Melanin Pigment Research Articles

Plumage polymorphism in the black sparrowhawk (Accipiter melanoleucus) is strongly associated with expression level of agouti signalling protein

Abstract Melanin-based plumage polymorphisms in birds are often associated with mutations in the melanogenesis genes, notably the melanocortin-1 receptor (MC1R), but may also arise through changes in the expression of these genes. Here we investigate the molecular basis of plumage polymorphism in both adult and juvenile black sparrowhawks (Accipiter melanoleucus), an African raptor that occurs in two adult colour morphs, light and dark, and also exhibits variation in juvenile plumage colouration. Our results confirmed that plumage differences in adult morphs were a result of differential deposition of eumelanin in their ventral contour feathers. No polymorphisms in the coding regions of the MC1R or the agouti signalling protein (ASIP) genes associated with adult colour morph were identified. However, lack of pigmentation in the developing breast feathers of light morph birds was strongly associated with elevated ASIP expression, and concomitant down-regulation of the downstream melanogenesis genes microphthalmia-associated transcription factor (MITF), tyrosinase (TYR) and tyrosinase-related protein 1 (TYRP1). Variation in the rufous coloured plumage of juveniles was found to be due to covariation in eumelanin and pheomelanin levels in dorsal and ventral contour feathers. As in adult birds, an inverse relationship between melanin pigmentation and ASIP expression was observed. This covariation between eumelanin and pheomelanin levels is not consistent with the pigment type-switching model of melanogenesis, where increased ASIP expression results in a switch from eumelanin to pheomelanin production. This highlights the need for caution when extrapolating results from model systems to other animals and the value of conducting research in wild species.

Esophageal melanosis: Two case reports and review of literature

BACKGROUND Esophageal melanosis (EM) is a rare condition characterized by melanin pigmentation in the esophageal mucosa. It is not well understood and has been documented in less than 100 cases worldwide. CASE SUMMARY We report two cases of African American patients who complained of significant weight loss (over 20 pounds in approximately six months) and abdominal pain during their first visit. The first case involves a 54-year female with a history of hepatic steatosis and polysubstance abuse, who also experiences nausea and vomiting. The second case is a 59-year-old male with hypertension and gastroesophageal reflux disease (GERD), who was diagnosed with esophageal squamous cell carcinoma. Both cases show benign melanocytes in the basal layer on the esophagus biopsy and are diagnosed as EM. CONCLUSION It is important to note that EM has been associated with malignancies such as carcinoma and melanoma. Therefore, accurate diagnosis and appropriate management are crucial. Patients with EM, especially those with concurrent risk factors (e.g. , GERD, smoking), should be carefully monitored for any signs of malignancy.

Retinal Patterns and the Role of Autofluorescence in Choroideremia

Background: Choroideremia is a monogenic inherited retinal dystrophy that manifests in males with night blindness, progressive loss of peripheral vision, and ultimately profound sight loss, commonly by middle age. It is caused by genetic defects of the CHM gene, which result in a deficiency in Rab-escort protein-1, a key element for intracellular trafficking of vesicles, including those carrying melanin. As choroideremia primarily affects the retinal pigment epithelium, fundus autofluorescence, which focuses on the fluorescent properties of pigments within the retina, is an established imaging modality used for the assessment and monitoring of affected patients. Methods and Results: In this manuscript, we demonstrate the use of both short-wavelength blue and near-infrared autofluorescence and how these imaging modalities reveal distinct disease patterns in choroideremia. In addition, we show how these structural measurements relate to retinal functional measures, namely microperimetry, and discuss the potential role of these retinal imaging modalities in clinical practice and research studies. Moreover, we discuss the mechanisms underlying retinal autofluorescence patterns by imaging with a particular focus on melanin pigment. Conclusions: This could be of particular significance given the current progress in therapeutic options, including gene replacement therapy.

Computational analysis of the deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) in TYR gene impacting human tyrosinase protein and the protein stability.

Tyrosinase, a copper-containing oxidase, plays a vital role in the melanin biosynthesis pathway. Mutations in the tyrosinase gene can disrupt the hydroxylation of tyrosine, leading to decreased production of 3,4-dihydroxyphenylalanine (DOPA). Consequently, this impairs the subsequent formation of dopaquinone, a key precursor in melanin pigment synthesis. This study aimed to identify the deleterious non-synonymous single nucleotide polymorphisms (nsSNPs) within the TYR gene that exert an influence on the human TYR protein. Additionally, we evaluated the impact of 10 FDA-approved drugs on the protein stability of mutated structures, exploring the potential for inhibitory pharmaceutical interventions. Through various bioinformatics tools, we detected 47900 nsSNPs, particularly K142M, I151N, M179R, S184L, L189P, and C321R, which were found to be the most deleterious variants, decreasing the protein stability. These drugs (Sapropterin, Azelaic Acid, Menobenzone, Levodopda, Mequinol, Arbutin, Hexylresorcinol, Artenimol, Alloin and Curcumin) interacted with the binding sites in four mutant models K142M, I151N, M179R, and S184L proving that these ligands directly bind with the active site of mutant tyrosinase protein to inhibit it's working. On the other hand, two mutant models L189P and C321R did not show any binding site residue interaction with any ligands. In conclusion, this in-silico analysis of deleterious nsSNPs in the TYR gene, coupled with the evaluation of ligands/drugs on mutated tyrosinase structures not only advances our understanding of molecular variations but also highlights promising pathways for targeted inhibitory interventions in the intricate network of melanin biosynthesis.

The Cryptococcus neoformans STRIPAK complex controls genome stability, sexual development, and virulence.

This study focused on a highly conserved protein signaling complex known as STRIPAK, which is important for various developmental processes in fungi and humans. By investigating the functions of this complex in Cryptococcus neoformans , it was discovered to play crucial roles in maintaining genome stability, sexual development, and pathogenesis. In particular, mutations in the genes encoding two subunits of the STRIPAK complex were found to lead to significant defects, including abnormal growth and cell morphology, compromised stress response, and impaired virulence. Interestingly, mutation of a third STRIPAK complex subunit resulted in hypervirulence, characterized by increased thermotolerance, enhanced production of melanin pigment and polysaccharide capsule, and reduced survival in infected animals. Our findings reveal that the STRIPAK complex is an important regulator of growth and virulence of C. neoformans , highlighting its potential as a target for therapies aimed at combating fungal infections. This work furthers understanding of how the STRIPAK complex functions in Cryptococcus , and also in other organisms including humans, where related protein phosphatase complexes govern key cellular processes.

Method for determination of gamma oryzanol in dietary supplement by high performance liquid chromatography

Gamma oryzanol (GO), a phytosterol found most abundantly in rice bran oil as well as corn, barley, rye, vegetable oils and wheat bran. Thanks to its ability to slow down the development of melanin pigments, prevent the effects and spread of ultraviolet rays on the skin's surface, limiting freckles and darkening of the skin, in recent years, GO has been added to dietary supplements to help reduce melasma, brighten and smooth the skin. For the purpose of evaluating and controlling product quality, the GO analysis method was developed and validated. GO was analyzed by HPLC using a PDA detector with a C18 chromatography column (250 mm × 4.6 mm, 5 µm) and a mobile phase consisting of methanol and acetonitrile in isocratic mode 35: 65 (v/v). The test sample was extracted with a mixture of n-hexane and ethanol at a ratio of 2: 5 (v/v). The method was evaluated for system suitability, specificity, calibration curve, precision and accuracy with limit of detection and limit of quantification were 15.0 µg/g and 50.0 µg/g, respectively. The analysis results of 10 real samples including 03 pellet samples and 07 powder samples showed that the method is suitable for analyzing samples with different concentration ranges.

Thyroid hormone regulates both melanin and non-melanin pigmentation in Sinibrama taeniatus via three types of chromophores

Thyroid hormone regulates both melanin and non-melanin pigmentation in Sinibrama taeniatus via three types of chromophores

Teratoid hepatoblastoma with small cell undifferentiated histology in polysplenia patient: a case report

Abstract Introduction/Objective Hepatoblastoma (HB) with teratoid is a uncommon variant of mixed epithelial and mesenchymal components. Conversely, HB with small cell undifferentiated (SCUD) is extremely rare, with only nine documented cases showing retained INI-1 expression in the literature. The prognosis of SCUD remains debatable. In this report, we describe the first case of combined teratoid HB with a SCUD component that preserved INI-1 expression with a favorable outcome. Methods/Case Report A 2-year-old girl with polysplenia syndrome presented with a right liver mass detected during ultrasound screening. The alpha fetoprotein levels were significantly elevated to 148,000. MRI revealed a 7.2 cm lesion, staged as Pre-Treatment Extent 2 (PRETEXT) in the right anterior liver. She underwent cholecystectomy and right hepatectomy. Resection specimen revealed a mixed neoplasm comprising epithelial components (fetal and embryonal) and mesenchymal components. Additionally, notable findings include small cell component and teratoid features, characterized by melanin pigment and neuroectodermal elements. All the neoplastic cells showed reactivity with CD34, reticulin, SALL4, beta-catenin, GPC-3, arginase-1, chromogranin, and glutamine synthetase. Notably, the teratoid area only displayed positivity for CD56 and NSE, while vimentin highlighted capillaries, vessels and focally staining small cells. Furthermore, CK19 highlighted the small cell components and the bile ducts in the background liver. Importantly, INI-1 staining was retained in all tumor cells, including the small cell component. Synaptophysin and Prussian blue were negative in all lesional cells. After a 2-year follow-up, no recurrence was observed. Results (if a Case Study enter NA) NA Conclusion This case underscores the diagnostic challenge posed by small cell undifferentiated (SCUD) hepatoblastoma. Moreover, it contributes to the understanding of this rare variant of hepatoblastoma and suggests a potential favorable prognosis associated with retained INI-1 staining in the SCUD component.

The Importance of Recognizing Vaginal Melanoma, A Unique and Aggressive Subtype of Mucosal Melanoma with Undefined Staging and Treatment Protocols: Case Report and Literature Review

Abstract Introduction/Objective Primary vaginal melanoma is a highly aggressive subtype of mucosal melanoma, with few cases reported in the literature. Mucosal melanomas represent a very small subset of melanoma cases, with even fewer found in the vagina. There is a frequent delay in diagnosis due to absent or nonspecific symptoms. Methods/Case Report We report two cases of primary vaginal melanoma that were found on biopsy due to abnormal postmenopausal bleeding. Case 1 is a 62-year-old woman that was found to have a necrotic mass originating from the vaginal apex, while case 2 is a 66-year-old woman that had a vaginal polyp. Microscopic examination of both cases revealed sheets of malignant cells with prominent nucleoli, brisk mitotic activity, and patchy melanin pigment. Immunohistochemical stains for MART-1 and SOX10 were positive in both cases, supporting the diagnosis. The patient in case 1 had an upper vaginectomy and is currently on immunotherapy as part of a clinical trial. Further treatment and status of the patient in case 2 is unknown. Results (if a Case Study enter NA) N/A Conclusion Due to the rarity of cases, little is known about the etiology and risk factors. A standardized staging system is not yet accepted, with most using a combination of the AJCC and FIGO systems, however, neither are specific for vaginal melanomas. Patients are often metastatic at the time of diagnosis due to delayed diagnosis and aggressive nature of the disease. Specific treatment protocols have not yet been defined, and it is debated whether a more conservative or aggressive approach is favored. The disease control and survival rates are dismal with a poor prognosis. The role of adjuvant and targeted molecular therapies is still being investigated. The addition of our cases to the literature will hopefully bring more awareness to vaginal melanoma as a diagnostic possibility and encourage more research to be done.

TFE3-Rearranged Tumors of the Kidney: An Emerging Conundrum

Background: Identical translocations involving the TFE3 gene and various partners have been found in both renal and soft tissue tumors, like alveolar soft part sarcoma (ASPSCR1), ossifying fibromyxoid tumor (PHF1), epithelioid hemangioendothelioma, and the clear cell stromal tumor of the lung (YAP1). Methods: Herein, we review in detail the clinicopathologic and molecular data of TFE3-rearranged renal tumors and propose our perspective, which may shed light on this emerging conundrum. Results: Among the kidney tumors carrying TFE3 translocations, most are morphologically heterogeneous carcinomas labeling for the tubular marker PAX8. The others are mesenchymal neoplasms known as PEComas, characterized by epithelioid cells co-expressing smooth muscle actin, cathepsin-K, melanogenesis markers, and sometimes melanin pigment deposition. Over the past 30 years, numerous TFE3 fusion partners have been identified, with ASPL/ASPSCR1, PRCC, SFPQ/PSF, and NONO being the most frequent. Conclusions: It is not well understood why similar gene fusions can give rise to renal tumors with different morpho-immunophenotypes, which may contribute to the recent disagreement regarding their classification. However, as these two entities, respectively, epithelial and mesenchymal in nature, are widely recognized by the pathology community and their clinicopathologic features well established, we overall believe it is still better to retain the names TFE3-rearranged renal cell carcinoma and TFE3-rearranged PEComa.

The Prognostic Significance of Tumoral Melanosis.

Tumoral melanosis (TM) is a histological term to describe a nodular aggregation of macrophages containing melanin pigment (melanophages) that is devoid of viable melanocytes. It is most often identified in skin, where it may be appreciated clinically as a pigmented lesion; however, it can also be found in other organs such as lymph nodes. The presence of TM is usually thought to signify the presence of a regressed melanoma or other pigmented tumor. Until recently, it was a relatively uncommon finding; however, with the use of effective systemic therapies against melanoma, its occurrence in histological specimens is more frequent. We identified and reviewed all histopathological diagnoses of TM at any organ site reported at a single institution from 2006 to 2018. TM cases were paired with non-TM cases of cutaneous melanoma through propensity score matching at a 1:2 ratio, and their survival outcomes were compared. The clinical outcomes examined included recurrence-free survival (RFS), distant disease-free survival (DDFS), melanoma-specific survival (MSS), and overall survival (OS). TM was reported in 79 patients. Their median age was 65 years (range 22-88), with a 2:1 male predominance (51 out of 79, 65%). The most common organ involved was the skin (67%), with a third of all cases localized to a lower limb (36%). TM had a strong association with the presence of melanoma (91%) and regression at other sites of melanoma (54%), suggesting that it is part of a systemic immune response against melanoma. Most patients with TM either previously or subsequently developed histologically confirmed melanoma in the same anatomical region as the TM (89%). Thirty-five TM patients were matched with 70 non-TM cases. Patients with melanoma who developed TM without prior regional or systemic therapy showed improved MSS (p = 0.03), whereas no statistically significant differences were observed in terms of RFS, DDFS, and OS. TM usually occurs in the context of a previous or subsequent cutaneous melanoma and is associated with improved MSS. It is important that TM is recognized by pathologists and documented in pathology reports.

Identification of Novel Tyrosinase Inhibitors with Nanomolar Potency Using Virtual Screening Approaches.

Hyperpigmentation disorders are caused by excess production of the pigment melanin, catalyzed by the enzyme tyrosinase. Novel tyrosinase inhibitors are needed as therapeutic agents to treat these conditions. To discover new inhibitors, we performed a virtual screening of the ZINC20 library containing 1.4 billion compounds. An initial filter for drug-likeness, ADMET properties, and synthetic accessibility reduced the library to 10,217 hits. Quantitative structure-activity relationship (QSAR) modeling of this subset predicted nanomolar inhibitory potency for several chemical scaffolds. Comparative molecular docking studies and rigorous binding energy calculations further prioritized four cysteine-containing dipeptide compounds based on predicted strong binding affinity and mode to tyrosinase. Microsecond-long molecular dynamics simulations provided additional atomistic insights into the stability of inhibitor-enzyme binding interactions. This integrated computational workflow effectively sampled an extremely large chemical space to discover four novel tyrosinase inhibitors with half-maximal inhibitory concentration values below 10 nM. Overall, this demonstrates the power of virtual screening and multi-faceted computational techniques to accelerate the discovery of potent bioactive ligands from massive compound libraries by efficiently sampling chemical space.

Identification of a T-box transcription factor TBX2 and its negative regulatory role in melanin production in the Pacific oyster Crassostrea gigas

Oyster shells exhibit varying color patterns—black, white, or black and white striations—attributable to differences in melanin content and distribution. In this study, we identified a new homolog of TBX2, a member of the T-box transcription factor family, in the Pacific oyster (Crassostrea gigas) named CgTBX2. The mRNA expression of CgTBX2 was higher in tissues from white-shelled oysters than in those from black-shelled oysters. Knockdown of CgTBX2 in C. gigas significantly upregulated the expression of two key genes involved in melanin synthesis, CgTYR and CgTYR2. The tissue expression profile revealed that CgTBX2 is highly expressed in gill and mantle. CgTBX2 protein is mainly localized in the nucleus and can combine with TBX-binding elements (TBEs) present in the CgOCA2 promoter. CgTBX2 repressed the activity of the CgOCA2 promoter, with a strong transcriptional inhibition effect on the −2000 to −878 and −211 to −1 regions. Furthermore, the combination of CgTBX2 with GTTGACACCTT sequence is responsible for the transcriptional inhibition on the −211 to −1 region of the CgOCA2 promoter. Our findings reveal that CgTBX2, a novel regulator of melanin pigmentation in C. gigas, negatively regulates melanin deposition by inhibiting tyrosinase genes expression and repressing the transcriptional activity of the CgOCA2 promoter.

The Production of Melanin Pigments From Some Pathogenic Fungi in Response to L-Tyrosine Under Laboratory Conditions

Background: This study aims to evaluate response of plant pathogenic fungi to the amino acid L-tyrosine through the production of melanin. Methods: Potato dextrose broth (PDB) and PDB with 1% L-tyrosine were used for current evaluation. Melanin was produced, extracted and characterized from pathogenic fungi that infected rice in Iraq. Results: Results indicated that L-tyrosine was used as a source of the precursor by fungi belonging to Bipolaris. spicifera R15, Alternaria. alternata R18, Exserohilum. rostratum R19, Alternaria. alternate R20, and Alternaria. tenuissima R23, also produced higher levels of condensed black pigment. While, fungi like Nigrospora oryzae R9, Curvularia lunata R7, C lunata R21 and A tenuissima R24 were used more than one pathway for melanin production. UV transmittance increased significantly from 600 nm to 300 nm whereas absorbance decreased at 260 and 280 nm for all of the studied fungi. Analysis of FT-IR spectra and related assignment group of resolved that melanin extracted from B. spicifera R15 (3408.22), A. alternate R20 (3392.79), and A. tenuissima R24 (3387). Wavenumbers 2924 cm−1 and 2854 cm−1 were found in E. rostratum R19, A. alternative R20, and A. tenuissima R24 melanin extracts, respectively. Meanwhile, B. spicifera R15 revealed a single peak at 2929 cm−1. 3007.02 cm−1, 3072.6 cm−1, 3074.53 cm−1, 2920.3 cm−1, 2704.2 cm−1, and 1861.31 cm−1 are also assigned wavenumbers. Conclusion: Melanin-like pigments are produced via L-tyrosine-dependent and independent pathways. All colors extracted from fungal hyphae were morphologically and chemically identical to melanin. A UV scan and FT-IR analysis revealed differences in the physical appearance of building units and the structure of the melanin pigment produced by plant pathogenic fungi.

Gallic acid melanin pigment hydrogel as a flexible macromolecule for articular motion sensing

In this study, water-soluble melanin was synthesized through the genetic recombination of Escherichia coli using gallic acid as a substrate. The recombinant host produced 2.83 g/L of gallic acid-based melanin (GA melanin) from 20 mM gallic acid. Notably, the isolated GA melanin demonstrated exceptional antioxidant and antimicrobial activities, exhibiting a 25.7 % inhibition ratio against Candida albicans. The structure and composition of GA melanin were analyzed using Fourier-transform infrared (FT-IR) spectroscopy, scanning electron microscopy with energy-dispersive X-ray spectroscopy (SEM-EDS), and X-ray diffraction (XRD). Remarkably, GA melanin displayed high thermal stability, maintaining integrity up to 1000 °C. Additionally, it exhibited unique electrical properties in terms of conductivity and resistivity compared to other common types of melanin. Subsequently, GA melanin was cross-linked with hydrogel to create a sensing template. The resulting GA melanin hydrogel demonstrated lower resistance (80.08 ± 3.0 kohm) compared to conventional hydrogels (108.62 ± 10.4 kohm), indicating an approximately 1.77-fold improvement in adhesion. Given its physical, biological, and electrical properties, the GA melanin hydrogel was further utilized as a flexible motion-sensing material to detect resistivity changes induced by knee, wrist, and finger bending, as well as vocal cord vibrations. In all cases, the sensing module displayed notable sensitivity to motion-induced resistivity variations.

Dynamic Transcriptome Profile Analysis of Mechanisms Related to Melanin Deposition in Chicken Muscle Development.

The pectoral muscle is an important component of skeletal muscle. The blackness of pectoral muscles can directly affect the economic value of black-boned chickens. Although the genes associated with melanogenesis in mammals and birds have been thoroughly investigated, only little is known about the key genes involved in muscle hyperpigmentation during embryonic development. Here, we analyzed melanin deposition patterns in the pectoral muscle of Yugan black-boned chickens and compared differentially expressed genes (DEGs) between the muscles of Wenchang (non-black-boned chickens) and Yugan black-boned chickens on embryonic days 9, 13, 17, and 21. Melanin pigments were found to gradually accumulate in the muscle fibers over time. Using RNA-seq, there were 40, 97, 169, and 94 genes were identified as DEGs, respectively, between Yugan black-boned chicken muscles and Wenchang chickens at embryonic day 9, 13, 17, and 21 stages (fold change ≥2.0, false discovery rate (FDR) < 0.05). Thirteen DEGs, such as MSTRG.720, EDNRB2, TYRP1, and DCT, were commonly identified among the time points observed. These DEGs were mainly involved in pigmentation, melanin biosynthetic and metabolic processes, and secondary metabolite biosynthetic processes. Pathway analysis of the DEGs revealed that they were mainly associated with melanogenesis and tyrosine metabolism. Moreover, weighted gene co-expression network analysis (WGCNA) was used to detect core modules and central genes related to melanogenesis in the muscles of black-boned chickens. A total of 24 modules were identified. Correlation analysis indicated that one of them (the orange module) was positively correlated with muscle pigmentation traits (r > 0.8 and p < 0.001). Correlations between gene expression and L* values of the breast muscle were investigated in Yugan and Taihe black-boned chickens after hatching. The results confirmed that EDNRB2, GPNMB, TRPM1, TYR, and DCT expression levels were significantly associated with L* values (p < 0.01) in black-boned chickens (p < 0.05). Our results suggest that EDNRB2, GPNMB, TRPM1, TYR, and DCT are the essential genes regulating melanin deposition in the breast muscle of black-boned chickens. MSTRG.720 is a potential candidate gene involved in melanin deposition in the breast muscles of Yugan black-boned chickens.

Isolation, purification, characterization and stability analysis of melanin pigment from Mesona chinensis

In this study, the isolation and purification of melanin pigment from Mesona chinensis (MCM) were conducted, and the structural characterization and stability evaluation of MCM were performed. The results indicate that MCM is consistent with the spectral features of catechins and polyphenols, identified the stretching vibrations of functional groups such as OH, CH, CO, and CO. It is inferred that the structure of MCM is consistent with that of theophylline and it is mainly composed of phenolic acids, terpenoids, and organic acids. Stability evaluations indicate that MCM exhibits stability under white light, ultraviolet (UV) light, neutral, and alkaline environments, and it shows low sensitivity to reducing agents.

Relationship of hemoglobin levels and distribution and severity of gingival melanin pigmentation: an exploratory cross-sectional study.

Relationship of hemoglobin levels and distribution and severity of gingival melanin pigmentation: an exploratory cross-sectional study.

Cell wall melanin impedes growth of the Cryptococcus neoformans polysaccharide capsule by sequestering calcium

Cryptococcus neoformans has emerged as a frontrunner among deadly fungal pathogens and is particularly life-threatening for many HIV-infected individuals with compromised immunity. Multiple virulence factors contribute to the growth and survival of C. neoformans within the human host, the two most prominent of which are the polysaccharide capsule and melanin. As both of these features are associated with the cell wall, we were interested to explore possible cooperative or competitive interactions between these two virulence factors. Whereas capsule thickness had no effect on the rate at which cells became melanized, build-up of the melanin pigment layer resulted in a concomitant loss of polysaccharide material, leaving melanized cells with significantly thinner capsules than their nonmelanized counterparts. When melanin was provided exogenously to cells in a transwell culture system we observed a similar inhibition of capsule growth and maintenance. Our results show that melanin sequesters calcium thereby limiting its availability to form divalent bridges between polysaccharide subunits required for outer capsule assembly. The decreased ability of melanized cells to incorporate exported polysaccharide into the growing capsule correlated with the amount of shed polysaccharide, which could have profound negative impacts on the host immune response.

Synchronous multiple primary malignancies or transdifferentiation?-A diagnostic challenge in a case of Xeroderma pigmentosum.

A diagnosis of synchronous tumors is always questionable when they show similar histology. We present a case of synchronous tumors, i.e. melanoma (MM) arising from the scalp and angiosarcoma (AS) from the cheek in a patient of Xeroderma pigmentosum (XP). The presence of melanin in AS of the cheek led to a differential diagnosis and a possibility of transdifferentiation of malignant melanoma in the first instance. Immunohistochemistry (IHC) was negative for melanoma markers (Melan A, SOX-10 & S 100) and positive for vascular markers (ERG, CD31 & CD34) ruling out transdifferentiation and concluding the cheek swelling as angiosarcoma. The presence of non-cutaneous malignancies is rare in XP and the presence of MM in a nearby site and the melanin pigment in the cutaneous malignancy mislead the diagnosis. The morphology of the tumor was the key which led to the further workup of the case.