Assessment of pathological features to improve accuracy of diagnosis, classification and prognosis of primary and metastatic melanoma

Abstract

The gold standard for the diagnosis of melanocytic lesions and provision of vital prognostic information for primary melanoma, is microscopic examination by a trained pathologist. When interpreting difficult to diagnose primary melanocytic lesions the challenges for the reporting pathologist include subjective diagnostic criteria leading to significant interobserver variability in diagnosis, definitive diagnosis when interpreting an initial partial diagnostic biopsy and, more recently, how to integrate the complex genomic information available from ancillary testing with the morphological clues to diagnosis which have been accumulated and learnt over the last 50 or so years by pathologists. Once the diagnosis is made the pathologist’s role is to report key prognostic information to ensure the lesion is appropriately classified, staged and managed.

Traditionally pathologists role in the reporting of patients with advanced (macroscopically detectable metastatic melanoma) has been minimal, usually limited to the initial diagnosis and identification of further adverse features including tumour bulk and extranodal extension4. However, the recent development of effective systemic therapies, particularly immune checkpoint inhibitors, have been tested with proven superior survival in the neoadjuvant setting compared with the adjuvant setting5, 6. This provides the opportunity for pathologists to provide crucial information when analysing these neoadjuvant specimens to assist in predicting clinical outcomes in patients and guide further management.

The ensuing body of work studies novel ways in which pathological assessment, through morphological and immunohistochemical techniques, of both primary melanocytic lesions and neoadjuvant specimens in metastatic melanoma can lead to more appropriate management and improved patient outcomes.