CSF cytology of atypical teratoid/rhabdoid tumor of the brain in a two-year-old girl: a case report

Atypical teratoma/rhabdoid tumor (AT/RT) of the central nervous system is a highly malignant neoplasm in infants and early childhood. Approximately one third of patients develop intracranial dissemination with involvement of cerebral spinal fluid (CSF). The clinical, radiological, and pathological features have been described, but cytology of the tumor cells in CSF has not. Multiple CSF samples were examined in a case of AT/RT in a 2-yr-old girl. The most consistent cytologic features of AT/RT are the large size of the tumor cells, eccentricity of the nuclei, and prominent nucleoli. The differential diagnosis includes medulloblastoma/primitive neuroectodermal tumor (PNET) of the brain. Because AT/RT often contains PNET-like regions, the differential diagnosis mainly relies on the presence or absence of large rhabdoid tumor cells. Cytological examination of CSF from a patient with AT/RT is important in the early diagnosis, disease progression analysis, and therapy modulation.     

Cytomorphological features of atypical teratoid/rhabdoid tumor: An account of 12 years' experience

Atypical teratoid rhabdoid tumor (AT/RT), an aggressive neoplasm mostly affecting young children, is characterized by rhabdoid cells together with epithelial, mesenchymal and primitive differentiation. Diagnosing AT/RT in intraoperative consultation and cerebrospinal fluid (CSF) samples may therefore pose problems. Fourteen immunohistochemically proven AT/RTs diagnosed between 2000 and 2012 were collected. Material consisted of squash smears prepared during intraoperative consultation (thirteen) and CSF smears (three). MGG‐stained CSF smears and H&E stained squash smears were reviewed by a neuropathologist and a cytopathologist. The intraoperative diagnoses were based on squash preparations and 3 out of 13 were consistent with AT/RT, 4 were considered medulloblastoma/primitive neuroectodermal tumors (PNET), 3 were deferred to paraffin section for tumor typing, and another 3 were misdiagnosed as ependymoma, germinoma and malignant glioma. Morphological assessment of intraoperative squash preparations showed that AT/RTs can have a mixture of pseudopapillary and diffuse smearing patterns. Cytomorphologic features consisted of characteristic rhabdoid cells (8/9); primitive appearing cells with a high nuclear to cytoplasmic ratio (7/9); bi‐/multinucleated cells (3/9); rare necrosis/apoptosis and mitoses. Three CSF smears showed high cellularity and inclusion‐bearing large cells. These cells are characterized by reniform/oval, eccentrically placed nuclei with cytoplasmic perinuclear light stained areas which are not seen in intraoperative squash preparations. Differential diagnosis of AT/RT in cytology involves medulloblastoma/PNET, ependymoma, glioma and germinoma among all others. Overlapping features of AT/RT with entities in differential diagnosis are discussed with a special emphasis of rhabdoid cells being the strongest feature to aid in reaching the diagnosis of AT/RT. Diagn. Cytopathol. 2014;42:856–862. © 2014 Wiley Periodicals, Inc.     

Endometrial Osteopontin mRNA Expression and Plasma Osteopontin Levels are Increased in Patients with Endometriosis

Problem  The aim of this study was to evaluate osteopontin (OPN) mRNA expression in eutopic endometrium and plasma OPN levels in patients with endometriosis.
Method of study  A total of 79 patients with histologically confirmed endometriosis and 43 patients without endometriosis participated in this study. OPN mRNA expression in endometrial tissues was measured by real-time quantitative polymerase chain reaction (PCR) and plasma concentrations of OPN were quantified using a specific commercial sandwich enzyme-linked immunosorbent assays (ELISA).
Results  Osteopontin mRNA expression in endometrial tissue was significantly higher in women with endometriosis than in controls ( P =  0.010). The mean plasma levels of OPN (mean ± S.E.M.) in patients with endometriosis and controls were 407.31 ± 37.80 ng/mL and 165.84 ± 19.29 ng/mL, respectively ( P  < 0.001). Receiver operating characteristic (ROC) analysis for plasma OPN revealed an area under the curve (AUC) of 0.894, with a sensitivity of 93.0%, specificity of 72.4%, positive likelihood ratio of 3.37, and negative likelihood ratio of 0.1 using a cut-off value of 167.68 ng/mL.
Conclusion  Osteopontin may be involved in the pathogenesis of endometriosis and plasma OPN may be a useful non-invasive marker for the diagnosis of endometriosis.     

中枢神经系统非典型畸胎瘤样/横纹肌样瘤临床病理特点

目的探讨中枢神经系统非典型畸胎瘤样／横纹肌样瘤(atypical teratoid／rhabdoid tumor，AT／RT)的临床病理特征、组织发生及预后。方法应用光镜、特殊染色及免疫组化染色观察1例2岁儿童大脑AT／RT的病理组织学特点，结合国内外文献进行讨论。结果肿瘤含有横纹肌样细胞、原始神经外胚层、上皮及间叶多向分化成分。肿瘤中网状纤维丰．富。免疫组化染色Vim、EMA、CKpan、GFAP、Syn及CgA均呈阳性表达，PLAP、CD117、SMA及：NF?呈阴性反应。结论AT／RT为发生在儿童中枢神经系统罕见的高度恶性肿瘤，多数患者1年内死亡。肿瘤极易误诊为髓母细胞瘤、原始神经外胚叶肿瘤(PNET)、脉络丛乳头状癌及生殖细胞肿瘤。免疫组化染色对确诊AT／RT十分重要。本瘤的组织发生仍不清楚。     

Primary atypical teratoid/rhabdoid tumor of central nervous system in children: a clinicopathological analysis and review of literature in China

Atypical teratoid/rhabdoid tumor (AT/RT) is a very rare and highly malignant embryonal tumor in the central nervous system (CNS). Five patients (4 girls and 1 boy) with AT/RT were treated in our hospital. The clinical histories, symptoms, neuroimaging aspects, therapies, histological and immunohistochemical findings and follow-up information were reviewed. The patients ranged from 8 to 40 months with a mean age of 20.6 months. One tumor was located in the spinal cord, two in cerebellum and two in the pineal region. The imagings of the tumors resemble medulloblastomas. Pathological examinations showed that one patient had medulloblastoma differentiation, one had choroid plexus carcinoma differentiation, and one had mesenchymal components. Immunohistochemical staining showed that all of the tumors lost the nuclear expression of integrase interactor 1 (INI1), and were positive for Vimentin, S-100 protein and epithelial membrane antigen. One case with no recurrence after 24 months may have benefited from radical excision and postoperative radiotherapy. The other 4 patients died 8, 4, 1 and 1-month respectively after operation without radiotherapy. The diagnosis of AT/RT depends on full sampling, careful observation the morphological characteristics and INI1 examination, even when the tumor are presented in uncommon sites, such as the spinal cord and the pineal region.     

Atypical teratoid/rhabdoid tumor: analysis of cytomorphologic features in CSF, focused on the differential diagnosis from mimickers

Atypical teratoid and rhabdoid tumor (AT/RT) is a rare tumor with fatal clinical consequences, usually affecting young children. A significant portion of patients present with dissemination to cerebrobspinal fluid (CSF). However, a limited number of studies are available regarding the cytomorphologic findings of AT/RT in CSF. We collected eight cases of CSF cytology of AT/RT and describe the cytomorphologic features of AT/RT in CSF. Typical rhabdoid cells are found in most cases and they are characterized by eccentric nuclei, abundant cytoplasm, and clustering of the tumor cells. The presence of these cells in CSF indicates disseminated diseases and aggressive therapeutic consideration for patient management is required.     

Plasma osteopontin levels are elevated in non-ST-segment elevation acute coronary syndromes

BACKGROUND: The regions of ruptured atherosclerotic plaques have numerous macrophages. Osteopontin that modulates macrophage function has been shown in atherosclerotic plaques. We aimed to study the plasma levels of osteopontin in patients with unstable angina or non-ST-seg ment elevation myocardial infarction (NSTEMI) and the rela tionship between osteopontin and the extent of the coronary artery disease (CAD). METHODS: We studied 65 patients with unstable angina or NSTEMI, 25 patients with stable angina and 18 patients as the control group. The extent of coronary artery stenosis was determined by the number of vessels with >50% stenosis. Plasma osteopontin concentrations were measured from the blood samples that were drawn immediately after admission to the emergency department in unstable angina/NSTEMI patients and before the coronary angiograph in the stable angina and control groups. RESULTS: The plasma osteopontin concentration was (495 118 ng/ml) significantly higher in the patients with unstable angina/NSTEMI compared to the stable angina group (319 106 ng/ml) and control group (125+/-54 ng/ml) (p=0.0001 The plasma osteopontin levels were lower in the patients with stable angina pectoris who had one-vessel disease compared to those with two-vessel disease (p=0.01). How ever, in the unstable angina/NSTEMI group, the plasma osteopontin levels were statistically not different among the patients with one-vessel, and two-vessel and three-vessel disease (p=NS). There was no correlation between the plasma osteopontin levels and the extent of coronary stenosis. CONCLUSIONS: The plasma osteopontin levels are elevatedin patients with unstable angina/NSTEMI, but there appears to be no correlation with the extent of CAD. These results ma suggest that osteopontin may have a role in the pathobiology of ACS.     

High thrombopoietin concentrations in the cerebrospinal fluid of neonates with sepsis and intraventricular hemorrhage may contribute to brain damage.

Thrombopoietin (TPO) and its receptor (TPOR) are expressed in the central nervous system (CNS). Although TPO shares significant homology with various neurotrophins, recent data indicate a proapoptotic function of TPO in the CNS. In this study, TPO concentrations were analyzed in the cerebrospinal fluid (CSF) of neonates. Human neuroblastoma-derived SH-SY5Y cells were established to elucidate the effects of inflammation and hypoxia on neuronal Tpo expression. TPO was detectable in the CSF of 6 of 15 neonates with bacterial infection/sepsis (median 140, range 2-613 pg/mL), 5 of 9 neonates with posthemorrhagic hydrocephalus (median 31, range 1.4-469 pg/mL), 3 of 4 neonates with posthemorrhagic hydrocephalus plus bacterial infection/sepsis or meningitis (median 97, range 6-397 pg/mL), but not in controls ( n = 3). Neither the presence of detectable TPO nor its level in the CSF significantly correlated with any clinical or laboratory parameter. In SH-SY5Y cells, TPO and TPOR expression was detected by RT-PCR and Western blot analysis. In vitro, interleukin-6 (IL-6) did not significantly change Tpo gene expression. In contrast, Tpo mRNA expression significantly decreased under hypoxia, whereas erythropoietin (EPO) mRNA expression increased. In conclusion, our data provide evidence that in neuronal cells, TPO production is regulated by different mechanisms than in hepatocytes.     

Cerebrospinal fluid HIV RNA and drug levels with combination ritonavir and saquinavir.

Combination antiretroviral therapy with ritonavir and saquinavir has established potent and durable activity on plasma viremia. CNS HIV infection may be sequestered from drug therapy that does not penetrate the blood-brain barrier. Penetration of these protease inhibitors into the cerebrospinal fluid (CSF) and CSF HIV RNA levels on such therapy has not been well described. DESIGN/METHODS: In a cross-sectional study, 28 HIV1-infected study subjects were evaluated either before initiation of or before maximal response to ritonavir-saquinavir therapy, during maximal plasma virologic response, and after virologic failure. Simultaneous samples of plasma and cerebrospinal fluid were obtained from 24 study subjects to measure HIV RNA and protease inhibitor levels. RESULTS: Across the treatment groups, a strong correlation was found between plasma and CSF HIV RNA levels (r = 0.870; p < .001). In each study subject with plasma HIV RNA levels below assay limit (80 copies/ml), the CSF HIV RNA level was also below the limit of quantitation. Low levels of saquinavir (<2 ng/ml) and ritonavir (<25 ng/ml) in the CSF were observed, with a CSF:plasma drug concentration ratio of < or = 0.005 (0.5%) in all study subjects evaluated (n = 11). The plasma:CSF HIV RNA ratio was high before or early in treatment (median, 38; interquartile range [IQR], 13,97), but low (median, 0.29; IQR, 0.17, 7.5) in those failing therapy (group C, p < .001). CONCLUSIONS: CSF ritonavir and saquinavir levels are consistent with the estimated known fraction of unbound drug in plasma (<2%). Across these treatment response groups, suppression of plasma viremia can predict low CSF HIV RNA levels. This correlation may represent HIV RNA transport and equilibrium between CSF and plasma, or it may represent CNS anti-HIV activity of protease inhibitors. The low drug levels and inverted ratio of HIV RNA in the CSF compared with plasma early in plasma virologic breakthrough suggests CSF virologic failure may contribute to failure of plasma virologic response.     

成人与儿童髓母细胞瘤的MRI特征分析

目的 分析成人与儿童髓母细胞瘤的MRI表现,提高对髓母细胞瘤的认识。方法 回顾性分析2009年1月—2017年12月广东省农垦中心医院经手术病理证实的髓母细胞瘤36例的影像学资料。将其分为两组:儿童组(＜18岁)25例,成人组(≥18岁)11例。36例患者术前行MRI平扫及增强扫描,观察并对比分析两组患者肿瘤的发生部位、瘤体最大径线、边界、囊变、实性部分强化程度、瘤周水肿、梗阻性脑积水、室管膜种植转移等影像学特征。结果 36例髓母细胞瘤均发生于幕下,儿童常见于小脑蚓部(21/25),成人病灶多位于小脑半球(9/11),差异有统计学意义(P=0.000)。儿童肿瘤最大径为(4.50±0.58) cm,其中17例肿瘤最大径超过4 cm;成年人瘤体最大径为(5.24±1.36) cm,其中8例肿瘤最大径超过4 cm;两者比较差异无统计学意义(Z=-0.895, P＞0.05)。成人组和儿童组囊变分别有16例和11例,瘤周水肿分别有4例和7例,差异均有统计学意义(P=0.034、0.008);而边界、梗阻性脑积水及室管膜种植转移方面组间差异均无统计学意义(P值均＞0.05)。36例患者髓母细胞瘤实性部分均表现为T₂WI及T₂WI-FLAIR稍高信号,T₁WI等偏低信号。12例做了弥散加权成像检查(5例儿童、7例成人),瘤体实性部分均表现为弥散受限;增强后,两组肿瘤实性区域均表现为轻度至中度强化。结论 儿童髓母细胞瘤好发于小脑蚓部,成人以小脑半球多见;儿童肿瘤囊变及瘤周水肿相对于成年人少。儿童与成人髓母细胞瘤均常表现为边界清楚肿块,实性区域轻度至中度强化,易发生梗阻性脑积水,可发生室管膜种植转移。     

Ependymoblastoma: Dear,Damned, Distracting Diagnosis,Farewell!

Ependymoblastoma is a diagnostic label that has been applied to a variety of rare central nervous system (CNS) tumors over the last eight decades. Consequently, there is uncertainty about whether such an entity exists and what its characteristic features might be. The current study, based on 14 cases from our institutional archives and identified by the search terms “ependymoblastoma,”“ependymoblastomatous,”“ependymoblastic” or “PNET with ependymal differentiation,” aimed to test the hypothesis that the ependymoblastoma is a distinct and recognizable entity. Ependymoblastic rosettes are a key diagnostic feature and were present in 11/14 (79%) tumors, eight (73%) of which were embryonal tumors with abundant areas of neuropil‐like differentiation. Three other cases showed rare ependymoblastic rosettes in the histopathological setting of a typical primitive neuroectodermal tumor (PNET), medulloblastoma (MB) or atypical teratoid/rhabdoid tumor (AT/RT). The remaining cases were all embryonal tumors with structures that mimicked ependymoblastic rosettes. Our results indicate that ependymoblastic rosettes are most frequently encountered in embryonal tumors with abundant neuropil and less frequently in other CNS embryonal neoplasms, including PNET, MB and AT/RT. We believe that ependymoblastoma as a diagnosis is neither precise nor specific and that it is time once and for all to retire this diagnosis from the lexicon of neuropathology.     

Osteopontin expression in ovarian carcinoma effusions is related to improved clinical outcome

Osteopontin, a soluble protein present in all body fluids, is involved in signaling pathways related to adhesion and extracellular matrix interactions, affecting multiple cellular functions, including inflammation, angiogenesis, and tumor metastasis. We studied osteopontin expression by immunohistochemistry and its clinical relevance in 170 effusions (140 peritoneal, 30 pleural) from women with advanced-stage ovarian carcinoma. Carcinoma cells expressed osteopontin in 126 (74%) of 170 effusions. Osteopontin expression was more frequent in effusions from patients with high-grade tumors (P = .036) but was significantly associated with better debulking at primary surgery (P = .019) and complete response to chemotherapy at diagnosis (P = .021). Osteopontin expression was positively associated to that of the previously studied nuclear factor κB inhibitor IκB (P = .019) and negatively related to expression of the inhibitor of apoptosis family member XIAP (P = .008) and the angiogenic marker endoglin (CD105; P = .018). In univariate survival analysis, the presence of osteopontin in carcinoma cells in primary diagnosis prechemotherapy effusions was associated with longer progression-free survival (P = .037), a finding that did not retain its significance in multivariate Cox analysis. This study demonstrates that osteopontin is frequently expressed in ovarian carcinoma effusions. However, its presence in tumor cells at this anatomical site is unexpectedly associated with less aggressive clinical course, suggesting different and yet undefined biological roles for this protein in serous effusions.     

Increase in adhesion molecules in cerebrospinal fluid of children with mumps and mumps meningitis

Adhesion molecules play a key role in leucocyte migration into the central nervous system (CNS). Concentrations of endothelial-derived soluble intercellular adhesion molecule-1 (sICAM-1) and leucocyte-originated soluble L-selectin (sL-selectin) in cerebrospinal fluid (CSF) of children with mumps meningitis (mononuclear pleocytosis, n = 33) and mumps (absence of pleocytosis, n = 9) were compared with values from age-matched control group (n = 19). In 14 patients from the meningitis group, adhesion molecule levels together with albumin concentration were estimated in paired CSF/serum samples to calculate concentration quotients and determine molecule intrathecal release. Both sICAM-1 (median 3.44 versus 0.86 ng/ml; P < 0.0001) and sL-selectin (median 29.91 versus 8.52 ng/ml; P < 0.0001) concentrations in CSF were increased in mumps meningitis patients compared with controls. Increased levels of the selected adhesion molecules were also observed in mumps patients without CNS involvement when compared with controls (median sICAM-1: 1.14 versus 0.86 ng/ml, sL-selectin: 13.54 versus 8.52 ng/ml; P < 0.01). Additionally, the concentration of adhesion molecules was found to correlate with CSF leucocyte count. Considerable correlation of sICAM-1 and sL-selectin quotients and corresponding albumin quotients suggests that a majority of the soluble adhesion molecules originated from the bloodstream. Analysis of adhesion molecule levels demonstrated indirect evidence of brain-derived fractions. Our results suggest the involvement of adhesion molecules during the early phase of mumps meningitis.     

中枢神经系统非典型畸胎样/横纹肌样瘤临床病理及免疫表型特征

目的 探讨中枢神经系统非典型畸胎样／横纹肌样瘤的临床病理特征、诊断及鉴别诊断。方法 对2例非典型畸胎样／横纹肌样瘤应用光镜行HE、网状纤维染色及免疫组织化学染色观察,并结合文献复习。结果 非典型畸胎样／横纹肌样瘤具有特征性的横纹肌样细胞,伴有不同程度的原始神经外胚叶、上皮和间质分化。肿瘤组织富于网状纤维,免疫组织化学标记示波形蛋白、CD99、上皮细胞膜抗原、细胞角蛋白、胶质纤维酸性蛋白、S-100蛋白、神经微丝蛋白、结蛋白、平滑肌肌动蛋白阳性,突触素、肌调节蛋白、胎盘碱性磷酸酶和HMB45阴性。结论 非典型畸胎样／横纹肌样瘤是中枢神经系统一种罕见的高度恶性肿瘤,好发于儿童,偶见于成人,呈异源性组织学和免疫组织化学表型。其诊断需与脑内其他多形性肿瘤鉴别。     

Distribution of beta2-microglobulin in cerebrospinal fluid and in cystic fluid of brain tumors. A preliminary study.

The concentrations of immuno-reactive beta2-microglobulin (beta2m) were measured in the cerebrospinal fluid (CSF) and the cystic fluid (CF) of Central Nervous System (CNS) tumours (gliomas, n = 5; craniopharyngiomas, n = 5) and in the culture medium of established cell lines derived from CNS tumors. These data are compared with plasma and CSF values of beta2m in normal subjects (n = 15) and in a group of peripheral solid tumors (metastatic breast carcinomas, n = 9). In the control group the absence of correlation between plasma and CSF values, suggests an independant production of beta2m in the two compartments considered. The capacity of CNS tumor cells to synthesize beta2m is demonstrated in vitro. In vitro beta-2m concentrations in the CF embryonic tumors (craniopharyngiomas) is significantly more elevated than in non malignant astrocytomas.     

SWI/SNF deficient central nervous system neoplasms

The SWItch/Sucrose Non-Fermentable (SWI/SNF) complexes are ubiquitous ATP dependent chromatin remodeling complexes that provide epigenetic regulation of gene expressions across the genome. Different combination of SWI/SNF subunits allow tissue specific regulation of critical cellular processes. The identification of SMARCB1 inactivation in pediatric malignant rhabdoid tumors provided the first example that the SWI/SNF complex may act as a tumor suppressor. It is now estimated at least 20% of all human tumors contain mutations in the subunits of the SWI/SNF complex. This review summarizes the central nervous system tumors with alterations in the SWI/SNF complex genes. Atypical teratoid/rabdoid tumor (AT/RT) is a highly aggressive embryonal tumor genetically characterized by bi-allelic inactivation of SMARCB1, and immunohistochemically shows complete absence of nuclear expression of its protein product INI1. A small subset of AT/RT show retained INI1 expression but defects in another SWI/SNF complex gene SMARCA4. Embryonal tumors with medulloblastoma, pineoblastoma, or primitive neuroectodermal morphology but loss of INI1 expression are now classified as AT/RT. Cribriform neuroepithelial tumor (CRINET) is an intra or para-ventricular tumor that has similar SMARCB1 alterations as AT/RT but generally has a benign clinical course. Besides AT/RT and CRINET, compete loss of nuclear INI1 expression has also been reported in poorly differentiated chordoma and intracranial myxoid sarcoma within the central nervous system. Families with non-truncating SMARCB1 mutations are prone to develop schwannomatosis and a range of developmental syndromes. The schwannomas in these patients usually demonstrate a mosaic INI1 staining pattern suggestive of partial residual protein function. Finally, clear cell meningioma is a WHO grade II variant meningioma characterized by bi-allelic inactivation of the SMARCE1 gene and immunohistochemically show loss of its protein product BAF57 expression in tumor cell nuclei.     

Severe fever with thrombocytopenia syndrome-associated encephalopathy/encephalitis

ObjectivesSevere fever with thrombocytopenia syndrome (SFTS) virus has a variety of central nervous system (CNS) manifestations. However, there are limited data regarding SFTS-associated encephalopathy/encephalitis (SFTSAE) and its mechanism.MethodsAll patients with confirmed SFTS who underwent cerebrospinal fluid (CSF) examination due to suspected acute encephalopathy were enrolled in three referral hospitals between January 2013 and October 2016. Real-time RT-PCR for SFTS virus and chemokine/cytokines levels from blood and CSF were analysed.ResultsOf 41 patients with confirmed SFTS by RT-PCR for SFTS virus using blood samples, 14 (34%) underwent CSF examination due to suspected SFTSAE. All 14 patients with SFTSE revealed normal protein and glucose levels in CSF, and CSF pleocytosis was uncommon (29%, 4/14). Of the eight patients whose CSF was available for further analysis, six (75%) yielded positive results for SFTS virus. Monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) level in CSF were significantly higher than those in serum (geometric mean 1889 pg/mL in CSF versus 264 pg/mL in serum for MCP-1, p = 0.01, and geometric mean 340 pg/mL in CSF versus 71 pg/mL in serum for IL-8, p = 0.004).ConclusionsThe CNS manifestation of SFTS as acute encephalopathy/encephalitis is a common complication of SFTS. Although meningeal inflammation was infrequent in patients with SFTSAE, SFTS virus was frequently detected in CSF with elevated MCP-1 and IL-8. These findings indicate that possible direct invasion of the CNS by SFTS virus with the associated elevated cytokine levels in CSF may play an important role in the pathogenesis of SFTSAE.     

Nodule formation and desmoplasia in medulloblastomas-defining the nodular/desmoplastic variant and its biological behavior

Among the variants of medulloblastoma in the current WHO classification of nervous system tumors, the desmoplastic variant, which has been reported to constitute 5%-25% of pediatric medulloblastomas, is defined by its nodular collections of neurocytic cells bounded by desmoplastic internodular zones. We have studied the frequency, morphological features and biological behavior of medulloblastomas in two contemporaneous SIOP/UKCCSG trial cohorts of children with medulloblastomas, CNS9102 (n = 315) and CNS9204 (n = 35), focusing on tumors with nodular and desmoplastic phenotypes. In children aged 3-16 years (CNS9102), the nodular/desmoplastic medulloblastoma represented 5% of all tumors, while in infants aged <3 years (CNS9204) this variant represented 57% of medulloblastomas. Using iFISH to detect molecular cytogenetic abnormalities in medulloblastomas with a nodular architecture, we demonstrated distinct genetic profiles in desmoplastic and non-desmoplastic (classic and anaplastic) tumors; in particular, abnormalities of chromosome 17 occurred in the latter, but not the former. Significantly different outcomes were demonstrated for classic, nodular/desmoplastic and large cell/anaplastic medulloblastomas in both cohorts. In conclusion, the nodular/desmoplastic medulloblastoma appears to have clinical, genetic and biological characteristics that set it apart from other variants of this tumor.     

Clinical efficacy of the Abbott Tacrolimus II assay for the IMx.

Monitoring tacrolimus is essential to maintain therapeutic concentrations. Performance of the new Abbott Tacrolimus assay (FK II) was evaluated and compared to the original tacrolimus assay (FK I). 189 trough whole blood samples from transplant cases were included in the study. Samples (n = 117) with FK I concentrations > 5 ng/mL were reanalyzed with the FK II assay. Patient samples (n = 43) that had FK I concentration < 5 ng/mL with apparent mean and range of 3.1 ng/mL and 0.7 to 4.5 ng/mL, respectively, were also reanalyzed with FK II to yield a mean of 5.9 ng/mL with a range of 2.9 to 10.8 ng/mL. Checking for patient compliance, samples (n = 10) with a FK I concentration of 0 ng/mL were re-analyzed. With one exception of a mislabeled cyclosporine sample, all samples (n = 9) showed FK506 levels greater than 2 ng/mL with the FK II assay. The FK II assay was shown to be a clinically efficacious assay, with improved sensitivity and acceptable precision versus the previous FK I assay.     

A monoclonal antibody-based enzyme-linked immunosorbent assay for quantitation of plasma thrombospondin

An enzyme-linked immunosorbent assay was developed to quantitate the platelet secretory glycoprotein, thrombospondin (TSP), in plasma. Specificity of the assay was provided by using an anti-TSP monoclonal antibody (McAb) to coat 96 well polystyrene assay plates. The effective range of the standard curve for the assay was between 2.5 ng/mL and 500 ng/mL. Interassay and intraassay variations were 6.9% and 7.5%, respectively. To avoid spontaneous release of TSP from platelets after the blood was drawn, and to obtain a valid measurement of plasma TSP concentration, it was essential to place and maintain blood samples on ice immediately after blood was drawn and to separate plasma from cellular constituents within two hours. The mean plasma TSP concentration of 24 healthy adults was 64.3 +/- 18.0 ng/mL (mean +/- SD). The TSP concentration of pooled normal human serum (n = 6) was 15.9 micrograms/mL. Interference occurred when undiluted plasma or serum samples were assayed. This interfering effect could be eliminated completely by a tenfold dilution of plasma or serum samples before the assay. The assay also was applied successfully to quantitate TSP release from platelets after induction of aggregation by different platelet-aggregating agents.