Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin Changes Research Articles

Prevalence of MGCS Among Patients With Monoclonal Gammopathies.

Prevalence of MGCS Among Patients With Monoclonal Gammopathies.

103 High rates of venous and arterial thrombotic events in POEMS patients

BackgroundArterial and venous thrombotic events occur in patients with POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes) syndrome with a previously reported rate of 20%. We reviewed the UK POEMS Registry to describe the rate of venous thromboembolism (VTE), arterial events and risk factors.MethodsThe UK POEMS Registry is the largest single-centre cohort in Europe and comprises 100 patients. Data were collected on arterial and venous thrombotic events from 1999 to present day.ResultsOf the 83 assessable patients, median age at presentation was 52 years. Twenty-five patients expe- rienced 35 clinically apparent arterial or venous events. Eleven patients had 14 VTEs including deep vein thrombosis (DVT, 4/14), pulmonary embolism (4/14) and peripherally inserted central catheter-associated DVT occurring during autologous stem cell transplant (4/14). Sixteen patients experienced 21 arterial events: stroke (7/21), peripheral arterial occlusion (6/21), myocardial infarction (4/21) and microvascular disease (2/21), with no discernible relationship with thrombocytosis or polycythaemia. The combined venous and arterial event rate was 42%, over double that previously reported. There were more arterial than venous events, and most occurred during active pre-treated disease indicating a need for a pre- emptive approach to thromboprophylaxis.ConclusionArterial and venous thromboses are more common in POEMS syndrome than previously reported and appear associated with disease pathology and activity. We propose a management strategy for appropriate thromboprophylaxis in POEMS patients throughout the course of disease.stephen.keddie@nhs.net

What Is in the Literature.

What is in the Literature focuses on peripheral neuropathies with new and practical information related to the diagnosis, treatment, and management. Diagnostic and treatment guidelines are available for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) but not all clinicians follow them resulting in erroneous diagnoses and prolonged treatment. Secondary axonal loss in CIDP causes increased connective tissue in muscle. Antibodies to proteins at the node of Ranvier are found in a small percentage of patients with CIDP. The differential diagnosis for CIDP-like neuropathies includes amyloid neuropathy and POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) and amyloidosis. Upper limits for cerebral spinal fluid protein are 0.45 g/L and cell count <10/µL, but both may be too low. Hyperactive reflexes may occur in Guillain-Barré syndrome and should not exclude the diagnosis. In severely affected Guillain-Barré syndrome patients, a second dose of intravenous immune globulin within 4 weeks of onset is not likely to be effective.

Monoclonal gammopathy of undetermined significance (MGUS): where is the hidden danger? Definition and work-up

SummaryMonoclonal gammopathy of undetermined significance (MGUS) is a premalignant hematological condition arising from B‑cells, characterized by the presence of monoclonal immunoglobulin production, also known as paraprotein. It is found in up to 3% of individuals over the age of 50 years. The overall progression rate is low at around 1% per year, with most patients progressing to multiple myeloma (MM). Other diseases that may arise from MGUS include non-Hodgkin lymphomas, Waldenström macroglobulinemia, amyloid light-chain (AL) amyloidosis, POEMS (polyneuropathy, organomegaly, endocrinopathy, M‑protein, skin changes), cryoglobulinemia, monoclonal gammopathy of renal significance (MGRS), and additional paraprotein-driven diseases. Every case of monoclonal gammopathy warrants careful investigation to rule out the presence of a malignant form. In recent years, paraprotein-associated conditions such as MGRS have been increasingly recognized. Accurate diagnosis and work-up of these cases require a multidisciplinary approach, and it is paramount to accurately distinguish them from true MGUS in order to prevent end-organ damage. Follow-up of MGUS should be lifelong; however, a risk-adapted approach involving the primary care setting is recommended.

Mass cytometry in POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome: looking for a needle in a haystack.

Mass cytometry in POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome: looking for a needle in a haystack.

Relapse of POEMS Following Autologous Stem Cell Transplantation: A Single Center Experience

Abstract 3101The POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome is a rare paraneoplastic disorder secondary to a clonal plasma cell process. The most experience with successful outcomes in POEMS with disseminated disease has been with high dose chemotherapy followed by autologous stem cell transplantation (ASCT). However, the risk of relapse of POEMS following an ASCT or the outcome of the patients who relapse is not known. We therefore performed a retrospective review of POEMS patients who underwent ASCT at our center and subsequently relapsed or progressed.Over the past 12 years, 58 patients with POEMS underwent autologous stem cell transplantation at the Mayo Clinic, Rochester between Mar 18, 1999 and Jun 22, 2011. With a median follow up of 40 months (1–147 months), 12 patients have relapsed. The median time to relapse was 41 months. The 1, 2, and 5 year PFS rates were 98%, 94%, and 75%, respectively (Figure 1), and the 1, 2, and 5 year OS rates were 98%, 98%, and 94%. [Display omitted] Of the 12 patients with documented relapse, 7 had baseline PET/CT scans all of which had FDG avid lesions. By 1 year, the FDG avidity had not resolved in 4 of these patients who then went on to either develop additional lesions or increasing SUV of existing lesions. Of the 12 patients with documented relapse, 8 had baseline VEGF measurements, and all but 1 had normalization by 1 year. The first sign of relapse was a clinical deterioration in 2, a rising M-protein in 3, and a rising plasma VEGF level in 5 patients. All of these patients had new or worsening of existing lesions on PET/CT scan (n= 9) or x-ray imaging (n= 3). The symptoms of clinical relapse included pain at the site of the lytic lesion and generalized pain with swelling. Of the patients who relapsed, 5 were treated with radiation therapy, 4 received lenalidomide or thalidomide, 2 had alkylator based therapy and 1 had bortezomib based therapy. One patient was treated with surgical resection of his hepatic plasmacytoma and 2 patients have been observed without needing definitive treatment as of yet. One patient also received anti-VEGF treatment with bevacizumab unsuccessfully after failing cyclophosphamide therapy.In this large cohort of POEMS patients treated with high dose chemotherapy and autologous stem cell transplantation in a single center, a relapse rate of 21% was noted. Not every patient who relapsed has been deemed to need further treatment, and most patients could be salvaged with chemotherapy or radiation. Only one patient died from relapsed POEMS following stem cell transplantation. Disclosures:No relevant conflicts of interest to declare.

A case of atypical POEMS syndrome without polyneuropathy

POEMS (Polyneuropathy, Organomegaly, Endocrinopathy, M-protein, Skin changes) syndrome is a rare hematological disease associated with overproduction of pro-inflammatory cytokines. Under the current nomenclature and diagnostic criteria for POEMS syndrome, the presence of characteristic polyneuropathy is required for diagnosis. We report a 43-year-old Japanese woman with organomegaly, endocrinopathy, M-protein, skin lesions, as well as typical renal lesions and sclerotic bone lesions. Of note, neurological examinations and peripheral nerve conduction tests were normal in this patient. In view of the overwhelming number of otherwise characteristic signs and symptoms, we made a provisional diagnosis of 'atypical POEMS syndrome without polyneuropathy'. If further similar cases are reported in the future, reconsideration of the nomenclature and/or diagnostic criteria for POEMS syndrome may be required.

Bilateral Optic Neuropathy Associated with Multiple Myeloma

A 51-year-old man had reduced vision and bilateral optic disc swelling as the initial clinical manifestation of multiple myeloma. Brain imaging failed to disclose any abnormalities. Before any therapy was begun, visual function began to improve substantially. Three months after chemotherapy was started, visual function and optic disc appearance returned to near normal. There were no features to suggest polyneuropathy-organomegaly-endocrinopathy-M protein-skin changes (POEMS) syndrome. Visual loss in myeloma is usually caused by compression or infiltration of the optic nerves by tumor. The mechanism of the optic neuropathy in this case remains unknown.

Uncompacted Myelin Lamellae in Peripheral Nerve Biopsy

Since 1979, the authors have studied 49 peripheral nerve biopsies presenting uncompacted myelin lamellae (UML). Based on the ultrastructural pattern of UML they propose a 3-category classification. The first category includes cases displaying regular UML, which was observed in 43 cases; it was more frequent in 9 cases with polyneuropathy organomegaly endocrinopathy m-protein skin changes (POEMS) syndrome as well as in 1 case of Charcot-Marie-Tooth 1B with a novel point mutation in the P0 gene. The second category consists of cases showing irregular UML, observed in 4 cases with IgM monoclonal gammopathy and anti-myelin-associated glycoprotein (MAG) activity. This group included 1 benign case and 3 B-cell malignant lymphomas. The third category is complex UML, which was present in 2 unrelated patients with an Arg 98 His missense mutation in the P0 protein gene. Irregular and complex UML are respectively related to MAG and P0, which play a crucial role in myelin lamellae compaction and adhesion.

Glomeruloid Hemangioma A Distinctive Cutaneous Lesion of Multicentric Castlemanʼs Disease Associated with POEMS Syndrome

A histologically distinctive cutaneous hemangioma occurring in two patients with biopsy-proven multicentric Castleman's disease associated with POEMS (polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes) syndrome are reported. The lesions were multiple, and appeared as red to purple papules over the trunk and proximal limbs. Microscopically, ecstatic dermal vascular spaces were seen filled with aggregates of capillaries, resulting in structures reminiscent of renal glomeruli. Interspersed between the blood-filled capillary loops were plump "stromal" cells possessing clear vacuoles and periodic acid-schiff-positive eosinophilic globules. These cells had the immunohistochemical profile of endothelial cells (positivity for factor VIII-related antigen, and negativity for leukocyte common antigen, macrophage marker, and muscle-specific actin), and probably represented immature elements that had accumulated immunoglobulins and other proteinaceous material from the circulation. Because vascular lesions may appear before the full-blown POEMS syndrome develops, we suggest careful evaluation and follow-up of all patients presenting with glomeruloid hemangioma or cherry-type capillary hemangioma with focal glomeruloid features for potential development of this syndrome.