Aim: To evaluate 18-fluoro-2-deoxyglucose (FDG) whole-body positron emission tomography/computed radiographic tomography (PET/CT) for lymph node and metastatic staging of patients with conjunctival melanoma.
Methods: Fourteen patients with T3 (n = 13) and T4 (n = 1) conjunctival melanoma (as defined in Chapter 42 of the AJCC staging manual) were staged for metastatic disease with PET/CT imaging with fusion. The patients had lymph node and clinical staging evaluations before PET/CT imaging. PET/CT images were studied for the presence and distribution of metastatic conjunctival melanoma (determined by standardised uptake values) and later confirmed by biopsy. MRI imaging was performed if abnormalities were noted on PET/CT images.
Results: Fourteen patients with conjunctival melanoma underwent PET/CT imaging. Seven were newly diagnosed (presurgical screening), and seven had undergone prior treatment (follow-up group). Only one patient with conjunctival melanoma (7.1%) was found to have metastatic disease on PET/CT imaging. Abnormal foci were found in the liver, lung, peritoneal cavity, lumbar spine as well as a supraclavicular node (T4N1M4). All liver function tests were normal. The mean length of follow-up after PET/CT imaging was 13 months (range 4–30 months).
Conclusions: PET/CT imaging did not reveal any regional or systemic metastasis among 14 patients with advanced, diffuse and multifocal disease.
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Conjunctival melanoma typically affects elderly, white individuals, and its incidence has been found to be increasing in the United States.1 These melanomas typically arise from a pre-existing nevus, primary acquired melanosis (PAM) or de novo. Folberg reported that 75% arise within pre-existing PAM.2 Therapeutic options for the treatment for conjunctival melanoma include primary surgical excision, excision combined with cryotherapy, radiotherapy and topical chemotherapy.3–6 Factors that influence prognosis for recurrence and metastatic disease include: the presence of multifocal tumours, mixed cell types, thickness greater than 4 mm, unfavourable tumour location (palpebral, forniceal, caruncle, corneal), prior tumour excision without adjuvant therapy, higher TNM grade and scleral extension.7 8
Patients are periodically monitored for local recurrence and metastatic disease. It has been reported in one study that 26% developed systemic metastases without regional lymph node involvement.9 Others have shown that regional lymph node metastases are found in 41% of patients, with the pre-auricular nodes most frequently involved.10 This is why research has focused on the utility of sentinel lymph node biopsy which is best performed prior to major surgical alteration of lymphatic drainage basins.9 10
PET/CT has been used for lymph node and metastatic staging of cutaneous melanoma, choroidal melanoma, systemic lymphoma, lung, breast and gastrointestinal malignancies.11 12 This study evaluates the use of PET/CT for local tumour imaging, preoperative staging and evaluations for metastatic conjunctival melanoma.
MATERIALS AND METHODS
In this series, 14 patients with conjunctival melanoma were evaluated with whole body PET/CT for detection of metastatic disease. Seven of these patients were newly diagnosed, and eight patients had previously undergone treatment with excision and adjuvant cryotherapy and/or chemotherapy (follow-up group). Patients underwent lymph node staging evaluations by clinical examinations, PET/CT and MRI imaging. Sentinel lymph node biopsies were not performed. Patients underwent subsequent computed radiographic tomography (CT) with contrast, magnetic resonance imaging (MRI) and fine-needle aspiration biopsy if abnormalities were noted on the PET/CT scan to aid in obtaining a histopathological confirmation of the diagnosis.
Patients were instructed to refrain from eating a carbohydrate-based dinner the previous night and to fast 4–6 h prior to injection of 18-fluoro-2-deoxyglucose (FDG) to diminish physiological glucose utilisation and to reduce insulin serum levels to baseline. Full-body PET/CT scans began at the top of the head and ended at the bottom of the feet.
The CT portion [General Electric Discovery ST, Piscataway, NJ with BGO (Bismuth Germanate) crystal] consisted of a multi-detector helical CT scanner. 18-Fluoro-2-deoxyglucose (FDG) was injected with a target dose of a 5 mCi. The dose was calculated by (weight (kg)×target dose (mCi)/70 kg).
The PET scan reconstructed the images on the fly and utilised the CT scan to correct for attenuation. Then, Xeleris workstation (General Electric software, Piscataway, NJ) was used to fuse and display the PET and CT images to produce the final images.
PET/CT image evaluation
The PET/CT images were studied for the presence of the local tumour, lymph node and distant metastases based on qualitative and quantitative analysis. Data were evaluated for areas of focally increased glucose uptake and by maximally standardised uptake values (SUV). Glucose uptake above levels of the surrounding tissue and a quantitative value above 2.5 SUV suggested malignancy. Distant metastases were determined on an organ-to-organ basis (figs 1–3).
False positives were determined by their location, symmetry and the patient’s medical history. Indeterminate lesions were subjected to further radiographic testing or biopsy.
Fourteen patients with conjunctival melanoma with a mean age of 66.6 years (range 30–94) were evaluated by whole-body PET/CT scan (table 1). According to the AJCC-UICC Classification, among the 14 patients with conjunctival melanoma, 13 had T3 tumours, and one patient had a T4 tumour.13
No patients screened with PET/CT prior to surgery were found to have regional or distant metastases. One patient (7.1%) in the follow-up group was found to have distant metastatic disease on PET/CT imaging. In this case, scans revealed increased FDG uptake in the nasal fossa (SUV 7.5) correlating with recurrent malignant melanoma. Metastases were also detected in the liver (SUV 9.6), pleural space (SUV 5), mediastinal lymph node (SUV>20), lungs, peritoneal cavity, lumbar spine (SUV 7) and right supraclavicular lymph node (SUV 6.6) (T3N1M3). Liver function tests were normal in this patient. MRI imaging confirmed the presence of nasal fossa and hepatic involvement.
None of the other 13 patients were found to have detectable local, regional or systemic involvement on PET/CT imaging.
PET/CT is a new imaging modality that combines the anatomic resolution of CT and the metabolic characterisation provided by PET. It has been used to assist in the diagnosis, staging and therapeutic monitoring of malignancies of the lung, breast, colon, lymph system and melanoma.11 12 Reinhardt and colleagues studied the diagnostic performance of whole body PET/CT imaging in 250 patients with cutaneous melanoma.14 They found that PET/CT imaging identified more visceral and nonvisceral metastases than with PET or CT alone. Treatment plans were changed based on PET/CT findings in 48% of patients. PET/CT has been compared with PET imaging alone and whole-body MRI imaging in the staging of malignancies.15 16 PET/CT imaging was found to be superior in lesion localisation and thereby to be of value in determining biopsy sites.15 When compared with whole-body MRI staging, PET/CT was found to be more valuable in TNM staging of tumours.16
PET/CT imaging has been found to be of value for staging and follow-up of patients with choroidal melanoma and orbital lymphoma.17–20 In evaluation of uveal melanoma, both hepatic and extrahepatic metastases were found. In those studies, more extrahepatic (primarily osseous) metastasis were uncovered with PET/CT.17–19
In this study, PET/CT was useful for imaging and staging of distant metastases in one patient with conjunctival melanoma. PET/CT did not reveal local lymph-node involvement or distant metastases in presurgical patients. Esmaeli and others have recommended sentinel lymph node biopsies as a method of identifying occult regional metastatic disease at an early stage.9 However, up to 26% of patients were found to have distant metastatic disease without local lymph-node involvement in another study.10
Our study showed that current methods of FDG PET/CT did not reveal metastatic disease in patients with diffuse, multifocal (T3) conjunctival melanoma. This conclusion is based on the reports that more than 25% of patients with such tumours will develop metastatic disease (despite successful local control). However, it is this group of patients who are at greatest risk and should be periodically evaluated for systemic metastases.
In our study, PET/CT played a limited role in the T and N staging of conjunctival melanoma. In our study, the role of PET/CT imaging in the intitial screening of patients with conjunctival melanoma was limited, but it may be of value in the follow-up and restaging of these patients. A larger, multi-centre, comparative study is warranted to evaluate the potential role of PET/CT imaging in the TNM staging of conjunctival melanoma.
Funding: Supported by The EyeCare Foundation, Inc., and Research to Prevent Blindness, New York City, New York, NY, USA.
Competing interests: The authors have no proprietary interest in the products mentioned in this study.
Ethics approval: This study was conducted in accordance with the Tenets of Helsinki and the United States Health Insurance Privacy and Accountability Act of 1996.
Patient consent: Standard radiology-related informed consents were obtained from all patients before PET/CT imaging.
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