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.

ABSTRACT Introduction: In view of the detailed histologic evaluation of prostate cancer (PC), it is usually advisable to provide a “second opinion” to confirm diagnosis. This study aimed to compare the Gleason score (GS) of initial diagnosis versus that of histopathologic review of patients with PC. The secondary objective was to compare initial GS versus histopathologic review versus post - surgical histopathology. Material and methods: Retrospective study based on chart review of patients with PC that attended the Uro - oncology Department of Hospital das Clínicas - UNICAMP - Campinas, Brazil, from April, 2002, to April, 2012. Data were divided in groups: patients with biopsies performed elsewhere, biopsies after pathological review and histopathological results following retropubic radical prostatectomy (RRP). These were evaluated in relation to GS difference using Fleis's Kappa concordance coefficient. Results: 402 PC patients, with a median age of 66 years, were evaluated. Reviewed GS showed worsening, with accuracy of 61.2%, and Kappa concordance value = 0.466. Among 143 patients submitted to surgery, GS varied widely, regarding initial evaluation, review and post - surgical RRP. Joint concordance of evaluations was weak (Kappa = 0.216), mainly due to almost no existence concordance between initial evaluation and following RRP (Kappa = 0.041). Conclusion: There is a great histopathological variation of initial GS versus reviewed GS. There is also a better correlation of reviewed GS and post - surgical GS than with initial GS. The second opinion by an uropathologist improves diagnosis and should be advised for better therapeutic decision.

SUMMARY A gonadal tumor was diagnosed in the first months of life in a patient with genital ambiguity, a 45,X/46,XY karyotype, and mixed gonadal dysgenesis. Gonadal biopsies at the age of 3 months revealed dysgenetic testes and a gonadoblastoma on the right testis. Even though gonadal tumors are rare in childhood, this case indicates that prophylactic removal of dysgenetic gonads should be performed as early as possible, especially when the female sex is assigned to a patient with a Y-chromosome sequence.

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.

ABSTRACT Introduction and Objectives: Reactive Stroma (RStr) is observed in many human cancers and is related to carcinogenesis. The objectives of the present study were to stablish a relationship of the RStr microenvironment with prostate cancer (Pca) through a morphological and molecular characterization, and to identify a possible relationship between RStr with worse prognosis factors and occurrence of malignant prostatic stem cells. Materials and Methods: Forty prostatic samples were selected from men with Pca diagnosis submitted to radical prostatectomy; they were divided in two groups: Group-1 (n=20): samples without reactive stroma; Group-2 (n=20): samples of PCa with intense stroma reaction. Prostatic samples were evaluated for RStr intensity by Masson Trichromic stain and posteriorly submitted to histopathological and immunohistochemistry analysis for antigens: α-actin, vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA, AR, Erα and ERβ. Results: Reactive stroma with intense desmoplastic reactivity was significantly more frequent in intermediate (Gleason 7, 3+4) and high grade tumors (Gleason 7, 4+3). The group with intense stromal reactivity showed significant higher levels of Vimentin, IGF-1, MMP-2, FGF-2, C-Myc, PSCA and ERα. Conclusions: It can be concluded that RStr may be a predictive marker of Pca progression, since it was associated with increase of growth factors, imbalance of androgen and estrogen receptors and presence of malign prostatic stem cells.

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.

Purpose To analyze controversial clinicopathologic predictors of biochemical recurrence after surgery: age, race, tumor extent on surgical specimen, tumor extent on needle biopsy, Gleason score 3 + 4 vs 4 + 3, and amount of extent of extraprostatic extension and positive surgical margins. Materials and Methods The needle biopsies and the correspondent surgical specimens were analyzed from 400 patients. Time to recurrence was analyzed with the Kaplan-Meier curves and risk of shorter time to recurrence using Cox univariate and multivariate analysis. Results Except for age, race, maximum percentage of cancer per core, and number of cores with cancer, all other variables studied were significantly predictive of time to biochemical recurrence using the Kaplan-Meier curves. In univariate analysis, except for focal extraprostatic extension, age, race, focal positive surgical margins, and maximum extent and percentage of cancer per core, all other variables were significantly predictive of shorter time to recurrence. On multivariate analysis, diffuse positive surgical margins and preoperative PSA were independent predictors. Conclusions Young patients and non-whites were not significantly associated with time to biochemical recurrence. The time consuming tumor extent evaluation in surgical specimens seems not to add additional information to other well established predictive findings. The higher predictive value of Gleason score 4 + 3 = 7 vs 3 + 4 = 7 discloses the importance of grade 4 as the predominant pattern. Extent and not simply presence or absent of extraprostatic extension should be informed. Most tumor extent evaluations on needle biopsies are predictive of time to biochemical recurrence, however, maximum percentage of cancer in all cores was the strongest predictor.

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.

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.

CONTEXTO: Paragangliomas extra-adrenais são tumores raros que têm sido relatados em muitas localizações, incluindo rim, uretra, bexiga, próstata, cordão espermático, vesícula biliar, útero e vagina. RELATO DE CASO: Este relato descreve, pela primeira vez em nosso conhecimento, um paraganglioma primário da vesícula seminal ocorrendo em um paciente do sexo masculino de 61 anos de idade. O paciente apresentou hipertensão arterial persistente e um diagnóstico prévio de carcinoma de células renais cromófobo (CCRC). Foi pensado que o tumor de vesícula seminal poderia ser uma metástase do CCRC. A caracterização imunoistoquímica revelou expressão de sinaptofisina e cromogranina nos ninhos de células tumorais e expressão de proteína S100 nas células sustentaculares. Expressão de succinato de-hidrogenase A e B relacionada (SDHA e SDHB) estiveram presentes em ambos os tumores CONCLUSÕES: Nenhuma alteração genética dos genes VHL e SDHB foi detectada nos tecidos tumorais e adjacentes ao tumor, o que nos levou a afastar uma síndrome hereditária que poderia explicar a associação entre o paraganglioma e o CCRC em um paciente com hipertensão arterial.

CONTEXT: Extra-adrenal paragangliomas are rare tumors that have been reported in many locations, including the kidney, urethra, urinary bladder, prostate, spermatic cord, gallbladder, uterus and vagina. CASE REPORT: This report describes, for the first time to the best of our knowledge, a primary paraganglioma of the seminal vesicle occurring in a 61-year-old male. The patient presented persistent arterial hypertension and a previous diagnosis of chromophobe renal cell carcinoma. It was hypothesized that the seminal vesicle tumor could be a metastasis from the chromophobe renal cell carcinoma. Immunohistochemical characterization revealed expression of synaptophysin and chromogranin in tumor cell nests and peripheral S100 protein expression in sustentacular cells. Succinate dehydrogenase A and B-related (SDHA and SDHB) expression was present in both tumors. CONCLUSIONS: No genetic alterations to the VHL and SDHB genes were detected in either the tumor tissue or tissues adjacent to the tumor, which led us to rule out a hereditary syndrome that could explain the association between paraganglioma and chromophobe renal cell carcinoma in a patient with arterial hypertension.