A rare cause of diplopia: Solitary extramedullary plasmacytoma of the skull base

Abstract

Diplopia is a common presenting complaint with a broad spectrum of differential diagnoses. Causative pathologies may affect the eye, extraocular muscles, neuromuscular junction, cranial nerves and central nervous system. Tumours, inflammatory and autoimmune conditions, vasculopathies and atypical infections are the most common underlying pathologies.

Solitary extramedullary plasmacytoma is a rare cause of diplopia. This case emphasises the importance of submucosal biopsies for diagnosis and early involvement of the multidisciplinary team. Moreover, we advocate a low threshold for a second opinion and further immunohistochemistry, particularly when there is diagnostic uncertainty with histological discordance.

Introduction

In the period between April 2018 and April 2019, 16,607 patients presented to English NHS trusts with diplopia.¹ Binocular diplopia is caused by pathologies that affect the extraocular muscles, neuromuscular junction, cranial nerves (III, IV and VI) and central nervous system. Differential diagnoses include tumours, inflammatory and autoimmune conditions, vascular conditions and atypical infections (Table 1).

Table 1.

List of differential diagnoses for binocular diplopia

Diagnosis	Description
Strabismus	Congenital and acquired
Trauma	Iatrogenic (following strabismus surgery) and non-iatrogenic
Tumour	Primary (intracranial and cranial) and metastatic (local and distant)
Vascular	Stroke and aneurysm (posterior cerebral and posterior communicating arteries)
Inflammatory	Giant cell arteritis, diabetic ophthalmoplegia and sarcoidosis
Infectious	Bacterial, viral and atypical (tuberculosis)
Cranial nerve palsy	Oculomotor nerve, trochlear nerve and abducens nerve
Autoimmune	Multiple sclerosis, granulomatosis with polyangiitis, myasthenia gravis, Graves’ disease

Solitary extramedullary plasmacytoma (SEP) is a rare plasma cell neoplasm. It is the least common of the plasma cell neoplasms, accounting for <5%.² However, 90% of these lesions are diagnosed in the head and neck region. Local treatment is effective for SEP and the prognosis is superior to other plasma cell neoplasms: multiple myeloma (MM) and solitary bone plasmacytoma.

We describe the case of a 67-year-old man with diplopia secondary to an isolated abducens nerve palsy. A skull base SEP was diagnosed after much difficulty. This case highlights the importance of submucosal biopsies, early multidisciplinary team (MDT) involvement and adopting a low threshold for further investigations, such as immunohistochemistry.

Case history

A 67-year-old man with a background of hypertension and diabetes mellitus type II was referred to our hospital with a five-day history of diplopia on right lateral gaze. There were no other systemic or worrying features and his baseline observations were normal. Examination elicited an isolated right abducens nerve palsy. Full blood count, urea and electrolytes, and C-reactive protein were all normal on admission.

Computed tomography (CT) of the head showed a hyperattenuating central skull base lesion (Fig 1). The lesion was uniformly T1 hypointense and STIR hyperintense on magnetic resonance imaging (MRI) with gadolinium (Fig 2).

Figure 1.

Axial and sagittal computed tomography of the head showing a hyperattenuating central skull base occupying lesion

A = anterior; I = inferior; L = left; P = posterior; R = right; S = superior

Figure 2.

Gadolinium enhanced coronal magnetic resonance imaging of the head showing uniformly T1 hypointense and STIR hyperintense lesion in the left sphenoid sinus, partially attached to the clivus

I = inferior; L = left; R = right; S = superior

The skull base MDT recommended a biopsy and CT of the chest/abdomen/pelvis to narrow the differential diagnoses (clival chordoma, chondrosarcoma or metastasis). The patient underwent examination under anaesthesia, wide sphenoidotomy and biopsy. A brownish mass was identified in the left sphenoid sinus, partially attached to the clivus.

Postoperatively, the patient recovered well and symptoms resolved. He remained asymptomatic at follow-up review and was informed that the biopsy demonstrated an organising haematoma (Fig 3).

Figure 3.

Haematoxylin and eosin stain of biopsy tissue showing sinonasal mucosa (upper right) and an organising haematoma

In view of the absence of risk factors for haematoma formation (notably anticoagulant use, recent surgery and trauma), the case was discussed again by the MDT. A three-month follow-up appointment with an interval MRI of the paranasal sinuses and a review of the histopathology (with further staining) were organised.

Immunohistochemistry revealed atypical plasma cells uniformly expressing CD56 in a membranous pattern (Fig 4a), suggestive of a neoplastic process. The atypical plasma cells expressed kappa light chain only (Figures 4b and 4c), excluding a reactive cause and suggesting a clonal process. A high proportion of the atypical plasma cells also expressed Ki-67, a marker of cell proliferation (Fig 4d).

Figure 4.

Immunohistochemistry slides (10x magnification) showing atypical plasma cells uniformly expressing CD56 in a membranous pattern (A); not expressing lambda (B); expressing kappa light chain (C); and expressing Ki-67 (D)

A revised diagnosis of SEP was made. The patient was informed of this at his three-month follow-up visit and CT of the chest/abdomen/pelvis showed no significant findings. The interval MRI of the paranasal sinuses demonstrated a less bulky, residual basioccipital component of the lesion, uniformly T1 hypointense and STIR hyperintense. The patient was referred to the myeloma MDT. A bone marrow biopsy and positron emission tomography CT were negative, confirming the diagnosis. The patient remains well and asymptomatic. A conservative management approach was adopted in view of this.

Discussion

Diplopia is a common presenting complaint. Binocular diplopia resolves on covering one eye and is due to pathologies affecting any extraocular level of the binocular visual pathway, from the extraocular muscles to the central nervous system. It is critical to elucidate red flag symptoms (sudden onset severe headache, focal neurology, fevers and signs of raised intracranial pressure) to exclude life threatening causes of binocular diplopia (Table 1).

SEP is a rare plasma cell neoplasm accounting for <1% of head and neck tumours.² The median age of onset is 55 years and it is 3 times more common in men.² It is characterised by a solitary, extraskeletal soft tissue mass consisting of monoclonal plasma cells. SEPs present with the signs and symptoms of tumour local pressure effects, and most commonly in the upper aerodigestive tract.² An isolated abducens nerve palsy secondary to SEP is incredibly rare despite 90% of the lesions arising in the head and neck region.² No similar cases were identified in a literature search of Embase™ (1946–2019) and MEDLINE^® (1946–2019), excluding non-English texts and using the search terms “solitary”, “extramedullary” and “plasmacytoma.”

Diagnosis relies on identifying atypical, neoplastic plasma cells on biopsy, and excluding the other features of MM and solitary bone plasmacytoma. Features of MM include bone marrow clonal plasma cells on biopsy, monoclonal antibodies in serum/urine, hypercalcaemia, renal dysfunction, anaemia and bone lesions on skeletal survey. The exclusion of MM during the workup is crucial as this affects both the treatment and prognosis. Prognosis is superior in SEP. Less than 30% of cases develop into MM and the ten-year survival rate is around 70%,² compared with 29% in MM.³ Follow-up review is therefore important in order to monitor disease progression to MM.

CT and MRI findings for SEP are non-specific but important to rule out other features of plasma cell neoplasms, for staging and for treatment planning. A deep biopsy is essential for the diagnosis as 80% of SEPs are submucosal.⁴ Figure 3 shows submucosal clusters and scattered atypical plasma cells demonstrating nuclear polymorphism. Other diagnostic histological features include monoclonal light chain restriction (kappa or lambda) and CD138 positive immunohistochemistry.

Management of SEP is with surgery or external beam radiotherapy. SEPs are very radiosensitive tumours, with the majority occurring in inaccessible areas in the head and neck, with associated morbidity after radical surgery. Local control rates range from 80% to 100% with radiotherapy alone, with local recurrence rates of <5% after radiotherapy.^2,5 Decision on treatment modality is dependent on many factors, most notably patient preference and MDT discussion. External beam radiotherapy is the first-line strategy, with radiotherapy also being advised in cases of incomplete surgical excision and local recurrence.²

Conclusions

SEP is an extremely rare cause of isolated abducens nerve palsy. This case demonstrates the importance of submucosal biopsies for diagnosis. We also advocate early MDT input, a low threshold for a second opinion and further immunohistochemistry when there is diagnostic uncertainty.