Multiple Core Biopsies Research Articles

Two cases of breast pseudoaneurysm following core biopsy: A very rare complication with different treatment options

Introduction: Breast pseudoaneurysm is a rare complication following breast interventional procedures such as core biopsies and vacuum-assisted biopsies. The occurrence of pseudoaneurysm increases with the conditions of increased breast vascularity like cancer, pregnancy and lactation. Case Report: We present two cases of pseudoaneurysm formation secondary to core biopsies of the breasts. The first patient was an 82-year-old female patient who presented with breast swelling and bruising after multiple clinical core biopsies of the left breast. Our second patient was a 47-year-old lady who presented with a palpable lump following ultrasound-guided core biopsies of the left breast. Ultrasound showed hypoechoic pulsating area with evidence of internal colour flow in connection with a vessel in both cases. Imaging appearances were in keeping with a pseudoaneurysm of the breast. Discussion: Most pseudoaneurysms are secondary to interventional procedures in the breast. Common clinical presentation is a pulsatile, palpable mass at the biopsy site soon after the biopsy or later. On B mode imaging, it presents as a well-circumscribed mass of mixed echogenicity. Typical waveform in spectral Doppler and ‘yin-yang’ sign in colour Doppler is demonstrated with a turbulent internal flow. There are different treatment options to manage pseudoaneurysms of the breast. Conclusion: Pseudoaneurysm of the breast should be considered if a patient presents with a breast mass/lump close to a recent biopsy site. On clinical examination, pulsatility of the mass should raise the suspicion and definite diagnosis can be made with spectral and colour Doppler US scan.

Multiregion sampling of de novo metastatic prostate cancer reveals complex polyclonality and augments clinical genotyping.

De novo metastatic prostate cancer is highly aggressive, but the paucity of routinely collected tissue has hindered genomic stratification and precision oncology. Here, we leveraged a rare study of surgical intervention in 43 de novo metastatic prostate cancers to assess somatic genotypes across 607 synchronous primary and metastatic tissue regions plus circulating tumor DNA. Intra-prostate heterogeneity was pervasive and impacted clinically relevant genes, resulting in discordant genotypes between select primary restricted regions and synchronous metastases. Additional complexity was driven by polyclonal metastatic seeding from phylogenetically related primary populations. When simulating clinical practice relying on a single tissue region, genomic heterogeneity plus variable tumor fraction across samples caused inaccurate genotyping of dominant disease; however, pooling extracted DNA from multiple biopsy cores before sequencing can rescue misassigned somatic genotypes. Our results define the relationship between synchronous treatment-sensitive primary and metastatic lesions in men with de novo metastatic prostate cancer and provide a framework for implementing genomics-guided patient management.

Oncodrivers for Immunotherapies in Triple-Negative Breast Cancer

Breast Cancer: Breast CancerMany advances have been made in therapies for patients having breast cancer driven by the estrogen receptor, the progesterone receptor, or the human epidermal growth factor 2 receptor (HER2). However, for patients with breast cancer not driven by any of these mechanisms, the disease, termed triple-negative, is characterized by an aggressive clinical course with poor patient outcomes. In a recent poster presented at the AACR Annual Meeting 2023, Saurabh K. Garg, PhD, a research scientist in the Czerniecki Lab at Moffitt Cancer Center, presented data from a retrospective study of triple-negative breast cancer patients who had undergone surgery at the Moffitt Cancer Center between January 2010 and February 2019 (Abstract 962). “Our team at the Czerniecki Lab and Moffitt Breast Clinic utilizes the power of dendritic cells, the primary antigen-presenting cells of the body, to present major histocompatibility complex Class II antigens from tumor-associated oncodrivers to prime the immune response against breast cancer,” Garg noted. “In our clinical trials, we are seeing a robust targeted response with dendritic cell-based therapies in HER2-positive breast cancer. This prompted us to identify immunogenic oncodrivers to develop targeted immunotherapies for triple-negative breast cancer, which accounts for 15-20 percent of breast cancer cases and presents as a more aggressive disease, with poor outcomes from current standard-of-care treatment options.” Regarding their study, Garg noted, “This is an institutional review board-approved, single institution retrospective study of 90 patients with triple-negative breast cancer who have undergone standard of care at Moffitt Cancer Center between January 2010 and February 2019. “Surgical biopsy tissue blocks of various stages, along with patient outcome data, were available to perform this downstream analysis,” he stated. “We utilized multiplex tissue microarray analyses, where multiple tissue core biopsies are arranged on a single slide for this immunofluorescence assay,” Garg explained. The tissue microarray analyses were divided into two panels: one for the oncodrivers and the other for tumor-infiltrating lymphocytes. In the first panel, “the expression of three oncodrivers: MET (MET proto-oncogene, receptor tyrosine kinase), EGFR (epidermal growth factor receptor), and HER3 (erb-b2 receptor tyrosine kinase 3) on surgical tissue blocks was scored by tumor microarray analysis,” Garg explained. “We also performed a second tissue microarray analysis to examine tumor-infiltrating lymphocytes expressing CD4, CD8, CD20, CD45, and CD56,” Garg noted about the second panel. “Subsequently, we correlated the expression of oncodrivers with patient outcome data and lymphocyte infiltration to catalog the immunogenicity of MET, EGFR, and HER-3 expression in triple-negative breast cancer settings.” Research Results When queried as to their findings, Dr. Garg answered, “The main finding of this study is that high expression of MET, EGFR, and HER3 correlated with higher occurrence of CD4, CD8, and CD45, respectively. This provided us invaluable information, indicating that these tumor-driving proteins have immunogenic potential to recruit lymphocytes to the tumor site, which could be harnessed to design targeted immunotherapies.” In addition, the elevated expression of HER3 was observed in the samples obtained from chemotherapy-treated patients, possibly implying a role in disease resistance. Interestingly, there was no correlation of prognoses with increased expression levels of the oncodrivers explored in this study. Another relevant observation was that better survival was observed in patients who had intermediate expression levels for EGFR with higher numbers of activated tumor-infiltrating lymphocytes. Future Directions “The present study provided a perfect segue for future targeted therapies that will be further developed and utilized in the clinic for triple-negative breast cancer patients,” Garg noted. “The identification of these immunogenic oncodrivers for triple-negative breast cancer will assist researchers at Moffitt and all over the world to target them with innovative therapies. “The next step in this study will be to identify the immunogenic regions of MET and EGFR proteins using our in-house peptide screening pipeline,” he stated. “This pipeline utilizes pre-clinical investigative tools to screen immunogenic major histocompatibility complex class II peptides to design dendritic cell-based cancer immunotherapies. Once identified and produced, we will test the efficacy of these treatments utilizing murine models of triple-negative breast cancer. “Furthermore, we have already performed peptide screening for the HER3 protein and have validated it in murine models of triple-negative breast cancer,” Garg said. “This HER3-based dendritic cell immunotherapy has been translated to a clinical trial, which is now underway at Moffitt for triple-negative breast cancer patients. Overall, successful completion of the pre-clinical translational research on all three triple-negative breast cancer oncodrivers will open the door for them to be incorporated in future dendritic cell immunotherapy clinical trials at the Moffitt Cancer Center with the potential of making significant improvements to the current triple-negative breast cancer standard of care and patient outcomes.” Richard Simoneaux is a contributing writer.

Among Multiple Needle Core Biopsy Samples, the One with the Highest Tumor Proportion Score Best Represents the PD-L1 Status of the Whole Surgical Specimen in Non-Small Cell Lung Cancer.

The heterogeneity of programmed death-ligand 1 (PD-L1) status between core needle biopsies (CNBs) from one tumor has not been well studied before. The current study attempts to find out the best index using multiple core biopsies from one tumor which can better reflect the actual PD-L1 status. Random CNB was performed in surgical specimens from 170 consecutive non-small cell lung cancer samples. Fifty-one cases (41 cases with PD-L1 positive and 10 cases with PD-L1 negative) and 216 matched CNBs were analyzed by DAKO 22C3 PharmDx Link 48 Autostainer. The PD-L1 status was compared between the surgical specimens and matched CNBs. Heterogeneity of PD-L1 status between CNBs from one tumor was observed in 56% of PD-L1 positive cases. Different tumor proportion score (TPS) statistical forms with regard to the highest, mean, median, weighted average TPS, as well as TPS showed by the longest biopsy specimen and the biopsy with most tumor volume were compared. At a cut-off of 1%, the concordance rates were 94.1%, 88.2%, 90.2%, 86.3%, 86.3%, and 86.3%; At a cut-off of 50%, the concordance rates were 92.2%, 86.3%, 84.3%, 82.4%, 82.4%, and 86.3%, respectively. The CNB with the highest TPS can best represent PD-L1 status estimated by whole surgical specimen. The highest TPS among the multiple biopsies is a robust evaluation of the PD-L1 status, but not mean TPS, at the 1% and 50% cut-offs.

A Hybrid Human-Machine Learning Approach for Screening Prostate Biopsies Can Improve Clinical Efficiency Without Compromising Diagnostic Accuracy.

Prostate cancer is a common malignancy, and accurate diagnosis typically requires histologic review of multiple prostate core biopsies per patient. As pathology volumes and complexity increase, new tools to improve the efficiency of everyday practice are keenly needed. Deep learning has shown promise in pathology diagnostics, but most studies silo the efforts of pathologists from the application of deep learning algorithms. Very few hybrid pathologist-deep learning approaches have been explored, and these typically require complete review of histologic slides by both the pathologist and the deep learning system. To develop a novel and efficient hybrid human-machine learning approach to screen prostate biopsies. We developed an algorithm to determine the 20 regions of interest with the highest probability of malignancy for each prostate biopsy; presenting these regions to a pathologist for manual screening limited the initial review by a pathologist to approximately 2% of the tissue area of each sample. We evaluated this approach by using 100 biopsies (29 malignant, 60 benign, 11 other) that were reviewed by 4 pathologists (3 urologic pathologists, 1 general pathologist) using a custom-designed graphical user interface. Malignant biopsies were correctly identified as needing comprehensive review with high sensitivity (mean, 99.2% among all pathologists); conversely, most benign prostate biopsies (mean, 72.1%) were correctly identified as needing no further review. This novel hybrid system has the potential to efficiently triage out most benign prostate core biopsies, conserving time for the pathologist to dedicate to detailed evaluation of malignant biopsies.

Utility of multiple core biopsies during transperineal template-guided mapping biopsy for patients with large prostates and PI-RADS 1-2 on multiparametric magnetic resonance imaging.

BackgroundWe investigated the necessity of multiple core biopsies when performing transperineal template-guided mapping biopsy (TTMB) for patients with large prostates and no suspicious lesions on multiparametric magnetic resonance imaging (mpMRI).Materials and methodsWe retrospectively analyzed 304 patients on active surveillance (AS), 212 patients with previously negative transrectal ultrasound-guided biopsy (TRUS-Bx) and 67 biopsy naïve patients who underwent TTMB between May 2017 and December 2020. The number of core biopsies and acute urinary retention (AUR) rates were analyzed in relation to the prostate volume (PV). Cancer detection rate according to the prostate volume and Prostate Imaging-Reporting and Data System (PI-RADS) scores were compared using the Pearson Chi-square test.ResultsAUR occurred more frequently in patients with PV over 39 cc (5.5% vs. 24.4%, P < 0.001). In addition, incidence of AUR was more in patients with PV over 39 cc and PI-RADS score of 1–2 on mpMRI (3.7% vs. 22.2%, P < 0.001). There was no significant difference in the detection rates of any prostate cancer or clinically significant prostate cancer (csPCA) between the patients on AS with PV < 39 cc and PV ≥ 39 cc and PI-RADS score 1–2 (57.4% vs. 50%, P = 0.507; 17% vs. 8.8%, P = 0.412, respectively). Additionally, no significant difference was found in the detection rates of any prostate cancer or csPCA between the patients with PV < 39 cc and PV ≥ 39 cc and PI-RADS score 1–2 who either had a previously negative TRUS-Bx or were biopsy naïve (27.9% vs. 16.2%, P = 0.101, 8.2% vs. 4.1%, P = 0.31, respectively).ConclusionIncreasing the number of core biopsies of prostates measuring ≥39 cc with PI-RADS 1–2 on mpMRI does not significantly increase the detection rates of any prostate cancer or csPCA.

Cognitively targeted transperineal prostate biopsy in patients with previous abdominoperineal excision of the rectum

Introduction: Prostate biopsy is performed using an ultrasound probe placed in the rectum with either a transrectal or, increasingly popular, transperineal approach. This is not possible in patients with abdominoperineal excision of the rectum due to the lack of rectum. In our case series, we present a technique for prostate biopsy in this cohort and our outcomes. Method: The study population consisted of three consecutive patients who presented to our institution between 2018–2019 with an elevated level of prostate-specific antigen, a history of abdominoperineal excision of the rectum and undergone multiparametric magnetic resonance imaging of the prostate at our institution before a biopsy. Transperineal prostate biopsies were performed under general anaesthesia using a curved uniplanar ultrasound transducer with an attached guide to stabilise the needle. Free-hand biopsies were taken using an 18-gauge biopsy needle with an automatic spring-driven device. Multiple biopsy cores were directed to multiparametric magnetic resonance imaging target areas by visual registration. Results: Three men with a median age of 69 years (range 68–75 years) were included in this case series with serum index prostate-specific antigen values between 6.5–14 ng/ml. All three patients had Prostate Imaging Reporting and Data System 5 lesions identified on multiparametric magnetic resonance imaging scans. All three men were diagnosed with clinically significant prostate cancer (&gt;Gleason grade group 2). On average, 13 biopsy cores (range: 12–15) were obtained with a median core length of 9 mm (range: 6–20 mm). All patients were discharged home on the day of the procedure and had none had postoperative complications. Conclusion: The use of multiparametric magnetic resonance imaging and cognitive targeted transperineal biopsy provides an option for diagnosing prostate cancer in this challenging group of patients. Level of evidence: 4

Augmented Reality-Assisted Biopsy of Soft Tissue Lesions.

Guided biopsy of soft tissue lesions can be challenging in the presence of sensitive organs or when the lesion itself is small. Computed tomography (CT) is the most frequently used modality to target soft tissue lesions. In order to aid physicians, small field of view (FOV) low dose non-contrast CT volumes are acquired prior to intervention while the patient is on the procedure table to localize the lesion and plan the best approach. However, patient motion between the end of the scan and the start of the biopsy procedure can make it difficult for a physician to translate the lesion location from the CT onto the patient body, especially for a deep-seated lesion. In addition, the needle should be managed well in three-dimensional trajectories in order to reach the lesion and avoid vital structures. This is especially challenging for less experienced interventionists. These usually result in multiple additional image acquisitions during the course of procedure to ensure accurate needle placement, especially when multiple core biopsies are required. In this work, we present an augmented reality (AR)-guided biopsy system and procedure for soft tissue and lung lesions and quantify the results using a phantom study. We found an average error of 0.75 cm from the center of the lesion when AR guidance was used, compared to an error of 1.52 cm from the center of the lesion during unguided biopsy for soft tissue lesions while upon testing the system on lung lesions, an average error of 0.62 cm from the center of the tumor while using AR guidance versus a 1.12 cm error while relying on unguided biopsies. The AR-guided system is able to improve the accuracy and could be useful in the clinical application.

Adverse reaction regarding titanium-based marker clip: case report of a potential complication.

Adverse reaction to titanium-based breast marker clip is a very uncommon complication in medicine. We report a 65-year-old female patient who was referred with left breast lumpiness to the assessment clinic. Breast radiology with interesting sequelae following titanium clip insertion, in combination with literature review, will be discussed. The patient had a history of adverse skin reactions to base metals. However, no allergy specifically to titanium was reported. Imaging findings with regard to the symptomatic breast were nonspecific; thus, multiple core biopsies were taken, and titanium clip was inserted. Subsequent histological examination showed benign changes. However, 7 weeks later, the marked area became very tender and the same patient re-presented to the clinic, requesting removal of the metallic component. Following multidisciplinary meetings and discussions, the person underwent ultrasound-guided vacuum biopsy and the clip was removed. The symptoms completely resolved after the successful procedure, and histological examination revealed lymphocytic infiltration of the tissues. Reactions to titanium-based marker clips are rare and only limited records have been found in the literature. More cases need to be reported in order to establish the full significance of such adverse sequelae. It is recommended that medical history with regard to allergies, prior titanium clip insertions, should be discussed.

Impact of a dominant intraprostatic lesion (DIL) boost defined by sextant biopsy in permanent I-125 prostate implants on biochemical disease free survival (bDFS) and toxicity outcomes

Background and purposeTo compare bDFS and toxicity outcomes in a population of intermediate risk prostate cancer patients treated using I-125 LDR brachytherapy with or without DIL boost based on multiple core biopsy maps. Materials and methodsBetween January 2005 and December 2013, all our intermediate risk prostate cancer patients treated with LDR I-125 brachytherapy were reviewed. All patients were given 144 Gy to the prostate. A pathologic DIL distribution (defined by sextant biopsy) was contoured prospectively prior to planning, to be covered by the 150% isodose line. Of the 165 patients treated, 55 received a DIL boost. Patients completed prospectively the IPSS questionnaire, a sexual and bowel function questionnaire. Gastro-intestinal toxicities were graded according to CTCAE v4.03. A patient was considered to have erectile dysfunction if he was unable to achieve erection to perform intercourse. BDFS was determined according to the Phoenix consensus definitions. ResultsThe median follow-up was 78 months. The estimated 7-year bDFS rate was 96% (95% CI, 74–99%) in the DIL group versus 89% (95% CI, 79–94%) in the control group (p = 0.188). There was no difference between groups in urinary, gastro-intestinal or sexual toxicities up to 5 years of follow-up. There was no difference in urinary obstruction with catheterization between DIL versus control groups (3,6 vs 2,8 %, p = 1.00). Only 1 patient in the DIL group had ≥grade 3 toxicity (TURP) and none in the control group. ConclusionsBoost to DIL defined by sextant biopsy with permanent seed prostate implant shows a trend toward improvement of biochemical control in intermediate risk prostate cancer patient without increasing toxicity.

Accuracy of core biopsy in predicting pathologic complete response in the breast in patients with complete/near complete clinical and radiological response (Complete Responders in the Breast – CRBr) – Trial design and conduct

IntroductionWith the advent of taxanes and targeted agents in neoadjuvant chemotherapy (NACT) for breast cancer, the rates of pathologic complete response (pCR) have been steadily increasing. One of the roles of surgery in these women is to serve as a biopsy to confirm or negate a pCR. DesignThis is a prospective validation study. All newly diagnosed non-metastatic breast cancers, of any luminal subtype, planned for neoadjuvant chemotherapy (NACT) with a titanium clip placed in the tumor, will be screened. Eligible patients who have a complete/near complete response to NACT as seen on a mammogram and ultrasound of the breast, will undergo multiple core biopsies of the tumor bed under ultrasound guidance as an outpatient procedure. A minimum of four core biopsy specimens will be mandatory. An MRI will also be done for these patients for documentation and analysis. The core biopsy will be compared to the final histopathology report after definitive surgery. ObjectivesThe objective is to study the false negative rate and accuracy of ultrasound guided core biopsies of the tumor bed in predicting pCR. Additionally, the correlation of pCR in the breast with axillary response and the incremental benefit of an MRI in predicting pCR will be evaluated. DiscussionThe concept of using image guided core biopsies to predict pCR could be useful in designing future studies aimed at avoiding redundant surgery in women with a complete response to NACT. This study is registered with Clinical Trials Registry of India (CTRI/2018/01/011122).

Can a Dominant Intraprostatic Lesion (DIL) Boost with Permanent I-125 Prostate Implants, Altered Outcomes and Improve Biochemical Disease-Free Survival (bDFS) in Intermediate Risk Prostate Cancer?

To compare bDFS and toxicity outcomes in population of intermediate risk prostate cancer patients treated using I-125 LDR brachytherapy with or without DIL boost based on multiple core biopsy maps.

Multi-quadrant biopsy technique improves diagnostic ability in large heterogeneous renal masses. Abel EJ, Heckman JE, Hinshaw L, Best S, Lubner M, Jarrard DF, Downs TM, Nakada SY, Lee FT Jr, Huang W, Ziemlewicz T.J Urol. 2015 Oct;194(4):886-91. [Epub 2015 Mar 30]. doi: 10.1016/j.juro.2015.03.106.

PurposePercutaneous biopsy obtained from a single location is prone to sampling error in large heterogeneous renal masses, leading to nondiagnostic results or failure to detect poor prognostic features. We evaluated the accuracy of percutaneous biopsy for large renal masses using a modified multi-quadrant technique vs. a standard biopsy technique. Materials and methodsClinical and pathological data for all patients with cT2 or greater renal masses who underwent percutaneous biopsy from 2009 to 2014 were reviewed. The multi-quadrant technique was defined as multiple core biopsies from at least 4 separate solid enhancing areas in the tumor. The incidence of nondiagnostic findings, sarcomatoid features and procedural complications was recorded, and concordance between biopsy specimens and nephrectomy pathology was compared. ResultsA total of 122 biopsies were performed for 117 tumors in 116 patients (46 using the standard biopsy technique and 76 using the multi-quadrant technique). Median tumor size was 10cm (IQR: 8–12). Biopsy was nondiagnostic in 5 of 46 (10.9%) standard and 0 of 76 (0%) multi-quadrant biopsies (P = 0.007). Renal cell carcinoma was identified in 96 of 115 (82.0%) tumors and nonrenal cell carcinoma tumors were identified in 21 (18.0%). One complication occurred using the standard biopsy technique and no complications were reported using the multi-quadrant technique. Sarcomatoid features were present in 23 of 96 (23.9%) large renal cell carcinomas studied. Sensitivity for identifying sarcomatoid features was higher using the multi-quadrant technique compared to the standard biopsy technique at 13 of 15 (86.7%) vs. 2 of 8 (25.0%) (P = 0.0062). ConclusionsThe multi-quadrant percutaneous biopsy technique increases the ability to identify aggressive pathological features in large renal tumors and decreases nondiagnostic biopsy rates.

Clinical features, histology, and histogenesis of combined hepatocellular-cholangiocarcinoma

Combined hepatocellular-cholangiocarcinoma (CHC) is a rare tumor with poor prognosis, with incidence ranging from 1.0%-4.7% of all primary hepatic tumors. This entity will be soon renamed as hepato-cholangiocarcinoma. The known risk factors for hepatocellular carcinoma (HCC) have been implicated for CHC including viral hepatitis and cirrhosis. It is difficult to diagnose this tumor pre-operatively. The predominant histologic component within the tumor largely determines the predominant radiographic features making it a difficult distinction. Heterogeneous and overlapping imaging features of HCC and cholangiocarcinoma should raise the suspicion for CHC and multiple core biopsies (from different areas of tumor) are recommended before administering treatment. Serum tumor markers CA19-9 and alpha-fetoprotein can aid in the diagnosis, but it remains a challenging diagnosis prior to resection. There is sufficient data to support bipotent hepatic progenitor cells as the cell of origin for CHC. The current World Health Organization classification categorizes two main types of CHC based on histo-morphological features: Classical type and CHC with stem cell features. Liver transplant is one of the available treatment modalities with other management options including transarterial chemoembolization, radiofrequency ablation, and percutaneous ethanol injection. We present a review paper on CHC highlighting the risk factors, origin, histological classification and therapeutic modalities.

MP35-17 MULTI-QUADRANT BIOPSY TECHNIQUE DECREASES SAMPLING ERROR IN LARGE HETEROGENEOUS RENAL TUMORS

You have accessJournal of UrologyKidney Cancer: Evaluation and Staging I1 Apr 2015MP35-17 MULTI-QUADRANT BIOPSY TECHNIQUE DECREASES SAMPLING ERROR IN LARGE HETEROGENEOUS RENAL TUMORS Jennifer E. Heckman, Timothy Ziemlewicz, Sara Best, Meghan Lubner, Louis Hinshaw, David F. Jarrard, Tracy Downs, Wei Huang, Fred T. Lee, Stephen Y. Nakada, and E. Jason Abel Jennifer E. HeckmanJennifer E. Heckman More articles by this author , Timothy ZiemlewiczTimothy Ziemlewicz More articles by this author , Sara BestSara Best More articles by this author , Meghan LubnerMeghan Lubner More articles by this author , Louis HinshawLouis Hinshaw More articles by this author , David F. JarrardDavid F. Jarrard More articles by this author , Tracy DownsTracy Downs More articles by this author , Wei HuangWei Huang More articles by this author , Fred T. LeeFred T. Lee More articles by this author , Stephen Y. NakadaStephen Y. Nakada More articles by this author , and E. Jason AbelE. Jason Abel More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2015.02.1118AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Standard percutaneous renal mass biopsy is prone to sampling error in large heterogeneous renal masses, which increases the risk for non-diagnostic results or failure to detect poor prognostic features. The purpose of this study was to compare the accuracy of percutaneous biopsy for large renal masses using a modified multi-quadrant technique (qBx) to standard biopsy technique. METHODS Clinical and pathologic data for all patients with ≥ cT2 renal masses who received percutaneous biopsy using standard or modified techniques at a single institution over a five year period (2009 – 2014) were reviewed with IRB approval. The qBx technique includes multiple core biopsies from at least four separate, solid enhancing areas within the tumor. Standard technique obtained core samples from < 4 areas within the tumor. An expert genitourinary pathologist (WH) performed a blinded review of each biopsy core. RESULTS In patients with ≥ cT2 renal masses, 110 biopsies were performed in 105 patients (45 standard technique and 65 qBx). Mean clinical tumor size was 10 cm (IQR 8-13). Biopsy was non-diagnostic in 5/45 (11.1%) standard and 0/65 (0%) qBx. Nephrectomy was performed after 66 biopsies (21 standard and 45 qBx). When comparing the concordance of biopsy pathology to nephrectomy specimens, biopsy correctly predicted the type of renal neoplasm in 17/18 (94.4%) standard biopsies and 45/45 (100%) qBx. In 57 RCC tumors, grade was assigned for both biopsy and nephrectomy specimens. Tumor grade was concordant in 2/14 (14.3%) of standard biopsies and 27/43 (62.8%) qBx. Sarcomatoid de-differentiation was identified in 16/88 (18.2%) of large RCC tumors studied. Sarcomatoid features were identified from biopsy in 10/16 (62.5%) tumors. The ability to identifying sarcomatoid features was higher using multi-quadrant technique compared to the standard technique, 8/10 (80.0%) vs 2/6 (33.3%). One patient who had a biopsy using the standard technique required hospital admission for hemorrhage. No complications were reported in patients when using the qBx technique. CONCLUSIONS Multi-quadrant biopsy technique increases diagnostic accuracy in large renal tumors. © 2015 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 193Issue 4SApril 2015Page: e426 Advertisement Copyright & Permissions© 2015 by American Urological Association Education and Research, Inc.MetricsAuthor Information Jennifer E. Heckman More articles by this author Timothy Ziemlewicz More articles by this author Sara Best More articles by this author Meghan Lubner More articles by this author Louis Hinshaw More articles by this author David F. Jarrard More articles by this author Tracy Downs More articles by this author Wei Huang More articles by this author Fred T. Lee More articles by this author Stephen Y. Nakada More articles by this author E. Jason Abel More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Multi-Quadrant Biopsy Technique Improves Diagnostic Ability in Large Heterogeneous Renal Masses

Percutaneous biopsy obtained from a single location is prone to sampling error in large heterogeneous renal masses, leading to nondiagnostic results or failure to detect poor prognostic features. We evaluated the accuracy of percutaneous biopsy for large renal masses using a modified multi-quadrant technique vs a standard biopsy technique. Clinical and pathological data for all patients with cT2 or greater renal masses who underwent percutaneous biopsy from 2009 to 2014 were reviewed. The multi-quadrant technique was defined as multiple core biopsies from at least 4 separate solid enhancing areas in the tumor. The incidence of nondiagnostic findings, sarcomatoid features and procedural complications was recorded, and concordance between biopsy specimens and nephrectomy pathology was compared. A total of 122 biopsies were performed for 117 tumors in 116 patients (46using the standard biopsy technique and 76 using the multi-quadrant technique). Median tumor size was 10 cm (IQR 8-12). Biopsy was nondiagnostic in 5 of 46 (10.9%) standard and 0 of 76 (0%) multi-quadrant biopsies (p=0.007). Renal cell carcinoma was identified in 96 of 115 (82.0%) tumors and nonrenal cell carcinoma tumors were identified in 21 (18.0%). One complication occurred using the standard biopsy technique and no complications were reported using the multi-quadrant technique. Sarcomatoid features were present in 23 of 96 (23.9%) large renal cell carcinomas studied. Sensitivity for identifying sarcomatoid features was higher using the multi-quadrant technique compared to the standard biopsy technique at 13 of 15 (86.7%) vs 2 of 8 (25.0%) (p=0.0062). The multi-quadrant percutaneous biopsy technique increases the ability to identify aggressive pathological features in large renal tumors and decreases nondiagnostic biopsy rates.

Heterogeneity of PTEN and ERG expression in prostate cancer on core needle biopsies: implications for cancer risk stratification and biomarker sampling.

ERG and PTEN biomarkers are increasingly being analyzed on prostate core biopsies (NBXs); ERG as a marker of clonality and number of separately arising tumor foci and PTEN for prognostic information. Yet, in patients with multiple biopsy cores positive for cancer (PCa), there is no standardized approach for interrogation of these biomarkers in terms of the number of positive cores to evaluate. A total of 194 NBX cases containing more than one positive core with cancer were evaluated for ERG overexpression and PTEN loss by immunostaining (immunohistochemistry) of all positive cores. ERG overexpression or PTEN loss in at least one cancer core was present in 111 (57%) and 69 (36%) cases respectively. ERG overexpression was significantly associated with PTEN loss (P < .0001), and PTEN loss was associated with a high Gleason score (P < .0001). Inter- and intra-tumor core staining heterogeneity for ERG overexpression occurred in 42% and 5% cases and for PTEN loss both intra- and inter-tumor core heterogeneity was 68%. PTEN staining was highly discordant between PCa sites regardless of laterality. When the Gleason score was non-uniform across PCa sites, the combination of cores showing the highest Gleason score and largest tumor volume provided the best representation of ERG overexpression (92%) and PTEN loss (98%). When grades were uniform across cancer sites, the highest tumor volume core was generally representative of ERG overexpression (90%) but was less representative for PTEN loss (76%). Our results suggest that knowledge of this heterogeneity is critical for developing optimal yet cost-effective strategies to identify these underlying molecular abnormalities.

Precise preoperative localization of prostate cancer employing 12-core needle biopsy with a tissue-marking method for effective surgical strategy.

Prostate needle biopsy plays a pivotal role not only in the diagnosis but also the management of patients with prostate cancer. Prostate cancer is often multifocal and diagnosis of the lesion could therefore be difficult with diagnostic imaging only; thus, multiple core biopsies are taken from several different regions of the prostate. In current practice, 10- or 12-core needle biopsy is considered the clinical standard. Several techniques have been reported to improve the orientation of the specimens, but tissue marking, which could theoretically provide important information on the location of the lesion in the prostate, has been rarely reported. Therefore, in this study, we evaluated the clinical significance of systematic 12-core needle biopsy with tissue marking for preoperative prediction of lesion sites and clinicopathological features of patients. We evaluated 93 patients who underwent 12-core prostate biopsy and subsequent radical prostatectomy. We correlated the biopsy results to the prostate sites in which biopsies were performed and prognostic factors of the patients, especially the degree of extraprostatic extension (EPE) obtained in surgical specimens. Among 253 cancer foci detected in 93 prostatectomy specimens, 168 (66.4%) foci were detected by biopsy. All patients had proven cancer. EPE-positive cancers were associated with a larger number of positive cores, larger tumor length, and higher percentage of cancer tissue in the corresponding cores. Systematic 12-core prostate biopsy with tissue marking is useful for preoperative detection of cancer foci and provides valuable information that enables effective surgical strategies.

Abstract 2233: Rearrangement of ERG and CHD1 genes in prostate cancer as a marker of tumor heterogeneity

Abstract Efforts to develop targeted therapy based on genomic findings are complicated by the polygenic nature of drug resistance and genetic heterogeneity between separate biopsy cores. These findings have led to the conclusion that analysis of multiple biopsy cores and consideration of multiple targeted agents will be important. Because of our concern that these assessments may be missing an additional layer of heterogeneity within even a single biopsy core, which sequencing alone may not identify, we studied the genetic heterogeneity of cells in focal areas using TMA. Using confocal microscopy, we analyzed the most common and prostate cancer specific gene rearrangement (TMPRSS2-ERG fusion and CHD1 deletion) in neighboring single cells in a tumor focus without changing the stromal microenvironment. We evaluated 56 patients that underwent radical prostatectomy at CINJ with pathological assessment, grading, and ERG rearrangement status. Overall, ERG rearrangements occurred in 24/56 (42.9%) patients. The most frequent mechanism of rearrangements was deletion (58%), while a split event was confirmed in 25% of the ERG-rearranged cases. In 88% of cases the ERG rearrangement was associated with TMPRSS2-ERG gene fusion. A copy number gain of the non-rearranged ERG gene occurred in 10/56 (17.6%) cases. A heterogeneous mix of ERG deletions, translocations, and copy number changes occurred in 8/24 (33%) patients, with a combination of deletions and translocations alone occurring in 3/24 (12.5%) cases. 20/21 (95%) of analyzed cases with ERG-rearrangement were negative for CHD1 gene rearrangement (p&amp;lt; 0.01). Overall, 14/45 (31.1%) of patients had CHD1 deletion, and 13/14 (93%) CHD1- cases correlate with ERG-rearrangement negative status (p&amp;lt; 0.01). 10/45 (22.2%) cases represent CHD1 gene copy number gain. These results support the notion that additional heterogeneity may be present even in a focus of a single biopsy core. These data are extremely important and urgently require further study to understand heterogeneity of genetic changes, because clinical studies have already been launched using genetic changes such as TMPRSS2-ERG fusions found in a single core biopsy to direct a specific therapy, including a trial using ABT-888 only in patients with this fusion now ongoing at CINJ. Citation Format: Irina V. Tereshchenko, Hua Zhong, Marina Chekmareva, Urmila Santanam, Whitney Petrosky, Noriko Kane-Goldsmith, Jay A. Tischfield, Robert DiPaola. Rearrangement of ERG and CHD1 genes in prostate cancer as a marker of tumor heterogeneity. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 2233. doi:10.1158/1538-7445.AM2014-2233

1051 Detection rate of Real-Time-Elastography (RTE) guided biopsy of the prostate: Impact of Gleason score (GS) and comparison to multiple core biopsy

1051 Detection rate of Real-Time-Elastography (RTE) guided biopsy of the prostate: Impact of Gleason score (GS) and comparison to multiple core biopsy