Melanocytic naevi undergo changes throughout the lifetime, with the total naevus count increasing in early adulthood up to midlife and thereafter decreasing due to involution (1, 2). Changes in melanocytic naevi and development of new naevi have been reported in pregnant women (3, 4). The association between pregnancy and melanoma has been a controversial topic for a long time. Also, data about pregnancy-associated melanoma (PAM), defined as melanoma that develops during pregnancy and up to 1 year postpartum, are controversial as some suggest a worse prognosis compared to melanoma in nonpregnant patients, the former being reported with a 17% higher mortality rate (3, 5). Furthermore, in a recent Swedish population-based study, melanoma was the most common malignancy during pregnancy, followed by breast and cervical cancer (6).

The identification of dermatoscopic criteria of pregnancy-related naevi changes and melanoma features would aid in the early diagnosis of a PAM. However, the literature regarding dermatoscopic changes of naevi and melanoma during pregnancy is limited and consists of case reports and small cohort studies. The aim of the present review is to provide an overview of the literature and to help identify dermatoscopic criteria of naevi and melanoma during pregnancy that could aid in the early diagnosis of PAM.

The initial search identified 73 studies and through manual searching of the reference lists a further three articles that matched the criteria were detected. After duplicate removal a total of 42 articles remained, which were narrowed by title, abstract and full-text review.

Six cohort studies were identified and included in the analysis with a total of 258 patients summing up to 1,167 naevi that were examined. An overview of the included studies in Tables 1, 2.

It has been reported that during pregnancy around 90% of women will undergo skin changes, including mole changes (16). The association between pregnancy and melanoma has been a hot topic for many years with reports supporting the idea that pregnancy increases the risk of melanoma (17). While single case reports of melanoma development during pregnancy (18) can be found in the literature, there are also several studies supporting the idea that pregnancy is not a risk factor for melanoma development (13, 19, 20).

In the present review, we included only cohort studies leaving out case reports.

Importantly, the main finding of our analysis is that none of the 258 women reported in the studies developed melanoma. However, this is not surprising: according to our calculations, the likelihood of this is at least 92%. Using a Bayesian model, we calculated that a study able to detect an increase in the incidence of melanoma should include between 30,000 and 100,000 women (Supplementary Figure 1).

The development of new lesions during pregnancy was mentioned in three out of the six studies with only two studies documenting objectively the incidence of new naevi developing; total body photography was used only in one of the studies for documenting new naevi. It is currently unclear whether these naevi developed physiologically given a relatively young age of the women or are indeed caused by hormonal changes during pregnancy. Based on our review, the former hypothesis seems to be the more convincing one.

Increase in size of the examined naevi was noticed in all but one study. While some studies found the majority of the lesion increased in size (13), another study found this only in lesion on anatomical sites who undergo distension during pregnancy such as abdomen or breast (15). In the study by Gunduz et al. (14), which included lesion on the back, face, and neck, increase in size was observed only in 2 naevi. It stands to reasons, that in naevi which increase in size during pregnancy and that are located in anatomic sites prone to distension, such as abdomen and breasts, the main cause for this change is mechanical rather than hormonal.

Changes in colour were addressed in four out of the six studies. An interesting finding was the observation that some lesions become more hyperpigmentated during the pregnancy, but the colour of the lesions lighten towards the end of the pregnancy or postpartum. It has been shown that melanocytes as well as melanoma cells express functional estrogen and androgen receptors and that their activity is influenced by several factors including anatomic location (21). In pregnancy the number of estrogen and progesterone receptors on melanocytes increases and is responsible for the pigmentary changes that can be observed during pregnancy (22).

Three studies used the TDS for assessing the naevi dermatoscopically and in all three studies the TDS was higher in the third trimester compared to the first one. When following up the patients postpartum, two studies, Zampino et al. (12) and Gunduz et al. (14), mentioned a decrease of the TDS and return to the baseline TDS (11).

The most frequent observed dermatoscopic change among the studies was the increase in the number of dots. In Strumia's study, it was noticed that naevi with a globular patter developed more peripheral brown globules and the studies by Rubegni et al. (11) and Gunduz et al. (14) also mention changes and increased number of dots and globules (15). The presence of peripheral dots and globules seen with dermatoscopy is generally a sign of naevus growth (23) at young age, however, these pregnancy-related observations could be also result of the mechanical distension of the skin resulting in an upward movement of the basal layer with junctional or dermal nests becoming more easily visible by dermatoscopy (15).

Network changes have been observed in five out of the six studies. While some studies reported a less prominent network or a change into a broader wide-meshed network, others found that the network became more thickened and in some cases even developed radial streams, a sign generally associated with a malignant phenotype. Again, most of these changes may be attributable to the distension of some body parts, resulting in a thinned epidermis and subsequently, better visualisation upon dermatoscopy.

Vessel formation during pregnancy was reported in two studies, in one being observed in 12.4% of the cases (13), but appears to decrease again after delivery in the post-partum period. It is known that physiologic vascular changes happen during pregnancy and that these are a response to the increased production of estrogens and human chorionic Gonadotrophin, which are placental hormones (24, 25). The dermatoscopic vascular changes noticed during pregnancy may therefore become visible due to the vascular modifications such as vasodilation and proliferation of dermal blood vessels.

Limitations of the present study are the relatively low number of women included and the lack of appropriate control groups, which would have facilitated a better statistical analysis of physiological and truly pregnancy-related changes. Additionally, the included studies are heterogeneous, thus not allowing head-to-head comparisons between them. Only one study used a control group and no study displays raw data facilitating a reanalysis, comparison or merging of information.

Robust studies of dermatoscopic evaluation of naevi in pregnant women are needed to determine high-risk dermatoscopic characteristics, which would improve the diagnostic accuracy of benign vs. malignant melanocytic lesion in this population.

IC and IZ contributed to the study conception. IC, MT-H, LU, and IZ contributed to the study design. Data collection and analysis was performed by IC, LU, and MT-H. IC, MT-H, LU, and IZ prepared and reviewed the manuscript. All authors contributed to the article and approved the submitted version.

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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