An Update on the Classification of Lung and Pleural Tumors
image: (a) Tumor cells are uniform with round to oval nuclei and inconspicuous nucleoli, arranged in a nested/organoid pattern. Other growth patterns include pseudoglandular, trabecular, and follicular with rosette formation. There is moderate to abundant eosinophilic cytoplasm (×20). (b) Tumor cells typically show immunoreactivity to CAM5.2, which is helpful to distinguish carcinoid tumor from paraganglioma (×10). (c) TTF-1 would help establish a pulmonary lineage and tend to be focal and weak (×20). Neuroendocrine markers (d) synaptophysin and (e) chromogranin are positive in tumor cells (×20), and (f) proliferation labeling index with Ki-67 should be low in typical carcinoid tumor (×20).
Credit: Haodong Xu, Liang Lu
The World Health Organization (WHO) Classification of Thoracic Tumors has undergone significant updates in its fifth edition. This review aims to provide a comprehensive summary of these updates, emphasizing the diagnostic, histological, and molecular advancements for lung and pleural tumors. These updates are crucial for pathologists and clinicians to enhance diagnostic accuracy and therapeutic strategies.
Small Diagnostic Samples
The accurate diagnosis of lung cancer from small biopsy samples remains a challenge due to the limited tissue availability and variability in tumor morphology. The 2021 WHO guidelines recommend minimizing the use of the term "non-small cell lung carcinoma-not otherwise specified (NSCLC-NOS)" and instead classifying NSCLC into specific subtypes such as adenocarcinoma or squamous cell carcinoma whenever possible. This precise classification is essential for guiding clinical therapy and improving patient outcomes.
Precursor Glandular Lesions
Precursor glandular lesions, including atypical adenomatous hyperplasia (AAH) and adenocarcinoma in situ (AIS), are recognized as initial stages in the tumorigenesis of lung adenocarcinoma. AAH presents with atypical pneumocytes lining the alveolar septa and has a size cutoff of 0.5 cm. AIS is characterized by a lepidic growth pattern without invasive features and a size limit of 3.0 cm. The progression from AAH to AIS and subsequently to invasive adenocarcinoma highlights the importance of early detection and intervention.
High-grade Patterns of Lung Adenocarcinoma
Recent studies have identified new high-grade patterns in lung adenocarcinoma, including micropapillary, solid, filigree, and complex glandular patterns. These patterns are associated with more aggressive clinical behavior and poorer prognosis compared to acinar and papillary patterns. For instance, the filigree micropapillary pattern, defined by delicate lace-like stacks of cells without fibrovascular cores, is linked to higher recurrence rates and advanced disease stages.
Updates on Grading
The grading system for lung adenocarcinoma has been refined to incorporate secondary high-grade patterns. The three-tier grading system now includes micropapillary, solid, cribriform, and complex glandular patterns if they comprise at least 20% of the tumor. This comprehensive grading approach better reflects the tumor's aggressiveness and guides therapeutic decisions.
Molecular Features of Large Cell Neuroendocrine Carcinoma
Large cell neuroendocrine carcinoma (LCNEC) is a rare and aggressive subtype of lung cancer with distinct molecular characteristics. The review highlights the significance of identifying molecular alterations in LCNEC, such as TP53 and RB1 mutations, which may provide insights into targeted therapies and prognostic markers. Understanding these molecular features is essential for developing personalized treatment strategies.
Rare Neoplasms
The updated WHO classification also addresses several rare thoracic neoplasms, including bronchiolar adenoma/ciliated muconodular papillary tumor (BA/CMPT), SMARCA4-deficient undifferentiated thoracic tumor (SMARCA4-UT), and primary pulmonary hyalinizing clear cell carcinoma (HCCC). These entities have unique histological and molecular profiles, necessitating specialized diagnostic criteria and therapeutic approaches.
Diagnostic Algorithm for Malignant Epithelioid Mesothelioma
The review introduces a new diagnostic algorithm for malignant epithelioid mesothelioma, focusing on histologic grading. Favorable prognostic features include myxoid/microcystic, tubulopapillary, trabecular, and adenomatoid patterns, while micropapillary and solid growth patterns are associated with worse outcomes. This algorithm aims to standardize the diagnosis and prognostication of mesothelioma, aiding in clinical management.
Perspective and Future Work
The 2021 WHO classification provides a detailed framework for diagnosing thoracic tumors, yet there are areas for future research. Key directions include refining diagnostic criteria for neuroendocrine tumors, exploring the clinicopathologic correlation of LCNEC, and elucidating molecular features of additional tumor types. These efforts will enhance prognostic accuracy and support the development of novel therapeutic strategies.
Conclusions
This review encapsulates the significant updates in the WHO classification of lung and pleural tumors, emphasizing the importance of accurate diagnosis from small samples, refined grading systems, and molecular profiling. These advancements serve as a valuable resource for pathologists, clinicians, and researchers, facilitating improved patient care and fostering ongoing scientific discovery.
Full text
https://www.xiahepublishing.com/2771-165X/JCTP-2023-00008
The study was recently published in the Journal of Clinical and Translational Pathology.
Journal of Clinical and Translational Pathology (JCTP) is the official scientific journal of the Chinese American Pathologists Association (CAPA). It publishes high quality peer-reviewed original research, reviews, perspectives, commentaries, and letters that are pertinent to clinical and translational pathology, including but not limited to anatomic pathology and clinical pathology. Basic scientific research on pathogenesis of diseases as well as application of pathology-related diagnostic techniques or methodologies also fit the scope of the JCTP.
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