Assessment and prognostic significance of mitotic index using the mitosis marker phospho-histone H3 in low and intermediate-grade infiltrating astrocytomas

Distinguishing between grade II and grade III diffuse astrocytomas is important both for prognosis and for treatment decision-making. However, current methods for distinguishing between grades based on proliferative potential are suboptimal, making identification of clear cutoffs difficult. In this study, we compared the results from immunohistochemical staining for phospho-histone H3 (pHH3), a specific marker of cells undergoing mitosis, with standard mitotic counts (number of mitoses/10 high-power fields) and MIB-1 labeling index values for assessing proliferative activity. We tested the relationship between pHH3 staining and tumor grade and prognosis in a retrospective series of grade II and III infiltrating astrocytomas from a single institution. The pHH3 index (per 1000 cells), MIB-1 index (per 1000 cells), and number of mitoses per 10 high-power fields were determined for each of 103 cases of grade II and III diffuse astrocytomas from patients with clinical follow-up. pHH3 staining was found to be a simple and reliable method for identifying mitotic figures, allowing a true mitotic index to be determined. The pHH3 mitotic index was significantly associated both with the standard mitotic count and with the MIB-1 index. Univariate analyses revealed that all 3 measurements of proliferation were significantly associated with survival. However, the pHH3 mitotic index accounted for a larger proportion of variability in survival than standard mitotic count or MIB-1/Ki-67 labeling index. After adjusting for age, extent of resection, and performance score, the pHH3 mitotic index remained an independent predictor of survival. Thus, pHH3 staining provides a simple and reliable method for quantifying proliferative potential and for the stratification of patients with diffuse astrocytomas into typical grade II and III groups. These results also suggest that pHH3 staining may be a useful method in other neoplasms in which accurate determination of proliferation potential is relevant to tumor grading or clinical treatment decision-making.     

Iatrogenic cerebellar implantation of a vestibular schwannoma. Case report

Metastatic seeding or iatrogenic implantation of numerous types of primary central nervous system tumors, typically along cerebrospinal fluid pathways, is a frequently described albeit rare phenomenon and has never been reported in association with vestibular schwannoma (VS). The authors present a case of inadvertent surgical implantation of VS into the cerebellar hemisphere during resection of a recurrent VS in the cerebellopontine angle and internal auditory canal. A 42-year-old man presented with a 2.5-cm right VS that was removed without complication via a retrosigmoid approach. Routine imaging performed 5 years later revealed a 1.5-cm recurrence of the VS that was subsequently removed by reopening the retrosigmoid craniotomy. Five years later--10 years after initial presentation--follow-up imaging revealed a 1-cm recurrence of the VS and a separate 2.2-cm tumor in the inferior cerebellar parenchyma with surrounding edema. Both tumors were removed without complication by reopening the previous retrosigmoid craniotomy. Histological evaluation of these tumors revealed features typical of VS and similar to those of the tissue obtained from the two prior resections. Given the similarities among these tumors in pathological appearance and mitotic index, the presence of the intraparenchymal cerebellar schwannoma was probably due to intraoperative iatrogenic implantation.     

β-Endorphin withdrawal: a possible cause of premenstrual tension syndrome

The authors propose that premenstrual tension syndrome (PMS) is the result of β-endorphin withdrawal. Sixteen women were included in this study which measured β-endorphin levels on the 7th and 24th day of each woman's menstrual cycle. A significant decline in β-endorphin levels was noted during the progression of the cycle. The severity of symptoms, however, was inversely proportional to the amount of decline in β-endorphin levels. It is hypothesized that the attenuation of endorphin decline may be a compensatory mechanism to moderate the severity of PMS symptoms.