Castleman disease of the hyaline vascular variant transforming to POEMS syndrome as endpoint: a case report
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POEMS syndrome is a rare neoplastic syndrome reflected by plasma cell disorder. It is composed by polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes. It is also reported to associate with Castleman disease. The early identification and treatment are pivotal to reduce the morbidity and mortality.
Here we report a 66-year-old man with treated Castleman disease developing with sequential presence of endocrinopathy polyneuropathy, skin changes, organomegaly and extravascular volume overload within 18 years, which was finally confirmed as POEMS syndrome by positive monoclonal protein. He was thereafter successfully treated with prednisone and azathioprine as primary therapy and thalidomide as maintenance therapy.
The diagnosis of POEMS is based on a cluster of disorder involved in varied organs. We report a rare case that triggers the need to consider POEMS syndrome diagnosis for patients carrying Castleman disease and polyneuropathy.
KeywordsPOEMS syndrome Castleman disease Polyneuropathy
Chronic inflammatory demyelinating polyneuropathy
The cerebrospinal fluid
Oral glucose tolerance test
Vascular epithelial growth factor
Castleman disease (CD) is a rare disorder known as angiofollicular lymph node hyperplasia, which occurs in around 11–30% of patients with POEMS syndrome (Crow-Fukase syndrome) . POEMS syndrome compromises polyneuropathy, organomegaly, endocrinopathy, monoclonal protein, and skin changes . Endocrinopathy is the core component of the syndrome, reflected by hypogonadism, thyroid abnormalities, glucose metabolism abnormalities and adrenal insufficiency. Due to the unclear pathogenesis of the syndrome, risk stratification mainly relies on clinical phenotype instead of molecular marker and the extent of the plasma cell disorder is prognostic to determine therapeutic options .
Discussion and conclusions
POEMS syndrome is a rare paraneoplastic syndrome compromising polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes . The diagnosis is easily missed as it is generally established on a group of clinical onset and laboratory features. The mandatory criteria of POEMS diagnosis include polyneuropathy (typical demyelinating) and monoclonal plasma cell-proliferative disorder (almost always λ). CD (separate of POEMS syndrome variant), sclerotic bone lesions, vascular endothelial growth factor elevation constitute other major but not obligatory criteria. Other important features known as minor criteria are defined as organomegaly, extravascular volume overload, endocrinopathy, skin changes, papilledema and thrombocytosis or polycythemia . Only those with two key components of the mandatory criteria could be diagnosed as standard POMES syndrome. Otherwise, the POEMS syndrome variant should be defined in case of complicated CD.
Our patient was initially diagnosed with Castleman disease without any clinical evidence of POEMS syndrome. The following radiotherapy showed good clinical response. After 4 years post radiotherapy, the first onset of manifestation was dysglycemia. The polyneuropathy in the form of limb numbness emerged in an interval of 2 years. The typical Castleman disease variant of POEMS syndrome has no clonal PCD and typically little to no peripheral neuropathy, therefore Castleman’s disease variant of POEMS syndrome could not be defined in our patient. Although he did not respond to the standard CIDP therapy and the alternative diabetic neuropathy standard therapy, the potential POEMS syndrome was not considered and obligatory laboratory tests including monoclonal protein (especially λ) test for its early diagnosis were therefore missed. The subsequent presence of skin pigmentation, splenomegaly and progressive polyneuropathy then elicitedthe clue of POEMS syndrome, which was confirmed by appearance of monoclonal protein(λ) (Fig. 3).
The incidence of POEMS in CD cases has not been accurately reported. Several published cases of CD with interesting features are likely cases of POEMS. In 30 POEMS syndrome cases, 19 biopsied lymph nodes showed Castleman disease of angiofollicular hyperplasia type in total of 32 samples . In another report, 25 of 43 biopsied lymph nodes were pathological of Castleman disease, 84% of which was diagnostic of hyaline vascular type . The concurrent cavity effusion and co-existing Castleman disease predicted poor prognostic and short survival, reflected by two-year survival interval post initiated therapy in this case [2, 5]. The pathogenesis of this syndrome is currently unknown, in which vascular epithelial growth factor (VEGF) might play a role as its remarkable elevation in most POEMS syndrome patients . Although the serum and plasma level of VEGF correlated with activity of this disease [7, 8, 9], the use of anti-VEGF antibody remains controversial. Due to its rarity and heterogeneity, randomized clinical trials are hardly published to establish the consensus management, therefore, the treatment is majorly based on case reports and series. The successful managements aim to the inhibition of clonal plasma cell disorder instead of targeting VEGF pathway. In the case of localized plasma cell disease with sole bone lesion and no bone marrow infiltration, radiation is recommended. In condition of bone marrow dissemination, systemic chemotherapy is considered as the priority. Lenalidomide or thalidomide combined with dexamethasone has also exhibited clinical benefit on VEGF, peripheral neuropathy and extravascular volume overload , especially for patients with poor PS or opposed to chemotherapy. In consideration of poor ECOG (score 3) and exclusive bone marrow dissemination, our patient was finally managed with prednisone, azathioprine and sequential thalidomide as maintenance therapy with good clinical response, in line with previous studies. Although azathioprine is not considered as the mainstay of conventional systemic therapy in POEMS syndrome, its combination with corticosteroids showed promise with managed toxicity. Its benefit against peripheral polyneuropathy needs to be weighted in the future clinical trials.
In conclusion, the diagnosis of POEMS was based on a cluster of clinical manifestations and laboratory investigations. Especially for patients with CD history, the presence of polyneuropathy requires clinicians to distinguish from POEMS syndrome variant of CD to standard POEMS syndrome, therefore a detailed history collection and physical examination in addition to essential laboratory tests (bone marrow biopsy, VEGF level test and monoclonal protein) are necessary to rule in the diagnosis. The mainstays of POEMS syndrome therapy mainly target to plasma cell disorder or local lesions, dependent on the status of bone marrow infiltration. In our case, the long-term transition of treated CD to POEMS syndrome might give a clue to elaborating the pathogenesis of this disease in the future.
This work was supported by the grant from Anhui University Natural Science Research (KJ2016A322). The funders had no role in study design, data collection and analysis, decision to publish or preparation of the manuscript.
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Data generated during this study are included in this published article.
YJG collected and interpreted the clinical data. QD completed the pathology analysis. YJG and YD wrote the manuscript and the graphical illustrations. All authors critically revised and approved the manuscript.
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