Small Melanoma Research Articles

Enteroenteric intussusception caused by a small bowel metastatic cutaneous melanoma.

Unlike in children, intussusception is very rare in adults and accounts for only 1% of ileus in that population. While intussusception in children is most often idiopathic, in adults the cause of intussusception in most cases is tumor and most often metastatic adenocarcinoma. It is an extremely rare phenomenon for intestinal melanoma metastasis to be the cause of intussusception and has been described in the literature so far only in a limited number of case reports. 41-year-old female patient was admitted to the emergency department with a clinical picture of ileus. The patient had a melanoma excision on her back five years ago, for which chemotherapy and radiotherapy were carried out. An MSCT of the abdomen was performed, which indicated an obstructive ileus of the small intestine with a typical sign of intussusception (target sign). Upon explorative laparotomy enteroenteric intussusception was found with an invaginated segment of the ileum in a length of about 20 cm. When the intussuscepted segment was reduced, a black tumor the size of a plum was verified as a leading point. Histological analysis indicated metastatic cutaneous melanoma with foci of melanocytes underneath normal intestinal epithelium.

Immunogenomic correlates of immune-related adverse events for anti-programmed cell death 1 therapy.

Despite impressive antitumor efficacy of programmed cell death 1 (PD-1) inhibitors, this inhibition can induce mild to severe autoimmune toxicities, termed immune-related adverse events (irAEs). Yet, predictive pretreatment biomarkers for irAEs development across cancer types remain elusive. We first assessed cellular and molecular factors. To determine factors predicting the risk of irAEs for anti-PD-1 immunotherapy across multiple cancer types, an integrative analysis of cellular and molecular factors from 9104 patients across 21 cancer types and 4865522 postmarketing adverse event reports retrieved from adverse event reporting system was then performed. Accuracy of predictions was quantified as Pearson correlation coefficient determined using leave-one-out cross-validation. Independent validation sets included small cell lung cancer and melanoma cohorts. Out of 4865522 eligible adverse events reports, 10412 cases received anti-PD-1 monotherapy, of which, 2997 (28.78%) exhibited at least one irAE. Among established immunogenomic factors, dendritic cells (DC) abundance showed the strongest correlation with irAEs risk, followed by tumor mutational burden (TMB). Further predictive accuracy was achieved by DC and TMB in combination with CD4+ naive T-cells abundance, and then validated in the small cell lung cancer cohort. Additionally, global screening of multiomics data identified 11 novel predictors of irAEs. Of these, IRF4 showed the highest correlation. Best predictive performance was observed in the IRF4 - TCL1A - SHC-pY317 trivariate model. Associations of IRF4 and TCL1A expression with irAEs development were verified in the melanoma cohort receiving immune checkpoint inhibitors. Collectively, pretreatment cellular and molecular irAEs-associated features as well as their combinations are identified regardless of cancer types. These findings may deepen our knowledge of irAEs pathogenesis and, ultimately, aid in early detection of high-risk patients and management of irAEs.

The Videocapsule Endoscopy Role in the Early Diagnosis of Small Bowel Melanoma Metastasis: A Particular “Coal Black” Endoscopic Appearance

The Videocapsule Endoscopy Role in the Early Diagnosis of Small Bowel Melanoma Metastasis: A Particular “Coal Black” Endoscopic Appearance

Primary Malignant Melanoma of The Small Intestine

Primary small intestinal melanoma is a rare malignant neoplasm, for which scarce literature offers limited evidence for optimal management. We present a case of a 60-year-old female with primary melanoma of ileum. She presented with left sided abdominal pain, decreased appetite, and history of diarrhoea for 15 days. She developed absolute constipation during her preoperative investigations, in which CT scan revealed ileoileal intussusception. She underwent laparotomy for the resection of intussuscepted bowel segment, which revealed a greyish brown mass attached to bowel, later confirmed by histopathology as melanoma. Postoperative detailed clinical investigation revealed no primary cutaneous, hepatic, pulmonary, ocular, or cranial melanotic lesion. Hence, the lesion was classified as primary small bowel melanoma. She was referred to oncologist who started her on adjuvant chemotherapy. The patient expired of cardiopulmonary arrest three months after her diagnosis due to post Chemotherapy side effects.

Characteristics of Giant Nodular Melanomas in Special Locations: a Case Series and Review of the Literature.

Nodular melanoma (NM) is a rare subtype of melanoma, responsible for more than 40% of melanoma deaths, characterized by rapid growth and high metastatic potential. Only a few case studies concerning the dermoscopic presentations of giant nodular melanoma have been reported so far. The aim of the study was to assess dermoscopic features of giant nodular melanomas in special locations, along with their clinical and histopathologic aspects. Among 120 patients with histopathologically confirmed melanoma treated by the Skin Cancer and Melanoma Team between September 2020 and February 2021, we identified six patients with giant nodular melanoma in special locations. We retrospectively assessed the archived dermoscopic images to determine the dermoscopic features of these tumors. The group consisted of six cases of giant melanoma in special locations, including the scalp (4/6) and the heel (2/6). The giant tumors were large in size (at least 5cm in diameter). The most common dermoscopic structures in polarized light included asymmetric distribution of dermoscopic structures, the presence of structureless, multicolored zones (showing three or more colors), and the presence of white perpendicular lines or small, pink globules. It seems that there are no significant differences in dermoscopy between small and giant melanomas; however, further studies should be conducted on a larger scale.

The Hunt for Baby Melanomas: A Prospective Study of the Dermoscopy Features on 100 Small Melanoma Cases with in Vivo Surface Diameters up to a Maximum of 6 mm.

Early diagnosis can improve melanoma prognosis. Dermoscopy can enhance early melanoma recognition. Examine the dermoscopy features of early melanoma up to a maximum surface diameter of 6 mm. Consecutive melanoma cases were collected from two medical practices in Sydney, Australia 2019-2021. Dermoscopy features were recorded for melanomas by maximum surface diameter, to the nearest 0.1 mm, to a limit of 6 mm. Total cases numbered 100; with males (N = 48) and females (N = 52), melanoma in situ (MIS, N = 96) and invasive (N = 4). The most frequent anatomic sites on both males and females were back (males N = 20, females N = 16) then knee or leg (males N = 8, females N = 12). Minimum respective MIS diameters for males/females was 1.2/2.0 mm and for invasive cases 2.0/3.4 mm. Highest frequency dermoscopy features were: light brown, dark brown, gray and asymmetric melanoma shape. Brown pigment in hair follicles were more frequent on legs compared to other anatomic sites (odds ratio [OR] 14.6; 95% CI 1.29-165.17, P 0.03). Pseudopods were substantially increased in frequency comparing diameters less than 4 mm with 4 up to 6 mm (OR 8.81; 95% CI 1.05-73.9, P 0.004). Structureless area cases recorded increased gray (OR 7.08; 95% CI 1.61-31.11, P=0.01). Melanomas with edge angulation were noted in 20%-50% of cases across diameters 1-6 mm, less frequent were pigmented circles and polygons. Watch out! MIS presented with a surface diameter of just 1.2 mm and invasive melanoma 2.5 mm. Pseudopods were a strong clue to melanomas with a surface diameter less than 5mm. We found melanomas on leg sites displayed more frequent pigmented hair follicles.

Survival benefits of primary tumor surgery for synchronous brain metastases: A SEER-based population study with propensity-matched comparative analysis.

Evidence about the prognostic value of primary tumor surgery (PTS) in patients with brain metastatic malignancies is ambiguous and controversial. This study assessed the survival benefits of primary tumor surgery in patients with brain metastases (BMs). Adults patients with BMs that originated from lung, breast, kidney, skin, colon, and liver diagnosed between 2010 and 2018 were derived from the Surveillance, Epidemiology, and End Results database (SEER). Propensity score matching (PSM) was used to balance the bias between patients with or without PTS. Then the prognostic value of PTS was estimated by Kaplan-Meier analysis and Cox proportional hazard regression models. A total of 32,760 patients with BMs secondary to non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), breast cancer, renal cancer, melanoma, colorectal cancer, and liver cancer were identified from the database. After PSM at 1:1 ratio, PTS appeared to significantly prolong cause-specific survival (CSS) time for patients with BMs secondary to NSCLC, breast cancer, renal cancer, and colorectal cancer (hazard ratio [HR]=0.60 [0.53-0.68], 0.56 [0.43-0.73], 0.47 [0.37-0.60], and 0.59 [0.37-0.95], respectively, all p < 0.05). Patients with earlier T and N classifications, no extracranial metastasis, and cancer-specific subtypes (adenocarcinoma in NSCLC, hormone receptor-negative breast cancer) may derive more survival benefits from PTS when suffering from BMs. This population-based study supported PTS could provide survival benefits for patients with BMs secondary to NSCLC, breast cancer, renal cancer, and colorectal cancer. More emphasis should be put on PTS of selected patients with BMs.

Lifetime Exposure to Welding Fumes and Risk of Some Rare Cancers.

We investigated the association between exposure to welding fumes and the risk of biliary tract, male breast, bone, and thymus cancer, as well as cancer of the small intestine, eye melanoma, and mycosis fungoides, among men in a European, multicenter case-control study. From 1995-1997, 644 cases and 1,959 control subjects from 7 countries were studied with respect to information on welding and potential confounders. We linked the welding histories of the participants with a measurement-based exposure matrix to calculate lifetime exposure to welding fumes. Odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression models, conditional on country and 5-year age groups, and adjusted for education and relevant confounders. Regular welding was associated with an increased risk of cancer of the small intestine (OR= 2.30, 95% CI: 1.17, 4.50). Lifetime exposure to welding fumes above the median of exposed controls was associated with an increased risk of cancer of the small intestine (OR= 2.00, 95% CI: 1.07, 3.72) and male breast (OR= 2.07, 95% CI: 1.14, 3.77), and some elevation in risk was apparent for bone cancer (OR= 1.92, 95% CI: 0.85, 4.34) with increasing lifetime exposure to welding fumes. Welding fumes could contribute to an increased risk of some rare cancers.

Unilateral Diffuse Uveal Melanocytic Proliferation

An 83-year-old woman presented with accumulations of pigment in the anterior chamber of her right (Fig A) but not left eye (Fig B). Fundus examinations, gonioscopy, B-scan ultrasonography (Fig C), and ultrasound biomicroscopy failed to identify an intraocular tumor. An iris biopsy revealed a proliferation of melanocytes without atypia (Fig D), which were intensively immunoreactive for Melan A (Fig E). A diagnosis of unilateral diffuse uveal melanocytic proliferation was established. Later, the patient revealed she had a small cutaneous melanoma removed from her back 50 years prior.

Online scaffolds: A constructivist approach to oncology fellow learning.

11010 Background: Oncology is a vast and fast-paced field. Fellows must expend significant effort to learn and stay updated. Up-to-date learning tools covering core oncology content in a digestible manner are lacking. Additionally, passive lectures are common in oncology, while constructivist approaches that may improve learning are rare. Therefore, we piloted updatable online modules (“scaffolds”) as a learning tool for oncology fellows. Methods: Author SB, a University of California, San Francisco (UCSF) solid-tumor oncologist, designed 12 scaffolds (breast, non-small cell lung, small cell lung, head/neck, salivary/thyroid, upper gastrointestinal, lower gastrointestinal, germ cell, bladder/renal/adrenal, prostate, melanoma, and sarcoma) using Google Slides between 12/2018 and 6/2019. The scaffolds included bullet points and tables/figures synthesized from the ASCO self-evaluation program textbook’s solid tumor chapters and the National Comprehensive Cancer Network (NCCN) guidelines. We emailed scaffold links to all UCSF and Stanford oncology fellows in 2019-2020, including instructions for fellows to update the scaffolds without exceeding 20 slides per scaffold, 5 lines per slide, or 7 words per line. The scaffolds were reintroduced to new fellows at the beginning of each academic year. SB audited to ensure no erroneous information was added. In December 2021 we reviewed updates tracked in Google Slides and conducted one UCSF and one Stanford focus group with four 1st-3rd year fellows each. Results: Between 7/2019 and 12/2021, fellows made 60 updates to the scaffolds, with a mean of 5 updates per scaffold ranging from new trials to changes in management. During the same period, the auditor made 9 updates and found no erroneous fellow updates. Fellow updates occasionally exceeded specified limits, requiring correction. Content analysis revealed that fellows considered the scaffolds to be accessible and succinct learning tools that 1) addressed a dearth of similar resources, 2) served as effective preparation for clinical work and examinations, 3) provided structured information for rapid review, and 4) made subsequent interactions with complex resources such as NCCN guidelines easier. Barriers to fellows updating the scaffolds included lack of ownership and low confidence in judgment regarding appropriate updates. Conclusions: In this two-institution pilot, oncology fellows used and subsequently updated online scaffolds in a constructivist fashion. This model has the potential to fill a crucial gap in available learning resources and can be applied to other specialties. Assigning scaffolds to fellows with faculty mentorship may facilitate ownership and bolster fellow confidence in updating these tools. Individual institutions may update their own versions of the scaffolds to align with institution-specific needs.

SETDB1 Restrains Endogenous Retrovirus Expression and Antitumor Immunity during Radiotherapy.

The identification of the SETDB1-mediated suppression of radiotherapy-induced viral mimicry reveals SETDB1 inhibition as a potential approach to sensitize tumors to radiotherapy by enhancing the type I interferon response.

Treatment of Metastatic Disease with Immune Checkpoint Inhibitors Nivolumab and Pembrolizumab: Effect of Performance Status on Clinical Outcomes.

IntroductionAlthough guidelines exist for appropriate use of chemotherapy in the metastatic setting based on performance status, such recommendations are less readily available for immune checkpoint inhibitors (ICIs). We sought to determine whether there is a relationship between Eastern Cooperative Oncology Group (ECOG) performance status and outcomes of immunotherapy in patients treated for metastatic disease at our community-based oncology practice.MethodsPatients (n = 253) were identified as receiving nivolumab or pembrolizumab for stage IV malignancy at Cancer Centers of Colorado, St. Joseph Hospital/SCL Health between June 2018 and November 2020. Patients who initiated therapy after May 2020 were excluded from analysis due to less than 6 months follow-up time. The remaining 183 patients were included in a retrospective cohort study comparing patients with ECOG 0, 1, and 2–4. Sex, age, type of cancer, line of therapy, time on therapy and best response to therapy were determined. These baseline factors and outcomes were compared using analysis of variance (ANOVA) for numeric variables and χ2 tests of association for categorical variables. Time from initiation of ICI to death or hospice was also compared using a log-rank test as well as a multivariate Cox proportional hazards model.ResultsOf the 183 patients included, 31.7% had an ECOG of 0, 48.6% an ECOG of 1, and 19.7% an ECOG of 2–4. Non–small cell lung cancer and melanoma represented the majority of patients in each group. Sex and line of therapy did not differ between groups. There was a significant difference in age, with mean age of 62, 66, and 70 in ECOG 0, 1, and 2–4, respectively. Patients (54.6%) remained on therapy for at least 6 months, with no significant difference between groups in ability to complete 6 months of therapy. For ECOG 0, 1, and 2–4, disease control was achieved in 67.2%, 59.6%, and 41.7%, respectively. Analysis of time to death or hospice with a log-rank test showed a significant difference between groups. A multivariate Cox proportional hazards model revealed that patients with ECOG 0 had significantly longer time to death or hospice compared with patients in both other groups after controlling for age, sex, and line of therapy.ConclusionIn this single institution retrospective study of patients receiving nivolumab or pembrolizumab for metastatic cancer, ECOG 0 was associated with disease control and increased time before death or transition to hospice.

Выживаемость пациентов с увеальной меланомой малых и средних размеров в зависимости от клинико-патоморфологической картины и клеточного микроокружения

Purpose. To assess the survival rate of patients with small and mediumsized uveal melanoma, depending on the clinical and pathomorphological picture and the cellular microenvironment. Material and methods. For a prospective study, 33 patients with T1-2N0M0 stage of the tumor were selected for the period from June 2005 to July 2018 at an average age of 54±2.7 years. In all cases, the enucleation of the affected eye was carried out with a morphological study of it and a study of the composition of the cellular microenvironment of the tumor node, which became the main criterion for compliance and inclusion in the study. Results. During the study period of observation after enucleation due to eye uveal tract melanoma, 9 (27.3%) of 33 patients died from metastatic disease. Of these, 2 with small and 7 with middle size of tumor. The timing of the appearance of metastases ranged from 15 to 96 (average 41.3±34.5) months. The median follow-up was 64.5 (95% confidence interval 29.3– 99.7) month. The 5-year survival rate of patients with small and medium sized uveal melanoma was 78.7%, and the 10-year survival rate was 72.7%. A significant dependence of the mortality of patients was revealed with the epithelioid cell type of melanoma, increase of tumor basal diameter, involvement of optic disc area and ciliary body, a significant degree of pigmentation, the presence of necrosis in tumor stroma, ingrowth into sclera emissarium and large number of tumor vessels. Survival decreases in patients with a large accumulation of lymphocytes around the tumor, the absence of macrophages, mast cells, fibroblasts on the one hand, and the presence of plasmocytes, myeloid-derived suppressor cells (promyelocytes, neutrophils, eosinophils) in tumor microenvironment. Conclusion. Studies have revealed a certain relationship between the life expectancy of patients and their mortality from metastatic disease with clinical and pathological signs and a specific composition of the cell microenvironment. Key words: uveal melanoma, survival, cell microenvironment

The MOLES system to guide the management of melanocytic choroidal tumours: can optometrists apply it?

ABSTRACTClinical relevanceAlthough melanocytic choroidal tumours of the choroid are a common eye pathology, no standardised protocol exists for their management in the community.BackgroundChoroidal naevi are found in approximately 6% of the adult White population, whereas choroidal melanomas are rare, with an annual incidence of 5–10/million/year. Multimodal imaging has advanced the understanding of malignancy imaging biomarkers, but distinguishing between a small melanoma and naevus remains difficult and an algorithm for their management by community practitioners has not been uniformly adopted. One of the authors (BD) devised the MOLES scoring system, which indicates malignancy likelihood according to mushroom shape, orange pigment, large size, enlargement, and subretinal fluid. When applied by ocular oncologists, the system accurately distinguishes choroidal naevi from melanomas. The aim of this study was to evaluate whether community optometrists can appropriately manage patients with melanocytic choroidal tumours using this system.MethodsClinical images of 25 melanocytic choroidal tumours were presented in an online survey, including colour fundus photographs, fundus autofluorescence, optical coherence tomography, and B-scan ultrasound images. Using the MOLES system, 39 optometrists diagnosed tumours as naevus or probable melanoma and decided between community monitoring and ophthalmologist referral. Responses were compared to MOLES grading of the same clinical images by ocular oncologists.ResultsUsing MOLES, optometrists correctly identified 389/406 probable melanomas (95.8% sensitivity) and 331/516 choroidal naevi (64.1% specificity); correctly referred 773/778 tumours to an ophthalmologist (99.4% sensitivity); and correctly managed 80/144 lesions (55.6% specificity) in the community.ConclusionOptometrists safely applied the MOLES scoring system in this survey. Further measures are indicated to reduce choroidal naevi over-referral and evaluate MOLES system usage in clinical optometric practice, where some imaging modalities may not be readily available.

Malignant melanoma with features of the small cell variant: A case report

Malignant melanoma can exhibit various cytomorphological features. Small cell pattern of growth is one of the rarest morphological variants.1 Immunohistochemical analyses play a very important role in the diagnosis of small cell malignant melanoma especially in amelanotic lesions.

Antiplatelet medications and risk of intracranial hemorrhage in patients with metastatic brain tumors

AbstractAlthough intracranial hemorrhage (ICH) is frequent in the setting of brain metastases, there are limited data on the influence of antiplatelet agents on the development of brain tumor–associated ICH. To evaluate whether the administration of antiplatelet agents increases the risk of ICH, we performed a matched cohort analysis of patients with metastatic brain tumors with blinded radiology review. The study population included 392 patients with metastatic brain tumors (134 received antiplatelet agents and 258 acted as controls). Non–small cell lung cancer was the most common malignancy in the cohort (74.0%), followed by small cell lung cancer (9.9%), melanoma (4.6%), and renal cell cancer (4.3%). Among those who received an antiplatelet agent, 86.6% received aspirin alone and 23.1% received therapeutic anticoagulation during the study period. The cumulative incidence of any ICH at 1 year was 19.3% (95% CI, 14.1-24.4) in patients not receiving antiplatelet agents compared with 22.5% (95% CI, 15.2-29.8; P = .22, Gray test) in those receiving antiplatelet agents. The cumulative incidence of major ICH was 5.4% (95% CI, 2.6-8.3) among controls compared with 5.5% (95% CI, 1.5-9.5; P = .80) in those exposed to antiplatelet agents. The combination of anticoagulation plus antiplatelet agents did not increase the risk of major ICH. The use of antiplatelet agents was not associated with an increase in the incidence, size, or severity of ICH in the setting of brain metastases.

Primary Small Bowel Melanoma or Small Bowel Metastasis with Vanishing Primary Cutaneous Lesion

The small bowel represents one of the main sites for cutaneous melanoma metastasis; however, numerous cases of primary intestinal melanoma have recently been described. In view of this, we present the case of a 39-year-old woman admitted for nausea, heartburn, abdominal pain, change in bowel habits and weight loss. Contrast-enhanced CT revealed a small bowel mass. Surgical resection of a 6 cm ileal tumour with regional mesenteric lymphadenectomy and end-to-end anastomosis was performed. Histopathological findings indicated the presence of an ileal melanoma metastasis. Subsequent dermatological examination identified a cutaneous lesion on the right forearm, however no malignant cells were found at the histopathological exam. Whole body PET CT with FDG identified multiple frontal and parietal lesions. Genetic testing was positive for BRAF gene V600 E mutation. The patient underwent multiple neurosurgical procedures for the resection of cerebral metastases. Palliative external radiation and chemotherapy was also attempted. After approximately 2 years after the diagnosis, the patient died following multiple episodes of intracranial hypertension.

Dermoscopy of Small Diameter Melanomas with the Diagnostic Feasibility of Selected Algorithms-A Clinical Retrospective Multicenter Study.

Simple SummaryThe early detection of melanoma determines the recovery of the patient. Dermoscopy, which is one of the diagnostic tools for pigmented lesions, is characterized by high sensitivity and specificity, giving the clinician the possibility to detect the presence of abnormal structures before their clinical presentation. There are a small number of dermoscopic analyses of pigmented lesions of less than 6 mm in diameter in the published literature. The authors attempted to identify characteristic dermoscopic structures typical for melanomas of less than 5 mm in diameter in comparison with a group of melanomas exceeding this dimension at an identical clinical stage. It was found that dermoscopy in the secondary prevention of micromelanomas (appearing mainly as brown lesions) revealed the presence of dotted or polymorphous vessels, with architectural disorder in half of cases. Moreover, spitzoid, multicomponent asymmetric or nonmelanoma-specific patterns prevailed. Knowledge of these dermoscopic features brings the clinician closer to an early diagnosis of melanoma with a diameter of 5 mm or less.Objective: The aim of the study was to verify two hypotheses. The first concerned the possibility of diagnostic dermoscopic differentiation between cutaneous melanomas of the histopathological category in situ (pTis) and thin melanomas (pT1a) in terms of their diameter. The second assessed the diagnostic feasibility of two dermoscopic algorithms aiming to detect ≤ 5.0 mm-sized melanomas histopathologically confirmed as pTis and pT1a. Methods: Dermoscopic images of consecutive cases of histopathologically confirmed melanomas were evaluated by three independent investigators for the presence of the predefined criteria. The melanomas were subdivided according to their diameter into small melanomas, so-called micromelanomas (microM)—sized ≤ 5.0 mm and >5.0 mm, according to published definitions of small melanocytic lesions. The Triage Amalgamated Dermoscopic Algorithm (TADA) and the revisited 7-point checklist of dermoscopy (7-point) algorithm were chosen for the diagnostic feasibility. Odds ratios and corresponding 95% confidence limits (CL) were calculated using the logistic regression adjusted for age for the melanoma-specific dermoscopic structures, the dermoscopic patterns and the diagnostic feasibility of the 7-point checklist and TADA algorithms. The p-values of the results were corrected using the Bonferroni method. Results: In total, 106 patients with 109 melanomas, 50 sized ≤ 5.0 mm and 59 exceeding the diameter of 5.0 mm, were retrospectively analyzed. The prevalent general pattern of microM was the spitzoid one (48% vs. 11.86%, p = 0.0013). Furthermore, 40% of microM vs. 6.78% melanomas sized > 5.0 mm (p = 0.0023) did not present melanoma-specific patterns. The asymmetric multicomponent pattern was present in 64.41% melanomas sized > 5.0 mm and in 26.00% microM (p = 0.0034). The asymmetry of structures or colors was detected in 56% microM vs. 89.83% (p = 0.0020) and 56% microM and 94.92% (p = 0.000034) melanoma sized > 5.0 mm, respectively. The differences in frequency of the detected dermoscopic structures specific to melanomas revealed that microM are almost deprived of negative networks (p = 0.04), shiny white structures (p = 0.0027) and regression features (p = 0.00003). Neither prominent skin markings nor angulated lines were found in the entire study group. Out of the vascular structures, microM presented only dotted (32%) or polymorphous (28%) vessels, although more rarely than melanomas sized > 5.0 mm (66.1% p = 0.017 and 49% p > 0.05, respectively). The diagnostic feasibility revealed a score ≥ 3 of the 7-point algorithm (indicative for malignancy) in 60% microM and 98.31% melanomas sized > 5.0 mm (p = 0.000006). The TADA algorithm revealed melanoma-specific patterns in 64% microM and 96.61% > 5.0 mm-sized melanomas (p = 0.00006) and melanoma-specific structures in 72% and 91.53% (p > 0.05), respectively. Conclusion: In the dermoscopy, 40% of micromelanomas histopathologically staged as pTis and pT1a did not reveal melanoma-specific patterns. Among the general melanocytic patterns, the spitzoid one was the most frequently found in melanomas sized ≤ 5.0 mm. The 7-point checklist and TADA dermoscopic algorithms were helpful in the identification of the majority of melanomas sized ≤ 5.0 mm.

Macrophage inhibitory cytokine-1 produced by melanoma cells contributes to melanoma tumor growth and metastasis in vivo by enhancing tumor vascularization.

Macrophage inhibitory cytokine-1 (MIC-1) has been reported to be elevated in various human cancers including melanoma; however, the function of MIC-1 in cancer remains unclear. In this study, we attempt to clarify the role of MIC-1 in tumor pathogenesis by employing the orthotopic B16F1 melanoma mouse model in which serum MIC-1 levels are positively correlated with tumor size. By stably transfecting a MIC-1 expression construct into B16F1 melanoma cells, we increased the expression and secretion levels of MIC-1. This increase in MIC-1 expression significantly enhanced the growth of tumors derived from B16F1 cells in vivo, despite not affecting in vitro cell growth. The elevated MIC-1 expression in B16F1 cells also resulted in lymph node metastasis in B16F1 tumor-bearing mice, significantly increasing mortality. Interestingly, among small melanoma tumors of similar size, tumors derived from the MIC-1-transfected B16F1 cells exhibited enhanced blood vessel formation compared with those of mock transfectant cells. Also, more MIC-1 was found in well-vascularized tumor regions than in poorly vascularized tumor regions. Moreover, conditioned medium (CM) of the MIC-1-transfected melanoma cells enhanced the angiogenic properties of endothelial cells more than CM of mock transfectant cells. Notably, hypoxic culture conditions forced parental B16F1 cells to secrete more endothelial cell-stimulating factors, among which the function of MIC-1 was confirmed by blocking the effects with an anti-MIC-1 antibody. Taken together, these results suggest that the MIC-1 produced by melanoma cells in response to oxygen deprivation promotes tumor vascularization during melanoma development in vivo, leading to enhanced tumor growth and metastasis.

ANALYSIS OF METASTASIS-FREE SURVIVAL IN PATIENTS WITH SMALL CHOROID MELANOMA DEPENDING ON THE TYPE OF PRIMARY TUMOR TREATMENT

Background. There is no unified approach to the management of patients with small choroid melanoma (CM) (thickness up to 3 mm, base diameter up to 10 mm). The study of the development of metastases in these patients is of great significance for choosing an appropriate treatment method.Purpose: to assess the incidence of metastatic disease in patients with small CM, who were treated with transpupillary thermotherapy (TTT), photodynamic therapy (PDT), and brachytherapy (BT).Material and Methods. The retrospective study included 149 patients with CM, who were treated at the National Cancer Center of Belarus from 2005 to 2018. All patients had tumors less than 10 mm in diameter, less than 3 mm in thickness, and had no signs of systemic progression before starting therapy. All tumors corresponded to stage T1N0M0 (American Joint Committee on Cancer (AJCC)). 44 patients were treated with PDT, 47 with TTT, and 58 with BT.Results. The median follow-up time was 154 months (12 years) in patients treated with brachytherapy, 128 months (10 years) in patients treated with TTT and 72 months (6 years) in patients treated with PDT. During the follow-up period, metastases were observed in 1 (2.3 %) patient after PDT and in 5 (10.6 %) patients after TTT. In patients treated with BT, systemic progression was not recorded during the follow-up period. All cases of metastatic disease were associated with local recurrence or continued growth of CM.Discussion. The 5-year metastasis-free survival after TTT was worse than after PDT (82 ± 8.0 % and 94 ± 6.0 %, respectively, p&lt;0.0001). However, in some cases, preference can be given to laser treatment methods, allowing the patients to avoid post-radiation retinopathies. The lack of local control of the tumor can be considered a surrogate marker for the development of metastatic disease. Conclusion. The highest metastasis-free rates were observed after brachytherapy. Positron emission tomography is recommended for early detection of systemic progression of the disease. Key words: choroid melanoma, uveal melanoma, transpupillary thermotherapy, photodynamic therapy, brachytherapy, metastatic-free survival, organ-preserving treatment.&gt;˂0.0001). However, in some cases, preference can be given to laser treatment methods, allowing the patients to avoid post-radiation retinopathies. The lack of local control of the tumor can be considered a surrogate marker for the development of metastatic disease.Conclusion. The highest metastasis-free rates were observed after brachytherapy. Positron emission tomography is recommended for early detection of systemic progression of the disease.