Features Of Small Cell Carcinoma Research Articles

Clinicopathological Characteristics of Small Cell Carcinoma of the Ovary, Hypercalcemic Type – a case Series

Abstract Introduction/Objective Small cell carcinoma of the ovary hypercalcemic type (SCCOHT) is a rare (<0.01%) and aggressive ovarian tumor primarily affecting young women (median of approximately 24 years), characterized by rapid growth, early metastasis, and association with hypercalcemia in two-thirds of cases. The diagnosis of SCCOHT is challenging due to its rarity and lack of specific clinical symptoms or biomarkers. Our study aims to delineate the clinicopathologic characteristics of SCCOHT based on our case series and add to the existing knowledge. Methods/Case Report A retrospective review of University of Pennsylvania Health system pathology database was conducted from 2012 to 2024. Our study identified four patients diagnosed with SCCOHT. Clinical information and histopathologic characteristics were reviewed. Results (if a Case Study enter NA) Among the four patients identified, the median age was 24 years, with a median tumor size of 14.5 cm, and all patients presented with weight loss, abdomen bloating, and elevated CA125 levels. Notably, two patients exhibited hypercalcemia, while one initially presented with normal calcium levels but developed hypercalcemia during disease recurrence. One patient maintained normal calcium levels throughout. Surgical intervention involved bilateral salpingo-oophorectomy in all cases, with pathological staging revealing two patients at pT1a, one at pT1c, and one at pT3c. Histopathological analysis consistently revealed similar morphology, including solid and cystic necrotic neoplasms with diffuse growth or nests/cords of undifferentiated small cells, which displaying vesicular chromatin and prominent nucleoli. Immunohistochemical staining demonstrated loss of BRG1 (SMARCA4) expression in two patients and diffuse positivity for WT1 in all patietns, while negative for cytokeratin, germ cell markers, and melanocytic markers. Genetic test revealed SMARCA4 mutation (p.E 717*, c.3169-1G>A) in one patient. Conclusion Small cell carcinoma of the ovary, hypercalcemic type, presents a diagnostic and therapeutic challenge due to its rarity and aggressive nature. Adequate treatment options are currently limited, highlighting the critical need for further research and development of targeted therapies in SCCOHT. Testing for mutations in the SMARCA4 gene is essential for accurate diagnosis of SCCOHT and may uncover new avenues for treatment and management strategies.

Cytomorphologic analysis of pulmonary neuroendocrine tumors – The physical effect of abrasion and aspiration on cytomorphology

Neuroendocrine tumors of the lung display characteristic cytomorphologic features allowing direct diagnosis. The specificity of these features in distinguishing subtypes of neuroendocrine tumors, and their differences among types of cytologic specimen poses as interpretative potential pitfalls. This study reviewed and compared bronchial, effusion fluid and fine-needle aspiration cytology specimens of neuroendocrine tumors of the lung to address these issues. Histology-proven cytology specimens of neuroendocrine tumors were reviewed for cytomorphological parameters focusing on reported specific neuroendocrine nuclear and background features. Totally, 46 cases (26 bronchial, 11 effusion and 9 aspirate specimens), corresponding to 37 small cell carcinomas, 7 neuroendocrine carcinomas and 2 carcinoids were reviewed. Nuclear moulding (n = 35/37, 95 %), naked nuclei (n = 33/37, 89 %) and marked nuclear irregularity (n = 32/37, 86 %) were the three most common features of small cell carcinoma. The only specific feature for small cell carcinoma was the lack of prominent nucleoli (p = 0.004). For pulmonary carcinoids, in addition to the above features, other features associated with neuroendocrine carcinoma reviewed including crush artifact and necrotic material were absent. Compared to bronchial and aspiration cytology, crush artifact (p < 0.001) and necrotic material (p = 0.014) were absent on effusion fluid specimens and naked nuclei were less frequently seen (p = 0.022), while prominent nucleoli were more often observed (p = 0.005). Nuclear moulding, irregularity and naked nuclei are common but not unique features to small cell carcinomas. Effusion fluid specimens have “cleaner” backgrounds while displaying greater nuclear atypia. The type of cytologic preparation/specimen is an important factor which must be considered during diagnostic interpretation.

Liquid-Based Cytology of Small Cell Carcinoma of the Cervix: A Multicenter Retrospective Study.

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. 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. 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. 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.

Identification of an anaplastic subtype of prostate cancer amenable to therapies targeting SP1 or translation elongation.

Histopathological heterogeneity is a hallmark of prostate cancer (PCa). Using spatial and parallel single-nucleus transcriptomics, we report an androgen receptor (AR)-positive but neuroendocrine-null primary PCa subtype with morphologic and molecular characteristics of small cell carcinoma. Such small cell-like PCa (SCLPC) is clinically aggressive with low AR, but high stemness and proliferation, activity. Molecular characterization prioritizes protein translation, represented by up-regulation of many ribosomal protein genes, and SP1, a transcriptional factor that drives SCLPC phenotype and overexpresses in castration-resistant PCa (CRPC), as two potential therapeutic targets in AR-indifferent CRPC. An SP1-specific inhibitor, plicamycin, effectively suppresses CRPC growth in vivo. Homoharringtonine, a Food And Drug Administration-approved translation elongation inhibitor, impedes CRPC progression in preclinical models and patients with CRPC. We construct an SCLPC-specific signature capable of stratifying patients for drug selectivity. Our studies reveal the existence of SCLPC in admixed PCa pathology, which may mediate tumor relapse, and establish SP1 and translation elongation as actionable therapeutic targets for CRPC.

An Atypical Presentation of GABA-B Encephalitis (P5-5.023)

<h3>Objective:</h3> N/A <h3>Background:</h3> GABA-B receptor encephalitis is a cell surface mediated paraneoplastic disease secondary to antibody production resulting in neuronal cells loss, microglial proliferation, and preferentially targets the limbic system. Symptoms include seizures, memory loss, confusion, and altered behavior. The infrequency with which it is encountered can create a diagnostic challenge. <h3>Case Description:</h3> A 73-year-old female presented as a referral months post hospitalization and outpatient evaluation. Initial presentation began with subacute progressive disorientation, crying spells, ageusia, anosmia, and memory loss without a known precedent illness. On initial exam she was alert, oriented only to self, inattentive, and without other focality. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> The results of the work up included contrasted MRI demonstrating T2 hyperintensities within the hippocampi. Lumbar puncture revealed antibodies against GABA-B receptors. High dose steroids were initiated with minimal improvement therefore IVIG was trialed in the outpatient setting resulting in stabilization and moderate improvement of symptoms. A PET scan was requested and revealed a mass within the left lower lobe of the lung. Biopsy identified features of small cell carcinoma confirming our suspicion of encephalitis secondary to paraneoplastic syndrome. Currently she is undergoing oncological evaluation and treatment. Symptoms remain stable, but emotional lability, poor short-term recall, ageusia and anosmia persist. No additional IVIG or long-term immunotherapy was initiated as treatment should be targeted toward the malignancy. She will remain under neurological surveillance with serial exams and MRIs. <h3>Conclusions:</h3> This case illustrates the importance of recognizing alternative causes of encephalitis. Localizing limbic symptoms were present although the lack of seizures and presence of ageusia and anosmia is highly unusual. We also discovered an extensive smoking history and family history of lung cancer. These red flags highlight the need for a complete history. Early consideration of a paraneoplastic process causing encephalitis will facilitate additional diagnostic testing, prompt initiation of immunotherapy and accurate diagnosis. <b>Disclosure:</b> Dr. DeHart-McCoyle has nothing to disclose. Dr. Chen has nothing to disclose.

Anaplastic features (AnaF) and DNA-damage repair pathway (DDR) mutations in metastatic castration-resistant prostate cancer (mCRPC).

92 Background: Anaplastic prostate cancer displays features of small-cell carcinoma, a type of neuroendocrine tumor. Treatments for anaplastic prostate cancer are based on small cell lung cancer regimens. Both AnaF and mutations in DDR pathways, including BRCA2 confer an aggressive phenotype. For patients (pts) with certain DDR mutations, olaparib (O) was recently FDA approved, and an ongoing study is evaluating whether the addition of durvalumab (D) confers additional benefit in mCRPC (NCT02484404). We evaluate a potential preliminary relationship between DDR mutations, treatment with D and O, and AnaF. Methods: This is a phase II study of O plus D in pts with mCRPC with disease that is amenable to biopsy. On-study core biopsies undergo mutational analysis. Prior treatment with enzalutamide (enza) and/or abiraterone (abi) is required. D is given at 1500 mg iv q28 days + O 300 mg tablets po q12 hours. The primary endpoint is PFS. Pts were categorized into those with and without AnaF as defined by Aparicio et al. (2013). AnaF include small-cell histology; exclusively visceral metastases; predominantly lytic bone metastases; bulky lymphadenopathy (≥5 cm) or high-grade (Gleason ≥8) mass in prostate/pelvis; low PSA (≤10 ng/mL) at initial presentation with high volume (≥20) bone metastases; neuroendocrine markers in histology or serum plus elevated LDH, malignant hypercalcemia, or elevated serum CEA; or short interval (≤6 months) to androgen-independent progression. Results: Of 55 pts accrued, 24 had prior abi and enza; 19 pts had prior taxane. Common adverse events include anemia, fatigue, and nausea. Also, 11 pts (20.0%) displayed clear AnaF (Table) and 43 pts lacked AnaF, including 8 (14.5%) with partial AnaF that did not meet the full criteria, 4 (7.3%) who likely did not have AnaF due to difficulty in quantifying disease burden, 29 (52.7%) who did not have AnaF, and 2 (3.6%) had unknown status. Four pts (36.4%) with clear AnaF had DDR aberrations, including 3 (27.3%) with BRCA2, 1 (9.1%) with both BRCA2 and CHEK2, and 1 (9.1%) with ATM. Conclusions: Pts with mCRPC with DDR mutations can also have AnaF. This preliminary data demonstrates that pts with anaplastic prostate cancer and pts with DDR mutations are two distinct populations with some degree of overlap. O+D is well-tolerated, and future studies should focus on finding optimal treatments for pts with AnaF without and without DDR mutations. Clinical trial information: NCT02484404. [Table: see text]

Small Cell Carcinoma of Bladder; Still A Diagnostic and Therapeutic Challenge: Seven Years of Experience and Follow-up in A Referral Center.

To report clinical, histopathological, and treatment features of small cell carcinoma of (SmccB) bladder during 7 years in a referral center. The clinical, histopathological features, treatment modalities, and outcome of all patients with bladder SmccB treated between 2009 and 2016 who were managed in Hasheminejad Kidney Center (HKC) were retrospectively collected. Thirteen patients were diagnosed and managed with SmccB. The average age of patients was 64.92 years. For each patient, 8 markers were used for IHC staining on average. Neuroendocrine markers such as CD 56, Neuron Specific Enolase, Synaptophysin, and Chromogranin were found in a significant percentage of patients (69%, 38%, 54%, and 31% respectively). Patients were managed with TURBT alone (N=3), chemotherapy after TURBT (N=4), chemotherapy plus radical surgery (N=4) and radical surgery alone (N=2). The best clinical result was seen in chemotherapy received patients with or without radical surgery. The mean(SE) of survival rate in patients who received only chemotherapy alone was 42.4 (10.0) months, while in those who were managed with chemotherapy plus radical surgery it was 47.7 (10.1) months. In our center immunohistochemistry was needed for definitive diagnosis in 17/19 samples. Misdiagnosis happened in two samples without IHC request. We think that use of immunohistochemistry should be mandatory for diagnosis of SmccB to exclude misdiagnosis. Chemotherapy is the most important part of treatment and the addition of radical surgery can slightly improve patients' survival.

Pulmonary small cell carcinoma: Review, common and uncommon differentials, genomics and management

Lung cancer is the leading cause of cancer-related death worldwide. It is divided into sub-categories based upon morphology, immunostaining pattern, biology, molecular profile, and/or treatment options. Up until the early 2000s when driver mutations with targeted therapies were identified in a subset of adenocarcinomas, the most critical distinction of lung carcinomas was driven by differences in treatment between small cell carcinoma (SCC) and nonsmall cell lung carcinoma (NSCLC). The distinction between SCC and NSCLC remains critical in the 21st century for management, especially for advanced stage cancer. In the vast majority of cases, morphological features are sufficient to separate SCC from other types of lung cancers. In some instances, however, cytomorphological features and immunohistochemical overlap with other tumors, limited sample availability, and/or crush artifact pose diagnostic challenges. The aim of this review is to highlight salient features of SCC and ancillary studies to distinguish it from common and uncommon potential mimickers, as well as provide updates in genomics and management.

Cytomorphologic features of small cell carcinoma of lung in effusion fluid using a liquid‐based cytology technique

Liquid-based cytology (LBC) testing induces morphologic changes due to the use of specific fixatives and preparation techniques, and the cytologies of effusions determined in this manner differ morphologically from those of conventional cytopreparation (CCP) smear methods. We compared the cytologic features of pulmonary small cell carcinoma in effusion fluid using CCP and LBC preparations. Fifty-three malignant effusion specimens from 36 patients with small cell carcinoma were examined, including 41 LBCs from 27 patients and 12 CCPs from 9 patients. LBC and CCP preparations preserved the typical features of small cell carcinoma, that is, nuclear molding, very high nuclear to cytoplasmic ratio and granular chromatin. The architectural patterns involved small cohesive clusters and chains with nuclear molding, tight three-dimensional clusters, or single cell dispersion were preserved in both preparations. Oval nuclei (83.3% vs 26.8%, P < .001) and a discernable rim of cytoplasm (66.7% vs 26.8%, P = .043) were more frequently identified in CCPs, whereas cellular degeneration and dry artifact were more frequent in LBC preparations (73.2% vs 8.3%, P < .001). LBC had a tendency to show frequent nuclear size variation (51.2% vs 25.0%) than CCP. LBC tends to show more degeneration and dry artifact with exaggerated irregular nuclear shape and nuclear size variation and scanty cytoplasm than CCP. Cytopathologists should be familiar with the cytomorphologic spectrum of this tumor in CCP and LBC prepared effusions.

1333 Not so Small Biliary Obstruction: A Case of Small Cell Carcinoma of the Ampulla of Vater

INTRODUCTION: Small cell carcinomas commonly arise in the lung, but can also originate in extrapulmonary sites. Extrapulmonary small cell carcinomas are rare and are most frequently found in the female genital tract, gastrointestinal tract and genitourinary tract. Small cell carcinoma of the ampulla of Vater is exceedingly rare, and there are currently less than 15 documented case reports. The neuroendocrine features of small cell carcinoma of the lung and extra pulmonary sites appear to be similar. CASE DESCRIPTION/METHODS: 64-year-old male with past medical history of hypertension and coronary artery disease presented to our hospital with weight loss and jaundice. At time of admission, labs demonstrated AST 114 U/L, ALT 168 U/L, alkaline phosphatase 715 U/L, total bilirubin 5.8 mg/dL (Dbili 4.5), INR 1.1, platelet 271 k/mm3, and albumin 3.5 g/dL. Notable findings on physical exam included jaundice and scleral icterus. Ultrasound of the biliary tree showed no visible stone. ERCP showed an ulcerated, bleeding ampullary mass. Subsequent cholangiogram revealed a distal bile duct stricture measuring approximately 1.5 cm with shelf effect from extension of ampullary mass into the bile duct. Sphincterotomy was performed, followed by distal bile duct biopsy and stent placement. Pathology report of ampullary mass showed findings consistent with small cell neuroendocrine carcinoma. Immunohistochemical staining showed malignant cells were positive for synaptophysin and chromogranin and negative for cytokeratin AE1/3 and CD45. Patient underwent a Whipple procedure with specimen demonstrating a 4.2 cm × 2.8 cm exophytic mass at the ampulla with invasion into the pancreas. Five of twenty peripancreatic lymph nodes were positive for metastatic small cell carcinoma. Following resection our patient was started on adjuvant chemotherapy with cisplatin and etoposide. DISCUSSION: The most common tumor involving the ampulla of Vater is adenocarcinoma. Small cell neuroendocrine carcinoma of the ampulla of Vater accounts for no more than 2% of ampullary malignancies. This case illustrates that although biliary obstruction is commonly attributed to choledocholithiasis and other intrinsic or extrinsic tumors, rarer forms of malignancy should be considered in the differential. Careful assessment of the ampulla during ERCP can aid with diagnosis. Final diagnosis is challenging and can only be confirmed with histopathological examination. Treatment involves a multidisciplinary approach involving surgical resection and chemotherapy.

Small cell carcinoma of the kidney: a case report and analysis of data from the Surveillance, Epidemiology, and End Results registry

BackgroundPrimary small cell carcinoma of the kidney is an extremely rare neoplasm. The clinical features of small cell carcinoma of the kidney are not well established due to its rarity and scarcity of case reports. We present an unusual case of small cell carcinoma of the kidney complicated by syndrome of inappropriate antidiuretic hormone secretion. We identify cases using a population-based dataset from the Surveillance, Epidemiology, and End Results registry and compare small cell carcinoma of the kidney with small cell carcinoma of the lung.Case presentationA 69-year-old Filipino man presented with hematuria for 1 month. A computed tomography scan demonstrated a large left kidney mass with biopsy demonstrating small cell carcinoma. Within 2 months he developed dizziness and was found to have a metastatic lesion to his brain. He was hyponatremic due to syndrome of inappropriate antidiuretic hormone secretion. He did not receive chemotherapy due to his poor functional status. He died within 8 months of presentation.ResultsFrom 1973 to 2013, 60 cases with small cell carcinoma of the kidney were identified in the Surveillance, Epidemiology, and End Results registry. Most (62%) presented with extensive stage, which occurred predominantly in white men in their seventh decade. The median overall survival with extensive stage small cell carcinoma of the kidney was 3 months versus 11 months with limited stage of small cell carcinoma of the kidney; this was worse than small cell carcinoma of the lung with a median survival of 5 and 13 months, respectively.ConclusionWe present a rare case of small cell carcinoma of the kidney complicated by syndrome of inappropriate antidiuretic hormone secretion. This adds to our understanding of the clinical features of small cell carcinoma of the kidney. Furthermore, this is the first population-based study of small cell carcinoma of the kidney using the Surveillance, Epidemiology, and End Results database. Analysis shows that overall survival is worse in small cell carcinoma of the kidney relative to that of small cell carcinoma of the lung. Small cell carcinoma of the kidney presents very aggressively, and further studies are needed to develop a standard of care.

Clinicopathological features of small cell carcinoma of the uterine cervix in the surveillance, epidemiology, and end results database.

To investigate the clinicopathological characteristics and survival of small cell carcinoma of the cervix using Surveillance, Epidemiology, and End Results database. Patients with a diagnosis of small cell carcinoma of the cervix were included between 1988 and 2012. Kaplan-Meier method and Cox regression models were used. A total of 487 patients were included. Of the patients with known International Federation of Gynecology and Obstetrics stage and tumor grade, the stage IV disease was diagnosed in 37.9% patients, and 98.5% patients had poorly or undifferentiated histology. The 5-year cause specific survival and overall survival were 33.0% and 29.4%, respectively. In multivariate analysis, increasing age, advanced stage, and treatment by primary radiotherapy were associated with worse survival outcomes. Small cell carcinoma of the cervix is a rare disease with aggressive characteristics and prone to metastasize and is dismal in prognosis. Reduced survival was associated with increasing age, advanced stage, and treatment by primary radiotherapy.

Cytomorphologic and Immunophenotypic Profile of a Cohort of Small Cell Carcinoma of the Urinary Bladder

Background: The incidence of primary small cell carcinoma (SCC) of the urinary bladder is extremely rare. We sought to analyze the cytologic and immunophenotypic features of SCC of the urinary bladder in urine and reassert the importance of cytologic examination of urine specimens for diagnosis of this tumor. Methods: We studied the clinical and cytomorphologic features in the presurgical urine specimens (4 voided urine and 2 bladder-washing specimens) of histopathologically and immunohistochemically proven cases of SCC of the urinary bladder. Results: There were 6 cases, all males, with an age range of 61-81 years. On cytologic and histopathologic examination, typical SCC morphology was present in all cases. On immunohistochemistry, synaptophysin and CD56 were positive in all 6 cases, while chromogranin was positive in only 3. The Ki-67 labeling index ranged from 30 to 100%. Conclusions: SCC should be kept in the differential diagnosis, when high-grade urothelial carcinoma is suspected in a urine cytology specimen, as this distinction has important therapeutic and prognostic implications. Therefore, a careful observation and, if required, the use of an appropriate immunocytochemical panel on the presurgical urine specimens can lead to a correct diagnosis.

Small cell carcinoma of the rectum: A report of imaging results from four cases.

Small cell carcinoma of the rectum is extremely rare. The present study aimed to improve the recognition of computed tomography (CT) and magnetic resonance imaging (MRI) features observed in patients with small cell carcinoma of the rectum. A total of 4 cases of patients with histologically confirmed small cell carcinoma of the rectum were retrospectively reviewed. The imaging features assessed consisted of the thickening of the rectal wall, local tumor invasion, CT density, MRI signal intensity, lesion texture, contrast enhancement characteristics, lymphadenopathy and distant metastasis. All 4 patients displayed ring-like rectal wall thickening and hypodensity in comparison to the gluteus muscles on non-enhanced CT images. MRI demonstrated isointensity on T1-weighted images and hyperintensity on T2-weighted images. Thickening of the left wall of the rectum with patchy low attenuation and the presence of an exophytic mass was observed in 1 patient. Local tumor invasion was observed in the perirectal fat spaces of 4 patients, in the prostate gland and seminal vesicle of 1 patient, and in the left seminal vesicle of 1 patient. Heterogeneous attenuation was exhibited on non-enhanced CT images in 3 lesions, and 1 lesion exhibited heterogeneous intensity on non-enhanced MRI images. All the lesions observed demonstrated strong enhancement following contrast imaging. Lymphadenopathy was observed in 4 patients, liver metastasis in 3 patients, pulmonary metastasis in 2 patients and multiple bone metastases in 1 patient. Overall, small cell carcinoma of the rectum appeared to be more likely to metastasize to the liver, pulmonary, lymph nodes and bone. Distinguishing features of small cell carcinoma of the rectum were noted as a thickening rectal wall, the presence of soft-tissue tumors, local tumor invasion, lymphadenopathy and distant metastases. Pre-operative CT and MRI are required as an aid in selecting the correct treatment plan and for the prognosis assessment of patients.

Small cell carcinoma of ovary, hypercalcemic type: analysis of clinicopathologic characteristics and the diagnostic utility of loss expression of SMARCA4 protein

To study the clinicopathologic features of small cell carcinoma of ovary, hypercalcemic type (SCCOHT) and to evaluate the diagnostic significance of loss of SMARCA4 expression. The clinicopathologic characteristics of 5 cases of SCCOHT were reviewed. The expression of SMARCA4 protein was detected by immunohistochemistry in the cases of SCCOHT and 240 cases of other primary malignant tumors of ovary and peritoneum. The mean and medium age of these patients was 30 years and 28 years, respectively. The presenting symptoms included abdominal pain, distention and a pelvic mass. Hypercalcemia was found in 3 patients. The maximum diameter of tumors ranged from 13.5 to 22.0 cm. Extraovarian spread was demonstrated in all of the patients on presentation. Histologically, the tumors were composed of closely packed small round cells with scanty cytoplasm, hyperchromatic nuclei and irregular chromatin clumps. The tumor cells grew in sheets, nests, cords or trabecular pattern. Follicle-like spaces were observed in 4 cases. Three of the tumors contained large cells with abundant eosinophilic cytoplasm. Spindle cell morphology was found in 1 case. There were 2 cases with myxoid or hyaline stroma. Four out of five of SCCOHT cases showed loss of SMARCA4 protein while only 6.3% (15/240) of the other primary malignant tumors of ovary and peritoneum , including undifferentiated carcinoma (1/5), high-grade serous carcinoma (4.6%, 5/109), endometrioid carcinoma (7.7%, 2/26), clear cell carcinoma (1/9), mucinous carcinoma (1/5), mixed carcinoma (4.9%, 3/61), carcinosarcoma (1/9) and high-grade serous carcinoma of peritoneum (1/9), were negative. SCCOHT is a rare malignant tumor and often misdiagnosed as other types of ovarian small cell tumor. Loss expression of SMARCA4 protein is characteristic and facilitates the diagnosis and differential diagnosis of SCCOHT.

Extrapulmonary Small Cell Carcinoma: Imaging Features with Radiologic-Pathologic Correlation

Extrapulmonary small cell carcinoma (EPSCC) refers to small cell carcinoma arising outside of the lungs. EPSCC extrapulmonary small cell carcinoma is a rare aggressive neoplasm, representing a minority of all small cell carcinomas. Despite its uncommon occurrence, EPSCC extrapulmonary small cell carcinoma has been described in nearly every organ, most commonly in the gastrointestinal and genitourinary systems. As such, it is important for radiologists to be aware of the entity. Although imaging is neither sensitive nor specific for EPSCC extrapulmonary small cell carcinoma , it plays an important role by helping exclude metastases from a primary pulmonary tumor, establish tumor staging, and assess response to therapy. EPSCC extrapulmonary small cell carcinoma is diagnosed by demonstrating pathologic features of small cell carcinoma in an extrapulmonary site. There are two ways to stage EPSCC extrapulmonary small cell carcinoma . One method uses the Veterans Administration Lung Study Group system developed for small cell lung cancer that allocates patients into limited or extensive disease categories. The second approach is the American Joint Committee on Cancer tumor-node-metastasis system applied to other tumor subtypes arising from the same organ. Because of its rare and varied manifestations, the most effective treatment for EPSCC extrapulmonary small cell carcinoma has not been established. Current management recommendations are derived from retrospective studies and single-institution experiences or are extrapolated from small cell lung cancer data. Regardless of therapy, overall survival rates are poor, with 5-year survival rates around 13%. To help radiologists increase their familiarity with EPSCC extrapulmonary small cell carcinoma , this article provides (a) a background for EPSCC extrapulmonary small cell carcinoma based on the literature and (b) a pictorial review of EPSCC extrapulmonary small cell carcinoma in multiple organs, with radiologic-pathologic correlation.

NUT midline carcinomas in the thymic region

NUT midline carcinomas (NMCs) are rare tumors described predominantly in the pediatric age group. We recently reported two cases of these tumors occurring in the thymic region. In order to establish the true incidence of these tumors, we examined a large series of thymic carcinomas for morphological features of NUT tumor and further assessed the expression of NUTM1 (also known as NUT) protein by immunohistochemistry. The histological review of slides from 110 cases of thymic carcinoma was undertaken to identify carcinomas with mixed undifferentiated and squamous features that are typically associated with NUT carcinomas. The presenting symptoms, morphological spectrum of tumors and outcome data of patients with these histologies are presented. Immunohistochemistry for NUTM1 was performed on 35 cases of thymic carcinoma with available blocks (3 with these histological features and 32 without these features) to exclude the possibility of midline carcinoma. Tumors from 10 patients had features of mixed small cell undifferentiated squamous cell carcinoma (M:F, 1.5:1; age range, 22–79). These patients predominantly presented with advanced disease and had respiratory-related symptoms or chest pain; four had paraneoplastic syndromes. The squamous component in all cases was well differentiated with little or no atypia. The undifferentiated component varied in cell size and lacked characteristic features of small cell carcinoma. All but one patients developed metastases or died within 3 years of diagnosis. NUTM1 expression was seen in two of three tumors with these histological features and in none of the 32 cases without. Mixed small cell undifferentiated carcinomas share histological and immunohistochemical similarity with NMCs and have aggressive clinical course. These tumors are not uncommon and should be considered in the differential diagnosis of carcinomas in the thymic region as novel therapies might be available.

Prostate cancer with Paneth cell–like neuroendocrine differentiation has recognizable histomorphology and harbors AURKA gene amplification

Aurora kinase A (AURKA) gene amplification has been documented in 67% of hormone-naive prostate cancer cases that progress to a highly aggressive variant of castrate-resistant disease, clinically referred to as "neuroendocrine" prostate cancer, "small cell" prostate carcinoma, or "anaplastic" prostate cancer. Therefore, AURKA amplification is a potential prognostic biomarker that may help to identify patients with prostate cancer who are at high risk for developing castrate-resistant disease with clinical features of small cell carcinoma. Furthermore, AURKA inhibitors are currently being tested in clinical trials. In a previous study, we found AURKA amplification in 6 cases of prostate cancer with Paneth cell-like cells. This morphologic pattern has been suggested to represent low-grade neuroendocrine differentiation (NED) with generally favorable prognosis. We sought to investigate the frequency of AURKA amplification and the histologic characteristics of prostate cancer with Paneth cell-like NED. Twenty-five cases from 172 prostatectomies were evaluated for the presence of 18 morphologic features and AURKA amplification. Most prostate cancers with Paneth cell-like NED had macronucleoli (92%), basophilic appearance (88%), perineural invasion (72%), and nuclear stratification (76%). The frequency of AURKA amplification was 45%, present throughout the examined tumor nodule including areas without Paneth cell-like cells. When histologically similar cases with and without AURKA amplification were compared, this gene alteration was associated with larger extent of Paneth cell-like NED identified at magnification ×20 (P = .015), higher percentage of Paneth cell-like NED throughout the tumor nodule (P = .033), ductal features (P = .02), and higher overall Gleason grade (P = .039). AURKA amplification was not associated with age, serum prostate specific antigen, or tumor stage. The high frequency of AURKA amplification (45%) in localized prostate cancer with Paneth cell-like NED and its potential prognostic significance warrant further investigation.

Proposed Morphologic Classification of Prostate Cancer With Neuroendocrine Differentiation

On July 31, 2013, the Prostate Cancer Foundation assembled a working committee on the molecular biology and pathologic classification of neuroendocrine (NE) differentiation in prostate cancer. New clinical and molecular data emerging from prostate cancers treated by contemporary androgen deprivation therapies, as well as primary lesions, have highlighted the need for refinement of diagnostic terminology to encompass the full spectrum of NE differentiation. The classification system consists of: Usual prostate adenocarcinoma with NE differentiation; 2) Adenocarcinoma with Paneth cell NE differentiation; 3) Carcinoid tumor; 4) Small cell carcinoma; 5) Large cell NE carcinoma; and 5) Mixed NE carcinoma - acinar adenocarcinoma. The article also highlights "prostate carcinoma with overlapping features of small cell carcinoma and acinar adenocarcinoma" and "castrate-resistant prostate cancer with small cell cancer-like clinical presentation". It is envisioned that specific criteria associated with the refined diagnostic terminology will lead to clinically relevant pathologic diagnoses that will stimulate further clinical and molecular investigation and identification of appropriate targeted therapies.

Small cell carcinoma of the urinary bladder and prostate: Cytological analyses of four cases with emphasis on the usefulness of cytological examination

The occurrence of small cell carcinoma in the urinary bladder and prostate is rare. Only a few reports on the cytological features of small cell carcinoma of the urinary bladder in the urine specimen have been documented and, moreover, the urinary cytological features of prostate small cell carcinoma have been rarely reported. In this study, we analyzed the cytological features of four cases of small cell carcinoma of the urinary bladder and prostate, and discussed the usefulness of cytological examination of urine specimen for this type of tumor. This study included two urinary bladder and two prostate small cell carcinoma cases. Analyses of the cytological features of these cases revealed the following: i) the background was mostly inflammatory and necrotic material was also occasionally observed; ii) numerous tumor cells were present in two cases, whereas only a few neoplastic cells were observed in the remaining cases; iii) the neoplastic cells were small in size, had scant cytoplasm and a high nuclear/cytoplasmic ratio, and were arranged in small clusters or occasionally as single cells; iv) the tumor cell clusters showed prominent nuclear moldings; and v) the nuclei of the neoplastic cells were round to oval in shape with finely granular chromatin containing inconspicuous nucleoli. The cytological features of small cell carcinoma in the urine specimen are characteristic. Therefore, careful observation of the urine specimen may lead to a correct diagnosis of small cell carcinoma of the urinary bladder and, moreover, cytodiagnosis of prostate small cell carcinoma may also be possible.