WHO Classification Of Lung Tumors Research Articles

Quel bilan anatomo-pathologique ?

The WHO classification of lung tumours on which pathologists base their diagnosis was revised in 2015 on the basis of an international consensus established in 2011 between clinicians, radiologists and pathologists. This resulted in a histo-molecular and prognostic classification of adenocarcinomas. The use of immunohistochemistry for the classification of poorly differentiated non-small cell carcinomas and a new classification adapted to small specimens were defined. These concepts are still relevant today, as the management of small specimens is a key point in the collaboration between the sampling physician and the pathologist.This classification was revised in 2021 and remains broadly the same except for the appearance of new entities: SMARCA4-defident undifferentiated thoracic tumour; bron-chiolar adenoma / muconodular ciliated papillar tumour. Although rare, these lesions have histopathological, clinical and/or molecular appearances that merit their presence as new entities.For invasive adenocarcinomas, the 5 architectural patterns are maintained but the IASLC proposes a grading system which has shown a prognostic impact for early stages.Some clarifications regarding the diagnosis of neuroendocrine tumours/carcinomas were provided.Regarding pleural pathology, mesothelioma in situ is defined and characterised. 1877-1203/© 2024 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Bronchial oncocytic carcinoma in an adult: a case report and literature review

BackgroundLung salivary-type tumors originating from bronchial submucosal glands are rare, only four types of salivary gland-type tumors are listed in 2015 WHO classification of lung tumors. Here, we report a rare case of oncocytic carcinoma (OC) in the right main bronchus.Case presentationA 34-year-old man presented to our hospital with a two-month history of recurrent hemoptysis and with one month of inspiratory dyspnea. Pulmonary function tests showed mild restrictive ventilatory dysfunction and severe diffusion dysfunction. Furthermore, the flow volume loop showed a variable extra-thoracic obstruction. Computed tomography (CT) of the chest revealed that a polypiform nodule of 13 mm in diameter was at the proximal right main bronchus. Testing for purified protein derivative was positive (category 2). The nodule was resected under bronchoscopy. The bronchial aspirate was negative for mycobacterium tuberculosis and tumor cells. The biopsy sample showed a solid and acinar predominant pattern with abundant eosinophilic cytoplasm. The bronchial mucosa was destroyed and replaced by tumor cells. The loose edematous stromal reaction could be seen in a local area. Immunohistochemically, tumor cells were positive for CK, EMA, Vimentin, CD117, CK7, S100, Mammaglobin and SOX10. Only scattered tumor cells were stained by basal cell markers, including CK5/6, P40 and P63. Electron microscopy revealed numerous swelling mitochondria with lacking mitochondrial cristae in tumor cells. Fluorescence in situ hybridization (FISH) testing for MAML2 and ETV6 rearrangement were negative. Next-generation sequencing analysis of 520 genes in the tissue biopsy specimen showed no somatic mutation. The diagnosis of OC was made. Subsequently, the patient underwent a right upper lobectomy with sleeve resection of the main bronchus and lymph dissection. No recurrent evidence was seen during two years of chest CT follow-up.ConclusionsTo our knowledge, this is the first case of primary OC in the bronchus. This patient has no recurrence during two years of follow-up, indicating that primary OC in the bronchus has the same favorable prognosis as in salivary glands. Moreover, complete excision and thorough sampling to know the invasive growth pattern is important to reach the correct diagnosis.

Comprehensive clinicopathological characteristics and mucin core protein expression profiles of bronchiolar adenoma.

Bronchiolar adenoma (BA) is a novel entity in the 2021 WHO classification of lung tumours. The expression profile of mucin core proteins in BAs is not clear. The aim of this study was to clarify the expression profiles of mucins and to validate the clinicopathologic and molecular features of BAs. We examined the clinicopathological, immunohistochemical, and molecular features of 20 BAs. Our cohort comprised 10 proximal and 10 distal BAs. Only seven of 18 patients (39%) were accurately diagnosed with BA at the time of intraoperative consultation. The frequent genetic alterations were BRAF V600E (35%) and KRAS (30%) mutations, which were mutually exclusive. The expression of MUC1, MUC4, and MUC5B was observed in all cases and that of MUC5AC and MUC6 was observed in nine (45%) and five (25%) cases, respectively. MUC4 was diffusely expressed in 18 cases. In contrast, MUC1, MUC5AC, MUC5B, and MUC6 displayed a patchy expression pattern. These expression patterns were similar to that of bronchiolar epithelium in normal lung tissue. In addition, overexpression of MUC1 and MUC4 on the entire cell surface was not observed in any of the BAs, suggesting their benign nature. BA commonly exhibits diffuse MUC4 and patchy MUC1 and MUC5B expression. Its unique expression pattern is probably attributed to mucin expression specific to the bronchiolar epithelium. These results confirm the clinicopathologic and molecular characteristics of BA, including the difficulty in intraoperative frozen section diagnosis and the broad morphologic spectrum of BA derived from the bronchiolar epithelium.

Progression from Malignant Mesothelioma in Situ to Malignant Mesothelioma: A Case Report Spanning 13 Years

Malignant mesothelioma is an aggressive neoplasm associated with poor prognosis. Identification of in-situ phase of malignant mesothelioma can help detect disease at an earlier stage and potentially improve outcome by early therapeutic intervention. The concept of malignant mesothelioma in-situ (MIS) has re-emerged, diagnostic criteria based on use of immunohistochemistry and molecular techniques have been described recently and the latest WHO classification of lung tumors includes MIS as a distinct diagnostic entity. Here we present morphologic and immunohistochemical findings from a patient presenting with multiple peritoneal and pleural in-situ malignant mesothelioma lesions with eventual progression to pleural invasive malignant mesothelioma over a protracted period of 13 years. There are very few well documented cases of malignant mesothelioma in-situ and this unique case provides insight into the morphologic variants and natural behavior of malignant mesothelioma in-situ over an extended period of time.

CT findings of basaloid squamous cell carcinoma of the lung in 12 patients: A distinct category of squamous cell carcinoma in 2015 WHO classification of lung tumors.

Basaloid squamous cell carcinoma (SCC) is very rare subtype of SCC of the lung and it is important to distinguish basaloid to other subtypes of SCCs, since the prognosis of basaloid subtype is considered poorer than that of other non-basaloid subtypes of SCCs. Aim of this study was to assess computed tomography (CT) findings of basaloid SCC of the lung in 12 patients.From January 2016 to April 2021, 12 patients with surgically proven basaloid SCC of the lung were identified. CT findings were analyzed, and the imaging features were compared with histopathologic reports. Clinical and demographic features were also analyzed.Axial location of the tumor was central in 5 patients, while 7 was in peripheral. Of the 7 patients whose tumors were located in the peripheral, margin of the tumor were smooth (n = 2), lobulated (n = 2), or spiculated (n = 3). After contrast injection, net enhancement value ranged from 15.8 to 71.8 HU (median, 36.4 HU). Endobronchial growth were seen in 5 patients and these patients accompanied obstructive pneumonia or atelectasis. Internal profuse necrosis, cavitation, or calcifications were not seen.On CT, basaloid squamous cell presents as solitary nodule or mass with moderate enhancement. Tumor was located either peripheral or central compartment of the lung and cavitation was absent.

P40.02 Pemetrexed in Advanced-stage Lymphoepithelioma Carcinoma of Lung

Lymphoepithelioma Carcinoma of Lung （former pulmonary lymphoepithelioma-like carcinoma) is a rare primary lung cancer, which was a subtype of large-cell lung cancer and other and unclassified carcinomas in third and 4th edition WHO classification of tumors, respectively. In the new 5th WHO classification, lymphoepithelioma carcinoma of lung is classified as a subtype of squamous cell carcinoma. As we all known, Pemetrexed isn’t recommended for squamous cell carcinoma. However, little is known about the role of pemetrexed in treatment of advanced-stage lymphoepithelioma carcinoma of lung. From January 2008 to December 2020, we retrospectively analyzed patients who were diagnosed as stage ⅢC-Ⅳ lymphoepithelioma carcinoma of lung and received pemetrexed alone or combination with cisplatin/ carboplatin or checkpoint inhibitor in Guangdong Lung Cancer Institute. A total of 23 patients were included in this study. The majority of patients were female (14/23,60.9%). The median age was 49 years (range 13 to 76 years old). All of patients were EGFR wild type. Among the 10 patients who received first-line pemetrexed alone (2) or combination with cisplatin/ carboplatin (3) or checkpoint inhibitor (5), the response and stable disease (SD) was observed in 2(20%) patients and 7(70%) patients, respectively. In second-line or more treatment, pemetrexed alone achieved stable disease and progress disease in 5 patients (42.7%), 7 patients (57.3%), respectively, except for one patient didn’t received CT scan for assessing response. After median 19.3 months follow-up, PFS and MST in first line and second line or more line were6.8, 36.6, and 2.8, 18.9 months, respectively. Although lymphoepithelioma carcinoma of lung is classified as subtype of squamous cell carcinoma in 5th WHO classification of lung tumors, pemetrexed showed moderate response in advanced stage disease and warrant further study.

Quel bilan anatomo-pathologique ?: What anatomo-pathological assessment?

The WHO classification of lung tumours on which pathologists base their diagnosis was revised in 2015 on the basis of an international consensus established in 2011 between clinicians, radiologists and pathologists. This resulted in a histo-molecular and prognostic classification of adenocarcinomas. The use of immunohistochemistry for the classification of poorly differentiated non-small cell carcinomas and a new classification adapted to small specimens were defined. These concepts are still relevant today, as the management of small specimens is a key point in the collaboration between the sampling physician and the pathologist.This classification was revised in 2021 and remains broadly the same except for the appearance of new entities: SMARCA4-deficient undifferentiated thoracic tumour; bronchiolar adenoma/muconodular ciliated papillar tumour. Although rare, these lesions have histopathological, clinical and/or molecular appearances that merit their presence as new entities.For invasive adenocarcinomas, the 5 architectural patterns are maintained but the IASLC proposes a grading system which has shown a prognostic impact for early stages. Some clarifications regarding the diagnosis of neuroendocrine tumours/carcinomas were provided.Regarding pleural pathology, mesothelioma in situ is defined and characterised.© 2021 SPLF. Published by Elsevier Masson SAS. All rights reserved.

Long-Term Prognosis of Patients With Resected Adenocarcinoma In Situ and Minimally Invasive Adenocarcinoma of the Lung

IntroductionThe WHO classification of lung tumors defines adenocarcinoma in situ (AIS) and minimally invasive adenocarcinoma (MIA) as cancers with no or limited histologic invasive components. The probability of patients with AIS or MIA being recurrence free for 5 years postoperatively has been found to be 100%. This study aimed to analyze the prognosis of patients with AIS or MIA after more than 5 postoperative years. MethodsWe reviewed the pathologic findings of 4768 patients who underwent resection for lung cancer between 1998 and 2010. Of these, 524 patients with curative resection for AIS (207 cases, 39.5%) and MIA (317 cases, 60.5%) were included. Postoperative recurrence, survival, and development of secondary primary lung cancer (SPLC) were analyzed. ResultsOf the included patients, 342 (65.3%) were of female sex, 333 (63.5%) were nonsmokers, and 229 (43.7%) underwent sublobar resection. Average pathologic total tumor diameter was 15.2 plus or minus 5.5 mm. Median postoperative follow-up period was 100 months (range: 1–237). No recurrence of lung cancer was observed for either AIS or MIA cases. Estimated 10-year postoperative disease-specific survival rates were 100% and 100% (p = 0.72), and overall survival rates were 95.3% and 97.8% (p = 0.94) for AIS and MIA cases, respectively. Estimated incidence rates of metachronous SPLC at 10 years after surgery were 5.6% and 7.7% for AIS and MIA, respectively (p = 0.45), and these were not correlated with the EGFR mutation status. ConclusionsAlthough the development of metachronous SPLC should be noted, the risk of recurrence is quite low at more than 5 years after resection of AIS and MIA. This finding strengthens the clinical value of distinguishing AIS and MIA from other adenocarcinomas of the lung.

Clear cell lung carcinoma: A case report and a literature review

Clear cell carcinoma in lung is an extremely rare subtype of lung tumors; first described by Liebow and Castle man in 1963 and since only 60 cases have been reported in the literature. CCLC (Clear cell lung carcinoma) was considered by the 2011 WHO classification of lung tumors as a rare cytologic feature of squamous cell or adenocarcinomas. We describe a rare case of a clear cell tumor of the lung, in a 63 year-old male patient, and a brief literature review. The main of this presentation is to emphasize the importance of a multidisciplinary approach including pathologists, oncologists and radiologists to confirm the diagnosis as well for an adequate therapeutic management of this unusual entity of lung cancer.

Abstract PO-088: A deep-learning based approach to assess heterogeneity of histologies in non-small cell lung cancer

Abstract Adenosquamous carcinomas of the lung carry a poor prognosis compared to other non-small cell lung cancers (NSCLC) (Tian. 2017, Baine et al. 2018, Wood et al. 2017, 2015 WHO Classification of Lung Tumors). Adenosquamous carcinoma (ASC) has features of both Adenocarcinoma (ADC) and Squamous cell carcinoma (SCC) in the same tumor. The incidence of ASC varies between studies but is estimated to account for 0.4 to 4% of all lung cancers (2015 WHO Classification of Lung Tumors). Diagnosis of these cancers depends on several factors including adequate sampling of the tumor, careful review and objective interpretation of histologic criteria. An automated method for light microscopy review could help standardize and speed up correct identification of this important subtype and lead to better targeted therapies. In addition, an automated technique to quantify the relative contributions of histologies in heterogeneous tumors would lead to a better understanding of tumor biology. 476 tissue samples from NSCLC patients were scanned at 0.5pixel/um resolution, and the tumor area was selected by a pathologist. Each slide tumor area was divided into smaller image ‘patches’ of 512 × 512 pixels. We trained a Convolution Neural Network based on the Inception V3 and Resnet18 architecture using transfer learning and weakly-supervised learning, to classify tissue patches using the whole-slide level labels. Once the network was trained, a patch-level prediction was performed on 20 unseen test slides. A whole-slide diagnosis was performed by choosing the most common histology predicted among all patches extracted for each slide. In addition, a patch-based heatmap was created to identify the heterogeneity of histologies within a single tissue sample. The model’s whole slide prediction of ADC or SCC histologies on the test set, matched the pathologist’s whole-slide diagnosis, with an F1-score of 0.91 at the individual tile level and 1.0 (perfect) in slide level. The trained model also identified a few likely adenosquamous carcinomas, where slides were found to have patches with features from both ADC and SCC at high proportions. We are currently examining whether samples identified as heterogeneous can be confirmed by pathologists’ visual inspection, and whether we can visualize the network features that contribute to the patch-level classification decision. The development of an algorithm to identify mixed histologic subtypes may enable better selection of patients responsive to drug treatment and elucidate the biological mechanism leading to tumor heterogeneity. Citation Format: Reheman Baikejiang, Jennifer Giltnane, Eloisa Fuentes, Cleopatra Kozlowski. A deep-learning based approach to assess heterogeneity of histologies in non-small cell lung cancer [abstract]. In: Proceedings of the AACR Virtual Special Conference on Tumor Heterogeneity: From Single Cells to Clinical Impact; 2020 Sep 17-18. Philadelphia (PA): AACR; Cancer Res 2020;80(21 Suppl):Abstract nr PO-088.

Abstract 1571: Inter- and intra- tumorheterogeneity of the microenvironment in pulmonary adenocarcinoma

Abstract BACKGROUND: Recent findings indicate that the currently approved predictive biomarker for immune checkpoint blockade (ICB), i.e. PD-L1 expression, is imperfect. Hence, additional biomarkers are warranted, and ICB-related gene expression profiling (GEP) was advocated as a promising approach enabling comprehensive interrogation of the ICB-effector compartment. Here, we assessed inter- and intra-tumor heterogeneity (ITH) of the immunological microenvironment using a comprehensive gene expression profiling approach (770 genes) to further elucidate the biological basis for new diagnostic applications. METHODS: All formalin-fixed paraffin-embedded tissue specimens used for this study were derived from surgically resected lung adenocarinomas at the Thoraxklinik at Heidelberg University Hospital and diagnosed (according to 2015 WHO Classification of lung tumors) at the Institute of Pathology at Heidelberg University Hospital. To evaluate the significance of ITH on gene expression profiling, multi-regional gene expression analysis (2-4 samples per tumor) was performed for 24 ADC using the NanoString IO 360 Panel. ANOVA was used to compare inter-tumor variance to intra-tumor variance of mRNA expression. The F statistics was calculated as ratio of these quantities. A list of genes with significantly higher inter-tumor variance was isolated using the F-test. Multiple testing was addressed using the Benjamini-Hochberg method to control the false discovery rate (FDR). RESULTS: In an unsupervised hierarchical clustering analysis of the entire set of 770 genes, the two to four segments of each of the tumors clustered together. For 752 of the 770 genes (97.7%) the inter-tumor variance was significantly higher than the intra-tumor variance (FDR<5%). For 257 of the 770 genes (33.4%) the inter-tumor variance was more than ten-fold higher than the intra-tumor variance. CONCLUSION: In our preliminary analysis of ICB-GEP, variance of expression levels between tumors was substantial and exceeded ITH for the majority of analyzed genes. In-depth analyses are ongoing to further delineate the influence on gene signatures and ICB related pathways. Citation Format: Daniel Kazdal, Jan Budczies, Martina Kirchner, Klaus Kluck, Michael Allgäuer, Olaf Neumann, Regine Brandt, Eugen Rempel, Carolin Ploeger, Moritz von Winterfeld, Marc Schneider, Steffen Dietz, Hauke Winter, Thomas Muley, Holger Sülmann, Michael Meister, Felix Herth, Claus Heussel, Roland Penzel, Volker Endris, Peter Schirmacher, Michael Thomas, Petros Christopoulos, Albrecht Stenzinger. Inter- and intra- tumorheterogeneity of the microenvironment in pulmonary adenocarcinoma [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 1571.

Elevated Pulmonary Artery Systolic Pressure is Associated with Poor Survival of Patients with Non-Small Cell Lung Cancer.

PurposePulmonary hypertension (PH) is an important comorbidity of lung cancer, PH in lung cancer patients is gradually gaining interest because of its apparent high prevalence, but the impact of PH on the outcomes of lung cancer remains uncertain and had rarely been discussed. We aimed to evaluate the prevalence, determinants and prognosis value of elevated pulmonary artery systolic pressure (PASP) in non-small cell lung cancer patients.Patients and MethodsIn this retrospective study, subjects with a new and pathological confirmed diagnosis of lung cancer were enrolled. All patients underwent transthoracic echocardiography before received treatment. Pulmonary artery systolic pressure was measured by transthoracic echocardiography. Lung cancer subtypes were categorized by WHO classification of lung tumors. Hazard ratios (HR) were estimated by using Cox regression models.ResultsAmong 612 non-small cell lung cancer (NSCLC) patients, 19.8% coexisted with PH. After adjustment for age, symptom, coagulation disorders, lymph node metastasis, distant metastasis, histological type, clinical stage, PASP ≥35mmHg was significantly associated with the decreased overall survival (OS) of NSCLC (P= 0.028). Moreover, PASP ≥45mmHg was an independent predictor for perioperative death. Independent factors of comorbid elevated PASP were age, the presence of intrapulmonary metastasis and coagulation disorders.ConclusionThese findings suggest that PASP is an independent prognostic risk factor for NSCLC patients. Main determinants of elevated PASP are age, the presence of intrapulmonary metastasis and coagulation disorders.

Analysis of lung biopsies using the 2015 WHO criteria and detection of sensitizing mutations\u2014\u2014a single-institution experience of 5032 cases

BackgroundA specialized classification for small biopsies was added to the 2015 WHO classification of lung tumors. The purpose of this study is to explore and summarize the experience of applying the newly proposed classifications and criteria to clinical practice.MethodsWe used the 2015 WHO criteria to sort out 5032 small lung biopsies from a group of Chinese patients, and demonstrated their clinicopathological features, mutational status and the relationship between these factors.ResultsThe most common diagnosis was primary lung carcinoma (3130, 62.2%), among which adenocarcinoma (1421, 28.2%) was the most frequent histological type. The mutational assays using ARMS-PCR technology demonstrated that EGFR was positive in 56.1% cases(499/889, from adenocarcinoma and NSCC, favor adenocarcinoma), ALK in 5.7% cases(12/211, from NSCC, which comprised all the primary lung carcinomas except small cell carcinomas), and ROS1 in 0.9% cases(2/211, from NSCC). Another 898 NSCC specimens went through an immunohistochemical (IHC) examination for ALK (D5F3) and 38 of them were positive (4.2%). The overall mutation rate of ALK was 4.5% (50/1119). There was no significant difference between ARMS-PCR and immunohistochemistry in the positive rate of ALK mutation detection (P = 0.359). EGFR mutations (P = 0.02) and ALK mutations (P < 0.001) both decreased with an increasing patient age. Furthermore, the amount of EGFR mutations was higher in adenocarcinoma (64.1% vs 34.1%, P < 0.001) than in NSCC, favor adenocarcinoma. In contrast, ALK mutations were more common in NSCC, favor adenocarcinoma (4.2% vs 8.4%, P = 0.021).ConclusionsThis single-center study exhibited a large subset of small lung biopsies from a Chinese institution and demonstrated that applying the 2015 WHO classification for small lung biopsies can help predict the mutational status of primary lung carcinomas.

Prognostic impact of cancer-associated active fibroblasts and invasive architectural patterns on early-stage lung adenocarcinoma

BackgroundInvasion is a crucial indicator of the prognosis in lung adenocarcinoma. The 2015 WHO classification of lung tumors defined invasion of adenocarcinoma mainly by the presence of non-lepidic histological subtypes including papillary, acinar, micropapillary and solid patterns, and the presence of cancer-associated active fibroblasts (CAF). In this study, we focused specifically on early-stage lepidic adenocarcinoma with CAF to evaluate its prognostic significance. MethodsWe included 1032 resected cases of lung adenocarcinoma, which consisted of pathological stage IA invasive cancer and adenocarcinoma in situ (AIS). Invasive adenocarcinoma was classified into two subgroups according to the type of invasion, INV-1 and INV-2. We defined INV-1 as adenocarcinoma of a non-lepidic histological subtype with or without CAF, and INV-2 as lepidic adenocarcinoma with CAF. The clinicopathological characteristics and prognosis were retrospectively analyzed. ResultsIncluded cases were classified into 696 (67.4 %) INV-1, 170 (16.5 %) INV-2, and 166 (16.1 %) AIS. The estimated 5-year recurrence-free probabilities of INV-1, INV-2, and AIS were 92.9 %, 100 %, and 100 %, respectively (p < 0.001). Although there were significant differences between INV-1 and INV-2 in terms of gender (more males in INV-1, p = 0.039), smoking habit (more smokers in INV-1, p = 0.046), and lymphovascular invasion (more invasion in INV-1, p < 0.001), there was no difference between AIS and INV-2. ConclusionThe presence of CAF is not always associated with a worse prognosis, and therefore it does not seem appropriate to include the presence of CAF alone in diagnostic criteria for invasion in early-stage lung adenocarcinoma.

Role of imaging in predicting tumor spread through airspaces (STAS): what are the next steps.

Tumor spread through airspaces (STAS) has been identified as a new pattern of invasion in the 2015 WHO classification of lung tumors (1) and is associated with a lower overall survival in resected non-small cell lung cancers (2). As a consequence, sublobar resection may not be the best surgical option for cancers with STAS.

2020 challenges in diagnosis and staging of lung cancer

Pathology plays an important role in diagnosis and management of patients with non-small cell lung carcinoma (NSCLC). The current (2015) WHO classification of lung tumours includes histologic and immunophenotypic (IHC) criteria. Adenocarcinomas are the primary focus of shifting nomenclature, emphasising histologic patterns with clinical and biological relevance. Minimally invasive and lepidic-predominant non-mucinous adenocarcinomas represent well-differentiated tumours, while solid and/or micropapillary growth patterns signify poorly-differentiated adenocarcinomas. Poorly-differentiated carcinomas that cannot be classified on the basis of histology alone can instead be subclassified using a limited IHC panel targeting TTF-1 and p63/p40. For adenocarcinomas with non-invasive (lepidic) components, pT staging hinges on the size and extent of only the invasive component. Multifocal tumours are staged based on a combination of gross growth characteristics and histologic findings. Pathology’s role extends beyond diagnosis and staging in response to expectations that cells and tissues will be available for expanded biomarker testing in patients with advanced stage disease. Testing strategies for predictive biomarkers frequently include a combination of immunohistochemistry and increasingly comprehensive molecular profiling as single gene assays become less common. Panels are constructed to balance the number of actionable targets over and against our ability to test extremely small amounts of viable tumour.

Advances In Research Of Spreading Through Air Spaces And The Effects On The Prognosis Of Lung Cancer.

The concept of spread through air spaces (STAS) has been described as a new form of invasion in the lung in the 2015 WHO classification of Lung Tumors, namely invasion through alveolar spaces. STAS is a prognostic factor independent of growth pattern and tumor stage, and it is also an independent risk factor for unfavorable prognosis of stage I lung adenocarcinoma (ADC) and stage I lung squamous cell carcinoma (SCC). The pathological characteristics are different between ADC and SCC. STAS is not reported as routine, so setting a unified pathological reading standard, and hunting for STAS as a regular reading process is urgently advocated. We write this review to investigate the research progress of STAS and its effects on the prognosis of lung cancer.

Clinical, radiographic features and histopathology classification of lung cancer

Background: Lung cancer is one of the most frequently occurring neoplasms and usually has poor prognosis in the world as well as in Vietnam. Clinical signs and symptoms, chest X-ray, CT-Scanner only have a role to guide the diagnosis. Histopathology helps to diagnose and classify some of histological types of lung cancer. Objectives: 1. To describe some clinical features and radiographic pulmonary lesions in patients with primary malignant lung tumors. 2. To diagnose and classify histopathological types of lung cancer and to initially determine immunohistochemical markers exposure in the 2015 WHO classification of lung tumors. Materials and Methods: Cross-sectional research on 80 patients diagnosed by chest X-ray, CT Scanner and histopathology at the Hospital of Hue University of Medicine and Pharmacy and at the Hue Central Hospital from 4.2018 to 4.2019. Results: Chronic coughing was the most common chief complain (58.8%). Frequent respiratory symptoms were chronic coughing (81.3%), chest pain (60%). The most frequent mediastinal symptom was apnea (28.8%). Majority of patients presented general symptoms such as malaise (80%), rapid weight loss (43.8%). The percentage of bone metastasis was 20% and that of peripheral lymph node metastasis was 17.5%. Most cases (90%) had a single tumor and 57.5% of total cases have tumors that were 3 to 6 cm in size. Lesions in left and right lung had similar proportions which were evenly distributed throughout the lung lobes. Regarding to clinical stages, most of cases were in stage IIIA and above (93.7%). Epithelial carcinoma accounted for the highest number (67.5%), squamous carcinoma contributed 22.5% and others were responsible for low rates. Epithelial carcinoma had high positive rates for CK AE1/3, CK7, CK19, TTF1, CEA. Squamous carcinoma had high positive rates for CK AE1/2, P63, Ki67. There was a statistically moderate correlation between the results of histopathology and the conclusions of immunohistochemistry. Conclusions: majority of hospitalized patients were not in early stages and presented combinations of symptoms which were not only manifested in lung but in other locations, including distant metastases. Computerized tomography is almost the main test helping in diagnosis and staging. There was a statistically moderate correlation between the results of histopathology and the conclusions of immunohistochemistry. Key words: lung cancer, pulmonary carcinoma, X-ray, computerized tomography, histopathology, immunohistochemistry

Significance and Perspective for WHO Classification of Lung Tumours (4th ed.)

Significance and Perspective for WHO Classification of Lung Tumours (4th ed.)

Interobserver Variation among Pathologists and Refinement of Criteria in Distinguishing Separate Primary Tumors from Intrapulmonary Metastases in Lung

Multiple tumor nodules are seen with increasing frequency in clinical practice. On the basis of the 2015 WHO classification of lung tumors, we assessed the reproducibility of the comprehensive histologic assessment to distinguish second primary lung cancers (SPLCs) from intrapulmonary metastases (IPMs), looking for the most distinctive histologic features. An international panel of lung pathologists reviewed a scanned sequential cohort of 126 tumors from 48 patients and recorded an agreed set of histologic features, including tumor typing and predominant pattern of adenocarcinoma, thereby opining whether the case was SPLC, IPM, or a combination thereof. Cohen κ statistics of 0.60 on overall assessment of SPLC or IPM indicated a good agreement. Likewise, there was good agreement (κ score 0.64, p < 0.0001) between WHO histologic pattern in individual cases and SPLC or IPM status, but the proportions diversified for histologic pattern and SPLC or IPM status (McNemar test, p < 0.0001). The strongest associations for distinguishing between SPLC and IPM were observed for nuclear pleomorphism, cell size, acinus formation, nucleolar size, mitotic rate, nuclear inclusions, intraalveolar clusters, and necrosis. Conversely, the associations for lymphocytosis, mucin content, lepidic growth, vascular invasion, macrophage response, clear cell change, acute inflammation keratinization, and emperipolesis did not reach significance with tumor extent. Comprehensive histologic assessment is recommended for distinguishing SPLC from IPM with good reproducibility among lung pathologists. In addition to main histologic type and predominant patterns of histologic subtypes, nuclear pleomorphism, cell size, acinus formation, nucleolar size, and mitotic rate strongly correlate with pathologic staging status.