Fumarate hydratase-deficient renal cell carcinoma: A tumor with diverse morphology including cannibalism, lymphocytic emperipolesis, and defective autophagy.

We report the clinicopathological findings of the first series of 3 patients from Brazil with fumarate hydratase-deficient renal cell carcinoma. The clinicopathological findings disclosed a very aggressive tumor. All 3 patients had solitary tumor at the left side, metastasis and advanced stage at the time of diagnosis; were females with a median age of 40 years; had a history of uterine leiomyomas; and, at follow-up two patients are deceased and one patient alive. The microscopic findings of these 3 patients are in accordance with the literature disclosing a variety of morphologic features being papillary arrangement, eosinophilic cytoplasm, and prominent nucleoli surrounded by clear halo the constant and most frequent findings. Previously not reported in this tumor, we describe presence of cannibalism, lymphocytic emperipolesis, and cytoplasmic vacuoles with eosinophilic inclusions associated with overexpression of p62 in immunohistochemistry which is considered to be evidence of defective autophagy. Lymphocytic emperipolesis was a more frequent finding than cannibalism and immunohistochemistry for p62 was overexpressed only in the 2 patients disclosing cytoplasmic vacuoles with eosinophilic inclusions. The presence, frequency and significance of these novel findings should be checked in large series of this rare and aggressive tumor aiming to associate with clinical behavior and eventually influence the strategy of treatment.

Prognostic significance of architectural subtypes of Gleason grade 4 prostate cancer in radical prostatectomy: A semiquantitative method of evaluation.

Studies have shown that Gleason grade 4 extent as well as architectural subtypes provide prognostic information. We aimed to evaluate the influence on biochemical recurrence following radical prostatectomy of patients with organ-confined tumor, Gleason score 7, and negative surgical margins. Total tumor extent, Gleason grade 4 total extent and the extent of each architectural subtype (fused glands, poorly defined glands, cribriform glands, and glomeruloid glands) were evaluated by a semiquantitative point-count method using different colors to identify each subtype. Microscopic morphology of glomeruloid glands was considered regardless of morphology: size (small or large), attachment (narrow or extensive), and cribriform or solid intraluminal protrusion. Gleason grade 4 total extent significantly predicted shorter time to biochemical recurrence in univariate and multivariate analysis. Stratifying extent, Gleason grade 4 with >30% of the total grade 4 extent was significantly predictive for time of recurrence. Considering architectural subtypes, cribriform and glomeruloid glands but not fused and poorly formed glands extent, significantly predicted shorter time to recurrence in univariate analysis. An important issue related to the studies on prognostic significance of Gleason grade 4 subtypes is the lack of uniformity in the definition of microscopic morphology of the subtypes particularly of the glomeruloid architecture.

Lower Urinary Tract Symptoms Due to Xanthoma of the Prostate After Kidney Transplantation: A Case Report.

BACKGROUND: Prostatic xanthoma is a lesion of unknown cause that is often an incidental finding in patients undergoing needle biopsy or transurethral resection. To the best of our knowledge, we report on a unique case of a pure xanthoma without benign prostatic hyperplasia of the prostate in a patient with lower urinary tract symptoms manifested after kidney transplantation. METHODS: A 62-year-old man was submitted for a kidney transplant in April 2018. He had no urinary complaints previous to the transplant. Since July 2019, he had complained of lower urinary tract symptoms. In October 2019, he had acute urinary retention being submitted to a transurethral resection of an estimated 47 g prostate. All measures of cholesterol, high-density lipoproteins (HDL), and low-density lipoproteins (LDL) were within the normal range-except triglycerides, which were mildly elevated in 2 measures. RESULTS: The pathologic examination of the resected prostate showed pure xanthoma without benign prostatic hyperplasia. A similar lesion with a xanthomatous cell component is verruciform xanthoma. It is a rare benign lesion of unknown etiology not associated with underlying disorders of lipid metabolism that has been reported in patients with bone marrow, kidney, and liver transplant. CONCLUSIONS: We report a unique case of prostate enlargement caused by pure xanthoma in a patient with renal transplant. In absence of any apparent infection, normal cholesterol measures, and appearance of symptoms after the transplant and considering the morphologic similarity with verruciform xanthoma, a lesion also reported in transplanted patients, we speculate that the pathogenesis of the lesion in this particular patient may be related to immunosuppression.

The TNM 8th edition: Validation of the proposal for organ - confined (pT2) prostate cancer

ABSTRACT Purpose: The 8th edition of the TNM has been updated and improved in order to ensure a high degree of clinical relevance. A major change in prostate includes pathologically organ - confined disease to be considered pT2 and no longer subclassified by extent of involvement or laterality. The aim of this study was to validate this major change. Materials and Methods: Prostates were step - sectioned from 196 patients submitted to radical prostatectomy with organ confined disease (pT2) and negative surgical margins. Tumor extent was evaluated by a semiquantitative point count method. The dominant nodule extent was recorded as the maximal number of positive points of the largest single focus of cancer from the quadrants. Laterality was considered as either total tumor extent (Group 1) or index tumor extent (Group 2). Time to biochemical recurrence was analyzed with the Kaplan - Meier product limit analysis and prediction of shorter time to biochemical recurrence with Cox proportional hazards model. Results: In Group 1, 43 / 196 (21.9%) tumors were unilateral and 153 / 196 (78.1%) bilateral and in Group 2, 156 / 196 (79.6%) tumors were unilateral and 40 / 196 (20.4%) bilateral. In both groups, comparing unilateral vs bilateral tumors, there was no significant clinicopathological difference, and no significant association with time as well as prediction of shorter time to biochemical recurrence following surgery. Conclusions: Pathologic sub - staging of organ confined disease does not convey prognostic information either considering laterality as total tumor extent or index tumor extent. Furthermore, no correlation exists between digital rectal examination and pathologic stage.

The TNM 8th edition: Validation of the proposal for organ - confined (pT2) prostate cancer.

PURPOSE: The 8th edition of the TNM has been updated and improved in order to ensure a high degree of clinical relevance. A major change in prostate includes pathologically organ - confined disease to be considered pT2 and no longer subclassified by extent of involvement or laterality. The aim of this study was to validate this major change. MATERIALS AND METHODS: Prostates were step - sectioned from 196 patients submitted to radical prostatectomy with organ confined disease (pT2) and negative surgical margins. Tumor extent was evaluated by a semiquantitative point count method. The dominant nodule extent was recorded as the maximal number of positive points of the largest single focus of cancer from the quadrants. Laterality was considered as either total tumor extent (Group 1) or index tumor extent (Group 2). Time to biochemical recurrence was analyzed with the Kaplan - Meier product limit analysis and prediction of shorter time to biochemical recurrence with Cox proportional hazards model. RESULTS: In Group 1, 43 / 196 (21.9%) tumors were unilateral and 153 / 196 (78.1%) bilateral and in Group 2, 156 / 196 (79.6%) tumors were unilateral and 40 / 196 (20.4%) bilateral. In both groups, comparing unilateral vs bilateral tumors, there was no significant clinicopathological difference, and no significant association with time as well as prediction of shorter time to biochemical recurrence following surgery. CONCLUSIONS: Pathologic sub - staging of organ confined disease does not convey prognostic information either considering laterality as total tumor extent or index tumor extent. Furthermore, no correlation exists between digital rectal examination and pathologic stage.

Renal outcome in IgA nephropathy according to Oxford classification and ultrastructural analysis in a Brazilian center
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AIMS: Correlate clinical and histologic features with renal outcome in patients with biopsy-proven IgA nephropathy (IgAN). MATERIALS AND METHODS: Retrospective analysis of records and renal tissue of IgAN patients. Histology was revised according to MEST score of Oxford classification. Focal segmental glomerulosclerosis (FSGS) features were assessed by light microscopy. Electron microscopy review searched for podocyte effacement. RESULTS: 67 patients were included, 56.7% men, mean age 34.5 ± 12.5 years, mean arterial pressure (MAP) 106 ± 18 mmHg, estimated glomerular filtration rate (eGFR) 63.32 ± 43.07 mL/min/1.73m2 and proteinuria 3.1 ± 2.2 g/24 h. M1 was seen in 38 patients (56.7%), E1 in 12 (17.9%), S1 in 49 (73.1%), T1 in 18 (26.8%), and T2 in 17 (25.3%). Mean effacement index (EI) was 0.81 ± 0.18 and did not correlate with proteinuria. 27 patients (40.2%) had end-stage renal disease (ESRD) which correlated with MAP (p = 0.002), eGFR (p = 0.0003), T1 (p = 0.0008) and T2 (p = 0.0001), follow-up MAP (p = 0.02) and follow-up proteinuria (p = 0.01 for 1.0 - 4.0 g/24 h and p = 0.005 for ≥ 4.0 g/24 h). T score correlated with MAP and proteinuria at baseline (p = 0.0001 and 0.0097, respectively) and during follow-up (p = 0.0001 and < 0.0001, respectively). Podocyte hypertrophy correlated with MAP at baseline and during follow-up (p = 0.0046 and 0.0295, respectively). Tip lesion correlated with MAP at baseline (p = 0.0228). There was no correlation between FSGS features or EI with proteinuria or ESRD. CONCLUSIONS: Our data corroborate eGFR, proteinuria, MAP and T score as risk factors for ESRD in IgAN. Most patients had diffuse podocyte effacement, probably secondary to factors unrelated to proteinuria.
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Does index tumor predominant location influence prognostic factors in radical prostatectomies?

ABSTRACT Purpose To find any influence on prognostic factors of index tumor according to predominant location. Materials and Methods Prostate surgical specimens from 499 patients submitted to radical retropubic prostatectomy were step-sectioned. Each transverse section was subdivided into 2 anterolateral and 2 posterolateral quadrants. Tumor extent was evaluated by a semi-quantitative point-count method. The index tumor (dominant nodule) was recorded as the maximal number of positive points of the most extensive tumor area from the quadrants and the predominant location was considered anterior (anterolateral quadrants), posterior (posterolateral quadrants), basal (quadrants in upper half of the prostate), apical (quadrants in lower half of the prostate), left (left quadrants) or right (right quadrants). Time to biochemical recurrence was analyzed by Kaplan-Meier product-limit analysis and prediction of shorter time to biochemical recurrence using univariate and multivariate Cox proportional hazards model. Results Index tumors with predominant posterior location were significantly associated with higher total tumor extent, needle and radical prostatectomy Gleason score, positive lymph nodes and preoperative prostate-specific antigen. Index tumors with predominant basal location were significantly associated with higher preoperative prostate-specific antigen, pathological stage higher than pT2, extra-prostatic extension, and seminal vesicle invasion. Index tumors with predominant basal location were significantly associated with time to biochemical recurrence in Kaplan-Meier estimates and significantly predicted shorter time to biochemical recurrence on univariate analysis but not on multivariate analysis. Conclusions The study suggests that index tumor predominant location is associated with prognosis in radical prostatectomies, however, in multivariate analysis do not offer advantage over other well-established prognostic factors.

Does index tumor predominant location influence prognostic factors in radical prostatectomies?

PURPOSE: To find any influence on prognostic factors of index tumor according to predominant location. MATERIALS AND METHODS: Prostate surgical specimens from 499 patients submitted to radical retropubic prostatectomy were step-sectioned. Each transverse section was subdivided into 2 anterolateral and 2 posterolateral quadrants. Tumor extent was evaluated by a semi-quantitative point-count method. The index tumor (dominant nodule) was recorded as the maximal number of positive points of the most extensive tumor area from the quadrants and the predominant location was considered anterior (anterolateral quadrants), posterior (posterolateral quadrants), basal (quadrants in upper half of the prostate), apical (quadrants in lower half of the prostate), left (left quadrants) or right (right quadrants). Time to biochemical recurrence was analyzed by Kaplan-Meier product-limit analysis and prediction of shorter time to biochemical recurrence using univariate and multivariate Cox proportional hazards model. RESULTS: Index tumors with predominant posterior location were significantly associated with higher total tumor extent, needle and radical prostatectomy Gleason score, positive lymph nodes and preoperative prostate-specific antigen. Index tumors with predominant basal location were significantly associated with higher preoperative prostate-specific antigen, pathological stage higher than pT2, extra-prostatic extension, and seminal vesicle invasion. Index tumors with predominant basal location were significantly associated with time to biochemical recurrence in Kaplan-Meier estimates and significantly predicted shorter time to biochemical recurrence on univariate analysis but not on multivariate analysis. CONCLUSIONS: The study suggests that index tumor predominant location is associated with prognosis in radical prostatectomies, however, in multivariate analysis do not offer advantage over other well-established prognostic factors.

Predictive criteria of insignificant prostate cancer: what is the correspondence of linear extent to percentage of cancer in a single core?

OBJECTIVE: The aim of active surveillance of early prostate cancer is to individualize therapy by selecting for curative treatment only patients with significant cancer. Epstein's criteria for prediction of clinically insignificant cancer in surgical specimens are widely used. Epstein's criterion "no single core with >50% cancer has no correspondence in linear extent. The aim of this study is to find a possible correspondence. MATERIALS AND METHODS: From a total of 401 consecutive patients submitted to radical prostatectomy, 17 (4.2%) met criteria for insignificant cancer in the surgical specimen. The clinicopathologic findings in the correspondent biopsies were compared with Epstein's criteria for insignificant cancer. Cancer in a single core was evaluated in percentage as well as linear extent in mm. RESULTS: Comparing the clinicopathologic findings with Epstein's criteria predictive of insignificant cancer, there was 100% concordance for clinical stage T1c, no Gleason pattern 4 or 5, ≤ 2 cores with cancer, and no single core with >50% cancer. However, only 25% had density ≤ 0.15. The mean, median and range of the maximum length of cancer in a single core in mm were 1.19, 1, and 0.5-2.5, respectively. Additionally, the mean, median, and range of length of cancer in all cores in mm were 1.47, 1.5, and 0.5-3, respectively. CONCLUSION: To pathologists that use Epstein's criteria predictive of insignificant cancer and measure linear extent in mm, our study favors that "no single core with >50% cancer" may correspond to >2.5 mm in linear extent.

Predictive criteria of insignificant prostate cancer: what is the correspondence of linear extent to percentage of cancer in a single core?

Objective The aim of active surveillance of early prostate cancer is to individualize therapy by selecting for curative treatment only patients with significant cancer. Epstein’s criteria for prediction of clinically insignificant cancer in surgical specimens are widely used. Epstein’s criterion “no single core with >50% cancer” has no correspondence in linear extent. The aim of this study is to find a possible correspondence. Materials and Methods From a total of 401 consecutive patients submitted to radical prostatectomy, 17 (4.2%) met criteria for insignificant cancer in the surgical specimen. The clinicopathologic findings in the correspondent biopsies were compared with Epstein’s criteria for insignificant cancer. Cancer in a single core was evaluated in percentage as well as linear extent in mm. Results Comparing the clinicopathologic findings with Epstein’s criteria predictive of insignificant cancer, there was 100% concordance for clinical stage T1c, no Gleason pattern 4 or 5, ≤2 cores with cancer, and no single core with >50% cancer. However, only 25% had density ≤0.15. The mean, median and range of the maximum length of cancer in a single core in mm were 1.19, 1, and 0.5-2.5, respectively. Additionally, the mean, median, and range of length of cancer in all cores in mm were 1.47, 1.5, and 0.5-3, respectively. Conclusion To pathologists that use Epstein’s criteria predictive of insignificant cancer and measure linear extent in mm, our study favors that “no single core with >50% cancer” may correspond to >2.5 mm in linear extent. .

Focal prostatic atrophy: morphologic classification and immunohistochemistry.

OBJECTIVE: To describe the morphology of focal prostatic atrophy and propose a comprehensive histologic classification for a proper diagnostic recognition. STUDY DESIGN: A broad immunohistochemical study was performed as an adjunct to its recognition as well as a contribution to pathogenesis. RESULTS: A morphologic continuum was seen on needle biopsies. Chronic inflammation was present only in complete atrophy. Immunohistochemical findings in partial atrophy are similar to normal acini. Luminal compartment in complete atrophy shows aberrant expression of 34betaE12 favoring an intermediate phenotype. ERG negativity in all variants of atrophy may have value in the identification of the lesion. CONCLUSION: The morphologic findings favor a continuum probably partially preceding complete atrophy. Chronic inflammation may be a secondary phenomenon seen only in complete atrophy. Overexpression in complete atrophy of glutathione S-transferase pi relates to oxidative stress possibly related to chronic ischemia, of c-Met favors the concept that intermediate cells may be target for carcinogenesis, and of CD44 may be related to the recruitment of inflammatory cells.

The value of the 2005 International Society of Urological Pathology (ISUP) modified Gleason grading system as a predictor of biochemical recurrence after radical prostatectomy.

PURPOSE: To compare time and risk to biochemical recurrence (BR) after radical prostatectomy of two chronologically different groups of patients using the standard and the modified Gleason system (MGS). METHODS: Cohort 1 comprised biopsies of 197 patients graded according to the standard Gleason system (SGS) in the period 1997/2004, and cohort 2, 176 biopsies graded according to the modified system in the period 2005/2011. Time to BR was analyzed with the Kaplan-Meier product-limit analysis and prediction of shorter time to recurrence using univariate and multivariate Cox proportional hazards model. RESULTS: Patients in cohort 2 reflected time-related changes: striking increase in clinical stage T1c, systematic use of extended biopsies, and lower percentage of total length of cancer in millimeter in all cores. The MGS used in cohort 2 showed fewer biopsies with Gleason score ≤ 6 and more biopsies of the intermediate Gleason score 7. Time to BR using the Kaplan-Meier curves showed statistical significance using the MGS in cohort 2, but not the SGS in cohort 1. Only the MGS predicted shorter time to BR on univariate analysis and on multivariate analysis was an independent predictor. CONCLUSIONS: The results favor that the 2005 International Society of Urological Pathology modified system is a refinement of the Gleason grading and valuable for contemporary clinical practice.

Higher prostate weight is inversely associated with Gleason score upgrading in radical prostatectomy specimens.

Background. Protective factors against Gleason upgrading and its impact on outcomes after surgery warrant better definition. Patients and Methods. Consecutive 343 patients were categorized at biopsy (BGS) and prostatectomy (PGS) as Gleason score, ≤6, 7, and ≥8; 94 patients (27.4%) had PSA recurrence, mean followup 80.2 months (median 99). Independent predictors of Gleason upgrading (logistic regression) and disease-free survival (DFS) (Kaplan-Meier, log-rank) were determined. Results. Gleason discordance was 45.7% (37.32% upgrading and 8.45% downgrading). Upgrading risk decreased by 2.4% for each 1 g of prostate weight increment, while it increased by 10.2% for every 1 ng/mL of PSA, 72.0% for every 0.1 unity of PSA density and was 21 times higher for those with BGS 7. Gleason upgrading showed increased clinical stage (P = 0.019), higher tumor extent (P = 0.009), extraprostatic extension (P = 0.04), positive surgical margins (P < 0.001), seminal vesicle invasion (P = 0.003), less "insignificant" tumors (P < 0.001), and also worse DFS, χ (2) = 4.28, df = 1, P = 0.039. However, when setting the final Gleason score (BGS ≤6 to PGS 7 versus BGS 7 to PGS 7), avoiding allocation bias, DFS impact is not confirmed, χ (2) = 0.40, df = 1, P = 0.530.Conclusions. Gleason upgrading is substantial and confers worse outcomes. Prostate weight is inversely related to upgrading and its protective effect warrants further evaluation.

Adenocarcinoma on needle prostatic biopsies: does reactive stroma predicts biochemical recurrence in patients following radical prostatectomy?

OBJECTIVE: There is evidence that reactive stroma in different cancers may regulate tumor progression. The aim of this study is to establish any possible relation of reactive stroma grading on needle prostatic biopsies to biochemical recurrence. MATERIALS AND METHODS: The study group comprised 266 biopsies from consecutive patients submitted to radical prostatectomy. Reactive stroma was defined as stroma surrounding neoplastic tissue and graded as 0 (absent), 1 (slight), 2 (moderate), and 3 (intense) according to tumor stroma area relative to total tumor area. RESULTS: From the total of 266 needle prostatic biopsies, 143 (53.8%), 55 (20.7%), 54 (20.3%), and 14 (5.3%) showed grades 0, 1, 2, and 3, respectively. Increasing reactive stroma grade was significantly associated with clinical stage T2, higher preoperative PSA, higher biopsy and radical prostatectomy Gleason score, more extensive tumors in radical prostatectomy, and pathologic stage > T2. Only grade 3 was significantly associated with time and risk to biochemical recurrence. On multivariate analysis only preoperative PSA and 2 methods of biopsy tumor extent evaluation were independent predictors. CONCLUSION: Increasing reactive stroma grade on biopsies is significantly associated with several clinicopathologic adverse findings, however, only grade 3 predicts time and risk to biochemical recurrence following radical prostatectomy on univariate but not on multivariate analysis. We have not been able to show that reactive stroma grade 3 on biopsies is an independent predictor of biochemical recurrence beyond that of preoperative PSA and other pathologic findings on biopsy.

Adenocarcinoma on needle prostatic biopsies: Does reactive stroma predicts biochemical recurrence in patients following radical prostatectomy?

Objective There is evidence that reactive stroma in different cancers may regulate tumor progression. The aim of this study is to establish any possible relation of reactive stroma grading on needle prostatic biopsies to biochemical recurrence. Materials and Methods The study group comprised 266 biopsies from consecutive patients submitted to radical prostatectomy. Reactive stroma was defined as stroma surrounding neoplastic tissue and graded as 0 (absent), 1 (slight), 2 (moderate), and 3 (intense) according to tumor stroma area relative to total tumor area. Results From the total of 266 needle prostatic biopsies, 143 (53.8%), 55 (20.7%), 54 (20.3%), and 14 (5.3%) showed grades 0, 1, 2, and 3, respectively. Increasing reactive stroma grade was significantly associated with clinical stage T2, higher preoperative PSA, higher biopsy and radical prostatectomy Gleason score, more extensive tumors in radical prostatectomy, and pathologic stage > T2. Only grade 3 was significantly associated with time and risk to biochemical recurrence. On multivariate analysis only preoperative PSA and 2 methods of biopsy tumor extent evaluation were independent predictors. Conclusion Increasing reactive stroma grade on biopsies is significantly associated with several clinicopathologic adverse findings, however, only grade 3 predicts time and risk to biochemical recurrence following radical prostatectomy on univariate but not on multivariate analysis. We have not been able to show that reactive stroma grade 3 on biopsies is an independent predictor of biochemical recurrence beyond that of preoperative PSA and other pathologic findings on biopsy. .

Prostate total tumor extent versus index tumor extent--which is predictive of biochemical recurrence following radical prostatectomy?

PURPOSE: It is controversial whether tumor extent in radical prostatectomies predicts biochemical recurrence following surgery. We compared the predictive value of total tumor extent vs dominant nodule (index tumor) extent. MATERIALS AND METHODS: A mean of 32 paraffin blocks was processed from prostate surgical specimens step sectioned at 3 to 5 mm intervals from 300 patients treated with radical retropubic prostatectomy. Each transverse section was subdivided into 2 anterolateral and 2 posterolateral quadrants. Tumor extent was evaluated by a semiquantitative point count method. Dominant nodule extent was recorded as the maximal number of positive points of the largest single focus of cancer in the quadrants. Time to biochemical recurrence was analyzed by Kaplan-Meier product limit analysis. Prediction of shorter time to biochemical recurrence was determined by univariate and multivariate Cox proportional hazards models. RESULTS: Except for age and race, total and index tumor extent was significantly associated with higher preoperative prostate specific antigen, clinical stage T2, pathological stage greater than T2, positive surgical margins and higher radical prostatectomy Gleason score. Total and index tumor extent was significantly associated with time to biochemical recurrence in Kaplan-Meier estimates. Total and index tumor extent significantly predicted shorter time to biochemical recurrence on univariate analysis but only index tumor extent was an independent predictor of time to biochemical recurrence on multivariate analysis. CONCLUSIONS: The study indicates that any tumor extent estimate in surgical specimens should be related to the dominant nodule (index tumor) and not to total tumor extent.

Influence of focal and diffuse extraprostatic extension and positive surgical margins on biochemical progression following radical prostatectomy.

PURPOSE: The amount of extraprostatic extension and positive surgical margin correlates in most studies with biochemical recurrence following radical prostatectomy. We studied the influence of focal and diffuse extraprostatic extension and positive surgical margins on biochemical progression using a simple method for quantification. MATERIALS AND METHODS: A total of 360 prostates were step-sectioned and totally processed from 175 patients with stage T1c and 185 patients with clinical stage T2 submitted to radical retropubic prostatectomy. Extraprostatic extension was stratified into 2 groups: present up to 1 quadrant and/or section from the bladder neck or apex (Group 1, focal) and in more than 1 quadrant or section (Group 2, diffuse); and, positive surgical margin present up to 2 quadrants and/or sections (Group 1, focal) and in more than 2 quadrants or sections (Group 2, diffuse). The Kaplan-Meier product-limit analysis was used for the time to biochemical recurrence, and an univariate and multivariate Cox stepwise logistic regression model to identify significant predictors. RESULTS: Extraprostatic extension was found in 129/360 (35.8%) patients, 39/129 (30.2%) in Group 1 and 90/129 (69.8%) in Group 2. In univariate analysis but not in multivariate analysis, patients showing diffuse extraprostatic extension (Group 2) had a significant higher risk to develop biochemical recurrence in a shorter time. Positive surgical margin was present in 160/360 (44.4%) patients, 81/160 (50.6%) patients in Group 1 and 79/160 (49.4%) patients in Group 2. Patients with diffuse positive surgical margins (Group 2) had a significant higher risk in both univariate and multivariate analyses. Diffuse positive surgical margin was the strongest predictor on both analyses and an independent predictor on multivariate analysis. CONCLUSION: Diffuse extraprostatic extension in univariate analysis and positive surgical margins on both univariate and multivariate analyses are significant predictors of shorter time to biochemical progression following radical prostatectomy.

Influence of focal and diffuse extraprostatic extension and positive surgical margins on biochemical progression following radical prostatectomy

PURPOSE: The amount of extraprostatic extension and positive surgical margin correlates in most studies with biochemical recurrence following radical prostatectomy. We studied the influence of focal and diffuse extraprostatic extension and positive surgical margins on biochemical progression using a simple method for quantification. MATERIALS AND METHODS: A total of 360 prostates were step-sectioned and totally processed from 175 patients with stage T1c and 185 patients with clinical stage T2 submitted to radical retropubic prostatectomy. Extraprostatic extension was stratified into 2 groups: present up to 1 quadrant and/or section from the bladder neck or apex (Group 1, focal) and in more than 1 quadrant or section (Group 2, diffuse); and, positive surgical margin present up to 2 quadrants and/or sections (Group 1, focal) and in more than 2 quadrants or sections (Group 2, diffuse). The Kaplan-Meier product-limit analysis was used for the time to biochemical recurrence, and an univariate and multivariate Cox stepwise logistic regression model to identify significant predictors. RESULTS: Extraprostatic extension was found in 129/360 (35.8%) patients, 39/129 (30.2%) in Group 1 and 90/129 (69.8%) in Group 2. In univariate analysis but not in multivariate analysis, patients showing diffuse extraprostatic extension (Group 2) had a significant higher risk to develop biochemical recurrence in a shorter time. Positive surgical margin was present in 160/360 (44.4%) patients, 81/160 (50.6%) patients in Group 1 and 79/160 (49.4%) patients in Group 2. Patients with diffuse positive surgical margins (Group 2) had a significant higher risk in both univariate and multivariate analyses. Diffuse positive surgical margin was the strongest predictor on both analyses and an independent predictor on multivariate analysis. CONCLUSION: Diffuse extraprostatic extension in univariate analysis and positive surgical margins on both univariate and multivariate analyses are significant predictors of shorter time to biochemical progression following radical prostatectomy.

Various morphometric measurements of cancer extent on needle prostatic biopsies: which is predictive of pathologic stage and biochemical recurrence following radical prostatectomy?

OBJECTIVES: To find whether any particular method of measuring cancer extent on needle prostatic biopsies is superior to others in predicting pathological stage >T2 and biochemical recurrence following radical prostatectomy. MATERIALS AND METHODS: The study was based on 168 extended biopsies and the correspondent step-sectioned surgical specimens. Tumor extent was evaluated as: (1) number and percentage of cores with carcinoma; (2) total length and percentage of cancer in mm in all cores; and (3) the greatest length and percentage of cancer in a single core. RESULTS: All measurements significantly predicted stage >pT2 using logistic regression. With the exception of the greatest length and percentage of cancer in a single core, all other methods were also associated with a higher risk for biochemical recurrence (Cox method). Percentage of length of carcinoma in all cores was significantly and consistently stronger than other measures in all comparisons and combined to preoperative PSA and Gleason grade in multivariate analysis gained prediction for pathologic stage >T2 and was independent of risk of biochemical recurrence. CONCLUSIONS: Percentage of total length of carcinoma in mm in all cores of a needle biopsy had the strongest predictive positive value for stage >pT2 and risk for biochemical recurrence following radical prostatectomy. Combined with preoperative PSA and Gleason grade on biopsy may improve the predictive value for stage >pT2.

Should pathologists continue to use the current pT2 substaging system for reporting of radical prostatectomy specimens?

OBJECTIVES: Pathologic staging tries to maintain symmetry with clinical staging, allowing a direct comparison of both. However, in contrast to clinical substaging of T2 prostate cancers, is controversial whether pathologic T2 substaging conveys prognostic information. The aim of our study is to analyze the clinicopathologic findings and the prognostic information comparing the clinical with the pathological T2 substaging of patients submitted to radical prostatectomy. MATERIALS AND METHODS: Using the 2009 TNM staging system, 169 patients with clinical stage T2a were compared with patients with stage T2b/T2c, and 142 patients with pathological stage T2a were compared with patients with stage T2c. All surgical specimens were step-sectioned. Using a semiquantitative point-count method for tumor extent evaluation, all insignificant tumors were excluded from analysis. Clinicopathological characteristics were compared between the groups. Biochemical recurrence data were compared using log-rank analysis, and significant predictors of time to biochemical recurrence were determined using univariate and multivariate Cox proportional hazards model. RESULTS: There was significant difference in biochemical recurrence rates between men with clinical T2a versus T2b/T2c tumors but no difference between men with pathological T2a versus T2c tumors. No patient in pathologic stage T2b was found. On multivariate analysis, clinical stage T2b/T2c was independent predictor of time to biochemical recurrence following surgery but not pathological stage T2c. CONCLUSIONS: There is lack of symmetry between clinical and pathological T2 substaging as predictors of time to biochemical recurrence following surgery. The findings support a reevaluation of the TNM pathologic T2 stage, which should not be substratified.