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Yun Liu,1,* Meirong Li,2,* Yan Liu,3 Yu Wan,1 Bo Yang,1 Dan Li,4 Shaohua Wang1 1Department of Pathology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China; 2Department of Pathology, Deyang People’s Hospital, Deyang, Sichuan Province, 618099, People’s Republic of China; 3Department of Pathology, Chengdu Women and Children’s Central Hospital, Chengdu, Sichuan Province, 610073, People’s Republic of China; 4Department of Oncology, Affiliated Hospital of Southwest Medical University, Luzhou, Sichuan Province, 646000, People’s Republic of China*These authors contributed equally to this workCorrespondence: Shaohua Wang, Department of Pathology, the Affiliated Hospital of Southwest Medical University, No. 25, Taiping Street, Luzhou, Sichuan, 646000, People’s Republic of China, Email wangshaohua20006@163.comBackground/Aims: There are currently few reports describing the liquid-based cytological characteristics of small cell neuroendocrine carcinoma of the cervix. This study aimed to retrospectively analyze these features to reduce missed or misdiagnosis.Methods: A total of 11 patients with histologically diagnosed small cell carcinoma of the cervix from three hospitals between 2017 and 2023 were included in this study. The cytological morphology of small cell carcinoma of the cervix and causes of missed or misdiagnosis were analyzed and summarized through a review of clinical data, liquid-based cytology, histology, immunohistochemistry, and human papillomaviruses (HPV) test results.Results: In this study, the positivity rate of preliminary cytological screening was 63.6% (7/11); however, no cases were accurately diagnosed as small cell carcinoma of the cervix. A total of 36.4% (4/11) of small cell carcinoma of the cervix cases were cytologically negative; retrospective cytology found that two of these were false negatives. The main cytological features of small cell carcinoma of the cervix were summarized. Most of the liquid-based cytology smear cells were dense, and almost all cases showed clustered and scattered cytoplasm-scanty tumor cells. The tumor cells were all deeply stained and relatively consistent small cells. Most cases showed typical nuclear molding, chromatin stippling, and no obvious nucleoli. Mild nuclear smears, nuclear fragments, and mitotic figures were seen in most cases.Conclusion: Liquid-based cytology has a high rate of missed diagnosis and misdiagnosis in small cell carcinoma of the cervix. This study confirms that reviewing cytology results can effectively reduce this proportion and that increasing understanding of small cell carcinoma of the cervix morphology is conducive to improving the cytology-based diagnosis rate.Keywords: cervical cytology, small cell carcinoma, cervical cancer, diagnostic rate, neuroendocrine

Background: Small cell carcinoma of cervix (SCCC) is a rare disease. SCCC is highly invasive and prone to distant metastatic spread and lymph node involvement. Here we aim to present a patient and her treatment. Case Presentation: We report 47-year-old patient with history of breast cancer manifesting with abnormal vaginal bleeding diagnosed with SCCC. Patient underwent radical hysterectomy and bilateral salpingo-oophorectomy. Then, she received adjuvant chemoradiation postoperatively. Conclusion: Small cell carcinoma of cervix is an aggressive form of cervical cancer with poor prognosis. Optimal treatment remains unsettled.

Small cell esophageal carcinoma (SCEC) is a poorly differentiated esophageal neuroendocrine neoplasm with a poor prognosis. This study aimed to explore the factors and treatment approaches influencing the prognosis of SCEC. In this retrospective study, we collected data from the 18 Surveillance, Epidemiology, and End Results (SEER) registries cohort between 2004 and 2019, as well as from a Chinese institutional registry covering the period from 2012 to 2022. We assessed the annual percentage change (APC) in incidence of SCEC. Kaplan-Meier and Cox regression analyses were conducted to evaluate survival outcomes. Additionally, nomograms were developed for overall survival (OS) and cancer-specific survival (CSS) in the SEER cohort for SCEC and validated in an independent Chinese cohort. This analysis included 299 SCEC patients from the SEER cohort and 66 cases from the Chinese cohort. During the period of 2004–2019, the incidence of SCEC reached a plateau, with an APC of -1.40 (95% confidence interval [CI]: -4.3 to 1.40, P > 0.05). Multivariable Cox regression analysis revealed that age, distant metastasis, and chemotherapy were independent factors for OS, while distant metastasis and chemotherapy were independent factors for CSS. The nomograms developed for OS and CSS in SCEC exhibited remarkable accuracy and reliable predictive capacity in estimating 1-year, 3-year, and 5-year OS and CSS. SCEC is a rare malignancy with aggressive behavior. Distant metastasis is significantly associated with worse OS and CSS in patients with SCEC. Currently, chemotherapy remains the primary treatment approach for SCEC.

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

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.

Introduction: Multiple Primary Malignant Tumors (MPMT) are two or more distinct primary cancers in a single patient, either occurring simultaneously (synchronous) or at different times (metachronous). MPMTs are very rare, with an incidence of 0.73% to 11.7% among cancer patients. Breast and lung cancers are the most common malignancies in women, but their coexistence as MPMT is uncommon. Case presentation: We report the case of a 51-year-old non-smoking woman who had a productive cough with bloody sputum for a week, after a two-month history of dry cough. She was diagnosed with a high-grade, poorly differentiated non-keratinizing squamous-cell carcinoma in the right lung. A PET scan also revealed a poorly defined soft tissue mass in the central sector of the right breast, which was confirmed to be a primary invasive ductal carcinoma. Discussion: The etiology and pathogenesis of MPMT are unclear, but several factors such as genetic predisposition, environmental exposure, immunodeficiency, and treatment-related effects have been proposed. The diagnosis and management of MPMT are challenging, as they require careful evaluation of each tumor and individualized treatment plans. The prognosis of MPMT depends on the stage and histology of each tumor, as well as the patient’s performance status and comorbidities. Conclusion: This case report highlights the rare occurrence of synchronous primary malignancies in the lung and breast, underreported in the medical literature. This case adds to the existing knowledge of MPMT and may stimulate further research on this topic. Clinicians should be aware of the possibility of MPMT in cancer patients and perform thorough investigations to rule out secondary or metastatic tumors.

Introduction Small cell carcinoma (SCC) of the kidney is extremely rare. Although the majority of patients with advanced renal small cell carcinoma were treated with a combination of cisplatin and etoposide, the efficacy was limited. We report the first case with renal small cell carcinoma who received nivolumab and cabozantinib. Case presentation A 57‐year‐old woman was referred to our hospital with a massive left kidney mass and several bone, lymph nodes, liver, and lung metastases. A left renal mass biopsy made the diagnosis of small cell carcinoma. Nivolumab and cabozantinib were used in combination therapy. The tumors were stable during the treatment for 4 weeks. However, the treatment was halted due to a serious adverse event, immune‐related hemophagocytic lymphohistiocytosis. Although immune‐related hemophagocytic lymphohistiocytosis was resolved with corticosteroids, the patient died 3 months after the initiation of nivolumab and cabozantinib. Conclusion We reported the first case of renal small cell carcinoma treated with nivolumab and cabozantinib.

Neuroendocrine small cell cervical carcinoma is an aggressive cancer which accounts for approximately 1 to 3% of all cervical neoplasms. Therapy must be altered in pregnancy to optimize maternal–fetal outcomes. A 39-year-old woman presented for a routine prenatal visit and was noted to have a grossly abnormal cervix. Cervical biopsies confirmed small cell carcinoma. At 19 weeks' gestation, chemotherapy was initiated. The patient delivered at 34 weeks' gestation to initiate radiation therapy. Six months later, she was diagnosed with metastatic disease and died from cancer complications. In pregnancy, treatment modalities for small cell cervical carcinoma are based on the patient's gestational age at diagnosis. While aggressive early treatment is preferred, platinum-based chemotherapy can be initiated in the second trimester and radiation therapy delayed until delivery. Small cell cervical carcinoma complicating pregnancy requires aggressive treatment. Chemotherapy in the second trimester with planned delayed radiation therapy, may optimize fetal outcomes.

Non-urothelial tumors account for less than 5% of all bladder malignant neoplasms. The most common non-urothelial tumor is squamous cell carcinoma, often found in the Middle East (about 30% of all cases of bladder cancer BC) due to the spread of schistosomiasis. The glandular type is the second most common non-urothelial morphological variant; it includes 5 tumor subtypes (intestinal, mucinous, signet ring cell, mixed, and adenocarcinoma not otherwise specified). The neuroendocrine variant is divided into 4 subgroups (small cell, large cell, highly differentiated, and paragangliomas), of which small cell is the most common, though still rare, and accounts for only about 1% of all BCs. The article presents the clinical cases of three rare BC subtypes: squamous cell, glandular, and neuroendocrine. In the first clinical case, a radical cure of a patient with signet ring cell BC was described: at the first stage, the bladder, prostate, and vesicles were removed with a cystoplasty using a small intestine segment according to the Bricker technique with an extended pelvic lymph node dissection; the second stage included 8 courses of adjuvant drug treatment according to the XELOX regimen. In the second clinical case, the treatment of the metastatic neuroendocrine BC was described using the following regimens: EP (etoposide + cisplatin), carboplatin + irinotecan, GemOx (gemcitabine + oxaliplatin). The third clinical case described a patient with bladder squamous cell carcinoma. The stage I treatment was based on the GC regimen; at stage II, the bladder, prostate, and vesicles were removed with intestinal orthotopic cystoplasty and extended lymph node dissection; due to progression revealed during the follow-up examination, the patient received another GC course. Although non-urothelial BCs are very rare, studies are currently being conducted on the effectiveness of immunotherapy and targeted therapy in treating this cohort of patients.

Abstract Background Urothelial carcinoma is a major subtype of bladder cancer and small cell carcinoma (SCC) is a rare type of cancer in clinical practice. Pathologic collision of urinary bladder urothelial carcinoma with SCC is not common in clinical settings. Case presentation Here, we report a patient with high-grade papillary carcinoma which changed to collision tumor with SCC. The patient underwent radical cystectomy; however, neck and mediastinum lymph nodes metastases were detected 11 months after the operation. The lymph nodes were diagnosed pathologically as SCC. Chemoradiotherapy was subsequently prescribed. Unfortunately, this patient died of COVID-19 in early 2023. Discussion We hypothesized the mechanism underlying this pathological transformation. For patients with urothelial bladder cancer, pathological analysis should be conducted to allow standardized and persistent treatment. Moreover, drugs should be selected depending on the type of pathology, especially for patients who develop relapse, since collision tumor or other pathological tumors may be present. Conclusions We recommend that radical cystectomy be performed early enough for patients with non-muscle invasive bladder cancer, who are at a high risk of tumor recurrence. However, this conclusion needs to be validated in a larger number of patients.

An undifferentiated carcinoma (UC) of the gall bladder behaves aggressively and has a grave prognosis. Small cell type undifferentiated carcinoma of the gall bladder is a rare variant. This paper reports a case of UC of gall bladder with PAS-positive diastase- resistant eosinophilic hyaline globules present as liver mass (on imaging) in a male patient. The microscopic findings of the liver and gall bladder after a right tri-segmentectomy showed an un-differentiated malignant neoplasm composed of cells with round to oval nuclei, prominent nucleoli, and scanty neoplasm. No definite cell pattern was identified with these neoplastic cells. A section from the gall bladder revealed a tumor arising from the lining epithelium and infiltrating through the muscularis. This tumor was infiltrating the adherent liver tissue directly and forming a mass of undifferentiated malignant cells. The focal area within the tumor mass showed the presence of PAS-positive, diastase-resistant, eosinophilic hyaline globules within the neoplastic cells. The immunohistochemistry test was diffusely positive for perinuclear anti-neutrophil cytoplasmic antibodies and negative for chromogranin, vimentin, Desmin, alpha-fetoprotein, leukocyte common antigen, CD34, and bcl2. When the clinical and radiological data are inconclusive, careful analysis of the histological and immunophenotypic features is needed to make the final diagnosis of UC of the gall bladder. The biological behavior and prognosis of this tumor remain unclear because of its rarity. Further studies will be needed to understand the characteristics of this deadly tumor and to establish an effective therapy for it.

Introduction Small‐cell carcinoma of the urinary bladder has a poor prognosis, and no standard treatment has been established. We encountered a case of a patient with metastasis in which complete response and long‐term survival were obtained by treating the primary lesion with a combination of irinotecan, carboplatin chemotherapy, and radiation therapy. Case presentation An 83‐year‐old man was diagnosed with a bladder tumor with liver metastasis. Small‐cell carcinoma was diagnosed via transurethral resection. Second‐line chemotherapy with irinotecan and carboplatin and irradiation of the primary lesion were significantly effective. The imaging evaluation showed a complete response. The therapeutic effect was maintained for 1 year, even after the discontinuation of chemotherapy. Conclusion Irinotecan and carboplatin should be considered for the treatment of small‐cell carcinoma of the bladder. Irradiation of the primary lesion may also be useful if the extent of metastasis is low.

Abstract An 83‐year‐old Japanese man visited our hospital with dyspnea and general fatigue. Computed tomography (CT) revealed a tumor in the anterior mediastinum, bilateral pleural effusion, pericardial fluid, and multiple liver nodules. We performed a CT‐guided tumor biopsy, and the patient was diagnosed with thymic small‐cell carcinoma, Masaoka–Koga stage classification IVb. The patient received four cycles of carboplatin and etoposide, and all lesions disappeared on CT. However, after 6 months, CT revealed a recurrent tumor in the anterior mediastinum. After one cycle of rechallenge chemotherapy, we performed extended total thymectomy followed by another three cycles of chemotherapy. More than 2.5 years after the last chemotherapy session, the patient's carcinoma did not recur. Thus, this case suggests that salvage surgery may be a treatment option for local recurrence of thymic carcinoma after complete remission with chemotherapy, even in patients with stage IV cancer.

Abstract Background Small cell bladder carcinoma (SCBC) is a rare and aggressive malignant tumor with no established treatment guidelines. Its treatment algorithm has been based on the small cell lung cancer (SCLC) guidelines. Metastatic SCBC has poor prognosis (even when treated with platinum-based chemotherapy, which is usually used for extensive-disease SCLC). Case presentation Herein, we report a case of a 71-year-old man with SCBC who underwent radical cystectomy and received adjuvant chemotherapy with gemcitabine and cisplatin. However, recurrent tumors were found 6 months postoperatively. The patient was then treated with carboplatin, etoposide, and atezolizumab and achieved complete response. He continues receiving maintenance therapy with atezolizumab monotherapy without any evidence of recurrence over the 12 months follow up. Conclusion To our knowledge, this is the first case of metastatic SCBC where carboplatin, etoposide, and atezolizumab achieved long-term complete response.

Metastatic small cell carcinoma to the breast from the uterine cervix is an extremely rare case. We report a case of a 58-year-old postmenopausal woman who presented with postmenopausal bleeding. Further investigations confirmed the diagnosis of mixed types of squamous and small cell cervical carcinoma. She underwent chemoradiotherapy and brachytherapy. A few months later, she presented with a palpable left breast lump three months after the diagnosis. Diagnosis of metastatic small cell carcinoma of the breast was confirmed by biopsy. Due to its rarity, we report on this case along with its relevant literature review.

Small cell lung cancer (SCLC) and large cell neuroendocrine carcinoma (LCNEC) have recently been grouped as lung neuroendocrine carcinomas (NECs). Because these lung NECs are clinically malignant and their treatment strategies differ from those of non-SCLC, the quality of diagnosis has a significant prognostic impact. The diagnosis of LCNEC requires positive immunohistochemical staining with chromogranin A, synaptophysin, and CD56, along with a morphological diagnosis, and insulinoma-associated protein 1 (INSM1) has been proposed as an additional marker but is still not an ideal or better marker. We investigated Musashi-1 as a novel immunohistochemical marker in 42 patients with SCLCs and 44 with LCNECs who underwent lung resection between 1998 and 2020 at our institution. We found Musashi-1 expression in 98% (41/42) SCLC and in 90% (40/44) LCNEC. These findings were similar to CD56 expression and superior to synaptophysin, chromogranin A, and INSM1. Musashi-1 also tended to show more diffuse and intense staining, especially in LCNEC, with more cases staining > 10% than any other existing markers (Musashi-1, 77%; INSM1, 45%; chromogranin A, 34%; synaptophysin, 41%; and CD56, 66%). In conclusion, we identified Musashi-1 as a novel immunohistochemical staining marker to aid in the diagnosis of lung NEC.

Abstract Background Primary small cell carcinoma (SmCCa) of the ureter is rare. The majority of patients present with visible haematuria. Diagnosis is confirmed by histopathology. Associated hyponatraemia in GU lesion can be due SmCCa can be useful for early diagnosis aggressive ureteric tumors. The current management includes radical surgery or radiotherapy with concomitant chemotherapy to improve survival and quality of life. Case presentation We present a case of a 77 years female who was found to have unilateral hydronephrosis with a 5 cm filling defect in the distal ureter on CT urogram. Further staging showed organ-confined disease. Serum sodium levels were low at presentation. At the time of planned nephroureterectomy (NU), cystoscopy revealed a bladder tumor obstructing the right ureteric orifice. TURBT was performed instead. After TURBT, there was marked hyponatremia and histology was small cell carcinoma (SmCCa). Paraneoplastic SIADH was the likely cause. Neoadjuvant chemotherapy (NACT) followed by radiotherapy (RT) was chosen for definitive treatment. This resulted in an excellent response supported by radiological evidence of almost complete resolution of the tumor. Conclusion The presence of genitourinary lesion and hyponatremia should raise suspicion of paraneoplastic SIADH. The case suggests the emphasis of histological diagnosis of the genitourinary lesion with existing hyponatraemia to provide better outcome with NACT followed by definitive treatment. We share our experience of NACT and RT in the management of ureteric SmCCa extension to the bladder.

Wenru Qin,1,2,* Bing Zou,2,* Xinyu Fan,2,3 Bingjie Fan,2 Shijiang Wang,2 Linlin Wang2 1Department of Oncology, Weifang Medical University, Weifang, Shandong, People’s Republic of China; 2Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, Shandong, People’s Republic of China; 3Department of Oncology, Cheeloo College of Medicine, Shandong University, Jinan, Shandong, People’s Republic of China*These authors contributed equally to this workCorrespondence: Linlin Wang, Department of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jiyan Road 440, Jinan, Shandong, 250117, People’s Republic of China, Tel +86-531-67626142, Email wanglinlinatjn@163.comAbstract: The most common pathologic type of thymic carcinoma (TC) is squamous cell carcinoma (SCC). Small cell carcinoma is relatively rare, accounting for approximately 2% to 5% of all thymic tumors. Histologic transformation of TC has not yet been reported. Available treatments for TC patients who progress after first-line therapy are limited, which contributes to their poor prognosis. We reported an extraordinary case of a 66-year-old man who was diagnosed with thymic small cell carcinoma that transformed into SCC after third-line treatment. Surprisingly, the patient had a progression-free survival (PFS) of 25 months and an overall survival (OS) of 10 years on anlotinib as fourth-line therapy. The tolerance was well. Thus, anlotinib may be a safe and promising treatment for TC patients, especially those who undergo histologic transformation.Keywords: thymic carcinoma, squamous cell carcinoma, small cell carcinoma, histologic transformation, anlotinib

Introduction: In the present era, the classification of lung carcinoma is not confined to Small Cell Lung Carcinoma (SCLC) and Non Small Cell Lung Carcinoma (NSCLC). Precise subtyping of lung carcinoma has a direct impact on patient management and prognosis. Further molecular study helps in identifying adenocarcinoma receptors, such as Epidermal Growth Factor Receptor (EGFR) and Anaplastic Lymphoma Kinase (ALK), which are useful in targeted therapy. Aim: To assess the role of Immunohistochemistry (IHC) in accurate diagnosis and subtyping of lung carcinoma and to analyse the prevalence of EGFR mutations and ALK rearrangement in lung adenocarcinoma. Materials and Methods: A retrospective hospital-based, observational study was conducted at the Department of Pathology of American International Institute of Medical Sciences, Udaipur, Rajasthan from January 2020 to August 2021. Total of 105 cases of guided core needle biopsies from lung and bronchoscopic biopsies were included. IHC markers were applied based on histopathological diagnosis from a panel of p63, Cytokeratin 7 (CK7), AE1/AE3, Thyroid Transcription Factor (TTF1), Napsin A, p40, synaptophysin, chromogranin, CD56 and Ki67. Adenocarcinoma cases were further analysed for EGFR mutations and ALK rearrangements. Data was tabulated and analysed statistically using Microsoft Excel to determine the percentage frequency distribution of cases. Results: Among 105, there were 88 males and 17 females and the mean age of the population was 60.57 years. The most prevalent subtype of lung malignancy was squamous cell carcinoma (44.7%) followed by adenocarcinoma (29.5%). The diagnostic accuracy of squamous cell carcinomas and adenocarcinomas on morphology was 93.1% and 84.6%, respectively and for small cell carcinoma it was 100%. Amongst 28 cases of adenocarcinoma, EGFR mutation was found in 46.42% cases whereas ALK mutation was found only in 21.42% cases. Conclusion: The study highlights the importance of IHC, and a substantial prevalence of EGFR mutations was found in patients with lung carcinoma.

Abstract Introduction Notwithstanding the diagnostic and therapeutic advancements, the incidence of cardiac metastases has increased in recent decades. Lung cancers are the most common primary malignant neoplasms with cardiac metastasis potential. The clinical presentation of cardiac metastases is either silent or vague, and largely depends on the infiltrated location and tumor burden. Although arrhythmias are not uncommon in metastatic cardiac tumors, complete heart block is relatively a rare manifestation. We present a case of complete heart block due to a metastatic small cell carcinoma in a 67-year-old male of African origin. Case presentation A 67-year-old male of African origin from rural Tanzania was referred to us for expert management. He is a retired agromechanic with over 30 years exposure to asbestos-containing brake linings. His past medical history was unremarkable, but the family-social history was evident for a heavy alcohol intake and chronic cigarette smoking. He presented with a 24-week history of progressive shortness of breath and an 8-week history of recurrent syncopal attacks coupled with a significant weight loss. He had normal echocardiographic findings, however, the electrocardiogram showed features of complete heart block. Chest X-ray showed a homogeneous opacification on the right side and computed tomography scan revealed a solid right lung mass with metastases to the liver, heart, bowels, and bone. He underwent bronchoscopy, which revealed an endobronchial mass obstructing the bronchus intermedius. Histological examination of a section of lung biopsy taken during bronchoscopy confirmed the diagnosis of a small cell carcinoma. The patient underwent dual chamber pacemaker implantation with successful sinus rhythm restoration. He made an informed refusal of chemotherapy and inevitably died 18 months post pacing. Conclusions Despite the advancements in medical diagnostics and management, lung cancers are often diagnosed in advanced stages, with an inevitable grave prognosis. Small cell carcinoma has the potential to metastasize to the heart, resulting in complete heart block.

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

Small cell carcinoma is associated with a number of paraneoplastic syndromes. We report a case of a 42-year-old female who presented with primary laryngeal small cell carcinoma associated with concurrent paraneoplastic dermatomyositis and paraneoplastic angioedema secondary to acquired C1 esterase inhibitor deficiency. The patient required extensive treatment for her dermatomyositis including high-dose corticosteroid therapy and intravenous immunoglobulin followed by steroid-sparing disease-modifying immunosuppression. Her angioedema also required multiple lines of therapy including bradykinin inhibitors and human recombinant C1 esterase. We believe this is the first reported case of either of these paraneoplastic syndromes arising from an extrapulmonary small cell carcinoma and highlights the difficulty of its initial diagnosis as well as concurrent management.

The review shows the features of rare tumors extrapulmonary small cell carcinomas (EPSCC). The possible approaches for the treatment of this unfavorable group of tumors are discussed. EPSCC can occur in every organ. The clinical course and morphology of EPSCC are similar to small lung cell carcinoma (SCLC). EPSCC belongs to the group of low-grade neuroendocrine tumors with high proliferative activity. There are a small number of publications in the literature concerning EPSCC. Basically, these publications concerning the various clinical cases with comments. Most often, EPSCC occurs in the female genital tract, gastrointestinal tract, genitourinary SCC and known cases of SCC of the head and neck. The cases concerning SCC in other organs are also described. For the treatment of EPSCC are usually applied guidelines developed for SCLC, and several publications on the use of immunotherapy in the treatment of EPSCC have already appeared. The analysis of the available literature let us suggest EPSCC is a big problem that requires a more in-depth study and consensus guidelines adoption for the management of these patients.

Small cell prostate neuroendocrine carcinoma (SCPC) is a rare and highly aggressive malignant tumor. We present a case of a 52-year-old Iranian man, presenting with complaints of occasional gross hematuria and perineal pain for 6 months. PSA was 0.8 ng/ml. A digital rectal examination found a huge and hard prostate mass. He underwent a transrectal ultrasound-guided (TRUS) biopsy of the prostate. Histopathology showed high-grade small cell neuroendocrine carcinoma. Immunohistochemical markers were positive for synaptophysin with a Ki67 index of almost 100%. However, CD56 and chromogranin A markers were negative. Magnetic resonance imaging (MRI) of the prostate showed a prostate mass with invasion to the rectum, while contrast-enhanced computed tomography of the thorax, abdomen, and pelvis (CT TAP) ruled out metastasis. A multidisciplinary team discussion was carried out, and a decision was made for concurrent chemotherapy and radiation (cisplatin and etoposide for 4 cycles and 70 Gy, 35 fractions). There is a lack of consensus on the management of SCPC. The main modality of management in advanced (stage IV) disease is chemotherapy. It is a highly aggressive tumor with a poor prognosis and is not responsive to hormonal therapy.

Abstract Background Standard treatments for small cell carcinoma of the cervix (SCCC) have not been established. In this study, we aimed to estimate the optimal treatment strategy for SCCC. Methods This was a multicenter retrospective study. Medical records of patients with pathologically proven SCCC treated between 2003 and 2016 were retrospectively analyzed. Overall survival (OS) was plotted using the Kaplan-Meier method. Log-rank tests and Cox regression analysis were used to assess the differences in survival according to stage, treatment strategy, and chemotherapy regimen. Results Data of 78 patients were collected, and after excluding patients without immunohistopathological staining, 65 patients were evaluated. The median age of the included patients was 47 (range: 24–83) years. The numbers of patients with International Federation of Gynecology and Obstetrics (FIGO) 2018 stages I-IIA, IIB-IVA, IVB were 23 (35%), 34 (52%), and 8 (12%), respectively. Of 53 patients who had undergone chemotherapy, 35 and 18 received SCCC and non-SCCC regimens as their first-line chemotherapy regimen, respectively. The 5-year OS for all patients was 49%, while for patients with FIGO stages I-IIA, IIB-IVA, IVB, it was 60, 50, and 0%, respectively. The 5-year OS rates for patients who underwent treatment with SCCC versus non-SCCC regimens were 59 and 13% (p

Abstract Background Paraneoplastic neurologic syndromes (PNS) are rare, however, are important to recognize as oftentimes they precede the detection of an occult malignancy. Our case highlights a rare circumstance of paraneoplastic radiculoneuropathy and the importance of recognizing PNS in antibody negative disease, as is the case in up to 16% of sensory neuronopathies, and the process of excluding other etiologies. Case presentation We discuss a 51-year-old man who presented with asymmetric subacute sensorimotor deficits in the lower limbs. Initial clinical examination showed weakness throughout the right lower limb and normal strength on the left with objective numbness in a mixed dermatomal and stocking-glove distribution. Electrophysiology was consistent with axonal sensorimotor neuropathy. Cerebrospinal fluid showed pleocytosis and elevated protein. Intravenous immunoglobulin treatment was given with some improvement in pain symptoms but no measurable motor improvement. Following clinical and electrophysiologic deterioration the patient was transferred to a tertiary centre. Magnetic resonance imaging of the spine showed smooth enhancement of the ventral caudal nerve roots. Chest computed tomography revealed left lower vascular scarring. Further positron emission tomography scan imaging identified fluorodeoxyglucose avid right lung lymphadenopathy. Bronchoscopy-guided biopsy revealed small cell lung carcinoma. Onconeural and antiganglioside antibodies were negative. The patient was then transferred to a medical oncology ward where he underwent chemoradiotherapy and subsequently experienced improvement in his motor function, supporting that his neurological condition was indeed secondary to a paraneoplastic process. Conclusions Onconeural negative paraneoplastic radiculoneuropathy can precede diagnosis of small cell lung carcinoma. If considered early and adequately investigated, it can allow earlier diagnosis and treatment of underlying malignancy, improving overall and neurological prognosis.

Abstract Background Small cell carcinoma is a highly aggressive and often fatal cancer that most commonly arises in the lung, although it can occasionally arise from other sites, such as the gastrointestinal tract, prostate or cervix. Cardiac involvement, however, is extremely uncommon and therefore has been poorly documented in the literature. Case presentation We describe a rare case of a 31-year-old male with small cell carcinoma presenting as a massive, 15-cm cardiac tumor invading the bilateral atria, interatrial septum, and pericardium without an apparent primary malignancy on PET CT and cardiac MRI. With extensive tissue necrosis, traditional methods of obtaining a right atrial endomyocardial biopsy via internal jugular venous access failed and a diagnosis was made via endoscopic ultrasound guided transesophageal fine needle aspiration of the left atrial mass. Due to the extensive tumor invasion, the patient was not a suitable candidate for surgical resection, debulking, or heart transplant. The patient was treated with etoposide, carboplatin, atezolizumab, and radiation therapy with initial monitoring in the intensive care unit due to concern that tumor lysis may cause rapid cardiac decompensation. Unfortunately, 4 months after chemoradiation therapy, the malignancy progressed and the patient passed away 6 months after the initial diagnosis. Conclusion We describe a rare occurrence of small cell carcinoma presenting as a massive cardiac tumor without apparent primary malignancy. This case demonstrates useful alternative diagnostic strategies and treatment considerations for patients presenting with a rare cardiac mass.

Small cell carcinoma (SmCC) is a type of neuroendocrine tumor commonly originating in the lung, with only about 2-4% of cases arising at extrapulmonary sites. Extrapulmonary SmCC of the head and neck has a poor prognosis and a high rate of distant metastasis. The paranasal sinus is a rare location for extrapulmonary SmCC and only a few related papers have been published to date. We report a rare case of SmCC originating from the sphenoid sinus in a patient with a recurrent pituitary tumor with a literature review.

Neuroendocrine small cell carcinomas (SCCs) are most commonly seen in the lung, and they rarely may arise in the extra pulmonary sites. Small cell neuroendocrine carcinoma of the tongue is an extremely rare entity with only seven cases reported in literature till date. Herein, we present a case of a 59-year-old male with a limited-stage small cell neuroendocrine carcinoma of the base of the tongue. We discuss clinical, pathological, radiological findings, and management of SCC of the base of tongue. Histopathological examination using immunohistochemistry, clinical features, and radiologic findings are all important for the correct diagnosis of extrapulmonary SCCs. As no standard therapeutic regimen exists, it is important to be aware of and to know how to deal with such rare cases.

Lung cancer is one of the most commonly diagnosed cancer types. Studying the molecular changes that occur in lung cancer is important to understand tumor formation and identify new therapeutic targets and early markers of the disease to decrease mortality. Glycosaminoglycan chains play important roles in various signaling events in the tumor microenvironment. Therefore, we have determined the quantity and sulfation characteristics of chondroitin sulfate and heparan sulfate in formalin-fixed paraffin-embedded human lung tissue samples belonging to different lung cancer types as well as tumor adjacent normal areas. Glycosaminoglycan disaccharide analysis was performed using HPLC-MS following on-surface lyase digestion. Significant changes were identified predominantly in the case of chondroitin sulfate; for example, the total amount was higher in tumor tissue compared to the adjacent normal tissue. We also observed differences in the degree of sulfation and relative proportions of individual chondroitin sulfate disaccharides between lung cancer types and adjacent normal tissue. Furthermore, the differences in the 6-O-/4-O-sulfation ratio of chondroitin sulfate were different between the lung cancer types. Our pilot study revealed that further investigation of the role of chondroitin sulfate chains and enzymes involved in their biosynthesis is an important aspect of lung cancer research.

Small-cell carcinomas are highly malignant tumors with neuroendocrine function and which often occur in the lungs. Primary small-cell neuroendocrine carcinomas of the gynecologic tract are extremely rare. This study aimed to evaluate the prevalence of independent predictors related to the prognosis and overall survival of patients with small-cell neuroendocrine carcinomas of the gynecologic tract. Patients with gynecologic small-cell neuroendocrine carcinomas diagnosed between 1973 and 2015 were identified from the Surveillance, Epidemiology, and End Results database. Univariate and multivariate Cox risk regression analyses were performed to determine the independent predictors of overall survival. Overall survival was calculated using the Kaplan–Meier method, and the log-rank test was used for comparison. We included 5,15,393 eligible carcinomas in the present study; the prevalence of gynecologic small-cell neuroendocrine carcinomas was 0.121% (N = 622). Multivariate analysis indicated that advanced age, stage III and IV cancer, and no chemotherapy treatment may be predictors of poor small-cell neuroendocrine cervical carcinoma prognosis. Stage III and IV cancer and lack of surgery, radiotherapy, or chemotherapy were identified as potential predictors of poor prognosis in patients with ovarian small-cell neuroendocrine carcinoma. Kaplan–Meier analysis suggested that the median survival was 19, 11, and 12 months for cervical, ovarian, and endometrial small-cell neuroendocrine carcinomas, respectively. The 1-, 3-, and 5-year overall survival rates were as follows: 58.8, 31.4, and 26.1%, respectively, for small-cell neuroendocrine cervical carcinoma; 46.3, 23.5, and 22.0%, respectively, for ovarian small-cell neuroendocrine carcinoma; and 49.4, 29.4, and 25.9%, respectively, for endometrial small-cell neuroendocrine carcinoma. Our findings indicate that comprehensive and individualized treatment of small-cell neuroendocrine carcinomas of the gynecologic tract may prolong patient survival, although further studies are required.

BackgroundPrimary small cell breast carcinoma (SCBC) is an uncommon malignancy with highly invasive behavior. The aim of this study was to find out more about the incidence, clinicopathologic characteristics and identify potential prognostic factors of SCBC.MethodsData of patients with primary diagnosis of SCBC between 1975 and 2018 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. The incidence after adjustment for age and percentage change per year in incidence were calculated. Disease-specific survival (DSS) and overall survival (OS) were analyzed among these SCBC patients identified from the SEER database. The whole cohorts were randomized into training and validation cohorts as ratio of 7: 3. Cox regression analysis was performed to determine predictors of survival with the training cohorts. Predictive models were constructed with training cohorts, and nomogram validation was performed using receiver operating characteristic curves, concordance indices and calibration curves in both training and validation cohorts.Results323 SCBC patients were enrolled finally during the research period. The overall incidence after adjustment for age between 1990 and 2018 was 0.14 per million per year, and the prevalence of the incidence has plateaued. Most of these tumors were poorly differentiated or undifferentiated. The most prevalent presenting stage was Stage II. Patients identified in this study were randomly divided into training (n = 226) and testing (n = 97) cohorts. Multivariate Cox proportional hazards model showed that chemotherapy, surgery and stage were important predictors of DSS and OS.ConclusionSCBC is considered an infrequent breast neoplasm with aggressive characteristics. Tumor stage is associated with poor prognosis. Combination of surgery and chemotherapy is the main treatment for SCBC.

Neuroendocrine tumours of the bladder are less common than other histologic types (e.g., urothelial carcinoma, squamous cell carcinoma, adenocarcinoma), constituting 1% of malignant bladder cancers. Based on the “2016 World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs”, neuroendocrine tumours are classified into four subtypes: small cell neuroendocrine carcinoma (SCNC), large cell neuroendocrine carcinoma (LCNC), well-differentiated neuroendocrine tumour (carcinoid tumour) and paraganglioma. SCNC is more common than other subtypes, and LCNC is exceedingly rare in the bladder. Although neuroendocrine tumours are not as common as neuroendocrine neoplasms of the lungs, the differential diagnosis of these tumours remains crucial and should be considered in uropathology. Neuroendocrine tumours of the bladder can present with distinctive morphology and grades, similar to their pulmonary counterparts. The knowledge of this diagnosis is critical to advance the uropathological field and accelerate drug development with inclusion, rather than exclusion, of patients with SCNC and other variants of neuroendocrine tumours of the bladder. Therefore, in this review, the bladder’s clinical and uropathological aspects of neuroendocrine tumours are reviewed. This classification provides a useful platform to discuss the aetiology, pathogenesis, clinical and pathological characteristics and treatment of the neuroendocrine tumours of the urinary bladder. The overall prognosis of urinary bladder neuroendocrine tumours is worse than urothelial carcinoma. Various advances are expected in the clinical characterisation, prognostication and treatment of neuroendocrine tumours of the bladder with the technologies developed in genetic and cellular investigations.

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

Respiratory Papillomatosis is a rare disease in which multiple exophytic squamous wart-like lesions occur within the respiratory tract. Recurrent Respiratory Papillomatosis (RRP) has the potential for malignant transformation to squamous lung cell carcinoma with a dismal prognosis. Most of the prior literature has shown malignant transformation of respiratory papillomatosis into squamous cell carcinoma. Here, we report a rare presentation of respiratory papillomatosis coexisting with small cell carcinoma and a review of relevant literature.

Abstract Background Small cell carcinoma of the prostate is a rare condition with important differences from prostatic adenocarcinoma in terms of clinical and prognostic characteristics. A low prostate-specific antigen and a symptomatic patient, including paraneoplastic symptoms, characterize small cell carcinoma of the prostate. Diagnosis is made on the basis of prostate biopsy, and fluorodeoxyglucose positron emission tomography/computed tomography is often used for staging because up to 60% of patients present with de novo metastatic disease. Patients with metastatic disease are usually treated with platinum-based cytotoxic chemotherapy regimens similar to those used for small cell carcinoma of the lung. However, prognosis remains poor, with a median overall survival of 9 to 17 months despite therapy. Case presentation This report describes a case of an 80-year-old Caucasian patient with lymph node and bone metastatic small cell carcinoma of the prostate following low-dose-rate brachytherapy for a low-risk prostate carcinoma and treated with chemotherapy and immunotherapy. Conclusion Low-dose-rate brachytherapy might be an etiology of small cell prostate cancer.

Herein, we summarize two rare cases of salivary neuroendocrine carcinoma arising in the parotid gland. The patients were a 54-year-old Japanese female and a 74-year-old Japanese male. In the first case, the tumor presented as a typical small cell carcinoma with extensive crush artifacts and nuclear molding, but metastatic foci of the lymph node revealed characteristic ribbon-like trabecular arrangements or sheet-like solid growths of tumor cells with moderate amounts of pale eosinophilic cytoplasm intermingled with bizarre giant or multinucleated cells. In the second case, the tumor was initially diagnosed as a small cell neuroendocrine carcinoma, but a retrospective review revealed that the large cell component was dominant and that it should be strictly considered a mixed large and small cell neuroendocrine carcinoma. The difference in prognoses between these two salivary subtypes remains unknown, and distinction between the small and large cell subtypes of neuroendocrine carcinomas seems merely simple and convenient in the salivary glands.

Small cell carcinoma (SCC) of vagina is extremely rare. The association between this tumor and high-risk HPV infection is unclear. To our knowledge, HPV status has been reported in only 3 previous cases of SCC of vagina. Herein, we present a unique case of vaginal small cell carcinoma with discordant HPV testing results between vaginal and cervical samples. We also review and discuss findings from previously reported cases of small cell carcinoma of vagina.

Abstract Background Primary small cell carcinoma of the bladder (SCCB) is a rare disease of the genitourinary tract and reported limitedly. SCCB is very aggressive and always mixed with other histologic components, but coexistence of SCCB and prostate adenocarcinoma is extremely rare. Cases presentation Two aged males (72 and 58 years) were included in this study. Both of them presented with gross hematuria as initial symptom. Magnetic resonance imaging (MRI) demonstrated protruding lesions in the urinary bladder. Pathological examination after radical cystectomy and prostatectomy showed the concurrence of SCCB and prostate adenocarcinoma. One patient died of liver and lung metastasis 8 months after surgery, and the other patient was still alive after 19 months of follow-up. Conclusion In this paper, we reported two unusual cases of coexistence of SCCB and prostate adenocarcinoma, and reviewed relative literatures with respect to the epidemiology, clinical features, pathologic features, diagnosis, treatment and prognosis of SCCB.

Introduction: Lung carcinomas are one of the most common malignancies and major cause of cancer-related deaths worldwide. India also shares a great burden of this disease. Computed topography (CT)-guided fine-needle aspiration cytology of lung masses is a widely used and simple diagnostic tool which is being replaced increasingly by CT-guided core biopsies. This study shows our experience at a diagnostic center. Materials and Methods: This was a prospective study conducted over a period of 1 year from April 2018 to April 2019 and consisted of 107 cases. After taking detailed history, CT-guided core biopsies were obtained using coaxial needles of 17–19 gauge and biopsy needles of 18–20 gauge. The tissues were then examined histopathologically and the results were noted. Results: Out of the 107 patients, 81.3% were male and 18.7% were female. The age range of patients was from 33 to 92 years, with mean age being 63.7 years. Majority of the lesions were located in the right lung (57.9%). The most common histopathological diagnosis was squamous cell carcinoma 74.7%, followed by small cell carcinoma (12.1%) and adenocarcinoma (9.3%), Hodgkin lymphoma (1.8%), malignant mesothelioma (0.9%), and angiosarcoma (0.9%). Conclusions: This study shows our experience regarding lung malignancies in a diagnostic center in Western India. The epidemiology of lung malignancies seen across the Indian subcontinent reflects in our study. CT-guided core needle biopsies though less invasive may cause complications in some patients. Hence, utmost care should be taken during the procedure to ensure patient safety.

We report a case of recurrent small cell carcinoma of the uterine cervix that showed a complete response to paclitaxel, carboplatin, and bevacizumab (TC + Bev) combination therapy. Small cell carcinoma of the uterine cervix is extremely rare, with an incidence of only 1.3% in Japan, and a poor outcome. The patient was a 62-year-old woman with a chief complaint of irregular vaginal bleeding. Magnetic resonance imaging showed a 10-cm irregular mass from the uterine corpus’s posterior wall to the cervix. Abdominal total hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymph node sampling were performed for suspected uterine sarcoma. Histopathological findings revealed small cell carcinoma with lymph node metastasis. Although 6 cycles of etoposide + cisplatin were performed, para-aortic lymph node recurrence was found 3 months after chemotherapy. Subsequently, the patient received 8 cycles of TC + Bev, which eliminated the metastases. The patient is currently alive at 24 months.

Jinbo Bai,1,* Fen Zhao,2,* Shuang Pan3 1Department of Oral and Maxillofacial Surgery, Shandong Provincial Hospital Affiliated to Shandong University, Jinan, Shandong 250021, People Republic of China; 2Department of Stomatology, Qilu Children’s Hospital of Shandong University, Jinan, Shandong 250022, People Republic of China; 3Department of Orthodontics, Jinan Stomatological Hospital, Jinan, Shandong 250001, People Republic of China*These authors contributed equally to this workCorrespondence: Shuang PanDepartment of Orthodontics, Jinan Stomatological Hospital, 101 Jingliu Road, Jinan, Shandong 250001, People’s Republic of ChinaEmail pansoral@163.comBackground: Small cell carcinoma (SmCC) of the salivary gland is rare, and the characteristics and survival are not well defined due to only case reports or case series being reported. The present study aimed to describe the clinicopathological characteristics and determine the factors associated with survival of this rare cancer.Materials and methods: A population-based study was carried out to investigate clinical characteristics and prognosis of SmCC of the salivary gland using prospectively extracted data from the Surveillance, Epidemiology and End Results (SEER) database between 1988 and 2016.Results: Totally, 198 patients with SmCC of the salivary gland were identified with an average age of 72.6±12.4 and a male to female ratio of 3.4:1. The lesions of most patients (167/198) were located in the parotid gland. The median overall survival (mOS) of all patients is 25.0 months. The 1-, 3-, 5- and 10-year survival rate was 65.7%, 40.9%, 33.0% and 22.7%, respectively. Surgery could prolong significantly the mOS by almost 17.0 months (28.0 months vs 11.0 months; P72 years), lymph node (N3) and distant metastases were independent factors for poor survival, whereas radiotherapy was an independent factor for favorable survival.Conclusion: Small cell carcinoma of the salivary gland is a rare disease, and old age, lymph node and distant metastases, and radiotherapy were significantly associated with prognosis. In order to understand this disease more thoroughly, more cases with adequate information are required.Keywords: small cell carcinoma, salivary gland, outcomes, SEER database

Abstract Background Paraneoplastic limbic encephalitis (PLE) is a rare autoimmune neurological syndrome observed in cancer patients. PLE is difficult to diagnose and presents a variable response to treatment, depending on the characteristics of the tumor and neuronal autoantibodies. Case presentation A 64-year-old, Caucasian, non-smoker man presented with a rapidly developing cognitive impairment, personality change, spatial disorientation, and short-term memory loss associated with anorexia and cervical and inguinal lymph nodes. The 18F-FDG PET scan documented intensely hypermetabolic lymph nodes, which histologically corresponded to a metastasis from a small cell neuroendocrine carcinoma. The brain MRI revealed a high T2-weighted FLAIR signal of the hippocamps, consisted with a PLE. The presence of anti-neuronal Hu antibodies confirmed the diagnosis. The patient underwent plasmapheresis, associated to a systemic chemotherapy resulting in a partial and temporary improvement of the neurological symptoms. Four cycles of intravenous immunoglobulins were also necessary. After six cures of chemotherapy, the lymph node metastases regressed. However, a new anorectal lesion was detected and was histologically confirmed as a primary small cell neuroendocrine carcinoma, which was treated with concomitant chemoradiotherapy. At the end of this treatment, the patient showed a rapid tumor progression leading to his death. Conclusions This case highlights the rare entity, PLE, which is difficult to diagnose and manage. In addition, this is the first published case of PLE associated with an anorectal small cell neuroendocrine carcinoma, which appeared after completion of systemic chemotherapy.

Abstract Objective To determine the accurate age‐adjusted incidence of prostate small cell carcinoma (SCC), update the clinical and pathological characteristics, as well as survival data of prostate SCC from Surveillance, Epidemiology, and End Results (SEER) datasets. Methods A total of 260 patients with prostate SCC were selected from the SEER database of the National Cancer Institute between 2004 and 2015. Age‐adjusted incidence (AAI) rates, the observed and relative survival rates were evaluated over time by the SEER*Stat Software version 8.3.5. Overall survival (OS) rates that stratified by summary stage and treatment effects were evaluated by Kaplan‐Meier method. The significant differences were assessed in a log‐rank test. Univariate and multivariate cox hazard regression analysis were performed to determine independent predictors of OS. Results The incidence of prostate SCC has increased over time. The average age of prostate SCC patients was 70.25 years. More than 90% of tumors were poorly differentiated or undifferentiated. The majority of prostate SCC (77.7%) was at stage IV. 49% of patients had lymph node metastases and 68% of patients presented distant metastases (Compared with 60.5% of patients with distant metastases between 1973‐2003). Interestingly only 23.5% patients had high level PSA (>10 ng/mL). 58.8% of patients underwent chemotherapy, 25.4% of patients were treated by surgery, and 31.9% of patients were treated by radiotherapy. The observed survival rates of 1‐year, 2‐year, and 5‐year were 42.1%, 22.1%, and 12.5%, respectively (Compared with 47.9%, 27.5%, and 14.3%, respectively, between 1973 and 2003). Chemotherapy prolonged the OS of patients with regional (distant) metastases from 3 months (2 months) to 12 months (9 months). Multivariate cox regression analysis showed age, race, and stage were independent prognostic factors for prostate SCC patients. Conclusion Prostate SCC is a highly malignant cancer and our analysis of recent data has shown its incidence is increasing. Incidence rate of metastatic prostate SCC has increased and the survival rates have worsened in recent years. However, chemotherapy shows some survival benefit for prostate SCC patients with regional and distant metastasis over other treatment methods. Further work is needed to understand the reason prognosis of this type prostate cancer is worsening.

BackgroundMelanoma has a wide range of histologic variants and cytomorphologic features that make its diagnosis challenging. Melanoma can also rarely have neuroendocrine markers adding further diagnostic uncertainty particularly given that unrelated tumor types, such as prostate cancer, can also display focal neuroendocrine differentiations.Case presentationOur patient is a 74-year-old Caucasian man found to have a lung mass. Initial biopsy revealed typical microscopic morphology and neuroendocrine differentiation consistent with small cell carcinoma. Despite standard chemoradiation treatment, the patient continued to progress with new metastasis in the brain, liver and bone. Subsequent chest wall biopsy revealed golden-brown pigment associated with melanin. Further tumor immunohistochemistry revealed extensive neuroendocrine differentiation with CD56, synaptophysin, and INSM1, as well as strong immunoreactivity for melanocyte markers including SOX10, S100, PRAME, and MITF, consistent with metastatic melanoma with neuroendocrine differentiation. Genomic testing revealed increased tumor mutational burden and alterations in NF1, BRAF, CDKN2A/B, TERT. The patient was transitioned to checkpoint inhibitor therapy with nivolumab and ipilimumab and had resolution of his intracranial mass and decrease in size of other metastatic lesions.ConclusionOften the combination of anatomic findings such as a lung mass, typical microscopic morphology, and confirmation of neuroendocrine differentiation correctly identifies a patient with small cell carcinoma. However, in a patient who fails to respond to treatment, a broader immunohistochemical workup along with molecular testing with additional tissue may be warranted.

Small cell carcinoma (SCC)/neuroendocrine prostate cancer (NEPC) is a rare and highly aggressive subtype of prostate cancer associated with an AR(androgen receptor)-null phenotype and visceral metastases. This study presents a 44-year-old man originally diagnosed with metastatic hormone-sensitive prostatic adenocarcinoma. After 6-month androgen deprivation therapy (ADT) combined with docetaxel, the patient developed paraplegia. Laminectomy was performed, and a thoracic vertebral biopsy revealed neuroendocrine differentiation and mixed adenocarcinoma. The patient developed liver metastases and experienced stable disease for 4 months following etoposide combined with cisplatin and pembrolizumab. Seminal vesicle biopsy after chemotherapy revealed small-cell cancer. The prostate biopsy specimen also indicated pure SCC. We witnessed the dynamic evolution from pure adenocarcinoma to fully differentiated SCC, leading to obstruction and death. In addition, whole-exome sequencing was performed on both biopsy specimens of the thoracic vertebra at the beginning of castration resistance and that of seminal vesicle after multiple lines of treatment failure. Utilizing phylogenetic reconstruction, we observed that both samples shared a common ancestor clone harboring aberrations in the TP53, RB1, and NF2 genes. We also discovered that driver events in the private subclones of both samples, such as alterations in CDC27 and RUNX1, might have played a significant role in tumor progression or even neuroendocrine differentiation. Tumor biopsy and IHC assessment must be repeated at different stages of progression, because of intrapatient spatial and temporal heterogeneity of adenocarcinoma versus SCC/NEPC. Although, typical treatments including ADT, docetaxel, etoposide, cisplatin, and pembrolizumab provided temporary response, the patient still had a poor prognosis.

Neuroendocrine carcinoma of the cervix is a rare and aggressive form of cervical cancer that presents with frequent metastasis at diagnosis and high recurrence rates. Primary treatment is multimodal, which often includes chemotherapy with or without radiation therapy. There are no data available to guide treatment for recurrence, and second-line therapies are extrapolated from small-cell lung carcinoma data. Close monitoring of these patients for recurrence is paramount. Evaluation of circulating tumor DNA (ctDNA) in the peripheral blood is an attractive approach due to its non-invasive nature. Ultra-low-pass whole-genome sequencing (ULP-WGS) can assess tumor burden and response to therapy and predict recurrence; however, data are lacking regarding the role of ULP-WGS in small-cell carcinoma of the cervix. This study demonstrates a patient whose response to chemotherapy and cancer recurrence was accurately monitored by ctDNA analysis using ULP-WGS and confirmed with radiologic imaging findings.

Nearly all tumors have multiple mutations in cancer-causing genes. Which of these mutations act in tandem with other mutations to drive malignancy and also provide therapeutic vulnerability? To address this fundamental question, we conducted a pan-cancer screen of co-mutation enrichment (looking for two genes mutated together in the same tumor at a statistically significant rate) using the AACR-GENIE 11.0 data (AACR, Philadelphia, PA, USA). We developed a web tool for users to review results and perform ad hoc analyses. From our screen, we identified a number of such co-mutations and their associated lineages. Here, we focus on the RB1/TP53 co-mutation, which we discovered was the most frequently observed co-mutation across diverse cancer types, with particular enrichment in small cell carcinomas, neuroendocrine carcinomas, and sarcomas. Furthermore, in many cancers with a substantial fraction of co-mutant tumors, the presence of concurrent RB1/TP53 mutations is associated with poor clinical outcomes. From pan-cancer cell line multi-omics and functional screening datasets, we identified many targetable co-mutant-specific molecular alterations. Overall, our analyses revealed the prevalence, cancer type-specificity, clinical significance, and therapeutic vulnerabilities of the RB1/TP53 co-mutation in the pan-cancer landscape and provide a roadmap forward for future clinical translational research.

Introduction: Small cell carcinoma of the urinary tract (SCCUT) is a rare finding with poor clinical course. This study sheds light on the molecular subtype and identifies risk factors in patients diagnosed with SCCUT.Methods: Immunohistochemical expression of immunotherapy target programmed death ligand 1 (PD-L1) and luminal (GATA3), basal (p63), and p53 markers are assessed in patients diagnosed with SCCUT. Univariate analysis identified risk factors. Overall survival (OS) is computed using the Kaplan–Meier method.Results: Tissue was available for 70.2% (33/47). All showed a high PD-L1 expression phenotype. p53 is seen in 93.9% (31/33), mostly as overexpression, GATA3 in 45.5% (15/33), and p63 in 57.6% (19/33). For the entire cohort (n = 47), 1-year survival was 59.6%, and the median OS was 17 months. Univariate analysis shows that chemotherapy [hazard ratio (HR) = 0.29, 95% confidence interval (CI) = 0.14–0.61, p = 0.001], radical surgery (HR = 0.37, 95% CI = 0.18–0.76, p = 0.007), and diagnosis of non-pure SCCUT (HR = 0.44, 95% CI = 0.22–0.86, p = 0.02) are favorable prognostic features. Metastasis had negative associations with survival (HR = 2.1, 95% CI = 1.1–4.2, p = 0.03).Conclusions: In this series, pure and mixed SCCUT are characterized by p53 overexpression and a high PD-L1 phenotype. Histology of non-pure SCCUT is a positive prognosticator, and radical cystectomy or chemotherapy can improve OS. These findings demonstrate that SCCUT may be eligible for PD-L1 immunotherapy.