Congenital Nevi Research Articles

Surgical Therapy of Congenital Nevi in the First Year of Life-Psychological Impact on Parents.

The birth of a child with a congenital melanocytic nevus (CMN) can lead to distress in the parents. Surgical treatment of CMN can begin in infancy. To provide insight into the perspective of parents of children with CMN regarding their experienced psychological burden and motivation to undergo surgery as well as their satisfaction. Retrospective analysis of patient data of infants (< 1 year of age), who were surgically treated by power stretching for CMN using subcutaneous infiltration anesthesia (SIA) from 01/01/2020 to 08/31/2021. To evaluate the parent's motivation and psychological burden during the surgical treatment of their child, a questionnaire was designed to interview them in a standardized telephone-based interview. Out of 45 interviewed parents, 62.2% indicated "severe" or "very severe" distress at the time of their child's birth. Distress was mostly reduced by information about diagnosis and treatment (n = 34) and treatment-progress (n = 27). Stigmatization was experienced by 35.6% of parents. 84,5% of parents were highly satisfied with early initiation of surgical therapy. 69% felt "very satisfied" or "satisfied" with the outcome of surgery. Motivation for surgical therapy was concern about malignant transformation of the, possible stigmatization of the child due to the nevus, while most of the parents (73.3%) mentioned both. Surgical treatment of CMN by power stretching in SIA in infancy is associated with high levels of satisfaction among the children's parents. Early initiation of surgical therapy and education about the diagnosis can reduce the psychological burden of the parents and can prevent psychosocial problems in affected children.

Mosaic BRAF Fusions Are a Recurrent Cause of Congenital Melanocytic Nevi Targetable by MAPK Pathway Inhibition

Among children with multiple congenital melanocytic naevi (CMN), 25% have no established genetic cause, of which many develop a hyperproliferative and severely pruritic phenotype resistant to treatment. Gene fusions have been reported in individual cases of CMN. Here, we study 169 CMN patients, 38 of whom were double wild-type for NRAS/BRAF mutations. Nineteen of these 38 patients had sufficient tissue to undergo RNAseq, which revealed mosaic BRAF fusions in 11/19 patients and mosaic RAF1 fusions in 1/19. Recurrently, fusions involved the loss of the 5' regulatory domain of BRAF or RAF1 but preserved the kinase domain. We validated all cases and detected the fusions in two separate naevi in 5/12 patients, confirming clonality. The absence of the fusion in blood in 8/12 patients indicated mosaicism. Primary culture of BRAF-fusion naevus cells from 3/12 patients demonstrated highly increased MAPK activation, despite only mildly increased BRAF expression, suggesting additional mechanisms of kinase activation. Trametinib quenched MAPK hyperactivation in vitro and treatment of two patients caused rapid improvement in bulk tissue, improving bodily movement, and reducing inflammation and severe pruritus. These findings offer a genetic diagnosis to an additional group of patients and trametinib as a treatment option for the severe associated phenotypes.

UV-radiation and MC1R germline mutations are risk factors for the development of conventional and spitzoid melanomas in children and adolescents

Genomic characterisation has led to an improved understanding of adult melanoma. However, the aetiology of melanoma in children is still unclear and identifying the correct diagnosis and therapeutic strategies remains challenging. Exome sequencing of matched tumour-normal pairs from 26 paediatric patients was performed to study the mutational spectrum of melanomas. The cohort was grouped into different categories: spitzoid melanoma (SM), conventional melanoma (CM), and other melanomas (OT). In all patients with CM (n=10) germline variants associated with melanoma were found in low to moderate melanoma risk genes: in 8 patients MC1R variants, in 2 patients variants in MITF, PTEN and BRCA2. Somatic BRAF mutations were detected in 60% of CMs, homozygous deletions of CDKN2A in 20%, TERTp mutations in 30%. In the SM group (n=12), 5 patients carried at least one MC1R variant; somatic BRAF mutations were detected in 8.3%, fusions in 25% of the cases. No SM showed a homozygous CDKN2A deletion nor a TERTp mutation. In 81.8% of the CM/SM cases the UV damage signatures SBS7 and/or DBS1 were detected. The patient with melanoma arising in giant congenital nevus (CNM) demonstrated the characteristic NRAS Q61K mutation. UV-radiation and MC1R germline variants are risk factors in the development of conventional and spitzoid paediatric melanomas. Paediatric CMs share genomic similarities with adult CMs while the SMs differ genetically from the CM group. Consistent genetic characterization of all paediatric melanomas will potentially lead to better subtype differentiation, treatment, and prevention in the future. Found in Acknowledgement.

3D Printing and Surgical Simulation for Management of Large and Giant Congenital Melanocytic Nevi.

Tissue expansion with subsequent adjacent tissue transfer is often the preferred and sometimes the only option for reconstruction of large and giant congenital melanocytic nevi. Successful reconstruction with maximal efficiency and optimal aesthetic outcome requires careful planning of the tissue transfer, which itself requires careful selection of the tissue expander size and positioning. Unfortunately, there is little opportunity to gain experience in these skills due to the rarity of this condition. In situations where there is a rare condition that requires a complex technical procedure with much interoperative decision-making, surgical experience can be supplemented with the use of surgical simulation. In this article, we report on the use of three-dimensional patient imaging, three-dimensional printing, and surgical simulation for planning the reconstruction of large and giant congenital melanocytic nevi. We describe how this technology allows us to simulate multiple different approaches to expander placement and adjacent tissue transfer. We also describe how these simulations can be used to create cutting guides to guide final incision design and reduce intraoperative decision-making. Finally, we discuss how these models can be used to educate patients and families about the process and outcomes of nevus excision and reconstruction.

Wanita 74 Tahun Dengan Metastasis Pada Lobus Parieto-Oksipital Pada Melanoma Maligna

Melanoma is a tumor that is produced by the malignant transformation of melanocyte cells. Melanoma is the leading cause of premature death from cancer. Known risk factors include personal or family history of melanoma, large numbers of naevi and/or dysplastic naevi, congenital melanocytic naevi, sun-damaged skin, history of non-melanoma skin cancer, and immunodeficiency. Based on the Basic Health Research Results (Riskesdas) report, skin cancer as a whole ranks 3rd in Indonesia. Epidemiological studies of skin cancer have reported in Jakarta in 2014–2017, where out of 263 cases of skin cancer, malignant melanoma ranks third with the highest incidence of skin cancer (5.7%). Diagnosis of melanoma can be made by assessing the skin lesions with the naked eye and also by the patient's clinical symptoms. A person's risk of metastases is directly related to the depth of invasion and ulceration of their primary lesion. Among solid tumors, melanoma has one of the highest propensities to cause brain metastases with a proportion of more than 25% of patients. Although the current cancer treatment paradigm may reflect a combination of surgery, chemotherapy, radiotherapy, and immunotherapy with medical management, options for the treatment of metastatic brain cancer remain limited.

Transformed Giant Congenital Melanocytic Nevus on 18 F-FDG PET/CT.

A 50-year-old man experienced cough and bloody sputum for 1 month. CT detected a mass in the right lung. Staging 18 F-FDG PET/CT revealed multiple hypermetabolic lesions in the lung, mediastinum, liver, and bones. Further physical examination revealed black patches in the skin covering most parts of the body, which presented at his birth and were growing very slowly, consistent with giant congenital melanocytic nevus. Pathology examination after biopsy of the lung demonstrated metastatic melanoma.

Serum levels of S-100 protein are directly proportional to the size, number, thickness and degree of cellularity of congenital melanocytic nevi

Serum levels of S-100 protein are directly proportional to the size, number, thickness and degree of cellularity of congenital melanocytic nevi

The influence of intensive care treatment in infancy on cortisol levels in childhood and adolescence

BackgroundInfants admitted to the intensive care unit experience numerous early-life stressors, which may have long-term effects on hypothalamic-pituitary-adrenal axis functioning. AimsTo determine the effects of intensive care treatment and related exposure to stress, pain, and opioids in infancy on cortisol levels in childhood and adolescence. Study designCross-sectional study. SubjectsChildren and adolescents aged 8 to 18 years with a history of intensive care treatment in infancy and healthy controls. The intensive care treatment cohort consisted of four subgroups with varying levels of exposure to stress, pain, and opioids in infancy. They received either mechanical ventilation, extracorporeal membrane oxygenation, major surgery, or excochleation of a giant congenital melanocytic nevus. Outcome measuresBetween-group differences in stress reactivity to a study visit consisting of pain threshold testing and an MRI examination and diurnal cortisol levels, as measured in saliva. ResultsAfter adjustment for age, sex, and gestational age, the diurnal cortisol output (AUCg) in the overall intensive care group (N = 76) was 18 % (approximately 1000 nmol/L) (95 % CI [−31 %, −3 %], P = 0.022) lower than that in the control group (N = 67). Cortisol awakening response, diurnal decline, and stress reactivity neither differed significantly between the overall intensive care group and control group, nor between the intensive care subgroups and control group. ConclusionChildren and adolescents with a history of intensive care treatment in infancy have similar cortisol profiles to those of healthy controls, except for an 18 % lower diurnal cortisol output. The clinical relevance of this reduction is yet to be determined.

Single Stage Excision and Thick Split Thickness Skin Graft Technique for Facial Giant Congenital Melanocytic Nevi with Consideration of Facial Aesthetic Subunits: A Case Report and Literature Review

Due to their three-dimensional anatomy, functional importance, and esthetic appeal, giant congenital melanocytic nevus (GCMN) of the face pose the greatest challenge to reconstructive surgeons, especially when there are few donors and a significant deformity. A 25-year-old male patient presented with a facial GCMN. GCMN management involves complete nevus removal and reconstruction using tissues of the same color, thickness, and as the surrounding skin. Some defect closure options were inapplicable due to the almost complete forehead defect. This study aims to report the author's successful experience treating an adult case of GCMN with single-stage excision and subunit facial restoration using thick split-thickness skin graft (STSG). In this case, thick STSG is considered to prevent the risk of secondary contracture and conspicuous discoloration. In addition to esthetic and functional outcomes, the patient's social status and self-esteem also improved. This technique promises esthetic results, such as reduced downtime, and improved psychological function.

Congenital Melanocytic Nevus: An Unusual Presentation

The overgrowth of melanocytes produces congenital melanocytic nevus. They are commonly present since birth, and the common terms used to describe them are called 'bathing trunk,' 'coat-sleeve,' or 'stocking naevi,' and they are usually found over thighs and back. The giant congenital nevus of size larger than twenty centimeters is highly pigmented and usually hairy. It is more commonly found in females compared to males. It is well recognized that the lesion's displeasing nature might have psychological and social ramifications, negatively affecting the patient's self-esteem, particularly females. Although congenital melanocytic nevus is mostly clinically diagnosed, the histological investigation is required to confirm the diagnosis and rule out malignant changes. The likelihood of transforming the giant nevus to malignant melanoma accounts for approximately five percent; fifty percent of melanomas develop before age two, and eighty percent develop before age seven. The risk of transformation to malignant melanoma is early in giant melanocytic nevus cases and adolescence in small and medium-sized nevi cases. Other complications like transformation to neurocutaneous melanosis consisting of the spread of melanoma to the central nervous system and leptomeninges are also dreadful. Hence, early removal is recommended. Here, we have reported a rare case of a six-year-old patient with a medium-sized nevus on their face with hairy tufts in between. On biopsy, the diagnosis was made as a junctional nevus. After which, the patient was managed with subsequent lesion excision and split skin grafting with an uneventful postoperative period. Our case report aims to report a rare case of congenital melanocytic nevus and to determine the importance of timely diagnosis and intervention. Keywords: , , , ,

A high-hydrostatic pressure device for nevus tissue inactivation and dermal regeneration for reconstructing skin defects after giant congenital melanocytic nevus excision: a clinical trial

BackgroundA novel treatment has been developed to reconstruct large skin defects caused by the excision of giant congenital melanocytic nevi. It involves the reimplantation of high-hydrostatic pressurized nevus tissue as a cell-inactivated autologous scaffold for dermal regeneration, followed by the implantation of cultured epithelial autografts on the regenerated dermis. Because this treatment has shown promise in a first-in-human clinical trial which used a prototype pressure machine, a novel pressure device was specifically designed for clinical use. MethodsIn a prospective investigator-initiated clinical trial involving three patients, we evaluated the safety and efficacy of the skin regeneration treatment using a pressure device. All three patients underwent surgical excision of the nevus tissue, primary reimplantation of the inactivated nevus tissue, and secondary implantation of cultured epithelial autografts. ResultsEngraftment of inactivated nevus tissue and cultured epithelial autografts was successful in all three cases, with over 90% epithelialization at 8 weeks post-surgery. No serious adverse events or device malfunction were observed during the trial. ConclusionThe novel pressure device safely and effectively enabled dermal regeneration using the nevus tissue as an autologous scaffold. This innovative approach offers several advantages, including reduced invasiveness due to minimal sacrifice of normal skin for skin grafting and high curative potential resulting from full-thickness removal of the nevus tissue.

Clinical management of a rare melanoma case arising from congenital melanocytic nevus

Clinical management of a rare melanoma case arising from congenital melanocytic nevus

A case series of congenital nevus and their various manifestations

A nevus is characterized by collection of partially differentiated or well-differentiated cells normally found in the skin. Some nevi are associated with disorders such as autism, epilepsy, ophthalmogical disorders, intracranial abnormalities, and others. In this case series, we aim to analyze six cases with congenital nevus, matched our findings with case reports published and reviewed the literature, to come to a conclusion that would help the clinician to do focused clinical examination and investigations when they come across such nevi. Furthermore, as these sort of skin lesions cause psychological morbidity to both parents and patients, proper counseling is required along with dermatological therapy and treatment of comorbid conditions. As well as regular follow-up with monitoring of the lesions. The following are the cases: Case-1, is a case of congenital melanocytic nevi who presented with delayed milestone, epilepsy and neuroimaging revealed intracranial melanosis. Case-2 nevus of Ota on face with scleral nevus and glaucoma in the left eye. In Case-3: Nevus achromicus was present over the abdomen and scalp in a child who presented with status epilepticus and there was focal cortical dysplasia of left frontal cortex on imaging. Nevus sebaceous was present in case-4 who had seizure disorder but neuroimaging was normal. Case-5 child had nevus spilus over left frontal area with melanocytic satellite nevi who presented with febrile convulsion but normal neuroimaging. The sixth case is a 5-year-old male child with linear nevus without any other association.

Reconstruction of Hemifacial Congenital Giant Nevus with Pre-expanded Scalp Flaps and Deltopectoral Skin Flaps.

The hemifacial congenital giant nevus impacts both physical and mental health of the patients. Excision is typically the most suitable option in these situations, but reconstructing the subsequent surgical defects is always a serious challenge. Between February 2012 and January 2021, a retrospective review of 4 patients who suffered from hemifacial congenital giant nevus was conducted, and they were treated by pre-expanded scalp flap and deltopectoral flap simultaneously. All patients receive tissue expansion, nevus resection, expanded skin flap transfer, and pedicle division. Four patients with hemifacial congenital giant nevi were successfully treated with no major complications. One patient with a transferred deltopectoral flap experienced distal necrosis of the flap, and healed after dressing changes. No recurrence of the nevus was found during the follow-up period, and the transferred skin flaps match well with facial skin in contour and color. This modified pre-expanded scalp flap combined with a deltopectoral flap provides an easy and reliable way for hemifacial reconstruction in patients with a congenital giant nevus.

Refinements in the Preexpanded Distant Flap for Giant Melanocytic Nevi of the Upper Extremity in Pediatric Patients.

Surgical treatment of large and giant congenital melanocytic nevi (GCMN) of the upper extremity is challenging because of limited options for reconstruction. A preexpanded distant flap is considered an important option in upper extremity reconstruction, where the soft tissue available for use is limited. The authors aimed to refine the preexpanded distant flap after excision of the GCMN in the upper extremity. Large (>10 cm) and giant (>20 cm) congenital melanocytic nevi of the upper extremities treated with tissue expansion and distant flaps over 10 years were retrospectively reviewed, and the authors describe in detail the surgical strategies for reconstruction of the upper extremity with a distant flap. From March of 2010 to February of 2020, 13 patients (mean age, 2.87 years) treated with 17 preextended distant flaps were included. The mean flap dimension was 154.87 cm 2 , ranging from 15 × 5 to 26.5 × 11 cm. All procedures were successfully completed except for one, in which partial flap necrosis occurred. Preconditioning was performed before flap transfer in 5 patients with larger rotation arcs and flap dimensions. The mean duration of postoperative follow-up was 51.85 months. A new reconstructive protocol was proposed that combined the 3 elements, including a distant flap, tissue expander, and preconditioning. In the treatment of GCMN in the upper extremities, careful planning and multiple stages are required. For pediatric patients, the preextended distant flap with preconditioning is useful and effective for reconstruction. Therapeutic, IV.

“Paradoxical” p16 overexpression in cutaneous melanoma: Molecular and immunohistochemical analysis of a rare phenomenon with a focus on cell cycle regulatory molecules

BackgroundOne of the most relevant genetic alterations in cutaneous melanoma (CM) is the biallelic inactivation/loss-of-heterozygosis (LOH) of cyclin-dependent kinase inhibitor 2 A (CDKN2A), which results in the immunohistochemical loss of p16 frequently found in CM. However, we recently described a rare case of dermal/deep-seated melanoma arising in giant congenital nevus (DDM-GCN) with p16 overexpression combined with p53 loss and tumor protein 53 (TP53) mutation. Herein, we reported a case series of CM with p16 overexpression and analyzed their clinicopathologic features, immunohistochemical expression of the cell cycle regulatory molecules (CCRM: p53, p21, Cyclin D1, Rb), and mutational landscape. MethodsWe retrospectively tested for p16 all cases of CM diagnosed at our institution between January 1st 2019-April 1st 2022. In CM with p16 overexpression, we reported clinicopathologic features, immunohistochemical results for melanocytic markers and CCRM, and mutational landscape investigated with a next-generation sequencing (NGS) panel. In cases with zonal p16 overexpression, the immunohistochemical assessment for melanocytic markers and CCRM, as well as the NGS analysis have been performed in both components {with and without p16 overexpression [p16(+)c and p16(-)]}. ResultsOverexpression of p16 was found in 10/2879 (0.35%) CM [5/10 (50%) diffuse and 5/10 (50%) zonal]. We combined the immunohistochemical results for CCRM and molecular data to classify the cases as follows: a) Group 1 with altered expression of at least one CCRM but no TP53 mutations [3/10 (30%), all with Rb altered/lost]; b) Group 2 with altered expression of at least one CCRM and TP53 mutations [4/10 (40%), all with p53 altered]; c) Group 3 with normal expression of CCRM and no TP53 mutations [3/10 (30%), all with mutations in MAPK pathway genes (NRAS and BRAF)]. In CM with zonal p16 overexpression, the histologic appearance of p16(+)c was heterogeneous, whereas combining CCRM profiles and molecular data the cases could be categorized as follows: a) cases with the same CCRM and molecular profiles in both p16(+)c and p16(-)c; b) cases with p16(+)c showing additional genetic mutations and/or modifications of CCRM expression. Conclusionsp16 overexpression is a rare event, occurring in advanced-stage, clinically- and histologically-heterogeneous CM. These lesions may be classified into three different groups based on CCRM expression and mutational profiles (including TP53 mutation). The analysis of CM with zonal p16 overexpression suggests that, at least in a subset of cases, this phenomenon could represent a sign of “molecular progression” due to the acquisition of additional genetic mutations and/or modifications of the CCRM profile.

Impact of public exhibition on the perception of birthmarks.

The importance of photographs in social media, the steep rise in popularity of tattoos, and the prominence of individuals with visibly different skin in fashion are likely to be changing the landscape of self- and public perception of birthmarks. Study objectives were to assess the impact of a photoshoot and public exhibition on the self-perception of individuals with extensive birthmarks, and to explore the viewing public's reactions. Thirty individuals with congenital melanocytic nevi (CMN) were recruited internationally. Each had a professional photoshoot portrait with their skin exposed, resulting in a public exhibition in London entitled "How do you C Me Now?" Participants/parents completed pre- and post-questionnaires relating to self-perception and the impact of their birthmarks on behavior. Over 8000 members of the public viewed the exhibition, 464 completing an on-site questionnaire on its effects. All participants/parents rated the experience as positive, valuable and helpful. Scores on self-appreciation and self-confidence were significantly higher after the photo shoot. Members of the general public overwhelmingly reported the exhibition increased their positive feelings towards people with birthmarks. The majority of public respondents also reported that the exhibition made them feel better about their own skin and about their looks in general. This unique exhibition and the associated research has provided a striking new perspective on potential psychological interventions for individuals with birthmarks.

Photo gallery. Rare dermatoses. Part I

Orphan dermatoses are caused by both genetic causes and a number of autoimmune, inflammatory and infectious processes in the body. Congenital giant nevus is associated with serious complications: malignant melanoma, CNS lesions (neurocutaneous melanosis). Multiple epidermoid cysts are often a component of Gardner's syndrome. Angiolymphoid hyperplasia with eosinophilia, a vascular tumor formation with proliferation of histiocytoid endothelial cells, with severe lymphocytic and eosinophilic infiltration, recurs in 1/3 of cases. Morbigan's disease is persistent erythema and swelling of the middle third and upper part of the face. Skin mastocytosis in children is prone to spontaneous resolution during puberty. Squamous cell skin cancer accounts for 20% of all skin cancers and has a high risk of recurrence, metastasis, and death. Buschke's scleroderma is a scleroderma-like disease that causes progressive fibrous-mucinous thickening of the skin affecting the neck, shoulders, proximal upper extremities, and face. Fulminant (lightning) acne is a sharply exacerbated form of acne vulgaris, characterized by an acute onset and the appearance of confluent abscesses. Cases of acne fulminans have been observed during treatment with isotretinoin. Norwegian (crustose) scabies is associated with a compromised immune response, which allows the mites to multiply and can number in the millions. Pretibial myxedema (thyroid dermopathy) is a rare extrathyroid manifestation of Graves' disease along with thyrotoxicosis, thyroid hypertrophy, ophthalmopathy, and acropachy. Porokeratosis Mibelli predisposing factors of development are immunosuppressive conditions, malignancy is possible. Osteomas are formations from bone tissue in the dermis or subcutaneous fat as a result of metaplasia of fibroblasts into osteoblasts, or differentiation of primitive mesenchymal cells into osteoblasts and their migration to an ectopic site. Sarcoidosis of the skin is characterized by a variety of clinical forms, rarely observed before 40 years. Xanthomas with histiocytosis X ― a violation of lipid metabolism. The rural type of leishmaniasis (acute necrotizing) has a short incubation period, a significant spread of rashes and healing with the formation of scar tissue. The giant condyloma of BuschkeLevenshtein is characterized by progressive growth, large size and recurrent course, it can transform into squamous cell carcinoma. Degos disease ― malignant atrophic papulosis ― a rare disease caused by blockage of the arteries and veins.

Ganglioneuroma Arising in Congenital Melanocytic Nevus in a Patient with Cardiac Anomalies: A Case Report.

A congenital melanocytic nevus is a benign melanocyte proliferation, that may be complicated by malignant transformation. We are reporting a three-year-old girl, who had a giant congenital melanocytic nevus on her back, that was treated by serial surgical excisions with tissue expander insertion. Histopathological examination confirmed the diagnosis of congenital melanocytic nevus with ganglioneuroma. Out of approximately 250 case reports on congenital melanocytic nevus, we identified only two reports of medium/large congenital melanocytic nevus with cutaneous ganglioneuroma. Due to the potential malignant transformation of congenital melanocytic nevus, reporting the features and characteristics of such rare findings may help in further understanding congenital melanocytic nevus, its associations, and prognosis.

Transcriptome Analysis Identifies Oncogenic Tissue Remodeling during Progression from Common Nevi to Early Melanoma

Early detection and treatment of melanoma, the most aggressive skin cancer, improves the median 5-year survival rate of patients from 25% to 99%. Melanoma development involves a stepwise process during which genetic changes drive histological alterations within nevi and surrounding tissue. Here, we perform a comprehensive analysis of publicly available gene expression datasets of melanoma, common or congenital nevi (CN), and dysplastic nevi (DN), and assess molecular & genetic pathways leading to early melanoma. Our results demonstrate several pathways reflective of ongoing local structural tissue remodeling activity likely involved during the transition from benign to early-stage melanoma. These processes include the gene expression of cancer associated fibroblasts (CAF), collagens, extracellular matrix (ECM) and integrins, which assist early melanoma development and the immune surveillance which plays a substantial role at this early stage. Further, we show genes upregulated in dysplastic nevi (DN) are also overexpressed in melanoma tissue, supporting the notion DN may serve as a transitional phase towards oncogenesis. Lastly, we reveal CN collected from healthy individuals exhibit different gene signatures compared to histologically benign nevi tissue located adjacent to melanoma (adjacent nevi, AN). We show the expression profile of micro-dissected AN tissue is more similar to melanoma compared to CN, revealing the melanoma influence on this annexed tissue.