Cell Carcinoid Tumors Research Articles

ODP278 A rare case of Ectopic ACTH secretion associated with Primary Gastric Choriocarcinoma

Abstract Background Ectopic ACTH production contributes to 10-15% of cases of Cushing's syndrome. Most cases are caused by neuroendocrine tumors of the lung, pancreas, or thymus. Other rare tumors causing ectopic ACTH secretion include esophageal tumor, gastric carcinoid tumor and squamous cell carcinoma of the larynx (1). We present a rare case of ectopic ACTH production causing Cushing syndrome due to primary gastric choriocarcinoma. Case Presentation A 27-year-old lady, not known to have any chronic illnesses, presented with two days history of epigastric pain. The patient also reported facial puffiness, leg swelling, generalized weakness and oligomenorrhea for the last four months. There was no history of easy bruisability or weight. She was not taking any medications. The patient did not smoke or use alcohol. Physical examination revealed conjunctival pallor, facial acne, wide striae on her thighs and hepatomegaly. The rest of the examination was normal. Lab tests showed microcytic anemia with hemoglobin of 7 gm/dl (12-15 gm/dl), hypokalemia (2.5 mmol/L; normal 3.5-5.3 mmol/L), AST 38 U/L (0-40 U/L) and ALT 45 U/L (0-41 U/L). β HCG was 1,506 mIU/mL (0 -5 mIU/ml). An abdominal ultrasound showed hepatomegaly with multiple echogenic solid mass lesions suspicious of metastatic origin. A CT abdomen showed a solid lesion in the fundal region of the stomach with multiple liver metastases and moderate ascites. An esophagogastroduodenoscopy showed fungating mass originating from the stomach fundus. Biopsy of the gastric mass revealed primary gastric adenocarcinoma, which was positive forCK 7, CK 19, beta hCG, CDX2 and CEA, consistent with the diagnosis of primary gastric choriocarcinoma. Due to widespread metastasis, the patient was started on palliative chemotherapy with dexamethasone 2 mg injection once daily along with capecitabine, cisplatin and pembrolizumab. In view of persistent hypokalemia and physical examination findings, a workup for Cushing's syndrome was performed. Early-morning serum cortisol was 1054 nmol/L (138–689 nmol/L), and plasma ACTH was 174 pg/ml (7.2-63.3 pg/ml) despite the patient being on intravenous 2 mg dexamethasone once daily for more than ten days. An MRI of the brain showed a normal pituitary gland. Based on these findings, the patient was diagnosed with Cushing's syndrome due to ectopic ACTH secretion. Unfortunately, her hospital course was complicated by massive upper gastrointestinal bleeding from the tumor, leading to her demise. Conclusion Gastric choriocarcinoma is a rare tumor associated with ectopic ACTH secretion leading to Cushing's syndrome. Reference: Imura H, Matsukura S, Yamamoto H, Hirata Y, Nakai Y. Studies on ectopic ACTH-producing tumors. II. Clinical and biochemical features of 30 cases. Cancer. 1975 May;35(5): 1430-7 Presentation: No date and time listed

A rare case report of renal ewing sarcoma/primitive neuroectodermal tumor with ACTH production

BackgroundEwing sarcoma/primitive neuroectodermal tumor (PNET) of the renal is extremely rare. The common cause of ectopic ACTH syndrome is pulmonary neuroendocrine tumors, such as small cell carcinomas and carcinoid tumors. Here, we present an unusual case of ectopic ACTH syndrome and hypothyroidism caused by Ewing sarcoma/PNET of the right kidney.Case presentationA 19-year-old girl presented with a history of right lumbar pain and discomfort for 2 months, aggravated for 2 days. Abdominal contrast-enhanced computed tomography and computed tomography angiography showed an upper pole occupancy of the right kidney occupancy with subepithelial hemorrhage. Preoperative hormone levels including plasma total cortisol (PTC), adrenocorticotrophic hormone (ACTH) and thyroid hormone measurements were abnormal, indicating that the patient had Cushing syndrome and hypothyroidism. The patient underwent right radical nephrectomy. Histopathological analysis revealed a renal small round blue cell tumor (consistent with a primitive neuroectodermal tumor), with positive immunohistochemistry for CD99 and Ki67 (about 10%) and molecular pathology for EWSR1 gene fusions. PTC, ACTH and thyroid hormone returned to normal after surgery.ConclusionsWe report a rare ectopic ACTH syndrome and hypothyroidism due to renal Ewing sarcoma/PNET. The clinical manifestation of renal Ewing sarcoma/PNET is non-specific and the diagnosis relies on pathological morphology, immunohistochemistry and fusion gene detection. At present, surgery combined with radiotherapy and chemotherapy is used in the treatment, but the prognosis is still not optimistic.

The single-cell transcriptional landscape of lung carcinoid tumors.

Lung carcinoid tumors, also referred to as pulmonary neuroendocrine tumors or lung carcinoids, are rare neoplasms of the lung with a more favorable prognosis than other subtypes of lung cancer. Still, some patients suffer from relapsed disease and metastatic spread. Several recent single-cell studies have provided detailed insights into the cellular heterogeneity of more common lung cancers, such as adeno- and squamous cell carcinoma. However, the characteristics of lung carcinoids on the single-cell level are yet completely unknown. To study the cellular composition and single-cell gene expression profiles in lung carcinoids, we applied single-cell RNA sequencing to three lung carcinoid tumor samples and normal lung tissue. The single-cell transcriptomes of carcinoid tumor cells reflected intertumoral heterogeneity associated with clinicopathological features, such as tumor necrosis and proliferation index. The immune microenvironment was specifically enriched in noninflammatory monocyte-derived myeloid cells. Tumor-associated endothelial cells were characterized by distinct gene expression profiles. A spectrum of vascular smooth muscle cells and pericytes predominated the stromal microenvironment. We found a small proportion of myofibroblasts exhibiting features reminiscent of cancer-associated fibroblasts. Stromal and immune cells exhibited potential paracrine interactions which may shape the microenvironment via NOTCH, VEGF, TGFβ and JAK/STAT signaling. Moreover, single-cell gene signatures of pericytes and myofibroblasts demonstrated prognostic value in bulk gene expression data. Here, we provide first comprehensive insights into the cellular composition and single-cell gene expression profiles in lung carcinoids, demonstrating the noninflammatory and vessel-rich nature of their tumor microenvironment, and outlining relevant intercellular interactions which could serve as future therapeutic targets.

Expression of Estrogen and Progesterone Receptors in a Tailgut Cyst with Carcinoid Tumor

Abstract Introduction/Objective Tailgut cysts (TC) are congenital lesions that arise in the presacral space. They originate from the embryonic hindgut and usually present between the ages of 30-60, with female predominance. TCs are usually asymptomatic or can present with lower back, perianal or pelvic pain. Malignant transformation of a TC is a rare complication, with adenocarcinoma being the most common, followed by carcinoid tumor. About thirty cases of carcinoid tumors arising in a TC have been reported in the literature so far with a slight female predominance (1.5:1). Methods/Case Report We describe a 40-year-old Hispanic woman with a 9-year history of cyclic pelvic pain related to her menstrual cycles. She was diagnosed with adenomyosis and underwent hysterectomy that did not completely resolve her symptoms. Follow-up serial imaging showed a growing complex-cystic presacral mass, which was eventually excised. Grossly, there was a 3.6×3.1×2.5 cm multiloculated cystic mass filled with mucoid material. Microscopically, there were multiple cystic spaces lined by benign squamous and mucinous columnar epithelium and surrounded by smooth muscle cells. A 6-mm carcinoid tumor was found within a cyst wall and confirmed by positive synaptophysin and chromogranin staining with a Ki-67 proliferation index of <2%. Estrogen and progesterone receptor immunostains were positive in the epithelial cyst linings and the stromal cells but not in the carcinoid tumor cells. Results (if a Case Study enter NA) NA Conclusion We conclude that the diagnosis of TC should be considered in the differential of gynecologic patients with unresolved cyclic pelvic pain and that estrogen and progesterone could have an important role in the pathogenesis of TCs. Furthermore, estrogen receptors can be a therapeutic target in patients with this entity.

P38.04 3D Analysis of Spread Through Air Spaces in Squamous Cell Carcinoma and Carcinoid Tumor Using Whole Block Imaging by Micro CT

P38.04 3D Analysis of Spread Through Air Spaces in Squamous Cell Carcinoma and Carcinoid Tumor Using Whole Block Imaging by Micro CT

Human bronchial carcinoid tumor initiating cells are targeted by the combination of acetazolamide and sulforaphane

BackgroundBronchial carcinoids are neuroendocrine tumors that present as typical (TC) and atypical (AC) variants, the latter being more aggressive, invasive and metastatic. Studies of tumor initiating cell (TIC) biology in bronchial carcinoids has been hindered by the lack of appropriate in-vitro and xenograft models representing the bronchial carcinoid phenotype and behavior.MethodsBronchial carcinoid cell lines (H727, TC and H720, AC) were cultured in serum-free growth factor supplemented medium to form 3D spheroids and serially passaged up to the 3rd generation permitting expansion of the TIC population as verified by expression of stemness markers, clonogenicity in-vitro and tumorigenicity in both subcutaneous and orthotopic (lung) models. Acetazolamide (AZ), sulforaphane (SFN) and the AZ + SFN combination were evaluated for targeting TIC in bronchial carcinoids.ResultsData demonstrate that bronchial carcinoid cell line 3rd generation spheroid cells show increased drug resistance, clonogenicity, and tumorigenic potential compared with the parental cells, suggesting selection and expansion of a TIC fraction. Gene expression and immunolabeling studies demonstrated that the TIC expressed stemness factors Oct-4, Sox-2 and Nanog. In a lung orthotopic model bronchial carcinoid, cell line derived spheroids, and patient tumor derived 3rd generation spheroids when supported by a stroma, showed robust tumor formation. SFN and especially the AZ + SFN combination were effective in inhibiting tumor cell growth, spheroid formation and in reducing tumor formation in immunocompromised mice.ConclusionsHuman bronchial carcinoid tumor cells serially passaged as spheroids contain a higher fraction of TIC exhibiting a stemness phenotype. This TIC population can be effectively targeted by the combination of AZ + SFN. Our work portends clinical relevance and supports the therapeutic use of the novel AZ+ SFN combination that may target the TIC population of bronchial carcinoids.

Three-Dimensional (3D) Imaging Spectroscopy of Carcinoma, Sarcoma, Leukemia, Lymphoma, Multiple Myeloma, Melanoma, Brain and Spinal Cord Tumors, Germ Cell Tumors, Neuroendocrine Tumors and Carcinoid Tumors under Synchrocyclotron Radiation

Three-Dimensional (3D) Imaging Spectroscopy of Carcinoma, Sarcoma, Leukemia, Lymphoma, Multiple Myeloma, Melanoma, Brain and Spinal Cord Tumors, Germ Cell Tumors, Neuroendocrine Tumors and Carcinoid Tumors under Synchrocyclotron Radiation

Three–dimensional (3D) imaging spectroscopy of carcinoma, sarcoma, leukemia, lymphoma, multiple myeloma, melanoma, brain and spinal cord tumors, germ cell tumors, neuroendocrine tumors and carcinoid tumors under synchrotron radiation

Three–dimensional (3D) imaging spectroscopy of carcinoma, sarcoma, leukemia, lymphoma, multiple myeloma, melanoma, brain and spinal cord tumors, germ cell tumors, neuroendocrine tumors and carcinoid tumors under synchrotron radiation

Relationship of Serotonin to Neuron Specific Enolase In Serum Samples of Patients with Advanced Stages of Cancer Tumors

Cancer is heterogeneous disorders characterized by cellular different genetic alterations and diverse clinical behaviours results from uncontrolled division leads to loss of control of the cells growth. Neuron Specific Enolase(NSE) is considered as a marker of many diseases such as brain damage (traumatic brain injury), stroke and anoxic encephalopathy after cardiac arrest. Generally, in adults NSE accepted as a marker protein in the brain. Serotonin exhibits a growth stimulatory effect on several types of carcinoma, carcinoid and other tumor cells. In contrast, a few data are available on serotonin involvement in cancer cell migration and metastatic processes. Serum serotonin level was found to be suitable for prognosis evaluation of urothelial carcinoma in the urinary bladder, adenocarcinoma of the prostate and renal cell carcinoma. 201 patients with malignant tumors, 74 patients with different benign tumors and, 83 healthy individuals were enrolled in the present study. Our results show a significant increase ( p = 0.011, and 0.043) of serum serotonin levels in malignant tumors group when compared with those of benign tumors (as a pathological control) group, and healthy individuals groups; respectively. No such results were shown when the two control (benign tumors and healthy individuals) groups were compared together. While evaluation of the NSE concentrations revealed a significant decrease in patients with malignant tumors when compared with those of benign tumors ( p = 0.028), and healthy individuals ( p < 0.000). According to ANOVA test, Same variations ( p < 0.000) were obtained when benign tumors and healthy controls groups were compared together. Results shows a significant decrease in the serotonin concentration ( p < 0.05) as well as the NSE ( p < 0.01) levels, correlation between the levels of the two examined parameters has been negative and statically acceptable ( r = - 0.723 at p <0.05) at malignant tumor patients group after treatment by chemotherapy or radiotherapy. Before treatment with chemotherapy or radiotherapy, negatively significant correlation ( r = - 0.792 at p < 0.001) was observed for the concentrations of Serotonin to the NSE in the sera of malignant tumor patients group, while no such correlations were noted at this relation examined in the benign tumor patients. Serotonin and NSE correlations together can be used as primary diagnostic tools for distinguishing between cancerous and benign tumors, this correlation increases the sensitivity of the two biomarkers together comparing to measure everyone alone.

Serotonin as a Marker to the Response of Patients with Advanced Stages of Cancer during Treatment with Chemotherapy and Radiotherapy

Serotonin is synthesized by conversion L-tryptophan into 5-hydroxytryptamine in the body by using two catalyze factors are tryptophan hydroxylase and 5-hydroxytryptophan decarboxylase, it exhibits a growth stimulatory effect on several types of carcinoma, carcinoid and other tumor cells. In contrast, few data are available on serotonin involvement in cancer cell migration and metastatic processes. Serum serotonin level was found to be suitable for prognosis evaluation of urothelial carcinoma in the urinary bladder, adenocarcinoma of the prostate and renal cell carcinoma. Subjects: 201 patients with malignant tumors, 74 patients with different benign tumors and 83 healthy individuals were enrolled in the present study. Results: Outresults show a significant increase (p=0.011 and 0.043) of serum serotonin levels in malignant tumors group when compared with those of benign tumors (as a pathological controls) group, and healthy individuals groups; respectively. No such results were shown when the two control (benign tumors and healthy individuals) groups were compared together. Conclusion: Increase of serotonin could be related to activation of the serotonergic receptors sensitivity.

Metachronous Primary Carcinoid Tumor and Spindle Cell Carcinoma of the Lung

Metachronous Primary Carcinoid Tumor and Spindle Cell Carcinoma of the Lung

C4-P-10Three-dimensional ultrastructural analysis of secretory granules in histological paraffin sections of endocrine tumors using low-vacuum SEM

Secretory granules of endocrine tumors are traditionally identified by transmission electron microscopy of tissue samples. Recently, we developed a simple method for three-dimensional morphological analysis of conventional paraffin sections using low-vacuum scanning electron microscopy (SEM) [1], and showed that this technique was useful for pathological diagnosis of renal biopsy samples [2]. In this study, we investigated whether this method is useful as an adjunct in pathological diagnosis of endocrine tumors. Preparations were processed according to our original method. Paraffin sections (5 μm thick) obtained from a normal rat pancreas as a control, a human pituitary adenoma and a colorectal carcinoid tumor were generated by the conventional method. After deparaffinization, the sections were stained only with platinum blue aqueous solution (TI-blue staining kit: Nisshin EM, Tokyo) for 15 min at room temperature, and then observed by low-vacuum SEM (TM-1000, TM3030 plus: Hitachi, Tokyo) at high magnification (~30,000×). Under low-vacuum SEM, secretory granules of each cell could be identified as bright spherical granules in each paraffin-sectioned tissue, depending on the contrast of BSE signals. Figure shows low-vacuum SEM image (a) and TEM image (b) of endocrine secretory granules 100–260nm in diameter (arrows) in colorectal carcinoid tumor cells. Our results suggest that low-vacuum SEM of conventional paraffin sections is suitable for the pathological diagnosis of endocrine tumors. [1] Inaga et al., Arch. Histol. Cytol., 72 (2009) 101-106. [2] Okada et al., Biomed. Res., 35 (2014) 345-350. C4-P-09 doi:10.1093/jmicro/dfv327

Microscopic Carcinoid: An Unusual Presentation of Gastric Carcnioid

51 year old Caucasian male with history of hyperlipidemia presented with complain of melena. Patient had noticed one episode of bright red blood per rectum. On questioning patient also complained of feeling tired lately with generalized body aches. He also had some numbness and tingling in both lower extremities which had been gradually worsening. Neurological exam showed decreased sensation, vibration and position sensation in both lower extremities. Digital rectal exam was positive for frank blood in rectal vault. Initial laboratory work up showed hemoglobin of 8.5 with MCV of 110. Patient underwent upper endoscopy which showed non-bleeding gastric ulcer. Also there were few scattered small focal areas of erythematous lesions in gastric cardia and proximal body with significant loss of the gastric folds. Biopsy of the lesions showed increase in fibrous tissue with moderate active inflammation of lamina propria and Chronic atrophic gastritis while rapid urease test was negative. Interestingly, carcinoid changes with chronic intestinal metaplasia were found on biopsy suspicious for carcinoid tumor. Given the finding on biopsy, fasting serum Gastrin Chromogranin A levels, Parietal cell antibodies, Intrinsic Factor antibodies, 24 hour urine for 5-HIAA, Computerized tomography (CT) scan of the abdomen and pelvis, and Octreotide scan were ordered to look for primary location of carcinoid tumor. Fasting serum Gastrin Chromogranin A levels, Parietal cell antibodies, Intrinsic Factor antibodies were found to be elevated the diagnosis of Carcinoid Tumor but there were no mass lesions but only scattered cells in the stomach. Patient subsequently underwent frequent endoscopies with biopsies which reconfirmed well differentiated carcinoid tumor cells scattered in the stomach but no mass lesion. Meanwhile patient underwent extensive work up for peripheral neuropathy and was found to have vitamin B12 deficiencies in setting of atrophic gastritis leading towards diagnosis of pernicious anemia which was likely cause of the underlying carcinoid changes. Patient is currently treated with vitamin B12 with marked improvement in his symptoms and is undergoing Surveillance endoscopies of carcinoid changes. Discussion: Carcinoid tumors Originate from Enterochromaffin-like (ECL) cells, found in gastric wall. There are three types of gastric carcinoid tumors. Type 1 are smaller and less than 1 cm, multiple, polypoid lesions with central ulceration associated with chronic atrophic gastritis and pernicious anemia. Type 2 occurs in association with gastrinomas (Zollinger-Ellison syndrome), often in setting of MEN type 1 and are mostly indolent in nature. While type 3 are Sporadic as they occur in the absence of atrophic gastritis or the Zollinger-Ellison /MEN1 syndromes and are very aggressive in nature. They are characterized by normal gastrin level. Diagnosis for carcinoid tumors include biochemical testing including urinary excretion of 5-HIAA, Chromogranin level, Blood serotonin concentration, Gastrin level and Anti parietal cell antibodies. Tumor localization is done by CT, Magnetic resonance Imaging, Octreotide scan. Type 1 and 2 are treated with endoscopic resections and survelliant endoscopies. Treatment for type 3 gastric carcinoid tumors is partial or total gatstrectomy considering the aggressive nature. Conclusions: Carcinoid tumors usually appear as discrete masses but microscopic carcinoid tumor in stomach is a very rare.

An Incidental Finding of Rectal Carcinoid Tumor

Adenocarcinoma is the most common malignancy found in the rectum. However, the incidence of rectal carcinoid has been rising after implementation of screening colonoscopy. The rectum is the second most common anatomic site for carcinoid tumor. Embryologically, rectal carcinoids are hindgut tumors which are non secretory. Hence, they rarely present with carcinoid syndrome even in patients with metastatic disease. A recent systematic review of rectal carcinoid by McDermott et.al was unable to perform a metaanalysis on optimal treatment strategies for localized and widespread disease due to the wide variety of data recorded from various sources. Our aim is to make physicians aware that the rectal carcinoid is becoming a common diagnosis thus clinicians should have current knowledge of classification, management and treatment options available. A 62-year-old African American male with a significant past medical history of hypertension and tobacco abuse presented to the gastrointestinal (GI) lab for colorectal cancer screening colonoscopy. Patient had no specific GI complaints and a 10-point review of symptoms was unremarkable except for decreased exercise tolerance. Physical examination was unremarkable including digital rectal exam. During colonoscopy, a 7-10 mm firm polypoid submucosal lesion was noted in distal rectum and was resected using an electrocautery snare and ERBE endocut current. Histologic evaluation of the resected polyp demonstrated a well-differentiated neuroendocrine neoplasm that stained positive for chromogramin, synaptophysin, and Ki-67 proliferation marker. Patient underwent repeat colonoscopy about a month later. Biopsy obtained from previous polypectomy site was negative for carcinoid tumor cells. The rectal carcinoid classification, management and treatment options have been defined based on the size and aggressiveness of the lesion. As there is no defined TNM system classification, there is no homogenous data available yet on how to manage rectal carcinoid. Treatment strategy is based on tumor size, radiologic testing and surveillance examination including use of rectal EUS.Figure 1

Abstract P5-03-04: The role of lung biopsy in the management of lung nodules in breast cancer patients

Abstract Background: A biopsy of lung nodules in patients, who had received previous surgery for breast cancer, can be performed with three aims: to confirm that the lesion is lung metastasis, to confirm the diagnosis of other diseases including primary lung cancer, and to reassess tumor’s characteristics. Discordance in estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor 2 (HER2) status between primary breast cancer and metastatic lesions has been reported. The aim of this study was to assess the role of lung biopsy in the diagnosis and to determine the changes in hormonal receptor and HER2 status of the metastatic lesions. Methods: A total of 38 consecutive patients who underwent surgery in 31 or transbronchial lung biopsy (TBLB) in 7 for lung nodules between 1997 and 2014 after curative operation for breast cancer were reviewed. Results: Eighteen patients (47%) had a solitary lung nodule. The pathologic diagnoses of lung nodules were lung metastases of breast cancer in 20 patients, primary lung tumor in 14 (Adenocarcinoma in 10; Large cell carcinoma in 2; Small cell carcinoma and Carcinoid tumor in 1 each), and other diagnoses in 4 (Inflammation and organizing pneumonia in 2 each). Median follow up duration were 118.8 months in metastatic breast cancer patients and 105.3 months in other histology patients (p=0.392). The average disease-free interval from the surgery for primary breast cancer were 68.6 months in metastatic breast cancer patients and 66.3 months in other histology patients (p=0.897). The 10-year survival rate after the surgery for primary breast cancer was significantly longer in other histology patients (92.3%), including primary lung cancer patients than in metastatic breast cancer patients (55.1%) (p=0.0308). In 20 cases of metastatic breast cancer, rates of discordance were 5%, 10% and 10% for ER gain, PgR gain and HER2 loss, respectively. Sixteen of patients maintained the same tumor phenotype, whereas 4 changed during progression. Especially, 2 cases of ER, PgR gain could receive endocrine therapy instead of chemotherapy. Conclusion: As lung nodules that appear in breast cancer patients are not always lung metastases, the pathologic diagnosis should be confirmed, and surgery is an option for the pathologic confirmation. Furthermore, discordance in biomarker status between primary breast cancer and the lung metastasis occurred in 20% of cases. It is necessary for clinicians to check biomarker status in recurrent breast cancer patients as it may assist a shift in the treatment plan. Citation Format: Kazuo Matsuura, Takayuki Kadoya, Norio Masumoto, Hideo Shigematsu, Akiko Emi, Keiko Kajitani, Morihito Okada, Tsuyoshi Kataoka, Rumi Haruta, Koji Arihiro, Midori Noma, Toshiyuki Itamoto. The role of lung biopsy in the management of lung nodules in breast cancer patients [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P5-03-04.

Small Duodenal Carcinoids

We sought to compare the efficacy and safety of endoscopic ultrasound-guided endoscopic resection (ER) and endoscopic band ligation (EBL) for autoamputation of small duodenal carcinoids. The ideal management of small duodenal carcinoid tumors remains unclear. A retrospective review of duodenal carcinoids over a 10-year period (2002 to 2012) was performed at our tertiary-care teaching hospital. All patients with duodenal carcinoids ≤10 mm in size treated with either ER or EBL were included. The main outcome measurements were the efficacy and safety of endotherapy. A total of 37 patients with 39 subcentimeter duodenal carcinoids were identified. In the EBL group, the mean (SD) tumor size was 6.7±2.1 mm compared with 6.7±1.7 mm in the ER group (P=0.943). The mean Ki-67 index was ≤2% in specimens available for histologic analysis in both groups (16/23 EBL and 15/16 ER). The positive deep margin rate in the ER group was 68.8%. Residual carcinoid tumor cells were detected on follow-up biopsies in 1 patient after EBL, and 2 patients after ER. All underwent subsequent successful endotherapy. No adverse events occurred in the EBL group compared with an 18.8% adverse event rate in the ER group (P=0.066). Endoscopic ultrasound-guided EBL is a safe, effective method for removal of small superficial duodenal carcinoids and seems to be a lower risk alternative to conventional ER with cautery.

Gastric Glomus Tumour: A Rare Cause of Gastrointestinal Bleeding.

A 62-year-old man was referred to the Gastroenterology Department with complaints of haematemesis and maleana since past four days. His general physical examination showed no organomegaly. Cancer antigen (CA) 19.9 levels were normal. An esophago-gastro duodenoscopy revealed a 4x3 cm polypoid endophytic soft tissue mass lesion at the body and greater curvature on the posterior surface of stomach with an overlying normal mucosa. Computed tomography (CT) abdomen showed well-circumscribed submucosal masses in stomach with homogeneous density and no attached peritoneal soft tissue infiltration; findings were suspicious of gastrointestinal stromal tumour (GIST). Laproscopically wedge resection was performed with no complications. A wedge gastrectomy specimen was received measuring 2.5x2.0x1.5 cm with a stapled margin. On cut section a mass was noted in the wall measuring 2.0x1.0x1.0 cm which was homogenous on cut section. Mucosa was unremarkable. Histopathology showed multiple well circumscribed solid nests of tumour cells with dilated blood vessels in the submucosa separated by bundles of smooth muscle and fibrous tissue with hyalinization. Cells were small monomorphic, round cells with sharply demarcated margins, vescicular chromatin and scanty cytoplasm [Table/Fig-1a-c]. Mitosis was inconspicuous. There was no vascular invasion. Immunohistochemistry (IHC) revealed diffuse positivity for smooth muscle actin (SMA) (Dako, IA4) [Table/Fig-1d] and vimentin (Dako, V9) immunostains. Ki 67 (Dako; MIB-1) index was <1%. Cytokeratin (CK) (Biogenix; AE1 and AE3), CD 34 (Dako, QBE nd 10), CD117 (Biogenix, YR117) [Table/Fig-1e], S-100 (Dako, 5Y38), Synaptophysin (Dako;SY38), Chromogranin (Dako;IS 502), Desmin (Dako;D33) and DOG-1 (Thermo-Scientific;SP 31) were negative. Focal ulceration with necrosis was noted. Resection margin of stomach as well as circumferential margin was free. Diagnosis of Glomus tumour of stomach was given. One month follow-up period was uneventful. [Table/Fig-1a-e]: Well circumscribed lesion in submucosa (a, haematoxylin and eosin,100X) composed of monomorphic small round cells along with dilated vessels surrounded by glomus cells (b, haematoxylin and eosin,200X) with stippled chromatin and scanty cytoplasm (c, haematoxylin ... Glomus tumours are rare mesenchymal tumours arising from the neuromyoarterial canal (the canal of Sucquet-Hoyer) or glomus body. It commonly occurs in the peripheral soft tissue and extremities, but can grow anywhere in the body. As gastric glomus tumour lacks specific clinical and endoscopic characteristics, it is difficult to distinguish from more common gastrointestinal stromal tumour (GIST), paraganglioma or carcinoid tumours [1]. The epithelioid pattern of GIST is confused with glomus tumour. However, GIST usually lacks dilated capillaries and tumour cells are positive for CD117, DOG-1 and CD34. Paraganglioma cells are arranged in a characteristic Zellballen pattern with rich thin-walled blood vessels in stroma which can mimic glomus tumour. On IHC the tumour cells are positive for synaptophysin, chromogranin A and neuron specific enolase. These nests are surrounded by sustanticular cells which are positive for S-100 protein. Carcinoid tumour is a neuroendocrine carcinoma and comprised of oval or spindle tumour cells arranged in cords or nests with thin-walled blood vessels. Carcinoid tumour cells are positive for CK, S-100 protein, synaptophysin, chromogranin A, and neuron specific enolase, but negative for SMA. Glomus tumour of stomach is rare and the diagnosis is mostly dependent on the histopathologic (presence of uniform small round glomus cells) and IHC findings (Vimentin, SMA positivity and S-100 protein, CD34, CD117, DOG-1, desmin, CD56, synaptophysin, chromogranin A, neuron specific enolase and cytokeratin negativity) [2,3].

Generation and Sequencing of Pulmonary Carcinoid Tumor Cell Lines

Pulmonary carcinoid tumors account for approximately 5% of all lung malignancies in adults, and comprise 30% of all carcinoid tumors. There are limited reagents available to study these rare tumors, and consequently no major advances have been made for patient treatment. We report the generation and characterization of human pulmonary carcinoid tumor cell lines to study underlying biology, and to provide models for testing novel chemotherapeutic agents. Tissue was harvested from three patients with primary pulmonary typical carcinoid tumors undergoing surgical resection. The tumor was dissociated and plated onto dishes in culture media. The established cell lines were characterized by immunohistochemistry, Western blotting, and cell proliferation assays. Tumorigenicity was confirmed by soft agar growth and the ability to form tumors in a mouse xenograft model. Exome and RNA sequencing of patient tumor samples and cell lines was performed using standard protocols. Three typical carcinoid tumor lines grew as adherent monolayers in vitro, expressed neuroendocrine markers consistent with the primary tumor, and formed colonies in soft agar. A single cell line produced lung tumors in nude mice after intravenous injection. Exome and RNA sequencing of this cell line showed lineage relationship with the primary tumor, and demonstrated mutations in a number of genes related to neuronal differentiation. Three human pulmonary typical carcinoid tumor cell lines have been generated and characterized as a tool for studying the biology and novel treatment approaches for these rare tumors.

Incidental Discovery of Hidden Carcinoid in a Meckel’s Diverticulum

Introduction: Meckel’s diverticulum is a common congenital anomaly of the small intestine that occurs in approximately 2% of the population and is often discovered incidentally at the time of abdominal exploration using laparotomy or laparoscopy. A 75-year-old male underwent gastrectomy 4 weeks ago for newly diagnosed stage IIIB gastrointestinal stromal tumor, currently on gleevac, presented to the hospital with abdominal pain and multiple episodes of nausea and vomiting. On presentation, his vital signs were: blood pressure 208/82 mm Hg, respiratory rate 22/min, pulse 96/min, temperature 99.3° F, and pulse ox 93% on room air. Physical examination was remarkable for hypoactive and tinkling bowel sounds, and diffuse tenderness in all 4 quadrants. Initial lab work revealed a blood glucose of 238 mg/dL; complete blood count was unremarkable except for leukocytosis with a WBC count of 10.6 U/L. Abdominal x ray and small bowel follow-through was performed, which confirmed multiple dilated loops of small bowel. High-grade mid small bowel obstruction was confirmed by a computed tomography. Initial conservative management was performed with placement of a nasogastric tube, but the patient’s condition continued to worsen, so an emergent open exploratory laparotomy was performed for adhesion lysis causing the obstruction. Incidentally, Meckel’s diverticulum was found in the distal small bowel and was also excised. Pathologic analysis revealed 2 mm of carcinoid tumor in the distal part of diverticulum (Figure 1). The patient had an uneventful recovery post-operatively and had complete resolution of symptoms on the day of discharge. The majority of patients with Meckel’s diverticulum remain asymptomatic throughout their lives. The most common complications include bleeding, perforation, ileus, intussusception, and diverticulitis. The removal of asymptomatic Meckel’s diverticulum in adults is controversial, but resection is recommended in children. Incidental discovery of carcinoid tumors in a Meckel’s diverticulum have rarely been reported in the literature.Figure 1: Carcinoid tumor cells with finely granular chromatin.

Abstract 1982: TCEB3C (Elongin A3) on chromosome 18 presents a putative tumor suppressor gene of small intestine neuroendocrine tumors.

Abstract Small intestine neuroendocrine tumors (SI-NETs) arise from the enterochromaffin cells and produce hormones which can cause the carcinoid syndrome. The incidence is increasing and the five-year survival rate is 60-80 %. Loss of one copy of chromosome 18 is a very frequent event in these tumors, supporting the presence of a crucial tumor suppressor gene. This study investigated whether TCEB3C, encoding Elongin A3, presents a putative tumor suppressor gene in SI-NETs. This gene is currently the only known imprinted gene on chromosome 18, requiring only one gene copy inactivation event to fulfill the Knudson hypothesis. Elongin A3 expression in SI-NETs (n=47) was heterogeneous and negative in most cells. 5-Aza-2’-deoxycytidine induced expression of Elongin A3 in a carcinoid tumor cell line and in tumor derived primary cell cultures, but not in a control cell line. Also the general histone methyltransferase inhibitor 3-deazaneplanocin A induced TCEB3C expression in the carcinoid tumor cell line, but not in control cells suggesting further that the TCEB3C gene was epigenetically suppressed in neuroendocrine tumor cells. The TCEB3C gene encompasses an CpG island and quantitative cytosine CpG methylation analysis will be presented. Furthermore, overexpression of Elongin A3 led to a decrease in clonogenic survival of carcinoid tumor cells, but not of control cells strongly supporting a growth-regulatory role. These results support a putative tumor suppressor role of TCEB3C in neuroendocrine cells of the small intestine. Citation Format: Katarina Edfeldt, Tanvver Ahmad, Göran Åkerström, Eva Tiensuu Janson, Per Hellman, Peter Stålberg, Peyman Björklund, Gunnar Westin. TCEB3C (Elongin A3) on chromosome 18 presents a putative tumor suppressor gene of small intestine neuroendocrine tumors. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 1982. doi:10.1158/1538-7445.AM2013-1982