Pregnancy and Melanoma

Introduction

There has been significant controversy regarding the relationship between pregnancy and malignant melanoma (MM). The origin of this concern arises from case reports published over the past 50 years, suggesting a poor prognosis for women developing MM during pregnancy and observations that MM may be a hormonally responsive tumor. This has become an increasingly important issue as more women delay childbearing until the fourth or even fifth decade of life. As the age-specific incidence of MM increases during these decades, a rising incidence of MM during pregnancy may be seen in the coming years.

History

The controversy concerning the influence of pregnancy on the prognosis of MM began with multiple case reports dating back to 1951. Pack and Scharnagel reviewed 1050 cases of MM and reported that of 10 patients diagnosed with MM during pregnancy, five died within 30 months of diagnosis. Another 11 patients noted changes in nevi during pregnancy and were subsequently diagnosed with MM in the postpartum period. Two of these women died of widely metastatic disease within 3 years and one was noted to have probable brain metastases. These investigators concluded that ‘some benign nevi are incited to undergo malignant degeneration during pregnancy . . . such melanomas grow with unusual rapidity and metastasize widely . . . the prognosis of pregnant women with melanoma is bad and few cures are obtained’. In 1954, Byrd and McGanity stated that the risk of pregnancy, in women with a history of MM, was significant enough to ‘justify surgical sterilization in those women who were amenable to terminating their child bearing career’.

In addition to case reports, there were observations which supported a relationship between hormones and MM, including: the rare occurrence of MM before puberty, the increasing incidence of MM during the childbearing years, the darkening and enlargement of nevi during pregnancy, the presence of receptors for estrogen and progesterone in some MMs, the augmentation of MM cell growth in tissue culture on addition of steroid hormones, and the enhancement of MM growth in mice after administration of estrogen. Over the past several years, data from recent laboratory and clinical studies have been unable to substantiate most of the above hypotheses and observations. However, recent data concerning estrogen receptor β expression in MMs raises some new questions about hormonal effects on MM.

Epidemiology

One-third of women with MM are of childbearing age at the time of diagnosis. The incidence of MM during pregnancy is estimated as 2.6 cases per 1000 births. MM is one of the most common cancers diagnosed during pregnancy, representing 8% of all malignancies occurring during pregnancy. A recent Norwegian registry-based cohort study observed that MM was the most frequent malignancy diagnosed during pregnancy, representing 160 of 516 (31%) malignancies. A Swedish study reported that MM represented 24.5% of all malignancies diagnosed during pregnancy. MM is the most likely tumor to metastasize to the placenta, although this is still a rare occurrence. If transplacental metastases occur, there is an estimated 25% risk that the fetus will be affected.