CNS germinoma with extensive calcification: An unusual histologic finding.

INTRODUCTION: Intratumoral calcification is a feature that is more often observed in pineal parenchymal tumour than germinoma. We describe a 13-year-old male with pineal region germinoma demonstrating extensive intratumoral calcification. CASE REPORT: He presented with worsening headache that was associated with fatigue, nausea and vomiting. Radiologic examination revealed a multilobular mass in the pineal region with internal calcifications. Biopsy showed a pure germinoma with unusually extensive calcification. DISCUSSION: Although a diagnosis may be suggested with a careful evaluation of imaging, there is no pathognomonic pattern. Thus, histologic verification is necessary for most pineal region masses.

Survivin, Survivin-2B, and Survivin-deItaEx3 expression in medulloblastoma: biologic markers of tumour morphology and clinical outcome.

Survivin is an apoptotic inhibitor that is expressed at high levels in a variety of malignancies. Survivin has four known alternative splice forms (Survivin, Survivin-2B, Survivin-deltaEx3, and Survivin-3B), and the recent literature suggests that these splice variants have unique functions and subcellular localisation patterns. We evaluated 19 fresh-frozen paediatric medulloblastomas for the expression of three Survivin isoforms by quantitative PCR. Survivin was most highly expressed when compared with normal cerebellar tissue. We also investigated Survivin protein expression in 40 paraffin-embedded paediatric medulloblastoma tumours by immunohistochemistry. We found a statistically significant association between the percentage of Survivin-positive cells and histologic subtype, with the large-cell-anaplastic variant expressing Survivin at higher levels than the classic subtype. We also found a statistically significant relationship between the percent of Survivin-positive cells in the tumours and clinical outcome, with higher levels of Survivin correlating with a worse prognosis. In summary, our study demonstrates a role for Survivin as a marker of tumour morphology and clinical outcome in medulloblastoma. Survivin may be a promising future prognostic tool and potential biologic target in this malignancy.

Nuclear expression of Survivin in paediatric ependymomas and choroid plexus tumours correlates with morphologic tumour grade.

Survivin is a gene that is widely expressed throughout the development of the normal mammalian embryo. Subcellular localisation of Survivin to both the nucleus and cytoplasm has suggested multiple functional roles, including inhibition of cell death, especially as demonstrated within a variety of malignant cell types, as well as regulation of the mitotic spindle checkpoint. The expression of Survivin has been associated with an adverse clinical outcome in a large number of malignancies. However, nuclear Survivin expression has been described as an independent variable of favourable prognosis in two large clinical studies of breast and gastric carcinomas. Reports of Survivin expression in normal postnatal, differentiated tissues have been restricted to cell types with high proliferative capacities, including vascular endothelium, endometrium, colonic epithelium, and activated lymphocytes. Prior to this report, expression within the normal human brain had not been characterised. Here, we analyse the expression of Survivin in human brain sections obtained from perinatal and paediatric autopsy cases. We report a strikingly high level of expression of Survivin within normal ependyma and choroid plexus (CP). Analysis of corresponding neoplastic tissue in paediatric ependymomas and CP tumours shows that expression of the nuclear form of Survivin correlates with morphologic tumour grade, with a loss of nuclear expression associated with progressive cytologic anaplasia. This pattern of expression supports a hypothesis that Survivin plays a functional role in normal ependymal growth and/or neural stem cell differentiation, and that abnormally low levels of expression of the nuclear form of this protein may be a marker of more aggressive disease and/or higher morphologic grade in ependymal and CP tumours.

Clinicopathologic study of ectomesenchymomas from Intergroup Rhabdomyosarcoma Study Groups III and IV.

Ectomesenchymomas (EM) are rare malignant neoplasms usually consisting of rhabdomyosarcoma (RMS) with a neural component. Only 21 cases have been previously reported. Here we extend the clinicopathologic spectrum of EM by describing our findings in 15 cases. Only 5 patients were infants; 10 were < or =3 years old and 5 were > or =6 years old. No male predilection was observed; 7 were female. The originating institutional diagnoses were; RMS (12), undifferentiated sarcoma (1), or EM (2), suggesting underdiagnosis of this entity. The primary tumor sites included external genital (5), pelvis/abdomen (6), head and neck (3), and extremity (1). The size of the primary neoplasm was usually > or =5 cm at diagnosis but dissemination only occurred in a minority. Local infiltration was not uncommon. These neoplasms were typically multilobate, thinly encapsulated, hemorrhagic, and necrotic. Light microscopic features were highly variable, but embryonal RMS with scattered or clustered ganglion cells, often in lacunae, was characteristic. In some cases, primitive neuroblastic or neuroectodermal areas were found and/or a component of alveolar RMS was seen. Focal anaplasia was occasionally observed. Mitotic activity appears higher than previously appreciated and some necrosis was invariably present. Electron microscopy was performed in 11 cases, which confirmed skeletal muscle +/- neural differentiation. Cytogenetic studies performed in five cases revealed no specific abnormality. Monoclonal neuron-specific enolase was the best marker of ganglion cells and primitive neural elements. MIC-2 (CD99) membrane expression was not definitively present in any of the six cases examined. A number of the above parameters appear to be of some prognostic significance, but overall, these neoplasms appear to have a similar outcome as would be predicted for their RMS element alone (exclusive of any neural component), with respect to the RMS subtype, age of the patient, and anatomic location of the neoplasm.

Importance of hypoxic/ischemic conditions in the development of cerebral lenticulostriate vasculopathy.

BACKGROUND: We have observed many infants with lenticulostriate vasculopathy (LSV) on neurosonograms who do not have classic histories of prenatal infection, trisomy, or prenatal drug exposure. OBJECTIVE: To investigate the underlying clinical conditions in patients with LSV. MATERIALS AND METHODS: Sixty-three cases of LSV were identified among approximately 2,400 neurosonograms performed over 42 months. All neurosonograms were reviewed. Medical records were reviewed for information regarding prenatal infection, chromosomal abnormality, respiratory and cardiac disease, and other pertinent diagnoses. RESULT: Hypoxic/ischemic conditions accounted for 33 cases: cardiac disease in 13, respiratory distress syndrome in 15, and perinatal asphyxia in 5. Twelve of these 33 had initially normal or minimal findings, with LSV developing or progressing on subsequent neurosonograms. The remaining 30 cases had varied clinical associations: congenital infection in 5, trisomies in 9, fetal substance exposure in 4, and unclear etiology in 12. Coexistent anomalies included posterior urethral valves, MCDK, myelomeningocele, placental abruption, and others. Thirty patients were premature. Fifteen patients died; histologic changes of LSV were found at autopsy in one patient. CONCLUSION: LSV has varied clinical associations. The common association with hypoxic/ischemic conditions and the progressive changes seen in 12 patients with cardiac and pulmonary disease suggest that postnatal hypoxia/ischemia is an important etiologic factor.

Effect of neutrophil depletion in acute cerebritis.

Inhibition of the host's neutrophil response has been proposed as one means to reduce tissue damage in acute inflammation. If this approach can be applied in acute central nervous system (CNS) infection, the long-term morbidity, which occurs in CNS infection, might be reduced. Previous studies in models of CNS infection yielded conflicting results whether neutrophil depletion might be protective. To determine whether neutrophil depletion reduces tissue necrosis and cerebrovascular injury in experimental bacterial cerebritis, we depleted circulating neutrophils with an IgM monoclonal antibody, RP3, given after the start of the infection. RP3 treatment successfully depleted circulating neutrophils and reduced the extent of neutrophil influx into the cerebritis region. The extent of tissue necrosis, measured histologically, and the regional increase of blood-brain barrier (BBB) permeability were not inhibited by neutrophil depletion, and in animals treated with RP3 alone, the extent of tissue necrosis and BBB permeability tended to be larger than in S. aureus inoculated controls. We conclude that host neutrophils do not add to the tissue and cerebrovascular damage created by the intracerebral inoculation of a pathogenic bacteria, and the neutrophils serve to diminish local damage in the setting of a cerebritis.

Lingual bronchogenic cyst in a child: an unusual site of presentation.

We describe a 4-year-old hispanic male with a bronchogenic cyst (BC) in the base of the tongue. To our knowledge, a BC has not been previously reported in the oral cavity. BC is a developmental anomaly believed to originate from abnormal detachments of accessory lung buds from the ventral foregut. We postulate that the unusual location of the BC in the present case is related to the primitive foregut origin of tongue epithelium posterior to the foramen cecum and the sulcus terminalis. A BC in the base of the tongue appears to represent the most proximal expression of aberrant accessory lung bud detachment from the primitive foregut.

Expression and structure of CD22 in acute leukemia.

The purpose of this study was to examine the expression and structure of CD22 in B cell precursor acute lymphoblastic leukemia (BCP-ALL), acute myeloid leukemia (AML), and T cell acute lymphoblastic leukemia (T-ALL). By using immunofluorescence microscopy and flow cytometry we observed that CD22 is expressed not only in the cytoplasm (as previously reported) but also on the cell surface of virtually all (15/16) BCP-ALL examined. CD22 that was biosynthetically labeled with 35S-cysteine and immunoprecipitated from the uncommon cytoplasmic CD22-positive/surface CD22-negative BCP-ALL cells was analyzed by single-dimension sodium dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE). Our results indicated that the cytoplasmic form of CD22 comigrated with 125I/lactoperoxidase-labeled surface CD22. Therefore, cytoplasmic CD22 is probably a pool of fully processed glycoprotein. We also observed unusual cases of AML (approximately 20%) that expressed cytoplasmic CD22 based on immunofluorescent staining; however, biosynthetic labeling and immunoprecipitation revealed an apparently cross-reactive protein(s) of approximately 250 to 300 kd in AML cells. No T-ALL cell lines examined expressed either cytoplasmic or surface CD22. Thus, cytoplasmic and surface expression of bona fide CD22 appears restricted to B cells, which suggests that this molecule subserves a function unique to B cells.

Structural characterization of the human B lymphocyte-restricted differentiation antigen CD22. Comparison with CD21 (complement receptor type 2/Epstein-Barr virus receptor).

CD22 and CD21 are glycoproteins primarily expressed on normal and neoplastic human B cells. The surface expression of these two molecules parallel each other during normal B cell differentiation, and the reported relative mobilities for CD22 and CD21 are 130/140 kDa and 140 kDa, respectively. Herein we present a detailed analysis of the biosynthesis and structure of CD22 and also compare it directly to CD21. Electrophoresis under reducing and nonreducing conditions suggested that CD22 and CD21 may have similarities in intra-chain disulfide bond formation. Biosynthesis and processing of CD22 and CD21 were very similar with respect to kinetics and post-translational modification, and both could be phosphorylated. However, endoglycosidase digestion (using N-glycanase and endoglycosidase H) and peptide mapping (using V8 protease and N-chlorosuccinimide) strongly suggested that CD22 and CD21 are distinct gene products.

Antibody affinity may influence antigenic modulation of the common acute lymphoblastic leukemia antigen in vitro.

We have produced a new monoclonal antibody designated BA-3. An extensive side-by-side serologic comparison of BA-3 with the anti-common acute lymphoblastic leukemia antigen (CALLA) monoclonal antibody J-5 was undertaken. Cells examined included established leukemic cell lines, malignant cells from patients with newly diagnosed leukemia/lymphoma, and normal hematopoietic tissues. In all experiments the cellular distribution of the antigens recognized by BA-3 and J-5 were identical when analyzed by immunofluorescent microscopy and the FACS. Iodination of NALM-6 cells, followed by radioimmunoprecipitation and SDS-PAGE, indicated that BA-3 (like J-5) precipitated a glycoprotein of approximately 100,000 daltons. Competitive binding studies using 125I-labeled BA-3 indicated that BA-3 and J-5 were binding to closely associated (if not identical) epitopes on CALLA. Calculation of the equilibrium constant (K value) for BA-3 and J-5, and the approximate number of CALLA molecules per cell, was graphically determined using Scatchard plots. BA-3 and J-5 were shown to have K values of approximately 2.7 x 10(7) M-1 and 7.2 x 10(7) M-1, respectively, with NALM-6 cells expressing 1 x 10(5) to 2 x 10(5) CALLA molecules per cell. Additional studies with BA-3 failed to demonstrate significant antigenic modulation of CALLA in vitro using fresh leukemic cells and leukemic cell lines. Thus, we suggest that antibody affinity may be a significant factor influencing antigenic modulation of CALLA in vitro.