Ultrasound-guided fine needle aspiration cytology as an addendum to sentinel lymph node biopsy can perfect the staging strategy in melanoma patients

Abstract

Background

Ultrasound guided fine needle aspiration cytology (US-guided FNAC) can identify microscopic involvement of lymph nodes as in breast cancer and avoid surgical sentinel node (SN). Its utility in melanoma patients is controversial and subject of this study.

Methods

Between 2001 and 2010 over 1000 stage I/II consecutive melanoma patients prospectively underwent US-FNAC prior to SN biopsy. All patients underwent lymphoscintigraphy prior to US-FNAC. The Berlin US morphology criteria: Peripheral perfusion (PP), loss of central echoes (LCE) and balloon shaped (BS) were registered. FNAC was performed in case of presence of any of these factors. SN tumour burden was measured according to the Rotterdam criteria. All patients underwent SN or lymph node dissection (LND) in case of positive FNAC.

Findings

Mean/median Breslow thickness was 2.58/1.57 mm. Mean/median follow-up was 56/53 months (1–132). SN positivity rate was 21%. US-FNAC Sensitivity was 71% (US only) and 51% (US-FNAC). Sensitivity of US-FNAC was highest for T4 (76%) and ulcerated melanomas (63%). PP, LCE and BS had sensitivity of 69%, 24% and 24% respectively. Sensitivity of US-FNAC increased with increasing SN tumour burden. PP was an early sign of metastasis (58% in <0.1 mm metastases). Threshold size of a metastasis for FNAC was 0.3 mm. Five-year survival correlated to US-FNAC status (95% in negative and 59% in positive).

Interpretation

Ultrasound guided FNAC (US-FNAC) according to the Berlin morphology criteria could correctly identify at least half of all tumour positive sentinel nodes, prior to the surgical SN procedure. Peripheral perfusion is an early sign of metastasis, which is very sensitive, but with lower positive predictive value (PPV). It is responsible for the sensitivity of the procedure. Balloon shape is a sign of advanced metastases, with lower sensitivity, but high PPV. US-FNAC sensitivity correlated with increasing T-stage, ulceration of the primary and increasing SN tumour burden. US-FNAC status accurately predicts survival.

Introduction

Over recent decades the incidence of malignant melanoma has been rising throughout Europe, the United States of America (USA) and Australia [1], [2], [3], [4], but mortality has remained virtually unchanged [4].

The most important prognostic factor of early stage melanomas (stage I/II) is lymph nodal status. Therefore, adequate staging of these patients is very important to be able to determine their prognosis [5], [6]. Worldwide, the sentinel node (SN) procedure has been accepted during the past two decades as the most accurate staging procedure [7]. Sentinel node biopsy (SNB) is a surgical procedure with a complication rate between 5% and 10% [8], [9]. In the absence of proof that SNB is associated with a survival benefit alternative methods to identify positive SNs are being considered. The diagnostic algorithm of other cancers, such as thyroid and breast cancer, already includes pre-operative ultrasound (US) and fine needle aspiration cytology (FNAC) and it is conceivable to apply this to melanomas.

Previously, we have demonstrated that ultrasound can identify the same node, which is later excised and considered the sentinel node with an accuracy of 79% [10]. Another study by our group has demonstrated that US-FNAC could identify up to 65% of all SN involvement preoperatively [11]. Finally, we have described specific US patterns, which were used to achieve such a high sensitivity, the so called Berlin morphology criteria, which include Peripheral perfusion (PP) as an early sign of involvement followed by loss of central echo (LCE) and balloon shape (BS) as signs of advanced involvement [12].

The number of evaluated patients and their mean and median follow-up have increased significantly. The aim of the current study was to evaluate our increased experience with this modern approach comprising the highest amount of US-FNAC of SNs and to test its application as a completion to SNB. This is especially en vogue with the background of the just now published results of the MSLT1 trial [13], which is literally a confirmation of the results in 2006 and the importance of the non-sentinel node status, which can be assessed by performing completion lymph node dissection (CLND) after a positive sentinel lymph node biopsy (SLNB) [14]; or even – as an alternative-directly after a positive FNAC of the sentinel node.