NIH, National Cancer Institute, Division of Cancer Treatment and Diagnosis (DCTD) NIH - National Institutes of Health National Cancer Institute DCTD - Division of Cancer Treatment and Diagnosis

Interobserver agreement in determining non-small cell lung cancer subtype in specimens acquired by EBUS-TBNA.

Author(s): Steinfort DP, Russell PA, Tsui A, White G, Wright G, Irving LB

Publication: Eur Respir J, 2012, Vol. 40, Page 699-705

PubMed ID: 22323573 PubMed Review Paper? No

Purpose of Paper

This paper compared the diagnostic concordance for cytological smears and H&E, or immunohistochemistry (IHC)-stained sections among 3 pathologists.

Conclusion of Paper

The three pathologists agreed on the diagnosis for 39% of cytological smears, 55% of H&E stained specimens, and 77% of IHC specimens with higher agreement for each in the diagnosis of small cell lung cancer (SCLC) versus non-SCLC (NSCLC) than for NSCLC subtype. For both cytological and IHC-based diagnoses, concordance was 100% when the pathologists were confident in their diagnosis. Discordance between H&E, IHC, and cytology diagnosis occurred in 5-11 of 36 cases depending on the pathologist in question. For cases where the pathologist was not confident in the H&E diagnosis, IHC increased concordance but changed the diagnosis in some cases where the pathologist was confident in the H&E-based diagnosis.

Studies

  1. Study Purpose

    This study compared the diagnostic concordance between pathologists for cytological smears and H&E or IHC stained sections. Transbronchial needle aspiration (TBNA) was performed under endobronchial ultrasound (EBUS) guidance from 60 patients. Up to three passes were ethanol-fixed and Papanicolaou-stained. Subsequent material was formalin-fixed, centrifuged, embedded in agar, and sectioned for H&E staining or, for some cases, IHC staining. IHC antibodies were determined by the pathologist. All 60 H&E specimens and the matched 49 cytology and 36 IHC specimens were reviewed by each of three pathologists and diagnosed as NSCLC adenocarcinoma, squamous cell carcinoma (SCC) or not otherwise specified/large cell carcinoma (NOS), or as SCLC.

    Summary of Findings:

    The three pathologists agreed on the diagnosis of cytological smears in 19 of 49 (39%) of cases, with much better agreement in the diagnosis of SCLC versus NSCLC than in NSCLC subtype (κ=0.701 versus κ=0.095). However, the diagnosis based on cytology was 100% concordant when the pathologists were confident in the diagnosis and only 17% if one or more of the pathologists were not confident.

    Complete agreement on diagnosis was found for 28 of 36 (78%) IHC specimens with 100% agreement observed in differentiating NSCLC versus SCLC and moderate agreement in NSCLC subtype (κ=0.564). Complete agreement was observed for the 19 cases where all three pathologists were confident, but only 53% (9 of 17) of the cases if one or more of the pathologists expressed doubt (P=0.008).

    The three pathologists agreed on diagnosis in 33 of 60 (55%) H&E specimens, with agreement between 2 pathologists observed for an additional 23 cases. Similar to cytological smear, the agreement in differentiating NSCLC versus SCLC was much better than that between NSCLC subtypes (κ=0.814 versus κ=0.278). When all three pathologists were confident in their diagnosis, the overall diagnosis was concordant in 81% of cases (21 of 26), but if one or more of the pathologists expressed doubt, concordance was seen in 11 of 34 cases (32%, P=0.0002).

    When there was doubt in the diagnosis based on H&E, the addition of IHC allowed for concordant diagnosis in an additional 10 of 20 cases. Evaluation of IHC in specimens for which the pathologist was confident in the H&E diagnosis changed the NSCLC subtype in 3 of 9 cases. Disagreement between H&E and IHC diagnosis for individual pathologists occurred in 5, 6, and 11 of the 36 cases with the majority changing from SCC on H&E evaluation to adenocarcinoma after IHC (7 of 22).

    Biospecimens
    Preservative Types
    • Formalin
    • Ethanol
    Diagnoses:
    • Neoplastic - Carcinoma
    Platform:
    AnalyteTechnology Platform
    Morphology Light microscopy
    Protein Immunohistochemistry
    Morphology H-and-E microscopy
    Pre-analytical Factors:
    ClassificationPre-analytical FactorValue(s)
    Preaquisition Diagnosis/ patient condition NSCLC adenocarcinoma
    NSCLC squamous cell carcinoma (SCC)
    NSCLC not otherwise specified/large cell carcinoma (NOS)
    SCLC
    H-and-E microscopy Specific Data handling 3 different pathologists
    Immunohistochemistry Specific Data handling 3 different pathologists
    Light microscopy Specific Data handling 3 different pathologists
    H-and-E microscopy Specific Technology platform Cytology
    IHC

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