Histologic grading of breast cancer: linkage of patient outcome with level of pathologist agreement.

In the histologic grading of invasive breast cancer with the Nottingham modification of the Scarff-Bloom-Richardson grading scheme (NSBR), it has been found that when pathologists disagree, they tend not to disagree by much. However, if tumor grade is to be used as an important parameter in making treatment decisions, then even this generally small degree of pathologist variability in assessing grade needs to be correlated with patient outcome. Findings from the Nottingham/Tenovus Primary Breast Cancer Study were used for patient outcome data. Kaplan-Meier survival curves were constructed for NSBR scores grouped according to the level at which pathologists tend to agree in assessing grade, from a reproducibility perspective. For example, if a given tumor were assessed by several pathologists as having either an NSBR score of 5 or 6, then what is the correct score--the intermediate-grade Score 6 assessments or the low-grade Score 5 assessments? By "regrouping" the Nottingham outcome data such that data from patients with Score 5 tumors are grouped with patients having Score 6 tumors (a 5-6 group), then the level in which the pathologists agreed with each other (that the tumor was either score 5 or 6) is better matched with patient outcome. In response to the above example, it was not surprising to find that patients with Score 5-6 tumors had a probability of survival between the established low and intermediate NSBR final combined grades. However, it is the discussion of this approach that highlights that optimal use of grading requires awareness of the level of pathologist agreement and understanding the value of pathologists' reaching consensus in assessments. Also, knowledge of possible clinical decision thresholds can help in providing relevant interpretations of grading results.

Histologic grading of breast carcinoma. A reproducibility study.

BACKGROUND: A concern with the histologic grading of breast cancer is that tumor grading is a subjective evaluation that may have problems with reproducibility. METHODS: A single slide from 10 invasive breast cancers was submitted to 25 pathologists who practice in six separate groups. Pathologists graded the tumors using a modified Bloom-Richardson (B-R) scheme, and the results were compared. RESULTS: In 8 of the 10 cases, there was greater than 87% agreement by the pathologists as to the final combined B-R grade, with complete agreement in 2 cases. Only one case had any discrepant opinions that ranged from low to high grade, and this involved only 3 of the 25 pathologists. With respect to B-R score, the pathologists tended to score the tumors as either one of two adjacent scores. Due to this clustering, the B-R scheme appears reproducible into five groups: very low and very high grade tumors and B-R score "5,6," "6,7," and "7,8" tumors. This clustering was especially noticeable in two cases with split decisions, in which the discrepancy in final combined grade was largely due to the tumors being given B-R scores that straddled and were then condensed into two B-R grades. A consensus from each pathology group tended to merge with the majority opinion of all 25 pathologists and was correct for outliers. CONCLUSIONS: This study indicates that reproducibility of grading breast cancers can be achieved when a histologic grading scheme with specified guidelines is used. Pathologists must be aware of the limits of reproducibility, with appropriate guidelines being followed to help optimize agreement, and there should be an awareness of how pathologists group in their evaluations. Also, it may be advisable to better correlate or link reproducibility data with prognostic data in the design of grading schemes.

Ductal carcinoma in situ of the breast. Heterogeneity of individual lesions.

BACKGROUND: The increased prevalence of ductal carcinoma in situ (DCIS) has produced a growing awareness of the importance of its diverse patterns. These differences in pattern have become clinically significant as predictive indicators of success for planned local excisions of small DCIS lesions. METHODS: The authors reviewed 100 sequentially collected DCIS cases from a consultation practice. Recognizing the bias of such a series toward exclusion of easily recognizable comedo DCIS, the authors investigated the spectrum of mixed pattern lesions to identify variations and common features in the architectural arrangement of the various histologic patterns. RESULTS: Patterns of atypical ductal hyperplasia (ADH) with specific criteria of recognition were intermixed in 17 cases (11 cribriform, 1 solid, 1 micropapillary, 4 mixed). Thirty-three cases of DCIS consisted of mixed patterns of comedo and noncomedo types. No case of comedo DCIS with associated areas of ADH was identified. In all cases of combined DCIS and ADH, the more advanced patterns of DCIS were present in the central portion of the lesion, with the ADH components arranged peripherally. This tendency for the more severely atypical areas to be located centrally was present throughout the study. CONCLUSIONS: Different patterns of DCIS are frequently present within individual lesions (46 of 100), and the more advanced features of architectural atypia are regularly present centrally. This strongly supports the hypothesis that these lesions develop from a central focus and expand peripherally. Also, those lesions with low-grade DCIS at the periphery may be as amenable to local excision for cure as purely low-grade lesions.

Computer-based image analysis of prostate cancer: comments with emphasis on use of commercially available systems.

This review is concerned with computer-based image analysis (CBIA) in prostate cancer. The emphasis is placed on evaluating extent and grade of prostate cancer. The quest for reproducibility in these evaluations has provided an important area of possible application for CBIA studies. Commercially available CBIA systems allow an opportunity for increased efforts in studying the merits of CBIA in prostate cancer. Many CBIA systems with various capabilities are currently on the market. They can be described as either "general" or "dedicated" CBIA systems and are exemplified by two systems: the Werner Frei Imlab/Imtool (Werner Frei Associates, Venice, CA) and the CAS 200 (Cell Analysis Systems, Inc, Lombard, IL), respectively. "General" systems are composed of individual components with data being stored and analyzed using a personal computer (Werner Frei Imlab/Imtool). "Dedicated" systems are integrated systems, usually with little variability of either software or hardware specifications (CAS 200). It is helpful to be cognizant of the contrasting abilities provided by these two systems when evaluating which CBIA system would be most appropriate for a particular application in the study of prostate cancer.

Comparison of keratin monoclonal antibodies MAK-6, AE1:AE3, and CAM-5.2.

Two routinely used antikeratin monoclonal antibodies, AE1:AE3 (Hybritech Inc., La Jolla, CA) and CAM-5.2 (Becton-Dickinson, Mountain View, CA), were compared with a new antikeratin monoclonal antibody mixture, MAK-6 (Triton Biosciences, Inc., Alameda, CA). Various poorly differentiated epithelial neoplasms, lymphomas, melanomas, and sarcomas were studied with the use of the avidin-biotin-peroxidase technic. All three antibodies had similar staining profiles, however, some differences were noted. The MAK-6 and CAM-5.2 antibodies illustrated stronger staining for some grade III transitional cell carcinomas, whereas the AE1:AE3 was variably positive to negative in all cases. Three renal cell carcinomas were positive with all three antibodies, two were negative with all three, and one had scattered positive cells with MAK-6 only. All lymphomas and plasmacytomas were negative with MAK-6 and CAM-5.2, however, AE1:AE3 faintly stained two of three plasmacytomas and two of the seven large cell lymphomas. Two out of three hepatomas evaluated were strongly positive with CAM-5.2 and MAK-6 and variably positive with AE1:AE3. The third case had both positive and negative cells with all three antibodies. In conclusion, MAK-6 antikeratin antibody is as useful as AE1:AE3 and CAM-5.2 for identification of poorly differentiated epithelial neoplasms.