Search

Neuroendocrine neoplasms (NENs) of the liver represent a rare entity. Amongst this group of uncommon diseases primary hepatic neuroendocrine neoplasm (PH‐NEN) represent only 0.3% of all NENs. Moreover, PH‐NEN has very rarely been reported in pregnancy. We report a 28‐year‐old young patient with metastatic small cell neuroendocrine carcinoma of the liver complicated with pregnancy. She was evaluated and managed through a multidisciplinary team approach and received two cycles of chemotherapy with a cisplatin/etoposide regimen during the antenatal period and delivered at 37 weeks period of gestation (POG). This case highlights the importance of major challenges faced during the diagnosis and management of this very rare disease in pregnancy and the successful fetomaternal outcome. Synopsis: Primary hepatic neuroendocrine neoplasms (PH‐NENs) constitute 0.3% of all NENs, and are rarely reported in pregnancy. A 28‐year‐old pregnant woman was managed successfully, emphasizing diagnostic and management challenges. [ABSTRACT FROM AUTHOR]

The article discusses a case report of a 53-year-old woman with Birt-Hogg-Dubé syndrome (BHD) who developed metastatic chromophobe renal cell carcinoma (RCC) after the removal of a primary tumor smaller than 3 cm. The patient underwent partial nephrectomy followed by radical nephrectomy, and later developed omental metastases. Genetic testing confirmed the diagnosis of BHD, and the patient was treated with immunotherapy. The article raises questions about the effectiveness of the 3 cm rule in BHD patients and calls for further research in large BHD case series to reconsider screening recommendations. [Extracted from the article]

Arising from the urachal epithelial lining, the urachal carcinoma is a rare tumor, which accounts for 0.35%–0.7% of all bladder cancers. Urachal carcinoma has a higher predilection in men with median age around 50–60 years old. The most common clinical symptom is intermittent painless gross hematuria, and less‐reported presentations include suprapubic mass, dysuria, lower abdominal pain, and frequent urination. The pathological study reveals that most cases (90%) are categorized as an intestinal adenocarcinoma subtype, while other morphological variants, including mucinous, enteric, signet ring cell subtype, not otherwise specified (NOS), squamous cell carcinoma, urothelial carcinoma, sarcoma, small cell carcinoma, and undifferentiated carcinoma, totally account for about 10%. The urachal carcinoma occurs mostly in the lower segment of urachal tube and bladder dome or anterior wall. However, due to the classically silent nature of the early lesions and high malignancy, urachal carcinoma patients are commonly diagnosed in advanced stage. Treatment modalities for local recurrence or metastatic urachal cancer include surgery and chemotherapy (cisplatin and 5‐FU based‐chemotherapy). Meanwhile, the EGFR‐, PD‐L1‐, and MEK‐targeted therapies in the metastatic urachal carcinoma cases showed satisfactory response. We presented a rare case of Sheldon stage IVB urachal adenocarcinoma with pulmonary metastasis, and the patient had no progression of disease 6 months following surgical treament without chemoradiotherapy. [ABSTRACT FROM AUTHOR]

Ocular metastasis is a rare type of distant metastasis of lung cancer. Limited information is available regarding ocular symptoms, diagnosis, treatment, and prognosis. We reported 16 patients diagnosed with ocular metastasis from lung cancer treated at our hospital from January 1988 to March 2024 and conducted a systematic review of 100 patients retrieved from the PubMed database from January 2014 to December 2023. A pooled analysis was performed using individual‐level patient data to generate the hazard ratio (HR) of the association between patient characteristics and overall survival. A total of 116 patients, 100 patients from the literature and 16 patients from our center, diagnosed with ocular metastasis from lung cancer were included in this study. Choroid metastasis was presented in 77 (66.4%) patients and was significantly associated with the onset of lung cancer with ocular symptoms and decreased vision; iris metastasis was significantly associated with small cell lung cancer (SCLC), high intraocular pressure, and ocular pain. Multivariate analyses revealed that males (HR, 2.488; 95% confidence interval [CI], 1.127–5.495), age ≥ 60 years (HR, 3.196; 95% CI, 1.391–7.341), and onset with ocular symptoms (HR, 4.312; 95% CI, 1.675–11.099) were significantly associated with overall survival. For non‐SCLC (NSCLC) patients, compared with chemotherapy, targeted therapy (HR, 0.238; 95% CI, 0.087–0.651) and combined therapy (HR, 0.133; 95% CI, 0.017–0.822) have greater therapeutic efficacy. Chemotherapy combined with immunotherapy and targeted therapy are more effective than chemotherapy alone for ocular metastatic NSCLC patients. For patients with targetable mutations, new‐generation tyrosine kinase inhibitors (TKIs) are preferred. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Background: The presence of collateral vessels (CVs) on contrast-enhanced computed tomography is a poor prognostic factor in renal cell carcinoma (RCC), but its value in small RCC (sRCC; < 4 cm) remains unknown. In this study, we investigated whether presence of CVs is a predictor of high potential for metastasis in sRCC. Methods: We retrospectively reviewed clinical and imaging data of patients with pathologically confirmed sRCC evaluated at our institution between 2011 and 2021. All sRCCs were pathologically diagnosed by biopsy, metastasectomy, partial nephrectomy, or radical nephrectomy. CVs were defined as blood vessels of any diameter connecting the tumor with the surrounding perirenal tissues on contrast-enhanced computed tomography. The rate of metastasis-free survival (MFS), defined as the time from pathological diagnosis to confirmed metastasis, was compared among patients without CVs, those with one CV, and those with two or more CVs. Results: Of 141 patients, 4 (2.8%) had metastatic sRCC at initial diagnosis. In the 137 patients with nonmetastatic sRCC, the diagnosis was pathologically confirmed following radical surgery. The median follow-up period from pathological diagnosis was 73.9 months, and the overall 5-year MFS was 93.5%. The 5-year MFS was significantly poorer in patients with two or more CVs than in those with one CV (63.8% vs. 96.3%; p = 0.0003) and those without CVs (63.8% vs. 100%; p < 0.0001). Conclusions: sRCCs with two or more CVs might have high potential for metastasis. Conversely, sRCCs without CVs might not be aggressive and be suitable for active surveillance. [ABSTRACT FROM AUTHOR]

Simple Summary: Lung cancer is one of the leading causes of cancer-related mortality. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) differ in aggressiveness, proliferation speed, metastasis propensity, and prognosis. Since tumor cells notably change lipid metabolism, especially phospholipids and fatty acids (FA), this study aimed to identify FA alterations in lung cancer tissues. We detected significant changes in lipid metabolism in both lung cancer types compared to healthy tissues (especially higher levels of pro-inflammatory arachidonic acid), and we pointed out differences in FA profiles in tissue between SCLC and NSCLC. Our findings can be useful for further research concerning molecular lung cancer therapies. Background: Lung cancer is one of the leading causes of cancer-related mortality. Non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC) differ in aggressiveness, proliferation speed, metastasis propensity, and prognosis. Since tumor cells notably change lipid metabolism, especially phospholipids and fatty acids (FA), this study aimed to identify FA alterations in lung cancer tissues. Methods: Our study included patients with newly diagnosed, histologically confirmed SCLC (n = 27) and NSCLC (n = 37). Samples were collected from both malignant and healthy tissues from each patient, providing they were within subject design. Results: In both NSCLC and SCLC tumor tissues, FA contents were shifted toward pro-inflammatory profiles, with increased levels of some individual n-6 polyunsaturated FA (PUFA), particularly arachidonic acid, and elevated activity of Δ6 desaturase. Compared to healthy counterparts, lower levels of alpha-linolenic acid (18:3n-3) and total saturated FA (SFA) were found in NSCLC, while decreased levels of linoleic acid (18:2n-6) and all individual n-3 FA were found in SCLC tissue in comparison to the healthy tissue control. When mutually compared, SCLC tissue had higher levels of total SFA, especially stearic acid, while higher levels of linoleic acid, total PUFA, and n-3 and n-6 PUFA were detected in NSCLC. Estimated activities of Δ6 desaturase and elongase were higher in SCLC than in NSCLC. Conclusions: Our findings indicate a notable impairment of lipid metabolism in two types of lung cancer tissues. These type-specific alterations may be associated with differences in their progression and also point out different therapeutic targets. [ABSTRACT FROM AUTHOR]

Classic colon carcinomas are defined as adenocarcinomas, characterized by groups of medium/large cells with basophilic and polymorphous nuclei and an eosinophilic elongated cytoplasm, that rearrange on glandular structures. Signs of poor prognosis include high tumor budding, lymphovascular and perineural invasion, poor differentiation, positive margins, and CDX2 loss. Less frequent colon carcinoma subtypes are: mucinous, medullary, signet-ring cell, squamous cell, small cell and undifferentiated carcinoma, among others. In the following case report, we present a 65-year-old woman with a T2N0Mx colon carcinoma with a remarkable papillary and follicular histological appearance. The immunohistochemical stains confirmed an intestinal origin (CDX2+) and excluded a thyroid, gynecological, and urological metastasis, with tumor cells negative for GATA3, PAX8, TTF-1, and thyroglobulin. There was no loss of mismatch repair proteins and p53 showed a wild-type staining. next generation sequencing showed a platelet-derivated growth factor receptor alpha (PDGFRA) mutation. To the best of our knowledge, there have been only two examples of primary papillary colon carcinoma reported in the literature, and neither of them with a PDGFRA mutation. We describe one tumor and discuss its pathological features. [ABSTRACT FROM AUTHOR]

The study aims to acquaint readers with six widely used machine learning (ML) techniques (Principal Component Analysis (PCA), Uniform Manifold Approximation and Projection (UMAP), k-means, hierarchical clustering and the decision tree models (rpart and random forest)) that might be useful for the analysis of laboratory data. Utilizing a recently validated data set from lung cancer diagnostics, we investigate how ML can support the search for a suitable tumor marker panel for the differentiation of small cell (SCLC) and non-small cell lung cancer (NSCLC). The ML techniques used here effectively helped to gain a quick overview of the data structures and provide initial answers to the clinical questions. Dimensionality reduction techniques such as PCA and UMAP offered insightful visualization and impression of the data structure, suggesting the existence of two tumor groups with a large overlap of largely inconspicuous values. This impression was confirmed by a cluster analysis with the k-means algorithm, indicative of unsupervised learning. For supervised learning, decision tree models like rpart or random forest demonstrated their utility in differential diagnosis of the two tumor types. The rpart model, which constructs binary decision trees based on the recursive partitioning algorithm, suggests a tree involving four serum tumor markers (STMs), which were confirmed by the random forest approach. Both highlighted pro-gastrin-releasing peptide (ProGRP), neuron specific enolase (NSE), cytokeratin-19 fragment (CYFRA 21-1) and cancer antigen (CA) 72-4 as key tumor markers, aligning with the outcomes of the initial statistical analysis. Cross-validation of the two proposals showed a higher area under the receiver operating characteristic (AUROC) curve of 0.95 with a 95 % confidence interval (CI) of 0.92–0.97 for the random forest model compared to an AUROC curve of 0.88 (95 % CI: 0.83–0.93). ML can provide a useful overview of inherent medical data structures and distinguish significant from less pertinent features. While by no means replacing human medical and statistical expertise, ML can significantly accelerate the evaluation of medical data, supporting a more informed diagnostic dialogue between physicians and statisticians. [ABSTRACT FROM AUTHOR]

Backrgound: Merkel cell carcinoma (MCC) is a rare, aggressive primary cutaneous neuroendocrine carcinoma, frequently associated with clonal Merkel cell polyomavirus integration. MCC can pose significant diagnostic challenges due to its diverse clinical presentation and its broad histological differential diagnosis. Histologically, MCC presents as a small-round-blue cell neoplasm, where the differential diagnosis includes basal cell carcinoma, melanoma, hematologic malignancies, round cell sarcoma and metastatic small cell carcinoma of any site. We here report strong aberrant immunoreactivity for BCOR in MCC, a marker commonly used to identify round cell sarcomas and other neoplasms with BCOR alterations. Methods: Based on strong BCOR expression in three index cases of MCC, clinically mistaken as sarcoma, a retrospective analysis of three patient cohorts, comprising 31 MCC, 19 small cell lung carcinoma (SCLC) and 5 cases of neoplasms with molecularly confirmed BCOR alteration was conducted. Immunohistochemical staining intensity and localization for BCOR was semi-quantitatively analyzed. Results: Three cases, clinically and radiologically mimicking a sarcoma were analyzed in our soft tissue and bone pathology service. Histologically, the cases showed sheets of a small round blue cell neoplasm. A broad panel of immunohistochemistry was used for lineage classification. Positivity for synaptophysin, CK20 and Merkel cell polyoma virus large T-antigen lead to the diagnosis of a MCC. Interestingly, all cases showed strong positive nuclear staining for BCOR, which was included for the initial work-up with the clinical differential of a round cell sarcoma. We analyzed a larger retrospective MCC cohort and found aberrant weak to strong BCOR positivity (nuclear and/or cytoplasmic) in up to 90% of the cases. As a positive control, we compared the expression to a small group of BCOR-altered neoplasms. Furthermore, we investigated a cohort of SCLC as another neuroendocrine neoplasm and found in all cases a diffuse moderate to strong BCOR positivity. Conclusions: This study demonstrates that neuroendocrine neoplasms, such as MCC and SCLC can express strong aberrant BCOR. This might represent a diagnostic challenge or pitfall, in particular when MCC is clinically mistaken as a soft tissue or a bone sarcoma. [ABSTRACT FROM AUTHOR]

This article presents a case study of a 74-year-old female patient with rheumatoid arthritis who developed adenosquamous carcinoma within a long-standing intrapulmonary bronchogenic cyst. The patient was asymptomatic for 43 years before experiencing dropping serum sodium levels, which led to the discovery of the malignancy. The article emphasizes the importance of surgical excision for bronchogenic cysts due to the risk of malignant transformation, even after a long period of time. It also discusses the molecular characteristics of adenosquamous carcinomas and potential targeted therapies. [Extracted from the article]

Background: Breast metastasis from small cell neuroendocrine carcinoma (SNEC) is very rare. In the present report, we describe a case of a female patient who was initially diagnosed with triple negative primary bilateral breast cancer, but during systemic examination, the diagnosis was bilateral breast metastasis from SNEC. Case presentation: A 62-year-old woman with no history of smoking presented to the Department of General Medicine with left-sided chest pain, and computed tomography revealed masses in both breasts and left pleural thickening that was further confirmed by mammography and ultrasound of the breasts. A needle biopsy was performed, and triple negative primary bilateral breast cancer was diagnosed. Because progastrin-releasing peptide (ProGRP) 37,300 pg/ml (normal range, 0–81.0 pg/ml) and neuron-specific enolase 35.0 ng/ml (normal range, 0–16.3 ng/ml) levels were elevated, thoracoscopic biopsy was performed, and SNEC was diagnosed. Pathological examinations showed that the bilateral breast masses were also positive for immunohistochemical staining of chromogranin A, synaptophysin, and CD56, leading to a diagnosis of bilateral breast metastasis of neuroendocrine tumor. Conclusion: Although very rare, the possibility of breast metastasis should be considered when malignancy is suspected in other organs. [ABSTRACT FROM AUTHOR]

Neuroendocrine neoplasms of the thymus (tNENs), including typical carcinoid, atypical carcinoid, large cell neuroendocrine carcinoma, and small cell carcinoma, are rare tumors with scarce clinical and pathological data available in the literature. They share many common features with neuroendocrine neoplasms in other organs, such as those in the lungs, while demonstrating some distinct clinical and pathological features. This review aims to give an updated overview of each category of tNENs, focusing primarily on the pathologic diagnosis and differential diagnosis of these tumors. [ABSTRACT FROM AUTHOR]

Background: Small cell lung carcinoma (SCLC) is characterized by -poor prognosis, -high predilection for -metastasis, -proliferation, and -absence of newer therapeutic options. Elucidation of newer pathways characterizing the disease may allow for development of targeted therapies and consequently favorable outcomes. Methods: The current study explored the combinatorial action of arsenic trioxide (ATO) and apatinib (APA) in vitro and in vivo. In vitro models were tested using -H446 and -H196 SCLC cell lines. The ability of drugs to reduce -metastasis, -cell proliferation, and -migration were assessed. Using bioinformatic analysis, differentially expressed genes were determined. Gene regulation was assessed using gene knock down models and confirmed using Western blots. The in vivo models were used to confirm the resolution of pathognomic features in the presence of the drugs. Growth factor receptor bound protein (GRB) 10 expression levels of human small cell lung cancer tissues and adjacent tissues were detected by IHC. Results: In combination, ATO and APA were found to significantly reduce -cell proliferation, -migration, and -metastasis in both the cell lines. Cell proliferation was found to be inhibited by activation of Caspase-3, -7 pathway. In the presence of drugs, it was found that expression of GRB10 was stabilized. The silencing of GRB10 was found to negatively regulate the VEGFR2/Akt/mTOR and Akt/GSK-3β/c-Myc signaling pathway. Concurrently, absence of metastasis and reduction of tumor volume were confirmed in vivo. The immunohistochemical results confirmed that the expression level of GRB10 in adjacent tissues was significantly higher than that in human small cell lung cancer tissues. Conclusions: Synergistically, ATO and APA have a more significant impact on inhibiting cell proliferation than each drug independently. ATO and APA may be mediating its action through the stabilization of GRB10 thus acting as a tumor suppressor. We thus, preliminarily report the impact of GRB10 stability as a target for SCLC treatment. [ABSTRACT FROM AUTHOR]

Thoracic cancers comprise non-small cell lung cancers (NSCLCs), small cell lung cancers (SCLCs) and malignant pleural mesotheliomas (MPM). Collectively, they account for the highest rate of death from malignancy worldwide. Genomic instability is a universal feature of cancer, which fuels mutations and tumour evolution. Deficiencies in DNA damage response (DDR) genes amplify genomic instability. Homologous recombination deficiency (HRD), resulting from BRCA1/BRCA2 inactivation, is exploited for therapeutic synthetic lethality with poly-ADP ribose polymerase (PARP) inhibitors in breast and ovarian cancers, as well as in prostate and pancreatic cancers. However, DDR deficiency and its therapeutic implications are less well established in thoracic cancers. Emerging evidence suggests that a subset of thoracic cancers may harbour DDR deficiency and may, thus, be effectively targeted with DDR agents. Here, we review the current evidence surrounding DDR in thoracic cancers and discuss the challenges and promise for achieving clinical benefit with such therapeutics. [ABSTRACT FROM AUTHOR]

Key Clinical Message: Neuroendocrine tumors of the bladder are rare, accounting for less than 1% of all bladder tumors. Among these, large cell neuroendocrine carcinoma is an extremely uncommon subtype. We report on a histologically confirmed case of mixed both large and small cells neuroendocrine tumor of the bladder in a 64‐year‐old male with a history of bilharzial cystitis. The diagnosis was made after radical cystectomy with Immunohistochemical staining revealing positivity for synaptophysin, CD56, and AE1/3. While bilharzia is commonly linked to squamous cell carcinoma in the bladder, the potential relationship with neuroendocrine tumors is still relatively unexplored in this context. This case marks the first reported instance of the atypical coexistence of bilharzial cystitis and mixed large and small cell neuroendocrine carcinoma of the bladder. This unique case of coexisting highlights a rare phenomenon warranting further study. Similar associations have been documented in other organs, emphasizing the importance of exploring underlying mechanisms and clinical implications for improved patient care and outcomes. [ABSTRACT FROM AUTHOR]

Simple Summary: It is known that there are sex differences in adverse events experienced following cancer treatment. However, little is known about sex differences in adverse events experienced in individuals with metastatic cancer. Here, using SEER-Medicare data, we investigate sex differences in adverse events in lung cancer individuals with brain metastasis who are 66 years old and older. Sex differences in adverse events were observed and were dependent on lung cancer histology, age at diagnosis, year of diagnosis and treatment as well as potential interplay between these variables. Sex differences are evident in adverse events (AEs) related to brain tumors, yet sex differences in AEs specific to brain metastases (BrMs) are underexplored. Lung cancer BrMs dominate among BrM, comprising over half of cases. This study examined sex differences in AEs associated with lung cancer BrMs in individuals aged 66 or older using the SEER-Medicare dataset. Multivariable logistic regression, adjusted for demographic factors and comorbidities, stratified by histological subtype, treatment, age, and year of diagnosis were used to analyze AEs among those with BrMs from primary lung tumors. Year of diagnosis was grouped into prior/post-2013, to account for shifts in treatment paradigms. The results showed nuanced sex-specific AEs. Females diagnosed post-2013 with small-cell, squamous-cell, or other non-small-cell carcinoma BrMs had a higher headache likelihood than males. Males with adenocarcinoma post-2013 were more likely to experience brain herniation. Females aged 76 and older with small-cell BrM exhibited increased vision difficulty risk compared to males of the same age, with no significant difference in other age groups. Males treated for adenocarcinoma faced heightened hemorrhagic stroke risk. This study reveals sex-specific disparities in AEs among older individuals with lung cancer BrMs, varying by histological subtype, age, diagnosis year, and treatment. [ABSTRACT FROM AUTHOR]

Simple Summary: The rare ovarian cancer subtypes ovarian clear cell carcinoma (OCCC) and Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), can have mutations in members of a complex known as SWI/SNF that regulates the accessibility of chromatin to factors involved in DNA repair and gene expression. Some mutations in a particular complex member also occur in endometrioid ovarian cancer (EnOC) and endometriosis. Patients with endometriosis have a greater risk of developing OCCC and EnOC, with endometriosis frequently present at the time of diagnosis of these malignancies. The OCCC and SCCOHT ovarian cancer subtypes are notoriously difficult to treat with chemotherapies based on platinum-drugs that are standard-of-care for most cases of ovarian cancer. Mutations in members of this chromatin-remodelling complex offer new opportunities for molecular therapeutics using drugs that inhibit different aspects of cellular processes, including DNA repair, epigenetic regulation, kinase activity, and immune checkpoints. SWI/SNF (SWItch/Sucrose Non-Fermentable) is the most frequently mutated chromatin-remodelling complex in human malignancy, with over 20% of tumours having a mutation in a SWI/SNF complex member. Mutations in specific SWI/SNF complex members are characteristic of rare chemoresistant ovarian cancer histopathological subtypes. Somatic mutations in ARID1A, encoding one of the mutually exclusive DNA-binding subunits of SWI/SNF, occur in 42–67% of ovarian clear cell carcinomas (OCCC). The concomitant somatic or germline mutation and epigenetic silencing of the mutually exclusive ATPase subunits SMARCA4 and SMARCA2, respectively, occurs in Small cell carcinoma of the ovary, hypercalcaemic type (SCCOHT), with SMARCA4 mutation reported in 69–100% of SCCOHT cases and SMARCA2 silencing seen 86–100% of the time. Somatic ARID1A mutations also occur in endometrioid ovarian cancer (EnOC), as well as in the chronic benign condition endometriosis, possibly as precursors to the development of the endometriosis-associated cancers OCCC and EnOC. Mutation of the ARID1A paralogue ARID1B can also occur in both OCCC and SCCOHT. Mutations in other SWI/SNF complex members, including SMARCA2, SMARCB1 and SMARCC1, occur rarely in either OCCC or SCCOHT. Abrogated SWI/SNF raises opportunities for pharmacological inhibition, including the use of DNA damage repair inhibitors, kinase and epigenetic inhibitors, as well as immune checkpoint blockade. [ABSTRACT FROM AUTHOR]

Lineage plasticity in small cell lung carcinoma (SCLC) causes therapeutic difficulties. This study aimed to investigate the pathological findings of plasticity in SCLC, focusing on combined SCLC, and elucidate the involvement of YAP1 and other transcription factors. We analysed 100 surgically resected SCLCs through detailed morphological observations and immunohistochemistry for YAP1 and other transcription factors. Component‐by‐component next‐generation sequencing (n = 15 pairs) and immunohistochemistry (n = 35 pairs) were performed on the combined SCLCs. Compared with pure SCLCs (n = 65), combined SCLCs (n = 35) showed a significantly larger size, higher expression of NEUROD1, and higher frequency of double‐positive transcription factors (p = 0.0009, 0.04, and 0.019, respectively). Notably, 34% of the combined SCLCs showed morphological mosaic patterns with unclear boundaries between the SCLC and its partner. Combined SCLCs not only had unique histotypes as partners but also represented different lineage plasticity within the partner. NEUROD1‐dominant combined SCLCs had a significantly higher proportion of adenocarcinomas as partners, whereas POU2F3‐dominant combined SCLCs had a significantly higher proportion of squamous cell carcinomas as partners (p = 0.006 and p = 0.0006, respectively). YAP1 expression in SCLC components was found in 80% of combined SCLCs and 62% of pure SCLCs, often showing mosaic‐like expression. Among the combined SCLCs with component‐specific analysis, the identical TP53 mutation was found in 10 pairs, and the identical Rb1 abnormality was found in 2 pairs. On immunohistochemistry, the same abnormal p53 pattern was found in 34 pairs, and Rb1 loss was found in 24 pairs. In conclusion, combined SCLC shows a variety of pathological plasticity. Although combined SCLC is more plastic than pure SCLC, pure SCLC is also a phenotypically plastic tumour. The morphological mosaic pattern and YAP1 mosaic‐like expression may represent ongoing lineage plasticity. This study also identified the relationship between transcription factors and partners in combined SCLC. Transcription factors may be involved in differentiating specific cell lineages beyond just 'neuroendocrine'. [ABSTRACT FROM AUTHOR]

Lung neuroendocrine neoplasms (NENs) are a diverse group of tumors characterized by neuroendocrine (NE) differentiation. Among lung NENs, lung carcinoid (LC) is a rare tumor with unique characteristics. Recent research has highlighted the importance of transcription factors (TFs) in establishing gene expression programs in lung NENs such as small cell lung carcinoma. However, the TFs that control the gene expression of LC are largely unknown. In this study, we report the expression and potential function of a TF called Prospero homeobox protein1 (PROX1) in LC. Publicly available transcriptome data suggested that PROX1 was highly expressed in LC tissues, which was confirmed by immunohistochemical analysis on a tissue microarray. Knockdown of PROX1 did not impact the cellular viability of an LC-derived cell line, NCI-H727. Meanwhile, transcriptome analysis revealed that PROX1 knockdown altered the expression of genes involved in NE differentiation. ASCL1, CHGA, CALCA, and LINC00261 were suggested as downstream genes of PROX1. These findings indicate that PROX1 may play an important role in the NE identity of LC by regulating the expression of key target genes. [ABSTRACT FROM AUTHOR]

The standard treatment for patients in good general condition with limited-disease small cell lung cancer (LD-SCLC) is concurrent platinum/etoposide chemotherapy and thoracic radiotherapy (TRT). However, the efficacy and safety of chemoradiotherapy (CRT) in older patients with LD-SCLC has not been fully explored; moreover, the optimal treatment for this patient group remains unclear. This study aimed to investigate the feasibility and efficacy of CRT in older patients with LD-SCLC. From April 2007 to June 2021, consecutive older patients (aged ≥ 75 years) with stage I to III SCLC who received concurrent or sequential CRT at two institutions were retrospectively evaluated for efficacy and toxicity of CRT. A total of 32 older patients underwent concurrent (n = 19) or sequential (n = 13) CRT for LD-SCLC. The median ages of the patients in the concurrent and sequential CRT groups were 77 (range: 75–81) years and 79 (range: 76–92) years, respectively. The median number of chemotherapeutic treatment cycles was four (range, 1–5), and the response rate was 96.9% in all patients (94.7% in concurrent and 100% in sequential CRT groups). The median progression-free survival (PFS) and median overall survival (OS) for all patients were 11.9 and 21.1 months, respectively. The median PFS was 13.0 and 9.0 months in the concurrent CRT and sequential CRT groups, respectively, with no statistically significant difference (p = 0.67). The median OS from the initiation of CRT was 19.2 and 23.5 months in the concurrent and sequential CRT groups, respectively (p = 0.46). The frequencies of Grade ≥ 3 hematological adverse events were as follows: decreased white blood cell count, 20/32 (62.5%); decreased neutrophil count, 23/32 (71.9%); anemia, 6/32 (18.8%); decreased platelet count, 7/32 (21.9%); and febrile neutropenia, 3/32 (9.4%). Treatment-related deaths occurred in one patient from each group. Although hematological toxicities, particularly reduced neutrophil count, were severe, CRT showed favorable efficacy in both concurrent and sequential CRT groups. However, concurrent CRT may not be feasible for all older patients with LD-SCLC; accordingly, sequential CRT may be considered as a treatment of choice for these patients. Further prospective trials are warranted to identify optimal treatment strategies for this patient group. [ABSTRACT FROM AUTHOR]

Introduction: Primary extrapulmonary small cell carcinoma (EPSCC) is a rare and aggressive tumor with diverse clinical manifestations. In the realm of head and neck pathology, EPSCC most commonly presents in the larynx or oral cavity. Sinonasal small cell neuroendocrine carcinoma represents a particularly infrequent and aggressive neoplasm affecting the nasal cavity and paranasal sinuses. Case Presentation: Here in, we are presenting a case of a 40-year-old nonsmoking male with left maxillary sinus EPSCC, demonstrating extensive local invasion and regional lymphadenopathy. The patient presented with nasal obstruction, ocular swelling, visual loss, and multiple neck swellings. Diagnosis was challenging, requiring a multidisciplinary approach and histopathological confirmation. Immunohistochemistry revealed positive cytokeratin AE1/AE3 and synaptophysin markers validating the diagnosis of small cell carcinoma. Conclusion: This case underscores the diagnostic complexities and highlights the importance of swift intervention and a multidisciplinary treatment approach for optimizing patient outcomes in rare and aggressive tumors like EPSCC. Early detection and prompt management are crucial in resource-limited settings to mitigate morbidity and mortality.

Abstract 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.

Background: Lung cancer is a leading public health concern worldwide. Previous evidence suggests that chronic obstructive pulmonary disease (COPD) and asthma may contribute to its development. However, whether these common chronic pulmonary diseases are causal factors of lung cancer remained unclear. Methods: Summary statistics from genome-wide association studies (GWAS) were used for Mendelian randomization (MR) analysis. Genetic data for COPD were obtained from the Global Biobank Meta-Analysis Initiative, and asthma data were retrieved from the UK Biobank cohort. Suitable instrumental variables were selected based on quality control measures. GWAS summary data for lung cancer were obtained from a large study involved 85,716 participants. MR analysis was performed using various methods, and sensitivity analyses were conducted. Multivariable MR (MVMR) analysis was employed to account for potential confounding factors. Results: Our MR analysis revealed a significant causal association between COPD and lung cancer, including its subtypes such as lung squamous cell carcinoma, lung adenocarcinoma, and small cell lung carcinoma. Genetically predicted COPD was associated with a 64% increased risk of lung cancer and a 2.3 to 2.8-fold increased risk of the different subtypes. However, in the MVMR analysis adjusting for smoking, alcohol drinking, and body mass index, the association between COPD and lung cancer became non-significant. No significant association was observed between asthma (childhood-onset and adult-onset) and lung cancer and its histological subtypes. Conclusions: Our study suggests a potential causal association between COPD and lung cancer. However, this association became non-significant after adjusting for smoking in the multivariable analysis. [ABSTRACT FROM AUTHOR]

Background: With a series of clinical trials confirming the sensitivity of small cell lung cancer (SCLC) to immunotherapy, research on personalized treatment for SCLC has gained increasing attention. Currently, the most widely accepted subtype of SCLC is based on the expression levels of Achaete-Scute Family BHLH Transcription Factor 1 (ASCL1), neurogenic differentiation factor 1 (NEUROD1), and POU class 2 homeobox 3 (POU2F3). However, real-world studies on this classification remain limited. Methods: We retrospectively collected biopsy specimens from patients who received immunotherapy at Shandong Provincial Hospital between January 2019 and July 2021. After determining the patient subtypes using immunohistochemistry, we analyzed the relationships between each subtype and survival as well as some clinical characteristics. Results: In our study, we found that the subtype I achieved a significant survival advantage compared to the other groups. Additionally, the subtype A demonstrated a significant survival disadvantage. Among patients in the subtype I, there was a higher proportion of early brain metastasis and patients with a family history of tumors, while the subtype A had a lower proportion. Furthermore, the subtype A exhibited relatively poor immune infiltration. Conclusion: In a diverse cohort of SCLC patients receiving immunotherapy, the subtype-I showed significant survival advantages while the subtype-A experienced a worse survival. [ABSTRACT FROM AUTHOR]

Background: According to long-term follow-up data of malignant tumor patients, assessing treatment effects requires careful consideration of competing risks. The commonly used cause-specific hazard ratio (CHR) and sub-distribution hazard ratio (SHR) are relative indicators and may present challenges in terms of proportional hazards assumption and clinical interpretation. Recently, the restricted mean time lost (RMTL) has been recommended as a supplementary measure for better clinical interpretation. Moreover, for observational study data in epidemiological and clinical settings, due to the influence of confounding factors, covariate adjustment is crucial for determining the causal effect of treatment. Methods: We construct an RMTL estimator after adjusting for covariates based on the inverse probability weighting method, and derive the variance to construct interval estimates based on the large sample properties. We use simulation studies to study the statistical performance of this estimator in various scenarios. In addition, we further consider the changes in treatment effects over time, constructing a dynamic RMTL difference curve and corresponding confidence bands for the curve. Results: The simulation results demonstrate that the adjusted RMTL estimator exhibits smaller biases compared with unadjusted RMTL and provides robust interval estimates in all scenarios. This method was applied to a real-world cervical cancer patient data, revealing improvements in the prognosis of patients with small cell carcinoma of the cervix. The results showed that the protective effect of surgery was significant only in the first 20 months, but the long-term effect was not obvious. Radiotherapy significantly improved patient outcomes during the follow-up period from 17 to 57 months, while radiotherapy combined with chemotherapy significantly improved patient outcomes throughout the entire period. Conclusions: We propose the approach that is easy to interpret and implement for assessing treatment effects in observational competing risk data. [ABSTRACT FROM AUTHOR]

Few effective treatments are available for small cell lung cancer (SCLC), indicating the need to explore new therapeutic options. Here, we focus on an antibody–drug conjugate (ADC) targeting the L1 cell adhesion molecule (L1CAM). Several publicly available databases reveal that (1) L1CAM is expressed at higher levels in SCLC cell lines and tissues than in those of lung adenocarcinoma and (2) the expression levels of L1CAM are slightly higher in SCLC tissues than in adjacent normal tissues. We conducted a series of in vitro experiments using an anti-L1CAM monoclonal antibody (termed HSL175, developed in-house) and the recombinant protein DT3C, which consists of diphtheria toxin lacking the receptor-binding domain but containing the C1, C2, and C3 domains of streptococcal protein G. Our HSL175-DT3C conjugates theoretically kill cells only when the conjugates are internalized by the target (L1CAM-positive) cells through antigen–antibody interaction. The conjugates (an ADC analog) were effective against two SCLC-N (NEUROD1 dominant) cell lines, Lu-135 and STC-1, resulting in decreased viability. In addition, L1CAM silencing rendered the two cell lines resistant to HSL175-DT3C conjugates. These findings suggest that an ADC consisting of a humanized monoclonal antibody based on HSL175 and a potent anticancer drug would be effective against SCLC-N cells. [ABSTRACT FROM AUTHOR]

Background: Usage of immune checkpoint inhibitors (ICIs) has prolonged the overall survival (OS) of patients with extensive‐stage small‐cell lung cancer (ES‐SCLC). In clinical trials, males accounted for a large proportion, leading to the uncertainty of its efficacy in female patients. We therefore conducted this study to explore the efficacy and safety of using ICIs in female patients with ES‐SCLC. Methods: We retrospectively enrolled female SCLC patients and subdivided them into two groups. Group A (n = 40) was defined as ES‐SCLC patients who received first‐line standard chemotherapy with or without ICIs. Group B (n = 47) included relapsed SCLC patients who were administered with second‐line therapies. Kaplan–Meier methodology was used to calculate survival analysis. Chi‐squared tests were used to analyze the incidence of adverse events (AEs). Results: Median progression‐free survival (PFS) and median OS favored the ICI‐contained cohorts (Group A PFS: 8.3 vs. 6.1 months; OS: not reached vs. 11.3 months; Group B PFS: 15.1 vs. 3.3 months; OS: 35.3 vs. 8.3 months), especially in those patients who received second‐line immunotherapies. Patients who received immunotherapy had a slightly higher incidence rate of grade ≥3 AEs (Group A: 71.4% vs. 46.2%; Group B: 44.5% vs. 13.2%). Those who developed grade ≥3 AEs in first‐line ICIs cohort had a more favorable survival (PFS: 8.3 vs. 3.2 months; OS: not reached vs. 5.1 months). Conclusions: Our study suggested that female ES‐SCLC patients treated with immunotherapy tended to achieve a relatively longer survival. The incidence of AEs (grade ≥3) was higher in women patients receiving ICIs, which requires monitoring more closely. [ABSTRACT FROM AUTHOR]

This article presents several cases of rare tumors and their clinical and pathological characteristics. The first case discusses a highly aggressive tumor called sinonasal teratocarcinosarcoma, which can be difficult to diagnose due to its morphological heterogeneity. The second case focuses on oncocytic lesions in the salivary glands, highlighting the challenges in distinguishing them from other conditions. The third case examines papillary thyroid carcinoma arising within a branchial cleft cyst, emphasizing the need for further investigation. The fourth case explores an unusual presentation of hepatocellular carcinoma as an intraoral mass. Additionally, the article discusses IgG4-related disease in the head and neck region, emphasizing the importance of accurate diagnosis based on histological features, radiology, and serum IgG4 levels. [Extracted from the article]

Human papillomavirus (HPV) is a major cause of cervical cancer. As the natural history of HPV‐associated cervical lesions is HPV genotype‐dependent, it is important to understand the characteristics of these genotypes and to manage them accordingly. Among high‐risk HPVs, HPV16 and 18 are particularly aggressive, together accounting for 70% of HPV genotypes detected in cervical cancer. Other than HPV16 and 18, HPV31, 33, 35, 45, 52, and 58 are also at a high risk of progression to cervical intraepithelial neoplasia (CIN)3 or higher. Recent studies have shown that the natural history of HPV16, 18, 52, and 58, which are frequently detected in Japan, depends on the HPV genotype. For example, HPV16 tends to progress in a stepwise fashion from CIN1 to CIN3, while HPV52 and 58 are more likely to persist in the CIN1 to CIN2 state. Among the high‐risk HPVs, HPV18 has some peculiar characteristics different from those of other high‐risk HPV types; the detection rate in precancerous lesions is much lower than those of other high‐risk HPVs, and it is frequently detected in highly malignant adenocarcinoma and small cell carcinoma. Recent findings demonstrate that HPV18 may be characterized by latent infection and carcinogenesis in stem cell‐like cells. In this context, this review outlines the natural history of HPV‐infected cervical lesions and the characteristics of each HPV genotype. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Context.--: Nuclear protein in testis (NUT) carcinoma is an aggressive carcinoma defined by NUTM1 gene rearrangement. Diagnostic challenges include morphologic overlap with poorly differentiated squamous cell carcinoma, small cell carcinoma, thoracic SMARCA4-deficient undifferentiated tumor, and other small round blue cell tumors. Objective.--: To comprehensively study the immunohistochemistry (IHC) features of a large cohort of NUT carcinomas. Design.--: Fifty-seven NUT carcinoma cases were identified from 2012-2022, including 38 thoracic/mediastinal, 13 head and neck/sinonasal, and 6 from other sites. Pathology reports and available slides were reviewed. Comprehensive IHC studies were performed on available cases. Results.--: Keratin stains showed variable positivity and were entirely negative in 15% (8 of 55) of cases. p40 was only positive in 65% (24 of 37) of cases, implying inferior sensitivity when compared to p63 (87% sensitivity, 20 of 23 cases) and other squamous cell markers. Neuroendocrine markers were focally/weakly positive in few cases; however, INSM1 was positive in 54% (7 of 13) of cases, indicating a possible diagnostic pitfall. TTF-1 was mostly negative with focal positivity in 26% (10 of 38) of cases. Occasional CD34 (15%, 3 of 20 cases) and CD99 (21%, 3 of 14 cases) positivity could also cause potential diagnostic confusion. S100, desmin, CD45, and SALL4 were rarely positive. BRG1 and INI1 were retained in all cases. Ki-67 proliferative index was high (median, 60%). PD-L1 was negative in all tested cases. Conclusions.--: This comprehensive IHC study demonstrates the immunohistochemical spectrum of NUT carcinoma. The findings can help narrow the differential diagnosis and recognize potential pitfalls. [ABSTRACT FROM AUTHOR]

A study published in Clinical & Translational Medicine suggests that the antiviral drug oseltamivir (Tamiflu) may have potential as a treatment for hearing loss. The researchers found that oseltamivir protected against hair cell loss in mouse cochlear explants caused by the chemotherapy drug cisplatin, without affecting cisplatin's ability to kill tumors. In mouse models, oseltamivir also protected against cisplatin-induced hearing loss and outer hair cell loss. Furthermore, oral oseltamivir therapy showed promise in protecting against noise-induced hearing loss. The study suggests that oseltamivir could be a promising candidate for treating hearing loss caused by chemotherapy and noise exposure. [Extracted from the article]

Purpose (i) To analyze age-adjusted incidence rates of synchronous bone metastases diagnosed alongside primary malignancy from 2010 to 2018 in the US population, (ii) determine the incidence proportions (IPs) and characteristics of synchronous bone metastases among newly diagnosed cancer patients in the USA especially pediatric cases, and (iii) assess the implications of synchronous bone metastases on cancer patient's survival, and identify the survival risk factors for these cancer patients. Methods Utilizing data from the Surveillance, Epidemiology, and End Results (SEER) program (2010–2018), we calculated age-adjusted IPs and annual percentage change (APC), and employed logistic regression and Cox regression models for our analysis. Results 3 300 736 cancer patients were identified. The age-adjusted incidence rates of synchronous bone metastases increased from 2010 (18.04/100 000) to 2018 (20.89/100 000; APC: 2.3, 95% confidence interval [CI], 1.4–3.1), but decreased in lung cancer (average APC: –1.0, 95% CI, −1.8 to −0.3). The highest IPs were observed in pediatric neuroblastoma (43.2%; 95% CI, 39.8%–46.7%) and adult small cell carcinoma (23.1%; 95% CI, 22.7%–23.4%). Multivariate logistic analyses revealed that primary tumor characteristics were correlated with higher bone metastases risk. Survival analyses also showed varied prognostic outcomes based on metastasis sites and demographics among cancer patients. Landmark analyses further indicated among long-term cancer survivors (≥3 and ≥5 years), patients with de novo bone metastases had the poorest survival rates compared with those with other synchronous metastases (P  < 0.001). Conclusion This study provides a population-based estimation of the incidence and prognosis for synchronous bone metastases. Our findings highlight the need for early identification of high-risk groups and multidisciplinary approaches to improve prognosis of cancer patients with de novo bone metastases. What is already known on this topic: The incidence of de novo bone metastases between 2010 and 2015 that SEER database documented was average 18.8 per 100 000 per year. In adult patients, the most frequent sites for de novo metastases are the lungs, prostate, and breast. The cancer patients with synchronous bone metastases are likely to have a modest reduction in survival. What this study adds: The age-adjusted incidence rates of synchronous bone metastasis steadily rose from 18.04 per 100 000 in 2010 to 20.89 per 100 000 in 2018. Pediatric patients had higher incidence proportions of synchronous bone metastases compared to adult patients, among pediatric patients specifically, those diagnosed with neuroblastoma had the highest risk of synchronous bone metastases. In the short term, cancer patients with synchronous brain metastases had the poorest survival rates. However, among long-term cancer survivors, those with synchronous bone metastases had the worst prognosis. How this study might affect research, practice, or policy: Pediatric clinicians need to be acutely aware of the significant possibility of simultaneous development of bone metastases and neuroblastoma in pediatric patients. For long-term survivors, Clinicians should prioritize the care of them with synchronous bone metastases over those with metastases from other sites. For cancer patients with synchronous bone metastases, we advocate for surgery of the primary cancer sites to improve prognosis. Remained research questions: How does the differential utilization of bone scans across different tumors affect the accuracy of detecting synchronous bone metastases in cancer patients? What is the impact of bone metastases on patients' physical status, comorbidities, performance status, and quality of life? How do radiotherapy, chemotherapy, and surgical treatments for sites of bone metastases affect the prognosis of cancer patients with synchronous bone metastases? [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purkinje cell cytoplasmic antibody type 2 (PCA-2), identified in 2000, targets the widely distributed microtubule-associated protein 1B in the central and peripheral nervous systems, leading to diverse clinical phenotypes of neurological disorders. We report two cases of PCA-2-associated encephalitis, each presenting with distinct onset forms and clinical manifestations, thereby illustrating the phenotypic variability of PCA-2- related diseases. The first patient was diagnosed with PCA-2-associated autoimmune cerebellitis and undifferentiated small cell carcinoma with metastasis in mediastinal lymph nodes of unknown primary origin. The second patient was diagnosed with PCA-2-associated limbic encephalitis. Our findings underscore the superior sensitivity of positron emission tomography-computed tomography over brain magnetic resonance imaging in the early detection of PCA-2-associated encephalitis. Given the high risk of relapse and suboptimal response to traditional immunotherapy in PCA-2-related neurological disorders, this study highlights the need for a deeper understanding of their pathogenesis to develop more effective treatments to control symptoms and improve patient prognosis. [ABSTRACT FROM AUTHOR]

Background: Systemic inflammation is believed to contribute to small cell lung cancer (SCLC) progression, but the underlying relationship remains unclear. Lipocalin‐2, a potential biomarker of inflammation, has been implicated in various cancers but its prognostic value in SCLC is underexplored. Methods: We retrospectively analyzed 191 patients with SCLC (72 with limited‐stage [LD] and 119 with extensive‐stage) treated using platinum‐based chemotherapy. Lipocalin‐2 expression was evaluated using immunohistochemistry. Optimal cutoff values for lipocalin‐2 and neutrophil‐to‐lymphocyte ratio (NLR) were determined using time‐dependent receiver operating characteristic curve analysis. The pectoralis muscle index was used to assess sarcopenia. Results: In LD‐SCLC, high lipocalin‐2 expression was associated with worse progression‐free survival (PFS; median: 7.0 vs. 15.9 months, p = 0.015) and overall survival (OS; median: 12.9 vs. 30.3 months, p = 0.035) compared with low lipocalin‐2 expression. Patients were stratified into three prognostic groups by combining lipocalin‐2 with NLR: low lipocalin‐2/low NLR, high lipocalin‐2/low NLR or low lipocalin‐2/high NLR, and high lipocalin‐2/high NLR (median PFS: 17.3 vs. 11.0 vs. 6.3 months, p = 0.004; median OS: 30.5 vs. 17.3 vs. 8.6 months, p = 0.002). Similar trends were observed when combining lipocalin‐2 with the pectoralis muscle index. High lipocalin‐2 expression was also associated with lower complete response rates (18.9% vs. 34.3%, p = 0.035). No significant prognostic implications were found for lipocalin‐2 in extensive‐stage SCLC. Conclusions: High lipocalin‐2 expression is potentially associated with poorer survival in LD‐SCLC. Combining lipocalin‐2 with other inflammation‐related markers could improve prognostic stratification. [ABSTRACT FROM AUTHOR]

Although small cell neuroendocrine carcinoma of the ureter (ureteral SCNEC) is rare, it always leads to a poor prognosis. Also, no treatment recommendation has been given for ureteral SCNEC, with only PD-1/PD-L1 inhibitors being used for its treatment. Here, we report a case of atypical symptoms of cardiac infarction caused by a PD-1 inhibitor used in the treatment of ureteral SCNEC and hope to address concerns regarding the possible cardiac toxicity caused by PD-1/PD-L1 inhibitors in ureteral SCNEC patients. [ABSTRACT FROM AUTHOR]

INTRODUCTION: Paraneoplastic Neurological Syndromes (PNS) represent a heterogeneous group of diseases associated with the presence of neoplasm. The appearance of PNS can precede cancer diagnosis. The estimated frequency amongst cancer patients is about 1%. Malignant tumors represent a serious health problem and are the second leading cause of death in Poland. The aim of this study is to collect information about PNS focusing on cancers mostly diagnosed in Polish adults. REVIEW METHODS: The analysis was conducted based on information regarding PNS gathered from PubMed and Google Scholar within the context of selected cancers. THE STATE OF KNOWLEDGE: PNS develop from an autoimmune reaction in which onconeural antibodies are produced. The recent classification divides PNS to high risk, indicating a likely paraneoplastic origin and intermediate risk, if this association is less evident. Diagnosis is difficult and usually relies on exclusion methods. The symptoms described are non-specific and the diagnostic process may require the involvement of various specialists. The main approaches include cancer treatment, especially tumor removal and immunotherapy, which in certain may prove to be effective. SUMMARY: Although PNS is relatively rare, its detectability has recently increased. Many syndromes are especially associated with lung cancer (mainly small cell carcinoma). Breast and prostate cancers have also shown associations with certain syndromes. They can present with nonspecific symptoms related to different organ systems. Awareness and understanding of this phenomenon can be helpful amongst many specialists. [ABSTRACT FROM AUTHOR]

Background: Former research has emphasized a correlation between lung cancer (LC) and sepsis, but the causative link remains unclear. Method: This study used univariate Mendelian Randomization (MR) to explore the causal relationship between LC, its subtypes, and sepsis. Linkage Disequilibrium Score (LDSC) regression was used to calculate genetic correlations. Multivariate MR was applied to investigate the role of seven confounding factors. The primary method utilized was inverse-variance-weighted (IVW), supplemented by sensitivity analyses to assess directionality, heterogeneity, and result robustness. Results: LDSC analysis revealed a significant genetic correlation between LC and sepsis (genetic correlation = 0.325, p = 0.014). Following false discovery rate (FDR) correction, strong evidence suggested that genetically predicted LC (OR = 1.172, 95% CI 1.083-1.269, p = 8.29 × 10-5, Pfdr = 2.49 × 10-4), squamous cell lung carcinoma (OR = 1.098, 95% CI 1.021-1.181, p = 0.012, Pfdr = 0.012), and lung adenocarcinoma (OR = 1.098, 95% CI 1.024-1.178, p = 0.009, Pfdr = 0.012) are linked to an increased incidence of sepsis. Suggestive evidence was also found for small cell lung carcinoma (Wald ratio: OR = 1.156, 95% CI 1.047-1.277, p = 0.004) in relation to sepsis. The multivariate MR suggested that the partial impact of all LC subtypes on sepsis might be mediated through body mass index. Reverse analysis did not find a causal relationship (p > 0.05 and Pfdr > 0.05). Conclusion: The study suggests a causative link between LC and increased sepsis risk, underscoring the need for integrated sepsis management in LC patients. [ABSTRACT FROM AUTHOR]

Introduction: Febrile neutropenia (FN) is an oncologic emergency requiring immediate empiric antibiotic therapy. Although carboplatin plus etoposide combination chemotherapy is associated with a relatively high frequency of FN, the risk factors are unclear. Hence, this retrospective study aimed to identify predictive markers of carboplatin/etoposide-induced FN. Methods: We conducted a retrospective cohort analysis of patients with previously untreated small-cell lung cancer (SCLC) who received combination chemotherapy with carboplatin (area under the concentration curve: 5 mg/mL·min, day 1) and etoposide (80 or 100 mg/m2, days 1–3) between July 2007 and June 2022. FN was assessed during the 21 days after initiation of carboplatin and etoposide therapy according to the Japanese Society of Medical Oncology's definition. Fisher's exact test for categorical variables and Mann-Whitney U test for continuous variables were used to compare the two groups. Statistical significance was set at p values <0.05. Explanatory variables with p values <0.05 in the univariate analysis were included in the multivariate logistic regression analysis. Results: Among the 176 eligible patients, the incidence of FN during the first cycle of chemotherapy was 25.0% (44/176). Multivariate analysis revealed that co-administration of proton pump inhibitors (PPIs) or potassium-competitive acid blockers (PCABs) and body mass index (BMI) were significantly associated with FN (p = 0.0035 and 0.0011, respectively). Patients with both co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 presented with significantly higher frequencies of FN compared with the other patients (13/24 [54.2%] vs. 31/152 [20.4%] patients; odds ratio: 4.56, 95% confidence interval: 1.70–12.48; p = 0.00147). Conclusion: Patients who received carboplatin plus etoposide for SCLC with co-administration of PPIs or PCABs and a BMI ≤22.509 kg/m2 more frequently present with FN than those without the two factors. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Objective: In this study, we collected data over 8 years (2012-2019) from the Japan Society of Obstetrics and Gynecology (JSOG) tumor registry to determine the status of endometrial cancer in Japan, and analyzed detailed clinicopathological factors. Methods: The JSOG maintains a tumor registry that gathers information on endometrial cancer treated at the JSOG-registered institutions. Data from the patients whose endometrial cancer treatment was initiated from 2012 to 2019 were analyzed retrospectively. Results: A total of 82,969 patients with endometrial cancer underwent treatment from 2012 to 2019. Chemotherapy alone or in combination with hormonal therapy is more common among endometrial cancer patients under 40 years compared with those over 40 years. The number of patients with endometrial cancer, treated with laparoscopic or robot-assisted surgery was observed to have increased yearly. Small cell carcinomas and undifferentiated carcinomas were more likely to be diagnosed at an advanced stage. Lymphadenectomy was most commonly performed for stage IIIC2 disease, whereas positive peritoneal washing cytology was most common for stage IVB and serous carcinoma. Conclusion: Multi-year summary reports provided detailed clinicopathological information regarding endometrial cancer that could not be obtained in a single year. These reports were useful in understanding treatment strategies and trends over time based on age, histology, and stage. [ABSTRACT FROM AUTHOR]

Few efficacious treatment options are available for patients with small cell lung carcinoma (SCLC), indicating the need to develop novel therapeutic approaches. In this study, we explored kinesin family member 11 (KIF11), a potential therapeutic target in SCLC. An analysis of publicly available data suggested that KIF11 mRNA expression levels are significantly higher in SCLC tissues than in normal lung tissues. When KIF11 was targeted by RNA interference or a small-molecule inhibitor (SB743921) in two SCLC cell lines, Lu-135 and NCI-H69, cell cycle progression was arrested at the G2/M phase with complete growth suppression. Further work suggested that the two cell lines were more significantly affected when both KIF11 and BCL2L1, an anti-apoptotic BCL2 family member, were inhibited. This dual inhibition resulted in markedly decreased cell viability. These findings collectively indicate that SCLC cells are critically dependent on KIF11 activity for survival and/or proliferation, as well as that KIF11 inhibition could be a new strategy for SCLC treatment. [ABSTRACT FROM AUTHOR]

Background and Aims: Lurbinectedin is a novel oncogenic transcription inhibitor active in several cancers, including small cell lung cancer (SCLC). We aimed to describe the first Australian experience of the clinical efficacy and tolerability of lurbinectedin for the treatment of SCLC after progression on platinum‐containing therapy. Methods: Multicentre real‐world study of individuals with SCLC initiating lurbinectedin monotherapy (3.2 mg/m2 three‐weekly) on an early access programme between May 2020 and December 2021. Key outcomes were clinical utilisation, efficacy and tolerability. Progression‐free survival (PFS) and overall survival (OS) were calculated using the Kaplan–Meier method. Outcome data were collected within the AUstralian Registry and biObank of thoRacic cAncers (AURORA). Results: Data were analysed for 46 individuals across seven sites. Lurbinectedin was given as second‐ (83%, 38/46) or subsequent‐ (17%, 8/46) line therapy, mostly with prior chemoimmunotherapy (87%, 40/46). We report dose modifications (17%, 8/46), interruptions/delays (24%, 11/46), high‐grade toxicities (28%, 13/46) and hospitalisations (54%, 25/46) during active treatment. The overall response rate was 33% and the disease control rate was 50%. Six‐month OS was 44% (95% confidence interval (CI): 29.0–57.1). Twelve‐month OS was 15% (95% CI: 6.5–26.8). From lurbinectedin first dose, the median PFS was 2.5 months (95% CI: 1.8–2.9) and OS was 4.5 months (95% CI: 3.5–7.2). From SCLC diagnosis, the median OS was 12.9 months (95% CI: 11.0–17.2). Individuals with a longer chemotherapy‐free interval prior to lurbinectedin had longer PFS and OS. Conclusion: This real‐world national experience of lurbinectedin post‐platinum chemotherapy and immunotherapy for individuals with SCLC was similar to that reported in clinical trials. [ABSTRACT FROM AUTHOR]

Background/Aims: There are currently few reports describing the liquid-based cytological characteristics of small cell neuroendocrine carcinoma of the cervix. This study aimed to retrospectively analyze these features to reduce missed or misdiagnosis. Methods: A total of 11 patients with histologically diagnosed small cell carcinoma of the cervix from three hospitals between 2017 and 2023 were included in this study. The cytological morphology of small cell carcinoma of the cervix and causes of missed or misdiagnosis were analyzed and summarized through a review of clinical data, liquid-based cytology, histology, immunohistochemistry, and human papillomaviruses (HPV) test results. Results: In this study, the positivity rate of preliminary cytological screening was 63.6% (7/11); however, no cases were accurately diagnosed as small cell carcinoma of the cervix. A total of 36.4% (4/11) of small cell carcinoma of the cervix cases were cytologically negative; retrospective cytology found that two of these were false negatives. The main cytological features of small cell carcinoma of the cervix were summarized. Most of the liquid-based cytology smear cells were dense, and almost all cases showed clustered and scattered cytoplasm-scanty tumor cells. The tumor cells were all deeply stained and relatively consistent small cells. Most cases showed typical nuclear molding, chromatin stippling, and no obvious nucleoli. Mild nuclear smears, nuclear fragments, and mitotic figures were seen in most cases. Conclusion: Liquid-based cytology has a high rate of missed diagnosis and misdiagnosis in small cell carcinoma of the cervix. This study confirms that reviewing cytology results can effectively reduce this proportion and that increasing understanding of small cell carcinoma of the cervix morphology is conducive to improving the cytology-based diagnosis rate. [ABSTRACT FROM AUTHOR]

This document provides information on the diagnosis and characteristics of NUT carcinoma, a rare and aggressive form of cancer. It emphasizes the importance of accurate diagnosis through immunohistochemistry and molecular testing, as well as the potential diagnostic pitfalls and differential diagnoses. The document also mentions ongoing clinical trials investigating the efficacy of BET protein inhibitors in treating NUT carcinoma. It concludes by highlighting the challenges in diagnosing NUT carcinoma and the need for caution in interpreting cytology specimens. [Extracted from the article]

Background: Growing evidence has shown that atopic dermatitis (AD) may decrease lung cancer (LC) risk. However, the causality between the two diseases is inconsistent and controversial. Therefore, we explored the causal relationship between AD and different histological subtypes of LC by using the Mendelian randomization (MR) method. Materials and methods: We conducted the MR study based on summary statistics from the genome‐wide association studies (GWAS) of AD (10,788 cases and 30,047 controls) and LC (29,266 cases and 56,450 controls). Instrumental variables (IVs) were obtained after removing SNPs associated with potential confounders. We employed inverse‐variance weighted (IVW), MR‐Egger, and weighted median methods to pool estimates, and performed a comprehensive sensitivity analysis. Results: The results of the IVW method suggested that AD may decrease the risk of developing lung adenocarcinoma (LUAD) (OR = 0.91, 95% CI: 0.85‐0.97, P = 0.007). Moreover, no causality was identified between AD and overall LC (OR = 0.96, 95% CI: 0.91–1.01, P = 0.101), lung squamous cell carcinoma (LUSC) (OR = 1.04, 95% CI: 0.96–1.036, P = 0.324), and small cell lung carcinoma (SCLC) (OR = 0.95, 95% CI: 0.82–1.10, P = 0.512). A comprehensive sensitivity test showed the robustness of our results. Conclusion: The present study indicates that AD may decrease the risk of LUAD in the European population, which needs additional investigations to identify the potential molecular mechanisms. [ABSTRACT FROM AUTHOR]

Background: Previous studies have highlighted the crucial role of immune cells in lung cancer development; however, the direct link between immunophenotypes and lung cancer remains underexplored. Methods: We applied two-sample Mendelian randomization (MR) analysis, using genetic variants as instruments to determine the causal influence of exposures on outcomes. This method, unlike traditional randomized controlled trials (RCTs), leverages genetic variants inherited randomly at conception, thus reducing confounding and preventing reverse causation. Our analysis involved three genome-wide association studies to assess the causal impact of 731 immune cell signatures on lung cancer using genetic instrumental variables (IVs). We initially used the standard inverse variance weighted (IVW) method and further validated our findings with three supplementary MR techniques (MR-- Egger, weighted median, and MR-PRESSO) to ensure robustness. We also conducted MR--Egger intercept and Cochran's Q tests to assess heterogeneity and pleiotropy. Additionally, reverse MR analysis was performed to explore potential causality between lung cancer subtypes and ident ified immunophenotypes, using R software for all statistical calculations. Results: Our MR analysis identified 106 immune signatures significantly associated with lung cancer. Notably, we found five suggestive associations across all sensitivity tests (P<0.05): CD25 on IgD- CD24- cells in small cell lung carcinoma (ORIVW =0.885; 95% CI: 0.798--0.983; PIVW =0.022); CD27 on IgD+ CD24+ cells in lung squamous cell carcinoma (ORIVW =1.054; 95% CI: 1.010-- 1.100; PIVW =0.015); CCR2 on monocyte cells in lung squamous cell carcinoma (ORIVW =0.941; 95% CI: 0.898--0.987; PIVW =0.012); CD123 on CD62L+ plasmacytoid dendritic cells (ORIVW =0.958; 95% CI: 0.924--0.992; PIVW =0.017) as well as on plasmacytoid dendritic cells (ORIVW =0.958; 95% CI: 0.924--0.992; PIVW =0.017) in lung squamous cell carcinoma. Conclusion: This study establishes a significant genomic link between immune cells and lung cancer, providing a robust basis for future clinical research aimed at lung cancer management. [ABSTRACT FROM AUTHOR]