Integrative and comparative genomic analyses identify clinically relevant pulmonary carcinoid groups and unveil the supra-carcinoids.

The worldwide incidence of pulmonary carcinoids is increasing, but little is known about their molecular characteristics. Through machine learning and multi-omics factor analysis, we compare and contrast the genomic profiles of 116 pulmonary carcinoids (including 35 atypical), 75 large-cell neuroendocrine carcinomas (LCNEC), and 66 small-cell lung cancers. Here we report that the integrative analyses on 257 lung neuroendocrine neoplasms stratify atypical carcinoids into two prognostic groups with a 10-year overall survival of 88% and 27%, respectively. We identify therapeutically relevant molecular groups of pulmonary carcinoids, suggesting DLL3 and the immune system as candidate therapeutic targets; we confirm the value of OTP expression levels for the prognosis and diagnosis of these diseases, and we unveil the group of supra-carcinoids. This group comprises samples with carcinoid-like morphology yet the molecular and clinical features of the deadly LCNEC, further supporting the previously proposed molecular link between the low- and high-grade lung neuroendocrine neoplasms.

Rare tracheal tumor: Solitary plasmacytoma.

Primary tracheal tumors are rare and trachea is an exceedingly rare site of extramedullary plasmacytoma (EMP). We report a case of solitary tracheal plasmacytoma causing symptoms of airway obstruction in a 59-year-old man. Flow/volume loop indicated the fixed central airway obstruction. Computerized tomography and bronchoscopy demonstrated a sessile tumor on posterior tracheal wall obstructing 80% of the lumen. Partial tracheal resection with T-T anastomosis was performed. Pathologic analysis of resected mass revealed EMP. Additional investigations excluded multiple myeloma. There are no signs of disease recurrence after 7-year follow-up.

Characteristics of local recurrence of lung cancer and possibilities for surgical management.

PURPOSE: To investigate the correlation between stage and histopathological characteristics of patients with lung cancer and local recurrence, as well as the incidence and the characteristics of local recurrence along with the possibility of surgical retreatment. METHODS: Studied were 51 patients with locally relapsing lung cancer, initially treated surgically from 2003 to 2007. The operations performed ranged from conservative wedge resections, standard lobectomies and pneumonectomies to extensive resections of the entire lung and chest wall. All patients underwent regular follow-up including thoracic CT scan every 3 months. RESULTS: All patients were diagnosed with local recurrence after a median of 10 months (range 1-30) after primary surgery with curative intent. There was no statistically significant link between type of surgery and time to local recurrence. Patients with pathological stage I,II, and IIIa had a significantly longer time to local recurrence than those with stage IIIb and IV. Local recurrence sites were the bronchial stump, mediastinal lymph nodes, the remaining lung parenchyma, chest wall and a combination of these. Surgical retreatment was possible in 20 of 51 patients (39.27percnt;). Chest wall was the commonest localization (20 of 51; 39.2%), also the most frequent in the group of surgically retreated patients (13 of 20; 65%). Squamous cell cancer (SCC) was the predominant histological type (38 of 51; 74.5%), followed by adenocarcinoma (9 of 51; 17.7%). CONCLUSION: SCC is the commonest locally relapsing lung cancer. The type of the initial surgical procedure didn't have any impact on the incidence of local recurrence, but the extent and completeness of surgery did. The time to local recurrence heavily depended on the primary tumor pathological stage. Chest wall was the commonest relapse site, and the most suitable for surgical retreatment, which was related to the quality of surgery.

Contribution of immunohistochemistry in the differential diagnosis of non-small cell lung carcinomas on small biopsy samples.

PURPOSE: Targeted therapy increases survival and the quality of life of non-small cell lung cancer (NSCLC) patients but it needs precise histological subtyping. The present study evaluated 6 monoclonal antibodies for the differential diagnosis of NSCLC on small-sized tissue samples. METHODS: 50 small-sized tissue samples were obtained by bronchoscopy or fine needle aspiration biopsy (FNAB). According to morphology before immunohistochemistry 2 squamous cell carcinomas (SCC), 6 adenocarcinomas (AC), 9 NSCLC-probably SCC, 11 NSCLC-probably AC and 22 unclassified NSCLCs were diagnosed. Thyroid transcription factor-1 (TTF-1), cytokeratin 5/6, cytokeratin 7, p63, and the neuroendocrine markers CD56 and synaptophysin were used in the differential diagnosis of NSCLC. RESULTS: After immunohistochemistry 13 (26.0%) SCC, 27 (54.0%) AC, 3 (6.0%) NSCLC with neuroendocrine differentiation (NSCLC-NE) and 7 (14.0%) NSCLC- unclassified were diagnosed. Twenty-two NSCLC- unclassified were further diagnosed as SCC (n=7), AC (n=7) NSCLC-NE (n=2) and 6 remained NSCLC- unclassified. Significant difference was found between definitely diagnosed 8 NSCLCs and 15 ACs (20.5 vs. 38.57percnt;, p=0.008). TTF-1 and cytokeratin 7 were expressed in 85.2% (23/27) of AC, and cytokeratin 5/6 and p63 in 100% (13/13) of SCC. Positivity of CD56 and synaptophysin in 3 NSCLC determined NSCLC-NE. CONCLUSION: No one monoclonal antibody is totally specified for one histological type of tumor and its origin. Combination of TTF-1, cytokeratin 7, p63, cytokeratin 5/6, CD56 and synaptophysin allows for differentiation of NSCLC but Napsin-A for AC differentiation and chromogranin A for NSCLC-NE differentiation should be added in an optimal panel.

Clinical patterns and treatment outcome in resected elderly lung cancer patients.

PURPOSE: Lung cancer is the leading cause of cancer related morbidity and mortality worldwide. The aim of this study was to determine the clinical patterns and their impact on surgical resection in patients with non-small cell lung cancer (NSCLC)> 70 years. METHODS: We reviewed the records of 2050 resected lung cancer patients in a 5-year period from 2002-2007, out of whom 93 were > 70 years. RESULTS: There were 73 males and 20 females with median age of 71 years (range 70-78). Nineteen (20.43%) patients underwent pneumonectomy, 6 (6.45%) extended pneumonectomy, 54 (58.06%) lobectomy, 8 (8.61%) extended lobectomy, and 3 (3.23%) bilobectomy and wedge resection each. There were 37 (39.8%) resected patients with locally advanced (IIIA, IIIB) or advanced stage (IV) of NSCLC. A total of 48 complications occurred. The 30-day mortality rate was 1.08% (one patient). Pathological stage (p<0.001) and application of adjuvant therapy (p<0.001) were predictors of long-term survival. The overall 3- and 5-year actuarial survival rates were 46% and 28%, respectively. CONCLUSION: Advanced age should not be considered as a contraindication for NSCLC resection. However, careful preoperative assessment must be undertaken. The presence of comorbidities and extent of resection predict increased operative risk. Pathological stage and application of adjuvant therapy were the only predictors of long-term survival.

Multidisciplinary approach in diagnosis of lung carcinoma.

AIM: To employ multidisciplinary approach in order to make the correct diagnosis of lung carcinoma clinically and morphologically mimicking lymphoma. METHODS: Immunostaining was performed by incubating tissue sections with appropriate antibodies, using the streptavidin-biotin technique. Antigen-antibody complexes were visualized with 3-amino-9-ethylcarbasole or diaminobenzidine hydrochloride substrate solution. We have investigated p53 gene mutations by polymerase chain reaction and DNA sequence analysis of exons 5, 6, 7, 8 and 9. RESULTS: Tumor cells expressed cytokeratin AE1/AE3, epithelial membrane antigen (EMA) and thyroid transcription factor-1 (TTF-1) without thyreoglobulin positivity. Further, tumor cells expressed neuroendocrine mar kers: synaptophysin, chromogranin A, neuron-specific enolase (NSE), CD56/NCAM, CD57/Leu-7 and protein gene product 9.5 (PGP9.5). P53 was also expressed. Diffuse large cell lymphomas of B and T cell origin were excluded. Direct sequencing analysis of exon 6 of the p53 gene revealed ATC to ACC mutation at codon 195. Final diagnosis of large cell lung neuroendocrine carcinoma (LCNEC) was established. CONCLUSIONS: Morphological pattern of tumor complied with large cell non-Hodgkin's lymphoma, but large cell lung carcinoma with neuroendocrine differentiation was proved immunohistochemically and confirmed by genetic analysis of p53 mutations in tumor tissue sample. Multidisciplinary approach in diagnosis of lung carcinoma is useful for its final diagnosis.

Gender and age trends of histological types of lung cancer in a 20-year period: pathological perspective.

PURPOSE: To find out the trends of distribution in different histological types of lung cancer in both genders in a period of 20 years. METHODS: The most frequent histological types of lung cancer in tissue specimens obtained by bronchoscopy or percutaneous needle biopsy were analysed in terms of age and gender. The studied population included 6289 patients (16.6% females and 83.1% males). Statistical significance was established by x(2) test at the level p<0.05. RESULTS: Squamous cell carcinoma (SCC) prevailed in the total number of patients in all investigated years (58.0%), and separately in male (60.4%) and female (45.7%) patients. This histological type was predominant in all age groups in both genders (41.6% in males and 38.1% in females). CONCLUSION: SCC has the highest incidence in Serbia. Continuous campaign against smoking and helping its cessation, improving working and socioeconomic conditions is a strategy for decreasing all histological types of lung cancer patients.

Psychological well-being in advanced NSCLC patients in Serbia: impact of sociodemographic and clinical factors.

UNLABELLED: Patients with advanced non-small cell lung cancer (NSCLC) usually undergo toxic treatment (chemotherapy and/or radiotherapy). They can experience devastating effects of illness and therapies on their psychological and emotional well-being. On the other hand, untreated psychological distress is associated with reduced quality of life and inadequate palliation of physical symptoms.
In order to estimate frequency of anxiety and depressive symptoms and influence of demographic, socioeconomic and clinical factors on psychological well-being, we performed this cross-sectional study in group of 100 patients with advanced stage of disease. Symptoms of anxiety and depression were assessed using the Hamilton Anxiety Rating Scale (HARS) and Hamilton Depression Rating scale (HDRS). Health-related quality of life data are obtained by EORTC QLC C30 and SF 36.
Patients with poor performance status (PS) experienced significantly more anxiety and depressive symptoms (p=0.001) and worse emotional (p=0.001) and mental functioning (p=0.001). Treated patients had significantly better mental (p=0.011) and emotional (p=0.001) functioning in compared to newly diagnosed ones. Somewhat unusual, unemployed participants reported significantly less anxiety (p=0.029) and depressive (p=0.002) symptoms, better mental (p=0.030) and emotional functioning (p=0.007). Additionally, nausea and vomiting adversely affected mental health and emotional functioning and correlated significantly positively with HARS and HDRS scores.
Our findings suggest significant impact of some disease-related factors (PS, active treatment) and treatment-related factors (chemotherapy -induced nausea and vomiting) on psychological well-being of patients with advanced NSCLC. This should be taking an account when appropriate interventions are planned. KEYWORDS: lung cancer, anxiety, depression, quality of life, chemotherapy, chemotherapy-induced nausea and vomiting.

Pure red-cell aplasia as the presenting feature of the carcionoid tumor of the thymus: case report.

Acquired pure red-cell aplasia (PRCA) is an uncommon disorder of erythrocytopoiesis that can develop in association with thymic tumors. We present the very rare case of a severely anemic 62-year-old man with PRCA and a concurrent neuroendocrine carcinoid tumor of the thymus. The anterior mediastinal thymus tumor was completely excised, and following histological and immunohistochemical analyses (showing positive staining for cytokeratin, chromogranin A, synaptophysin, and neuron-specific enolase) the diagnosis of a (grade I; T(1)N(0)M(0)) typical carcinoid tumor of the thymus was made. Postoperatively the anemia persisted despite no signs of residual tumor on CT chest. A hematological work up found: normocellularity with <0.5% erythroblasts and preserved megakaryocytopoiesis and granulocytopoiesis in a trephine biopsy; reduced numbers of Colony Forming Unit Erythroid (CFU-E) and normal numbers of Burst-Forming Unit Erythroid (BFU-E) in bone marrow colony-forming assays; a markedly increased level of serum erythropoietin; normal T and B-cell numbers with a normal CD4/CD8 ratio; and no clonal T-cell receptor -gamma and -delta gene rearrangement) The patient responded favorably to a therapeutic trial of glucocorticoid immunosuppressive treatment (prednisone 1 mg/kg/day) with a normalization of the reticulocyte count and hematocrit, suggesting an immunologic mechanism for the PRCA. Though the exact mechanisms underlying the association between the PRCA and the carcinoid tumor of the thymus remain unknown.

Diagnostic procedures of pleural malignant mesothelioma: our experience.

PURPOSE: The morphology of the epithelioid malignant mesothelioma (MM) of the pleura is similar to lung adenocarcinoma involving pleura. The aim of this study was to evaluate the value of immunohistochemistry in the accurate diagnosis of MM, especially of the epithelioid type with needle biopsy of the pleura. MATERIALS AND METHODS: The diagnosis of MM was established with pleural needle biopsy and tumor immunophenotyping in 30 patients. A broad spectrum of monoclonal antibodies was applied: HBME-1, E-cadherin, calretinin, cytokeratin 5/6, vimentin, thyroid transcription factor (TTF-1) and surfactant apoprotein A (SP-A). RESULTS: We diagnosed 24 epithelioid, 2 biphasic and 4 sarcomatoid MM. HMBE-1 was the most sensitive tumor marker of the epithelioid type, being positive in 100% of the cases. Calretinin, E-cadherin and cytokeratin 5/6 were positive in 70%, 73%, and 50% of all tumors, respectively. TTF-1 and SP-A were negative in all MM. Vimentin was positive in spindle cells of all sarcomatoid and biphasic MM (20%). CONCLUSION: The accurate diagnosis of MM is mandatory for appropriate treatment decision (surgical or nonsurgical). Our results demonstrate that HMBE-1 is a most useful diagnostic antibody for epithelioid MM, and TTF-1 for lung adenocarcinoma (its thyroid origin excluded) involving pleura.