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POEMS syndrome, characterized as a rare multisystem paraneoplastic syndrome, arises from plasma cell abnormalities. Coined by Bardwick in 1980, the acronym POEMS delineates the distinctive features of the syndrome: Peripheral nerve Lesions, Organomegaly, Endocrinopathy, Monoclonal gammopathy, and Skin changes. The prevalence of POEMS syndrome stands at approximately 0.3 per 100,000 individuals. Owing to its low prevalence and the paucity of prospective studies, current treatment approaches largely hinge on retrospective studies and revolve around the use of plasma cell-directed therapy typically used in multiple myeloma treatments. This article presents the pioneering case of utilizing a fourdrug combination regimen of DKRd (daratumumab, carfilzomib, lenalidomide, and dexamethasone) as a first-line treatment. This is succeeded by induction therapy and subsequently, autologous hematopoietic stem cell transplantation. A comprehensive review of related literature is conducted. [ABSTRACT FROM AUTHOR]

Summary: This open‐label, prospective trial evaluated the combination of ixazomib, cyclophosphamide and dexamethasone (ICD) in 12 newly diagnosed POEMS syndrome patients. The study is registered with the Chinese Clinical Trials Registry (ChiCTR2000030072). The treatment protocol consisted of 12 cycles of the ICD regimen compromising ixazomib (4 mg on Days 1, 8 and 15), oral cyclophosphamide (300 mg on Days 1, 8 and 15) and dexamethasone (20 mg weekly). A total of 12 patients received a median of 10 (range: 3–23) cycles of the ICD regimen. The haematological response could be evaluated in 10 patients. The overall haematological response rate was 80% (8/10), with 30% (3/10) achieving complete haematological response, and the overall serum VEGF response rate and neurological response were 100% and 83.3% respectively. Two patients experienced grade 3/4 AEs, including diarrhoea (n = 1) and leukopenia (n = 1). The combination of ixazomib, cyclophosphamide and dexamethasone demonstrated both efficacy and safety in newly diagnosed POEMS syndrome, making it a viable treatment option. [ABSTRACT FROM AUTHOR]

The diagnostic evaluation of a peripheral neuropathy includes testing for the presence of monoclonal gammopathy, which can be found in about 10% of patients with peripheral neuropathy. Our role, as physicians, is to determine whether the neuropathy is directly related to the gammopathy or whether the co‐occurrence of these two disorders is purely coincidental. The evaluating physician needs to be familiar with the different types of neuropathies associated with monoclonal gammopathies, their clinical and electrodiagnostic characteristics, and their appropriate diagnostic evaluation and management. Testing for monoclonal protein disorders includes serum protein electrophoresis (SPEP) and immunofixation of blood, and in some cases of urine, as well as measurement of free light chains and quantitative immunoglobulins. Specific antibody testing is directed by paraprotein type and neuropathy phenotype. Patients with abnormal free light chains in association with sensory and autonomic neuropathy should be evaluated for AL amyloidosis. When a lambda monoclonal protein is identified together with a clinical phenotype of chronic inflammatory demyelinating neuropathy (CIDP), a diagnosis of polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, skin changes (POEMS) syndrome should be considered. Patients with IgM paraprotein associated neuropathy should be assessed for distal acquired demyelinating sensorimotor (DADS) neuropathy, with or without anti myelin associated glycoprotein (MAG) antibody or CANOMAD syndrome. In many cases, a monoclonal gammopathy of uncertain significance (MGUS) is incidental and unrelated to the neuropathy. Collaboration with oncology is critical in evaluating patients with monoclonal proteins to assess for underlying plasma cell neoplasms or B cell lymphomas. [ABSTRACT FROM AUTHOR]

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.

Abstract POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein [M-protein], and skin changes) is a rare systemic disorder characterized by various symptoms caused by underlying plasma cell (PC) dyscrasia. Detection of monoclonal PCs is mandatory for the diagnosis of POEMS syndrome; however, the usefulness of EuroFlow-based next-generation flow cytometry (EuroFlow-NGF) in POEMS syndrome for detecting monoclonal PCs in bone marrow (BM) and the gating strategy suitable for flow cytometry study of POEMS syndrome remain unknown. We employed EuroFlow-NGF-based single-tube eight-color multiparameter flow cytometry (MM-flow) and established a new gating strategy (POEMS-flow) to detect the monoclonal PCs in POEMS syndrome, gating CD38 broadly from dim to bright and CD45 narrowly from negative to dim compared to MM-flow. MM-flow detected monoclonal PCs in 9/25 (36.0%) cases, including 2/2 immunofixation electrophoresis (IFE)-negative cases (100%). However, POEMS-flow detected monoclonal PCs in 18/25 cases (72.0%), including 2/2 IFE-negative cases (100%). POEMS-flow detected monoclonal PCs with immunophenotypes of CD19− in 17/18 (94.4%). In six cases where post-treatment samples were available, the size of the clones was significantly reduced after the treatment (P = 0.031). POEMS-flow can enhance the identification rate of monoclonal PCs in POEMS syndrome and become a valuable tool for the diagnosis of POEMS syndrome.

Purpose: Retrospectively analyse the 99mTc-MDP SPECT whole-body bone scan in POEMS syndrome to explore its clinical value. Methods: Twenty-four untreated patients with pathologically confirmed POEMS syndrome were included in the study. 24 of them underwent 99mTc-MDP SPECT whole-body bone scan, 24 underwent CT examination and 18 patients underwent X-ray examination in different parts. Features of bone lesions in 99mTc-MDP SPECT, and X-ray, CT were analysed. Three experienced radiologists read the images and gave diagnosed results for bone lesions. Results: Of the 24 POEMS syndrome patients, three types of bone lesions were found: osteosclerotic lesions, osteolytic lesions and mixed lesions, of which the most common type was osteosclerotic. 54.16% (13/24) patients were found bone lesions by SPECT; 44.44% (8/18) patients underwent X-ray and 62.50% (15/24) patients underwent CT were detected bone lesions. We compared the difference of the X-ray, CT and SPECT scans of the bone lesions by chi-square and found that there was no difference (P = 0.51) in detection of bone lesions among the three methods. Conclusion: 99mTc-MDP SPECT wholebody bone scan also useful in evaluating patients with suspected POEMS syndrome. We can use it as a supplement examination of the CT in the confirmation of one minor diagnostic criterion for POEMS syndrome: bone lesions. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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Abstract Low serum cholesterol levels are associated with increased tumor morbidity and mortality. However, the relationship between serum lipid profile and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is still unclear. The aim of our study was to clarify the importance of the serum lipid profile in predicting the severity and prognosis of patients with POEMS syndrome. Forty-three patients with newly diagnosed POEMS syndrome admitted to the Department of Hematology of Jiangsu Provincial People's Hospital between August 2013 and February 2023 were selected. They had explicit serum lipid profiles. There were 27 males and 16 females with a median age of 54 years (range, 28–77 years). Survival curves were plotted using the Kaplan–Meier method, and comparisons between the two groups were performed using the log-rank test. The Cox proportional-hazards model examined risk factors associated with the prognosis of POEMS syndrome. Receiver-operator characteristic (ROC) curves assessed the predictive accuracy. 23 (53.5%) patients had low total cholesterol (TC) levels. Low levels of TC were concerned with unfavorable progression-free survival (PFS) (p = 0.007) and overall survival (OS) (p = 0.004), and at the same time, the low circulating TC concentration was an independent risk factor for PFS (p = 0.020) and OS (p = 0.011). Low TC values could improve the risk stratification, especially in high-risk patients. In conclusion, low serum TC levels may predict inferior prognosis in patients with POEMS syndrome; in future clinical application, low TC may be a reliable indicator of prognosis.

Gangliosidosis is one of the hereditary metabolic diseases caused by the accumulation of Gangliosid in the central nervous system, leading to severe and progressive neurological deficits. Regarding phenotype, GM1 and GM2-Gangliosidosis are divided into Infantile, Juvenile, and Adult. Materials & Methods In this study, thirty-seven patients with GM1 and GM2-Gangliosidosis were referred to the neurology department of Mofid Children's Hospital in Tehran, Iran, whose disease was confirmed from September 2019 to December 2021. This study assessed age, sex, and developmental status before the onset of the disease, clinical manifestations, brain imaging, and electroencephalography. Results 97.20% of patients were the result of family marriage. Approximately 80% of juvenile patients were developmentally normal before the onset of the disease. Developmental delay was more common among infantile GM1-Gangliosidosis than infantile GM2-Gangliosidosis, but in total, more than 50% of GM1&GM2-Gangliosidosis patients had reached their developmental milestone before the onset of the disease. With the onset of disease symptoms, 100% of patients regressed in terms of movement, 97.20% of them mentally, and 75% of them had seizures during the disease. The most common clinical findings were cherry-red spot, Mongolian spot, macrocephaly, organomegaly, hyperacusis, and scoliosis. The most common brain imaging findings included bilateral thalamus involvement, brain atrophy, PVL, and delayed myelination. The most common finding in electroencephalography was background low voltage with abnormal sharp waves. Conclusion This study concluded that most of the patients are the result of family marriage, and most of the juvenile patients are developmentally normal before the onset of the disease. In addition, more than 50% of infantile patients reach their developmental milestones before the onset of the disease. The most common clinical findings of these patients are seizures, cherry-red spot, macrocephaly, hyperacusis, Mongolian spot, and bilateral involvement of the thalamus. [ABSTRACT FROM AUTHOR]

Low serum cholesterol levels are associated with increased tumor morbidity and mortality. However, the relationship between serum lipid profile and POEMS syndrome (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) is still unclear. The aim of our study was to clarify the importance of the serum lipid profile in predicting the severity and prognosis of patients with POEMS syndrome. Forty-three patients with newly diagnosed POEMS syndrome admitted to the Department of Hematology of Jiangsu Provincial People's Hospital between August 2013 and February 2023 were selected. They had explicit serum lipid profiles. There were 27 males and 16 females with a median age of 54 years (range, 28–77 years). Survival curves were plotted using the Kaplan–Meier method, and comparisons between the two groups were performed using the log-rank test. The Cox proportional-hazards model examined risk factors associated with the prognosis of POEMS syndrome. Receiver-operator characteristic (ROC) curves assessed the predictive accuracy. 23 (53.5%) patients had low total cholesterol (TC) levels. Low levels of TC were concerned with unfavorable progression-free survival (PFS) (p = 0.007) and overall survival (OS) (p = 0.004), and at the same time, the low circulating TC concentration was an independent risk factor for PFS (p = 0.020) and OS (p = 0.011). Low TC values could improve the risk stratification, especially in high-risk patients. In conclusion, low serum TC levels may predict inferior prognosis in patients with POEMS syndrome; in future clinical application, low TC may be a reliable indicator of prognosis. [ABSTRACT FROM AUTHOR]

We present the case of a 54-year-old woman with reasonable blood sugar control who presented with a diabetic foot combined with severe peripheral neuropathy and vascular disease. Lower limb muscle weakness, muscle atrophy, skin pigmentation, and emaciation were also observed. Although her muscle strength improved after glucocorticoid treatment, it remained challenging to account for the other symptoms in this particular patient with chronic inflammatory demyelinating polyneuropathy. Plump liver and spleen, hidden bone lesions combined with seemingly unexplained cerebral infarction, and serous effusion led us to suspect polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome. The abnormal proliferation of monoclonal plasma cells and a significant increase in vascular endothelial growth factor (VEGF) levels confirmed the diagnosis of POEMS syndrome. After 1 month of treatment with lenalidomide and dexamethasone, the diabetic foot ulcers healed, and the symptoms of myasthenia and fatigue improved. Diabetic feet may represent only the tip of the iceberg of an underlying POEMS syndrome. Our report aimed to increase awareness of this rare yet significant situation, advocating for the prompt identification and treatment of POEMS syndrome. [ABSTRACT FROM AUTHOR]

Papillary hemangioma (PH) is a recently described vascular tumor with a predilection for the skin of the head and neck. Histopathologically, it is characterized by a bland endothelial proliferation arranged in a papillary configuration, bearing resemblance to glomeruloid hemangioma seen in the context of polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, skin changes syndrome. The largest cutaneous PH reported to date measured 1.5 cm in greatest dimension. Here, we report a case of PH with an alarming size of 10 cm. We present this case to add to the limited literature on this rare tumor, highlight the histopathologic differences between PH and its mimics, and emphasize the variable nature of PH tumor size. [ABSTRACT FROM AUTHOR]

Background: To investigate the utility of regular serum VEGF (sVEGF) levels assessment in the monitoring of POEMS syndrome. Methods: We retrospectively reviewed data of 30 patients with POEMS syndrome whose sVEGF was tested regularly every 6 months. sVEGF levels after treatment were measured and correlated with disability (Overall Neuropathy Limitations Scale, ONLS), clinical impairment (measured with the modified Clinical Response Evaluation Scale, mCRES), and relapse-free survival. The ability of sVEGF to predict disease flares during remission and refractory disease was also analysed. Results: Patients with normalised serum VEGF levels (< 1000 pg/ml) at 6 months showed prolonged relapse-free survival (at 3-year 94% for complete VEGF response, 57% partial, 0% none, p < 0.001) and greater later clinical improvement (median ΔmCRES complete VEGF response -5 vs partial -4, p = 0.019, and vs no VEGF response -2, p = 0.006). After remission, the sensitivity of 6-month sVEGF monitoring in predicting clinical relapse was 58% with a specificity of 100%. In patients refractory to treatment, the sensitivity in predicting further clinical worsening was 15%. In addition, in 25% of the patients in remission and 16% of those refractory to therapy, sVEGF levels only increased at the time of relapse. Conclusions: Regular sVEGF assessment is a valid biomarker in the prediction of disease reactivation in POEMS syndrome and was particularly useful during the phase of remission. [ABSTRACT FROM AUTHOR]

This patient was an elderly patient with abdominal distension and shortness of breath. According to relevant examinations, his condition was initially considered to be related to cirrhosis, but pathological biopsy confirmed the diagnosis of noncirrhotic portal hypertension of unknown etiology. The portal vein pressure was significantly reduced after transjugular intrahepatic portosystemic shunt (TIPS). Nevertheless, the relief of the hydrothorax and ascites was not significant, and the numbness in both lower limbs gradually worsened. POEMS syndrome was ultimately diagnosed following a comprehensive examination. After two courses of bortezomib combined with dexamethasone, the patient died due to a systemic infection. The clinical symptoms of the patient were atypical, as was the presence of portal hypertension, which hindered the diagnosis of POEMS. Due to the patient’s advanced age, the diagnosis was delayed, and the prognosis was poor. This case reminds clinicians that POEMS patients can also have portal hypertension as the main manifestation.

Objective To improve the awareness of POEMS syndrome among clinicians, and to increase the experience in the clinical diagnosis and treatment of atypical POEMS syndrome. Methods A retrospective analysis was performed for the cli-nical data of a patient with Castleman disease variant of POEMS syndrome who were hospitalized in Department of Endocrinology in our hospital in September 2020, and a literature review was performed. Results The patient had the initial manifestation of endocrine abnormality (hypogonadism), followed by other manifestations such as skin damage, neurogenic damage, multiple serous effusion, and multiple lymph node enlargement, which were consistent with the diagnostic criteria for POEMS syndrome, but hematological examination showed no evidence of clonal plasma cells. After multidisciplinary consultation and lymph node biopsy, pathological examination suggested Castleman disease, with an increase in the level of vascular endothelial growth factor (VEGF) in plasma, and finally the patient was diagnosed with Castleman disease variant of POEMS syndrome. Conclusion Clinicians need to have pluralistic thinking in the diagnosis and treatment of POEMS syndrome, and when POEMS syndrome is highly suspected in clinical practice without fully meeting necessary diagnostic criteria, they should actively look for relevant evidence and emphasize the value of lesion biopsy and plasma VEGF level in the diagnosis of this disease, so as to reduce missed diagnosis and misdiagnosis.

Abstract Background Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare multisystemic clonal plasma cell disorder. Pulmonary involvement is frequently found in patients with POEMS syndrome, manifesting various clinical features. Therefore, to improve diagnostic accuracy and provide treatment strategies, a comprehensive analysis of pulmonary manifestations of POEMS syndrome is needed. Methods This retrospective study included patients with POEMS syndrome at Peking Union Medical College Hospital, a major referral medical center in China, between June 1, 2013, and June 1, 2023. Demographic data, laboratory findings, pulmonary function test results, echocardiograms, and chest imaging data were extracted. Continuous variables were compared using the t-test or Mann–Whitney method. Pearson’s chi-square test or Fisher’s exact test was conducted to compare categorical data. Results Overall, 282 individuals diagnosed with POEMS syndrome were included in this study, of which 56% were male with an average age of 48.7 years. Respiratory symptoms were found in 40.1% of the patients, with dyspnea as the most common symptom (34.4%). Chest computed tomography and echocardiography findings showed that 56.4% of patients exhibited pleural effusion, 62.8% displayed mediastinal or hilar lymphadenopathy, 46.5% presented pleural thickening, 27.3% demonstrated bone lesions of the ribs or thoracic vertebra, 7.8% showed lung interstitial abnormalities, and 35.5% had pulmonary hypertension. Decreased diffuse capacity and restrictive ventilatory patterns were identified in 85.2% (115 cases) and 47.4% (64 cases) of patients, respectively. Patients with respiratory symptoms exhibited higher declined lung function measures than those having no respiratory symptoms. High-risk patients with poor prognosis showed more pulmonary function abnormalities. Conclusion Abnormalities in pulmonary manifestations constitute the significant features of POEMS syndrome. Several patients with POEMS syndrome presented with respiratory symptoms at the initial evaluation. These findings underscore the importance of early identification and accurate diagnosis of POEMS syndrome by clinicians, particularly in cases involving lung and multisystem.

Background: Due to the rarity of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, the best first-line treatment has not been established, although there are several options in guidelines. The preferred treatments vary according to the preference of the physician and anecdote. Objectives: First, to analyze the efficacy of a new treatment mode in POEMS syndrome that uses the four-cycle treatment as the induction regimen, followed by sequential transplantation as the consolidation regimen for transplantation-eligible patients, or received another two-cycle treatment for transplantation-ineligible patients. Second, to compare the efficacy and safety of regimens with a proteasome inhibitor (bortezomib–cyclophosphamide–dexamethasone, BCD) or without a proteasome inhibitor (cyclophosphamide–dexamethasone ± thalidomide, CD ± T). Design: We conducted a retrospective study using real-world data from Capital Medical University, Xuanwu Hospital. Methods: A total of 34 newly diagnosed POEMS syndrome patients met Dispenzieri's diagnostic criteria, and those who completed at least four cycles of treatment from July 2013 to March 2021 were included. Results: The overall vascular endothelial growth factor (VEGF) response rate of this new treatment mode was 100%. The cumulative VEGF complete remission (CRV) rate was 67.9%, and the cumulative complete hematological response (CRH) rate was 55.6%. During the median 49-month follow-up, the 5-year-overall survival (OS) rate was 90.7%, the 3-year-progression-free survival (PFS) rate was 78.4%, and the 5-year-PFS rate was 73.8%. The BCD regimen achieved a 75% CRV rate (median time from diagnosis to CRV = 130 days) and 66.7% CRH rate (median time from diagnosis to CRH = 218 days). In addition, the VEGF response was less than the partial remission (PRV) after four-cycle induction treatment, which, together with a decrease on the Overall Neurological Limitation Scale of less than three points 1 year after consolidation treatment, was an independent poor prognostic factor. Conclusion: Bortezomib was well-tolerated by patients with POEMS syndrome. Compared with CD ± T regimen, BCD as the induction regimen achieved better VEGF response and earlier hematological remission. Autologous stem cell transplantation used as consolidation therapy further improved the neurological and hematological remission rates, resulting in better OS and PFS. [ABSTRACT FROM AUTHOR]

POEMS syndrome is a rare disorder which has been increasingly recognized. The clonal origin is controversial. Some people argue that POEMS syndrome originates from abnormal plasma cell clones. So, treatment frequently targets the plasma cell clone. Nevertheless, others believe that both plasma cells and B cells can be the potential culprit in POEMS syndrome. A 65-year-old male came to the emergency department of our hospital with the complaints of bilateral soles numbness and weight loss for half a year, abdominal distension for half a month, and chest tightness and shortness of breath for one day. He was then diagnosed as POEMS syndrome complicated with monoclonal B-cell lymphocytosis (non-CLL type). A standard bendamustine plus rituximab (BR) regimen combined with low dose of lenalidomide was administered. After four cycles of treatment, the ascites of the patient was absent and the neurological symptom disappeared. The renal function, the IgA level, and the VEGF level all returned to normal. POEMS syndrome, a multi-system disorder, is easily misdiagnosed. The clonal origin of POEMS syndrome is controversial and needs further study. For now, there are no approved treatment regimens. Treatments mainly target the plasma cell clone. This case suggested that other therapy besides anti-plasma cell treatment may also be effective in POEMS syndrome. We report a patient with POEMS syndrome who achieved complete response after treatment with the combination of a standard BR regimen and low dose of lenalidomide. POEMS syndrome's pathological mechanisms and therapies warrant further studies. [ABSTRACT FROM AUTHOR]

Introduction/Aims: Vascular thrombosis is prevalent among patients with polyneuropathy, organomegaly, endocrinopathy M‐protein, and skin changes (POEMS) syndrome. The endothelial cells in the endoneurium are often hypertrophied and the lumen is frequently occluded. Consequent local hypoxia may increase vascular endothelial growth factor (VEGF), which induces hypercoagulation and vascular permeability. Methods: This study presents two patients in the fifth decade of life, who had rare nerve biopsy findings of vascular occlusion mainly by platelets. Before the cases presented here, we encountered nine confirmed POEMS patients whose nerve biopsies did not show similar findings. Results: A small artery and a vein were occluded, but no atherosclerotic changes were observed. The endothelial cells that adhered to the packed platelets lost their junctions. Discussion: Platelet aggregation, degranulation, and ischemia may cause a loose endothelial barrier and leak proinflammatory cytokines, such as interleukin‐12. This may increase production of VEGF and may cause nerve demyelination. Small vessel platelet thrombosis may contribute to the pathogenesis of this disorder. [ABSTRACT FROM AUTHOR]

Background: Polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome is a rare multisystemic clonal plasma cell disorder. Pulmonary involvement is frequently found in patients with POEMS syndrome, manifesting various clinical features. Therefore, to improve diagnostic accuracy and provide treatment strategies, a comprehensive analysis of pulmonary manifestations of POEMS syndrome is needed. Methods: This retrospective study included patients with POEMS syndrome at Peking Union Medical College Hospital, a major referral medical center in China, between June 1, 2013, and June 1, 2023. Demographic data, laboratory findings, pulmonary function test results, echocardiograms, and chest imaging data were extracted. Continuous variables were compared using the t-test or Mann–Whitney method. Pearson's chi-square test or Fisher's exact test was conducted to compare categorical data. Results: Overall, 282 individuals diagnosed with POEMS syndrome were included in this study, of which 56% were male with an average age of 48.7 years. Respiratory symptoms were found in 40.1% of the patients, with dyspnea as the most common symptom (34.4%). Chest computed tomography and echocardiography findings showed that 56.4% of patients exhibited pleural effusion, 62.8% displayed mediastinal or hilar lymphadenopathy, 46.5% presented pleural thickening, 27.3% demonstrated bone lesions of the ribs or thoracic vertebra, 7.8% showed lung interstitial abnormalities, and 35.5% had pulmonary hypertension. Decreased diffuse capacity and restrictive ventilatory patterns were identified in 85.2% (115 cases) and 47.4% (64 cases) of patients, respectively. Patients with respiratory symptoms exhibited higher declined lung function measures than those having no respiratory symptoms. High-risk patients with poor prognosis showed more pulmonary function abnormalities. Conclusion: Abnormalities in pulmonary manifestations constitute the significant features of POEMS syndrome. Several patients with POEMS syndrome presented with respiratory symptoms at the initial evaluation. These findings underscore the importance of early identification and accurate diagnosis of POEMS syndrome by clinicians, particularly in cases involving lung and multisystem. [ABSTRACT FROM AUTHOR]

Osteosclerosis in multiple myeloma (MM) is typically associated with rare POEMS syndrome, characterized by polyneuropathy (P), organomegaly (O), endocrinopathy (E), M-protein (M), and skin changes (S). However, osteosclerosis in multiple myeloma (MM) without POEMS syndrome, defined as non-POEMS Osteosclerotic MM, is exceedingly rare. We report a 70-year-old man with rib pain, remarkably high bone mineral density and diffuse osteosclerosis. The diagnosis of non-POEMS osteosclerotic MM was confirmed by biopsy and aspiration of bone marrow through surgery. A literature review spanning from 1990 identified 12 cases of similar non-POEMS osteosclerotic MM, including 5 males and 7 females with a mean age of 59.7 ± 10.6 years. The non-POEMS osteosclerotic MM can be divided into two subtypes, the osteosclerotic lesion subtype and the diffuse osteosclerosis subtype. Absence of polyneuropathy and organomegaly are the main factors that differentiate non-POEMS osteosclerotic MM from POEMS. A hyperactive osteoblastic process might be the etiology of diffuse osteosclerosis. Further research is needed to understand its etiology and pathophysiology.

ABSTRACTObjectives POEMS syndrome is a rare disorder which has been increasingly recognized. The clonal origin is controversial. Some people argue that POEMS syndrome originates from abnormal plasma cell clones. So, treatment frequently targets the plasma cell clone. Nevertheless, others believe that both plasma cells and B cells can be the potential culprit in POEMS syndrome.Methods A 65-year-old male came to the emergency department of our hospital with the complaints of bilateral soles numbness and weight loss for half a year, abdominal distension for half a month, and chest tightness and shortness of breath for one day. He was then diagnosed as POEMS syndrome complicated with monoclonal B-cell lymphocytosis (non-CLL type). A standard bendamustine plus rituximab (BR) regimen combined with low dose of lenalidomide was administered.Results After four cycles of treatment, the ascites of the patient was absent and the neurological symptom disappeared. The renal function, the IgA level, and the VEGF level all returned to normal.Discussion POEMS syndrome, a multi-system disorder, is easily misdiagnosed. The clonal origin of POEMS syndrome is controversial and needs further study. For now, there are no approved treatment regimens. Treatments mainly target the plasma cell clone. This case suggested that other therapy besides anti-plasma cell treatment may also be effective in POEMS syndrome.Conclusion We report a patient with POEMS syndrome who achieved complete response after treatment with the combination of a standard BR regimen and low dose of lenalidomide. POEMS syndrome's pathological mechanisms and therapies warrant further studies.

Castleman disease (CD) is a rare lymphoproliferative disorder known to represent at least four distinct clinicopathologic subtypes. Large advancements in our clinical and histopathologic description of these diverse diseases have been made, resulting in subtyping based on number of enlarged lymph nodes (unicentric versus multicentric), according to viral infection by human herpes virus 8 (HHV-8) and human immunodeficiency virus (HIV), and with relation to clonal plasma cells (POEMS). In recent years, significant molecular and genetic abnormalities associated with CD have been described. However, we continue to lack a foundational understanding of the biological mechanisms driving this disease process. Here, we review all cases of CD with molecular abnormalities described in the literature to date, and correlate cytogenetic, molecular, and genetic abnormalities with disease subtypes and phenotypes. Our review notes complex karyotypes in subsets of cases, specific mutations in PDGFRB N666S in 10% of unicentric CD (UCD) and NCOA4 L261F in 23% of idiopathic multicentric CD (iMCD) cases. Genes affecting chromatin organization and abnormalities in methylation are seen more commonly in iMCD while abnormalities within the mitogen-activated protein kinase (MAPK) and interleukin signaling pathways are more frequent in UCD. Interestingly, there is a paucity of genetic studies evaluating HHV-8 positive multicentric CD (HHV-8+ MCD) and POEMS-associated CD. Our comprehensive review of genetic and molecular abnormalities in CD identifies subtype-specific and novel pathways which may allow for more targeted treatment options and unique biologic therapies.

We present a case of POEMS syndrome from Turkiye, a rare, multisystemic condition resulting from plasma cell dyscrasia. POEMS is an acronym representing its cardinal features: Peripheral neuropathy; Organomegaly; Endocrinopathy; Monoclonal plasma-cell proliferative disorder; and Skin changes. The syndrome has an estimated prevalence of 0.3 per 100,000 individuals and typically manifests in the fifth or sixth decade of life. Progressive peripheral neuropathy is the syndrome's most prominent symptom. To ensure an accurate diagnosis, a thorough medical history, physical examination, and comprehensive diagnostic evaluations are essential. These evaluations should include serum immunoelectrophoresis, serum cytokines, and growth factors, a skeletal survey, and a bone marrow biopsy. Early recognition and treatment of POEMS syndrome are crucial to prevent debilitating progression and to optimize clinical outcomes. [ABSTRACT FROM AUTHOR]

Background: POEMS syndrome is a rare and complex plasma cell disorder characterized by polyneuropathy, organomegaly, endocrinopathy, high M protein levels, and skin changes. Understanding of POEMS syndrome has advanced rapidly since the 21st century. This study aims to summarize and evaluate the research status of POEMS syndrome in the past 23 years through a bibliometric and visualization analysis, and identify research focuses and emerging hotspots for the future. Methods: POEMS syndrome-related articles published between January 1, 2000, and March 8, 2023, were systematically retrieved from the Web of Science Core Collection. Data processing and visualization analysis were carried out using a combination of R software, HistCite, VOSviewer, and CiteSpace. Results: Since entering the 21st century, 3677 authors from 1125 institutions in 68 countries/regions have published 830 original and review articles on POEMS syndrome in 408 journals so far, among which the USA, Japan, and China published the most articles, and Mayo Clinic, Udice French Research Universities, and Peking Union Medical College listed the top three most prolific institutions. However, collaborative research across countries and groups in the study of POEMS syndrome remain significantly limited. Angela Dispenzieri ranked first in POEMS syndrome research from every aspect of authors, producing the most papers and contributing the most-cited article, followed by Satoshi Kuwabara and Sonoko Misawa. Internal medicine was the most productive journal on POEMS syndrome. ''endothelial growth factor'' was the keyword with the highest occurrence except for ''POEMS syndrome'', and ''bevacizumab'', ''lenalidomide'', ''dexamethasone'', and ''management'' were recognized as emerging topics. Conclusion: This study utilized bibliometric and visualization analysis to systematically summarize the research of POEMS syndrome in the first two decades of the 21st century, offering a data-based and objective perspective on the field of POEMS syndrome and guiding researchers in the identification of novel research directions.

Polyneuropathy, organomegaly, endocrinopathy, monoclonal plasma cell disorder, and skin changes (POEMS) syndrome is a multisystem disorder that has limited treatment options. Here, we described a case of a 55-year-old female subject who was treated for multiple drugs, but the skin symptoms continued to progress; the patient responded well to baricitinib. This suggests that JAK/STAT signaling pathways play an essential role in the pathological process of POEMS syndrome.

POEMS syndrome is a paraneoplastic disorder manifested by peripheral neuropathy and monoclonal plasma cell dyscrasia. Due to its clinical and electrophysiological aspect, POEMS syndrome is often mistaken as a chronic inflammatory demyelinating polyneuropathy (CIDP) [1]. Its acronym is derived from its principal characteristics: polyneuropathy, organomegaly, endocrinopathy, M proteins, and skin changes [2]. The purpose of this paper is to present the case of a patient who was lately diagnosed with POEMS syndrome after he was mistreated for CIDP in order to show the importance of a complete physical examination. [ABSTRACT FROM AUTHOR]

POEMS syndrome is a rare paraneoplastic syndrome associated with a plasma cell proliferative disorder. Gallbladder adenocarcinoma is a rare malignancy, with no association with POEMS syndrome. The plasma cell dyscrasia is routinely evaluated with advanced hybrid imaging to assess both anatomic and functional components. We present a case of a 59-year-old female with a known diagnosis of POEMS syndrome who underwent a whole-body restaging evaluation with hybrid positron emission tomography (PET) and magnetic resonance imaging (MR) to restage her plasma cell dyscrasia. She also had a prior diagnosis of gallbladder adenocarcinoma. Our case focuses on the value of PET/MR in this scenario as well as a rare case of osseous metastasis from gallbladder carcinoma.

Abstract Background Transplant-eligible patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome are treated with induction therapy and autologous stem cell transplantation. Conventional induction therapies may exacerbate neuropathy and a high rate of disease progression within 5 years. Furthermore, only 50% of patients are able to walk independently after the therapies. Daratumumab, lenalidomide, and dexamethasone therapy has been reported as a less neurotoxic, highly effective therapy for patients with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome who are ineligible for transplant or whose syndrome is relapsed/refractory, but no reports have provided data from untreated transplant-eligible patients. Case presentation A 34-year-old Japanese woman displayed weakness, pain and edema in the lower limbs, decreased grip strength, amenorrhea, and abdominal distention. She was unable to walk independently. The patient was diagnosed with polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome and performed four courses of daratumumab, lenalidomide, and dexamethasone therapy, which enabled her to walk independently and did not exacerbate the neuropathy. Hematopoietic stem cells were collected using plerixafor and filgrastim in combination. Autologous stem cell transplantation was performed with high-dose melphalan. At 3-month post-transplantation follow-up, most of her clinical symptoms had disappeared. Conclusions Daratumumab, lenalidomide, and dexamethasone therapy followed by autologous stem cell transplantation may be more effective than conventional therapy for newly diagnosed polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome. Although there was concerns that daratumumab, lenalidomide, and dexamethasone therapy might lead to poor mobilization of hematopoietic stem cells, this was overcome with the combination of plerixafor and filgrastim. The benefit of daratumumab, lenalidomide, and dexamethasone as induction therapy prior to autologous stem cell transplantation should be confirmed in future clinical trials.

Cardiac bradyarrhythmia and conduction disorder may be rare, but recurrent adverse events caused by bortezomib. Here we report a case with POEMS syndrome presenting severe heart block after bortezomib plus dexamethasone therapy. After permanent pacemaker implantation, bortezomib was restarted and maintained, resulting in sustained complete response for POEMS syndrome. [ABSTRACT FROM AUTHOR]

POEMS syndrome—characterized by polyneuropathy, organomegaly, endocrinopathy, M-protein, and skin changes—is an uncommon and complex paraneoplastic disorder encompassing a diverse array of symptoms. Here we report the challenging case of a 34-year-old female who sought medical attention at the emergency department due to distal lower limb weakness. She was breastfeeding her first child at that time. Her condition rapidly deteriorated, making it difficult for her to perform simple tasks independently. Initially, she struggled with activities like jumping or climbing stairs. Eventually, her ability to walk was also compromised. These symptoms underscored the swift evolution of her polyneuropathy. Nerve conduction studies and electromyography confirmed a diagnosis of mixed demyelinating and axonal polyneuropathy. Subsequent investigations, including bone marrow biopsy and immunochemistry testing, revealed a plasma cell disorder characterized by lambda monoclonal gammopathy, along with elevated levels of vascular endothelial growth factor (VEGF > 8000 pg/mL). This pivotal finding led to the diagnosis of POEMS syndrome, prompting the initiation of antineoplastic therapy (daratumumab-lenalidomide-dexamethasone) to manage this condition. An autologous cell transplantation was planned. The rarity of POEMS syndrome and its diverse clinical manifestations often lead to an incorrect or delayed diagnosis. Our case underscores the importance of considering this syndrome in patients presenting with acute or subacute polyneuropathy, even if the patients are young. In conclusion, this case elucidates the diagnostic complexities of POEMS syndrome, emphasizing the integral role of comprehensive multidisciplinary evaluations and the potential influence of increased VEGF as a diagnostic key element and possible therapeutic target.

Background: Myopathies associated with monoclonal gammopathy are relatively uncommon and underrecognized, treatable myopathies, and include sporadic late onset nemaline myopathy, light chain amyloid myopathy, and a recently described vacuolar myopathy with monoclonal gammopathy and stiffness (VAMGS). Herein, we report a new subtype of monoclonal gammopathy‐associated myopathy (MGAM) in a polyneuropathy, organomegaly, endocrinopathy, M protein, and skin changes (POEMS) patient. Method: Case report. Results: A 51‐year‐old woman presented with a 6‐month history of progressive bilateral foot drop, lower limb edema, and a 15‐lb weight loss. She denied muscle stiffness. Neurologic exam showed severe distal weakness, mild proximal weakness, and length‐dependent sensory deficits. Laboratory studies revealed biclonal gammopathy (IgG kappa and IgA lambda), thrombocytosis, and elevated vascular endothelial growth factor. Creatine kinase was normal. Electrodiagnostic studies identified mixed demyelinating and axonal polyradiculoneuropathy and a superimposed proximal myopathy. Gluteus medius biopsy demonstrated scattered fibers with glycogen‐filled vacuoles, similar to VAMGS, with additional rare myofibers containing polyglucosan bodies. She was diagnosed with POEMS syndrome and concomitant glycogen storage myopathy. Next‐generation sequencing of glycogen storage and polyglucosan body myopathy‐related genes was unrevealing. Proximal weakness resolved after autologous stem cell transplant. Conclusions: This patient expands a spectrum of MGAM. Recognition of this condition and other subtypes of MGAM is of utmost important because they are treatable. [ABSTRACT FROM AUTHOR]

Abstract Background POEMS syndrome is a rare paraneoplastic syndrome caused by plasma cell disorder almost always lambda restricted. Secondary Raynaud’s phenomenon is an overlooked skin manifestation of the disease even though it is present in twenty percent of patients. On POEMS syndrome have not been described positive antinuclear antibodies (ANA) and this could lead to a misdiagnosis of autoimmune disease, mainly systemic sclerosis. Case presentation A 47-year-old man presented with color changes on fingertips consistent with biphasic Raynaud’s phenomenon; an antinuclear antibody test was positive (at 1:320 titers in a speckled pattern) with normal nailfold capillaroscopy. Clinical features of systemic sclerosis were absent. Twenty-four months later, the patient presented symmetric sensorimotor demyelinating polyneuropathy, and he was diagnosed with Guillain–Barre syndrome; treatment with intravenous gammaglobulin had an incomplete response. Raynaud’s phenomenon persisted associated with acrocyanosis, white nails, and positive ANA (1:1280 in a nucleolar pattern). POEMS syndrome was suspected, and serum protein electrophoresis (SPEP) was done. The SPEP revealed polyclonal gammopathy, and serum immunofixation showed monoclonal (M)-protein (IgG lambda). Serum vascular endothelial growth factor concentration showed increased levels. The patient was diagnosed with POEMS syndrome, and treatment with lenalidomide and dexamethasone improved the Raynaud’s phenomenon, acrocyanosis, and white nails, but the neurological response was partial. Conclusions POEMS syndrome may mimic clinical manifestations of systemic sclerosis v.g. Raynaud’s phenomenon, skin thickening, telangiectasia, and positive ANA. Raynaud’s phenomenon may precede other clinical manifestations of POEMS syndrome by several months. It is necessary to have a high index of suspicion for the diagnosis, especially in patients with peripheral polyneuropathy and monoclonal paraprotein. The significance of positive ANA in this condition is unknown and deserves further investigation.

Abstract Cardiac bradyarrhythmia and conduction disorder may be rare, but recurrent adverse events caused by bortezomib. Here we report a case with POEMS syndrome presenting severe heart block after bortezomib plus dexamethasone therapy. After permanent pacemaker implantation, bortezomib was restarted and maintained, resulting in sustained complete response for POEMS syndrome.