Clinical Relevance of Subcentimetric Lymph Node Biopsy in the Diagnosis of Ocular Sarcoidosis.

PURPOSE: To evaluate the clinical relevance of subcentimetric lymph node biopsy via mediastinoscopy in patients with presumed ocular sarcoidosis (OS). METHODS: Retrospective study of consecutive patients who underwent biopsy via mediastinoscopy for suspected OS. The biopsy outcomes and clinical features of patients with subcentimetric nodes and of those with lymph nodes >1 cm were compared. RESULTS: A total of 67 patients with presumed OS were included. Forty-two patients (63%) had lymph nodes ≥1 cm in diameter, while 25(37%) showed subcentimetric lymph nodes. Biopsy was consistent with sarcoidosis in 83% of patients with lymph nodes ≥1 cm and in 76% of patients with subcentimetric lymph nodes (p = .60). Patients with OS who had subcentimetric lymph nodes had less lymphopenia (p = .01), lower lysozyme values (p = .03) and a longer diagnostic delay compared to those with larger lymph nodes. CONCLUSIONS: The biopsy of subcentimetric lymph nodes via mediastinoscopy may provide a histological diagnosis and reduce diagnostic delay.

Thoracic Hyper-IgG4-Related Disease Mimicking Malignant Pleural Mesothelioma.

We report a rare case of a IgG4-related disease presenting with recurrent pleural effusion, pleural thickness and multiple mediastinal lymphadenopathies and no involvement of other extrathoracic organs. A 65-year-old man with a previous asbestos exposure presented with cough and pain discomfort. A large right pleural effusion was detected and evacuated (siero-haematic liquid). With the suspicious of a pleural mesothelioma, a CT-scan before and a 18F-FDG PET/CT-scan later were performed revealing multiple pleural thickenings and multiple mediastinal lymphadenopathies with radiotracer uptake. EBUS-TBNA EBUS-TBNA did not result in a formal pathological diagnosis; thus, multiple pleural biopsy were performed via right thoracoscopy. At pathology the pleura was markedly thickened by a chronic fibroinflammatory process with scattered lymphoid follicles and a large number of mature plasma cells. Immunohistochemistry shows a mixed B (CD20+) and T (CD3+) population of lymphocytes, without light chain restriction and an increased number of IgG4-positive plasma cells. A presumptive diagnosis of IgG4-related disease was formulated. Total body CT-scan excluded other organ involvement. Blood test showed elevated serum IgG4 concentrations (253 mg/dL) and mild elevation of acute-phase reactants (C-reactive protein 10.7 mg/L). Autoimmune profile was negative. A diagnosis of definite IgG4-related disease was made, and treatment with prednisone 50 mg/day was started.

PUREAIR protocol: randomized controlled trial of intensive pulmonary rehabilitation versus standard care in patients undergoing surgical resection for lung cancer.

BACKGROUND: Non-small cell lung cancer is the most common type of lung cancer. Surgery is proven to be the most effective treatment in early stages, despite its potential impact on quality of life. Pulmonary rehabilitation, either before or after surgery, is associated with reduced morbidity related symptoms and improved exercise capacity, lung function and quality of life. METHODS: We describe the study protocol for the open-label randomized controlled trial we are conducting on patients affected by primary lung cancer (stages I-II) eligible for surgical treatment. The control group receives standard care consisting in one educational session before surgery and early inpatient postoperative physiotherapy. The treatment group receives, in addition to standard care, intensive rehabilitation involving 14 preoperative sessions (6 outpatient and 8 home-based) and 39 postoperative sessions (15 outpatient and 24 home-based) with aerobic, resistance and respiratory training, as well as scar massage and group bodyweight exercise training. Assessments are performed at baseline, the day before surgery and one month and six months after surgery. The main outcome is the long-term exercise capacity measured with the Six-Minute Walk Test; short-term exercise capacity, lung function, postoperative morbidity, length of hospital stay, quality of life (Short Form 12), mood disturbances (Hospital Anxiety and Depression Scale) and pain (Numeric Rating Scale) are also recorded and analysed. Patient compliance and treatment-related side effects are also collected. Statistical analyses will be performed according to the intention-to-treat approach. T-test for independent samples will be used for continuous variables after assessment of normality of distribution. Chi-square test will be used for categorical variables. Expecting a 10% dropout rate, assuming α of 5% and power of 80%, we planned to enrol 140 patients to demonstrate a statistically significant difference of 25 m at Six-Minute Walk Test. DISCUSSION: Pulmonary Resection and Intensive Rehabilitation study (PuReAIR) will contribute significantly in investigating the effects of perioperative rehabilitation on exercise capacity, symptoms, lung function and long-term outcomes in surgically treated lung cancer patients. This study protocol will facilitate interpretation of future results and wide application of evidence-based practice. TRIAL REGISTRATION: ClinicalTrials.gov Registry n. NCT02405273 [31.03.2015].

18F-fluorodeoxyglucose positron emission tomographic scan in solid-type p-stage-I pulmonary adenocarcinomas: what can produce false-negative results?

Objective: False-negative (FN) uptake of 18F-fluorodeoxyglucose (FDG) can be divided into those cases related to technological limitations of positron emission tomography (PET) and those related to inherent properties of neoplasms. Our goal was to clarify possible factors causing FN PET results in patients with solid-type pulmonary adenocarcinomas (PAs). Methods: From January 2007 to December 2014, of the 255 patients with p-stage-1 non-small-cell lung cancer observed and treated (surgically) in our institution, we retrospectively reviewed the PET/computed tomography (CT) records, the clinical information, the preoperative thin-section CT images, and the pathological features [classified by the International Association for the Study of Lung Cancer/American Thoracic Society/European Respiratory Society (IASLC/ATS/ERS) subtyping criteria] of 94 consecutive solid-type p-stage-1 PAs. Univariable and multivariable logistic analyses were used to identify and weigh the independent predictors of the PET findings using the following variables: body weight, blood glucose level, tumour size, tumour location, and histological classification. Results: There were 58 men and 36 women (mean age = 68.7 ± 8.9 years, range 42-85). Considering the maximum standardized uptake value (SUVmax) ≥ 2.5 as a 'PET-positive' result, 77 lesions (81.9%) proved PET positive and 17 lesions (18.1%), PET negative (with SUVmax < 2.5). Overall, the median SUVmax value was 5.7 [interquartile range (IQR) 2.8-10.3]. Higher SUVmax values ( P < 0.001) were observed in those PAs larger than 2 cm in their major axis (median SUVmax = 9.0; IQR 4.6-14.6); in PAs < 2 cm, the median SUVmax was 4.1; IQR 2.2-5.9. When clustering the cohort in two histological classes (class A, colloid/mucinous/lepidic versus class B, micropapillary/solid/acinar/papillary), the radiometabolic patterns were significantly different (median SUVmax = 2.8; IQR 1.7-4.9 in class A vs median = 7.4 IQR 4.5-13.9 in class B, P < 0.001). Significant PET FN rates were reported in (i) PAs measuring < 2 cm in their major axis (27.9%), (ii) lesions located in the lower zones of the lung (31.0%), and (iii) class A tumours (37.5%). In the multivariable logistic analysis, histological type (IASLC/ATS/ERS aggregated clusters) proved to be the only independent relevant factor for determining whether PET results were negative or positive (OR:7.23, 95% CI: 2.05-25.43, P = 0.002). Conclusions: The IASLC/ATS/ERS pattern significantly influences FDG uptake in solid-type p-stage-1 PAs. The fact that colloid/mucinous/lepidic adenocarcinomas have a notable tendency to produce negative findings on PET scans warrants particular attention.

Pathologic Findings and Long-Term Results After Surgical Treatment for Pulmonary Sarcomatoid Tumors: A Multicenter Analysis.

BACKGROUND: Pulmonary sarcomatoid carcinoma (PSC) is a very rare subtype of non-small cell lung cancer (NSCLC). The aim of this study was to clarify the pathologic characteristics and long-term survival after surgical treatment in patients with PSC. METHODS: From January 2003 to December 2013, we retrospectively reviewed the clinical findings, surgical notes, and pathologic and follow-up data from 148 consecutive patients who underwent curative resection for PSC in 5 institutions. The Kaplan-Meier method, log-rank test, and Cox regression analysis were used. RESULTS: Mean age and male to female ratio were 66.6 ± 9.9 years and 120:28, respectively. Surgical resection (pneumonectomy in 8 patients, bilobectomy in 132 patients, and sublobar resection in 8 patients) was complete in 142 cases (96%). At pathologic evaluation, 36 patients (24%) had stage I, 69 patients (47%) had stage II, 33 patients (22%) had stage III, and 10 patients (7%) had stage IV disease. A "biphasic tumor" (PSC with an NSCLC component) was observed in 77 patients (52%). We detected a high rate of vascular emboli in the surgical specimens (overall, 68%; 57% in pathologic stage I tumors), whereas lymphatic emboli were found in 30% of cases (5% of pathologic stage I tumors). Overall median and 5-year long-term survival (LTS) was 19 months and 12.6% (LTS, 16.3% in pathologic stage I), respectively. Distant recurrences frequently occurred after surgical treatment (81%), even in pathologic stage I tumors that underwent R0 resection (62%). Multivariable survival analysis identified R+ resection (hazard ratio [HR],12.3; 95% confidence interval [CI], 3.67-41.28; p < 0.0001), advanced pathologic stage (HR, 5.75; 95% CI, 2.55-12.98; p < 0.0001), and the presence of vascular emboli (HR, 1.67; 95% CI, 1.05-2.67; p = 0.0327) as independent negative prognostic factors. CONCLUSIONS: PSCs have very aggressive behavior and high metastatic potential even in early stages. R+ resection, pathologic TNM status, and the presence of vascular emboli are independent prognostic factors.

Occasional detection of thymic epithelial tumor 4 years after diagnosis of adult onset Still disease: A challenging case report and immuno-oncological considerations coming from pertinent literature review.

BACKGROUND: Thymoma is a T cell neoplasm arising from the thymic epithelium that due to its immunological role, frequently undercover derangements of immunity such a tumors and autoimmune diseases. METHODS: Herein, we report, to the best of our knowledge, the first description of an association between thymoma and adult onset Still disease (AOSD) in a 47-year-old man. The first one was occasionally detected 4 years later the diagnosis of AOSD, and surgically removed via right lateral thoracotomy. Histology confirmed an encapsulated thymic tumor (type AB sec. WHO-classification). RESULTS: The AOSD was particularly resistant to the therapy, requiring a combination of immunosuppressant followed by anti-IL1R, that was the only steroids-sparing treatment capable to induce and maintain the remission. The differential diagnosis was particularly challenging because of the severe myasthenic-like symptoms that, with normal laboratory tests, were initially misinterpreted as fibromyalgia. The pathogenic link of this association could be a thymus escape of autoreactive T lymphocytes causing autoimmunity. CONCLUSION: Clinicians should be always include the possibility of a thymoma in the differential diagnosis of an unusual new onset of weakness and normal laboratories data, in particular once autoimmune disease is present in the medical history.

Primary Sarcomatoid Carcinoma of the Lung: Radiometabolic ((18)F-FDG PET/CT) Findings and Correlation with Clinico-Pathological and Survival Results.

INTRODUCTION: Pulmonary sarcomatoid carcinoma (PSC) is a very rare and uninvestigated subtype of non-small cell lung cancer (NSCLC). METHODS: The aims of this study were to define the radiometabolic features (by (18)F-FDG PET/CT) in a bi-centric cohort of 49 PSC patients and to explore their relation with clinico-pathological characteristics and long-term survival results after surgical treatment. RESULTS: There were 40 males and 9 females aged 65.2 ± 10.47 years. Overall long-term survival was 26.7 % at 5 years. Mean and median values of SUVmax were 15.21 and 15, respectively (SD ±5.5). Performing an age-, gender- and staging-matched analysis comparing PSC Stage-I only with a cohort of Stage-I NSCLC (n = 93), we observed significantly higher SUVmax values in PSC group (15.11 vs 7.66, p = 0.001). CONCLUSIONS: No differences in terms of SUVmax were found with regard to tumour dimensions, histology (pure vs mixed, pleomorphic vs others), pathological stage and pattern of recurrence. P-stage, surgical radicality, vascular/lymphatic invasion but not SUVmax affected long-term survival in PSC.

Time-Trend Analysis of Pulmonary and Diaphragmatic Functionality in Patients with Diaphragmatic Palsy or with Chronic Diaphragmatic Hernia after Surgical Treatment.

Background The aim of this study was to assess long-term pulmonary and diaphragmatic function in two cohorts of patients: the first one affected by diaphragmatic palsy (DP) who underwent plication reinforced by rib-fixed mesh and the second one affected by chronic diaphragmatic hernia (TDH) who underwent surgical reduction and direct suture. Materials and Methods From 1996 to 2011, 10 patients with unilateral DP and 6 patients with TDH underwent elective surgery. Preoperative and long-term (12 months) follow-up assessments were completed in all patients, including pulmonary function tests (PFTs) with diffusion of the lung for carbon monoxide (DLCO), measure of maximum inspiratory pressure (MIP) assessed both in standing and in supine positions, blood gas analysis, chest computed tomographic (CT) scan, and dyspnea score. The Pearson chi-square test, Fisher exact test, and Student t-test were applied when indicated. Results At long-term (12 months) postoperative follow-up, patients operated for DP showed a significant improvement in terms of forced expiratory volume in 1 second (FEV1%) (+ 18.2%, p < 0.001), forced vital capacity (FVC%) (+ 12.8%, p < 0.001), DLCO% (+ 8.3%, p = 0.04), and Po 2 (+ 9.86 mm Hg, p < 0.001) when compared with baseline values. Conversely, when considering the TDH group, only the levels of Po 2 were found to be significantly higher in the postoperative assessment (+ 8.3 mm Hg, p = 0.04). Although MIP increased in both the groups after surgery, a persistent and significant decrease of MIP was detected in TDH group when comparing the levels assessed in supine position with those measured in the standing position (p < 0.001). Medical Research Council dyspnea scale improved in the DP group by a factor of 0.80 (p < 0.001) and in the TDH group by a factor of 0.33 (p = 0.175). Conclusion In patients who underwent surgery for DP, good long-term results may be predicted in terms of pulmonary flows, volumes, and DLCO. Conversely, in patients who underwent elective surgery for chronic TDH, a persistent overall restrictive pattern, lower MIP values in supine position, and paradoxical motion could be expected.

A 79-Year-Old Man With Interstitial Lung Disease and Cryptic Area of High 18 Fluorodeoxyglucose Uptake in Left Upper Lobe.

Seven years after left hemicolectomy and radical lymph nodal dissection followed by adjuvant chemotherapy for colorectal cancer (histotype, adenocarcinoma; stage, pT3N2M0; grading, G2), a slight increase in carcinoembryonic antigen levels (6.2 ng/mL; range, 0-5 ng/mL) was detected in a 79-year-old man. He was a heavy smoker with history of an interstitial fibrotic lung disease with associated areas of emphysema.

PET/CT assessment of neuroendocrine tumors of the lung with special emphasis on bronchial carcinoids.

Pulmonary neuroendocrine tumors (pNETs) arise from bronchial mucosal cells known as enterochromaffin cells which are part of the diffuse neuroendocrine system. The pathological spectrum of pNETs ranges from low-/intermediate-grade neoplasms such as bronchial carcinoids (BCs), also known as typical or atypical carcinoids, to high-grade neoplasms as large-cell neuroendocrine carcinoma and small-cell lung cancer. The tumor biology of pNETs still represents a matter of open debate. The distinct features among the different pNETs include not only their pathologic characteristics but also their clinical behavior, epidemiology, treatment, and prognosis. In this sense, a correct pathological identification in the preoperative setting is a key element for planning the best strategy of care in pNETs and especially in BCs. Controversial results have been reported on the diagnostic accuracy of fluorine-18-fluorodeoxyglucose positron emission tomography or positron emission tomography/computed tomography (F-18-FDG PET or PET/CT) in BCs. On the other hand, there is increasing evidence supporting the use of PET with somatostatin analogues (DOTA-TOC, DOTA-NOC, or DOTA-TATE) labeled with gallium-68 (Ga-68) in pNETs. Herein, we review the pertinent literature aiming to better define the current state of art of PET/CT in the detection and histological differentiation of pNETs with special emphasis on BCs.

"Dry" pleural mesothelioma successfully diagnosed on endobronchial ultrasound (EBUS)-guided transbronchial needle aspiration (TBNA).

The acquisition of histologic material is obligatory in order to establish the diagnosis of malignant pleural mesothelioma (MPM). In particular, tissue acquisition in cases of "dry" MPM (focal pleural thickening without pleural effusion or mediastinal lymph node involvement) is usually performed via a thoracoscopic pleural biopsy. In contrast, the techniques for performing echoendoscopic (transbronchial or transesophageal) needle aspiration of pleural lesions have only rarely been reported due to the theoretical limitations of tissue acquisition in such cases. We herein report the first case of "dry" MPM successfully diagnosed via endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in a 73-year-old man presenting with a pleural mass in the right costovertebral recess, adjacent to the carina. The patient underwent radical resection, and a definitive pathological examination confirmed the diagnosis of epithelioid MPM.