David Y. Lu

Multifocality and Prostate Cancer Detection by Multiparametric Magnetic Resonance Imaging: Correlation with Whole-mount Histopathology

BACKGROUND Multiparametric magnetic resonance imaging (mp-MRI) is increasingly used in prostate cancer (CaP). Understanding the limitations of tumor detection, particularly in multifocal disease, is important in its clinical application. OBJECTIVE To determine predictors of CaP detection by mp-MRI as confirmed by whole-mount histopathology. DESIGN, SETTING, AND PARTICIPANTS A retrospective study was performed of 122 consecutive men who underwent mp-MRI before radical prostatectomy at a single referral academic center. A genitourinary radiologist and pathologist collectively determined concordance. OUTCOME MEASUREMENTS AND STATISTICAL ANALYSIS The odds of tumor detection were calculated for clinical, MRI, and histopathologic variables using a multivariate logistic regression model. RESULTS AND LIMITATIONS The 122 patients had 283 unique histologically confirmed CaP tumor foci. Gleason score was 6 in 21 (17%), 7 in 88 (72%), and ≥8 in 13 (11%) patients. Of the 122 cases, 44 (36%) had solitary and 78 (64%) had multifocal tumors. Overall mp-MRI sensitivity for tumor detection was 47% (132/283), with increased sensitivity for larger (102/141 [72%] >1.0 cm), higher-grade (96/134 [72%] Gleason ≥7) tumors, and index tumors (98/122 [80%]). Index tumor status, size, and prostate weight were significant predictors of detection in a multivariate analysis, and multifocality did not adversely impact detection of index tumors. A prostatectomy population was necessary by design, which may limit the ability to generalize these results. CONCLUSIONS Sensitivity for tumor detection increased with tumor size and grade. Index tumor status and tumor size were the strongest predictors of tumor detection, regardless of tumor focality. Some 80% of index tumors were detected, but nonindex tumor detection, even of high-grade lesions, was poor. These findings have important implications for focal therapy. PATIENT SUMMARY We evaluated the ability of magnetic resonance imaging (MRI) to detect cancer in patients undergoing prostatectomy. We found that tumor size and grade were important predictors of tumor detection, and although cancer is often multifocal, MRI is often able to detect the worst focus of cancer.

Effect of Ischemic Time, Fixation Time, and Fixative Type on HER2/neu Immunohistochemical and Fluorescence In Situ Hybridization Results in Breast Cancer

Accurate determination of HER2/neu status in breast carcinoma is essential. Alteration of preanalytic variables is known to affect HER2/neu results. American Society of Clinical Oncology (ASCO) and the College of American Pathologists (CAP) issued guidelines to standardize fixation for increased HER2/neu accuracy. We studied the effects of changing preanalytic variables on HER2/neu immunohistochemical and fluorescence in situ hybridization (FISH) results in a known HER2/neu+ invasive carcinoma. The clinical specimen was processed according to ASCO/CAP guidelines, with remaining tumor stored fresh without any fixatives for 4 days at 4°C and cut into core biopsy-sized pieces. Each was fixed in 10% formalin, 15% formalin, Pen-Fix (Richard-Allan Scientific, Kalamazoo, MI), Bouin solution, Sakura molecular fixative (Sakura Tissue-Tek Xpress, Torrance, CA), or zinc formalin for 0 to 168 hours. Immunohistochemical studies and FISH were performed. Compared with the clinical specimen, the samples showed no tumor degradation or marked difference by immunohistochemical studies, except the 1-hour 10% formalin and Bouin samples, or FISH, except the Bouin-fixed samples. Our study demonstrates that HER2/neu results remain accurate beyond ASCO/CAP-recommended preanalytic variables, with the exception of Bouin solution for FISH analysis.

Characteristics of Detected and Missed Prostate Cancer Foci on 3-T Multiparametric MRI Using an Endorectal Coil Correlated With Whole-Mount Thin-Section Histopathology

OBJECTIVE The objective of this study was to determine the characteristics of prostate cancer foci missed on 3-T multiparametric MRI performed with an endorectal coil. MATERIALS AND METHODS The MRI examinations of 122 patients who underwent 3-T multiparametric MRI of the prostate with an endorectal coil were compared with whole-mount histopathology obtained after radical prostatectomy. The mean age of the patients was 60.6 years (SD, 7.6 years), and the mean prostate-specific antigen value was 7.2 ng/mL (SD, 5.9 ng/mL). The clinical, multiparametric MRI (i.e., T2-weighted imaging, diffusion-weighted imaging, and dynamic contrast-enhanced imaging), and histopathologic features were obtained. After an independent review, two blinded genitourinary radiologists matched each case with a genitourinary pathologist. A structured reporting system was used to classify the multiparametric MRI features of each MRI-detected lesion. A chi-square analysis was performed for categoric variables, and the t test was performed for continuous variables. RESULTS On whole-mount histopathology, 285 prostate cancer foci were detected in 122 patients. Of the 285 cancer foci detected at histopathology, 153 (53.3%) were missed on MRI and 132 (46.7%) were detected on MRI. Of the missed lesions, 75.2% were low-grade prostate cancer. Multiparametric MRI had a significantly higher sensitivity for prostate cancer foci 1 cm or larger than for subcentimeter foci (81.1% vs 18.9%, respectively; p < 0.001), for lesions with a Gleason score of 7 or greater than for lesions with a Gleason score of 6 (72.7% vs 27.3%; p < 0.01), and for index lesions than for satellite lesions (80.3% vs 20.8%; p < 0.01). The 3-T multiparametric MRI examinations showed a higher detection rate for lesions in the midgland or base of the gland compared with lesions in the apex (52.3% vs 22.0%, respectively; p < 0.01). CONCLUSION Compared with the prostate cancer lesions that were detected on multiparametric MRI, the prostate cancer lesions that were missed were significantly smaller, were more likely to be low-grade lesions (i.e., Gleason score of 6), were more commonly satellite lesions, and were more likely to be located in the prostatic apex.

In-Bore 3-T MR-guided Transrectal Targeted Prostate Biopsy: Prostate Imaging Reporting and Data System Version 2–based Diagnostic Performance for Detection of Prostate Cancer

Purpose To determine the diagnostic yield of in-bore 3-T magnetic resonance (MR) imaging-guided prostate biopsy and stratify performance according to Prostate Imaging Reporting and Data System (PI-RADS) versions 1 and 2. Materials and Methods This study was HIPAA compliant and institution review board approved. In-bore 3-T MR-guided prostate biopsy was performed in 134 targets in 106 men who (a) had not previously undergone prostate biopsy, (b) had prior negative biopsy findings with increased prostate-specific antigen (PSA) level, or (c) had a prior history of prostate cancer with increasing PSA level. Clinical, diagnostic 3-T MR imaging was performed with in-bore guided prostate biopsy, and pathology data were collected. The diagnostic yields of MR-guided biopsy per patient and target were analyzed, and differences between biopsy targets with negative and positive findings were determined. Results of logistic regression and areas under the curve were compared between PI-RADS versions 1 and 2. Results Prostate cancer was detected in 63 of 106 patients (59.4%) and in 72 of 134 targets (53.7%) with 3-T MR imaging. Forty-nine of 72 targets (68.0%) had clinically significant cancer (Gleason score ≥ 7). One complication occurred (urosepsis, 0.9%). Patients who had positive target findings had lower apparent diffusion coefficient values (875 × 10-6 mm2/sec vs 1111 × 10-6 mm2/sec, respectively; P < .01), smaller prostate volume (47.2 cm3 vs 75.4 cm3, respectively; P < .01), higher PSA density (0.16 vs 0.10, respectively; P < .01), and higher proportion of PI-RADS version 2 category 3-5 scores when compared with patients with negative target findings. MR targets with PI-RADS version 2 category 2, 3, 4, and 5 scores had a positive diagnostic yield of three of 23 (13.0%), six of 31 (19.4%), 39 of 50 (78.0%), and 24 of 29 (82.8%) targets, respectively. No differences were detected in areas under the curve for PI-RADS version 2 versus 1. Conclusion In-bore 3-T MR-guided biopsy is safe and effective for prostate cancer diagnosis when stratified according to PI-RADS versions 1 and 2. ©RSNA, 2016.

Genital rhabdomyoma of the urethra in an infant girl

Extracardiac rhabdomyomas are rare benign entities that usually occur in the head and neck region. Although genital rhabdomyoma is known to occur in the lower genital tract of young and middle-aged women, involvement of the anatomically adjacent urethra by rhabdomyoma is exceedingly rare. We present a case of genital rhabdomyoma arising from the urethra of an infant girl. The tumor was characterized by the submucosal presence of mature-appearing rhabdomyoblastic cells containing conspicuous cross-striations, with the cells set in a collagenous stroma. Necrosis and mitoses were absent. Skeletal muscle differentiation of the tumor cells was supported by positive immunohistochemical staining for desmin and myogenin. To our knowledge, this is the first case of urethral genital-type rhabdomyoma in a child.

Adult Patient with Synchronous Gastrointestinal Stromal Tumor and Xp11 Translocation-Associated Renal Cell Carcinoma: A Unique Case Presentation with Discussion and Review of Literature.

Gastrointestinal stromal tumor (GIST) is the most common primary mesenchymal tumor of the gastrointestinal tract. This entity comprises a wide spectrum of tumors that vary from benign to overtly malignant, with the majority of these tumors harboring oncogenic mutations of the KIT receptor tyrosine kinase that can aid in diagnosis as well as in targeted therapy. Although the majority of GISTs are sporadic, there are forms that are associated with a variety of syndromes including Carney-Stratakis syndrome and neurofibromatosis type 1, as well as a subset of familial GIST syndromes that are caused by germline mutations in KIT or PDGFRA. Here, we describe an unusual case of a patient who was found to have a large abdominal GIST with an incidentally found Xp11 translocation-associated renal carcinoma. The karyotype of the renal carcinoma revealed an unbalanced rearrangement involving an (X;22) translocation at Xp11.2 and 22p11.2, which has not been reported in the literature. Although GISTs have shown an association with other primary malignant neoplasms, including simultaneous presence with unilateral clear cell renal cell carcinoma and bilateral papillary renal cell carcinomas, we describe the first reported case of synchronous GIST and Xp11 translocation-associated renal cell carcinoma.

The Significance of Lymphovascular Invasion of the Spermatic Cord in the Absence of Cord Soft Tissue Invasion

CONTEXT - Testicular germ cell tumors with lymphovascular invasion (LVI) are staged pT2, and those with spermatic cord involvement are staged pT3. OBJECTIVE - To study the clinical significance of LVI within the spermatic cord without direct involvement of the cord soft tissues. DESIGN - A retrospective, multi-institutional review was performed on testicular GCTs with spermatic cord LVI in the absence of cord soft tissue invasion. RESULTS - Forty-four germ cell tumors had LVI in the spermatic cord without soft tissue invasion; 37 of 44 patients (84%) had nonseminomatous germ cell tumors (NSGCT), and 7 (16%) had pure seminomas. Patients with NSGCTs and spermatic cord LVI had worse clinical outcomes compared with patients with pure seminoma and spermatic cord LVI (P = .008). We then compared patients with NSGCTs and spermatic cord LVI (n = 37) to patients with NSGCTs and LVI limited to the testis (n = 32). A significantly greater percentage of patients with LVI in the spermatic cord presented with advanced clinical stage (76% versus 50%; P = .01). There was no statistically significant difference in disease recurrence/progression or death between patients with spermatic cord LVI and patients with LVI limited to the testis (P = .40; P = .50). There was no significant difference in the presence of embryonal dominant histology (P = .30) or rete testis invasion (P = .50) between the 2 groups. More hilar soft tissue invasion was seen in patients with LVI present in the spermatic cord (P = .004). CONCLUSIONS - In patients with NSGCTs, LVI in the spermatic cord, without soft tissue invasion, is associated with worse clinical stage at presentation compared with patients with LVI confined to the testis.

Fine-needle aspiration of bilateral small round blue cell tumors in neck in a 65-year-old man: Significance of a wider differential

Q1. What is your interpretation? a. Small cell carcinoma b. Diffuse large B‐cell lymphoma c. Human papillomavirus‐associated squamous cell carcinoma d. Olfactory neuroblastoma. This article may be cited as: Chang S, Hirschowitz S, Lu DY, Montoya RC, Vergara-Lluri M, Moatamed NA. Fine-needle aspiration of bilateral small round blue cell tumors in neck in a 65-year-old man: Significance of a wider differential. CytoJournal 2018;15:7. CytoJournal Co‐editors‐in‐chief: Lester J. Layfield, MD, (University of Missouri, Columbia, MO, USA) Vinod B. Shidham, MD, FIAC, FRCPath (WSU School of Medicine, Detroit, USA) Executive editor: Vinod B. Shidham, MD, FIAC, FRCPath Wayne State University School of Medicine, Detroit, MI, USA For entire Editorial Board visit : http://www.cytojournal.com/cptext/eb.pdf PDFs FREE for Members (visit http://www.cytojournal.com/CFMember.asp) OPEN ACCESS HTML format

Comparison of Cytopathologist-Performed Ultrasound-Guided Fine-Needle Aspiration With Cytopathologist-Performed Palpation-Guided Fine-Needle Aspiration: A Single Institutional Experience

CONTEXT.— Although fine-needle aspiration (FNA) practice by pathologists is now well established, it has been primarily performed by manual palpation. In recent years, pathologists have begun to venture into ultrasound-guided FNAs (UGFNAs). Reports on experiences with this relatively new technique for pathologists have shown promising results. However to date, there have been few studies in the literature comparing pathologist-performed UGFNA with the more traditional pathologist-performed palpation-guided FNA (PGFNA). OBJECTIVE.— To compare UGFNA to PGFNA by cytopathologists at an academic medical center. DESIGN.— A retrospective study of FNAs performed by cytopathologists within the University of California, Los Angeles (UCLA) pathology departmental FNA clinic was performed. Data collected included performance technique (UGFNA versus PGFNA), lesion site and size, adequacy status (nondiagnostic rate), and number of passes per procedure. Corresponding surgical pathology/flow cytometric/cytogenetic result follow-up was compared to FNA results. Findings between UGFNA and PGFNA cases were compared. RESULTS.— Of 1029 FNA cases during the study period, there were 449 UGFNA cases (43.6%) and 580 PGFNA cases (56.4%). Nondiagnostic rates with UGFNA and PGFNA were 6.7% (30 of 449 cases) and 20.7% (120 of 580 cases), respectively. Nondiagnostic rate was also significantly lower with UGFNA than with PGFNA for lesions within the thyroid (6.0% versus 33.3%), head and neck (6.6% versus 21.2%), and salivary gland (6.2% versus 17.1%), and across all nodule sizes. A total of 495 of 1029 FNA cases (48.1%) had follow-up. Discordance rate was significantly lower with UGFNA than with PGFNA (5.4% versus 12.8%). CONCLUSIONS.— This study shows improved performance characteristics of cytopathologist-performed UGFNA versus PGFNA.

Fine-needle aspiration of a right neck mass in a 10-year-old boy: Diagnostic clues and workup for tumors with small round blue cells

10.4103/cytojournal. cytojournal_31_16 Enlarging right neck mass in 10-year-old boy since 1 month with 5-pound weight loss, new onset cough, and change in voice. Examination of the oral cavity showed 8 cm × 8 cm oropharyngeal mass involving the entire right tonsillar region crossing the midline with deviation of the uvula. Computed tomography studies showed involvement of the parapharyngeal space from skull base to the omohyoid area with encasing of carotid artery. Fine-needle aspiration (FNA) [Figure 1] revealed highly cellular smears composed of small round blue cells with oval nuclei showing mild to marked anisonucleosis, lobulated to irregular nuclear contours, and intense hyperchromasia with occasional bare tumor nuclei and mitotic figures. Occasional loosely cohesive clusters and possible rosette formation were seen. Tumor karyotype was highly abnormal, complex, hyperdiploid with several structural and numerical aberrations, including gains of chromosomes 5, 8, 12 and 13. Fluorescence in situ hybridization (FISH) showed extra copy of the 13q14/ FOXO1-specific signal in 85.7% of interphase nuclei (gain of chromosome 13q) without 13q14 (FOXO1) rearrangement. Published: 27 December 2017 Received: 22 August 2016 CytoJournal 2017, 14:30 Accepted: 11 June 2017 This article is available from: http://www.cytojournal.com/content/14/1/30