Complementary value of electron microscopy and immunohistochemistry in the diagnosis of non-small cell lung cancer: A potential role for electron microscopy in the era of targeted therapy

ABSTRACT

With the identification of therapeutic targets for lung adenocarcinoma, it has become mandatory to distinguish it from other entities. Some cases remain classified as non-small cell lung carcinoma, not otherwise specified (NSCLC-NOS) with immunohistochemistry. Electron microscopy (EM) can be useful, allowing the identification of glandular differentiation. The aim of this study was to determine the complementary value of immunohistochemistry and EM.

Forty-eight NSCLC-NOS cases were selected (PSMAR-Biobank, Barcelona, Spain). Immunohistochemistry (TTF-1, p40) was performed. Tissue was retrieved from paraffin blocks. Results were compared to the final diagnosis, derived from combination of light microscopy, immunohistochemistry, EM, molecular studies and resection specimen.

Immunohistochemistry concurred with final diagnosis in 36 cases (75%, Kappa = 0.517). EM agreed with final diagnosis in 35 (72.9%, Kappa = 0.471). Immunohistochemistry had a sensitivity = 73%, specificity = 100%, positive predictive value (PPV) = 100% and negative predictive value (NPV) = 52.4% for adenocarcinoma. All adenocarcinoma cases not solved by immunohistochemistry (n = 10) were classified by EM, and vice versa. Data from EM were identical to those of immunohistochemistry: sensitivity = 73%, specificity = 100%, PPV = 100% and NPV = 52.4%. Combining both techniques, 47 cases were coincident with final diagnosis (97.9%, Kappa = 0.943).

EM can provide valuable information in subtyping NSCLC-NOS, being particularly useful when immunohistochemistry is inconclusive. EM could be considered as a complementary tool for decision-making in NSCLC-NOS.

KEYWORDS:

• Non-small cell lung carcinoma
• Not otherwise specified (NSCLC-NOS)
• Adenocarcinoma (ADC)
• Squamous Cell Carcinoma (SCC)
• Immunohistochemistry (IHC)
• Electron microscopy (EM)
• Targeted therapy

Acknowledgments

The authors are grateful to the Society for Ultrastructural Pathology (SUP-USCAP) for honoring this work with two Pathologist-In-Training Awards in the USCAP meetings of 2013 (J.M-C.) and 2016 (R.A-G.), in Baltimore and Seattle, respectively.

Conflict of interest statement

The authors declare no conflict of interest.