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Query: UMLS:C0684249 (lung carcinoma)
 23,830 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Two cases of primitive neuroectodermal tumor of the lung are reported. The first case is a 41-year-old man with a tumor in the left upper lung, and the second case is a 30-year-old woman with a tumor in the right lower lung. In both cases, the tumors originated in the lung but not in the chest wall. No distant metastasis was detected. In case 1, transcutaneous fine-needle biopsy (TCNB) revealed small round cell proliferation, although bronchoscopic examination showed no abnormal findings. Both the expression of Mic2 protein and t(11;22)(q24;q12) translocation were proved in the tumor cells. The tumor cells were positive for periodic acid-Schiff (PAS), neuron-specific enolase (NSE), and vimentin, but negative for Leu7, chromogranin A, and pro-gastrin-releasing peptide (ProGRP). In case 2, bronchoscopic examination showed only compressive change in right lower lobe bronchi. TCNB revealed small round tumor cells expressing Mic2 protein. The tumor cells were negative for leukocyte common antigen, S100 protein, pankeratin, chromogranin A, and desmin, but weakly positive for NSE and moderately positive for Ki-67 (MIB1). Both patients were successfully treated by the combination of surgical resection and chemotherapy, and are alive with no sign of recurrence for approximately 22 months in case 1 and 16 months in case 2.
Lung Cancer 2000 Jan
PMID:Primary primitive neuroectodermal tumor of the lung: report of two cases. 1067 84

Numerous epidemiologic studies suggest a relationship between lung cancer and peptic ulcer disease. Furthermore, various lung cancers synthesize and release a number of peptides such as gastrin and gastrin-releasing peptide that could cause acid hypersecretion; however, Zollinger-Ellison syndrome (ZES), because of a lung tumor, has never been described. We report such a patient for the first time. A 60-year-old man with a non-small cell lung carcinoma (large cell type) presented with diarrhea, heartburn, abdominal pain, and duodenal ulcers. Evaluation showed ZES was present (fasting hypergastrinemia, hyperchlorhydria) and control of all symptoms by omeprazole. No abdominal or cardiac tumor, the other known locations of gastrinomas causing ZES, was found on detailed tumor imaging studies. Resection of the lung tumor resulted in a decrease in gastrin levels to normal values. Plasma radioimmunoassays showed elevated gastrin, chromogranin A and normal levels of gastrin-releasing peptide, and 9 other hormones. The tumor showed similar immunocytochemical results. The characteristics of this case are compared with 100 cases of sporadic abdominal gastrinomas, and the evidence reviewed suggests why ZES should be considered in patients with lung cancer with peptic symptoms.
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PMID:A new cause of Zollinger-Ellison syndrome: non-small cell lung cancer. 1126 90

The group of small cell tumors of the lung includes fine following: (1) small cell carcinoma (SCC) of neuroendocrine (NE) origin, (2) poorly differentiated squamous carcinoma, (3) the rare basaloid (basal cell) carcinomas, and (4) malignant lymphomas, primitive neuroectodermal tumors (PNETs), and rhabdomyosarcomas. The differential diagnosis among these entities carries a heavy therapeutic impact but may be difficult in small biopsy specimens or in cytologic material, especially if necrosis or artifactual alterations are present. The use of additional techniques such as immunostaining for NE markers is not always helpful, since immunoreactive chromogranin A is detectable in only a small percentage of small cell carcinomas. It has recently been reported that in the aerodigestive tract 34betaE12 cytokeratin (CK) immunostaining selectively labels non-NE carcinomas, including squamous cell carcinoma, adenocarcinoma, and the rare basaloid carcinoma. We evaluated the role of such CK immunodetection in the differential diagnosis of small cell lung tumors in cytologic and biopsy specimens. Eighty-one lung tumors diagnosed by means of endoscopic bronchial biopsy, fine needle aspirate, or bronchial washing were collected. They included 43 small cell NE carcinomas and 38 cases used as controls (comprehensive of 2 large cell neuroendocrine carcinomas, 4 carcinoid tumors, 30 cases of non-NE lung carcinomas, 2 cases of bronchial infiltration by non-Hodgkin lymphomas). 34betaE12 CK immunoreactivity was found in 29/30 cases of non-NE carcinomas, but in only 3/43 SCCs. The latter showed positivity in only a few scattered cells. The 2 cases of bronchial infiltration by malignant lymphoma as well as the 4 cases of carcinoid tumors and the 2 cases of large cell neuroendocrine carcinomas were negative. These findings were confirmed in the surgical specimens of operatedon cases. We conclude that, in lung carcinoma biopsies showing a small cell pattern, presence of 34betaE12 CK immunoreactivity favors a non-NE carcinoma, whereas its absence supports the diagnosis of SCC. Int J Surg Pathol 8(4):317-322, 2000
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PMID:34betaE12 Cytokeratin Immunodetection in the Differential Diagnosis of Small Cell Tumors of Lung. 1149 8

Several studies have suggested that non-small cell lung cancer (NSCLC) patients whose tumors have neuroendocrine (NE) features may be more responsive to chemotherapy. In addition, increased expression of p53 and HER2 may confer relative chemotherapy resistance and shortened survival. The Cancer and Leukemia Group B performed a series of studies involving sequential chemotherapy followed by radiation for patients with unresectable stage III NSCLC. The objectives of this study were to analyze pathological specimens using immunohistochemistry for NE markers, p53 and HER2 to determine if there was a correlation between marker expression and response or survival. Of 160 eligible patients, 28 (18%) were not evaluable because of inadequate material. The percentage of specimens positive for markers was as follows: neuron-specific enolase 38%, Leu-7 2%, chromogranin A 0%, synaptophysin 5%, > or =2+NE markers 3%, p53 61%, and HER2 65%. There was no statistically significant correlation between any individual marker and response to induction chemotherapy or response to combined chemotherapy/radiation except for synaptophysin. Six of 6 (100%) synaptophysin positive tumors responded by the completion of all therapy compared with 69/125 (55%) synaptophysin negative tumors (P=0.04). None of the individual markers had a significant effect on survival in univariate analysis. Neuron-specific enolase was marginally significant in multivariate analysis (P=0.08). In conclusion, this study did not demonstrate that expression of NE markers, p53 and HER2 were predictive of response to chemotherapy, combined chemotherapy/radiation or for survival in this group of patients with stage III NSCLC. Future studies must employ either different markers or be performed on more adequate surgical specimens.
Lung Cancer
PMID:Use of neuroendocrine markers, p53, and HER2 to predict response to chemotherapy in patients with stage III non-small cell lung cancer: a Cancer and Leukemia Group B study. 1155 6

Patients with small-cell lung carcinoma (SCLC) rarely present with pleural effusions. Based on morphology alone, recognition of SCLC in effusion cytology may be challenging because of the resemblance of neoplastic cells to lymphocytes. Immunocytochemistry may be helpful in its diagnosis. The objective of this study was to review the morphology and evaluate the use of immunocytochemistry in diagnosing SCLC in pleural fluids. Patients with SCLC who presented with pleural effusions were identified during a 6-yr period. The cytology and medical records were reviewed. Formalin-fixed, paraffin-embedded cell blocks of fluid specimens were immunostained with neuroendocrine markers (chromogranin A and synatophysin), cytokeratin 20 (CK20), and thyroid transcription factor-1 (TTF-1). The latter is a nuclear transcription protein that is expressed in normal respiratory epithelium and also in more than 90% of SCLCs. Of the 256 patients diagnosed with SCLC during the study period, 8 (2.7%) patients (3 females and 4 males, age range from 56-85 yr) also developed pleural effusions. One patient had 2 fluid specimens during the course of their disease, giving a total of 9 specimens. Four specimens had a positive cytologic diagnosis of SCLC, and 2 were initially diagnosed as suspicious for SCLC. The remaining 3 specimens were negative for SCLS. The specimens with a positive or suspicious diagnosis showed single and aggregates of small to medium-sized single cells with a high nuclear:cytoplasmic (N:C) ratio, round to angulated nuclei, and salt-and-pepper chromatin. Nuclear molding was also noted. Five out of 6 (83%) specimens with a positive or suspicious diagnosis of SCLC were positive for both chromogranin A and TTF-1. Synaptophysin was positive in 3 of 6 (50%) positive or suspicious cases. None of the cases were positive for CK20. All cases with a negative cytologic diagnosis were negative for chromogranin A, synatophysin, CK20, and TTF-1. In conclusion, patients with SCLC rarely present with pleural effusions. The cytology of SCLC is characteristic. The use of immunocytochemistry, particularly with antibodies to chromogranin A, TTF-1, and CK 20, aids in the differential diagnosis.
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PMID:Malignant pleural effusions due to small-cell lung carcinoma: a cytologic and immunocytochemical study. 1174 31

Non-small-cell lung carcinoma (NSCLC) describes a histologically heterogeneous group of tumours with variable clinical behaviour. Performance status, tumour stage and histological type have important prognostic implications, but clinical outcomes in individual patients remain unpredictable. A significant minority of NSCLCs (10%-30%) show neuroendocrine (NE) differentiation, and a number of studies have attempted to evaluate the therapeutic and prognostic significance of the expression of NE markers on the basis of the theoretical assumption that NE-differentiated tumours may be associated with an adverse prognosis and greater chemosensitivity. However, the results of these studies are conflicting: some have found that NE differentiation has a negative impact on survival, but others have failed to demonstrate any correlation with prognosis. Similar discrepancies have also been observed in terms of chemosensitivity. Nevertheless, these data are difficult to interpret because there is no gold standard defining NE differentiation, as is shown by the fact that the proportion of NE-differentiated NSCLCs varies according to the technique and marker used, although chromogranin A and synaptophysin show the best correlation with ultrastructural evidence of NE differentiation. In conclusion, there is no doubt that caution is required when interpreting the results of a number of studies questioning the clinical impact of the NE features of NSCLCs.
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PMID:Clinical significance of neuroendocrine phenotype in non-small-cell lung cancer. 1176 37

The pulmonary neuroendocrine cell (PNEC) system consists of solitary cells and distinctive cell clusters termed neuroepithelial bodies (NEB) localized in the airway epithelium. PNEC/NEB express a variety of bioactive substances, including amine (serotonin, 5HT) and neuropeptides. We have previously shown that NEB cells are O(2) sensors expressing nicotinamide adenine diphosphate oxidase complex and O(2) sensitive K(+) channel. Recently, we demonstrated expression of functional cystic fibrosis transmembrane conductance regulator (CFTR) and Cl(-) conductances in NEB cells of rabbit neonatal lung. Because PNEC/NEB are sparsely distributed and difficult to study in native lung, we investigated small-cell lung carcinoma (SCLC) and carcinoid tumor cell lines (tumor counterparts of normal PNEC/NEB) as models for PNEC/NEB. SCLC (H146, H345) and carcinoid (H727) cell lines express neuroendocrine cell markers, including chromogranin A, neural cell adhesion molecule (N-CAM), 5HT, and tryptophan hydroxylase. We report that H146, H345, and H727 express CFTR messenger RNA (reverse transcription polymerase chain reaction) and protein (immunoblotting) and possess functional CFTR Cl(-) conductance, demonstrated by an iodide efflux assay inhibitable by transfection with antisense CFTR. Using an immunoassay to quantitate 5HT secretion, we also show that downregulation of CFTR abolishes hypoxia-induced 5HT release, and reduces secretory response to high potassium. Our findings suggest that CFTR may modulate neurosecretory activity of PNEC/NEB possessing O(2) sensor function. We propose that these tumor cell lines may be useful models for investigating the role of CFTR in PNEC/NEB functions in health and disease.
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PMID:Cystic fibrosis transmembrane conductance regulator modulates neurosecretory function in pulmonary neuroendocrine cell-related tumor cell line models. 1239 14

The clinical significance of neuroendocrine (NE) differentiation is unclear in large cell carcinoma (LCC) of the lung. Fifty-five surgically resected carcinomas of the lung with an original pathologic diagnosis of LCC were reviewed histologically with special attention to NE morphology. Antibodies against neural cell adhesion molecule (NCAM), chromogranin A (CGA) and synaptophysin (SY) were used to confirm the NE differentiation. Thirteen (24%) cases were classified as large cell neuroendocrine carcinoma, 9 (16%) as LCC with NE differentiation, and 33 (60%) as pure LCC. There was no significant difference in overall survival between the three groups. When the 55 carcinomas were divided into three groups depending on the number of NE marker expression, there was significantly better overall survival in the NE > or = 2 (P = 0.02). Multivariate analysis proved NE > or = 2 was an independent predictor of survival. The number of NE markers was more important in terms of survival than histological sub-classification.
Lung Cancer 2002 Nov
PMID:Immunohistochemical neuroendocrine differentiation is an independent prognostic factor in surgically resected large cell carcinoma of the lung. 1239 30

Histidine decarboxylase is one of the enzymes of the amine precursor uptake and decarboxylation system and is known to be distributed in mast cells and enterochromaffin-like cells. With the hypothesis that histidine decarboxylase expression is a marker for neuroendocrine differentiation, we studied the immunoreactivity of histidine decarboxylase in neuroendocrine cells and tumors of the thyroid gland, adrenal medulla, lung, and gastrointestinal tract. Formalin-fixed paraffin sections were subjected to immunohistochemistry using anti-histidine decarboxylase antibody, and the sensitivity and specificity were compared with those of conventional neuroendocrine markers (CD56, chromogranin A, synaptophysin, and neuron-specific enolase). Enterochromaffin or enterochromaffin-like cells, adrenal chromaffin cells, and thyroid C-cells were positive for histidine decarboxylase, and related tumors (carcinoid tumor, pheochromocytoma, medullary carcinoma) showed a high percentage of positive staining. Furthermore, we used the antibody to distinguish small cell lung carcinoma from non-neuroendocrine lung carcinoma and also to detect neuroendocrine differentiation in large-cell neuroendocrine carcinoma and gastrointestinal small-cell carcinoma. The anti-histidine decarboxylase antibody stained most small cell lung carcinoma (18 of 23, sensitivity 0.78), and was rarely reactive with non-neuroendocrine lung tumors (2 of 44; specificity, 0.95). These values were close to those obtained from CD56 staining (sensitivity/specificity, 0.87/0.98). Histidine decarboxylase was also positive for 6 of 12 large cell neuroendocrine carcinomas and 4 of 7 gastrointestinal small cell carcinomas. In conclusion, we demonstrated that histidine decarboxylase is useful to distinguish between small cell lung carcinoma and non-neuroendocrine carcinoma and to demonstrate neuroendocrine differentiation.
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PMID:Histidine decarboxylase expression as a new sensitive and specific marker for small cell lung carcinoma. 1252 16

This retrospective study aimed at determining the prognostic significance of neuroendocrine markers chromogranin A (CgA), pro-gastrin releasing peptide (ProGRP) and neuron-specific enolase (NSE), together with the cytokeratin 19 marker CYFRA 21-1 in small cell lung cancer (SCLC). A total of 148 histologically proven and previously untreated SCLC patients were included. Among them 118 patients received a cisplatin-etoposide combination or cisplatin-etoposide-cyclophosphamide-4'-epidoxorubicin combination. All tumour markers were tested using immunoradiometric assays except for ProGRP which was tested using an enzyme-linked immunosorbent assay. The thresholds for marker serum titrations were 53 pg/ml, 65, 17, and 3.6 ng/ml for ProGRP, CgA, NSE and CYFRA 21-1 respectively. Univariate analysis showed that patients affected by one of the following characteristics proved to have a significant shorter survival in comparison with the opposite status of each variable: age over 63 years, extensive-stage, serum LDH level higher than 600 U/l, serum NSE level higher than 17 ng/ml, serum CgA level higher than 65 ng/ml and serum CYFRA 21-1 level higher than 3.6 ng/ml. In addition, there was a trend towards a statistical significance for a high serum alkaline phosphatase level and a performance status equal to or worse than two. The following variables were independent determinants of a poor outcome: a poor performance status (hazard ratio [95% confidence interval]: 1.51 [1.02-2.22]), a high CgA level (HR: 1.61 [1.06-2.45]), a high CYFRA 21-1 level (HR: 2.10 [1.40-3.14]) and an age older than 63 years (HR: 1.68 [1.14-2.48]). When the multivariate analysis was restricted to patients receiving a cisplatin-etoposide-based chemotherapy, the same variables were prognostic determinants with nearly similar hazard ratios. In conclusion, aside classical variables such as age and performance status, high serum CYFRA 21-1 and high serum CgA level in SCLC are both prognostic determinants of prognosis, in particular in patients receiving conventional chemotherapy consisting of cisplatin and etoposide-based combinations.
Lung Cancer 2003 Feb
PMID:Neuroendocrine and cytokeratin serum markers as prognostic determinants of small cell lung cancer. 1258 64


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