Concurrence of peripunctal nevus and uveal melanoma with scleral pigment dispersion presenting as phthisis bulbi

Abstract

This case report demostrates an unusual occurence of peripunctal nevus and uveal melanoma, in which the clinical diganosis of uveal melanoma was masked by the atypical presentation as phthisis bulbi. Nevertheless, peculiar scleral pigment hinted at a possible intraocular tumour. The importance of meticulous clinical examination in assessment of ocular and periocular pigmented lesions is demonstrated. Further, clinicopathological differentials of correlation scleral pigmentation in diffuse necrotic uveal melanoma are illustrated.

Background

Uveal melanoma is the most common primary intraocular tumour in adults.¹ Asian population accounts for <1% of all uveal melanomas with a male preponderance, younger age at presentation and advanced clinical stage at presentation.^{1 2} Known risk factors for development of uveal melanomas include ocular and oculodermal melanocytosis (ODM), fair skin, light iris colour, inability to tan, cutaneous, iris and choroidal nevi and BReast CAncer gene (BRCA)-associated protein 1 mutations.¹ Choroidal melanomas are typically dome-shaped and less often diffuse.¹ On ultrasonography, choroidal melanoma appears as dome-shaped or mushroom-shaped lesions with acoustic hollowing, choroidal excavation and orbital shadowing.¹ However, necrotic tumour in a phthisical eye can have atypical ultrasonographic features and often enucleation with histopathological examination is warranted when an intraocular tumour cannot be ruled out.³ Malignancies are a rare but important cause of painful blind eyes with uveal melanoma being the most common among them, although few cases are reported in literature.^4–8 Necrotic melanomas can also incite inflammation, macrophage infiltration and pigment dispersion which can be quite extensive, sometimes involving all the ocular structures including the sclera.⁹

Peripunctal or circumpunctal lesions are rare entities with nevi being the most common among them.¹⁰ No association with ocular or systemic tumours and peripunctal nevi is known.

We describe a rare occurrence of peripunctal nevus and uveal melanoma with scleral pigment dispersion in a phthisical eye. Patient consent has been obtained for publishing identifiable photographs.

Case presentation

A 57-year-old Asian–Indian man presented with gradually progressive diminution of vision in his left eye following blunt trauma with a stick 10 months prior to presentation with occasional pain and watering. Ocular examination of the right eye was unremarkable except for a hypochromic iris. There was no light perception in the left eye and examination revealed a pigmented peripuntal nevus in the lower eyelid, a pigmented nevus on the margin of upper eyelid and diffuse scleral pigmentation from 11 to 2 o’ clock (figure 1). The left eye was phthisical with a hazy cornea, disorganised anterior segment and no view of fundus (figure 1). There was no evidence of any cutaneous or mucosal pigmented lesions elsewhere in the body and on retrospect the patient confirmed the presence of eyelid lesions since childhood with no increase in size.

Figure 1.

(A) External photograph of an Asian–Indian man with hypochromic iris in right eye and phthisical left eye. (B) Clinical photograph of the left eye showing a variably pigmented lesion encircling a patent and patulous punctal opening (arrow). The cornea is hazy with faintly visible iris and dispersed pigment is seen at 5 o’clock (arrowhead). (C) Clinical photograph of the left eye showing patches of stippled dark brown to blackish scleral pigmentation from 11:30 to 12:30 o’ clock and 1 to 2 o’clock hours (arrowheads). A small pigmented nevus is seen on the upper eyelid (arrow). (D) Ultrasonography B-scan of the left with diffuse dot echoes. (E) Photomicrograph of the enucleated left eye with tumour filling the globe (H&E, scanner view). (F) Photomicrograph showing tumour cells which are large, polygonal, with abundant eosinophilic cytoplasm and round to oval vesicular nuclei with prominent nucleoli suggestive of epithelioid melanoma (H&E; original magnification, 40×). (G) Photomicrograph showing necrotic areas (asterix) adjacent to the viable tumour cells (H&E; original magnification, 20×). (H) Photomicrograph showing macrophages with engulfed melanin (arrowheads) within the scleral fibres and episcleral connective tissue (H&E; original magnification, 20×). (I) Photomicrograph showing extensive pigment dispersion (asterix) in the retrolaminar and orbital segments of the optic nerve (H&E; original magnification, 4×). (J) External photograph of the patient with a custom ocular prosthesis and no tumour recurrence at 1-year follow-up.

Investigations

Ultrasonography B scan of the left eye showed a phthisical globe with diffuse intraocular dot echoes of medium to low echogenicity and lack of after movement, filing the vitreous cavity. No well-defined mass, choroidal excavation or acoustic shadowing could be appreciated owing to disorganised globe and ocular coats (figure 1).

Differential diagnosis and treatment

Though the patient attributed the long-standing loss of vision to trauma and ultrasonography revealed no definite signs of intraocular tumour, the presence of extensive scleral pigmentation was a red flag sign which prompted a possibility of ODM or pigment dispersion with uveal melanoma. Enucleation of the left eye was thus performed.

Outcome and follow-up

On gross examination of the enucleated eye, the anterior chamber could not be made out, lens was not seen and the entire vitreous cavity was filled with a dark tan pigmented mass. On microscopy, no clear distinction between the iris, ciliary body and choroid was seen. The lesion was largely necrotic with viable tumour cells and pigment laden macrophages in the periphery. The lesional cells were large, polygonal, with abundant eosinophilic cytoplasm and round to oval vescicular nuclei with prominent large red nucleoli. The lesional cells were infiltrating the inner sclera with multinucleate giant cell reaction to melanin. No tumours cells were seen reaching the middle or outer scleral fibres. Multiple areas of dispersed melanin were seen in the lamina cribrosa, sclera and within the substance of the optic nerve (figure 1). Meningeal covering of the optic nerve was normal. Histopathological features were thus consistent with an epithelioid variant of malignant uveal melanoma with extensive necrosis and secondary scleral and optic nerve melanosis in a phthisical eye. Immunohistochemistry with HMB45, S100 and MELAN-A was attempted, but was inconclusive due to paucity of viable tumour cells owing to extensive necrosis. A custom ocular prosthesis was fabricated for left socket and no tumour recurrence or metastatic disease was seen till 1 year.

Discussion

Peripunctal nevus, also known as a circumpunctal nevus arises at the junction where canalicular mucosa meets the conjunctival mucosa and the epidermis of the eyelid skin.¹⁰ It is a rare lesion and accounts for about 50% of peripunctal tumours.¹⁰ Hitherto, no association with any form of pigmentary disorders, syndromes or malignancies has been observed.

Epibulbar pigmentation can arise from a variety of conditions.¹¹ ODM is one such congenital pigmentary abnormality involving the periocular skin, sclera, uvea, orbit, meninges, palate and tympanic membrane.¹¹ Pigmentation in ODM appears as irregular patches of scleral or episcleral slate grey to brown coloured lesions.¹¹ Pigmentation around Axenfeld nerve loops is another common cause of scleral and episcleral pigmentation but the characteristic location, around ciliary vessels is typical and ultrasound biomicroscopy is diagnostic.¹¹ Careful evaluation of the pigmentation seen in our patient reveals a stippled dark brown appearance and its episcleral location was evident by the lustre and mobility of the overlying conjunctiva. The scleral pigmentation was not slate grey in colour as seen in ODM and there was no involvement of periocular skin, meninges, palate or tympanic membrane. In addition, no such pigment was observed in the contralateral eye unlike the case with Axenfeld loops.¹¹ A possibility of dispersed pigment was considered, and a diagnosis of uveal melanoma was considered. However, the ultrasonographic features were not classical for uveal melanoma. Necrotic malignant melanoma can have extensive pigment dispersion, explained by tumour necrosis and increased macrophage activity which were seen in our case as well.⁹ Spontaneous necrosis in melanoma can result from coagulative (ischaemic) necrosis due to vascular compromise or cellular necrosis.⁹ The cellular necrosis cascade results in release of intracytoplasmic pigment which deposits at various sites.⁹ In the present case, these deposits were noted in sclera and optic nerve. However, no viable or necrosed tumour cells were noted at these sites ruling out the possibility of an extrascleral extension. The pattern of pigment deposition in our case can be explained by the venous drainage from the choroid, that is, through the vortex veins and choroidopial veins¹² with foci of dispersed melanin pigment accumulating on the scleral surface and within the optic nerve. Periocular pigmentation therefore is an important clue which needs careful evalutation and in this case, was a strong clue towards a possible intraocular melanoma.

This case is of uveal melanoma was thus unusual in multiple aspects such a concomitant presence of a peripunctal nevus, presentation with phthisis bulbi and the presence of extensive pigment dispersion. A PubMed and Google search using combinations of terms “concomitant”, “coexistent”, “uveal melanoma”, “peripunctal nevi”, “peripunctal nevus” and “choroidal melanoma” did not reveal any similar reports of concomitant occurrence of uveal melanoma and peripunctal nevi.

Learning points.

• Periocular pigmentation needs careful evaluation and is a helpful clue towards an intraocular tumour in select cases.

• Necrotic melanoma can have diverse clinical features including phthisis bulbi.

• High index of suspicion is warranted in unexplained painful blind eyes to avoid intraocular surgery or evisceration.