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Small cell bladder carcinoma (SCBC) is a very rare entity. Compared to urothelial carcinoma they are more aggressive and have higher probabilities for metastases. Due to the aggressive nature of small cell bladder cancer, early diagnosis and treatment is imperative for the greatest chance of survival. We had two cases of non metastatic Small cell bladder carcinoma presenting at our institute and both were treated with definitive radiotherapy. One patient on follow up developed skeletal metastases and succumbed to disease, while the other patient is alive and disease free after 6 years. Here we present the challenges in diagnosis and treatment, and outcome of two SCBC patients treated at our institute. [ABSTRACT FROM AUTHOR]

Simple Summary: In the present study, the intraoperative fluorescence of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) is investigated in 80 cases. Brain metastases fluoresced in 57.5% of cases, with no significant correlation between fluorescence and primary tumor or histological subtype. Complete resection of brain metastases was detected in 82.5%, of which 56.1% were fluorescence positive, compared to 43.9% which were non-fluorescent. Thus, prior administration of 5-ALA tended to improve the resectability rate by 12.1%. Fluorescence-positive and -negative metastases showed significantly different overall survival in this study. Therefore, administration of 5-ALA as a surgical adjuvant may be beneficial in resecting brain metastases and may potentially optimize the surgical procedure. (1) Background: In this study, the intraoperative fluorescence behavior of brain metastases after the administration of 5-aminolevulinic acid (5-ALA) was analyzed. The aim was to investigate whether the resection of brain metastases using 5-ALA fluorescence also leads to a more complete resections and thus to a prolongation of survival; (2) Methods: The following variables have been considered: age, sex, number of metastases, localization, involvement of eloquent area, correlation between fluorescence and primary tumor/subtype, resection, and survival time. The influence on the degree of resection was determined with a control MRI within the first three postoperative days; (3) Results: Brain metastases fluoresced in 57.5% of cases. The highest fluorescence rates of 73.3% were found in breast carcinoma metastases and the histologic subtype adenocarcinoma (68.1%). No correlation between fluorescence behavior and localization, primary tumor, or histological subtype was found. Complete resection was detected in 82.5%, of which 56.1% were fluorescence positive. There was a trend towards improved resectability (increase of 12.1%) and a significantly longer survival time (p = 0.009) in the fluorescence-positive group; (4) Conclusions: 5-ALA-assisted extirpation leads to a more complete resection and longer survival and can therefore represent a low-risk addition to modern surgery for brain metastases. [ABSTRACT FROM AUTHOR]

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

Simple Summary: The evaluation of therapeutic approaches over a decade at a tertiary cancer center in Germany was undertaken due to the frequent and critical discussions surrounding the selection of chemotherapy regimens and the incorporation of prophylactic cranial irradiation (PCI) in the management of limited disease small cell lung cancer (LD-SCLC). We found significant differences in progression-free survival (PFS) and overall survival (OS) between patients treated with carboplatin and etoposide (CP) and those treated with cisplatin and etoposide (EP), with EP showing better outcomes. Concomitant chemotherapy was also associated with improved PFS and OS. Notably, PCI was found to significantly improve OS and showed a trend towards improved PFS. Female patients had better OS, and the type of chemotherapy and PCI remained independent predictors of survival. This research provides valuable insights into treatment patterns, outcomes, and survival predictors for LD-SCLC, emphasizing the importance of personalized treatment approaches and the potential benefits of PCI. However, the study's retrospective nature and sample-size limitations should be considered, highlighting the need for further prospective studies in this field. In this study, we investigated the outcomes and factors influencing treatment efficacy in 93 patients with limited disease small cell lung cancer (LD-SCLC), with a median age of 64 years. We focused on the impact of chemotherapy regimens, prophylactic cranial irradiation (PCI), and patient-related variables. The median follow-up for OS was 17.3 months. We observed a statistically significant difference in PFS between LD-SCLC patients treated with cisplatin and etoposide (EP) and those treated with carboplatin and etoposide (CP) (PFS: EP 13.63 months vs. CP 6.54 months, p < 0.01). Patients treated with EP had better overall survival (OS) than CP-treated patients (OS: EP 26.9 months vs. CP 16.16 months, p < 0.01). Concomitant chemotherapy was associated with improved PFS (p = 0.003) and OS (p = 0.002). Patients receiving PCI showed superior OS (p = 0.05) and a trend towards improved PFS (p = 0.057). Female gender was associated with better OS (p = 0.025). Most patients had an ECOG performance status of 0 (71%). This real-world study underscores the importance of multidisciplinary LD-SCLC management, emphasizing the roles of chemotherapy, radiotherapy, and PCI. These findings inform personalized treatment strategies and emphasize the need for prospective trials to validate these results and optimize LD-SCLC treatment. [ABSTRACT FROM AUTHOR]

The aim of this study was to investigate the feasibility of deep learning (DL) based on multiparametric MRI to differentiate the pathological subtypes of brain metastasis (BM) in lung cancer patients. This retrospective analysis collected 246 patients (456 BMs) from five medical centers from July 2016 to June 2022. The BMs were from small-cell lung cancer (SCLC, n = 230) and non-small-cell lung cancer (NSCLC, n = 226; 119 adenocarcinoma and 107 squamous cell carcinoma). Patients from four medical centers were assigned to training set and internal validation set with a ratio of 4:1, and we selected another medical center as an external test set. An attention-guided residual fusion network (ARFN) model for T1WI, T2WI, T2-FLAIR, DWI, and contrast-enhanced T1WI based on the ResNet-18 basic network was developed. The area under the receiver operating characteristic curve (AUC) was used to assess the classification performance. Compared with models based on five single-sequence and other combinations, a multiparametric MRI model based on five sequences had higher specificity in distinguishing BMs from different types of lung cancer. In the internal validation and external test sets, AUCs of the model for the classification of SCLC and NSCLC brain metastasis were 0.796 and 0.751, respectively; in terms of differentiating adenocarcinoma from squamous cell carcinoma BMs, the AUC values of the prediction models combining the five sequences were 0.771 and 0.738, respectively. DL together with multiparametric MRI has discriminatory feasibility in identifying pathology type of BM from lung cancer. [ABSTRACT FROM AUTHOR]

Neuroendocrine prostate neoplasms, encompassing small cell carcinoma, carcinoid, and large cell carcinoma, are infrequently observed in malignant prostate tumors. The occurrence of large cell neuroendocrine prostate cancer (LCNEPC) is exceedingly rare. In this study, the patient initially presented with a persistent dysuria for a duration of one year, accompanied by a serum prostate-specific antigen (PSA) level of 17.83ng/mL. Prostate magnetic resonance imaging (MRI) and chest computed tomography (CT) scan showed that a neoplastic lesion was considered, and prostate biopsy confirmed prostate adenocarcinoma with a Gleason score of 7 (4 + 3). Then, thoracoscopic lung tumor resection was performed, and the pathological examination revealed the presence of primary moderately differentiated invasive adenocarcinoma of the lung and metastatic prostate adenocarcinoma, the Gleason score was 8 (4 + 4). After 1 year of endocrine therapy with goserelin acetate and bicalutamide, he underwent a laparoscopic radical prostatectomy (LRP), the pathological report indicated the presence of adenocarcinoma mixed with NE carcinoma. Two months after the LRP, the patient experienced gross hematuria and sacral tail pain. Further examination revealed multiple metastatic lesions throughout the body. He also underwent transurethral resection of bladder tumor (TURBT) for bladder tumor and received etoposide+ cisplatin chemotherapy three weeks post-surgery. The patient eventually died of multi-organ failure due to myelosuppression after chemotherapy. This case report presents an uncommon instance of LCNEPC with widespread systemic metastases, while also providing a comprehensive review of existing literature to facilitate improved management and treatment strategies for similar patients in subsequent cases. [ABSTRACT FROM AUTHOR]

Background: Orbital metastasis is a possible complication of small cell lung cancer and a pattern of bilateral invasion of the extraocular muscles has rarely been reported in literature. Case presentation: A 46-year-old white male with a past medical history of smoking and stage IV small cell lung carcinoma presented with loss of vision and pain in the left eye. Examination revealed bilateral proptosis and left afferent pupillary defect, and visual acuity was hand motion on the left eye and 4/10 on the right eye. An orbital computed tomography scan showed a compression of the left optic nerve between the extraocular muscles at the apex, and a lateral canthotomy was performed for a new-onset compressive optic neuropathy, with residual visual improvement. There was also significant enlargement of the extraocular muscles in the right orbit. The patient was maintained in palliative treatment with both chemotherapy and local medical and surgical (amniotic membrane cover for exposure keratopathy) ophthalmological treatments until he eventually died 5 months after. Conclusion: Bilateral metastasis to the extraocular muscles is a very rare manifestation of small cell lung cancer and the palliative treatment in these cases is challenging. [ABSTRACT FROM AUTHOR]

Extrapulmonary small cell carcinoma (EPSCC) is very rare with an incidence of 0.1 to 0.4% in the United states and the exact incidence in other regions is unknown. Anal canal involvement is extremely rare contributing to < 1% of all EPSCC. Inspite of its rarity, it is of clinical importance due to its aggressive nature. Most of the patients present with lungs and liver metastasis at diagnosis even in early stage tumors. It has a dismal survival rate of 58% at 6-month and 6% at 5-years in contrast to squamous cell carcinoma of anal canal. Exact ethiopathogenesis is unknown. Association with HIV has been seen like squamous cell carcinoma of anal canal. There is very little literature evidence and management is not clear like that of squamous cell carcinoma anal canal. Here we present the case of a 63 year old HIV positive male who presented with small cell carcinoma of anal canal to our institute and the challenges we faced in diagnosis and management. [ABSTRACT FROM AUTHOR]

Background: Brain metastases (BMs) are common in small cell lung cancer (SCLC), and the efficacy of immune checkpoint inhibitors (ICIs) in these patients is uncertain. In this study we aimed to develop and validate a radiomics nomogram based on magnetic resonance imaging (MRI) for intracranial efficacy prediction of ICIs in patients with BMs from SCLC. Methods: The training and validation cohorts consisted of 101 patients from two centers. The interclass correlation coefficient (ICC), logistic univariate regression analysis, and random forest were applied to select the radiomic features, generating the radiomics score (Rad‐score) through the formula. Using multivariable logistic regression analysis, a nomogram was created by the combined model. The discrimination, calibration, and clinical utility were used to assess the performance of the nomogram. Kaplan–Meier curves were plotted based on the nomogram scores. Results: Ten radiomic features were selected for calculating the Rad‐score as they could differentiate the intracranial efficacy in the training (area under the curve [AUC], 0.759) and the validation cohort (AUC, 0.667). A nomogram was created by combining Rad‐score, treatment lines, and neutrophil‐to‐lymphocyte ratio (NLR). The training cohort obtained an AUC of 0.878 for the combined model, verified in the validation cohort (AUC = 0.875). Kaplan–Meier analyses showed the nomogram was associated with progression‐free survival (PFS) (p = 0.0152) and intracranial progression‐free survival (iPFS) (p = 0.0052) but not overall survival (OS) (p = 0.4894). Conclusion: A radiomics nomogram model for predicting the intracranial efficacy of ICIs in SCLC patients with BMs can provide suggestions for exploring individual‐based treatments for patients. [ABSTRACT FROM AUTHOR]

Objective: Thoracocentesis is a less invasive and expensive procedure than pleural biopsy, enabling sample collection for cytological evaluation. Cell blocks prepared from these samples provide histopathological diagnoses; further, immunohistochemistry (IHC) can be performed for subtyping malignancies, guiding the clinician in choosing the appropriate treatment modality for the patient. We aimed to determine the various histological subtypes of malignancies using cell block IHC and compare the cell block and conventional cytology methods for diagnosing malignant pleural effusion. Material and Methods: All pleural fluid samples from the clinically suspicious cases of malignancy collected at the Department of Pathology, Government Medical College Kottayam, India, during 18 months, except duplicate and inadequate samples, were included in this prospective observational study. IHC was performed on cell blocks that were positive for malignancy. Results: This study analyzed 630 samples, of which 121 cell blocks demonstrated the presence of malignancy. Overall, 80%, 13%, and 7% of cases were negative, suspicious, and positive for malignancy based on conventional cytology, and 81%, 0%, and 19% were negative, suspicious, and positive for malignancy based on cell blocks, respectively. Among all malignancies, adenocarcinomas from the lung (56%) were the most common, followed by adenocarcinomas from the breast (6%), squamous cell carcinomas (5%), and adenocarcinomas from the ovary (3%). Cell blocks helped detect more malignancies (19%) than conventional cytology (7%), despite a moderate agreement between both methods. Conclusion: Adenocarcinomas were the most common cause of malignant pleural effusions, and the most frequent site of origin was the lungs. Cell blocks helped diagnose more malignancies than conventional cytology. [ABSTRACT FROM AUTHOR]

OBJECTIVE We aimed to investigate the current status and use of thoracic radiotherapy (TRT) and prophylactic cranial irradiation (PCI) in extensive-stage small-cell lung cancer (ES-SCLC) patients who responded to chemotherapy (ChT) through a nationwide survey. METHODS An electronic survey was created. We invited all the Turkish Society of Radiation Oncology-registered radiation oncologists (ROs). RESULTS A total of 101 ROs participated. TRT was routinely recommended to patients who responded to ChT by 76% of ROs. The highest agreement for TRT indication (%94) was in the case of symptomatic residual disease. The most commonly used fractionation scheme was 30 Gy in 10 fractions. There was an increase in the use of 30 Gy in 10 fractions after the publication of the CREST trial. The implementation criteria for TRT were site and number of metastases for 65% and 42% of respondents, respectively. PCI was recommended by 89% routinely. The most commonly (93%) used fractionation scheme was 25 Gy in 10 fractions. CONCLUSION This survey highlights the absence of consensus on the eligibility criteria and dosage of TRT in ES-SCLC within the Turkish RO community. The highest agreement for the TRT indication was in patients with symptomatic intrathoracic residual disease. The CREST trial impacted TRT indications and fractionation. There was high consistency in practice in terms of PCI indication, dose, and fractionation. [ABSTRACT FROM AUTHOR]

OBJECTIVE Lung cancer (LC) is the leading cause of cancer death worldwide. Multiple studies have shown tumor progression and prognosis to be associated with immune status and nutritional condition. Alterations in blood lipid levels have been demonstrated to be a risk factor for LC. In the present study, we evaluate the effect of blood parameters on brain metastasis in LC. METHODS Patients identified with brain metastases during diagnosis or therapy and who subsequently underwent radiation therapy were included in the study. Patient characteristics, laboratory parameters, pathologic subtype, disease stage, treatment modalities, and outcome following treatment were recorded, and the patients' PFS and OS were calculated. RESULTS Univariate analysis revealed neutrophil, low-density lipoprotein (LDL), neutrophil-to-lymphocyte ratio (NLR), and C-reactive protein levels to be significantly different between groups according to brain metastases. In a subgroup analysis based on cancer subtypes, LDL and lymphocyte levels were found to be significantly different in squamous cancer, while LDL was different in the undifferentiated subtype. OS was different in the NLR low and high groups, favoring the NLR low group (p=0.015; OS: 12 vs. 9 months), and the monocyte/lymphocyte ratio was significant in terms of OS favoring the low group with a cutoff value of 0.56 (p=0.002; OS: 13 vs. 9 months). CONCLUSION Our study identified differences in the inflammatory and lipid profiles of LC patients in terms of brain metastases and survival. Other than the literature, LDL levels were different among groups and may be considered a valid subject for future study. [ABSTRACT FROM AUTHOR]

Background: Genitourinary small cell carcinoma is rare, and has a poor prognosis. However, effective treatment options for this disease are limited. We present a study to assess the efficacy of chemotherapy alone or combined with immunotherapy for locally advanced or metastatic genitourinary small cell carcinoma (GSCC). Methods: We performed a retrospective analysis of patients with locally advanced or metastatic GSCC from Jan 2013 to September 2022 at Sun Yat-sen University Cancer Center. The survival and safety profiles were analyzed. Results: Forty-two GSCC patients were enrolled, which included 20 with chemotherapy plus immunotherapy and 22 with chemotherapy alone. The median follow-up time was 15.13 months (95% CI, 8.84–21.42). The addition of immunotherapy to chemotherapy demonstrated no significant difference in median progression-free survival (p = 0.37). However, the median overall survival (OS) was 22.97 and 14.03 months with immunotherapy plus chemotherapy and chemotherapy alone, respectively (HR = 0.69, 95%CI 0.08–0.55, p = 0.017). Two patients with immunotherapy plus chemotherapy achieved clinical complete remission. The overall response rate for patients receiving chemotherapy combined with immunotherapy was 65%, which was higher in comparison to those treated with chemotherapy alone (50%). Univariate and multivariate analyses demonstrated that chemotherapy combined with immunotherapy independently achieved favorable OS. Four patients experienced immunotherapy-related adverse events, with one developing grade 3 hypothyroidism. Conclusions: Among patients with locally advanced or metastatic GSCC, immunotherapy combined with chemotherapy might be thought of as a potentially effective treatment option for patients with GSCC. [ABSTRACT FROM AUTHOR]

A 67‐year‐old male patient presented with extensive‐stage small cell lung cancer with the primary lesion located in the right upper lung, accompanied by multiple metastases to the pleura and abdominal cavity with enlarged mediastinal lymph nodes. A combination therapy approach was used to target the patient's multiple systemic metastases after localized radiotherapy. The approach involved adoptive transfer of programmed death ligand 1 (PD‐L1) enhanced exogenous natural killer (NK) cells, along with antiangiogenic treatment. Allogeneic cord blood NK cells were infused back into the patient over two consecutive days. On the first day, the treatment was followed by a dose of 1200 mg of atezolizumab. Subsequently, the patient received a daily dose of 10 mg of anlotinib administered orally for 14 days. This was followed by a 7‐day break, and each cycle lasted 21 days. After delivering localized radiation to the primary lesion in the right lung and metastatic mediastinal lymph nodes, complete remission was achieved in the local lesion, effectively avoiding the risk of superior vena cava syndrome. Following six cycles of combined therapy, most of the metastatic lesions had disappeared, and the remaining metastatic lesions had significantly reduced in size. The recent therapeutic effect resulted in partial remission. The combination therapy of immune checkpoint inhibitor PD‐L1‐enhanced exogenous adoptive transfer NK cells, along with antiangiogenic targeted treatment, demonstrated a satisfactory short‐term effect, with disappearance of most of the metastases and noticeable shrinkage in the remaining metastatic lesions. [ABSTRACT FROM AUTHOR]

Primary intracranial small cell carcinoma (SCC) is extremely rare with only 8 previously reported cases. We describe a case of primary intracranial SCC with intracranial metastasis. A 46-year-old man presented with decreased vision and a red and swollen left eye. Brain magnetic resonance imaging (MRI) revealed a heterogeneously enhanced tumor on the left frontal lobe. Preoperative systemic computed tomography (CT), MRI, and positron emission tomography (PET)-CT revealed no extracranial tumors. The tumor on the left frontal lobe was excised. Immunohistochemical staining on the excision showed positivity for CD56, synaptophysin (Syn), cytokeratin (CK), and Ki-67 (30%), and negativity for thyroid transcriptional factor-1 (TTF-1), glial fibrillary acidic protein (GFAP), Bcell lymphoma 6 (Bcl-6), multiple myeloma oncogene 1 (MUM-1), C-Myc, Vimentin, P40, P53, CK7, CD3, CD5, CD20, CD79a, CD10, and CD23. The pathological examination strongly suggested that the tumor was a primary intracranial SCC. One year after the surgery, the patient was readmitted with slurred speech and slow movements. Three well-defined tumors were found in the left upper frontal lobe by brain MRI. Tumor resection was then performed. Further immunohistochemical examination of the excised tissue displayed the same pattern as previously, indicating the recurrence of intracranial SCC in the left frontal lobe. The patient received adjuvant chemotherapy and radiotherapy after the tumor resection. At the 2-year follow-up, he remained asymptomatic. [ABSTRACT FROM AUTHOR]

Simple Summary: Chemoimmunotherapy (CT-IO) is the standard first-line treatment of advanced small cell lung cancer (SCLC). However, very limited efficacy data from real-life use of this combination are available. Moreover, patients included in pivotal phase III trials were highly selected. We conducted a retrospective multicentric (six academic centers) case–control study (n = 153), comparing two cohorts of patients who received first-line treatment, one treated with chemotherapy alone (between January 2017 and December 2018) and one with CT-IO (between January 2019 and December 2020), for an advanced SCLC. CT-IO confirmed its superiority compared to chemo alone. Interestingly, we showed that CT-IO was efficient in patients with brain and liver metastases. However, patients ≥70 years old and with a PS ≥2 did not benefit from CT-IO. This real-life study in one of the largest published to our knowledge on first-line CT-IO for advanced SCLC, with a large focus on specific populations (brain mets, elderly, and impaired PS). The current first-line standard treatment for advanced small cell lung cancer (SCLC) is a combination of chemotherapy and immunotherapy. However, few efficacy data are available in a real-life settings, including frail patients. The aim of this study is to describe the real-life efficacy of chemoimmunotherapy in an unselected SCLC population. We conducted a retrospective multicenter study, which compared two cohorts of patients with treatment-naive metastatic SCLC treated in six academic centers in the Greater Paris area. Cohort 1 included patients treated with chemotherapy between January 2017 and December 2018, and cohort 2 included patients treated with chemoimmunotherapy between January 2019 and December 2020. A total of 153 consecutive patients were included (cohort 1: n = 96; cohort 2: n = 57). Clinical characteristics were similar between the two cohorts. Overall survival (OS) was statistically higher in cohort 2 (median survival 15.47 months) than in cohort 1 (median survival 9.5 months) (p = 0.0001). OS for patients with a performance status ≥2 and for patients ≥70 years old was not statistically different between the two cohorts. Chemoimmunotherapy efficacy was better compared to chemotherapy alone in case of brain or liver metastases. In conclusion, the combination of chemoimmunotherapy in metastatic SCLC appears to provide a real-life OS benefit. Dedicated clinical trials are needed to test this strategy in patients with impaired performance status or advanced age. [ABSTRACT FROM AUTHOR]

Simple Summary: Metastatic spinal cord compression (MSCC) is characterised by the compression of the spinal cord due to direct or metastatic spread to the vertebrae, potentially leading to neurological deficits. This condition constitutes an urgent situation in oncology, demanding swift diagnosis and immediate intervention due to the considerable risk of spinal cord damage and irreversible neurological repercussions. Spinal tumours resulting from the metastasis of lung cancer are particularly connected with an unfavourable prognosis, often displaying rapid advancement and limited survival. Treatment approaches encompass a combination of radiotherapy and potential surgery, which are tailored to each patient's situation. Within this retrospective study, our goal was to pinpoint prognostic elements that impact the survival rates of lung cancer patients experiencing MSCC. Identifying such prognostic factors associated with shorter or longer survival subsequent to MSCC could contribute to tailoring distinct, more or less intensive therapeutic strategies for these individuals. Purpose: Metastatic spinal cord compression (MSCC) is a severe complication of cancer that can lead to irreversible neurological impairment, necessitating prompt recognition and intervention. This retrospective, single-centre study aimed to determine the prognostic factors and survival rates among patients presenting with MSCC secondary to lung cancer. Methods and Materials: We identified 74 patients with epidural metastases-related spinal cord compression and a history of lung cancer through the electronic database of Medway Maritime Hospital in the United Kingdom (UK), spanning the period from April 2016 to September 2021. Among them, 39 were below 55 years old, while 35 were aged 55 years or older; 24 patients were diagnosed with small cell lung cancer (SCLC), and 50 patients had non-small cell lung cancer (NSCLC). Results: The median overall survival (OS) was 5.5 months, with 52 out of 74 patients dying within 6 months of diagnosis with MSCC. For the entire cohort, the statistically significant variables on multi-variate analysis were cancer type (NSCLC had improved OS), the number of involved vertebrae (one to two vertebrae involvement had improved OS), and the time taken to develop motor deficits (≤10 days to develop motor deficits had worsened OS). For the NSCLC cohort, the statistically significant variables on multivariate analysis were molecular alterations (patients with epidermal growth factor receptor (EGFR) mutation), pre-treatment ambulatory status, Eastern Cooperative Oncology Group (ECOG) performance status, and the time taken to develop motor deficits. Conclusions: Within the entire cohort, patients diagnosed with NSCLC and spinal metastases affecting one to two vertebrae exhibited enhanced OS. Within the NSCLC subgroup, those with EGFR mutations who were ambulatory and possessed an ECOG performance status of 1–2 demonstrated improved OS. In both the entire cohort and the NSCLC subgroup, the development of motor deficits within a period of ≤10 days was associated with poor OS. [ABSTRACT FROM AUTHOR]

Introduction: Cutaneous metastases (CM) revealing lung carcinoma are extremely rare, accounting for 0.8%. The diagnosis is guided by histology and immunohistochemistry. Treatment is palliative. The prognosis is poor. Case presentation: This is a retrospective study of the available clinical and histological records of four North African patients with CM revealing lung cancer treated at our institute between 2004 and 2010. Three men and one woman were registered. The mean age was 54.5 years (38–74 years). Two patients had primary adenocarcinoma, one patient had small cell carcinoma and one had squamous cell carcinoma. Treatment was based on chemotherapy in two cases and antalgic radiotherapy in two cases, one patient underwent surgical resection as the lesion was infected. The overall survival after diagnosis was between one and four months. Conclusions: A skin nodule can be the first symptom revealing lung cancer. A rare clinical presentation that should not be taken for a benign nodule, the biopsy and histological study with immunohistochemistry confirm the diagnosis. [ABSTRACT FROM AUTHOR]

Several transcription factors in small cell lung cancer (SCLC), including achaete‐scute homolog 1 (ASCL1) and neurogenic differentiation factor 1 (NEUROD1), contribute to rapid tumor growth and early metastatic dissemination. Recent studies suggested that these molecular subtypes represent neuroendocrine differentiation in dynamic SCLC evolution. In the present case, a 62‐year‐old man was diagnosed with limited disease SCLC originating from the right upper lobe. Biopsy specimens were positive for ASCL1 but negative for NEUROD1. Six months after concurrent chemoradiotherapy and prophylactic cranial irradiation, the primary tumor had regrown and salvage surgery was performed. The pathological diagnosis was recurred SCLC, and postoperative histopathology was positive for both ASCL1 and NEUROD1. The patient was subsequently followed up; however, he had multiple bone metastases 9 months after surgery. It was speculated that the shift to NEUROD1‐high expression in tumor cells surviving concurrent chemoradiation therapy may be related to the poor outcome after combined modality treatment. [ABSTRACT FROM AUTHOR]

Neuroendocrine tumours (NET) are found to be aggressive and extremely rare tumour. Its annual incidence is approximately 2.5-5.0 per 100,000. NET which are arise from cells of the nervous and endocrine systems. Majority of NET are seen within the GIT(55%) and respiratory system(30%). Most common site are mainly 45% of small intestine,followed by 20% of rectum, 17% of appendix, 11% of colon and then 7% of stomach. Cancer of this type is highly aggressive, and can occur in younger patients.MRI – the best method to achieve because it provides precise information and clear images regarding their location, size and complexity of mass. Small cell NETis associated with thier early metastases to lymph nodes and liver and poor prognosis. Treatment for localized small cell NE carcinoma are done by mainly postoperative chemotherapy or radiation therapy with surgical excision. This type of tumor are characterized or identified by their aggressive behavior, natural history and often have widespread metastatic nature on presentation. [ABSTRACT FROM AUTHOR]

Background: Distant organ metastasis is a common event in lung cancer (LC). However, the preferential metastatic pattern of different pathological types of LC and its effect on prognosis have not been comprehensively elucidated. This study aimed to explore the distant metastasis pattern and construct nomograms predicting the metastasis and survival of LC patients using the Surveillance, Epidemiology, and End Results (SEER) database. Methods: LC data were downloaded from the SEER database to conduct logistic regression and investigate risk factors for developing organ metastasis. A Cox regression analysis was conducted to investigate prognostic factors of LC. A Kaplan-Meier analysis was used to estimate overall survival outcomes. Nomograms were constructed to predict the probability of organ metastasis and the 1-, 3- and 5-year survival probability of LC patients. Receiver operating characteristic curves were used to evaluate the diagnostic accuracy of the nomograms. All statistical analyses were conducted within R software. Results: The liver is the most common metastatic organ of small cell carcinoma. The brain is the most likely metastasis site of large cell carcinoma, and bone is the most likely metastasis site for squamous cell carcinoma and adenocarcinoma. Patients with triple metastases (brain-bone-liver) have the worst prognosis, and for nonsquamous carcinoma with single organ metastasis, liver metastases conferred the worst prognosis. Our nomograms based on clinical factors could predict the metastasis and prognosis of LC patients. Conclusion: Different pathological types of LC have different preferential metastatic sites. Our nomograms showed good performance in predicting distant metastasis and overall survival. These results will provide a reference for clinicians and contribute to clinical evaluations and individualized therapeutic strategies. [ABSTRACT FROM AUTHOR]

Simple Summary: Small cell lung cancer (SCLC) is an aggressive lung cancer subtype associated with an overall poor prognosis but a variable response rate to chemotherapy. The measurement of circulating tumor cells (CTCs) offers a non-invasive method to monitor the disease and may provide prognostic information as potential guidance to clinicians in the management of SCLC. However, the value of CTCs during and after chemotherapy appears inconclusive. Here, we show that the detection of CTCs at baseline correlates to overall survival in SCLC, and that persistently detectable CTCs after completion of treatment adds further prognostic value. This suggests that repetitive analysis of CTCs during and after the course of treatment may have a role in the management of SCLC, warranting further studies. Circulating tumor cells (CTCs) may provide a liquid biopsy approach to disease monitoring in small cell lung cancer (SCLC), a particularly aggressive tumor subtype. Yet, the prognostic role of CTCs during and after treatment in relation to baseline remains ill-defined. Here, we assessed the value of longitudinal CTC analysis and the potential of low-molecular-weight heparin (LMWH) to reduce CTC abundance in SCLC patients from a randomized trial (RASTEN). Blood samples were collected at baseline, before chemotherapy Cycle 3, and at 2-month follow-up from 42 patients in total, and CTCs were quantified using the FDA-approved CellSearch system. We found a gradual decline in CTC count during and after treatment, independently of the addition of LMWH to standard therapy. Detectable CTCs at baseline correlated significantly to reduced survival compared to undetectable CTCs (unadjusted hazard ratio (HR) of 2.75 (95% CI 1.05–7.20; p = 0.040)). Furthermore, a persistent CTC count at 2-month follow-up was associated with a HR of 4.22 (95% CI 1.20–14.91; p = 0.025). Our findings indicate that persistently detectable CTCs during and after completion of therapy offer further prognostic information in addition to baseline CTC, suggesting a role for CTC in the individualized management of SCLC. [ABSTRACT FROM AUTHOR]

Objectives: Our research aimed to evaluate the effectiveness of first‐line immune checkpoint inhibitors (ICIs) with etoposide and platinum (EP) for extensive‐stage small cell lung cancer (ES‐SCLC) and identify prognostic factors, as real‐world outcomes and the inconsistency of PD‐1 and PD‐L1 inhibitors are uncertain. Methods: We selected ES‐SCLC patients in three centers and conducted a propensity score‐matched analysis. The Kaplan–Meier method and Cox proportional hazards regression were conducted to compare the survival outcomes. We also performed univariate and multivariate Cox regression analyses to investigate predictors. Results: Among 236 patients included, 83 pairs of cases were matched. The EP plus ICIs cohort had a longer median overall survival (OS) (17.3 months) than the EP cohort (13.4 months) (hazard ratio [HR], 0.61 [0.45, 0.83]; p = 0.001). The median progression‐free survival (PFS) was also longer in the EP plus ICIs cohort (8.3 months) than in the EP cohort (5.9 months) (HR, 0.44 [0.32, 0.60]; p < 0.001). The EP plus ICIs group had a higher objective response rate (ORR) (EP: 62.3%, EP + ICIs: 84.3%, p < 0.001). Multivariate analysis presented that liver metastases (HR, 2.08; p = 0.018) and lymphocyte–monocyte ratio (LMR) (HR, 0.54; p = 0.049) were independent prognostic factors for OS, and performance status (PS) (HR, 2.11; p = 0.015), liver metastases (HR, 2.64; p = 0.002), and neutrophil‐lymphocyte ratio (NLR) (HR, 0.45; p = 0.028) were for PFS in patients with chemo‐immunotherapy. Conclusion: Our real‐world data demonstrated that ICIs with chemotherapy as the first‐line setting for ES‐SCLC are effective and safe. PS, liver metastases, and inflammatory markers could serve as valuable risk factors. [ABSTRACT FROM AUTHOR]

Background: To investigate whether whole‐brain radiotherapy (WBRT) decreases lymphocyte counts and evaluate the impact of treatment‐related lymphopenia on survival in patients with brain metastasis. Methods: Medical records from 60 small‐cell lung cancer patients treated with WBRT from January 2010 to December 2018 were included in the study. Total lymphocyte count (TLC) was obtained pre and post treatment (within 1 month). We performed linear and logistic regression analyses to identify predictors of lymphopenia. The association between lymphopenia and survival was analyzed using Cox regression analysis. Results: Thirty‐nine patients (65%) developed treatment‐related lymphopenia. The median TLC decrease was −374 cells/μL (interquartile range −50 to −722, p < 0.001). Baseline lymphocyte count was a significant predictor of TLC difference and percentage change in TLC. Logistic regression analysis found male sex (odds ratio [OR] 0.11, 95% confidence interval [CI] 0.00–0.79, p = 0.033) and higher baseline lymphocyte count (OR 0.91, 95% CI 0.82–0.99, p = 0.005) were associated with a lower risk of developing ≥grade 2 treatment‐related lymphopenia. Cox regression analysis showed that age at brain metastasis (hazard ratio [HR] 1.03, 95% CI 1.01–1.05, p = 0.013), ≥grade 2 treatment‐related lymphopenia, and percentage change in TLC (per 10%, HR 0.94, 95% CI 0.89–0.99, p = 0.032) were prognostic factors of survival. Conclusions: WBRT decreases TLC and the magnitude of treatment‐related lymphopenia is an independent predictor of survival in small‐cell lung cancer patients. [ABSTRACT FROM AUTHOR]

One year following bladder cancer surgery, a 65‐year‐old man had computed tomography (CT) that revealed bilateral pulmonary nodules. Pulmonary wedge resections were performed after the nodules were found to grow in follow‐up. Unusually, we found that these two lesions were not homologous, nor were they metastases from prior bladder cancer, and therefore, synchronous double primary lung cancer (sDPLC) was diagnosed. The immunohistochemical findings excluded the possibility of bladder cancer metastasis, but could not determine whether they were from the same source. Next generation sequencing (NGS) supported the diagnosis sDPLC because they amply demonstrated the two sources' distinct origins. Finally, after discussion with pathologists, this patient was diagnosed as small cell lung carcinoma (SCLC) and received postoperative EP chemotherapy. We also documented a few rather uncommon alterations that might serve as a foundation for further investigation. This case suggests that in addition to immunohistochemical, NGS is also helpful to clarify the etiology and refine the pathological classification of tumors, which has guiding significance for the establishment of precise diagnosis and optimal treatment. [ABSTRACT FROM AUTHOR]

Undifferentiated small round cell sarcomas (URCSs) represent a diagnostic challenge, and their optimal treatment is unknown. We aimed to define the clinical characteristics, treatment, and outcome of URCS patients. URCS patients treated from 1983 to 2019 at 21 worldwide sarcoma reference centres were retrospectively identified. Based on molecular assessment, cases were classified as follows: (1) CIC -rearranged round cell sarcomas, (2) BCOR::CCNB3 -rearranged round cell sarcomas, (3) unclassified URCSs. Treatment, prognostic factors and outcome were reviewed. In total, 148 patients were identified [88/148 (60%) CIC -rearranged sarcoma (median age 32 years, range 7–78), 33/148 (22%) BCOR::CCNB3 -rearranged (median age 17 years, range 5–91), and 27/148 (18%) unclassified URCSs (median age 37 years, range 4–70)]. One hundred-one (68.2%) cases presented with localised disease; 47 (31.8%) had metastases at diagnosis. Male prevalence, younger age, bone primary site, and a low rate of synchronous metastases were observed in BCOR::CCNB3- rearranged cases. Local treatment was surgery in 67/148 (45%) patients, and surgery + radiotherapy in 52/148 (35%). Chemotherapy was given to 122/148 (82%) patients. At a 42.7-month median follow-up, the 3-year overall survival (OS) was 92.2% (95% CI 71.5–98.0) in BCOR::CCNB3 patients, 39.6% (95% CI 27.7–51.3) in CIC -rearranged sarcomas, and 78.7% in unclassified URCSs (95% CI 56.1–90.6; p < 0.0001). This study is the largest conducted in URCS and confirms major differences in outcomes between URCS subtypes. A full molecular assessment should be undertaken when a diagnosis of URCS is suspected. Prospective studies are needed to better define the optimal treatment strategy in each URCS subtype. • Undifferentiated small round cell sarcomas (URCS) represent a therapeutic challenge. • Pathological, clinical and molecular data of these ultra-rare sarcomas are provided. • CIC-rearranged tumours have poor survival compared to BCOR:CCNB3/unclassified URCS. • Translational research and RNA-seq findings are discussed. [ABSTRACT FROM AUTHOR]

Small cell lung cancer (SCLC) is an aggressive malignancy associated with poor prognosis. Metastasis to sites outside the chest at the time of initial diagnosis, such as bone, brain, and liver metastasis have been found in most SCLC patients. Iris metastases from SCLC have rarely been previously reported, and often cause eye pain and blindness in patients. Here, we report a patient with SCLC who presented with iris metastasis in the right eye and metastasis in the left adrenal gland due to disease progression on first-line therapy, which subsequently caused pain and blindness in the right eye. The patient was treated with second-line irinotecan combined with anlotinib and atezolizumab and did not receive any local treatment in the right eye. After only one cycle of treatment, the iris metastases in the right eye were smaller than before, and the visual acuity in the right eye recovered. At the same time, her left adrenal metastases were also significantly smaller than before. Our case suggests that systemic therapy with effective treatment options can similarly improve iris metastases in patients. [ABSTRACT FROM AUTHOR]

Simple Summary: Studies have shown that JUNB and CXCR4 contribute to cell proliferation, migration and invasion, hence claiming an important role in tumor progression and metastasis, in various cancer types, including lung cancer. We have previously reported that JUNB and CXCR4 are overexpressed in circulating and disseminated tumor cells from breast cancer patients and are correlated with worse survival. In the present study, we investigated the expression of JUNB and CXCR4 in circulating tumor cells (CTCs) of non-small-cell lung cancer and small-cell lung cancer patients and determined their clinical significance. Our results showed that both JUNB and CXCR4 were overexpressed in CTCs from lung cancer patients. Furthermore, both proteins were correlated with poor survival in non-small-cell lung cancer patients, while only CXCR4 was associated with worse survival in small-cell lung cancer patients, suggesting that JUNB and CXCR4 are potentially important prognostic biomarkers for lung cancer. In the present study, we evaluated the expression of JUNB and CXCR4 in circulating tumor cells (CTCs) of lung cancer patients and investigated whether these proteins have prognostic clinical relevance. Peripheral blood from 30 patients with non-small-cell lung cancer (NSCLC) was filtered using ISET membranes, and cytospins from 37 patients with small-cell lung cancer (SCLC) were analyzed using confocal and VyCAP microscopy. Both JUNB and CXCR4 were expressed in the vast majority of lung cancer patients. Interestingly, the phenotypic patterns differed between NSCLC and SCLC patients; the (CK+/JUNB+/CXCR4+) phenotype was present in 50% of NSCLC vs. 71% of SCLC patients. Similarly, the (CK+/JUNB+/CXCR4–) was present in 44% vs. 71%, the (CK+/JUNB–/CXCR4+) in 6% vs. 71%, and the (CK+/JUNB–/CXCR4–) phenotype in 38% vs. 84%. In NSCLC, the presence of ≥1 CTCs with the (CK+/JUNB+/CXCR4+) phenotype was associated with worse progression-free survival (PFS) (p = 0.007, HR = 5.21) while ≥2 with poorer overall survival (OS) (p < 0.001, HR = 2.16). In extensive stage SCLC patients, the presence of ≥4 CXCR4-positive CTCs was associated with shorter OS (p = 0.041, HR = 5.01). Consequently, JUNB and CXCR4 were expressed in CTCs from lung cancer patients, and associated with patients' survival, underlying their key role in tumor progression. [ABSTRACT FROM AUTHOR]

A 77-year-old woman with suspected lung carcinoma had multiple bladder masses and lymphadenopathy outside the normal urinary bladder drainage area. Fine needle aspiration and immunocytochemistry of the cervical lymph node complex and transurethral biopsy of the bladder masses confirmed metastatic small-cell neuroendocrine carcinoma. Contribution: Clinical correlation, imaging findings, tumour markers and immunohistochemistry are necessary for metastatic bladder tumour work-up. [ABSTRACT FROM AUTHOR]

Introduction: Unusual metastatic sites of renal cell carcinoma (RCC) are not infrequent. We report a rare case of solitary pharyngeal metastasis as first presentation of RCC. Case description: A 74 years-old man was referred to our hospital due to rapidly progressive dyspnoea and dysphagia. Physical examination showed a large right para-pharyngeal mass. Imaging findings showed a 5.5 cm mass, suspicious for malignancy, which extended to right para and retro-pharyngeal spaces with compression of the major right cervical vessels, C2-C3 vertebral bodies osteolysis, dural sac compression and dislocation. Futhermore, a small (2.6 × 2 cm) mass located at the upper pole of the right kidney was shown. Patient underwent partial trans-oral removal of the mass. Pathological examination and immunochemistry resulting strongly suggestive for metastatic RCC. Considering the metastatic stage of the tumour and the rapidly progressive clinical worsening with poor performance status, we offered the patient a palliative treatment with tyrosine kinase and cytoreductive radiotherapy on vertebral bodies. The patient developed a rapidly progressive multifocal metastatic disease and died 4 months after the presentation. Conclusion: We think that our case is noteworthy for some aspects. Firstly, pharyngeal localizations of RCC are very rare and this is the first case of solitary pharyngeal metastasis. Secondly, this metastatic lesion was really particular because it was synchronous and twice as big than the primary tumour. Thirdly, this case is consistent with previous evidence that synchronous compared with metachronous metastasis RCC is associated with adverse effect on outcome and response to targeted treatment. [ABSTRACT FROM AUTHOR]

Pulmonary neuroendocrine neoplasms (PNENs) are currently classified into four major histotypes, including typical carcinoid (TC), atypical carcinoid (AC), large cell neuroendocrine carcinoma (LCNEC), and small cell lung carcinoma (SCLC). This classification was designed to be applied to surgical specimens mostly anchored in morphological parameters, resulting in considerable overlapping among PNENs, which may result in important challenges for clinicians' decisions in the case of small biopsies. Since PNENs originate from the neuroectodermic cells, epithelial-to-mesenchymal transition (EMT) gene expression shows promise as biomarkers involved in the genotypic transformation of neuroectodermic cells, including mutation burden with the involvement of chromatin remodeling genes, apoptosis, and mitosis rate, leading to modification in final cellular phenotype. In this situation, additional markers also applicable to biopsy specimens, which correlate PNENs subtypes with systemic treatment response, are much needed, and current potential candidates are neurogenic EMT genes. This study investigated EMT genes expression and its association with PNENs histotypes in tumor tissues from 24 patients with PNENs. PCR Array System for 84 EMT-related genes selected 15 differentially expressed genes among the PNENs, allowing to discriminate TC from AC, LCNEC from AC, and SCLC from AC. Functional enrichment analysis of the EMT genes differentially expressed among PNENs subtypes showed that they are involved in cellular proliferation, extracellular matrix degradation, regulation of cell apoptosis, oncogenesis, and tumor cell invasion. Interestingly, four EMT genes (MAP1B, SNAI2, MMP2, WNT5A) are also involved in neurological diseases, in brain metastasis, and interact with platinum-based chemotherapy and tyrosine–kinase inhibitors. Collectively, these findings emerge as an important ancillary tool to improve the strategies of histologic diagnosis in PNENs and unveil the four EMT genes that can play an important role in driving chemical response in PNENs. [ABSTRACT FROM AUTHOR]

Introduction: Unresectable and metastatic small cell carcinoma of the prostate (SCPC) is a rare and aggressive disease that is under-represented in clinical trials. We carried out a retrospective chart review of metastatic or unresectable SCPC patients at British Columbia (BC) Cancer centers, studying diagnosis and treatment patterns. Methods: Drug-dispensing records from the six BC Cancer centers were obtained from 2002-2017. For each patient, information was collected on baseline information prior to therapy and for each line of treatment. Treatments at each line were compared regarding time to progression and overall survival by Kaplan-Meier curves. Results: Forty-one patients received treatment; 65.6% had metastatic disease and 61% had pure small cell carcinoma. Median time from treatment to death was 10 months (95% confidence interval [CI] 6-16). Patients with initially prostate-confined disease had a better median overall survival (mOS) of 21 months (95% CI 13-34) compared to those with initially locally advanced (mOS 19 months, 95% CI 5-37) and metastatic disease (mOS 8 months, 95% CI 6-10) (log-rank p=0.0364). All patients received either cisplatin- or carboplatin-based combination chemotherapy as the first-line treatment and 36.7% received second-line therapy. Time to second-line therapy was eight months for those who presented with metastatic SCPC, compared to 13 months for those with initial non-metastatic SCPC. Conclusions: This single-province, multi-institution cohort reports data on unresectable and metastatic SCPC and highlights the poor prognosis of this rare disease entity. [ABSTRACT FROM AUTHOR]

Background: Cutaneous metastases from non‐cutaneous neuroendocrine neoplasms are rare; however, distinction from primary neuroendocrine carcinomas of the skin (Merkel cell carcinoma) guides clinical management. Methods: We performed a retrospective review from September 1, 2010 to September 30, 2020 of the histopathologic, immunohistochemical, and clinical characteristics of metastatic neuroendocrine neoplasms to the skin from non‐cutaneous primaries. Results: Fourteen patients were identified for the study (nine males and five females; mean age of 59.5 years). Fifteen skin specimens from 14 patients were available for review. At the time of skin biopsy, a known non‐cutaneous neuroendocrine neoplasm was present in 50% of patients. Primary sites of neuroendocrine carcinoma included lung (n = 5), terminal ileum (n = 2), and one each from prostate, breast, rectum, uterus, esophagus, and sinus, with one unknown (suspected bladder malignancy). Eleven of fourteen patients are dead of disease; one was lost to follow‐up. All 15 specimens showed subcutaneous/deep dermal involvement with six involving the papillary dermis and one involving the epidermis. The tumors ranged from well to poorly differentiated. Two of fifteen specimens showed focal CK20 positivity (one metastatic uterine small cell carcinoma and one metastatic ileal carcinoid). TTF‐1 was performed in 13 specimens and was positive in six, of which two were of non‐pulmonary origin. Conclusions: While immunohistochemical stains, in particular CK20, CK7, and TTF‐1, are integral in the workup of confirming the origin of neuroendocrine tumors found in the skin, results vary and are often non‐specific for a single primary site. Therefore, complete radiologic imaging as well as clinical correlation should be recommended to further aid in the identification of a non‐cutaneous primary neoplasm. [ABSTRACT FROM AUTHOR]

Background: Papillary thyroid carcinoma (PTC) is the most common primary malignant thyroid neoplasm and malignant diagnosis in thyroid aspirates. Metastatic adenocarcinoma of the lung is an under‐recognised mimicker which overlaps cytomorphologically and immunocytochemically with PTC. This case series reviews thyroid aspirates of metastatic lung carcinomas, aiming to address the similarities and methods of differentiating this entity from PTC. Methods: Thyroid aspirates of metastatic lung carcinomas were obtained by a computerised search. Clinico‐cytological features and ancillary test results were reviewed. A literature review was performed for published cases of metastatic lung carcinomas in thyroid aspirates. Results: A total of 14 cases were found, including nine adenocarcinomas, three TTF1‐positive non‐small cell lung carcinomas (NSCLCs), one small cell carcinoma and one squamous cell carcinoma. The adenocarcinomas and TTF1‐positive NSCLCs displayed PTC‐like features including papillae/papillary‐like fronds (n = 6/12, 50%), nuclear grooves (n = 5/12, 41.7%) and inclusions (n = 1/12, 8.3%), chromatin clearing (n = 3/12, 25%), calcifications (n = 3/12, 25%) and multinucleated giant cells (n = 2/12, 16.7%). Useful distinguishing features observed were prominent nucleoli, coarse chromatin, mitosis, and necrosis. TTF‐1 immunocytochemistry was positive in most cases (n = 5/6, 83.3%), while PAX8 and thyroglobulin were consistently negative. EGFR exon 19 deletion was detected on cell block preparation in a single case, corresponding to its lung primary. The literature search yielded 84 cases of metastatic malignancies, with lung carcinomas comprising of 3.6%–33.3% in case series of metastatic malignancies. Conclusion: Metastatic adenocarcinoma of lung and PTC share significant cytomorphological and immunocytochemical similarities. A high degree of caution, meticulous clinico‐cytological assessment and prudent use of ancillary techniques is necessary to avoid potential misdiagnosis. [ABSTRACT FROM AUTHOR]

Umbilical metastasis is a rare event, with a majority being adenocarcinomas. Metastatic squamous cell carcinoma, small cell carcinoma, lymphoma, melanoma, and rarely malignant mesenchymal tumours like leiomyosarcoma can occur as umbilical nodules. These often emerge during a known malignancy, but once in a while they may be an initial presentation of an undetected tumour. An extensive literature search failed to reveal a case of gastrointestinal stromal tumour (GIST) with umbilical metastasis as an initial presentation. We believe that this is an exceptional phenomenon. The diagnosis may easily be missed considering the rarity of this occurrence. A history of primary diagnosis of GIST, when available, is helpful. Here we present cytological findings of metastatic GIST presenting as an umbilical lump, where the diagnosis was reached with the help of limited immunocytochemistry. A timely diagnosis is valuable for locating the primary and initiating surgical management, which may have survival benefits for the patient. This case describes the cytological findings of umbilical metastasis of GIST as an initial presentation, where the diagnosis was reached with the help of limited immunocytochemistry. A timely diagnosis is crucial for locating the primary and initiating surgical management, which may have survival benefits for the patient. [ABSTRACT FROM AUTHOR]

Most parotid metastases have been reported to come from the head and neck; however, cases metastasized from the lung are extremely rare. Missed diagnoses and misdiagnoses occurred quite a few times. Thus, accurately identifying the clinical features of parotid metastasis of lung cancer is important. However, current studies about this issue are mostly case reports, and little is known about the detailed and systematic aspects. We reported three cases of parotid metastases from lung cancer and then systematically searched similar cases through “Pub-Med” and “Web of Science”. Finally, twenty-three patients were included in the study. Eighty-three percent of which were males, and 19 patients were over 50 years old. In all cases with smoking history mentioned, 93% were smokers. The predominant pathological type was small cell lung cancer (SCLC, 13 patients, 56%). Seventeen combined with other site metastasis, while more than half of which were brain metastases. The survival time ranged from 3months-17years, and as for SCLCs, it was only 3months-40months. It can be concluded that clinical features, such as sex, age, smoking history, pathological types, and metastasis patterns, could provide valuable evidence for diagnosis. The lung seems to be the most common primary site of parotid metastases except for head and neck tumors. The two circumstances, SCLC coexisting with Warthin’s tumor and parotid small cell carcinoma with lung metastasis, should be differentiated from parotid metastasis of lung cancer with caution For cases presented as SCLC, more aggressive strategies, such as chemotherapy with immunotherapy and maintenance therapy, may be more suitable. Due to the greater tendency of brain metastasis in such diseases, whole-brain radiation therapy, stereotactic radiosurgery or prophylactic cranial irradiation should be applied to corresponding patients in time. Additionally, lung cancer parotid metastases may be a marker of poor prognosis. [ABSTRACT FROM AUTHOR]

Simple Summary: Therapeutic efficacy of chemotherapy combined with immune checkpoint inhibitors as first-line therapy has been previously demonstrated in extensive-stage small cell lung cancer. However, there are no reports of any cytotoxic drug that is effective as second-line therapy in extensive-stage small cell lung cancer patients previously treated with chemotherapy and immune checkpoint inhibitors as a first-line treatment. In the present study, we retrospectively evaluated patients with extensive-stage small cell lung cancer to clarify whether the previous treatment with chemotherapy and immune checkpoint inhibitors impacts the efficacy and safety of amrubicin as a second-line treatment. This study shows that the efficacy and safety of amrubicin in extensive-stage small cell lung cancer remains unchanged irrespective of previous treatment with chemotherapy and immune checkpoint inhibitors. Adding an immune checkpoint inhibitor to chemotherapy to treat extensive-stage small cell lung cancer is effective. However, there are no reports of an effective second-line treatment in patients previously treated with chemotherapy and immune checkpoint inhibitors as a first-line treatment. Here, we assessed the efficacy and safety of amrubicin as a second-line treatment for extensive-stage small cell lung cancer after chemotherapy and immune checkpoint inhibitor combination therapy. The study enrolled 150 patients with extensive-stage small cell lung cancer. The efficacy and the incidence of adverse events were compared between patients previously treated with immune checkpoint inhibitors and patients without previous immune checkpoint inhibitor treatment. One hundred and twenty-three patients were eligible. There was no difference in objective response rate, time-to-treatment failure, progression-free survival, and overall survival between both groups. The incidence of adverse events was similar in both treatment groups. Pretreatment with immune checkpoint inhibitors was not associated with an increase in amrubicin-related adverse events. This study shows that the efficacy of amrubicin in extensive-stage small cell lung cancer remains unchanged irrespective of previous treatment with immune checkpoint inhibitors. Amrubicin-related adverse events did not increase in patients previously treated with immune checkpoint inhibitors. [ABSTRACT FROM AUTHOR]

Histological transformation from adenocarcinoma to small cell lung cancer (SCLC) occurs ~10% after acquired resistance to epidermal growth factor receptor (EGFR)‐tyrosine kinase inhibitors. Transformed SCLC generally responds well to chemotherapy regimens for SCLC such as platinum plus etoposide. After the response, histological nature and clinical course could be complicated by possible heterogeneity or transformation. Therefore, monitoring rebiospy is desirable to seize its histological nature at that moment. We report a case of EGFR‐mutated adenocarcinoma, where histological transformations from adenocarcinoma and SCLC alternated. In this case, first rebiopsy after gefitinib revealed adenocarcinoma, but second rebiopsy after osimertinib identified SCLC transformation. After failure of platinum plus etoposide, adenocarcinoma‐induced leptomeningeal metastases were controlled by osimertinib reintroduction. Optimal therapies could be provided according to the result of monitoring rebiopsy. [ABSTRACT FROM AUTHOR]

Radiation therapy can cause radiation pneumonitis, organizing pneumonia, and lung fibrosis. Radiation‐induced pseudomembranous bronchitis is a rare condition. Here, we describe a rare case each of pseudomembranous tracheobronchitis and pseudomembrane with total bronchial obstruction which developed after thoracic radiotherapy. A 50‐year‐old man presented paroxysmal severe cough 1 month after concurrent chemoradiotherapy for small‐cell lung cancer. Bronchoscopy revealed a whitish membrane in the trachea and bronchus, which were the fields of radiation. Another 60‐year‐old man complained of dyspnea 7 months after radiation therapy for metastatic lymph node adenocarcinoma. Bronchoscopy demonstrated a membrane with total obstruction of right lower lobar bronchus, which was the area of radiation. The pathological findings of histological examination in both cases demonstrated radiation‐induced pseudomembranous tracheobronchitis. Patients in both cases responded well to steroids and the pseudomembrane disappeared. If patients who have received thoracic radiation therapy complain of persistent cough, bronchoscopy may be helpful. [ABSTRACT FROM AUTHOR]

Sinonasal small cell neuroendocrine carcinoma (SNEC) is an extremely rare and aggressive neoplasm that can arise in the sinonasal region. These tumors are associated with high morbidity and mortality, are difficult to diagnose, and are hard to treat. We describe 2 cases of this poorly understood malignancy and review imaging, pathology, and treatment decisions. A 41-year-old male and a 64-year-old female presented to a tertiary center in 2019 after developing nasal obstruction and were found to have sinonasal masses on imaging. Both biopsies showed strong expression of pancytokeratin with dot-like reactivity and expression of neuroendocrine markers chromogranin and synaptophysin. The findings were diagnostic of SNEC. Staging positron emission tomography/computed tomography and brain MRI were performed, and patients were discussed at a multidisciplinary tumor board. Neither had distant metastatic disease at presentation. One patient had no intracranial or orbital disease and underwent a subtotal endoscopic resection with adjuvant chemoradiation. The other patient demonstrated middle cranial fossa, dural, and orbital involvement as well as cranial nerve V palsy. This patient was treated with induction chemotherapy, followed by concurrent chemoradiation. Both patients are presently alive at 4 months follow-up, but one with persistent local disease and the other distant metastasis. Sinonasal small cell neuroendocrine carcinoma is a rare and poorly understood malignancy with an aggressive clinical course. Continued careful review of pathology and study of molecular features are needed for improved understanding of SNEC, and particularly for head and neck SNEC, to establish a staging system and better formulate treatment protocols. [ABSTRACT FROM AUTHOR]

Key message: We report a very rare case of combined small cell lung carcinoma (C‐SCLC) which presented as persistent cough and was due to endotracheal metastases. Clinicians should be aware of this unusual site of metastases from a C‐SCLC. [ABSTRACT FROM AUTHOR]

Extrapulmonary small cell carcinoma (EPSCC) is a rare cancer with a poor prognosis. It can arise from almost any site and is usually associated with extensive metastasis at the time of diagnosis. Due to the rarity of this cancer, very limited data is available in the literature and most of the recommendations for its evaluation and treatment are based on retrospective studies and expert opinion. This case report shares one such presentation of EPSCC. A 78-year-old male was admitted to the hospital with presenting symptoms of abdominal pain and discoloration of the eyes and urine for 2 months. Initial laboratory investigation revealed obstructive jaundice and leukocytosis. His infectious workup was negative. An ultrasound abdomen was performed, showing multiple liver deposits. He received a computed tomography chest, abdomen, and pelvis with contrast also showing multiple liver deposits highly indicative of metastatic disease. No other obvious abnormality or mass in other visceral organs was reported. He underwent endoscopy and endoscopic retrograde cholangiopancreatography, showing normal pancreatic-biliary ducts. A plastic stent was deployed to help with biliary drainage. A liver biopsy was performed and showed poorly differentiated small cell carcinoma of extrapulmonary origin. His abdominal pain improved after stent placement; however, liver tests continued to worsen. During his hospital stay, he was seen by oncology and given metastatic disease; he was offered palliative chemotherapy. Understanding his poor prognosis, the patient himself opted for comfort care and decided to go home with hospice care. Within days, he became lethargic, likely secondary to hepatic encephalopathy, and expired in the span of the next few days. [ABSTRACT FROM AUTHOR]

Early detection of renal dysfunction can help clinicians plan optimal treatment strategies to manage the underlying cause, such as a paraneoplastic syndrome or tumor lysis syndrome. Effective management of renal dysfunction can help improve overall clinical outcomes of the lung cancer patient. [ABSTRACT FROM AUTHOR]

Malignant effusions can occur in patients with neoplasia. Once a metastatic diagnosis is confirmed, the primary site of origin of malignancy needs to be ascertained. This task can be challenging without a prior history of malignancy. In some patients their effusion may be the initial presentation of an underlying malignancy. Metastases usually present with a dual population of mesothelial and malignant cells. Combining cytomorphologic examination with ancillary testing such as immunocytochemistry can help identify the origin of the foreign malignant cell population. Helpful architectural clues include a single cell pattern, solid cell ball pattern, single file arrangement, papillary formation, psammoma bodies and background mucin. Useful cellular features include the presence of signet ring cells, small cells, pleomorphic and multinucleated giant cells, squamous cells, spindle cells and pigmentation. Rarely, despite an extensive work-up the primary site of origin for a malignant effusion may remain unresolved. This review article will be incorporated finally as one of the chapters in CMAS (CytoJournal Monograph/Atlas Series) #2. It is modified slightly from the chapter by the initial authors in the first edition of Cytopathologic Diagnosis of Serous Fluids. [ABSTRACT FROM AUTHOR]

Combined small-cell carcinoma and squamous cell carcinoma of the larynx is an exquisitely rare and underreported primary tumor the head and neck region, with an English literature review revealing only 17 documented cases. There is limited information on how best to treat these patients oncologically, given the low number of reported cases. A subset of the reported cases also detail a unique local spread of this combined carcinoma, further obscuring the clinical picture of these patients. Here, we detail an 18th case, with nodal metastasis of only one component of the primary tumor, and discuss the published literature surrounding this etiology. [ABSTRACT FROM AUTHOR]