Pregnancy-associated Melanoma Research Articles

Pregnancy-associated melanoma (PAM): A single institution retrospective review between 2005 and 2023.

30 Background: Melanoma is the most prevalent cancer during pregnancy, representing 31% of all gestational cancers, with its incidence rates rising globally. Pregnancy-associated melanoma (PAM) presents unique challenges in diagnosis and management due to maternal physiological and hormonal changes, as well as consideration of fetal impact. This study aims to understand the impact of pregnancy on melanoma outcomes to optimize patient care. Methods: We conducted a retrospective study of patients diagnosed with PAM at The University of Texas MD Anderson Cancer Center between 2005 and 2023. Eligible patients were diagnosed either during pregnancy or within one year of delivery. Frequencies and percentages were used to describe the study population. Our primary outcome was to describe melanoma characteristics and prognosis, and our secondary outcome was to investigate melanoma’s impact on obstetrical outcomes. Results: The study included 76 patients with a mean age of 31.3 ± 4.4 years, 93.4% of whom were of white or Caucasian origin. The median follow-up was 39.8 months. Diagnoses included Stage 0 (7.9%), Stage I (36.8%), Stage II (3.9%), Stage III (22.4%), and Stage IV (25%) melanoma. The mean Breslow Thickness was 2.1± 4.7 mm. Primary diagnoses occurred in 76.6% of patients, while 21.9% experienced recurrent episodes during pregnancy. At the time of their PAM event, 47.4% had localized disease, and 48.7% had metastatic disease. The average mean time from diagnosis to first surgery was 2.1 months in patients diagnosed during pregnancy (group 1) and 0.9 months in patients diagnosed after pregnancy (group 2). The average time from diagnosis to systemic therapy was 3.3 ± 2.8 months in group 1 and 1 ± 0.7 months in group 2. Patients diagnosed during pregnancy had an average gestational age of 17.8 weeks: 30.65% were diagnosed in the first trimester, 54.84% in the second, and 14.52% in the third trimester. Thirty-three (43.4%) patients had term deliveries, while fifteen (19.7%) patients gave birth prematurely. There were 75.0% live births, 5.3% spontaneous abortions and 3.9% elective terminations. Conclusions: Our findings contribute to the limited literature on PAM outcomes, emphasizing the importance of a collaborative approach in managing these patients. Close surveillance of pregnant patients with melanoma is essential to prevent treatment delays and ensure optimal maternal and fetal outcomes.

DS16 Incidence and management of pregnancy-associated melanoma in a district general hospital in the Southeast of England

DS16 Incidence and management of pregnancy-associated melanoma in a district general hospital in the Southeast of England

Cutaneous melanoma during pregnancy: Management and real-world outcomes.

e21554 Background: Pregnancy associated melanoma (PAM) occurs in 1% of female patients with melanoma and affects 1 in 2200 pregnancies. Antepartum evaluation of melanoma must incorporate both maternal and fetal factors, and currently there is lack of standardization. Our study aimed to review the incidence of antepartum melanoma at our institution and highlight patterns in management and treatment during this high-risk scenario. Methods: After IRB approval, the Mayo Clinic electronic medical record was searched with key words “melanoma” and “pregnancy”. 25 patients with melanoma during pregnancy were identified from 1987-2023. 6 patients were excluded as skin changes noted during pregnancy were not formally diagnosed as melanoma until after delivery. Abstracted data included demographic information, disease characteristics, staging (per AJCC guidelines at time of diagnosis), and clinical outcomes. Survival data were calculated. Results: 19 patients were included. Diagnosis occurred at an average maternal age of 30 years (range 24-38 years) and a mean gestational age of 20 weeks (range 6-35 weeks). All patients had a term delivery. 4 patients underwent labor induction at 37 weeks for staging/treatment. 60% of patients had a delay in imaging or treatment attributed to pregnancy, including 1 patient who was upstaged with metastatic disease based on postpartum imaging. 82% of stage I-III patients underwent wide local excision during pregnancy; however, 35% of sentinel lymph node sampling was delayed until postpartum. 3 stage II/III patients received adjuvant therapy (interferon or sargramostim) after delivery. Adjuvant immunotherapy was discussed with 2 patients in the postpartum period but ultimately not given due to the time lapse between surgery and delivery. 1 patient with stage IV disease diagnosed at a gestational age of 20 weeks was evaluated with MRI PET scan then treated with vemurafenib monotherapy during pregnancy. Workup and outcomes were reviewed by stage (Table 1). 7 of 19 patients had subsequent pregnancies, and 1 had recurrence of melanoma during a second pregnancy (stage II followed by stage IV). Due to a low number of censoring events, median progression free survival and overall survival were not reached. Conclusions: Melanoma diagnosed during pregnancy can be safely and effectively staged with sentinel lymph node surgery, MRI imaging (PET-MRI vs standard), and CT imaging with shielding without a need for early induction of labor nor a delay in cancer care. Furthermore, we report a patient with stage IV disease treated with vemurafenib during and immunotherapy after pregnancy, indicating that treating stage IV PAM with systemic therapy is a consideration. [Table: see text]

A rare case of choroidal melanoma in pregnant Indian female

Choroidal melanoma is a rare ocular malignancy in the Asian population but despite its rarity, it is the most common intraocular malignancy. In the Western population, it has been reported in younger men and females of childbearing age, particularly pregnant females. This is the first reported case of choroidal melanoma in pregnant Indian female in India, which reviews the imaging features of choroidal melanoma and emphasizes the need for further study to evaluate the causes of the increasing incidence of pregnancy-associated melanoma (PAM) in Indian females. We present a case of a 29-year-old pregnant female, diagnosed with choroidal melanoma in the right eye during the 7th month of pregnancy. Upon clinical and diagnostic imaging, the choroidal melanoma was treated by enucleation 20 days postpartum and the histopathology examination confirmed a mixed cell type choroidal melanoma. Systemic metastasis work-up was unremarkable both in the mother and the baby.

Pregnancy-associated melanoma: characteristics and outcomes from 2002 to 2020.

Melanoma diagnosed within 1 year of pregnancy is defined as pregnancy-associated melanoma (PAM). No robust data on how pregnancy influences melanoma nor guidelines for PAM management exist. With IRB approval, female patients with a pathology-confirmed melanoma diagnosis within 1 year of pregnancy treated at our institution from 2000 to 2020 were identified. Controls from the cancer registry were matched 1 : 4 when available on decade of age, year of surgery (±5), and stage. We identified 83 PAM patients with median follow-up of 86 months. Mean age at diagnosis was 31 years. 80% AJCC V8 stage I, 2.4% stage II, 13% stage III, 4.8% stage IV. Mean Breslow thickness was 0.79 mm and 3.6% exhibited ulceration. The mean mitotic rate was 0.76/mm 2 . In terms of PAM management, 98.6% of ESD patients and 86.7% of LSD patients received standard-of-care therapy per NCCN guidelines for their disease stage. No clinically significant delays in treatment were noted. Time to treatment from diagnosis to systemic therapy for LSD patients was an average of 46 days (95% CI: 34-59 days). Comparing the 83 PAM patients to 309 controls matched on age, stage, and year of diagnosis, similar 5-year overall survival (97% vs. 97%, P = 0.95) or recurrence-free survival (96% vs. 96%, P = 0.86) was observed. The outcomes of PAM following SOC treatment at a highly specialized center for melanoma care were comparable to non-PAM when matched by clinical-pathologic features. Specialty center care is encouraged for women with PAM.

A-161 - Pregnancy-associated melanoma- a pilot study

A-161 - Pregnancy-associated melanoma- a pilot study

The Association Between Pregnancy Timing and Cumulative Exposure on Survival in Melanoma.

As melanoma is common among young women, the impact of pregnancy on melanoma prognosis is of interest. The purpose of this study was to examine the association between pregnancy and survival in female melanoma patients of childbearing age. We performed a population-level, retrospective cohort study of women of childbearing age (18-45 years) diagnosed with melanoma from 2007 to 2017 using administrative data from Ontario, Canada. Patients were categorized according to pregnancy status (i.e. pregnancy before [conception from 60 to 13 months prior to melanoma], pregnancy-associated [conception 12 months prior to and after], and pregnancy after [conception 12 months after] melanoma). Cox models were used to examine melanoma-specific survival (MSS) and overall survival (OS) associated with pregnancy status. Of 1312 women with melanoma, most did not experience pregnancy (84.1%), with 7.6% experiencing a pregnancy-associated melanoma and 8.2% experiencing a pregnancy after melanoma. Pregnancy before melanoma occurred in 18.1% of patients. Pregnancy before (hazard ratio [HR] 0.67, 95% confidence interval [CI] 0.35-1.28), associated (HR 1.15, 95% CI 0.45-2.97), and after melanoma (HR 0.39, 95% CI 0.13-1.11) was not associated with a difference in MSS compared with those who did not experience a pregnancy during these time periods. Pregnancy status was also not associated with a difference in OS (p>0.05). Cumulative weeks pregnant were not associated with a difference in MSS (4-week HR 0.99, 95% CI 0.92-1.07) or OS (4-week HR 1.00, 95% CI 0.94-1.06). In this population-level analysis of female melanoma patients of childbearing age, pregnancy was not associated with a difference in survival, suggesting that pregnancy is not associated with a worse melanoma prognosis.

DS22 Pregnancy-associated melanoma: a case series

Abstract There are currently no guidelines in the UK regarding the management of pregnancy-associated melanoma (PAM). It is estimated that one-third of women diagnosed with melanoma are of child-bearing age and numbers are rising (Still R, Brennecke S. Melanoma in pregnancy. Obstet Med 2017; 10:107–12). A recent survey of all dermatologists in our region revealed five cases of PAM. We await the results of a similar survey disseminated to all UK dermatologists. Case 1 was a 22-year-old woman of 16 weeks’ gestation who presented with a 6-week history of a changing mole on her face. Histology confirmed a nodular malignant melanoma [Breslow thickness (BT) 3.5 mm]. A healthy baby was born at full term. Case 2 was a 36-year-old nulliparous woman who presented with a changing lesion on her right calf. Histology confirmed a malignant melanoma (BT 3.6 mm). At the 2-week follow-up, she was 4 weeks pregnant. A healthy baby was born at 38 weeks. Case 3 was a 33-year-old nulliparous woman who had a superficial spreading malignant melanoma (BT 2 mm) excised from her left scapula. Twenty-three months after this diagnosis, pulmonary metastases were evident on computed tomography (CT). Three months later, she became pregnant. A healthy baby was born at term. Case 4 was a 30-year-old nulliparous woman who had a malignant melanoma (BT 3 mm) excised from her right scapula. A sentinel lymph node biopsy (SLNB) was negative, and staging CT showed no evidence of metastatic disease. She received a course of interferon treatment. Three years after initial presentation, at 24 weeks’ gestation, she developed a painful swelling on her right axilla that was confirmed to be metastatic melanoma. A healthy baby was born at 35 weeks. Case 5 was a 27-year-old woman who had a melanocytic lesion that was shave excised by her general practitioner. Subsequent excision confirmed superficial spreading malignant melanoma (BT 1.5 mm, stage 1B). At the time of wide local excision and SLNB 1 month later, the patient was 6/40 gestation. Sentinel lymph node biopsy was negative so no further staging scans were required. A healthy baby was born at term. There are conflicting data on whether PAM carries a poorer prognosis than equivalent disease in nonpregnant women. However, melanoma is one of several cancers that can metastasize to the placenta. Therefore, a diagnosis of PAM complicates decisions regarding staging and treatment (Carter TJ, George C, Harwood C, Nathan P. Melanoma in pregnancy: diagnosis and management in early-stage and advanced disease. Eur J Cancer 2022; 166:240–53).

32543 Melanoma in pregnancy: Profiling the tumor microenvironment

Immunosurveillance is thought to play a critical role in eliminating nascent transformed melanoma, which is the most common malignancy occurring during pregnancy. Because pregnancy induces a state of immunosuppression, we sought to identify pregnancy-associated alterations to the melanoma tumor microenvironment. Our specific objective was to evaluate the immunophenotype of pregnancy-associated melanoma (PAM). We identified 7 cases of PAM from the electronic medical records of the University of California, Davis.

Melanoma in pregnancy: certainties unborn.

Melanoma diagnosed during childbearing period or up to 1 year after delivery is defined as pregnancy-associated melanoma (PAM). There is some evidence that PAM has worse prognosis if compared with melanoma in nonpregnant women, although literature is still inconclusive. Many biological mechanisms could explain this behavior, such as hormonal and immune status, increased lymphangiogenesis but also delay in diagnostic and therapeutic management. If PAM is suspected, a prompt excisional biopsy under local anesthesia can be performed regardless of the gestational period. Conversely, additional staging procedures (such as sentinel lymph node biopsy or imaging) and systemic therapy are still debatable during pregnancy. A multidisciplinary tailored approach should be preferred, together with exhaustive counseling of the mother.

420 Melanoma in pregnancy in California, 1994-2015: A population-based study

Melanoma is the most common malignancy during pregnancy. There is continued debate regarding the impact of pregnancy on the prognosis of melanoma. Prior studies have shown mixed results and the number of recent large population-based studies are limited, especially from the United States. To address this question, we used the California Cancer Registry data linked with Patient Discharge Data and Ambulatory Surgery Center Data to identify female patients, ages 15-44 years, diagnosed with melanoma in 1994-2015, including those who were pregnant. Women with pregnancy-associated melanoma (PAM) were compared with age-matched, non-pregnant women with melanoma. Multivariable logistic regression and multivariable cox proportional hazards regression models were used. We identified 13108 female patients diagnosed with melanoma, of which 1431 had PAM. PAM was associated with tumor site (more likely on lower than upper limb), tumor thickness (more likely in situ than invasive melanoma ≤1.0 mm), and histologic type (more likely superficial spreading than lentigo maligna). Lower overall survival was associated with non-Hispanic white race/ethnicity, lower neighborhood socioeconomic status, tumor site (head/neck, trunk or upper limb vs lower limb), greater tumor thickness, lymph node involvement, and more than 90 days to surgery (vs <30), but not pregnancy. In summary, we report a population-based analysis of melanoma in pregnancy in California. Although there were no differences in overall survival, pregnancy status was associated with tumor site, thickness, and histologic type, suggesting possible biological differences. Future studies are required to better understand the biological and molecular characteristics of melanoma in pregnancy.

Prognosis and Management of BRAF V600E-Mutated Pregnancy-Associated Melanoma.

Approximately one third of women who develop melanoma at childbearing age are diagnosed during gestation or the postpartum period, facing pregnancy-associated melanoma (PAM). However, only some retrospective studies with heterogeneous data have analyzed the impact of pregnancy on melanoma development, and no evidence exists about the behavior and the management of BRAF-mutated disease. In order to better describe the evolution of BRAF V600E-mutated PAM, we present here all consecutive cases diagnosed in our site during the last 7 years, recording oncological, obstetrical, and perinatal parameters, as well as the therapeutic decisions for both melanoma and gestation. Based on our institutional experience, we weigh the current published evidence and discuss upcoming clinical considerations about the prognosis of PAM, the role of BRAF status, and the possible treatment options during pregnancy in localized or advanced/metastatic disease. Five women were diagnosed with newly metastatic or relapsed BRAF V600E-mutated PAM (four during gestation and one in the 1st year postpartum) between 2012 and 2019. All of them developed extensive metastatic disease with multiple organ involvement, and four developed brain metastases. All cases experienced melanoma progression in less than 6 months under targeted therapy and died soon independently of the followed sequence of treatments. All the neonates were delivered alive and healthy, but one developed melanoma earlier than the second year of life. Reviewing the literature to confirm our unfavorable outcomes, no specific data on BRAF-mutated PAM were retrieved and current evidence still supports that the prognosis of PAM should be guided by the established risk factors, whereas the management of advanced/metastatic PAM should be evaluated on a case-by-case basis. More data are required to ascertain whether BRAF-mutated profile adversely affects PAM outcome, although the clinicians should be aware to detect any potential melanoma lesion during pregnancy as soon as possible, treating it locally, regardless of its BRAF status. The prognosis and management of pregnancy-associated melanoma whether BRAF-mutated or wild type, is currently guided by the same parameters as in the nonpregnant condition. In this special nontrial subpopulation, BRAF-mutated status seems to have a detrimental effect on disease outcome, independently of the following treatments. In early stage melanoma, wide local excision with or without sentinel lymph node dissection may be curative at any trimester of gestation, while in advanced/metastatic setting, therapeutic strategy including immune-checkpoint or BRAF/MEK inhibitors, is more challenging, regardless of BRAF status, and should be based on an individualized decision in each case at a multidisciplinary level.

Clinical features and response to immune checkpoint inhibitors (ICIs) in pregnancy-associated melanoma (PAM).

9564 Background: Melanoma is one of the most common malignancies diagnosed during pregnancy. Little is known about the clinical outcomes of PAM, in particular, response to ICIs. We performed a retrospective study to assess this issue. Methods: A multicenter retrospective study was performed at 4 large melanoma centers. Patients (pts) with PAM treated with ICIs were identified and examined. Clinical data and molecular data (RNA sequencing, IHC) were explored. PAM was defined as development of advanced melanoma during pregnancy or within 2 years post-partum. Results: 19 pts with PAM were treated with ICIs. Median follow-up was 11.7 months (range 1.4 – 41.9 months). Median age was 29 years (range 16-36). Most pts had a cutaneous primary (N = 17, 89%) including the extremity (N = 8) or trunk (N = 7), and 5% were occult. 11 pts (58%) had a BRAF V600E mutation and 6 (32%) pts received BRAF/MEK targeted therapy. Most pts had prior primary melanoma (N = 12, 63%) and presented with advanced melanoma in the post-partum setting (N = 11, 58%). At advanced presentation, 6 (32%) pts were stage III/M1a and 13 (68%) pts were stage M1b/c/d; 7 (41%) pts had elevated LDH and 13 (68%) had visceral involvement. Among 11 patients treated with combination ipilimumab + anti-PD-1 therapy, 7 (64%) had objective responses (OR) with a 1-year progression free survival (PFS) of 40% and 1-year overall survival (OS) of 100%. By contrast, ICI monotherapy (3 with anti-PD-1/L1 and 4 with ipilimumab) was associated with poorer outcomes (OR in 25% and 33% for ipilimumab and anti-PD-1/L1, respectively). Molecular features (RNA sequencing, immunohistochemistry) will be presented. Conclusions: Patients with PAM represent a unique population and may particularly benefit with combination ICI therapy compared with ICI monotherapy (in a limited sample size). Molecular underpinnings of PAM biology are still being elucidated.

Decreased T-Cell Programmed Death Receptor-1 Expression in Pregnancy-Associated Melanoma.

Pregnancy depends on tolerance of an immunologically foreign fetus through type 1 T-cell suppression. Worse melanoma outcomes have been described within 1 year of childbirth. We assessed immunopathologic factors that may account for the observed negative impact of pregnancy on outcome. Women of child-bearing age with ≥24 months follow-up were identified from our Institutional Melanoma Registry. Women with available primary tumor blocks were compared [history of childbirth within 1 year of diagnosis (CB1Y) (n = 18) vs. nonpregnant age-matched controls (n = 13)]. Immunohistochemical staining with quantification of immune infiltrates: CD68 tumor-associated macrophages, CD3 tumor-infiltrating T cells, and PD-1 activated/exhausted T cells; and hematolymphangiogenesis: CD31/D2-40 blood vessels and D2-40 lymphatics was performed by 2 blinded dermatopathologists. CB1Y tumors showed decreased CD3 tumor-infiltrating T cells (P < 0.05) with significantly reduced PD1 expression (P ≤ 0.05). The CD3:PD1 ratio was higher in CB1Y (P < 0.05). Other tested parameters did not significantly differ between the 2 groups. As PD1 expression is induced during type 1 T-cell activation, these data suggest that immune ignorance or suppression may predominate in CB1Y. Further studies are required to identify interventions that may promote tumor-associated T-cell inflammation in such patients.

Pregnancy and the apoptotic pathway in experimental melanoma.

Pregnancy-associated melanoma is defined as melanoma diagnosed during pregnancy or within 1 year of delivery. The association of pregnancy with melanoma is well known, but its underlying molecular mechanisms of association are poorly understood. The aim was to assess the expression of apoptosis-related genes in melanoma tumors during pregnancy in an attempt to elucidate the molecular mechanisms underlying apoptosis-driven activation of melanoma cells in this period. Mice were allocated across two experimental groups (nonpregnant and pregnant) and implanted with the melanoma cell line BF16-F10. Tumor tissue was collected for RNA extraction and purification, and gene expression was quantified using the mouse apoptosis RT2ProfilerTM PCR array. Different intracellular apoptotic pathways were activated (positively or negatively) by pregnancy in tumor cells: intrinsic (21.5%), extrinsic (32%), caspase (14%), apoptosis (21.5%), and caspase-activated DNase (11%). The proportion of upregulated genes for each of these pathways was 100, 30, 50, 17, and 0%, respectively. MetaCore software was then used to analyze gene ontology processes and pathways by building networks. Among the gene ontology processes, the majority of differentiated genes were related to the apoptotic process. The main pathway activated by pregnancy was the intrinsic one (genes Api-5, Bcl2-L1, Birc-2, Birc-3, Bok, and Trp53bp2). Pregnancy activates the intrinsic apoptosis pathway to stimulate caspases 7 and 9, but the final balance is inhibition of apoptosis mechanisms. In mice, pregnancy cannot promote or worsen melanoma.

Oestrogen receptor expression in melanoma.

Sexual hormones share a common cholesterol-derived steroid backbone and comprise oestrogens, gestagens and androgens. They elicit numerous physiological and pathological functions; for example androgens are known to contribute to prostatic cancer development, whereas oestrogens are of major importance in the pathogenesis of breast cancer. In 1986, the presence of oestrogen receptors (ER) on breast cancer cells was described as one of the first biomarkers in oncology.1 ER expression is still routinely used both for predictive and therapeutic purposes with the selective ER modulator tamoxifen remaining an efficacious breast cancer treatment both in the adjuvant and palliative setting. The ‘classical’ ERs (ERα and ERβ) are found in many other tissues, such as lung, colorectal mucosa, thyroid tissue or lymphoid cells. Observations of darkening or sometimes growing melanocytic nevi in pregnancy as well as of prognostic differences between female and male melanoma patients suggested that sexual hormones may also impact on melanocyte function and melanoma development.2 Both ‘classical’ ERs have been detected in melanoma tissue, with ERβ being the predominant subtype 3 Already over 20 years ago, tamoxifen was tested in combination with chemotherapy in the treatment of metastatic melanoma and demonstrated improved response rates compared to chemotherapy alone.4 However, a meta-analysis of subsequent clinical trials with tamoxifen did not detect a positive influence of additional tamoxifen treatment on overall survival in advanced melanoma.5 The pathogenetic impact of ER expression differs between different cancer types. For example, ERβ proves to have an antiproliferative effect in prostate cancer, while, in contrast, its expression is associated with poor prognosis in ovarian cancer.6, 7 Besides ER α and β, also ‘nonclassical’ oestrogen receptors such as the G protein-coupled oestrogen receptor (GPER) are investigated with growing interest. In the present issue of this journal, Fabian et al.8 report on differential expression of GPER in a total of 81 primary melanomas, either pregnancy-associated melanoma (PAM) or nonpregnancy-associated melanoma (NPAM). GPER is thought to allow for alternative oestrogen-mediated signalling via the MAP-kinase and other intracellular pathways in cells lacking classical ERs. As for other ERs, its role in the pathogenesis of hormone-related cancer is ambiguous with both tumour-promoting and tumour-protective effects proposed in the literature.9 In melanoma, Fabian and colleagues found a significantly higher immunohistochemical and immunofluorescent cytoplasmatic expression of GPER in PAM compared with NPAM (78.4% vs. 27.9%; P = 0.0000), while similar frequencies of ER β expression were reported in both groups (81.6% vs. 60.5%). For immunohistochemical analyses, the authors used ER antibody clones that have recently been considered as specific.10 This is important, because a number of other available ER antibodies have been shown not to stain consistently or to have problems with cross-reactivity. Double receptor expression of ER β and GPER was detected in 73% and 28% of PAM and NPAM, respectively, and was associated with established positive prognostic markers such as lower Breslow thickness, lower mitotic rate and presence of peritumoural lymphocyte infiltration. Hence, the authors suggest that immunohistochemical double ER expression may serve as a novel prognostic indicator in melanoma. This hypothesis needs additional investigation. First, because double receptor expression was not associated with improved disease-free survival in multivariate analysis, which may be attributed to the small sample size of the study, but may also reflect that ERs are predominantly expressed on thinner, less proliferative primary melanomas for other, yet unknown reasons. Second, although ER expression was significantly more frequent in PAM, no survival difference was demonstrated for PAM compared to NPAM, which is in line with the literature on melanoma in pregnancy.11 In addition, the relevance of driver mutations such as BRAF or NRAS for ER expression is not understood. Taken together, the influence of oestrogen and associated receptor expression patterns on melanoma development remains unclear. Further research in this field is needed, especially as the superior prognosis of female melanoma patients continues to imply a role of sexual hormones in melanoma pathogenesis. Contrary parts of oestrogens (tumour-promoting) and progestins (protective) have been recently suggested in this context.12 Moreover, the role of antihormonal therapeutics such as tamoxifen may be worth rethinking in selected melanoma patients.13

Does pregnancy influence melanoma prognosis? A meta-analysis.

The literature has not been able to conclude whether pregnancy influences the prognosis of melanoma. The aim of this study was to explore the prognosis of melanoma diagnosed during pregnancy or post partum [pregnancy-associated melanoma (PAM)] compared with melanoma in female patients who were not pregnant. We systematically searched for studies of female patients with melanoma that reported outcomes related to survival. Fifteen eligible studies were found. Overall, PAM was associated with a 17% higher mortality compared with melanoma diagnosed in female patients who were not pregnant (hazard ratio=1.17, 95% confidence interval: 1.03-1.33, P=0.02). The heterogeneity associated with this test was moderate (P=0.07; I=38%). PAM was also associated with a 50% higher recurrence rate compared with melanoma not associated with pregnancy (hazard ratio=1.50, 95% confidence interval: 1.19-1.90, P<0.001). The heterogeneity associated with this test was low (P=0.69; I=0%). A limitation of this meta-analysis is the definition of PAM, which is not unanimous among the studies included. Our results indicate that PAM is associated with a worse prognosis than melanoma not related to pregnancy, both in terms of overall survival and disease-free survival. On the basis of our data, we anticipate that the survival difference we report here will be further amplified with the addition of future well-carried out studies. We suggest that detection of PAM requires particular awareness by healthcare professionals.

Is Pregnancy-Associated Melanoma Associated with Adverse Outcomes?

Melanoma is the most common malignancy encountered during pregnancy. Conflicting data have led to ongoing confusion regarding pregnancy-associated melanoma (PAM) in themedia and among the public. The objective of this study was to better characterize both the clinical presentation of PAM and its prognostic implications. Female patients of reproductive age, with stage 0 to IV cutaneous melanoma, were identified from our prospectively maintained database. Clinical and histopathologic factors were analyzed with appropriate statistical methods. Univariable and then multivariable analysis were used on matched data to compare disease-free survival (DFS), overall survival (OS), and melanoma-specific survival (MSS) for stage 0-III PAMs vs non-PAMs. Kaplan-Meier survival curves were then plotted for OS and MSS and compared using the log-rank test. The clinical presentation of melanoma was similar for PAM and non-PAM patients. There was no significant difference in recurrence between the 2 groups; for PAM patients, 38.5% of patients had recurrence, as compared with 36.6% of non-PAM patients (p= 0.641). For PAM patients, median follow-up was 14.6 years (range 0 to 42.6 years) and 11.1 years (0 to 48.5 years) for the non-PAM patients. No significant differences in DFS, MSS, or OS were identified on univariable or multivariable analysis for PAM vs non-PAM patients in stage 0/I/IIand stage III cutaneous melanoma, respectively (p= 0.880 DFS, p= 0.219 OS, and p=0.670 MSS). We observed no difference in DFS, OS, or MSS between the 2 groups. Pregnant patients should be screened for melanoma in a similar manner to nonpregnant patients and should be counseled that their survival is not adversely affected by their pregnancy.

Maternal and perinatal outcomes in pregnancy-associated melanoma. Report of two cases and a systematic literature review

ObjetivesMelanoma is one of the most frequent malignancies during gestation. However, oncological and perinatal management is still challenging. Our first objective is to describe the cases of pregnancy-associated melanoma (PAM) diagnosed in our centre between January-2004 and May-2015. Secondly, to perform a systematic review of the published articles analysing the maternal-perinatal outcomes of patients diagnosed with PAM. Design, population and methodsObstetrical, oncological and perinatal variables were recorded in the case series. For the systematic review we include all published articles assessing the obstetric and neonatal outcomes in PAM cases in Pubmed, Web of Knowledge and Cochrane Library. The search was restricted to articles published in English, between January-2004 and May-2015. Study characteristics, oncological and maternal-perinatal variables were recorded in the systematic review. ResultsTwo patients were found: the first case presents a newly diagnosed metastatic melanoma at 26-weeks of gestation with fatal maternal and neonatal outcome. The second case presents a patient with metastatic melanoma who got pregnant during her treatment. For the systematic review we found 25 articles, providing data from 489 patients. Maternal-perinatal outcomes, including termination of pregnancy rates, vary depending on the country, gestational age and tumour stage at diagnosis. PAM is usually detected at advanced stages, even with metastasis affecting the placenta and the foetus. ConclusionsWhen diagnosed at early stages, melanoma does not seem to alter the evolution of gestation, whereas patients with advanced stages of melanoma frequently deliver prematurely, by caesarean section, with lower neonatal weight, higher neonatal morbidity and mortality rates.

Melanoma in pregnancy.

Melanoma is one of the most common cancers diagnosed in pregnancy and has a high metastatic potential. As the incidence of melanoma increases, careful clinical evaluation of suspicious skin lesions remains the mainstay of early diagnosis. There is controversy in the literature as to whether pregnancy-associated melanoma has worse survival than other melanomas. Any changing-pigmented lesion should be biopsied, regardless of pregnancy hyperpigmentation. Increased lymphangiogenesis in pregnancy is associated with increased metastasis - timely diagnosis is therefore imperative. While the effect of oestrogen and progesterone on melanoma is under investigation, it is generally accepted that oral contraceptive use in not contraindicated after a diagnosis of melanoma in pregnancy. Subsequent pregnancy should be delayed for two to three years after a diagnosis of melanoma with a high risk of recurrence.