POEMS syndrome associated with plasmacytoma of the clivus: "Time discovers the truth".

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is characterized by the presence of a monoclonal plasma cell disorder, peripheral neuropathy, and one or more of the following features: Osteosclerotic myeloma, Castleman's disease (angiofollicular lymph node hyperplasia), increased levels of serum vascular endothelial growth factor (VEGF), organomegaly, endocrinopathy, edema, typical skin changes, and papilledema. [1] Solitary plasmacytomas most frequently occur in the bone but can also be found in soft tissues (extramedullary plasmacytoma). [2] We report a case that showed a rare association of POEMS syndrome with a plasmacytoma of the clivus.

Introduction

Polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome is characterized by the presence of a monoclonal plasma cell disorder, peripheral neuropathy, and one or more of the following features: Osteosclerotic myeloma, Castleman's disease (angiofollicular lymph node hyperplasia), increased levels of serum vascular endothelial growth factor (VEGF), organomegaly, endocrinopathy, edema, typical skin changes, and papilledema.[1] Solitary plasmacytomas most frequently occur in the bone but can also be found in soft tissues (extramedullary plasmacytoma).[2] We report a case that showed a rare association of POEMS syndrome with plasmacytoma of the clivus.

Case Report

A 31-year-old male presented with a 6-months complaint of numbness and pain in both feet. He also had a clinical history of skin darkening all over his body, loss of appetite with resultant weight loss (>10% of body weight), night sweats, and intermittent low grade fever. He did not have any other comorbidities.

On physical examination, his vital signs were found to be normal and hyperpigmentation was noted over his face, arms, and legs. He had cervical and axillary lymphadenopathy, hepatosplenomegaly, diminished sensation in both the feet, and absent ankle reflexes bilaterally. Laboratory testing on the patient revealed an erythrocyte sedimentation rate (ESR) of 60 mm/h, normal liver and renal functions, elevated thyroid-stimulating hormone (TSH), that is, 7.8 mIU/L (normal range: 0.5-5.0 mIU/L), and low serum cortisol, that is, 3.82 μg/dL at 8 am (normal range: 4.3-22.4 μg/dL). Nerve conduction studies were suggestive of severe sensory motor neuropathy in both the lower extremities. Enzyme-linked immunosorbent assay (ELISA) for human immunodeficiency virus (HIV) and hepatitis viruses and antinuclear antibody (ANA) testing were negative. Excisional biopsy of an axillary node showed hyalinized germinal centers, mantle zone hyperplasia, and interfollicular plasma cells, suggestive of Castleman's disease [Figure 1].

Figure 1

Germinal center with hyalinized blood vessels and mantle zone hyperplasia

Serum and urine immunofixation electrophoresis test did not reveal any monoclonal proteins. The results of bone marrow aspiration and biopsy were found to be within normal limits. Skeletal survey was negative.

Nerve biopsy of the patient was performed at an outside facility, and it showed features of inflammatory neuropathy. Hence, he was started on azathioprine along with steroids for possible chronic inflammatory demyelinating polyneuropathy. Six months later, the patient presented with headaches and diplopia. Magnetic resonance image (MRI) of the brain at this time showed a well-defined oval smooth tissue mass lesion measuring 3.6 × 2.7 cm arising from the clivus with moderate heterogeneous contrast enhancement. No mass effect was noted [Figure 2]. Acute infarcts were seen in the right hemisphere, secondary to distortion and compression of the right internal carotid artery [cavernous segment] by the lesion. He underwent binasal endoscopic biopsy and decompression of the clival tumor, confirming a plasmacytoma. Repeat serum protein electrophoresis (SPEP) showed an immunoglobulin G (IgG) lambda (λ) M-spike. Serum free light chains showed a mildly elevated kappa (κ) (25.93 mg/L, normal range: 3.30-19.40 mg/L) and λ free light chain (26.99 mg/L, normal range: 5.71-26.30 mg/L) and normal ratio (0.96, normal range: 0.26-1.65). He continued to have normal renal and liver functions. Complete blood count with differentials did not show any thrombocytosis or erythrocytosis and no other cytopenias were noted.

Figure 2

Panel A. T1-weighted images showing a clival lesion. Panel B. Sagittal T1 postcontrast image showing lesion enhancement. Panel C. Axial T1 postcontrast image showing the clival lesion and displacement of the right internal carotid artery (ICA). Panel D. Diffusion-weighted magnetic resonance imaging (DW-MRI) showing multiple right hemispheric infarcts

Based on the presence of peripheral neuropathy, endocrinopathies, hyperpigmentation, λ restricted monoclonal protein (on SPEP and clivus plasmacytoma), and Castleman's disease, a diagnosis of POEMS syndrome was made. The patient was initially treated with limited radiation to the clivus plasmacytoma and was then treated systemically with melphalan and prednisone.

Discussion

POEMS syndrome, also known as Takatsuki syndrome or osteosclerotic myeloma, is a rare paraneoplastic syndrome arising from an underlying plasma cell disorder. The exact incidence is unknown. As with other plasma cell dyscrasias, POEMS syndrome commonly presents in the fifth to sixth decade. Nevertheless, 30% of the patients with this disorder may be younger than 45 years.[1] Our patient also falls into this category.

The diagnosis of POEMS syndrome is made based on a composite of clinical and laboratory features. The constellation of neuropathy and any of the following should elicit an in-depth patient evaluation for possible POEMS: A λ restricted monoclonal protein, thrombocytosis, anasarca, or papilledema. Castleman's disease or Castleman-like histology is found in 11-30% of patients with POEMS syndrome who have a documented plasma cell disorder.[134]

Solitary intracranial plasmacytomas are rare.[5] To date, there are very few cases of solitary clival plasmacytoma reported in the literature.[67] Ours is probably the first case of POEMS syndrome associated with a plasmacytoma of the clivus. In some cases, plasmacytoma precedes the development of POEMS syndrome but in this case it was the reverse.[8]

Due to the lack of randomized clinical trials, treatment recommendations are based on case series and anecdotal evidence. The course of POEMS syndrome is usually chronic, with a median patient survival time of nearly 14 years.[19] Only fingernail clubbing, extravascular volume overload (effusions, edema, and ascites), and respiratory symptoms have been associated with a significantly shorter overall survival.

In this case, the diagnosis was delayed as initial studies including a bone marrow biopsy were negative for a monoclonal protein. The presence of a monoclonal protein is required to make the diagnosis of POEMS syndrome. This is a low “tumor” burden disease and in 15% of the cases, monoclonal proteins may not be detected by immunofixation electrophoresis. In the study conducted by Dispenzieri et al., only 88% of the patients had a monoclonal protein in the serum and/or urine[1] and the magnitude of serum monoclonal protein may be very small. Serum protein electrophoresis is normal in one-fourth of the patients, and some patients can have a pattern suggesting the presence of a polyclonal gammopathy. In these patients, the monoclonal protein can be overlooked if immunofixation electrophoresis is omitted. A random bone marrow examination is often nondiagnostic, showing a hypercellular, “reactive-appearing,” or normal-appearing marrow. Less than 15% of the patients have a bone marrow plasmacytosis of greater than 10%.[13] In this setting of high clinical suspicion of POEMS syndrome, we suggest repeat testing after 3-6 months for monoclonal protein with serum and urine immunofixation electrophoresis and serum free light chains to ensure that the pure light chain disease is not missed.

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Conflict of interest

There are no conflicts of interest.