Nuclear Grading System Research Articles

Does the Fuhrman or World Health Organization/International Society of Urological Pathology Grading System Apply to the Xp11.2 Translocation Renal Cell Carcinoma?: A 10-Year Single-Center Study

The Fuhrman and World Health Organization/International Society of Urological Pathology (WHO/ISUP) grading systems are widely used to predict survival for patients with conventional renal cell carcinoma. To determine the validity of nuclear grading systems (both the Fuhrman and the WHO/ISUP) and the individual components of the Fuhrman grading system in predicting the prognosis of Xp11.2 translocation renal cell carcinoma (Xp11.2 tRCC), we identified and followed up 47 patients with Xp11.2 tRCC in our center from January 2007 to June 2017. The Fuhrman and WHO/ISUP grading was reassigned by two pathologists. Nuclear size and shape were determined for each case based on the greatest degree of nuclear pleomorphism using image analysis software. Univariate and multivariate analyses were performed to evaluate the capacity of the grading systems and nuclear parameters to predict overall survival and progression-free survival. On univariate Cox regression analysis, the parameters of nuclear size were associated significantly with overall survival and progression-free survival, whereas the grading systems and the parameters of nuclear shape failed to reach a significant correlation. On multivariate analysis, however, none of the parameters was associated independently with survival. Our findings indicate that neither the Fuhrman nor the WHO/ISUP grading system is applicable to Xp11.2 tRCC. The assessment of nuclear size instead may be novel outcome predictors for patients with Xp11.2 tRCC.

Relationships of nuclear, architectural and International Federation of Gynecology and Obstetrics grading systems in endometrial cancer.

Objective:To examine correlations among nuclear, architectural, and International Federation of Gynecology and Obstetrics (FIGO) grading systems, and their relationships with lymph node (LN) involvement in endometrioid endometrial cancer.Material and Methods:Histopathology slides of 135 consecutive patients were reviewed with respect to tumor grade and LN metastasis. Notable nuclear atypia was defined as grade 3 nuclei. FIGO grade was established by raising the architectural grade (AG) by one grade when the tumor was composed of cells with nuclear grade (NG) 3. Correlations between the grading systems were analyzed using Spearman’s rank correlation coefficients, and relationships of grading systems with LN involvement were assessed using logistic regression analysis.Results:Correlation analysis revealed a significant and strongly positive relationship between FIGO and architectural grading systems (r=0.885, p=0.001); however, correlations of nuclear grading with the architectural (r=0.535, p=0.165) and FIGO grading systems (r=0.589, p=0.082) were moderate and statistically non-significant. Twenty-five (18.5%) patients had LN metastasis. LN involvement rates differed significantly between tumors with AG 1 and those with AG 2, and tumors with FIGO grade 1 and those with FIGO grade 2. In contrast, although the difference in LN involvement rates failed to reach statistical significance between tumors with NG 1 and those with NG 2, it was significant between NG 2 and NG 3 (p=0.042). Although all three grading systems were associated with LN involvement in univariate analyses, an independent relationship could not be established after adjustment for other confounders in multivariate analysis.Conclusion:Nuclear grading is significantly correlated with neither architectural nor FIGO grading systems. The differences in LN involvement rates in the nuclear grading system reach significance only in the setting of tumor cells with NG 3; however, none of the grading systems was an independent predictor of LN involvement.

Nuclear grade and necrosis predict prognosis in malignant epithelioid pleural mesothelioma: a multi-institutional study.

A recently described nuclear grading system predicted survival in patients with epithelioid malignant pleural mesothelioma. The current study was undertaken to validate the grading system and to identify additional prognostic factors. We analyzed cases of epithelioid malignant pleural mesothelioma from 17 institutions across the globe from 1998 to 2014. Nuclear grade was computed combining nuclear atypia and mitotic count into a grade of I-III using the published system. Nuclear grade was assessed by one pathologist for three institutions, the remaining were scored independently. The presence or absence of necrosis and predominant growth pattern were also evaluated. Two additional scoring systems were evaluated, one combining nuclear grade and necrosis and the other mitotic count and necrosis. Median overall survival was the primary endpoint. A total of 776 cases were identified including 301 (39%) nuclear grade I tumors, 354 (45%) grade II tumors and 121 (16%) grade III tumors. The overall survival was 16 months, and correlated independently with age (P=0.006), sex (0.015), necrosis (0.030), mitotic count (0.001), nuclear atypia (0.009), nuclear grade (<0.0001), and mitosis and necrosis score (<0.0001). The addition of necrosis to nuclear grade further stratified overall survival, allowing classification of epithelioid malignant pleural mesothelioma into four distinct prognostic groups: nuclear grade I tumors without necrosis (29 months), nuclear grade I tumors with necrosis and grade II tumors without necrosis (16 months), nuclear grade II tumors with necrosis (10 months) and nuclear grade III tumors (8 months). The mitosis-necrosis score stratified patients by survival, but not as well as the combination of necrosis and nuclear grade. This study confirms that nuclear grade predicts survival in epithelioid malignant pleural mesothelioma, identifies necrosis as factor that further stratifies overall survival, and validates the grading system across multiple institutions and among both biopsy and resection specimens. An alternative scoring system, the mitosis-necrosis score is also proposed.

Nuclear pleomorphism-based cytopathological grading in human oral neoplasm

Objective ― The objective of the present study is record the nuclear pleomorphism in various stages of oral carcinogenesis and to analyse their utility in cytopathological grading for early detection of human oral cancer Material and Methods ― In this hospital based case-control study, oral site, age-group and sex-matched 272 subjects (136 cases and 136 normal healthy individuals) were included. Scraped exfoliated cytosmears were collected from the affected oral site of the subjects and smearing was done in the pre-cleaned-coded glass-slides. Two such slides were prepared from each subject. The cytosmears were immediately fixed in aceto-alcohol (1 part of glacial acetic acid: 3 part of absolute ethyl alcohol) fixative. One set of the slide was stained with Papanicolaou’s stain and the other set was counter-stained with Giemsa’s Solution for cytopathological analysis. Test of proportion (z-test) was followed and the critical ratio (z-value) was calculated for the test of significance. Results ― Nuclear pleomorphism in the form of round, oval, spindle, elongated fiber as well as irregular shapes were mostly observed in oral squamous cells during different stages of carcinogenesis. Appearance of such nuclear pleomorphism in human oral neoplasm may be considered as a sign of cellular alternation in general and index of oral carcinogenesis in particular. In the present study, the frank malignant cases mimic to be either premalignant lesions or benign/carcinoma in situ were detected on the basis of nuclear pleomorphism-based cytopathological grading and so an increasing trend was observed from precancerous lesions to malignant cases due to shifting of numbers. Diagnostic tests also indicated that the Sensitivity was calculated to be 83.5%, Specificity was 100%, positive predictive value (PPV) was 100%, negative predictive value (NPV) was 30% and the accuracy was found to be 84.6%. Therefore, the nuclear pleomorphism-based cytopathological grading system makes itself an ideal screening test for early detection of human oral cancer. Conclusion ― Pattern of nuclear pleomorphism corresponding to various cytological atypias is a common feature observed during different stages of oral carcinogenesis and thus, it has a practical implication in grading and early detection of oral cancer.

Validation of the Nuclear Cataract Grading System BCN 10

Purpose: To evaluate a new nuclear cataract grading system which is intended as a surgical guidance system to predict lens hardness before cataract surgery. Methods: The new BCN 10 grading system consists of frontal and cross-sectional slit-lamp images of human eye lenses, ranging from a completely transparent lens nucleus to a totally black nuclear cataract. Validation was done with 9 observers for 110 cases. Two modalities were applied, and observers were asked to use only whole digits and then half digits for grading. Results: Repeatability with regard to test-retest differences showed a mean limit of agreement of 1.70 for whole digits and 1.32 for half digits. The absolute test-retest difference was close to zero for low as well high degrees of cataracts. Reliability for the entire group of 9 observers yielded an intraclass correlation coefficient which was within the same confidence interval, i.e., 0.991-0.995, for whole digits and half digits. Conclusions: BCN 10 grading repeatability was not affected by the severity of the cataract. It showed very good repeatability. Repeatability was significantly higher when the observers used half digits compared to whole digits. Reliability was found to be very good as well, independently of the use of whole or half digits.

The Presence and Thickness of Pseudocapsule after Partial Nephrectomy in Renal Cell Carcinoma

Ya z›fl ma Ad re si/Ad dress for Cor res pon den ce: Dr. Fehmi Narter, Kartal Dr. Lutfi Kirdar Egitim ve Arastirma Hastanesi, Uroloji Klinigi, Istanbul, Turkiye E-mail: fehminarter66@gmail.com Ge lis Ta ri hi/Re cei ved: 20.06.2016 Ka bul Ta ri hi/Ac cep ted: 05.09.2016 © Uroonkoloji Bulteni, Ga le nos Ya yi ne vi ta ra fin dan ba sil mis tir. Bu makale “Creative Commons Alinti-Gayriticari-Turetilemez 4.0 Uluslararasi Lisansi (CC BY-NC 4.0)” ile lisanslanmistir. Objective: In this study, we aimed to evaluate the presence and thickness of pseudocapsule after partial nephrectomy in renal cell carcinoma (RCC) cases. Materials and Methods: A total of 100 patients who were admitted to our clinic and diagnosed with RCC were included in the study. Histopathological specimens of the patients who underwent partial nephrectomy were re-evaluated retrospectively. Results: The histopathological results revealed pseudocapsule in 87 cases (87%, median thickness: 0.708 mm). Pseudocapsule median thickness was noted respectively 0.483, 0.691, 0.737, 0.954 mm in Fuhrman Grade 0, 1, 2, 3/4 groups (p<0.05). Conclusion: In this study, a statistical significance was found between nuclear grading system and the thickness of pseudocapsule in RCC. We believe that it may be a prognostic factor for RCC in the future.

Nuclear grade plus proliferation grading system for invasive ductal carcinoma of the breast: validation in a tertiary referral hospital cohort.

For patients with invasive breast cancer, management decisions are informed by tumor grade according to the Nottingham Grading System (NGS), either on its own or as part of the Nottingham Prognostic Index (NPI). A system retaining the nuclear grade element but substituting the two subjective components, mitosis count and tubule formation, of the NGS with a proliferation index based on Ki-67 (MIB-1) has been proposed (nuclear grade plus proliferation [N+P] grading). We validated the prognostic value of this grading system on a population of 322 women. N+P grading resulted in more grade I tumors (47.9% vs 4.5%) and fewer grade II (32% vs 51.5%) and grade III (20.1% vs 44%) tumors compared with NGS. The NPI calculated based on N+P grade had a similar association with survival (P < .001; odds ratio, 1.729) as the NPI calculated on the basis of the NGS grade (P < .001; odds ratio, 1.668). The N+P system seems equivalent to the NGS system.

Evaluation of major histocompatibility complex class I expression in clear cell renal cell carcinoma as a prognostic tool.

469 Background: After nephrectomy for clear cell renal cell carcinoma (ccRCC) approximately one-third of patients develop metastases. Yet, with currently used prognostic tools such as the TNM staging and the Fuhrman nuclear grade (FNG) system, it is difficult to accurately assess prognosis for each patient. Here, we evaluated Major Histocompatibility Complex Class I (MHCI) expression as a potential prognostic immune marker in ccRCC. Methods: Fifty-five post-nephrectomy patients that presented with localized ccRCC were included. All patients had four or more years of follow up. MHCI was stained in the tumor sections via immunohistochemistry. Then, via an automated image analysis algorithm MHCI expression was quantitated with the Positivity score, the ratio of positively stained pixels over the total number of pixels. Results: Mean MHCI positivity score of the cohort was 0.75 (SE= ±0.20). At the end of the follow-up period, the patients who were alive had higher MHCI expression (0.80 positivity score; SE ±0.14) than those who died of disease (0.62 positivity score; SE= ±0.16; t test, p&lt;0.0001). MHCI positivity scores above the mean were associated with increased cancer specific survival (Mantel-Cox, p=0.0021). MHCI expression was higher among patients with no recurrence (0.80; SE= ±0.16) compared to those that recurred during the study period (0.70; SE= ±0.22; t test, p=0.017); and time-to-recurrence was longer in patients with above mean MHCI positivity scores (Mantel-Cox, p=0.017). Patients who were alive with recurrence had increased MHCI expression (0.81; SE= ±0.10) compared to those who succumbed to disease recurrence (0.62; SE= ±0.25; t-test, p=0.0009). No correlation was detected between FNG and tumor expression of MHCI (ANOVA, p=0.655, F=0.423) or between stage at presentation and MHCI tumor expression (ANOVA, p=0.734, F=0.311). Conclusions: With an automated high-throughput image analysis, this cohort shows that increased MHCI expression in ccRCC is associated with improved prognosis after curative nephrectomy.

The Fuhrman grading system has no prognostic value in patients with nonsarcomatoid chromophobe renal cell carcinoma.

The prognostic value of the Fuhrman nuclear grading system has been questioned for chromophobe renal cell carcinoma (chRCC) because this subtype frequently displays nuclear and nucleolar pleomorphism. The present study reevaluates this grading system in a series of patients with nonsarcomatoid chRCC. We identified 176 patients (3.6%) with nonsarcomatoid chRCC in a total of 4897 patients who underwent surgery for renal cell carcinoma at 5 centers in Germany between 1990 and 2010. The mean follow-up was 51.1 months. The 3 groups (G1 versus G2 versus G3/4) were comparable in terms of age, sex, tumor diameter, and lymph node metastasis. They only differed significantly in tumor stage (P = .01) and the incidence of synchronous visceral metastasis (P = .04). The 5-year cancer-specific survival rates were 84.4% for G1 (n = 32), 84.3% for G2 (n = 108), and 74.1% for G3/4 tumors (n = 33) (P = .58). Accordingly, multivariate analysis including age, sex, tumor stage, and metastatic disease did not identify Fuhrman grading as an independent predictor of cancer-specific survival in patients with chRCC (P = .4). We were able to demonstrate in a large multicenter cohort that the Fuhrman grading system does not qualify as a prognostic tool in patients with chRCC.

935 Reevaluation of prognostic value of Fuhrman nuclear grading system in renal cell carcinoma

935 Reevaluation of prognostic value of Fuhrman nuclear grading system in renal cell carcinoma

Role of Cytological Grading in Breast Cancer Prognosis and its Histo-pathological Correlation

Objective: Breast carcinoma is the most common cause of death in females globally, which should be detected early and treated promptly. This study aims at establishing Fine Needle Aspiration Cytology (FNAC) as an individual parameter in diagnosing & grading carcinoma breast and to correlate cytological grading with the histopathological grading done post-operatively. Materials & methods: We present here, a series of 44 cases, clinically suspected of carcinoma breast, presenting with hard, painful breast lump with or without axillary lymphadenopathy, sent for cytological examination to our department. Aspiration was done, following using 20G needle and smears were stained with Haematoxyline & Eosin, Papanicolau, and May-Grunwald-Giemsa. Results: The stained smear showed highly pleomorphic ductal cells in large number forming dyscohesive sheets & also lying singly. Cells had nuclei with hyperchromasia, irregular nuclear margin, open chromatin & conspicuous nucleoli. The diagnosis of carcinoma breast was offered and cytological grading was done according to Robinson's nuclear grading system in all cases. Urgent biopsy was also however, recommended. The mastectomy specimens of these patients, when grossed & stained with Haematoxyline & Eosin proved the cytological diagnosis conclusive and cytological grading of the tumors concordant in 80% of the cases. Higher cytological grades showed increased nodal metastasis. Conclution: So, early diagnosis & precise grading with the help of FNAC itself can prove to be a very good informative tool & prognostic indicator, leading to commencement of early treatment & can prevent many untimely deaths in future.

Evaluation of Nuclear Grading on FNAC Smears and Tissue Sections in Carcinoma Breast

Introduction: Fine needle aspiration is a very useful and widely used diagnostic tool for palpable and non palpable breast lumps. It has a sensitivity of 87% and positive predictive value of nearly 100%. Nuclear grading can also be done on FNAC smears. The present study has been undertaken to correlate the morphological features of FNAC and histological grading systems. Aims and Objectives: To asses and compare cytohistomorphological nuclear grading in breast malignancies. To qualitatively estimate the nuclear grading on cytology aspiration and cytologic grading. Materials and Methods : 100 patients were studied during the period of 5 years ranging from 2005 to 2010 who presented to the Department of Surgery with an palpable breast lump. Both FNAC and histology was done. Nuclear grading system of Robinson et al was used for cytological evaluation and Eiston and Ellis modified Bloom- Richardson method was used for histological grading. Observations: Study comprised of 100 cases of duct carcinoma, 97% of the patients diagnosed on cytology were confirmed on histological examination. There were 30 grade I tumors, 46 grade II tumors and 21 grade III tumors. Conclusions: Histological and cytological grading system were comparable to each other in predicting the grade of the tumor probability value >0.05. Sensitivity, specificity and accuracy were 98.9%, 100% and 99% respectively.

Correlation of Mean Nuclear Major Diameter Based Nuclear Morphometry Assessed by Image Analysis System and Fuhrman Nuclear Grading with Clinicopathologic Prognostic Parameters in Renal Cell Carcinoma

To evaluate mean nuclear major diameter (MNMjD) by using an image analysis system and to compare MNMjD-based nuclear morphometry with Fuhrman grading system in terms of correlation with clinicopathologic prognostic parameters in renal cell carcinoma (RCC). Ninety cases diagnosed as RCC were examined in terms of Furhman nuclear grade, histological subtype, renal capsular invasion, perinephric fat invasion, and renal vein and/or ureter invasion. MNMjD was assessed using a computer-assisted image analysis system on histological sections. In addition to the classic system, Fuhrman nuclear grades were examined by dividing into low grade and high grade groups. The correlation between parameters was evaluated statistically. Nuclear morphometry based on MNMjD has higher correlation with clinicopathologic prognostic parameters compared with the Fuhrman nuclear grading system, including individual grades and low grade and high grade groups. Nuclear morphometry is a valuable method in RCC grading and can be used as an alternative system considering its correlation with clinicopathologic prognostic parameters.

Lens slitlamp image grading and nuclear hardness

AbstractLens slitlamp image grading and nuclear hardness Purpose: To develop a lens nuclear grading system able to predict the hardness or surgical difficulty during cataract surgery. Methods: A 1 to 10 (plus 0) grading of the lens nuclear "density", thus called BCN‐10 was developed based on standardized clinical slit lamp photographs, from complete transparency (0) to a totally black cataract (10). The BCN‐10 scale was tested for intra‐observer and inter‐observer repeatibility, for correlation with forward scattering measurement (C‐Quant) and surgical difficulty (ultrasound time). Results: BCN‐10 grading shows good intraobserver and interobserver repeatibility, good correlation with surgical ultrasound times and fair correlation with forward scattering (glare) measurements. Discussion: Available lens grading systems as the LOCS III do not include the harder grades of cataract, precisely where prediction would help the surgeons. BCN‐10 is a novel and consistent lens nuclear grading system useful to predict the hardness and difficulty that will be encountered during cataract surgery, and to some extent correlates with cataract‐induced glare disability.

Interobserver Agreement in the Nuclear Grading of Primary Pulmonary Adenocarcinoma

Nuclear grading involves an evaluation of the size and shape of nuclei and the percentage of tumor cells that are in the mitotic phase. To estimate the degree of aggressiveness, this approach has been applied to various types of carcinomas, such as breast carcinoma and pulmonary adenocarcinoma (Nakazato et al.). In the present study, we estimated and evaluated the interobserver variability of nuclear grading in primary pulmonary adenocarcinomas. We selected 122 primary pulmonary adenocarcinomas measuring 2 cm or less in diameter. Eight pathologists independently evaluated the nuclear factors, using the nuclear grading system reported previously by Nakazato et al. The same pathologists also used both the international multidisciplinary classification of pulmonary adenocarcinoma (2011 International Association for the Study of Lung Cancer classification) and Noguchi's classification, and assessed the extent of the lepidic pattern in the largest cut surface of the tumor. Interobserver agreement was evaluated using the κ statistic. The disease-free survival curves of the patients were obtained using the Kaplan-Meier method and analyzed with the log-rank test. The mean (±SD) κ values for the two histological classifications, the extent of the lepidic pattern, and nuclear grading were 0.46 ± 0.09, 0.48 ± 0.09, 0.45 ± 0.16, and 0.58 ± 0.09, respectively. The cases judged as negative on the basis of nuclear grading showed a significantly better prognosis (5-year disease-free survival rate; 91.8% ± 2.7) than the positive cases did (68.6% ± 3.1). : Nuclear grading is practical for prognostic evaluation of pulmonary adenocarcinoma. The interobserver agreement for nuclear grading is significantly higher than for histological classifications and the extent of the lepidic pattern. Nuclear grading is a reliable prognostic indicator for small adenocarcinomas.

Prognostic factors for malignant pleural mesothelioma

The prognosis for patients with malignant pleural mesothelioma (MPM) is generally regarded as poor, although rare cases of long-term survivors are recognised. Previous prognostic scoring systems have been based on clinical trial populations and are not widely utilised. Population studies consistently confirm non-epithelioid histology, advanced age, and male gender as independent risk factors for poor outcome of MPM. Genetic and immunohistochemical studies continue to provide advances in tumour biology, but no clear validated prognostic factors have been identified to date. Nuclear mitotic and atypia grading systems may provide useful prognostic knowledge; further evaluation is needed. Such biomarkers as soluble mesothelin-related protein and osteopontin provide some prognostic information, though with limitations. The baseline serum neutrophil-to-lymphocyte ratio could also provide prognostic information. Modern metabolic imaging techniques, for example PET/CT, can indicate prognosis by use of baseline total glycolytic volumes (TGV). TGV may also be useful in identifying early responders to systemic chemotherapy treatment. Research to identify clinically useful prognostic factors in MPM remains a priority.

The Relationship Between Body Composition and Response to Neoadjuvant Chemotherapy in Women with Operable Breast Cancer

Overweight women diagnosed with breast cancer have greater recurrence and mortality risks. Recent studies in advanced cancer showed that the combination of sarcopenia and an overweight or obese body mass index (BMI) is associated with poor clinical outcomes. To compare pathological complete response (pCR) cases with controls and evaluate associations among a pCR, survival outcome, and sarcopenia as well as the combination of both sarcopenia and a BMI ≥25 kg/m(2). Sixty-seven breast cancer patients with a pCR to neoadjuvant chemotherapy (NC) were matched with controls who did not have a pCR to NC. Patients were matched by age, Black's nuclear grading system, clinical cancer stage, and estrogen receptor and progesterone receptor status. Body composition was analyzed using computed tomography images taken prior to NC. BMI was associated with pCR. Among normal weight patients, the pCR rate was higher in sarcopenic patients and the progression-free survival (PFS) interval was significantly longer than in overweight or obese BMI patients. The death hazard was 2% higher for each unit higher skeletal muscle index and 0.6% higher for each unit higher visceral adipose tissue. Overweight patients treated with NC had a lower pCR rate and shorter PFS time. Among patients with a normal BMI, the pCR rate was better in sarcopenic patients. More research is required to evaluate the negative impact of sarcopenic obesity on prognosis and the contributors to better response rates in operable, normal weight breast cancer patients with sarcopenia.

177 Ductal Carcinoma in Situ of the Breast – Modified Black Nuclear Grading System Revisited

Background: This study aims to determine the pathologists’ agreement of modified Black nuclear grading system and Holland classification applied to cases of ductal carcinoma in situ (DCIS). Methods: Forty-three cases of breast lesions diagnosed as DCIS were selected to interobserver analysis. Eight pathologists received the same set of digitized images from microscopy of DCIS cases, and answered a questionnaire containing the criteria to compose the modified Black nuclear grade and Holland classification. In order to determine interobserver agreement and diagnostic accuracy, a web-based survey was created. It organizes the information collected from each participant pathologist providing the histological grading of the cases in both classification systems. Result: Comparing the two classifications studied, there was a similar interobserver agreement among both schemes, showing Kappa value of 0.28 ± 0.02 for the modified Black nuclear grade and 0.32 ± 0.02 for the Holland classification. Hence the reliability for the applied to cases of DCIS was considered acceptable. The agreement among all pathologists and the gold standard pathologist similarly followed the results of the interobserver agreement, showing to be acceptable, with Kappa for de overall mode value 0.33 + 0.10 for modified Black nuclear grade and 0.55 + 0.10 for Holland classification (p = 0.07). The findings of Kappa for the mode values among specialists in breast pathology and general pathologists were, respectively, 0.34 + 0.11 (acceptable) and 0.26 + 0.10 (acceptable) for the modified Black nuclear grade and 0.50 + 0.10 (acceptable) and 0.26 + 0.10 (acceptable) for Holland classification. Breast pathology specialists showed similar reproducibility for both evaluated classifications than pathologists not devoted to this subject. Conclusion: The diagnostic accuracy was similar for modified Black nuclear grading system regarding Holland classification system. Original Article *Corresponding author: Fernando Schuh, Rua Duque de Caxias 1191/304, Porto Alegre, Brazil Phone: +91-55 51 3234 6137 E-mail: fernandoschuh@hotmail.com

A nuclear grading system is a strong predictor of survival in epitheloid diffuse malignant pleural mesothelioma

Epithelioid mesothelioma is the most prevalent subtype of diffuse malignant pleural mesothelioma in which only staging is prognostic for survival. In this study of epithelioid diffuse malignant pleural mesothelioma, we investigate the prognostic utility of nuclear features. The slides of 232 epithelioid diffuse malignant pleural mesothelioma patients (14 stage I, 54 stage II, 130 stage III, and 34 stage IV) from a single institution were reviewed for the following seven nuclear features: nuclear atypia, nuclear/cytoplasmic ratio, chromatin pattern, intranuclear inclusions, prominence of nucleoli, mitotic count, and atypical mitoses. MIB-1 immunohistochemistry was performed using tissue microarray, and MIB-1 labeling index was recorded as the percentage of positive tumor cells. Median overall survival of all patients was 16 months and correlated with nuclear atypia (P<0.001), chromatin pattern (P=0.031), prominence of nucleoli (P<0.001), mitotic count (P<0.001), and atypical mitoses (P<0.001) by univariate analysis. Multivariate analysis revealed nuclear atypia (P=0.012) and mitotic count (P<0.001) as independent prognostic factors, and these two factors were utilized to create a three-tier nuclear grade score. The resulting nuclear grade stratified patients into three distinct prognostic groups: grade I (n=107, median overall survival=28 months), grade II (n=91, 14 months), and grade III (n=34, 5 months). Not only was nuclear grade an independent predictor of overall survival (P<0.001), but it was also a stronger discriminator of survival than all currently available factors. Furthermore, nuclear grade was associated with time to recurrence (P=0.004) in patients who underwent complete surgical resection (n=159). MIB-1 labeling index correlated with mitotic count (P<0.001) and nuclear atypia (P=0.037) and stratified overall survival (P<0.001) and time to recurrence (P=0.048), confirming the prognostic value of the nuclear grade. Nuclear grading in epithelioid mesothelioma provides a simple, practical, and cost-effective prognostic tool that better stratifies clinical outcome and time to recurrence than currently available clinicopathologic factors.

The Chromophobe Tumor Grading System is the Preferred Grading Scheme for Chromophobe Renal Cell Carcinoma

The prognostic usefulness of the Fuhrman nuclear grading system has been questioned for chromophobe renal cell carcinoma due to its frequent nuclear and nucleolar pleomorphism. Chromophobe tumor grade, a novel 3-tier tumor grading system based on geographic nuclear crowding and anaplasia, was recently reported to be superior to the Fuhrman system. We compared the 2 scoring systems in a large sporadic chromophobe renal cell carcinoma cohort to determine which grading scheme provides the most predictive assessment of clinical risk. We identified a total of 84 cases of sporadic chromophobe renal cell carcinoma in 82 patients from a total of 2,634 cases (3.2%) spanning 1989 to 2010. A subset of 11 tumors had secondary areas of sarcomatoid transformation. All cases were reviewed for Fuhrman nuclear grade and chromophobe tumor grade according to published parameters by an expert genitourinary pathologist blinded to clinicopathological information. The distribution of Fuhrman nuclear grades 1 to 4 was 0%, 52.4%, 32.9% and 14.7% of cases, and the distribution of chromophobe tumor grades 1 to 3 was 48.8%, 36.5% and 14.7%, respectively. Metastasis developed in 20 patients (24.4%). Survival analysis revealed statistically significant differences in recurrence-free survival when adjusted for chromophobe tumor grade and Fuhrman nuclear grade. Chromophobe tumor grade showed a slightly higher AUC for recurrence-free survival and overall survival than the Fuhrman nuclear grading system. Neither chromophobe tumor grade nor Fuhrman nuclear grade was retained as an independent predictor of outcome in multivariate modeling when patients with sarcomatoid lesions were excluded. Chromophobe tumor grade effectively stratifies patients with chromophobe renal cell carcinoma across all grading levels. Since it does not rely on nuclear features, it avoids the hazard of overestimating the malignant potential of chromophobe renal cell carcinoma. Overall chromophobe tumor grade has higher predictive accuracy than the Fuhrman nuclear grading system.