Macfarlane et al. (1998) conducted a preoperative study in 23 patients with primary lesions larger than 1.5 mm who were scheduled for lymph node dissection with FDG-PET. In 13 of these patients therapeutic lymph node dissection (LND) of 14 node basins was performed, while 9 patients underwent elective LND of 10 node basins. With reference to the regional node basins, PET imaging demonstrated 11 true-positive, 10 true-negative, 2 false-negative, and 1 false-positive findings, resulting in an overall accuracy of 88%. It is important to note that PET failed to detect micrometastatic disease; nevertheless, Holder et al. (1998) suggested a role for FDG-PET as a first-line tool in the staging of melanoma. They examined 76 patients with stage II-IV malignant melanomas to compare FDG-PET and CT scanning. In 103 PET scans a sensitivity of 94.2% and a specificity of 83.3% were noted, as opposed to 55.3% and 84.4%, respectively, for CT.
Misinterpretations in the PET staging investigations occurred in cases with papillary carcinoma of the thyroid, bronchogenic carcinoma, inflamed epidermal cyst, Warthin's tumor of the parotid gland, surgical wound inflammation, leiomyoma of the uterus, suture granuloma, and endometriosis. Such lesions must be clinically excluded by topographical reflections and by the exclusion of inflammatory lesions, etc.
The 4 false-negative scans were thought to be due to small (<0.3-0.5 cm) and diffuse areas of melanoma without a mass effect. Several recent studies have demonstrated the limited value of anatomically based CT scans for evaluation of stage III patients.
In a prospective study, Tyler et al. (2000) performed 106 whole-body PET scans in 95 patients with clinically evident stage III lymph node(s) and/or in transit melanoma. In all, 234 areas were evaluated pathologically, 165 of which were confirmed by histological examinations to be melanoma. PET scanning identified 144 of the 165 areas of melanoma, yielding a sensitivity of 87.3%. The 21 areas of melanoma that were missed included 10 microscopic foci, 9 foci less than 1 cm in diameter, and 2 foci greater than 1 cm. There were 39 areas of increased PET activity that were not associated with malignancy, resulting in a positive predictive value of 78.6%. Of the 39 false-positive areas, 13 could be attributed to recent surgery, 3 to arthritis, 3 to infection, 2 to superficial phlebitis, 1 to a benign skin nevus, and 1 to a colonic polyp. However, by employing pertinent clinical information, the predictive value of a positive PET scan was improved to 90.6%. Thirty-six (19.7%) of the total of 183 abnormal areas scanned by PET proved to be unsuspected areas of metastatic disease. These findings led to a change in the planned clinical management of 16 patients following 106 PET scans (15.1%).
Eigtved et al. (2000) considered the value of FDG-PET in the detection of "silent metastases" from malignant melanomas by comparing FDG-PET findings and those obtained with conventional imaging methods. Thirty-eight patients with clinical stage II (local recurrence, in transit, and regional lymph node metastases) or stage III (metastases to other sites than those in stage II) were included in the study. For all foci, FDG-PET had a sensitivity of 97% and a specificity of 56%, as opposed to 62% and 22%, respectively, for the conventional imaging methods used. For intra-abdom-
inal foci, the sensitivity and specificity were 100% for both imaging approaches. However, corresponding figures for intrathoracic and pulmonary metastases were 100% and 33%, respectively. An important finding in this study was that 34% of patients would not have been staged correctly by conventional methods alone.
However, Krug et al. (2000) were not able to confirm such positive results for PET imaging. In a retrospective analysis of 94 melanoma patients, including 40 patients with evidence of lymphogen-ous and 42 with evidence of hematogenous metastasis, they found FDG-PET to be inferior to CT in the diagnosis of lung and liver metastases. In a meta-analysis of the 13 papers in the literature on detection of recurrent melanoma by FDG-PET, an overall sensitivity of 92% (95% confidence level 88.4%-95.8%) was calculated, together with an overall specificity of 90% (95% confidence level 83.3-96.1%) (Schwimmer et al. 2000). From the limited data available a directed change in management value of 22% was indicated for FDG-PET.
Overall, FDG-PET was found to be insensitive as an indicator of occult regional lymph node metastases in patients with melanoma, because of the small tumor volumes in this population (Wagner et al. 1999). In a prospective study the same authors included cutaneous melanoma with a Bres-low's depth greater than 1 mm (stage T2-4N0M0) or localized regional cutaneous recurrence (stage Tx,N2b,M0). Eighty-nine lymph node basins were evaluated by FDG-PET and sentinel node biopsy in 70 evaluable patients. Eighteen patients (25.7%) had lymph node metastases at the time of FDG-PET imaging: in 17 these were confirmed by sentinel node biopsy (24.3%) and in 1 by follow-up examination (1.4%). The sensitivity of sentinel node biopsy for detecting occult regional lymph node metastases was 94.4%, and the specificity was 100%. The sensitivity of FDG-PET was 16.7%, and its specificity 95.8%. These results clearly indicate that FDG-PET cannot help in the staging of regional nodes in patients with clinically localized melanoma. The inability of PET to identify microscopic disease suggests that it is of limited use in evaluating patients with stage I-II disease. Detection of brain metastases is also limited owing to the high glucose utilization of normal gray matter. Finally, small lung metastases may be detected with higher sensitivity by spiral CT of the chest.
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