肝原发血管肉瘤临床及病理学特点分析

目的 探讨肝原发性血管肉瘤的临床病理特点并复习相关文献.方法 搜集并分析解放军总医院病理科1988至2012年诊断的20例肝原发性血管肉瘤患者的临床表现、肿瘤病理形态特征及免疫表型特点(CD34、CD31、第八因子相关抗原、CK、GPC-3、Hepatocyte、波形蛋白、PTEN、结蛋白、CD117、Ki-67)等并进行随访.结果 20例患者中,男性11例,女性9例,平均年龄53.2岁(7～86岁),肿瘤发生部位:肝右叶11例,肝左叶6例,左右叶弥漫生长3例.大体观察:肿瘤组织呈暗红色,蜂窝状,伴出血坏死.镜下观察:形态多样,有海绵状血管瘤样、上皮样血管内皮细胞瘤样改变,移植肝复发肿瘤与肝原发肿瘤形态有差别,但均能找到较特异的血管肉瘤诊断特征.免疫组织化学染色显示肿瘤组织至少表达CD31、CD34、第八因子相关抗原中的1项,波形蛋白表达均为弥漫阳性(20/20),10例PTEN低表达(10/20),Ki-67阳性指数均大于10％,最高达60％.1例CK表达阳性(1/20),结蛋白、CD117、Hepatocyte及GPC-3均为阴性.结论 原发性肝血管肉瘤是一种罕见的预后很差的恶性肿瘤,结合组织学形态并联合应用多项血管内皮标志物可作出明确诊断.     

Serum amyloid A protein (SAA): a marker for liver allograft rejection in humans

Serum amyloid A protein (SAA) concentrations were monitored in 12 consecutive liver transplant recipients until the 70th postoperative day. Fourteen rejection episodes were identified histologically in 42 liver biopsies of the grafts. Of 12 rejections 8 (66.7%) were characterized by pronounced simultaneous increases in SAA concentrations in plasma, the mean peak value being 16.94 ± 8.82 mg/dl (range 4.58–28.55 mg/dl) compared with a mean normal value of 0.98 ±0.42 mg/dl in healthy controls. Of 42 biopsies 28 did not show histological evidence of graft rejection. Of 25 negative biopsies 24 (96.0%) were not accompanied by a parallel SAA increase in plasma. These findings demonstrate that measurements of SAA concentrations may provide a valuable non-invasive aid in identifying acute liver allograft rejection in humans.Abbreviations CRP C-reactive protein - ROC receiveroperating characteristic - SAA serum amyloid A protein Correspondence to: G. Feussner     

Seizure susceptibility and mortality in mice that over-express amyloid precursor protein

Alzheimer's disease and Fragile X syndrome both display synaptic phenotypes, and based on recent studies, likely share dendritic over expression of amyloid precursor protein (APP) and beta-amyloid (Abeta). In order to create a mouse model to specifically study the effects of APP and Abeta at synapses, we crossed Tg2576, which over-express human APP with the Swedish mutation (hAPPsw), with fmr-1 KO mice. The progeny, named FRAXAD, displayed increased mortality (23% by 30 days of age) compared to Tg2576 (3%) and WT and fmr-1 KO littermate controls (0%) consistent with a developmental defect. By 60 days of age, both the Tg2576 and FRAXAD mice approached a 40% mortality rate compared to 0% for WT and fmr-1 KO littermates. To understand the mechanism underlying increased mortality in APP over-expressing mice, we assessed seizure thresholds in response to pentylenetetrazol (PTZ). Both the Tg2576 and FRAXAD mice had a lower threshold to PTZ-induced seizures (average seizure score of >/=4.0) in comparison to nontransgenic littermates (average seizure score 1.9-2.9). Seizures are a major phenotype of AD, FXS, Down syndrome, autism and epilepsy, and these data suggested that developmental over-expression of dendritic APP or Abeta increased seizure susceptibility.     

肝纤维化指标的检测及临床意义

目的 研究血清纤维化指标透明质酸（HA）、IV型胶原（Ⅳ-c）、Ⅲ型前胶原肽（PCⅢ）、层粘连蛋白（LN）水平与肝纤维化指标的关系.方法 对确诊的慢性乙型肝炎及肝硬化患者124例和健康人18例,测定血清纤维化指标水平,33例患者进行肝穿行肝组织炎症及肝纤维化分期.血清纤维化指标行统计学分析.结果 血清中HA与CIV水平在慢性肝炎各相平行,而LN与PCⅢ在慢性肝炎病理分期相同时结果一致,在G4期时PCⅢ结果与正常对照相近.四项指标与对照组比较有明显升高.结论 血清纤维化指标与肝纤维化有一定的相关性,这些指标与临床结合对肝纤维化有一定的价值.LN与PCⅢ在慢性肝炎患者分期G_4前与纤维化程度相一致,联合多项指标检测可在一定程度上提高肝纤维化诊断.     

Immunohistology of islet amyloid polypeptide in diabetes mellitus: Semi-qantitative studies in a post-mortem series

Summary Immunoreactivity for islet amyloid polypeptide (IAPP) in the islets of Langerhans of non-insulin-dependent diabetic patients and non-diabetic patients of a non-selected post-mortem series was studied with a new polyclonal IAPP antibody. Out of 133 patients examined, 124 exhibited immunoreactivity for IAPP. Immunoreactivity was localized intra- and extracellularly and was limited to the islets of Langerhans. No extracellular immunoreactivity was observed in amyloid-negative cases. Co-localization of insulin and IAPP in the same islet-cells was verified by double staining with monoclonal insulin and polyclonal IAPP antibodies. Of 100 patients with non-insulin-dependent diabetes mellitus (NIDDM) and islet amyloid, 98 exhibited IAPP-positive deposits and 71 exhibited intracellular immunoreactivity. Evaluation of intracellular immunoreactivity and degree of islet amyloid deposition in cases of overt NIDDM revealed an inverse relationship, in that intracellular IAPP immunoreactivity were reduced in patients with developing islet amyloid deposition. Our data are consistent with the hypothesis of primary-cell dysfunction leading to amyloid formation, with subsequent disturbance of-cell homeostasis.Supported by the Johanna and Fritz Buch-Gedächtnisstiftung (Hamburg, FRG)     

Amyloid tumor: a clinical and cytomorphologic study

We describe the cytologic findings and clinical presentation of three unusual cases of amyloid tumor. Two of our patients had low-grade lymphoid malignancies and the third insulin-dependent diabetes mellitus. In no cases was amyloid suspected as the cause of mass lesion. Two of our cases presented with superficial soft tissue mass and the third with right breast masses and bilateral axillary lymph node enlargement. Air-dried slides from all aspirated cases were stained with Diff-Quik for specimen adequacy evaluation. The remaining fixed slides were stained with Papanicolaou stain. Amyloid appeared as dark-blue to purple clumps of acellular material on Diff-Quik stain, accompanied with chronic inflammatory cell infiltrates and multinucleated giant cells, simulating granulomatous inflammation. Papanicolaou stain demonstrated cyanophilic to orangophilic acellular material. Amyloid was suspected and subsequently confirmed by Congo red stain.     

Intracranial peripheral primitive neuroectodermal tumors of the cavernous sinus: a diagnostic peculiarity

Peripheral primitive neuroectodermal tumors (pPNETs) are aggressive, poorly differentiated neoplasms that occur in children and young adults. These tumors are associated with a peak incidence in the second decade and a slight male preponderance. Recently, Ewing sarcoma and pPNET tumors have been proven to carry identical translocations, the most common being t(11;22)(q24;q12). Intracranial Ewing sarcoma/pPNETs have rarely been described in the literature. We studied a case of intracranial pPNET arising in the right cavernous sinus of a 46-year-old man. On imaging, the tumor had both sellar and suprasellar components and was centered within the right parasellar region. Histologically, the tumor was composed of intermediate to large cells with round to oval hyperchromatic nuclei with distinct nucleoli. The cells contained a moderate amount of slightly basophilic cytoplasm. The tumor was markedly fibrotic and had collagen bands surrounding both individual and groups of cells. A large immunohistochemical panel was positive only for CD99 and vimentin. Fluorescence in situ hybridization did not show translocations associated with Ewing sarcoma/pPNET. However, a small percentage of these tumors can be negative for this translocation. In these cases, histology and immunohistochemical techniques in the absence of an alternative diagnosis are the only tools available to establish the diagnosis.     

Evidence that neurones accumulating amyloid can undergo lysis to form amyloid plaques in Alzheimer's disease

AIMS: Amyloid has recently been shown to accumulate intracellularly in the brains of patients with Alzheimer's disease (AD), yet amyloid plaques are generally thought to arise from gradual extracellular amyloid deposition. We have investigated the possibility of a link between these two apparently conflicting observations. METHODS AND RESULTS: Immunohistochemistry and digital image analysis was used to examine the detailed localization of beta-amyloid(42) (A beta 42), a major component of amyloid plaques, in the entorhinal cortex and hippocampus of AD brains. A beta 42 first selectively accumulates in the perikaryon of pyramidal cells as discrete, granules that appear to be cathepsin D-positive, suggesting that they may represent lysosomes or lysosome-derived structures. AD brain regions abundantly populated with pyramidal neurones exhibiting excessive A beta 42 accumulations also contained evidence of neuronal lysis. Lysis of these A beta 42-burdened neurones apparently resulted in a local, radial dispersion of their cytoplasmic contents, including A beta 42 and lysosomal enzymes, into the surrounding extracellular space. A nuclear remnant was found at the dense core of many amyloid plaques, strengthening the idea that each amyloid plaque represents the end product of a single neuronal cell lysis. The inverse relationship between the amyloid plaque density and pyramidal cell density in the AD brain regions also supports this possibility, as does the close correlation between plaque size and the size of local pyramidal cells. CONCLUSIONS: Our findings suggest that excessive intracellular accumulation of A beta 42-positive material in pyramidal cells can result in cell lysis, and that cell lysis is an important source of amyloid plaques and neuronal loss in AD brains.     

Study on diagnostic values of haptoglobin and serum amyloid A concentration in bovine heart diseases

Two hundred dairy breed cattle of different ages [42 were between 3 and 6 months (20 males and 22 females), 55 cases were heifers (16–24 months old) and the rest were adult dairy cattle] from four dairy farms were examined by auscultation. Seventy-seven cases out of 200 cattle had various types of functional (n = 50) and pathological (n = 10) murmurs, pericarditis (n = 10), and endocarditis (n = 7). Twenty normal cattle without any sign of heart disease and cardiac murmurs were also taken as a control group. Blood samples were taken from all cattle having cardiac disorders and control group for determination of haptoglobin (Hp), serum amyloid A (SAA), and complete blood count. White blood cell (WBC) of cases with endocarditis was significantly higher than other groups. Cases with pericarditis and endocarditis had the highest Hp and SAA levels, respectively. The optimal cutoff point was set, by the receiver operating characteristics method, to >4.74 μg/ml for SAA and >0.14 g/l for Hp with corresponding 58.44% sensitivity and 80.00% specificity for SAA and 22.08% sensitivity and 100% specificity for Hp. Our study showed that for differentiation of four types of cardiac disorders mentioned (functional murmurs, pathologic murmurs, endocarditis, and pericarditis), SAA determination is more suitable than Hp and WBC count.     

Trichomoniasis: its clinical significance and diagnostic challenges

Trichomoniasis is a significant STD worldwide. Clinical studies have demonstrated that trichomoniasis may have serious side effects both in pregnancy and in a predisposition to retrovirus infection. Therefore it is important that clinicians request the most accurate diagnostic test available. This is mandated by the significant percentage of both male and female patients that may be asymptomatic. Numerous clinical studies have indicated that the most sensitive test for T. vaginalis is with culture. The InPouch TV culture test has demonstrated high sensitivity, long shelf life, and microscopic advantages over other culture procedures.     

An ELISA assay for murine amyloid a and serum amyloid a utilizing monoclonal antibodies

An enzyme-linked immunoassay has been developed to quantitate the amyloid A (AA) and serum amyloid A (SAA) proteins of mice. The assay utilizes monoclonal rat anti-mouse AA as the antibody. The principle advantage of this method is that it avoids the need to denature the mouse sera before its SAA content can be measured.     

Vascular amyloid of unknown origin and senile transthyretin amyloid in the lung and gastrointestinal tract of old age: Histological and immunohistochemical studies

The histological and immunohistochemical characteristics and the incidence of amyloid deposits in the tissues of the lung and gastrointestinal tract were investigated in 64 autopsied individuals who were 80 years and older (age range: 80-92 years; mean: 83.3 years). Immunohistochemical examination was performed with antibodies against amyloid A, transthyretin, immunoglobulin lambda and kappa light chain amyloid fibril proteins, beta2-microglobulin, beta protein, apolipoprotein AI, apolipoprotein AII, atrial natriuretic peptide, apolipoprotein E, and amyloid P component. Transthyretin amyloid fibril protein (ATTR) deposits were observed in five cases (7.8%). Gastrointestinal amyloid deposits of unknown origin were observed in the veins of the gastrointestinal tract in 26 cases (40.6%). This amyloid was regarded as portal amyloid with respect to distribution pattern. Pulmonary vascular amyloid deposits of unknown origin were observed in 12 cases (18.8%). These amyloid deposits were found mainly in medium-sized veins in the lungs and did not react with any antibodies against amyloid fibril proteins except apolipoprotein E and amyloid P component. Eleven of the 26 cases (42.3%) showing portal amyloid also showed pulmonary vascular amyloid of unknown origin. The pulmonary vascular amyloid deposits were similar to the portal amyloid deposits with respect to their morphological features and their relation to elastic fibers in the vessels. Further morphological investigation and biochemical analysis of the pulmonary vascular amyloid and portal amyloid will resolve questions of their origins and relation.     

Concurrent hepatic adenomatoid tumor and hepatic hemangioma: a case report

A 45-year-old male with alleged asymptomatic hepatic hemangioma of 4 years duration had right upper-quadrant pain and was referred to a tertiary hospital. Computed tomography and magnetic resonance imaging scans revealed a hypervascular mass of about 7 cm containing intratumoral multilobulated cysts. A preoperative liver biopsy was performed, but this failed to provide a definitive diagnosis. The patient underwent a partial hepatectomy of segments IV and VIII. The histologic findings revealed multifocal proliferation of flattened or cuboidal epithelioid cells and a highly vascular edematous stroma. Immunohistochemistry findings demonstrated that the epithelioid tumor cells were positive for cytokeratin (AE1/AE3), vimentin, calretinin, and cytokeratin 5/6, and were focally positive for CD10, and negative for WT1 and CD34, all of which support their mesothelial origin. Immunohistochemistry for a mesothelial marker should be performed for determining the presence of an adenomatoid tumor when benign epithelioid cells are seen.     

Excessive hypernatremia in a patient with renal amyloid disease

Summary A 24-year-old Italian male presented with a nephrotic syndrome in September 1984. In February 1985 renal biopsy showed amyloid disease with tubular atrophy and interstitial fibrosis. Edema was treated with furosemide, and cholchicine was started. Because he feared side effects of drug therapy, the patient stopped all medication by July 1985. Instead, he decided to restrict severely fluids in order to fight edema. In early November 1985 his family noted he was becoming increasingly lethargic. Two weeks later, on his admission to the hospital, he had a serum sodium concentration of 193 mmol/l and serum osmolality of 397 mosm/kg. Apart from mild mental status changes neurological examination was normal. The fluid deficit was slowly corrected. He was discharged three weeks later with normal serum electrolytes. This case demonstrates that (1) severe hypernatremia can present with mild neurological symptoms and (2) it can be survived provided that it develops slowly and is corrected cautiously.     

Ubiquitin: its potential significance in murine AA amyloidogenesis.

Amyloid enhancing factor (AEF), which has recently been shown to have identity with ubiquitin (Ub), is believed to play a causative role in experimentally induced AA amyloidosis in mice. We have examined the profile of Ub in activated leukocytes and splenic reticulo-endothelial (RE) cells and its relationship with serum amyloid A protein (SAA) and AA amyloid deposits in an alveolar hydatid cyst (AHC)-infected mouse model of AA amyloidosis. Two monospecific antibodies, anti-ubiquitin (RABU) and anti-mouse AA amyloid, were used as immunological probes to localize Ub, SAA, and AA amyloid. In response to AHC infection, the dull and diffuse Ub immunoreactivity in normal mouse leukocytes and RE cells promptly changed to a discrete granular pattern suggesting an increase in the intracellular concentration of Ub and the formation of Ub-protein conjugates. This corresponded to an elevation in SAA levels, SAA uptake by RABU-positive phagocytic cells, co-localization of Ub-SAA immunoreactive splenocytes in the perifollicular areas, and deposition of Ub-bound AA amyloid in the splenic and hepatic tissues. These results suggest that Ub-loaded monocytoid cells may play an important role in the physiological processing of the sequestered SAA into AA amyloid. Aspects of AA amyloidogenesis are discussed in relation to other experimental models in which stress-induced Ub-protein conjugate formation and its transport to lysosomal vesicles have been studied.     

The diagnostic significance of periportal hepatic necrosis and inflammation

In this review the several types of cell damage and cell death which may be found in liver biopsy specimens are defined. We describe the different processes which occur at the portal/parenchymal or septal/parenchymal interface, viz. periportal spillover, periportal hepatitis, classic or lymphocytic piecemeal necrosis and biliary piecemeal necrosis. The diagnostic implications of these lesions in relation to the clinicopathological diagnosis and prognosis in various liver diseases are discussed.     

causing amyloid angiopathy and brain hemorrhage - clinical genetics in Iceland

Firstly, we review investigations of hereditary cystatin C amyloid angiopathy, which is caused by a mutation in the cystatin C gene. Symptoms of brain haemorrhages, which lead to death in young adults, are the hallmark of this disorder. The mutation can now be detected by the RFLP method using Alu I restriction enzyme and cystatin C cDNA probe. Secondly, we give an overview of other clinical genetic studies in Iceland with emphasis on activities initiated or sponsored by the Genetical Committee of the University of Iceland. The list of references covers most publications on genetic studies of Icelanders.