Characteristics of conjunctival myxomas on anterior segment optical coherence tomography

Conjunctival myxomas are benign mesenchymal tumors that are histologically characterized by sparsely arranged, spindle-shaped, stellate, or round cells, reticulin fibers and mature collagen distributed in abundant mucoid material. They are rare, and most reported cases are idiopathic, but the tumors may also be associated with trauma and systemic associations, such as Carney complex. Because of its rarity, conjunctival myxoma can be easily mistaken for other epithelial or subepithelial lesions of the conjunctiva, such as amelanotic nevus, conjunctival lymphoma, or conjunctival cyst. Definitive diagnosis requires biopsy, and excision is curative in most cases.^1-7

In recent years, optical coherence tomography (OCT) has provided rapid, high-resolution in vivo imaging of anterior segment structures. Specifically, anterior segment high-resolution OCT (HR-OCT) has demonstrated efficacy in guiding the diagnosis and management of pathologies of the ocular surface. In addition, it has shown utility in assessment of corneal dystrophies and ectasias, refractive surgery, and planning of glaucoma surgery.^8-13 We and others have described distinctive features of ocular surface lesions on HR-OCT, including ocular surface squamous cell neoplasia, conjunctival lymphoma, conjunctival melanoma and conjunctival nevus.^10,13-18 Anterior segment OCT can assist clinicians in correctly diagnosing ocular surface pathology, identifying tumor margins, monitoring response to treatment, determining when the tumor has resolved, and monitoring for tumor recurrence.^10,13-18 However, because of its rarity, previous studies have not systematically described the characteristics of conjunctival myxoma on HR-OCT and the utility of this important new imaging technique in the diagnosis and management of this condition. To bridge this knowledge gap, we review four cases of conjunctival myxoma and describe the characteristic features found on HR-OCT.

Case Report

Four cases presenting to a single tertiary care referral center with light pink elevations of the bulbar conjunctiva were all found to have subepithelial lesions with hypodense round or linear structures on anterior segment OCT. Excisional biopsy in 3 cases and debulking of 1 case all revealed conjunctival myxoma. The mean follow-up period was 4.2 ± 2.7 years with no sign of recurrence in the 3 excised myxomas and no change in the size of the debulked myxoma.

Case 1

A 53-year-old male presented with 2 months of injection and elevation of the temporal bulbar conjunctiva of the right eye. He described 3 months of variable fullness, redness, and prominence of the temporal bulbar conjunctiva over this time period. Visual acuity was 20/20 in the right eye and 20/25-2 in the left eye. Intraocular pressure and pupils were normal. Slit lamp examination of the right eye demonstrated trace sectoral injection of the temporal bulbar conjunctiva with mild subepithelial fullness and was otherwise unremarkable (Figure 1A). Anterior segment optical coherence tomography revealed a heterogeneous subepithelial lesion with hyperreflective material and subepithelial hypodense round or linear spaces (Figure 2A). The patient requested excision for improved cosmesis. The lesion was excised with application of sutured amniotic membrane and mitomycin C.^19-21 Histologic analysis revealed conjunctival myxoma (Figure 3A). Cardiac examination was normal with no concern for Carney complex. After 7.5 years of follow-up, there was no evidence of recurrence.

Fig. 1—

External photographs of conjunctival myxomas upon presentation in cases 1-4, denoting a pink, subepithelial elevation of the bulbar conjunctiva (panels A-D, respectively). (A) A 53-year-old male presented with a subtle, pinkish elevated lesion of the right eye bulbar conjunctiva. Biopsy confirmed conjunctival myxoma. (B) A 49-year-old male presented with a light pink lesion of the right eye temporal bulbar conjunctiva confirmed by biopsy to be myxoma. This had been present for a year and had not changed over this time. (C) A 51-year-old female had left eye nasal swelling of the bulbar conjunctiva associated with four months of pain, discomfort, and tearing. Biopsy confirmed conjunctival myxoma. (D) A 67-year-old male presented with an elevated, chemotic, inferior, diffuse subepithelial lesion. The lesion was debulked and confirmed to be myxoma. Arrows denote the conjunctival myxomas.

Fig. 2—

Anterior segment OCT images. (A) Case 1. High-resolution OCT (HR-OCT) of a conjunctival myxoma. Note normal, thin, hyporeflective epithelium (arrowheads) and heterogeneous subepithelial lesions with mostly hyporeflective and some hyperreflective tissues. Note linear hyporeflective spaces (arrows). (B) HR-OCT of case 2 demonstrates normal epithelium (arrowheads) and a heterogeneous subepithelial lesion consisting of both hyper- and hyporeflective tissue and scattered round, oval, and linear spaces (arrows). (C) HR-OCT of case 3 again demonstrates normal thickness overlying epithelium (arrowhead) with predominantly hyporeflective subepithelial tissue consisting of similar round, oval and linear spaces (arrows). (D) HR-OCT of case 4 once again consists of epithelium with normal thickness, which is hyperreflective (arrowhead), along with subepithelial lesion of mixed reflectivity again with linear, round, and oval spaces (arrows). In all images, inset shows location of raster.

Fig. 3—

Histopathologic features. (A) Case 1. (i) and (ii) Foci of paucicellular stroma (asterisks) with dilated blood vessels (arrowheads) are present within the substantia propria (hematoxylin and eosin, original magnification ×100) (hematoxylin and eosin, original magnification ×200). (iii) The Alcian blue stain demonstrates mucopolysaccharide deposition within the substantia propria (Alcian blue, original magnification ×200). (B) Case 2. (i) and (ii) Foci of paucicellular stroma (asterisks) with dilated blood vessels (arrowheads) are present within the substantia propria (hematoxylin and eosin, original magnification ×100) (hematoxylin and eosin, original magnification ×200). (iii) The Alcian blue stain demonstrates mucopolysaccharide deposition within the substantia propria (Alcian blue, original magnification ×200). (C) Case 3. (i) and (ii) Foci of paucicellular stroma (asterisks) with dilated blood vessels (arrowheads) are present within the substantia propria (hematoxylin and eosin, original magnification ×100) (hematoxylin and eosin, original magnification ×200). (iii) The Alcian blue stain demonstrates mucopolysaccharide deposition within the substantia propria (Alcian blue, original magnification ×200). (D) Case 4. (i) and (ii) Foci of paucicellular stroma (asterisks) with dilated blood vessels (arrowheads) are present within the substantia propria (Hematoxylin and eosin, original magnification ×100) (Hematoxylin and eosin, original magnification ×200). (iii) The Alcian blue stain demonstrates mucopolysaccharide deposition within the substantia propria (Alcian blue, original magnification ×200).

Case 2

A 49-year-old male presented with a light pink lesion of the right eye temporal bulbar conjunctiva (Figure 1B). The lesion had been present for about 2 years and had not changed in size or color over the last year. The patient had tried over-the-counter olopatadine 0.2% drops without improvement in the lesion. Because of the size of the lesion, he was unable to obtain an adequate fit in contact lenses. Past medical and ocular history was otherwise noncontributory. Examination revealed best-corrected distance vision of 20/20 in both eyes, and normal intraocular pressure and pupils. Slit lamp examination of the right eye demonstrated a thickened area of temporal bulbar conjunctiva with vessels to the lesion. The lesion was freely mobile. Because of the light pink appearance of the lesion, conjunctival lymphoma was on the differential. Anterior segment OCT was performed and revealed heterogeneous subepithelial tissue with hypodense round or linear structures (Figure 2B). While not a typical OCT for lymphoma, the lesion was excised using a no-touch technique and the margins of the conjunctiva were treated with a double-freeze thaw, cryotherapy technique.^19-21 Primary closure of the conjunctiva was undertaken. Flow cytometry was negative for kappa, lambda, CD34, CD38, CD23, CD19, CD10, CD20, CD5, CD45, CD8, CD4, HLA-DR, G1, CD56, CD2, CD7, CD3, CD5, and CD45. Pathology revealed conjunctival myxoma (Figure 3B). A systemic and cardiac workup was negative for Carney complex and any other cardiac abnormalities or systemic syndromes. There was no evidence of recurrence after 5.4 years of follow-up.

Case 3

A 51-year-old female presented with 4 months of pain, discomfort, and tearing associated with left eye nasal swelling of the bulbar conjunctiva. Examination revealed best-corrected distance visual acuity of 20/20 in the right eye and 20/25 in the left eye. Intraocular pressure and pupils were normal. Slit lamp examination revealed an elevated, mobile, nontender lesion with translucent, pinkish lesion of the nasal conjunctiva (Figure 1C). Anterior segment OCT was performed and demonstrated a heterogeneous subepithelial lesion with hypodense round or linear spaces and hyper- and hyporeflective subepithelial tissue, with a normal epithelium (Figure 2C). Because of the patient’s symptoms, removal was planned. The lesion was excised, double freeze-thaw technique applied to the remaining conjunctival margins, with mitomycin C application followed by sutured amniotic membrane application.^19-22 The patient tolerated the procedure well. Pathology confirmed the diagnosis of conjunctival myxoma (Figure 3C), and a workup was negative for any systemic or cardiac abnormalities, including Carney complex. After 2.3 years of follow-up, there was no evidence of recurrence.

Case 4

A 67-year-old male presented with pinkish elevation of the bulbar conjunctiva, which had been previously diagnosed by an outside provider as having viral conjunctivitis and chemosis. His symptoms did not improve with a course of topical tobramycin-dexamethasone drops. Three months later, his vision was 20/20 in both eyes, and pupils and intraocular pressure were normal. Examination revealed diffuse subconjunctival elevation of the inferior bulbar conjunctiva (Figure 1D) with an associated nasal dellen. Anterior segment OCT revealed a heterogeneous subepithelial mass with hypodense round or linear spaces and with normal overlying epithelium (Figure 2D). The lesion did not improve with ocular lubrication and a course of topical corticosteroids. Surgical debulking was performed, and pathology confirmed conjunctival myxoma (Figure 3D). The patient underwent a cardiac examination, which was normal with no concern for Carney complex. After 1.7 years of follow-up, there was no change in the size of the debulked tumor.

Discussion

This case series highlights the characteristics of conjunctival myxomas on HR-OCT. All cases shared several features in common on HR-OCT. Normal epithelium was present with a heterogeneous loose subepithelial tissue with hypodense round or linear spaces within the lesion. Comparable findings were noted on histologic analysis, with the round structures seen on HR-OCT correlating with blood vessels in all cases (Figure 3).¹ The ubiquity of hypodense round or linear spaces within a stringy, loose heterogeneous substantia on HR-OCT suggests that visualization of such structures, in the appropriate clinical context, may increase suspicion for conjunctival myxoma over other subepithelial growths.

The differential diagnosis for conjunctival myxoma is wide and includes lymphoma, amelanotic melanoma, conjunctival cyst, lymphangioma, nevus, fibrous histiocytoma, rhabdomyoma, rhabdomyosarcoma, lipoma, liposarcoma, and myxoid neurofibroma. In this series, conjunctival myxomas were initially mistaken for conjunctival cysts, lymphoid tumors, chemosis, or benign lymphoid hyperplasias. In previous publications, we have demonstrated that these latter lesions have their own characteristic features on HR-OCT, which allows differentiation from myxomas.^14,23-25 Conjunctival cysts demonstrate nonkeratinized squamous epithelium on histology with fluid-filled amorphous material on histology, which correlates with dark, hyporeflective fluid-filled areas on HR-OCT. Benign lymphoid hyperplasia and lymphomas may present similarly on HR-OCT with a normal epithelium over a homogeneous, solid mass of subepithelial tissue.^14,26,27 The characteristic findings of conjunctival myxoma on HR-OCT may help assist in identification, diagnosis, and, therefore, treatment of these rare tumors.

Estimates of incidence of conjunctival myxoma vary. In one review of 2,455 conjunctival lesions seen at a tertiary referral center with histopathologic confirmation, four (0.16%) were diagnosed as conjunctival myxoma.²⁸ In another review of 1 643 individuals seen at a different tertiary referral center, only 1 conjunctival myxoma was found (0.061%).²⁹ To the authors’ knowledge, this case series is the largest series, which includes anterior segment OCT features of conjunctival myxoma.

Conjunctival myxomas typically present as a slow-growing, subconjunctival mass. Conjunctival myxomas may present as diffuse or well-circumscribed, soft, gelatinous, or fleshy lesions with a granular or mucinous superficial appearance.^4,5,7,30-33 A well-circumscribed, yellow, pink or white, occasionally translucent, cystic lesion is the most common presentation, but conjunctival myxomas may also be pedunculated or present as diffuse lesions. Most myxomas readily transilluminate, leading to the common misdiagnosis of conjunctival cyst. Solid tumors, such as carcinomas or melanomas, are unlikely to transilluminate. The bulbar conjunctiva, followed by juxtalimbal areas, are the most commonly affected sites. Additional ophthalmic presentations of myxomas have been described in the eyelid, cornea, and orbit.^26,34-38 Most cases are idiopathic in nature. However, some cases have been known to develop near sites of previous ocular trauma or surgery, which has led some to postulate that an inflammatory mechanism may contribute to the pathogenesis of some conjunctival myxomas.^1,39,40 Additionally, association with mutation of the tumor suppressor gene PRKAR1A has also been found.⁷

Outside of the orbit, myxomas may also present in heart, skeletal muscle, bone, skin, genitourinary, and paranasal sinus tissue.^8,15-20 Unlike extraocular presentations, the conjunctival form often has cyst-like structures^2,41 and may contain mast cells.^2,41,42 Myxoma can also present as part of a Carney complex.⁴³ An autosomal dominant syndrome, Carney complex consists of 2 of 3 of the following: myxomas, such as cutaneous or cardiac; multiple pigmented mucocutaneous lesions; and endocrine abnormalities.² Since it is associated with high morbidity and mortality, patients with myxoma should undergo a full systemic workup, including an echocardiogram, magnetic resonance imaging, or computed tomography of the body, testicular ultrasound, and endocrine evaluation, including thyroid, adrenocorticotropic hormone, growth hormone, and thyroid-stimulating hormone.^1,2,39 In this series, all of our cases presented with isolated disease on the bulbar conjunctiva, and none had a history of trauma, skin, or endocrine abnormalities.

Most lesions develop over months to years, although acute presentations have been reported.^1,2,39 These lesions grow slowly and can present at any age, but are predominantly found in middle-aged adults, with a mean age of around 45 years.^1,2,39 A definitive sex predilection has not been demonstrated, although a recent comprehensive review suggested that the lesions may occur more commonly in men. Because of the lack of large-scale studies of this topic due to the rarity of the condition, there is some uncertainty over whether a sex predilection exists.^{1,2,8,14,23,44} In this series, all but one patient was male, but the sample size was small.

Additional histopathologic characteristics of conjunctival myxoma that are less readily visualized on HR-OCT include small numbers of spindle-shaped to stellate cells scattered within a thin mucinous matrix,^1,2 vascular structures, mature collagen fibers, delicate reticulin fibers, intracytoplasmic vacuoles made of dilated rough endoplasmic reticulum, cytoplasmic filaments arranged in wavy, loose bundles, and intranuclear vacuoles.^2,7 Histopathology reveals a mucinous matrix with sparse, scattered, spindle-shaped, round or stellate cells, and reticulin fibers loosely arranged within the matrix. Collagen fibers are loosely interspersed within this matrix, and described as mature, fibrillar, or ropey.^1,2 Within this mucoid stroma, glycosaminoglycans and hyaluronic acids are abundant, and bundles of intracytoplasmic vacuoles consisting of rough endoplasmic reticulum and cytoplasmic filaments are sparsely arranged.^2,41,42 Intranuclear vacuoles, likely representing highly folded nuclear membranes, are also present.^2,41 Pleomorphic nuclei have been reported within this matrix.¹ Histopathologic staining is generally positive for Alcian blue. Mucicarmine, vimentin, retinoblastoma protein 1, and anti-Ki67 may also stain positive. Staining is generally negative for S100. Many cases demonstrate immunoreactivity to CD34, CD68.^1,2,39,45 In this series, all myxomas shared in common a paucicellular stroma with dilated blood vessels within the substantia propria, and mucopolysaccharide deposition visible on Alcian blue staining.

Conjunctival myxoma is challenging to diagnose clinically due to its rarity and similarity in appearance to other lesions. Biopsy is required for definitive diagnosis. Complete excisional biopsy is usually the preferred treatment, except when the extensive surface area of the lesion is prohibitive, in which case debulking may be preferred. After resection of conjunctival myxoma, recurrence is exceedingly uncommon. Rare reports of recurrences in conjunctival myxomas have been related to incomplete excision or Carney complex. Since conjunctival myxomas lack a true capsule, nests of cells may hypothetically be inadvertently left behind. In all previously reported cases, patients remained recurrence-free after re-excision.^1,2 In our series, three conjunctival myxomas were excised, and one was debulked due to extensive ocular surface involvement and concern for limbal stem cell deficiency with complete excision. Additionally, there was no sign of recurrence in all 3 excised myxomas and no change in size of the debulked myxoma on follow-up, which ranged from 1.7 years to 7.5 years.

Our study is not without its limitations, among which is a small sample size, which is related to the relative rarity of conjunctival myxoma. Despite these limitations, our findings suggest that HR-OCT may be a helpful adjunct to histopathologic analysis when evaluating patients with potential conjunctival myxomas. The findings on HR-OCT parallel the histopathological findings and include a stringy, loose, heterogeneous subepithelial lesion containing hypodense round or linear spaces and a normal overlying epithelium. The noninvasive, high-resolution nature of HR-OCT makes it particularly valuable in the diagnostic workup of such lesions.