Accuracy of the preoperative PSA level for predicting clinically significant incidental transitional zone-prostate cancer before endoscopic enucleation of very large adenoma.

OBJECTIVE: To analyse the accuracy of high preoperative PSA levels for predicting transitional zone incidental PCa (TZ-PCa) in men with very large prostates. MATERIALS AND METHODS: Perioperative data from 375 consecutive patients who underwent endoscopic enucleation of the prostate (EEP) for benign prostatic obstruction between July 2013 and December 2018 were retrospectively reviewed. Patients were stratified into three groups according to the preoperative PSA level: low-PSA (< 4 ng/mL), intermediate-PSA (4 ≤ PSA < 10 ng/mL) and high-PSA (≥ 10 ng/mL). Men in each group were propensity score matched by age, 5α-reductase inhibitor (5-ARI) use, prostate volume and mpMRI. The TZ-PCa incidence rate was retrospectively compared by preoperative PSA level in a propensity score model including all predetermined variables. RESULTS: Age, prostate volume, 5-ARI use were similar between patient groups. The median PSA levels in the low-, intermediate- and high-PSA groups were 3 [2.3; 3.4], 6.6 [5.3; 8.1] and 12.7 [11; 16.7] ng/mL, respectively. The median prostate volume was > 100 grams in all groups (108, 105 and 120 cc, respectively). The T1a-Gleason 6 incidental TZ-PCa rate was statistically comparable between the three groups (3.4, 5.1 and 8.6% in the low-, intermediate- and high-PSA groups, respectively). The detection rate of clinically significant TZ-PCa was low for preoperative PSA levels > 4 ng/mL (1.7%); with no difference between the intermediate- and high-PSA groups. CONCLUSION: In men with large glands, the clinically significant incidental TZ-PCa detection rate was similar regardless of the preoperative PSA level stratum. Such details may help with patient counselling during BPH surgical management.

Does mechanical morcellation of large glands compromise incidental prostate cancer detection on specimen analysis? A pathological comparison with open simple prostatectomy.

OBJECTIVE: This study sought to compare the incidental prostate cancer (iPCa) detection rate between pathological specimens from green laser enucleation of the prostate (GreenLEP) and open simple prostatectomy (OSP). MATERIALS AND METHODS: In two institutions, the charts of all consecutive patients who underwent OSP between January 2005 and December 2010 were retrospectively reviewed, and the data of all consecutive patients who underwent GreenLEP with tissue morcellation between July 2013 and January 2018 were also collected. Preoperative demographics and pathological findings were recorded. iPCa detection rate was retrospectively compared between the GreenLEP and OSP groups in a propensity score model, including all predetermined variables: Age, preoperative PSA level and prostate volume. RESULTS: Of 738 patients, 402 were included in the propensity-score matching analysis, and they were equally distributed among groups. The overall iPCa detection rates were similar in both groups (9.9% vs. 8.5%; p = 0.73), and there were no statistically significant differences in terms of tumour stage, Gleason score or the rate of clinically significant iPCa, although the number of cassettes analysed was significantly higher in the morcellation group than in the OSP group. No predictive factors for iPCa were identified. CONCLUSIONS: The results of the present study suggest that the mechanical morcellation of large glands had no influence on iPCa detection. Compared with a specimen from standard OSP, a large morcellated tissue sample allows adequate pathological evaluation and does not alter a pathologist's ability to detect iPCa.

Activation of pro-oncogenic pathways in colorectal hyperplastic polyps.

BACKGROUND: In contrast to sessile serrated adenomas and traditional serrated adenomas which are associated with a significant cancer risk, the role of hyperplastic polyps (HP) in colorectal carcinogenesis as well as the molecular mechanisms underlying their development remain controversial and still need to be clarified. Several reports suggest that a subset of HP may represent precursor lesions of some colorectal cancers. However, biomarkers are needed to identify the subset of HP that may have a malignant potential. The hormone precursor, progastrin (PG) has been involved in colon carcinogenesis and is known to activate pro-oncogenic pathways such as the ERK or the STAT3 pathway. We therefore analyzed PG expression and the activation of these signaling factors in HP. METHODS: We retrospectively analyzed PG expression as well as the phosphorylation of ERK and STAT3 by immunohistochemistry in HP from 48 patients. RESULTS: Mean percentages of epithelial cells positive for PG or phospho-ERK were respectively, 31% and 33% in HP and were significantly higher in these lesions compared to normal colon (3%, p=0.0021 and 7%, p=0.0008, respectively). We found a significant correlation between PG and phospho-ERK expression in HP with ERK activation significantly stronger in lesions with high progastrin expression (p=0.015). In contrast, STAT3 was not significantly activated in HP compared to normal colon and we did not observe a significant correlation with PG expression. CONCLUSIONS: HP overexpressing PG that have the highest activation of the ERK pathway might reflect less latent lesions that might have a malignant potential.

[Locally advanced rectal cancer management: which role for the pathologist in 2011?]. / Prise en charge des cancers du rectum localement avancés : quel rôle pour le pathologiste en 2011 ?

Locally advanced rectal cancers mainly correspond to lieberkünhien adenocarcinomas and are defined by T3-T4 lesions with or without regional metastatic lymph nodes. Such tumors benefit from neoadjuvant treatment combining chemotherapy and radiotherapy, followed by surgery with total mesorectum excision. Such a strategy can decrease the rate of local relapse and lead to an easier complementary surgery. The pathologist plays an important role in the management of locally advanced rectal cancer. Indeed, he is involved in the gross examination of the mesorectum excision quality and in the exhaustive sampling of the most informative areas. He also has to perform a precise histopathological analysis, including the determination of the circumferential margin or clearance and the evaluation of tumor regression. All these parameters are major prognostic factors which have to be clearly included in the pathology report. Moreover, the next challenge for the pathologist will be to determine and validate new prognostic and predictive markers, notably by using pre-therapeutic biopsies. The goal of this mini-review is to emphasize the pathologist's role in the different steps of the management of locally advanced rectal cancers and to underline its implication in the determination of potential biomarkers of aggressiveness and response.

Follicular dendritic cell tumor of the spleen associated with diffuse large B-cell lymphoma.

We report the case of a 50-year-old woman with an isolated large mass of the lower pole of the spleen. Splenectomy was performed and revealed a follicular dendritic cell (FDC) tumor associated with diffuse large cell lymphoma. Dendritic cells were CD21(+), CD35(+), CNA42(+), CD20(-), and Epstein-Barr virus (EBV)(+). They contained a clonal EBV genome as shown by polymerase chain reaction analysis of the LMP-1 gene polymorphism. Interestingly, the lymphoma cells were intermingled with the neoplastic FDCs and displayed a germinal center cell phenotype (CD20(+), CD10(+), Bcl2(+), and EBV(-)). Double staining confirmed that EBV was restricted to the FDCs. Clinical, radiologic, and pathologic staging showed no other lymphoma localization. To the best of our knowledge, this association has never been reported. Based on the well-established role of FDCs in B-cell survival and proliferation, this observation suggests that the FDC tumor represented a favorable microenvironment for lymphoma cells with germinal center phenotype.

[Improving practice in breast pathology: 34-months experience of the regional SENOPATH network and webinars as a tool for diagnosis of difficult lesions of the breast]. / Amélioration des pratiques en pathologie mammaire : bilan à 34 mois du groupe régional de relecture SENOPATH et télépathologie pour les lésions de diagnostic difficile.

Pathologists commonly face breast lesions that are difficult to diagnose. To reduce second opinion delay, erase geographical barrier and provide continuing education, we aimed to develop a telepathology-based regional network of pathologists. With the support of ONCOMIP network, we founded a peer-group named SENOPATH, composed of experienced breast pathologists practising in private laboratories, university hospitals or comprehensive cancer center in the region of Midi-Pyrénées in France. Submitted cases are digitalized at the University Hospital, stored in a shared space with a possible access via Internet prior to the SENOPATH sessions. The group meets monthly, via a synchronized webinar and multihead microscope session. A consensual diagnosis and final pathology report is issued for each case, and sent to the referring clinician via the patient medical file securely hosted by ONCOMIP. Between 2012 and 2014, 142 cases were reviewed, for either diagnostic 'routine' difficulty or rare histological type. The SENOPATH group, also regularly called by oncologists to solve difficult cases, has considerably improved the pathologist network in Southern France. Supported by the webinar tool, its educational impact is prominent, with a considerable progress in the region with regards to standardization of pathology processes, literature review and knowledge sharing.

A new biomarker that predicts colonic neoplasia outcome in patients with hyperplastic colonic polyps.

The most frequently occurring lesions in the colon are the hyperplastic polyps. Hyperplastic polyps have long been considered as lesions with no malignant potential and colonoscopy for these patients is not recommended. However, recent works suggest that hyperplastic polyps may represent precursor lesions of some sporadic colorectal cancers. Until now, no biomarker allows to identify the subset of hyperplastic polyps that may have a malignant potential. Because the hormone precursor progastrin has been involved in colon carcinogenesis, we investigated whether its expression in hyperplastic polyps predicts the occurrence of colonic neoplasm after resection of hyperplastic polyps. We retrospectively analyzed progastrin expression in hyperplastic polyps from 74 patients without history of colorectal pathology. In our study, 41% of patients presenting an initial hyperplastic polyp subsequently developed adenomatous polyps, recognized as precursor lesions for colorectal adenocarcinomas. Progastrin was overexpressed in the hyperplastic polyps in 40% of the patients. We showed a significant association between progastrin overexpression and shortened neoplasm-free survival (P = 0.001). Patients with high overexpression of progastrin had a 5-year neoplasm-free survival rate of 38% as compared with 100% for the patients with low progastrin expression. In addition, we established a predictive test on the basis of progastrin staining and patients' age that predicts occurrence of neoplasm after developing a first hyperplastic polyp with a sensitivity of 100% [95% confidence interval (CI), 79%-100%] and a specificity of 74% (51%-90%). We show that progastrin expression evaluation in hyperplastic polyps is an efficient prognostic tool to determine patients with higher risk of metachronous neoplasms who could benefit from an adapted follow-up.