Cases highlight gray areas
Dermatologists and dermatopathologists can address the challenges of diagnosing and treating melanomas by using combination stains, a growing assortment of genetic tests and even new prognostic indicators, says Whitney A. High, M.D., J.D., M.Eng., an expert who spoke at the 2016 Fall Clinical Dermatology Conference (October 2016, Las Vegas).
"It has been asserted recently that the most mildly atypical nevi, and even moderately atypical nevi, are of clinical consequence," says Dr. High, an associate professor of dermatology and pathology at the University of Colorado School of Medicine in Denver.
While epidemiologic studies show an association between clinically or histologically dysplastic nevi (HDN) and melanoma, Dr. High explains, the odds of melanoma arising in any individual dysplastic nevus are low. In fact, a retrospective study showed that at a mean follow-up of 17.4 years, among 115 patients with HDN that extended to within 0.2 mm of a sample border, no melanomas occurred at the nevus location or at metastatic locations.1
However, critics of the aforementioned study noted that a narrow margin is not the same as a frankly involved margin, and that some challenging melanomas may be misidentified as HDN.2 In an editorial response to the study, these critics explained that "The gray zone of lesions with higher grade that extend to or closely approach a specimen margin is problematic, as one dermatopathologist's moderately atypical nevus may be another's melanoma."
Atypical Spitz nevi
Dr. High laments, "Perhaps dermatopathologists are not as good at distinguishing atypical nevi from melanoma as we think they are," and this may be another good reason to remove a concerning lesion. He shared images from a recent case, signed out by an experienced dermatopathologist without use of immunohistochemistry (IHC) or step levels as a "moderately atypical nevus," which proved to be melanoma. Retrospective analysis of the earlier sampling, using IHC and genetic testing, revealed the lesion was a melanoma, even from inception.
Dr. High addressed challenging spitzoid melanocytic proliferations and the emerging concept of "atypical Spitz tumors (ASTs)," which is a nosology used to differentiate these lesions of uncertain biologic potential from "classic" Spitz nevi, the latter being more common in children.
He presented a rapidly eruptive lesion on the leg of a healthy 17-year-old girl with no personal or family history of melanoma. IHC revealed evidence of spitzoid morphology and favorable expression of p16, but also some atypical features and dermal mitotic activity.
"Atypical Spitz tumors place the dermatopathologist in a real bind," Dr. High says. If a lesion is "overcalled" and treated as melanoma – considering that up to one-third of ASTs may have lymph node involvement, but without the same observed consequences of melanoma – surgical morbidity may quickly ensue. By the same token, if the lesion is "undercalled" when it is indeed a spitzoid melanoma, this can lead to medicolegal issues and great harm to the patient.
Dr. High next shared a case where an experienced dermatopathologist signed out a lesion located on the right neck of a 23-year-old as a "combined nevus, with features of a common nevus and Spitz nevus," only for the patient to develop right-sided cervical lymphadenopathy and lung metastases, clearly indicative of Spitzoid melanoma, three years later.
While admitting that in the past, and apparently correctly (per followup), he had himself diagnosed lesions as "combined nevi with spitzoid elements," Dr. High states that this was among "the most dangerous of creatures for dermatopathologists – great care must be taken."