Castleman disease: delineating the spectrum

Glanzmann thrombasthenia (GT) is caused by inherited defects of the α_IIbβ₃ platelet glycoprotein. This bleeding disorder can be treated with platelet transfusion therapy, but some patients will be immunized and begin to form anti‐human leucocyte antigen (HLA) and/or anti‐α_IIbβ₃ antibodies. These antibodies can bind and interfere with the function of the transfused platelets, rendering treatment ineffective. However, platelet transfusion refractoriness attributable to HLA antibodies may be managed by the selection of compatible donors, although they are not always readily available, particularly in an emergency. Thus, anti‐α_IIbβ₃ antibodies represent one of the most severe complications in GT. Both genetic and environmental factors may contribute to the risk of anti‐α_IIbβ₃ development, but the underlying pathogenic mechanisms are still unknown. This review will summarize the current knowledge of the risk factors for development of anti‐α_IIbβ₃ antibodies in patients with GT and discuss how these findings may influence the clinical management of patients.     

Castleman病1例报道及文献复习

目的：认识Castleman病的临床和病理特征。方法：报道1例以多克隆免疫球蛋白升高、低蛋白血症、蛋白尿为主要表现而无显著浅表淋巴结肿大的Castleman病的临床资料并结合文献复习，为其诊断和鉴别诊断提供一条思路。结果：患者女性，43岁，体检发现白蛋白减少、球蛋白增高。双侧颈部、腹股沟淋巴结轻度肿大，但没有进行性增大。有蛋白尿。淋巴结活检病理：血管滤泡性淋巴组织增生，浆细胞型。结论：Castleman病临床较少见，易误诊，应列为多克隆免疫球蛋白升高的鉴别诊断，确诊需进行病理和免疫组织化学检查。     

Multicentric Castleman disease mimicking IgG4-related disease: A case report

A 50-year-old woman was referred to our hospital for shoulder joint stiffness. She had a history of polyclonal hypergammaglobulinemia and an elevated C-reactive protein level. Her laboratory data revealed an elevated serum immunoglobulin G4 (IgG4) level, hypergammaglobulinemia, and rheumatoid factor positivity in the absence of anticyclic citrullinated peptide antibody. [18^F]-Fluorodeoxyglucose positron emission tomography showed significant [18^F]-fluorodeoxyglucose uptake in multiple lymph nodes (axillary, hilar, para-aortic, and inguinal). Biopsy of the inguinal lymph node showed expansion of the interfollicular areas by heavily infiltrating plasma cells, consistent with multicentric Castleman disease (MCD). Immunohistochemical analysis revealed a 37.3% IgG4-positive:IgG-positive plasma cell ratio, indicating overlapping IgG4-related disease. However, serological cytokine analysis revealed elevated levels of interleukin-6 (9.3 pg/ml) and vascular endothelial growth factor (VEGF) (1210 pg/ml), which are compatible with MCD. Corticosteroid treatment resolved the serological and imaging abnormalities. IgG4-related disease can mimic MCD, and it is crucial to distinguish between these two diseases. Serum interleukin-6 and VEGF levels may help to discriminate MCD from IgG4-related disease.     

Tentative diagnostic criteria and disease severity classification for Castleman disease: A report of the research group on Castleman disease in Japan

Objectives: To determine the tentative diagnostic criteria and disease severity classification for Castleman disease (CD) and describe the clinical and pathologic features among human herpesvirus 8 (HHV-8) negative idiopathic multicentric CD (iMCD) in the Japanese population.

Methods: We established the working groups for the research of CD in Japan and had meetings to discuss and define the tentative diagnostic criteria and disease severity classification for CD. We subsequently analyzed 142 patients classified into iMCD by using the nationwide Japanese patient registry.

Results: We proposed the preliminary diagnostic criteria and disease severity classification for CD based on our discussion. In addition, we made a proposal for the disease activity score. We identified clinical and pathological features of patients with iMCD diagnosed by these diagnostic criteria. In the disease severity classification, 37, 33 and 30% patients were categorized into mild, moderate and severe diseases, respectively.

Conclusion: This is the first proposal for diagnosis and classification of CD by the Japanese group. Further studies are required to validate whether they can distinguish CD from other inflammatory diseases and to determine their sensitivity and specificity.     

Metastatic liver cancer： A rare case

Hemangiopericytoma is a rare tumor especially when it rises in the peritoneal cavity. We present a case of a 60-year-old woman with an isolated recurrent hemangiopericytoma of the liver. The patient presented with a palpable right upper quadrant abdominal mass, which occurred 7 years after undergoing resection of a malignant hemangiopericytoma arising from the greater omentum. She had not followed up 6 mo after surgery. Various imaging studies showed a single large, well-capsulated liver tumor with central necrosis, accompanied by hypervascularity typical of a vascular tumor. Preoperative laboratory HBsAg and anti-HCV workup were both negative. Under the impression of recurrent malignant hemangiopericytoma, right triseg-mentectomy was performed to completely resect the tumor. Pathological examination confirmed the diagnosis of recurrent hemangiopericytoma. Even though the incidence of the hemangiopericytoma is relatively low, malignant hemangiopericytoma has a tendency to recur frequently after a long-term disease-free interval. Also, the recurrent hemangiopericytoma is not easily detected early during follow-up until it becomes symptomatic because there are no specific tumor markers, and because of the diversity with regard to site of recurrence. The authors suggest that Positron Emission Tomogram (PET) may be a useful tool for the detection of recurrent hemangiopericytoma. We describe herein some characteristics and behaviors of malignant hemangiopericytoma, particularly after surgical resection.     

A case of huge primary liposarcoma in the liver

Primary liver liposarcoma is a rare disease.Because ofits rarity,the knowledge of the clinical course,manage-ment,and prognosis of primary liver liposarcoma are alllimited for clinicians.A 61-year-old female patient whosuffered from a huge primary liposarcoma in the centralportion of the liver had the clinical presentations offever,nausea,vomiting,jaundice,and body weight loss.The huge tumor was resected successfully.However,the tumor recurred repeatedly and she had repeatedhepatectomies to remove the tumor.The tumor becameaggravating after repeated surgeries.Eventually,thepatient had cervical spinal metastasis of liposarcoma andshe survived for 26 months after liver liposarcoma wasdiagnosed.Although the tumor may become aggrava-ting after repeated surgeries,repeated hepatectomiesare still the best policy to achieve a long-term survivalfor the patients.     

Human herpesvirus 8-associated multicentric Castleman disease in a patient with advanced HIV infection: A case report

Rational:Multicentric Castleman disease (MCD) is a nonclonal lymphoproliferative disorder that is rarely reported from Southeast Asian countries. Here, we report a case of human herpesvirus 8 (HHV-8)-associated MCD in a patient with advanced human immunodeficiency virus (HIV) infection who presented with prolonged intermittent fever, urticarial rash, hepatosplenomegaly, and generalized lymphadenopathy.Patient concerns:A 34-year-old man with advanced HIV infection who was in good compliance with his antiretroviral treatment regimen presented with intermittent fever, weight loss, marked hepatosplenomegaly, and generalized lymphadenopathy. Recurrent symptoms of high-grade fever, abdominal discomfort, pancytopenia, and high C-reactive protein level occurred for 16 months.Diagnoses:Histopathological findings of left inguinal lymph node revealed diffuse effacement of lymph node architecture with coexpression of HHV-8 latency-associated nuclear antigen 1 from immunohistochemical staining. The HHV-8 viral load was 335,391 copies/mL.Interventions:The patient was treated initially with one dose of intravenous rituximab (375 mg/m²) followed by subcutaneous rituximab (1400 mg) weekly for 5 weeks.Outcomes:The patient''s recurrent systemic symptoms subsided dramatically, and he has now been in remission for almost two years.Lessons:HHV8-associated MCD remains a diagnostic challenge in advanced HIV disease and should be suspected in those with recurrent flares of systemic inflammatory symptoms. Lymph node histopathology is essential for diagnosis and for excluding clonal malignancy. HHV-8 viral load is also useful for diagnosis and for monitoring disease activity.     

统计参数图软件对Alzheimer病患者脑PET图像的初步分析

目的 探讨阿尔茨海默病(AD)患者脑葡萄糖代谢特点及正电子发射计算机断层扫描(PET)对AD的诊断价值。方法 应用统计参数图(SPM)软件对13例AD患者和13例年龄、性别和文化程度相匹配的健康对照者脑PET检查结果进行处理分析。结果 (1)健康老年人可出现顶叶葡萄糖代谢的减低，但程度较轻；AD组全脑葡萄糖代谢减低，以顶叶为最明显，其次为颞叶，再次为额叶；(2)AD组扣带回31、23、7、30区，顶枕40、39区，颞叶20区和额叶9、6、8区等部位葡萄糖代谢减退较明显，差异有显著性(P＜0．05、0．001)。降低区域双侧基本对称，但额叶和颞叶的降低区左侧明显大于右侧。结论 AD患者脑葡萄糖代谢普遍性降低，个别脑区较为明显。扣带回的31、23、7、30区，顶枕的40、39区，颞叶的20区和额叶的9、6、8区等部位的葡萄糖代谢半定量指标降低可作为诊断AD的重要依据之一。     

Prediction of tumor biological characteristics in different colorectal cancer liver metastasis animal models using 18F-FDG and 18F-FLT

Background: Positron emission tomography(PET) is a noninvasive method to characterize different metabolic activities of tumors, providing information for staging, prognosis, and therapeutic response of patients with cancer. The aim of this study was to evaluate the feasibility of~(18)F-fludeoxyglucose(~(18)F-FDG) and 3'-deoxy-3'-~(18)F-fluorothymidine(~(18)F-FLT) PET in predicting tumor biological characteristics of colorectal cancer liver metastasis.Methods: The uptake rate of~(18)F-FDG and~(18)F-FLT in SW480 and SW620 cells was measured via an in vitro cell uptake assay. The region of interest was drawn over the tumor and liver to calculate the maximum standardized uptake value ratio(tumor/liver) from PET images in liver metastasis model. The correlation between tracer uptake in liver metastases and VEGF, Ki67 and CD44 expression was evaluated by linear regression.Results: Compared to SW620 tumor-bearing mice, SW480 tumor-bearing mice presented a higher rate of liver metastases. The uptake rate of~(18)F-FDG in SW480 and SW620 cells was 6.07% ± 1.19% and2.82% ± 0.15%, respectively(t = 4.69, P = 0.04); that of~(18)F-FLT was 24.81% ± 0.45% and 15.57% ± 0.66%, respectively(t = 19.99, P 0.001). Micro-PET scan showed that all parameters of FLT were significantly higher in SW480 tumors than those in SW620 tumors. A moderate relationship was detected between metastases in the liver and~(18)F-FLT uptake in primary tumors(r = 0.73, P = 0.0019).~(18)F-FLT uptake was also positively correlated with the expression of CD44 in liver metastases(r = 0.81, P = 0.0049).Conclusions: The uptake of~(18)F-FLT in metastatic tumor reflects different biological behaviors of colon cancer cells.~(18)F-FLT can be used to evaluate the metastatic potential of colorectal cancer in nude mice.     

A case of small bowel adenocarcinoma in a patient with Crohn's disease detected by PET/CT and double-balloon enteroscopy

Small bowel adenocarcinoma (SBA) in patients with Crohn's disease (CD) is quite rare, difficult to diagnose without surgery, and has a poor prognosis. Here, we report a 48-year-old man with SBA and a 21-year history of CD who was diagnosed by a combination of positron emission tomography/computed tomography (PET/CT) and double-balloon enteroscopy (DBE). Since the age of 27 years, the patient had been treated for ileal CD and was referred to our hospital with persistent melena. Multiple hepatic tumors were found by CT. PET/CT detected an accumulation spot in the small bowel. DBE revealed an ulcerative tumor in the ileum about 100 cm from the ileocecal valve. An endoscopic forceps biopsy specimen showed poorly differentiated adenocarcinoma. There were some longitudinal ulcer scars near the tumor, and the chronic inflammation in the small bowel appeared to be associated with the cancer development. Previous reports suggest the risk of SBA in patients with CD is higher than in the overall population. Since early diagnosis is extremely difficult in these cases, novel techniques, such as PET/CT and DBE, may be expected to help in making a preoperative diagnosis of the development of SBA in CD.     

Actinomycotic liver abscess: A rare complication of colonic diverticular disease

We present the first case of hepatic actinomycosis requiring both medical and surgical intervention due to liver dissemination from a primary colonic abscess. A 52-year-old white male had a computerised (CT) abdominal scan following an episode of collapse and was found to have peri-colonic and hepatic abscesses. Prior to this episode, he suffered with a two month history of fever, unexplained weight loss, and anaemia suggesting possible malignancy. He was treated with both radiological and surgical drainage of the abscesses, alongside the antibiotic cover and underwent an anterior colonic resection with primary anastomosis. There have been no previous reports of an actinomycotic liver abscess complicating colonic diverticular abscess. A multi-team approach is recommended when disseminated actinomycotic infection is encountered.     

Bone marrow manifestations in multicentric Castleman disease

This study aimed to document the morphological and immunophenotypic features, and describe the diagnostic features of bone marrow (BM) involvement in human herpes virus 8 Multicentric Castleman disease (HHV8‐MCD). BM trephine biopsy (BMTB) specimens from 28 patients were revisited. Samples were evaluated for expression of CD3, CD20, CD138, CD68R, glycophorin C, CD42b, HHV8‐latency‐associated nuclear antigen (LANA1), Epstein–Barr virus‐encoded small RNA and light chains. Presence of significant numbers of HHV8‐LANA1⁺ lymphoid/plasmacytic cells, noted in 10/28 cases, was indicative of BM involvement and was associated with low CD4 and CD8 counts in peripheral blood. The characteristic morphological appearance of MCD seen in lymph nodes is a rare finding in BMTB. 4/5 cases with lymphoid aggregates were involved by MCD, whereas 6/23 cases without lymphoid aggregates were involved by MCD (P = 0·023). 9/18 cases with hypercellular marrow were involved by MCD, whilst only 1/8 cases with normo/hypocellular marrow showed involvement by MCD (P = 0·070). While 9/21 cases with increased marrow reticulin were involved by MCD, none of the cases with no increase in reticulin were involved by MCD (P = 0·080). Reactive plasmacytosis is a frequent finding. We conclude that bone marrow is involved in a significant proportion of patients with MCD (36%), and involvement can be identified by HHV8‐LANA1 immunohistochemistry.     

Unicentric Castleman disease presenting as a retroperitoneal peripancreatic mass: A report of two cases and review of literature

Castleman disease(CD) is a rare disorder of lymph nodes and related tissues. CD generally occurs in the mediastinum, as well as in cervical, retroperitoneal and axillary regions. The disease is classified into two major types: unicentric CD(UCD) and multicentric CD. The occurrence of UCD in the retroperitoneal peripancreatic region is quite rare. We encountered two cases of retroperitoneal peripancreatic UCD in our hospital during the past three years. Following a series of medical examinations, including magnetic resonance imaging, computed tomography, ultrasonography and postoperative histopathological examination, these two patients were diagnosed with UCD,which presented as a retroperitoneal peripancreatic mass.The mass in each patient was completely excised,and no postoperative radiochemotherapy was administered.Both patients recovered well without recurrence during a follow-up period of 30 mo and 8 mo.     

Use of rituximab as a salvage therapy for HIV-associated multicentric Castleman disease

Several approved therapies for multicentric Castleman disease (MCD) cannot be uniformly applied due to intolerable side effects. There is also a high percentage of recurrence of this disease despite treatment. Rituximab may be effective in controlling MCD in a subset of patients. This paper includes a brief case report and an extensive review of previously published cases. We observed an aggravation of concomitant cutaneous Kaposi sarcoma, and hypothesize that rituximab could have exacerbated it.     

成人型尼曼-匹克病合并严重肝损伤1例

患者女,37岁,因乏力、纳差、尿黄4个月,加重半个月于2009年12月16日入院.患者于4个月前无明显诱因出现高度乏力,休息后无缓解,食欲明显下降、厌油,尿色逐渐加深为浓茶色.在多家医院就诊,肝功能检查均明显异常,曾先后拟诊为"病毒性肝炎"和"原发性胆汁性肝硬化",予以泼尼松、硫唑嘌呤、熊去氧胆酸等保肝降酶药治疗.泼尼松最大剂量60mg/d,治疗3个月后维持剂量20mg/d.经上述治疗,症状曾有所缓解,血清ALT由542 U/L下降为128 U/L,总胆红素(Tbil)由225 μmol/L下降为80 μmol/L.     

Primary gastrointestinal stromal tumor of the liver： A case report

We report a case of primary gastrointestinal stromal tumor （GIST） of the liver. A 17-year-old man with a solid mass in the anterior segment of the right liver was asymptomatic with negative laboratory examinations with the exception of positive HBV. Contrast-enhanced ultrasound （CEUS） revealed a hypervascular lesion in the arterial phase and hypoechoic features during the portal and late phases. However, enhanced spiral computed tomography （CT） showed hypoattenuation in all three phases. Following biopsy, immunohistochemical evaluation demonstrated positive CDl17. Different imaging features of primary GISTs of the liver are due to pathological properties and different working systems between CEUS and enhanced spiral CT.     

Diagnostic value of 18F-FDG PET in the assessment of myocardial viability in coronary artery disease: A comparative study with 99mTc SPECT and echocardiography

ObjectiveTo investigate the diagnostic value of 18F-fluorodeoxyglucose positron emission tomography （18F-FDG PET） in the as-sessment of myocardial viability in patients with known coronary artery disease （CAD） when compared to99mTc single photon emission computed tomography （SPECT） and echocardiography, with invasive coronary angiography as the gold standard.MethodsThirty patients with diagnosed CAD met the selection criteria, with 10 of them （9 men, mean age 59.5 ± 10.5 years） undergoing all of these imaging proce-dures consisting of SPECT and PET, echocardiography and invasive angiography. Diagnostic sensitivity of these less invasive modalities for detection of myocardial viability was compared to invasive coronary angiography. Inter- and intra-observer agreement was assessed for di-agnostic performance of SPECT and PET.ResultsOf all patients with proven CAD, 50% had triple vessel disease. Diagnostic sensitivity of SPECT, PET and echocardiography was 90%, 100% and 80% at patient-based assessment, respectively. Excellent agreement was achieved between inter-observer and intra-observer agreement of the diagnostic value of SPECT and PET in myocardial viability （k= 0.9）. Conclusion18F-FDG PET has high diagnostic value in the assessment of myocardial viability in patients with known CAD when com-pared to SPECT and echocardiography. Further studies based on a large cohort with incorporation of18F-FDG PET into patient management are warranted.     

Paraneoplastic pemphigus uncovers distinct clinical and biological phenotypes of western unicentric Castleman disease

Unicentric Castleman disease (UCD) is a lymphoproliferative disease of unknown cause. Paraneoplastic pemphigus (PNP) is a major complication shown to be associated with a poor prognosis, with particular severity in patients with bronchiolitis obliterans (BO). This study describes the clinical and biological characteristics of UCD-PNP patients in a large Western cohort. A total of 148 patients diagnosed with UCD were identified, including 14 patients with a defined PNP. PNP was significantly associated with myasthenia gravis (MG) and FDC sarcoma during follow-up (FDCS). PNP was also significantly associated with reduced survival. These data, together with a multivariate analysis by principal components, led to the identification of UCD-PNP as a group at risk of MG, FDCS and death. PDGFRB sequencing performed on UCD lesions from six patients found the gain-of-function p.N666S variant in two. Interestingly, both patients had hyaline-vascular UCD subtype, were in the UCD-PNP subgroup and had FDCS. Sera from 25 UCD-PNP patients and 6 PNP patients without UCD were tested for PNP-associated autoantibodies. Sera from UCD-PNP patients had a strong reactivity against the N-terminal domain of recombinant periplakin (rPPL, 82%) and showed reactivity against at least two domains of rPPL. These features were not found in patients with UCD alone or in the PNP group without UCD. These data indicate that UCD-PNP patients belong to a subgroup sharing strong clinical and biological identity that might help to decipher the different dynamics of UCD natural history.