POEMS syndrome with undetectable M-protein: a case report and literature review

Abstract

Background: Polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes (POEMS) syndrome is a rare plasma cell (PC) neoplasm with associated paraneoplastic syndrome. According to the current diagnostic criteria, peripheral polyneuropathy and monoclonal PC proliferative disorder represent two mandatory criteria.

Case presentation: We report a 54-year-old male with peripheral neuropathy of bilateral lower limbs, sclerotic bone lesions, elevated vascular endothelial growth factor (VEGF) levels, splenomegaly, extravascular volume overload, endocrinopathy, and skin hemangiomas. Of note, serum and urine protein electrophoresis (PEP) and immunofixation electrophoresis (IFE) of this patient indicated undetectable M-protein and the normal ratio of free light chains κ and λ (FLC-R (κ/λ)). No monoclonal PCs were found in bone marrow examinations or biopsy of diseased bones. However, his clinical manifestations matched most of the diagnostic criteria. After excluding other diseases that are easily confused with POEMS syndrome, the diagnosis of variant POEMS syndrome with undetectable M-protein was proposed. The patient obtained clinically significant improvement and elevated VEGF returned to normal after 6 months of treatment with lenalidomide plus dexamethasone.

Conclusions: Monoclonal PC dyscrasia (M-protein) while being a mandatory criterion for POEMS syndrome is undetectable in a considerable amount of patients that otherwise demonstrate typical symptoms. Here, we reported a case of variant POEMS syndrome with featured clinical manifestations, elevated VEGF levels, and good response to therapies targeting PCs but no evidence of M-protein. Therefore, negative results in M-protein and monoclonal PCs aren't enough to reject the diagnosis of POEMS syndrome. It is imperative to recognize the variant form of POEMS syndrome.

Keywords: Diagnosis; M-protein; POEMS syndrome; Plasma cell.

Fig. 1

The results of the patient’s physical examination. (A) Breast protrusion on both sides could be seen through visual examination and CT; (B) Hemangiomas could be seen in the anterior chest and back; (C) The patient had concave edema in bilateral lower limbs. Abbreviations: CT: Computed Tomography

Fig. 2

The results of the patient’s serum IFE and urine BJP electrophoresis. (A) No abnormal monoclonal bands were found in IgA, IgG, IgM, κ and λ swimming lanes in serum IFE; (B) No abnormal monoclonal bands were found in IgD, IgE, κ and λ swimming lanes in serum IFE; (C) No abnormal monoclonal bands were found in swimming lanes in urine BJP electrophoresis and BJP was negative. Abbreviations: IFE: immunofixation electrophoresis; BJP: Bence-Jones protein; ELP: electrophoresis; GAM: IgG, IgA, and IgM; G: IgG; A: IgA; M: IgM; D: IgD; E: IgE; κ: κ chain; λ: λ chain; κf: free κ chain; λf: free λ chain

Fig. 3

The results of bone scintigraphy with [99mTc]-MDP SPECT/CT. (A) Three hours after intravenous injection of the imaging agent, bone scintigraphy revealed enhanced bone metabolism in multiple parts of the body. The local SPECT/CT fusion images showed the coexistence of osteogenic and osteolytic bone destruction of (B) bilateral iliac crest, and (C) vertebrae and ribs. Abbreviations: MDP SPECT/CT: methylene-diphosphonate Single Photon Emission Computed Tomography/Computed Tomography; R: right; L: left; ANT: anterior; POST: posterior

Fig. 4

The results of BM biopsy. We selected one piece of gray-yellow tissue with a volume of 1.50 cm×0.20 cm×0.20 cm. Under the microscope, (A) (original magnification×40) and (B) (original magnification×100) showed that there was no increase in immature cells and PCs. Reticular fiber staining was scored MF-1. Abbreviations: BM: bone marrow; cm: centimeter; PC: plasma cell; MF: myelofibrosis

Fig. 5

The results of bone biopsy (Envision 10 × 10). A CT-guided biopsy of the posterior superior iliac spine was performed. (A) was the H&E stained image, which showed no significantly abnormal distribution of hematopoietic tissues, with a few mineralized bone tissues and BM. The immunohistochemical results revealed (B) Langerin (-), (C) CD138 (-), and (D) Ki67 (80% +). Abbreviations: CT: Computed Tomography; H&E: hematoxylin-eosin; BM: bone marrow