Prognostic factors

Despite the increased incidence of melanoma, the prognosis has improved markedly in the last 20 years and this is due to an early diagnosis, in fact more and more superficial melanomas are removed. The thickness of the neoplasm must be considered among the most important prognostic factors. However, other elements also help to formulate a prognosis in patients with melanoma.

Thickness of the melanoma: Breslow’s index seems more accurate than Clark’s. The Breslow index is measured from the epidermal surface or from the base of the ulcer and is performed with a calibrated ocular micrometer. Patients with 1 mm thick melanomas have 20% mortality at 10 years, while patients with tumors > 4 mm thick have 50% mortality at 10 years. The Breslow index is an important prognostic index in mucosal tumors.

Ulceration: ulcerated lesions are generally thicker than non-ulcerated ones. The ulcerated lesions obviously appear thinner because the superficial part of the lesion has been eliminated. The tendency of these lesions to metastasize is high. The 5-year survival of stage I-II melanomas decreases from 80% to 55% in the presence of ulceration and in stage III from 53% to 12%.

Mitosis: it is the number of mitoses per square millimeter; the greater the number of mitoses, the worse the prognosis. Various studies have shown that with the same thickness, the prognosis is worse if the mitoses are greater. Patients with more than 6 mitoses appear to have a 5-year relative mortality 11.4 times greater. Normally, a distinction is made between low mitotic activity = 1 mitosis/mm2, moderate mitotic activity = 1-6 mitosis/mm2; high mitotic activity = > of 6 mitoses/mm2. A marker of mitotic activity can also be obtained from nuclear factors which serve as indicators of proliferative activity. MIB-1 which is a monoclonal antibody that recognizes Ki-67 epitope. Ramsey saw a reduction in survival in thick Breslow >4 mm Stage I melanomas with high reactivity to MIB-1. Furthermore, a progressively greater reactivity of MIB-1 by benign nevi, primary melanomas and metastases was seen. PCNA (Proliferating Cell Nuclear Antigen) can be considered another prognostic marker, it is a polymerase and an antibody capable of marking it has been obtained. The PCNA index is the number of labeled cells per 1000 tumor cells. In benign nevi the index averages 7.2 and in melanomas it is 248.5.

Regression: it is the replacement of tumor tissue with fibrosis, degenerated cells of melanoma, lymphatic proliferation and telangiectasias. There is often a thinned epidermis with loss of the retiform pattern, the dermis has fibroplasia with few inflammatory cells, melanophages, edema and telangiectasias and the vessels are perpendicular to the long axis of the epidermis. The results of the studies are conflicting. Regression is present in 58% of melanomas. It seems that this element has no prognostic value in melanomas deep, while in superficial melanomas regression can make one think of a thicker tumor. A study confirmed that in the case of melanomas < 1 mm, regression was present in 42% of melanomas that metastasized and in 5% of melanomas that did not metastasize.

Lymphocytic infiltration: lymphocytic infiltration of the tumor mass is believed to be the immune response to tumor cells, this response is measured by the level of lymphocytic infiltrate at the base of the vertical growth of the melanoma and is sometimes divided into: brisk, nonbrisk, absent. Some studies have shown that the greater the lymphocyte response, the better the prognosis. In cases in which a brisk lymphocytic infiltrate (infiltrated within the entire tumor mass) is detected, the 8-year survival is 77%, in cases of non-brisk lymphocytic infiltrate (focal infiltrate) the survival is 53% and in cases in which the infiltrate is absent, survival drops to 37%. The presence of macrophages and plasma cells is evaluated as a positive prognostic index

Angiolymphatic infiltration: some studies have shown a correlation between melanoma depth and angiolymphatic invasion, furthermore in cases of angiolymphatic invasion, metastases were more frequent with a reduction in survival. The presence of angiolymphatic invasion in a primary melanoma in the vertical growth phase reduces survival by 40 % at 8 years. Often the presence of focal invasion makes it difficult to differentiate with respect to some artifacts for which immunohistochemistry against CD31 and CD34 endothelial targets can facilitate the differential diagnosis.

Microscopic satellitosis: nodules larger than 0.05 mm in width are considered separated by the vertical tumor growth. If 2 cm away from the tumor, they are considered metastases in transit and are a sign of prognosis s