An unusual ocular manifestation of multiple myeloma

Abstract

A man in his 70s with a history of multiple myeloma presented with a 4-day history of right ptosis and a rapidly enlarging upper eyelid mass. On examination, a large, firm, smooth, pink lesion was found to descend from the conjunctiva of the superior fornix. The patient underwent excision biopsy. Histopathological analysis demonstrated monoclonal plasma cells expressing light-chain kappa, consistent with extramedullary plasmacytoma. Clinical ophthalmic manifestations of multiple myeloma are rare but also diverse. Ocular surface manifestations of multiple myeloma are extremely uncommon. Variable examination findings mean those involving the conjunctiva and may be particularly challenging to diagnose. Secondary ocular extramedullary plasmacytoma, despite its rarity, should be considered in patients with multiple myeloma.

Background

Plasma cells are the most mature form of B lymphocytes and are responsible for encoding the arrangement of mature immunoglobulins. Plasmacytomas are collections of clonal plasma cells that have become modified to produce large amounts of immunoglobulin or fragments thereof, light chains, for example.¹

Medullary plasmacytomas develop in bone, while extramedullary plasmacytomas develop in soft tissue. ‘Solitary’ extramedullary plasmacytomas are primary neoplasms that, while locally invasive, do not metastasise. They are found, most commonly, in the upper respiratory and gastrointestinal tracts as well as lymph nodes.² Solitary extramedullary plasmacytoma is a rare finding; 3 such cases are described for every 100 cases of multiple myeloma.³ They may remain solitary or may precede the development of multiple myeloma.

Plasmacytomas occur as secondary tumours in multiple myeloma. Along with, among others, solitary plasmacytoma and monoclonal gammopathy of unknown significance, multiple myeloma is a ‘plasma cell dyscrasia’ and the most severe at that. Its diagnosis requires the presence of clonal plasma cells, comprising greater than 10% of the cellularity in the bone marrow or a plasmacytoma and the presence of specific biomarkers or evidence of end organ damage.⁴ With the proliferation of plasma cells—most commonly in the bone marrow—that characterises multiple myeloma, there is widespread skeletal destruction by osteolytic lesions and associated hypercalcaemia, pathological fractures and/or spinal compression. The abnormal formation of monoclonal immunoglobulins and/or light chains results in the diagnostic finding of monoclonal hypergammaglobulinaemia. Anaemia, recurrent infections and/or renal insufficiency may result.

The age-adjusted incidence of multiple myeloma is 6.56 cases per 100 000 persons per year in the USA.⁵ It represents 10% of all haematological malignancies.⁶ The median age of diagnosis is 66 years.⁷ There is a slight male preponderance. It has a treated median overall survival of 5–7 years.⁸

Case presentation

A man in his 70s presented to the ophthalmology emergency department with a 4-day history of right upper eyelid swelling, ptosis and moderate globe pain. His right eye was known to be amblyopic as a result of strabismic amblyopia.

The patient had been diagnosed with kappa light-chain multiple myeloma 18 months previously. Bone marrow biopsy had shown plasma cells to comprise approximately 95% of all cells therein. He completed six cycles of induction chemotherapy with cyclophosphamide, bortezomib and prednisolone initially before treatment with an immunomodulating regimen of lenalidomide and dexamethasone with immunoglobulin. After 8 months, progressive cytopenia necessitating blood transfusion prompted cessation of lenalidomide and a return to treatment with bortezomib.

Snellen visual acuity was 1.0/60.0 and 6.0/7.5 from the right and left eyes, respectively. Pupil examination was normal. Right exotropia was apparent. No abnormalities of ocular motility were noted. Fundal examination was normal. As can be seen from figure 1, a large, smooth, pink mass extended from beneath the patient’s right upper eyelid. The lid was everted, and the lesion was found to originate from the conjunctiva of the superior fornix. Measuring approximately 20mm×15mm×10 mm, it was of firm consistency.

Figure 1.

A large, firm, pink lesion emanating from the conjunctiva of the superior fornix of the right eye.

An excisional biopsy of the conjunctival mass was performed under local anaesthesia.

Investigations

Histological examination identified a nodular neoplasm composed of plasma cells with cytological atypia, increased mitoses and numerous apoptotic bodies, a portion of which had undergone necrotic change. It was focally covered by a flattened layer of squamous epithelium. Immunohistochemical studies revealed plasma cells with monotypical expression of kappa light chain, consistent with the patient’s diagnosis of kappa light-chain multiple myeloma. Representative images are shown in figure 2.

Figure 2.

(A) A sheet of plasma cells extends to the squamous epithelium at the excision margin; H&E, ×10. (B) Monoclonal plasma cells with prominent ‘cartwheel’ nuclei and increased chromatin; H&E, ×400. (C) Immunohistochemistry; strong reactivity for CD-138; H&E, ×400. (D) Immunohistochemistry; monotypical kappa light-chain expression; H&E, ×400. (E) Immunohistochemistry; scant lambda light-chain expression, 42×23 mm; H&E, ×400.

Treatment

Treatment with pomalidomide and dexamethasone for relapsed multiple myeloma was commenced.

Outcome and follow-up

The patient’s eyelid oedema and ptosis resolved following surgery. The patient died approximately 2 months after his surgery.

Discussion

Ocular pathology in multiple myeloma may result from direct infiltration by malignant plasma cells, as here; displacement of ocular tissues by plasmacytomas; or haematological derangements with increased plasma viscosity and/or protein deposition in tissues.⁷ Thus, while clinical ophthalmic manifestations of multiple myeloma are uncommon, they are also diverse.

Ocular surface manifestations of multiple myeloma are rare. Conjunctival involvement is particularly unusual. ‘Sludging’ of red blood cells in conjunctival blood vessels⁹ and both crystalline¹⁰ and calcium conjunctival deposits¹¹ have been described, in addition to a small number of solitary extramedullary plasmacytomas of the conjunctiva in which systemic evaluation was methodically done, and multiple myeloma was excluded.^12–23

Conjunctival plasmacytoma, in association with systemic multiple myeloma, appears even more infrequently, with only six cases reported in the literature to date. These are summarised in table 1.^{7 24–28} Indeed, some authors have disputed the existence of the association at all.¹⁴

Table 1.

Previously reported conjunctival plasmacytoma secondary to multiple myeloma

Age (years)	Sex	Laterality and location	Duration of ocular symptoms	Description	Immunohistochemistry	Treatment	Outcome	Reference
33	♀	Left temporal bulbar conjunctiva, extension to both superior and inferior fornices	2 months	Salmon patch. 37×4×11mm	–	Chemotherapy	Death 6 months later	Artsi et al24
70	♂	Left temporal bulbar conjunctiva	1 week	Salmon patch. 10×9 mm	IgG kappa light chains	Chemotherapy and radiotherapy	Death 18 months later	Shen et al25
59	♀	Both eyes	2 weeks	Associated with iridocillary tumour	λ light chains	Chemotherapy	–	Zhou et al26
75	♀	Left nasal bulbar conjunctiva	–	Red and cystic, associated with foamy epithelial lesion extending 2 mm into the cornea, initially masqueraded as subconjunctival haemorrhage	IgD λ light chains	Chemotherapy	–	Bradley et al7
45	♂	Right superior nasal bulbar conjunctiva	24 hours	Vascularised mass	IgG kappa light chains	Chemotherapy, radiotherapy	Death 6 months later	Santos-Bueso et al27
45	♂	Left superior bulbar conjunctiva.	–	Nodule; pink, partially cystic, vascularised; engorged scleral vessels	IgG λ light chains	Chemotherapy, radiotherapy, 20 Gy in 10 fractions	Death 8 months later	Mohamed et al28

Those with conjunctival involvement by plasmacytoma may be particularly challenging to diagnose. Reported cases describe the appearance of lesions with variable gross examinations including those presenting as discrete masses,²⁸ as diffuse conjunctival thickening²⁷ or ‘conjunctivitis’ and as conjunctival ‘salmon patches’.^{24 25} One patient presented with recurrent subconjunctival haemorrhage which obscured the underlying growth.⁷ Biopsy with histopathological examination is required for definitive diagnosis.

Some reports have suggested that the involvement of the eye and/or conjunctiva in multiple myeloma heralds a much more aggressive phase of the disease and/or one which may be more difficult to treat.^{26 29} Indeed, the patient described herein died 2 months after surgery of conjunctival plasmacytoma. In another case, while systemic chemotherapy controlled the original disease, multiple plasmacytomas of the bulbar conjunctiva continued to progress until intravitreal bevacizumab was administered.²⁶

Learning points.

• Ocular surface manifestations of multiple myeloma are extremely uncommon.

• The appearance of related lesions involving the conjunctiva is highly variable.

• Definitive diagnosis is made by biopsy and histopathological examination of the tissue.

• Secondary ocular extramedullary plasmacytoma, despite its rarity, should be considered in patients with multiple myeloma.

Ethics statements

Patient consent for publication

Consent obtained from next of kin.