Optic disk Melanocytoma and Optical Coherence Tomography Angiography OCT-A

From EyeWiki

This page was enrolled in the International Ophthalmologists contest.


Optic disk photograph and multicolor showing a deeply pigmented lesion in the optic nerve head with adjacent choroid and retinal involvement. De Alba MA, Villegas VM, Gold AS, et al. Clinical findings and genetic expression profiling of three pigmented lesions of the optic nerve. Case Rep Ophthalmol Med. 2015;2015:590659.

Overview

Optic disk melanocytoma is a benign neoplasm, which seldom exhibits malignant transformation; nevertheless it can show growth and several complications. It is necessary to differentiate it from other neoplasms such as choroidal melanoma and choroidal nevus. OCT-A is a new swept-source device, it allows to penetrate deeper into the retinal layers and assess these lesions and identify its imaging features.

Disease

Melanocytoma is a rare bening pigmented neoplasm, that usually affects anywhere in the uvea and can affect the optic nerve head, even involves the adjacent retina and choroid in some cases.[1][2]
Photomicrograph and cytologic features of optic disk melanocytoma (hematoxylin-eosin). Shields JA, Demirci H, Mashayekhi A, Eagle RC Jr, Shields CL. Melanocytoma of the optic disk: a review. Surv Ophthalmol. 2006;51(2):93-104.

History

Historically, melanocytoma was considered a malignant neoplasm by ophthalmologists and pathologists and some enucleations were performed because this erroneous consideration . Reese in 1933 used the term "melanoma of optic disk" to describe pigmented lesions of the optic nerve head with clinical and histopatollogical features similar to melanocytoma.[3] Eventually Zimmerman and Garron revealed its benign nature in 1962, after performing a clinicopathological correlation on enucleated eyes with suspected melanoma; the term melanocytoma was first used by them, they chose it beacuse the appearance of tumor cells was similar to cells in ocular melanocytosis. [4]

Histopathological features

Histopathologically is composed of highly pigmented round cells with a cytoplasmic melanosomes and deficit of lipofuscin deposits. Usually affects anywhere in the uvea and can affect partially the optic nerve head, even involves the adjacent retina and choroid in some cases.[2][5]

Pathophysiology

Melanocytoma has a benign course and is derived from uveal melanocytes , such as uveal nevi and malignant melanoma. The pathogenesis of optic disk melanocytoma is unknown, but it is generally assumed to be a congenital lesion, which is clinically visible in adulthood. [1][3][6]

Demographic information of 27 korean patients with optic disk melanocytoma. Lee CS, Bae JH, Jeon IH, Byeon SH, Koh HJ, Lee SC. Melanocytoma of the optic disk in the Korean population. Retina. 2010;30:1714-20.

Demographics

Age

The diagnosis mean age is 50 years, with a range of 1 year to 91 years, (similar to the age at diagnosis of uveal melanoma); is possible to find an amelanotic lesion not clinically evident at birth, thath becomes pigmented in the next years.[3][2]

Race and gender

It has no predilection for races, nevertheless, the demographic features found in the some studies revealed a preponderance for caucasians (65%). [1] Otherwise, uveal melanoma is infrequent in Asians and African Americans. Is slightly more frequent in women in 63% of cases.[3]

Inferior optic disc melanocytoma and corresponding altitudinal visual field defect. Al-Rashaed S, Abboud EB, Nowilaty SR. Characteristics of optic disc melanocytomas presenting with visual dysfunction. Middle East Afr J Ophthalmol. 2010;17:242-5.

Signs and Symptoms

Visual acuity

Commonly is unilateral, asymptomatic and stable, it usually not causes compromise of visual acuity, however, visual symptoms may be present in 26% of cases and these are associated with exudation with foveal involvement or tumor necrosis.[1][2][5][7] In other cases are related to central retinal vein obstruction or more rarely malignant transformation. [7] Other symptoms can be present, such as flashes of light (4 %), floaters (4%) or none (76%).[1]

Pupillar chages

An afferent pupillary defect has been associated in presence of good visual acuity; optic disk melanocytoma; It is probably because of compression of the optic disk fibers by the melanocytoma cells.[3][8]

Visual field

The visual field is normal in 10% and abnormal in 90% of patients, these include temporal islands of vision, enlargement of blind spot related to the amount of tumor extension; arcuate defects associated to compression of axons, other patterns such as, nasal step (10%), relative nerve fiber bundle defect (20%) and and an absolute arcuate defect (20%).

Clinical features

It is usually unilateral, but in children may be bilateral. Clinically, the appearance of optic disk melanocytoma consist in a pigmented homogeneous mass with total absence of autofluorescence.[2][5]

However, an amelanotic lesion that becomes a pigmented lesion over time, has been described.[9]
A. Color photo of the left optic disk. B. Absence of autofluorescence. Mohmad Z, Kah TA, Yong KC, Abdul Halim WH, Kong Yong T. Melanocytoma of the optic nerve head - a diagnostic dilemma. Clin Pract. 2011;1(3):e60.
Nonpigmented lesion in the optic disk (A) and enlargement of the tumor with acquisition of pigmentation 44 months later. Lee CS, Bae JH, Jeon IH, Byeon SH, Koh HJ, Lee SC. Melanocytoma of the optic disk in the Korean population. Retina. 2010;30:1714-20.
It can be confined to the disk in 15% of cases, approximately 50% of melanocytomas involved one quadrant of the optic disk, the inferotemporal quadrant is the most common site (33%). as whereas the nasal side was the least common (12%). Melanocytoma can extends over the margin of the optic nerve head to involve the adjacent choroid in 54% of patients or the adjacent retina in 30% of them. Commonly remains stable, therefore the malignant transformation is very rare; in some cases, it can lead to progressive growth, vitreous seeding and neovascularization.[2][5][7]
Optic disk melanocytoma confined to the optic nerve head (left). Adjacent retinal involvement ( right). Shields JA, Demirci H, Mashayekhi A, Eagle RC Jr, Shields CL. Melanocytoma of the optic disk: a review. Surv Ophthalmol. 2006;51(2):93-104.

Systemic associations

It usually is an isolated disease , but some studies suggest that neurofibromatosis type 2, basal cell carcinoma, and vitiligo, seem to be coincidental, in other cases is related to hypertension (8%), tumors of neural crest origin, such as intracranial meningioma and adrenal gland schwannoma. [1][3]

Clinical course

Melanocytoma is a stable lesion , but 10-15% of them show enlargement over several years , the main predictive risk factor for growth is an initial thickness greater than 1.5 mm, it can produce tumor necrosis , ischemic optic neuropathy or retinal vein obstruction. A malignant trasnformation is estimated in about 1-2% of patients , the features of malignant transformation are extensive involvement of the optic disk with severe visual loss.

Malignant trasformation of melanocytoma. Shripaad Y, Shukla, Jerry A. Shields, Ralph C. Eagle, et al. Transformation of Optic Disc Melanocytoma Into Melanoma Over 33 Years. Arch Ophthalmol. 2012;130:1344-1347.
Central retinal vein obstruction secondary to melanocytoma of optic disk. Shields JA, Demirci H, Mashayekhi A, Eagle RC Jr, Shields CL. Melanocytoma of the optic disk: a review. Surv Ophthalmol. 2006;51(2):93-104.

Local complications

Optic disk melanocytoma can show ischemic necrosis, disk edema (25%), intraretinal edema (16%), subretinal fluid (14%), yellow intraretinal exudation (12%), focal hemorrhage (5%), vitreous seeds (4%), and retinal vein obstruction (3%).[3]

Clinical diagnosis

Patient without relevant past or familiar history, attended the ophthalmology service for assessment of a pigmented mass on optic nerve head, without documented growth. The visual acuity usually is normal, at slit-lamp examination the anterior segment is normal and ocular melanocytosis usually is not observed; fundus examination showed a pigmented dark brown lesion located enterelly or partially the optic nerve head, with or not extending over the margin with adjacent retinal or choroidal involvement, a swelling of inferior optic disk margin can be observe. At fundus examination can be found the presence of exudation, vitreous seeds or hemorrhages.

Imaging diagnosis

Melanocytoma usually is diagnosed using ophthalmoscopic features; nevertheless the imaging is necessary to confirm its benign nature and distinguishing it from other lesions and neoplasms. Several imaging modalities have been used for optic disk melanocytoma diagnosis and follow-up.

Ultrasonography

Ultrasound has been largely used for assessment of tumors that involve optic disk and choroid. A dome-shaped image is a frequent feature in melanocytoma and its high internal reflectivity indicate a benign lesion; contrarily, if has low internal reflectivity, indicate high-risk for growth and malignant transformation.[3] Although ultrasonography is a useful guide to suspect a malignant neoplasm, it not detects neovascularization, tumor extension into the retrolaminar portion and other findings as intraretinal edema. We not recommend the isolated use of this imaging resource in melanocytoma´s assessment and should be complemented with other diagnostic aids.

A) The lesion had a dome-shaped appearance; B) Adjacent choroidal extension of the tumor had low internal reflectivity.Mohmad Z, Kah TA, Yong KC, Abdul Halim WH, Kong Yong T. Melanocytoma of the optic nerve head - a diagnostic dilemma. Clin Pract. 2011;1(3):e60.

Fluorescein and Indocyanine Green Angiography

Other studies as fluorescein and indocyanine green angiography show a diffuse hypofluorescent lesion and hiperfluorescent areas related to subretinal fluid and disk edema. [1][2][5][9][3]However, these studies imply an invasive approach, provide less additional information than other imaging techniques.
A, Early phase of fluorescein angiogram of melanocytoma of the optic disk. Fine vessels within the tumor can be observed (white arrow). B, Late-phase angiogram showing diffuse leakage through the vessels within the tumor (white arrow). Lee CS, Bae JH, Jeon IH, Byeon SH, Koh HJ, Lee SC. Melanocytoma of the optic disk in the Korean population. Retina. 2010;30:1714-20.

Optical coherence Tomography (OCT)

Figure 1. A. Color fundus photography revealed a pigmented lesion located partially on the optic nerve head and adjacent superior retina, a noticeable swelling of optic nerve head inferiorly is shown on the image. B. Swept-source OCT B-Scan showing a bilobular dome-shape mass with a dense posterior shadowing and multiple hypereflective dots overlying the lesion continuous with the retinal inner layers (yellow arrows). Note the cystoid spaces in the outer retinal layers around the tumor (green arrows). C. Fundus autofluorescence showed a hypoautofluorecent imagef autofluorescence. D. OCT B-Scan revealed vitreous seeding (blue arrows), which not was clinically visible. Courtesy: Dr. Juan A Arias, MD, Ophthalmologist, supra-specialist in Retina, Vitreous and Oncology, Fundación Oftalmológica de Santander FOSCAL.
Over time, optical coherence tomography has evolved allowing to obtain images of high resolution. The identification of a nodular elevation with dense posterior shadowing, areas of irregular hyper-reflectivity overlaying the tumor, even, thin hyper-reflective lines delineating the vessels and anterior side of the tumor using spectral-domain OCT, are largely documented in the literature. [1][2][5][3]Currently, there are few reports of melanocytoma features using swept- source optical coherence tomography. At B-scan map are identified multiple irregular hyperreflective dots in anterior surface overlying the tumor, with or without perivascular distribution, these hyper-reflective dots may correspond to melanin-phagocytizing activity of macrophages;[2] [5]this phagocytizing activity induces the formation of subretinal and intraretinal fluid in adjacent retinal tissue.

Other findings are related to local complications; other authors concluded that choroidal involvement could be assumed by spectral- domain OCT by upward displacement of retinal pigment epithelium, significant retinal nerve fiber layer loss or choroidal hyperreflectivity;[10] [11][11]however, it is an assumption because it cannot visualized directly the choroidal vascularization, caused by posterior dense shadowing and the limitation of identify underlying structures.

Swept-source optical coherence tomography angiography (OCT-A)

OCT–A has increasingly become a noninvasive useful technique in assessment of different ophthalmic diseases. Currently, exist few reports regarding the optic disk melanocytoma features using swept-source OCT- A, this new technology will become in a good alternative for follow-up of these lesions, improving the tumor extension detection, identification of progression and finally to differentiate from other neoplasms, including choroidal malignant melanoma.

Figure 2. A. Color image of fovea, melanocytoma is partially visible. B and C. En face OCT and OCT angiograms of inner retinal plexus, revealed a honeycomb pattern (green area) corresponding to intraretinal cysts and hyper-reflective dots (blue area) around the lesion, notice the correspondence with OCT B-scan image (insert). D. OCT angiogram of choriocapillaris showing a blocking of signal related to the presence of pigment, visualized in inner layers. E. Color image of the optic disk, the borders of the melanocytoma are demarcate (yellow line) in this and next images. F and H. En face OCT and OCT angiogram of radial peripapillary capillaries layer  of optic nerve head (at the level of outer retinal plexus) demonstrated the hyper-reflectance of melanocytoma (F) and partially visualization of choroidal vessels (red line), it is shown more pronounced in depper layers (Choroid/disc layer) (H). Courtesy: Dr. Juan A Arias, MD, Ophthalmologist, supra-specialist in Retina, Vitreous and Oncology, Fundación Oftalmológica de Santander FOSCAL

OCT-A allows the visualization of vasculature using the motion contrast principle, providing a high definition images of different layers including choroid,[12] thus, theoretically it could shows intrinsically the choroidal involvement and neovascularization. OCT-A represent an important advantage, the determination of depth´s tumor despite the posterior dense shadowing observed in OCT B- scan.

Differential diagnosis

Melanocytoma usually is diagnosed using ophthalmoscopic features; nevertheless the imaging is necessary to confirm its benign nature and distinguishing it from other lesions and neoplasms such as malignant melanoma, choroidal nevus, optic nerve glioma, capillary hemangioma or metastases.[1]

Shields JA, Demirci H, Mashayekhi A, Eagle RC Jr, Shields CL. Melanocytoma of the optic disk: a review. Surv Ophthalmol.2006;51(2):93-104.

Management

This lesion does not require any type of treatment. Clinical and imaging follow-up should be performed annually.

Medical follow up

Optic disk melanocytoma requiring a complete clinical and imagenological assessment to characterize the principal features and distinguish it from other pathologies. Is requiring to perform different studies such as, fundus color photograph and Optical coherence tomography annually. OCT-A could be a non invansive alternative to assess the depth´s tumor and presence of intraretinal edema, choroidal involvement and vitreous seeds without a contrast medium.

Complications

Melanocytoma in some cases, can lead to progressive growth, vitreous seeding and neovascularization. [1][3]

Prognosis

Optic disk melanocytoma is a benign neoplasm, which seldom exhibits malignant transformation; nevertheless it can show growth and several complications. 10 % - 15 % of them show subtle enlargement over several years.[1]


References

  1. 1.00 1.01 1.02 1.03 1.04 1.05 1.06 1.07 1.08 1.09 1.10 Shields JA, Demirci H, Mashayekhi A, Shields C. Melanocytoma of optic disc in 115 cases: the 2004 Samuel Johnson Memorial Lecture, part 1. Ophthalmology. 2004;111:1739-46
  2. 2.0 2.1 2.2 2.3 2.4 2.5 2.6 2.7 2.8 Lee E, Sanjay S. Optic Disc Melanocytoma Report of 5 Patients From Singapore With a Review of the Literature. Asia Pac J Ophthalmol (Phila) 2015;4:273-8
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 Shields JA, Demirci H, Mashayekhi A, et al. Melanocytoma of the optic disc: a review. Surv Ophthalmol. 2006;51:93–104.
  4. Zimmerman LE, Garron LK. Melanocytoma of the optic disc. Int Ophthalmol Clin.1962;2:431-40.
  5. 5.0 5.1 5.2 5.3 5.4 5.5 5.6 Zhang P, Hui YN, Xu WQ, et al. Infrared autofluorescence, short-wave autofluorescence and spectral-domain optical coherence tomography of optic disk melanocytomas. Int J Ophthalmol, 2016;9:713-6.
  6. Eldaly H, Eldaly Z. Melanocytoma of the Optic Nerve Head, Thirty-Month Follow-Up. Semin Ophthalmol. 2015;30:464-9.
  7. 7.0 7.1 7.2 Lee CS, Bae JH, Jeon IH, et al. Melanocytoma of the optic disk in the Korean population. Retina. 2010;30:1714-20.
  8. Al-Rashaed S, Abboud EB, Nowilaty SR. Characteristics of optic disc melanocytomas presenting with visual dysfunction. Middle East Afr J Ophthalmol. 2010;17:242-5.
  9. 9.0 9.1 Mohmad Z, Kah TA, Yong KC, et al. Melanocytoma of the optic nerve head - a diagnostic dilemma. Clin Pract. 2011;1:e60.
  10. Saxena S, Sharma B, Bhasker SK. Three-dimensional spectral-domain optical coherence tomography of melanocytoma of the optic nerve head. J Ocul Biol Dis Infor.2010;3:112-6.
  11. 11.0 11.1 Okubo A, Unoki K, Yoshikawa H, et al. Hyperreflective dots surrounding the central retinal artery and vein in optic disc melanocytoma revealed by spectral domain optical coherence tomography. Jpn J Ophthalmol. 2013;57:108-12. 
  12. Koustenis A Jr, Harris A, Gross J, et al. Optical coherence tomography angiography: an overview of the technology and an assessment of applications for clinical research. Br J Ophthalmol 2017;101:16-20.