Patterns of Histological Alteration and Their Clinical Significance in Colorectal Liver Metastases Following Preoperative Chemotherapy
F Bao, J Park, D Klimstra, P Mastrodomenico, N Katabi, E Vakiani, L Tang, M D'Angelica, J Shia. Memorial Sloan-Kettering Cancer Center, NY
Background: An increasing number of patients with colorectal liver metastases (CRLM) undergoing surgical resection are being treated with preoperative chemotherapy regimens combining 5-fluorouracil, oxaliplatin, and/or irinotecan, with a resultant improved survival. This neoadjuvant approach presents a unique type of liver resection specimen in which the metastatic carcinoma is altered by the preoperative chemotherapy. The histopathological patterns and their clinical significance in such specimens have not been well characterized.
Design: Detailed histological characteristics, including fibrosis, necrosis, mucin pools, and viable tumor cells, were qualitatively and semi-quantitatively analyzed in 94 CRLM resection specimens that received 5-fluorouracil, oxaliplatin, and/or irinotecan-based preoperative chemotherapy. The histological findings were then correlated with the patient's clinical features and survival.
Results: In these CRLM specimens, the dominant histological pattern of non-viable tumor component in the lesion was necrosis (34% with >50% necrosis), followed by fibrosis (11% with >50% fibrosis) and acellular mucin (4% with >50% mucin pools). Tumors with extensive fibrosis tended to have no or only small amount of necrosis. The viable carcinoma had the conventional gland-forming colorectal carcinoma histology in the majority of the cases. Cellular alterations with features of neuroendocrine differentiation as seen in irradiated rectal carcinomas were observed in some cases with advanced CR. Over all, 6 (6%) had no residual viable tumor, and 18 (19%) had <30% viable tumor. With a median follow-up of 35.7 months, residual viable tumor <30%, and fibrosis >25% significantly correlated with a better overall survival (p=0.002 and 0.04 respectively), whereas necrosis alone did not (p=0.8).
Conclusions: This study provides a detailed morphological description of post-chemotherapy colorectal liver metastasis. These tumors show a histological pattern similar to the pattern seen in post-chemoradiation rectal carcinomas in some aspects (such as tumor fibrosis and neuroendocrine differentiation), but not in others (more necrosis in liver metastasis). The correlation of tumor fibrosis, but not necrosis, with patients' outcome suggests that tumor fibrosis is a more reliable histologic indicator for good tumor response to preoperative chemotherapy, and can potentially serve as a prognostic factor, in such colorectal liver metastasis patients.
Category: Liver & Pancreas
Tuesday, March 10, 2009 9:30 AM
Poster Session III # 179, Tuesday Morning