Melanoma indicators elusive

Kauai, Hawaii - Based on a review of recent articles about immunological markers ranging from growth and transcription factors to proliferation and adhesion molecules, histologic evaluation remains the most valuable feature in evaluation of melanomas.

"As the incidence of melanoma increases every year, we continuously search for new parameters that allow us to formulate a more precise diagnosis for patients," says David A. Mehregan, lab director, Pinkus Dermatopathology Laboratory, Monroe, Mich. "We like to be able to give the clinician some indication of what the prognosis is for their patient - is this a serious melanoma, is there potential for metastasis, or could this be less aggressive melanoma?"

Attempting to answer such questions, some researchers have considered the influence of blood and lymphatic vessels.

Other researchers have analyzed a wide variety of immunohistochemical markers as tools for both diagnosing malignant melanomas and assessing patients' prognoses (de Wit et al. Histopathology 2004(44):517-541; Lomuto et al. J Eur Acad Dermatol Venereol. 2004 May;18(3):291-300. ).

Dermatopathologists divide such markers into categories including cell adhesion molecule markers, proliferation markers, cell cycle regulators and immunoregulators. Each category includes several markers. Markers in the cell adhesion class, for example, include CD-44 and neural cell adhesion molecules. The classic proliferation markers are proliferating cell nuclear antigen (PCNA) and MIB-1.

"Unfortunately," Dr. Mehregan says, "there's no particular marker out there right now that helps us determine if a lesion is benign versus malignant, or provides a consistent indicator for the prognosis of a patient. The problem is, one institution will do a study with a new marker and that study will show it to be a very good prognostic indicator. Then another institution will look at that same marker, and it will conclude that the marker isn't helpful in determining prognosis. A lot of that has to do with the staining technique, the case selection and the length of follow-up times. Often when we're comparing different studies, it's an apples-to-oranges comparison."

One exception to this situation is a recent University of Michigan study. Rather than gathering patients from several different institutions, its authors evaluated 429 of their own patients who underwent SLN biopsies. Researchers considered histological factors, as well as patient age, lesion location and ulceration, to determine if they could use these characteristics to predict whether patients had a metastasis to the lymph node.

"You don't see a lot of large studies from one institution. That makes it very easy because you don't have to worry about differences between programs or studies. It's all done by one set of physicians, so there's no potential variation in the reading of the slides. Still, they found that when we look at melanomas, probably the most significant factor is the Breslow depth," Dr. Mehregan says.

In this study, researchers concluded that having more than five mitoses per square mm corresponds with a higher likelihood that a patient will possess a positive SLN. Patients under age 35 also were more likely to have a positive SLN (Sondak et al. Ann Surg Oncol. 2004 Mar;11(3):247-258.).

Conversely, a study involving 11 children revealed that melanoma in prepubescent patients often lacks hallmarks seen in adults (Mones JM, Ackerman AB. Am J Dermatopathol. 2003 Jun;25(3):223-238.).