Age-linked prognostic categorization based on a new histologic grading system of neuroblastomas. A clinicopathologic study of 211 cases from the Pediatric Oncology Group.

Histologic sections (minimum of four sections per patient) from 211 patients with neuroblastoma were reviewed. The tumors were resected before therapy, which was standardized according to age and stage. Low mitotic rate (MR) (less than or equal to ten per ten high-power fields) and calcification emerged as the most significant prognostic features after statistical analysis by stepwise log-rank tests (P less than 0.0001 and P = 0.0065, respectively). Histologic Grades 1, 2, and 3 were defined on the basis of the presence of both, any one, or none of these two prognostic features, respectively (Grade 3 had absence of low MR, i.e., these tumors had high MR [greater than ten per ten high-power fields]). Statistically significant differences in survival were observed in the grades after adjusting for age and stage (P less than 0.001). The degree of differentiation, although significant by itself, was no longer significant after adjusting for the grades. Age groups (less than or equal to 1 versus greater than 1 year of age), which also emerged as an independent prognostic feature (P less than 0.001), were linked with the grades to define two risk groups as follows: (1) a low-risk (LR) group consisting of patients in both age groups with Grade 1 tumors and patients 1 year of age or younger with Grade 2 tumors and (2) a high-risk (HR) group consisting of patients older than 1 year of age with Grade 2 tumors and patients in both age groups with Grade 3 tumors. The difference in survival between LR (160 cases) and HR groups (51 cases) was statistically significant (P less than 0.001). Concordance between these LR and HR groups and the Shimada classification was observed in 84% of cases. The new histologic grading system has the following advantages: (1) use of familiar terminology and histologic features in the grading system and (2) relative ease of assessment because the degree of differentiation does not need to be determined. The grading system should be tested on a new data set with an appropriate histologic sample of similar size to confirm these results.     

Neuroblastoma of the Anterior Mediastinum in an 80-Year-Old Woman

A 7-cm anterior mediastinal tumor in an 80-year-old woman was found by light and electron microscopy to be a neuroblastoma. Immunoreactivity for neuron-specific enolase, synaptophysin, and chromogranin supported the diagnosis. Neuroblastoma is an uncommon tumor in adults and we are not aware of a previous report of such a tumor in a patient of this age.     

Stress urinary incontinence in women

The aim of the study was the investigation of the biochemical condition of elements likely to directly participate in active closing of the urethral lumen. We estimated glycogenolysis in urinary bladder, perivesical connective tissue and levator ani muscle (LAM) samples obtained intraoperatively from 80 stress incontinent women. Glycogen content as well as activities of active and total glycogen phosphorylase and acid exo-1,4-alpha-glucosidase were measured. Material from the urinary bladder and perivesical connective tissue was insignificantly altered, and glycogen contents in the bladder (2.03±1.38 g/100 g wet tissue) were considered to be normal. In the LAM glycogenolysis was much more activated than in other tissues (p<0.001 by Fischer's exact test). Of LAM specimens 78% (22/28) revealed imbalanced biochemistry of glycogen with activation of hydrolytic decomposition. We conclude that stress urinary incontinence in women is frequently associated with metabolic alterations in the periurethral striated fibres. This study indirectly supports our recent hypothesis on the pathogenesis of the disease in terms of muscle fibre type transitions.     

Insulin-like growth factor I promotes leiomyoma cell growth in vitro

Objective: Our purpose was to determine whether insulin-like growth factors I and II preferentially stimulate uterine leiomyoma cells versus myometrial cells in monolayer culture.Study design: Leiomyomas and normal myometrium were obtained at hysterectomy from five premenopausal women. Specimens were enzymatically digested for use in primary monolayer cell cultures. By use of serum-free media, insulin-like growth factor I or II was added in 1, 10, and 100 ng/ml concentrations to both cell types with the patient serving as her own control. Cell number, prolactin production, and proliferative index values were measured on day 15 of cell culture.Results: Significant increases in cell number were found in the leiomyoma cultures (p < 0.05) treated with 10 and 100 ng/ml insulin-like growth factors I but not with insulin-like growth factos II. Neither factor exerted a stimulatory effect on myometrial cells.Conclusion: Insulin-like growth factor sI preferentially stimulates leiomyoma cells in monolayer culture. These results suggest an autocrine-paracine role in vivo for this factor in conjuction with gonadal steroids in promoting leiomyoma growth.