University of Groningen Nodular Histologic Subtype and Ulceration are Tumor Factors Associated with High Risk of Recurrence in Sentinel Node-Negative Melanoma Patients Faut,

Background. Since its introduction, the sentinel lymph node biopsy (SLNB) has become the standard staging procedure in clinical node-negative melanoma patients. A negative SLNB, however, does not guarantee a recurrencefree survival. Insight into metastatic patterns and risk factors for recurrence in SLNB negative melanoma patients can provide patient tailored guidelines. Methods. Data concerning melanoma patients who underwent SLNB between 1996 and 2015 in a single center were prospectively collected. Cox regression analyses were used to determine variables associated with overall recurrence and distant first site of recurrence in SLNB-negative patients. Results. In 668 patients, SLNBs were performed between 1996 and 2015. Of these patients, 50.4 % were male and 49.6 % female with a median age of 55.2 (range 5.7–88.8) years. Median Breslow thickness was 2.2 (range 0.3–20) mm. The SLNB was positive in 27.8 % of patients. Recurrence rates were 53.2 % in SLNB-positive and 17.9 % in SLNB-negative patients (p\ 0.001). For SLNBnegative patients, the site of first recurrence was distant in 58.5 %. Melanoma located in the head and neck region (hazard ratio 4.88, p = 0.003) and increasing Breslow thickness (hazard ratio 1.15, p = 0.013) were predictive for distant first site of recurrence in SLNB-negative patients. SLNB-negative patients with a nodular melanoma and ulceration had a recurrence rate of 43.1 %; the site of recurrence was distant in 64 % of these patients. Conclusions. The recurrence rates of SLNB-negative nodular ulcerative melanoma patients approach those of SLNB-positive patients. Stringent follow-up is recommended in this subset of patients. Cutaneous melanoma mainly spreads via the lymphogenic route from the sentinel lymph nodes to the adherent lymph node basin. After decades of experience, we now know that in negative sentinel lymph node biopsy (SLNB), skip metastases are rare. Since its introduction in the early 1990s by Donald Morton, SLNB has become a widely accepted staging procedure and has become one of the most important prognostic tools in predicting outcome in cutaneous melanoma. At time of primary staging, approximately 20 % of melanoma patients are SLNB positive, with a false-negative rate less than 5 %. SLNB positivity is associated with several clinicopathologic characteristics, such as Breslow thickness, mitosis, and the presence of ulceration. The risk for recurrent disease is associated with this SLNB status, resulting in higher recurrence rates of up to 47 % in SLNBpositive patients and lower recurrence rates of 24 % in SLNB-negative patients. Some of these SLNB-negative patients have a distant first site of recurrence and even seem to skip the lymphogenic metastatic route. These patients with direct hematogenous recurrences may either have different clinicopathologic characteristics or more aggressive tumor biology. The Author(s) 2016. This article is published with open access at Springerlink.com First Received: 20 July 2016; Published Online: 19 September 2016 B. L. van Leeuwen, MD, PhD e-mail: b.l. van.leeuwen@umcg.nl Ann Surg Oncol (2017) 24:142–149 DOI 10.1245/s10434-016-5566-8