Melanoma in pregnancy

Above: Amelanotic melanoma. Photo: Emily Y. Chu, M.D., PhD.

There are several controversies concerning melanoma and pregnancy, many of which still do not find global consensus among leading specialists. As such, one expert advises dermatologists to exercise their best clinical judgment when treating melanoma associated with pregnancy and stresses the need for a heightened vigilance and appropriate follow-up when managing this potentially higher risk patient population.

Dr. Chu“Unfortunately, there is no consensus in the current literature concerning many of the issues involving melanoma and pregnancy. One of the main reasons for this is that there are a limited number of people who develop melanoma during or before pregnancy, which makes it very challenging to study this patient population,” said Emily Y. Chu, M.D., Ph.D., assistant professor of dermatology and pathology, University of Pennsylvania. Dr. Chu recently spoke on this subject at the summer meeting of the American Academy of Dermatology in New York.

Melanoma is one of the most common malignancies to affect young women, and approximately one-third of women who are diagnosed with melanoma are of childbearing age. As women now are delaying pregnancy until their 30s and 40s, understanding the implications of pregnancy and melanoma has become paramount in the optimal management of this patient population.

Prognosis

One of the central controversies in melanoma and pregnancy is whether a patient’s prognosis is negatively impacted if melanoma is diagnosed before pregnancy. The consensus in the literature refutes this concern Dr. Chu said, as the studies to date show this to be untrue. However, it is important to note that relatively few studies have been done on this topic to date.

Another question whether melanomas diagnosed during pregnancy have a worse prognosis than those in non-pregnant patients remains unclear. According to Dr. Chu, this controversy is also confounded by the different definitions of ‘pregnancy-associated’ melanoma.

“Several studies have shown that melanomas diagnosed during pregnancy may be thicker, that they have increased Breslow depth than melanomas that are not associated with pregnancy. Clearly that in and of itself could be a factor in why it seems like the prognosis for pregnancy associated melanoma is worse than that for non-pregnancy associated melanoma,” Dr. Chu said.

There are several reasons why pregnancy associated melanoma seems worse, including a potential lag time in diagnosis in pregnant women and new mothers, the fact that melanoma is increasingly common particularly in patients of childbearing age, as well as actual pregnancy-induced biological changes.

It not entirely clear how much actual pregnancy-induced biological change impacts the development of melanoma and outcomes in patients Dr. Chu said, but historically, people have felt that pregnancy is associated with hormonal changes and that could affect melanoma growth. Melanomas are considered to be potentially hormone-responsive for a number of reasons. Pregnancy is associated with an increase in skin pigmentation (i.e. linea alba and melasma) and according to Dr. Chu, there is evidence of presence of receptors for estrogen and progesterone in some melanomas.

Immunosuppression

Pregnancy also is generally considered to be associated with immunosuppression and allows for a more advantageous environment for melanoma to grow. During pregnancy, there is likely an increased immune tolerance for foreign antigens, which may include cancer antigens, as well as an increase in circulating T-regulatory cells. However, there is little evidence to suggest that melanoma formation or progression is aided by immunosuppression of pregnancy.

“The answer is probably that it is not a uniform phenomenon but I think in some people it does play a role. It may be that the majority of patients are actually not affected, which is why some of the studies seem to show an effect and other studies seem to show no effect,” Dr. Chu said.

While it is ok for patients with a history of melanoma stage I and IIA to get pregnant without delay, Dr. Chu said it would be wise for those with high-risk melanoma (i.e. stages IIB, IIC, and III) to wait 3-5 years before going ahead with a pregnancy. This would allow for enough time for risk of recurrence to decrease (2-3 years), and gives the opportunity for additional imaging surveillance outside of pregnancy. According to Dr. Chu, high-risk patients should be counseled appropriately and should strictly adhere to the proposed follow-up visit schedule suggested by their doctor.

“Clinicians should use their best clinical judgment in their pregnant patients, especially the ones who have a prior history of melanoma. Patients with high risk melanomas should be a little bit more cautious about having a pregnancy very quickly after a melanoma diagnosis,” Dr. Chu said.