Clinical significance of immunohistochemically detected lymph node micrometastasis in patients with histologically node-negative esophageal carcinoma: a multi-institutional study

Background  In esophageal carcinoma, the clinical significance of immunohistochemically (IHC)-detected lymph node (LN) micrometastasis is still controversial. We designed this multicenter study to determine the clinical significance of IHC-detected LN micrometastasis in esophageal carcinoma. Methods  The subjects were 164 patients with histopathologically confirmed LN-negative esophageal carcinoma from eight hospitals. A similar IHC technique was used in all institutions, and micrometastasis was diagnosed by a researcher at each hospital as well as independently by pathologists with special interest in esophageal carcinoma. Results  IHC-related micrometastasis in LN was considered positive in 51 (31%) patients by the researchers and in 25 (15%) by the pathologists. The latter micrometastases were further classified into a single (n = 13) and clusters (n = 12) of immunopositive-LN. Kaplan–Meier analysis showed that researcher-based diagnosis of micrometastasis had no significant impact on prognosis whereas the cluster-type micrometastasis diagnosed by pathologists had a significant impact on prognosis. Conclusions  We speculate that the inconsistent results of IHC analyses reported in the literature are caused by the use of different definitions of micrometastasis and the subjective nature of diagnosis of micrometastasis, i.e., dependence on the examiner. Our multiinstitutional study also indicates that the morphological aspects of immunostained cells should be considered when assessing micrometastasis in LN by IHC and that only LN with clusters of IHC-positive cells are prognostically significant in esophageal carcinoma.