Primary Tumor Thickness as a Prognostic Factor in Merkel Cell Carcinoma: The Next Big Thing?

Abstract

Fifty years ago, there was a cutaneous malignancy that was rapidly increasing in incidence and beginning to receive serious scrutiny by surgical oncologists, dermatopathologists, and dermatologists. It nearly always presented at a locally advanced stage with an expectation of a poor outcome. Prognostic factors were poorly understood, so the occasional patient with advanced disease who defied expectations and survived long-term was a notable and mysterious case. Controversy surrounded the management of the regional lymph nodes, despite recognition that they were frequently the first (and sometimes the only) site of metastatic involvement—in part because of pessimism that distant dissemination of tumor had already occurred and hence treating the nodes was a futile effort. The name of this malignancy? Melanoma. So what changed over the past 5 decades? One of the most significant advances in understanding the prognosis of melanoma came in 1969, when Wallace Clark and colleagues called attention to the prognostic significance of the level of tumor invasion into the dermis. Soon thereafter, Alexander Breslow introduced the micrometer measurement of tumor thickness that now bears his name. Importantly, Breslow showed that tumor thickness was a better prognostic marker than Clark’s levels of invasion or measured tumor diameter, while noting that ‘‘in general all measurements of tumor size increased with the stage of invasion, but there was a great deal of overlap.’’ Unfortunately, in 1970, relatively few melanomas were diagnosed at the earliest stages of thickness and invasion that portended a favorable prognosis. A second transformational event was the introduction of easily understandable and applicable diagnostic criteria for identifying pigmented lesions suspicious for representing early melanoma (and hence requiring biopsy)—the ABCD criteria. Increasingly, melanomas were diagnosed at an early stage where the expectation was for an excellent outcome, and those few patients who developed distant disease were an exception to the norm. Indeed, outcomes quickly improved to the point that aggressive surgical management of the regional nodes became controversial because of the perception that most patients would not have evidence of metastasis and hence were being subjected to morbidity without prospect of benefit. Of course, this set the stage for the third revolutionary development—sentinel lymph node biopsy. At last, melanomas with early dissemination to the regional nodes could be reliably identified and treated, and the number of cases with truly unexpected outcomes dramatically decreased. Even with recognizing how far we have come in this disease, thick melanomas are still a major challenge, especially in elderly patients. Once a melanoma exceeds 4 mm in thickness, while ulceration and sentinel node status retain prognostic importance, our ability to predict which patients will do well or poorly is fairly limited. Nonetheless, the recognition of the clinical significance of that 4 mm thickness cutoff has unequivocally improved our understanding of the natural history of melanoma. Today, there is another cutaneous malignancy, Merkel cell carcinoma, that is rapidly increasing in incidence and beginning to receive serious scrutiny by surgical oncologists, dermatopathologists, and dermatologists. It nearly always presents at a locally advanced stage, usually in This is an Editorial commentary regarding the article by Lim et al. doi:10.1245/s10434-012-2509-x.