Regression in primary cutaneous melanoma: etiopathogenesis and clinical significance

Abstract

Though not required currently for staging, regression is a histopathologic parameter typically reported upon diagnosis of an invasive primary cutaneous melanoma. The studies examining the prognostic significance of regression in patient outcome have yielded controversial findings; likely because the definition and assessment of regression have not been consistent, in addition to subjectivity of pathologists' interpretation. Regression is histologically characterized by variable decrease in the number of melanoma cells accompanied by the presence of a host response consisting of dermal fibrosis, inflammatory infiltrate, melanophages, ectatic blood vessels, epidermal attenuation, and/or apoptosis of keratinocytes or melanocytes; the relative extent of these features depends on the stage of the regression. However, the magnitudes to which these individual changes must be present to meet the threshold of histologic regression have not been well defined or agreed upon, and thus, the definition and classification of histologic regression in melanoma varies considerably among institutions and even among individual pathologists. In order to determine the clinical significance of histologic analysis of regression, there is a compelling need for a universal scheme to objectively define and assess histologic regression in primary cutaneous melanoma, so that the biologic and prognostic significance of this process may be completely understood.

Clinicopathologically problematic melanocytic tumors: a case-based review

“…Spontaneous regression is a relatively common event in melanoma, characterized by an overall incidence that ranges from 10% to 35%. The biological mechanism behind regression has not been completely elucidated; however, it seems that it is mainly attributed to host-immune-mediated responses that ultimately result in partial or complete disappearance of the neoplasm [ 5 , 6 ].…”

Advances in Proteomic Techniques for Cytokine Analysis: Focus on Melanoma Research

“…Melanoma regression occurs probably in 3–5% of tumours [ 15 , 16 ], although regression rates up to 50% have been documented [ 17 ]. Such a large variation in reported regression prevalence may be caused by various evaluation criteria used among studies [ 18 ]. Nonetheless, regression occurs more frequently in early stages of tumours (Breslow’s thickness bellow 1.5 mm) [ 15 ] and is very rare (0.23%) in melanoma metastases [ 17 ].…”

“…Spontaneous regression is frequently accompanied by tumour infiltration by CD8+ and also CD4+ T-cells [ 18 ] and vitiligo, a hypopigmented skin lesion, which may be associated with an antitumour response to melanocytes [ 19 ]. Interestingly, in patients with multiple asynchronous melanomas, the incidence of spontaneous regression was higher in successive melanomas compared to primary tumour, suggesting an increased anti-cancer immunity evoked by the primary lesion [ 20 ].…”

A diagnostic autoantibody signature for primary cutaneous melanoma

“…The inclusion of previously identified melanoma or cancer associated biomarkers such as VEGFb, p53, BAD, KIT MITF and MLANA [ 22 ] in the top 139 antigen list, further highlights the validity of our findings. Histologic tumour regression status significantly affected the number of positive AAb responses but although the correlation between regression and patient outcome has been investigated extensively, whether the presence of histologic regression features have a good or bad prognostic significance remains controversial and is to be elucidated [ 34 ]. Autoantibody responses were not affected by any other patient characteristic or tumour feature.…”