Track

Clinical Studies

Abstract

It is unclear whether histopathologic pigmentation is associated with melanoma prognosis independent of current staging criteria.  Prior studies suggest that amelanotic melanomas are associated with higher Breslow thickness (likely due to delayed diagnosis) but may be less likely to have lymph node metastasis. We investigated the associations of histopathologic melanin pigmentation (absent, light, or heavy) with clinicopathologic characteristics and 5-year risk of melanoma-specific death using multivariable logistic regression in an international, multicenter, case-control study designed to uncover novel prognostic features in stage IIA-IIID melanoma (n=829).  Cases died of melanoma within 5 years (n=343); controls survived for at least 5 years without evidence of recurrence (n=486).  Absent, light, and heavy melanin pigmentation was observed in 326 (39%), 381 (46%), and 122 (15%) of tumors, respectively.  Relative to absent pigmentation, light or heavy pigmentation was independently associated (each P<0.05) with lower T stage, brisk/non-brisk tumor infiltrating lymphocyte grade, and higher N stage (OR for N1-3 vs. N0 = 2.0, 95% CI: 1.41-2.86).  Among stage II melanomas, ORs for 5-year risk of melanoma death for light and heavy pigmentation were 1.64 (95% CI: 0.96-2.81) and 3.25 (95% CI: 1.56-6.81), respectively, relative to absent pigmentation, adjusted for age, sex, log of Breslow thickness and ulceration (P_trend=0.001).  No statistically significant survival association with pigmentation was found among stage III melanomas.  Our findings suggest that increased histopathologic melanin is associated with a significantly higher risk of melanoma-specific death for stage II melanoma, independent of other AJCC staging criteria, but not for stage III melanoma.