Theranostics of Primary Prostate Cancer: Beyond PSMA and GRP-R.

The imaging of Prostate-Specific Membrane Antigen (PSMA) is now widely used at the initial staging of prostate cancers in patients with a high metastatic risk. However, its ability to detect low-grade tumor lesions is not optimal. METHODS: First, we prospectively performed neurotensin receptor-1 (NTS1) IHC in a series of patients receiving both [68Ga]Ga-PSMA-617 and [68Ga]Ga-RM2 before prostatectomy. In this series, PSMA and GRP-R IHC were also available (n = 16). Next, we aimed at confirming the PSMA/GRP-R/NTS1 expression profile by retrospective autoradiography (n = 46) using a specific radiopharmaceuticals study and also aimed to decipher the expression of less-investigated targets such as NTS2, SST2 and CXCR4. RESULTS: In the IHC study, all samples with negative PSMA staining (two patients with ISUP 2 and one with ISUP 3) were strongly positive for NTS1 staining. No samples were negative for all three stains-for PSMA, GRP-R or NTS1. In the autoradiography study, binding of [111In]In-PSMA-617 was high in all ISUP groups. However, some samples did not bind or bound weakly to [111In]In-PSMA-617 (9%). In these cases, binding of [111n]In-JMV 6659 and [111In]In-JMV 7488 towards NTS1 and NTS2 was high. CONCLUSIONS: Targeting PSMA and NTS1/NTS2 could allow for the detection of all intraprostatic lesions.

Weight-loss with activation of brown fat: Suspect pheochromocytoma.

INTRODUCTION: Excess catecholamine stimulates heat production in brown adipose tissue (BAT). Activation of BAT can be detected in patients presenting pheochromocytoma. CASE STUDY: A 58-year-old female patient sought medical advice due to 13 kg weight loss over 2 years accompanied by sweating and high blood pressure. Thoracic-abdominal-pelvic CT-scan revealed a solid 40 mm mass in the left adrenal compartment with peri-adrenal nodules and a solid 80 mm mass at the lower end of the right kidney. 18FDG-PET scan exhibited intense uptake in the supraclavicular, intercostal, mediastinal, peri-renal, mesenteric, iliac and inguinal spaces. Renal tumor with locoregional infiltration and remote metastases was initially considered. Diagnosis of pheochromocytoma was subsequently confirmed by a 10-fold increase in urinary catecholamine, metanephrine and normetanephrine levels. Left adrenalectomy confirmed the diagnosis of pheochromocytoma, with 3 lymph-node metastases in the adjacent adipose tissue surrounded by brown fat. The patient was clinically asymptomatic with normal blood pressure at 3 months post-surgery. A weight gain of 6 kg was recorded, with normalisation of catecholamines/metanephrine/normetanephrine levels. Bilateral peri-renal infiltration (including the right renal mass) disappeared on CT-scan, and TEP-18-FDG no longer showed hypermetabolism. Recurrent mediastinal metastases were diagnosed 6 months after surgery. CONCLUSION: Brown fat activation may mislead diagnosis of pheochromocytoma, suggesting multi-metastatic extra-adrenal tumor, if clinicians are not aware of it.

Comparison of the radiolabeled PSMA-inhibitor 111In-PSMA-617 and the radiolabeled GRP-R antagonist 111In-RM2 in primary prostate cancer samples.

PURPOSE: Prostate-specific membrane antigen (PSMA) and gastrin-releasing peptide receptor (GRP-R) are expressed in prostate cancer and can be targeted with radiolabeled inhibitors and antagonists. Their performances for the initial characterization of prostatic tumors have been barely evaluated but never compared. We aimed to gather comparative preclinical data of the role of PSMA and GRP-R targeting in prostate cancer. PROCEDURES: We retrospectively studied 20 frozen prostatectomy samples with various metastatic risks of the D'Amico classification. Tissue samples were investigated by tissular microimaging using the radiolabeled PSMA inhibitor 111In-PSMA-617 and the radiolabeled GRP-R antagonist 111In-RM2. Bindings of the two radiopharmaceuticals were compared to histology and clinico-biological data (Gleason score, PSA values, metastatic risks). RESULTS: Binding of 111In-PSMA-617 was high whatever the metastatic risk (p = 0.665), Gleason score (p = 0.555), or PSA value (p = 0.404) while 111In-RM2 exhibited a significantly higher binding in the low metastatic risk group (p = 0.046), in the low PSA value group (p = 0.001), and in samples with Gleason 6 score (p = 0.006). CONCLUSION: PSMA and GRP-R based imaging might have complementary performances for the initial characterization of prostatic tumors. Prospective clinical studies comparing the two tracers in this setting are needed.

Cytological diagnosis of vitreoretinal lymphomas: A case series.

OBJECTIVE: To assess the cytological diagnosis and follow-up of patients suffering from vitreoretinal lymphoma (VRL) diagnosed in our institution. METHODS AND RESULTS: From January 2010 to June 2017, we collected 15 patients with VRL. Twelve patients had diffuse large B-cell lymphoma (DLBCL); of these, 11 had primary central nervous system (CNS) DLBCL, one had ocular localisation of follicular lymphoma, one had extranodal NK/T-cell nasal type lymphoma and one had chronic lymphocytic leukaemia. The results of the cytological examination (cell morphology and immunocytochemistry) of the vitreous fluid were available for 9/15 VRL. The interleukin-10/-6 ratio was >1 in eight of 12 DLBCL. Molecular testing was useful in 6/15 cases (clonality evaluation or MYD88 L265P mutation testing). Eight out of 11 primary CNS DLBCL patients had CNS involvement, with 22-month progression-free survival. In our series, only two out of 11 CNS DLBCL patients died of disease after 2 and 5 years, respectively. CONCLUSIONS: The short delay to assert the diagnosis of VRL could explain the quite good prognosis in our series, which highlights the need to consider a diagnosis of DLBCL as first step. The cytological features, as a reliable way to identify VRL, must always guide the choice of techniques for further investigations given the small amount of vitreous fluid available for analysis.

Refining the risk-stratification of transrectal biopsy-detected prostate cancer by elastic fusion registration transperineal biopsies.

PURPOSE: To evaluate image-guided Transperineal Elastic-Registration biopsy (TPER-B) in the risk-stratification of low-intermediate risk prostate cancer detected by Transrectal-ultrasound biopsy (TRUS-B) when estimates of cancer grade and volume discorded with multiparametric Magnetic Resonance Imaging (MRI). METHODS: All patients referred for active surveillance or organ-conservative management were collegially reviewed for consistency between TRUS-B results and MRI. Image-guided TPER-B of the index target (IT) defined as the largest Prostate Imaging-Reporting Data System-v2 ≥ 3 abnormality was organized for discordant cases. Pathology reported Gleason grade, maximum cancer core length (MCCL) and total CCL (TCCL). RESULTS: Of 237 prostate cancer patients (1-4/2018), 30 were required TPER-B for risk-stratification. Eight cores were obtained [Median and IQR: 8 (6-9)] including six (IQR: 4-6) in the IT. TPER-B of the IT yielded longer MCCL [Mean and (95%CI): 6.9 (5.0-8.8) vs. 2.6 mm (1.9-3.3), p < 0.0001] and TCCL [19.7 (11.6-27.8) vs. 3.6 mm (2.6-4.5), p = 0.0002] than TRUS-B of the gland. On TPER-B cores, longer MCCL [Mean and (95%CI): 8.7 mm (6.7-10.7) vs. 4.1 mm (0.6-7.6), p = 0.002] were measured in Gleason score-7 cancers. TPER-B cores upgraded 13/30 (43.3%) patients. 14/30 (46.7%) met University College London-definition 1 and 18/30 (60.0%) definition 2, which correlate with clinically significant cancers > 0.5 mL and > 0.2 mL, respectively. 7/16 (43.8%) patients under active surveillance were re-allocated toward prostatectomy (n = 5) or radiation therapy (n = 2). In 14 patients not yet assigned, TPER-B risk-stratification spurred the selection (13/14, 92.9%) of treatments with curative intent. CONCLUSION: Image-guided TPER-B of the index target provided more cancer material for pathology. Subsequent re-evaluation of cancer volume and grade switched a majority of patients towards higher-risk groups and treatments with curative intent.

One year of experience using the Paris System for Reporting Urinary Cytology.

BACKGROUND: The Paris System for Reporting Urinary Cytology (TPS) was published in November 2015. It focuses on the diagnosis of high-grade urothelial carcinoma (HGUC) and provides criteria with which to define the category of atypical urothelial cells (AUC). The objective of the current study was to compare two 1-year consecutive periods before and after use of TPS. METHODS: A total of 1634 and 1814 urine cytology cases, respectively, were analyzed before and after use of TPS. Histological diagnosis within 6 months was available for 330 and 299 cases, respectively. RESULTS: After use of TPS, the authors reported significantly fewer low-grade urothelial neoplasms (0.94% vs 1.84%; P<.05) and more cases that were suspicious for HGUC (2.09% vs 0.73%; P<.01) compared with before use of TPS. For the AUC category, there was no significant change in frequency noted for before versus after TPS (6.12% vs 5.18%), whereas the rate of detection of HGUC on histology significantly increased after TPS when compared with before TPS (49.02% vs 28.17%; P<.02). For the HGUC category, neither the frequency (4.69% vs 4.47%) nor the risk of malignancy (89.39% vs 91.04% with HGUC on histology) were found to be significantly different when comparing before and after use of TPS. CONCLUSIONS: In the authors' practice, TPS helped to better characterize the categories of AUC, low-grade urothelial neoplasm, and suspicious for HGUC, which were associated with a higher risk of HGUC compared with the authors' previous classification. Cancer Cytopathol 2018;126:430-6. © 2018 American Cancer Society.

IDEAL 2a Phase II Study of Ultrafocal Brachytherapy for Low- and Intermediate-risk Prostate Cancer.

PURPOSE: Focal therapy of prostate cancer requires precise positioning of therapeutic agents within well-characterized index tumors (ITs). We assessed the feasibility of low-dose-rate ultrafocal brachytherapy. METHODS AND MATERIALS: The present study was an institutional review board-approved European Clinical Trials Database-registered phase II protocol. Patients referred (October 2013 to August 2016) for active surveillance (prostate-specific antigen <10 ng/mL, cT1c-cT2a, Gleason score on referring biopsy specimens ≤6 (3+3), ≤3 positive biopsy cores, ≤50% of cancer) were preselected. Inclusion was confirmed when complementary image-guided biopsy findings informed a single Prostate Imaging Reporting and Data System (PI-RADS) ≥3, Gleason score ≤7a (3+4) lesion. A ultrasound-visible ancillary marker was positioned within the IT using a magnetic resonance imaging (MRI)/3-dimensional transrectal ultrasound (TRUS) elastic fusion-guided system (Koelis). Ultrafocal transperineal delivery of 125I seeds used classic 2-dimensional TRUS (Bard-FlexFocus) and dose optimization (Variseed Treatment Planning System). Following Simon's optimal design, 17 patients were required to assess the feasibility of delivering ≥95% of the prescribed dose (160 Gy) to the IT (primary objective). Adverse events (Common Terminology Criteria for Adverse Events) and quality of life (5-item International Index of Erectile Function, International Prostate Symptom Score) were recorded. One-year control biopsy specimens were obtained from the IT and untreated segments. RESULTS: Of the 44 preselected patients, 27 did not meet the inclusion criteria. Of the 17 ultrafocal brachytherapy-treated patients, 16 met the primary objective (per protocol success). The prescription dose was delivered to 14.5% ± 6.4% of the prostate volume, resulting in negligible urethral and rectal irradiation and toxicity. No recurrence was evidenced on the 1-year follow-up MRI studies or IT biopsy specimens. Seven nonclinically significant cancers and one Gleason score 7a (3+4) cancer (salvage prostatectomy) were observed in the untreated parenchyma. CONCLUSIONS: Recent technology has allowed for selective and effective brachytherapy of small MRI targets.

[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.

[Micro-invasive vulvar Paget's disease and lymph node metastasis: a same disease?]. / Maladie de Paget vulvaire micro-invasive et métastase ganglionnaire : une même maladie ?

Vulvar Paget's disease is sub-classified into three types based upon its origin. It might be a primary vulvar disease (type 1) or associated with a non-cutaneous adenocarcinoma-rectal, colonic, cervical (type 2) or linked with an urothelial neoplasia (type 3). Type 1lesions must be considered as potentially invasive. Their immunophenotype is CK7+/CK20-. Classically, in case of depth of invasion below 1mm, nodal metastases are exceptional. We report a case of type 1 Paget's disease in a postmenopausal woman with superficial invasion and multiple inguinal nodal metastases.

[Vaginal adenoid cystic carcinoma: a case report]. / Carcinome adénoïde kystique vaginal: à propos d'un cas.

Adenoid cystic carcinoma generally arises from the salivary glands and is rarely found in the female genital tract. Infection with HPV is implicated in this cervical lesion. Differential diagnosis includes adenoid basal carcinoma, polymorphous low-grade adenocarcinoma and basaloid squamous cell carcinoma. Only one case of vaginal localisation was previously described. We report a case of adenoid cystic carcinoma in a 48-year-old woman with previous cervical HPV infection. Histological examination revealed nests of cells with peripheral palisading organisation and glandular lumina containing material produced by the tumor cells.