From Neuropathy to Neoplasm: Unraveling a Case of POEMS Syndrome

A 64-year-old male with type 2 diabetes mellitus (T2DM), hypothyroidism, hypogonadism, diastolic heart failure, and complete heart block presented to the emergency department for worsening bilateral lower extremity (BLE) weakness and neuropathy over the past six months. Despite evaluation by his PCP and neurologist, no clear explanation had been found. An outpatient electromyogram was reportedly concerning for chronic inflammatory demyelinating polyneuropathy; however, a recent 5-day course of intravenous immunoglobulin (IVIG) therapy was ineffective.

Additional history noted a 25-pound unintentional weight loss over 3 months and new diagnoses of T2DM, hypothyroidism, and hypogonadism within the past 6-18 months. He also reported bilateral upper extremity numbness. Further review noted a 3 year history of a T8 vertebral lytic bony lesion on CT imaging and a nuclear medicine bone scan 6 months prior to this presentation revealing a low-grade uptake pattern without extraneous lesions. A follow up CT scan completed just 1 week prior showed enlargement of the T8 lytic lesion with extension into T7 and T9 with well-defined, sclerotic margins. No further workup had been done to this point.

Initial labs were unremarkable, with no signs of anemia or electrolyte derangements. On examination, the patient demonstrated BLE weakness with decreased sensation, bilateral hand weakness, absent bilateral Achilles, patellar, and biceps tendons reflexes, 1+ BLE edema, hypertrichosis, right inguinal lymphadenopathy, and plethora. Reassuringly, cauda equina signs were absent, but given his progressive course he was admitted for further evaluation.

Due to non-MRI compatible pacemaker, CT Myelogram of the cervical, thoracic, and lumbar regions was performed revealing a large lytic lesion involving T8, extending to incorporate T7-T9, mild soft tissue extension into the spinal canal without cord compression, and progressive increase in lesion size. A broad differential was considered, including hemangioma, plasmacytoma, multiple myeloma, and POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal plasma cell disorder, Skin changes) syndrome.

Further lab evaluations, including folate, vitamin B12, vitamin B1, vitamin B6, renal function, uric acid, LDH, SPEP, UPEP, sIFE, serum FLC ratio, acute hepatitis panel, HIV, RPR, ACE, beta-2-microglobulin, 24-hour UPEP, 24-hour uIFE, 24-hour SPEP, ANA, and VEGF were all normal. A PET/CT scan revealed no other metabolically active lesions aside from the T8 lesion. Given the negative serum and urine studies, the patient underwent a bone marrow biopsy with Oncology to assess for non-secretory myeloma, which was also negative. Ultimately, a decision was made to pursue MRI despite unclear MRI compatibility of the patient's pacemaker. This was completed without issue and showed a mildly enhancing geographic marrow-replacing lesion centered at T8 with extension into T7 and T9, and possible mild left lateral epidural extension at T8-9. A brain MRI was also done and was unremarkable.

The patient then underwent CT-guided bone biopsy of the T8 lesion, with pathology confirming a solitary plasmacytoma with lambda-restricted abnormal plasma cells. Overall, his demyelinating polyneuropathy and monoclonal plasma cell disorder with a sclerotic bone lesion, accompanied by his inguinal lymphadenopathy, hypertrichosis, plethora, and recent diagnoses of T2DM, hypothyroidism, and hypogonadism were consistent with a diagnosis of atypical POEMS syndrome. He was discharged to acute inpatient rehab and completed 4400 Gy of radiation therapy. Unfortunately, his symptoms persist, and further work up and consideration of systemic therapies are ongoing.

POEMS Syndrome is a rare, complex disorder involving multiple systems, requiring high clinical suspicion to diagnose. Diagnosis requires that both polyneuropathy and a monoclonal plasma cell disorder are present, along with at least one major criterion (sclerotic bone lesion, Castleman disease, VEGF elevation) and one minor criterion (organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema, thrombocytosis/polycythemia). This case highlights the diagnostic challenges and complexity, particularly when serum and urine studies for monoclonal gammopathy are normal, prompting the need for site-specific biopsy to confirm the presence of a monoclonal plasma cell neoplasm.

No relevant conflicts of interest to declare.