Clinical and histopathological correlations of melanoma in the molecular era

Abstract

In just over a decade the outlook for patients with melanoma has radically altered due to a comprehensive understanding of melanoma's genomic topography and the development of effective targeted and immune-based treatments.

Foundations of this progress were laid by pathological observations of “fatal black tumours with metastases” that span centuries. In the current molecular era, assessment of tissue specimens by pathologists continues to be central to understanding primary and metastatic melanoma and guiding management.

The humble light-microscopic evaluation of morphological features such as tumour thickness, derived from observations that melanoma progression is a function of tissue depth of invasion, remain critical to prognostication and surgical decision making. There is, however, a lack of rigorous study of variation of all prognostic parameters across tissue levels and features of residual disease in surgical beds.

At the other end of the spectrum, pathologists are faced with the promise, and challenges, of integrating complex genomic data with morphology to improve the diagnosis of melanocytic lesions. Such techniques offer a chance to improve over-diagnosis, under-diagnosis and misdiagnosis of melanoma and other similar tumours in daily practice. There is a need to understand the sensitivity and specificity of molecular tests, interpreted in the context of clinical and pathological data.

Finally, as promising oncogenic therapeutic targets continue to be identified, pathologists will play an increasing role in the use of tissue to guide treatment selection and its effectiveness. An understanding of the biological and quality aspects of emergent predictive biomarkers will be key to ensure patient tissues are used appropriately for such purposes and will ultimately influence patient outcomes.

The ensuing body of work evaluates novel aspects of established techniques and evolving technologies in the pathological evaluation of melanoma in our molecular era.