背景：肺硬化性肺泡细胞瘤（PSP）是一种罕见的肺部肿瘤，具有低恶性潜能，主要影响女性。PSP的初步研究主要集中在分析利用常规X射线或CT成像发现的特征上。近年来，由于下一代测序（NGS）的广泛应用，PSP在分子水平上的研究已经出现。方法：进行了涉及基因组学、放射组学和病理组学的分析方法。基因组学研究包括DNA和RNA分析。 DNA分析包括患者的肿瘤和生殖系组织，涉及目标面板测序和拷贝数分析。RNA分析包括肿瘤和相邻正常组织，涉及表达突变、基因差异表达、基因融合和分子途径的研究。放射组学方法被用于临床成像研究，病理组学技术被应用于肿瘤全切片图像。结果：生成了涉及50多个基因组分析的综合分子分析项目，对该罕见的肺部新生物的16个测序数据集进行详细的放射组学和病理组学分析，以揭示患者肿瘤的发病机理和分子行为。发现了驱动突变（AKT1）和受损的肿瘤抑制途径（TP53）。为确保这项研究的准确性和可重复性，使用了一种称为NPARS的软件基础设施和方法，该方法封装了NGS和相关数据、开源软件库和工具版本，以及面向大型和复杂基因组学研究的报告功能。结论：超越描述性分析，向更深入的肿瘤发病机理、行为和治疗预测的功能理解需要一系列定量的分子医学方法和整合。迄今为止，这是一项针对PSP患者的最全面的研究，该肺部罕见肿瘤进行了详细的放射组学、病理组学和基因组分子分析，揭示了发病机理和分子行为方面的见解。在复发的情况下，将根据发现的分子结果提出合理的治疗方案。版权所有©2023 Ma，Peterson，Shin，Muesse，Marino，Steliga，Atiq，Arnaoutakis，Wardell，Wooldridge，Prior和Johann。

Background: Pulmonary Sclerosing Pneumocytoma (PSP) is a rare tumor of the lung with a low malignant potential that primarily affects females. Initial studies of PSP focused primarily on analyzing features uncovered using conventional X-ray or CT imaging. In recent years, because of the widespread use of next-generation sequencing (NGS), the study of PSP at the molecular-level has emerged. Methods: Analytical approaches involving genomics, radiomics, and pathomics were performed. Genomics studies involved both DNA and RNA analyses. DNA analyses included the patient's tumor and germline tissues and involved targeted panel sequencing and copy number analyses. RNA analyses included tumor and adjacent normal tissues and involved studies covering expressed mutations, differential gene expression, gene fusions and molecular pathways. Radiomics approaches were utilized on clinical imaging studies and pathomics techniques were applied to tumor whole slide images. Results: A comprehensive molecular profiling endeavor involving over 50 genomic analyses corresponding to 16 sequencing datasets of this rare neoplasm of the lung were generated along with detailed radiomic and pathomic analyses to reveal insights into the etiology and molecular behavior of the patient's tumor. Driving mutations (AKT1) and compromised tumor suppression pathways (TP53) were revealed. To ensure the accuracy and reproducibility of this study, a software infrastructure and methodology known as NPARS, which encapsulates NGS and associated data, open-source software libraries and tools including versions, and reporting features for large and complex genomic studies was used. Conclusion: Moving beyond descriptive analyses towards more functional understandings of tumor etiology, behavior, and improved therapeutic predictability requires a spectrum of quantitative molecular medicine approaches and integrations. To-date this is the most comprehensive study of a patient with PSP, which is a rare tumor of the lung. Detailed radiomic, pathomic and genomic molecular profiling approaches were performed to reveal insights regarding the etiology and molecular behavior. In the event of recurrence, a rational therapy plan is proposed based on the uncovered molecular findings.Copyright © 2023 Ma, Peterson, Shin, Muesse, Marino, Steliga, Atiq, Arnaoutakis, Wardell, Wooldridge, Prior and Johann.