Neoadjuvant therapies have unique advantages and opportunities in lung cancer but also present some challenges; including a lack of established guidance on how to process and evaluate resected lung cancer specimens in both clinical practice and clinical trials. The IASLC provided guidance for specimen processing and is now conducting this interobserver study for PR evaluation.

Recognizing invasion in pulmonary adenocarcinomas is important since, in the 8th edition of UICC/AJCC TNM classification system, the primary tumor T stage is determined based on presence and size of the invasive components. The aim of this study was to identify histological features in tumors with lepidic growth pattern that may be used to establish criteria for distinguishing invasive from non-invasive areas.

The pathological diagnosis of MPM allows to identify different biological aggressiveness contributing to therapeutic decisions. OBJECTIVES: Analyze the morphological and immunohistochemical profile of a series of MPM and describe incidence of their histological types. Recognize the transitional pattern proposed as an aggressive clinical-pathological entity. A retrospective and multicenter study was carried out by 8 Argentinian pathology laboratories. We review slides with MPM diagnosis (2009-2018) according the 2015 WHO criteria and iMig 2018 recommendations. We described: types, necrosis, nuclear atypia and mitosis/10HPF. The transitional pattern was considered extensive or focal. Cases: 398. Men: 59%, female 41 %, median age: 66 (24-91). Samples: 78% surgical biopsies, 16.5% small biopsies; 2.5% from pleurectomies and 3% from pleuroneumonectomies. Histological types: 77% epithelioid (E-MPM), 12% biphasic, 10% sarcomatoid and 1% transitional. Patients ≥66 years had no E-MPM more than <66 (X2: p<0.028). Predominant patterns of E-MPM were: 36.5% tubular/acinar, 33% solid, 12% trabecular, 11% papillary, 3% pleomorphic, 2% micropapillary, 2% adenomatoid and one case was deciduoid. We highlight that 59% of the E-MPM presented a second pattern: papillary (16%), solid (15%), tubular (11%), trabecular (7.5%) and micropapillary (5%). Immunohistochemistry: There were no differences in Calretinin expression between E-MPM and no E-MPM. The E-MPM had cytokeratin 5 expression in 91% of the cases and WT-1 in 90%; no E-MPM in 68% and 70% (p<0.001). Transitional morphological features were found in 12 surgical samples: 4 cases extensive and 8 cases focally (4 biphasic, 3 sarcomatoid and 1 epithelioid solid predominant). 3/4 extensive cases were ≥ 66 years old, 4/4 had necrosis and nuclear score II and III. The findings show the intra-tumoral heterogeneity of MPM and that the variability of composite grading can be analyzed in routine cases. Standardizing immunohistochemical panels for MPM diagnosis is mandatory. Detailed histopathological diagnosis can help to select the appropriate treatment for each patient.

PD-L1 immunohistochemistry (IHC) is now performed for advanced non-small cell lung cancer (NSCLC) patients to examine their eligibility for pembrolizumab treatment, as well as in Europe for durvalumab therapy after chemoradiation for stage III NSCLC patients. Four PD-L1 clinical trial validated assays (commercial assays) have been FDA/EMA approved or are in vitro diagnostic tests in multiple countries, but high running costs have limited their use; thus, many laboratories utilize laboratory-developed tests (LDTs). Overall, the PD-L1 testing seems to be diversely implemented across different countries as well as across different laboratories. The Immune biomarker working group of the IASLC international pathology panel conducted an international online survey for pathologists on PD-L1 IHC testing for NSCLC patients from 2/1/2019 to 5/31/2019. The goal of the survey was to assess the current prevalence and practice of the PD-L1 testing and to identify issues to improve the practice globally. The survey included more than 20 questions on pre-analytical, analytical and post-analytical aspects of the PDL1 IHC testing, including the availability/type of PD-L1 IHC assay(s) as well as the attendance at a training course(s) and participation in a quality assurance program(s). 344 pathologists from 310 institutions in 64 countries participated in the survey. Of those, 38% were from Europe (France 13%), 23% from North America (US 17%) and 17% from Asia. 53% practice thoracic pathology and 36%, cytopathology. 11 pathologists from 10 countries do not perform PD-L1 IHC and 7.6% send out to outside facility. Cell blocks are used by 75% of the participants and cytology smear by 9.9% along with biopsies and surgical specimens. Pre-analytical conditions are not recorded in 45% of the institutions. Clone 22C3 is the most frequently used (61.5%) (59% with the commercial assay; 41% with LDT) followed by clone SP263 (45%) (71% with the commercial assay; 29% with LDT). Overall, one or several LDTs are used by 57% of the participants. A half of the participants reported turnaround time as 2 days or less, while 13% reported it as 5 days or more. Importantly, 20% of the participants reported no quality assessment, 15%, no formal training session for PD-L1interpretation and 14%, no standardized reporting system. There is marked heterogeneity in PD-L1 testing practice across individual laboratories. In addition, the significant minority reported a lack of quality assurance, formal training and/or standardized reporting system that need to be established to improve the PD-L1 testing practice globally.

Latin America is the name given to those countries of South, Central and North America that share cultures and languages of origin Spanish and Portuguese (also French for some by its Latin origin). We all know that lung cancer is the first cause of cancer mortality all over the world but is less known what it is happens in Latin- America. Our objective is to analyze the available cancer mortality data in the region in order to contribute to plan strategies for prevention, diagnosis and treatment. We analyzed the data corresponding to year 2012, available from Global Cancer Observatory, IARC, WHO (Http://gco.iarc.fr/today/home), for 20 Latino-American countries. We also reviewed statistics of the Ministries of Health and/or National Institutes of Cancer, but we exclude them because their heterogenity. We consider age-standarized rates per 100000 (ASR) to make fairer comparisons between groups with different age distributions. Analysis was performed by tumor site (excluding non-melanoma skin) and by country, and sex. Cancer mortality for the region is 94.9 for both sexes and lung cancer mortality is the third cause (12.0) behind prostate and breast cancer (16.6, 13.0). For men, cancer mortality rate is 108.4 and lung cancer is the first cause (16.7) followed closely by prostate cancer (16.6). For women cancer mortality is 84.7 and lung cancer is the third cause (8.1), mama and cervix are the first (13.0, 8.7). The lung cancer mortality in males by country showed that Uruguay, Cuba and Argentina present the higher mortality (47.1, 39.6, 30.9). It was the first cause cancer mortality in those countries and in Brazil and Paraguay also, and the second in Mexico, Dominican Republic and Venezuela. In women, lung cancer mortality is higher in Cuba, Venezuela, Argentina and Brazil (21.6, 10.5, 10.0, 9.5), but it is the principal cause of cancer mortality only in Cuba and the second one in Brazil. The analysis is limited by registry quality. Latin America lung cancer mortality is heterogenous between countries. In men is the first cause in only 25% of the countries analyzed, the second in 15 %. In women it is only first in one country and second in another. Better understanding the region could adapt screening and early detection plans and may improve patients access to diagnosis and treatment in a precise way and opportunity.

ABSTRACT Introduction Malignant pleural mesothelioma (MPM) is a rare and aggressive disease arising from the pleural mesothelium, with a reported survival (OS) of less than 12 months. However, patients with early-stage disease and good-performance status are suitable for multimodality ther¬apy (MT) involving surgery, radiotherapy (PORT), and chemotherapy. Objective Epidemiological description and analysis of effectiveness in patients with MPM who performed MT. Methods Retrospective study of patients treated by multimodality therapy between April 1990 and April 2011 in three institutions from Argentina. Results Of 110 patients, 24 (22%) went to MT. Median (Md) follow-up of 21 months (2-139). Of 21 patients with complete data, 90.5% were epithelioid. 67% male, Md age 54, 95% PS 0, 43% smokers, mean of 7.6 packs/year, 29% had contact with asbestos. 60% presented with chest pain or pleural effusion, 3 month (R: 0-38) Md time to diagnosis. 60% in the right pleura. Treatment: 90.5% extrapleural pneumonectomy, 9.5% pleurectomy/decortications, by single surgical team 92%. Perioperative mortality 8%, morbidity 63%, 32% bleeding complications (32%). 52% T3N0M0 postoperative staging. 15 performed neoadjuvant, 3 adjuvant chemotherapy and 10 PORT. 67% received pemetrexed associated with platinum. 57% relapse after MT, 80% locoregional, 80% performed chemotherapy. Md disease free survival (DFS) 20.7 months (95% CI 8-46). OS 34.3 months (95% CI 17-43). Conclusions Epidemiological and efficiency data obtained are similar to reported series. The present work shows that MT achieves higher DFS and OS than those obtained with other treatments that do not include surgery. Disclosure All authors have declared no conflicts of interest.

ABSTRACT Background Standard therapy for refractory or resistant relapsed small-cell lung cancer (SCLC) has not yet been established. We conducted an open-label, multicenter, non-randomized phase II study to confirm the efficacy and safety of amrubicin, a topoisomerase inhibitor, in the treatment of refractory or resistant SCLC. Material and methods Patients with SCLC that is refractory or relapsed within 90 days of completing previous treatment received amrubicin at a dose of 40 mg/m2 for 3 consecutive days, every 21 days.The study treatment was repeated until disease progression or intolerable toxicity. The primary end point was overall response rate (ORR), and secondary end points were progression-free survival (PFS), overall survival (OS), and safety. Planned sample size was 80 patients to achieve power of at least 80% with one-sided alpha of 0.05, and expected and threshold value for primary endpoint as 20% and 10%. All patients were followed-up until one year after the last patient enrollment. Results Between November 2009 and February 2011, 82 patients were enrolled from 25 institutions. The median number of treatment cycles was four (range, one to 22 cycles).The ORR was 32.9% (p  Conclusions Amrubicin demonstrated the favorable tumor response and survival with acceptable toxicity. Single-agent amrubicin could be considered as a standard regimen in the treatment of refractory or resistant relapsed SCLC. Disclosure All authors have declared no conflicts of interest.

Background: Prognosis for non-small cell lung cancer (NSCLC) patients is very poor. Prediction of the response to treatment in individual patients may be possible using molecular biological alterations such as clinical biomarkers. We investigated the predictive value of apoptosis and cell cycle regulator proteins for neoadjuvant chemotherapy response in stage IIIA/IIIB NSCLC patients.Methods: We evaluated p53, bcl-2, p21WAF1/CIP1, p27Kip1, and Ki67 immunohistochemical expression and apoptotic index in mediastinal lymph node metastases from 23 IIIA and 10 IIIB NSCLC patients before treatment with neoadjuvant platinum-based chemotherapy. Univariate analysis was performed to evaluate the relationship between protein expression and survival or time to progression (TTP).Results: Median follow-up was 25 months (range, 4-112), median TTP was 11 months (range, 0-112), and median overall survival was 22 months (range, 4-112). Of 32 assessable patients, 18 (56%) had stable disease, 12 (38%) had a PR, and two (6%) had progressive disease. Of the 22 patients assessable for pN2 following chemotherapy, 16 (77%) were positive. Univariate analysis showed that shorter TTP correlated with progressive disease (p = 0.000), positive pN2 after chemotherapy (p = 0.026), high Ki67 (p = 0.022), and high p21WAF1/CIP1 (p = 0.038).Conclusion: Our results suggest that in IIIA/IIIB NSCLC patients, a high level of p21WAF1 expression in mediastinal lymph node metastases before neoadjuvant platinum-based chemotherapy is associated with a poor outcome. Our results suggest that expression of p21WA-F1, which plays a role in preventing apoptosis, may be significant when selecting chemotherapy for NSCLC patients.

STUDY OBJECTIVE:To evaluate the prognostic value of histopathologic variables and molecular markers in a group of patients with stage I non-small cell lung cancer (NSCLC).SETTING:"María Ferrer" Hospital of Buenos Aires, Argentina.PATIENTS:Pathologic stage IA and IB patients who underwent radical surgery and nonneoadjuvant therapy for NSCLC between January 1985 and December 1999.MEASUREMENTS AND RESULTS:Fifty-three patients fulfilling the inclusion criteria were identified. The overall survival was 52.8%, and 28% of patients had recurrent disease. We found significant differences between squamous cell carcinoma (SCC) and adenocarcinoma in mitotic counting (p = 0.001) and lymphatic permeation (p = 0.01). SCCs showed higher proliferation (MIB-1 grades 2 and 3) [p = 0.001], Bcl-2 expression (p = 0.038), and CD44 expression (p = 0.019) than adenocarcinomas. The log-rank test showed that mitosis count, necrosis, MIB-1, and Bcl-2 were predictive factors for relapse. All of them were associated with increased relapse and a shorter time to recurrence. Multivariate analysis using the Cox proportional hazards regression model showed that mitosis count, Bcl-2 expression, and grade 3 of MIB-1 emerged as independent prognostic factors of recurrence.CONCLUSIONS:We found that mitosis count and MIB-1 expression had significant value to predict recurrence, reflecting the aggressiveness of high-rate proliferative tumors. We could also show that patients with positive Bcl-2 tumors had a poor outcome, probably related to the uncontrolled cell growth that the expression of Bcl-2 promotes. Our observations are of potential interest for the development of rational postresection treatment strategies based on the estimated risk of recurrence of patients with NSCLC.

An increase in incidence of malignant pleural mesotheliomas has been noted recently. In order to assess our own experience, we reviewed all medical records and biopsies of patients who were seen with this diagnosis in Hospital Maria Ferrer between January 1986 and December 1997. Clinical data of 17 patients were analyzed. Mean age was 59 years, 76% were male. Industrial or environmental exposure to asbestos was established in 9 patients (53%). Most common symptoms at presentation were dyspnea (88%) and chest pain (65%). Pleural thickening with or without effusion was the usual finding in chest X rays and CAT scans. Biochemical analysis of pleural fluids was consistent with exudate. Diagnosis was performed by thoracotomy (47%), needle biopsy (23.5%) and videothoracoscopy (29.5%). Histological samples were available for review in 16 of the 17 patients: they were epithelial (10), sarcomatoid (2) and mixed tumors (4). Treatment reflected varying approaches. Palliative methods (pleurodesis, chemotherapy and radiotherapy) were preferred at the beginning while more aggressive interventions are performed nowadays. Pleuroneumonectomy alone or in combination with other therapies was carried out in 5 patients with no operative mortality although some complications occurred such as empyema, bronchopleural fistula and severe chest pain. Survival rate for all groups was 10.5 +/- 5.9 months. However, the mean survival of patients who underwent surgery was 17.5 +/- 2.1 months (p < 0.04) with an associated improvement in quality of life. Therefore, we consider that surgery associated with other therapies offers at present, the best therapeutic option for this bad prognosis condition.

An increase in incidence of malignant pleural mesotheliomas has been noted recently. In order to assess our own experience, we reviewed all medical records and biopsies of patients who were seen with this diagnosis in Hospital Maria Ferrer between January 1986 and December 1997. Clinical data of 17 patients were analyzed. Mean age was 59 years, 76% were male. Industrial or environmental exposure to asbestos was established in 9 patients (53%). Most common symptoms at presentation were dyspnea (88%) and chest pain (65%). Pleural thickening with or without effusion was the usual finding in chest X rays and CAT scans. Biochemical analysis of pleural fluids was consistent with exudate. Diagnosis was performed by thoracotomy (47%), needle biopsy (23.5%) and videothoracoscopy (29.5%). Histological samples were available for review in 16 of the 17 patients: they were epithelial (10), sarcomatoid (2) and mixed tumors (4). Treatment reflected varying approaches. Palliative methods (pleurodesis, chemotherapy and radiotherapy) were preferred at the beginning while more aggressive interventions are performed nowadays. Pleuroneumonectomy alone or in combination with other therapies was carried out in 5 patients with no operative mortality although some complications occurred such as empyema, bronchopleural fistula and severe chest pain. Survival rate for all groups was 10.5 +/- 5.9 months. However, the mean survival of patients who underwent surgery was 17.5 +/- 2.1 months (p < 0.04) with an associated improvement in quality of life. Therefore, we consider that surgery associated with other therapies offers at present, the best therapeutic option for this bad prognosis condition.

An increase in incidence of malignant pleural mesotheliomas has been noted recently. In order to assess our own experience, we reviewed all medical records and biopsies of patients who were seen with this diagnosis in Hospital Maria Ferrer between January 1986 and December 1997. Clinical data of 17 patients were analyzed. Mean age was 59 years, 76% were male. Industrial or environmental exposure to asbestos was established in 9 patients (53%). Most common symptoms at presentation were dyspnea (88%) and chest pain (65%). Pleural thickening with or without effusion was the usual finding in chest X rays and CAT scans. Biochemical analysis of pleural fluids was consistent with exudate. Diagnosis was performed by thoracotomy (47%), needle biopsy (23.5%) and videothoracoscopy (29.5%). Histological samples were available for review in 16 of the 17 patients: they were epithelial (10), sarcomatoid (2) and mixed tumors (4). Treatment reflected varying approaches. Palliative methods (pleurodesis, chemotherapy and radiotherapy) were preferred at the beginning while more aggressive interventions are performed nowadays. Pleuroneumonectomy alone or in combination with other therapies was carried out in 5 patients with no operative mortality although some complications occurred such as empyema, bronchopleural fistula and severe chest pain. Survival rate for all groups was 10.5 +/- 5.9 months. However, the mean survival of patients who underwent surgery was 17.5 +/- 2.1 months (p<0.04) with an associated improvement in quality of life. Therefore, we consider that surgery associated with other therapies offers at present, the best therapeutic option for this bad prognosis condition.

Sarcomatoid carcinomas of the lung are very uncommon tumors and their biological behavior remains controversial. Here we describe a case of a 62 year old male with an endobronchial mass and subjected thereafter to right upper and middle bilobectomy. A squamous carcinoma with a sarcomatous component resembling a fibrosarcoma was found at microscopic examination. Although there is neither agreement on the denomination nor on the histogenesis of these tumours, it is recognized that they are highly aggressive. Therefore, in order to provide the best possible treatment it appears recommendable to supply a detailed description of the different components of the tumor at the time of the histopathological diagnosis.

This study is a retrospective analysis of clinical parameters and pulmonary function in seven male patients receiving lung transplantation between June 1993 and February 1996 as a treatment for pulmonary emphysema. The patients were suffering severe airway obstruction, functional class III-IV, and were dependent on home therapy with oxygen. Their mean age was 54.9 years (+/- 5.4 years) and their mean waiting list time was 266 +/- 158 days. Transplantation was sequential bilateral (TPb) in one case and unilateral (Tpu) in the remaining 6. A triple inmunosuprresant protocol was employed (Cyclosporina A - Azathioprin-Prednisone) and bronchoscopy was performed on a regular basis and on evidence of infection or rejection. The patient who received the bilateral transplant died 76 days later due to necrohemorrhagic pancreatitis. The 6 unilateral transplant patients were discharged in good condition 31.3 +/- 9.0 days after transplant. One patient died 69 days after transplantation due to hypertensive pneu-mothorax of the native lung. All patients presented acute rejection between 10 and 86 days after transplantation, responding well to treatment with Methylprednisone or increased immunosuppression. All patients receiving unilateral transplantation showed marked improvement in functional class, gas exchange, and pulmonary function.

Rounded atelectasis or Blesovsky's syndrome (also called pleuroma, folded lung or shrinking pleuritis with atelectasis) is the association of plaque-like pleural fibrosis with a folding visceral pleura and nodular atelectasis of the underlying lung. It can mimic a peripheral lung tumor or a mesothelioma. Radiography and computed tomography (CT) show a characteristic opacity with a comet-tail sign. The pathogenesis in some of the cases is considered to be secondary to pleural effusions and in others to a contraction of a focus of pleural fibrosis, not associated with effusion. In many cases, there was a history of asbestos exposure. We report the case of a 44-year-old, man who had smoked and worked with materials containing asbestos. He referred thoracic pain of 6 months duration and dyspnea. An X-ray of the chest (Fig. 1, 2) and a CT scan (Fig. 3) revealed a round peripheral mass in the left lower lobe. A fine needle aspiration biopsy of the lung was performed revealing clusters of large atypical cells with abundant cytoplasm. A thoracotomy was decided upon and no frozen section was requested. Gross examination of the resected lobe (Fig. 4) demonstrated a 2.5 cm white, irregular, firm and retracting pleural plaque. On sectioning, a peculiar folding of the visceral pleura delimited by anthracotic pigmentation was noted below the fibrotic plaque. The folding extended perpendicularly deep into the parenchyma. It was possible to separate the folding and liberate the underlying parenchyma, which was firm, fibrotic and atelectatic. No tumor was found anywhere within the lobe.(ABSTRACT TRUNCATED AT 250 WORDS)