Thick primary melanoma has a heterogeneous tumor biology: an institutional series

Abstract

BackgroundThick melanomas (TM) ≥4 mm have a high risk for nodal and distant metastases. Optimal surgical management, prognostic significance of sentinel node biopsy (SLNB), and benefits of interferon (IFN) for these patients are unclear. As a continuum of increasing tumor thickness is placed into a single TM group, differences in biologic and clinical behavior may be lost. The purpose of this study was to better characterize the diverse biology in TM, including the value of increasing thickness and nodal status information, potentially identifying high risk TM subgroups that may warrant more aggressive treatment/follow up.Methods155 consecutive TM patients treated at a single institution between 1971 and 2007 were retrospectively reviewed. Patient, disease and treatment features were analyzed with respect to disease-free (DFS) and overall survival (OS).ResultsMedian patient age was 66 years and 68% of patients were men. The trunk was the most common TM location (35%), followed by the head and neck (29%) and lower extremities (20%). Median thickness was 6 mm and 61% were ulcerated. 6% patients had stage IV disease, 12% had clinical nodal metastases. Clinically negative lymph node basins were treated by observation (22 patients - 15.4%), elective lymph node dissection (ELND) (24 patients - 17.6%) or SLNB (91 patients - 67%). 75% of ELND's and 53% of SLNB's were positive. Completion node dissection was performed in 38 SLNB+ patients and 22% had additional positive nodes. 17% of the study patients received IFN. At median follow up of 26 months, 5 year DFS and OS were 42% and 43.6%. For SLNB positive vs negative, median DFS were 22 vs 111 months (p = 0.006) and median OS were 41 vs 111 months (p = 0.006). When stratified by tumor thickness ≤ vs > 6 mm, 5 year DFS was 58.3% vs 20% (p < 0.0001) and OS was 62% vs 20% (P < 0.0001). IFN had no impact on DFS or OS (p = 0.98 and 0.8 respectively).ConclusionWithin the high risk group of patients with TM, cases with tumor thickness > 6 mm or a positive SLNB had a significantly worse DFS and OS (p < .0001, <.0001 and .006, .006).

Sentinel Lymph Node Biopsy in Patients with Thick Primary Cutaneous Melanoma: Patterns of Use and Underuse Utilizing a Population-Based Model

“…This is higher than the 19.5% underuse rate reported by Meguerditchian et al Most in an institutional review of 113 similar patients [16]. There are several possible explanations for this discrepancy.…”

The International Classification of Diseases for Oncology Integrated with the Melanoma Histogenetic Model

“…The unique exception to this is represented by nodular melanoma, in which either RGP is rapidly overrun by VGP or the tumour arises directly from dermal melanocytes [6]. Today, the Breslow depth remains the single most important prognostic factor for clinically localised primary melanoma -it allows the identification of melanoma as ultra-thin (≤ 0.5 mm), thin (≤ 1 mm), thick (> 1 mm) or ultra-thick (> 6 mm) [7,8]. The systematic application of the histogenetic model to the Breslow depth explains the debated reason why some thin melanoma behave aggressively, because they possess an early tumorigenic VGP inside them [9].…”

Prognostic Value of Sentinel Lymph Node Biopsy Compared with that of Breslow Thickness: Implications for Informed Consent in Patients with Invasive Melanoma

“…Data were lacking in both of the medium-thickness groups (1-2 and 2-4 mm) to perform reliable statistical analysis, and thus the value of SLNB in these groups is less clear. We did not control for patients receiving adjuvant treatment in the instance of SLN positivity (therapeutic lymph node dissection and systemic therapy such as interferon), so any effect these interventions might have were not accounted for in Goppner, 2011 11 Bedrosian et al, 12 Bleicher et al, 14 Cecchi et al, 17 Herschko et al, 25 Nahabedian et al, 29 Ranieri et al, 31 Vermeeren et al, 36 Wong et al 39 1 15 Essner et al, 20 Gajdos et al, 21 Gershenwald et al, 22 Gutzmer et al, 24 Scoggins et al, 33 Vuylsteke et al 38 2B (weak recommendation, low-quality evidence) B Survival advantage exists for SLNÀ patients; actual importance of survival difference must be considered for patients individually Belli et al, 13 Cecchi et al, 16 Cherpelis et al, 18 Curaco et al, 20 Goppner et al, 23 Kettlewell et al, 26 Meguerditchian et al, 28 Nowecki et al, 30 Schachter et al, 32 Thompson and Shaw, 35 Vermeeren 37 SLNB, sentinel lymph node biopsy. *According to criteria by Robinson et al, 43 and Ebell et al 44 .…”