The Areola study: design and rationale of a cohort study on long-term health outcomes in women with implant-based breast reconstructions.

BACKGROUND: Implant-based breast reconstructions contribute considerably to the quality of life of breast cancer patients. A knowledge gap exists concerning the potential role of silicone breast implants in the development of so-called "breast implant illness" (BII) and autoimmune diseases in breast cancer survivors with implant-based reconstructions. BII is a constellation of non-specific symptoms reported by a small group of women with silicone breast implants. METHODS: The Areola study is a multicenter retrospective cohort study with prospective follow-up aiming to assess the risk of BII and autoimmune diseases in female breast cancer survivors with and without silicone breast implants. In this report, we set out the rationale, study design, and methodology of this cohort study. The cohort consists of breast cancer survivors who received surgical treatment with implant-based reconstruction in six major hospitals across the Netherlands in the period between 2000 and 2015. As a comparison group, a frequency-matched sample of breast cancer survivors without breast implants will be selected. An additional group of women who received breast augmentation surgery in the same years will be selected to compare their characteristics and health outcomes with those of breast cancer patients with implants. All women who are still alive will be invited to complete a web-based questionnaire covering health-related topics. The entire cohort including deceased women will be linked to population-based databases of Statistics Netherlands. These include a registry of hospital diagnostic codes, a medicines prescription registry, and a cause-of-death registry, through which diagnoses of autoimmune diseases will be identified. Outcomes of interest are the prevalence and incidence of BII and autoimmune diseases. In addition, risk factors for the development of BII and autoimmune disorders will be assessed among women with implants. DISCUSSION: The Areola study will contribute to the availability of reliable information on the risks of BII and autoimmune diseases in Dutch breast cancer survivors with silicone breast implants. This will inform breast cancer survivors and aid future breast cancer patients and their treating physicians to make informed decisions about reconstructive strategies after mastectomy. REGISTRATION: This study is registered at ClinicalTrials.gov on June 2, 2022 (NCT05400954).

Familial clustering of giant congenital melanocytic nevi.

Giant congenital melanocytic nevus (GCMN) is an infrequently occurring congenital malformation. GCMN generally occurs in isolation but rare familial occurrence points to a genetic background. We present two cases of familial GCMN: one with two affected siblings and another with two affected double second cousins. Familial occurrence of GCMN reported in literature is reviewed and an overview of the embryology and proliferation given, illustrating the plethora of factors that might lead to GCMN formation. The pattern of inheritance is likely not Mendelian and discordance in identical twins and the segmental distribution of lesions suggest a post-zygotic mutation. A polygenic paradominant inheritance best explains the clinically observed transmission pattern. Candidate genes include those influencing neural crest development and melanocyte proliferation.

Results of the early use of tissue expansion for giant congenital melanocytic naevi on the scalp and face.

SUMMARY INTRODUCTION: Giant congenital melanocytic naevi (GCMN) are uncommon, have a significant morbidity and require extensive treatment. This paper presents results after complete excision of GCMN on the scalp, forehead or periorbita after early tissue expansion. Based on 15 years of experience, we want to show that performing tissue expansion at a young age is advisable. PATIENTS AND METHODS: We included 17 consecutive patients in whom 38 tissue expanders were used. Early and late complications were noted. Patients were seen for a clinical follow up in which scars and re-pigmentation were evaluated with a validated scar scale (POSAS). RESULTS: All GCMN could be excised completely with early tissue expansion. The age at treatment ranged from 4 months to 2 years of age. With a mean follow-up period of 8.7 years, mild re-pigmentation was seen in only three patients and none of the patients developed a malignant melanoma. Complication rates are comparable with the literature. CONCLUSION: Tissue expansion is a good method for removing GCMN located at the scalp or face with good cosmetic and oncological results. Performing tissue expansion at a young age is advisable.

Risk of malignant transformation of congenital melanocytic nevi: a retrospective nationwide study from The Netherlands.

PURPOSE: Since the risk of malignant transformation is the most important reason to remove congenital melanocytic nevi, and data vary in the literature, we aimed to determine the incidence of malignant transformation in congenital melanocytic nevi in The Netherlands. METHODS: The Dutch nationwide pathology database, PALGA (Pathologisch Anatomisch Landelijk Geautomatiseerd Archief), provided anonymous pathology descriptions of all patients registered with congenital melanocytic nevi (giant or nongiant nevus) and of patients with a malignant melanoma within a congenital melanocytic nevus who were diagnosed between January 1, 1989, and December 31, 2000. A comparison was made between cancer incidence in our cohort of patients and the general population by applying the person-year distribution in the cohort to sex-, age- and calendar period-specific reference data obtained from The Netherlands Cancer Registry. Our cohort consisted of 3929 patients. RESULTS: After a median follow-up time of 4.7 years, a total of 15 cases of malignant melanoma were observed in 19,253 person-years, against 1.23 expected cases. The incidence rate of malignant melanoma was greater than expected on the basis of population rates, overall standardized incidence rate of 12.2 (95 percent confidence interval 9.6 to 15.3). Compared with the general population rates, we observed an increased risk for malignant melanoma, both in men (standardized incidence ratio = 6.4; 95 percent confidence interval 4.1 to 9.6) and women (standardized incidence ratio = 14.1; 95 percent confidence interval 10.5 to 18.7). This is comparable with the higher propensity of women to develop a malignant melanoma. Patients with a giant nevus had a 51.6 percent higher risk of developing a malignant melanoma compared with the general population rates. CONCLUSION: Our study shows that congenital melanocytic nevi have a significantly higher risk of developing a malignant melanoma compared with the age-, sex-, calendar-period-specific reference data from The Netherlands Cancer Registry.