Pulmonary Carcinoid Tumors Research Articles

Identification of Small Molecule Hes1 Modulators as Potential Anticancer Chemotherapeutics

Hes1 is a key transcriptional regulator primarily controlled by the Notch signaling pathway, and recent studies have demonstrated both an oncogenic and tumor suppressor role for Hes1, depending on the cell type. Small molecules that activate and inhibit Hes1 activity hold promise as future anticancer chemotherapeutics. We have utilized a cell-based dual luciferase assay to identify modulators of Hes1 expression in a medium-throughput format. A modest screen was performed in HCT-116 colon cancer cell lines, and two small molecules were identified and characterized as Hes1 regulators. Compound 3 induced Hes1 expression and exhibited anticancer effects in pulmonary carcinoid tumor cells, a cell type in which the upregulated Notch/Hes1 signaling plays a tumor suppressive role. Treatment of HCT-116 cells with compound 12 resulted in Hes1 downregulation and antitumor effects.

Lung parenchymal invasion in pulmonary carcinoid tumor: An important histologic feature suggesting the diagnosis of atypical carcinoid and poor prognosis

The majority of previous studies on pulmonary carcinoid tumor have usually focused on clinical behavior or outcome, seldom considering histopathologic features. We retrospectively collected 63 cases of resected pulmonary carcinoid tumors from 1995 to 2011 at Samsung Medical Center, Seoul, Korea. The clinical and pathological features were correlated and survival analyses were performed. Forty cases (63.5%) were classified as typical carcinoid (TC) and 23 cases (36.5%) were classified as atypical carcinoid (AC) according to WHO classification criteria. AC patients showed a higher frequency of current smoking status and a higher stage of the tumor by the American Joint Committee on Cancer than TC patients. The disease was associated with death and recurrence in five and seven patients, respectively, with almost all of the associations found in AC patients. The five-year survival rate of TC and AC were 100% and 83.5%, respectively, with AC showing poorer prognosis than TC in overall survival (OS) and disease free survival (DFS) (p=0.005 and p=0.002). Lung parenchymal invasion was observed more commonly in AC than in TC (39.1% vs 12.5%, p=0.01) and was a poor prognostic factor in OS and DFS. Rosette-like arrangements were found only in six cases of AC, while abundant basophilic cytoplasm mimicking paraganglioma and ossification were found only in TC. Through the comprehensive study of pulmonary carcinoid tumor in Korea, we suggest that lung parenchymal invasion could be a useful histologic feature to suspect the diagnosis of AC in daily practice as well as to predict the prognosis of carcinoid tumor.

Two Different Types of Carcinoid Tumors of the Lung: Immunohistochemical and Ultrastructural Investigation and Their Histogenetic Consideration

Carcinoid tumors have been an interesting clinical and pathological entity for pathologists because of their unique histopathologic pattern of “Zellballen” (cell ball) and the hormones they produce demonstrable by histochemical and biochemical methods, including immunohistochemistry, and the presence of cytoplasmic dense-core particles demonstrable by electron microscopy. Since carcinoid tumors were established as an entity more than a century ago by Oberndorfer, who was credited with coining the term “carcinoid,” meaning carcinoma-like tumors, tumors presenting with similar characteristics have been reported in most of parenchymal organs, including lungs.Carcinoid tumors in the lungs usually occur as bronchocentric tumors and present with typical histopathologic characteristics of carcinoid tumors, but they may present with significant variation in their cellular compositions, in contrast to the midgut carcinoid tumors. In the latter, tumor cells are quite similar to enterochromaffin granule containing c...

Carcinoid Tumor Presenting as Acute Coronary Syndrome: A Case Report

Pulmonary carcinoid tumors are neuroendocrine tumors that have an incidence of 1.2-2.1/100,000 among general population. Forty percent of patients with disseminated disease experience cardiac involvement, whither due to carcinoid heart disease or due to the vasospastic effect of secreted serotonin. Acute coronary syndrome is one of the rare entities that carinoid patients can present with. Few cases are reported in literature with similar presentation. Herein we are reporting a case of a 45-year-old Yamani male patient presented to the emergency department of our hospital with chest pain for 12 hours duration. He also reported a history of watery diarrhea for the last four months. He was diagnosed to have acute coronary syndrome. Further radiological investigations showed numerous enlarged mediastinal lymph nodes. Biopsy showed moderately differentiated neuroendocrine tumor consistent with atypical carcinoid. J Med Cases. 2013;4(9):641-643 doi: http://dx.doi.org/10.4021/jmc1216w

58 Test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours

58 Test performance of PET-CT for mediastinal lymph node staging of pulmonary carcinoid tumours

A Case of DIPNECH and Review of the Current Literature

Diffuse Idiopathic Neuroendocrine Cell Hyperplasia (DIPNECH) is a rare pulmonary disease. It was first described by Aguayo et al. in 1992, and recognised by the World Health Organisation in 2004 as a precursor lesion to the development of pulmonary carcinoid tumour. DIPNECH has been described in several isolated case reports and series. This article describes a case of DIPNECH and summaries the recent literature in an attempt to raise awareness of this disease and management options.

Limited role of Ki-67 proliferative index in predicting overall short-term survival in patients with typical and atypical pulmonary carcinoid tumors

Limited role of Ki-67 proliferative index in predicting overall short-term survival in patients with typical and atypical pulmonary carcinoid tumors

Diffuse Intrapulmonary Neuroendocrine Cell Hyperplasia

Diffuse intrapulmonary neuroendocrine cell hyperplasia is a rare, potential precursor lesion to typical pulmonary carcinoid tumours. Fewer than 50 cases have been reported in the literature. Their pathogenesis, clinical significance and management is controversial. A patient who presented with diffuse intrapulmonary neuroendocrine cell hyperplasia associated with a primary typical carcinoid tumour of the lung is reported.

Synchronous bilateral multiple typical pulmonary carcinoid tumors: a unique case with 10 typical carcinoids.

Bilateral multiple typical carcinoid tumors of the lung are uncommon malignancies. We discuss the case of a 64 year-old female with a nonproductive cough as the initial symptom. Thoracic computed tomography revealed multiple nodular lesions on both sides, which were initially misdiagnosed as multiple metastases of the lung with an unknown primary. After resection of nodules in the right hemithorax, pathologic examination revealed a typical carcinoid tumor. Bilateral sequential thoracotomy was performed and all ten nodules, (six on the right side and four on the left side), were treated by sublobar resection due to poor respiratory function. Pathological examination revealed all nodules to be typical carcinoid tumors. Following the resections, the patient has remained disease-free for ten months.

Primary pulmonary carcinoid tumor with metastasis to endometrial polyp

INTRODUCTIONA carcinoid tumor occurring in the endometrium has been documented in the literature, but there is no report in regard to carcinoid tumor metastasis to endometrium. PRESENTATION OF CASEWe report a case of a malignant carcinoid metastasis to an endometrial polyp. Patient underwent hysteroscopy, and polypectomy. The pathology demonstrated an endometrial polyp containing a 4 mm x 5 mm nodule of metastatic carcinoid tumor, consistent with metastasis from patient's known pulmonary carcinoid. The tumor was morphologically similar to the tumors of the right lung, with similar immune-profile. DISCUSSIONThis patient presented with a suspicious pelvic ultrasound. Due to her age, the first priority was to exclude uterine cancer. The endometrial polyp, which was found, had a small focus of metastatic carcinoid tumor. To the best of our knowledge, this finding has not been previously recorded in the literature. Our patient also had a history of metastatic carcinoid tumor to breast. This finding is also very uncommon. CONCLUSIONThis is the first case in the literature described a malignant carcinoid metastasis to an endometrial polyp.

Surgical management of pulmonary carcinoid tumors: sublobar resection versus lobectomy

BackgroundSurgical resection of bronchopulmonary carcinoid tumors can be curative and remains the primary treatment modality. There are limited data to delineate the optimal extent of resection for this disease. MethodsA retrospective review of the 3,270 patients diagnosed with typical and atypical carcinoid tumors between 2000 and 2007 in the Surveillance Epidemiology and End Results registry was performed. ResultsThe mean follow-up period was 46 months (range, 1–95 mo). Overall survival (OS) and disease-specific survival at 5 years was 80% and 90%, respectively. The mean OS was slightly better in the lobectomy group compared with those undergoing sublobar resection (86 vs 83 mo; P = .008). After adjusting for age, this finding was no longer present (P = .513). By using multivariate analysis, sublobar resection was noninferior to lobectomy with regard to disease-specific survival and OS (P < .05). ConclusionsCompared with lobectomy, sublobar resection is associated with noninferior survival in patients with typical carcinoid of the lung.

Primary Pulmonary Carcinoid Tumor With Crohn's Disease: A Case Report and Review of Literatur

Primary Pulmonary Carcinoid Tumor With Crohn's Disease: A Case Report and Review of Literatur

Limited role of Ki-67 proliferative index in predicting overall short-term survival in patients with typical and atypical pulmonary carcinoid tumors

Pulmonary carcinoid tumors are currently classified as typical or atypical based on the mitotic index (2 per 10 hpf) and/or the presence of necrosis. Following incorporation of the Ki-67 index into the classification of GI carcinoid tumors, our oncologists have also been requesting this test as part of the work-up of pulmonary carcinoid tumors although there are currently no established criteria for interpreting Ki-67 index in these neoplasms. We utilized the Ariol® SL50 Image Analyzer system to measure the Ki-67 index in 101 pulmonary carcinoid tumors (78 typical and 23 atypical) and then correlated the Ki-67 index and the histological diagnoses in univariate and multivariable analysis with overall survival. The mean Ki-67 indices for the typical carcinoids (3.7 s.d.±4.0) and the atypical carcinoids (18.8 s.d.±17.1) were significantly different (P<0.001) although the frequency distributions of Ki-67 indices in the two groups overlapped considerably. Receiver operating characteristic curve analysis showed that a Ki-67 index cutoff value of 5% provided the best fit for specificity and sensitivity in predicting overall survival. Histological diagnosis and the Ki-67 index cutoff of 5% were each independently strong predictors of survival (P<0.001 and P=0.003, respectively). When considered together in multivariable analysis, histological diagnosis was the stronger predictor of overall survival and a Ki-67 index cutoff of 5% did not provide additional significant predictive survival information within either the typical carcinoid or the atypical carcinoid patient group. A few typical carcinoid patients with Ki-67 indices of 5% appeared to have worse survival after 5 years than those with Ki-67 indices <5%, but the data set was insufficiently powered to further analyze this. These findings do not provide best evidence for the routine use of Ki-67 index to prognosticate overall short-term survival in patients with pulmonary carcinoid tumors.

Somatostatin receptor scintigraphy with 111In-octreotide in pulmonary carcinoid tumours correlated with pathological and 18FDG PET/CT findings

Pulmonary carcinoid (PC) tumors are rare neoplasms of the lung with good prognosis but diagnosis may be demanding since there is no exclusive modality alone to clearly differentiate a PC tumor. The purpose of this study is to establish the diagnostic features of somatostatin receptor scintigraphy (SRS), comparatively (where available) with 18FDG PET/CT (PET/CT) correlated with histopathologic findings. Twenty-one patients who underwent SRS with 111In-octreotide and were diagnosed as having PC tumors were retrospectively studied. Thirteen patients were performed PET/CT. Primary tumour size, Ki-67 indexes, image analysis data of SRS and PET/CT including maximum standardized uptake values (SUVmax) together with false negative, false positive, true positive and true negative lesions were documented and discussed. Eleven (52.4%) patients were typical (TC) and 10 (47.6%) were atypical carcinoids (AC) with mean Ki-67 indexes of 2.1 and 24%, respectively. Patients underwent SRS for solitary pulmonary nodule (SPN) characterization (n = 12) and determination of disease extension (n = 9). Overall sensitivity and specificity of SRS in the detection of primary tumour, lymph nodes (LN) and distant metastasis (DM) were 76 and 97 %, respectively, whereas, positive and negative predictive values were 95 and 86 %. PET/CT was performed for determining disease spread (n = 3) and metabolic characterization (n = 10) of SPNs. Mean SUVmax in the primary pulmonary lesion in TCs and ACs were 2.9 ± 0.8 and 7.9 ± 5.4, respectively. Nodal involvement (n = 5) and DM (n = 3) were also detected. Sensitivity and specificity of PET/CT in the detection of primary tumour, LNs and DM were 85 and 89.4 %, respectively. SRS is useful in the diagnosis and monitoring of PC tumors when incorporated with 18FDG PET/CT as a primary staging tool particularly in the determination of disease spread.

Differential expression of biomarkers in gastrointestinal versus pulmonary carcinoid tumors.

e13571 Background: Carcinoid tumors are endocrine neoplasms that commonly arise in the GI and pulmonary system. About 12,000 cases of carcinoid tumor are diagnosed a year with a 5-year survival rate of 67.2% .The majority of the cases present with advance disease with limited treatment options,therefore evaluation of predictive markers for chemotherapeutic agents is highly desirable. We studied the biomarker expression in carcinoid tumors and evaluated any differences based on site of origin. Methods: By computer search we retrospectively identified all cases submitted to Caris Life Sciences with the diagnosis of “carcinoid”. The cases were classified by primary site into three groups: Pulmonary, GI tract (including esophagus, stomach, small bowel, colon, rectum, appendix and pancreas) and miscellaneous. Biomarker expression performed by IHC and scored semi quantitatively by a pathologist for SPARC mono, SPARC poly, Her2, TOPO2, TOPO1, PGP, MRP1, PTEN, TS, ERCC1, RRM1,MGMT, C-KIT, ER, PR and AR and SSTR2 and SSTR5 analysis by DNA Microarray were compared between the groups. Results: 146 carcinoid tumors were interrogated for biomarkers, 33 pulmonary, 97 GI and 16 miscellaneous (mediastinum, thymus, cervix, breast and unknown primary site). Due to small number of tumors in the miscellaneous category, analysis was restricted to pulmonary and GI carcinoid tumors only. Based on our analysis the pulmonary carcinoids differentially express Topo2, PGP, MGMT, CKIT and PR, while the GI carcinoids differentially express Topo1, RRM1 and ER and SSTR2 and SSTR5. There is equivalent expression of SPARC, MRP1, PTEN, TS, ERCC1 at both sites . All pulmonary and GI carcinoid tumors were negative for Her2. Conclusions: Based on this study it appears that there are differences in biomarker expression in GI and Pulmonary Carcinoid tumors. Treatment with irinotecan, gemcitabine, anti-estrogens and Octreotide may be more relevant in GI carcinoids based on molecular markers present while targets associated with response to anthracyclines, temozolomide, imatinib may be more commonly expressed in pulmonary carcinoid tumors. Further studies are needed to understand the underlying biology and molecular drivers in this group of tumors.

Pulmonary Carcinoid Tumors and Asbestos Exposure

The hypothesis that asbestos exposure may have more specific associations with particular histological types of lung cancer remains controversial. The aim of this study was to analyze the relationships between asbestos exposure and pulmonary carcinoid tumors. A retrospective case-control study was conducted in 28 cases undergoing surgery for pulmonary carcinoid tumors and aged >40 years and in 56 controls with lung cancer of a different histological type, matched for gender and age, from 1994 to 1999, recruited in two hospitals in the region of Paris. Asbestos exposure was assessed via expertise of a standardized occupational questionnaire and mineralogical analysis of lung tissue, with quantification of asbestos bodies (AB). Definite asbestos exposure was identified in 25% of cases and 14% of controls (ns). Cumulative asbestos exposure was significantly higher in cases than in controls (P < 0.05), and results of the quantification of AB tended to be higher in cases than in controls (24 and 9% had >1000 AB per gram dry lung tissue, respectively, P = 0.09). Mean cumulative smoking was lower in cases than in controls (P < 0.05). This study argues in favor of a relationship between asbestos exposure and certain pulmonary carcinoid tumors.

Pulmonary Carcinoid Tumor in a Patient on Adalimumab for Crohnʼs Disease

Pulmonary Carcinoid Tumor in a Patient on Adalimumab for Crohnʼs Disease

A case of typical pulmonary carcinoid tumor treated with bronchoscopic therapy followed by lobectomy

Carcinoid bronchopulmonary tumors represent approximately 25% of all carcinoid tumors and 1%–2% of all lung neoplasms. The most common symptoms are: persistent cough, asthma-like wheezing, chest pain, dyspnea, hemoptysis and obstructive pneumonitis. We present a case of a young adult diagnosed with a typical carcinoid tumor. The diagnosis was established on the basis of imaging examination and bronchoscopic biopsy. The patient was treated with bronchoscopic electrocautery therapy to relieve the obstructed airway, followed by surgical lobectomy in order to entirely remove the exophytic damage. This approach was not only a palliative management to bronchial obstruction but also avoided pneumonectomy. Recent studies support the use of such interventional resection methods, as they may result in a more conservative surgical resection.

Growth of a solitary pulmonary nodule after 6 years diagnosed as oncocytic carcinoid tumour with a high 18‐fluorodeoxyglucose (18F‐FDG) uptake in positron emission tomography‐computed tomography (PET‐CT)

Pulmonary carcinoid tumour is low-grade neuroendocrine malignancy that is seen 1%-2% of all lung neoplasms. Oncocytic carcinoid type is a rarely seen variant of pulmonary carcinoids. As carcinoid tumours have hypometabolic activity, they usually have lower 18-fluorodeoxyglucose (18F-FDG) uptake than expected for lung carcinoma on positron emission tomography (PET). A 45-year-old non-smoking man had a stable solitary pulmonary nodule followed for 6years; the tumour remained the same size (1.5×2.4cm) during this period. The patient was admitted to the hospital with complaints of repetitive sneezing and rhinorrhoea. He also experienced flushing and bronchospasm. His chest X-ray revealed a minimal increase in the size of the solitary pulmonary nodule (2.0×2.8cm). In PET-computed tomography (CT), the parenchymal nodule in the anterior segment of the right lung had a standard uptake value of 38.0mg/mL, which was interpreted as a malignant nodule. He underwent fibre-optic bronchoscopy, but cytology showed no evidence of malignancy. Right upper and middle bilobectomy was performed, and a pulmonary carcinoid tumour with an oncocytic subgroup was diagnosed. The diagnosis of carcinoid syndrome was further confirmed by an elevated 24-h urinary excretion of 5-hydroxyindoleacetic acid. We present a rare case of an oncocytic carcinoid tumour with an increase in the size of a solitary pulmonary nodule after 6years' follow-up. In addition, PET-CT showed a very high 18F-FDG uptake in this patient, which is an unexpected finding with a pulmonary carcinoid tumour.

Comparison of Patient Survival after Resection for Pulmonary Carcinoid Tumors Compared to Other Neuroendocrine Tumors: A United States Population Study

Background: We hypothesized: 1) resected pulmonary typical carcinoid (TC) will show a favorable clinical pattern compared to other bronchopulmonary neuroendocrine tumors (BPNETs); and 2) Atypical carcinoid (AC) and large-cell neuroendocrine carcinoma (LCNEC) patients will have similar outcomes. Methods: The Surveillance Epidemiology and End Result database was queried to compare demographics and tumor specific variables in patients undergoing resection for TC, AC, LCNEC and small cell lung cancer (SCLC) from 2001 to 2006. Results: Similar to LCNEC, AC patients had greater incidence of histologic positive lymph nodes compared to TC (P < 0.001). Survival analysis showed a mean survival of 40.0 ± 1.9 months for SCLC, 46.2 ± 2.2 months for LCNEC, 58.3 ± 2.3 months for AC, and 70.2 ± 0.2 months for TC tumors. TC patients demonstrated favorable survival, and SCLC patients poorer survival, compared to AC and LNEC patients (P < 0.01). Conclusion: AC tumors are a BPNET histology that exhibits clinical behavior distinct from TC. AC tumors should be staged, and treated with stage appropriate therapeutic strategies similar to other non-small cell lung cancers.