Intraoperative Frozen-Section Evaluation Can Reduce Accuracy of Pathologic Assessment of Sentinel Nodes in Melanoma Patients

Ariyan and colleagues recently reported their experience with sentinel lymph node (SLN) biopsies from 263 patients with primary cutaneous melanoma. The SLNs were evaluated by intraoperative frozen section (F/S). Paraffin-embedded sections of the SLNs, stained with hematoxylin and eosin and immunohistochemically for S100 and HMB45, were assessed subsequently. Twentyeight patients (10.6%) had melanoma in a SLN, 23 (82%) of whom had tumor identified intraoperatively on F/S. The authors concluded that their series “attests to the reliability of frozen sections in identifying SLN harboring metastases.” Although we do not dispute that F/S examination of SLNs, when performed by a practiced and committed group such as that of Dr Aryian and his colleagues, can have an occasional role in some specialist melanoma treatment centers, we are concerned that use of this technique in other professional contexts can reduce the accuracy and reliability of the SLN biopsy procedure. Although the authors went to some length to suggest that their low yield of positive nodes (10.6%) compared with most large series (15% to 34%) reflected the high percentage of patients with thin primary tumors and fewer thick melanomas in their series, we cannot draw the same conclusion from the limited data presented. Indeed, the rate of positive SLNs for most groups of tumor thicknesses is lower than in the other series referenced in their article, and considerably lower than in a published (but uncited) report from the M D Anderson Cancer Center (Table 1). Unfortunately, the very limited clinicopathologic details provided prevent statistical comparison with other series. The inexplicably low rate of SLN positivity in the study raises the disturbing possibility that use of F/S might have led to a substantial number of false-negative SLNs resulting from loss of diagnostic tissue during the technical manipulations required for the F/S procedure, and/or that subsequent permanent section analysis may have been rendered more difficult by earlier freezing of some or all of the tissue. Our extensive combined experience with intraoperative F/S evaluation of SLNs, obtained during development of the modern SLN approach, was associated with a failure to identify melanoma micrometastases in 4% to 8% of ultimately positive patients. In view of this, and the practical considerations detailed below, we have long discontinued performing routine F/S examination on SLNs from melanoma patients. There is a major possibility that limited amounts of relatively localized diagnostic material in an SLN may be lost as a consequence of examining the node by F/S. First, substantial tissue is inevitably lost when “facing up” the frozen tissue block. Facing up is removal of tissue to obtain a section that contains all areas of the tissue. Melanoma micrometastases are most likely to lodge in the subcapsular region of an SLN and in adjacent and abutting lymphoid tissues around the central plane through the hilum and longest dimension of the node. It is absolutely critical that this portion of the SLN is included in the F/S and examined carefully. To obtain a full-face F/S that includes the subcapsular sinus region of the entire SLN, it is unavoidable that substantial nodal tissue is lost during facing up. Because it is difficult to make the cut surface of the SLN sit flat during freezing of the tissue, some discarded tissue inevitably derives from the critical subcapsular region. When a fresh SLN is bisected, the nodal capsule retracts and central tissue bulges from the cut surface. Metastases that are localized only in the central part of the node, as is occasionally observed, may also be discarded as a result of the facing-up procedure. Second, because tissue and cellular preservation is generally inferior in frozen