Identification of histological features associated with metastatic potential in thin (<1.0 mm) cutaneous melanoma with metastases. A study on behalf of the EORTC Melanoma Group

Abstract

Contrary to expectations, a small number of thin (<1 mm) melanomas do metastasize. This collaborative study was performed in an attempt to identify the morphological basis of such aggressive behaviour. Regression was expected to be the explanation for the lack of thickness in some cases. Whether a vertical growth phase (VGP) was present in the remainder was carefully assessed. A pilot study had identified two other patterns associated with metastasis in thin melanomas. These were termed 'junctional expansion nodules' and 'melanomatous follicular invasion'. Both were seen in the absence of other dermal invasion. These two patterns were included in the study, which comprised 54 cases and 56 controls, which were thin melanomas which had not metastasized 5 years after excision. Regression was present in 50% of test cases (30.4% in controls, p=0.036) and VGP was present in 59.3% of cases and 48.2% of controls. The thinnest metastasizing melanoma without regression was 0.27 mm. Eight (14.8%) cases, however, had metastasized but showed neither regression nor VGP; seven of these showed a junctional expansion nodule, present in only three controls (p=0.016). Five of these seven also showed melanomatous follicular invasion. One of these five showed this follicular involvement without a junctional nodule. Melanomatous follicular invasion was not seen in the control cases (p=0.012). Mitoses were seen in the VGP of both test and control cases, but high counts (>3 per mm(2)) were much more common in the metastasizing lesions (p=0.007). These findings support the idea that in most cases, regression and/or a VGP are required for metastasis to occur. However, a small number of thin melanomas without these features, as conventionally described, still metastasize. This implies that VGP may require redefinition and that junctional expansion nodules and melanomatous follicular invasion may be variants of VGP.