Contribution of Intrasellar Pressure Elevation to Headache Manifestation in Pituitary Adenoma Evaluated With Intraoperative Pressure Measurement.

BACKGROUND: Headache frequently occurs in patients with pituitary adenoma and is reported in large as well as small adenomas. However, the exact mechanism of headache derived from pituitary adenoma remains unknown. OBJECTIVE: To evaluate the contribution of intrasellar pressure (ISP) to headache manifestation by using intraoperative ISP measurement. METHODS: The records of 108 patients who had first-time transsphenoidal surgery for pituitary adenoma were reviewed retrospectively. Measurement of intraoperative ISP was undergone using intracranial pressure monitoring sensors and compared with radiological assessment. RESULTS: Among 30 patients with headache, 29 (96.7%) presented with significant headache (Headache Impact Score-6, 50 or greater). Intraoperative ISP measurement was conducted successfully in all cases, and revealed higher ISP in patients with headache (35.6 ± 9.2 mm Hg) than in those without headache (15.8 ± 5.2 mm Hg). The ISP reduction after sella floor decompression was greater in patients with headache than that in patients without headache. In patients with headache, the frequency of invasion into the cavernous sinus or sphenoid sinus was significantly lower, and the diameter of the foramen at the diaphragm sellae was narrower. In addition, intratumoral cyst or hematoma was more common in patients with headache. Postoperatively, headache was either diminished or improved in 28 patients (93.3%). CONCLUSION: Headache in patients with pituitary adenomas associated with ISP elevation, results from compromised dural integrity at the sella and intratumoral hemorrhage. The increased stretch force of the sella dura may be a notable etiology of headache in patients with pituitary adenoma.

Correlation of gamma-catenin expression with good prognosis in medulloblastomas.

OBJECT: Medulloblastoma is a malignant cerebellar tumor of childhood and is difficult to cure due to frequent cerebrospinal fluid dissemination. Amplification of the c-myc gene (4%) and messenger (mRNA) overexpression (50%) are known to be adverse prognostic indicators. Because mRNA overexpression cannot be explained by gene amplification alone, mechanisms other than gene amplification are postulated. Molecules on the Wnt signal pathway in primary tumors were examined. METHODS: Immunohistochemical and cytogenetic examinations of beta- and gamma-catenin, c-myc, N-myc, and cyclin D1 in 24 primary medulloblastomas were conducted, and their clinical relevance was evaluated. Cytoplasmic/membranous staining of beta- and gamma-catenin was detected in 19 (79%) and nine (37%) cases, respectively, and nuclear expression of cyclin D1 and c-myc was detected in six (25%) and 21 (83%) cases, respectively. The expression levels of gamma-catenin in Western blot analysis and immunohistochemistry were similar. By differential polymerase chain reaction, c-myc and N-myc were amplified separately in two large cell/anaplastic medulloblastomas. No cyclin D1 amplification, or beta- or gamma-catenin mutations were found. Kaplan-Meier analysis revealed no dissemination at diagnosis (Chang Grade M0) and gamma-catenin expression was correlated with good prognosis (p = 0.0002 and 0.003, respectively). Expression of gamma-catenin was also significant in the M0 group (p = 0.022). Expression of cyclin D1 showed a trend toward adverse outcome (p = 0.057) and all patients in whom cyclin D1 expression was found died of disease. CONCLUSIONS: Expression of gamma-catenin is of great prognostic value and its immunohistochemistry may be useful for further stratification of treatment. Cyclin D expression may have the potential to be an adverse prognostic indicator.

Cyclin D1 is overexpressed in atypical teratoid/rhabdoid tumor with hSNF5/INI1 gene inactivation.

OBJECT: Although atypical teratoid/rhabdoid tumor (AT/RT) is known to generate through inactivation of the hSNF5/INI1 gene on chromosome 22q, the downstream molecular mechanism remains unclear. We histologically and molecularly reviewed our pediatric brain tumors for unrecognized AT/RTs and evaluated the role of cyclin D1, a potential molecular target of hSNF5/INI1. METHODS: We analyzed 16 tumors under three years of age: seven medulloblastomas, three anaplastic ependymomas (E IIIs), two each of supratentorial primitive neuroectodermal tumors (sPNETs) and choroid plexus carcinomas (CPCs), and one each of neuroblastoma and pineoblastoma. Immunohistochemistry for glial fibrillary acidic protein, vimentin, epithelial membrane antigen, smooth muscle actin and cyclin D1 was performed. Polymerase chain reaction (PCR)-single-strand conformation polymorphism analysis with direct sequencing, differential PCR and microsatellite analysis were conducted for hSNF5/INI1mutation, homozygous deletion and loss of heterozygosity (LOH) on 22q, respectively. Because of the presence of rhabdoid cells and the polyimmunophenotypic features, the diagnosis was revised to AT/RT in five (31%) tumors, namely, two E IIIs and one each of medulloblastoma, CPC and pineoblastoma. Three of them harbored such hSNF5/INI1 aberrations as germline single base deletion (492/6 delC) and missense mutation (C157T) together with LOH 22q or homozygous deletion. Cyclin D1 was overexpressed in those three tumors but not in the two that lacked hSNF5/INI1 inactivation. CONCLUSION: AT/RT can be misdiagnosed as a variety of tumors, including ependymoma that potentially harbors LOH 22q. Our data indicate that cyclin D1 is a target of hSNF5/INI1in primary tumors.