Regression a negative predictor?

Vancouver, British Columbia - What causes regression to occur in melanoma and what is the significance of regression when it does occur?

This debate has been going on for more than 30 years, according to Lynn From, M.D., a dermatologist in the division of dermatology at Sunnybrook ? Women's College Health Sciences Centre in Toronto, but it hasn't clarified understanding regression.

Dr. From discussed the presentation and possible implications of regression at the Sixth World Congress on Melanoma. She notes that early regression tends to be characterized by dense lymphocytic infiltration with degenerating melanoma cells.

Mechanisms of regression

Intermediate regression may present as a decrease in tumor volume, again with lymphocytes, increased fibrous tissue, telangiectasia and melanophages. In more advanced regression there is dense fibroplasia in the dermis along with atypical melanocytes.

Late regression shows an expansion of the papillary dermis with telangiectasia and melanophages. Dr. From says there seems to be two different forms in late regression: one with dense fibrous tissue, the other with very loose stroma with delicate fibroplasia.

"This resembles the type of regression seen in other lesions such as lichen planus. Could there possibly be two different mechanisms?" she asks.

Dr. From notes the mechanisms of regression were thought of in terms of cell-mediated immunity for many years. A study from the Sydney Melanoma Unit looked at patients with three or more melanomas and found marked regression in the third melanoma and a decrease in antigenicity in that melanoma on immunohistochemical studies. Findings were similar in occult melanoma including the finding of circulating specific cytotoxic T-lymphocytes.

Dr. From says such results would suggest there is definitely cell-mediated immunity that can explain regression in some cases.

"In other cases, perhaps with fibroplasia, it's less clear. While we know this dense fibroplasia can produce various factors that will stimulate melanoma, is it possible that some of this could be regressive and actually a good thing, and is it possible that we might be able to stimulate this in other ways?"

Melanocytic cells that are highly atypical are also occasionally found in dense fibroplasia, complicating where to measure such lesions. When there's total regression, some have suggested just measuring the thickness of the fibroplasia and saying that's what the original melanoma must have been.

Thinner is not better

Many studies have suggested regression is seen more often in thin melanomas, possibly because regression has been obliterated in thick melanomas.

A letter from Hungary to the editor in the British Journal of Dermatology outlined a study of a large number of melanomas less than 2 millimeters thick; the study discovered that regression predicted a 10 times higher risk of sentinel node positivity.

Dr. From notes that both early and intermediate regressions usually exhibit a large amount of melanoma adjacent to or beneath the regression.

"When thickness is measured there, it's probably quite representative of the overall lesion. In early and intermediate regression, a vertical height such as 2 millimeters is probably close to that in real life. If it's a thin melanoma and there's extensive regression, vertical height of what is left probably is not relevant at all."

For prognostic recording, Dr. From recommends consideration only of late extensive regression when perhaps more than 50 percent of the melanoma is regressed.

"Especially in thin melanomas, it might be possible to identify cases where the extent of regression could be a predictor of metastases. The pathologist should caution the clinician that the vertical thickness may not reflect prognosis when there is a large amount of regression in thin melanomas."

Disclosure: Dr. From reports no conflicts of interest.