Mediastinal Node Involvement Research Articles

Invasive mediastinal staging by endosonography or video-assisted mediastinoscopy in PET-CT clinical N1 non-small cell lung cancer.

Patients with clinical N1 (cN1) non-small cell lung cancer (NSCLC) based on PET-CT imaging are often found to have occult mediastinal nodal involvement (N2-disease) at invasive staging or resection although the PET-CT was negative on the mediastinum. Two multicenter prospective studies in patients with PET-negative mediastinum but suspected cN1-disease were performed to measure sensitivity of two invasive mediastinal staging strategies to detect mediastinal nodal disease, one with endosonography and one with video-assisted mediastinoscopy (VAM) or video-assisted mediastinoscopic lymphadenectomy (VAMLA). Consecutive patients with operable and resectable cN1 (suspected) NSCLC underwent endosonography, if negative followed by mediastinoscopy in the first study (n=100). In the second study with identical inclusion criteria, patients (n=105) underwent a VAM or VAMLA [VAM(LA)]. All patients underwent FDG-PET and CT scan prior to invasive mediastinal staging. The primary study outcome was sensitivity to detect N2-disease. Secondary endpoints were the prevalence of N2-disease, negative predictive value (NPV) and accuracy of the invasive staging procedure. In both studies, 25% of patients with cN1 disease on imaging had eventually pathology-proven N2-disease. Endosonography alone reached a sensitivity (38%) to detect mediastinal nodal disease. Invasive mediastinal staging with VAM(LA) had a sensitivity of 73% to detect N2-disease. The NPV was 92% and accuracy 93%. At endosonography, a mean of 2.1 mediastinal nodal stations were biopsied vs. 3.9 at VAM(LA). VAM(LA) has a satisfactory sensitivity of 73% to detect mediastinal nodal disease in cN1 lung cancer and could be the technique of choice for pre-resection mediastinal lymph node assessment in this patient group with a one in four chance of occult positive mediastinal nodes after negative PET-CT.

Akciğer Karsinomu Tedavisi Sırasında Beyin Metastazı Gelişimini Etkileyen Faktörler

INTRODUCTION: Brain metastases are frequently seen in lung carcinomas and increase mortality. The aim of this study is to evaluate the factors affecting brain metastases occurrence and to determine survival after brain metastases in patients with lung cancer. METHODS: The study included 72 patients who were diagnosed with lung carcinoma and had no brain metastasis at the time of diagnosis. RESULTS: The diagnosis of adenocarcinoma was 40.3%, while small cell lung carcinoma (SCLC) was 31.9% and squamous cell carcinoma was 26.4%. At the time of diagnosis 30.6% of patients were in stage IVB, 29.2% in stage IIIB and 18.1% in stage IIIA group. There were 5 (6.9%) patients in stage I and II. N2 involvement was found in 66.7% of the patients and N3 involvement was found in 23.6% of the patients. In the initial diagnosis, distant metastasis was not present in 63.9% of the patients. The time to brain metastasis development was 10.0 months. The survial of the patients was 2.0 months after the development of brain metastasis. Only 8,3% (n: 6) of the patients are still alive. All these alive patients were diagnosed as adenocarcinoma. DISCUSSION AND CONCLUSION: In our study, despite the adequate treatment responses in the primary tumor, brain metastasis developed in the patients within one year and caused loss of life in two months. Mediastinal lymph node involvement, local advanced and metastatic stage disease and adenocancer histology are effective factors in the development of brain metastasis in lung carcinoma.

International guidelines on stage III N2 nonsmall cell lung cancer: surgery or radiotherapy?

Stage III N2 nonsmall cell lung cancer (NSCLC) is a complex disease with poor treatment outcomes. For patients in whom the disease is considered technically resectable, the main treatment options include surgery (with neoadjuvant or adjuvant chemotherapy/neoadjuvant chemoradiotherapy (CRT)) or CRT followed by adjuvant immunotherapy (dependent on programmed death ligand 1 status). As there is no clear evidence demonstrating a survival benefit between these options, patient preference plays an important role. A lack of a consensus definition of resectability of N2 disease adds to the complexity of the decision-making process. We compared 10 international guidelines on the treatment of NSCLC to investigate the recommendations on preoperatively diagnosed stage III N2 NSCLC. This comparison simplified the treatment paths to multimodal therapy based on surgery or radiotherapy (RT). We analysed factors relevant to decision-making within these guidelines. Overall, for nonbulky mediastinal lymph node involvement there was no clear preference between surgery and CRT. With increasing extent of mediastinal nodal disease, a tendency towards multimodal treatment based on RT was identified. In multiple scenarios, surgery or RT-based treatments are feasible and patient involvement in decision-making is critical.

Mediastinal staging: when and how?

Mediastinal staging for lung cancer includes both the assessment of mediastinal lymph nodes status before treatment and the postoperative pathological staging obtained by lymph-node removal performed during surgery. In patients with early stage NSCLC, the aim is to exclude with the highest certainty and the lowest morbidity the presence of mediastinal node involvement. Before treatment, mediastinal staging is based on imaging techniques, endoscopic techniques, and surgical procedures. Final pathological staging is based on lymph-node removal performed with lung resection according with different modalities (sampling, systematic dissection, etc.) and various approaches (thoracotomy, VATS, robotic). Data and indications from literature evidences are reported and discussed.

Beyond Margin Status: Population-Based Validation of the Proposed International Association for the Study of Lung Cancer Residual Tumor Classification Recategorization

The International Association for the Study of Lung Cancer's (IASLC's) proposal to recategorize the residual tumor (R) classification for resected NSCLC needs validation. Using a 2009 to 2019 population-based multi-institutional NSCLC resection cohort from the United States, we classified resections by Union for International Cancer Control (UICC) and IASLC R criteria and compared the distribution of R classification variables and their survival associations. Of 3361 resections, 95.3% were R0, 4.3% were R1, and 0.4% were R2 by UICC criteria; 33.3% were R0, 60.8% were R-uncertain, and 5.8% were R1/2 by IASLC criteria; 2044 patients (63.8%) migrated from UICC R0 to IASLC R-uncertain. Median survival was not reached, 69 (95% confidence interval [CI]: 64-77), and 25 (95% CI: 18-36) months, respectively, for patients with IASLC R0, R-uncertain, and R1 or R2 resections. Failure to achieve nodal dissection criteria caused 98% of migration to R-uncertainty, metastasis to the highest mediastinal node station, 5.8%. Compared with R0, R-uncertain resections with mediastinal nodes, no mediastinal nodes, and no nodes had adjusted hazard ratios of 1.28 (95% CI: 1.10-1.48), 1.47 (95% CI: 1.24-1.74), and 1.74 (95% CI: 1.37-2.21), respectively, suggesting a dose-response relationship between nodal R-uncertainty and survival. Accounting for mediastinal nodal involvement, the highest mediastinal station involvement was not independently prognostic. The incomplete resection variables were uniformly prognostic. The proposed R classification recategorization variables were mostly prognostic, except the highest mediastinal nodal station involvement. Further categorization of R-uncertainty by severity of nodal quality deficit should be considered.

EORTC Lung Cancer Group survey on the definition of NSCLC synchronous oligometastatic disease

BackgroundSynchronous oligometastatic disease (sOM) has been described as a distinct disease entity; however, there is no consensus on OM definition (OM-d) in non–small-cell lung cancer (NSCLC). A consensus group was formed aiming to agree on a common OM-d that could be used in future clinical trials. A European survey was circulated to generate questions and input for the consensus group meeting. MethodsA European Organisation for Research and Treatment of Cancer Lung Cancer Group (LCG)/sOM-d consensus group survey was distributed to LCG, sOM-d consensus group, and several European thoracic oncology societies’ members. Results444 responses were analysed (radiation oncologist: 55% [n = 242], pulmonologist: 15% [n = 66], medical oncologist: 14% [n = 64]). 361 physicians (81%) aimed to cure sOM NSCLC patients and 82% (n = 362) included the possibility of radical intent treatment in their sOM-d. The maximum number of metastases considered in sOM-d varied: 12% replied 1 metastasis, 42% ≤ 3, and 17% ≥ 5 metastases. 79% (n = 353) stated that number of organs involved was important for sOM-d, and most (80%, n = 355) considered that only ≤3 involved organs (excluding primary) should be included. 317 (72%) included mediastinal lymph node involvement in the sOM-d and 22% (n = 70/317) counted mediastinal lymph node as a metastatic site. Most physicians completed sOM staging with brain magnetic resonance imaging (91%, n = 403) and positron emission tomography/computed tomography (98%, n = 437). Pathology proof of metastatic disease was a requirement to define sOM for 315 (71%) physicians. The preferred primary outcome for sOM clinical trials was overall survival (73%, n = 325). ConclusionAlthough consensual answers were obtained, several issues remain unresolved and will require further research to agree on a sOM-d.

SYSTEMIC AIR EMBOLISM AFTER PERCUTANEOUS CT-GUIDED LUNG BIOPSY

SESSION TITLE: Global Case Report Posters SESSION TYPE: Global Case Reports PRESENTED ON: 10/23/2019 09:45 AM - 10:45 AM INTRODUCTION: Computed-tomography (CT) guided transthoracic needle biopsy (TTNB) is widely performed to establish a histological diagnosis of peripheral lung tumors. Systemic air embolism is described as a rare complication. CASE PRESENTATION: In a 70-year-old man with systemic arterial hypertension and benign prostatic hypertrophy a peripheral pulmonary consolidation in the left upper lobe and multiple brain nodules were detected after an acute episode of epilepsy. As a primary lung tumor was suspected, he underwent a total body positron emission tomography-CT scan, showing pathological glucose uptake in the left lung lesion (Figure 1) and metastatic involvement of mediastinal lymph nodes, adrenal glands and vertebral bodies. His coagulation profile, hemoglobin and platelets levels were normal, so a bronchoscopy with transbronchial lung biopsy under fluoroscopy was set. The histological analysis showed bronchial inflammatory cells, so the patient underwent a CT-guided TTNB. Under local anesthesia, two bioptic samples were collected using the 18-gauge outer coaxial needle by an expert interventional radiologist (Figure 2A). During the procedure the onset of air embolism in both heart ventricles, main pulmonary artery and ascending aorta was immediately detected on CT scans (Figure 2B). A layer of ipsilateral pneumothorax (maximum thickness 12 mm) together with chest wall subcutaneous emphysema were present. The patient complained about general malaise with signs of hypotension and desaturation. No electrocardiographic alterations were recorded. After he was administered 100% oxygen through a mask and hydrated, his clinical conditions rapidly improved. Two hours later a chest and brain CT scans were repeated. While cardiac, aortic and pulmonary artery air embolisms were solved, the pneumothorax layer increased (20 mm) (Figure 3). No ischemic lesions were detected in brain CT scans. The patient was maintained on close monitoring and after four days the pneumothorax was no longer radiologically detectable. An invasive lung adenocarcinoma was diagnosed and the patient was referred to the Oncology Department. DISCUSSION: Systemic air embolism is described in 0.02-0.07% of TTNB (1). Direct exposure of pulmonary vein to air through the needle, bronchovenus fistula formation and air penetration from the pulmonary arterial circulation to the pulmonary vein are all possible pathogenic mechanisms (2). Possible prevention strategies include avoiding coughing and straining during the procedure and ventilation with positive pressure (3). No specific treatment has established yet other than supplying 100% oxygen and hyperbaric chamber. The patient has to be strictly monitored because potential life-threatening complications may rise and the repetition of a chest-brain CT scan may be urgently needed (3). CONCLUSIONS: Even if uncommon, systemic air embolism after TTBN must be always considered and rapidly handled. Reference #1: Sinner WN. Complications of percutaneous transthoracic needle aspiration biopsy. Acta Radiol. 1976;17:813-28 Reference #2: Mokhlesi B, Ansaarie I et al. Coronary artery air embolism complicating CT.guided transthoracic needle biopsy of the lung. Chest. 2002;121:993-996 Reference #3: Hare SS, Gupta ATC et al. Systemic arterial air embolism after percutaneous lung biopsy. Clin Radiol. 2011;66:589-596. DISCLOSURES: No relevant relationships by Paolo Ceruti, source=Web Response No relevant relationships by SARA ALESSANDRA LONNI, source=Web Response

ES02.01 Biomarker Testing in LA Disease

ES02.01 Biomarker Testing in LA Disease

Prognostic significance of anaplastic lymphoma kinase rearrangement in patients with completely resected lung adenocarcinoma.

Reports of the prognostic significance of anaplastic lymphoma kinase (ALK) rearrangement in early stage lung adenocarcinoma have been contradictory. This study aimed to identify the associations of ALK rearrangement with clinicopathologic features and prognosis in patients with surgically resected stage I-IIIA lung adenocarcinoma. Analysis of ALK status was performed by a fully-automated immunochemistry assay (with rabbit monoclonal Ventana D5F3 antibody) in tissue sections of 2,103 patients with surgically-resected stage I-IIIA lung adenocarcinoma. ALK positive patients were matched with negative patients in a 1:1 ratio using propensity score matching (PSM). Clinical outcomes were assessed by disease-free survival (DFS) and overall survival (OS) after surgery. Initial recurrence pattern was also investigated according to ALK status. Among 2,103 stage I-IIIA lung adenocarcinoma cases, 81 (3.9%) were ALK positive. ALK positivity was significantly associated with younger age (P<0.001), solid predominant adenocarcinoma (P<0.001), variants of invasive adenocarcinoma (P<0.001), higher frequency of pleura invasion (P=0.040), smaller tumor size (P=0.014), mediastinal lymph node involvement (N2; P<0.001) and later pathologic stage (IIIA; P=0.001). In the match cohort, ALK positivity was not associated with DFS [hazard ratio (HR), 0.58; 95% confidence interval (CI): 0.33-1.03, P=0.063] or OS (HR, 0.61; 95% CI: 0.22-1.67, P=0.334). Lymph node involvement (HR: 5.36, 95% CI, 3.01-9.65, P<0.001) and solid predominant adenocarcinoma subtype (HR, 2.02; 95% CI: 1.07-3.79; P=0.029) were the independent prognostic factors of inferior DFS, and lymph node involvement was the independent prognostic factors of worse OS (HR, 6.61; 95% CI: 2.43-17.94; P<0.001). ALK positive patients had a higher risk of developing tumor recurrence in liver (P=0.043). ALK rearrangement was not an independent prognostic factor in stage I-IIIA lung adenocarcinoma patients but leaded to a higher risk of developing recurrence in liver.

GR01.01 Definition and Minimal Staging in Oligometastatic Disease

Oligometastatic non-small cell lung cancer (NSCLC) is perceived as a separate entity of metastatic NSCLC with limited metastatic potential and possibility of long term survival when treated with local radical treatment1-3. However, uniform definition of oligometastatic NSCLC does not exist. We showed in a recent systematic review (21 papers) that the number of metastasis, allowed in the definition of oligometastatic NSCLC, varies between 1 and 8, in only 2 out of 21 papers > 5 metastasis were allowed4. This has led to an European Organisation on Research and Treatment of Cancer (EORTC) –Lung Cancer Group (LCG) initiative to formulate a consensus definition of synchronous oligometastatic NSCLC. A pan-European multidisciplinary consensus group was established. Results from the systematic review, a European survey and real patient cases were taken into account when. It was concluded that the definition of synchronous oligometastatic NSCLC is relevant when a radical treatment is technically feasible for all tumor sites with acceptable toxicity, that may modify the disease course leading to long-term disease control. Based on the review, a maximum of 5 metastases and 3 organs is proposed. Mediastinal lymph node involvement is not counted as a metastatic site5. In addition staging with PET-CT and imaging of the brain is mandatory. This is in line with the advice of the EORTC-imaging group6. The eligibility criteria of recent and ongoing clinical trials in this setting will be discussed in this presentation. 1. Gomez D, Tang C, Zhang J, et al. Local Consolidative Therapy (LCT) Improves Overall Survival (OS) Compared to Maintenance Therapy/Observation in Oligometastatic Non-Small Cell Lung Cancer (NSCLC): Final Results of a Multicenter, Randomized, Controlled Phase 2 Trial. ASTRO 2018 2018;abstract LBA3. 2. Gomez DR, Blumenschein GR, Jr., Lee JJ, et al. Local consolidative therapy versus maintenance therapy or observation for patients with oligometastatic non-small-cell lung cancer without progression after first-line systemic therapy: a multicentre, randomised, controlled, phase 2 study. The lancet oncology 2016;17:1672-1682. 3. Iyengar P, Wardak Z, Gerber DE, et al. Consolidative Radiotherapy for Limited Metastatic Non-Small-Cell Lung Cancer: A Phase 2 Randomized Clinical Trial. JAMA oncology 2018;4:e173501. 4. GiajLevra N, Levra MG, Durieux V, et al. Defining synchronous oligometastatic non-small cell lung cancer: a systematic review. Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer 2019. 5. Dingemans A, Hendriks L, Berghmans T, et al. MA25.02 - Searching for a Definition of Synchronous Oligometastatic (sOMD)-NSCLC: A Consensus from Thoracic Oncology Experts WCLC 2018. Toronto: 2018:abstract MA 25.02. 6. deSouza NM, Liu Y, Chiti A, et al. Strategies and technical challenges for imaging oligometastatic disease: Recommendations from the European Organisation for Research and Treatment of Cancer imaging group. European journal of cancer 2018;91:153-163. Non-Small Cell Lung Cancer, Oligometastatic

MS06.04 Approaches to Overcoming the Nodal Staging Quality Gap

MS06.04 Approaches to Overcoming the Nodal Staging Quality Gap

2669 Mucosa-Associated Lymphoid Tissue Lymphoma: Crossing the Borders!

INTRODUCTION: Mucosa-associated lymphoid tissue (MALT) lymphoma or MALTomas are responsible for half of the primary gastric lymphomas and up to 8% of B-cell lymphomas. It mostly affects patients in their 5th or 6th decade of life. MALT lymphoma is well known to remain localized in the stomach and to follow a benign course. Despite that gastric MALToma is well defined in the literature, it is rather uncommon to present as a peri-pancreatic mass. Herein, we present the case of a patient with an incidental peri-pancreatic mass diagnosed as an aggressive form of MALT lymphoma. CASE DESCRIPTION/METHODS: A 76-year-old male with hypertension presented to the gastroenterology clinic for the evaluation of peri-pancreatic mass incidentally found during computed tomography (CT) scan performed for renal colic. Physical examination was remarkable for an epigastric fullness with no tenderness. Laboratory tests were remarkable for iron deficiency anemia. CT showed a 7 cm ill-defined soft tissue mass within the pancreaticoduodenal groove abutting the pancreatic head and encasing the gastroduodenal artery suspicious for a pancreatic neoplasm (Figure 1). Endoscopic ultrasound (EUS) showed a hypoechoic heterogeneous mass arising from the gastric wall in close proximity to the pancreas (Figure 2). EUS-guided biopsies were consistent with extra-nodal marginal zone lymphoma of MALT (Figure 3). Gastric biopsies confirmed the presence of MALToma and revealed positive Helicobacter Pylori (HP) infection. Staging workup confirmed extensive bone marrow as well as para-aortic, mediastinal and paratracheal lymph node involvement. The patient received curative HP treatment and was started on bendamustine and rituximab. DISCUSSION: The stomach is the most commonly affected organ by MALT lymphoma. Helicobacter Pylori is a major precursor for the development of gastric MALT lymphoma as up to 90% of affected patients show H.Pylori on stomach biopsies. Chronic HP infection leads to lymphoid tissue proliferation within the stomach and progression towards lymphoma. In this setting, the course is usually indolent with the disease usually confined to the stomach but aggressive tumor behavior has been reported. HP antibiotic eradication remains the first line therapy for early-stage HP positive gastric MALT lymphoma. In other instances, a patient-tailored approach is recommended based on the stage, involved site, HP status and clinical characteristics. Therapeutic options include radiation therapy, chemotherapy and surgery accordingly.

Accuracy of positron emission tomography and computed tomography (PET/CT) in detecting nodal metastasis according to histology of non-small cell lung cancer.

Positron emission tomography and computed tomography (PET-CT) is the non-invasive gold standard method for determining the oncological stage of patient with diagnosis of lung cancer. A correct preoperative staging is significant because only patients who do not have a history of regional or distant disease are those who will benefit from a surgical treatment. However, due to the different values of the PET-CT in terms of sensitivity and specificity to evaluate the mediastinal lymph node involvement, it is often necessary to perform a surgical mediastinal sampling through a cervical video mediastinoscopy (VM). Patient's risk factors which could modify the results of the PET scan, performing differences between non-invasive staging and the lymph node sampling due to VM are not yet clearly established in the literature. This knowledge will allow to identify in whom a surgical staging by sampling the mediastinal lymph nodes is needed. We included 234 patients with diagnosis of lung cancer who underwent a mediastinal lymph node staging by PET-CT images and histopathological results of mediastinal sampling by VM, analyzing the sensitivity and specificity of this non-invasive imaging study. We also analyzed variables that could modify the results of PET-CT, such as tumor type, location of the tumor and patient's history. We showed that those PET-CT presented an overall sensitivity and specificity of 93.8 and 62.7%, respectively, with negative and positive predictive values of 95.05 and 57.1%, respectively. The false-positive rate was 25% (57 of 234 patients). Analyzing risk factors involved in this false-positive rate (n = 57), we found that the only statistically significant factor that could explain these results was the histology of squamous carcinoma (p < 0.03). In this group of patients, it is essential to perform a mediastinal lymph node biopsy to know the real state of lymph node involvement.

Primary Mediastinal Nodal and Extranodal Non-Hodgkin Lymphomas: Current Concepts, Historical Evolution, and Useful Diagnostic Approach: Part 2.

Primary mediastinal non-Hodgkin lymphomas (PM-NHLs) represent ∼5% of all non-Hodgkin lymphomas (NHLs) and comprise lymphomas of B-cell and T-cell origin. PM-NHLs are defined as involvement of mediastinal lymph nodes, thymus, and/or mediastinal organs (heart, lung, pleura, pericardium) by NHL without evidence of systemic disease at presentation. The clinical scenario is variable and depends on the lymphoma subtype. The radiologic presentation is also variable ranging from a mediastinal mass with or without superior vena cava syndrome, a pleural or a cardiac mass associated with effusion, or as an effusion only. The diagnosis of PM-NHLs can only be established by microscopic evaluation, and therefore, general pathologists should be aware of these tumors and familiar with their diagnostic approach. The most common anterior mediastinal NHLs (90% to 95%) are primary mediastinal (PM) large B-cell lymphoma and T-lymphoblastic lymphoma. Thymic marginal zone lymphoma and mediastinal gray zone lymphoma are very rare. The remainder PM-NHLs involving middle or posterior mediastinum include diffuse large B-cell lymphoma (DLBCL) and rare cases of T-cell lymphoma, including anaplastic large cell lymphoma and breast implant-associated anaplastic large cell lymphoma extending to the anterior mediastinum. Primary pleural and cardiac NHLs are mostly DLBCLs. Other rare subtypes of PM-NHLs include DLBCL associated with chronic inflammation/pyothorax-associated lymphoma, fibrin-associated DLBCL (both Epstein-Barr virus positive), and pleural and/or pericardial primary effusion lymphoma (human herpesvirus-8 positive/Epstein-Barr virus positive). We review the historical aspects, epidemiology, clinicoradiologic features, histopathology, immunohistochemistry, differential diagnosis, and relevant cytogenetic and molecular features of the remaining mediastinal B-cell lymphomas, including primary thymic marginal zone lymphoma of the mucosa-associated lymphoid tissue type, other PM small B-cell lymphomas, PM plasmacytoma, and the most relevant PM T-cell lymphomas.

Primary Mediastinal Nodal and Extranodal Non-Hodgkin Lymphomas: Current Concepts, Historical Evolution, and Useful Diagnostic Approach: Part 1

Primary mediastinal non-Hodgkin lymphomas (PM-NHLs) represent ~5% of all NHLs and comprise lymphomas of B-cell and T-cell origin. PM-NHLs are defined as involvement of mediastinal lymph nodes, thymus, and/or mediastinal organs (heart, lung, pleura, pericardium) by NHL without evidence of systemic disease at presentation. The clinical scenario is variable and depends on the lymphoma subtype. The radiologic presentation is also variable ranging from a mediastinal mass with or without superior vena cava syndrome, a pleural or a cardiac mass associated with an effusion, or as an effusion only. The diagnosis of PM-NHLs can only be established by microscopic evaluation, and therefore, general pathologists should be aware of these tumors and familiar with their diagnostic approach. The most common anterior mediastinal NHLs (90% to 95%) are primary mediastinal large B-cell lymphoma and T lymphoblastic lymphoma. Thymic marginal zone lymphoma and mediastinal gray zone lymphoma are very rare. The remainder PM-NHLs involving middle or posterior mediastinum include diffuse large B-cell lymphoma (DLBCL) and rare cases of T-cell lymphoma, including anaplastic large cell lymphoma and breast implant-associated anaplastic large cell lymphoma extending to the anterior mediastinum. Primary pleural and cardiac NHLs are mostly DLBCLs. Other rare subtypes of PM-NHLs include DLBCL associated with chronic inflammation/pyothorax-associated lymphoma, fibrin-associated DLBCL (both EBV), and pleural and/or pericardial primary effusion lymphoma (HHV-8/EBV). We review the historical aspects, epidemiology, clinico-radiologic features, histopathology, immunohistochemistry, differential diagnosis, and relevant cytogenetic and molecular features of PM (thymic) LBCL, PM "nonthymic" DLBCL, BCL, unclassifiable, with features intermediate between DLBCL and classic Hodgkin lymphoma (mediastinal gray zone lymphoma), DLBCL associated with chronic inflammation (pyothorax-associated lymphoma), fibrin-associated DLBCL, and primary effusion lymphoma. This review represents the first part of 2 manuscripts covering PM-NHLs.

Statistical approach to mediastinal staging in NSCLC with M.E.S.S.i.a. software.

The exclusion of pathological involvement of mediastinal lymph nodes in patients affected by NSCLC plays a central role in assessing their prognosis and operability. Ceron et al. developed a software - called M.E.S.S.i.a (Mediastinal Evaluation with Statistical Support; instan approach) - that allows the calculation of the residual probability of lymph node involvement after a certain number of tests has been done, by integrating every test result with the pre-test prevalence. M.E.S.S.i.a. bridges a gap of current American College of Chest Physicians (ACCP) guidelines, providing probability values of mediastinal metastasis for a correct clinical decision. We conducted a preliminary retrospective study in a series of 108 patients affected by non small cell lung cancer (NSCLC). Pathological staging was compared to the probability of nodal involvement calculated by M.E.S.S.i.a. software. Forty-two out of 108 subjects (39%) had a calculated post-test probability <8%; none of these had proven N2/N3 metastasis at surgical staging (negative predictive value, NPV: 100%). In 12/41 cases M.E.S.S.i.a. was able to avoid invasive procedures. The remaining 66 (61%) patients did not reach the surgical threshold; among these, 11 displayed N2 positivity at pathological staging. Receiving operator curve (ROC) analysis produced an area under curve (AUC) value of 0.773 (p<0.001). These preliminary data show high accuracy of M.E.S.S.i.a. software in excluding N2/N3 lymph node involvement in NSCLC. We have therefore promoted a prospective multicenter study in order to to get a validation of the calculator at different levels of probability of lymph node involvement. The recruitable subjects are potentially operable NSCLC patients; the gold standard for detection of mediastinal disease is the surgical lymph node dissection.

Miliary Tuberculosis with Mediastinal and Cervical Lymph Node Involvement Complicated by an Eso- Mediastinal Fistula

Esophageal involvement in tuberculosis is rare even in highly endemic areas for tuberculosis and is most often secondary to concomitant mediastinal lymph node infection. Endoscopy and imaging are essential for diagnosis. Conservative treatment is possible but the major risk is mediastinitis secondary to an eso-mediastinal fistula.

Definition of Synchronous Oligometastatic Non–Small Cell Lung Cancer—A Consensus Report

IntroductionImproved outcome has been shown in patients with synchronous oligometastatic (sOM) NSCLC when treated with radical intent. As a uniform definition of sOM NSCLC is lacking, we developed a definition and diagnostic criteria by a consensus process. MethodsA pan-European multidisciplinary consensus group was established. Consensus questions were built on the basis of current controversies, and definitions were extracted from a survey, cases and a systematic review. This statement was formulated during a consensus meeting. ResultsIt was determined that definition of sOM NSCLC is relevant when a radical treatment that may modify the disease course (leading to long-term disease control) is technically feasible for all tumor sites with acceptable toxicity. On the basis of the review, a maximum of five metastases and three organs was proposed. Mediastinal lymph node involvement was not counted as a metastatic site. Fludeoxyglucose F 18 positron emission tomography–computed tomography and brain imaging were considered mandatory. A dedicated liver magnetic resonance imaging scan was advised for a solitary liver metastasis, and thoracoscopy and biopsies of distant ipsilateral pleural sites were recommended for a solitary pleural metastasis. For mediastinal staging, fludeoxyglucose F 18 positron emission tomography–computed tomography was deemed the minimum requirement, with pathological confirmation recommended if this influences the treatment strategy. Biopsy of a solitary metastatic location was mandated unless the multidisciplinary team is of the opinion that the risks outweigh the benefits. ConclusionA multidisciplinary consensus statement on the definition and staging of sOM NSCLC has been formulated. This statement will help to standardize inclusion criteria in future clinical trials.

Osseous sarcoidosis: A multicenter retrospective case-control study of 48 patients.

To describe the clinical presentation, distribution of lesions, treatment, and outcomes of osseous sarcoidosis. A French retrospective multicenter study of patients with biopsy-proven sarcoidosis analyzed patients with 1) a biopsy-proven granuloma without caseous necrosis, and either 2) osseous clinical manifestations, or 3) abnormal osseous imaging. Sarcoidosis patients with osseous involvement (cases) were compared with 264 age- and sex-matched sarcoidosis patients with no osseous manifestations (controls). In the osseous sarcoidosis group (n=88), forty-two (48%) patients had osseous-related symptoms involving the axial (69%) and/or appendicular (58%) skeleton. On imaging, the most commonly affected bones were in the spine (52%), pelvis (42%), hands (22%) and femur (19%). Compared with controls, cases had higher rates of mediastinal (93% vs. 47%) and extra-thoracic lymph node involvement (66% vs. 21%), pulmonary (90% vs. 65%) and cutaneous involvement (44% vs. 23%) (all P<0.0001), and hypercalcemia (8.5% vs. 2%, P=0.014). Spleen/liver and gastrointestinal involvement were less frequent in the osseous sarcoidosis group (29% vs. 45%, and 1% vs. 17%, respectively, P<0.0001). Response rates to with glucocorticoids alone, glucocorticoids plus methotrexate or glucocorticoids plus hydroxychloroquine were 23/44 (52%), 9/13 (69%) and 4/6 (67%), respectively. In patients with osseous sarcoidosis the spine and pelvis were the most commonly affected bones. Compared with controls, cases with osseous sarcoidosis have higher rates of thoracic and extra-thoracic lymph node involvement, pulmonary and cutaneous involvement, and hypercalcemia. Most patients with osseous sarcoidosis had a good response to glucocorticoids in combination with methotrexate or hydroxychloroquine.

Malignant Pleural Effusion at Presentation in Patients with Small-Cell Lung Cancer

Background: Malignant pleural effusion (MPE) is commonly seen in patients with non-small cell lung cancer. However, the prevalence of MPE at presentation in small-cell lung cancer (SCLC) is not reported and the clinical impact of MPE at presentation on patients with SCLC remains largely unknown. Objective: The objective of this study is to assess the occurrence rate of MPE and its prognostic implications at presentation in patients with SCLC. Method: We used the Surveillance Epidemiology and End Results (SEER) registry to extract data from patients with SCLC diagnosed between 2004 and 2014. The Kaplan–Meier method was used to estimate the overall survival and the Cox proportional hazard model was used to evaluate whether MPE was an independent risk for outcome. Results: Among the 68,443 patients with SCLC, MPE was present in 7,639 (11.16%). The probability of MPE was higher in older patients with larger tumors and mediastinal lymph node involvement at presentation. Median overall survival (3 vs. 7 months), estimated 1-year survival (17 vs. 30%), and 2-year survival (6 vs. 14%) were significantly lower in patients with MPE than without MPE, respectively (hazard ratio [HR] 1.46, 95% confidence interval [CI] 1.41–1.50, p< 0.001). MPE was also an independent factor for worse survival in multivariate analysis (HR 1.36, 95% CI 1.32–1.41, p < 0.001). Conclusions: MPE is common at presentation (11%) in patients with SCLC and may be associated with decreased survival. Additional studies are required to assess the treatment-adjusted survival rate in the setting of MPE.