An autopsy case of lung adenocarcinoma with immune checkpoint inhibitor-induced pneumonia and fulminant myocarditis following pembrolizumab administration: a case report.

Immune checkpoint inhibitors (ICIs) are the current standard of care for non-small-cell lung cancer (NSCLC). Myocarditis is a rare but serious immune-related adverse event (irAE) associated with ICI therapy. We present a patient who received a single dose of pembrolizumab for NSCLC and developed ICI-associated pneumonia. Although pneumonia improved with corticosteroid therapy, the patient subsequently developed ICI-associated fulminant myocarditis. Despite high-dose corticosteroid therapy, the patient died on day 30 after pembrolizumab initiation. Even if an observed irAE was effectively treated, clinicians should remain vigilant for other irAEs, especially those that are difficult to control with low-dose corticosteroids.

Neoadjuvant chemoimmunotherapy for small cell carcinoma of the esophagus: Clinical efficacy and biomarker exploration.

Small cell carcinoma of the esophagus (SCCE) is a rare and highly malignant type of esophageal cancer with no standard treatment, facing challenges of resistance to conventional therapies. This study presents the cases of one extensive-stage and two limited-stage SCCE patients treated with chemoimmunotherapy. The two limited-stage patients underwent surgery post-treatment and experienced notable and enduring positive responses. This represents the first documented application of neoadjuvant chemoimmunotherapy in limited-stage SCCE patients. Additionally, comprehensive immunohistochemical analysis and whole exome sequencing were performed on the case patients. The findings revealed that infiltration of CD8+ T cells and PD-L1 expression in the SCCE tumor were key factors for favorable responses in SCCE patients receiving chemoimmunotherapy.

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

Small cell carcinomas (SMC) of the lung are now molecularly classified based on the expression of transcriptional regulators (NEUROD1, ASCL1, POU2F3, YAP1) and DLL3, which has emerged as an investigational therapeutic target. PLCG2 has been shown to identify a distinct subpopulation of lung SMC with stem cell-like and pro-metastasis features and poor prognosis. We analyzed the expression of these novel neuroendocrine markers and their association with traditional neuroendocrine markers and patient outcomes in a cohort of bladder neuroendocrine carcinoma (NEC) consisting of 103 SMC and 19 large cell neuroendocrine carcinomas (LCNEC) assembled in tissue microarrays. Co-expression patterns were assessed and integrated with detailed clinical annotation including overall (OS) and recurrence free survival (RFS) and response to neoadjuvant/adjuvant chemotherapy. We identified five distinct molecular subtypes in bladder SMC based on expression of ASCL1, NEUROD1 and POU2F3: ASCL1+/NEUROD1- (n=33; 34%), ASCL1-/NEUROD1+ (n=21; 21%), ASCL1+/NEUROD1+ (n=17; 17%), POU2F3+ (n=22, 22%), and ASCL1-/NEUROD1-/POU2F3- (n=5, 5%). POU2F3+ tumors were mutually exclusive with those expressing ASCL1 and NEUROD1 and exhibited lower expression of traditional neuroendocrine markers. PLCG2 expression was noted in 33 tumors (32%) and was highly correlated with POU2F3 expression (p < 0.001). DLL3 expression was high in both SMC (n=72, 82%) and LCNEC (n=11, 85%). YAP1 expression was enriched in non- neuroendocrine components and negatively correlated with all neuroendocrine markers. In patients without metastatic disease who underwent radical cystectomy, PLCG2+ or POU2F3+ tumors had shorter RFS and OS (p<0.05), but their expression was not associated with metastasis status or response to neoadjuvant/adjuvant chemotherapy. In conclusion, NEC of the bladder can be divided into distinct molecular subtypes based on the expression of ASCL1, NEUROD1 and POU2F3. POU2F3 expressing tumors represent an ASCL1/NEUROD1-negative subset of bladder NEC characterized by lower expression of traditional neuroendocrine markers. Marker expression patterns were similar in SMC and LCNEC. Expression of PLCG2 and POU2F3 was associated with shorter recurrence-free and overall survival. DLL3 was expressed at high levels in both SMC and LCNEC of the bladder, nominating it as a potential therapeutic target.

Small Cell Carcinoma Prostate: A Case Report with Findings on 18-F FDG PET/CT.

Small-cell carcinoma of the prostate (SCCP) is a rare and very aggressive malignancy with neuroendocrine differentiation. In contrast to conventional prostate adenocarcinoma, SCCP is an aggressive carcinoma and portends to have a poor prognosis. Around 50% of these patients have metastatic disease at the first clinical presentation. We report the findings of 18-F fluorodeoxyglucose positron emission tomography/computed tomography in a case of histologically proven SCCP with an unusual finding of the left internal mammary lymph node.

Gastrointestinal stromal tumor with small cell carcinoma infiltration: a case report.

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the digestive system. They usually occur in the gastrointestinal tract. However, we discovered a rare phenomenon in which small cell carcinoma infiltrated the GIST of a patient. The patient came to the hospital and presented with chest tightness and shortness of breath for 2 months and a dry cough for half a month. As the ancillary tests were refined, it was discovered that he also had a lesion in the pelvic cavity. After pathological examination of the core needle biopsy (CNB) samples from the pelvic cavity lesion, the patient was diagnosed with GIST with small cell carcinoma infiltration. The patient is currently receiving a chemotherapy regimen of etoposide combined with cisplatin.

Multiple Somatic Mutations of SMARCA4 in Small Cell Carcinoma of the Ovary, Hypercalcemic Type: A Case Report.

Small-cell carcinoma of the ovary, the hypercalcemic type (SCCOHT) is a rare, aggressive tumor that primarily affects young females. It is a monogenic disorder caused by germline and/or somatic SWI/SNF-related, matrix-associated, actin-dependent regulator of chromatin, subfamily a, member 4 (SMARCA4) mutations. Here, we report a case of SCCOHT harboring multiple previously unreported somatic mutations in SMARCA4 (c.2866_2867delC>T; c.3543del). A 28-year-old breastfeeding Japanese female presented to a previous hospital with nausea and vomiting. She had no family history of relevant malignancies, including ovarian cancer. Based on an evaluation performed at another institution, she was referred to a gynecologist for suspected ovarian cancer. Imaging studies revealed a 16×15 cm heterogenous enhancing mass within the right ovary without lymph node or distant metastasis. She had mild ascites without peritoneal dissemination, but there was an elevation in the serum calcium level (15.1 mg/dL). The patient underwent cytoreductive surgery and was pathologically diagnosed with SCCOHT. Auxiliary immunohistochemical staining confirmed the loss of SMARCA4 protein expression. The patient was diagnosed with the International Federation of Gynecology and Obstetrics (FIGO) 2014 stage IA (pT1a pN0 M0). The serum calcium levels returned to normal post-surgery. Matched-pair analysis using tumor tissue and peripheral blood revealed multiple somatic mutations in SMARCA4, but no deleterious germline mutations were present. Microsatellite instability was not significant, and the patients had a heterozygous mutation of uridine diphosphate glucuronosyl transferase 1A1 (UGT1A1)*6. She underwent six cycles of irinotecan hydrochloride plus cisplatin chemotherapy and achieved complete remission. The patient was finally examined and evaluated 45 months postoperatively; there was no evidence of the disease. Overall, the genetic findings will not aid in the SCCOHT diagnosis and relevant genetic counseling; however, they may have implications for the treatment of this disease in the future.

The Localized Neuroendocrine Transformation of Prostate Adenocarcinoma: A Case Report and Literature Review of Current Treatment Modalities.

Most prostate cancers are adenocarcinomas. However, there is a rare and aggressive subtype known as small cell carcinoma of the prostate (SCCP). This variant of prostate cancer is marked by its distinctive features, including high-grade malignancy, neuroendocrine differentiation, and a unique clinical presentation, often involving metastases. This report details the presentation and management of a 66-year-old African-American male who was originally diagnosed with high-risk adenocarcinoma of the prostate. At initial diagnosis, the patient was suboptimally treated with radiation alone without androgen deprivation therapy (ADT). On re-biopsy several years later, he was found to have localized recurrent disease with transformation into SCCP. The prognosis for SCCP is poor with a mean survival. Patients typically present with metastases, commonly to the brain, liver, bones, or bladder. SCCP after treatment for adenocarcinoma of the prostate is more common than de novo presentation. The amount of neuroendocrine differentiation of SCCP often increases with treatment, particularly after treatment with ADT. This report emphasizes the importance of timely and optimal care when treating prostate cancer and suggests potential consequences that inappropriate treatment or treatment delays may entail.

Oropharyngeal Mixed Neuroendocrine-Nonneuroendocrine Neoplasm (MiNEN): A Case Report and Literature Review.

Mixed neuroendocrine-nonneuroendocrine (MiNEN) neoplasms in the head and neck are exceptionally rare biphasic tumors with unclear pathogenesis and an aggressive clinical behavior. This is the first reported case of an oropharyngeal MiNEN with the nonneuroendocrine component being an HPV-associated adenocarcinoma. The tumor arose in a 56 year-old male with history of long-term cigarette smoking and was composed of an adenocarcinoma intermixed with a small cell neuroendocrine carcinoma. P16 immunohistochemical stain and HPV16/18 in-situ hybridization were strongly and diffusely expressed in both components.

Surgery and Stereotactic Radiotherapy for Stage I Small-Cell Lung Carcinoma: A 25-Year Experience.

OBJECTIVES: Small-cell lung carcinoma (SCLC) is usually a wide-spread, highly-lethal malignancy but occasionally presents as localized, limited stage cancer amenable to local treatment. We reviewed our experience using surgery or stereotactic body radiotherapy (SBRT) to assess safety, survival rates and treatment toxicity in clinical stage I SCLC patients. MATERIALS AND METHODS: Electronic medical records of patients with clinical stage I lymph node-negative SCLC who underwent surgical resection or SBRT between 1996 and 2021 were retrospectively reviewed. A multivariable Cox Proportional Hazards model was constructed. RESULTS: Of 96 patients meeting inclusion criteria, 77 underwent resection and 19 underwent SBRT. Surgical patients were younger (mean 68.4 ± 9.2 years surgery versus 74.3 ± 6.6 years SBRT, P = .005) and had better pulmonary function (81.5 ± 19.6 FEV1% of predicted surgery versus 44.0 ± 20.9% SBRT, P < .001). SBRT patients had significantly more comorbidities. For both cohorts, 59 tumors were pure SCLC and 37 were mixed SCLC/NSCLC histology. Median survivals were 21 months versus 31 months for SBRT and surgery patients respectively (P = .07). There were no treatment-related mortalities. Mean length of hospital stay for surgical patients was 5.4 ± 5.7 days. Survival was longer in lymph node-negative surgery patients (median 48 months node-negative versus 19 months node-positive, P = .04). For node-negative-surgery patients, the estimated 2- and 5-year survival rates are 60% and 48%. CONCLUSIONS: Our single-institutional experience over 25 years demonstrates that local treatment with surgery or SBRT for clinical stage I SCLC is safe and effective, with survivals lower than similar stage non-small-cell carcinoma patients. However, our results compare favorably with prior small-cell surgical series and far better than reported results of chemoradiotherapy for similar stage patients, thereby validating current recommendations for employing surgery or SBRT for stage I SCLC.

Association between waterpipe smoking and lung cancer: a multicentre case-control study in Iran.

OBJECTIVES: This study investigated the association between lung cancer and waterpipe smoking, which is an emerging global public health concern. STUDY DESIGN: Multicentre case-control study. METHODS: This study included 627 cases and 3477 controls from the Iranian Study of Opium and Cancer (IROPICAN) study, which was conducted between 2017 and 2020. One frequency-matched control for each lung cancer patient was selected by age, gender and residential place; however, this study used controls of four cancer types in the analyses. The multivariable logistic regression model estimated the odds ratio (OR) and 95% confidence intervals (CIs). Additional analyses were performed among 181 lung cancer cases and 2141 controls who were not cigarette smokers or opium or nass/pipe users. RESULTS: The odds of lung cancer were higher among waterpipe smokers than never-smokers (OR = 1.3, 95% CI: 1.0-1.7). Results showed a higher OR of lung cancer for those who smoked the waterpipe daily (OR = 2.1, 95% CI: 1.4-3.0), smoked more than two heads per day (OR = 2.7, 95% CI: 1.8-4.0), had smoked for >20 years (OR = 1.9, 95% CI: 1.3-2.7), smoked more than 20 head-years (OR = 2.8, 95% CI: 1.9-4.1) and initiated smoking before the age of 30 years (OR = 1.7, 95% CI: 1.1-2.5). The association was only statistically significant for squamous cell carcinomas (OR = 1.8, 95% CI 1.2-2.7). Furthermore, this study observed a higher OR of lung cancer among exclusive waterpipe smokers (OR = 2.3, 95% CI: 1.6, 3.5). CONCLUSIONS: Waterpipe smoking was associated with an increased risk of lung cancer. The association was stronger with higher frequency, duration and intensity of exposure to waterpipe smoking. The association increases in exclusive waterpipe smokers, which is likely due to controlling for residual confounding by cigarette smoking and opium consumption, and higher exposure levels in this subpopulation.

Supernatant fluid from endobronchial ultrasound-guided transbronchial needle aspiration for rapid next-generation sequencing.

INTRODUCTION: There is an increasing demand to optimize the workflow and maximize tissue available for next-generation sequencing (NGS) for non-small cell carcinoma. We looked at transbronchial needle endobronchial ultrasound-guided bronchoscopy with transbronchial needle aspiration samples and evaluated the performance of supernatant (SN) fluid processed from a dedicated aspirate collected for NGS testing. MATERIALS AND METHODS: Nineteen samples were collected and processed using a new workflow. Five aspirates were collected in formalin. One additional dedicated pass was collected fresh and centrifuged. The resulting cell pellet was added to formalin for cell block (CB) processing. DNA and RNA were extracted from concentrated SN for targeted testing using the Oncomine Precision Assay (Thermo Scientific, Waltham, MA). NGS results from the corresponding CB samples were used as "controls" for comparison. RESULTS: Thirty-one mutations were detected in SN (Table 1). The most frequently mutated genes were TP53 (35%), EGFR (23%), KRAS (13%), CTNNB1 (6%), and ERBB2 (6%). There was 100% concordance between the mutations detected in SN and corresponding CBs with comparable variant allele frequencies. Turnaround time of NGS results was 1 day for SN compared to 4-10 days for CB. CONCLUSIONS: We were able to demonstrate the usefulness of SN for reliable rapid molecular results. We successfully incorporated the workflow for tissue handling and processing among our clinical, cytopathology, and molecular teams. Molecular results were available at the same time as the cytologic diagnosis, allowing for timely reporting of a comprehensive diagnosis. This approach is particularly useful in patients with advanced disease requiring urgent management.

Prognostic nomogram to predict cancer-specific survival with small-cell carcinoma of the prostate: a multi-institutional study.

Objective: The aim of this study is to examine the predictive factors for cancer-specific survival (CSS) in patients diagnosed with Small-Cell Carcinoma of the Prostate (SCCP) and to construct a prognostic model. Methods: Cases were selected using the Surveillance, Epidemiology, and End Results (SEER) database. The Kaplan-Meier method was utilized to calculate survival rates, while Lasso and Cox regression were employed to analyze prognostic factors. An independent prognostic factor-based nomogram was created to forecast CSS at 12 and 24 months. The model's predictive efficacy was assessed using the consistency index (C-index), calibration curve, and decision curve analysis (DCA) in separate tests. Results: Following the analysis of Cox and Lasso regression, age, race, Summary stage, and chemotherapy were determined to be significant risk factors (P < 0.05). In the group of participants who received training, the rate of 12-month CSS was 44.6%, the rate of 24-month CSS was 25.5%, and the median time for CSS was 10.5 months. The C-index for the training cohort was 0.7688 ± 0.024. As for the validation cohort, it was 0.661 ± 0.041. According to the nomogram, CSS was accurately predicted and demonstrated consistent and satisfactory predictive performance at both 12 months (87.3% compared to 71.2%) and 24 months (80.4% compared to 71.7%). As shown in the external validation calibration plot, the AUC for 12- and 24-month is 64.6% vs. 56.9% and 87.0% vs. 70.7%, respectively. Based on the calibration plot of the CSS nomogram at both the 12-month and 24-month marks, it can be observed that both the actual values and the nomogram predictions indicate a predominantly stable CSS. When compared to the AJCC staging system, DCA demonstrated a higher level of accuracy in predicting CSS through the use of a nomogram. Conclusion: Clinical prognostic factors can be utilized with nomograms to forecast CSS in Small-Cell Carcinoma of the Prostate (SCCP).

Bilateral Metastatic Gynecomastia from Small-Cell Lung Tumors in a Man: A Report of a Rare Case.

A case of a man with the recent onset of painful bilateral firm gynecomastia is reported. Mammography confirmed increased breast density. Biopsy characterized both masses as metastases of a small-cell lung tumor. This case highlights the atypical presentation and complements the literature regarding the rarity of breast metastases from small-cell lung cancer in men. Teaching point: Bilateral gynecomastia in a man with a long history of cigarette smoking should be considered with caution.

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

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

A Case of Hypercalcemic-Type Stage IVB Small-Cell Carcinoma of the Ovary in a Young Woman.

A 38-year-old nulliparous woman with severe obesity (BMI 66) and hypertension presented with constipation, fatigue, weakness, and poor appetite that had progressively worsened over the prior two to three weeks. Upon admission, the patient was found to have significant hypercalcemia, leukocytosis, and lactic acidosis. Computed tomography (CT) scan of the chest, abdomen, and pelvis revealed an adnexal mass with extensive lesions throughout her pelvis, abdomen, and chest. An ultrasound-guided omental core biopsy was performed, which was confirmatory for metastatic ovarian small cell carcinoma. Given her poor prognosis and clinical status, chemotherapy was likely to provide minimal benefit and ultimately the patient decided to pursue a comfort-oriented plan of care and passed away on day 9 of admission.

Pan-Canadian Analysis of Practice Patterns in Small Cell Carcinoma of the Cervix: Insights from a Multidisciplinary Survey.

Small-cell neuroendocrine carcinoma of the cervix (SCNECC) is a rare cancer with poor prognosis, with limited data to guide its treatment. The objective of this study was to evaluate practice patterns in the management of SCNECC. A 23-question online survey on management of SCNECC was disseminated to Canadian gynecologic oncologists (GO), radiation oncologists (RO) and medical oncologists (MO). In total, 34 practitioners from eight provinces responded, including 17 GO, 13 RO and four MO. During staging and diagnosis, 74% of respondents used a trimodality imaging approach, and 85% tested for neuroendocrine markers. In early-stage (1A1-1B2) SCNECC, 87% of practitioners used a surgical-based approach with various adjuvant and neoadjuvant treatments. In locally advanced (1B3-IVA) SCNECC, 53% favored primary chemoradiation, with cisplatin and etoposide, with the remainder using surgical or radiation-based approaches. In metastatic and recurrent SCNECC, the most common first-line regimen was etoposide and platinum, and 63% of practitioners considered clinical trials in the first line setting or beyond. This survey highlights diverse practice patterns in the treatment of SCNECC. Interdisciplinary input is crucial to individualizing multimodality treatment, and there is a need for prospective trials and intergroup collaboration to define the optimal approach towards managing this rare cancer type.

Clinical and Pathologic Differences between Small-Cell Carcinoma and Large-Cell Neuroendocrine Carcinoma of the Lung.

BACKGROUND: Both small-cell carcinoma (SCLC) and large-cell neuroendocrine carcinoma (LCNEC) of the lung are often clinically dealt with as being in the same category as neuroendocrine carcinoma, and their clinical differences have not been adequately assessed. METHODS: The postoperative prognosis was retrospectively analyzed using the data of 196 patients who underwent resection for SCLC or LCNEC. RESULTS: Of the patients included, 99 (50.5%) had SCLC and 97 (49.5%) had LCNEC. The median duration of follow-up was 39 months (interquartile range [IQR] 21-76) and 56 months (IQR 21-87) for SCLC and LCNEC, respectively. The estimated 5-year overall survival (OS) probabilities were 53.7% and 62.7% (p = 0.133) for patients with SCLC and LCNEC, respectively. In the SCLC group, a multivariate analysis showed that adjuvant chemotherapy (hazard ratio 0.54, 95% confidence interval 0.30-0.99, p = 0.04) was the only factor that was significantly associated with OS. In the LCNEC group, univariate analyses demonstrated that pathologic stage I (p = 0.01) was the only factor that was associated with better OS after surgery. CONCLUSIONS: We found different clinical features in SCLC and LCNEC; in patients with SCLC, because OS could be expected to significantly improve with postoperative adjuvant chemotherapy, patients with resected SCLC of any pathologic stage should receive adjuvant chemotherapy. For patients with LCNEC, because pathologic stage I LCNEC is related to better prognosis than any other stages, a thorough clinical staging, including invasive staging, according to present guidelines should be performed to identify clinical stage I LCNEC with the highest certainty.

Primary Small Cell Carcinoma of the Kidney: A Case Study with Emphasis on Fluorodeoxyglucose Positron Emission Tomography-Computed Tomography Findings.

Small cell carcinoma (SCC) of the kidney is included in extrapulmonary SCC which is a group of extremely rare but highly aggressive cancers. There have been only a few case reports and small retrospective series in the literature describing the malignancy in kidneys. Most of the published reports describe the entity as a variant mixed with other tumor subtypes such as urothelial carcinoma, adenocarcinoma, and squamous cell carcinoma. Pure-form SCC in kidneys is exceedingly rare. Fluorodeoxyglucose positron emission tomography-computed tomography plays an essential role in the accurate staging evaluation of this cancer.

Hiding in Plain Sight: An Atypical Presentation of the Uncommon Merkel Cell Carcinoma.

Merkel cell carcinoma (MCC) is a cutaneous neoplasm that is challenging to diagnose secondary to its rarity. We report a case involving a 76-year-old Caucasian female with a seemingly benign skin nodule on her right forearm. Histopathological analysis revealed characteristics of MCC, including uniform round cells with minimal cytoplasm and fine granular chromatin. Immunohistochemical staining confirmed insulinoma-associated protein 1 (INSM1) positivity, a marker with high sensitivity and specificity in localized MCC diagnosis. The subsequent treatment plan involved wide local excision, sentinel lymph node evaluation, and radiation therapy, aligning with therapeutic standards for MCC. Negative positron emission tomography (PET) scans and follow-up for one year have demonstrated no evidence of recurrence or additional lesions. This case demonstrates the challenges in diagnosing MCC and the need for histopathological and immunohistochemical assessments for an accurate diagnosis. Diagnostic markers, INSM1, are important distinguishing factors between MCC and other skin cancers. In conclusion, our case contributes to the literature in diagnosing MCC and successful treatment, while emphasizing the need for immunohistochemical markers for accurate diagnosis and guiding therapeutic decisions.