Three-dimensional tumor visualization of invasive breast carcinomas using whole-mount serial section histopathology: implications for tumor size assessment.

PURPOSE: Linear tumor size (T-size) estimated with conventional histology informs breast cancer management. Previously we demonstrated significant differences in margin and focality estimates using conventional histology versus digital whole-mount serial sections (WMSS). Using WMSS we can measure T-size or volume. Here, we compare WMSS T-size with volume, and with T-size measured conventionally. We also compare the ellipsoid model for calculating tumor volume to direct, WMSS measurement. METHODS: Two pathologists contoured regions of invasive carcinoma and measured T-size from both WMSS and (simulated) conventional sections in 55 consecutive lumpectomy specimens. Volume was measured directly from the contours. Measurements were compared using the paired t-test or Spearman's rank-order correlation. A five-point 'border index' was devised and assigned to each case to parametrize tumor shape considering 'compactness' or cellularity. Tumor volumes calculated assuming ellipsoid geometry were compared with direct, WMSS measurements. RESULTS: WMSS reported significantly larger T-size than conventional histology in the majority of cases [61.8%, 34/55; means = (2.34 cm; 1.99 cm), p < 0.001], with a 16.4% (9/55) rate of 'upstaging'. The majority of discordances were due to undersampling. T-size and volume were strongly correlated (r = 0.838, p < 0.001). Significantly lower volume was obtained with WMSS versus ellipsoid modeling [means = (1.18 cm3; 1.45 cm3), p < 0.001]. CONCLUSIONS: Significantly larger T-size is measured with WMSS than conventionally, due primarily to undersampling in the latter. Volume and linear size are highly correlated. Diffuse tumors interspersed with normal or non-invasive elements may be sampled less extensively than more localized masses. The ellipsoid model overestimates tumor volume.

Budget impact analysis of a breast rapid diagnostic unit.

BACKGROUND: The Odette Cancer Centre's recent implementation of a rapid diagnostic unit (rdu) for breast lesions has significantly decreased wait times to diagnosis. However, the economic impact of the unit remains unknown. This project defined the development and implementation costs and the operational costs of a breast rdu in a tertiary care facility. METHODS: From an institutional perspective, a budget impact analysis identified the direct costs associated with the breast rdu. A base-case model was also used to calculate the cost per patient to achieve a diagnosis. Sensitivity analyses computed costs based on variations in key components. Costs are adjusted to 2015 valuations using health care-specific consumer price indices and are reported in Canadian dollars. RESULTS: Initiation cost for the rdu was $366,243. The annual operational cost for support staff was $111,803. The average per-patient clinical cost for achieving a diagnosis was $770. Sensitivity analyses revealed that, if running at maximal institutional capacity, the total annual clinical cost for achieving a diagnosis could range between $136,080 and $702,675. CONCLUSIONS: Establishment and maintenance of a breast rdu requires significant investment to achieve reductions in time to diagnosis. Expenditures ought to be interpreted in the context of institutional patient volumes and trade-offs in patient-centred outcomes, including lessened patient anxiety and possibly shorter times to definitive treatment. Our study can be used as a resource-planning tool for future rdus in health care systems wishing to improve diagnostic efficiency.

Assessment of endometrial sampling as a predictor of final surgical pathology in endometrial cancer.

BACKGROUND: The histology and grade of endometrial cancer are important predictors of disease outcome and of the likelihood of nodal involvement. In most centres, however, surgical staging decisions are based on a preoperative biopsy. The objective of this study was to assess the concordance between the preoperative histology and that of the hysterectomy specimen in endometrial cancer. METHODS: Patients treated for endometrial cancer during a 10-year period at a tertiary cancer centre were identified from a prospectively collected pathological database. All pathology reports were reviewed to confirm centralised reporting of the original sampling or biopsy specimens; patients whose biopsies were not reviewed by a dedicated gynaecological pathologist at the treating centre were excluded. Surgical pathology data including histology, grade, depth of myometrial invasion, cervical stromal involvement and lymphovascular space invasion (LVSI) as well as preoperative histology and grade were collected. Preoperative and final tumour cell type and grade were compared and the distribution of other high-risk features was analysed. RESULTS: A total of 1329 consecutive patients were identified; 653 patients had a centrally reviewed epithelial endometrial cancer on their original biopsy, and are included in this study. Of 255 patients whose biopsies were read as grade 1 (G1) adenocarcinoma, 45 (18%) were upgraded to grade 2 (G2) on final pathology, 6 (2%) were upgraded to grade 3 (G3) and 5 (2%) were read as a non-endometrioid high-grade histology. Overall, of 255 tumours classified as G1 endometrioid cancers on biopsy, 74 (29%) were either found to be low-grade (G1-2) tumours with deep myometrial invasion, or were reclassified as high-grade cancers (G3 or non-endometrioid histologies) on final surgical pathology. Despite these shifts, we calculate that omitting surgical staging in preoperatively diagnosed G1 endometrioid cancers without deep myometrial invasion would result in missing nodal involvement in only 1% of cases. CONCLUSIONS: Preoperative endometrial sampling is only a modest predictor of surgical pathology features in endometrial cancer and may underestimate the risk of disease spread and recurrence. In spite of frequent shifts in postoperative vs preoperative histological assessment, the predicted rate of missed nodal metastases with a selective staging policy remains low.

Intraoperative margin assessment of the radical trachelectomy specimen.

OBJECTIVE: To summarize our experience in the frozen section (FS) assessment of the trachelectomy surgical margin. METHODS: All surgeries from 1994 to 2007 were performed by one surgeon. The FS examination was consistently carried out by a group of gynecologic pathologists according to the protocol described in details in this article. Cases were retrieved from the pathology files and the slides were reviewed by two pathologists. RESULTS: 132 patients were identified with complete pathology records. They ranged from 17 to 46 years old (median 31). Surgeries were performed for clinical Stages 1A (n=39) and 1B (n=93) tumors (63 adenocarcinoma, 59 squamous cell carcinoma, 7 adenosquamous and 3 others). In 78 cases, no residual tumor was seen in the trachelectomy specimens as it was resected by the preceding LEEP or cone. The margin was reported as negative in 123, suspicious in 3 and positive in 6 cases. It was revised in 16 cases (6 positive, 2 suspicious and 8 negative but <5 mm). Final margin assessment agreed with the FS diagnosis in 130 (98.5%) and showed interpretational overcall in 2 cases (1.5%); only one of which resulted in a revised margin. No false negative intraoperative assessment was found. CONCLUSIONS: We describe our FS protocol and summarize our data. This protocol is reliable since none of the patients was under-treated.