Melanoma in pregnancy

At the 2024 EADV Congress, Dr Gabriele Roccuzzo (Turin, Italy) presented an in-depth analysis of pregnancy-associated melanoma (PAM).

At the EADV 2024 Congress, Dr. Gabriele Roccuzzo (Turin, Italy) presented an in-depth analysis of pregnancy-associated melanoma (PAM), a condition defined as melanoma diagnosed during pregnancy or within one year postpartum. The talk addressed various aspects of PAM, from its epidemiology to the challenges in diagnosis and management during pregnancy.

Pregnancy-Associated Melanoma (PAM)

Dr. Roccuzzo highlighted that PAM is of particular concern because approximately 35% of women diagnosed with melanoma are of reproductive age. Women between the ages of 20 and 24 are at a higher risk of melanoma compared to men, and the incidence of PAM is about 50 cases per 100.000 maternalities. Melanoma is recognized as the most common malignancy during pregnancy, making it a significant issue for dermatologists and oncologists working with pregnant patients.

Diagnostic challenges in pregnancy

One of the key challenges in managing PAM is the potential delay in diagnosis. Physiological changes during pregnancy, such as darkening and enlargement of moles, as well as the appearance of new pigmented lesions like chloasma, can complicate the early detection of melanoma. These changes, often visible as early as the first trimester, can mask melanoma and lead to diagnostic delays. Furthermore, there are limitations in the use of diagnostic tools and treatment options during pregnancy due to concerns about fetal safety, sometimes necessitating delays in optimal treatment until after delivery.

The role of hormones in melanoma progression

The presentation also delved into the biological aspects of melanoma in pregnancy, particularly the role of estrogen receptors. Estrogen receptor beta, more prevalent in cutaneous melanomas, may have a protective effect against melanoma progression, potentially explaining some of the gender differences in prognosis. Dr. Roccuzzo also discussed the debated impact of hormonal therapies, including oral contraceptives and hormone replacement therapy, on melanoma risk, noting that combined oral contraceptives with progesterone appear to pose very little risk based on current evidence. The discussion on hormonal influence extended to IVF treatments, where no strong association with melanoma risk was found.

Metastatic melanoma and placental involvement

While pregnancy can influence the development of melanoma, with hormonal changes and hyperpigmentation potentially delaying detection, there is no definitive evidence that primary melanoma diagnosed during pregnancy worsens fetal outcomes. Though rare, metastatic spread to the placenta can occur, as melanoma is the malignancy with the highest rate of placental metastasis. The presentation emphasized the importance of monitoring the placenta and the newborn post-delivery in cases of metastatic melanoma, as the prognosis for fetal involvement is generally poor.

Surgical and diagnostic management during pregnancy

On the subject of management, Dr. Roccuzzo stressed the need for a multidisciplinary approach. Surgical excision of melanoma under local anesthesia is considered safe during pregnancy and should not be delayed, with the second trimester being the ideal time for the procedure. Sentinel lymph node biopsy is not contraindicated, though blue dye should be avoided, and the procedure is generally deferred until after the first trimester to minimize fetal risk.

Imaging during pregnancy should balance the risk to the fetus with the clinical benefit. Ultrasound is a safe option, even in the first trimester, while whole-body MRI without contrast is preferred during the second and third trimesters. Breastfeeding should be interrupted for 12-24 hours following the administration of contrast agents. Adjuvant therapies, including immunotherapy and targeted therapies, are typically not recommended during pregnancy due to the potential for fetal harm. However, in cases of high-risk recurrence in the first trimester, early termination of pregnancy may be considered to allow for earlier treatment.

Treatment considerations for advanced stage 4 melanoma

For advanced stage 4 melanoma, managing the disease during pregnancy is extremely challenging, and the option of termination or early delivery should be discussed. Although there is limited data supporting the use of immunotherapy or targeted therapies during pregnancy, some case reports exist. Dr. Roccuzzo shared several examples, including one of a patient successfully treated with pembrolizumab during pregnancy, leading to uneventful fetal growth and a positive postnatal outcome.

Conclusion and multidisciplinary management

In conclusion, the diagnosis and management of melanoma in pregnant women require careful, individualized consideration, involving dermatologists, oncologists, gynecologists, and neonatologists. It is essential to perform both gross and histological examinations of the placenta and fetus after birth to detect any metastasis. Regular skin checks and early detection of melanoma according to the ABCD rule are crucial to improving patient outcomes. Dr. Roccuzzo's talk underscored the importance of a tailored, multidisciplinary approach to ensure the best possible outcomes for both mother and child.

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