The AgNOR quantity as prognostic parameter in choroidal melanomas: a standardised analysis.

In order to assess the prognostic significance of silver-stained nucleolar organizer region (AgNOR) proteins, a standardised analysis has been performed on 34 ocular globes with choroidal melanomas. On formalin-fixed paraffin-embedded sections, the visualisation and quantification of AgNORs were achieved according to the guidelines of the Committee on AgNOR Quantification (1995); statistical analysis was performed on the mean AgNOR area values (NORA). We have encountered significantly higher NORA values in nonspindle shaped elements, in tumours of larger dimensions as well as in those with worse clinical course; no correlations were achieved when the AgNOR quantity was compared with age, sex and amount of pigment. The comparison of Kaplan-Meier survival curves revealed that patients affected by melanomas with higher NORA values (>3.327 microm2), non-spindle cell histotype and increased size of tumour had a worse prognosis; finally, by Cox multivariate analysis, the AgNOR quantity appeared the only independent prognostic variable to predict the final outcome of patients.     

Neural network-based segmentation and classification system for automated grading of histologic sections of bladder carcinoma

OBJECTIVE: To develop an image analysis system for automated nuclear segmentation and classification of histologic bladder sections employing quantitative nuclear features. STUDY DESIGN: Ninety-two cases were classified into three classes by experienced pathologists according to the WHO grading system: 18 cases as grade 1, 45 as grade 2, and 29 as grade 3. Nuclear segmentation was performed by means of an artificial neural network (ANN)-based pixel classification algorithm, and each case was represented by 36 nuclei features. Automated grading of bladder tumor histologic sections was performed by an ANN classifier implemented in a two-stage hierarchic tree. RESULTS: On average, 95% of the nuclei were correctly detected. At the first stage of the hierarchic tree, classifier performance in discriminating between cases of grade 1 and 2 and cases of grade 3 was 89%. At the second stage, 79% of grade 1 cases were correctly distinguished from grade 2 cases. CONCLUSION: The proposed image analysis system provides the means to reduce subjectivity in grading bladder tumors and may contribute to more accurate diagnosis and prognosis since it relies on nuclear features, the value of which has been confirmed.     

Use of nuclear image cytometry, histopathological grading and DNA cytometry to make breast cancer prognosis more objective.

Feulgen-stained tissue sections of 187 invasive ductal carcinomas (94 with lymph node metastases; mean follow-up: 44 months) were studied using computer assisted image cytometry. Based on survival time, the prognostic significance of nuclear image analysis was compared with the results using conventional histopathological grading according to Bloom and Richardson, as well as with image cytometric DNA measurements. The histopathological grading has the disadvantage of poor interobserver reproducibility (71.1%). Despite statistically significant differences between the actuarial survival curves of grade 1 and grade 3 patients, the prognostic significance of the conventional grading method for individual patients seems to be low and the number of grade 2 cases (42.8%) is large. The quantitative morphological method for analyzing nuclear images gives more reproducible results. Compared to histopathological grading, the predictive values for good or poor prognosis are clearly higher and the number of cases with uncertain prognosis is significantly smaller (20.9%). DNA ploidy measurements also make it possible to distinguish statistically significant differences between favorable and unfavorable prognoses with respect to over-all survival time. However, the classification accuracy based on the best single parameter (DNA-histogram type according to Auer) is 70.2% compared with 78.9% for nuclear image analysis.     

Quantity of AgNORs in gastric endocrine carcinoid tumours as a potential prognostic tool

In order to assess if the quantity of silver-stained nucleolar organizer region (AgNOR) proteins represents a prognostic tool in gastric carcinoids, a standardised AgNOR analysis was performed on 24 samples collected from the pathology archives of the Universities of Messina and Parma; the samples were taken at surgery from 11 males and 13 females (mean age 55 yrs, age range 28-77 yrs); 13 cases were defined as Type I, 1 case as Type II and 10 cases as Type III; 16 cases showed a diameter <1 cm, 8 >1 cm. Only 6 tumours were deeply invasive, breaking through the muscularis propria or the subserosa. The proliferative status of carcinoids performed by Ki67 protein antibodies was available in 20/24 cases. The quantification of AgNORs was performed according to the guidelines of the Committee on AgNOR Quantification and the mean area (microm2) of AgNORs per nucleus (NORA) was determined by means of image analyser and specific software programs. The relationship between NORA values and Ki67 data was investigated by Spearman correlation test. The mean NORA value of all 24 gastric carcinoids was 1.279 microm2 (SD 0.404); values ranged from 0.734 to 2.142 microm2. A significantly higher (p < 0.001) mean NORA value (1.736 microm2; SD 0.283) was found in tumours larger than 1 cm, in comparison to the smaller neoplasms (1.051 microm2; SD 0.214); moreover, cases showing deep wall invasion exhibited a mean NORA value of 1.765 microm2 (SD 0.276), significantly higher (p < 0.001) than those with superficial growth (1.118 microm2; SD 0.296). Finally, a similar highly significant difference was seen between type III carcinoids (1.615 microm2; SD 0.375) and type I-II (1.040 microm2; SD 0.208). A linear relationship between Ki67 and corresponding NORA values was obtained by the Spearman correlation test (p = 0.001). No other significant correlations were found between mean NORA values and other clinico-pathological parameters. The AgNOR method seems to be an additional tool potentially able to predict the prognosis of this kind of endocrine tumour, facilitating the identification of fast-growing tumours and being able to directly correlate with the size, deep invasion of gastric wall and tumour type, generally considered as the best prognostic indicators.     

Cell kinetics analysis in stage I endometrial carcinoma as determined by image cytometry and immunohistochemistry. Correlation with clinicopathologic characteristics

OBJECTIVE: To test the significance of various proliferative indices in endometrial carcinoma (EC) since previous investigations failed to yield consistent results that would establish them as factors of clinical importance. STUDY DESIGN: Seventy patients with EC were evaluated for various proliferative indices (mitotic index, Ki-67 index, argyrophilic nucleolar organizer (AgNOR) number and area per nucleus, and p53 protein expression) in relation to image cytometry (nuclear area, diameter and roundness) and standard clinicopathologic features (age, histologic type and grade, and depth of invasion). We also tested the proliferation index (PI), which combines the Ki-67 index and AgNOR area in Ki-67-positive nuclei. Slides from each case were double stained for Ki-67 antigen and AgNOR proteins for this purpose. RESULTS: Mitotic counts were significantly higher in papillary-serous (vs. endometrioid) tumors (P = .0001), high grade (vs. low grade) tumors (P = .0001), deeply invasive (P = .017) and p53-positive tumors (P = .017). AgNOR counts correlated only with age (higher in older women, P = .002), while the PI correlated with mitotic counts (P = 0.28) and marginally with depth of invasion (P = .06). Morphometric variables were associated just with histologic type and grade. p53 Protein was expressed exclusively in invasive tumors and was related strongly to histologic type (P = .0029) and grade (P = .0001). CONCLUSION: Our data reestablish the value of classic histopathologic features (mitotic index, histologic type and grade) as the most important tools for EC evaluation. In addition, we suggest that p53 immunostaining may be used for predicting aggressive behavior in EC.     

Prognostic significance of standardized AgNOR analysis and Ki-67 immunostaining in gastrointestinal stromal tumors

OBJECTIVE: To evaluate the prognostic utility of argyrophilic nucleolar organizer region (AgNOR) protein parameters and Ki-67-immunostained growth fraction (Ki-67 labelling index) and to correlate AgNORs with Ki-67 LI and the main clinicopathologic parameters in gastrointestinal stromal tumors (GISTs). STUDY DESIGN: On 55 patients with surgically excised GISTs, visualization and quantification of AgNORs were performed as specified in the guidelines of the Committee on AgNOR Quantification. RESULTS: AgNOR protein area (NORA) > or = 5.28 microns 2 was statistically associated with mitotic rate > or = 5 x 10 high-power fields (hpfs) (P < .001) and presence of necrosis (P < .001); Ki-67 LI > or = 9.69% was significantly associated with mitotic rate > or = 5 x 10 hpfs (P < .001), size > or = 5 cm (P = .033) and presence of necrosis (P < .001). Ki-67 LI and NORA strongly correlated. Preliminary Kaplan-Meier survival analysis showed that an increased value of NORA, Ki-67 LI, mitotic rate, tumor size and presence of necrosis had a negative influence on patient survival. Multivariate regression analysis showed that only NORA and Ki-67 LI were independent parameters in predicting the clinical outcome for patients with GISTs. Mitotic rate and necrosis remained as independent prognostic factors when NORA and Ki-67 LI were not allowed to enter in models. CONCLUSION: AgNOR protein quantity, as determined by image cytometry, and Ki-67 immunostaining seem to represent reliable predictive parameters in GISTs and are independent of mitotic rate, tumor dimension and necrosis.     

Interpreting microbiopsies in cervical smears. A cytohistologic approach

OBJECTIVE: To assess interobserver variation in the diagnosis of thick tissue specimens (microbiopsies) in cytology smears and histologic sections taken from them, to evaluate the applicability of MIB-1 in histologic sections from microbiopsies and to evaluate whether processing microbiopsies in inconclusive smears has additional diagnostic value. STUDY DESIGN: Cytologic smears were selected in which there were diagnostic disagreements between pathologists and cytologists and microbiopsies were present. Interobserver variation among three pathologists and three cytologists in the diagnosis of these microbiopsies was investigated. The smears were processed for histologic sections, and interobserver variation between pathologist diagnoses were analyzed. An additional histologic slide stained for MIB-1 was used for consensus diagnosis. The consensus diagnosis was compared with available follow-up and its sensitivity and specificity determined. The value of applying the microbiopsy technique in slides diagnosed as inadequate or atypical squamous cells of undetermined significance (ASCUS) was analysed. RESULTS: From a series of 62,334 cervical smears, 49 with microbiopsies were selected. It was possible to derive histologic slides from 38 cases. Interobserver variability in the diagnosis of microbiopsies and histologic sections from them was moderate--kappa = .44 (SE = .06) and kappa = .44 (SE = .09), respectively. In the consensus meeting for all cases, a conclusive diagnosis was reached. The Pearson correlation coefficient between the consensus diagnosis and MIB-1 staining was r = .62. The sensitivity of the consensus diagnosis for the follow-up diagnosis was 71% and the specificity 60%. Diagnosis on approximately 50% of slides diagnosed as inadequate or ASCUS could be made. CONCLUSION: The histotechnical workup of microbiopsies is not difficult; however, their diagnosis can be a problem. Adequate diagnostic criteria are not available. Aided by MIB-1 staining, histologic sections from microbiopsies can be diagnosed, and the diagnoses correlated with follow-up in most cases. Processing of microbiopsies in smears with an inconclusive cytologic diagnosis or a diagnosis of ASCUS allowed correct diagnosis in 50% of cases in this study.     

AgNOR analysis of atypical ductal hyperplasia and intraductal carcinoma of the breast

OBJECTIVE: To determine the diagnostic and prognostic value of argyrophilic nucleolar organizer regions (AgNORs) in atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS) and microinvasive ductal carcinoma (MDCA) of the breast. STUDY DESIGN: Image analysis of histologic sections from biopsies of 46 breast ADH and DCIS and 18 cases of MDCA. Determination of morphometric features of cell nuclei and nucleolar organizer regions by using AMBA software system. Data were compared with the estrogen receptor/progesterone receptor (ER/PR) content as well as with the growth fraction, determined immunohistochemically. RESULTS: AgNOR number and total AgNOR area increased from ADH to DCIS. The highest values were recorded in cases of DCIS with microinvasion. Differences between ADH and intraductal or microinvasive ductal carcinoma were statistically significant. Within the group of intraductal carcinomas, the lowest values were measured in the solid type and highest values in the comedo type. A correlation was found between AgNOR features and growth fraction but not between these features and ER/PR status. CONCLUSION: Selected AgNOR features are relevant for differentiation between ADH and DCIS as well as between low and high grade DCIS and microinvasive ductal carcinoma. Therefore, objective and reproducible data obtained by AgNOR analysis may allow better evaluation of the prognostic significance of these lesions.     

Further testing of morphometric grading in T(A,1) urothelial carcinomas of the urinary bladder and the additional value of p53 immunoquantitation

OBJECTIVE: To analyze the value for grading of a previously developed quantitative morphometric/cytometric multivariate grading model (consisting of the mean nuclear area of the 10 largest nuclei (MNA-10, mitotic activity index = MAI and Ki-67 area% = Ki-67) in two new independent test sets of urothelial carcinomas (UCs) of the urinary bladder and to evaluate the additional value of p53 area% (p53) in this model. STUDY DESIGN: Ki-67 immunoquantitation, morphometric MAI and MNA-10 assessments using a previously described, strict protocol and matching of the resulting morphometric grade with subjective grade in two test sets of 154 T(A,1) UCs of the bladder (consensus grade between two independent observers). Further testing of this morphometric grading model was performed in 57 cases that lacked initial interobserver agreement on grade. Single and multivariate analysis of all features (including p53) was performed. RESULTS: With the previously developed morphometric/cytometric grading model, 93% (grade 1 vs. 2) and 91% (grade 2 vs. 3) of the consensus cases were correctly classified. These percentages were very similar to previous results, suggesting that the model is robust. Of the 57 cases that lacked initial interobserver agreement on grade, 53/57 (93%) were classified unambiguously as grade 1, 2 or 3 with the quantitative morphometric/ cytometric grading model. In the exploratory analysis, p53 was significant but with more overlap than the other features had. In multivariate analysis p53 did not improve the overall classification result of the original morphometric/cytometric model. CONCLUSION: The value of MNA-10, MAI and Ki-67 for grading in T(A,1) urothelial carcinomas of the urinary bladder was confirmed. p53 Did not improve overall grading classification of this combination.     

Recent trends in gleason grading of prostate cancer. II. Prognosis, reproducibility and reporting

Gleason grading of prostate cancer is the most important histopathologic predictor of prognosis. In recent years, a number of changes have been made in how Gleason grading is performed and reported. A consensus conference was organized in 2005 by the International Society of Urological Pathology for the purpose of standardizing both the perception of histologic patterns and how the grade information is compiled and reported. The recommendations regarding reporting are summarized and discussed in this review. The prognostic importance of the Gleason score, its reproducibility and its role in preoperative assessment are also discussed.     

A comparative study in morphometric grading of transitional cell carcinoma of the urinary bladder

To overcome the considerable observer inconsistency in the histologic grading of transitional cell carcinomas, the value of four different morphometric grading methods was investigated in 61 tumors of the bladder. Only two methods showed satisfactory reproducibility. Both methods, one based on random nuclear sampling and the other on selective nuclear sampling, showed an increase in the mean and standard deviation of the nuclear area with higher tumor grades (P less than .00001). Morphometric classification of the learning set (44 cases) was in agreement with the unequivocally assessed histologic grade in 35 cases (79.5%) using random sampling and in 38 cases (86.4%) using selective sampling. By reducing the grading classes to "low" (grades 1 and 2) and "high" (grade 3) and by introducing a classification probability threshold (0.80), an accurate morphometric classification was achieved in 38 cases (86.4%) using random sampling and in 41 cases (93.2%) using selective sampling. Of the 17 cases with histologic grading discrepancies, all 10 low-grade tumors (with discrepancies of grade 1 versus grade 2) were correctly classified as low-grade carcinomas by both of the morphometric methods; in the remaining 7 cases, with low-versus-high discrepancies (grade 2 versus grade 3), the selective method yielded better correlation with the tumor stage and clinical follow-up. It is concluded that morphometric classification is an acceptable alternative for histologic grading by pathologists, provided that the reproducibility of the method is confirmed. Although both random and selective sampling yielded satisfactory classifications, the selective method gave more reliable results as confirmed by the clinical behavior.     

Is there any potential link among caspase-8, p-p38 MAPK and bcl-2 in clear cell renal cell carcinomas? A comparative immunohistochemical analysis with clinical connotations

Background

Management of endometrial precancerous lesions has been of much debate due to inconsistencies in their classification, natural history and histologic diagnosis. Endometrial hyperplasia constitutes a wide range of histomorphologic features associated with high intra and interobserver diagnostic variability. Although traditional microscopic diagnosis is by far the most applicable method and the gold standard for histomorphologic diagnosis, digitized image analysis has been used as a powerful adjunct to maximize the histologic data retrieval and to add some detailed objective criteria for correct diagnosis in difficult cases.

Methods

A series of 100 endometrial curettage specimens with diagnosis of endometrial hyperplasia or well differentiated adenocarcinoma were blindly reviewed by 5 pathologists; their intra and interobserver reproducibility determined and further compared to the objective morphometric data i.e. D-score and volume percent of stroma (VPS).

Results

The results were assessed using the weighted kappa statistics. Mean intraobserver kappa value was 0.8690 (99.44% agreement). Mean interobserver kappa values by diagnostic category were: simple hyperplasia without atypia: 0.7441; complex hyperplasia without atypia: 0.3379; atypical hyperplasia: 0.3473, and well-differentiated endometrioid carcinoma: 0.6428; with a kappa value of 0.5372 for all cases combined. Interobserver agreement was in substantial rate for simple hyperplasia (SH) and well differentiated adenocarcinoma (WDA) but was in fair limit for complex hyperplasia (CH) and atypical hyperplasia (AH). Intraobserver agreement was almost perfect. The specimens were divided in two groups according to the computerized morphometric analysis: Endometrial Hyperplasia (EH) ( D Score ≥ 1 or VPS ≥ 55%) and Endometrial Intraepithelial Neoplasia (EIN) (D-Score < 1 or VPS < 55%). Morphometric findings were closely compatible with routine WHO classification made by one expert pathologist; however; diagnosis of (CH) and (AH) made by other pathologists were not concordant with morphometric data.

Conclusion

It may be necessary to make some revisions in WHO classification for endometrial hyperplasia and precancerous lesions.     

Pathologic significance of proliferative activity and oncoprotein expression in astrocytic tumors

OBJECTIVE: To clarify the clinicopathologic significance of immunohistochemistry for proliferative activity and oncoprotein expression in astrocytic tumors. STUDY DESIGN: Ninety-seven cases of brain astrocytic tumors with histologic grading and follow-up data were investigated with immunohistochemistry and image analyzer to detect the expression of proliferating cell nuclear antigen (PCNA), silver-binding nucleolar organizer regions (AgNORs) and several oncoproteins. RESULTS: PCNA was significantly related to AgNORs, grading and prognosis of astrocytomas. The frequency of mutant p53 protein expression was higher in grade 2-4 astrocytomas than in grade 1. Epidermal growth factor (EGF) (37.1%), EGF receptor (83.5%) and p21ras (42.3%) expression levels were related to neither the grade nor prognosis of the tumors. The positive ratios of p53 antibodies were higher in grades 2-4 than in grade 1, and the intensities correlated with PCNA but not with prognosis. CONCLUSION: Aberrations of c-erbB-2, p21ras, EGF and EGF receptor might be early events in the initiation and progression of astrocytomas, whereas p53 overexpression is involved in all the stages. Immunohistochemical detection had no prognostic value. PCNA could be important to the evaluation of astrocytoma malignancy.     

MIB-1 counting methods in meningiomas and agreement among pathologists

OBJECTIVE: To evaluate the correlation of MIB-1 labeling index (LI) obtained by 2 counting methods with histologic grade and investigate interobserver variability between these methods. STUDY DESIGN: A total of 65 meningiomas were analyzed for proliferation with 2 counting methods by 2 pathologists using MIB-1 antibody. In the first method, the most densely staining areas were counted (HL method). In the second method, randomly selected areas were counted (RS method). RESULTS: MIB-1 values correlated well with histologic grade in both methods. As expected, the tumors with recurrence had significantly higher LIs than the nonrecurrent tumors in each method. However, there was a statistically significant difference in the mean MIB-1 values of between the HL and RS methods. When MIB-1 LI was compared between 2 pathologists, perfect agreement in the HL method and substantial agreement in the RS method were achieved. CONCLUSION: Our results showed that values of MIB LIs differ with different counting methods. Nonetheless, both methods showed good correlation with World Health Organization grades. Therefore standardization of 1 counting method is of great importance for determining a reliable and specific cutoff value in assessing the risk of recurrence in meningiomas.     

Actinic keratosis associated with squamous and basal cell carcinomas: an evaluation of neoplastic progression by a standardized AgNOR analysis

In an attempt to investigate the neoplastic progression in different stages of actinic keratosis (AK), a standardized AgNOR analysis was performed in 94 cases of AK, 35 of which were associated with squamous cell carcinoma (SCC) or basal cell carcinoma (BCC), and in 31 cases of SCC and 22 cases of BCC. The cases were subdivided into low- and high-AgNOR-expressing (AgNOR status) AK by using the mean area of AgNORs per cell (NORA) value (3.996 micro(2)) as the cut-off. In AK samples, a progressive increase of the mean NORA value from Stage I to Stage IV was encountered. In addition, a significantly higher mean NORA value was found in the AK cases associated with SCC, in comparison to those without SCC; by contrast, no significant differences in the mean NORA value were noted between AK cases with or without BCC. A highly significant association between a high AgNOR quantity and the coexistence of SCC was encountered in AK; no association was appreciable between the AgNOR quantity and the co-occurrence of BCC. Moreover, when the co-existence of SCC in AK was considered as the reference point, the AK cases associated with SCC mostly (95.5%) presented a high AgNOR quantity (high sensitivity), but only 57.6% of cases without SCC displayed a low AgNOR quantity (low specificity). Additionally, our data document that the standardised AgNOR analysis represents a strong negative predictor for the association between SCC and AK. Indeed, a low AgNOR quantity mostly is associated with AK cases without SCC.     

Grading of ductal breast carcinoma by cytomorphology and image morphometry with histologic correlation

OBJECTIVE: To investigate the relevance of image analysis for grading breast carcinoma. STUDY DESIGN: Twenty-five ductal breast carcinoma cases were chosen randomly from routine fine needle aspiration clinics. The results of cytomorphologic grading and image morphometry were correlated with those of histologic grading. The five image morphometric parameters studied were nuclear diameter, nuclear area, nuclear roundness, nuclear perimeter and grey level to compare with chromatin texture. RESULTS: Cytologic grading alone had a high correlation with histologic grading. The lowest correlation was found in grade 2 tumors. When cytologic grading was supplemented with image morphometric parameters, the correlation was higher than that of cytologic grading alone. CONCLUSION: Cytologic grading has a high correlation with histologic grading. The correlation improves further on supplementation with image morphometric parameters.     

Grading ovarian tumors. Evaluation of decision making by different pathologists

Although grading of ovarian tumors is widely performed, the criteria for each grade are not well defined; as a result, pathologists tend to establish their own criteria without, however, assessing the actual predictive value of the criteria. In order to investigate this relationship, four gynecologic pathologists independently reviewed and carefully graded as benign, borderline or malignant (grade I, II or III) 40 "common" epithelial tumors of the ovary, without reference to clinical, prognostic or other findings. Intermediate grades were allowed. Subsequently, a subjective grading form was completed for each case; the form contained questions regarding the histologic and cytologic features. The sets of features with the biggest correlation with the tumor grades differed among the pathologists. This may indicate that the observers use different features in their grading processes. Moreover, the pathologist with the highest number (five) of significant microscopic features in the multivariate model had the lowest coefficient of correlation between his tumor grade and his feature set. The correlation coefficients for the other pathologists were quite similar, although the features used (no more than two or three) varied. The participants in the study felt that the methodologic approach had an educational value for them. Further investigations are required to evaluate whether the differences in the underlying decision making process also result in frank disagreement in ovarian tumor grading.     

Karyometric features of low and high grade glial tumors as compared with their MRI appearance

OBJECTIVE: To compare the results of a magnetic resonance imaging (MRI) grading designed to identify low and high grade gliomas with karyometry used as a tool to grade primary brain tumors. STUDY DESIGN: A consecutive series of 23 primary brain tumors was selected for this study. The neuroradiologist, not knowing the histologic diagnoses, divided the cases into low and high grade categories on the basis of the following 7 features: border sharpness, heterogeneity without contrast, cavitation, contrast enhancement, hypervascularity, mass effect and perifocal T2 hyperintensity. To each feature was given a numerical value, ranging from 1 to 3. All the cases were reviewed and classified by the same pathologist, blinded to the MRI diagnosis. Two hundred nuclei per case were recorded, and 93 karyometric features related to nuclear area, total optical density and chromatin distribution were analyzed for each nucleus. Statistical analysis included discriminant analysis, Kruskal-Wallis test, nonsupervised learning algorithm P-index and Beale statistic. RESULTS: Ten cases were classified as low grade on the basis of their MRI features. The corresponding histopathologic diagnoses were: grade 2 astrocytoma in 2 cases and grade 2 oligodendroglioma in 8 cases. An MRI diagnosis of high grade tumor was made in 13 cases. In 10 cases it was confirmed by the histopathologic diagnosis (3 grade 3 astrocytomas, 1 grade 3 oligodendroglioma and 6 glioblastomas). In the remaining 3 cases the histologic examination revealed a low grade tumor, 1 grade 2 astrocytoma and 2 grade 2 oligodendrogliomas. For the purposes of the karyometric analysis the cases were allocated to the low or high grade category according to their histologic diagnosis (13 cases low grade and 10 cases high grade). Nuclei from low and high grade tumors showed clearly different karyometric characteristics. The oligodendroglioma nuclei had abnormality values close to the low grade standard, while the astrocytoma nuclei were a highly dispersed group with characteristics indicative of a higher degree of nuclear abnormality than the oligodendroglioma nuclei. The results of karyometric analysis showed that grade 2 tumors, corresponding to the low grade group, form a rather distinct category from grade 3 and 4 tumors belonging to the high grade group. CONCLUSION: The results of MRI grading based on a series of features that are routinely assessed by the neuroradiologist to reach a final diagnosis correlate highly with the histopathologic diagnosis. Karyometry can be a useful adjunct to histologic grading.     

Prognostic significance of nuclear morphometry in superficial bladder cancer

OBJECTIVE: To evaluate the significance of nuclear morphometry in predicting the clinical course in superficial (pTa and pT1) bladder cancer. STUDY DESIGN: The study included 73 patients with superficial transitional cell carcinoma of the bladder who were followed for a median of 21 months (range, 1-90). Nuclear morphometry was performed by a computer-assisted image analyzer system on hematoxylineosin-stained histologic sections and characterized by five nuclear variables: area, perimeter, major and minor diameter, and form factor. Patient charts and microscopic slides were reviewed to record tumor stage, grade and size. Tumor proliferative activity was assessed by immunohistochemical staining with Ki-67 antibody. RESULTS: None of the morphometric variables showed a significant relation to tumor progression and recurrence. Higher values of mean nuclear area, perimeter, and major and minor diameter were significantly related to higher grade and proliferative activity. Mean nuclear area and minor diameter were associated with advanced stage. Of established prognostic factors, only histologic grade was significant in predicting progression. CONCLUSION: The results suggest that nuclear morphometry may be valuable in determining proliferative activity and may be well correlated with histologic grade in superficial bladder cancer. However, like many other potential prognostic factors, it seems to be unreliable in predicting clinical behavior.