Retrograde Lymphatic Spread of Esophageal Cancer

The concept of the retrograde lymphatic spread of cancer cells appears to account for a subset of the essential mechanisms of cancer metastasis in various organs. However, no adequate data currently exist to illustrate the pathology of the retrograde lymphatic metastasis of cancer cells in human bodies. To shed light on this phenomenon, we report a case of a 63-year-old Japanese man who underwent an esophagectomy and lymph node dissection for early-stage esophageal cancer. The patient’s clinical information was evaluated by board-certified surgeons and internists. Surgically excised materials were histopathologically evaluated by attending pathologists. Postoperative pathological examination revealed that the patient’s tumor was a well-differentiated squamous cell carcinoma with negative surgical margins (T1N0M0, stage I). Apart from the primary lesion, a single lymphatic vessel invasion was found between the lamina propria and lamina muscularis of the esophagus where intralymphatic cancer cells had spread against the direction of backflow prevention valves and skipped beyond these valves without destroying them. The present case demonstrated that the retrograde lymphatic spread of cancer cells can occur in valve-equipped lymphatic vessels. Our study may not only provide a scientific basis for the concept of retrograde lymphatic metastasis but also explain a portion of the complexities associated with the lymphogenous metastasis of esophageal cancer. (Medicine 94(27):e1139) Abbreviation: LN = lymph node. INTRODUCTION L ymph node (LN) metastasis is an important prognostic predictor for esophageal squamous cell carcinoma. The bidirectional or skip nodal spread of cancer cells is thought to be a key feature of lymphatic metastasis in patients with thoracic MD, PhD, Shingo , PhD, D, PhD, and Toshitaka Nagao, MD, PhD The concept of the retrograde lymphatic spread of cancer cells appears to account for a subset of the essential mechanisms of cancer metastasis in not only the esophagus but also various other regions, such as the lungs, pleura, mediastinum, heart, pericardium, axilla, spleen, retroperitoneum, perinephritic space, testis, ovary, prostate, penis, and vulva. However, questions remain regarding the term retrograde lymphatic metastasis, which appears in the literature but may sometimes be incorrectly used to describe anterograde lymphatic metastasis to an unusual site due to anatomical variation in the lymphatic distribution and/or caused by the alteration of the lymphatic distribution by a particular pathological condition. An anterograde lymph flow can be defined as a flow in the direction of a lymphatic valve, and a retrograde lymph flow can be defined as a flow against the direction of a lymphatic valve. To the best of our knowledge, if these definitions are rigorously followed, no adequate data currently exist to illustrate the pathology of the retrograde lymphatic metastasis of cancer cells in human bodies. Thus, our central question is whether the retrograde lymphatic spread of cancer cells actually occurs in human bodies. In this report, we describe an illustrative case of esophageal cancer in which cancer cells exhibited retrograde lymphatic spread. We also discuss the mechanisms and significance of this phenomenon.