Lung carcinoma remains one of the leading causes of cancer-related deaths worldwide. Accurate and timely diagnosis is critical for effective treatment and patient management. Immunohistochemistry (IHC) has emerged as a pivotal technique in the histopathological diagnosis of lung cancer, particularly in distinguishing between different types and subtypes of tumors. This blog will explore the stepwise algorithmic approach to IHC-based diagnosis of lung carcinoma, incorporating the latest updates and guidelines.
Overview of types of lung carcinoma
Introduction to Immunohistochemistry in Lung Cancer
Immunohistochemistry involves the use of specific antibodies to detect antigens in cells of a tissue section, visually represented through a colorimetric reaction. In lung cancer, IHC is essential not only for diagnosing but also for prognostic and predictive insights, helping to tailor individual treatment plans.
Step 1: Clinical and Histological Assessment
Before IHC staining, a thorough clinical evaluation and histological assessment using Hematoxylin and Eosin (H&E) stained slides are performed. The aim is to observe the morphological features that might suggest lung carcinoma, including cell type and architectural patterns.
Step 2: Initial IHC Markers for Lung Carcinoma and Subtyping Lung Carcinoma
Once a preliminary diagnosis of lung carcinoma is suspected based on histology, IHC is employed to confirm the diagnosis and categorize the carcinoma. Initial markers used include:
- TTF-1 (Thyroid Transcription Factor-1): Predominantly stains adenocarcinomas of lung origin but not squamous cell carcinomas.
- p40 or p63: These markers are generally positive in squamous cell carcinoma and negative in adenocarcinoma.
- Napsin A: Supports the diagnosis of adenocarcinoma, often used in conjunction with TTF-1.
Depending on the results of the initial panel, further markers may be used to refine the diagnosis:
- For Small Cell Lung Carcinoma: Synaptophysin, chromogranin, and CD56 are specific markers.
- For Neuroendocrine Tumors: A combination of CD56, Synaptophysin, and Chromogranin helps confirm this subtype.
- ALK, ROS1, and PD-L1 Testing: These markers are critical for identifying actionable mutations in adenocarcinomas, guiding targeted therapy decisions.
If NSCLC is suspected, further differentiation between adenocarcinoma and squamous cell carcinoma is necessary:
- CK5/6 and CK7: Useful markers to differentiate between adenocarcinoma (CK7 positive, CK5/6 negative) and squamous cell carcinoma (CK5/6 positive, CK7 negative).
Step 3: Molecular Profiling
Advanced molecular profiling can be considered for further characterization and treatment planning:
- EGFR, KRAS, BRAF Mutations: Determine the presence of mutations for potential targeted therapy.
- PD-L1 Expression: Determines immunotherapy options. High PD-L1 expression can indicate a good response to anti-PD-1 and anti-PD-L1 therapies.
Conclusion
The stepwise IHC algorithm for diagnosing lung carcinoma provides a structured path for accurately distinguishing between different types of lung cancers and selecting appropriate treatments. As advancements in molecular techniques continue to evolve, the integration of IHC with molecular diagnostics is likely to enhance the precision of lung cancer therapies further, offering hope for improved patient outcomes.
A quick and concise illustration
TRY TO ANSWER THIS QUESTION
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Correct answer is B: The image shows a tumor with large cell morphology. All lineage specific markers are negative. However, cytokeratin is positive. Hence the tumor can be large cell carcinoma NOS.
This tumor according to WHO 2021 is not reported in biopsies. Only can be reported on resection specimen with examining all representative areas and ruling out any possible differentiation.
Reference: WHO Tumors of Lung an Pleura 5th edition.
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