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Uveal melanoma presenting as panophthalmitis in the absence of an intraocular mass

Published:October 26, 2021DOI:https://doi.org/10.1016/j.jcjo.2021.09.016
      Uveal melanoma is the most common primary intraocular malignancy in adults, with 90% of cases originating from the choroid. While many patients are asymptomatic and the tumour is often diagnosed incidentally on routine eye examination, presenting symptoms can include decreased vision, flashes, or floaters.
      • Kaliki S
      • Shields CL.
      Uveal melanoma: relatively rare but deadly cancer.
      Less frequently, uveal melanoma can present with ocular or periocular inflammation simulating endophthalmitis or orbital cellulitis.
      • Buckley CA
      • Cheng H.
      Intraocular melanoma, diabetes, and Turner's syndrome: presentation with proptosis.
      • Eagle Jr, RC
      • Grossniklaus HE
      • Syed N
      • Hogan RN
      • Lloyd 3rd, WC
      • Folberg R
      Inadvertent evisceration of eyes containing uveal melanoma.
      • Goh AS
      • Francis IC
      • Kappagoda MB
      • Filipic M.
      Orbital inflammation in a patient with extrascleral spread of choroidal malignant melanoma.
      • Lea SJ
      • Livesey SJ
      • Lowe J
      • Rothwell I
      • Haworth SM.
      Disappearance of ocular malignant melanoma on computerised scan after spontaneous necrosis: clinical, radiological and pathological features.
      • Macedo SS
      • Teixeira M
      • Correia A
      • Novais A
      • Cabral C.
      Ocular melanoma presenting as masquerade syndrome.
      • Oh LJ
      • Dunn H
      • Cherepanoff S
      • Giblin M.
      Orbital cellulitis and secondary angle closure: a rare presentation of choroidal melanoma.
      In the majority of these cases, an intraocular mass will be identified on either computed tomography (CT), B-scan ultrasonography, or magnetic resonance imaging (MRI).
      • Oh LJ
      • Dunn H
      • Cherepanoff S
      • Giblin M.
      Orbital cellulitis and secondary angle closure: a rare presentation of choroidal melanoma.
      ,
      • Li AL
      • Kang JY
      • Berry DE
      • Patel KB
      • Hendrick AM.
      Necrotic uveal melanoma presenting as orbital cellulitis with intraocular hemorrhage: a case report.
      Rarely, necrotic uveal melanoma can masquerade as an infectious or inflammatory process without evidence of an intraocular mass, leading to a presumed diagnosis of orbital cellulitis or endophthalmitis. In these cases, profound inflammation and concern for infection often result in removal of the globe after intravitreal and intravenous antibiotics have failed; histopathology reveals the unsuspected melanoma.
      • Buckley CA
      • Cheng H.
      Intraocular melanoma, diabetes, and Turner's syndrome: presentation with proptosis.
      • Eagle Jr, RC
      • Grossniklaus HE
      • Syed N
      • Hogan RN
      • Lloyd 3rd, WC
      • Folberg R
      Inadvertent evisceration of eyes containing uveal melanoma.
      • Goh AS
      • Francis IC
      • Kappagoda MB
      • Filipic M.
      Orbital inflammation in a patient with extrascleral spread of choroidal malignant melanoma.
      • Lea SJ
      • Livesey SJ
      • Lowe J
      • Rothwell I
      • Haworth SM.
      Disappearance of ocular malignant melanoma on computerised scan after spontaneous necrosis: clinical, radiological and pathological features.
      • Macedo SS
      • Teixeira M
      • Correia A
      • Novais A
      • Cabral C.
      Ocular melanoma presenting as masquerade syndrome.
      Herein we describe a case of necrotic uveal melanoma presenting as panophthalmitis without evidence of an intraocular mass and review the literature surrounding these rare and challenging cases. This report adheres to the Declaration of Helsinki and is compliant with the Health Insurance Portability and Accountability Act.
      An 80-year-old man presented with 2 days of right periorbital swelling in the absence of trauma or recent illness. Past medical history was significant for advanced Alzheimer disease (from which the patient was nonverbal and minimally responsive), deep vein thrombosis treated with warfarin, and hypertension. Past ocular history was significant for bilateral cataract surgery 10 years prior. Visual acuity and extraocular movements were unable to be obtained secondary to the patient's mental status. Left eye examination was unremarkable. The right eye showed severe orbital edema, chemosis, conjunctival injection, and corneal opacification with a small central epithelial defect limiting the view of the anterior or posterior chamber on the right (Fig. 1A). Intraocular pressure was elevated to 70 mm Hg, and a reverse afferent pupillary defect was noted. B-scan ultrasonography demonstrated dense vitreous debris concerning for endophthalmitis. Orbital CT showed preseptal inflammation, possible tenting of the right globe, and vitreous debris.
      Fig 1
      Fig. 1(A) External photograph revealing periorbital edema and erythema, marked chemosis, and conjunctival injection. (B) MRI T1 fat-saturated axial image revealing vitreous debris without evidence of intraocular mass, contrast-enhancing periorbital edema, and fat stranding within the orbit. (C) B-scan ultrasonography demonstrating persistent loculated and septated debris, a prominent T-sign, and choroidal detachments. (D) Foci of viable tumour (T) surrounded by areas of extensive necrosis (N) (H&E stain, low power). (E) Spindle melanoma cells with focal intracytoplasmic melanin pigment (black arrow) (H&E stain, high power). Scattered balloon cells with foamy, vacuolated cytoplasm are seen (black arrowhead). (F) The neoplastic cells are strongly immunopositive for Melan-A (Melan-A immunohistochemistry, high power).
      Blood and vitreous cultures were obtained, the patient was treated with intravitreal vancomycin and ceftazidime, and broad-spectrum antibiotics were initiated. Two days later, brain and orbital MRI demonstrated extensive intraocular loculated material, with worsening inflammation concerning for orbital cellulitis (Fig. 1B). The results of blood cultures were negative. Three days after initial presentation, the patient's condition had worsened with new purulent conjunctival discharge and no view of the anterior chamber. Repeat B-scan ultrasonography demonstrated persistent loculated and septated debris, a prominent T-sign, and choroidal detachments consistent with panophthalmitis (Fig. 1C).
      After 5 days of intravenous antibiotics, no clinical improvement, and concern for progression of orbital disease, enucleation was performed to remove the source of infection. No extraocular extension or orbital involvement was noted during enucleation. Histopathologic examination of the enucleated globe demonstrated a spindle cell melanoma with extensive ischemia, hemorrhage, and necrosis (Fig. 1D–F).
      Postoperatively there was marked resolution of the periocular inflammation. The patient was discharged home after completion of 7 days of intravenous antibiotics. His family elected not to pursue further work-up or care for the uveal melanoma.
      In this case, the uveal melanoma was necrotic and presented as panophthalmitis with no identifiable intraocular mass by B-scan ultrasonography, CT, or MRI. The diagnosis of uveal melanoma was made only after primary enucleation on histopathology. A review of the literature revealed 7 previously reported cases of uveal melanoma presenting with inflammatory features in the absence of an identifiable intraocular mass. These cases present a unique diagnostic challenge and require careful consideration of the optimal surgical management.
      Multiple studies have described inflammatory symptoms associated with uveal melanoma. Uveal melanoma presenting with predominantly inflammatory features is most often associated with tumour necrosis.
      • Buckley CA
      • Cheng H.
      Intraocular melanoma, diabetes, and Turner's syndrome: presentation with proptosis.
      • Eagle Jr, RC
      • Grossniklaus HE
      • Syed N
      • Hogan RN
      • Lloyd 3rd, WC
      • Folberg R
      Inadvertent evisceration of eyes containing uveal melanoma.
      • Goh AS
      • Francis IC
      • Kappagoda MB
      • Filipic M.
      Orbital inflammation in a patient with extrascleral spread of choroidal malignant melanoma.
      • Lea SJ
      • Livesey SJ
      • Lowe J
      • Rothwell I
      • Haworth SM.
      Disappearance of ocular malignant melanoma on computerised scan after spontaneous necrosis: clinical, radiological and pathological features.
      Additionally, cases of uveal melanoma necrosis and involution over time have been reported.
      • Lea SJ
      • Livesey SJ
      • Lowe J
      • Rothwell I
      • Haworth SM.
      Disappearance of ocular malignant melanoma on computerised scan after spontaneous necrosis: clinical, radiological and pathological features.
      Ocular inflammation presumably results from initial rapid tumour growth, which causes the tumour to outgrow its blood supply, undergo necrosis, and release inflammatory mediators that incite an inflammatory response.
      • Biswas J
      • Ahuja VK
      • Shanmugam MP
      • Kurian R
      • Fernandez T.
      Malignant melanoma of the choroid presenting as orbital cellulitis: report of two cases with a review of the literature.
      In the 7 previously documented cases of uveal melanoma presenting with inflammation in the absence of intraocular mass, the most common presenting symptoms were vision loss (86%) and pain (57%). Presenting visual acuity was no light perception in 57% of eyes, with noted loss of vision and doubtful light perception in the remaining 43% of eyes. Common findings on examination included periorbital edema (71%), chemosis (57%), proptosis (43%), and extraocular motility restriction (43%). There was no view of the posterior segment in 86% of cases.
      When uveal melanoma presents with inflammation, an intraocular mass is commonly identified on examination or on imaging.
      • Eagle Jr, RC
      • Grossniklaus HE
      • Syed N
      • Hogan RN
      • Lloyd 3rd, WC
      • Folberg R
      Inadvertent evisceration of eyes containing uveal melanoma.
      ,
      • Oh LJ
      • Dunn H
      • Cherepanoff S
      • Giblin M.
      Orbital cellulitis and secondary angle closure: a rare presentation of choroidal melanoma.
      ,
      • Li AL
      • Kang JY
      • Berry DE
      • Patel KB
      • Hendrick AM.
      Necrotic uveal melanoma presenting as orbital cellulitis with intraocular hemorrhage: a case report.
      Fundoscopy is the most accurate method for diagnosis, but occasionally opaque media prevent a thorough funduscopic examination. In these cases, CT, MRI, and B-scan ultrasonography can be used to rule out an intraocular mass. In our literature review, CT scan was performed on the initial evaluation of 71% of the cases, with concurrent B-scan ultrasonography in 40%. There was no common finding on CT scan among these cases. B-scan ultrasonography, performed in 57% of cases, failed to identify an intraocular mass but did demonstrate immobile, dense echoes (75%) and features consistent with nonclearing vitreous hemorrhage (25%).
      Careful consideration should be given to the surgical management of these patients. In the 7 previously reported cases, 3 patients eventually underwent evisceration, 3 patients underwent enucleation, and 1 patient with pulmonary and hepatic metastases had no surgical intervention. Evisceration of eyes harbouring an intraocular malignancy is not recommended because of the increased risk of orbital recurrence and distant metastasis.
      • Lemaître S
      • Lecler A
      • Lévy-Gabriel C
      • et al.
      Evisceration and ocular tumors: what are the consequences?.
      Necrotic uveal melanoma can present with intraocular and periorbital inflammation, leading to a diagnostic challenge. While careful clinical examination and multimodal imaging can help identify an intraocular mass in most cases, we report a case of necrotic uveal melanoma in which B-scan ultrasonography, CT scan, and MRI failed to identify an intraocular mass prior to enucleation. A robust inflammatory response may occur secondary to tumour necrosis, with tumour involution precluding its delineation on imaging. The diagnosis of intraocular malignancy should be strongly considered in cases with severe ocular and/or orbital inflammation in the absence of a known inflammatory syndrome or infectious source, especially when visualization of the posterior segment is limited. When globe removal is warranted, we recommend enucleation rather than evisceration to limit the risk of tumour dissemination, even if an intraocular tumour is not identified clinically. Table 1
      Table 1Clinical characteristics of patients presenting with uveal melanoma not evidenced on imaging
      AuthorsAge, ySexPresenting SignsImaging FindingsTreatmentHistopathologyMalignancy Suspicion
      Eagle et al.
      • Eagle Jr, RC
      • Grossniklaus HE
      • Syed N
      • Hogan RN
      • Lloyd 3rd, WC
      • Folberg R
      Inadvertent evisceration of eyes containing uveal melanoma.
      89FNLP, eyelid erythema, conjunctival injection, chemosis, IOP 70 mm HgCT scan: hyperdense vitreous, choroidal thickeningIV antibiotics and methylprednisone followed by eviscerationNecrotic mixed-cell-type melanomaNo
      Eagle et al.
      • Eagle Jr, RC
      • Grossniklaus HE
      • Syed N
      • Hogan RN
      • Lloyd 3rd, WC
      • Folberg R
      Inadvertent evisceration of eyes containing uveal melanoma.
      49MNLP, painful neovascular glaucoma, IOP 80 mm HgUltrasound: nonclearing vitreous hemorrhageEviscerationLarge uveal malignant melanomaNo
      Eagle et al.
      • Eagle Jr, RC
      • Grossniklaus HE
      • Syed N
      • Hogan RN
      • Lloyd 3rd, WC
      • Folberg R
      Inadvertent evisceration of eyes containing uveal melanoma.
      56MBlind, painful eye, neovascular glaucoma, hypopyon, with history of treated lymphomaCT scan: No evidence of intraocular tumourEviscerationNecrotic mixed-cell-type melanomaNo
      Goh et al.
      • Goh AS
      • Francis IC
      • Kappagoda MB
      • Filipic M.
      Orbital inflammation in a patient with extrascleral spread of choroidal malignant melanoma.
      85FFever, NLP, chemosis, edema, proptosis, corneal edema, IOP 50 mm HgCT scan: periorbital soft tissue swelling and proptosis with retrobulbar mass Ultrasound: solid retrobulbar mass with homogeneous echogenicityIV antibiotics, enucleationNecrotic mixed epithelioid and spindle cell type choroidal melanomaUnclear
      Lea et al.
      • Lea SJ
      • Livesey SJ
      • Lowe J
      • Rothwell I
      • Haworth SM.
      Disappearance of ocular malignant melanoma on computerised scan after spontaneous necrosis: clinical, radiological and pathological features.
      82FNLP, proptosis, conjunctival injection, IOP 50 mm HgCT scan: proptosis, scleral thickening, no evidence of massPrednisone, acetazolamide, atropine, dexamethasone, enucleationCompletely necrotic choroidal melanomaYes
      Buckley et al.
      • Buckley CA
      • Cheng H.
      Intraocular melanoma, diabetes, and Turner's syndrome: presentation with proptosis.
      32FChemosis, proptosis, corneal edema, IOP 35 mm HgCT: enlargement of globe with thickening of its coats Ultrasound: Immobile echos, thickening of eye wallEnucleationNecrotic malignant choroidal melanomaYes
      Macedo et al.
      • Macedo SS
      • Teixeira M
      • Correia A
      • Novais A
      • Cabral C.
      Ocular melanoma presenting as masquerade syndrome.
      75FPain, loss of vision, periorbital edema, chemosis, anterior chamber hemorrhageUltrasound: Low mobility of vitreous cavity and dense echogenicityIV antibiotics, topical ciprofloxacin, dexamethasone, timolol, dorzolamide, methylprednisoneUnavailableNo
      Kasetty et al.80MOrbital edema, chemosis, conjunctival injection, IOP 70 mm Hg, APDCT scan: preseptal inflammation, tenting of right globe, vitreous debris Ultrasound: dense vitreous debris MRI: exudative or loculated materialIV antibiotics, enucleationSpindle cell melanoma with extensive ischemia, hemorrhage, and necrosisNo
      NLP = no light perception; IOP = intraocular pressure; CT = computed tomography; IV = intravenous; APD = afferent pupillary defect; MRI = magnetic resonance imaging

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