The World Health Organization reporting system for lung cytopathology–a review of the first edition

Lung cancer remains the leading cause of cancer-related mortality and is the second most frequently diagnosed cancer globally in both men and women. Early and accurate diagnosis through lung cytopathology, which examines specimens such as sputum, bronchial brushings (BB), bronchial washings (BW), bronchoalveolar lavage (BAL), and fine needle aspiration biopsy (FNAB), is critical for effective treatment. The advent of endobronchial ultrasound (EBUS) has significantly enhanced the diagnostic utility of FNAB by allowing simultaneous diagnosis and staging. Given the increasing importance of precise lung tumor classification for molecular testing, there is a pressing need for standardized terminology and reporting standards in lung cytopathology. The World Health Organization (WHO) has developed a new reporting system aimed at achieving this standardization to improve communication between cytopathologists and clinicians, enhance diagnostic accuracy, and facilitate research and clinical trial participation.

The WHO Reporting System for Lung Cytopathology is the first international system designed to standardize the reporting of lung cytopathology specimens across different clinical settings. Developed by the International Academy of Cytology (IAC) in collaboration with the International Agency for Research on Cancer (IARC), this system introduces five diagnostic categories: Insufficient/Inadequate/Non-diagnostic, Benign/Negative for Malignancy, Atypical, Suspicious for Malignancy, and Malignant. Each category includes cytomorphologic criteria, an estimated risk of malignancy (ROM), and clinical management recommendations.

Diagnostic Categories and Criteria

Insufficient/Inadequate/Non-diagnostic: This category covers specimens that are inadequate for a definitive diagnosis due to insufficient cellular material or poor specimen quality. It emphasizes the need for proper sample collection and handling to avoid misdiagnosis and unnecessary repeat procedures. Examples of insufficient samples include poorly prepared slides with significant blood or inflammation that obscures cellular details.

Benign/Negative for Malignancy: Specimens classified as benign exhibit cellular features consistent with non-neoplastic processes. This category includes a broad range of benign conditions and helps to avoid overtreatment. Common benign findings might include normal respiratory epithelial cells, benign inflammatory conditions, or benign neoplasms such as hamartomas.

Atypical: Atypical specimens contain cells with mild to moderate abnormalities that are not sufficient for a definitive diagnosis of malignancy but are suspicious enough to warrant further investigation. This category acknowledges the grey zone in cytopathologic diagnosis and the need for follow-up testing. Atypical findings may include cellular changes that could be reactive or represent a low-grade neoplastic process.

Suspicious for Malignancy: This category is used when the cytomorphologic features suggest malignancy, but the sample is not adequate for a definitive malignant diagnosis. It prompts further diagnostic steps, including additional biopsies or molecular tests, to confirm the diagnosis. For example, specimens with highly atypical cells that resemble cancer but lack definitive criteria for malignancy fall into this category.

Malignant: Specimens classified as malignant show definitive cytomorphologic evidence of cancer. This category includes specific recommendations for further diagnostic and therapeutic interventions based on the type and location of the malignancy. Malignant findings include clear features of carcinoma, small cell lung carcinoma, or other specific cancer types.

The WHO system provides tailored clinical management recommendations for each diagnostic category. For example, specimens classified as "Malignant" typically lead to immediate further diagnostic steps such as bronchoscopy or imaging, followed by EBUS- or CT-guided FNAB. Depending on the tumor's characteristics and the patient's condition, management may include surgical resection or systemic treatment. For benign diagnoses, monitoring and follow-up may be appropriate, while atypical or suspicious categories necessitate further testing to clarify the diagnosis.

The system also emphasizes the role of ancillary tests, including molecular and genetic tests, which are essential for accurate diagnosis and personalized treatment planning. The selection of appropriate ancillary tests is guided by best practice recommendations and takes into account the varying availability of resources across different practice settings. Ancillary tests such as immunohistochemistry (IHC) and molecular assays help to confirm the diagnosis and provide crucial information for targeted therapies, especially in cases of lung adenocarcinoma and other specific cancer subtypes.

The introduction of the WHO Reporting System for Lung Cytopathology marks a significant advancement in the standardization of lung cytopathology reporting. By providing clear diagnostic categories and criteria, it enhances the reproducibility of diagnoses among cytopathologists and improves communication with clinicians, thereby optimizing patient care. The system's emphasis on standardized cytomorphologic criteria and ancillary testing recommendations supports precise and effective diagnosis and treatment of lung cancer. Moreover, standardization facilitates better data collection for epidemiological studies and clinical trials, which are essential for advancing our understanding and treatment of lung cancer.

The system's implementation is expected to face challenges, particularly in resource-limited settings where access to advanced diagnostic tools and training may be limited. However, the guidelines provide flexibility and adaptability to various practice environments, ensuring that the principles of accurate and standardized reporting can be applied universally. Continuous training and education for cytopathologists and clinicians, alongside the development of affordable and accessible diagnostic technologies, will be crucial for the successful global implementation of the WHO system.

The WHO Reporting System for Lung Cytopathology represents a significant step forward in the quest for standardized, accurate, and communicative lung cancer diagnostics. By establishing clear categories and criteria, it improves diagnostic consistency, enhances patient management, and promotes further research. The integration of ancillary testing and attention to resource variability ensures the system's applicability across diverse clinical settings. As the system becomes widely adopted, it is expected to significantly improve outcomes for patients with lung cancer and contribute to the global effort in combating this pervasive disease. Continued refinement and research will further enhance its clinical utility and impact, ensuring that the system remains at the forefront of lung cancer diagnostics.

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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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