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Small cell carcinoma of the ovary (SCCO) is a rare type of ovarian cancer with high aggressiveness. The optimal treatment modality remains elusive. This study aims to comprehensively investigate the survival impact of clinical characteristics and treatments including lymphadenectomy in SCCO. A retrospective cohort study was performed and included patients from the Surveillance, Epidemiology, and End Results (SEER) database. Data collected included demographics, therapeutic details, and pathologic characteristics. Propensity-score matching analysis (PSM) was carried out to balance baseline variables between SCCO and non-SCCO. Cox regression, Kaplan–Meier, and stratified analyses were conducted before and after PSM. After filtering, 80 records on SCCO and 39,662 records on non-SSCO were obtained. Patients with SCCO were more prone to present unilateral tumor (57.6% and 85.0%, p < 0.001), larger tumor size (>15 cm: 9.5% and 32.5%; 10–15 cm: 13.2% vs. 22.5%, p < 0.001), younger age (59.1 ± 14.91 vs. 37.2 ± 19.05; p < 0.001), single status (17.0% vs. 45.0%; p < 0.001), single malignant tumor in a lifetime (76.1% vs. 87.5%; p = 0.0244), and pathologic grade IV diseases (14.5% vs. 40.0%; p < 0.001) compared with non-SCCO. After balancing the baseline clinical characteristics with a 1:4 ratio PSM, a total of matched 72 patients with SCCO and 254 patients with non-SCCO were identified. The survival rate of SCCO was distinctly inferior to non-SCCO, particularly in FIGO I, II, and III stages. Lymphadenectomy was performed in 37 (51.39%) SCCO patients, of whom 12 (32.43%) were found to have pathologically positive lymph nodes. Lymphadenectomy was linked to favorable overall survival in SCCO, particularly in the advanced stage, and was also an independent prognostic factor, whereas lymphadenectomy did not reveal an edge in matched non-SCCO. There was a pronounced survival benefit for SCCO when at least 10 or more nodes were resected. Lymphadenectomy in a non-stage-dependent way should be considered and deserves further clinical validation to promote the overall survival in SCCO.

Introduction: Lung cancer is the most common malignancy worldwide. Squamous cell carcinoma (SQ) and adenocarcinoma (LUAD) are the two most frequent histological subtypes. Small cell carcinoma (SCLC) subtype has the worst prognosis. Differential diagnosis is essential for proper oncological treatment. Life science associated mid- and near-infrared based microscopic techniques have been developed exponentially, especially in the past decade. Vibrational spectroscopy is a potential non-destructive approach to investigate malignancies.Aims: Our goal was to differentiate lung cancer subtypes by their label-free mid-infrared spectra using supervised multivariate analyses.Material and Methods: Formalin-fixed paraffin-embedded (FFPE) samples were selected from the archives. Three subtypes were selected for each group: 10-10 cases SQ, LUAD and SCLC. 2 μm thick sections were cut and laid on aluminium coated glass slides. Transflection optical setup was applied on Perkin-Elmer infrared microscope. 250 × 600 μm areas were imaged and the so-called mid-infrared fingerprint region (1800-648cm−1) was further analysed with linear discriminant analysis (LDA) and support vector machine (SVM) methods.Results: Both “patient-based” and “pixel-based” approaches were examined. Patient-based analysis by using 3 LDA models and 2 SVM models resulted in different separations. The higher the cut-off value the lower is the accuracy. The linear C-support vector classification (C-SVC) SVM resulted in the best (100%) accuracy for the three subtypes using a 50% cut-off value. The pixel-based analysis gave, similarly, the linear C-SVC SVM model to be the most efficient in the statistical indicators (SQ sensitivity 81.65%, LUAD sensitivity 82.89% and SCLC sensitivity 88.89%). The spectra cut-off, the kernel function and the algorithm function influence the accuracy.Conclusion: Mid-Infrared imaging could be used to differentiate FFPE lung cancer subtypes. Supervised multivariate tools are promising to accurately separate lung tumor subtypes. The long-term perspective is to develop a spectroscopy-based diagnostic tool, revolutionizing medical differential diagnostics, especially cancer identification.

Background: This study aimed to develop a prognostic model based on the Surveillance, Epidemiology, and End Results (SEER) database to predict the overall survival (OS) of small cell carcinoma of the uterine cervix (SmCC). Methods: Between 1975 and 2016, a total of 401 patients were included, and their comprehensive sociodemographic and clinicopathological characteristics were collected. Univariate and multivariate Cox regression models were used to screen for independent prognostic factors. The identified factors were used to conduct a nomogram for predicting the OS of SmCC. The performance of the nomogram was determined using area under the receiver operating characteristic curve (AUC), concordance index (C-index), calibration curve, and decision curve analysis (DCA) metrics. Results: The median survival time of all patients was about 24 months (95% confidence interval [95% CI] [1.50-2.17]). Age (hazard ratio [HR] = 1.693 for 45-59 vs 21-34, 95% CI [1.140-2.513], P = .009; HR = 2.836 for 60-92 vs 21-34, 95% CI [1.851-4.345], P

It may be challenging to diagnose metastatic prostatic carcinoma (PC). This study focused on clinicopathologic correlation, and pitfalls of cytomorphology and immunostains of metastatic PCs. A total of 146 metastatic PCs including 134 (92%) PC without neuroendocrine differentiation-prostatic adenocarcinoma (PAC) and 12 (8%) with neuroendocrine differentiation (PC-NED) were retrieved. Triplicate tissue microarrays (TMA) of 54 surgically excised PCs were constructed for immunostains. Most cases showed Gleason 4 or 5 patterns. Nine percent of cases did not have a prior history of PC and 7% had 2 or more primary malignancies. PAC metastasized more commonly to lymph nodes (49%), and PC-NED metastasized more commonly to liver (58%). Cytologically, metastatic PCs show acini, cribriform, nest, and solid clusters. Most PACs showed conspicuous or prominent nucleoli. PC-NEDs showed typical cytologic features of low-grade or high-grade neuroendocrine neoplasm, or small cell carcinoma features. PACs could be immunoreactive to CDX2 (25%), CK20 (11%), NKX3.1 (99%), PSA (88%), PSAP (78%), and PSMA (92%). PC-NEDs were immunoreactive to neuroendocrine immunomarkers (CD56 [100%], chromogranin [67%], and synaptophysin [100%]) and p63 (25%), and lost expression of prostate-specific markers (NKX3.1, PSA, PSAP, and PSMA). Both PACs and PC-NEDs might be immunoreactive to CK7 (18% versus 33%), GATA3 (4% versus 0%), PAX8 (2% versus 50%, P .05), and TTF1 (3% versus 57%, P .05). It is critical to recognize these cytologic features and abbreviation of immunomarkers of metastatic PCs to avoid misinterpretation as metastatic carcinoma from nonprostate organs and inappropriate treatment. In addition, NED may be seen after hormone and chemoradiation treatment.

Small cell lung cancer (SCLC) is the most malignant and common form of neuroendocrine lung cancer with pure (P-SCLC) and combined subtypes (C-SCLC). However, little is known about the differences between these two groups and in this study we aimed to provide a more comprehensive insight into SCLC.Data from 580 postoperative patients with pathologically confirmed SCLC in Shanghai Chest Hospital from January 2010 to December 2020 were collected retrospectively. The clinical characteristics and prognosis were analyzed.A total of 357 P-SCLC patients and 223 C-SCLC patients were included. The results indicated that P-SCLC appeared to have a higher proportion of being located in the middle lobe than C-SCLC. The incidences of P-SCLC in patients with visceral pleural invasion (VPI) and in stage II were higher than C-SCLC, while C-SCLC was more likely to be accompanied by higher incidences of epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) rearrangement, and higher levels of CEA, SCCA and CYFRA21-1 than P-SCLC. The most common were SCLC combined with large cell neuroendocrine components among 223 C-SCLCs. Survival analysis confirmed a more favorable disease-free survival (DFS) (p = 0.016) and overall survival (OS) (p = 0.024) in patients with P-SCLCs compared with C-SCLCs. Histological type, tumor location, pN stage, adjuvant chemotherapy, serum NSE and CA125 levels were independent risk factors for survival rate in SCLC. In addition, adjuvant chemotherapy was beneficial in improving stage I P-SCLC and C-SCLC DFS and OS rates, and similar results were not seen in adjuvant radiation therapy.Patients with C-SCLC have a poorer prognosis than P-SCLC patients. We determined that large cell neuroendocrine carcinoma was the most common additional component of C-SCLC, and patients with this component appeared to have a longer DFS and OS than other combined components.

Opium use was recently classified as a human carcinogen for lung cancer by the International Agency for Research on Cancer. We conducted a large, multicenter case-control study evaluating the association between opium use and the risk of lung cancer. We recruited 627 cases and 3477 controls from May 2017 to July 2020. We used unconditional logistic regression analyses to estimate the odds ratios (OR) and 95% confidence intervals (CI) and measured the association between opium use and the risk of lung cancer. The ORs were adjusted for the residential place, age, gender, socioeconomic status, cigarettes, and water pipe smoking. We found a 3.6-fold risk of lung cancer for regular opium users compared to never users (95% CI: 2.9, 4.6). There was a strong dose-response association between a cumulative count of opium use and lung cancer risk. The OR for regular opium use was higher for small cell carcinoma than in other histology (8.3, 95% CI: 4.8, 14.4). The OR of developing lung cancer among opium users was higher in females (7.4, 95% CI: 3.8, 14.5) than in males (3.3, 95% CI: 2.6, 4.2). The OR for users of both opium and tobacco was 13.4 (95% CI: 10.2, 17.7) compared to nonusers of anything. The risk of developing lung cancer is higher in regular opium users, and these results strengthen the conclusions on the carcinogenicity of opium. The association is stronger for small cell carcinoma cases than in other histology.

Thymic neuroendocrine tumours are rare anterior mediastinal neoplasms often associated with paraneoplastic syndromes. A patient presented with intractable hyponatraemia and a DOTATATE-avid mediastinal mass. Following medical optimization, she underwent thoracoscopic thymectomy with en bloc thymic small-cell carcinoma resection. Her symptoms resolved and her sodium levels normalized. In localized disease, curative-intent, minimally invasive thymic neuroendocrine tumour resection is safe and effective following preoperative staging and paraneoplastic syndrome management.

The goal of this paper was to summarize the recent evidence on rare subtypes of cervical cancer including small-cell carcinoma of the cervix (SCCC), gastric-type adenocarcinoma, and carcinosarcoma.All three cervical cancer subtypes are aggressive with poor treatment response and high recurrence rates. Molecular studies have identified various actionable mutations in both SCCC (PIK3CA, MYC, TP53, PTEN, ARID1A, KRAS, BRCA2) and gastric-type adenocarcinoma (KRAS, ARID1A, PTEN). While there are a limited number of case reports demonstrating a favorable response for recurrent SCCC to immune checkpoint inhibitors, a larger case series failed to show benefit. The checkpoint inhibitors role in gastric-type adenocarcinoma and carcinosarcoma is yet to be determined. Ninety-one percent of SCCC cases show PARP expression, suggesting a possible role for PARP inhibitors; however, this has yet to be examined in future clinical trials. More studies are needed, with a focus on targeted therapies. The role of PARP inhibitors in SCCC is potentially promising, but significant collaboration between centers/groups will be required to achieve this.

Combined small-cell lung cancer (cSCLC) is a rare type of small-cell lung cancer (SCLC) that includes both SCLC and non-small-cell lung cancer (NSCLC). The molecular biological mechanisms underlying the heterogeneity of histological types in combined or metachronously transformed SCLC (mtSCLC) remain unclear. This study aimed to investigate the relationship between genetic alterations and each histological component heterogeneously detected in cSCLC and mtSCLC.This study included four cSCLC cases and one mtSCLC case. Formalin-fixed and paraffin-embedded sections of each histological component of these tumors were subjected to next-generation sequencing (NGS) and quantitative reverse transcription-polymerase chain reaction to investigate the genetic mutations and expression levels of neuroendocrine cell-specific transcription factors (achaete-scute homolog-1 [ASCL1], brain-2 [BRN2] also known as POU domain class 3 transcription factor 2, nuclear factor 1 B [NF1B], insulinoma-associated protein 1 [INSM1], and thyroid transcription factor-1 [TTF-1]).NGS analysis revealed that SCLC and NSCLC components share the same somatic mutations detected most frequently in TP53, and also in RB1 and EGFR. Gene expression analysis showed ASCL1 expression was significantly lower in the NSCLC component than in the SCLC component.We conclude that the morphological evolution of heterogeneous histological components in cSCLC may be associated with differences in ASCL1 expression levels, but not in acquired somatic gene mutations.

This study aimed to investigate the efficacy of surgery in the treatment of small cell carcinoma of the esophagus (SCCE) and explore potential prognostic factors.We screened patients with SCCE who underwent esophagectomy from 2010 to 2018 at three institutes. Differences in survival were analyzed using the Kaplan-Meier method and log-rank test. The prognostic factors were identified using univariate and multivariate analyses.A total of 69 patients were included. Multivariate analysis showed that TNM stage (hazard ratio [HR]: 4.10, 95% confidence interval [CI]: 1.57-10.75, p = 0.004) and adjuvant therapy (HR: 0.28, 95% CI: 0.16-0.51, p 0.001) were independent prognostic factors. Stage I, stage IIA, and stage IIB disease were merged into the surgery response disease (SRD), whereas stage III disease into the surgery nonresponse disease (SNRD). The SRD group had significantly improved survival compared to the SNRD group (HR: 0.33, 95% CI: 0.19-0.58, p 0.001). In addition, adjuvant therapy increased survival benefit in the SNRD group (p 0.001) but not in the SRD group (p = 0.061).Surgery alone appears to be adequate for disease control in the SRD group, whereas multimodality therapy was associated with improved survival in the SNRD group.

Gastrointestinal extrapulmonary small cell carcinoma (GI EPSCCa) is a rare, aggressive neuroendocrine tumor. Factors affecting survival, including the prognostic significance of primary tumor site, remain under investigation.Data from the surveillance, epidemiology, and end results (SEER) program were extracted to identify patients diagnosed with GI EPSCCa between 2000 and 2018. Cox proportional hazard models were used to assess prognostic factors based on primary tumor site.A total of 1687 patients were included in the survival analysis. The distribution of the primary tumor location was as follows: 31.5% colorectum (CRC), 22.1% esophageal, 20.6% pancreatic, 13.3% hepatobiliary (HB), 10.6% stomach, and 1.8% small intestine (SI). Esophagogastric and SI EPSCCa were more common among Black individuals, whereas CRC, HB, and pancreatic EPSCCa were more common among White patients (p = 0.012). There were no racial differences in OS for GI EPSCCa. HB EPSCCa was associated with inferior OS compared with esophageal tumors (adjusted hazard ratio [aHR] 1.21, 95% confidence interval [CI] 1.00-1.46; p = 0.048), and SI EPSCCa was associated with prolonged survival compared with esophageal EPSCCa (aHR 0.76, 95% CI 0.48-1.20; p = 0.237) but did not reach statistical significance. Surgical intervention and a treatment period after 2006 were associated with superior OS.The prognosis for GI ESPCCa varies based on site. Chemotherapy, radiation, and surgical resection are associated with improved outcomes; however, the prognosis for patients with EPSCCa remains dismal. Prospective studies are needed to guide therapy for this aggressive tumor.

Small cell carcinoma (SCC) of the uterine cervix is a rare and aggressive form of neuroendocrine carcinoma, which resembles small cell lung cancer (SCLC) in its histology and poor survival rate. Here, we sought to define the genetic underpinning of SCCs of the uterine cervix and compare their mutational profiles with those of human papillomavirus (HPV)-positive head and neck squamous cell carcinomas, HPV-positive cervical carcinomas, and SCLCs using publicly available data. Using a combination of whole-exome and targeted massively parallel sequencing, we found that the nine uterine cervix SCCs, which were HPV18-positive (n = 8) or HPV16-positive (n = 1), harbored a low mutation burden, few copy number alterations, and other than TP53 in two cases no recurrently mutated genes. The majority of mutations were likely passenger missense mutations, and only few affected previously described cancer-related genes. Using RNA-sequencing, we identified putative viral integration sites on 18q12.3 and on 8p22 in two SCCs of the uterine cervix. The overall nonsilent mutation rate of uterine cervix SCCs was significantly lower than that of SCLCs, HPV-driven cervical adeno- and squamous cell carcinomas, or HPV-positive head and neck squamous cell carcinomas. Unlike SCLCs, which are reported to harbor almost universal TP53 and RB1 mutations and a dominant tobacco smoke-related signature 4, uterine cervix SCCs rarely harbored mutations affecting these genes (2/9, 22% TP53; 0% RB1) and displayed a dominant aging (67%) or APOBEC mutational signature (17%), akin to HPV-driven cancers, including cervical adeno- and squamous cell carcinomas and head and neck squamous cell carcinomas. Taken together, in contrast to SCLCs, which are characterized by highly recurrent TP53 and RB1 alterations, uterine cervix SCCs were positive for HPV leading to inactivation of the suppressors p53 and RB, suggesting that these SCCs are convergent phenotypes.

Primary vaginal neuroendocrine carcinoma (NEC) is extremely rare among female genital tract tumors. Here, we report 2 cases of vaginal small cell NEC (SCNEC) using immunohistochemistry and next-generation sequencing (NGS) analysis. The 2 patients were in their mid-to-late 70s, presented with abnormal vaginal bleeding and had a vaginal submucosal mass. The biopsied or resected tumors showed a typical neuroendocrine morphology consisting of solid nests of atypical tumor cells, with no specific organoid patterns, and proliferating in the vaginal submucosa. Immunohistochemical analysis showed strong and diffuse expression of chromogranin A, synaptophysin, and p16, but no thyroid transcription factor 1 expression. Additionally, both cases were positive for human papillomavirus (HPV) 18. An NGS-based cancer panel analysis revealed that the tumors carried NF1 and AR mutations, but no major driver mutations were detected. The results of this study suggested that HPV18 infection is linked to vaginal SCNEC.

Background Small cell neuroendocrine carcinoma of the prostate (SCNECP) is a rare, aggressive subtype of prostate carcinoma. Most SCNECP arise from conventional prostate adenocarcinoma (CPAC) treated with androgen deprivation therapy (ADT). Case presentations We identified four cases of CPAC treated with ADT, which evolved to SCNECP with liver metastasis. The average interval between the diagnosis of CPAC and SCNECP was 102 months (range: 12 to 168). Histologically, the tumors showed nests of cells with high nuclear:cytoplasmic ratios, granular chromatin, and frequent mitoses. All cases were synaptophysin, chromogranin, and AE1/AE3 positive, with a Ki-67 labeling index ≥70%. NKX3.1 was negative in all but one case and TTF-1 was positive in half. Weak ERG positivity by IHC was seen in one case which also demonstrated the TMPRSS2-ERG gene rearrangement; all other cases were negative for ERG by IHC. Serum prostate specific antigen (PSA) levels were normal to near-normal in all. The median interval between the diagnosis of SCNECP and death was 3.25 months (range: 0.75 to 26). Conclusions Our case series highlights the importance of considering a prostate primary, even in the setting of normal PSA levels and loss of prostate markers, when diagnosing neuroendocrine carcinoma in the liver. Further, we emphasize the significance of diagnosing SCNECP that metastasizes to the liver, as it portends a particularly dismal prognosis.

Background The aim of this study was to discuss the safety and efficacy of administering reduced doses (3 mg) of pegylated recombinant human granulocyte‐colony stimulating factor (PEG‐rhG‐CSF) at approximately 24 h or up to three days following treatment with etoposide and cisplatin (EP). Methods A total of 104 cycles from 31 patients were divided into a PEG‐rhG‐CSF prophylaxis group (PP‐Group) and a control group (No‐PP‐Group). The PP‐Group received a reduced dose of 3 mg of PEG‐rhG‐CSF within a minimum of 15 h and a maximum of 72 h following EP chemotherapy, while the rest did not receive any G‐CSF prophylaxis (No‐PP‐Group). For both groups, complete blood counts, incidence of febrile neutropenia (FN), grade III or IV neutropenia, and the use of antibiotics to treat neutropenia were recorded. Results There was statistically no significant difference in the incidence of FN (0% vs. 1.4%, p = 1), antibiotic use due to neutropenia (0% vs. 2.7%, p = 0.881), estimated lowest mean marginal (EM) platelet (106.56 × 109/L vs. 127.70 × 109/L, p = 0.056) and hemoglobin (110.48 g/L vs. 110.14 g/L, p = 0.906) levels between the two groups. However, when compared with the No‐PP‐group, the white blood cell count in the PP‐group was significantly higher (EM means: 4.95 × 109/L vs. 2.80 × 109/L, p, Even though cisplatin is slowly metabolized by the body, the routine administration time of PEG‐rhG‐CSF following cisplatin was safe. A reduced dose (3 mg) of PEG‐rhG‐CSF was also effective in preventing grade III and IV neutropenia.

Background: Lung cancer remains the most common cause of cancer-related deaths in China and worldwide. Traditional surgery and chemotherapy do not offer an effective cure, although gene therapy may be a promising future alternative. Kallistatin (Kal) is an endogenous inhibitor of angiogenesis and tumorigenesis. Recombinant adeno-associated virus (rAAV) is considered the most promising vector for gene therapy of many diseases due to persistent and long-term transgenic expression. Objective: The aim of this study was to investigate whether rAAV9-Kal inhibited NCI-H446 subcutaneous xenograft tumor growth in mice. Methods: The subcutaneous xenograft mode was induced by subcutaneous injection of 2×107 H446 cells into the dorsal skin of BALB/c nude mice. The mice were administered with ssrAAV9-Kal (single- stranded rAAV9) or dsrAAV9-Kal (double-stranded rAAV9) by intraperitoneal injection (I.P.). Tumor microvessel density (MVD) was examined by anti-CD34 staining to evaluate tumor angiogenesis. Results: Compared with the PBS (blank control) group, tumor growth in the high-dose ssrAAV9-Kal group was inhibited by 40% by day 49, and the MVD of tumor tissues was significantly decreased. Conclusion: The results indicate that this therapeutic strategy is a promising approach for clinical cancer therapy and implicate rAAV9-Kal as a candidate for gene therapy of lung cancer.

Objective. The development of effective cancer treatments depends on the availability of cell lines that faithfully recapitulate the cancer in question. This study definitively re-assigns the histologic identities of two ovarian cancer cell lines, COV434 (originally described as a granulosa cell tumour) and TOV-112D (originally described as grade 3 endometrioid carcinoma), both of which were recently suggested to represent small cell carcinoma of the ovary, hypercalcemic type (SCCOHT), based on their shared gene expression profiles and sensitivity to EZH2 inhibitors. Methods. For COV434 and TOV-112D, we re-reviewed the original pathology slides and obtained clinical followup on the patients, when available, and performed immunohistochemistry for SMARCA4, SMARCA2 and additional diagnostic markers on the original formalin-fixed, paraffin-embedded (FFPE) clinical material, when available. For COV434, we further performed whole exome sequencing and validated SMARCA4 mutations by Sanger sequencing. We studied the growth of the cell lines at baseline and upon re-expression of SMARCA4 in vitro for both cell lines and evaluated the serum calcium levels in vivo upon injection into immunodeficient mice for COV434 cells.Results. The available morphological, immunohistochemical, genetic, and clinical features indicate COV434 is derived from SCCOHT, and TOV-112D is a dedifferentiated carcinoma. Transplantation of COV434 into mice leads to increased serum calcium level. Re-expression of SMARCA4 in either COV434 and TOV-112D cells suppressed their growth dramatically. Conclusions. COV434 represents a bona fide SCCOHT cell line. TOV-112D is a dedifferentiated ovarian carcinoma cell line.(c) 2020 Elsevier Inc. All rights reserved.

Introduction: Extrapulmonary small-cell cancer (EPSCC) is a relatively rare malignancy. The management of EPSCC is usually extrapolated from small-cell lung cancer (SCLC). In spite of the morphological similarity of the 2 malignancies, there are many differences in clinical features, prognosis, and recommendations of treatment of these disorders. The data on the correlation of clinical-pathological characteristics of EPSCC and treatment results is scarce. Materials and Methods: This retrospective analysis of 41 consecutively treated patients diagnosed with EPSCC in 2015–2018 was performed in a tertiary medical center. The correlation between the clinical and pathological characteristics and the treatment outcome (response rate, disease-free interval, and overall medial survival) was done using the standard statistics, Kaplan-Meier method, and multivariate analyses. The stratification was done on the stage of the disease, Ki-67 proliferative index, the location of the tumor, and smoking. Results: Forty-one patients were included with a median age of 66.3 years. The most common primary site was the gastrointestinal tract (28, 68.3%) including the pancreas. The most common distant metastasis site was the liver (23, 56.1%). Only 2 patients (4.9%) had brain metastases. Unlike in SCLC, most patients did not have any history of smoking (23, 56.1%). Nineteen patients with metastatic disease received systemic treatment, mostly cisplatin-based chemotherapy, with a response rate of 57.9%. The results of treatment were significantly better in patients with disseminated EPSCC with Ki-67 Discussion: The results of our study show the unique entity of EPSCC. The rarity of brain metastases proves that prophylactic brain irradiation should not be recommended in practice. The provocative idea of prophylactic liver irradiation in limited-stage EPSCC of gastrointestinal origin can be evaluated in future studies. The predictive role of Ki-67 is important in metastatic EPSCC. There is probably no role of smoking in developing EPSCC.

Background Immune checkpoint blockade has made a significant impact on the clinical outcomes of patients with metastatic urothelial carcinoma (UC). However, evidence for this approach in patients with non‐UC of the urinary tract is limited. Methods This was a phase II open‐label study of durvalumab 1500 mg and tremelimumab 75 mg every 4 weeks for four cycles followed by durvalumab 1500 mg every 4 weeks. Eligible patients had metastatic non‐UC with ECOG PS 0–1 regardless of prior therapy (except small cell carcinoma who were pretreated). The primary endpoint was overall response rate per RECIST v1.1. A Simon's minimax two‐stage design was employed, with 13 patients planned for stage one. Pre‐treatment tumors underwent PD‐L1 staining and next‐generation sequencing. Results Thirteen patients were treated, including seven small cell carcinoma, three squamous cell carcinoma, and three adenocarcinoma. Eleven patients had visceral metastases. No responses were observed; 11 patients had PD and 2 patients had SD. Median PFS was 1.8 months (95% CI, 1.25‐not reached [NR]) with a median follow‐up of 7.38 months (range, 5.23–21.99 months). Median OS was 6.97 months (95% CI, 4.34‐NR). One patient's tumor was PD‐L1 positive and all sequenced tumors (n = 8) were microsatellite stable. Grades 3–4 treatment‐related adverse events occurred in 38.4% of patients. Conclusions In a poor prognosis cohort of patients with non‐UC, durvalumab and tremelimumab lacked clinical activity while demonstrating a manageable safety profile., Metastatic, non‐UC tumors of the urinary tract have an aggressive clinical course and dismal prognosis. This phase II trial evaluating durvalumab and tremelimumab demonstrated a manageable safety profile but lack of clinical activity.

Clinicopathologic characterisation of a contemporary series of neuroendocrine (NE) differentiation in the setting of prostatic carcinoma (PCa) was examined.We reviewed institutional databases for in-house cases with a history of PCa and histopathologic evidence of NE differentiation during the disease course. In all, 79 cases were identified: 32 primary and 47 metastases. Metastatic lesions were in liver (n = 15), lymph node (n = 9), bone (n = 6), lung (n = 3), brain (n = 1), and other sites (n = 13). In all, 63 of 76 (82%) cases with NE differentiation and available history were posttherapy: six postradiation therapy (RT), 24 post- androgen-deprivation therapy (ADT), and 33 post-RT + ADT. Morphologic assessment (n = 79): (i) 23 pure small-cell/high-grade NE carcinoma (HGNEC): 20/23 metastatic; (ii) 10 combined high-grade PCa and small-cell/HGNEC: 9/10 primary; (iii) 15 PCa with diffuse NE immunohistochemistry (IHC) marker positivity/differentiation, associated with nested to sheet-like growth of cells with abundant cytoplasm and prominent nucleoli, yet diffuse positivity for at least one prostatic and one NE IHC marker: all metastatic; (iv) 11 PCa with patchy NE differentiation, displaying more than single-cell positivity for NE IHC: five primary / six metastatic; (v) nine PCa with focal NE marker positive cells: four primary / five metastatic; (vi) 11 PCa with 'Paneth cell-like' change: all primary.In this contemporary series, the majority of NE differentiation in the setting of PCa was seen posttherapy. We highlight the tendencies of small-cell/HGNEC and PCa with diffuse NE differentiation by IHC to occur in metastatic settings, while morphologically combined high-grade PCa + small-cell/HGNEC and 'Paneth cell-like' change occur in primary disease.

Purpose Current research has shown a link between ABO blood group and many diseases. The purpose of this study aimed to investigate the influence of the ABO blood group on the risk of developing different pathological types of lung cancer. Materials and methods This retrospective study was composed of 7681 patients with lung cancer and 12, 671 non-lung cancer patients who were admitted to the First Affiliated Hospital of Nanchang University from January 2016 to January 2021. The subjects with lung cancer were grouped into small cell lung cancer group (n = 725), lung adenocarcinoma group (n = 4520), and lung squamous cell carcinoma group (n = 2286) according to pathological types. The ABO blood group distribution of each lung cancer type group was compared with that of the control group. Statistical analysis was determined with chi-square and logistic regression. Results Univariate analysis showed that the ABO blood group distribution of lung adenocarcinoma, lung squamous cell carcinoma, and small cell lung cancer was different from that of the control group (P < 0.01). After adjusting for age, sex, smoking history, and drinking history, logistic regression analysis showed that the risk of lung adenocarcinoma in blood type O was higher than that in blood type A (P < 0.01). There was no significant difference in ABO blood group composition between small cell lung cancer group, lung squamous cell carcinoma group, and control group (P > 0.05). In addition, gender and age have an influence on all three types of lung cancer (P < 0.01). Smoking was a risk factor in lung squamous cell carcinoma and small cell carcinoma (P < 0.01). Alcohol consumption was a risk factor in lung adenocarcinoma (P < 0.01). Conclusion ABO blood group may be correlated with the occurrence of lung adenocarcinoma in Jiangxi province, but not with lung squamous cell carcinoma and small cell carcinoma.

Tuft cells are chemosensory epithelial cells in the respiratory tract and several other organs. Recent studies revealed tuft cell-like gene expression signatures in some pulmonary adenocarcinomas, squamous cell carcinomas (SQCC), small cell carcinomas (SCLC), and large cell neuroendocrine carcinomas (LCNEC). Identification of their similarities could inform shared druggable vulnerabilities. Clinicopathological features of tuft cell-like (tcl) subsets in various lung cancer histotypes were studied in two independent tumor cohorts using immunohistochemistry (n = 674 and 70). Findings were confirmed, and additional characteristics were explored using public datasets (RNA seq and immunohistochemical data) (n = 555). Drug susceptibilities of tuft cell-like SCLC cell lines were also investigated. By immunohistochemistry, 10–20% of SCLC and LCNEC, and approximately 2% of SQCC expressed POU2F3, the master regulator of tuft cells. These tuft cell-like tumors exhibited “lineage ambiguity” as they co-expressed NCAM1, a marker for neuroendocrine differentiation, and KRT5, a marker for squamous differentiation. In addition, tuft cell-like tumors co-expressed BCL2 and KIT, and tuft cell-like SCLC and LCNEC, but not SQCC, also highly expressed MYC. Data from public datasets confirmed these features and revealed that tuft cell-like SCLC and LCNEC co-clustered on hierarchical clustering. Furthermore, only tuft cell-like subsets among pulmonary cancers significantly expressed FOXI1, the master regulator of ionocytes, suggesting their bidirectional but immature differentiation status. Clinically, tuft cell-like SCLC and LCNEC had a similar prognosis. Experimentally, tuft cell-like SCLC cell lines were susceptible to PARP and BCL2 co-inhibition, indicating synergistic effects. Taken together, pulmonary tuft cell-like cancers maintain histotype-related clinicopathologic characteristics despite overlapping unique molecular features. From a therapeutic perspective, identification of tuft cell-like LCNECs might be crucial given their close kinship with tuft cell-like SCLC.

A 60-year-old woman was not accompanied by any symptom. She had a gallstone which was identified 20 years prior. Ultrasonography performed by a local doctor revealed that the gallbladder was filled with small stones, and the patient was referred to our department for further examination and treatment for gallbladder stone. Tumor markers are elevated. Contrast- enhanced CT revealed gallbladder stones and thickening in the gallbladder body. PET-CT showed abnormal accumulation of FDG-PET with SUVmax 3.6 in the body of the gallbladder. With a diagnosis of gallbladder cancer, extended cholecystectomy and gallbladder bed resection with regional lymph node dissection were performed. The tumor was diagnosed histologically as small cell type neuroendocrine carcinoma of the gallbladder(pT2a[SS], pN0, pStage ⅡA; Japanese society of hepato-biliary-pancreatic surgery, the 7th edition). The postoperative course was uneventful. This patient has been followed up for 8 years without obvious signs of recurrence. R0 resection and lack of lymph node metastasis can allow long- term survival.

Few cytological reports have described small-cell neuroendocrine carcinoma (SCNEC) in the female genital tract. In the present study, we describe a cytological case of SCNEC accompanied by adenocarcinoma, as well as high-grade squamous intraepithelial lesion (HSIL). A Japanese woman (42 years old) presented with abnormal genital bleeding. A conventional Papanicolaou smear revealed an inflammatory condition with three neoplastic components: SCNEC as irregular aggregates of neoplastic small round cells with nuclear molding and granular chromatin; adenocarcinoma as columnar cell clusters with peripherally located large nuclei, and HSIL as sheets or clusters of dysplastic basal-type squamous cells with irregular hyperchromatic nuclei. Accordingly, a cytodiagnosis of SCNEC with adenocarcinoma and HSIL was made. Owing to the rarity of cervical SCNEC, cytological diagnosis may be difficult. Due to its aggressive clinical behavior, the presence of an SCNEC component should be verified in any cytodiagnosis of adenocarcinoma or HSIL.

Cervical SCNEC is a rare and highly malignant invasive tumor. The incidence is low, at less than 5% of all cervical cancers. Moreover, most patients with small cell carcinoma are interrelated with high risk HPV (more familiar HPV 18). Compared to squamous cell carcinoma or adenocarcinoma, patients of cevical SCNEC are more prone to lymph node invasion early, so the clinical manifestation is usually local or distant metastasis. We summarized the clinical features of 19 patients with cervical small cell carcinoma in the Second Affiliated Hospital of Dalian Medical University from 2012 to 2021, and retrospectively analyzed data from 1576 patients in 20 related studies and more than 50 pieces of literature in recent years by searching PubMed, Google schalor, Cochrane Library, Clinicalkey, and other databases. The collected patient data included age, clinical manifestation, TCT, HPV detection, the size and morphology of the tumor, local invasion depth, stage, lymph node status, initial treatment method, tumor-free survival, and so on. The positive rates of CGA, SYN, and CD56 in our cases were high, and NSE was a moderately sensitive index. P16 and Ki67 were the most sensitive, and all patients were positive. We found that multimodal treatment can indeed improve tumor-free survival (DFS), but the prognosis of patients is still very poor. For the early stages, our treatment principles refer to the guidelines of SGO, international gynecological cancer Cooperation (GCIG), and NCCN. We suggest a combination of surgery, radiotherapy, and chemotherapy. However, the general state of advanced patients is poor, whether they can tolerate the operation after neoadjuvant chemotherapy, whether the operation area can remain tumor-free, and whether this treatment will prolong the survival time of patients still need to be further discussed. In order to better prolong the tumor-free survival and prognosis of patients, we need to find gene changes suitable for targeted therapy, so as to complete the clinical application of these treatment methods. Further works are needed to explore more effective therapy for cervical SCNEC.

Gall bladder small cell carcinoma (scc) comprises of 0.5% of all GB cancers. It carries a poor prognosis in view of its aggressive nature. We here report a case of small cell carcinoma GB 55-year old lady presented with features of obstructive jaundice with significant weight loss. Examination revealed hard lump in right upper abdomen with multiple scratch marks all over the body. Clinically she had jaundice. Blood investigations revealed hyperbilirubinemia. Tumour markers showed raised CA 19-9. Staging CECT thorax and Abdomen reported polypoidal enhancing wall thickening of gall bladder with multiple metastatic deposits close to pancreatic head encasing main portal vein and common bile duct. Histopathology was suggestive of small cell carcinoma. Patient was referred to Oncology department and is receiving palliative cisplatin-etoposide chemotherapy

Preoperative diagnosis in liquid-based cytology preparation in voided urine specimen and cyto-histologic correlation of small cell carcinoma of the urinary bladder has not been described in detail in the literature. A 79-year old male presented at our institution with gross hematuria. He was accurately diagnosed with small cell carcinoma of the bladder on liquid-based cytology in urine. The patient subsequently proceeded to transurethral resection of the bladder tumor, confirming the diagnosis. In this article, we present a detailed report of primary urothelial carcinoma with dominant neuroendocrine differentiation of the bladder describing the cytologic and histologic morphologic features, its differential diagnosis with a review of the literature.

Background Active surveillance (AS) is one of the treatment methods for patients with small renal masses (SRMs; Methods A total of 130 consecutive patients with pathologically confirmed non-metastatic SRMs (fat-poor angiomyolipomas [fpAMLs; n = 7] and RCCs [n = 123]) were retrospectively enrolled. Between 2011 and 2019, SRM diagnoses in these patients were confirmed after biopsy or surgical resection. All RCCs were surgically resected. Regardless of diameter, a collateral vessel (CV) was defined as any blood vessel connecting the tumor from around the kidney using CECT. First, we analyzed the role of CV-detection in differentiating between fpAML and RCC. Then, we evaluated the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of RCC diagnosis based on CV-detection using CECT. We also assessed the prognostic value of CV-detection using the Fisher exact test, and Kaplan-Meier method and the log-rank test. Results The sensitivity, specificity, PPV, NPV, and accuracy of CV-detection for the diagnosis of small RCCs was 48.5, 45.5, 100, 100, and 9.5% respectively. Five of 123 (4.1%) patients with RCC experienced recurrence. CV-detection using CECT was the only significant factor associated with recurrence (p = 0.0177). Recurrence-free survival (RFS) was significantly lower in patients with CV compared with in those without CV (5-year RFS 92.4% versus 100%, respectively; p = 0.005). In addition, critical review of the CT images revealed the CVs to be continuous with the venous vessels around the kidney. Conclusions The detection of CVs using CECT is useful for differentiating between small fpAMLs and RCCs. CV-detection may also be applied as a predictive parameter for small RCCs prone to recurrence after surgical resection. Moreover, AS could be suitable for small RCCs without CVs.

Malignant tumors of the temporal bone are rare. They include a wide histological variety. They are mostly primary tumors with an estimated incidence of 0.8-1.0 per 1,000,000 inhabitants per year [1]. Metastases form an uncommon subgroup. The clinical features of these temporal bone metastases are nonspecific and predominantly consist of hearing loss, vertigo, facial palsy, tinnitus, headache, otalgia or otorrhoea [2]. The aim of our publication is to report a rare case of metastasis in the temporal bone as initial manifestation of lung cancer. Our patient was a 44-year-old man who presented for a right mastoid swelling with a grade VI right facial nerve palsy. Imaging and biopsy confirmed the diagnosis of small cell lung carcinoma petrous metastasis. The treatment was palliative. An osteolytic lesion of the temporal bone in an elderly patient may fit with a primary tumor of the temporal bone. It must, also, suggest the diagnosis of metastasis. The malignant tumor most frequently responsible is breast cancer, but lung cancer must also be considered in smoking patients.

The aim of this study was to review the clinicopathological characteristics of small cell neuroendocrine cervical cancer (SCNEC) and to identify the optimal treatment.The Japanese Society of Gynecologic Oncology conducted a retrospective cohort study of SCNECs enrolled in the Gynecological Tumor Registry of the Japan Society of Obstetrics and Gynecology between 2004 and 2015. All cases were modified and unified by International Federation of Gynecology and Obstetrics 2008 (Union for International Cancer Control 7th edition).There were 822 registered patients diagnosed with SCNEC from 2004 to 2015 which comprised 1.1% (822/73,698) of all uterine cervical cancer cases. Rates of lymph-node and distant metastasis were significantly higher in T1b2 (38.9% and 13.7%, respectively) than T1b1 (14.2% and 4.4%, respectively) (p0.01). In IB2 and T1bN1M0 SCNEC, the 5-year survival rate with surgery followed by chemotherapy was significantly higher than that with surgery followed by radiation therapy/concurrent chemoradiation therapy (p0.01).SNCEC tumors4 cm in size had greater rates of lymph-node and distant metastasis when compared with tumors ≤4 cm. Adjuvant chemotherapy, rather than radiotherapy, may improve prognosis after surgery in T1bN1M0 SCNEC.

BACKGROUND Small cell carcinoma (SCC) is usually aggressive and associated with a poor prognosis. This type of cancer is rarely found in extra-pulmonary or digestive-tract locations. This report describes an unusual presentation in terms of clinical symptoms and primary location (even among head and neck presentations), and unexpected occupational exposure. CASE REPORT This case report is a novel observation of SCC in the paranasal sinuses and is to the best of our knowledge the first case associated with occupational exposure to sawdust, with almost no ear, nose, and throat (ENT) symptoms related to the primary tumor location. Our patient had no past medical history and none of the usual risk factors, apart from a smoking history of 32 pack-years. He was not taking any regular treatment. The inaugural clinical presentation was mainly digestive, with neither ENT nor neurological symptoms. Diagnostic wavering ensued and numerous paraclinical tests were performed. This is one of the very few cases of an ethmoidal location ever reported for SCC. This cancer type is unusual in neck and head locations, but has occasionally been reported in the larynx and hypopharynx. To the best of our knowledge, this is only the second report of an ethmoidal location. In addition, this patient was a carpenter, implying exposure to sawdust, which is usually associated with adenocarcinoma of the ethmoid. We illustrate here that SCC, which has been described elsewhere without sawdust exposure, is also possible. CONCLUSIONS Exposure to sawdust should suggest a possible ethmoidal cancer location, even if there are few ENT symptoms. Adenocarcinoma is the most prevalent but clearly not the only possible histological pattern.

A 65-year-old man with fluciclovine-avid metastatic prostate small cell carcinoma with prostate-specific antigen (PSA) 19.4 ng/mL at diagnosis underwent system therapy and subsequent surgery and achieved hormonal response with PSA

The prognosis of the small cell esophageal cancer (SCEC) patient in our study was poor due to lack of treatment options which were limited to surgery and chemotherapies, with a median overall survival (OS) of only 11.1 months according to previous studies. Herein, we adopted the regimen of immunotherapy plus chemotherapy, which exerted superior and durable benefit (OS > 19 months) in the patient in our study. Immunotherapy plus chemotherapy might therefore be a reasonable option for selected SCEC patients. In addition, well‐designed trials for better evidence are required to verify the findings in this study., The prognosis of the small cell esophageal cancer (SCEC) patient in our study was poor due to lack of treatment options. Immunotherapy plus chemotherapy might therefore be a reasonable option for selected SCEC patients.

Lack of tumor targeting and low drug payload severely impedes various nanoagents further employed in small-cell lung cancer (SCLC). Therefore, how to develop a new targeting ligand and enhance drug payload has been an urgent need for SCLC therapy. Herein, we first sift and verify that capreomycin (Cm) has a high affinity toward CD56 receptors overexpressed on SCLC cells. Motivated by the concept of self-targeted drug delivery, Cm is selected as the specific targeting ligand toward CD56 receptors and chemodrug doxorubicin (Dox) is adopted to be covalently linked via the redox-responsive disulfide linkage. The synthesized self-distinguishing prodrug (Dox-ss-Cm) and FDA-approved photosensitizer indocyanine green (ICG) as structural motifs can be self-assembled into theranostic nanoagents (ICG@Dox-ss-Cm NPs) within an aqueous solution. Such carrier-free nanoagents with high drug payload can exert targeted on-demand drug release under multiple stimuli of intracellular lysosomal acidity, glutathione (GSH), and an external near-infrared (NIR) laser. Besides, our nanoagents can be specifically self-targeted to SCLC sites in vivo and self-distinguishing via SCLC cells in vitro; thus, they decrease the undesirable effects on normal tissues and organs. Further in vitro and in vivo studies uniformly confirm that such nanoagents show highly synergistic effects for SCLC chemo-photothermal therapy (PTT) under the precise guidance of NIR fluorescence (NIRF)/photoacoustic (PA) imaging. Taken together, our work can provide a novel and promising strategy for the targeted treatment of SCLC.

Small cell carcinoma of the ovary of hypercalcemic type (SCCOHT) is a rare and rapidly lethal disease affecting young women. Cytoreductive surgery associated with chemotherapy followed by a high dose chemotherapy regimen (HDC) demonstrated improved outcomes in a unique prospective and several retrospective studies, and this report aimed to confirm these results in an independent and larger cohort.Between 2006 and 2018, we conducted a multicentric prospective study on 44 women diagnosed with SCCOHT. Patients were treated homogeneously with optimal cytoreductive surgery and chemotherapy protocol for four to six cycles (PAVEP). In case of complete response, patients received HDC with stem-cell support, followed by pelvic radiotherapy. The primary endpoint was the event-free survival (EFS) in the per-protocol cohort. Secondary analysis explored the effect of HDC with outcomes.Mean age at diagnosis was 33 years old (range 13.8-75.8). 14 patients presented with stage FIGO I, 21 with stage III and 9 with stage IV. Median follow-up was 53.4 months. 38 patients underwent optimal surgery with up to 6 cycles of PAVEP. 30 received HDC, and 21 pelvic radiotherapy. 21 relapses were reported leading to death for 18 patients. Median EFS in the per-protocol cohort was 18.2 months, and 2-year EFS rate was 40%. HDC was significantly associated with better overall survival (p .001). Grades 3/4 adverse events were frequent but, in most cases, manageable, although one grade-5 adverse-event occurred during HDC.Intensive regimen containing multidrug chemotherapy, HDC and pelvic radiotherapy, for the management of SCCOHT, demonstrated encouraging survival and should be proposed for all patients. However, the significant toxicity cost associated is of concern and it should be restricted to expert centers.

The management of metastatic lung cancers, either of the small-cell (SCLC) or the non-small cell (NSCLC) subtype, largely based on systemic treatments so far, has been the subject of breakthrough advances over the past few years, with notably the wide use of immunotherapy changing the landscape of these harmful prognosis diseases. In parallel with this major progress, the increasing use of radiotherapy (RT) for the treatment of the primary thoracic lesion ± the distant lesions, may contribute to improving the condition of these metastatic patients, both in terms of progression-free survival (PFS) and overall survival (OS). This review proposes to summarize and explain the findings provided by the different studies published in the last years experiencing RT of the primary tumor in metastatic lung cancers, either associated or not with the local ablative treatment of a low number of distant lesions. It will also expose the respective limits encountered in these studies and, in the light of all these elements, suggests various promising issues and fields of research for the future.

We aim to discuss comprehensively the role of long noncoding RNAs (lncRNAs) and circular RNAs (circRNAs) in small-cell lung cancer (SCLC) biology and their clinical utility as cancer biomarkers. We searched the scientific literature to select articles related to the role of lncRNAs and circRNAs in SCLC biology or as cancer biomarkers. We identified that a number of lncRNAs and circRNAs can regulate key biological processes involved in SCLC development, including cell proliferation, metastasis and chemoresistance mainly acting as miRNA sponges. Also, the expression of a few lncRNAs and circRNAs predicted survival outcome depicting their utility as prognostic biomarkers. Further investigations on the role of lncRNAs and circRNAs in SCLC tumors may yield novel therapeutic targets for SCLC.

SCCOHT is an aggressive malignancy linked to alterations of SMARCA4. We describe the diagnosis and therapy of a 32 year old who received multi-agent chemotherapy and underwent a second look operation with HIPEC followed by high-dose chemotherapy with stem cell transplant. Supportive care, oncofertility, and genetic counseling are described.