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Prognostic Role of Histologic Regression in Primary Cutaneous Melanoma

Published on May 2, 2017

The prognosis for a melanoma is very closely correlated to how deeply it has invaded into the skin (“Breslow Depth”). The for deeper melanomas the risk of spead to lymph nodes is large enough to merit “sentinal node biopsy”. a surgery where radioactive die is injected to tract the first lymphnodes that drain the area of the melanoma, and those nodes are surgically removed to be tested. However some thin melanomas, have signs on pathology indicating they “used to be deeper” but have “regressed” probably becuase the patients immune system has attacked the deper part of the melanoma. No one was sure if the regression was an indication for sentinal node biopsy because we could not be sure how deep the melanoma “used to be”. Or if the regression was a good sign as it indicated an immune respose against the cancer and so sentinal node biopsy was not idicated just because of regression.

This study shows the latter to be the case. So patients with thin melanomas with evidence of “regression” now do not need to worry about “how deep did my melanoma used to be”. They infact have a better prognosis than other patients with thin melanomas becuase thier immune system is putting up a fight!

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For years, there has been a running debate regarding the significance of regression. Some articles have reported that regression improved prognosis by reflecting the patient’s enhanced immune response and therefore ability to fight the malignancy. Others implied that prognosis was likely made worse when regression was identified because the actual depth of the melanoma could no longer be accurately measured and was almost certainly deeper.
This collaborative review from Italy culled the literature to attempt to finally establish the prognostic significance of histologic regression in primary melanoma. Using various search engines, they reviewed 1876 articles published from January 1966 through August 2015 that dealt with regression. Due to strict criteria, only 10 studies were eligible to be included in their analysis. These 10 studies included 8557 patients. Their meta-analysis revealed that patients who demonstrated histologic regression in their primary melanoma had a lower likelihood of death, allowing the authors to conclude that histologic regression is a protective feature for survival.
This conclusion is extremely important. It will finally resolve and stop the performance of sentinel lymph node biopsies in those patients with a thin melanoma because of the presence of regression. However, this retrospective study based on observational studies has limitations and potential flaws, including but not limited to, the heterogeneity of the melanoma features (ulceration, thickness) in the studies reviewed, the confounding impact of meta-regression, the different definitions of histologic regression in the various studies, and the lack of information regarding the percentage of the lesion that was regressed.
Melanoma is an immunogenic tumor, and therefore it is not surprising that regression, due to the host response, would be associated with an improved prognosis. Nonetheless, additional studies with an agreed-upon definition of regression are needed to confirm these results.

Written by Jane Grant-Kels MD

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