The growth potential of ependymomas with varying grades of malignancy measured by the Ki-67 labelling index and mitotic index

The prognostic significance of histopathological grade for postoperative outcome is not yet known for ependymomas. Data on proliferation kinetics of these tumors are few.In our study, the growth fraction was immunohistochemically determined by labelling cell nuclei with the monoclonal antibody Ki-67 in 24 tumors of the ependymoma group (2 malignant ependymomas grade III, 11 ependymomas grade II, 8 spinal ependymomas, and 3 subependymomas). The results were compared with the mitotic index in the same tumor areas. Both growth parameters are related to the grade of malignancy. The differences between the results of spinal ependymomas (grade I) and of intracranial tumors (grade II) were statistically signifcant. Malignant ependymomas had the highest values. Variable growth potentials could be demonstrated in a few tumors. A non-linear relationship between growth fraction and mitotic index was found, indicating a variable generation time in ependymomas (as in astrocytomas). Thus, with rising grade of malignancy the growth fraction increases and the generation time decreases.     

Surgical treatment of intramedullary spinal cord tumors: prognosis and complications

STUDY DESIGN: Retrospective case series. OBJECTIVE: To evaluate our recent treatment strategy for intramedullary spinal cord tumors. SETTING: Department of Orthopaedic Surgery, Keio University, Japan. METHODS: We reviewed 68 cases of intramedullary tumors (ependymoma, 33; astrocytoma, 23; hemangioblastoma, 12), treated surgically between 1994 and 2003. There were 42 males and 26 females whose mean age at the time of surgery was 43 years. The mean follow-up period was 6.2 years. The tumor malignancy grade according to the WHO classification was astrocytoma grade I, 3; grade II, 8 (low-grade: 11 cases); grade III, 10; grade IV, 2 (high-grade: 12 cases). All ependymomas were grade II. Three of the 12 hemangioblastomas were associated with von Hippel-Lindau disease. RESULTS: Total excision was achieved in 90% of the ependymomas and functional improvement was obtained when the preoperative neurological deficit was mild. Approximately 50% of low-grade astrocytomas could be totally excised with favorable survival outcomes, suggesting that total excision should be attempted for low-grade astrocytomas. However, total excision of high-grade tumors was difficult and the functional outcomes were poor. Cordotomy should be considered in patients with a thoracic high-grade astrocytoma. Total resection was possible in 92% of hemangioblastoma, and the functional outcomes were good, however, more attention should be paid for tumors with feeding arteries on the ventral side and for those associated with von Hippel-Lindau disease. CONCLUSIONS: Predictors of good surgical outcome for intramedullary spinal cord tumors were histological grades of the tumors, surgical margins, and neurological status of the patient before surgery.     

Nogo-a expression in glial CNS tumors: a tool to differentiate between oligodendrogliomas and other gliomas?

Gliomas are the most frequent primary brain tumors. In a minority of cases, the differentiation between astrocytomas and oligodendrogliomas based on morphologic characteristics alone can be difficult; though it is important, as patients with oligodendrogliomas follow a more favorable clinical course. Here we report on the immunohistochemical expression pattern of the oligodendrocytic marker Nogo-A in 113 central nervous system tumors including 28 oligodendrogliomas [15, World Health Organization (WHO) grade II; 13, grade WHO III], 50 astrocytomas [10, grade WHO II; 11, grade WHO III; 29 glioblastoma multiforme (GBM)], 11 ependymomas WHO grade II, 7 central neurocytomas, 2 dysembryoplastic neuroepithelial tumors (DNTs), 5 clear cell meningiomas, and 10 metastases to the brain. The oligodendrocytic marker Nogo-A was found to be strongly expressed in 71% of oligodendrogliomas, but in 0% of ependymomas WHO grade II, astrocytomas WHO grade II or III, DNTs, central neurocytomas, or clear cell meningiomas. In GBM, a subgroup of tumors (24%) showed strong expression of Nogo-A coincidently with Ki67 positivity but glial fibrillary acidic protein-negativity. However, neither in oligodendrogliomas nor GBM was a correlation between the loss of 1p19q and the extent of Nogo-A expression observed. Our findings indicate that Nogo-A is strongly expressed in the majority of oligodendrogliomas and might be a helpful marker to distinguish oligodendrogliomas from astrocytomas WHO grades II and III as well as ependymomas. They also support the hypothesis that GBM may be a heterogeneous group of tumors derived from different progenitor cells.     

Intracranial ependymomas in adult patients. Retrospective analysis of 121 cases from the multicentric French study

Ependymomas are rare intracranial tumors observed in adults. Prognostic factors as well as proper therapeutic management remain controversial. We report a retrospective study of 121 cases intracranial ependymomas diagnosed between 1990 and 2004 in adult patients. Mean age was 46 years with a 1/1 sex-ratio. Supratentorial and infratentorial localization was noted for 41 (33.9%) and 80 (66.1%) patients respectively. Total gross resection was achieved for 62.8% of tumors. WHO staging was grade II for 72.7% and III for 27.3%. Recurrence developed in 41 (33.9%) patients. Median follow-up was 70 months. The 5-year and 10-year overall survivals were 85 and 76% respectively; the respective progression-free survivals were 64 and 43%. At univariate analysis, age, KPS, localization, extent of surgery and histological grade were correlated with overall survival. At multivariate analysis age, location, histological grade and extent of surgery contributed most to prediction of overall survival. Concerning progression-free survival, univariate analysis found age, KPS, localization, extent of surgery, complementary treatment and histological grade to be correlated with recurrence. Multivariate analysis retained extent of surgery, histological grade and complementary treatment as the most important predictors of progression-free survival. This study demonstrated that extent of surgery and tumor grade are the two main prognostic factors in adult intracranial ependymomas with respect to overall and progression-free survival. Furthermore, our data suggest that postoperative radiotherapy significantly increases progression-free survival in patients with incompletely resected grade II tumors.     

Prognostic relevance of DNA ploidy and proliferative activity in urothelial carcinoma of the renal pelvis and ureter. A study on a follow-up period of 6 years

In 55 patients with urothelial carcinoma of the renal pelvis or ureter, the ploidy, the DNA heterogeneity and the counts of cell cycle phases in the tumor were examined by means of single-cell DNA cytophotometry in order to find more prognostic factors than those already known (stage and grade). Follow-up periods ranged from 1 to 6 years. At the time of first diagnosis, 42 (76%) of the patients had tumors of the renal pelvis, 13 (24%) of them had ureteral tumors. 23 (42%) patients were in stage pT 1 N 0, 15 (27%) in stage pT 2 N 0, 12 (22%) in stage pT 3 N 0, and 5 (9%) were in stage pT 3 N+. The histological malignancy grade most frequently seen in the patients examined--i.e. in 51% of cases--was malignancy grade II. 25% of the patients had grade III tumors whereas only 24% had grade I tumors. With malignancy grade I, DNA cytophotometry showed DNA frequency peaks to be in the diploid range while tumors with malignancy grade II showed heterogenous DNA patterns. 71% of the patients with malignancy grade III showed aneuploid DNA values; 29% of them had polyploid DNA values. For malignancy grades II and III, the proliferation rate of the tumor cells was statistically significantly higher than for malignancy grade I. The determination of tumor heterogeneity and tumor cell proliferation by means of DNA cytophotometry gives valuable clues regarding prognosis.     

Supratentorial ependymomas in childhood: Clinicopathological findings and prognosis

Summary Out of 29 supratentorial ependymomas in children under 10 years of age, operated on between 1951 and 1989, 18 were situated in the hemispheres and 11 in the midline.15 of the 18 hemispheric tumours, but only 4 of the 11 intra- or paraventricular ependymomas allowed complete removal. The operative mortality within the observation period of nearly 40 years was 27% for tumours in the midline and 11% for those in the hemispheres.The grade of malignancy rose with increasing distance from the ventricular level. 5-year survival without recurrence was 75% in grade 2 and 31% in grade 3 ependymomas. The total rate of recurrence was 58%.New tumour growth can be delayed by postoperative irradiation, at least in grade 2 ependymomas. It can be prevented, if at all, only by total resection of the primary tumour.Part of this paper was presented at the 41st Annual Meeting of the German Society for Neurosurgery in Düsseldorf, F.R.G., May 27–30, 1990.     

Postoperative radiotherapy in the management of spinal cord ependymoma

Fifty-eight patients with histologically verified spinal cord ependymomas were treated at the Royal Marsden Hospital and Atkinson Morley's Hospital between 1950 and 1987. The median age in this series was 40 years (range 1 to 79 years) and the male:female ratio was 1.8:1. Ten patients had tumors in the cervical cord and 10 in the thoracic cord; 14 tumors involved the conus medullaris and 24 the cauda equina. Forty ependymomas were grade I and 13 were grades II to IV (in five patients there was insufficient material for grading). Eleven patients underwent biopsy only, 33 had partial or subtotal resection, and 14 had complete resection. Forty-three patients received postoperative radiotherapy. The median follow-up period was 70 months (range 3 to 408 months). Cause-specific survival rates were 74% and 68% at 5 and 10 years, respectively. On univariate analysis, age, histological grade, postoperative neurological function, and era of treatment were significant prognostic factors for survival. The histological grade was the only significant independent prognostic factor. The relative risk of death from ependymoma was 9.0 for patients with tumor grades II to IV compared to grade I (p less than 0.005, 95% confidence interval 2.7 to 30). The survival rates of patients following complete excision were significantly better compared to those after incomplete surgery (p less than 0.025). The majority of completely resected neoplasms were low-grade cauda equina tumors. Despite incomplete surgery, 5- and 10-year progression-free survival rates following radical radiotherapy were both 59%, and cause-specific survival rates were 69% at 5 years and 62% at 10 years. This suggests that radiotherapy may achieve long-term tumor control in over half of those patients with residual spinal ependymoma.     

Supratentorial lobar ependymomas: Reports on the grading and survival periods in 80 cases,including 46 recurrences

We report 80 supratentorial lobar ependymomas, including 46 recurrences. All underwent operation. In the total collection 34.5% survived for more than 5 years. The behaviour of children and adults was nearly identical. Based on a histological grading into three steps of malignancy (E1, E2, E3), the ependymomas in low grade 1 showed a 5 years' survival time of 41.5%. Compared to a 28.5% survival in group E2 at the same time. Results in group E3, which histologically resembled malignant glioma or glioblastoma, are not relevant because of the small number of cases. More than 50% of the E1 recurrences showed transformation to E2. No transformation into a lower grade of malignancy has been observed.     

Infratentorial ependymomas: prognostic factors and outcome analysis in a multi-center retrospective series of 106 adult patients

Object

This study was undertaken to analyze outcomes and to assess the prognostic impact of age, location, surgery, radiotherapy (RT), and histopathology in a series of adult infratentorial ependymomas.

Methods

This was a retrospective study of a population of 106 adult patients with infratentorial ependymomas diagnosed between 1990 and 2004. A central pathological review of all cases was performed. Grading was according to the WHO and Marseille’s neograding classifications.

Results

The series consisted of 58 males (54.7%) and 48 females (45.3%) in the age range of 18-82 years. Using the WHO classification, 88 patients (83.0%) had grade II and 18 patients (17.0%) grade III ependymomas. Using the Marseille’s neograding system, 91 patients were low-grade and 15 high-grade. Gross total resection was achieved in 66 patients (62.3%). Thirty-seven patients (35.0%) received adjuvant RT. The 5- and 10-year overall survival rates for the entire cohort were 86.1% and 80.5%, respectively. On multivariate analysis, a preoperative Karnofski performance status score?>?80, no recessus lateral extension and a low histological grade (Marseille’s grading) were associated with a longer overall survival. The 5- and 10-year progression-free survival rates for the entire cohort were 70.8% and 57.7%, respectively. On multivariate analysis, no recessus lateral extension, gross total resection and a low histological grade (Marseille’s grading) were associated with a longer progression-free survival. Adjuvant RT was significantly associated with a better overall and progression-free survival in incompletely resected WHO grade II ependymomas.

Conclusions

This study highlights the key role of histology in the clinical outcome and the fact that gross total resection is a main prognostic factor and the treatment of choice for posterior fossa ependymomas. The use of adjuvant RT in patients with incompletely resected WHO grade II ependymomas appears beneficial, but its effect on high-grade tumors remains to be determined.

     

Flow cytometry analysis of urothelial cell DNA content according to pathological and clinical data on 100 bladder tumors

DNA content of 100 bladder tumors (34 grade I, 42 grade II and 24 grade III, WHO classification) were studied by flow cytometry. Ten normal bladder samples were used as control. The 100 bladder tumors could then be separated into two groups. A first group of 60 tumors (60%) had a unimodal distribution with a diploid peak and a DNA index close to 1.0, 32 grade I, 22 grade II and 6 grade III tumors displayed this pattern as did the 10 normal bladders. The second group (40%) had a bimodal distribution with two peaks, the first one (diploid peak) with a DNA index of 1.0, the second (aneuploid peak) with a DNA index greater than 1.0. Two grade I, 20 grade II and 18 grade III tumors belonged to this group. Frequency of the aneuploid peak increased with tumor grade and infiltration progression. Hence 6% of grade I, 48% of grade II and 75% of grade III tumors showed an aneuploid peak as well as 8% of Pa, 46% of P1, 73% of P2 and 87.5% of P3 stage tumors. This study showed that a good correlation exists between flow-cytometric, pathological and clinical data.     

Stage means more than grade in adenoid cystic carcinoma.

Our experience with 184 previously untreated patients who had adenoid cystic carcinoma of salivary gland origin is reviewed. Retrospective staging was possible in all but nine patients who had minor salivary gland primary tumors. Sixty-three percent of patients were diagnosed as having stage I or stage II disease (stage I, 64 patients; stage II, 47 patients), whereas 43 and 21 patients had stage III and IV tumors, respectively. Grading was as follows: cribriform pattern only (grade 1, 126 patients; 68%), mixed cribriform and solid features (grade 2, 48 patients; 26%), and solid only (grade 3, 10 patients; 5%). Treatment was predominantly surgical (174 patients), and relatively few patients received adjunctive, postoperative irradiation (27 patients). Cumulative 10-year survival was 75%, 43%, and 15% for stage I, stage II, and stage III and IV patients, respectively, and cause-specific survival at 10 years was as high as 94% in patients with stage I disease. Only the clinical stage had a significant impact on survival. Neither survival, regional metastases (16 patients; 11%), nor distant dissemination (64 patients; 43%) was predictable on the basis of tumor grade alone. The prognosis in patients with early stage lesions may be better than has been appreciated.     

New perspectives in brachycurietherapy of malignant brain tumors. Preliminary report

Between 1980 and 1988, 16 patients (9 females, 7 males) with malignant neuroepithelial tumors of the brain were treated by brachycurietherapy (BCT) and external radiation therapy (ERT) in a phase II nonrandomized study. There were 13 grade III and 3 grade IV tumors according to the WHO classification. Five patients in the grade III group who showed anaplastic foci in a generally grade II background were separately examined. Six patients received only BCT whereas 10 patients were treated by a combination of BCT and ERT, according to the tumor volume. We utilized as radioactive sources 192Ir in 14 cases and 125I in 2. Thirteen patients underwent permanent implant, 3 others received temporary irradiation with removable afterloaded catheters. The target volume was less than 50 cc in 8 cases, between 50 and 100 cc in 7, and larger than 100 cc in 1 patient. The total dose at the periphery of these volume ranged between 70 and 144 Gy. The result were analyzed referring to the following aspects: performance status, survival, side effects, grading. The impact of BCT was analyzed especially in a grade III with anaplastic foci group which showed a median survival of 6 years compared with only 2 years median survival of the pure grade III group.     

Ependymomas of the lateral ventricle. A series of 27 cases with review of the literature

Twenty-seven cases of ependymoma were collected in the French multicentric study dedicated to lateral ventricle tumors. The mean age of patients was 31,5 years. All patients underwent surgery, with complete resection of the tumor in 76% of cases. Histologic examination disclosed 23 grade 2 ependymomas and four grade 3 ependymomas. Postoperative mortality was 7%. Four patients underwent radiotherapy, and five chemotherapy. Local recurrence of the tumor occurred in seven cases, with a mean delay of 48 months. Disseminated disease within the central nervous system was found in only one patient. Median survival in all the 27 patients was 181 months, and median progression-free survival was 106 months. The relevant series of the literature are reviewed in order to precise the prognostic factors of ependymomas and therapeutic strategies.     

Malignancy grade and clinical stage T0-T3 in prostate cancer

The frequency of malignancy grade I-III (grading system according to B?cking and Sommerkamp, 1980) and of clinical stages T0-T3 in 393 unselected prostatic carcinomas (227 punch biopsies and 166 transurethral resections) were investigated over a period of 2 years. G III carcinomas were represented most frequently in the whole material (54%) as well as in punch biopsies (62%). G I carcinomas with a favorable prognosis make up 20% of the tumors in the whole material and only 10% in punch biopsies. In contrast, 54.9% of incidental carcinomas (T0) are G I tumors, 18.6% G III carcinomas with an unfavorable prognosis. The advanced clinical stages T2 and T3 predominate in the whole material with 62.4%, compared to stages T0 and T1 comprising 37.6%. Malignancy grade and clinical stage are clearly correlated in the whole material. In incidental carcinoma, there is also a correlation between malignancy grade and histologic extension. The percentage of higher malignancy grades G II and G III increases with age. This is true for incidental carcinoma as well. The findings emphasize the prognostic significance of the grading system.     

c-myc oncogene family expression in glioblastoma and survival.

BACKGROUND: In gliomas, c-myc proto-oncogene expression has been found to correlate with the grade of malignancy, with low expression in Grade I and II and high expression in Grade III and IV tumors. We aimed to discover if myc expression is of prognostic significance in glioblastomas. METHODS: Expression of the c-myc, N-myc, and L-myc proto-oncogenes and of the max gene was investigated in 46 supratentorial glioblastomas from adult patients using in situ hybridization. RESULTS: Seventy-eight percent of the tumors expressed c-myc m-RNA, 84% max m-RNA, 57% N-myc m-RNA, and 57% L-myc m-RNA. The postoperative survival of patients over 60 years of age and that of patients under 60 years of age were analyzed separately, since advancing age was found to be negatively correlated with the duration of postoperative survival (p = 0.004). There was no significant difference in postoperative survival in either age group between patients whose tumors expressed either c-myc, N-myc, or L-myc, respectively, and those whose tumors did not exhibit this characteristic. A difference in postoperative survival, however, was found in the over 60-year age group between patients whose tumors expressed max to an equal or lesser extent than c-myc and those whose tumors expressed max to a greater extent than c-myc or neither max nor c-myc. CONCLUSION: The biologic behavior of glioblastomas in older patients may depend on the relative, but not on the absolute content of the c-myc protein and interacting proteins.     

Thymoma needs a new staging system

Despite the wide use of the Masaoka staging system for thymoma, the distribution of survival by stage group is not well balanced. The new staging systems for testing were defined as follows: stage I was created by merging Masaoka's stages I and II, and stage IV remained unchanged. Stages II and III were defined as thymomas with invasive growth and the following combinations of tumor diameter and number of involved structures/organs. Scheme 1: stage II included tumors less than 10 cm in diameter and involving one neighboring structure/organ. Stage III included tumors with all combinations of diameter and number of involved structures/organs other than those in stage II. Scheme 2: stage II included tumors of all combinations other than those in stage III. Stage III included tumors 10 cm or more in diameter and involving two or more structures/organs. The survival curves were assessed for 138 patients treated at the National Cancer Center, Tokyo. The 10-year survival rates for each stage according to the Masaoka, Scheme 1, and Scheme 2 systems were as follows: stage I (100%, 100%, 100%), stage II (100%, 86%, 83%), stage III (70%, 64%, 34%), and stage IV (34%, 34%, 34%), respectively. The survival curves for Scheme 1 gave the most balanced distribution of survival in each staging group. By considering both tumor diameter and number of involved structures/organs, Masaoka's stages I-III could be rearranged with more balanced distribution of survival.     

Malignant salivary tumors--analysis of prognostic factors and survival

A group of 113 patients with malignant salivary gland tumors was retrospectively reviewed to analyze the association of clinical and histologic factors with survival. These factors were patient sex and age, tumor site, clinical stage, histologic diagnosis, tumor grade, and whether or not final surgical margins were clear. There were 57 parotid, 40 minor salivary, and 16 submandibular gland cancers. The histologic groups were mucoepidermoid carcinoma (49 patients), adenoid cystic carcinoma (31), adenocarcinoma not otherwise specified (18), acinic cell carcinoma (7), malignant mixed tumor (5), squamous cell carcinoma (2), and undifferentiated carcinoma (1). Univariate analysis of clinical factors showed that age and clinical stage significantly influenced survival. At 10 yr the predicted cumulative survival rates for Stage I, II, III, and IV tumors were 74%, 56%, 32%, and 10%, respectively. Tumor grade was the only significant histologic factor. This was most obviously reflected among patients with mucoepidermoid carcinomas. Cumulative survival at 5 yr was 94% for those with low-grade tumors and 26% for high-grade tumors. By multivariate analysis, clinical stage, age, and tumor grade remained highly significant. Analysis of patients with only Stage I and II disease demonstrated that the significant factors were patient age, tumor site, tumor grade, and whether or not surgical clearance was achieved. These results suggest that clinical stage should not be the exclusive determinant of the extent of surgery and that the selection of patients, for adjuvant therapy may be improved by an awareness of these prognostic factors.     

Malignant salivary tumors—analysis of prognostic factors and survival

A group of 113 patients with malignant salivary gland tumors was retrospectively reviewed to analyze the association of clinical and histologic factors with survival. These factors were patient sex and age, tumor site, clinical stage, histologic diagnosis, tumor grade, and whether or not final surgical margins were clear. There were 57 parotid, 40 minor salivary, and 16 submandibular gland cancers. The histologic groups were mucoepidermoid carcinoma (49 patients), adenoid cystic carcinoma (31), adenocarcinoma not otherwise specified (18), acinic cell carcinoma (7), malignant mixed tumor (5), squamous cell carcinoma (2), and undifferentiated carcinoma (1). Univariate analysis of clinical factors showed that age and clinical stage significantly influenced survival. At 10 yr the predicted cumulative survival rates for Stage I, II, III, and IV tumors were 74%, 56%, 32%, and 10%, respectively. Tumor grade was the only significant histologic factor. This was most obviously reflected among patients with mucoepidermoid carcinomas. Cumulative survival at 5 yr was 94% for those with low-grade tumors and 26% for high-grade tumors. By multivariate analysis, clinical stage, age, and tumor grade remained highly significant. Analysis of patients with only Stage I and II disease demonstrated that the significant factors were patient age, tumor site, tumor grade, and whether or not surgical clearance was achieved. These results suggest that clinical stage should not be the exclusive determinant of the extent of surgery and that the selection of patients, for adjuvant therpay may be improved by an awareness of these prognostic factors.     

Primary angiosarcoma of breast: A case report

INTRODUCTIONPrimary breast angiosarcoma is a rare form of breast cancer, accounting for only 0.04% of all malignant breast tumours.PRESENTATION OF CASEA 28-year-old woman presented with a progressive lump in the right breast for one month. Fine needle aspiration cytology (FNAC) was highly suspicious of angiosarcoma, and this diagnosis was confirmed on core needle biopsy. Modified radical mastectomy was performed as sole treatment.DISCUSSIONPrimary breast angiosarcoma is a rare type of breast malignancy, usually occurring in the third to fourth decade and only reported in women. The histological features of angiosarcoma of the breast are conventionally graded I, II or III. Total mastectomy appears to be the only treatment conferring benefit, chemotherapy and radiation therapy being of little proven value to date. The 5-year disease-free survival for grade I tumours can be as high as 76%, and up to 70% for grade II tumours whereas for grade III tumours it is reportedly about 15%.CONCLUSIONPrimary angiosarcoma of the breast is a rare malignancy with a poor prognosis, even after complete resection. Surgery is the mainstay of treatment with a limited role for chemotherapy and radiotherapy.     

Urinary polyamine levels in the diagnosis of carcinoma of the prostate.

Urinary excretion of the basic polyamine, spermidine, was significantly elevated in patients with prostatic carcinoma as compared to a control group of patients, Of 44 urine specimens from patients with prostatic malignancy 31 had spermidine levels more than 2 mg. per 24 hours, while only 3 of 13 urine specimens from the control groups had levels in excess of this value. The increase in spermidine appeared to be correlated with the histologic grading of the tumor, that is 30 of 34 specimens from patients with grade II, III or IV carcinoma had excessive spermidine excretion and only 1 of 10 urine specimens from patients with grade I tumors had similiar spermidine elevations. High spermidine levles were found in tumors localized to the prostate and in 7 of 8 patients with negative pelvic and para-aortic lymph node biopsies. This study raises the possibility that urinary spermidine determinations may aid in the development of a biochemical screening test for prostatic neoplasms.