Bilateral proptosis as the initial manifestation of multiple myeloma with orbital involvement: case report and literature review

Abstract

Orbital plasmacytoma (OP) is a rare extramedullary manifestation of multiple myeloma (MM), typically presenting unilaterally during the course of previously diagnosed disease. Bilateral OP as the initial manifestation of MM is exceedingly uncommon. We report a 40-year-old woman who presented with rapidly severe bilateral proptosis, visual impairment, and ocular surface damage. Cranio-orbital imaging demonstrated bilateral extraconal masses and diffuse lytic lesions. Immunoelectrophoresis identified monoclonal IgA kappa, and bone marrow aspiration showed 48% dystrophic plasma cells. Histopathological examination of a conjunctival biopsy confirmed extramedullary plasmacytoma, establishing the diagnosis of IgA kappa MM with bilateral OP. Despite a marked early local response after one month of treatment with high-dose corticosteroids and immunochemotherapy, the patient died shortly after. This case highlights an exceptionally rare and aggressive initial presentation of MM with bilateral OP, underscoring the high tumor burden and poor prognosis associated with this unusual manifestation.

Introduction

Multiple myeloma (MM) is a mature B-cell neoplasm defined by the presence of ≥10% of clonal plasma cells in the bone marrow or a biopsy-proven plasmacytoma, in conjunction with evidence of end-organ damage [1]. MM is the second-most prevalent hematological malignancy after non-Hodgkin’s lymphoma, accounting for approximately 2% of all cancer-related deaths [2, 3]. In 2022, 188 000 new cases of MM and 121 000 deaths were estimated worldwide [4].

Although plasma cell proliferation in MM typically remains confined to the bone marrow, a small subset of patients presents with extramedullary disease (EMD). EMD most commonly occurs as localized masses, called soft-tissue plasmacytomas, or as diffuse infiltration of myelomatous cells [5]. These lesions may arise either through direct extension of skeletal tumors following bone disruption or through hematogenous dissemination to soft tissues and organs without bone involvement.

Most EMD cases occur in the upper aerodigestive tract (≈80%) [6]. Ophthalmic involvement is uncommon and has been described in the form of orbital, conjunctival, uveal, and lacrimal gland infiltration [7]. Orbital plasmacytoma (OP) is a rare form of orbital involvement, accounting for approximately 3% of all orbital tumors. It typically occurs as a unilateral mass, most frequently causing slowly progressive proptosis. Its scarcity, coupled with the insidious onset of symptoms, poses significant diagnostic challenges [8]. Management is equally complex, requiring a careful balance between systemic disease control and preservation of ocular function, with caution to treatment-related toxicity to orbital structures.

In this report, we describe an exceptionally rare case of a young female patient presenting with bilateral OP as the initial manifestation of MM, characterized by rapidly progressive severe bilateral proptosis, ocular surface lesions, and visual impairment.

Case report

A 40-year-old female patient, with no personal medical history, presented with a 2-month rapidly progressive bilateral proptosis, followed by diplopia and decreased visual acuity. She also complained of headaches and a 44-pound weight loss. No family history was reported. Ophthalmic examination demonstrated grade 3 bilateral proptosis, more pronounced in the left eye, associated with complete paralysis of ocular motility. Severe chemosis, scleromalacia, lagophthalmos, and multiple corneal ulcerations were noted (Fig. 1). Visual acuity, measured using the logarithm of the minimum angle of resolution (LogMAR), was reduced to positive light perception in the right eye (LogMAR 2.9) and no light perception in the left eye (LogMAR 3.0). Posterior segment evaluation was not possible due to the severely damaged anterior segment.

Figure 1.

Patient’s initial presentation with severe bilateral proptosis, chemosis, lagophthalmos, and scleromalacia.

Cranial and orbital MRI showed bilateral extraconal soft-tissue masses that compressed the optic nerves, infiltrated adjacent tissues, and eroded the orbital roof and temporal bones. The lesions appeared hypointense on T1, isointense on T2, with restricted diffusion and moderate gadolinium enhancement. Additional masses were found arising from the right frontal, left parietal, and sphenoid bones, along with multiple lytic lesions in the cranial vault and skull base (Figs 2 and 3). Cervicothoracic and abdominopelvic CT scans revealed diffuse skeletal lytic lesions involving the spine, ribs, log bones and pelvis.

Figure 2.

Axial brain MRI sequences demonstrating bilateral orbital masses with osseous and dural invasion. A. Axial T2-weighted imaging shows the orbital masses (yellow arrow) with intermediate signal intensity and extensive bilateral involvement of the osseous structures, including the lateral orbital walls, temporal bones, and zygomatic processes (white asterisks), exhibiting a lytic appearance. This is accompanied by a bilateral mass effect on the ocular globes, resulting in a strawberry shape as well as the optic nerves, with no evidence of direct invasion (white arrows). B. Axial T1-weighted imaging post-gadolinium administration reveals mild enhancement of the orbital masses (yellow arrow), with extension into the temporal osseous structures (white asterisks), associated with regular pachymeningeal enhanced thickening along the temporal dura (red arrows), and bulging into the infratemporal fossa.

Figure 3.

Sagittal T1-weighted brain MRI showing the orbital mass with multiple lytic bony lesions. Two sagittal T1-weighted slices (A and B) demonstrate an orbital mass with low signal intensity (yellow arrows) and ill-defined margins. Additional osseous lesions involving the calvarium and skull base (white arrow) display intermediate signal intensity on T1 and are associated with cortical bone lysis of the inner table (red arrow). These lesions extend into the extradural space, exerting a slight mass effect on the adjacent cerebral parenchyma (white arrowheads).

Laboratory results included normochromic normocytic anemia (Hb: 7 g/dl), without renal dysfunction or hypercalcemia. Serum protein electrophoresis demonstrated two narrow peaks in the beta-2 (30 g/l) and gamma (13 g/l) regions. Immunoelectrophoresis identified monoclonal IgA kappa light chains bands. Serum free light chain assay showed kappa at 1700 mg/l, lambda at 8 mg, with a ratio of 215. The 24-hour proteinuria was 3.42 g/d, with urine electrophoresis confirming IgA kappa bands. Bone marrow aspiration revealed 48% dystrophic plasma cells, and bone marrow biopsy showed diffuse plasma cell infiltration, with CD138 and kappa light chain restriction. Conjunctival biopsy confirmed plasmacytoma, establishing the diagnosis of IgA kappa MM with bilateral OP.

Prognostic assessment revealed a beta-2 microglobulin level of 4 mg/l, a lactate dehydrogenase of 547 UI/l, and a serum albumin of 25 g/l. Cytogenetic analysis was not performed due to limited financial resources. Based on these parameters, MM was classified as an International Staging System (ISS) stage 2 disease.

Given the severe ocular involvement, an intravenous pulse of methylprednisolone (1 g/d for 3 days) was administered, followed by oral prednisone (1 mg/kg/d), which was progressively tapered. The planned MM regimen consisted of immunochemotherapy with bortezomib (1.3 mg/m² subcutaneously), cyclophosphamide (300 mg/m² orally), and dexamethasone (40 mg orally) on days 1, 8, 15, and 22 of 28-day cycles, for a minimum of 6 cycles in the event of a favorable response, followed by maintenance therapy with bortezomib.

After completing the 1^st cycle of treatment, the patient remained clinically stable and asymptomatic, with normal laboratory results and no adverse events noted at the one-month follow-up visit. Ophthalmologic reevaluation demonstrated a significant regression of proptosis and ocular surface complications (Fig. 4). Visual acuity improved in the right eye from light perception (LogMAR 2.9) to 1/10 (LogMAR 1.0) and in the left eye from no light perception (LogMAR 3.0) to 0.5/10 (LogMAR 1.3). Despite significant local improvement, the patient passed away a few days later at home.

Figure 4.

On-month follow-up showing marked regression of bilateral proptosis and improvement of ocular surface complications.

Discussion

This case highlights an exceptionally rare presentation of bilateral OP as the initial manifestation of MM in a young female patient. The disease presented with an unusually rapid onset of severe bilateral proptosis and ocular surface involvement, leading to profound visual impairment. Although immunochemotherapy achieved a significant early local response, the patient died within the first month of follow-up, most likely reflecting the aggressive biology and advanced systemic burden associated with EMD at diagnosis.

Orbital involvement is an uncommon manifestation of MM. In a comprehensive literature review by Burkat et al. (2009), 52 documented cases of orbital involvement were identified, most of which occurred in the context of MM (65%) [9]. OP, which represents the most common form of orbital involvement, typically manifests during the course of previously diagnosed MM rather than at initial presentation. Our literature review using MEDLINE (PubMed) identified fewer than 30 case reports published in English describing OP in newly diagnosed MM patients (Supplementary file). Consistently, a multicenter retrospective study in Australia reported that 84% of patients with OP had a known diagnosis of MM [10]. This aligns with broader data showing that approximately 1–2% of MM patients present with EMD at diagnosis, whereas up to 8% develop EMD later in the disease course [11].

Bilateral involvement represents another layer of rarity. In the review by Burkat et al, only 13% of patients with orbital MM had bilateral involvement. Similarly, an American retrospective multicenter cohort study described bilateral involvement in only 17% of MM patients with OP [12]. When focusing specifically on orbital plasmacytoma as the initial manifestation of MM, bilateral involvement is even more uncommon. Within our literature review of OP in newly diagnosed MM patients, our patient represents one of the very few documented cases to describe bilateral OP as the initial manifestation of MM (Supplementary file).

Clinically, proptosis is the major feature of OP, occurring in about 80% of cases [13]. However, unlike the slowly progressive onset commonly described in the literature, our patient presented with a rapidly evolving proptosis, reaching severe protrusion within only two months. Other frequently reported symptoms include diplopia, ptosis, vision impairment, swelling, and orbital mass (Supplementary file). In our case, ophthalmological examination revealed complete ophthalmoplegia secondary to extensive extraconal infiltration. Restricted ocular motility, particularly in abduction, has also been described in previous reports and is likely attributable to the mechanical mass effect on extraocular muscles [14].

Radiologically, OP typically appears on orbital MRI as a bulky soft-tissue mass, iso- to hypointense on T1, iso- to hyperintense on T2, with mild-to-moderate enhancement and restricted diffusion, indicative of high cellularity [15]. In line with prior reports, the lesions in our patient predominantly originated in the superotemporal quadrant of the orbits [9]. This predilection may relate to the region’s rich vascular supply, proximity to the lacrimal gland, and the extensive marrow content of the adjacent sphenoid bone [9]. Although imaging findings may strongly suggest OP, definitive diagnosis requires immunohistochemical confirmation.

Our patient’s prognosis was markedly poor due to several factors, most notably the presence of EMD at diagnosis [16]. EMD is a well-established marker of adverse outcomes, linked to high-risk genetic features, reflecting the clone’s ability to proliferate independently of the marrow microenvironment [17]. EMD is independently associated with significantly inferior overall survival and progression-free survival compared with MM without EMD [5, 18, 19]. Within the spectrum of EMD, orbital involvement represents one of the most aggressive forms of plasmacytoma, associated with a high mortality rate [20, 21]. The bilaterality of orbital lesions further underscores disease severity, as it likely reflects a higher systemic tumor burden and more extensive hematogenous dissemination. Finally, the IgA kappa subtype, as in our patient, has been reported to carry a less favorable prognosis compared with IgG MM, although prognostic heterogeneity exists across studies [22].

There are currently no specific guidelines for MM with EMD; however, the aggressive biological nature of this subset supports a systemic-first strategy aimed at rapid eradication of the pathological plasma cell clone. Combinations including proteasome inhibitors, immunomodulatory agents, and corticosteroids are preferred, as they achieve rapid cytoreduction and may improve tissue penetration [23]. In our patient, the regimen combining bortezomib, cyclophosphamide, and dexamethasone resulted in a prompt and substantial reduction of orbital tumor burden after a single cycle.

As plasma cells are highly radiosensitive, radiotherapy is considered the gold standard for local treatment for plasmacytomas, especially when solitary [24]. Nevertheless, in the setting of MM, radiotherapy is not mandatory as treatment priority shifts from immediate local control to global disease management. Moreover, when considering treatment options for orbital tumors, the potential toxicity of radiation to ocular structures must be carefully weighed against the expected benefit [22]. In our case, given the rapid and significant local response to high-dose corticosteroids and systemic immunochemotherapy, radiotherapy was not deemed necessary.

Despite early local control, our patient died shortly after completing the first cycle of treatment. The exact cause of death remains uncertain, as the patient passed away at home and no autopsy was performed. Although fatal intracranial progression was considered, the absence of preceding neurological symptoms and marked clinical regression of orbital lesions argues against uncontrolled local progression. Infection was also deemed unlikely, as the patient remained asymptomatic and afebrile in the days and hours preceding death. Acute metabolic complications, including hypercalcemia-related arrhythmia, were excluded, based on recent normal laboratory results. While a thromboembolic event cannot be entirely ruled out, anticoagulation prophylaxis had reportedly been taken as prescribed.

After multidisciplinary discussion, the most plausible explanation was the rapid systemic progression of an already advanced and biologically aggressive MM. Importantly, local tumor regression does not necessarily reflect adequate systemic disease control, particularly in high-burden or extramedullary presentations, where early clinical or radiological improvement may precede hematologic response. A comparable outcome was described by Lin et al, who reported a 41-year-old male with unilateral OP associated with MM. In their report, despite regression of proptosis following radiotherapy and chemotherapy, the patient died three months later [25].

In conclusion, this case highlights an exceptionally rare and diagnostically challenging initial presentation of MM with bilateral OP, revealed by rapidly progressive proptosis in a young female patient. The abrupt clinical course, severe bilateral orbital involvement, and fatal outcome despite early local response to immunochemotherapy underscore the aggressive biology and substantial systemic burden associated with this presentation.

Conflicts of interest

No conflicts of interest.

Funding

This work received no funding.

Ethics approval

Ethics approval was not required, given the retrospective and observational nature of the study.

Consent

Written informed consent for publication of this case report and accompanying images was obtained from the patient’s mother, acting as the legally authorized representative following the patient’s death.

Guarantor

Sarra Chadli (S.C.).