The 2021 WHO Classification of Lung Tumors
Page 1: Introduction to the 2021 WHO Classification of Lung Tumors
Authors: Andrew G. Nicholson et al.
Publication Date: 20 November 2021
Content Overview: Discusses updates in the classification of lung tumors by the WHO based on advances in pathology since 2015.
Key Updates in 2021
Morphology First: Classification method starts with morphology, enhanced by immunohistochemistry and molecular techniques.
Molecular Pathology Emphasis: Increased focus on molecular pathology across all tumor types compared to the 2015 edition.
Genetic Testing and Documentation: Significant change in emphasizing genetic testing, detailed documentation of histopathologic patterns, and tumor grading systems.
Major Features
Genetic Testing: Expanded emphasis compared to 2015 classification.
Small Diagnostic Samples: Dedicated section for classifying small biopsy samples.
Histologic Patterns: Continued recommendation to document histologic patterns in nonmucinous adenocarcinomas.
Prognostic Features: Recognition of spread through airspaces (STAS) now included as a histological feature with prognostic significance.
Page 2: Classification Enhancements
New Entities and Updates
Changes in Categories:
Lymphoepithelial carcinoma moved under squamous cell carcinomas.
Updates in classifications for lung neuroendocrine neoplasm.
Recognition of new tumors such as bronchiolar adenoma/ciliated muconodular papillary tumor as a formal entity.
Introduction of thoracic SMARCA4-deficient undifferentiated tumors.
Essential diagnostic criteria for each tumor included.
Clinical Implications
Lung Cancer Mortality Trends: Decline in lung cancer mortality linked to improved diagnostic accuracy and therapeutic strategies established in prior classifications.
Early Detection and Treatment Advances: The role of histologic and molecular characterization in improving patient outcomes and therapy responses.
Page 3: Clinical Impact of Classification Updates
Continued Major Developments
Prognostic Features: The importance of accurately grading tumors.
Histologic Features: Recognition of features like STAS affecting clinical management.
Surgical Treatments: Ongoing debate on the efficacy of sublobar resections for small cancers.
Systemic Therapies: not only targetted therapies but also their respective timing in relation to therapy efficacy in patients with specific genomic abnormalities.
Summary of Updates in 2021
Continued evolution of tumor classification to reflect advances in molecular pathology and understanding of disease prognostics.
Page 4: Diagnostic Samples and Their Importance
Small Diagnostic Samples
70% of Lung Cancers: Present at advanced stages, highlighting reliance on small biopsies for diagnosis.
Methods of Sample Collection: Utilization of techniques like fine-needle aspiration and cytology.
Molecular Testing Efficiency: Next-generation sequencing revealing high diagnostic yield from cytology samples.
Recommendations for Sample Handling
Ensure the use of various techniques for sample acquisition to maximize diagnostic accuracy including the implementation of immunohistochemistry and molecular testing.
Page 5: Guiding Best Practices
Guidelines for Small Biopsies and Cytology
Classify NSCC more specifically whenever possible.
Minimize the use of non-specific diagnoses like NSCC-NOS.
Clearly state methods used for classification in pathology reports.
Avoid using large cell carcinoma as a diagnosis in small samples; must be specified on resection specimens.
Evidence linking specific histological features to treatment headway, calling for stringent diagnostic protocols.
Page 6: Predictive Biomarker Testing
Current Clinical Guidelines
Routine testing for established driver mutations in tumors.
Use of archival or fresh biopsy samples in determining PD-L1 status.
The presence of at least 100 assessable tumor cells required for PD-L1 assessment.
Page 7: Pathology Reporting in Lung Cancer
Recommendations on Pathology Reports
Adhere to a classification based on the latest WHO guidelines.
Clearly document results from immunohistochemical studies and mention any differential diagnoses.
Note materials submitted for molecular testing for better inter-communication within treatment frameworks.
Page 8: Overview of Adenocarcinomas
Classification of Adenocarcinomas
Invasive adenocarcinomas distinctions mainly remain consistent since 2015.
New Grading System: Introduction of grading for invasive nonmucinous adenocarcinomas based on histological patterns and stratification based on clinical outcomes.
Page 9: Spread Through Air Spaces (STAS)
Definition and Impact: STAS is linked to tumor spread significance and affects clinical practice.
Morphological identification criteria established to separate STAS from artifacts.
Page 10: Variants of Adenocarcinoma
Mucinous and Nonmucinous Types
Invasive Mucinous Adenocarcinomas: Defined and differentiated at histological and genetic levels, emphasize notable NP45 or mucinous characteristics in such cases.
Page 11: Molecular Pathology of Adenocarcinoma
Recent Advances
Molecular pathology increasingly integrated into adenocarcinoma classification, emphasizing key driver mutations for targeted therapy.
Clinical Relevance: The diagnosis and management of lung cancers increasingly rely on genomic profiles of tumors to tailor treatment.
Page 12: Neuroendocrine Neoplasms
Classification Updates
2021 WHO classification consolidates neuroendocrine tumors into a single group while retaining specific diagnostic criteria for subtypes.
Page 13: Criteria for Carcinoid Tumors
Mitotic Counting: Emphasized as key for distinguishing carcinoid tumors, highlighting the requisite thoroughness for pathological evaluation.
Page 14: Genetic Data in NEN Classification
Emerging Concepts
Importance of molecular profiling in assessing NENs and identifying distinct groups.
Page 15: Squamous Cell Carcinoma
Minor Adjustments in Classification
“Epidermoid carcinoma” phased out, with clearer categorizations under squamous cell carcinoma including criteria for lymphoepithelial carcinoma.
Page 16: Bronchiolar Adenoma and CMPT
Definition and Histologic Features
Recognized as benign lesions with specific diagnostic markers.
Page 17: Molecular Characteristics of BA/CMPT
Highlighting driver mutations in BA/CMPT that may influence clinical management and therapeutic approaches.
Page 18: SMARCA4-Deficient Undifferentiated Thoracic Tumor
New Malignant Entity Update
High-grade neoplasm now categorized as a distinct entity with unique clinical and pathological characteristics compared to conventional lung carcinoma.
Page 19: Other Tumor Types and Considerations
Mention of various tumors including hyalinizing clear cell carcinoma and the importance of genetic investigations in diagnosing ectopic tumors.
Page 20: Future Directions
Ongoing Research Needs
Highlights areas for future research, including validating new grading systems, molecular testing, and refining classifications according to recent discoveries.