Distinct Clinicopathological and Prognostic Features of Thin Nodular Primary Melanomas: An International Study from 17 Centers

Abstract

Background Nodular melanoma (NM) is more likely to be fatal compared with other melanoma subtypes, an effect attributed to its greater Breslow thickness. Methods Clinicopathological features of NM and superficial spreading melanoma (SSM) diagnosed in 17 centers in Europe (n = 15), the United States, and Australia between 2006 and 2015, were analyzed by multivariable logistic regression analysis, with emphasis on thin (T1 ≤ 1.0 mm) melanomas. Cox analysis assessed melanoma-specific survival. All statistical tests were two sided. Results In all, 20 132 melanomas (NM: 5062, SSM: 15 070) were included. Compared with T1 SSM, T1 NM was less likely to have regression (odds ratio [OR] = 0.46, 95% confidence interval [CI] = 0.29 to 0.72) or nevus remnants histologically (OR = 0.60, 95% CI = 0.42 to 0.85), and more likely to have mitoses (OR = 1.97, 95% CI = 1.33 to 2.93) and regional metastasis (OR = 1.77, 95% CI = 1.02 to 3.05). T1 NM had a higher mitotic rate than T1 SSM (adjusted geometric mean = 2.2, 95% CI = 1.9 to 2.5 vs 1.6, 95% CI = 1.5 to 1.7 per mm2, P < .001). Cox multivariable analysis showed a higher risk for melanoma-specific death for NM compared with SSM for T1 (HR = 2.10, 95% CI = 1.24 to 3.56) and T2 melanomas (HR = 1.30, 95% CI = 1.01 to 1.68), and after accounting for center heterogeneity, the difference was statistically significant only for T1 (HR = 2.20, 95% CI = 1.28 to 3.78). The NM subtype did not confer increased risk within each stratum (among localized tumors or cases with regional metastasis). Conclusions T1 NM (compared with T1 SSM) was associated with a constellation of aggressive characteristics that may confer a worse prognosis. Our results indicate NM is a high-risk melanoma subtype that should be considered for inclusion in future prognostic classifications of melanoma.

Dermatoscopic features of thin (≤2 mm Breslow thickness) vs. thick (>2 mm Breslow thickness) nodular melanoma and predictors of nodular melanoma versus nodular non‐melanoma tumours: a multicentric collaborative study by the International Dermoscopy Society

“…In contrast, atypical network, regression structures and irregular streaks were rarely found in our overall sample of NM. The latter finding is consistent with pre-existing literature 8,10,22,23 and is explained by the fact that these features correspond to histopathologic alterations at the level of the dermo-epidermal junction, which are absent or minimal in NM. 11,24,25 The multivariate analysis revealed three important predictors of NM ≤2 mm Breslow thickness as compared to non-melanomas: dotted vessels, white shiny streaks/lines and irregular blue structureless area (Fig.…”

“…However, in line with previous publications, we found that an important proportion of NMs (up to 30%) remain symmetric in terms of dermatoscopic colours and structures. 2,[8][9][10]21,22 Irregular brown dots/globules, irregular blue structureless area, ulceration, white shiny blotches/strands and white shiny streaks were the most frequently encountered dermatoscopic structures in the group of thin NMs (Fig. 1).…”

The 2018 World Health Organization Classification of Cutaneous, Mucosal, and Uveal Melanoma: Detailed Analysis of 9 Distinct Subtypes Defined by Their Evolutionary Pathway

“…Because they are tumorigenic from close to their initiation, NMs present as rapidly growing lesions. Nodular melanomas have a worse prognosis, on the average, than other melanomas, but this difference disappears, perhaps not completely, 179 when multivariable analyses are done.…”

Phenotypic characterisation of immune cells associated with histological regression in cutaneous melanoma

“…Morphological evaluation of histological regression 13,14 Histological regression: definition and phases…”