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First published online October 16, 2008, 10.2967/jnumed.108.055350
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Journal of Nuclear Medicine Vol. 49 No. 11 1769-1775
© 2008 by Society of Nuclear Medicine
doi: 10.2967/jnumed.108.055350

Clinical Investigation

Optimal Detection of Sentinel Lymph Node Metastases by Intraoperative Radioactive Threshold and Molecular Analysis in Patients with Melanoma

Gianpiero Manca1, Antonella Romanini2, Daniela Pellegrino1, Elisa Borsò1, Marianna Rondini2, Cinzia Orlandini2, Vanna Zucchi3, Francesco Pasqualetti4 and Giuliano Mariani1

1 Regional Center of Nuclear Medicine, University of Pisa Medical School, Pisa, Italy; 2 Division of Medical Oncology, University Hospital, Pisa, Italy; 3 Pathology Unit, General Hospital, Livorno, Italy; and 4 Division of Radiotherapy, University Hospital, Pisa, Italy

Correspondence: For correspondence or reprints contact: Gianpiero Manca, Regional Center of Nuclear Medicine, University of Pisa Medical School, Via Roma, 67 I-56126 Pisa, Italy. E-mail: g.manca{at}med.unipi.it

The aim of this study was to optimize a protocol for radioguided biopsy of the sentinel lymph node (SLN) in patients with melanoma. The protocol was based on a combination of ex vivo counting of the nodes detected intraoperatively and analysis of the harvested nodes by hematoxylin and eosin staining plus immunohistochemistry (conventional histopathology [PATH]) and by molecular biology (reverse-transcriptase polymerase chain reaction [RT-PCR]). Methods: A total of 124 patients with primary clinical stage I–II (according to the American Joint Committee on Cancer) cutaneous melanoma underwent successful radioguided SLN biopsy. SLNs harvested for analysis included any additional nodes whose ex vivo counting rate exceeded 20% of the hottest node. All removed SLNs were examined by conventional PATH and with RT-PCR analysis for the expression of messenger RNA for tyrosinase and the melanoma antigens recognized by T cells. Complete lymph node dissection (CLND) was performed only in the case of SLN metastasis detected by PATH. Different combinations of the intraoperative parameters (only the hottest node and all nodes harvested) and of analysis (PATH and RT-PCR) were tested as predictors of clinical outcome on the basis of long-term follow-up (12–81 mo; median, 55 mo). Results: A total of 197 SLNs were harvested, 41 of which harbored metastasis as detected by RT-PCR analysis; PATH detected metastasis in only 24 of 41 metastatic SLNs. In 5 of 41 instances, metastasis was not in the hottest SLN. The main factor determining correct classification of the SLN status was RT-PCR, which significantly improved detection of metastasis, even if applied only to the hottest node (P < 0.0001 vs. PATH analysis of either the hottest SLN or all nodes above the 20% threshold). Metastatic disease recurred locally in 5 patients who had not undergone CLND; RT-PCR analysis showed metastasis in 4 of these patients. The false-negative rate of SLN biopsy progressively decreased when applying PATH only to the hottest node (32.1%), additional RT-PCR to the hottest node (21.4%), PATH to all nodes (17.9%), and RT-PCR to all nodes (3.6%, P = 0.015 vs. PATH analysis of only the hottest SLN). Conclusion: On the basis of long-term follow-up (the gold standard for final clinical outcome of SLN biopsy), both 20% threshold and RT-PCR analysis should be applied for optimal detection of nodal metastases in patients with melanoma.

Key Words: malignant cutaneous melanoma • radioguided sentinel lymph node biopsy • intraoperative ex-vivo counting • radioactive threshold • molecular analysis • clinical outcome

COPYRIGHT © 2008 by the Society of Nuclear Medicine, Inc.


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