RETINAL OXIMETRY IS ALTERED IN EYES WITH CHOROIDAL MELANOMA BUT NOT IN EYES WITH CHOROIDAL NEVI.

PURPOSE: To compare retinal vessel oxygenation in eyes with an untreated choroidal nevus or choroidal melanoma. METHODS: The affected and fellow eye of patients with an untreated choroidal nevus (n = 42) or choroidal melanoma (n = 45) were investigated using noninvasive retinal oximetry (Oxymap T1). Oxygen saturation of arterioles (ArtSat) and venules (VenSat) was determined, together with the arteriovenous difference (AV-difference). RESULTS: In choroidal nevus patients, retinal oximetry did not differ between the affected and fellow eye: the mean ArtSat was 94.5% and 94.2% (P = 0.56), the VenSat was 60.5% and 61.3% (P = 0.35), and the AV-difference was 34.0% and 32.9% (P = 0.18), respectively. In choroidal melanoma patients, alterations were detected: the mean ArtSat was 94.8% and 93.2% (P = 0.006), the VenSat was 58.0% and 60.0% (P = 0.014), and the AV-difference was 36.8% and 33.2% (P < 0.001), respectively. The largest increase in AV-difference was observed between the retinal halves without the lesion in melanoma eyes compared with the corresponding half in the fellow eye (37.5% vs. 32.1%, P < 0.001). CONCLUSION: Although retinal oximetry was not significantly altered in eyes with a choroidal nevus, eyes with choroidal melanoma showed an increased ArtSat and decreased VenSat, leading to an increased AV-difference. These changes may be caused by inflammation and a higher metabolism, with larger oxygen consumption, leading to altered blood flow and intraocular oxygen relocation.

Involvement of circulatory disturbance in optic disk melanocytoma with visual dysfunction.

PURPOSE: This study aims to examine the relationship between ocular circulation changes and visual field defects in optic disk melanocytoma (ODM). METHODS: Five eyes of five patients were enrolled in this study. All patients were diagnosed with ODM in the Department of Ophthalmology, Hokkaido University Hospital from March 2009 to November 2017. Ophthalmological data including optical coherence tomography angiography (OCTA) and laser speckle flowgraphy (LSFG) findings were retrospectively analyzed. RESULTS: The five ODM cases consisted of two females and three males. Ages of the patients ranged from 47 to 82 years (mean 54 years). Follow-up periods were from 4 to 105 months. Fluorescein angiography showed hypo-fluorescence throughout the examination in all four eyes examined with this modality. OCTA detected dense blood vessel networks in the tumor in two out of the five eyes. Nasal visual field defects were found in two other eyes, which were correlated with locations of tumors free of vessel networks. One ODM eye without marked visual field defects and pigmentations showed lower mean blur rates determined by LSFG in optic disk vessels and tissue circulations than those in the contralateral eye. During follow-up, there was no tumor enlargement in any case. CONCLUSIONS: This study showed the relationship between the deficit of blood vessel networks and visual field defects in ODM patients. LSFG demonstrated reduced blood flow in the tumor, suggesting that circulatory disorder caused by the optic disk tumor might be correlated with visual field defect.

Sparing of the nipple-areola complex by capillary malformations: Vascular variant of the Bork-Baykal phenomenon.

The"Bork-Baykal phenomenon" refers to the sparing of the nipple-areola complex in large congenital melanocytic nevi involving the breast. So far, this finding has not been reported in vascular anomalies. We present four patients with an extensive capillary malformation (CM) involving the breast that was found to exhibit a similar sparing of the nipple and areola. All of these capillary nevi were associated with asymmetric overgrowth.

Papular Epidermal Nevus with Skyline Basal Cell Layer (PENS): Three New Cases and Review of the Literature.

BACKGROUND/OBJECTIVE: Papular epidermal nevus with skyline basal cell layer (PENS) is a recently described type of epidermal nevus with characteristic histopathologic findings, mainly regular, rectangular acanthosis and a well-demarcated basal cell layer with clear palisading and separation between basal cell nuclei and the first row of Malpighian cell nuclei. Although the first reports described randomly distributed lesions appearing sporadically in otherwise healthy patients, cases of Blaschkoid distribution, lesions associated with extracutaneous manifestations, and familial cases have been reported. METHODS: We performed a review of the clinical charts of all patients with histologic diagnosis of PENS in our hospital. We evaluated epidemiologic, clinical, and histologic features. We then reviewed the literature with a particular emphasis on the presence or absence of extra-cutaneous associations. RESULTS: Three patients with PENS are described. One had a single lesion, one had three lesions, and one, a patient with mild developmental delay, a curved penis, and hypospadias, had multiple lesions. CONCLUSION: The probability of having extracutaneous manifestations is 6.3 times as great in individuals with more than four lesions. Therefore these patients may need closer follow-up.

Pigment Loss in Patients with Large Congenital Melanocytic Nevi: Various Clinical Presentations Documented in a Large Series.

BACKGROUND/OBJECTIVES: The association between vitiligo and congenital melanocytic nevi remains incompletely understood. The objective of this study was to investigate the frequency of depigmentation, including vitiligo, in patients with a large congenital melanocytic nevus (LCMN), which is a rare melanocytic tumor variant. METHODS: We retrospectively reviewed the files of 92 patients with an LCMN, including photographic documentation regarding the presence of pigment loss on the nevus mass, around the nevus, around the satellites, and elsewhere on the body. RESULTS: Depigmentation was observed in 8 (8.7%) of 92 patients with an LCMN. Depigmented areas within the main nevus mass were observed in six patients, and adjacent or remote vitiligo was observed in four patients. One patient also demonstrated halo depigmentation around some satellite nevi. CONCLUSION: The coexistence of an LCMN with vitiligo does not appear to be rare and may occur with a spectrum of clinical presentations.

Growth and hormone profiling in children with congenital melanocytic naevi.

BACKGROUND: Multiple congenital melanocytic naevi (CMN) is a rare mosaic RASopathy, caused by postzygotic activating mutations in NRAS. Growth and hormonal disturbances are described in germline RASopathies, but growth and hormone status have not previously been investigated in individuals with CMN. OBJECTIVES: To explore premature thelarche, undescended testes, and a clinically abnormal fat distribution with CMN through prospective endocrinological assessment of a cohort of subjects with CMN, and a retrospective review of longitudinal growth of a larger group of patients with CMN from outpatient clinics (which included all subjects in the endocrinological assessment group). PATIENTS AND METHODS: Longitudinal growth in a cohort of 202 patients with single or multiple CMN was compared with the U.K. National Child Measurement Programme 2010. Forty-seven children had hormonal profiling including measurement of circulating luteinizing hormone, follicle-stimulating hormone, thyroid stimulating hormone, adrenocorticotrophic hormone, growth hormone, prolactin, pro-opiomelanocortin, estradiol, testosterone, cortisol, thyroxine, insulin-like growth factor-1 and leptin; 10 had oral glucose tolerance testing 25 had dual-energy X-ray absorptiometry scans for body composition. RESULTS: Body mass index increased markedly with age (coefficient 0·119, SE 0·016 standard deviation scores per year), at twice the rate of the U.K. population, due to increased adiposity. Three per cent of girls had premature thelarche variant and 6% of boys had persistent undescended testes. Both fat and muscle mass were reduced in areas underlying large naevi, resulting in limb asymmetry and abnormal truncal fat distribution. Anterior pituitary hormone profiling revealed subtle and variable abnormalities. Oral glucose tolerance tests revealed moderate-severe insulin insensitivity in five of 10, and impaired glucose tolerance in one. CONCLUSIONS: Interpersonal variation may reflect the mosaic nature of this disease and patients should be considered individually. Postnatal weight gain is potentially related to the underlying genetic defect; however, environmental reasons cannot be excluded. Naevus-related reduction of fat and muscle mass suggests local hormonal or metabolic effects on development or growth of adjacent tissues, or mosaic involvement of these tissues at the genetic level. Premature thelarche and undescended testes should be looked for, and investigated, as for any child.

Higher psychological and psychovegetative strain in adolescents with atypical pigment naevi.

An observational, exploratory, cross-sectional study was performed to assess whether the presence of atypical naevi (AN) in adolescents is associated with psychological and psychovegetative stress parameters. Fifty-one students of a secondary school in Graz, Austria, completed a defined test procedure consisting of an initial period of rest, a standardised mental stress task, another period rest and a questionnaire, the change-sensitive symptom list (ASS-SYM). Electrocardiogram and blood pressure were recorded continuously. The study population was divided in two groups: probands without AN (NAN, n = 33), and probands with at least one AN (n = 18). We found higher values for the AN group in all scales of ASS-SYM, reaching statistical significance in the dimensions "nervousness and mental tension" (p = 0.025), "psychophysiological dysregulation" (p = 0.020), burden of pain" (p = 0.023) and "general symptoms and problems" (p = 0.031). Regarding physiological parameters, the AN group showed higher vegetative strain reflected in heart rate and heart rate varibility during the periods of rest as well as a reduced baroreceptor sensitivity. On the basis of our results, the presence of AN in adolescents seems to be associated with a higher vegetative arousal. Additionally, participants with AN complained significantly more often about stress-associated general psychological symptoms and problems.

Natural history of atypical and equivocal melanocytic lesions in children: an observational study of 19 cases.

Digital dermoscopy follow-up helps to identify patterns of change typical of common atypical nevi and early melanoma and improves the follow-up of patients with atypical nevi. We report the morphologic changes observed over time in 19 atypical or equivocal acquired melanocytic nevi that underwent dermoscopic follow-up. Two observers retrospectively examined digitalized dermoscopic images of 19 atypical melanocytic nevi from 15 children and young adults (median age 12 years, range 3-26 years). The images were assessed for global dermoscopic patterns at baseline and after a median 25-month (range 6-138 mos) follow-up. Ten (52.6%) nevi changed and nine (47.4%) retained a stable dermoscopic pattern. Of the 10 changing lesions, 2 of 4 homogeneous nevi evolved into a reticular pattern and 2 into a mixed pattern; 1 of 2 nevi with a mixed pattern evolved into a homogeneous nevus and 1 into a regressing nevus; 1 of 2 nevi with "other" patterns, such as negative pigment network and peppering throughout the lesion, evolved into a mixed nevus and 1 into a regressing nevus; 1 globular nevus evolved into a mixed pattern; and 1 starburst nevus evolved into a homogeneous nevus. The most striking results of our study were that atypical nevi can evolve into common nevi or they can regress, as documented by long-term dermoscopic follow-up. In children and young adults, dermoscopic follow-up of atypical nevi might be a valid alternative to surgical excision and enables us to achieve new insights into the natural history of these nevi.

Phacomatosis pigmentokeratotica--a patient with hypophosphatemic rickets.

The epidermal naevus syndrome (ENS) is a sporadic condition characterized by congenital epidermal naevi associated with anomalies in other organ systems, most commonly the central nervous system and skeleton. We report a case of ENS presenting hypophosphataemic rickets resistant to traditional therapeutic agents.

Eruptive melanocytic nevi in a patient with amelanotic melanoma: a paraneoplastic phenomenon?

Eruptive melanocytic nevi (EMN) describes the sudden onset of cutaneous nevi over weeks or months. Such a clinical event is generally seen in young adult patients and may be related to several possible causes. We report here a case of EMN in an old male patient followed up for a thick amelanotic cutaneous melanoma. A few months after the eruption, multiple hepatic masses, diagnosed as melanoma metastasis, were detected. The presented case may suggest that EMN may be a paraneoplastic phenomenon of alert in patients being followed for melanoma or other malignancies.

The correlation of TRPM1 (Melastatin) mRNA expression with microphthalmia-associated transcription factor (MITF) and other melanogenesis-related proteins in normal and pathological skin, hair follicles and melanocytic nevi.

BACKGROUND: Melastatin (TRPM1), a.k.a. transient receptor potential cation channel, subfamily M, member 1 (TRPM-1) regulates melanocyte differentiation and proliferation. TRPM1 is transcriptionally regulated by the essential melanocyte transcription factor MITF (microphthalmia-associated transcription factor). For the most part, MITF expression is preserved during melanoma progression, while TRPM1 mRNA expression decreases or is completely lost. The loss of TRPM1 is associated with melanomas that are more aggressive. OBJECTIVE: To assess the relationship between TRPM1 mRNA expression and the expression of MITF and nine other markers of melanocytes and melanin-related proteins by immunohistochemistry in normal skin, scars, hair follicles and ordinary melanocytic nevi. METHODS: Samples of normal skin (n = 102; from tumor excisions and plastic procedures), scars (n = 5; from re-excision specimens) and compound melanocytic nevi (n = 4) were evaluated for the presence of TRPM1 mRNA transcripts as detected by chromogenic in situ hybridization (CISH). Immunohistochemical techniques were used to detect melanin-related proteins including: MITF, S100 protein, Mart-1, tyrosinase, Mel5, HMB45, tyrosinase-related protein-1 (TRP1), TRP2 and alpha-melanocyte stimulating hormone (alphaMSH). The labeling index (LI) was defined as the number of intraepidermal cells expressing mRNA or protein per one hundred basal keratinocytes. RESULTS: A wide range of LI was found for all markers (0-33 positive cells/100 keratinocytes). When these LI were compared, no significant differences in the expression of MITF, S100, Mart1, tyrosinase proteins and TRPM1 mRNA were identified. The LI for TRPM1 mRNA expression ranged from 74% of that for MITF to 86% for tyrosinase. The LI for TRP-1, TRP-2 and Mel5 was similar to that of TRPM1, while HMB-45 had a significantly lower LI than all other markers. TRPM1 mRNA correlated most tightly with MITF and tyrosinase expression (r = 0.81 and 0.68, respectively, both p = 0.0001). Likewise, the strongest correlation among all the melanin-related proteins existed between tyrosinase and MITF (r = 0.79, p = 0.0001). There was variable expression of melanin-related proteins when LI were analyzed by anatomic site, patient age, extent of sun-damage and proximity to a melanocytic tumor. Anogenital skin showed the highest and acral skin the lowest LI for TRPM1, MITF, S100 protein, Tyrosinase, Mel5 and HMB45. Advanced age (> 60 years) was associated with decreased TRPM1 expression. Sun-damaged skin exhibited significantly increased LI as measured by MITF, S100 protein, Mart1, tyrosinase and HMB-45, but no differences for TRPM1. However, the MITF-TRPM1 differential (i.e. MITF LI-TRPM1 LI = MITF+TRPM1--melanocytes) was significantly increased in site-matched skin (4.6 +/- 4.4 vs. 1.5 +/- 2.5, p = 0.01). There was a suggestion of reduced LI in normal skin in the proximity of melanoma (from melanoma re-excision specimens) for S100, HMB45 and TRPM1 mRNA. TRPM1 LI was significantly decreased in scars compared to normal skin (5.6 +/- 1.4 vs. 9.7 +/- 4.3, p = 0.02), this was reflected in an increase in the MITF-TRPM1 differential (9.6 +/- 7.5 vs. 3.2 +/- 3.1, p = 0.0001). MITF LI were consistently higher than MSLN LI at all levels of the hair follicle; notably, MITF was expressed by isthmic-bulge cells. In ordinary melanocytic nevi, MITF and TRPM1 expression decreased with melanocyte descent: there was more signal for both markers in superficial epithelioid type A melanocytes than deeper type C melanocytes. CONCLUSIONS: By CISH, TRPM1 mRNA expression is specific for melanocytes and strongly associated with MITF and tyrosinase expression, the latter implicating a mature melanocyte phenotype. However, in normal skin, TRPM1 mRNA expression appears to be dynamic, labeling most but not all melanocytes, with variable expression ostensibly related to local environmental factors.

Simplified management of a giant forehead congenital nevus allows for early reconstruction.

We report simplified surgical management of giant congenital forehead nevus that customarily requires the use of tissue expander for complete excision. Commencing treatment at the age of 3 months, the TopClosure tension relief system (TRS) was applied as an external tissue expander allowing preoperative skin stretching by mechanical creep. This was followed by partial excision of the nevus. Intraoperative stress-relaxation allowed further expansion of the skin. Postoperative wound closure was secured with the aid of the TRS. Repeated, six simple staged excisions of the forehead lesion and a minor skin graft to the eyelid part, allowed for delayed primary closure of the entire lesion by the age of 2. This simple alternative approach, which allows the early start and early conclusion of the reconstructive process, should be considered as the primary option in the treatment of these patients.

Bathing trunks nevus: case report of giant congenital melanocytic nevus.

Bathing trunks nevi, a subtype of giant congenital melanocytic nevi (CMN), are skin tumors that present by 2 years of age and occur in a low percentage of all births. We report a case of bathing trunks nevus that was initially suspected to be melanoma, and describe the history, pathophysiology, and treatment options for CMN. We also discuss the risk for neurocutaneous melanosis (NCM), which is a rare syndrome in patients with giant CMN.

Management of pigmented skin lesions in childhood and adolescence.

BACKGROUND: Pigmented skin lesions in childhood and adolescence can be diagnostically challenging. It is important for general practitioners to be aware of the spectrum of benign, atypical and malignant pigmented lesions occurring in these patient groups and of features that should raise concern. OBJECTIVE: The aims of this article are to assist recognition of high-risk skin lesions encountered in childhood and adolescence and to provide an understanding of the features and management of suspected melanoma in this population. DISCUSSION: In children and adolescents, there exist a variety of congenital and acquired naevi and other pigmented skin lesions that can be diagnostically problematic. Additionally, conventional detection criteria for melanoma seen in adults are often not present in children and adolescents, making diagnosis more difficult. Melanoma, if diagnosed in these populations, should be treated at a specialist centre whenever possible.

Spontaneous involution of congenital melanocytic nevi of the scalp.

Large or giant congenital melanocytic nevi are rare. They are associated with a risk of melanoma, which is poorly quantified, and often represent a major cosmetic problem. Surgical intervention is the most common treatment, although dermabrasion or curettage in the first weeks of life is used in some centers. When these nevi occur in the scalp, the risk of melanoma has been reported to be lower. Here we describe a series of children in whom large congenital melanocytic nevi on the scalp appeared to spontaneously involute. Therefore, our findings indicate that these nevi also have a better prognosis cosmetically. It is suggested that the decision about surgical treatment should be deferred until the maximal improvement in appearance has occurred during the first 2 years of life.

Orofacial signs and dental abnormalities in patients with Mulvihill-Smith syndrome: A literature review on this rare progeroid pathology.

BACKGROUND: Mulvihill-Smith syndrome is a rare sporadic condition that was first recognized in 1975. A total of 11 cases have been described in the literature. The aim of this study was to describe the orofacial signs and dental anomalies, their frequency, and the relationship between Mulvihill-Smith syndrome and other progeroid syndromes via a review of the literature. METHODS: A systematic PubMed search was performed to retrieve articles published between 1975 and the present day that described patients affected by Mulvihill-Smith syndrome. The search identified 14 articles, and data on 11 patients were extracted from the selected articles. RESULTS: A total of 7 patients (63.6%) affected by Mulvihill-Smith syndrome were described as having a typical "bird" face. Dental abnormalities, including irregular shape, enamel defects, hypodontia, and taurodontism, were described in 6 patients (54.5%). All patients (100%) had multiple pigmented nevi on the face and a lack or thinning of subcutaneous tissue around the neck and face. Three patients with Mulvihill-Smith syndrome exhibited early onset of tumors of the gastrointestinal tract, including the tongue. CONCLUSION: Mulvihill-Smith syndrome is a clinically complex disease that may be caused by a single gene mutation. Numerous different tissues of the body are affected. This analysis of the orofacial signs may help clinicians to diagnose this rare pathology.

Visual acuity in 3422 consecutive eyes with choroidal nevus.

OBJECTIVE: To evaluate visual acuity in eyes with choroidal nevus. DESIGN: This was an observational case series. Of 3422 consecutive eyes with choroidal nevus, vision loss at 15 years occurred in 2% of eyes with extrafoveolar nevus and in 26% of eyes with subfoveolar nevus, particularly those with overlying retinal pigment epithelial detachment and foveal edema. A retrospective medical record review was conducted, with evaluation of visual acuity at presentation and at final examination. The main outcome measure was visual acuity. RESULTS: The median visual acuity at presentation was 20/20 for eyes with either extrafoveolar or subfoveolar choroidal nevus. Using Kaplan-Meier estimates, vision loss of 3 or more logarithm of the minimum angle of resolution (logMAR) lines at 5, 10, and 15 years occurred in less than 1%, 1%, and 2% of eyes with extrafoveolar nevus compared with 15%, 20%, and 26% of eyes with subfoveolar choroidal nevus, respectively. By multivariate analysis, factors predictive of visual loss of 3 or more logMAR lines included subfoveolar nevus location (relative risk [RR], 15.52), juxtapapillary nevus location (RR, 4.52), initial visual acuity of 20/50 or worse (RR, 15.40), overlying retinal pigment epithelial detachment (RR, 22.16), and foveal edema (RR, 9.02). Factors predictive of poor final visual acuity of 20/200 or worse included subfoveolar nevus location (RR, 11.32), overlying orange pigment (RR, 3.68), overlying retinal pigment epithelial detachment (RR, 12.80), and foveal edema (RR, 18.72). CONCLUSION: Mild vision loss over many years should be anticipated in patients with subfoveolar choroidal nevus, particularly those with overlying retinal pigment epithelial detachment, orange pigment, and foveal edema.

Desmoplastic giant congenital nevus with progressive depigmentation.

Desmoplastic hairless hypopigmented nevus is an extremely rare sclerotic, alopecic, and progressively hypopigmented giant congenital melanocytic nevus, which is histologically characterized by an intense desmoplasia. A significant trend toward spontaneous involution has been described. We report a case of desmoplastic hairless hypopigmented nevus that underwent a progressive depigmentation associated with loss of its woody consistency. The loss of induration appears to be the main marker for the complete regression of these nevi.

Optic disc melanocytoma and glaucoma.

An 82-year-old man presented with optic disc melanocytoma and glaucomatous optic neuropathy. The coexistence of these findings is particularly challenging, as there is no specific means for differentiating whether the optic nerve damage is glaucoma- or melanocytoma-related.

A dual concept of nevogenesis: theoretical considerations based on dermoscopic features of melanocytic nevi.

The dermoscopic features of melanocytic nevi in children are clearly different from those in adults. While nevi in children show almost exclusively globular patterns, those in adults usually exhibit reticular patterns. These remarkable differences could be explained by a dual concept of nevogenesis, based on current clinico-epidemiologic, dermoscopic, histopathologic and genetic data.