Diagnosis Of Small Cell Carcinoma Research Articles

A case of alpha-fetoprotein-positive thymic small cell carcinoma: a case report

BackgroundAn alpha-fetoprotein (AFP)-positive neuroendocrine tumor of the thymus is a rare thoracic malignancy. Few cases of AFP-positive thymic large cell neuroendocrine carcinoma have been reported, with no known previous report of an AFP-positive thymic small cell carcinoma. We encountered a patient with an AFP-positive small cell carcinoma and report here the clinical course.Case presentationA 40-year-old man was transferred to our hospital for a large anterior mediastinal tumor and showed an elevated serum AFP level. Computed tomography-guided biopsy results led to diagnosis of small cell carcinoma. Induction chemoradiotherapy was performed before surgery because of pulmonary artery invasion. The response to Induction chemoradiotherapy varied among sites, with the main tumor showing shrinkage and the metastasis site growth. This discrepancy suggested a histologic type unresponsive to or cancer cells potentially resistant to chemotherapy, thus a surgical re-biopsy was performed and histological findings revealed AFP-positive small cell carcinoma. Additional chemotherapy was performed, though could not control cancer progression, and the patient died 8 months after the first medical examination.ConclusionsOur present clinical experience indicates the importance of histological examination for determining AFP-positive anterior mediastinal tumor treatment. Although AFP-positive neuroendocrine tumor of the thymus is relatively rarer than germ cell carcinoma, differential diagnosis with use of a histological examination should be considered because of the potentially poorer prognosis. The present clinical findings for an AFP-positive neuroendocrine tumor of the thymus case are considered useful for establishing an optimal treatment strategy in the future.

S2899 A Rare Case of Small Cell Lung Cancer in the Posterior Mediastinum Diagnosed With Endoscopic Ultrasound-Guided Fine Needle Biopsy

Introduction: Lung cancer is the leading cause of cancer mortality worldwide, accounting for 2 million diagnoses and 1.8 million deaths in 2020.1 10-15% of all lung cancers are small cell lung cancer (SCLC), an aggressive form that grows more rapidly and metastasizes more easily than NSCLC. Thus, in patients with suspected lung cancer, a tissue diagnosis is crucial. Here, we present a unique case of a man with a posterior mediastinal mass for whom obtaining a tissue diagnosis presented a diagnostic challenge. Case Description/Methods: A 49 y/o M, with a 30 pack-year smoking history, presented with worsening left-sided chest pain and a 10-pound unintentional weight loss over 2 months. Vital signs and physical exam were unremarkable. Labs demonstrated a mild anemia (Hb 11-12, MCV 82) and elevated inflammatory markers (ESR 54, CRP 70.9). CT scan demonstrated a 12.0x10.7x8.4 cm hypodense soft tissue density mass in the left posterior mediastinum, extending from the level of T1 to T7 vertebral bodies. The mass displaced the trachea, esophagus, and adjacent vessels. Several enlarged mediastinal lymph nodes were seen, the largest measuring up to 1.5 cm. However, there was no lymphadenopathy seen elsewhere and no convincing evidence of metastatic disease in the abdomen or pelvis. CT surgery recommended a CT-guided biopsy with IR vs. endoscopic bronchial US-guided biopsy. IR was unable to find a safe access point to go in for the biopsy as there was no window, as the lung was seen overlying the mass. The patient was discharged, and he returned the next week for outpatient EUS-FNB, which demonstrated a 72x39 mm mediastinal mass (Fig 1A). EUS-FNB was performed and EUS-guided transesophageal biopsies were performed. He was also found to have erosive gastritis, healing superficial sub-cm gastric ulcers, and multiple healing superficial duodenal ulcers. Pathology results demonstrated SCLC (Fig 1B-E) and H. pylori. He was treated with standard quadruple therapy, referred to his PCP to confirm eradication in 6 weeks, and referred to Oncology. For stage III-b SCLC treatment, he completed external beam RT and chemotherapy. Repeat PETCT demonstrated a decrease in the residual mass to 5.5x3.5x5.8 cm. Discussion: For patients presenting with a posterior mediastinal mass, for whom IR may not be able to perform a biopsy, obtaining a tissue diagnosis may be a diagnostic challenge. EUS-FNB provides a useful tool to assess the mediastinum and can provide timely diagnosis and staging of patients with rare forms of lung cancer.Figure 1.: A) A posterior mediastinal mass vs. esophageal mass measuring 72.1 mm by 39.2 mm was identified status-post EUS with FNB x 6. This mass appeared to arise from the muscularis propria of the esophagus; however, an extrinsic mediastinal mass could not be definitively ruled out due to the severe compressive effects of the mass on the esophagus. Mediastinal mass, needle biopsy: -Minute fragments of malignant neoplasm with necrosis. -Tumor cells are positive for AE1/3, CAM5.2, Chromogranin, Synaptophysin, CD56 and negative for p40, CD3, CD20, and CD45. Ki-67 demonstrats about 60% positivity. Combined with morphological features, this immunoprofile supports the diagnosis of small cell carcinoma. B) Hematoxylin and eosin (H&E) stain. C) CAM5.2. D) CD56. E) Chromogranin.

Broncoscopía virtual como herramienta diagnóstica de cáncer de pulmón periférico

Introduction: virtual bronchoscopy is a non-invasive method that produces a three-dimensional view of the airway, based on data obtained from helical computed tomography, that provides a view similar to that produced by conventional bronchoscopy. Clinical case: a 49-year-old female patient with symptoms of hemoptysis, weight loss, dyspnea and chest pain. Chest tomography revealed a spiculated nodule with a positive bronchial sign, subsegment C of the anterior segment of the left upper lobe was identified through virtual navigation and, under fluoroscopic guidance, a transbronchial forceps biopsy was performed, with histopathological diagnosis of small cell carcinoma, that reduced surgical time and radiation exposure to the patient and healthcare personnel. Conclusion: computed tomography and bronchoscopy can be used as complementary techniques, for this reason, virtual bronchoscopy provides both diagnostic and potentially therapeutic information.

Electrochemical immunosensor based on hollow porous Pt skin AgPt alloy/NGR as a dual signal amplification strategy for sensitive detection of Neuron-specific enolase

Neuron-specific enolase (NSE) is a specific marker for small cell carcinoma (SCLC). Sandwich-type electrochemical immunosensors are powerful for biomarker analysis, and the electrocatalytic activity of the signal amplification platform and the performance of the substrate are critical to their sensitivity. In this work, N atom-doped graphene functionalized with hollow porous Pt-skin Ag–Pt alloy (HP–Ag/Pt/NGR) was designed as a dual signal amplifier. The hollow porous Pt skin structure improves the atomic utilization and the larger internal cavity spacing significantly increases the number of electroactive centers, thus exhibiting more extraordinary electrocatalytic activity and durability for H2O2 reduction. Using NGR with good catalytic activity as the support material of HP-Ag/Pt, the double amplification of the current signal is realized. For the substrate, polypyrrole-poly(3,4-ethylenedioxythiophene) (PPy-PEDOT) nanotubes were synthesized by a novel chemical polymerization route, which effectively increased the interfacial electron transfer rate. By coupling Au nanoparticles (Au NPs) with PPy-PEDOT, the immune activity of biomolecules is maintained and the conductivity is further enhanced. Under optimal conditions, the linear range was 50 fg mL−1 - 100 ng mL−1, and the limit of detection (LOD) was 18.5 fg mL−1. The results confirm that the developed immunosensor has great promise for the early clinical diagnosis of SCLC.

1114P Comparative study of combined large cell neuroendocrine carcinoma and combined small cell carcinoma in resected high-grade neuroendocrine tumors of the lung

Large cell neuroendocrine carcinoma (LCNEC) and small cell carcinoma (SCLC) are both classified as pure and combined subtypes. Due to the low incidence and difficult diagnosis of combined LCNEC (C-LCNEC) and combined SCLC(C-SCLC), no studies have been conducted to compare their clinical features and prognosis.

Identification of potential serum biomarkers for simultaneously classifying lung adenocarcinoma, squamous cell carcinoma and small cell carcinoma.

Histological subtypes of lung cancer are crucial for making treatment decisions. However, multi-subtype classifications including adenocarcinoma (AC), squamous cell carcinoma (SqCC) and small cell carcinoma (SCLC) were rare in the previous studies. This study aimed at identifying and screening potential serum biomarkers for the simultaneous classification of AC, SqCC and SCLC. A total of 143 serum samples of AC, SqCC and SCLC were analyzed by 1HNMR and UPLC-MS/MS. The stepwise discriminant analysis (DA) and multilayer perceptron (MLP) were employed to screen the most efficient combinations of markers for classification. The results of non-targeted metabolomics analysis showed that the changes of metabolites of choline, lipid or amino acid might contribute to the classification of lung cancer subtypes. 17 metabolites in those pathways were further quantified by UPLC-MS/MS. DA screened out that serum xanthine, S-adenosyl methionine (SAM), carcinoembryonic antigen (CEA), neuron-specific enolase (NSE) and squamous cell carcinoma antigen (SCC) contributed significantly to the classification of AC, SqCC and SCLC. The average accuracy of 92.3% and the area under the receiver operating characteristic curve of 0.97 would be achieved by MLP model when a combination of those five variables as input parameters. Our findings suggested that metabolomics was helpful in screening potential serum markers for lung cancer classification. The MLP model established can be used for the simultaneous diagnosis of AC, SqCC and SCLC with high accuracy, which is worthy of further study.

SMALL CELL CARCINOMA OF ESOPHAGUS: A CASE SERIES OF SIX PATIENTS

Objective: To study the clinicopathological and oncological outcomes of all the patients presenting with a diagnosis of small cell carcinoma of the esophagus at Shaukat Khanum Memorial Cancer Hospital and Research Center (SKMCH&RC). Methodology: From 1997 to 2017 all patients with a diagnosis of small cell carcinoma of the esophagus were included in the study. Demographic variables were collected. Clinico-pathological outcomes of disease were recorded. All data were entered and analyzed in SPSS ver 21. Results: A total of 6 patients were included in the study. The median age was 63.5 +/- 8.09 years. There were 1 male and 5 female patients. The most common presentation was dysphagia in all 6 patients. Upper gastrointestinal endoscopy was used to detect the location and diagnosis of the disease. A computed tomography scan is used for staging the disease. All patients received neoadjuvant chemoradiotherapy, one patient had surgical resection of the tumour. Almost all patients developed metastases or progression of the disease. Conclusion: Small cell carcinoma of the esophagus is rare and needs to be managed aggressively. All patients are best treated with formal systemic and local treatment.

TRIPLE THREAT: A CASE OF MULTIPLE PRIMARY LUNG CANCERS

SESSION TITLE: Medical Student/Resident Lung Cancer Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: October 18-21, 2020 INTRODUCTION: Multiple primary lung cancers (MPLC) are a rare occurrence and have 2 forms – synchronous (sMPLC) and metachronous (mMPLC). The sMPLCs are physically distinct with different histological subtypes. If they are the same subtype, they must be in different lobes of the lung, originating from carcinoma in situ, and no tumor in common lymphatics and extrapulmonary metastases. The mMPLCs tumors must be histologically different or if they are histologically identical, there must be a >2 year cancer free interval, originate from carcinoma in situ, and second cancer must be in a different lobe or lung with no carcinoma in the common lymphatics and no extrapulmonary metastases. mMPLC is common and secondary to treatment of initial lesions. Tobacco smoke may also create a “field effect” in which multicentric lung cancers manifest more frequently. CASE PRESENTATION: A 66-year-old female presented for follow up of sMPLC Stage IB left upper lobe adenocarcinoma/Stage IA right middle lobe squamous cell carcinoma. Patient was treated in 2015 via left upper lobectomy and right middle lobe pulmonary wedge resection. Patient history includes 40-pack-years of smoking, COPD, and continued smoking after treatment of prior sMPLC. Surveillance chest CT showed increase in size of subcarinal lymph node and right lymph node conglomerate encasing the right upper lobe pulmonary artery, consistent with metastasis. Fine needle aspiration of level 4R lymph nodes revealed cells clusters with nuclear molding, high nuclear to cytoplasmic ratio, inconspicuous nuclei, minimal cytoplasm, and crush artifacts. Immunohistochemically tumor cells were positive for TTF-1 and synaptophysin, and negative for P40 – confirming diagnosis of small cell carcinoma. DISCUSSION: Small cell lung cancer (SCLC) and non-small cell lung cancer (NSCLC) are known to be linked with tobacco, creating a “field effect” that promotes the possibility of MPLCs. NSCLC include adenocarcinoma and squamous cell carcinoma (SCC). SCLC and NSCLC are differentiated based on morphology and immunohistochemical staining, the results of which confirmed diagnosis of small cell carcinoma and thus qualified as mMPLC in our case. Treatment of mMPLC is often surgical resection, however, feasibility must be assessed based on pulmonary reserve. Limited resections should be attempted in all cases as segmentectomies have similar outcomes to lobectomies in terms of recurrence-free survival, notably in tumors under 3 cm. CONCLUSIONS: In patients with a history of MPLC associated with smoking, physicians should be cognizant of additional malignancies different from the original lesion subtype. Biopsy and histopathology are the gold standard for diagnosis. Surgery is the standard treatment in MPLC, but clinicians should assess for sufficient pulmonary reserve to ensure viability. Reference #1: Chen C, Huang X, Peng M, Liu W, Yu F, Wang X. Multiple primary lung cancer: a rising challenge. Journal of thoracic disease. 2019; 11(Suppl 4):S523-S536. Reference #2: Chen TF, Xie CY, Rao BY, et al. Surgical treatment to multiple primary lung cancer patients: a systematic review and meta-analysis. BMC surgery. 2019; 19(1):185. Reference #3: Jiang L, He J, Shi X, et al. Prognosis of synchronous and metachronous multiple primary lung cancers: systematic review and meta-analysis. Lung cancer (Amsterdam, Netherlands). 2015; 87(3):303-10. DISCLOSURES: No relevant relationships by jayanth keshavamurthy, source=Web Response No relevant relationships by Diana Kozman, source=Web Response No relevant relationships by Samantha Mattox, source=Web Response No relevant relationships by Rohit Munagala, source=Web Response No relevant relationships by Nikhil Patel, source=Web Response No relevant relationships by Kanwar Singh, source=Web Response No relevant relationships by Asad Ullah, source=Web Response

A Case of Delayed Diagnosis of Small Cell Carcinoma Originated from the Maxillary Sinus with Bilateral Fungal Sinusitis

Extrapulmonary small cell carcinoma originated from the paranasal sinus is extremely rare, and its local and distant metastasis is common and the prognosis is poor. We recently experienced a rare case of small cell carcinoma that originated from the maxillary sinus. However, the diagnosis was delayed for several reasons, one of which included accompanied bilateral fungal sinusitis. The patient received chemotherapy for four times, but the therapy was discontinued due to poor general conditions. We report our case with a review of the literature.

Unidentical Double Trouble- A Rare Case Report

Collision tumours are relatively rare entities and are thus, not well recognised. Collision tumour can be defined as two coexisting but histologically different malignancies involving the same organ or adjacent organ with an equivocal intermediate transitional zone between them. Collision tumours of the lung and oesophagus are very rare. Such cases are diagnosed by Computerised Tomogram (CT) Scan or Chest X-Ray for complaint of dysphagia. Definitive diagnosis is made by tissue biopsy. Here, a 66-year-old male is admitted for evaluation of an anterior mediastinal mass. Radiology revealed an anterior mediastinal mass extending in to the left hilar region and upper lobe of right lung anteriorly and in to the lower end of oesophagus posteriorly. Biopsy was performed. Microscopically, transbronchial biopsy revealed a cellular lesion, composed of round-to-oval cells with streaming nucleus, positive for Immunohistochemistry (IHC) markers, CD-56 and Synaptophysin pertaining to a diagnosis of small cell carcinoma. Biopsy of the oesophageal growth shows nest of dysplastic squamous epithelium which infiltrates into underlying muscularis propria showing features of a squamous cell carcinoma. Multiple fragments of squamous epithelium are also seen with necrotic tissue in vicinity and acute inflammatory exudate. Few cells show multinucleation, molding and margination of chromatin, showing the characteristic morphological features of Herpes oesophagitis. The patient was administered platinum-based Chemotherpy.

KNOCK KNOCK, HU'S THERE? POSITIVE ANTI-HU ANTIBODY IN EXTRAPULMONARY SMALL CELL CARCINOMA OF LYMPH NODE

SESSION TITLE: Tuesday Medical Student/Resident Case Report Posters SESSION TYPE: Med Student/Res Case Rep Postr PRESENTED ON: 10/22/2019 01:00 PM - 02:00 PM INTRODUCTION: To date, small cell carcinoma (SCC) has been primarily recognized as a pulmonary malignancy and research has been skewed towards this area. Extrapulmonary SCC is rare, accounting for 2.5% of SCC, out of which lymph node SCC are far and few between. CASE PRESENTATION: A 59-year-old gentleman was initially admitted to neurology for sensory neuropathy and weight loss. He was referred to the respiratory medicine team after imaging revealed subcarinal and left hilar lymphadenopathy. He is a chronic smoker and there was a concern for malignancy. Initial endobronchial ultrasound transbronchial needle aspiration (EBUS-TBNA) using 22 gauge needle showed lymphoid yield. Serum paraneoplastic panel (Hu, Yo, Ri, CV2, Amphiphysin, PNMA2/Ta, recoverin, SOX1, titin, zic4, GAD65, Tr(DNER)) was performed as part of the diagnostic work up. Anti-Hu antibody was 1:101 (strongly positive); reference titer 1:<10. Fluorodeoxyglucose-positron emission tomography-computed tomography (FDG-PET-CT) scan revealed FDG avid subcarinal (SUVmax:11.1) and left hilar (SUVmax:13.2) nodes. In view of the anti-Hu antibody results and FDG-PET-CT findings, a repeat EBUS-TBNA using 19 gauge needle was performed and histology confirmed SCC. DISCUSSION: Paraneoplastic syndrome was first described by M. Auché in 1890 and is known to affect up to 8% of patients with cancer; most notably small cell lung cancer. Anti-Hu is an onconeural antibody first discovered by F. Grouse in 1985. Its moniker is type I anti-neuronal nuclear antibody (ANNA-1) and has been a signpost for paraneoplastic sensory neuropathy or encephalomyelitis. (Positive anti-Hu antibody titers have a reported specificity of 99% and sensitivity of 82%). It is recognized as a distinct clinical disease, “anti-Hu syndrome”, with characteristic clinical picture and imaging findings. A Dutch study in 2002 found that 85% of patients with positive anti-Hu antibody also have a tumor. Of note, anti-Hu antibodies can also be positive in antecedent inflammatory diseases like systemic lupus erythematosus or Sjogren’s syndrome which can confound the diagnosis. Thus, positive anti-Hu antibody levels should prompt further evaluation and follow up even in absence of concurrent malignancy. Early diagnosis of lymph node SCC has prognostic implications when compared to pulmonary and extrapulmonary SCC, thus making the distinction necessary. CONCLUSIONS: This study highlights the diagnostic implications of an abnormal paraneoplastic panel, emphasizing the role of anti-Hu antibody in its specificity for SCC. The presence of FDG avid thoracic lymph nodes with elevated anti-Hu antibody titers warrants a repeat biopsy. It is imperative for clinicians to identify occult neoplasms in the setting of paraneoplastic syndromes. Reference #1: Koike H, Sobue G. Paraneoplastic neuropathy. Handb Clin Neurol. 2013;115:713-26. Reference #2: Graus F, Cordon-Cardo C, Posner JB. Neuronal antinuclear antibody in sensory neuronopathy from lung cancer. Neurology. 1985 Apr;35(4):538–43. Sehgal IS, Kaur H, Dhooria S, et al. Extrapulmonary small cell carcinoma of lymph node: Pooled analysis of all reported cases. World J Clin Oncol. 2016;7(3):308-20. Graus F, Keime-Guibert F, Reñe R, Benyahia B, Ribalta T, Ascaso C, Escaramis G, Delattre JY. Anti-Hu-associated paraneoplastic encephalomyelitis: analysis of 200 patients. Brain. 2001;124(6):1138-1148. Senties-Madrid H, Vega-Boada F. Paraneoplastic syndromes associated with anti-Hu antibodies. Isr Med Assoc J. 2001 Feb;3(2):94-103. Reference #3: Benyahia B, Amoura Z, Rousseau A, Le Clanche C, Carpentier A, Piette JC, Delattre JY. Paraneoplastic antineuronal antibodies in patients with systemic autoimmune diseases. J Neurooncol. 2003 May;62(3):349-51. Sillevis Smitt P, Grefkens J, de Leeuw B, van den Bent M, van Putten W, Hooijkaas H, Vecht C. Survival and outcome in 73 anti-Hu positive patients with paraneoplastic encephalomyelitis/sensory neuronopathy. J Neurol. 2002 Jun;249(6):745-53. Kim KO, Lee HY, Chun SH, et al. Clinical overview of extrapulmonary small cell carcinoma. J Korean Med Sci. 2006;21(5):833-7. Kannoth S. Paraneoplastic neurologic syndrome: A practical approach. Ann Indian Acad Neurol. 2012;15(1):6-12. DISCLOSURES: No relevant relationships by John Abisheganaden, source=Web Response No relevant relationships by Caroline Choong, source=Web Response No relevant relationships by Sharlene Ho, source=Web Response No relevant relationships by Chuen Peng Lee, source=Web Response No relevant relationships by Ziqin Ng, source=Web Response No relevant relationships by Ser Hon Puah, source=Web Response No relevant relationships by HUIJIA WANG, source=Web Response No relevant relationships by Kim Hoong Yap, source=Web Response

A Case of Small Cell Carcinoma With Adenocarcinoma Found in a Rectal Fissure

Abstract Small cell carcinomas are aggressive high-grade malignancies most commonly diagnosed in the lung, but can also be found in extrapulmonary sites such as the breast, kidney, urinary bladder, uterus, ovary, pancreas, hepatobiliary tree, thymus, skin, and salivary glands. Although the gastrointestinal system has an abundance of neuroendocrine cells, small cell carcinomas in this region have a low incidence. We present the case of a 51-year-old man with a history of pain with bowel movements and recent weight loss. Colonoscopy was performed, which revealed a rectal fissure with a lesion involving the rectum and anal canal. Biopsy of the lesion revealed invasive carcinoma with 2 distinct morphologies, a poorly differentiated small cell component and a minor adenocarcinoma component. We discuss the differential diagnosis of small cell carcinoma that includes mixed adenoneuroendocrine carcinomas and other neuroendocrine neoplasms.

Triple marker composed of p16, CD56, and TTF1 shows higher sensitivity than INSM1 for diagnosis of pulmonary small cell carcinoma: proposal for a rational immunohistochemical algorithm for diagnosis of small cell carcinoma in small biopsy and cytology specimens

Pulmonary small cell carcinoma (SCLC) can be usually diagnosed based on the morphological evaluation of routine histological or cytological preparations. However, immunohistochemistry may be also necessary in problematic cases. Insulinoma-associated 1 (INSM1) has recently been reported as a highly sensitive and specific marker that displays positivity in ~90%-100% of poorly differentiated pulmonary neuroendocrine tumors. We compared diagnostic performance of INSM1 and previously reported composite marker CD56 + p16 + thyroid transcription factor-1 (TTF1) in the diagnosis of SCLC in small biopsy specimens and cytoblocks. The composite marker CD56 + p16 + TTF1 correctly classified 100% of SCLC cases, and its sensitivity was significantly higher than the sensitivity of INSM1. Among 100 SCLC cases, CD56, TTF1, and p16 each individually classified more specimens correctly than INSM1 (CD56: 84%, TTF1: 89%, p16: 95%, INSM1: 81%); the difference was statistically significant only for p16. INSM1 showed the lowest classification agreement between paired biopsy and cytoblock specimens (κ = 0.182), whereas CD56 and p16 displayed perfect agreement (κ = 1) and TTF1 showed moderate agreement (κ = 0.4). Although INSM1 is reportedly the most specific marker of SCLC, its sensitivity is not superior to p16 or composite marker CD56 + TTF1 + p16. Based on this study, we propose the following algorithm, which, in the appropriate clinical and histological context, may be useful in establishing the correct diagnosis of SCLC: First, INSM1 detection is performed, and if the result is negative, CD56 is added, followed successively by p16 and TTF1 if all previously applied markers are negative. This approach should detect most, if not all, SCLC cases, while successively trading specificity for sensitivity.

Insulinoma-associated protein 1 is a novel sensitive and specific marker for small cell carcinoma of the prostate

The correct diagnosis of small cell carcinoma (SCC) of the prostate is critical because of its aggressive behavior and poor prognosis. The histopathologic diagnosis could be challenging without neuroendocrine markers, which currently has limitations. Insulinoma-associated protein 1 (INSM1), a zinc-finger transcription factor, is considered to play an important role in the development of several neuroendocrine precursor cells. Its diagnosis value has only recently been evaluated. In this study, we analyzed the expression of INSM in three high-throughput RNA sequencing data sets and performed INSM1 immunohistochemistry on a large series of prostatic SCCs and non-neuroendocrine prostate tissues. To validate its possible utility as a diagnostic marker, the performance of chromogranin and synaptophysin was used for comparison. We found INSM1 mRNA is up-regulated in neuroendocrine prostate carcinoma samples from the published data sets. The results were verified by the immunohistochemistry performance. INSM1 was positive in 92.3% of prostatic SCCs, compared with 53.8% positive for chromogranin, and 84.6% positive for synaptophysin. INSM1 was also stained all of the mixed SCC-acinar adenocarcinomas and metastatic SCCs progression from acinar adenocarcinoma. Only 3.4% of benign prostate tissues and 4.0% of prostate adenocarcinomas were INSM1 positive. Our data suggest that INSM1 is a novel sensitive and specific marker for detection of SCC of the prostate. Application of INSM1 in clinical pathologic diagnosis will be valuable.

Cervical small cell carcinoma frequently presented in multiple high risk HPV infection and often associated with other type of epithelial tumors

BackgroundSmall cell carcinoma of the uterine cervix is a rare and highly malignant tumor, and its etiopathogenesis is strongly related to high-risk HPV infections.MethodsThe clinicopathological data of 30 cases of cervical primary small cell carcinoma were retrospectively analyzed. In situ hybridization, polymerase chain reaction and reverse dot-blot hybridization were employed to detect HPV DNA in both small cell carcinoma and other coexisting epithelial tumors. Immunohistochemistry was used to detect the protein expression of p16 and p53.ResultsAmongst 30 patients with cervical primary small cell carcinoma, 15 patients simultaneously exhibited other types of epithelial tumors, including squamous cell carcinoma, adenocarcinoma, squamous cell carcinoma in situ, and adenocarcinoma in situ. Most tumor cells infected with HPV presented integrated patterns in the nuclei by in situ hybridization. HPV DNA was detected in every small cell carcinoma case (100%) by polymerase chain reaction and reverse dot blot hybridization. 27 cases (90%) harbored type 18, and 15 (50%) displayed multiple HPV18 and 16 infections. The prevalence of HPV 18 infection in small cell carcinoma was higher than in cervical squamous and glandular epithelial neoplasms (P = 0.002). However, similar infection rates of HPV 16 were detected in both tumors (P = 0.383). Both small cell carcinoma and other types of epithelial tumors exhibited strong nuclear and cytoplasmic staining for p16 in all cases. Three cases of small cell carcinoma revealed completely negative p53 immunohistochemical expression in 15 cases of composite tumors, which suggested TP53 nonsense mutation pattern. The pure small cell carcinoma of uterine cervix had similar mutation or wild type pattern for TP53 compared with composite tumor (P = 0.224).ConclusionsCervical small cell carcinomas are often associated with squamous or glandular epithelial tumors, which might result from multiple HPV infections, especially HPV 16 infection. Multiple HPV infections were not correlated with tumor stage, size, lymphovascular invasion, lymph node metastasis, or prognosis. Furthermore, careful observation of specimens is very important in finding little proportion of small cell carcinoma in the composite lesions, specifically in cervical biopsy specimens, in order to avoid the missed diagnosis of small cell carcinoma.

Refractory pleural small cell carcinoma in never smoker. A case report

A 47-year-old woman who had never smoked was evaluated for chest wall pain, cough and dyspnea that proved to be due to neoplastic right pleural disease with effusion. Cytological examination of the pleural fluid and histological analysis of a biopsy specimen of the pleural mass obtained during thoracoscopy were consistent with a diagnosis of small cell carcinoma. The patient was treated with two lines of chemotherapy and with octreotide, but without any clinical or radiological benefit. Since there was immunohistochemical overexpression of epidermal growth factor receptor, the patient was treated with gefitinib. Despite an initial clinical improvement she died due to disease progression. This case of a refractory pleural small cell carcinoma, which is an extremely rare disease, is the first reported in a never smoker and the first to be fully characterized for EGFR status.

Small cell carcinoma of upper urinary tract

Introduction: Small cell carcinoma (SCC) of upper urinary tract is not common and often associated with poor prognosis. We aimed to analyze the prognostic factors based on the pooled cases published in the literature. Patients and Methods: In addition to 10 cases treated at our hospital since 1990, 52 additional published cases with SCC of renal pelvis and ureter were enrolled into this study. We investigated the following risk factors associated with clinical outcome: age at diagnosis, gender, tumor location, histology, tumor stage, and treatment modality using univariate log-rank test and multivariate Cox analyses. Results: A total of 62 cases were enrolled into the study, including ten added by us. There were 30 cases from renal pelvis, 26 from the ureter, and 6 both sites. The mean age is 65.8 ± 13.0 years, and the median survival is 12 months. Patients with SCC of renal pelvis were significantly younger than did those of the ureter (P = 0.004), as well as higher stage (P = 0.043). Univariate analysis showed that both tumor stage and the presence of radiotherapy were significant predictors of disease-specific overall survival (P = 0.015 and 0.029, respectively), as well as the overall survival (P = 0.035 and 0.036, respectively). Cox's multivariate analysis showed tumor stage is an independent prognostic factor for disease-specific overall survival (hazard ratio, 2.11; 95% confidence interval, 1.08–4.13; P = 0.029). Conclusions: In the current study, tumor stage is significantly associated with disease-specific overall survival. This finding warns us the importance of early diagnosis of SCC.

P16 is a useful supplemental diagnostic marker of pulmonary small cell carcinoma in small biopsies and cytology specimens.

Pulmonary small cell carcinoma (SCLC) is usually diagnosed in small biopsy or cytological specimens based on cytomorphology; however in ambiguous cases diagnosis requires additional support by immunohistochemistry. While TP53 and RB1 alterations with secondary overexpression of p16 are mainstay events in SCLC pathogenesis, diagnostic value of p16-positivity in the diagnosis of SCLC has not yet been fully investigated. We examined the expression of p16, CD56, synaptophysin (SYP), chromogranin A and thyroid transcription factor-1 (TTF1) in a series of pulmonary and extrapulmonary small cell carcinomas, pulmonary carcinoids and non-small cell lung carcinomas, and compared diagnostic performance of these markers in the diagnosis of SCLC. P16 was positive in 95 of 101 SCLCs, and displayed highest diagnostic sensitivity of ~94%. Composite biomarkers CD56+p16+TTF1 and CD56+p16+SYP were both able to detect correctly all SCLC cases. Importantly, three (~3%) SCLC cases completely negative for all conventional markers displayed diffuse positivity for p16. CD56 and p16 demonstrated highest concordance between paired small biopsy and cytology specimens. 50% of squamous cell carcinomas, ~41% of adenocarcinoma/NSCLC-favour adenocarcinoma cases, and ~93% of extrapulmonary small cell carcinomas also showed p16-positivity. Combination of CD56, p16 and TTF1 produced diagnostic classifier that outperformed best single marker CD56 in differential diagnosis between SCLC and NSCLC. In conclusion, in the appropriate morphological context p16 represents a useful supplementary marker for diagnosis of SCLC, even in cases where only cytological material is available.

Metastatic small cell carcinoma with psammoma bodies: A diagnostic pitfall

Large three‐dimensional neoplastic cell aggregates and psammoma bodies are rare in metastatic small cell carcinoma and could represent a diagnostic pitfall, given their more frequent associations with adenocarcinoma. Careful attention to other classic cytomorphologic features is cardinal to the diagnosis of small cell carcinoma.

Paraneoplastic Cushing Syndrome: A Sign of Occult Malignancy

SESSION TITLE: Metastatic and Other Primary Lung Tumors SESSION TYPE: Affiliate Case Report Poster PRESENTED ON: Tuesday, October 31, 2017 at 01:30 PM - 02:30 PM INTRODUCTION: Cushing Syndrome (CS) results from prolonged hypercortisolism. While often caused by iatrogenic administration of exogenous steroids or Cushing Disease, CS is also rarely caused by secretion of ACTH from ectopic sources, such as malignancies. Though rare - with ectopic ACTH secretion (EAS) accounting for only >15% of endogenous CS cases - diagnosis of CS can lead to earlier discovery of occult malignancy and increase potential for successful treatment. Clinicians therefore need a high degree of suspicion when faced with such presentations. CASE PRESENTATION: 57-yo man with CKD, CAD, HTN, DM and a long smoking history was admitted with respiratory failure due to CAP with dyspnea, weight gain, abdominal distention, and extremity weakness x 1 month. Physical exam showed reduced breath sounds over his right lower lung fields and abdominal obesity, but no Cushingoid appearance. He had marked refractory HTN. Labs showed profound hypokalemia with metabolic alkalosis, hypoxemia, hypercapnia and leukocytosis. CXR showed a right pleural effusion and basilar infiltrate. Elevated serum cortisol and ACTH levels helped diagnose CS. Abdominal CT showed no adrenal mass. Lab tests ruled out pheochromocytoma. A negative dexamethasone suppression test led to suspicion for EAS. CT Chest showed a mass with RML bronchial obstruction, mediastinal LAD and bilateral noncalcified lung nodules concerning for metastatic disease. While pleural fluid analysis showed a transudative effusion and microbiology was negative, cytology showed atypical cells suspicious for malignancy. Biopsy of the RML mass allowed for a unifying diagnosis of small cell carcinoma (SCLC) as the cause of the paraneoplastic CS. Chemotherapy was promptly started. DISCUSSION: Current standard practice for CS diagnostic work-up includes 8 mg dexamethasone suppression and CRH stimulation tests, inferior petrosal sinus sampling (IPPS), and imaging including CT, MRI, octreotide scans and venous sampling. In cases of EAS, the majority did not respond to CRH stimulation or dexamethasone suppression. IPPS was found most likely to identify the disease. Hypercortisol control treatments range from medications such as ketoconazole, metyrapone, or etomidate to surgical bilateral adrenalectomy. The highest rate of cure, up to 65%, came with the surgical removal of the ectopic ACTH-secreting neoplasm though recurrence was a possible complication. While cure in nonsurgical candidates is relatively rare, survival was common except in those cases of paraneoplastic CS caused by aggressive diseases. CONCLUSIONS: Though rare and difficult to recognize, Paraneoplastic CS may be the first sign of malignancy. While the source of EAS may be benign, it can be seen with SCLC, gastrinoma, medullary thyroid cancer and other such aggressive malignancies. Early identification may be lifesaving. Reference #1: Bertherat J. Cushing syndrome due to ectopic ACTH secretion. Orpha Net. 2012; ORPHA:99889 DISCLOSURE: The following authors have nothing to disclose: Vandana Pai, Kim Phung Nguyen, Jennifer Treece, Badar Siddiqui, Lisa McKinney-Smith No Product/Research Disclosure Information