Risk Stratification and Clinical Characteristics of Patients with Late Recurrence of Melanoma (>10 Years)

Abstract

Background: Most patients with high-risk melanomas develop metastasis within the first few years after diagnosis. However, late recurrence of melanoma is seen in patients that metastasize more than 10 years after the primary diagnosis; a metastasis after 15 years is considered an ultra-late recurrence. It is critical to better understand the clinical and biological characteristics of this subset of melanoma patients in order to offer an individual treatment plan and prevent metastasis.

Methods: We retrospectively analyzed melanoma patients with recurrence ≥10 years after a primary diagnosis documented between 1993 and 2012 at the skin cancer center of the University Medical Center Leipzig, Germany. We conducted a comprehensive review of the literature and compared the results with our data. Available archived primary melanoma tissue was investigated with a seven-marker immunohistochemical signature (immunoprint^®) previously validated to reliably identify high-risk patients within stages IB-III.

Results: Out of 36 analyzed patients, a third metastasized ultra-late (≥15 years). The mean age at initial diagnosis was 51 years, with women being diagnosed comparatively younger than men. The largest proportion of patients with late recurrence had primary melanomas located on the trunk. The immunoprint^® signature of the available primary melanomas allowed the accurate prediction of a high risk. However, it is difficult to draw a definitive conclusion from the small number of cases that could be analyzed with immunoprint^® (n = 2) in this study. Apart from the primary tumor characteristics, the laboratory values at time of metastasis, comorbidities and outcome are also shown.

Conclusion: Late and ultra-late recurrent melanomas seem not to differ from melanomas in general, apart from a distinctly higher proportion of lower leg localizations in ultra-late recurrent melanomas. The immunoprint^® signature may help to identify high-risk primary tumors at the time of initial diagnosis. However, apart from the risk profile of the primary tumor, it seems that individual immune surveillance can control residual tumor cells for more than a decade. Advanced age and increasing comorbidities may contribute to a disturbed immunological balance.

Keywords: melanoma; metastasis; prognosis.

Figure 1

Immunohistochemical staining and risk score stratification Patient A. 1+: weak cytoplasmic staining or less than 20% of cell nuclei stained; 2+: moderate cytoplasmic staining or 21 to 50% of cell nuclei stained. COX-2 = Cyclooxygenase-2, PTEN = Phosphatase and Tensin Homolog, Bax = Bcl-2-associated X protein, MTAP = S-methyl-5′-thioadenosine phosphorylase.

Figure 2

Immunohistochemical staining and risk score stratification Patient B. 0% of cell nuclei stained; 1+: weak cytoplasmic staining or less than 20% of cell nuclei stained; 2+: moderate cytoplasmic staining or 21 to 50% of cell nuclei stained. COX-2 = Cyclooxygenase-2, PTEN = Phosphatase and Tensin Homolog, Bax = Bcl-2-associated X protein, MTAP = S-methyl-5′-thioadenosine phosphorylase.