False‐negative sentinel node biopsy in melanoma

Abstract

The sentinel lymph node biopsy was a valuable addition to our diagnostic armamentarium. The procedure improves staging, results in better prognostic information that we can share with our patients, and increases the chance of survival in node-positive patients. But, there is room for further improvement. How well does the procedure do what it is supposed to do, and how does one examine this? The main question is the following: if there is a metastasis in the nodal basin, how often does the sentinel node biopsy reveal it? This is the sensitivity. And, how often is there a recurrence in the nodal basin in a situation that no node dissection was carried out because the sentinel node was tumorfree? If this happens, the procedure was false-negative. A falsenegative result means that a metastasis was present in the nodal basin, but the sentinel node biopsy did not find it. The false-negative rates that have been published in the past few years are not good. For instance, the false-negative rate in Morton's multicenter selective lymphadenectomy Trial now stands at 20% [1]. This means that one of every five patients with nodal involvement from melanoma is missed by the sentinel node procedure.There are many potential reasons for false-negative procedures. Perhaps the concept that melanoma disseminates through the lymphatic system in a step-wise fashion from one node to the next is not watertight. Rather than to disseminate in clusters, melanoma tends to disseminate as individual cells that perhaps can pass through a node or narrow collateral lymphatics and settle in the next node downstream. The lack of a commonly accepted definition of a sentinel node implies that one man's sentinel node is not necessarily somebody else's [2]. Analysis of 33 patients with a false-negative sentinel node biopsy at the Melanoma Institute Australia showed that there were process deficiencies in nuclear medicine for 31% of these cases, in pathology for 31%, and in surgery for 13% [3]. The lymph flow may be diverted to another node-a ''neo''sentinel node-because the original sentinel node is largely replaced by metastatic disease or because the afferent lymph vessel is blocked by in-transit metastases. Lymph drainage from a melanoma is variable. Reproducibility studies show drainage to another node in 12-15% of the patients in whom lymphoscintigraphy is done twice [4]. False-negativity has also been found to be associated with increasing age, lower Breslow thickness, higher Breslow thickness, ulceration, and less lymphovascular invasion. A complete regression of a metastasis in the sentinel node but not in a subsequent node may also be a potential cause for failure [3].How does the false-negative rate for melanoma compare to that for other cancers? A recent study of 153 patients who underwent sentinel lymph node biopsy for Merkel cell carcinoma revealed a false-negative rate of 15% [5]. The median duration of follow-up was 41 months. The false-negative rate was 19.2% in a series of 92 penile cancer patients with a median follow-up duration of...

Predictors of false negative sentinel lymph node biopsy in trunk and extremity melanoma

“…The current study focuses on of risk factors for failure of SLNB within this group, which is important as conventional 2‐dimensional lymphoscintigraphy remains common practice for these patients. The FNR of SLNB for melanoma is generally reported between 10% and 20%, with NPV ranging from 94% to 97% . While at first this FNR may appear high, FN SLNB is still a relatively uncommon event overall.…”

“…A low NPV indicates a relatively high likelihood of nodal recurrence despite negative SLNB. Reported NPVs range from 94% to 97% with 94.3% in MSLT‐1 …”

“…7 Previously reported FNRs from the larger cohorts range from 10% to 20%. 1,2,5,[8][9][10][11][12][13] The FNR in the Multicenter Selective Lymphadenectomy Trial (MSLT-1) was 19.3%. 14 The NPV (number of true negatives divided by total number of all negative SLNB) describes the likelihood that a patient with a negative SLNB will be truly free of regional disease in the future, which carries more importance in consultation postoperatively.…”

Analysis of Melanoma Recurrence Following a Negative Sentinel Lymph Node Biopsy

“…While the FN rate of SLNBx for cutaneous melanoma has been reported to broadly range from 1 to 32%, attention should be paid to the manner of calculation of this value [16]. The FN rate (FNR) for a SLNBx has been previously calculated as the number of patients who develop disease recurrence in the locally draining lymph node basin (FN) divided by the number of patients with an initially negative SLNBx, or as the number of patients who recur in the locally draining lymph node basin divided by the total number of patients with a positive SLNBx (true positive + FN) [17]. While, the former definition (FN/initially negative SLNBx) provides an estimate of the false omission rate (FOR or FN predictive value) of a SLNBx for cutaneous melanoma [12], the more accurate method of calculating the FNR is represented by the latter definition (FN/true positive+FN).…”

Implications of the MSLT-1 for sentinel lymph node biopsy in cutaneous head and neck melanoma

“…However, when the false negative rate is calculated by dividing the number of patients with a false negative sentinel lymph node biopsy by the total number of patients with positive regional lymph nodes (i.e. patients with false negative sentinel node biopsy plus patients with a positive sentinel node biopsy), as suggested in the literature [16], this percentage is considerably higher in the MSLT-1 trial: for all melanomas 19.4% vs. 4.8%, for intermediate thickness melanoma 20.3% vs. 4.0%, and for thick melanoma 17.4% vs. 6.9%. The negative predictive value of sentinel node biopsy was extremely high (94%, 95% and 90%, respectively), but this is mainly due to the high proportion of patients with metastasis free lymph nodes [3].…”