Does a diagnosis of poorly differentiated non-small cell carcinoma (NSCLC), favor adenocarcinoma, confirm that the tumor is adenocarcinoma?

Understanding "Poorly Differentiated Non-Small Cell Carcinoma, Favor Adenocarcinoma" Diagnosis

A diagnosis of "poorly differentiated non-small cell carcinoma, favor adenocarcinoma" does not definitively confirm that the tumor is adenocarcinoma, but rather indicates a high likelihood of adenocarcinoma that requires additional testing for confirmation.

Diagnostic Terminology in Small Samples

When pathologists examine small biopsy specimens with poorly differentiated features, they use specific terminology recommended by the WHO classification system:

• "NSCLC favor adenocarcinoma" is used when the tumor has undifferentiated morphology but shows positive TTF-1 immunohistochemistry (IHC) staining 1
• This terminology is specifically designed for small biopsy specimens where definitive classification based on morphology alone is challenging

Why This Terminology Is Used

1. Limited Sample Material: Small biopsies often don't show all the characteristic architectural features needed for definitive diagnosis

2. Preservation of Tissue: The WHO and IASLC guidelines recommend judicious use of IHC to preserve tissue for molecular studies, particularly in patients with advanced disease 1

3. Diagnostic Challenges: Poorly differentiated carcinomas lack the specific phenotypes and morphological features of either glandular or squamous differentiation, making definitive classification difficult 1

Diagnostic Approach for NSCLC

The current WHO guidelines discourage using the generic term "non-small cell lung cancer (NSCLC)" as a single diagnostic term 1. Instead:

• Immunohistochemical markers are used to differentiate between subtypes:

  • TTF-1 and Napsin A are typically positive in adenocarcinomas
  • p63, p40, and CK5/6 are typically positive in squamous cell carcinomas 1

• When morphology is inconclusive but IHC findings are characteristic of adenocarcinoma, the term "NSCLC favor adenocarcinoma" is appropriate 2

Clinical Implications

This distinction has important clinical implications:

1. Treatment Selection: Accurate subtyping is critical for selecting appropriate targeted therapies, particularly tyrosine kinase inhibitors 1

2. Molecular Testing: Patients with "NSCLC favor adenocarcinoma" should undergo molecular testing for driver mutations such as EGFR 1

3. Prognosis: Research suggests that patients with definitive adenocarcinoma morphology may have better outcomes compared to those diagnosed with "NSCLC favor adenocarcinoma" when treated with platinum-pemetrexed combination chemotherapy 2

Important Considerations

• Additional Testing: Further immunohistochemical and molecular testing is often necessary to confirm the diagnosis

• Potential for Combined Tumors: Some tumors (approximately 4%) may have combined histology (e.g., adenosquamous carcinoma) 3

• Need for Adequate Sampling: In some cases, re-biopsy may be necessary if initial sampling is inadequate for definitive diagnosis and molecular testing 1

Bottom Line

When a pathology report states "poorly differentiated non-small cell carcinoma, favor adenocarcinoma," it indicates a strong suspicion of adenocarcinoma based on available evidence, but not a definitive diagnosis. This terminology acknowledges diagnostic uncertainty while providing the most likely histologic subtype to guide immediate clinical decisions while further testing is performed.