False negative sentinel lymph node biopsies in melanoma may result from deficiencies in nuclear medicine, surgery, or pathology

Objective: To investigate a cohort of melanoma patients with false negative (FN) sentinel node (SN) biopsies (SNBs) to identify the reasons for the FN result. Summary of Background Data: SNB is a highly efficient staging method in melanoma patients. However, with long-term follow-up FN SNB results of up to 25% have been reported. Methods: Seventy-four SNs from 33 patients found to have had an FN SNB were analyzed by reviewing the lymphoscintigraphy, surgical data, and histopathology, and by assessing nodal tissue using multimarker real-time quantitative reverse transcription (qRT) polymerase chain reaction, and antimony concentration measurements (as a marker of "true" SN status) using inductively coupled plasma mass spectroscopy. Results: Nine SNs (12%) from 9 patients (27%) had evidence of melanoma on histopathologic review. Twelve SNs (16%) from 10 patients (30%) were qRT(+). Four of these 12 SNs were positive on histopathology review and 8 were negative. Four patients (12%) were upstaged by qRT. Sixteen patients had their SNB histology, lymphoscintigraphy, and surgical data reviewed. Identifiable causes of the FN SNBs were not found after review of all modalities in 4 patients. SNs from all 4 patients had antimony levels indicative of an SN. Of the SNs evaluable by qRT, I was qRT(+) and 7 SNs from 2 patients were qRT(-). Conclusions: An FN SN can occur because of deficiencies in nuclear medicine, surgery, or pathology. qRT can detect "occult" metastatic melanoma in SNs that have been identified as negative by histopathology.