of three cases and literature review.

BACKGROUND: There is currently scarcity of information on small cell neuroendocrine carcinoma of the nasopharynx (SCNEC-nasopharynx). It is believed that this type of cancer is not associated with Epstein-Barr virus (EBV) infection and is indistinguishable from classic SCNEC occurring in other organs. MATERIALS AND METHODS: Herein we provided 3 cases of nasopharyngeal mass in our hospital, two males and one female. On admission, these patients were considered nasopharyngeal carcinoma with lymph node metastasis, and one of them had liver metastasis. The nasopharyngeal mucosal tissues were biopsied for pathological examination including immunohistochemistry and in situ hybridization. PubMed database was searched for articles about SCNEC-nasopharynx published up to April 2024 in any language. RESULT: The 3 cases had similar histological features of SCNEC in other organs but differed in rich- tumor-infiltrating lymphocytes (TILs). All of them stained for pancytokeratin (panCK) and epidermal growth factor receptor (EGFR). Case 1 and Case 2 diffusely expressed insulinoma-associated protein 1(INSM-1) and synaptophysin (Syn), Case 3 strongly stained for CD56 and Syn. Immunostaining of all 3 cases for p40, p63, TTF-1, CK20, S-100 and NUT showed negative. BRG-1, INI-1 and Rb were retained. And p53 all showed wild-type expression. The Ki-67 labeling indiced of case 1, 2, and 3 were 80%, 90%, and 80%, respectively. In situ hybridization showed strong and uniform nuclear positivity of EBV-encoded small RNAs (EBER) in the neoplastic cells of 3 cases. CONCLUSION: EBV-positive SCNEC-nasopharynx was exactly rare. The origin of this tumor is still controversial. It may originate from EBV-infected mucosal epithelium like nasopharyngeal carcinoma. Based on our cases and relevant literature, we found EBV-positive SCNEC-nasopharynx as a probably site-specific subtype of SCNEC with differing pathogenetic mechanism. The subtype not only virus positivity but also that it was associated with TILs and did not show p53 or Rb alterations by immunohistochemistry. It may be more responsive to treatment and have a better prognosis than classic SCNEC. We will continue to follow-up these patients and collect additional cases to further understand the unique biology of this rare solid tumor.

Urachal mixed adenocarcinoma and small cell neuroendocrine carcinoma with widespread metastasis and resistance to chemotherapy: a case report.

Neuroendocrine carcinoma arising from the urachus is extremely rare. We describe a case of a 33-year-old gentleman who presented with hematuria and diagnosed to have a composite adenocarcinoma and small cell neuroendocrine carcinoma arising from the urachus. The patient also had widespread metastasis at the time of presentation, therefore, he was referred for chemotherapy. However, the disease showed progression despite treatment. Recognition of neuroendocrine carcinoma component in urachal tumors, although rare, is very essential as this histologic type carries poor prognosis with aggressive clinical outcome.

Small cell neuroendocrine carcinoma and poorly differentiated rhabdomyosarcomas of the urinary bladder in adults-A comparative analysis in favor of a common histogenesis.

Rhabdomyosarcoma (RMS) of the urinary bladder in adults and elderly is an exceptionally rare neoplasm that displays poorly differentiated solid (alveolar-like) small cell pattern, frequently indistinguishable from small cell neuroendocrine carcinoma (SCNEC). However, the histogenesis of RMS and SCNEC and their inter-relationship have not been well studied and remained controversial. We herein analyzed 23 SCNEC and 3 small round cell RMS of the bladder for neuroendocrine (synaptophysin + chromogranin A) and myogenic (desmin + myogenin) marker expression and for TERT promoter mutations. In addition, the RMS cohort and one SCNEC that was revised to RMS were tested for gene fusions using targeted RNA sequencing (TruSight Illumina Panel which includes FOXO1 and most of RMS-related other genes). Overall, significant expression of myogenin and desmin was observed in one of 23 original SCNEC justifying a revised diagnosis to RMS. On the other hand, diffuse expression of synaptophysin was noted in 2 of the 4 RMS, but chromogranin A was not expressed in 3 RMS tested. TERT promoter mutations were detected in 15 of 22 (68%) SCNEC and in two of three (67%) assessable RMS cases, respectively. None of the four RMS cases had gene fusions. Our data highlights phenotypic and genetic overlap between SCNEC and RMS of the urinary bladder. High frequency of TERT promoter mutations in SCNEC is in line with their presumable urothelial origin. In addition, the presence of TERT promoter mutation in 2 of 3 RMS and lack of FOXO1 and other gene fusions in all 4 RMSs suggest a mucosal (urothelial) origin, probably representing extensive monomorphic rhabdomyoblastic transdifferentiation in SCNEC.

Multiomics sequencing and immune microenvironment characteristics define three subtypes of small cell neuroendocrine carcinoma of the cervix.

Small cell cervical carcinoma (SCCC) is the most common neuroendocrine tumor in the female genital tract, with an unfavorable prognosis and lacking an evidence-based therapeutic approach. Until now, the distinct subtypes and immune characteristics of SCCC combined with genome and transcriptome have not been described. We performed genomic (n = 18), HPV integration (n = 18), and transcriptomic sequencing (n = 19) of SCCC samples. We assessed differences in immune characteristics between SCCC and conventional cervical cancer, and other small cell neuroendocrine carcinomas, through bioinformatics analysis and immunohistochemical assays. We stratified SCCC patients through non-negative matrix factorization and described the characteristics of these distinct types. We further validated it using multiplex immunofluorescence (n = 77) and investigated its clinical prognostic effect. We confirmed a high frequency of PIK3CA and TP53 alterations and HPV18 integrations in SCCC. SCCC and other small cell carcinoma had similar expression signatures and immune cell infiltration patterns. Comparing patients with SCCC to those with conventional cervical cancer, the former presented immune excluded or 'desert' infiltration. The number of CD8+ cells in the invasion margin of SCCC patients predicted favorable clinical outcomes. We identified three transcriptome subtypes: an inflamed phenotype with high-level expression of genes related to the MHC-II complex (CD74) and IFN-α/ß (SCCC-I), and two neuroendocrine subtypes with high-level expression of ASCL1 or NEUROD1, respectively. Combined with multiple technologies, we found that the neuroendocrine groups had more TP53 mutations and SCCC-I had more PIK3CA mutations. Multiplex immunofluorescence validated these subtypes and SCCC-I was an independent prognostic factor of overall survival. These results provide insights into SCCC tumor heterogeneity and potential therapies. © 2024 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.

A case of metastatic HPV-related cervical small cell neuroendocrine carcinoma with varying cytomorphology found in cytological specimens of a solid organ transplant recipient.

Small cell neuroendocrine carcinoma (NEC) of the cervix is a rare gynecological malignancy, constituting 2%-5% of all such cases. As high-risk Human Papilloma Virus (HR-HPV) infections contribute to 85% of these tumors, small cell NEC poses a significant risk for solid organ transplant recipients, increasing their risk of progressive disease. We present a case of an uterine cervix small cell NEC with metastasis to the bladder and pleural cavities in a 53-year-old woman with a past medical history of kidney transplantation, who presented with abnormal uterine bleeding. The initial liquid preparation (ThinPrep) cytology stained with Papanicolaou (Pap) showed an adenocarcinoma not otherwise specified. At the time of diagnosis, the patient had diffusely metastatic disease. A subsequent uterine cervix biopsy was consistent with a small cell NEC. Despite treatment with chemotherapy, the patient's condition deteriorated, evidenced by a worsening right-sided pleural effusion one-month postdiagnosis. A pleural effusion showed a tumor with glandular features, with immunohistochemistry suggestive of metastatic adenocarcinoma. HR HPV E6/E7 RNA in situ hybridization (ISH) was positive. Bladder washing showed cytopathologic findings consistent with bladder involvement by small cell carcinoma. The patient's lesions in both urine and pleural fluids showed distinct cytomorphology. Within a year of diagnosis, the patient was declared deceased. This case highlights the existence of carcinoma admixed with NEC tumor, such as an HPV associated adenocarcinoma admixed with a NEC and underscores the elevated risk of HPV-related genital lesions in renal transplant patients. In patients with a history of solid organ transplant or other immunosuppressive conditions, there is an increased necessity for enhanced surveillance and appropriate cancer screening.

Clinical characteristics and status of treatment of small-cell carcinoma of the ovary, hypercalcemic type in the Chinese population: a meta-analysis.

OBJECTIVE: This study aimed to comprehensively analyze the clinical characteristics and treatment status of Chinese small cell carcinoma of the ovary hypercalcemic type (SCCOHT) patients, providing insights into this unique population and comparing findings with international literature. METHODS: Through a meta-analysis, we collected data from published case reports and records from the Obstetrics & Gynecology Hospital of Fudan University. Demographic information, clinical presentations, tumor attributes, treatment modalities, and survival outcomes were extracted and examined alongside relevant global studies. RESULTS: The analysis encompassed 80 Chinese SCCOHT patients, of which 62 from 33 previously reported literatures, and the other 18 were from Obstetrics & Gynecology Hospital of Fudan University. In 62 cases with stage information, A total of 25 tumors were International Federation of Gynecology and Obstetrics stage I, 3 were stage II, 19 were stage III, and 15 were stage IV. Most patients received surgery and chemotherapy, but regimens were varied. Median follow-up was 10 months (range=4-120). Elevated carbohydrate antigen 125 and serum calcium levels were consistent findings. Recurrence rates were notable, especially among stage I patients. Platinum-based chemotherapy, paclitaxel and carboplatin (n=11, 13.4%), constituted common treatment regimens. CONCLUSION: This study observed demographic and clinical similarities with international datasets. And the findings emphasize the urgency for innovative therapeutic approaches to improve outcomes in SCCOHT patients. Continued research efforts are essential to enhance the knowledge surrounding this rare malignancy and to optimize its clinical management.

Small-cell neuroendocrine carcinoma of the female genital tract: A comprehensive overview.

Small-cell neuroendocrine carcinomas (SCNECs) of the female genital tract are rare and aggressive tumors that are characterized by a high rate of recurrence and poor prognosis. They can arise from various sites within the female genital tract, including the cervix, endometrium, ovary, fallopian tube, vagina, and vulva. They are composed of cells with neuroendocrine features, such as the ability to produce and secrete hormones and peptides, and a high mitotic rate. Immunohistochemical staining for neuroendocrine markers, such as chromogranin A, synaptophysin, and CD56, can aid in the diagnosis of these tumors. This article provides an overview of the epidemiology, etiology, and risk factors associated with these tumors, as well as their clinical presentation, cellular characteristics, diagnosis, and finally the current treatment options for SCNECs, including surgery, chemotherapy, and radiation therapy, alone or in combination.