Melanocytic lesions: A review of the troublemakers

Victoria, British Columbia - In the United States, the rate of malignant melanoma (MM) is rising faster than that of any other cancer.

Between 1935 and 2001, the lifetime risk of development surged from 1 in 1,500 to 1 in 71, and it is projected to be 1 in 50 in 2010. Skin specialists are therefore faced with the demanding task of predicting biological behavior of melanocytic lesions, and must strive to timely diagnose and treat these lesions.

"Dermatologists faced with this difficult task find themselves in a labyrinth of contested nomenclature," said James E. Fitzpatrick, M.D., professor in the department of dermatology at the University of Colorado Health and Sciences Center, during the 79th Annual Canadian Dermatology Association Conference here.

Disputed issuePerhaps the most disputed issue in the histology of melanocytic lesions is the atypical nevus.

This lesion goes by many different names, including dysplastic nevus, Clark's nevus and nevus with cytologic atypia and architectural disorder - the latter recommended and preferred by the NIH Consensus Panel.

Another point of dispute is the clinical definition of "dysplastic nevus syndrome," formerly known as the B-K mole syndrome. Here, the NIH Consensus Panel recommends the term "familial atypical moles and malignant melanoma syndrome" (FAMMM syndrome), but again, this is not universally accepted.

Dr. Fitzpatrick affirms that "the importance of atypical nevi is that in 10 studies of patients with malignant melanoma, anywhere from 6.6 percent to 70.3 percent of biopsies demonstrated histologic evidence of contiguous dysplastic nevi."

He cited an ongoing study of his, where 15 percent of melanomas arise in association with benign nevi and 16 percent arise in association with an atypical nevus.

In patients with classic syndrome (B-K mole syndrome, dysplastic nevus syndrome, familial atypical moles), the incidence of MM approaches 100 percent. The incidence of dysplastic nevi in the United States lies between 1.8 percent and 4.9 percent.

"The histologic diagnosis of the atypical nevus and separation from benign nevi at one end of the spectrum and melanoma at the other end of the spectrum is sometimes a difficult judgment, especially since so many of the findings are subjective," Dr. Fitzpatrick says.

Panel recommendationsThe NIH Consensus Panel recommends that atypical nevi should be graded according to their degree of cytological atypia: mild, moderate or severe, which seems easy to say but, practically, harder to do, and it is even harder to achieve a consistent reproducibility. Therefore, Dr. Fitzpatrick believes it is reasonable for clinicians to surgically remove any clinically solitary dysplastic nevi, and that patients with sporadic or familial dysplastic nevi should have the most atypical looking nevi removed and then followed.

Dr. Fitzpatrick dismisses any notion that atypical nevi (dysplastic nevi) do not exist and points to the extensive epidemiological and biological data that validates their existence including: Cyclin D1 expression, microsatellite instability at 1p and 9p, loss of heterozygosity and microsatellite instability, expression of 12-lipoxygenase, and expression of versican and mel-CSPG.

"Those who argue that atypical nevi are a marker for the propensity for the development of melanoma are totally ignoring the data," he says. "Dysplastic nevi by every measurable epidemiological, pathological, genetic and molecular parameter are more likely than either normal skin or benign nevi to develop into malignant melanoma," Dr. Fitzpatrick asserts.

One of the most difficult problems in dermatopathology are Spitz nevi (also known as benign juvenile melanoma, and spindle and epithelioid nevus).This clinically benign but histologically malignant neoplasm can spread to sentinel or regional lymph nodes (malignant Spitz nevus), causing bewilderment to dermatologists, pathologists and melanoma oncologists.