Ultrastaging Confirms the Superior Sensitivity of Quantitative Immunocytology for Detection of Lymph Node Spread in Non-Small Cell Lung Cancer Patients.

[CONTEXT.—] Histopathologic lymph node (LN) status has a high prognostic impact in patients with non-small cell lung cancer (NSCLC). However, there are no detailed recommendations for LN workup beyond routine hematoxylin-eosin (H&E) sections in current guidelines.

[OBJECTIVE.—] To systematically compare the results of routine H&E, ultrastaging (US), and immunocytology (IC) LN workup for the reporting of LN involvement in NSCLC patients.

[DESIGN.—] Extensive US including 10 additional step sections with serial sections for H&E and immunohistochemistry for pancytokeratin, BerEP4, and transcription termination factor 1 (TTF1) and/or p40 was performed on 122 LNs previously assessed as metastasis free during initial pathologic workup by H&E slides. One-half of each LN had also been examined by IC after disaggregation.

[RESULTS.—] Twenty-four of the initially negative 122 LNs (19.7%) were positive using US and 74 of 122 (60.7%) were positive by IC, resulting in a 3.1-fold higher detection rate by IC (P = .01, χ2 test). Comparisons between initiating colony detection by US and disseminated cancer cell density (number of disseminated cancer cells per million LN cells) revealed that a disseminated cancer cell density value of about 60 reflects metastatic colony formation. Applying this value for LN staging predicted poor outcome better than histopathologic routine, at least in univariate analysis in this relatively small NSCLC cohort.

[CONCLUSIONS.—] Routine histopathologic workup underestimates LN spread in NSCLC patients and occasionally misses even macrometastases. US confirms and validates the significantly higher sensitivity of IC over routine histopathologic workup. In particular, IC has the potential to improve appropriate staging and prognostic stratification of patients in the future.