Nonsecretory Recurrence of Multiple Myeloma Presenting as Sixth Nerve Palsy Secondary to Clival Plasmacytoma

Clinical Correspondence Section Editors: Robert Avery, DO Karl C. Golnik, MD Nonsecretory Recurrence of Multiple Myeloma Presenting as Sixth Nerve Palsy Secondary to Clival Plasmacytoma Aaron R. Kaufman, MD, Karen Quillen, MD, MPH, Alberto G. Distefano, MD, J. Mark Sloan, MD Downloaded from http://journals.lww.com/jneuro-ophthalmology by BhDMf5ePHKav1zEoum1tQfN4a+kJLhEZgbsIHo4XMi0hCywCX1AWnYQp/IlQrHD3i3D0OdRyi7TvSFl4Cf3VC4/OAVpDDa8KKGKV0Ymy+78= on 05/04/2022 S kull base plasmacytoma is a rare manifestation of multiple myeloma (MM) (1). We herein report a case of unilateral sixth cranial nerve (CN VI) palsy secondary to clival plasmacytoma as a presenting sign of a nonsecretory recurrence of MM in a patient who had previously achieved clinical remission after autologous stem cell transplantation. A 44-year-old man with a history of immunoglobulin G (IgG) kappa MM and catheter-associated deep vein thrombosis of the internal jugular vein presented to the emergency department with a chief complaint of binocular diplopia of 3 weeks’ duration. Diplopia had sudden onset and was associated with a persistent left-sided headache that worsened with positional changes. He denied blurry vision, transient visual obscurations, pulsatile tinnitus, weakness, numbness, and problems with balance or co-ordination. The patient’s MM had been in remission for 2 years after induction chemotherapy with bortezomib, lenalidomide, and dexamethasone followed by autologous stem cell transplantation. While in remission, he was maintained on lenalidomide. His earlier MM manifestations had included multiple plasmacytomas, the most significant of which were a vertebral lesion causing T11 spinal cord compression (treated with local radiotherapy) and a large sternal lesion. His secretory markers had previously only ever been mildly elevated. On examination, he was found to have a complete left abduction deficit with no other extraocular movement abnormalities. Pupils were symmetric in light and dark with no afferent pupillary defect. The optic nerve head had normal appearance bilaterally on direct ophthalmoscopy. Visual acuity was not checked with the Snellen chart on the first day of presentation but was grossly intact bilaterally. The remainder of the patient’s physical examination, including Department of Internal Medicine (ARK), Boston University School of Medicine, Boston, Massachusetts; Department of Ophthalmology and Visual Sciences (ARK), University of Illinois at Chicago, Chicago, Illinois; and Departments of Hematology/Oncology (KQ, JMS) and Ophthalmology (AGD), Boston University School of Medicine, Boston, Massachusetts. The authors report no conflicts of interest. Address correspondence to J. Mark Sloan, MD, Department of Hematology/Oncology, Boston University School of Medicine, 820 Harrison Avenue, FGH Building Room 1020, Boston, MA 02118; E-mail: [e-mail] Kaufman et al: J Neuro-Ophthalmol 2021; 41: e77-e78 assessment of cranial nerve functions, peripheral strength and sensation, co-ordination, and gait, was unrevealing. The patient underwent MRI of the brain with and without contrast, which revealed numerous intracranial lesions. There was a large enhancing skull base lesion (4.3 · 1.8 · 2.3 cm) centered in the left petrous apex, encasing the left internal carotid artery, extending into the clivus, and protruding into the right sphenoid sinus (Fig. 1A). There were multiple other enhancing calvarial lesions, a right anterior parietal lesion and a large lesion at the occiput with dural involvement. There were no brain intraparenchymal lesions. The location of the skull base lesion was amenable to surgical biopsy. However, because the patient had been taking aspirin daily, the risk for intracranial bleed from biopsy of this lesion would have necessitated delaying biopsy for 5–7 days while aspirin was held. To facilitate timely biopsy, computed tomography (CT) of the chest/abdomen/pelvis was consequently obtained to survey for other lesions accessible to less invasive biopsy. The patient was found to have numerous new soft-tissue lytic lesions of the ribs, sternum, and clavicles. These lesions, which involved the patient’s bone marrow, were further shown on positron emission tomography (PET)/CT to be hypermetabolic (Fig. 1B). Biopsy (core and fine needle) of a new large sternal lesion demonstrated sheets of atypical plasma cells with slightly more open chromatin and small-sized to medium-sized nucleoli. Blood work again showed a small monoclonal band of IgG kappa without impressive elevation of secretory markers. Diagnosis was thus found to be a nonsecretory recurrence of MM. Because of high clinical suspicion for MM recurrence and concern for compression of the left CN VI by the clival lesion, the patient began empiric treatment with a 5-day burst of 40mg oral dexamethasone daily before tissue diagnosis was made. The patient received urgent intensity-modulated radiation therapy, 30 Gy fractionated over 10 sessions. He also began treatment with daratumumab infusions and bortezomib. In longitudinal neuro-ophthalmic follow-up, the patient had gradual improvement in his left CN VI palsy. At 1-month follow-up, the patient had left esotropia in primary gaze of 25 prism diopters (PDs), which improved to 10 PD by 4-month follow-up. At 7-month follow-up, the patient had complete resolution of his extraocular motor deficit, with an unremarkable e77 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited. Clinical Correspondence FIG. 1. A. T1-weighted MRI with gadolinium contrast on the patient’s initial presentation with left sixth nerve palsy demonstrating large plasmacytoma (arrow) centered in the left petrous apex, encasing the left internal carotid artery, extending into the clivus, and protruding into the right sphenoid sinus. Hypermetabolic activity of this lesion, observed on PET/CT during initial presentation (B), had resolved on repeat scan at 5 months (C) after local radiation therapy and ongoing systemic therapy with daratumumab and bortezomib. CT, computed tomography; PET, positron emission tomography. neuro-ophthalmic examination, including best-corrected visual acuity of 20/20 bilaterally. On repeat PET/CT scan at 5 months, the patient was found to have complete resolution of the abnormal metabolic activity in the skull base lesion (Fig. 1C); however, the scan otherwise demonstrated a mixed systemic response of improvement in some lesions, worsening in some lesions, and new pleural lesions. Sixth nerve palsy secondary to a clival lesion from intracranial plasmacytoma has been previously reported, including presentations as solitary plasmacytoma (2), as initial presentation of MM (2), and in the setting of MM recurrence (3). The mechanism for injury to the CN VI may be related to direct compressive mass effect or to intracranial pressure perturbations that distort the course of the nerve in Dorello’s canal. We believe this to be the first case in which CN VI palsy was the initial sign of disease recurrence in a patient who had previously achieved clinical remission by autologous stem cell transplantation. In addition, this patient has an unusual plasmacytoma-prone phenotype, in which his symptomatic skull base lesion heralded a larger burden of disseminated plasmacytomatous lesions with only minimal elevation of secretory markers. We also describe utilization of extracranial imaging to identify a less invasive biopsy site in a patient presenting with a symptomatic clival lesion but suspected larger burden of recurrent metastatic disease. This case illustrates the importance of a patient’s risk factors and medical comorbidities in the formulation of the individualized differential diagnosis for unilateral sixth nerve palsy. Although ischemic mononeuropathy is the most common cause of sixth nerve palsy (4), this patient’s age and lack of vascular risk factors suggested an alternate etiology to be more likely. Moreover, his history of malignancy raised the possibility for a neoplastic etiology. Clinical suspicion was high for MM recurrence in this patient, despite minimal secretory marker elevation. In this case, tissue diagnosis was achieved by a less invasive and lower risk approach than by direct biopsy of the skull base lesion. Tissue diagnosis is essential to guide e78 the treatment of skull base lesions (5). Surgical biopsy of the symptomatic skull base lesion in this patient would have necessitated delay because of high risk for intracranial bleed from daily aspirin use. Given this patient’s prior plasmacytoma-prone phenotype, surveillance for other subclinical lesions using a CT scan of the body was pursued, and the imaging identified other new extracranial plasmacytomatous lesions more readily accessible for needle biopsy and diagnostic confirmation. The radiosensitive behavior of skull base plasmacytomas has been previously described (1,5) and was observed in this patient who on chemotherapy had marked improvement in his irradiated clival lesion, despite lesion progression and emergence of new lesions at other sites. STATEMENT OF AUTHORSHIP Category 1: a. Conception and design: A. R. Kaufman and J. M. Sloan; b. Acquisition of data: A. R. Kaufman; c. Analysis and interpretation of data: A. R. Kaufman, K. Quillen, A. G. Distefano, and J. M. Sloan. Category 2: a. Drafting the manuscript: A. R. Kaufman; b. Revising it for intellectual content: K. Quillen and A. G. Distefano. Category 3: a. Final approval of the completed manuscript: A. R. Kaufman, K. Quillen, A. G. Distefano, and J. M. Sloan. REFERENCES 1. Na’ara S, Amit M, Gil Z, Billan S. Plasmacytoma of the skull base: a meta-analysis. J Neurol Surg Part B Skull Base 2016;77:61–65. 2. Movsas TZ, Balcer LJ, Eggenberger ER, Hess JL, Galetta SL. Sixth nerve palsy as a presenting sign of intracranial plasmacytoma and multiple myeloma. J Neuroophthalmol 2000;20:242–245. 3. Rahman EZ, Barros Palau AE, Morgan ML, Lee AG. Neuroophthalmic presentations of clival plasmacytoma. Can J Ophthalmol. 2016;51:e49–e53. 4. Patel SV, Mutyala S, Leske DA, Hodge DO, Holmes JM. Incidence, associations, and evaluation of sixth nerve palsy using a population-based method. Ophthalmology 2004;111:369–375. 5. Lee J, Kulubya E, Pressman BD, Mamelak A, Bannykh S, Zada G, Cooper D. Sellar and clival plasmacytomas: case series of 5 patients with systematic review of 65 published cases. Pituitary 2017;20:381–392. Kaufman et al: J Neuro-Ophthalmol 2021; 41: e77-e78 Copyright © North American Neuro-Ophthalmology Society. Unauthorized reproduction of this article is prohibited.