Melanin Deposition Research Articles

Esophageal Melanocytosis in African American Male

Esophageal melanocytosis is usually regarded as a benign finding with potential progression to malignant melanoma, Endoscopic surveillance has been suggested to prevent disease progression. We describe a case report with incidental finding of esophageal melanocytosis during an upper endoscopy. A 64-year-old African American male with a past medical history of GERD, erosive esophagitis and chronic hepatitis C was admitted for workup of anemia. He was noted to have guiac positive stool without any overt symptoms of bleeding. On admission, vital signs were stable and physical examination was unremarkable. Prior endoscopic workup included negative colonoscopy, multiple upper endoscopies for gastric ulcers, erosive esophagitis and portal hypertensive gastropathy. After negative routine blood workup to diagnose anemia, an upper endoscopy was performed. He was noted to have a discolored patch of mucosa in the posterior pharynx extending into epiglottis and proximal esophagus. Gastric and duodenal biopsies showed chronic inflammation. Biopsy from esophagus showed esophageal squamous mucosa with benign melanin staining cells in the basal epithelium. Histological pattern was consistent with benign melanocytosis. Esophageal melanocytosis is a rare, benign condition, with unclear etiology and pathogenesis. There seems to be an association with chronic inflammatory stimuli like acid reflux and heavy alcohol consumption. Some studies report association with conditions like esophageal squamous cell carcinoma, Laugier-Hunziker syndrome, Addison's disease, oral melanoma. 25 to 30% of surgical specimens of primary malignant melanoma showed melanocytosis indicating that it could be a precursor of melanoma. Histologically, esophageal melanocytosis is characterized by proliferation of melanocytes in the basal layer of squamous epithelium with melanin deposition in mucosa. The lesions should be differentiated histologically from blue nevus or malignant melanoma. It commonly found in mid to lower esophagus, but our patient had involvement of proximal esophagus. Esophageal melanocytosis is assumed to be a benign condition without need for surveillance or follow-up with further endoscopies and biopsies. Without definitive evidence for ongoing surveillance, our patient was treated for gastritis/esophagitis with Proton pump inhibitors and discharged home. To date, there is no clear and definitive evidence of progression of Esophageal melanocytosis to melanoma.Figure 1Figure 2Figure 3

Ions switch off darkness: role of TPC2 in melanosomes

Ions switch off darkness: role of <scp>TPC</scp>2 in melanosomes

Primary Malignant Melanoma of Liver–A Report of 2 Cases

Background: Malignant melanoma is extremely aggressive cancer arising from melanocytes. 90% of all melanomas are of cutaneous origin, although liver is a frequent site of metastasis from melanoma. Primary hepatic melanoma (PHM) is rare. Case Report: In this case report, we present 2 patients of PHM, who came with jaundice, ascites, abdominal pain, for a short duration (1–2 months) and progressively worsened in a short span and finally succumbed. CT scans of both patients revealed diffusely distributed nodules of varying sizes in both the lobes of liver with no evidence of portal hypertension. Liver biopsy showed tumour cells with poor differentiation, which were in nests with prominent melanin deposits. The pigmentation distributed sinusoidally, which was heavy enough to obscure cell morphology. Pigment could be bleached with potassium permanganate. Immunohistochemical stain showed, tumour cells were positive for HMB-45, s100, melanin A. Comprehensive dermatologic, ophtholmological examination revealed no evidence of cutaneous or ocular primary lesion. Other sites like brain, respiratory tract, lung, GIT, were not involved. Our case report showed that, primary malignant melanoma of liver has a histological diversity and immunohistochemical staining may aid in differential diagnosis from other hepatic neoplasms. Both of the above patients died in a short duration after diagnosis, which confirms PHM are extremely aggressive tumours associated with short life span (months). Conclusion: The rare occurrence and aggressive nature of PHM eludes the development of optimal treatment regimen and study of natural history of tumor. The usefulness of chemotherapy, radiation, and immunotherapy in treatment of PHM has potential for further research. The authors have none to declare.

Antimelanogenic effects of luteolin 7-sulfate isolated fromPhyllospadix iwatensisMakino

Abnormal deposition of melanin may cause an aesthetic skin problem; therefore, the control of unwanted excessive melanin synthesis is the major goal of cosmetic research. To identify novel tyrosinase (TYR) inhibitors from marine plants and examine their cellular antimelanogenic effects. The extracts of 50 marine plants endemic to Korea were screened against human TYR. Active constituents were then isolated from the selected plant extracts that showed potential and their chemical structures elucidated. Furthermore, their antimelanogenic effects were examined using murine melanoma B16/F10 cells and human epidermal melanocytes (HEM). Among the tested extracts, that of Phyllospadix iwatensis Makino exhibited the strongest human TYR inhibitory activity. The active constituents were purified from the butanol fraction of the P. iwatensis extract and identified as hispidulin 7-sulfate and luteolin 7-sulfate. Luteolin 7-sulfate inhibited human TYR more strongly than hispidulin 7-sulfate, luteolin, hispidulin and arbutin. Furthermore, luteolin 7-sulfate showed lower cytotoxicity than luteolin in both B16/F10 cells and HEM. Luteolin 7-sulfate attenuated cellular melanin synthesis more effectively in B16/F10 cells and HEM stimulated by α-melanocyte-stimulating hormone and l-tyrosine than arbutin. This study demonstrates that luteolin 7-sulfate isolated from P. iwatensis is a human TYR inhibitor with advantageous antimelanogenic properties, and would be useful for development as a therapeutic agent for the control of unwanted skin pigmentation.

Melanin 'dust' or 'ghost'?

Melanin 'dust' or 'ghost'?

First record of leucism in Glossophaga soricina valens (Phyllostomidae: Chiroptera) from Peru

Leucism is a genetic condition that manifest as the total or partial lack of coloration, as result of a deficiency in the melanin deposit in the skin and fur. We present the first occurrence of leucism in Glossophaga soricina valens from Peru, a nectarivorous species of the western slope of the Andes from Peru and Ecuador, and the Maranon valley. Also, we discuss some implications of this occurrence, and update the checklist of bat species recorded with leucism in the America.

Melanocortin 1 Receptor: Structure, Function, and Regulation.

The melanocortin 1 receptor (MC1R) is a melanocytic Gs protein coupled receptor that regulates skin pigmentation, UV responses, and melanoma risk. It is a highly polymorphic gene, and loss of function correlates with a fair, UV-sensitive, and melanoma-prone phenotype due to defective epidermal melanization and sub-optimal DNA repair. MC1R signaling, achieved through adenylyl cyclase activation and generation of the second messenger cAMP, is hormonally controlled by the positive agonist melanocortin, the negative agonist agouti signaling protein, and the neutral antagonist β-defensin 3. Activation of cAMP signaling up-regulates melanin production and deposition in the epidermis which functions to limit UV penetration into the skin and enhances nucleotide excision repair (NER), the genomic stability pathway responsible for clearing UV photolesions from DNA to avoid mutagenesis. Herein we review MC1R structure and function and summarize our laboratory’s findings on the molecular mechanisms by which MC1R signaling impacts NER.

Age related changes in brain MR appearance in the course of neurocutaneous melanosis

BackgroundPatients with giant congenital melanocytic nevi (GCMN) have increased risk of neurocutaneous melanosis (NCM). Brain MRI is mandatory in GCMN. ObjectivesTo present the age related changes in brain MRI in children with NCM during several-year follow-up. MethodsIn 7 NCM children following data were analyzed: main nevus localization, surgical treatment phase, histology of excised nevi, time of NCM diagnosis, number of MRI studies, neurological symptoms, changes of melanin deposits in brain during follow-up. ResultsFour children had bathing trunk nevus, two main nevus on back, one on head. Surgical excision is finished in 3 patients, 4 are in the course of multistage surgery. In one melanoma arising in GCMN was diagnosed. Six patients are neurologically healthy, one suffers from seizures. Age of patients at first MRI ranged from 12days to 7 years. All patients underwent more than one MRI. Follow-up period ranges from 2.5 to 8.5 years. Most of T1-hyperintense foci in brains regressed with time. In one case new lesion appeared, in one more lesions were visible on second MRI. ConclusionsIn all patients with NCM on subsequent MRI image changes were found with respect to original location and size of melanin deposits in CNS. Changes of NCM appearance on MRI with advancing age of patients reflect natural history of this disorder. Theory of gradual disappearance of intracerebral melanin deposits with age seems to be more likely than theory of their worse visualization on MRI with time.

Conditional Knockout in Mice Reveals the Critical Roles of Ppp2ca in Epidermis Development.

The epidermis is an important tissue in Homo sapines and other animals, and an abnormal epidermis will cause many diseases. Phosphatase 2A (PP2A) is an important serine and threonine phosphatase. The α isoform of the PP2A catalytic subunit (Ppp2ca gene encoding PP2Acα) is critical for cell proliferation, growth, metabolism and tumorigenesis. However, to date, no study has revealed its roles in epidermis development. To specifically investigate the roles of PP2Acα in epidermis development, we first generated Ppp2caflox/flox transgenic mice, and conditionally knocked out Ppp2ca in the epidermis driven by Krt14-Cre. Our study showed that Ppp2caflox/flox; Krt14-Cre mice had significant hair loss. In addition, histological analyses showed that the morphogenesis and hair regeneration cycle of hair follicles were disrupted in these mice. Moreover, Ppp2caflox/flox; Krt14-Cre mice had smaller size, melanin deposition and hyperproliferation at the base of the claws. Accordingly, our study demonstrates that PP2Acα plays important roles in both hair follicle and epidermis development. Additionally, the Ppp2caflox/flox mice generated in this study can serve as a useful transgene model to study the roles of PP2Acα in other developmental processes and diseases.

Adrenal pigmentation in PPNAD is a result of melanin deposition and associated with upregulation of the melanocortin 1 receptor

Adrenal pigmentation in PPNAD is a result of melanin deposition and associated with upregulation of the melanocortin 1 receptor

Pigmented desmoplastic trichilemmoma

Desmoplastic trichilemmoma (DT), the pseudomalignant variant of conventional trichilemmoma described by Hunt et al in 1990, displays a superficial lobular growth pattern of glycogen-rich cells with peripheral nuclear palisading surrounded by a thickened basement membrane. DT differs from its conventional counterpart by showing a central hyalinized area with epithelial cords and strands mimicking invasive carcinoma. We report a case that fully satisfies the criteria for DT and, in addition, shows an extensive melanocytic cell component and prominent melanin deposition. To our knowledge, a pigmented variant of DT has not been reported and should be recognized in order to appropriately face the differential diagnosis with malignant pigmented tumors particularly pigmented basal cell carcinoma (BCC).

Clinical and Histopathologic Assessment of Facial Melasma After Low-Fluence Q-Switched Neodymium-Doped Yttrium Aluminium Garnet Laser.

Melasma is a frequent and difficult to treat skin disorder. Results of laser therapy are inconsistent. To determine the safety and efficacy of low-fluence Q-switched neodymium-doped yttrium aluminum garnet (QS Nd:YAG) laser for melasma treatment and assess recurrence rates and histopathologic findings before and after treatment. Twenty patients were treated with 10 weekly sessions of low-fluence 1064-nm QS Nd:YAG laser at 1-week intervals. The modified Melasma Area and Severity Index (mMASI) score was evaluated at baseline; 1 week; and 1, 3, and 6 months after treatment. Epidermal melanin quantification was performed on 10 biopsy samples and compared before and after treatment. All patients showed improvement by mMASI scores, range (21%-75%) compared with that at baseline. No permanent side effects occurred. The recurrence rate was 81%. By histopathology, a slight, nonsignificant (p = .305) decrease in melanin deposition was seen in all layers of the epidermis 1 week after the laser treatments ended. The results confirm the safety and effectiveness of low-fluence QS Nd:YAG laser for treating melasma; however, the high recurrence suggests poor long-term results when the laser is used as a monotherapy.

Anti-Melanogenic Effects of Aceriphyllum rossii Leaf Ethanol Extract on Melanocytes

We evaluated the skin whitening effects of Aceriphyllum rossii leaf ethanol extract (ARLEE) in vitro using melan-a cells. The maximum permissible level for ARLEE application to melan-a cells was 50 μg/mL. In gross observation, ARLEE reduced melanin deposition and melanocyte dendricity in a dose-dependent manner. When compared to treatment with vehicle, ARLEE treatment (50 μg/mL) significantly decreased melanin contents by 33.0% (p<0.001), an even greater decrease than arbutin (positive control) treatment (27.2%). ARLEE treatment (50 μg/mL) significantly decreased intracellular tyrosinase activity by 48.8% (p<0.001), an even greater decrease than seen after arbutin treatment (36.0%). ARLEE treatment (50 μg/mL) significantly decreased tyrosinase protein and mRNA expression by 30.5% and 37.7% (p<0.01), respectively. These results suggest that ARLEE has better skin whitening activity than arbutin in melan-a cells, and this activity is likely mediated at the level of tyrosinase transcription. These results suggest that ARLEE could be used in functional cosmetic materials to prevent or alleviate skin pigmentation.

Electron Probe Microanalysis of Exogenous Pigmentation of Oral Mucosa Originating from Dental Alloy: Two Case Reports

Pigmentation of the oral mucosa is relatively common and has a wide variety of etiologies. Although most pigmented lesions of the oral mucosa are associated with deposition of melanin and accidental displacement of a dental alloy, accurate differential diagnosis of a pigmented lesion is important, especially in the case of malignant melanoma. We report two cases of oral mucosal pigmentation associated with accidental displacement of a dental alloy in which malignant melanoma was suspected. Excisional biopsy was carried out in these cases with the incision line set at approximately 5 mm from the lesions. Histopathologically, brownish foreign substances were observed in the lamina propria. Metal quantitative analyses of the extracted specimens were carried out by electron probe microanalysis (EPMA). The metal components and the mass concentration revealed that the metals were derived from a dental casting silver alloy in Case 1 and from a gold-silver palladium alloy in Case 2. Although exogenous pigmentation originating from a dental alloy is not rare, differential diagnosis of oral pigmented lesions is sometimes very difficult. In such cases, histopathological examination may be necessary for the diagnosis to exclude melanocytic lesions and EPMA may be effective to identify the causative dental alloy.

A Comparative Study of Two Modalities, 4% Hydroquinone Versus 30% Salicylic Acid in Periorbital Hyperpigmentation and Assessment of Quality of Life Before and After Treatment.

Background:Periorbital hyperpigmentation (POH) is a common hyperpigmentary problem of the face, which can be psychologically distressing and it can influence an individual's quality of life. However, this condition has received less attention in literature.Aims and Objectives:To study the clinico-etiological features and the effect of two therapeutic modalities on the quality of life in patients of POH before and after treatment.Materials and Methods:Fifty patients attending the outpatient clinic of Dermatology Department, with clinically evident POH were included. All patients were divided randomly into two groups of 25 each and one group was treated with 4% hydroquinone and another group with 30% salicylic acid for 12 weeks. Assessment with visual analog scale (VAS) was done at 4, 6, and 12 weeks, and outcome of the patients was analyzed statistically.Results:Majority of the cases, i.e. 26 (52%) were in the age group of 20–30 years. Females comprised 74% of the study population. On VAS, most of the patients showed mild improvement (10–30%) at 12 weeks of treatment in both the groups. Separately, both the treatments significantly improved the dermatological life quality index of the patients although there was no significant difference found between the two groups.Conclusion:POH is less responsive to standard treatments due to its multifactorial etiology and deposition of melanin in both dermis and epidermis. However, even the mild to moderate improvement in appearance can cause an improvement in the quality of life of the patients.

Activation of Melanin Synthesis in Alternaria infectoria by Antifungal Drugs.

The importance of Alternaria species fungi to human health ranges from their role as etiological agents of serious infections with poor prognoses in immunosuppressed individuals to their association with respiratory allergic diseases. The present work focuses on Alternaria infectoria, which was used as a model organism of the genus, and was designed to unravel melanin production in response to antifungals. After we characterized the pigment produced by A. infectoria, we studied the dynamics of 1,8-dihydroxynaphthalene (DHN)-melanin production during growth, the degree of melanization in response to antifungals, and how melanization affected susceptibility to several classes of therapeutic drugs. We demonstrate that A. infectoria increased melanin deposition in cell walls in response to nikkomycin Z, caspofungin, and itraconazole but not in response to fluconazole or amphotericin B. These results indicate that A. infectoria activates DHN-melanin synthesis in response to certain antifungal drugs, possibly as a protective mechanism against these drugs. Inhibition of DHN-melanin synthesis by pyroquilon resulted in a lower minimum effective concentration (MEC) of caspofungin and enhanced morphological changes (increased hyphal balloon size), characterized by thinner and less organized A. infectoria cell walls. In summary, A. infectoria synthesizes melanin in response to certain antifungal drugs, and its susceptibility is influenced by melanization, suggesting the therapeutic potential of drug combinations that affect melanin synthesis.

TEKNIK BEDAH DENGAN SKALPEL PADA HIPERPIGMENTASI GINGIVA

Background: Gingival pigmentation is the coloring/staining of the gingiva in the form of a dark purplish color or irregular light brown spots. This staining is derived from melanin granules produced by cells melanoblas. Gingival hyperpigmentation caused by excessive melanin deposition . The cause of this gingival hyperpigmentation is multifactorial : genetic factors , local and systemic . The aims of this article is to overbear the gingival hyperpigmentation with simple techniques , does not require several equipments , but gives contentment results to the patient . Discussion : The gingival melanin hyperpigmentation is not cause medical problems , usually to the point the appearance especially when talking and smiling . Depigmentation is periodontal plastic surgery to remove or reduce gingival hyperpigmentation . There are many ways to eliminate gingival hyperpigmentation , one of them is a surgical using scalpel . Depigmentation surgery does not require any special tools but gives satisfactory results for the patient. Conclusion : Hyperpigmentation gingival surgery techniques can be overcome by using scalpel surgery.

Mosquito hemocytes preferentially aggregate and phagocytose pathogens in the periostial regions of the heart that experience the most hemolymph flow

When a mosquito acquires an infection in the hemocoel, dedicated immune cells called hemocytes aggregate around the valves of the heart. These sessile hemocytes are called periostial hemocytes. In the present study we scrutinized the immune response mounted by the periostial hemocytes of the malaria mosquito, Anopheles gambiae, against bacterial pathogens, and tested the relationship between periostial hemocyte aggregation, immune activity, and hemolymph flow. Initially, we quantified the process of periostial hemocyte aggregation and found that hemocytes migrate to the periostial regions in response to infection with Escherichia coli, Staphylococcus aureus, Staphylococcus epidermidis, and Micrococcus luteus (all infections tested). Then, we investigated whether the periostial hemocytes are evenly distributed along the six periostial regions of the heart, and found that they preferentially aggregate in the periostial regions of the mid-abdominal segments (4, 5 and 6). This distribution perfectly correlates with the spatial distribution of phagocytic activity along the surface of the heart, and to a lesser extent, with the distribution of melanin deposits. Finally, experiments measuring circulatory physiology found that the majority of hemolymph enters the heart through the ostia located in the periostial regions of abdominal segments 4, 5, and 6. These data show that periostial hemocytes aggregate on the surface of the heart in response to diverse foreign stimuli, and that both hemocytes and immune activity preferentially occur in the regions that experience the swiftest hemolymph flow. Thus, these data show that two major organ systems – the immune and circulatory systems – interact to control infections.

Adrenal pigmentation in PPNAD is a result of melanin deposition and associated with upregulation of the melanocortin 1 receptor

Adrenal pigmentation in PPNAD is a result of melanin deposition and associated with upregulation of the melanocortin 1 receptor

Mysterious Black Crystalline Pigment in the Duodenum

Introduction: Pigment deposit in small intestine is rare. Cases of melanosis-like or pseudomelanosis of the duodenum have been reported and usually associated with essential hypertension with patients taking antihypertensive medicines, chronic renal failure, or gastric bleeding. Melanin, lipofuscin, or hemosiderin deposits are pigments that may be contributing. We present a case of a rare black pigmentation of the duodenum. Case: 72 year-old African American female was seen in consultation for anemia and recent drop in hemoglobin. Although her INR was elevated at 4.5, she had no overt bleeding source. She has multiple co-morbidities including essential hypertension, chronic kidney disease, history of left colon cancer status post resection with no chemotherapy or radiation therapy, and previous metallic mitral and aortic valves replacements. Her medications included hydralazine, warfarin, insulin glargine, ergocalciferol, atorvastatin, isosorbide mononitrate, amlodipine, levothyroxine, minoxidil, clonidine, ferrous sulfate, montelukast, esomeprazole, and Colace (docusate). Physical exam was unremarkable. Specifically no skin rash or bruises were noted. Hemoglobin was 7.4 g/dl with a hematocrit of 21.9%. Iron was 13 mcg/dl, transferrin 87 mg/dl, iron saturation 12%, and ferritin 624 ng/ml. She had a recent unremarkable colonoscopy. Upper endoscopy was performed with no signs of active or recent bleeding. Blackish mucosa with intact villi was seen in the duodenal bulb and the second part of duodenum. Duodenal biopsies showed intact duodenal mucosa with slender villi and normal crypt to villous ratio. In the lamina propria, a black crystalline pigment was identified. There was no tissue reaction to this pigment with iron stain was negative and control adequate. Etiology of this pigment was deemed unknown. Discussion: While the clinical significance of pigment deposits in the duodenum is not known, observations suggest an association with chronic illnesses or the use of antihypertensive medications. Such association and the composition of those pigments are worth further exploration.