RESUMO
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.
Assuntos
Carbolinas , Carcinoma Neuroendócrino , Compostos Heterocíclicos de 4 ou mais Anéis , Neoplasias da Próstata , Humanos , Masculino , Carbolinas/administração & dosagem , Carbolinas/uso terapêutico , Carbolinas/efeitos adversos , Idoso , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Compostos Heterocíclicos de 4 ou mais Anéis/administração & dosagem , Compostos Heterocíclicos de 4 ou mais Anéis/efeitos adversos , Pessoa de Meia-Idade , Idoso de 80 Anos ou mais , Neoplasias da Próstata/tratamento farmacológico , Neoplasias da Próstata/patologia , Resultado do Tratamento , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Antineoplásicos/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Estudos Retrospectivos , Intervalo Livre de ProgressãoRESUMO
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.
Assuntos
Carcinoma de Células Pequenas , Neoplasias Hepáticas , Humanos , Masculino , Evolução Fatal , Neoplasias Hepáticas/secundário , Neoplasias Hepáticas/patologia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/secundário , Carcinoma de Células Pequenas/complicações , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/secundário , Neoplasias Pulmonares/diagnóstico , Neoplasias Colorretais/patologia , Neoplasias do Colo/patologiaAssuntos
Biomarcadores Tumorais , Carcinoma de Células Pequenas , DNA Helicases , Hipercalcemia , Proteínas Nucleares , Neoplasias Ovarianas , Fatores de Transcrição , Humanos , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , DNA Helicases/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análiseAssuntos
Biomarcadores Tumorais , Carcinoma de Células Pequenas , DNA Helicases , Hipercalcemia , Proteínas Nucleares , Neoplasias Ovarianas , Fatores de Transcrição , Humanos , Feminino , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/genética , DNA Helicases/genética , Proteínas Nucleares/genética , Fatores de Transcrição/genética , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/genética , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/análise , Imuno-HistoquímicaAssuntos
Carcinoma Neuroendócrino , Carcinoma de Células Escamosas , Neoplasias Hipofaríngeas , Humanos , Feminino , Neoplasias Hipofaríngeas/patologia , Pessoa de Meia-Idade , Carcinoma de Células Escamosas/patologia , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/terapia , Carcinoma de Células Pequenas/patologiaAssuntos
Neoplasias Hipofaríngeas , Humanos , Neoplasias Hipofaríngeas/patologia , Neoplasias Hipofaríngeas/diagnóstico , Neoplasias Hipofaríngeas/cirurgia , Neoplasias Hipofaríngeas/diagnóstico por imagem , Masculino , Hipofaringe/patologia , Hipofaringe/diagnóstico por imagem , Hipofaringe/cirurgia , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/cirurgia , Carcinoma de Células Pequenas/diagnóstico por imagemRESUMO
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.
Assuntos
Carcinoma de Células Pequenas , Neoplasias Esofágicas , Centros de Atenção Terciária , Humanos , Masculino , Neoplasias Esofágicas/patologia , Neoplasias Esofágicas/terapia , Neoplasias Esofágicas/mortalidade , Neoplasias Esofágicas/diagnóstico , Feminino , Pessoa de Meia-Idade , Adulto , Idoso , Carcinoma de Células Pequenas/terapia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/mortalidade , Centros de Atenção Terciária/estatística & dados numéricos , Prognóstico , Quimiorradioterapia/métodos , Estudos Retrospectivos , Taxa de Sobrevida , Terapia Neoadjuvante/métodos , Resultado do Tratamento , EsofagectomiaRESUMO
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.
Assuntos
Carcinoma de Células Pequenas , Neoplasias Uretrais , Humanos , Feminino , Pessoa de Meia-Idade , Carcinoma de Células Pequenas/diagnóstico por imagem , Carcinoma de Células Pequenas/terapia , Carcinoma de Células Pequenas/patologia , Neoplasias Uretrais/patologia , Neoplasias Uretrais/diagnóstico por imagem , Neoplasias Uretrais/terapia , Metástase Linfática , Evolução Fatal , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Tomografia Computadorizada por Raios XRESUMO
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.
Assuntos
Carcinoma Neuroendócrino , Infecções por Vírus Epstein-Barr , Neoplasias Nasofaríngeas , Humanos , Masculino , Feminino , Carcinoma Neuroendócrino/virologia , Carcinoma Neuroendócrino/patologia , Neoplasias Nasofaríngeas/virologia , Neoplasias Nasofaríngeas/patologia , Pessoa de Meia-Idade , Infecções por Vírus Epstein-Barr/complicações , Infecções por Vírus Epstein-Barr/patologia , Infecções por Vírus Epstein-Barr/virologia , Carcinoma Nasofaríngeo/virologia , Carcinoma Nasofaríngeo/patologia , Imuno-Histoquímica , Biomarcadores Tumorais/análise , Herpesvirus Humano 4/isolamento & purificação , Herpesvirus Humano 4/genética , Carcinoma de Células Pequenas/virologia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/química , Adulto , IdosoRESUMO
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.
Assuntos
Adenocarcinoma , Carcinoma Neuroendócrino , Resistencia a Medicamentos Antineoplásicos , Neoplasias da Bexiga Urinária , Humanos , Masculino , Adulto , Carcinoma Neuroendócrino/tratamento farmacológico , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/secundário , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/tratamento farmacológico , Adenocarcinoma/tratamento farmacológico , Adenocarcinoma/secundário , Adenocarcinoma/patologia , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Evolução Fatal , Neoplasias Complexas Mistas/patologia , Neoplasias Complexas Mistas/tratamento farmacológico , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/secundárioRESUMO
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.
Assuntos
Carcinoma Neuroendócrino , Microambiente Tumoral , Neoplasias do Colo do Útero , Humanos , Feminino , Neoplasias do Colo do Útero/genética , Neoplasias do Colo do Útero/imunologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Microambiente Tumoral/imunologia , Microambiente Tumoral/genética , Carcinoma Neuroendócrino/genética , Carcinoma Neuroendócrino/imunologia , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/mortalidade , Carcinoma de Células Pequenas/genética , Carcinoma de Células Pequenas/imunologia , Carcinoma de Células Pequenas/patologia , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Adulto , Mutação , Transcriptoma , Classe I de Fosfatidilinositol 3-Quinases/genética , Prognóstico , Perfilação da Expressão Gênica/métodos , Idoso , MultiômicaAssuntos
Anticorpos Monoclonais Humanizados , Protocolos de Quimioterapia Combinada Antineoplásica , Bevacizumab , Carcinoma de Células Pequenas , Ciclofosfamida , Neoplasias Ovarianas , Humanos , Feminino , Bevacizumab/administração & dosagem , Ciclofosfamida/administração & dosagem , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Neoplasias Ovarianas/tratamento farmacológico , Neoplasias Ovarianas/patologia , Carcinoma de Células Pequenas/tratamento farmacológico , Carcinoma de Células Pequenas/patologia , Hipercalcemia/tratamento farmacológico , Pessoa de Meia-IdadeRESUMO
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.
Assuntos
Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Infecções por Papillomavirus , Neoplasias do Colo do Útero , Humanos , Feminino , Pessoa de Meia-Idade , Carcinoma Neuroendócrino/patologia , Carcinoma Neuroendócrino/virologia , Neoplasias do Colo do Útero/patologia , Neoplasias do Colo do Útero/virologia , Infecções por Papillomavirus/patologia , Infecções por Papillomavirus/complicações , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/virologia , Transplante de Rim/efeitos adversos , TransplantadosRESUMO
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.
Assuntos
Carcinoma de Células Pequenas , Hipercalcemia , Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/terapia , Neoplasias Ovarianas/patologia , Neoplasias Ovarianas/mortalidade , Hipercalcemia/etiologia , Carcinoma de Células Pequenas/terapia , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/mortalidade , Pessoa de Meia-Idade , Adulto , China/epidemiologia , Idoso , Estadiamento de Neoplasias , Paclitaxel/administração & dosagem , Carboplatina/administração & dosagem , Povo Asiático , Antígeno Ca-125/sangue , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , População do Leste AsiáticoRESUMO
OBJECTIVE: This study aimed to evaluate the efficacy of CT and MRI findings to differentiate small cell neuroendocrine carcinoma (SCNEC) from urothelial carcinoma (UC) of the urinary bladder. MATERIALS AND METHODS: This study included 90 patients with histopathologically confirmed bladder cancer (10 SCNECs and 80 UCs). Eight patients with bladder SCNEC and 80 with UC underwent CT and MRI, whereas the remaining two patients with SCNEC underwent CT alone before treatment. CT and MRI findings were retrospectively evaluated and compared between the two pathologies. RESULTS: The maximum diameter (36.5 mm vs. 19.0 mm, p < 0.01) and height (22.0 mm vs. 14.0 mm, p < 0.01) of the tumor in bladder SCNEC were higher than in UC. The pedunculated configuration (20% vs. 61%, p < 0.05) and irregular tumor margins (20% vs. 76%, p < 0.01) in bladder SCNEC were less common than in UC. The CT attenuation of the solid component in unenhanced CT images was higher in bladder SCNEC than in UC (37 Hounsfield unit [HU] vs. 34 HU, p < 0.01). The apparent diffusion coefficient (ADC) of the solid component in bladder SCNEC was lower than in UC (0.49 × 10-3 mm2/s vs. 1.02 × 10-3 mm2/s, p < 0.01). CONCLUSION: In comparison with UC, bladder SCNEC was larger, had higher unenhanced CT attenuation, and had a lower ADC value. The pedunculated configuration and irregular tumor margins were typical of bladder UC.
Assuntos
Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Imageamento por Ressonância Magnética , Tomografia Computadorizada por Raios X , Neoplasias da Bexiga Urinária , Humanos , Masculino , Feminino , Neoplasias da Bexiga Urinária/diagnóstico por imagem , Neoplasias da Bexiga Urinária/patologia , Pessoa de Meia-Idade , Carcinoma Neuroendócrino/diagnóstico por imagem , Carcinoma Neuroendócrino/patologia , Idoso , Estudos Retrospectivos , Tomografia Computadorizada por Raios X/métodos , Imageamento por Ressonância Magnética/métodos , Carcinoma de Células Pequenas/diagnóstico por imagem , Carcinoma de Células Pequenas/patologia , Diagnóstico Diferencial , Idoso de 80 Anos ou mais , Adulto , Carcinoma de Células de Transição/diagnóstico por imagem , Carcinoma de Células de Transição/patologia , Meios de ContrasteRESUMO
POU class 2 homeobox 3 (POU2F3)-positive small cell bladder carcinoma (SCBC) is an extremely rare entity, and its clinicopathologic features have not been fully described. Here, we investigated the clinicopathologic features of 4 cases of POU2F3-positive small cell bladder carcinoma (SCBC) and reviewed the literature. We collected 12 cases of SCBC from our departmental archives and detected the expression of POU2F3 by immunohistochemical (IHC) staining. Selected cases with or without POU2F3 expression were subjected to gene expression analysis between two different groups using DESeq2 software. We identified 4 POU2F3-positive SCBC patients, 2 males and 2 females, with a mean age of 77 years. Three patients had hematuria, and 1 patient had dysuria. Radiologic findings showed a bladder mass. Pathologic diagnosis showed that 3 cases were pure SCBC and 1 was mixed urothelial cancer (UC). Histopathologically, four POU2F3-positive SCBC tumors were composed of small round cells with sparse cytoplasm, the nuclei were salt-and-pepper-like or finely granular. Tumor cells showed characteristic cytoplasmic staining with punctate positive signals for cytokeratin. Syn and CD56 were diffusely positive in all the 4 patients. CgA was positive in only one patient. POU2F3-positive SCBC showed higher expression levels of POU2F3, HMGA2 and PLCG2 genes by RNA-Seq. Our data showed the specific clinicopathologic features of 4 rare POU2F3-positive SCBC cases, and the distinct molecular feature was observed between POU2F3-positive and negative SCBC in the limited number of cases.
Assuntos
Biomarcadores Tumorais , Carcinoma de Células Pequenas , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/patologia , Neoplasias da Bexiga Urinária/metabolismo , Neoplasias da Bexiga Urinária/genética , Masculino , Feminino , Idoso , Carcinoma de Células Pequenas/patologia , Carcinoma de Células Pequenas/metabolismo , Carcinoma de Células Pequenas/genética , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/metabolismo , Idoso de 80 Anos ou mais , Pessoa de Meia-Idade , Fator 3 de Transcrição de Octâmero/metabolismo , Fator 3 de Transcrição de Octâmero/análiseRESUMO
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.
Assuntos
Carcinoma Neuroendócrino , Carcinoma de Células Pequenas , Neoplasias dos Genitais Femininos , Humanos , Feminino , Carcinoma Neuroendócrino/diagnóstico , Carcinoma Neuroendócrino/terapia , Carcinoma Neuroendócrino/patologia , Carcinoma de Células Pequenas/terapia , Carcinoma de Células Pequenas/diagnóstico , Carcinoma de Células Pequenas/epidemiologia , Carcinoma de Células Pequenas/patologia , Neoplasias dos Genitais Femininos/terapia , Neoplasias dos Genitais Femininos/diagnóstico , Neoplasias dos Genitais Femininos/patologia , Neoplasias dos Genitais Femininos/epidemiologia , Fatores de RiscoRESUMO
Pulmonary large-cell neuroendocrine carcinoma (LCNEC), a disease with poor prognosis, is classified as pulmonary high-grade neuroendocrine carcinoma, along with small-cell lung cancer. However, given its infrequent occurrence, only a limited number of preclinical models have been established. Here, we established three LCNEC tumoroids for long-term culture. Whole-exome sequencing revealed that these tumoroids inherited genetic mutations from their parental tumors; two were classified as small-cell carcinoma (S-LCNEC) and one as non-small cell carcinoma (N-LCNEC). Xenografts from these tumoroids in immunodeficient mice mimicked the pathology of the parent LCNEC, and one reproduced the mixed-tissue types of combined LCNEC with a component of adenocarcinoma. Drug sensitivity tests using these LCNEC tumoroids enabled the evaluation of therapeutic agent efficacy. Based on translational research, we found that a CDK4/6 inhibitor might be effective for N-LCNEC and that Aurora A kinase inhibitors might be suitable for S-LCNEC or LCNEC with MYC amplification. These results highlight the value of preclinical tumoroid models in understanding the pathogenesis of rare cancers and developing treatments. LCNEC showed a high success rate in tumoroid establishment, indicating its potential application in personalized medicine.