The prognostic significance of PD-1 and its ligands in non-small cell lung cancer.

Background: In this study, we aimed to investigate the prognostic value of programmed cell death protein 1 (PD-1), programmed cell death ligand 1 (PD-L1), and programmed cell death ligand 2 (PD-L2) expressions on immune and cancer cells in terms of survival in patients with lung adenocarcinoma, squamous cell carcinoma, and large cell carcinoma. Methods: Between January 2000 and December 2012, a total of 191 patients (172 males, 19 females; mean age: 60.3±8.4 years; range, 38 to 78 years) who were diagnosed with non-small cell lung cancer and underwent anatomic resection and mediastinal lymph node dissection were retrospectively analyzed. The patients were evaluated in three groups including lung squamous cell carcinoma (n=61), adenocarcinoma (n=66), and large-cell carcinoma (n=64). The survival rates of all three groups were compared in terms of immunohistochemical expression levels of PD-1, PD-L1, and PD-L2. Results: The mean follow-up was 71.8±47.9 months. In all histological subtypes, PD-1 expressions on tumor and immune cells were observed in 33% (61/191) and in 53.1% (102/191) of the patients, respectively. Higher expression levels of PD-L1 and PD-L2 at any intensity on tumor and immune cells were defined only in lung adenocarcinomas, and PD-L1 and PD-L2 values were detected in 36.4% (22/64) of these patients. The PD-L1 expressions on tumor and immune cells were observed in 41.7% (10/24) and 25% (6/24) of the patients, respectively. The PD-L2 expressions on tumor and immune cells were detected in 16.7% (4/24) and 8.4% (2/24) of the patients, respectively. Univariate and multivariate analyses revealed that PD-1 expression in tumor cells was an independent prognostic factor in all histological subtypes. Conclusion: Our study results suggest that PD-1 expression is a poor prognostic factor for overall survival in patients with completely resected adenocarcinoma, squamous cell carcinoma, and large cell carcinoma.

The relation between distant metastasis and genetic change type in stage IV lung adenocarcinoma patients at diagnosis.

INTRODUCTION: Brain metastasis prevalence is higher in patients with positive epidermal growth factor receptor (EGFR) mutation, anaplastic lymphoma kinase (ALK) and C-ROS oncogene 1 (ROS-1) fusion change in lung adenocarcinoma. OBJECTIVES: The purpose of our study is to investigate the relation between the genetic change type and the initial distant metastasis in stage IV lung adenocarcinoma patients with genetic changes. METHODS: The study was conducted between January 2007 and December 2018 in a retrospective fashion with patients who had lung cancer diagnosed as stage IV adenocarcinoma. The relation between genetic mutation change (EGFR, ALK or ROS-1) and distant metastasis was analysed. RESULTS: A total of 845 patients were included in the study. The median age was 62 (28-88). It was determined that lung and pleura metastases were more frequent at a significant level in patients with positive EGFR mutation (P = 0.032, P = 0.004, respectively). In patients with positive ALK fusion change, pleura metastasis was determined to be more frequent (P = 0.001). Multiple metastases were determined to be significantly more in patients with positive ALK fusion change than single metastasis (P = 0.02). CONCLUSION: In patients with EGFR mutant lung adenocarcinoma, lung and pleura metastasis is more frequent and pleura metastasis is more frequent in ALK positive adenocarcinoma. Additionally, multiple organ metastases are higher in ALK positive lung adenocarcinoma.

Characteristics of Patients with Large-Cell Neuroendocrine Carcinoma of the Lung.

OBJECTIVES: Neuroendocrine tumors of the lungs are a clearly different group of tumors with definite ultrastructural, immunohistochemical, and molecular features. We reported and analyzed the incidence, clinicopathological features, surgery rates, responses to first-line therapy, and survival outcomes of this rare condition according to our lung cancer patient database. MATERIALS AND METHODS: We retrospectively collected the data of 62 patients who were histopathologically diagnosed with large cell neuroendocrine carcinoma of lung (LCNEC) between January 2010 and January 2016. RESULTS: The patients were predominantly (95%) men (male:female=59:3) with their average age being 60.3±8.6 years. Diagnosis was made by the fine-needle aspiration biopsy (NAB) in 7 patients, bronchoscopic transbronchial biopsy in 13, and surgery in 42. Nearly 43.5% of the patients presented with the tumor in the right upper lobe. Additionally, tumors of 46.8% patients could be observed in peripheral locations. Sixteen patients presented with stage 1, 17 with stage 2, 15 with stage 3, and 14 with stage 4. Median progression-free survival (PFS) was 29 months (SE: 12.2) (95% CI, 5.2-52.8 months). Progression-free survival (PFS) was significantly better in patients with low N, M0, early stage, p63 positive, and TTF-1 positive across the entire cohort. Overall survival (OS) was significantly better in patients with comparatively lower N, M0, low stage, and peripheral location. CONCLUSION: This study demonstrated a single-center experience with clinicopathologic factors and survival outcomes of LCNEC patients.

EUS-B-FNA for Left Adrenal Lesions in Non-Small Cell Lung Cancer Patients: Report of Cases and Literature Review.

The left adrenal gland (LAG) is a common metastatic site in patients with non-small-cell lung cancer. In practice, staging mainly relies on radiologic studies and endoscopic ultrasound-guided fine-needle aspiration (EUS-FNA). Recently, a new technique using convex probe-endobronchial ultrasound (CP-EBUS) scope through the esophagus (EUS-B) has been introduced. A complete mediastinal staging and a reach for upper-abdominal structures in a single session naturally attract attention. However, scientific data are not sufficient to clearly judge the role of this technique in the cytological diagnosis of left adrenal lesions. Therefore, we present cases in which our patients have undergone EUS-B for LAG lesions to increase the data in the literature with regard to accessibility, diagnostic performance, and rate of complications.

Contribution of Cell Block Obtained by Thoracentesis in the Diagnosis of Malignant Pleural Effusion.

AIM: The aim of this study wass to compare the cytological features of pleural exudative fluids by conventional smear (CS) method and cell block (CB) method and also to assess the utility of the combined approach for cytodiagnosis of these effusions. MATERIALS AND METHODS: In all, 113 pleural exudative fluid samples were subjected to evaluation by both CS and CB methods over a period of 2 years. Cellularity, architecture patterns, morphological features, and yield for malignancy were compared, using the two methods. Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy for diagnosis of malignancy were calculated for both the methods, using histology as a gold standard. RESULTS: CB method provided higher cellularity, better architectural patterns, and additional yield for malignancy when compared with CS method. For 22 (40%) patients, histologic subtype was determined with CB especially for adenocarcinoma. The sensitivity, specificity, positive, and negative predictive values of cytology and CB were 48%, 100%, 100%, 67.8% and 59.2%, 100%, 100%, 72.8%, respectively. CONCLUSION: CB technique definitively increased detection of malignancy in pleural fluid effusion when used as an adjunct to CSs. Also, CB provides material suitable for molecular genetic analysis for targeted therapies especially in the treatment of adenocarcinoma.

Prognostic Effects of Predominant Histologic Subtypes in Resected Pulmonary Adenocarcinomas

Background: Predominant histologic subtypes have been reported as predictors of survival of patients with pulmonary adenocarcinoma. Aims: To evaluate the predictive value of histologic classification in resected lung adenocarcinoma using the classification systems proposed by the International Association for the Study of Lung Cancer, American Thoracic Society, European Respiratory Society, and World Health Organization (2015). Study Design: Cross-sectional study. Methods: The histologic classification of a large cohort of 491 patients with resected lung adenocarcinoma (stages I-III) was retrospectively analyzed. The tumors were classified according to their predominant component (lepidic, acinar, papillary, solid, micropapillary, and mucinous), and their predictive values were assessed for clinicopathologic characteristics and overall survival. Results: The patient cohort comprised 158 (32.2%) patients with solid predominant, 150 (30.5%) with acinar predominant, 80 (16.3%) with papillary predominant, 75 (15.3%) with lepidic predominant, 22 (4.5%) with mucinous, and 5 (1.0%) with micropapillary subtype, and 1 (0.2%) with adenocarcinoma in situ. Overall 5-year survival of 491 patients was found to be 51.8%. Patients with lepidic, acinar, and mucinous adenocarcinoma had 70.9%, 59.0%, and 66.6% 5-year survival, respectively, and there was no statistically significant difference between them. Whereas patients with solid, papillary, and micropapillary predominant adenocarcinoma had 41.0%, 40.5%, and 0.0% 5-year survival, respectively. Compared to other histologic subtypes, patients with solid and papillary predominant adenocarcinoma had significantly lower survival than those with lepidic (p<0.001, p=0.002), acinar (p<0.001, p=0.008), and mucinous (p=0.048, p=0.048) subtypes, respectively. The survival difference between patients with solid subtype and those with papillary subtype was not statistically significant (p=0.67). Conclusion: Solid and papillary histologic subtypes are poor prognostic factors in resected invasive lung adenocarcinoma.

Papillary predominant histological subtype predicts poor survival in lung adenocarcinoma.

BACKGROUND: This study aims to investigate whether papillary predominant histological subtype can predict poor survival in lung adenocarcinoma. METHODS: Between January 2005 and December 2016, a total of 80 patients with papillary predominant subtype lung adenocarcinoma (70 males, 10 females; mean age 60.7 years; range, 42 to 79 years) operated in our clinic were included in the study. These patients were compared with those having lepidic, acinar, and mucinous subtypes. Overall and five-year survival rates were evaluated. RESULTS: Five-year survival was 40.5% in papillary predominant histological subtype, while this rate was 70.9%, 59.0%, and 66.6% in lepidic, acinar, and mucinous subtypes, respectively. Papillary subtype showed significantly poor survival compared to lepidic (p=0.002), acinar (p=0.008), and mucinous subtypes (p=0.048). In Stage 1 disease, it was more evident (papillary, 47.5%, lepidic 86.9% [p=0.001], acinar 69.3% [p=0.040], and mucinous 90.0% [p=0.050]). CONCLUSION: Our study results suggest that papillary predominant subtype predicts poor survival in lung adenocarcinoma and these cases may be candidates for adjuvant treatment modalities even in the earlier stages of disease.

Atypical deep somatic soft-tissue leiomyoma of extrathoracic chest wall: first case of the literature.

Leiomyomas are benign soft-tissue tumours which take origin from the smooth muscles. Pleura and chest wall are uncommon location for such tumours. Here, we report a case of a 26-year-old female patient presented with 3 months history of chest pain. Chest X-ray and CT showed a calcified mass of 6×12 cm in size in the left lateral of the chest wall. After resection of the mass, pathological examination diagnosed it as atypical deep somatic soft-tissue leiomyoma of extrathoracic chest wall. No pathological finding was detected during follow-up.

[A case of endometrium adenocarcinoma with multiple cavitary pulmonary metastasis]. / Multipl kaviter akciger metastazi yapan endometriyum adenokarsinom olgusu.

Pulmonary metastases are usually seen as parenchymal nodules, lymphatic-interstitial spread and pleural effusion, however cavitary and cystic metastatic lesions are rare. While breast cancer, gastrointestinal tumors, kidney tumors, malignant melanoma, sarcomas, lymphoma and leukemia mostly metastasize to the lung, endometrial adenocarcinoma rarely metastasizes. A 73-year-old woman with multiple cystic-cavitary lung lesions was referred to our clinic because of chronic cough. She had endometrial adenocarcinoma metastasis to the lung. We wanted to present our case because of the rare occurrence of cystic-cavitary lung metastases and the rare presentation of metastasis of endometrial carcinomas to the lung.

The Contribution of Ultrasonographic Characteristics of Mediastinal Lymph Nodes on Differential Diagnosis of Tuberculous Lymphadenitis from Sarcoidosis.

BACKGROUND: Sarcoidosis and Mediastinal Tuberculous Lymphadenitis (MTLA) are two granulomatous diseases. Differentiation between these two diseases is dependent on clinical presentation, microbiological investigation, and cytopathological examination. In endemic regions, differential diagnosis of MTLA and sarcoidosis might be difficult. Endobronchial ultrasound guided Transbronchial Needle Aspiration (EBUS-TBNA) is a new diagnostic procedure for the diagnosis of mediastinal lymphadenopathy. EBUS not only enables the sampling of Lymph Nodes (LN), but also visualization of sonographic features of them. We hypothesized that the sonographic features of LN may help to differentiate MTLA from sarcoidosis. MATERIALS AND METHODS: This is a retrospective analysis of patients with intrathoracic lymphadenopathy who underwent EBUS-TBNA and were finally diagnosed as sarcoidosis or MTLA. Size, shape, margin, echogenicity, and coagulation necrosis were compared between the groups. RESULTS: A total of 257 LNs (215 sarcoidosis, 42 MTLA) were examined in 101 patients. A heterogeneous echotexture of lymph nodes was significantly more common (P <0.0001) in MTLA (69%) than sarcoidosis (36.2%). Also, necrosis was statistically significantly higher in MTLA compared to sarcoidosis (P<0.0001). The vascular pattern was similar in both groups (P=0.9050). Nearly half of the patients had grade 1 vascular pattern in both groups. The odds for diagnosis of MTLA were significantly higher in the presence of heterogeneous echotexture (odds ratio [OR], 7,00) or necrosis sign (OR, 131,2). CONCLUSION: Vascular patterns of two diseases were similar. Heterogeneous echotexture and necrosis sign in the LNs on EBUS are specific for MTLA. Combination of these findings with a positive tuberculin skin test, favors the diagnosis of MTLA over sarcoidosis.

The diagnostic accuracy of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in mediastinal tuberculous lymphadenitis

Background/aim: Mediastinal lymph nodes are the second most commonly affected lymph nodes in tuberculous lymphadenitis. It is often difficult to diagnose tuberculosis in patients with lymphadenopathy without parenchymal lesions. The aim of this study was to describe the diagnostic utility of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in patients with isolated mediastinal tuberculous lymphadenitis (MTLA). Materials and methods: This study included 527 patients who had undergone EBUS-TBNA between December 2012 and December 2014. Patients with the final diagnosis of MTLA were evaluated. The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of EBUS-TBNA were calculated.Results: The prevalence of MTLA in all patients who had undergone EBUS-TBNA for mediastinal lymphadenopathy of unknown etiology was 5.2% (28/527). EBUS-TBNA was diagnostic in 21/28 (75%) patients, and the remaining 7 patients required additional procedures for confirmation of diagnosis. Sensitivity, specificity, PPV, NPV, and accuracy of combined cytopathological and microbiological examinations of EBUS-TBNA in the diagnosis of MTLA were 87.5%, 98.5%, 91.4%, 98%, and 94.4%, respectively. There were no major complications.Conclusion: EBUS-TBNA is a safe and effective procedure for the diagnosis of MTLA. When microbiological and cytopathological examinations of samples are combined, EBUS-TBNA demonstrates good diagnostic accuracy and NPV for the diagnosis of MTLA.

Diagnostic yield of EBUS-TBNA for lymphoma and review of the literature.

AIM: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA), which enables cytological examination of mediastinal lymph node (LN) aspiration samples, is a safe and minimally invasive method for diagnosis and staging of lung cancer and diagnosis of diseases affecting mediastinal LNs. In this study, we investigated the yield of EBUS-TBNA for diagnosis of lymphoma and reviewed the literature since the British Thoracic Society (BTS) guidelines were published. MATERIALS AND METHODS: We retrospectively evaluated our database for patients who underwent EBUS between March 2011 and December 2014. One hundred eighty-nine patients with isolated mediastinal lymphadenopathy were included in the study. Patients with other causes of lymphadenopathy, such as lung cancer or extrathoracic malignancy, and those with pulmonary lesions accompanying mediastinal lymphadenopathy were excluded from the study. Patients with final diagnosed lymphoma were included in the study on the basis of a history of lymphoma or newly evaluated mediastinal lymphadenopathy. The sensitivity and negative predictive value (NPV) of EBUS-TBNA were calculated. RESULTS: There were 13 patients with the final diagnosis of lymphoma. Eleven of them were new diagnoses and 2 patients were known chronic lymphocytic leukemia (CLL), and underwent EBUS-TBNA for determination of recurrence. Twelve EBUS-TBNA procedures were performed for suspected new cases. Three (25%) were diagnostic, 2 (16.7%) were suspicious for lymphoma and underwent further interventions for definite diagnosis, and 7 (58.3%) were false negative. All 3 patients diagnosed with EBUS-TBNA were non-Hodgkin lymphoma (NHL). None of the Hodgkin lymphoma (HL) cases could be diagnosed with EBUS-TBNA. The overall diagnostic sensitivity and NPV of EBUS-TBNA in detecting lymphoma was 65% and 96.1%, respectively. For the newly diagnosed lymphoma cases, EBUS-TBNA had a sensitivity of 61.1%. CONCLUSION: In conclusion, we believe that since the publication of the BTS guidelines, the value of EBUS-TBNA in the diagnosis of lymphoma still remains controversial. EBUS-TBNA can be the first diagnostic modality in diagnosis of recurrent lymphomas. However, for suspected new cases, especially for HL, the diagnostic yield of EBUS-TBNA is low and negative results do not exclude lymphoma. Further interventions such as mediastinoscopy should be performed for high-suspicion patients.

Contribution of cell block obtained by endobronchial ultrasound-guided transbronchial needle aspiration in the diagnosis of malignant diseases and sarcoidosis.

AIM: Endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) is a safe and minimally invasive procedure that can be performed in outpatient settings. Several studies have demonstrated the usefulness of EBUS-TBNA in the diagnosis of sarcoidosis and malignant diseases. This study focused on the role of cell block (CB) analysis in determining the diagnostic yield of EBUS-TBNA in malignant diseases and sarcoidosis. MATERIALS AND METHODS: The study was conducted at a training and research hospital. Records of patients who underwent EBUS-TBNA between March 2011 and December 2014 for diagnosed sarcoidosis or malignancy were retrospectively analyzed. Results of all EBUS-TBNA smears and CB were separately evaluated to determine the diagnostic value of each. RESULTS: There were 84 sarcoidosis and 179 malignancy patients. In the malignancy group, CB contributed to cancer diagnosis in 15 (8.3%) patients and subclassification in 19 (10.6%) patients. In the sarcoidosis group, for 45.2% of patients (38/84), smears were not diagnostic but CB showed granulomatous inflammation. CONCLUSION: CB significantly increases the diagnostic yield of EBUS-TBNA for sarcoidosis. In our study, in the malignancy group the diagnostic yield was low but it was helpful for subclassification, especially for adenocarcinoma.

Anti-inflammatory and Anti-apoptotic Effect of Valproic Acid and Doxycycline Independent from MMP Inhibition in Early Radiation Damage.

BACKGROUND: Matrix metalloproteinase (MMP) inhibitors decrease inflammation in normal tissues and suppress cancer progress in normal tissues. Valproic acid (VA) and doxycycline (DX) are MMP inhibitors that have radio-protective effects. Their ability to inhibit MMPs in irradiated tissue is unknown and the role of MMPs in radio-protective effects has not been tested to date. AIMS: The purpose of this study was to examine whether administration of VA and DX to rats before irradiation affects tissue inflammation and apoptosis in the early phase of radiation, and whether the effect of these drugs is mediated by MMP inhibition. STUDY DESIGN: Animal experimentation. METHODS: Twenty-six Wistar rats were randomized into four groups: control (CTRL), radiation (RT), VA plus radiation (VA+RT), and DX plus radiation (DX+RT). Three study groups were exposed to a single dose of abdominal 10 Gy gamma radiation; the CTRL group received no radiation. Single doses of VA 300 mg/kg and DX 100 mg/kg were administered to each rat before radiation and all rats were sacrificed 8 hours after irradiation, at which point small intestine tissue samples were taken for analyses. Levels of inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and matrix metal-loproteinases (MMP-2 and MMP 9) were measured by ELISA, MMP activities were measured by gelatin and casein zymography and apoptosis was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assay. RESULTS: VA decreased the levels of TNF-α and IL-1ß proteins insignificantly and decreased apoptosis significantly in the irradiated tissue, but did not inhibit MMPs. In contrast, VA protected the basal MMP activities, which decreased in response to irradiation. No effect of DX was observed on the levels of inflammatory cytokines or activities of MMPs in the early phases of radiation apoptosis. CONCLUSION: Our findings indicated that VA protects against inflammation and apoptosis, and DX exhibits anti-apoptotic effects in early radiation and these effects are independent from MMP inhibition.

Pulmonary Strongyloides stercoralis infection.

The 17-year-old male patient presented with fever, weakness, dyspnea and weight loss. His chest radiography demonstrated diffuse reticulonodular density, and high-resolution lung tomography indicated diffuse micronodules and prevalent ground-glass pattern. The findings were consistent with miliary involvement. The patient underwent examinations for rheumatology, immunology, cytology and infectious conditions. His immune system was normal and had no comorbidities or any history of immunosuppressive treatment. Strongyloides stercoralis larvae were noted upon direct inspection of the feces. Clinical and radiological improvement was achieved with albendazole 400 mg/day. This case is being presented since miliary involvement in the lungs caused by S. stercoralis infection in an individual with intact immune system is rare and difficult to diagnosis.

Inflammatory pseudotumor of the liver diagnosed by needle biopsy: report of three cases (one with neuroendocrine tumor of the rectum and lung).

Inflammatory pseudotumor of the liver is a rare disorder that can histologically and radiologically resemble malignant neoplasms. The prognosis of the patients with hepatic inflammatory pseudotumor is usually good with conservative therapy. Most of the reported cases are diagnosed in the surgical resection specimens; only very few reported cases have been diagnosed by needle biopsy. We report three additional cases of inflammatory pseudotumor of the liver diagnosed by liver biopsy. Two of these cases were treated successfully with antibiotics. The other case, who was resistant to medical treatment, had coexisting neuroendocrine neoplasms of the rectum and the lung. Since her general condition did not allow an extensive surgery, the mass of the liver could not be resected and she died approximately five months after she was voluntarily discharged from the hospital. Many of the inflammatory pseudotumor of the liver are found to be associated with variable neoplasms, but to our knowledge, the latter case is the first case of inflammatory pseudotumor associated with a neuroendocrine tumor.

Hydatid cyst presenting as an eosinophilic pleural effusion.

A 61-year-old woman presented with an eosinophilic pleural effusion, secondary to transdiaphragmatic intrapleural spread of an hepatic hydatid cyst. Right posterolateral thoracotomy and frenotomy revealed a loculated pleural effusion associated with a 10 x 8 cm hydatid cyst in the posterior segment of the liver. Hydatid disease should be included in the differential diagnosis of eosinophilic pleural effusions in endemic regions.