Superior Oblique Muscle Extramedullary Plasmacytoma in a Patient with Multiple Myeloma and a Review of Literature

Multiple myeloma (MM), a plasma cell malignancy, accounts for 1% of all cancers and 10% of hematologic neoplasms. It includes a range of diseases from monoclonal gammopathy of unknown significance (MGUS), extramedullary disease (EMD), and plasma cell leukemia [1]. MM is a multisystem disease affecting more commonly the bones as bone-related plasmacytoma (BP) or less frequently the soft tissues outside the bone as extramedullary plasmacytoma.

Extramedullary involvement worsens the prognosis of MM and is a sign of a more aggressive disease. The incidence of EMD varies among different studies and differs based on the MM phase. In newly diagnosed MM, the incidence is 0.5–4.8%, while in relapse/refractory MM, the incidence ranges from 3.4 to 14% [2]. While the orbit can also be a site of both bone-related plasmacytoma and extramedullary involvement, the EMD in the orbital cavity is relatively rare [3].

Herein, we present a 51-year-old woman with EMD in the superior oblique (SO) muscle secondary to a refractory MM. To our knowledge, extramedullary involvement of SO muscle has not been reported yet. We also performed a literature review of MM involving orbital EOMs. The CARE Checklist, describing the multiple parts of the case report, has been completed by the authors for this case report and is attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000538120).

A 51-year-old female presented to the oculoplastic clinic with a 20-day history of gradual protrusion of the left eye, which was accompanied by ocular pain. The patient had been diagnosed with MM 2 years previously but was otherwise systemically well apart from hypertension and controlled on medication. The patient had been undergoing chemotherapy for 8 months since the diagnosis of the disease until the bone marrow transplant. The patient was in remission 1 year after the transplant, until she presented with left eye protrusion. Because of previous amblyopia, her best corrected visual acuity was 1/10 in the right eye and 7/10 in the left eye. Ocular examination showed proptosis and a moderate fullness of the left eye with no dystopia or ptosis (Fig. 1a, b). Limitation in adduction and limitation in inferonasal gaze (−1) were detected. Pupils were equal and reactive with no relative afferent pupillary defect. The slit-lamp examination and dilated fundoscopy were normal. The corneal sensation was normal in both eyes. Optic nerves were normal in both eyes. A computed tomography (CT) scan of the orbits showed no evidence of bone involvement. Magnetic resonance imaging (MRI) of the brain and orbits (Fig. 1d–f) demonstrated a mass in the left superior oblique muscle belly with relatively homogenous contrast enhancement.

In order to obtain a definitive diagnosis, an anterior superonasal orbitotomy was performed through an extended incision at the medial end of the upper lid crease. After tissue dissection, we realized that the mass was within the superior oblique muscle belly. For this reason, it was not possible to completely excise the mass, and the mass was subjected to debulking and biopsy. After controlling the bleeding and placing a drain, the wound was sutured with nylon 6-0 (Fig. 1c).

Histopathologic examination revealed fibromuscular tissue containing a neoplasm composed of sheets of plasmacytoid cells in a varying degree of differentiation with intervening scantly vascularized stromal components. Immunohistochemistry (IHC) revealed that the plasmacytoid cells were diffusely positive for a cluster of differentiation 138(CD138). Thus, histopathology and IHC confirmed the diagnosis of plasma cell myeloma involving extraocular muscle and soft tissue of orbit (Fig. 2a–d).

The patient underwent palliative external beam radiotherapy. On systemic workup, positron emission tomography-computed tomography scan (PET-CT) revealed evidence of extramedullary disease (soft tissue density) on the left side of the pelvic cavity and left calf, compatible with active MM. The patient underwent an intensive chemotherapy regimen. The patient’s ocular symptoms resolved over a follow-up period of 6 months, with no sign of tumor activity in the orbit. Seven months after presentation, despite augmented chemotherapy, recurrence of plasmacytoma in the pelvic region and subsequent pressure on the pelvic veins resulted in progressive edema of the left lower limb and secondary thrombosis in Doppler ultrasound reports. Although the patient underwent intensive antibiotic and anticoagulant therapy, she succumbed to her illness due to severe sepsis and cardiogenic shock.

This report has documented extramedullary plasmacytoma in the SO muscle in a patient with MM. Despite treatment for 2 years before presentation, the disease was still active in our patient. To the best of our knowledge, EMD in SO muscle is being reported for the first time. In our patient, systemic workup confirmed the involvement of other organs which meant systemic activity of the disease.

The ophthalmic manifestations of MM can appear in many ocular structures. These include crystalline corneal deposits, chorioretinopathies, retinal hemorrhage, extraocular muscle paresis, and papilledema [4, 5].

Similar to other organs, orbital manifestations in MM are mainly caused by plasma cell infiltration into the bone (solitary plasmacytoma of bone) or extraocular soft tissue (EMD). Most plasmacytomas occur in the superotemporal quadrant due to the rich blood supply in the lacrimal gland and the sphenoid bone [6]. EMD affecting EOM is a relatively rare phenomenon. Studies reporting EOM involvement in MM are summarized in Table 1 [7‒14]. EOMs are usually affected in combination with adjacent soft tissue or bone. To date, isolated involvement of EOM has been reported in 3 patients [7, 15, 16]. Whether isolated or in combination with other tissues, the hematogenous spread of neoplastic plasma cells could result in extramedullary involvement of EOM [2].

The mechanism explaining the development of EMD in MM has not yet been clarified. Both extramedullary and bone relapses have been reported in MM. However, the cell morphology and CD expressions might have differences between SPB and EMD. The presence of Ki 67 on extramedullary plasma cells is also a sign of mitotic activity in these escaping cells. The extramedullary plasmacytoma cells are considered to be more aggressive [17].

Determining whether EMD is a local relapse or a manifestation of MM activity or relapse requires systemic workup including immunoelectrophoresis of serum and urine, skeletal survey, CT scan, and, in some cases, bone marrow aspiration. We think the tumor in our patient is a sign of MM activity, as a result of insufficient treatment. Based on the current literature, orbital metastasis is an unfavorable prognostic factor leading to a reduced survival rate [18, 19].

There are various treatments for EMD, depending on whether it is local or systemic. Solitary bone lesions are often treated with radiotherapy alone and extramedullary plasmacytomas are more likely to undergo surgery or in combination with radiotherapy [20]. Since MM is a systemic disease, treatment of MM typically involves chemotherapy, and in younger patients, hematopoietic stem cell transplantation is considered in combination with chemotherapy [1]. Our patient was under a chemotherapy regimen with bortezomib and dexamethasone and zoledronic acid at the time ophthalmic signs arose, but the pelvic cavity involvement suggested that the chemotherapy regimen was not adequate. Therefore, the chemotherapy regimen was changed to a more robust form.

In conclusion, a patient with MM may encounter extramedullary disease in the orbital cavity even under chemotherapy. Since early recognition of disease recurrence and insufficiency of treatment is lifesaving in MM patients, ophthalmic manifestations should be seriously considered as a sign of MM activity.

Written informed consent was obtained from the patient’s husband for the publication of the details of the medical case and any accompanying images. Ethical approval is not required for this study in accordance with local or national guidelines.

The authors declare no conflict of interest.

The authors received no funding for this report.

A.V. and M.N. made the diagnosis, performed the surgery, and supervised the draft. S.H., K.D., and K.H. gathered the data and drafted the manuscript. P.M.T. confirmed the pathological diagnosis, prepared the pathology figures, and confirmed the final manuscript. All authors approved the final version.

All data generated and analyzed during this study are included in this article. Further inquiries can be directed to the corresponding author.