Digital Quantification of Tumor Cellularity as a Novel Prognostic Feature of Non–Small Cell Lung Carcinoma

Cancer; Image analysis; Thoracic pathologyCàncer; Anàlisi d'imatges; Patologia toràcicaCáncer; Análisis de imágenes; Patología torácicaNon–small cell lung carcinoma is currently staged based on the size and involvement of other structures. Tumor size may be a surrogate measure of the total number of tumor cells. A recently revised reporting system for adenocarcinoma incorporates high-risk histologic patterns, which may have increased cellular density. Modern digital image analysis tools can be utilized to automate the quantification of cells. In this study, we tested the hypothesis that tumor cellularity can be used as a novel prognostic tool for lung cancer. Digital slides from The Cancer Genome Atlas lung adenocarcinoma (ADC) data set (n = 213) and lung squamous cell carcinoma (SCC) data set (n = 90) were obtained and analyzed using QuPath. The number of tumor cells was normalized with the surface area of the tumor to provide a measure of tumor cell density. Tumor cellularity was calculated by multiplying the size of the tumor with the cell density. Major histologic patterns and grade were compared with the tumor density of the lung ADC and lung SCC cases. The overall and progression-free survival were compared between groups of high and low tumor cellularity. High-grade histologic patterns in the ADC and SCC cases were associated with greater tumor densities compared with low-grade patterns. Cases with lower tumor cellularity had improved overall and progression-free survival compared with cases with higher cellularity. These results support tumor cellularity as a novel prognostic tool for non–small cell lung carcinoma that considers tumor stage and grade elements.Funding support is gratefully acknowledged from the Megan J. Davey Opportunity Fund used to support a workstation to facilitate the computational analysis in this study and travel costs to present an earlier version of this content at the United States & Canadian Academy of Pathology 111th Annual Meeting (2022)

Reliability of histopathologic diagnosis of fibrotic interstitial lung disease: an international collaborative standardization project

Malaltia pulmonar intersticial; Fibrosi pulmonar; Pneumònia intersticial habitualEnfermedad pulmonar intersticial; Fibrosis pulmonar; Neumonía intersticial habitualInterstitial lung disease; Pulmonary fibrosis; Usual interstitial pneumoniaBackground Current interstitial lung disease (ILD) diagnostic guidelines assess criteria across clinical, radiologic and pathologic domains. Significant interobserver variation in histopathologic evaluation has previously been shown but the specific source of these discrepancies is poorly documented. We sought to document specific areas of difficulty and develop improved criteria that would reduce overall interobserver variation. Methods Using an internet-based approach, we reviewed selected images of specific diagnostic features of ILD histopathology and whole slide images of fibrotic ILD. After an initial round of review, we confirmed the presence of interobserver variation among our group. We then developed refined criteria and reviewed a second set of cases. Results The initial round reproduced the existing literature on interobserver variation in diagnosis of ILD. Cases which were pre-selected as inconsistent with usual interstitial pneumonia/idiopathic pulmonary fibrosis (UIP/IPF) were confirmed as such by multi-observer review. Cases which were thought to be in the spectrum of chronic fibrotic ILD for which UIP/IPF were in the differential showed marked variation in nearly all aspects of ILD evaluation including extent of inflammation and extent and pattern of fibrosis. A proposed set of more explicit criteria had only modest effects on this outcome. While we were only modestly successful in reducing interobserver variation, we did identify specific reasons that current histopathologic criteria of fibrotic ILD are not well defined in practice. Conclusions Any additional classification scheme must address interobserver variation in histopathologic diagnosis of fibrotic ILD order to remain clinically relevant. Improvements to tissue-based diagnostics may require substantial resources such as larger datasets or novel technologies to improve reproducibility. Benchmarks should be established for expected outcomes among clinically defined subgroups as a quality metric.This research did not receive any specific grant from funding agencies in the public, commercial or not-for-profit sectors

Valor predictiu de la càrrega tumoral axil·lar en càncer de mama pel mètode OSNA

Aquest treball de tesi preten valorar la importància pronòstica de l'estadificació axil·lar en càncer de mama obtinguda per mètodes moleculars (OSNA). Està estructurada en torn a dues publicacions de treballs on s'ha demostrat que l'estadificació convencional de l'aixella infraestima la càrrega tumoral de la mateixa i que la nova variable càrrega tumoral total (TTL) és, amés d'una eina per calcular el risc de malaltia local, un possible substitut del pN en aquelles pacients en les que no es fa limfadenectomi axil·lar.Este trabajo de tesis pretende valorar la importancia pronóstica de la estadificación axilar en cáncer de mama obtenida por métodos moleculares (OSNA). Está estructurada en torno a dos publicaciones de trabajos donde se ha demostrado que la estadificación convencional de la axila infraestimando la carga tumoral de la misma y que la nueva variable carga tumoral total (TTL) es, además de una herramienta para calcular el riesgo de enfermedad local , un posible sustituto del pN en aquellas pacientes en las que no se hace linfadenectomía axilar.This thesis aims to assess the prognostic importance of axillary staging in breast cancer obtained by molecular methods (OSNA). It is structured around two publications where it has been shown that the conventional staging of the axilla, underestimates its tumor burden and that the new variable total tumoral load (TTL) is, in addition to a tool to calculate the risk of local disease, a possible substitute of pN in those patients in whom axillary lymphadenectomy is not performed.Universitat Autònoma de Barcelona. Programa de Doctorat en Cirurgia i Ciències Morfològique

Combining graph neural networks and computer vision methods for cell nuclei classification in lung tissue

Database of the article "Combining graph neural networks and computer vision methods for cell nuclei classification in lung tissue "

Combining graph neural networks and computer vision methods for cell nuclei classification in lung tissue

Database of the article "Combining graph neural networks and computer vision methods for cell nuclei classification in lung tissue "

Pulmonary adenofibromas : a clinicopathologic correlation of 13 cases

Q1Q1Thirteen cases of primary pulmonary adenofibromas are presented. The patients are 8 women and 5 men between the ages of 41 and 73 years (average: 57 y). The patients presented with nonspecific symptomatology or their tumor was identified during routine chest films. A wedge resection was performed in all cases with lymph node sampling. Grossly, the tumors varied in size from 1 to 2.5 cm in greatest dimension. The entire tumor was histologically evaluated in all cases. All the tumors shared similar histologic features namely leaf-like/phyllodes-like growth patterns with varying areas of sclerosis, focal inflammation, and entrapped epithelium. A wide panel of immunohistochemical studies was performed including epithelial, neural, muscle, and vascular markers, all of which showed negative staining. The tumors were positive only for vimentin in the stroma and keratin in the entrapped epithelium. Further evaluation in 6 cases using in situ hybridization for the solitary fibrous tumor was performed and was negative. Clinical follow-up in all the patients showed no evidence of recurrence or metastatic disease, during a period of 12 to 36 months. The current cases highlight the unusual occurrence of pulmonary adenofibromas and the importance of separating these tumors from other tumors that may have the potential to recur or metastasize. The use of proper immunohistochemical stains/molecular analysis aids in the proper classification of these tumors.N/

Molecular profiling of long-term responders to immune checkpoint inhibitors in advanced non-small cell lung cancer

Càrrega d'alteracions cromosòmiques; Inhibidors del punt de control immunitari; Càrrega mutacional del tumorChromosomal alterations burden; Imune checkpoint inhibitors; Tumor mutational burdenCarga de alteraciones cromosómicas; Inhibidores de los puntos de control inmunitarios; Carga mutacional del tumorImmunotherapy has transformed advanced non-small cell lung cancer (NSCLC) treatment strategies and has led to unprecedented long-lasting responses in some patients. However, the molecular determinants driving these long-term responses remain elusive. To address this issue, we performed an integrative analysis of genomic and transcriptomic features of long-term immune checkpoint inhibitors (ICIs)-associated responders. We assembled a cohort of 47 patients with NSCLC receiving ICIs that was enriched in long-term responders [>18 months of progression-free survival (PFS)]. We performed whole-exome sequencing from tumor samples, estimated the tumor mutational burden (TMB), and inferred the somatic copy number alterations (SCNAs). We also obtained gene transcription data for a subset of patients using Nanostring, which we used to assess the tumor immune infiltration status and PD-L1 expression. Our results indicate that there is an association between TMB and benefit to ICIs, which is driven by those patients with long-term response. Additionally, high SCNAs burden is associated with poor response and negatively correlates with the presence of several immune cell types (B cells, natural killers, regulatory T cells or effector CD8 T cells). Also, CD274 (PD-L1) expression is increased in patients with benefit, mainly in those with long-term response. In our cohort, combined assessment of TMB and SCNAs burden enabled identification of long-term responders (considering PFS and overall survival). Notably, the association between TMB, SCNAs burden, and PD-L1 expression with the outcomes of ICIs treatment was validated in two public datasets of ICI-treated patients with NSCLC. Thus, our data indicate that TMB is associated with long-term benefit following ICIs treatment in NSCLC and that TMB, SCNAs burden, and PD-L1 are complementary determinants of response to ICIs.Instituto Carlos III-ISCIII. Grant Number: FIS PI17/00938. Fundacion Cientifica Asociación Española Contra el Cancer. Grant Number: GCB14142170. Catalan Government/AGAUR. Grant Number: 2017 – SGR – 173

Typical and atypical carcinoid tumors of the lung: A Clinicopathological correlation OF OF 783 cases with Emphasis on histological features.

We present 783 surgical resections of typical and atypical carcinoid tumors of the lung identified in the pathology files of 20 different pathology departments. All cases were critically reviewed for clinical and pathological features and further correlated with clinical outcome. Long-term follow-up was obtained in all the patients and statistically analyzed to determine significance of the different parameters evaluated. Of the histopathological features analyzed, the presence of mitotic activity of 4 mitoses or more per 2mm, necrosis, lymphatic invasion and lymph node metastasis were identified as statistically significant. Tumors measuring 3 cm or more were also identified as statistically significant and correlate with clinical outcome. Based on our analysis, we consider that the separation of low and intermediate grade neuroendocrine neoplasms of the lung needs to be readjusted in terms of mitotic count as the risk of over grading these neoplasms exceeds 10% under the current criteria. We also consider that tumor size is an important feature to be considered in the assessment of these neoplasms and together with the histological grade of the tumor offers important features that can be correlated with clinical outcome