FDG PET/CT in staging of advanced epithelial ovarian cancer: Frequency of supradiaphragmatic lymph node metastasis challenges the traditional pattern of disease spread
Highlights
► Pretreatment FDG PET/CT finds more distant ovarian cancer metastasis than CT. ► We analyzed the anatomic distribution of supradiaphragmatic lymph node metastasis. ► Cardiophrenic and parasternal nodes are frequently involved in advanced disease.
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.
Section snippets
Patients
This study was conducted at the Department of Obstetrics and Gynecology, Turku University Hospital, Finland and was approved by the local Ethics committee (ClinicalTrials.gov Identifier: NCT01276574). All patients suspected of having advanced ovarian, fallopian, or peritoneal cancer due to physical examination, ultrasound, presence of ascites or increased CA 125 antigen level were eligible to participate in this clinical trial, which included FDG PET/CT imaging in the preoperative work-up and
Results
The preoperative FDG PET/CT suggested supradiaphragmatic LNMs in 20/30 patients, and seven of them had FIGO stage IV disease. The data are presented in Table 2. Three of the FIGO stage IV patients had other distant metastases (positive pleural cytology in two and multiple metastases in liver and umbilicus in one patient). Four patients were upstaged to FIGO stage IV due to supradiaphragmatic LNM detected in FDG PET/CT and confirmed microscopically by US-guided LN biopsy. Three abnormal axillary
Discussion
The preoperative FDG PET/CT indicated supradiaphragmatic LNM in 20/30 (67%) of the patients with FIGO stage IIC-IV EOC. This incidence is higher compared to that usually found when conventional imaging is utilized. In conventional imaging, lymph nodes are evaluated by size and structure. Ultrasound has inherent limitations for imaging the mediastinal lymph node groups. On cross-sectional imaging normal lymph nodes show homogenous appearance and well-defined borders. Most benign nodes have a
Conflict of interest statement
The authors declare that there are no conflicts of interest.
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