Esophageal cancer: The mode of lymphatic tumor cell spread and its prognostic significance

dPurpose: Data on skip metastases and their significance are lacking for es ophageal cancer. This issue is important to determine the extent of lymphad enectomy for esophageal resection. In this study we examined the lymphatic spread in esophageal cancer by routine histopathology and by immunohistoche mistry. Patients and Methods: A total of 1,584 resected lymph nodes were obtained f rom 86 patients with resected esophageal carcinoma and evaluated by routine histopathology. Additionally, frozen tissue sections of 540 lymph nodes cl assified as tumor-free by routine histopathology were screened for micromet astases by immunohistochemistry with the monoclonal antibody Ber-EP4. The l ymph nodes were mapped according to the mapping scheme of the American Thor acic Society modified by Casson et al. Results: Forty-four patients (51%) had pN1 disease, and 61 patients (71%) h arbored lymphatic micrometastases detected by immunohistochemistry. Skip me tastases detected by routine histopathology were present in 34% of pN1 pati ents. Skipping of micrometastases detected by immunohistochemistry was foun d in 66%. The presence of micrometastases was associated with a significant ly decreased relapse-free and overall survival (56.0 v 10.0 months and > 64 v 15 months, P < .0001 and P = .004, respectively). Cox regression analysi s revealed the independent prognostic influence of micrometastases in lymph nodes. Lymph node skipping had no significant independent prognostic influ ence on survival. Conclusion: Histopathologically and immunohistochemically detectable skip m etastases are a frequent event in esophageal cancer. Only extensive lymph n ode sampling, in conjunction with immunohistochemical evaluation, will lead to accurate staging. An improved staging system is essential for more indi vidualized adjuvant therapy. <(c)> 2001 by American Society of Clinical Onc ology.