Search

Oculocutaneous albinism (OCA) is a rare condition characterized by hypopigmentation. A female proband and her sister, both with primary amelanotic/hypopigmented melanoma, underwent three-dimensional total-body photography and dermoscopy. Both sisters had exome sequencing along with their brother, who had OCA but no history of melanoma. Imaging analysis was consistent with OCA in terms of individual typology angle scores, degree of sun damage, and high naevus counts. Exome data filtered for variants in known OCA and melanoma/naevi susceptibility genes (n = 98) found all siblings were compound heterozygous for TYR mutations (Arg402Ter and Val275Phe), previously reported as causative OCA variants. A rare missense variant in PARP1 (p.Pro377Ser) was solely present in the melanoma-unaffected brother, which is noteworthy as this was previously reported as potentially protective in a familial melanoma pedigree positive for CDKN2A mutations. Evaluation and confirmation of functional impact in larger cohorts could personalize melanoma screening in OCA.

Acral lentiginous melanoma is commonly misdiagnosed, and when detected late it portends a poor prognosis. Acral lentiginous melanoma can be mistaken for verruca, pyogenic granuloma, poroma, an ulcer, or other benign skin conditions. Patients with acral skin growths often present initially to a podiatric physician or their primary care physician. It is at this point when the growth is triaged as benign or potentially malignant. Dermoscopy aids in this decision making. Historically, dermoscopy training has been geared toward dermatologists, but there is increasing recognition of the need for dermoscopy training in primary care and podiatric medicine. Dermoscopy is particularly helpful in pink (amelanotic) growths, which can lack the traditional clinical findings of melanoma. A literature review of acral melanoma and dermoscopy was performed in PubMed. We also describe a case of amelanotic acral melanoma in a 58-year-old with a rapidly enlarging painful mass on her heel. The lesion was initially thought to be a pyogenic granuloma and was treated with debridement (curettage). She was ultimately seen in the dermatology clinic, and the findings under dermoscopy were worrisome for amelanotic melanoma. Biopsy confirmed the diagnosis. The cancer metastasized, and the patient died less than 2 years later.

BackgroundMelanoma is a cutaneous form of disease with an increasing incidence since 1970s, especially in western countries, accounting for nearly 75% of the death related to skin cancer. Clinical outcome varies a lot among different subtypes, and highest recurrence and mortality were observed within the type with distal metastasis. Furthermore, high incidence of gastrointestinal (GI) metastasis of malignant melanoma is frequently misdiagnosed due to lack of specific clinical manifestations. Amelanotic melanoma metastasis, especially the gastrointestinal metastasis, was rarely observed in clinical practice, accounting for only about 2% of all metastatic cases.Case presentationIn the present study, we report a 36-year-old male patient with gastric cancer, who was diagnosed as amelanotic melanoma by Immunohistochemical (IHC) staining, demonstrating positive staining for melanoma markers including Melan A, S-100, Hmb45 and CD79a.ConclusionsIn conclusion, for the colorless tumor metastases found during gastroscopy in melanoma patients, detailed pathological examination should be carried out in combination with previous medical history to determine the nature of the tumor and treatment regime.

Amelanotic melanoma (AM) is a subtype of melanoma characterized by a diminished or lacking melanin synthesis. AM, especially ulcerated variants of the plantar region (AMP), are often clinically misdiagnosed, leading to a delay in treatment initiation. We present a case series of 4 AMP and give a detailed overview about clinical features and the subsequent medical history of this severe disease. AMP shows a variety of clinical presentations and particularly elderly patients with many accompanying medical conditions are in danger of incorrect clinical diagnoses. Therefore, we recommend to biopsy any amelanotic plantar ulcer or tumor that does not respond to treatment within 6 weeks to rule out AM. Das Amelanotische Melanom (AM) ist ein Subtyp des Melanoms, bei dem die Melanozyten wenig oder keine Melaninsynthese betreiben. Da es klinisch nicht die typische, dunkle Pigmentierung des Melanoms zeigt, wird es oftmals als gutartiger Hauttumor oder entzündliche Dermatose verkannt und daher zu spät oder fehlerhaft behandelt. Diese Übersicht aus 4 Fällen dient der Veranschaulichung der Warnzeichen von plantaren AM (PAM), die jedem klinisch tätigen Mediziner bekannt sein sollten. Wir präsentieren eine Fallserie aus 4 Patienten mit PAM und beschreiben detailliert die Bandbreite des klinischen Erscheinungsbildes sowie den Krankheitsverlauf. PAM können verschiedene klinische Ausprägungen annehmen und insbesondere ältere Patienten mit multiplen Nebenerkrankungen sind gefährdet für eine Fehldiagnose. Wir empfehlen daher generell eine diagnostische Biopsie bei jeder plantaren Ulzeration, wenn diese nach 6 Wochen kein Therapieansprechen zeigt.

A Himalayan Rex guinea pig was presented with a history of nodular, partially ulcerated masses in the subcutis of the left shoulder. Histological examination revealed a garland-like to nodular, infiltrative neoplastic mass of the epidermis and hair follicle epithelium, which obscured the dermoepidermal junction. Neoplastic cells were immunopositive for S100, PNL-2, vimentin and melan-A antigens. No immunolabelling of CD3, CD79, Iba-1 or pancytokeratin was observed. This is the first detailed description of spontaneous amelanotic malignant melanoma in this species.

Background Amelanotic melanoma is an extremely rare subtype of cutaneous melanoma. The tumor characteristics are still not well understood, especially for those located in the head and neck. Methods Tumor characteristics of patients diagnosed with amelanotic melanoma of the head and neck (AMHN) from January 1, 2004, to December 31, 2015, were analyzed by querying the National Cancer Database. Characteristics of AMHN were subsequently compared with common malignant melanoma of the head and neck (CMMHN). Results Three hundred and sixty-eight patients were diagnosed with AMHN, and 69,267 were diagnosed with CMMHN. Of those with AMHN, 128 (34.8%) had melanoma located on the scalp and neck, and 172 (46.7%) were diagnosed with an early disease stage (i.e., 0, I, or II). When compared with CMMHN, patients with AMHN were more likely to be diagnosed after 80 years of age (25.3% vs. 18.2%; odds ratio [OR], 3.28; 95% CI, 1.09-9.84; P = 0.03), when Breslow depth was between 2.01 and 4.00 mm (28.5% vs. 6.5%; OR, 1.92; 95% CI, 1.15-3.19; P = 0.01), when ulceration was present (36.7% vs. 9.0%; OR, 1.99; 95% CI, 1.34-2.97; P = 0.001), and when mitotic count was 1 or more/mm2 (40.5% vs. 12.8%; OR; 2.53; 95% CI, 1.09-5.89; P = 0.03). No statistical difference was found for sex, specific location, stage, or lymph node involvement. Conclusion Our study determined that AMHN is associated with older age, increased Breslow depth, presence of ulceration, and greater mitotic count when compared with CMMHN.

Mucosal melanomas are aggressive tumors, rarely observed in the oral cavity. The diagnosis is based on the clinical and microscopical features. Often these tumors had variable amounts of melanin pigmentation. However, when melanin is absent, the tumors are denominated amelanotic, presenting a tendency to misdiagnosis and delayed treatment. The aim of this study was to describe the clinicopathologic features of a series of oral amelanotic melanomas (OAM). Records of all cases of OAM were retrospectively retrieved from oral pathology services from January 2002 to January 2019. Data regarding the clinical features, morphological aspects, immunohistochemical reactions, treatment, and follow-up status were collected. Eight cases of OAM were included, 6 in men and 2 in women (ratio of 3:1) ranging in age from 33 to 77 years (mean 53.6 years). Clinically, the tumors presented as masses or ulcerated swellings. The most common intraoral locations of the tumors were gingiva and palate. Cervical lymph node metastasis was detected in 3 patients at the first examination. All but one patient died from complications of the tumors after a mean follow-up period of 8.5 months. In conclusion, OAM is a very aggressive malignant tumor, and when melanin is absent, an immunohistochemical panel comprising S100, melan A, HMB45, and SOX10 should be performed.

Nodular posterior scleritis represents a small percentage of all cases of posterior scleritis. Because of the scarcity of nodular posterior scleritis, it may be confused or even misdiagnosed as an intraocular tumor or posterior uveitis. Here, we are reporting a case of nodular posterior scleritis in a 25-year-old medically free male. Furthermore, we reviewed previously reported cases of nodular posterior scleritis. Our patient presented with a choroidal mass of about one disc diameter in size. In addition, the patient had exudative retinal detachment and chorioretinal folds. B scan ultrasonography showed subretinal fluid, macular nodular thickening and underlying echolucent area along with medium internal reflectivity on A scan. Fluorescein angiography revealed early pinpoint areas of hyperfluorescence and late pooling under the detached retina. Indocyanine green angiography demonstrated early diffuse hypofluorescence corresponding to the area of detachment and late multiple pinpoint spots of hyperfluorescence. After intravenous methylprednisolone 1 g for 3 days followed by a course of oral prednisolone along with mycophenolate mofetil, the patient experienced rapid recovery with improvement in vision and complete resolution of subretinal fluid. On further follow-up, the patient regained 20/20 vision. Nodular posterior scleritis is a rare unilateral disease with strong female predominance. Multimodal imaging should be employed to confirm the diagnosis. The disease must be diagnosed correctly to avoid any unnecessary diagnostic work-up and aggressive management. Most cases carry excellent prognosis with no recurrence.

A rare disease in an unusual site can closely mimic a typical presentation of a common disease, sometimes with devastating consequences. We present a case of primary amelanotic malignant melanoma of the urethra in a male, with clinical and histological characteristics that could have led to a mistaken diagnosis of high-grade urothelial carcinoma. Amelanotic mucosal melanoma should be suspected in all cases of high-grade mucosal tumors with practically any appearance (epithelioid, sarcomatoid, anaplastic, mixed). Morphological hints pointing toward melanoma—such as the presence of sparse melanin pigment or melanoma in situ—should be sought, and if absent, an immunohistochemical panel comprising S100 and HMB45 should be performed.

Die Unterscheidung von spindelzelligem Melanom (SM) und desmoplastischem Melanom (DM) ist klinisch aufgrund der Unterschiede in der Metastasierungstendenz und Prognose wichtig. Diese Unterscheidung ist allerdings nicht immer problemlos. Die Routinedurchsicht einiger Fälle zeigte interessante unterschiede in der Zellkernform zwischen SM und DM. Primäres Ziel dieser Studie war es herauszufinden, ob die Unterschiede in der Form der Zellkerne als diagnostischer Klassifikator zur Unterscheidung von SM und DM dienen können. Die Form der Zellkerne wurde dazu mittels einer ImageJ-basierten Schwellenwertextraktion gewonnen und analysiert. Die Be-stimmung der Rundheit zeigte sich hierbei den anderen Messwerten als Überle-gen. Die retrospektive Analyse einer bestehenden Patientenkohorte (SM n=9, DM n=9) wurde benutzt, um die Trennschärfe des Algorithmus zu bestimmen. Repräsentative Bildausschnitte (= ROIs; insgesamt n=108; 6 Bilder pro Fall) wur-den aus gescannten, H&E-gefärbten, histologischen Schnitten ausgewählt und die Zellkern-Rundheit unter Einsatz von Open-Source-Programmen (Plugins für ImageJ) computergestützt extrahiert und quantifiziert. Die extrahierten, quantitativen Form-Messwerte wurden durch Mann-Whitney-Test, Kruskal-Wallis-Test und einfache Varianzanalysen verglichen; p-Werte

Nevoid melanoma (NeM) is a rare variant of melanoma resembling melanocytic nevus. The aim of the study was to systematically review the dermoscopic features of NeM.A hospital-based retrospective study was conducted. Dermoscopic features of NeMs diagnosed through excisional biopsy between January 2015 1, and March 1, 2021, were compared to superficial spreading melanomas (SSMs) matched by Breslow's thickness. Then, a literature search was performed. Electronic searches on PubMed database via Medline were conducted to retrieve any manuscript reporting detailed dermoscopic features of histopathologically confirmed NeM.A total of 60 malignant melanomas (MM) comprising 20 NeM and 40 SSM were collected. Twelve out of 20 (60%) NeM showed a nevus-like appearance, including reticular and globular patterns, and in 35% of these cases it was detected because of dermoscopic changes. Then, a total of seven original manuscripts were retrieved from the literature review, comprising 56 cases overall. NeM showed nevus-like pattern in 53% of the cases, multicomponent pattern in 21% and amelanotic in 9%. Enlargement, irregularly distributed dots/globules, irregular pigmentation, and atypical vascular pattern were found in NeM with nevus-like appearance. NeM with multicomponent pattern were characterized by irregular pigmentation, blue-white veil, irregular dots and atypical vascular pattern. Amelanotic NeM is rare and show atypical vascular pattern and milia-like cysts.Dermoscopy of NeM is challenging as it frequently shows a nevus-like pattern, but clues and detection of dermoscopic changes may help to identify it.

Background Dermoscopy and reflectance confocal microscopy (RCM) are noninvasive techniques for the diagnosis of skin lesions. Their accuracy for amelanotic/hypomelanotic melanoma (AHM) has not been systematically studied. Objectives We aimed to investigate systematically the accuracy of dermoscopy and RCM and to compare the accuracy between them for diagnosing AHM. Methods We searched the PubMed, Web of Science, Embase and Cochrane Library databases for eligible studies about dermoscopy, RCM and AHM from inception to 31 June 2019. The quality of the studies was assessed with the Quality Assessment of Diagnostic Accuracy Studies tool. The pooled results were calculated using a random effects model in Stata 14, Meta-DiSc, RevMan 5·3 and SAS 9·4. We also explored the sources of heterogeneity by sensitivity analysis. Results Seven studies with a total of 1111 lesions were included. The pooled sensitivity and specificity of dermoscopy for the diagnosis of AHM were 61% [95% confidence interval (CI) 0·37-0·81] and 90% (95% CI 0·74-0·97), respectively. The corresponding respective values of RCM for the diagnosis of AHM were 67% (95% CI 0·51-0·81) and 89% (95% CI 0·86-0·92). In three studies including the performance of both RCM and dermoscopy, the relative diagnostic odds ratio of RCM over dermoscopy was 4·69 (95% CI 0·81-27·3) (P = 0·068). Conclusions Our study demonstrates that both dermoscopy and RCM offer good diagnostic accuracy with high specificity and moderate sensitivity in the diagnosis of AHM. RCM is more accurate than dermoscopy in diagnosing AHM but the comparison needs to be confirmed. What's already known about this topic? Amelanotic/hypomelanotic melanoma (AHM) is the most lethal skin cancer. The diagnosis of AHM is a great challenge because of its nonspecific clinical manifestation. Early diagnosis can improve the prognosis. Dermoscopy and reflectance confocal microscopy (RCM) have high diagnostic accuracy for pigmented melanoma. What does this study add? Both dermoscopy and RCM offer good diagnostic accuracy with high specificity and moderate sensitivity for AHM. RCM might be more accurate than dermoscopy for diagnosis of AHM. More research on the diagnostic accuracy of dermoscopy and RCM for AHM is required in support of these findings.

This report presents the clinical and pathologic findings of three cases of metastatic amelanotic melanoma to the parotid gland. Two of the patients had a primary cutaneous tumor. Fine-needle aspiration of the parotid showed clusters of epithelioid cells and/or spindle-shaped cells with vesicular nuclei, macronucleoli, and abundant eosinophilic cytoplasm. In addition, one had striking balloon-cell features. In the immunohistochemical study, the tumors expressed S-100, HMB-45 antigen, Melan-A, and SOX10, and focally smooth-muscle actin, cytokeratin, CD56, p63, and synaptophysin. The diagnosis was challenging because the tumors were clinically thought to be primary parotid lesion and showed unusual immunohistochemical labeling for SMA, cytokeratins, p63, and neuroendocrine markers. Furthermore, the long clinical history in two of the cases made the diagnosis of a metastatic lesion less likely. Diagnostic errors can be reduced by integrating cytomorphologic, histologic, immunohistochemical, and clinical findings.

Background Baicalin and baicalein have antioxidant, anti-inflammatory, hepatoprotective and anti-cancer properties. However, it is not known how a static magnetic field will modify these properties. Therefore, the aim of our study was to evaluate the simultaneous exposure of melanoma cells to flavones and the static magnetic fields that are generated by permanent magnets on the gene expression and the activity of the antioxidant enzymes that are associated with the antioxidant defense system. Methods and results Melanoma cells that had been treated with baicalin or baicalein were subjected to a static magnetic fields with a moderate induction. The static magnetic field was emitted by permanent magnets and the cell cultures were carried out in special test chambers. The research included determining the activity of the antioxidant enzymes (superoxide dismutase, glutathione peroxidase and catalase) as well as the gene expression profile. The addition of the flavones to the cell cultures at a concentration of 50 µmol/L resulted increase in the expression of the SOD1, SOD2 and GPX1 genes compared to the nontreated cell cultures. Simultaneous exposure of the melanoma cells to static magnetic field and baicalin or baicalein reduced their mRNA levels compared to the cultures to which only baicalin or baicalein had been added. The change in gene expression was accompanied by changes at the protein level associated with an increase in the activity of antioxidant enzymes. Conclusion We showed that baicalin or baicalein have anticancer properties by disturbing the redox homeostasis in melanoma cells and also increases the antioxidant system gene expression. There was also an antagonistic interaction between the studied flavones and the static magnetic field, which cause a decrease in the anticancer effects of baicalin or baicalein.

Amelanotic melanoma is a rare type of melanoma that shows little or no melanin pigmentation. When tumor lesions are not detected in cutaneous sites, the presence of melanin is the hallmark sign of malignant melanoma. We herein report a case of amelanotic melanoma with a BRAF V600E mutation mimicking primary lung cancer that was finally diagnosed on an autopsy. The current case suggests important caveats for the differential diagnosis of patients with BRAF V600E mutation-positive poorly differentiated lung tumors. In terms of the pathological diagnosis, routine immunohistochemical staining may be useful, especially in patients with a poorly differentiated lung tumor without TTF-1 expression.

Mcl-1 is a potent antiapoptotic protein and amplifies frequently in many human cancer. Currently, it is considered that the extensively expressed of Mcl-1 protein in melanoma cells is associated with rapid tumor progression, poor prognosis and low chemosensitivity. Therefore, the antiapoptotic protein Mcl-1 could be considered as a potential target for malignant melanoma treatment. The aim of this study was to assess the effect of MIM1 a specific low molecular Mcl-1 protein inhibitor and mixture of MIM1 and dacarbazine on the viability, cell cycle progression and apoptosis induction in amelanotic C32 melanoma cells. The cytotoxic activity of MIM1 towards C32 melanoma cells was examined by the WST-1 test. The Mcl-1 protein level as a drug target in amelanotic melanoma cells was defined by Western blot analysis. Cell cycle progression, DNA fragmentation as well as GSH depletion were determined by fluorescence image cytometer NucleoCounter NC-3000. The obtained results demonstrate that the specific Mcl-1 protein inhibitor - MIM1 decreases cell viability and induce apoptosis (S-phase arrest, DNA fragmentation and redox imbalance) in amelanotic melanoma cells and intensify the proapoptotic properties of DTIC, as a result of interactions with Mcl-1 protein. Taken together, the presented data suggest that Mcl-1 protein is a an important target in malignant melanoma treatment and provide for the first time convincing evidence that MIM1, which inhibits Mcl-1 antiapoptotic protein is able to induce apoptosis and sensitize melanoma cells to alkylating agent.

A 51-year-old man was diagnosed with stage IIC nodular malignant melanoma (T4bN0M0) of the right upper arm. The tumor was treatment-refractory, and left-sided pleural effusion emerged 1.5 years later. Aspiration of pleural fluid revealed abundant amelanotic, atypical cells that resembled epithelial malignant mesothelioma or lung adenocarcinoma cells; these cells were positive for melanoma-associated antigen recognized by T cells (MART-1)/Melan-A, HMB-45, and S-100 on immunocytochemistry. Thoracic computed tomography (CT) revealed marked diffuse pleural thickening in the left hemithorax that mimicked malignant mesothelioma; thus, the present report describes the unique cytological and radiological findings of this case.

Interferon β (IFN-β) is considered a signaling molecule with important therapeutic potential in cancer since IFN-β-induced gene transcription mediates antiproliferation and cell death induction. Whereas, TNF-related apoptosis inducing ligand/Apo2 ligand (TRAIL/Apo2L) has emerged as a promising anticancer agent because it induces apoptosis specifically in cancer cells. In this study, we elucidated that IFN-β augments TRAIL-induced apoptosis synergistically using five human malignant melanoma cells. All of these cells were induced apoptosis by TRAIL. Whereas, the response against IFN-β was different in amelanotic cells (A375 and CRL1579) and melanotic cells (G361, SK-MEL-28, and MeWo). The responsibility of amelanotic cells against IFN-β was higher than those of melanotic cells. The synergism of IFN-β and TRAIL were correlated with the responsibilities of the cells against IFN-β. The synergistic interaction was confirmed by a combination index based on the Chou-Talalay method. The upregulation of apoptosis in amelanotic cells was caused by very low doses of IFN-β (over 0.1 IU/ml). Both of p53-mediated intrinsic pathway and Fas-related extrinsic pathway were activated by IFN-β alone and combination with TRAIL. Further, TRAIL death receptors (DR4 and DR5) were upregulated by a low-dose IFN-β (over 0.1 IU/ml) and the expression was more promoted by the combination with TRAIL. It was clarified that the upregulation of DR5 is associated with the declination of viability.

Malignant melanoma is commonly known for its high probability of metastasizing to distant organs. Metastases to gastrointestinal tract are well documented, but resulting jaundice is only scarcely seen. We present a case of histologically verified metastasis of amelanotic melanoma to the head of pancreas infiltrating the common bile duct and consequently causing obstructive jaundice which constituted its first clinical manifestation. Multidisciplinary approach is essential in patients with malignant melanoma since early detection of the melanoma or its metastases may improve patients’ clinical outcome, especially owing to the use of targeted biological treatment without any delay.

A 47-year-old woman was admitted to our clinic for intensive pain in the left flank region. The transvaginal ultrasound showed a left adnexal solid mass with ascites. She had undergone surgical removal of skin melanoma in 2008, but in September 2019, intracardiac metastasis resulting from it had been discovered. CT performed in March 2020 had been negative for other metastases. A full abdomen ultrasound was not performed. During the night, the patient began to show signs and symptoms of hypovolaemic shock. The patient was urgently transferred to the operating room for a video laparoscopy. A vast left retroperitoneal haematoma was diagnosed along with voluminous enlargement of the left ovary. We proceeded with a left adnexectomy and blood transfusion. Subsequent contrast-enhanced CT revealed a left subcapsular, perirenal haematoma and a voluminous retroperitoneal haematoma. Kidney metastasis was also seen. The final histological diagnosis was metastatic amelanotic malignant melanoma of the ovary.

A 73-year-old man presented with anemia, and gastroscopy showed a nonpigmented tumor in the esophagogastric junction. The result of the tumor biopsy initially suspected poorly differentiated adenocarcinoma. However, additional immunohistochemical examination revealed malignant melanoma. The final diagnosis was amelanotic malignant melanoma of the esophagogastric junction with adrenal and spinal metastasis. Although immunotherapy was performed, the patient died 132 days after diagnosis.

Copyright © Ordem dos Médicos 2021, Acral melanomas are rare, representing 2% - 3% of all melanomas. However, the fatality rate is higher because of delayed diagnosis. They are more common on weight-bearing areas of the foot and are frequently amelanotic sometimes mimicking fungal infections, diabetic foot ulcers or even plantar warts.

N/A

Amelanotic/hypomelanotic melanoma (AHM) represents a clinical diagnostic challenge. Dermoscopy improves AHM diagnosis thanks to visualization of little pigment and vascular pattern. Reflectance confocal microscopy (RCM) increases further the diagnostic accuracy of AHM but few and small studies have described in detail RCM features of AHM. We evaluated dermoscopic and RCM features of nine cases of difficult to diagnose hypomelanotic melanomas (HMs) to find clues for their diagnosis. The RCM score was suggestive of melanoma in all cases. The major criteria of nonedged papillae and/or cytological atypia at the dermo-epidermal junction were seen in all cases. Among the minor criteria, roundish pagetoid cells, including hyporeflective pagetoid cells, were found in four out of nine lesions. Dermoscopically, four out of nine HMs did not show prevalent suspicious criteria while revealing suspicious RCM features that were visible only after careful RCM examination by zooming mosaic images. RCM can improve HM diagnostic accuracy but only after extensive evaluation of images. Atypical cells were less reflective and the architectural irregularity was less visible than in pigmented melanoma and zooming was needed to identify both features.

Primary amelanotic melanoma is an infrequent occurrence in the oral cavity. Owing to the high rate of local invasion and distant metastasis, oral amelanotic melanoma (OAM) carries a very poor prognosis. The absence of pathognomonic clinical and routine histological features in OAM is the reason for diagnosticdelay, which further worsens the prognosis. This case report discusses the masquerading nature of OAM that was clinically and histologically mimicking several malignant neoplasms. This case also demonstrates the poor prognosis of OAM. The objective of presenting this case is that the diagnostic delay of OAM can be avoided through enhanced clinical awareness and subsequent appropriate immunohistochemical investigations, in addition to the routine H&E-stained histopathological evaluation.

Amelanotic and hypomelanotic melanomas (AHM) comprise 2-8% of all melanomas. They are usually diagnosed late and are more advanced at diagnosis compared with pigmented melanomas (MM). As a result, AHMs are associated with higher mortality and morbidity (1). Some reports have described the dermoscopic features of amelanotic melanomas (AMM) and hypomelanotic melanomas (HMM) to aid the diagnosis of such lesions (2-4).

A 13-year-old castrated male ragdoll cat’s left eye was evaluated for dyscoria, iridal thickening and color change of 2 years duration, as well as elevated intraocular pressure. The primary lesion seen on ophthalmic examination was a pale pink-white mass observed in the dorsomedial aspect of a diffusely thickened iris. Metastatic workup revealed hepatic and splenic nodules, but cytology was inconclusive. The left eye was enucleated, and histopathology was consistent with uveal amelanotic melanoma.

E-cadherin, a glycoprotein involved in cell-cell adhesion, has a pivotal role in epithelial-mesenchymal transition, a process through which neoplastic epithelial cells develop an invasive phenotype. In human cutaneous melanomas, decreased E-cadherin expression is associated with shorter survival and increased Breslow thickness, whereas in the dog its role is poorly understood. Tumor thickness and modified Clark level were recently proposed as useful features to assess canine melanocytic tumors, but no studies investigated their association with E-cadherin expression. We performed immunohistochemistry on 77 formalin-fixed, paraffin-embedded primary canine melanocytic tumors. A 3-tier and a 2-tier classification system for assessing E-cadherin expression were tested, with the latter being more informative for the assessment of canine melanocytic tumors. E-cadherin expression was lower in cutaneous melanomas than melanocytomas, as well as in amelanotic tumors compared to pigmented tumors. In amelanotic melanomas, absent E-cadherin expression was associated with an unfavorable outcome, suggesting a potential use of this marker in defining the prognosis of amelanotic melanomas. E-cadherin expression was lower in tumors with greater tumor thickness and modified Clark level ≥IV, suggesting its possible utility in identifying the most invasive tumors. The expression of E-cadherin in oral melanomas was heterogeneous, but was associated with pigmentation and clinical outcome; thus, E-cadherin evaluation could be advantageous to detect the most aggressive neoplasms. However, cutaneous melanomas without E-cadherin expression frequently had a favorable clinical outcome. Hence, its importance as prognostic factor should be carefully considered depending on the tumor origin.

The tumour microenvironment is rich in multiple cells that influence cancer development. Among them, macrophages are the most abundant immune cells, which secrete factors involved in carcinogenesis. Since protein-bound polysaccharides (PBP) from the4T1 cells were cultured in conditioned media (CM) collected after: stimulation of the macrophages with PBP (CM-PBP) or incubation of non-treated macrophages (CM-NT). A co-cultured model of both cell lines was also employed to investigate the crosstalk between the cells. Cell viability was measured using the MTT assay. The levels of cytokines and chemokines were determined by ELISA methods. Commercial assay kits were used to assess the activity of both arginase 1 and inducible nitric oxide synthase (iNOS) and the level of cell migration.The results revealed that CM-NT promotes proliferation and migration of 4T1 cells, and increases the secretion of pro-angiogenic factors (VEGF, MCP-1) by cancer cells. In contrast, CM-PBP inhibits 4T1 cell growth and migration, decreases the secretion of pro-angiogenic factors (VEGF, MCP-1) and upregulates the production of pro-inflammatory mediators (IL-6, TNF-α) with certain anti-tumoral properties Moreover, PBP-treated CM significantly decreases the level of M2 macrophage markers (arginase 1 activity, IL-10 and TGF-β concentrations), but upregulates iNOS activity and IL-6 and TNF-α production, which are M1 cell markers.The results suggest that PBP suppress the favourable tumour microenvironment by inhibiting the crosstalk between 4T1 cells and macrophages through the regulation of production of angiogenic and inflammatory mediators, and modulating the M1/M2 macrophage subtype.

Background: The prognosis of mucosal melanoma is poor, and the difference in clinical prognosis between patients with and without pigment needs further study.Aim: To analyze data with head and neck...

Vanicosides A and B are the esters of hydroxycinnamic acids with sucrose, occurring in a few plant species from the Polygonaceae family. So far, vanicosides A and B have not been evaluated for anticancer activity against human malignant melanoma. In this study, we tested these two natural products, isolated from Reynoutria sachalinensis rhizomes, against two human melanoma cell lines (amelanotic C32 cell line and melanotic A375 cell line, both bearing endogenous BRAFV600E mutation) and two normal human cell lines&mdash, keratinocytes (HaCaT) and the primary fibroblast line. Additionally, a molecular docking of vanicoside A and vanicoside B with selected targets involved in melanoma progression was performed.&nbsp, Cell viability was studied using an MTT assay. A RealTime-Glo&trade, Annexin V Apoptosis and Necrosis assay was used for monitoring programmed cell death (PCD). Vanicoside A demonstrated strong cytotoxicity against the amelanotic C32 cell line (viability of the C32 cell line was decreased to 55% after 72 h incubation with 5.0 &micro, M of vanicoside A), significantly stronger than vanicoside B. This stronger cytotoxic activity can be attributed to an additional acetyl group in vanicoside A. No significant differences in the cytotoxicity of vanicosides were observed against the less sensitive A375 cell line. Moreover, vanicosides caused the death of melanoma cells at concentrations from 2.5 to 50 &micro, M, without harming the primary fibroblast line. The keratinocyte cell line (HaCaT) was more sensitive to vanicosides than fibroblasts, showing a clear decrease in viability after incubation with 25 &micro, M of vanicoside A as well as a significant phosphatidylserine (PS) exposure, but without a measurable cell death-associated fluorescence. Vanicosides induced an apoptotic death pathway in melanoma cell lines, but because of the initial loss of cell membrane integrity, an additional cell death mechanism might be involved like permeability transition pore (PTP)-mediated necrosis that needs to be explored in the future. Molecular docking indicated that both compounds bind to the active site of the BRAFV600E kinase and MEK-1 kinase, further experiments on their specific inhibitory activity of these targets should be considered.

AimsTo investigate the success and recurrence rates and visual outcomes in a large case series of amelanotic posterior choroidal melanomas treated by means of primary photodynamic therapy (PDT) with verteporfin.MethodsRetrospective case series from a single specialist ocular oncology centre. All patients had a clinical diagnosis of choroidal melanoma and were selected for PDT based on tumour characteristics. Included patients had at least 24 months of follow-up from initiation of treatment and all but one had not received treatment prior to PDT.Results69 patients were included. Mean tumour thickness was 1.9 mm (range 0.5–4.4), while the mean basal diameter was 6.9 mm (range 2.4–11.0). Included lesions were stage cT1a (n=66) or cT2a (n=3). The mean duration of follow-up from treatment initiation was 57 months (range 24–116 months). Seven lesions (10%) failed to respond to PDT. 10 patients (16%) experienced recurrence during follow-up. Overall success rate in this series was 75% (n=52). 83% of successfully treated patients (n=43) maintained or gained vision by final follow-up. Visual outcomes were significantly better in those patients who received PDT therapy alone in comparison to those who needed other treatments for their melanoma (Fisher’s exact test, p=0.004). Unfortunately, one patient (1.4%) in the series developed systemic metastases and died.ConclusionSelected amelanotic posterior uveal melanomas may be successfully treated with PDT with retention of good vision in the majority of cases, maintained with a mean of 57 months (minimum of 24 months) of follow-up.

The biology of three amelanotic melanoma cell lines (Ab, B16F10, and A375) of different species origin was analyzed during in vitro induced melanization in these cells. Melanin production was induced by DMEM medium characterized by a high level of L-tyrosine (a basic amino acid for melanogenesis). The biodiversity of amelanotic melanoma cells was confirmed by their different responses to melanogenesis induction; Ab hamster melanomas underwent intensive melanization, mouse B16F10 darkened slightly, while human A375 cells did not show any change in melanin content. Highly melanized Ab cells entered a cell death pathway, while slight melanization did not influence cell biology in a significant way. The rapid and high melanization of Ab cells induced apoptosis documented by phosphatidylserine externalization, caspase activation, and mitochondrial energetic state decrease. Melanoma cell type, culture medium, and time of incubation should be taken into consideration during amelanotic melanoma cell culture in vitro. L-tyrosine, as a concentration-dependent factor presented in the culture media, could stimulate some amelanotic melanoma cell lines (Ab, B16F10) to melanin production. The presence of melanin should be considered in the examination of antimelanoma compounds in vitro, because induction of melanin may interfere or be helpful in the treatment of amelanotic melanoma.