Posttreated POEMS Syndrome With Concurrent Follicular Lymphoma Revealed by 18F-FDG and 68Ga-Pentixafor PET/CT.

A 59-year-old man with history of POEMS syndrome was found with a painless mass in the right neck for 9 months. In F-FDG and Ga-pentixafor PET/CT, there were multiple neck nodes and left inguinal nodes that showed intense F-FDG and Ga-pentixafor uptake. In addition, osteoblastic bone lesions with mild F-FDG and Ga-pentixafor uptake were noted in the pelvis, which was consistent with posttreated osseous involvement of POEMS syndrome. However, considering lymphoadenopathy with such intense F-FDG uptake is not usually seen in POEMS syndrome, the patient underwent biopsy of the right cervical nodes. The histopathology with immunohistochemistry confirmed follicular lymphoma.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin (POEMS) changes syndrome presenting with a pseudosensory level: a case report.

INTRODUCTION: Polyneuropathy is a key feature of polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome, which is a paraneoplastic manifestation of an underlying lymphoproliferative neoplasm. We report the first case of polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome presenting with a pseudosensory level. CASE PRESENTATION: A 59-year-old Tamil woman with long-standing diabetes mellitus and hypertension developed painless, progressive inguinal lymphadenopathy. A contrast-enhanced computed tomography scan showed mild hepatomegaly and intra-abdominal lymphadenopathy. A histological examination of an enlarged inguinal lymph node showed features of a plasma cell-type Castleman disease. She was treated with rituximab. Six months later, she developed gradually ascending numbness and weakness of both lower limbs. On examination, she had flaccid paraparesis (power 3/5) with a sensory level to pinprick at thoracic level 9. Joint position sense was preserved. Her cranial nerves and upper limbs were neurologically normal. Nerve conduction studies confirmed peripheral neuropathy with conduction slowing and a magnetic resonance imaging of her spine did not show cord or root compression. Serum protein electrophoresis showed a monoclonal band. A bone marrow biopsy showed a hypercellular marrow with 30% plasma cells. A repeat contrast-enhanced computed tomography scan showed sclerotic bony lesions involving multiple vertebrae in addition to mild hepatomegaly and intra-abdominal lymphadenopathy. Polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome was diagnosed and she was treated with intravenously administered pulse therapy of dexamethasone and cyclophosphamide. After three cycles of treatment, she regained normal muscle power and sensation. CONCLUSIONS: Polyneuropathy in polyneuropathy, organomegaly, endocrinopathy, monoclonal band, and skin changes syndrome can present as a pseudosensory level.

POEMS Syndrome Showing Left Ventricular Dysfunction and Extracellular Edema Assessed by Cardiac Magnetic Resonance Imaging.

Although cardiac involvement is rare in polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) syndrome, the clinical course becomes considerably worse on complication with cardiac lesions. The increased release of various cytokines has been observed in the pathogenesis of POEMS syndrome, and serum vascular endothelial growth factor (VEGF) levels are known to be associated with the disease activity. We herein report a patient with POEMS syndrome who showed left ventricular systolic dysfunction and was treated with lenalidmide therapy. Of note, the reduction in extracellular edema in the left ventricular wall was clearly visualized by changes in the native T1 values and extracellular volumes on cardiac magnetic resonance imaging.

POEMS syndrome.

PURPOSE OF REVIEW: To provide an overview of polyneuropathy organomegaly endocrinopathy M-protein and skin changes (POEMS) syndrome, detailing new insights into pathogenesis, prognostic factors, treatments, and outcome scores. RECENT FINDINGS: With the development of large multicentre national cohorts of patients, POEMS syndrome is evolving into a well characterized multisystem hematoneurological syndrome. Without early diagnosis significant disability results from the neuropathy. Vascular endothelial growth factor (VEGF) is a useful and accurate biomarker supporting diagnosis and following disease activity. The past decade has seen a number of therapeutics become available to patients with POEMS, repurposed from myeloma treatment. Simple treatment algorithms are based on the extent of monoclonal proliferation and the performance status of patients. Risk factors, prognostic scores, and their impact on outcome measures have been developed from deeply phenotyped patient cohorts to predict response rate, progression-free survival and overall survival. SUMMARY: Understanding links between the monoclonal lambda plasma cell disorder and resulting proinflammatory cytokine milieu is fundamental to determining POEMS syndrome pathophysiology. Similarities to chronic inflammatory demyelinating polyradiculoneuropathy and some other monoclonal proliferative diseases makes POEMS misdiagnosis common. A range of treatments are available, and more work to identify pathogenic mechanisms and treatment targets and prognostic scores will further enable treatment stratification for optimum outcomes.

51-year old man with tingling, burning and progressive limb weakness.

Peripheral neuropathy is a common reason for referral to neurology. Chronic acquired demyelinating neuropathies are an important and varied group with overlapping presentations, and may have an immune-mediated cause. Their correct diagnosis is important as they respond to different treatments; timely intervention can prevent irreversible axonal degeneration. We present a case that highlights the approach to an adult presenting with a chronic demyelinating neuropathy.

Cranial Pachymeningeal Involvement in POEMS Syndrome: Evaluation by Pre- and Post-contrast FLAIR and T1-weighted Imaging.

PURPOSE: To evaluate the cranial pachymeningeal involvement of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, skin changes (POEMS) syndrome using pre- and post-contrast fluid-attenuated inversion recovery (FLAIR) and T1-weighted imaging (T1WI). METHODS: The appearance of pachymeningeal involvement in nine cases of POEMS syndrome was evaluated using pre- and post-contrast FLAIR and T1WI. The degree of pachymeningeal thickening was graded as normal or abnormal using pre-contrast FLAIR. The degrees of contrast enhancement effect were evaluated based on pre- and post-contrast images, and recorded in each of three separate anatomical areas, i.e., the falx cerebri, cerebral convexity, and tentorium cerebelli. The degrees of contrast enhancement of pachymeninges were graded as not detected (ND), positive, or prominent on post-contrast FLAIR, and normal range (NR), positive, and prominent on post-contrast T1WI. RESULTS: Pre-contrast FLAIR demonstrated 41% of pachymeningeal anatomical regions as areas of thickening. Post-contrast FLAIR did not detect any contrast enhancement on 26% of the regions but showed positive enhancement on 30% and prominent enhancement on 44%. Post-contrast T1WI showed normal range enhancement on 48%, positive enhancement on 11%, and prominent enhancement on 41% of the regions. Post-contrast FLAIR showed the highest percentage for detection of pachymeningeal abnormalities (74%). CONCLUSION: Post-contrast FLAIR may contribute to objective judgment in the evaluation of pachymeningeal involvement in POEMS syndrome.

Acutely deteriorated extravascular volume overload during peripheral blood stem cell mobilization in POEMS syndrome: A case series with cytokine analysis.

We describe two cases of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes (POEMS) syndrome patients with deteriorated extravascular volume overload without increased levels of vascular endothelial growth factor after the administration of cyclophosphamide + granulocyte colony-stimulating factor for stem cell mobilization. We then measured the serum levels of 27 cytokines from these cases using a multiplex suspension array system. The analysis revealed the changes of cytokine profiles before cyclophosphamide + granulocyte colony-stimulating factor and after the development of capillary leak symptoms in both cases. This may improve our current level of understanding of the pathogenesis of POEMS syndrome not driven by vascular endothelial growth factor.

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.

Autologous cytokine-induced killer (CIK) cell immunotherapy combined with cyclophosphamide in five patients with POEMS syndrome.

The primary objective of this study was to evaluate the safety and clinical efficacy of autologous cytokine-induced killer (CIK) cells combined with cyclophosphamide in the treatment of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy and skin changes (POEMS) syndrome patients. We evaluated five POEMS syndrome patients treated with autologous CIK cell immunotherapy combined with cyclophosphamide from 1 May 2012 to 30 November 2014. The Overall Neuropathy Limitation Scale (ONLS), computed tomography of the chest and abdomen, ultrasound of the abdomen, serum vascular endothelial growth factor (VEGF) level and lymphocyte count findings in the five patients were recorded. The median age of the patients was 40 years (range: 25-62), and all the patients were male. CIK cells were generated routinely from peripheral blood mononuclear cells (PBMCs) of all five patients, and the numbers of CIK cells increased by approximately 105-fold after 14 days of culture. All five patients (100%) responded to their neuropathy treatment, the ONLS scores were reduced by at least 1 and a paired-sample t-test revealed a significant difference (t = 5·715, P = 0·003 < 0·01). The extravascular volume overload responses indicated partial remission (PR = 60%) or stable disease (SD = 40%), and no cases of progressive disease (PD) or complete remission (CR) were observed. During clinical treatment, the serum VEGF of patient 5 decreased after one cycle of transfusion within 1 month. The lymphocyte counts of all the patients increased significantly after CIK transfusion, and a paired-sample t-test revealed a significant difference (t = 5·101, P = 0·004 < 0·01). Autologous CIK cell infusion combined with cyclophosphamide was found to be highly safe and elicited no adverse reactions. CIK cells can improve both the symptoms and quality of life, decrease serum VEGF levels and increase lymphocyte counts in patients with POEMS syndrome.

Successful Treatment of Bing-Neel Syndrome Accompanying Waldenström's Macroglobulinemia with R-MPV: A Case Report.

Waldenström's macroglobulinemia (WM) is a neoplasm of lymphoplasmacytic cells that produces monoclonal IgM protein. Although hyperviscosity syndrome is a common feature of WM, central nervous system (CNS) involvement in WM is rare and is known as Bing-Neel syndrome. A 60-year-old woman was referred to our hospital with bed-bound polyneuropathy, edema, splenomegaly, IgM-λ-type monoclonal protein and CD20-positive lymphocyte infiltration in the bone marrow. She was diagnosed with WM accompanying POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes) and was treated with rituximab and thalidomide. She achieved partial remission of WM, and thalidomide was continued for POEMS syndrome. She visited our outpatient clinic 6 years later with sudden onset of vertigo and nausea. Magnetic resonance imaging (MRI) revealed a low-density area 4 cm in diameter in her right cerebrum and right mid-brain and she was referred to our hospital. Pathological analysis of brain biopsy samples revealed diffuse large B-cell lymphoma (DLBCL) in the CNS. Nucleic acid sequence analysis of the VDJ region using DNA obtained from the original WM tumor cells and brain tissue revealed that the DLBCL cells were derived from the original WM malignant lymphoma cells. She received five cycles of rituximab, methotrexate, procarbazine, and vincristine (R-MPV) therapy and 23.4 Gy of whole-brain irradiation followed by two cycles of high-dose cytarabine, which resolved her neurological symptoms in association with reduction of IgM levels to 367 mg/dL. MRI and computed tomography of the brain demonstrated complete remission of her CNS lymphoma.

Pulmonary morbidity improves after autologous stem cell transplantation in POEMS syndrome.

BACKGROUND: POEMS syndrome is a plasma cell disorder manifested by Polyneuropathy, Organomegaly, Endocrinopathy, Monoclonal gammopathy and Skin changes. Pulmonary morbidity includes restriction, decreased diffusing capacity for carbon monoxide (DLCO), respiratory muscle weakness, abnormal imaging, and pulmonary hypertension. Autologous peripheral blood stem cell transplantation (aPBSCT) is an effective treatment for POEMS syndrome. It is unknown if aPBSCT improves pulmonary morbidity. We hypothesize pulmonary morbidity will improve following aPBSCT. METHODS: Retrospective cohort study of POEMS syndrome aPBSCT recipients from 2000 to 2010. Demographic, pulmonary function test (PFT), echocardiogram, cytokine, and imaging data at baseline and after aPBSCT were abstracted. Pre- and post-transplant data were compared using Wilcoxon signed-rank and McNemar's tests. RESULTS: 53 patients met criteria. Median improvements in forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), and total lung capacity (TLC) after transplant were 180, 315 and 350 ml respectively (median follow-up of 1.1 years). DLCO, maximal inspiratory pressure (MIP), and maximal expiratory pressure (MEP) improved by a median of 11, 12.5 and 10% predicted respectively. RVSP and chest imaging also improved. Vascular endothelial growth factor and IL-6 decreased by a median of 334 and 2 pg/ml respectively. All comparisons were statistically significant. Longitudinal data demonstrated stability in FEV1, MEP, and TLC and continued improvement in FVC, MIP and DLCO on subsequent PFTs (median follow-up 26.5 months). CONCLUSION: Patients with POEMS syndrome treated with aPBSCT have significant improvement in PFTs, respiratory muscle strength, imaging, and post-transplant IL-6. The improvement in PFTs persists during long-term follow-up.

[Multiple myeloma with diffuse osteosclerosis: distinct from POEMS syndrome]. / Mieloma múltiple con osteosclerosis difusa, diferente al síndrome de POEMS.

Diffuse osteosclerotic lesions are a very uncommon radiologic presentation in multiple myeloma. These lesions affect the axial skeleton and proximal limbs; they may be accompanied by osteolytic lesions in the course of the disease. In fact, in cases of diffuse osteosclerosis, the diagnosis of multiple myeloma is reached only after ruling out other, more common diseases. We present an exceptional case of multiple myeloma with diffuse osteosclerosis and highlight the differences between this entity and POEMS syndrome.

Efficacy of lenalidomide in POEMS syndrome: a retrospective study of 20 patients.

POEMS syndrome is a rare disorder characterized by polyneuropathy, monoclonal gammopathy, multiorgan involvement, and elevated vascular endothelial growth factor levels. Localized bone lesions require irradiation, whereas young patients with disseminated disease receive intensive treatment with stem cell support. Treatment of older and non responding patients is not yet standardized. We report the use of a combination of lenalidomide and dexamethasone in 20 patients with POEMS syndrome. Four patients were newly diagnosed, and 16 had relapsed or progressed after treatment. All but one of the patients responded: clinical improvements were noted in neuropathies (16/20) organomegaly (13/13), peripheral edema (14/15), and pulmonary hypertension (5/5). At least a very good partial response was noted in 68% of patients, with partial responses in 26%. Serum VEGF levels fell markedly in all 17 patients with available values. Twelve patients had 18-FDG-PET/CT at diagnosis (11 with positive findings), and nine patients during follow-up. The number of lesions fell markedly in five cases and remained stable in two cases, while two patients became negative. During a median follow-up of 22 months, four patients relapsed. Toxicity, predominantly hematological, was mild and manageable. Lenalidomide thus appears to be effective in POEMS syndrome, inducing high rate of clinical and biological responses.

Imaging of multiple myeloma and related plasma cell dyscrasias.

Multiple myeloma (MM) is an incurable plasma cell malignancy of the bone marrow. MM has 3 components: diffuse marrow infiltration, focal bone lesions, and soft-tissue (extramedullary) disease. The hallmark biomarker in blood or urine is a monoclonal immunoglobulin, the monoclonal protein. Waldenstrom macroglobulinemia is a similar disease with secretion of IgM. Staging is classically performed with the 1975 Durie-Salmon system, which includes conventional radiographs. Recently updated, the Durie-Salmon Plus staging system includes CT, MRI, and (18)F-FDG PET/CT. The hallmark radiographic lesion of symptomatic MM is a well-demarcated, focal osteolytic bone lesion. The number of focal bone lesions correlates inversely with outcome. Extramedullary disease is typically an aggressive, poorly differentiated form of MM that confers inferior outcome, with median survival of less than 1 y if present at diagnosis. Achievement of a complete response on (18)F-FDG PET before stem-cell transplantation correlates with a superior outcome.

Usefulness of F-18 FDG PET/CT in the follow-up of POEMS syndrome after autologous peripheral blood stem cell transplantation.

We report a case of a patient with relapse of POEMS syndrome (peripheral neuropathy, organomegaly, endocrinopathy, monoclonal plasma proliferative disorder, skin changes) that occurred 6 years after an autologous peripheral blood stem cell transplantation. F-18 FDG PET/CT showed several hypermetabolic as well as nonhypermetabolic bone lesions. Based on these findings, the patient was referred for radiotherapy to the hypermetabolic bone lesions. After autologous peripheral blood stem cell transplantation, F-18 FDG PET/CT may play a pivotal role in detecting new bone lesions in patients with POEMS syndrome, which may be treated by a focalized radiotherapy and/or systemic therapy.

[Usefulness of (18)F-FDG PET/CT for detecting lesions in patients with POEMS syndrome].

Many patients with POEMS syndrome have osteosclerotic plasmacytoma. Radiation therapy is useful for patients who have localized lesions, although chemotherapy is necessary for patients who have widespread lesions. Thus, evaluation of these lesions is important to determine the therapeutic strategy. We evaluated the activities of lesions in two patients with POEMS syndrome by (18)F-FDG positron emission tomography (PET)/computed tomography (CT) scan. In the first patient, PET/CT scan revealed osteosclerotic lesions, which were not detected by Ga-scintigraphy or plain X-ray. It also detected residual disease activity and relapse. In the second patient, lymph node involvement was suggested by (18)F-FDG uptake, and plasmacytoma was confirmed by subsequent biopsy. In the extramedullary lesions of this case, FDG uptake was as marked as in myeloma, whereas bone lesion was only detectable by CT scan. In POEMS syndrome, the PET and CT are complementary, and the combined PET/CT scan is considered to be very useful for evaluation of involved lesions.