Advertisement

Neuro-ophthalmic presentations of clival plasmacytoma

      Neurologically isolated cranial mononeuropathy (e.g., sixth nerve palsy) leading to diplopia is a common presentation to ophthalmologists. Although rare, clival lesions can cause isolated unilateral or bilateral abducens palsies with or without papilledema. Intracranial plasmacytomas (ICPC) are rare tumours that constitute less than 1% of intracranial neoplasms. They may present as a solitary plasmacytoma or may be part of a systemic malignant plasmacytosis, as in multiple myeloma (MM).
      We describe 2 novel cases of ICPC presenting with abducens nerve palsies. The first patient had previously treated MM, but developed new binocular diplopia with fluid and decreased hearing in the right ear. The second patient presented with bilateral abducens palsies and associated right-sided V2 hypothesia and subsequently was diagnosed with both clival plasmacytoma and MM.
      A 59-year-old African-American female presented with a 3-week history of horizontal binocular diplopia. She also had a headache and “fluid sensation” in her right ear causing mild hearing loss. Her medical history included MM successfully treated with chemotherapy 3 years ago, well-controlled hypertension, and hypothyroidism. Surgical history included spinal surgery and knee replacement for degenerative joint disease 8 years previously. She denied any drug allergies and was taking levothyroxine, amlodipine, amoxicillin, and low-dose prednisone. She denied alcohol, tobacco, or drug use. Her family history was significant for colon cancer in her sister, and diabetes, hypertension, and stroke in her father. Review of systems was otherwise negative. On neuro-ophthalmic examination, best corrected visual acuity (BCVA) was 20/25 OD and 20/20-2 OS. Ishihara colour plates were 14/14 OU. Humphrey automated visual fields were within normal limits OU. Pupils measured 4 mm in dark and 2 mm in light, and no relative afferent pupillary defect (RAPD) was noted. Intraocular pressure measured 19 mm Hg OU. There was no disk edema or pallor. Her ocular motility showed a −4 deficit of abduction OD. She had an incomitant 30 prism diopter (PD) esotropia (ET) in primary gaze, which increased in right gaze and decreased in left gaze. The remainder of her ophthalmologic examination was unremarkable.
      Magnetic resonance imaging (MRI) of the brain with and without contrast showed a large enhancing lesion centred in the clivus measuring 3.2 × 1.9 × 3.1 cm (Fig. 1). The mass invaded the right cavernous sinus and extended through the posterior table of the sphenoid sinus on the right with invasion of the sellar floor and superior displacement of the pituitary gland. Heterogeneous enhancement throughout the calvarium was suspicious for infiltration, and a biopsy showed ICPC. Immunohistochemistry stained positive for CD38, CD138, CD56, and antilambda. Bone marrow biopsy showed 49% lambda light chain–restricted plasma cells consistent with plasma cell myeloma. The eye was patched for symptomatic relief, and she was treated with radiation therapy and bortezomib.
      Figure thumbnail gr1
      Fig. 1Magnetic resonance imaging of clival plasmacytoma, case 1. Images demonstrate the heterogeneously enhancing clival-based mass with extension into the right cavernous sinus. T1 axial precontrast (A) and postcontrast (B), sagital postcontrast (C), and coronal postcontrast (D).
      An 84-year-old female presented with headache, blurry vision, and progressive binocular horizontal diplopia over 2 weeks. Her medical history was significant for stroke, hypertension, coronary artery disease, congestive heart failure, aortic aneurysm, thyroidectomy, recent acute kidney injury, renal cysts, angiomyolipoma, hiatal hernia, gastrointestinal bleeding, multiple gastric polyps, and diverticulosis. Surgical history included coronary stenting and cholecystectomy. She denied any drug allergies and was on amlodipine, atorvastatin, carvedilol, dexlansoprazole, furosemide, meloxicam, potassium, and ranolazine. She denied tobacco, alcohol, and illicit drug use. Her family history was significant for fatal abdominal cancer in her mother and fatal cerebral aneurysm in her father. On neuro-ophthalmic examination, the visual acuity was 20/60 OD and 20/25 OS. Pupils were symmetric in light and dark without anisocoria or RAPD. Intraocular pressure measurements were 13 mm Hg OU. There was no disk edema or pallor. There was a 50 PD ET in primary position, which increased in both right and left gazes. Motility showed −4 abduction deficits bilaterally. The remainder of her ophthalmologic examination was unremarkable.
      Sensation to pinprick was decreased in the right V2 distribution. Findings were consistent with a bilateral abducens palsy and right V2 anaesthesia. MRI revealed a 3 × 4 × 6-cm clival mass extending into the sphenoid and posterior ethmoid sinuses (Fig. 2). Trans-sphenoidal biopsy showed abundant pleomorphic plasma cells in a hemorrhagic background with occasional Dutcher and Russell bodies, and immunohistochemical staining for CD138 and lambda light chain were diffusely and strongly positive, consistent with plasmacytoma. Bone marrow biopsy showed lambda-restricted, immunophenotypic aberrant monotypic plasma cells comprising 19% of the total cellularity. Findings suggested hyperdiploid MM. The patient was started on radiation therapy and bortezomib. She suffered from a fatal cardiorespiratory arrest during her hospitalization.
      Figure thumbnail gr2
      Fig. 2Magnetic resonance imaging of clival plasmacytoma, case 2. Images show the large heterogeneously enhancing clival mass with greater involvement of the left than right cavernous sinuses. T1 axial postcontrast (A), coronal postcontrast (B), sagital precontrast (C), and sagital postcontrast (D).
      Clival masses may often be differentiated clinically and radiographically by location. Lesions may arise from the skull base itself (e.g., plasmacytoma, chordoma, chondrosarcoma, neuroenteric cysts, intraosseous lymphoma, and metastasis); the intracranial compartment with secondary contiguous involvement of the clivus (e.g., meningioma, craniopharyngioma, and pituitary macroademoma); or from the adjacent sinuses (e.g., nasopharyngeal carcinomas, mucoceles, or squamous cell carcinomas). Cranial nerve palsies have been identified in a subset of these skull base pathologies. Chordoma, chondroma, and chondrosarcoma have all been reported to produce sixth nerve palsy, and in some of these cases the diplopia spontaneously resolved.
      • Takoudes T.G.
      • Haddad J.
      • Feldstein N.A.
      Pediatric ethmoid chondroma incidentally found during evaluation of a third cranial nerve palsy.
      • Frassanito P.
      • Massimi L.
      • Rigante M.
      • et al.
      Recurrent and self-remitting sixth cranial nerve palsy: pathophysiological insight from skull base chondrosarcoma.
      • Harada T.
      • Ohashi T.
      • Ohki K.
      • et al.
      Clival chordoma presenting as acute esotropia due to bilateral abducens palsy.
      • Volpe N.J.
      • Liebsch N.J.
      • Munzenrider J.E.
      • Lessell S.
      Neuro-ophthalmologic findings in chordoma and chondrosarcoma of the skull base.
      • Desjardins L.
      • Maudet J.M.
      • Banchereau A.
      • Pierre-Kahn A.
      • Habrand J.L.
      • Putterman M.
      Eye manifestations and treatment of brain chordoma. Apropos of a case. [Article in French].
      • Watson D.
      • Smith D.R.
      Chondroid chordoma: case report and literature review.
      • Galetta S.L.
      • Smith J.L.
      Chronic isolated sixth nerve palsies.
      • Takahashi T.
      • Asai T.
      • Isayama Y.
      • Tamaki N.
      • Matsumoto S.
      Chordoma.
      The clinical presentations for these lesions varied from isolated sixth nerve palsy to sixth nerve palsy in association with headache, diplopia, facial numbness, and papilledema.
      • Harada T.
      • Ohashi T.
      • Ohki K.
      • et al.
      Clival chordoma presenting as acute esotropia due to bilateral abducens palsy.
      • Volpe N.J.
      • Liebsch N.J.
      • Munzenrider J.E.
      • Lessell S.
      Neuro-ophthalmologic findings in chordoma and chondrosarcoma of the skull base.
      • Desjardins L.
      • Maudet J.M.
      • Banchereau A.
      • Pierre-Kahn A.
      • Habrand J.L.
      • Putterman M.
      Eye manifestations and treatment of brain chordoma. Apropos of a case. [Article in French].
      • Watson D.
      • Smith D.R.
      Chondroid chordoma: case report and literature review.
      • Galetta S.L.
      • Smith J.L.
      Chronic isolated sixth nerve palsies.
      • Takahashi T.
      • Asai T.
      • Isayama Y.
      • Tamaki N.
      • Matsumoto S.
      Chordoma.
      It is often difficult to distinguish primary clival lesions (e.g., chordoma) from plasmacytoma, but chordomas typically occur in younger patients, whereas plasmacytomas are more prevalent in the elderly population. The presence of MM can also suggest the diagnosis of plasmacytoma. Although both plasmacytoma and chordomas extend from the clivus, the tumors may often be distinguished from imaging. A single trabeculated expansile lytic lesion accompanied by cortical thinning and destruction in the absence of sclerotic reactions is the hallmark of clival plasmacytoma. On computed tomography scan, an expansile lytic lesion with a thin cortex is similarly observable.
      • Ooi G.C.
      • Chim J.C.
      • Au W.Y.
      • Khong P.L.
      Radiologic manifestations of primary solitary extramedullary and multiple solitary plasmacytomas.
      On MRI, a curvilinear low-intensity signal resembling sulci may be noted within the lesion. This finding has high specificity for plasmacytoma and may obviate the need for biopsy especially in patients with known systemic disease.
      • Major N.M.
      • Helms C.A.
      • Richardson W.J.
      The “mini brain”: plasmacytoma in a vertebral body on MR imaging.
      On MRI T2-weighted images, the plasmacytoma lesions are isointense to hyperintense, whereas chordomas demonstrate a high T2 signal.
      • Brown R.V.
      • Sage M.R.
      • CT Brophy BP.
      and MR findings in patients with chordomas of the petrous apex.
      Nevertheless, some patients still require tissue biopsy and histologic and immunohistochemical confirmation of the diagnosis.
      To our knowledge, these cases represent distinct presentations of ICPC. Our first patient presented with fluid in the ear, decreased hearing, and a new sixth nerve palsy after successful treatment for MM. Our second patient presented with V2 hypothesia and new onset bilateral sixth nerve palsy without a prior MM diagnosis. Two prior cases of plasmacytoma involving trigeminal parasthesias have been reported
      • Ustuner Z.
      • Basaran M.
      • Kiris T.
      • et al.
      Skull base plasmacytoma in a patient with light chain myeloma.
      • Wein R.O.
      • Popat S.R.
      • Doerr T.D.
      • Dutcher P.O.
      Plasma cell tumors of the skull base: four case reports and literature review.
      ; however, neither of these cases reported concurrence with bilateral sixth nerve palsy. ICPC as the underlying cause of sixth nerve palsy is uncommon, but at least 26 prior clival plasmacytoma cases presented with diplopia.
      • Campisi P.
      • Frenkiel S.
      • Glikstein R.
      • Mohr G.
      Unilateral sixth cranial nerve palsy caused by skull base mass lesions: case series.
      • Schwartz T.H.
      • Rhiew R.
      • Isaacson S.R.
      • Orazi A.
      • Bruce J.N.
      Association between intracranial plasmacytoma and multiple myeloma: clinicopathological outcome study.
      • Movsas T.Z.
      • Balcer L.J.
      • Eggenberger E.R.
      • Hess J.L.
      • Galetta S.L.
      Sixth nerve palsy as presenting sign of intracranial plasmacytoma and multiple myeloma.
      • Nofsinger Y.C.
      • Mirza N.
      • Rowan P.T.
      • Lanza D.
      • Weinstein G.
      Head and neck manifestations of plasma cell neoplasms.
      • Bindal A.K.
      • Bindal R.K.
      • van Loveren H.
      • Sawaya R.
      Management of intracranial plasmacytoma.
      • Liu Z.
      • Qi X.
      • Wu X.
      • Luo C.
      • Lu Y.
      Solitary intracranial plasmacytoma located in the spheno-clival region mimicking chordoma: a case report.
      • Yamaguchi S.
      • Terasaka S.
      • Ando S.
      • Shinohara T.
      • Iwasaki Y.
      Neoadjuvant therapy in a patient with clival plasmacytoma associated with multiple myeloma: a case report.
      • Montalban C.
      • Martín-Aresti J.
      • Patier J.L.
      • Martínes-San Millan J.
      • Garcia Cosio M.
      Unusual cases in multiple myeloma and a dramatic response in metastatic lung cancer: case 3. Intracranial plasmacytoma with cranial nerve neuropathy in multiple myeloma.
      • Brannan S.O.
      • Matthews B.N.
      • Savant V.
      • Brown R.D.
      • Matthews T.D.
      Solitary intracranial extra-osseous plasmacytoma presenting with ophthalmic signs.
      • Higurashi M.
      • Yagishita S.
      • Fujitsu K.
      • Kitsuta Y.
      • Takemoto Y.
      • Osano S.
      Plasma cell myeloma of the skull base: report of two cases.
      • Kloecker G.H.
      • Kannan C.R.
      • Laber D.A.
      Brain stem and clivus plasmacytoma.
      • Oishi T.
      • Kasai H.
      • Sakurai Y.
      • Kawamoto K.
      Extramedullary plasmacytoma extensively affecting the sella turcica and paranasal sinuses.
      Of these 26 cases, 2 reported bilateral abducens nerve palsies.
      • Brannan S.O.
      • Matthews B.N.
      • Savant V.
      • Brown R.D.
      • Matthews T.D.
      Solitary intracranial extra-osseous plasmacytoma presenting with ophthalmic signs.
      • Higurashi M.
      • Yagishita S.
      • Fujitsu K.
      • Kitsuta Y.
      • Takemoto Y.
      • Osano S.
      Plasma cell myeloma of the skull base: report of two cases.
      ICPC presentation may vary depending on the involved site. Raised intracranial pressure leading to papilledema, confusion, cranial nerve palsies, and seizures is sometimes observed in skull base lesions. These ICPC lesions have a high rate of progression to MM and a significantly worse prognosis than extramedullary plasmacytomas.
      • Bindal A.K.
      • Bindal R.K.
      • van Loveren H.
      • Sawaya R.
      Management of intracranial plasmacytoma.
      • Corwin J.
      • Lindberg R.D.
      Solitary plasmacytomas of bone vs. extramedullary plasmacytoma and their relationship to multiple myeloma.
      The rate of progression in these lesions may be as high as 50% with a variable 10-year survival rate ranging from 16% to 100%.
      • Schwartz T.H.
      • Rhiew R.
      • Isaacson S.R.
      • Orazi A.
      • Bruce J.N.
      Association between intracranial plasmacytoma and multiple myeloma: clinicopathological outcome study.
      • Nofsinger Y.C.
      • Mirza N.
      • Rowan P.T.
      • Lanza D.
      • Weinstein G.
      Head and neck manifestations of plasma cell neoplasms.
      Systemic surveillance is generally recommended for at least 1 year after discovery of ICPC for the possible development of MM.
      • Schwartz T.H.
      • Rhiew R.
      • Isaacson S.R.
      • Orazi A.
      • Bruce J.N.
      Association between intracranial plasmacytoma and multiple myeloma: clinicopathological outcome study.
      Fifteen (62.5%) of the 26 clival plasmacytoma cases harboured underlying MM,
      • Campisi P.
      • Frenkiel S.
      • Glikstein R.
      • Mohr G.
      Unilateral sixth cranial nerve palsy caused by skull base mass lesions: case series.
      • Schwartz T.H.
      • Rhiew R.
      • Isaacson S.R.
      • Orazi A.
      • Bruce J.N.
      Association between intracranial plasmacytoma and multiple myeloma: clinicopathological outcome study.
      • Movsas T.Z.
      • Balcer L.J.
      • Eggenberger E.R.
      • Hess J.L.
      • Galetta S.L.
      Sixth nerve palsy as presenting sign of intracranial plasmacytoma and multiple myeloma.
      • Nofsinger Y.C.
      • Mirza N.
      • Rowan P.T.
      • Lanza D.
      • Weinstein G.
      Head and neck manifestations of plasma cell neoplasms.
      • Bindal A.K.
      • Bindal R.K.
      • van Loveren H.
      • Sawaya R.
      Management of intracranial plasmacytoma.
      • Liu Z.
      • Qi X.
      • Wu X.
      • Luo C.
      • Lu Y.
      Solitary intracranial plasmacytoma located in the spheno-clival region mimicking chordoma: a case report.
      • Yamaguchi S.
      • Terasaka S.
      • Ando S.
      • Shinohara T.
      • Iwasaki Y.
      Neoadjuvant therapy in a patient with clival plasmacytoma associated with multiple myeloma: a case report.
      • Montalban C.
      • Martín-Aresti J.
      • Patier J.L.
      • Martínes-San Millan J.
      • Garcia Cosio M.
      Unusual cases in multiple myeloma and a dramatic response in metastatic lung cancer: case 3. Intracranial plasmacytoma with cranial nerve neuropathy in multiple myeloma.
      • Brannan S.O.
      • Matthews B.N.
      • Savant V.
      • Brown R.D.
      • Matthews T.D.
      Solitary intracranial extra-osseous plasmacytoma presenting with ophthalmic signs.
      • Higurashi M.
      • Yagishita S.
      • Fujitsu K.
      • Kitsuta Y.
      • Takemoto Y.
      • Osano S.
      Plasma cell myeloma of the skull base: report of two cases.
      as was also described in our second case. Although our second patient had multiple vasculopathic risk factors and no history of neoplasm, the atypical findings prompted neuroimaging. Clinicians should be aware that, although a sixth nerve palsy may be ischemic in a vasculopathic patient, neuroimaging may be warranted in patients with lack of improvement or progression over time, other neurologic signs/symptoms (nonisolated), bilateral involvement, or lack of vasculopathic risk factors. ICPC should especially be considered in patients with a prior diagnosis of MM.

      Disclosure

      The authors have no proprietary or commercial interest in any materials discussed in this article.

      References

        • Takoudes T.G.
        • Haddad J.
        • Feldstein N.A.
        Pediatric ethmoid chondroma incidentally found during evaluation of a third cranial nerve palsy.
        Ann Otol Rhinol Laryngol. 1999; 108: 1177-1180
        • Frassanito P.
        • Massimi L.
        • Rigante M.
        • et al.
        Recurrent and self-remitting sixth cranial nerve palsy: pathophysiological insight from skull base chondrosarcoma.
        J Neurosurg Pediatr. 2013; 12: 633-636
        • Harada T.
        • Ohashi T.
        • Ohki K.
        • et al.
        Clival chordoma presenting as acute esotropia due to bilateral abducens palsy.
        Ophthalmologica. 1997; 211: 109-111
        • Volpe N.J.
        • Liebsch N.J.
        • Munzenrider J.E.
        • Lessell S.
        Neuro-ophthalmologic findings in chordoma and chondrosarcoma of the skull base.
        Am J Ophthalmol. 1993; 115: 97-104
        • Desjardins L.
        • Maudet J.M.
        • Banchereau A.
        • Pierre-Kahn A.
        • Habrand J.L.
        • Putterman M.
        Eye manifestations and treatment of brain chordoma. Apropos of a case. [Article in French].
        J Fr Ophtalmol. 1992; 15: 423-429
        • Watson D.
        • Smith D.R.
        Chondroid chordoma: case report and literature review.
        Indiana Med. 1991; 84: 18-21
        • Galetta S.L.
        • Smith J.L.
        Chronic isolated sixth nerve palsies.
        Arch Neurol. 1989; 46: 79-82
        • Takahashi T.
        • Asai T.
        • Isayama Y.
        • Tamaki N.
        • Matsumoto S.
        Chordoma.
        J Clin Neuroophthalmol. 1983; 3: 251-257
        • Ooi G.C.
        • Chim J.C.
        • Au W.Y.
        • Khong P.L.
        Radiologic manifestations of primary solitary extramedullary and multiple solitary plasmacytomas.
        Am J Roentgenol. 2006; 186: 821-827
        • Major N.M.
        • Helms C.A.
        • Richardson W.J.
        The “mini brain”: plasmacytoma in a vertebral body on MR imaging.
        Am J Roentgenol. 2000; 175: 261-263
        • Brown R.V.
        • Sage M.R.
        • CT Brophy BP.
        and MR findings in patients with chordomas of the petrous apex.
        Am J Neuroradiol. 1990; 11: 121-124
        • Ustuner Z.
        • Basaran M.
        • Kiris T.
        • et al.
        Skull base plasmacytoma in a patient with light chain myeloma.
        Skull Base. 2003; 13: 167-171
        • Wein R.O.
        • Popat S.R.
        • Doerr T.D.
        • Dutcher P.O.
        Plasma cell tumors of the skull base: four case reports and literature review.
        Skull Base. 2002; 12: 77-86
        • Campisi P.
        • Frenkiel S.
        • Glikstein R.
        • Mohr G.
        Unilateral sixth cranial nerve palsy caused by skull base mass lesions: case series.
        J Otolaryngol. 2001; 30: 184-186
        • Schwartz T.H.
        • Rhiew R.
        • Isaacson S.R.
        • Orazi A.
        • Bruce J.N.
        Association between intracranial plasmacytoma and multiple myeloma: clinicopathological outcome study.
        Neurosurgery. 2001; 49 (discussion 1044–5): 1039-1044
        • Movsas T.Z.
        • Balcer L.J.
        • Eggenberger E.R.
        • Hess J.L.
        • Galetta S.L.
        Sixth nerve palsy as presenting sign of intracranial plasmacytoma and multiple myeloma.
        J Neuroophthalmol. 2000; 20: 242-245
        • Nofsinger Y.C.
        • Mirza N.
        • Rowan P.T.
        • Lanza D.
        • Weinstein G.
        Head and neck manifestations of plasma cell neoplasms.
        Laryngoscope. 1997; 107: 741-746
        • Bindal A.K.
        • Bindal R.K.
        • van Loveren H.
        • Sawaya R.
        Management of intracranial plasmacytoma.
        J Neurosurg. 1995; 83: 218-221
        • Liu Z.
        • Qi X.
        • Wu X.
        • Luo C.
        • Lu Y.
        Solitary intracranial plasmacytoma located in the spheno-clival region mimicking chordoma: a case report.
        J Int Med Res. 2010; 38: 1868-1875
        • Yamaguchi S.
        • Terasaka S.
        • Ando S.
        • Shinohara T.
        • Iwasaki Y.
        Neoadjuvant therapy in a patient with clival plasmacytoma associated with multiple myeloma: a case report.
        Surg Neurol. 2008; 70: 403-407
        • Montalban C.
        • Martín-Aresti J.
        • Patier J.L.
        • Martínes-San Millan J.
        • Garcia Cosio M.
        Unusual cases in multiple myeloma and a dramatic response in metastatic lung cancer: case 3. Intracranial plasmacytoma with cranial nerve neuropathy in multiple myeloma.
        J Clin Oncol. 2005; 23: 233-235
        • Brannan S.O.
        • Matthews B.N.
        • Savant V.
        • Brown R.D.
        • Matthews T.D.
        Solitary intracranial extra-osseous plasmacytoma presenting with ophthalmic signs.
        J Neuroophthalmol. 2003; 23: 268-271
        • Higurashi M.
        • Yagishita S.
        • Fujitsu K.
        • Kitsuta Y.
        • Takemoto Y.
        • Osano S.
        Plasma cell myeloma of the skull base: report of two cases.
        Brain Tumor Pathol. 2004; 21: 135-141
        • Kloecker G.H.
        • Kannan C.R.
        • Laber D.A.
        Brain stem and clivus plasmacytoma.
        Am J Med Sci. 2008; 336: 503
        • Oishi T.
        • Kasai H.
        • Sakurai Y.
        • Kawamoto K.
        Extramedullary plasmacytoma extensively affecting the sella turcica and paranasal sinuses.
        Clin Neuropathol. 2006; 25: 44-47
        • Corwin J.
        • Lindberg R.D.
        Solitary plasmacytomas of bone vs. extramedullary plasmacytoma and their relationship to multiple myeloma.
        Cancer. 1979; 43: 1007-1013