Is optical coherence tomography angiography helpful in the differential diagnosis of choroidal nevus versus melanoma?

PURPOSE: To describe the imaging features of choroidal nevus and melanoma using optical coherence tomography angiography, and evaluate the ability of this technique to establish the differential diagnosis based on the display of the tumor's intrinsic vasculature. METHODS: Comparative analysis of optical coherence tomography angiography findings in consecutive patients diagnosed with choroidal nevus or choroidal melanoma following a complete ophthalmic evaluation, including best-corrected visual acuity and several imaging studies: color fundus photography, B-scan ultrasound, spectral-domain optical coherence tomography, and optical coherence tomography angiography. Optical coherence tomography angiography was used to investigate qualitative differences in the tumor vasculature. RESULTS: Thirty-six eyes (18 cases of choroidal nevus and 18 cases of choroidal melanoma) from 36 consecutive patients were included in the study. Only cases located posterior to equator were included to enable performance of all tests. On optical coherence tomography angiography, choroidal nevus showed well-delimited margins (78%), hyperreflective choroid capillary vasculature (83%), fewer avascular areas (17%), and neovascular membrane in one case (6%). Choroidal melanoma showed imprecise margins (72%), hyporeflective choroidal capillary vasculature (72%), multiple avascular areas (78%), and choroidal vascular changes (e.g. thick vascular networks or vascular loops; 45%). CONCLUSION: Optical coherence tomography angiography can provide useful information for assessing and differentiating between choroidal nevi and small melanomas. Significant differences between these conditions were found for the pattern of reflectivity, and presence/absence of avascular zones and vascular anomalies, which could be helpful for supporting the diagnosis.

Inflammatory juvenile compound nevi: A melanoma is not all that it appears to be. / Nevus compuesto inflamatorio juvenil: no es melanoma todo lo que parece.

An 11 year-old girl presented with a recent growth pigmented conjuntival lesion in the bulbar conjunctiva of left eye. Due to the the biomicroscopic and ultrasound findings, an excisional biopsy was performed on the lesion using the «no touch¼ technique, as well as cryo-coagulation of surgical margins. Histopathological examination revealed an inflammatory compound nevus. Melanotic conjunctival tumours are mostly benign. However, the recent growth of a lesion, its vascularisation, irregularities of the margins, and colour change must suggest it has turned malignant. In such case, excision of the lesion is mandatory. Despite all the clinical changes, especially in young patients, it can still be an inflammatory compound nevus.

Identification of Feeder Vessels in Ocular Surface Neoplasia Using Indocyanine Green Angiography.

PURPOSE: To evaluate indocyanine green angiography (ICGA) for the identification and characterization of afferent (feeding) and efferent (draining) vessels in patients with ocular surface neoplasia. MATERIALS AND METHODS: Consecutive patients with biopsy-proven benign, pre-invasive, or invasive ocular surface tumors of the bulbar conjunctiva were included. Patients underwent anterior segment optical coherence tomography, ICGA, and color photography for the evaluation of the thickness, location, number, and diameter of afferent and efferent vessels of the lesions. RESULTS: Twenty-two eyes of 22 patients with papillomas (n = 4), intra-epithelial neoplasia lesion (n = 2) in situ or invasive carcinomas (n = 6), nevus (n = 5), conjunctival melanocytic intra-epithelial neoplasia lesion (n = 1), and in situ or invasive melanomas (n = 4) were investigated. Afferent (feeder) vessels were identified in all lesions. There were fewer afferent (3.1 ± 1.6) than efferent (7.5 ± 3.5) vessels per lesion (p < 0.001) and the mean diameter was smaller for afferent (101 ± 62 µm, 28-281) than efferent vessels (137 ± 51 µm, 31-652; p = 0.017). The number of afferent and efferent vessels was associated with the thickness of the lesion (p = 0.037, p < 0.01). Lesion filling times differed between benign and invasive or pre-invasive lesions (p = 0.018). CONCLUSIONS: ICGA is a useful adjunctive in vivo imaging method for the assessment of the vasculature in patients with suspected ocular surface neoplasia.

A pilot study to image the vascular network of small melanocytic choroidal tumors with speckle noise-free 1050-nm swept source optical coherence tomography (OCT choroidal angiography).

PURPOSE: To visualize and measure the vascular network of melanocytic choroidal tumors with speckle noise-free swept source optical coherence tomography (SS-OCT choroidal angiography). METHODS: Melanocytic choroidal tumors from 24 eyes were imaged with 1050-nm optical coherence tomography (Topcon DRI OCT-1 Atlantis). A semi-automated algorithm was developed to remove speckle noise and to extract and measure the volume of the choroidal vessels from the obtained OCT data. RESULTS: In all cases, analysis of the choroidal vessels could be performed with SS-OCT without the need for pupillary dilation. The proposed method allows speckle noise-free, structure-guided visualization and measurement of the larger choroidal vessels in three dimensions. The obtained data suggest that speckle noise-free OCT may be more effective at identifying choroidal structures than traditional OCT methods. The measured volume of the extracted choroidal vessels of Haller's layer and Sattler's layer in the examined tumorous eyes was on average 0.982463955 mm(3) /982463956 µm(3) (range of 0.209764406 mm(3) /209764405.9 µm(3)to 1.78105544 mm(3) /1781055440 µm(3)). Full thickness obstruction of the choroidal vasculature by the tumor was found in 18 cases (72 %). In seven cases (18 %), choroidal vessel architecture did not show pronounced morphological abnormalities (18 %). CONCLUSION: Speckle noise-free OCT may serve as a new illustrative imaging technology and enhance visualization of the choroidal vessels without the need for dye injection. OCT can be used to identify and evaluate the choroidal vessels of melanocytic choroidal tumors, and may represent a potentially useful tool for imaging and monitoring of choroidal nevi and melanoma.

A pilot study to compartmentalize small melanocytic choroidal tumors and choroidal vessels with speckle-noise free 1050 nm swept source optical coherence tomography (OCT choroidal "tumoropsy").

PURPOSE: The purpose was to illustrate small melanocytic choroidal tumors with speckle-noise free swept-source optical coherence tomography (SSOCT). METHODS: Twenty-five small melanocytic choroidal tumors in 24 eyes underwent 1050 nm OCT. All tumors were measured manually with the built-in caliper tool and compared to data derived from a semiautomated algorithm that removed speckle noise but preserved the structure of the tumors from the SSOCT data. RESULTS: The average manual measurements for the horizontal, vertical, and axial diameters were 1535.28 µm (range, 547-2807 µm), 1713.8 µm (range, 574-3921 µm), and 227.28 µm (range, 115-489 µm), respectively. The measured average volumes of the tumors were 835,248,212 µm(3) (range, 48,818,700 to 4,567,401,810 µm(3)) and 228,588,535 µm(3) (range, 22,879,641 to 787,668,886 µm(3)) for caliper measurements, respectively, for the extracted volumes. The average volume variation between the two methods was 66.16 % (range, 46.5 % to 82.75 %). The average ratio between the caliper and extracted volumes was 3.402 (range, 1.346-8.198, SD 1.681), 2.367 (range, 1.346-3.258, SD 0.618), 2.321 (range, 1.346-3.258, SD 0.611), 2.402 (range, 1.518-3.258, SD 0.591), and 1.749 (range, 1.518-1.733, SD 0.239) for all tumors, all tumors with the exclusion of extreme parameters, tumor <3 mm, tumor <2 mm, and tumor <1 mm, respectively. The average ratio (tumor index) between the tumor volume and the choroidal vessel volume was 12.539 (range, 0.489-73.701). CONCLUSION: Speckle-noise free swept-source OCT may be an illustrative OCT imaging technology. OCT may be useful for describing and monitoring small melanocytic choroidal tumors and the choroidal vessels.

MuSIC report III: tumour microcirculation patterns and development of metastasis in long-term follow-up of melanocytic uveal tumours.

PURPOSE: To statistically determine differences in microcirculation patterns between nevi and uveal melanomas and the influence of these patterns on metastatic potential in the long-term follow-up of 112 patients with melanocytic uveal tumours. In vivo markers indicating malignancy and metastatic potential have implications for treatment decision. METHODS: Primary diagnosis and work-up included clinical examination, fundus photography, standardized A and B scan echography as well as evaluation of tumour microcirculation patterns via confocal fluorescein and indocyanine green angiography (ICGA). Patient data were collected from the patient files, the tumour registry or personal contact. Statistical analysis was performed with spss 22.0 using chi-square, Fisher's exact test and Kaplan-Meier survival analysis. RESULTS: Forty-three uveal melanocytic lesions remained untreated and were retrospectively classified as benign nevi, whereas 69 lesions were malignant melanomas (T1: 32, T2: 28, T3: 6 and T4: 3). 'Silent' and 'arcs without branching' were found significantly more often in nevi (p = 0.001 and p = 0.010), whereas 'parallel with cross-linking' and 'networks' were significantly more frequent in melanomas (p = 0.022 and p = 0.029). The microcirculation pattern 'parallel with cross-linking' proved significantly more frequent in patients who developed metastases (p = 0.001). CONCLUSIONS: Certain microcirculation patterns may guide us in differentiating uveal nevi from malignant melanomas. A non-invasive prognostic marker can be of great value for borderline lesions in which cytology is less likely taken. 'Parallel with cross-linking' did not only indicate malignancy, but it was also associated with later tumour metastasis.

Usefulness of confocal microscopy in distinguishing between basal cell carcinoma and intradermal melanocytic nevus on the face.

The clinical distinction between basal cell carcinoma (BCC) and intradermal melanocytic nevus lesions on the face can be difficult, particularly in young patients or patients with multiple nevi. Dermoscopy is a useful tool for analyzing characteristic dermoscopic features of BCC, such as cartwheel structures, maple leaf-like areas, blue-gray nests and dots, and ulceration. It also reveals arborizing telangiectatic vessels and prominent curved vessels, which are typical of BCC, and comma vessels, which are typical of intradermal melanocytic nevi. It is, however, not always easy to distinguish between these 2 conditions, even when dermoscopy is used. We describe 2 facial lesions that posed a clinical and dermoscopic challenge in two 38-year-old patients; confocal microscopy showed separation between tumor nests and stroma and polarized nuclei, which are confocal microscopy features of basal cell carcinoma.

Assessment of vascularity in common blue nevi, small/medium congenital nevocellular, common and dysplastic acquired melanocytic nevi and melanomas: a comparative study.

Angiogenesis and vascularity are researched in melanocytic tumors for their importance in carcinogenesis. For the first time, to the best of our knowledge, the authors compared the microvascular characteristics between small/medium congenital nevocellular nevi (CN), common blue nevi (BN), common and dysplastic acquired melanocytic nevi (AMN), and melanomas. The authors collected 31 BN, 48 CN (≤5 cm), 35 AMN (14 common, 21 dysplastic), and 26 melanomas. Vessels were stained with factor VIII. Microvascular density (MVD) and total vascular area (TVA), where evaluated in high capillary density areas. Student t and Mann-Whitney tests were used. MVD (mean ± SD) was low in BN (3.52 ± 1.21) and significantly higher in CN (7.56 ± 2.47) (P < 0.001). TVA was low in BN and significantly higher in CN (Mann-Whitney U = 141, n1 = 48, n2 = 31, P < 0.001, 2-tailed). MVD was not significantly different between common and dysplastic AMN (20.64 ± 7.87 and 20.38 ± 9.54, respectively) (P > 0.05). TVA was not significantly different between common and dysplastic AMN (Mann-Whitney U = 164, n1 = 14, n2 = 21, P > 0.05, 2-tailed). MVD was significantly lower in CN (7.56 ± 2.47) compared with AMN (20.49 ± 8.79) (P < 0.001). TVA was significantly lower in CN compared with AMN (Mann-Whitney U = 1486, n1 = 48, n2 = 35, P < 0.001, 2-tailed). MVD was significantly lower in AMN (20.49 ± 8.79) compared with melanomas (33.77 ± 14.32) (P < 0.001). TVA (mean ± SD) was significantly smaller in AMN (18473.94 ± 7050.61) compared with melanomas (29308.50 ± 11307.22) (P < 0.001). Vascularity increased from BN to CN to AMN with melanomas being the most vascular. Common and dysplastic AMN had comparable vascularity. The implications of our results regarding melanoma transformation risk are considered.

Angioadnexocentric nevus.

An association of melanocytic nevus with eccrine glands has been well-documented and well-known as eccrine-centered nevus. Non-giant congenital nevi sometimes contain angiocentric and/or adnexocentric growth of nevus cells. Blood vessels are the most prominent site of nevus cell infiltration and propagation. In our specimen, the second was eccrine ducts. These selective sites of infiltration gave rise to a linear pattern of nevus cell distribution. Upon cursory examination at low magnification, vascular pathologies such as lymphocytic perivasculitis and particularly "coat-sleeve-like" pattern of erythema annulare centrifugum were suggested. S-100 immunostained perivascular and periductal lymphocytoid cells while CD3, 4 and 8 for T cells, and CD20 and 79a for B cells, were all negative. S-100 detected some invasive behavior of nevus cells penetrating into the vascular and ductal walls. However, Ki-67 was negative in all cells, suggesting a benign nature of this lesion. It is postulated that intradermal nevus cells of fetal skin freely migrate through mesenchymal tissue and stop when they hit barriers such as blood vessels and eccrine ducts and propagate in situ. How does this random migration theory explain the blood vessels and eccrine ducts getting the largest share of nevus cells? It is because they are the largest barriers of fetal dermis.

Assessment of melanocytic skin lesions with a high-definition laser Doppler imaging system.

BACKGROUND: Early detection is a major goal in the management of malignant melanoma. Besides clinical assessment many noninvasive technologies such as dermoscopy, digital dermoscopy and in vivo laser scanner microscopy are used as additional methods. Herein we tested a system to assess lesional perfusion as a tool for early melanoma detection. METHODS: Laser Doppler flow (FluxExplorer) and mole analyser (MA) score (FotoFinder) were applied to histologically verified melanocytic nevi (33) and malignant melanomas (12). RESULTS: Mean perfusion and MA scores were significantly increased in melanoma compared to nevi. However, applying an empirically determined threshold of 16% perfusion increase only 42% of the melanomas fulfilled the criterion of malignancy, whereas with the mole analyzer score 82% of the melanomas fulfilled the criterion of malignancy. CONCLUSION: Laser Doppler imaging is a highly sensitive technology to assess skin and skin tumor perfusion in vivo. Although mean perfusion is higher in melanomas compared to nevi the high numbers of false negative results hamper the use of this technology for early melanoma detection.

Key points in dermoscopy for diagnosis of melanomas, including difficult to diagnose melanomas, on the trunk and extremities.

Early diagnosis and prompt surgical excision are the most important aims in the secondary prevention of cutaneous melanoma. Dermoscopy has increased the accuracy in the detection of melanoma because of dermoscopic-specific features that can be easily detected by trained dermoscopists. However, the classical melanoma-specific criteria such as multicomponent pattern, atypical pigmented network, irregular dots/globules, irregular streaks, multiple colors, blue-whitish veil or regression structures may not be present in all of these lesions. For some early melanomas change, as evidenced by sequential dermoscopic monitoring, may be the only feature suggesting malignancy. At present, even with dermoscopy, the diagnosis of these early melanomas remains to be a challenge for dermatologist. Patient education, digital dermoscopic follow up and consensus diagnosis have been proposed to overcome this problem.

Spectrophotometric analysis of melanocytic naevi during pregnancy.

Malignant melanoma is the most common cancer during pregnancy, but it is unknown whether melanocytic naevi in general are activated. A total of 381 melanocytic naevi in 34 Caucasian primigravidae were examined using spectrophotometric intracutaneous analysis (SIAscopy) technology in early pregnancy and prior to delivery. The Siagraphs of each naevus were then compared in order to evaluate changes over time. A total of 163 melanocytic naevi in 21 nulliparous women served as an additional control group. At the first visit none of the Siagraphs examined for the case or control groups aroused suspicion of dysplastic naevus or melanoma and no significant structural changes were noted during the observation period. However, 2.1% of the melanocytic naevi in the pregnant group increased and 1.3% decreased in size. Corresponding figures in the non-pregnant group were 1.8% and 0%, respectively. Only one naevus in a pregnant woman increased slightly in epidermal pigmentation, and a decrease in pigmentation was noted in 3.7% of the melanocytic naevi in the cases and 1.8% in the controls. None of the differences within or between the groups was statistically significant. We conclude that pregnancy does not influence the appearance of pigmented naevi. A changing naevus during pregnancy should be examined carefully and considered for excision and histopathology.

Nestin expression in cutaneous melanomas and melanocytic nevi.

BACKGROUND: Nestin is one of the intermediate filaments that are expressed in proliferating neural progenitor cells during development of the central nervous system (CNS) and peripheral nervous system. Postnatal re-expression of the protein occurs mainly under pathological conditions, including injury and neoplasia. In this study, nestin expression was detected in both benign and malignant melanocytic skin lesions and its diagnostic relevance was then evaluated. METHODS: Altogether 139 bioptic tissue samples consisting of 42 nodular melanomas, 32 superficial spreading melanomas, 12 metastatic melanomas, 10 dysplastic nevi and 43 common melanocytic intradermal and dermoepidermal nevi were analysed using indirect immunohistochemical staining. RESULTS: We demonstrated that nestin immunostaining was significantly increased in melanomas where it correlated with more advanced stages of the disease. CONCLUSION: We conclude that expression of the intermediate filament protein nestin might be an indicator of tumor dedifferentiation and more aggressive behaviour. Furthermore, we suggest that nestin might be a relevant marker of tumorous and non-tumorous angiogenesis.