Clinicopathological evaluation of 78 astrocytomas in Taiwan with emphasis on a simple grading system

Summary The grading systems of astrocytic tumors have long been the subject of controversy. A simple, objective and effective grading method is urgently needed for the evaluation of prognosis and the planning of treatment. This study investigated the relationship of clinical prognostic factors to the grading method of Daumas-Duport. This method determines the grade of tumor based on the presence or absence of four morphological criteria: nuclear atypia, mitosis, endothelial proliferation, and necrosis. A total of 143 astrocytic tumors were reviewed and screened, of which 65 ordinary and 13 pilocytic astrocytomas were selected for grading and comparison. Among ordinary astrocytomas, the grading method distinguished 9.2% grade 1, 26.2% grade 2, 36.9% grade 3, and 27.6% grade 4. At least 2-year follow-up was available on all surviving patients. Median survival was 57, 32, 12.5, and 8 months in grades 1, 2, 3, and 4 tumors, respectively. By a multiple regression model and analysis of variance, grade is significantly associated with survival (total regression coefficient r = 0.711). Age lost its significance on survival after multiple regression analysis. Sex, location, and surgical procedure were all unrelated to survival after regression. The age distribution and survival of patients with pilocytic astrocytomas revealed that this is a distinct disease entity and should not be admixed with ordinary astrocytomas in a grading scheme.This paper is part of his master thesis.     

Original and reviewed nuclear grading according to the Fuhrman system: a multivariate analysis of 388 patients with conventional renal cell carcinoma

BACKGROUND: The objective of the current study was to evaluate the reproducibility of the Fuhrman nuclear grading system as well as its independent predictive value in a series of patients with conventional renal cell carcinoma (RCC). METHODS: The authors selected 388 patients who had undergone surgical treatment for conventional RCC between 1986 and 2000. Pathology slides from the selected patients were reviewed by a single pathologist, who reassigned a Fuhrman nuclear grade and assessed the presence of tumor necrosis. The pathologist was blinded to both the original pathologic diagnosis and follow-up data. The kappa statistic was used to evaluate concordance between original and reviewed nuclear grades. The log-rank test was used for univariate analyses, and a Cox proportional hazards model was used for multivariate analyses. RESULTS: The original Fuhrman nuclear grade was Grade 1 (G1) in 111 patients (28.6%), G2 in 141 patients (36.3%), G3 in 108 patients (27.8%), and G4 in 28 patients (7.3%). After pathology slide review, nuclear grades were reassigned as follows: G1 in 49 patients (12.6%), G2 in 138 patients (35.6%), G3 in 150 patients (38.7%), and G4 in 51 patients (13.1%). The grade of concordance was moderate (kappa=0.44; P <0.001). Univariate analyses identified three separate prognostic categories defined by nuclear grade (G1 and G2 vs. G3 vs. G4). Both the original and the reviewed Fuhrman nuclear grading systems were capable of independently predicting disease-specific survival in patients with conventional RCC. CONCLUSIONS: The interobserver reproducibility of Fuhrman nuclear grading was moderate. The substantial overlap in survival curves for G1 and G2 tumors provided an opportunity to cluster those categories, and the resulting three-tiered nuclear grading system was an independent predictor of cause-specific survival in patients with conventional RCC. Other independent predictors of survival included pathologic stage and tumor necrosis status.     

Clinicopathological features, MIB-1 labeling index and apoptotic index in recurrent astrocytic tumors

This is a study of 64 cases of recurrent astrocytic tumors of all four WHO grades wherein a comparative evaluation of initial vs. recurrent tumor was done with respect to histological grading, MIB-1 labeling index (LI) and apoptotic index (AI). The aim was to identify factor/s that could influence interval to recurrence and/or malignant progression. Recurrence was noted in all grades and upon recurrence, 93.3% of grade II (low grade diffuse) astrocytomas and 63.6% of grade III anaplastic astrocytomas underwent malignant progression. However, none of the Grade I tumors showed evidence of malignant progression. Though interval to recurrence varied considerably, there was a correlation with histological grade of the initial tumor in that grade I and II tumors had a significantly longer mean interval to recurrence (43 months and 54.8 months respectively) as compared to grade III and IV (glioblastoma multiforme) tumors (17.6 and 12.8 months respectively). The interval to recurrence was also longer for grade II and III tumors which showed progression on recurrence (55.3 months for Grade II->Grade III; 54 months for Grade II->Grade IV and 20.6 months for Grade III->IV) as compared to tumors which recurred to the same grade (12.5 months for Grade III->Grade III and 12.8 months for Grade IV->Grade IV). A statistically significant inverse correlation of MIB-1 LI with interval to recurrence was noted. Higher the MIB-1 LI, shorter was the interval to recurrence. Further a cut off MIB-1 LI value of 2.8% could be proposed in predicting recurrence free survival. Interestingly, MIB-1 LI of grade II tumors, which had progressed to grade IV was significantly higher than MIB-1 LI of grade II tumors which had progressed to grade III. Thus, this study establishes the potential role of MIB-1 LI of the initial tumor in determining interval to recurrence. However, apoptotic index has no role in predicting either interval to recurrence or malignant progression.     

Prognostic relevance of a novel TNM classification system for upper gastroenteropancreatic neuroendocrine tumors

BACKGROUND: Neuroendocrine tumors (NETs) of the gastroenteropancreatic (GEP) system comprise a rare but challenging group of malignant neoplasms and occur at virtually any site of the GEP system. In 2006, a new TNM classification system was proposed for the staging and grading of upper GEP NETs. METHODS: The prognostic relevance of the TNM classification system was analyzed retrospectively in 202 patients from a referral center with histologically proven foregut NET. Patients were classified according to previous classification systems and the TNM classification. Survival data were acquired and statistical analyses were performed by using log-rank and Cox regression testing. RESULTS: Primary tumors were gastric (n = 48), duodenal (n = 23), and pancreatic (n = 131). During the observation period, 21% of patients died. The overall 5- and 10-year survival rates were 75% and 64%, respectively. Previous classification systems discriminated between low-grade and high-grade malignant NETs but did not allow further prognostic differentiation. In contrast, the proposed TNM classification was able to differentiate significantly between different tumor stages (stages I-III vs stage IV; P < .01) and cellular proliferation rates according to Ki-67 labeling (grade 1 vs grade 2, P = .04; grade 1 vs grade 3 and grade 2 vs grade 3, P < .01). Cox regression analysis confirmed an increased risk of reduced survival for patients with stage III or IV NET and grade 2 or 3 NET. CONCLUSIONS: The current results demonstrated the prognostic relevance of the newly proposed TNM classification system for foregut NETs with statistical significance for the subgroups of both the staging classification and the grading system. Thus, the new classification system provides a valid and powerful tool for prognostic stratification of GEP NETs in clinical practice and research.     

Grading of astrocytomas. A simple and reproducible method

This study determines the effectiveness and reproducibility of a previously published method of grading gliomas. The method under study is for use on "ordinary astrocytoma" cell types, i.e., fibrillary, protoplasmic, gemistocytic, anaplastic astrocytomas and glioblastomas, and is based upon the recognition of the presence or absence of four morphologic criteria: nuclear atypia, mitoses, endothelial proliferation, and necrosis. The method results in a summary score which is translated into a grade as follows: 0 criteria = grade 1, 1 criterion = grade 2, 2 criteria = grade 3, 3 or 4 criteria = grade 4. The histologic material and clinical data were derived from a previously reported series of patients with astrocytomas, radiotherapeutically treated at Mayo Clinic between the years 1960 and 1969. From this series, initially graded 1 to 4, according to the Kernohan system, 287 "ordinary astrocytomas" were entered into the study; 51 pilocytic astrocytomas and microcystic cerebellar-type astrocytomas also were included for comparison. Among ordinary astrocytomas, the grading method under study distinguished 0.7% of grade 1, 17% of grade 2, 18% of grade 3, and 65.3% of grade 4. A 15-year period of follow-up was available on all surviving patients. Statistical analysis showed that in ordinary astrocytomas, each of the four histologic criteria, as well as the resultant grade, were strongly correlated to survival (P less than 0.0001). Median survival was 4 years in grade 2, 1.6 years in grade 3, and 0.7 years in grade 4 tumors. Of the two patients with grade 1 ordinary astrocytomas, 1 had 11 years of survival, and the other was alive at 15 years. Furthermore, based upon the Cox Model, grade was found to be the major prognostic factor, superceding the effects of age, sex, and location. Among ordinary astrocytomas, the grading system under consideration clearly distinguished four distinct grades of malignancy, whereas, the Kernohan grading system accurately distinguished only two major groups of patients. Survival curve of patients with our grade 2 tumors coincided with the grade 1 and 2 Kernohan survival curves. Similarly, our grade 4 survival curve coincided with the Kernohan grade 3 and 4 survival curves. As a result, our proposed grading method generated an individualized curve corresponding to grade 3 tumors. Double-blind grading between two independent observers was concordant in 94% of ordinary astrocytomas; reproducibility was 81% in low-grade (grades 1 and 2) and 96% in high-grade (grades 3 and 4) astrocytomas of ordinary type.(ABSTRACT TRUNCATED AT 400 WORDS)     

Expression of apoptosis and its related protein in astrocytic tumors

The relationship between malignant potential and apoptosis in astrocytic tumors has not been clearly defined, and further classification of astrocytic tumors is necessary. To elucidate the relationship between the histopathological grade of astrocytic tumors and apoptosis, we studied 25 cases of astrocytic tumors, comprising 10 cases of glioblastoma (GB), 7 cases of anaplastic astrocytoma (AA), and 8 cases of astrocytoma (AC). We detected apoptosis using the TdT-mediated dUTP-biotin nick-end labeling (TUNEL) method. We studied immunohistochemical expression of bcl-2 protein and p53 protein, which are apoptosis-related factors, and cell proliferative activity using Ki-67 antibody. No significant change was noted between apoptotic index and the histological grade of the tumors. In GB, apoptotic cell-rich foci were present at the pseudopalisading necrosis. No correlation between histopathological grades and expression of either p53 or bcl-2 was observed. In GB, however, poor distribution of bcl-2 was found in the areas of pseudopalisade formation. bcl-2 is one of the regulatory factors in the cell cycle and inhibits apoptosis. Expression of apoptosis had no correlation with histopathological grade. However, in GB, the distribution of apoptotic cells showed a correlation with bcl-2-poor foci. It was thought that apoptosis was one of the regulatory factors in the formation of pseudopalisading necrosis in GB.     

Quality assurance of an image guided intracranial stereotactic positioning system for radiosurgery treatment with helical tomotherapy

According to World Health Organization (WHO) and Daumas-Duport grading systems, progression of oligodendrogliomas (ODGs) to a higher grade (WHO grade III, grade B) is associated with increased angiogenesis. Based on multivariate assessment of molecular, pathological, and radiological parameters, we further assessed the influence of tumor angiogenesis on tumor progression and patient survival. Patients with a diagnosis of ODG, consecutively treated in a single institution, were reviewed and reclassified according to WHO and Daumas-Duport grading systems. MRI scans were reviewed to assess contrast enhancement and necrosis. Tissue sections were used for pathology review and to evaluate immunostaining of vascular endothelial growth factor (VEGF), vascular endothelial growth factor receptor (VEGF-R), Ki-67, and CD34. Multivariate analysis was performed to assess the impact of tumor angiogenesis-related pathological and radiological factors on patient survival. One hundred thirty-four patients with pure ODG were included in this study. Multivariate analysis identified four independent poor prognostic factors: necrosis, absence of seizure, increased vascularization, and age >55 years. A subgroup of patients with tumor necrosis, increased vascularization, and absence of seizures had a significantly worse outcome than predicted, with a median overall survival of 14.2 months. VEGF expression was significantly higher in this subgroup and correlated with disease progression regardless of histologic grade. Based on the presence of radiological or pathological necrosis, contrast enhancement or endothelial hyperplasia, and absence of seizures, a high risk group of ODG can be identified with significantly worse overall survival. Also, VEGF over-expression in ODG constitutes an early marker for predicting tumor progression.     

Neuroendocrine tumors of midgut and hindgut origin: tumor-node-metastasis classification determines clinical outcome

BACKGROUND:

Prognostic classification of neuroendocrine tumor (NET) patients is difficult due to the complexity of current classification systems. A recent proposal for a tumor‐node‐metastasis (TNM) classification and a grading system based on the proliferative fraction proved valid in NETs of foregut origin. The purpose of this study was to test the efficacy of a proposal for TNM staging and grading for midgut and hindgut NETs.

METHODS:

Two hundred seventy patients with histologically proven midgut and hindgut NETs were investigated. Epidemiological, clinicopathological, and tumor‐specific data at initial diagnosis were recorded. Tumors were classified according to the World Health Organization (WHO) and the recent European Neuroendocrine Tumor Society‐TNM staging and grading proposal. Survival analysis and statistical testing for independent prognostic factors were performed using log‐rank tests and Cox regression.

RESULTS:

Of 270 NETs originating in the midgut or hindgut, 7% (5‐year survival rate [YSR], 100%) were stage 1, 8% (5‐YSR, 100%) were stage 2, 19% (5‐YSR, 89.5%) were stage 3, and 66% (5‐YSR, 83.3%) were stage 4 NETs; 62% (5‐YSR 95.2%) were grade 1, 32% (5‐YSR 82.0%) were grade 2, and 6% (5‐YSR, 51.4%) were grade 3 NETs. WHO classification significantly separated poorly from well‐differentiated NET or carcinomas but did not further discriminate. TNM staging significantly separated stages 1, 2, and 3 from stage 4 NETs, as did grading according to proliferative capacity for all grades. Multivariate analysis confirmed these results, particularly for Ki67 grading.

CONCLUSIONS:

The acquired data confirmed the prognostic relevance of the proposed TNM staging and grading system and demonstrated the applicability of these classification tools. The TNM system can therefore facilitate therapeutic stratification and comparison of data from different institutions. Cancer 2011. © 2011 American Cancer Society.     

FDG-PET as a Prognostic Factor in High-grade Astrocytoma

Background: The prognostic value of the metabolic status of cerebral gliomas determined by positron emission tomography with [¹⁸F]-fluoro-deoxy-D-glucose (FDG-PET) has been established in populations with a mixture of grades 2, 3 and 4 gliomas, but remains uncertain when only malignant gliomas are considered (grade 3 and 4). Methods: FDG-PET performed in 30 patients with anaplastic astrocytoma (grade III) and 61 patients with glioblastoma (grade 4) were classified according to a metabolic grading. The uptake of FDG was lower in the tumor compared to white matter (WM) in grade 1 (4 glioblastoma, 4 anaplastic astrocytoma), it was intermediate between WM and cortex in grade 2 (20 glioblastoma, 22 anaplastic astrocytoma), and it was superior to cortex in grade 3 (38 glioblastoma, 4 anaplastic astrocytoma). Results: Kaplan–Meier survival curves were similar in patient with grades 1 and 2, but were significantly worse (p = 0.007) in grade 3. In multivariate analysis considering age, pathological grade (anaplastic astrocytoma versus glioblastoma), and metabolic grades, the metabolic grade did not appear to be an independent prognostic factor. When anaplastic astrocytomas and glioblastomas were considered separately, metabolic grade is of predictive value only in the group of glioblastomas. Conclusion: In malignant gliomas, metabolic grading determined by FDG-PET was not superior to the pathological grading for survival prediction. Still, it remains of predictive value when applied to malignant gliomas histologically classified as glioblastoma.     

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.     

Outcome of follicular lymphoma grade 3: is anthracycline necessary as front-line therapy?

A grading system (grades 1-3) for follicular lymphoma (FL) is used in the WHO classification for lymphoid malignancies based on the absolute number of centroblasts in the neoplastic follicles. Grade 3 FL is further subdivided into 3a and 3b depending on the presence or absence of centrocytes. A total of 231 patients with FL, referred from 1970 to 2001, were identified from our prospectively maintained database. Original diagnostic materials were available for review on 215 patients and these were reclassified according to the WHO grading system. Follicular lymphoma grades 1, 2 and 3 accounted for 92, 68 and 55 patients, respectively. No significant overall survival (OS) differences were observed among FL grades 1-3 (log rank P=0.25) or between grades 3a and 3b (log rank P=0.20). No significant failure-free survival (FFS) differences were observed among FL grades 1-3 (log rank P=0.72) or between grades 3a and 3b (log rank P=0.11). First-line anthracyclines did not influence OS or FFS (log rank P=0.86, P=0.58, respectively) in patients with FL grade 3. There are long-term survivors among patients with FL grade 3 with a continuing risk of relapse. Anthracyclines did not appear to influence survival or disease relapses when given as front-line therapy in our series. The role of anthracyclines should be further evaluated in large randomised studies.     

Simple mastectomy with postoperative irradiation versus extended radical mastectomy in breast cancer. A twenty-five-year follow-up of a randomized trial

From November 1951 to December 1957, all patients with untreated breast cancer admitted to the Radium Centre in Copenhagen were randomized before their operability was evaluated into two groups, if the patients were operable, viz. simple mastectomy with postoperative x-ray treatment or extended radical mastectomy. Twenty-five-year results are presented, showing no difference in survival or recurrence-free survival of the operable patients. Histological grading was performed in nearly all cases. Patients with grade 1 tumours had a better survival than grades 2 and 3, but there was no difference in survival between the two treatment groups, when histological grading was taken into account. Histological node positive patients had more grades 2 and 3, tumours, whereas node negative patients had more grade 1 than grades 2 and 3 tumours. Premenopausal women had a significantly better survival than postmenopausal in all stages.     

RELATION BETWEEN MORPHOMETRIC GRADES OF BLADDER TUMOR AND PROGNOSIS

The relation between morphometric grades (M grading) of 84 cases of bladder tumor and prognoses was evaluated. The results shown that the higher the M grading, the lower the survival rate and the higher the recurrence rate. As the M grade increases, the tumor has partial of total absence of ABO(H) antigens of tumor cell surface and could be accompanied with muscular invasion. When recurring, the tumor has a poor prognosis if M grading increases from lower to higher grades. The morphometric grading system is able to make a quantitative pathologic diagnosis and can predict the biological behavior of bladder tumors.     

分段诊刮对子宫内膜癌术前诊断的临床价值评价

目的：探讨分段诊断性刮宫对子宫内膜癌病理分级及术前I晦床分期的价值。方法：回顾性分析102例子宫内膜癌患者手术前分段诊断性刮宫和手术病理结果,并分析其可能的临床病理影响因素。结果：分段诊刮和术后病理组织学结果组织类型完全符合78例,符合率为76．5％。其中子宫内膜样腺癌符合率为85．4％,非子宫内膜样腺癌符合率为50％,两者差异有统计学意义,P〈0．05。组织学分级一致,符合率为66．3％。在其余患者中,术后病理学分级升高者24例,降低者9例。组织学分级本身是影响诊刮与术后病理分级一致性的因素,P〈0．05。患者的年龄、是否绝经、有无高血压、糖尿病史、肌层侵犯及宫颈受累情况,在术后病理分级升高患者与其他患者间差异均无统计学意义,P〉0．05。分段诊刮判断宫颈受累的敏感性71．4％,特异性94．7％,阳性预测值50％,阴性预测值97．8％。结论：在FIGO新分期标准下,分段诊刮仍然是子宫内膜癌术前病理分级及分期的有效方法;宫颈搔刮的阴性结果对判断宫颈受累情况更有意义;部分患者存在术后病理分级升高的情况。     

Radioresponse of human astrocytic tumors across grade as a function of acute and chronic irradiation

Astrocytomas make up the largest group of primary brain tumors of glial origin. Long term survival is rare with high grade tumors (grades 3 and 4), which recur despite subtotal resection, chemotherapy, and aggressive postoperative radiation therapy. In contrast, the 5-year survival for low grade astrocytomas (grades 1 and 2) following subtotal resection and postoperative radiotherapy approaches 50%. Variable sensitivity across grade may contribute to the difference in the behavior of these tumors. To investigate this possibility, the radioresponse of human glial tumors across grade as a function of the dose rate of irradiation was studied. Cell lines derived from a low grade astrocytoma (grade 1) and two high grade astrocytomas (grades 3 and 4) were established in culture. Clonal survival was determined following irradiation of the three cell lines with Cesium 137 gamma rays at high dose rate, 78 Gy/hr, and at low dose rate, range 14 cGy to 79 cGy/hr. The low grade astrocytoma was found to be more radiosensitive than either of the high grade tumors. The alpha/beta (Gy-1/Gy-2) values (linear quadratic model) were 0.35/0.082 for the grade 1 line and 0.20/0.036 and 0.30/0.045 for the grade 3 and 4, respectively. D0 (cGy) values (single-hit multi-target model) were 99, 144, and 117 for grades 1, 3, and 4, respectively. A dose rate effect was present for all three tumor lines irradiated from 14 cGy/hr to 78 Gy/hr. An inverse dose rate effect was also noted at 37 cGy/hr for each of the astrocytic lines. These findings may be useful in the development of strategies to treat astrocytic brain tumors which use high and/or low dose rate irradiation.     

A grading study of gliomas using computer aided malignancy classification and histologic morphometry

Forty three cases of astrocytic tumors and mixed gliomas were studied with the aim of evaluating the reproducibility of the Kernohan grading system vis a vis (a) grading using computer-aided malignancy classifier TESTAST 268 and (b) grading by quantitative morphometric evaluation of the various histological parameters of TESTAST 268. These patients were then followed up for variable periods with a maximum of forty months.High inter and intra-observer variability were observed in the Kernohan grading system. TESTAST 268 was found to be simpler, rapid and more reproducible. However, one drawback observed of this system was that it did not completely eliminate inter-observer variability because there was still some subjectivity in assignment of the categorical values against the histological features. Morphometric evaluation of the semiquantitative assignment values of the 4 histological variables in the TESTAST 268 classifier using Zeiss Morphomat-30 revealed a statistically significant difference between the clusters of the measured quantitative values. A repeat grading using TESTAST 268 and categorical assignment values of histological features derived from the absolute values obtained by morphometry resulted in complete elimination of inter-observer variability. Thus, this study highlights the importance of objectivisation using TESTAST 268 and histologic morphometry in the grading of gliomas. However, since this is a preliminary study on a small number of cases, no cut off values of these measurements have been proposed.     

High and Low Grade Oligodendrogliomas (ODG): Correlation of Amino-Acid and Glucose Uptakes Using PET and Histological Classifications

Classification and treatment strategy of oligodendrogliomas (ODG) remain controversial. Imaging relies essentially on contrast enhancement using CT or MRI. The aim of our study was to use positron emission tomography (PET) using [18F]-flurodeoxyglucose (FDG) and [11C]-L-methyl-methionine (MET) to evaluate metabolic characteristics of ODG. We studied 19 patients with proven ODG, comparing standardized uptake values (SUV) and maximal tumor/contralateral normal tissues ratios (T/N). Imaging findings were compared with WHO, Smith and Daumas-Duport classifications. Uptake of FDG was decreased only in 8 patients, independently of grading, while MET uptake was always increased. MET uptake was significantly higher for high grade tumors grouped according to Smith or Daumas-Duport classifications, while no significant difference in MET uptake was found when using WHO classification. A different correlation was found between FDG and MET uptakes in normal tissues and high grade tumors. A trend for improved progression free survival was found for tumors that lacked contrast enhancement on MRI or those showing low FDG or MET uptake. In conclusion, MET appeared more sensitive than FDG to detect proliferation in ODG. The preferential protein metabolism, already noticeable for low-grade tumor, correlated with glucose metabolism and helped to separate, in vivo, high and low grade tumors.     

Multicenter determination of optimal interobserver agreement using the Fuhrman grading system for renal cell carcinoma: Assessment of 241 patients with > 15-year follow-up

BACKGROUND: The Fuhrman system is the most widely used nuclear grading system for renal cell carcinoma (RCC). Although Fuhrman nuclear grade is widely accepted as a significant prognostic factor, its reproducibility, as reported in the limited number of series available in the literature, appears to be low. METHODS: Between 1980 and 1990, 255 cases of RCC (pT1-3bN0M0) were treated with radical nephrectomy at the Department of Urology, University Hospital, Strasbourg, France. In a retrospective multicenter study, 3 pathologists independently classified 241 of these 255 cases according to the Fuhrman grading system. The authors searched for optimal interobserver agreement by collapsing the grading system to a three-tiered scheme and then to a two-tiered scheme. In addition, overall survival curves were generated according to the classic four-tiered scheme and also according to the best collapsed scheme. The kappa index was used to assess the level of agreement between each pair of observers, and the Cox model was used for multivariate survival analyses. RESULTS: The mean interobserver kappa value was 0.22 (range, 0.09-0.36). The best concordance was obtained by collapsing to a system in which low-grade (Grade 1-2) disease was compared with high-grade (Grade 3-4) disease. Doing so improved the mean interobserver kappa value to 0.44 (range, 0.32-0.55). Fuhrman grade was an independent prognostic factor for all 3 pathologists (P = 0.01, P < 0.0001, and P = 0.004, respectively), and nuclear grade continued to have independent prognostic value after the optimal collapsing algorithm was performed (P = 0.004, P = 0.0003, and P = 0.005). CONCLUSIONS: Collapsing of the Fuhrman grading system to a two-tiered scheme led to an improvement in interobserver agreement while preserving the independent prognostic value of nuclear grade.     

Histological malignancy grading of oral squamous cell carcinomas

A modification of Jakobsson's criteria that determines the mode of cancer invasion (Yamamoto, 1982) has been reported to be useful in predicting the prognosis in patients with an oral squamous cell carcinoma. In this retrospective study, a five-factorial grading system of the histological malignancy (+ the differentiations, the nuclear polymorphism, the mitoses, and the cellular response) was evaluated in relation to clinical course of each patient. Result: 75 cases were classified into four grades from Grade 1, the lowest malignancy, to Grade 4, the highest malignancy. The percentage metastases was 10, 24, 54, and 75% for each grade, respectively. The percentage of survival was 75, 75, 35, and 25% for each grade, respectively. From these results, this grading system was seen to have a close-correlation with the clinical course of each patient.     

A correlative study of gliomas usingIn vivo bromodeoxyuridine labeling index and computer-aided malignancy grading

An in vivo bromodeoxyuridine (BrdU) labeling index (LI) was estimated in 43 cases of astrocytic tumors and mixed gliomas by one hour intra-operative intravenous infusion at a dose of 200 mg/m2 and correlated with (a) histological grading using a computer aided malignancy classifier TESTAST-268; and (b) histological typing using WHO classification. The lowest BrdU LI was seen in pilocytic and gemistocytic astrocytomas followed by astrocytomas, anaplastic astrocytomas and glioblastoma multiforme in that order. Mixed oligoastrocytomas followed the pattern of their astrocytic counterparts. Tumors of similar histological type showed different BrdU LI values especially amongst astrocytomas and glioblastomas. A statistically significant difference in the BrdU LI was also noted between the higher TESTAST grades of astrocytomas (T III and IV) versus the lower TESTAST grades (T II). Unlike earlier reports in literature, in the present study the category of BrdU LI of <1 contained no case of anaplastic astrocytoma or glioblastoma multiforme (TESTAST grades III and IV). Likewise, the category of BrdU LI >5 contained only anaplastic astrocytoma and glioblastoma multiforme (TESTAST grades III and IV). Maximum spread of cases was seen in the BrdU LI category of 1-5, not only in terms of histological types but also TESTAST grades. Thus there appeared to be a positive trend of increasing BrdU LI values both with histological types and increasing TESTAST grades. Further, an interesting observation was that by using a combination of TESTAST grades and BrdU LI, the histologically homogenous glioblastoma group could be further subdivided into 4 categories which showed a trend towards prognostic correlation. Thus, this study though preliminary with number of cases being small in some groups, highlights the possible usefulness of combined histological typing, TESTAST grading and in vivo BrdU LI for prognostication of gliomas especially glioblastoma multiforme.