Clinical Vignettes for Urology The following urologic pathology clinical vignettes highlight patient cases where the Inform Diagnostics diagnosis made a difference.Clinical Vignettes Mystery solved of “a small focus of 3+3=6 prostate cancer” with a very high aggressiveness score by a popular genetic prognostic test An outside pathology lab sent a prostate biopsy to Inform Diagnostics for consultation and ERG status testing. The materials comprised a two-part prostate core biopsy-the original HE slides and one PIN3 cocktail immunostain slide for part A. The Inform Diagnostics uropathologist diagnosed both parts as benign prostate tissue. Due to the request for ERG status, the uropathologist requested and obtained additional information from the urologist: Part A had been diagnosed by the outside pathology lab as a small focus of 3+3=6 prostate cancer, which was sent for genetic testing and showed a very high aggressiveness score, suggesting a poor prognosis. The Inform Diagnostics uropathologist worked closely with the genetic testing company to compare the pictures of the different foci of the core, and finally determined that an area with prominent acute inflammation and basal cell hyperplasia was circled and tested. The area that the outside pathologist had called cancer was not recognized as abnormal. We performed an additional PIN4-ERG immunostain and confirmed our benign diagnosis in both areas that the outside pathologist had called cancer and the area with prominent basal cell hyperplasia, which was tested for cancer aggressiveness. The few benign glands had been interpreted as cancer by the outside pathologist, based on lacking of basal cell stain. However, the glands had similar morphology with adjacent glands with patchy basal cell stain and showed no cytological atypia. Our Diagnosis Benign prostate tissue The Inform Diagnostics Difference Definitive diagnosis of a benign condition was rendered by the Inform Diagnostics expert uropathologist. The Inform Diagnostics expert uropathologist thoroughly investigated the case, and solved the mystery that confused the urologist, pathologist and patient. The patient avoided the potential unnecessary surgery due to the wrong diagnosis and misleading information from genetic prognostic testing. Rare Benign Condition that Mimics Cancer Recognized A 64-year-old man presented with difficulty in voiding urine and elevated serum PSA. The patient underwent transurethral resection of the prostate (TURP) to relieve urinary obstruction. The pathologist at a physician-owned lab had rendered the diagnosis of prostate cancer, Gleason score 4+4=8. The treating urologist requested a second opinion by Inform Diagnostics, and, after examining the biopsy materials and clinical information, our expert uropathologist diagnosed the patient with sclerosing adenosis, a recognized rare but important benign mimic of high-grade prostate adenocarcinoma due to its complex architecture. Our Diagnosis Benign sclerosing adenosis The Inform Diagnostics Difference Definitive diagnosis of a benign condition mimicking cancer was rendered by the Inform Diagnostics expert uropathologist. The patient avoided the psychological, physical, and financial cost of a cancer diagnosis. Different Diagnosis Rendered for Follow-up Biopsy A 60-year-old male, with a history of high-grade bladder cancer diagnosed at an outside lab, underwent a follow-up bladder biopsy which was sent to Inform Diagnostics. The Inform Diagnostics expert uropathologist confirmed that there was residual malignancy but suspected a diagnosis of high-grade lymphoma. Due to major disagreement with previously rendered diagnoses of high-grade urothelial carcinoma at the outside institution, the Inform Diagnostics subspecialist pathologist requested and obtained additional case history and the previous pathology report. Further work-up at Inform Diagnostics confirmed the diagnosis of high-grade B-cell lymphoma. Due to this difference in diagnosis, the treating urologist requested a second opinion. Miraca’s diagnosis of lymphoma was confirmed by an outside academic consultant. Our Diagnosis High-grade B-cell non-Hodgkin lymphoma The Inform Diagnostics Difference The Inform Diagnostics expert uropathologist reviewed previous materials and performed additional studies to make a definitive diagnosis. Inform Diagnostics’s diagnosis was confirmed by an outside consultant. The patient received chemotherapy appropriate for lymphoma and avoided unnecessary surgery. New Inform Diagnostics Test Correctly Predicts Prostate Cancer at Repeat Biopsy A 60-year-old man was found to have a high blood PSA level and then underwent a set of 12 prostate biopsies to exclude cancer. The Inform Diagnostics uropathologist diagnosed a pre-cancerous condition, HGPIN (high-grade prostatic intraepithelial neoplasia) in two separate sites (one on each side of the prostate). Using our PINgenius™ test, the patient was classified as being High Risk, and Inform Diagnostics recommended a repeat biopsy right away. The client requested a second opinion from a highly prestigious academic and research hospital, which interpreted just one site with HGPIN and the other with low-grade PIN. The pathologist at the academic hospital recommended follow-up with a repeat biopsy after three years. Despite the difference of opinion, and after a discussion of the results with the Inform Diagnostics uropathologist, the urologist decided to follow Inform Diagnostics’s recommendations and performed a repeat biopsy shortly after the initial biopsy. The repeat biopsy showed significant volume of adenocarcinoma of prostate with a Gleason score 3+4. Our Diagnosis Bilateral HGPIN with PINgenius test result: High Risk. Cancer confirmed on follow-up biopsy. The Inform Diagnostics Difference The patient’s malignant diagnosis was not delayed, and he benefitted from immediate treatment. Our uropathologist utilized Inform Diagnostics’s PINgenius™ test, a unique test developed at Inform Diagnostics which is now widely available to the medical community. Although a prestigious hospital recommended follow-up at three years, our client trusted the Inform Diagnostics diagnosis. The urologist may have saved the life of his patient by not delaying the follow-up biopsy. Previous Pathology Materials and Second Opinion Confirm Inform Diagnostics Diagnosis 60-year-old man had been diagnosed with aggressive (high-grade) bladder cancer by an outside pathologist. Upon review of his bladder biopsy, Inform Diagnostics’s expert uropathologists suspected that the patient actually had lymphoma, a significant difference from the original diagnosis. We requested additional medical history for the patient and the previous pathology materials. With further evaluation, we confirmed the diagnosis of high-grade (aggressive) B cell lymphoma. Due to this difference in diagnosis, the patient’s urologist requested a second opinion, and an outside academic consultant confirmed Inform Diagnostics’s diagnosis of lymphoma. Our Diagnosis High-grade B cell lymphoma The Inform Diagnostics Difference Patient received appropriate treatment and avoided unnecessary surgery. Inform Diagnostics provided a definitive diagnosis through biopsy, patient medical history and previous pathology materials. Outside academic pathologist confirmed Inform Diagnostics’s diagnosis. Signet-Ring Adenocarcinoma Is Subtle Histologic Difference 36-year-old man was sent to a urologist with pain in the abdomen and radiologic evidence of hydronephrosis. During a cystoscopy, the urologist saw that the bladder appeared nodular and scarred. A biopsy was performed, and an outside pathologist diagnosed “ruptured cystitis glandularis/cyst.” The urologist requested a second opinion from Inform Diagnostics. Our expert uropathologist identified a subtle, yet malignant signet-ring adenocarcinoma of the colon that had metastasized to the patient’s bladder. Our Diagnosis Metastatic signet-ring adenocarcinoma The Inform Diagnostics Difference Appropriate treatment for the patient Subspecialist expert uropathologist at Inform Diagnostics recognized a subtle histologic difference Definitive diagnosis by Inform Diagnostics Benign Tissue Fragment Poses as Cancer 58-year-old man underwent a prostate biopsy due to an elevated PSA. The specimens were sent to a physician-owned lab where the patient was diagnosed with cancer, Gleason score 3+3=6. Wanting a second opinion, the patient’s urologist sent the biopsy slides to Inform Diagnostics. Inform Diagnostics’s expert uropathologist saw that the slides included a tissue fragment that actually represented benign rectal mucosa with ischemic changes (the prostate is biopsied through the rectum) that the previous lab had misinterpreted as prostate cancer. Our Diagnosis Benign rectal tissue The Inform Diagnostics Difference Inform Diagnostics expert uropathologists recognized the common misinterpretation of normal tissue. Patient avoided unnecessary major surgery. Prostate Surgery Was Unnecessary A man in his mid-sixties underwent the removal of his prostate following a diagnosis of cancer, Gleason score 3+3=6, by a solo pathologist at a physician-owned lab. After the prostatectomy, the hospital’s pathology department could not find any cancer in the removed prostate, so they decided to cut the entire prostate into 180 slides, and still no cancer was found. All 180 slides were sent to Inform Diagnostics, and our expert uropathologist did not find cancer either, and therefore asked for the original biopsies. Upon receipt, the Inform Diagnostics uropathologist found that the original biopsies contained atrophied glands that were over-interpreted as cancer. Subsequently, a review by an outside academic institution confirmed atrophy in the original biopsies. Our Diagnosis Atrophied glands The Inform Diagnostics Difference Diligent review of 180 slides as well as request for pre-surgery biopsy slides. Definitive diagnosis by Inform Diagnostics confirmed by outside academic institution. Patient could have avoided surgery and its cost, pain, time and complications.