FDG PET/CT in staging of advanced epithelial ovarian cancer: Frequency of supradiaphragmatic lymph node metastasis challenges the traditional pattern of disease spread

Abstract

Objective

Epithelial ovarian cancer (EOC) spreads intra-abdominally and to the retroperitoneal lymph nodes. A greater number of distant metastases are revealed by ¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) compared to conventional imaging methods. We aimed to investigate the presence and anatomic distribution of supradiaphragmatic lymph node metastasis (LNM) detected with pretreatment FDG PET/CT.

Methods

Thirty women with advanced stage (IIC-IV) EOC were scanned with whole body contrast-enhanced FDG PET/CT prior to surgery/neoadjuvant chemotherapy. We performed PET/CT analysis qualitatively and quantitatively. Additionally, contrast-enhanced CT was analyzed blinded to PET/CT scan. Intra-abdominal dissemination was verified by surgery and histopathology. Metabolically active lymph nodes were biopsied when possible. The clinical characteristics of patients with and without supradiaphragmatic LNM were compared.

Results

In 20/30patients (67%) FDG PET/CT detected supradiaphragmatic LNM in one or more locations, whereas conventional CT found LNM in 10 patients (33%). Fourteen patients had parasternal, 14 cardiophrenic, 8 other mediastinal, 6 axillar, and 1 subclavian LNM. Microscopy of all four biopsied lymph nodes (three axillar and one subclavian) confirmed metastatic dissemination. The patients with supradiaphragmatic LNM had significantly more ascites (p < 0.01), higher CA 125 levels, and more frequent subdiaphragmal carcinomatosis (p < 0.03) compared to patients without supradiaphragmatic LNM in preoperative FDG PET/CT.

Conclusions

A significant number of patients with advanced EOC showed supradiaphragmatic LNM in pre-treatment PET/CT. Our findings suggest that the route of EOC cells from the peritoneal cavity to the lymphatic system permeates the diaphragm mainly to the cardiophrenic and continues to parasternal lymph nodes.

Introduction

Epithelial ovarian cancer (EOC) classically spreads intra-abdominally along with the peritoneal fluid circulation and via lymphatic channels to the retroperitoneal pelvic and para-aortic lymph nodes (LNs). Approximately two-thirds of cases are diagnosed in advanced stage. The FIGO staging system is surgical and based on histological confirmation of tumor lesions obtained during laparotomy [1]. The recommended preoperative work-up consists of abdominal computed tomography (CT) and chest X-ray, which serves to screen for pleural metastases. Extra-abdominal disease is considered infrequent, and the most common lesions that cause upstaging of the disease to FIGO stage IV are cytologically confirmed malignant pleural effusion and intraparenchymal liver metastases [2].

¹⁸F-fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) reveals metabolically active lesions that are often considered normal according to CT results. Previous studies on FDG PET/CT and EOC staging have demonstrated that PET/CT detects a greater number of distant metastases compared to CT alone [3], [4], [5]. Increasing evidence indicates that the involvement of supradiaphragmatic lymph nodes plays a role in advanced EOC dissemination. Nam et al. reported that distant lymph node metastasis (LNM) outside the pelvis and abdomen was the most common finding in radiologic staging by FDG PET/CT to classify stage III and IV disease [4]. Risum et al. evaluated preoperative FDG PET/CT on 66 advanced stage EOC patients (64 FIGO stage III and 2 stage IV). Twenty-four of these subjects had LNM above the diaphragm according to PET/CT [5]. The use of FDG PET/CT for patients with disease recurrence has also revealed isolated LNM in anatomically unorthodox sites such as the internal mammary chain [6].

The lymph nodes at the thoracic aspect of diaphragm were classified and divided into two groups by Rouviere in 1932 [7]. The lymphatic drainage from the anterior prepericardial group continues to the parasternal lymph nodes (also known as the internal mammary chain) whereas the lateral paracardiac group generally drains to the anterior mediastinal chain (Fig. 1). Several animal studies have suggested that the anterior route of lymph drainage from the peritoneal cavity is dominant compared to the posterior lymphatic pathway, which penetrates the diaphragm in aortic hiatus and drains further to the thoracic duct [8], [9] (Fig. 1). Since EOC often presents with carcinomatosis in the subdiaphragmal peritoneum and accumulation of ascites, the transdiaphragmal invasion of cancer cells to the lymphatic system seems to be a logical route for the spread of disease. FDG PET/CT is a potentially useful tool to study this hypothesis due to its superior sensitivity to detect distant LNM in EOC patients. Previous studies on staging FDG PET/CT have focused on the comparison of imaging methods [3], [4], [10] and LNM anatomic distribution has garnered little attention.

In the present study, we used preoperative FDG PET/CT to evaluate the lymph nodes above the diaphragm. We focused particularly on the anatomic distribution of metabolically active nodes in order to evaluate the hypothesis on transdiaphragmal EOC spread from peritoneal cavity to the thoracic lymphatics. In this prospective study of 30 patients with advanced EOC we discuss the lymphatic drainage of the peritoneal cavity to the supradiaphragmatic nodes, and the role of integrated PET/CT in thoracic lymph node imaging.