Histopathological Changes After Microwave Coagulation Therapy for Patients With Hepatocellular Carcinoma: Review of 15 Explanted Livers Noriyo Yamashiki, M.D., Tomoaki Kato, M.D., Pablo A. Bejarano, M.D., Mariana Berho, M.D., Berta Montalvo, M.D., Robert T. Shebert, M.D., Zachary D. Goodman, M.D., Toshihito Seki, M.D., Eugene R. Schiff, M.D., and Andreas G. Tzakis, M.D. Division of Transplantation, Department of Surgery, Divisions of Hepatology and Neurology, Department of Medicine, Department of Pathology, and Department of Radiology, University of Miami School of Medicine, Miami, Florida; Armed Forces Institute of Pathology, Washington, DC; and Third Department of Internal Medicine, Kansai Medical University, Osaka, Japan OBJECTIVES: Microwave coagulation therapy (MCT) is a well established local ablation technique for hepatocellular carcinoma (HCC). However, pathological changes in liver tissue after this therapy have not been well described. We examined the histological changes of HCC after MCT ob- served in explanted livers in relation to CT findings. METHODS: A total of 15 patients with 18 lesions of HCC underwent MCT and subsequent liver transplantation. Ex- planted livers were examined macro- and microscopically, and an evaluation of mitochondrial activity of ablated tissue was accomplished by using succinic dehydrogenase (SDH) stain in frozen sections. RESULTS: Of the 18 lesions, 16 were ablated completely and another two had residual tumor. The size of the ablated areas on CT scan corresponded to the macroscopic findings. His- tologically the area of ablation was rimmed by a palisading, histiocytic, giant cell, inflammatory reaction associated with fibrotic bands. Coagulative necrosis with faded nuclei and eosinophilic cytoplasm were the predominant findings in the ablated areas. There were also areas in which the tumor cells had cytoplasmic eosinophilia, but nuclei were present and the cells seemed to be viable. On the SDH stain of frozen tissue taken from the edge of the ablated area, SDH activity was negative in both necrotic and nonnecrotic ablated areas. CONCLUSIONS: Most of the treated areas after microwave ablation develop coagulative necrosis accompanied by a foreign body–like inflammatory reaction and fibrosis. Path- ologists need to be aware that after this form of therapy, portions of the tumor maintain their native morphological features as if the area is fixed, but their cellular activity is destroyed. (Am J Gastroenterol 2003;98:2052–2059. © 2003 by Am. Coll. of Gastroenterology) INTRODUCTION Hepatocellular carcinoma (HCC) is one of the most com- mon malignant neoplasms worldwide (1–3). Because of the increasing incidence of HCC complicating cirrhosis, local ablation therapy has become an important treatment option. For unresectable cases, various types of local ablation meth- ods are used. Techniques of local tumor ablation are cate- gorized into three groups: a) injectable substances such as ethanol (4), acetic acid (5), and hot saline (6); b) heating including radiofrequency (7, 8) and microwave (9, 10); and c) freezing (cryotherapy) (11). Microwave coagulation therapy (MCT) is a form of local ablation therapy by which tumors are destroyed by thermal coagulation (9, 10). The passage of microwaves into cells or other materials containing water results in the rotation of individual molecules. This rapid molecular rotation gener- ates and uniformly distributes heat, which is instantaneous and continuous until the radiation is stopped (9). MCT irradiation creates a necrotic area around the needle in a column or a round shape, depending on the type of needle used and the generating power (9, 10). This irradiated area is seen on CT scans with i.v. contrast as hypodense and nonenhanced (12). A few surgical and postmortem exami- nations have described the histological changes after MCT as consistent with necrosis (9, 10, 13, 14). However, there are no prospective detailed studies on histopathological evaluation after this therapy in humans. In our preliminary report (15), we found that MCT is clinically effective for ablation of HCC before liver transplantation but that the procedure may affect the tissue in such a way that parts of the tumor seem viable, even after it has been targeted by microwave. This study was conducted to describe the patho- logical changes in liver tumors after microwave irradiation in explanted liver specimens with corresponding radio- THE AMERICAN JOURNAL OF GASTROENTEROLOGY Vol. 98, No. 9, 2003 © 2003 by Am. Coll. of Gastroenterology ISSN 0002-9270/03/$30.00 Published by Elsevier Inc. doi:10.1016/S0002-9270(03)00553-7