Chia Sui Kao

All Publications

• Characterizing relaxin receptor expression and exploring relaxin's effect on tissue remodeling/fibrosis in the human bladder. BMC urology Diaz, E. C., Briggs, M., Wen, Y., Zhuang, G., Wallace, S. L., Dobberfuhl, A. D., Kao, C., Chen, B. C. 2020; 20 (1): 44

  Abstract

  BACKGROUND: Relaxin is an endogenous protein that has been shown to have antifibrotic properties in various organ systems. There has been no characterization of relaxin's role in the human bladder. Our objective was to characterize relaxin receptor expression in the human bladder and assess relaxin's effect on tissue remodeling/fibrosis pathways in bladder smooth muscle cells.METHODS: Relaxin family peptide receptor 1 (RXFP1) and RXFP2 expression was assessed using quantitative reverse transcriptase-PCR (qRT-PCR) and immunohistochemistry (IHC) on primary bladder tissue. Primary human smooth muscle bladder cells were cultured and stimulated with various concentrations of relaxin. Western blot, qRTPCR, ELISA, and zymogram assays were used to analyze fibrosis/tissue remodeling pathway proteins.RESULTS: There was universal mRNA transcript detection and protein expression of relaxin receptors in primary bladder specimens. Immunohistochemistry demonstrated RXFP1 and RXFP2 localizing to both urothelial and smooth muscle cell layers of the bladder. 24h of in vitro relaxin stimulation did not affect mRNA expression of selected proteins in human bladder smooth muscle cells. However, 48h of in vitro relaxin stimulation resulted in upregulation of active (p=0.004) and latent (p=0.027) MMP-2 in cell lysate, and upregulation of active MMP-2 in supernatant (p=0.04). There was a dose dependent relationship with increasing expression of MMP-2 with increasing relaxin concentration. Relaxin stimulation resulted in decreased levels of active and total TGF-beta1 in supernatant and extracellular matrix (p<0.005 with 100ng/mL relaxin stimulation).CONCLUSIONS: In the human bladder, relaxin receptors are expressed at the dome and trigone and localize to the urothelium and smooth muscle cell layers. Stimulation of human bladder SMCs with relaxin in vitro affects expression of MMP-2 and TGF-beta1.

  View details for DOI 10.1186/s12894-020-00607-4

  View details for PubMedID 32321501

• Co-Manifestations of Genital Neurofibromatosis in a Patient with Neurofibromatosis Type 1. Urology Ku, S., Balasubramanian, A., Kao, C., Eisenberg, M. L., Skinner, E. C. 2020

  Abstract

  Genitourinary (GU) presentation of neurofibromatosis type 1 (NF-1) is rare, amongst which bladder involvement is the most common. Sporadic case reports do highlight infrequent external genitalia involvement in NF-1. We present a 21-year-old male with prior childhood history of partial cystectomy for an NF-1 related bladder tumor, who more recently presented with gross hematuria. Workup revealed multiple ganglioneuromas involving the bladder, prostate, and penis, and the patient underwent radical cystoprostatectomy and penile mass excision. Recurrences of previously excised urologic tumors or new tumors may appear many years later, and long-term monitoring of NF-1 patients with urologic involvement is necessary.

  View details for DOI 10.1016/j.urology.2020.03.030

  View details for PubMedID 32289361

• Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: IV: Current and Future Utilization of Molecular-Genetic Tests for Testicular Germ Cell Tumors. The American journal of surgical pathology Looijenga, L. H., Van der Kwast, T. H., Grignon, D., Egevad, L., Kristiansen, G., Kao, C., Idrees, M. T. 2020

  Abstract

  The International Society of Urological Pathology (ISUP) organized a Consultation Conference in March 2019 dealing with applications of molecular pathology in Urogenital Pathology, including testicular tumors (with a focus on germ cell tumors [GCTs]), preceded by a survey among its members to get insight into current practices in testicular germ cell tumor (TGCT) diagnostics and adoption of the ISUP immunohistochemical guidelines published in 2014. On the basis of the premeeting survey, the most commonly used immunomarker panel includes OCT3/4, placental alkaline phosphate, D2-40, SALL4, CD117, and CD30 for GCTs and the documentation of germ cell neoplasia in situ (GCNIS). Molecular testing, specifically 12p copy gain, is informative to distinguish non-GCNIS versus GCNIS related GCTs, and establishing germ cell origin of tumors both in the context of primary and metastatic lesions. Other molecular methodologies currently available but not widely utilized for TGCTs include genome-wide and targeted approaches for specific genetic anomalies, P53 mutations, genomic MDM2 amplification, and detection of the p53 inactivating miR-371a-3p. The latter also holds promise as a serum marker for malignant TGCTs. This manuscript provides an update on the classification of TGCTs, and describes the current and future role of molecular-genetic testing. The following recommendations are made: (1) Presence of GCNIS should be documented in all cases along with extent of spermatogenesis; (2) Immunohistochemical staining is optional in the following scenarios: identification of GCNIS, distinguishing embryonal carcinoma from seminoma, confirming presence of yolk sac tumor and/or choriocarcinoma, and differentiating spermatocytic tumor from potential mimics; (3) Detection of gain of the short arm of chromosome 12 is diagnostic to differentiate between non-GCNIS versus GCNIS related GCTs and supportive to the germ cell origin of both primary and metastatic tumors.

  View details for DOI 10.1097/PAS.0000000000001465

  View details for PubMedID 32205480

• Identification of Diagnostic Metabolic Signatures in Clear Cell Renal Cell Carcinoma Using Mass Spectrometry Imaging. International journal of cancer Vijayalakshmi, K., Shankar, V., Bain, R. M., Nolley, R., Sonn, G. A., Kao, C., Zhao, H., Tibshirani, R., Zare, R. N., Brooks, J. D. 2019

  Abstract

  Clear cell renal cell carcinoma (ccRCC) is the most common and lethal subtype of kidney cancer. Intraoperative frozen section (IFS) analysis is used to confirm the diagnosis during partial nephrectomy (PN). However, surgical margin evaluation using IFS analysis is time consuming and unreliable, leading to relatively low utilization. In this study, we demonstrated the use of desorption electrospray ionization mass spectrometry imaging (DESI-MSI) as a molecular diagnostic and prognostic tool for ccRCC. DESI-MSI was conducted on fresh-frozen 23 normal-tumor paired nephrectomy specimens of ccRCC. An independent validation cohort of 17 normal-tumor pairs were analyzed. DESI-MSI provides two-dimensional molecular images of tissues with mass spectra representing small metabolites, fatty acids, and lipids. These tissues were subjected to histopathologic evaluation. A set of metabolites that distinguish ccRCC from normal kidney were identified by performing least absolute shrinkage and selection operator (Lasso) and log-ratio Lasso analysis. Lasso analysis with leave-one-patient-out cross validation selected 57 peaks from over 27,000 metabolic features across 37,608 pixels obtained using DESI-MSI of ccRCC and normal tissues. Baseline Lasso of metabolites predicted the class of each tissue to be normal or cancerous tissue with an accuracy of 94% and 76%, respectively. Combining the baseline Lasso with the ratio of glucose to arachidonic acid could potentially reduce scan time and improve accuracy to identify normal (82%) and ccRCC (88%) tissue. DESI-MSI allows rapid detection of metabolites associated with normal and ccRCC with high accuracy. As this technology advances, it could be used for rapid intraoperative assessment of surgical margin status. This article is protected by copyright. All rights reserved.

  View details for DOI 10.1002/ijc.32843

  View details for PubMedID 31863456

• Predicting Gonadal Germ Cell Cancer in People with Disorders of Sex Development; Insights from Developmental Biology. International journal of molecular sciences Looijenga, L. H., Kao, C., Idrees, M. T. 2019; 20 (20)

  Abstract

  The risk of gonadal germ cell cancer (GGCC) is increased in selective subgroups, amongst others, defined patients with disorders of sex development (DSD). The increased risk is due to the presence of part of the Y chromosome, i.e., GonadoBlastoma on Y chromosome GBY region, as well as anatomical localization and degree of testicularization and maturation of the gonad. The latter specifically relates to the germ cells present being at risk when blocked in an embryonic stage of development. GGCC originates from either germ cell neoplasia in situ (testicular environment) or gonadoblastoma (ovarian-like environment). These precursors are characterized by presence of the markers OCT3/4 (POU5F1), SOX17, NANOG, as well as TSPY, and cKIT and its ligand KITLG. One of the aims is to stratify individuals with an increased risk based on other parameters than histological investigation of a gonadal biopsy. These might include evaluation of defined susceptibility alleles, as identified by Genome Wide Association Studies, and detailed evaluation of the molecular mechanism underlying the DSD in the individual patient, combined with DNA, mRNA, and microRNA profiling of liquid biopsies. This review will discuss the current opportunities as well as limitations of available knowledge in the context of predicting the risk of GGCC in individual patients.

  View details for DOI 10.3390/ijms20205017

  View details for PubMedID 31658757

• A Clinicopathologic and Molecular Analysis of Fumarate Hydratase-Deficient Renal Cell Carcinoma in 32 Patients. The American journal of surgical pathology Lau, H. D., Chan, E., Fan, A. C., Kunder, C. A., Williamson, S. R., Zhou, M., Idrees, M. T., Maclean, F. M., Gill, A. J., Kao, C. 2019

  Abstract

  Fumarate hydratase-deficient renal cell carcinoma (FH-deficient RCC) is a rare and recently described entity associated with hereditary leiomyomatosis and RCC syndrome. FH-deficient RCC may show variable clinical and pathologic findings, but commonly presents with locally advanced and metastatic disease and carries a poor prognosis. We identified 32 patients with FH-deficient RCC, confirmed by FH immunohistochemistry (IHC) and/or FH mutation analysis, and performed a retrospective review of the clinical and pathologic features. Median age at presentation was 43 years (range, 18 to 69y), and the M:F ratio was 2.2:1. Median tumor size was 6.5cm (range, 2.5 to 28cm), and 71% presented at stage ≥pT3a. After a median follow-up of 16 months (range, 1 to 118mo) in 26 patients, 19% showed no evidence of disease, 31% were alive with disease, and 50% were dead of disease. The vast majority of cases showed multiple histologic growth patterns, with papillary (52%) being the most common predominant pattern, followed by solid (21%), cribriform/sieve-like (14%), sarcomatoid (3%), tubular (3%), cystic (3%), and low-grade oncocytic (3%). Viral inclusion-like macronucleoli with perinucleolar clearing were present in almost all cases (96%). All cases were evaluated using FH IHC, and 3 cases (9%) showed retained FH expression. Nineteen cases had germline or tumor mutation analysis confirming a FH mutation, with 79% (11/14) of cases showing mutations within coding regions and 21% (3/14) showing mutations within intronic splice-sites. By IHC, 97% (32/33) of cases were negative for CK7, 93% (27/29) were negative for p63, and 52% (15/29) were negative for GATA3. All cases stained were positive for PAX8 and showed retained succinate dehydrogenase B expression. Our overall findings show that FH-deficient RCC is considerably heterogenous in morphology and frequently behaves aggressively. Suspicion for this entity should be raised even in the absence of predominantly papillary architecture and characteristic nucleolar features. We have included cases with uncommonly seen features, including 4 cases with predominantly cribriform/sieve-like architecture as well as one case with pure low-grade oncocytic morphology (9y of clinical follow-up without evidence of disease). Although FH IHC is a useful tool for identifying cases of FH-deficient RCC, not all cases of FH-deficient RCC show loss of FH staining, and FH mutation analysis should be considered for patients with suspicious clinical or pathologic features, even in cases with retained FH IHC expression.

  View details for DOI 10.1097/PAS.0000000000001372

  View details for PubMedID 31524643

• 2 year outcome for 8 year old female managed with partial cystectomy for primary bladder clear cell carcinoma. Urology case reports Diaz, E. C., Velasquez, M. G., Kao, C., Wu, H. 2019; 26: 100948

  Abstract

  Bladder cancer is rare in the pediatric population, and clear cell carcinoma is extremely rare with one other pediatric case reported. Here we report the clinical outcome for a medically complicated pediatric patient with muscle invasive clear cell carcinoma treated with partial cystectomy without neoadjuvant or adjuvant therapy. Final pathology was stage T2bN0M0 with negative margins. At 2 years, there is no disease recurrence by cystoscopy, chest and abdominal imaging. Postoperative issues have been related to reduced bladder capacity and compliance and the patient is currently managed with continuous urinary diversion and will require future definitive lower tract reconstruction.

  View details for DOI 10.1016/j.eucr.2019.100948

  View details for PubMedID 31293899

• Plasmacytoid/diffuse urothelial carcinoma: a single-institution immunohistochemical and molecular study of 69 patients HUMAN PATHOLOGY Perrino, C. M., Eble, J., Kao, C., Whaley, R. D., Cheng, L., Idrees, M., Hashemi-Sadraei, N., Monn, M., Kaimakliotis, H. Z., Bandali, E., Grignon, D. 2019; 90: 27–36

  View details for DOI 10.1016/j.humpath.2019.04.012

  View details for Web of Science ID 000478711400005

• Clinicopathologic Features and Chromosome 12p Status of Pediatric Sacrococcygeal Teratomas: A Multi-institutional Analysis PEDIATRIC AND DEVELOPMENTAL PATHOLOGY Mylonas, K. S., Kao, C., Levy, D., Lordello, L., Dal Cin, P., Masiakos, P. T., Oliva, E. 2019; 22 (3): 214–20

  View details for DOI 10.1177/1093526618798771

  View details for Web of Science ID 000475685300004

• Renal Cell Carcinomas with Borderline Features of Eosinophilic Solid and Cystic Renal Cell Carcinoma are Most Likely Papillary Renal Cell Carcinomas Williamson, S., Al-Obaidy, K., Kao, C., Rogers, C., Grignon, D., Schwartz, L., Tretiakova, M., Antic, T., Cheng, L., Gupta, N. NATURE PUBLISHING GROUP. 2019

  View details for Web of Science ID 000478915502406

• Urothelial Carcinoma in Situ Versus Early High-Grade Papillary Urothelial Carcinoma: A Survey of Pathologist and Urologist Interpretations Williamson, S., Sangoi, A., Kao, C., Deebajah, M., Barletta, J., Paner, G., Smith, S., Grignon, D., Comperat, E., Amin, M., Maclean, F., Shah, R., Iczkowski, K., Delprado, W., Cheng, L., Pan, C., McKenney, J., Ro, J., Khani, F., Montironi, R., Robinson, B., Al-Ahmadie, H., Epstein, J., Trpkov, K., Tretiakova, M., Shen, S., Alanee, S., Hirsch, M. NATURE PUBLISHING GROUP. 2019

  View details for Web of Science ID 000478915502407

• Clear Cell Renal Cell Carcinoma With a Poorly-Differentiated Component: A Novel Variant Causing Potential Diagnostic Difficulty Taneja, K., Cheng, L., Al-Obaidy, K., Kao, C., Barletta, J., Howitt, B., Wasco, M., Palanisamy, N., Gupta, N., Rogers, C., Carskadon, S., Chen, Y., Antic, T., Tretiakova, M., Williamson, S. NATURE PUBLISHING GROUP. 2019

  View details for Web of Science ID 000478915502388

• Clear Cell Renal Cell Carcinoma With a Poorly-Differentiated Component: A Novel Variant Causing Potential Diagnostic Difficulty Taneja, K., Cheng, L., Al-Obaidy, K., Kao, C., Barletta, J., Howitt, B., Wasco, M., Palanisamy, N., Gupta, N., Rogers, C., Carskadon, S., Chen, Y., Antic, T., Tretiakova, M., Williamson, S. NATURE PUBLISHING GROUP. 2019

  View details for Web of Science ID 000478081101429

• Renal Cell Carcinomas with Borderline Features of Eosinophilic Solid and Cystic Renal Cell Carcinoma are Most Likely Papillary Renal Cell Carcinomas Williamson, S., Al-Obaidy, K., Kao, C., Rogers, C., Grignon, D., Schwartz, L., Tretiakova, M., Antic, T., Cheng, L., Gupta, N. NATURE PUBLISHING GROUP. 2019

  View details for Web of Science ID 000478081101447

• Urothelial Carcinoma in Situ Versus Early High-Grade Papillary Urothelial Carcinoma: A Survey of Pathologist and Urologist Interpretations Williamson, S., Sangoi, A., Kao, C., Deebajah, M., Barletta, J., Paner, G., Smith, S., Grignon, D., Comperat, E., Amin, M., Maclean, F., Shah, R., Iczkowski, K., Delprado, W., Cheng, L., Pan, C., McKenney, J., Ro, J., Khani, F., Montironi, R., Robinson, B., Al-Ahmadie, H., Epstein, J., Trpkov, K., Tretiakova, M., Shen, S., Alanee, S., Hirsch, M. NATURE PUBLISHING GROUP. 2019

  View details for Web of Science ID 000478081101448

• Native kidney cytomegalovirus nephritis and cytomegalovirus prostatitis in a kidney transplant recipient TRANSPLANT INFECTIOUS DISEASE Tan, S. K., Cheng, X. S., Kao, C., Weber, J., Pinsky, B. A., Gill, H. S., Busque, S., Subramanian, A. K., Tan, J. C. 2019; 21 (1)

  View details for DOI 10.1111/tid.12998

  View details for Web of Science ID 000457744400019

• The asymptomatic bladder: gross and histological findings in a series of patients Briggs, M., Wen, Y., Zhuang, G., Kao, C., Wallace, S. L., Dobberfuhl, A. D., Chen, B., Diaz, E. C. WILEY. 2019: S37–S38

  View details for Web of Science ID 000462357800042

• Optical biopsy of penile cancer with in vivo confocal laser endomicroscopy. Urologic oncology Shkolyar, E., Laurie, M. A., Mach, K. E., Trivedi, D. R., Zlatev, D. V., Chang, T. C., Metzner, T. J., Leppert, J. T., Kao, C. S., Liao, J. C. 2019

  Abstract

  Surgical management of penile cancer depends on accurate margin assessment and staging. Advanced optical imaging technologies may improve penile biopsy and organ-sparing treatment. We evaluated the feasibility of confocal laser endomicroscopy for intraoperative assessment of benign and malignant penile tissue.With institutional review board approval, 11 patients were recruited, 9 with suspected penile cancer, and 2 healthy controls. Confocal laser endomicroscopy using a 2.6-mm fiber-optic probe was performed at 1 or 2 procedures on all subjects, for 13 imaging procedures. Fluorescein was administered intravenously approximately 3 minutes prior to imaging for contrast. Video sequences from in vivo (n = 12) and ex vivo (n = 6) imaging were obtained of normal glans, suspicious lesions, and surgical margins. Images were processed, annotated, characterized, and correlated with standard hematoxylin and eosin histopathology.No adverse events related to imaging were reported. Distinguishing features of benign and malignant penile tissue could be identified by confocal laser endomicroscopy. Normal skin had cells of uniform size and shape, with distinct cytoplasmic membranes consistent with squamous epithelium. Malignant lesions were characterized by disorganized, crowded cells of various size and shape, lack of distinct cytoplasmic membranes, and hazy, moth-eaten appearance. The transition from normal to abnormal squamous epithelium could be identified.We report the initial feasibility of intraoperative confocal laser endomicroscopy for penile cancer optical biopsy. Pending further evaluation, confocal laser endomicroscopy could serve as an adjunct or replacement to conventional frozen section pathology for management of penile cancer.

  View details for DOI 10.1016/j.urolonc.2019.08.018

  View details for PubMedID 31537485

• Plasmacytoid/diffuse urothelial carcinoma: a single institution immunohistochemical and molecular study of 69 patients. Human pathology Perrino, C. M., Eble, J., Kao, C. S., Whaley, R. D., Cheng, L., Idrees, M., Hashemi-Sadraei, N., Monn, M. F., Kaimakliotis, H. Z., Bandali, E., Grignon, D. 2019

  Abstract

  Accurate diagnosis of plasmacytoid urothelial carcinoma (PUC) is important given its poor prognosis and frequent presentation at high stage. We aim to assess the clinicopathologic features, molecular aberrations, and follow-up data in a series of PUC cases from a single tertiary cancer center. Seventy-two urinary bladder, ureteral, and renal pelvic specimens with urothelial carcinoma with plasmacytoid differentiation were identified. Immunohistochemical (IHC) stains were performed on 48 cases. Among urinary bladder origin markers, GATA3 was most sensitive (96%). Breast carcinoma markers (ER, mammaglobin) were usually negative, but PR stained 1 case (4%). Neuroendocrine markers CD56 and TTF-1 were each positive in 1 case (4% and 4%, respectively). Gastrointestinal adenocarcinoma marker CDX2 was positive in 4 cases (15%), but nuclear β-catenin was negative in all cases. CD138 was positive in 83% and e-cadherin expression was lost in 57% of cases. Fluorescence in situ hybridization (FISH) using the UroVysion Bladder Cancer Kit and FGFR3 mutational analysis using polymerase chain reaction (PCR) were performed on 15 cases; deletion of chromosome 9p21 was common (60%) and FGFR3 mutations were detected in 60% of cases (5 cases had both deletion 9p21 and FGFR3 mutations). Cases were divided into 3 morphologic groups: classic (29%), desmoplastic (35%), and pleomorphic (36%). The three morphologic subtypes had distinct survival outcomes (P=.083), with median survival for all patients 18 being months versus 10months for the desmoplastic group.

  View details for PubMedID 31054897

• A Contemporary Review of Common Adult Non-germ Cell Tumors of the Testis and Paratestis. Surgical pathology clinics Mooney, K. L., Kao, C. 2018; 11 (4): 739–58

  Abstract

  This article provides a comprehensive review of non-germ cell tumors of the testis and paratestis in adults, incorporating the latest 2016 World Health Organization updates. Clinical features, gross pathologic findings, key morphologic details, immunohistochemical profiles, and differential diagnoses are covered, with an emphasis on how to resolve commonly encountered, and sometimes difficult, differential diagnoses.

  View details for PubMedID 30447839

• A Clinicopathologic and Molecular Analysis of 34 Mediastinal Germ Cell Tumors Suggesting Different Modes of Teratoma Development AMERICAN JOURNAL OF SURGICAL PATHOLOGY Kao, C., Bangs, C. D., Aldrete, G., Cherry, A. M., Ulbright, T. M. 2018; 42 (12): 1662–73

  View details for Web of Science ID 000450434700010

• A Case Report of Pediatric Clear Cell Carcinoma of the Urinary Bladder Associated With Polyomavirus AJSP-REVIEWS AND REPORTS Saleem, A., Brown, R. A., Higgins, J. T., Troxell, M. L., Kunder, C. A., Pinsky, B. A., Zambrano, E., Kao, C. 2018; 23 (6): 291–95

  View details for DOI 10.1097/PCR.0000000000000284

  View details for Web of Science ID 000457629000012

• Adrenal Myelolipomas Involved by Plasma Cell Myeloma AMERICAN JOURNAL OF CLINICAL PATHOLOGY Lin, C., Levy, D., Higgins, J. T., Kunder, C. A., Kao, C. 2018; 150 (5): 406–14

  View details for DOI 10.1093/AJCP/AQY068

  View details for Web of Science ID 000446081500004

• P16 Expression in Extramammary Paget's Disease of the Vulva and Scrotum Is Not Human Papillomavirus Related INTERNATIONAL JOURNAL OF SURGICAL PATHOLOGY Al-Obaidy, K. I., Kao, C., Idrees, M. T. 2018; 26 (7): 617–20

  Abstract

  Extramammary Paget disease (EMPD) of the vulva has been shown to express p16 by immunohistochemistry (IHC), however, p16 expression in the vulva and scrotum has not been extensively studied in relation to human papillomavirus (HPV) within EMPD of both the vulva and scrotum.Twenty-two cases of EMPD (vulva, 16; scrotum, 6) were found in our laboratory information system. P16 and HPV IHC were performed. Any p16 reactivity less than 10% was considered negative. HPV in situ hybridization for both low- and high-risk HPV was also performed on all cases.Of the 6 scrotal EMPD, 3 (50%) showed weak to moderate positive reactivity for p16 by IHC. Of the 16 vulvar EMPD, 13 (81%) were positive for p16, with at least moderate (2+) intensity with a mean expression of 33.3% (range = 10% to 80%) and 62% (range = 20% to 95%) in scrotal and vulvar EMPD, respectively. None of the scrotal or vulvar cases showed positive reactivity for HPV either by IHC or in situ hybridization.Both vulvar and scrotal EMPD can express p16 by IHC, more commonly vulvar than scrotal; however, no HPV was detected either by IHC or in situ hybridization. EMPD of vulva and scrotum does not appear to be related to HPV, and p16 expression may be regulated through a different mechanism.

  View details for PubMedID 29745285

• A Clinicopathologic and Molecular Analysis of 34 Mediastinal Germ Cell Tumors Suggesting Different Modes of Teratoma Development. The American journal of surgical pathology Kao, C., Bangs, C. D., Aldrete, G., Cherry, A. M., Ulbright, T. M. 2018

  Abstract

  Mediastinal teratomas are enigmatic; those in children and women are almost invariably benign but in men they may be benign or malignant. There are few data on the chromosome 12p status of mediastinal germ cell tumors (GCT), whereas increased 12p copy number is virtually uniform in malignant testicular GCTs. We therefore studied chromosome 12p copy number in 34 diverse mediastinal GCTs and correlated the results with morphology and follow-up to gain insight into possible pathogenesis. Four prepubertal (below 12y) children (3 females and 1 male), 7 postpubertal females (14 to 52y) and 6 postpubertal males (12 to 40y old) had pure, previously untreated teratomas; 15 were mature and 2 had low-grade immaturity. All lacked 12p copy number increase and cytologic atypia, and most (14/17) showed organoid morphology. On follow-up of 16, 1 died of postoperative complications and the remaining 15 were disease free (1 to 119mo, mean: 39mo). Eight postpubertal males (19 to 44y old) had pure teratomas in postchemotherapy resections; 5/8 showed 12p copy number increase. All 8 had distinct cytologic atypia, with organoid morphology in 3. On follow-up, 6 were disease free after surgical resection (1.5 to 94mo, mean 38mo); 1 died of disease at 14.5 months, and 1 was alive with metastases at 176 months. Two postpubertal patients, 1 male (29y) and 1 female (31y), had teratoma with secondary somatic-type malignancies, with positive 12p copy number increase in the former but not the latter. The man's tumor occurred after chemotherapy and was a nonorganoid teratoma with primitive neuroectodermal tumor and malignant glioma; the woman's was a previously untreated organoid teratoma with an undifferentiated carcinoma component. The man died of disease (16mo) and the woman was alive with metastases (27mo). Seven patients had resections for mixed GCTs (4) or pure nonteratomatous tumors, all after chemotherapy; 5/7 had positive 12p copy number increase. The teratoma component of the 2 cases having one showed distinct cytologic atypia and lacked organoid morphology. On follow-up, 1 died of disease (5mo), 2 were alive with disease (1, 1.5mo), 3 were disease free (1 to 43mo; mean: 18mo), and 1 was alive with unknown status (31mo). Our results support that mediastinal teratomas likely develop from 2 separate pathways. Those in children, women and some men arise as pure neoplasms from a nontransformed precursor cell and, therefore, lack 12p copy number increase, show no cytologic atypia, often have organoid morphology and are benign. Common 12p copy number increase, uniform atypia, infrequent organoid structures and malignant behavior support that pure teratomas after chemotherapy in postpubertal males derive from a malignantly transformed precursor cell. Interestingly, we identified organoid pancreatic differentiation only in the benign group and neuroglia more commonly in the malignant teratomas.

  View details for PubMedID 30256256

• Native Kidney Cytomegalovirus Nephritis and Cytomegalovirus Prostatitis in a Kidney Transplant Recipient. Transplant infectious disease : an official journal of the Transplantation Society Tan, S. K., Cheng, X. S., Kao, C., Weber, J., Pinsky, B. A., Gill, H. S., Busque, S., Subramanian, A. K., Tan, J. C. 2018: e12998

  Abstract

  We present a case of cytomegalovirus (CMV) native kidney nephritis and prostatitis in a CMV D+/R- kidney transplant recipient who had completed six months of CMV prophylaxis four weeks prior to the diagnosis of genitourinary CMV disease. The patient had a history of benign prostatic hypertrophy and urinary retention that required self-catheterization to relieve high post-voiding residual volumes. At 7 months post-transplant, he was found to have a urinary tract infection, moderate hydronephrosis of the transplanted kidney, and severe hydroureteronephrosis of the native left kidney and ureter, and underwent native left nephrectomy and transurethral resection of the prostate. Histopathologic examination of kidney and prostate tissue revealed CMV inclusions consistent with invasive CMV disease. This case highlights that CMV may extend beyond the kidney allograft to involve other parts of the genitourinary tract, including the native kidneys and prostate. Furthermore, we highlight the tissue-specific risk factors that preceded CMV tissue invasion. In addition to concurrent diagnoses, health care providers should have a low threshold for considering late-onset CMV disease in high-risk solid organ transplant recipients presenting with signs and symptoms of genitourinary tract pathology. This article is protected by copyright. All rights reserved.

  View details for PubMedID 30203504

• Evaluation of Diagnostic Accuracy and a Practical Algorithmic Approach for the Diagnosis of Renal Masses by FNA. Cancer cytopathology Lau, H. D., Kong, C. S., Kao, C. 2018

  Abstract

  BACKGROUND: The classification of renal neoplasms is essential for oncologic risk stratification and clinical management, and an accurate pretreatment pathologic diagnosis can provide useful guidance for active surveillance, minimally invasive ablative therapy, or surgical resection and can reduce the incidence of overtreatment. Previous studies evaluating the diagnostic accuracy of fine-needle aspiration (FNA) and core-needle biopsy (CNB) for renal masses are limited and show variable results.METHODS: Two hundred forty-seven renal FNA cases with or without concurrent CNB performed and/or reviewed at the Stanford University School of Medicine over the course of 20 years were identified. Cytohistopathologic correlation was performed for 77 cases with subsequent resection specimens. All available case materials were reviewed, and select cases were worked up further and reclassified as necessary.RESULTS: Cytohistopathologic correlation showed 96% diagnostic specificity and 83% sensitivity for renal FNA with or without concurrent CNB. Discordant cases were mostly attributed to sampling errors or suboptimal specimens (79%) and also included 2 non-renal cell carcinoma entities (1 case of angiomyolipoma and 1 case of a benign peripheral nerve sheath tumor) and 1 case involving misclassification of the renal cell carcinoma subtype.CONCLUSIONS: There is considerable value in FNA/CNB for the initial diagnosis of renal masses because of the high diagnostic specificity and sensitivity. Sensitivity is predominantly dependent on sufficient sampling, and additional potential diagnostic pitfalls include nonepithelial and rare entities. Judicious use of ancillary techniques is encouraged, especially when one is presented with a limited specimen, and this article presents a practical algorithmic approach to the diagnosis of renal masses using salient morphologic features and results from ancillary studies. Fine-needle aspiration is an accurate method for the diagnosis of renal masses. A practical diagnostic algorithm, based on salient morphologic and ancillary findings, is presented.

  View details for PubMedID 30193011

• Clinicopathologic Features and Chromosome 12p Status of Pediatric Sacrococcygeal Teratomas: A Multi-institutional Analysis. Pediatric and developmental pathology : the official journal of the Society for Pediatric Pathology and the Paediatric Pathology Society Mylonas, K. S., Kao, C., Levy, D., Lordello, L., Dal Cin, P., Masiakos, P. T., Oliva, E. 2018: 1093526618798771

  Abstract

  Chromosome 12p gains are typically present in postpubertal male patients with testicular malignant germ cell tumors, including most teratomas, and absent in pure ovarian teratomas, both mature and immature. We sought to evaluate the clinicopathologic features and chromosome 12p status of pediatric patients with sacrococcygeal teratomas (SCTs) using the institutional databases of 2 tertiary medical centers. Seven mature teratomas (3 pure, 2 with yolk sac tumor, 1 with medulloepithelioma, and 1 with ependymoma) and 3 immature teratomas (2 pure: grade 2 and grade 3 and 1 mixed: grade 3 with yolk sac tumor) were identified. All patients underwent surgery and 2 received adjuvant chemotherapy. Fluorescence in situ hybridization analysis was performed to elucidate chromosome 12p gains, including isochromosome 12p. All 10 tumors analyzed lacked 12p gains regardless of the components. No patient had evidence of disease at their most recent interval follow-up (mean: 30, range: 7-91 months), irrespective of margin status or of receiving chemotherapy. Overall, our study suggests an absence of chromosome 12p abnormalities in clinically nonaggressive SCTs. Additional data are required to confirm these findings before definitive patient care recommendations can be made.

  View details for PubMedID 30176765

• Evaluation of Diagnostic Accuracy and a Practical Algorithmic Approach for the Diagnosis of Renal Masses by FNA CANCER CYTOPATHOLOGY Lau, H. D., Kong, C. S., Kao, C. 2018; 126 (9): 782–96

  View details for DOI 10.1002/cncy.22037

  View details for Web of Science ID 000454533300006

• Serous Neoplasms of the Pancreas A Comprehensive Review ARCHIVES OF PATHOLOGY & LABORATORY MEDICINE Charville, G. W., Kao, C. 2018; 142 (9): 1134–40

  View details for DOI 10.5858/arpa.2017-0195-RS

  View details for Web of Science ID 000442630100016

• Adrenal Myelolipomas Involved by Plasma Cell Myeloma. American journal of clinical pathology Lin, C., Levy, D., Higgins, J. P., Kunder, C. A., Kao, C. 2018

  Abstract

  Objectives: To report the presence and evaluate the frequency of plasma cell neoplasms within adrenal myelolipomas.Methods: Adrenal myelolipomas within our institution were reviewed for the presence of hematologic neoplasia, and a review of the literature was performed.Results: Two (9%) of 23 adrenal myelolipomas were involved by plasma cell myeloma. The patients were 71 and 81 years old, one woman and one man, with tumors measuring 7 cm and 8.5 cm, respectively. Both tumors contained large aggregates of dysplastic plasma cells occupying at least one *10 field and demonstrated light chain restriction. Neither had an established diagnosis of plasma cell neoplasm previously. After receiving therapy, one patient exhibited a stable clinical course 1 year after diagnosis while the other died of disease 3 years later.Conclusions: We report the first two cases of adrenal myelolipoma involved by plasma cell myeloma, a rare and subtle finding that has significant clinical implications.

  View details for PubMedID 30052719

• Clinicopathologic Characteristics of Fumarate Hydratase-Deficient and Hereditary Leiomyomatosis and Renal Cell Carcinoma-Associated Renal Cell Carcinoma: A Series of 10 Cases Lau, H., Williamson, S. R., Kunder, C., Fan, A. C., Kao, C. NATURE PUBLISHING GROUP. 2018: 358

  View details for Web of Science ID 000429308602336

• Clinicopathologic Characteristics of Fumarate Hydratase-Deficient and Hereditary Leiomyomatosis and Renal Cell Carcinoma-Associated Renal Cell Carcinoma: A Series of 10 Cases Lau, H., Williamson, S. R., Kunder, C., Fan, A. C., Kao, C. NATURE PUBLISHING GROUP. 2018: 358

  View details for Web of Science ID 000459341001466

• Evaluation of Diagnostic Accuracy and a Practical Algorithmic Approach for the Diagnosis of Renal Masses by Fine Needle Aspiration Lau, H., Kong, C., Kao, C. NATURE PUBLISHING GROUP. 2018: 155

  View details for Web of Science ID 000459341000425

• Expanding the Clinicopathological Spectrum of Succinate Dehydrogenase-Deficient Renal Cell Carcinoma: 42 Novel Tumors in 38 Patients Maclean, F., McKenney, J., Hes, O., Kao, C., Ellis, C. L., Turchini, J., Samaratunga, H., Jonathan, Z., Bhattarai, S., Ryan, A., Bonert, M., Leroy, X., Kunju, L., Schwartz, L., Williamson, S. R., Matsika, A., Rao, P., Divatia, M., Guarch, R., Algaba, F., Brimo, F., Agaimy, A., Balancin, M., da Cunha, I. W., Zhou, M., Trpkov, K., Gill, A. J. NATURE PUBLISHING GROUP. 2018: 362

  View details for Web of Science ID 000459341001476

• The Significance of Isolated Linear Tumor Nests within the Tunica Albuginea in Stage I Seminoma: A Multi-Institutional Study Al-Obaidy, K., Kao, C., Levy, D. R., Trevino, K., Idrees, M., Ulbright, T. NATURE PUBLISHING GROUP. 2018: 324

  View details for Web of Science ID 000459341001367

• Evaluation of Diagnostic Accuracy and a Practical Algorithmic Approach for the Diagnosis of Renal Masses by Fine Needle Aspiration Lau, H., Kong, C., Kao, C. NATURE PUBLISHING GROUP. 2018: 155

  View details for Web of Science ID 000429308601077

• The Significance of Isolated Linear Tumor Nests within the Tunica Albuginea in Stage I Seminoma: A Multi-Institutional Study Al-Obaidy, K., Kao, C., Levy, D. R., Trevino, K., Idrees, M., Ulbright, T. NATURE PUBLISHING GROUP. 2018: 324

  View details for Web of Science ID 000429308602237

• Plasmacytoid urothelial carcinoma: A clinicopathological study Hashemi-Sadraei, N., Perrino, C. M., Monn, M., Bandali, E., Cheng, L., Idrees, M., Bihrle, R., Koch, M. O., Eble, J., Kao, C., Albany, C., Pili, R., Grignon, D. A., Kaimakliotis, H. Z. AMER SOC CLINICAL ONCOLOGY. 2018

  View details for DOI 10.1200/JCO.2018.36.6_suppl.482

  View details for Web of Science ID 000436179500475

• Serous Neoplasms of the Pancreas: A Comprehensive Review. Archives of pathology & laboratory medicine Charville, G. W., Kao, C. S. 2018; 142 (9): 1134–40

  Abstract

  Serous neoplasms are uncommon, usually cystic tumors that account for less than 1% of all primary pancreatic lesions. They consist predominantly of a monomorphic epithelial cell population with a glycogen-rich, clear cytoplasm, reminiscent of clear cell renal cell carcinoma, with which serous neoplasms share an association with underlying VHL loss-of-function mutations. Serous neoplasms have no metastatic potential. Accurate recognition of this entity, including its various architectural subtypes, is critical to appropriate prognostication and treatment. Immunohistochemical detection of inhibin and calponin expression, along with the absence of both estrogen and progesterone receptors and nuclear β-catenin, can help to distinguish serous neoplasms from mimics. With the advent of minimally invasive and molecularly driven diagnostic techniques, the pathologist's role in the assessment and management of serous neoplasms has become increasingly complex and important. We provide an update on the histologic, immunohistochemical, and molecular features of pancreatic serous neoplasms for the practicing pathologist.

  View details for PubMedID 30141993

• Do Nonseminomatous Germ Cell Tumors of the Testis With Lymphovascular Invasion of the Spermatic Cord Merit Staging as pT3? AMERICAN JOURNAL OF SURGICAL PATHOLOGY Gordetsky, J., Sanfrancesco, J., Epstein, J. I., Trevino, K., Xu, H., Osunkoya, A., Xiao, G. Q., Kao, C., Unger, P., Hashemi-Sadraei, N., Albany, C., Jorns, J. M., Lu, D. Y., Matoso, A., Rais-Bahrami, S., Schwartz, L. E., Ulbright, T. M., Idrees, M. T. 2017; 41 (10): 1397–1402

  Abstract

  The staging of testicular nonseminomatous germ cell tumors (NSGCTs) with lymphovascular invasion (LVI) of the spermatic cord in the absence of cord parenchymal involvement remains controversial. Our previous study showed that tumors with spermatic cord LVI present at a higher clinical stage than tumors with LVI confined to the testis (pT2). We compared NSGCTs with LVI of the spermatic cord without direct involvement of the spermatic cord soft tissues to pT3 tumors to help clarify the appropriate staging of this histologic finding. A retrospective, multi-institutional review was performed to identify cases of NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord. The clinical-pathologic findings were compared with NSGCTs with spermatic cord soft tissue invasion (pT3). We identified 38 pT2 NSGCTs with LVI in the spermatic cord without soft tissue invasion of the cord and 89 pT3 tumors. There were no significant differences in patient age, tumor size, or clinical stage at presentation between the 2 groups. There were no significant differences in dominant histologic subtype, rete testis invasion, hilar soft tissue invasion, or margin status. There were no significant differences in disease recurrence/progression (P=0.63), recurrence/progression after chemotherapy (P=0.35), or death (P=0.51) between patients with only spermatic cord LVI versus patients with cord soft tissue invasion. In patients with pT2 NSGCTs according to the current staging, LVI in the spermatic cord without cord soft tissue invasion is comparable with pT3 tumors in terms of clinical stage at presentation as well as disease recurrence and survival.

  View details for Web of Science ID 000410661700010

  View details for PubMedID 28719463

• Variant morphology in upper urinary tract urothelial carcinoma: a fourteen-year case series of biopsy and resection specimens. Human pathology Hayashi, H., Mann, S., Kao, C., Grignon, D., Idrees, M. T. 2017

  Abstract

  Upper urinary tract urothelial carcinoma exhibiting variant morphology, especially in higher-grade tumors, is a recognized phenomenon but has not been comparatively studied in biopsy versus resection material. We studied the morphologic patterns and clinicopathological features, and provide a comparison between biopsy and resection specimens. Consultation cases were evaluated separately to investigate for possible consultation bias. A total of 383 in-house cases from 352 patients including 314 resection specimens and 69 biopsies from 2001-2014 were reviewed from a single institution. Histologic type, tumor grade, invasion, pathologic stage, nodal status, metastasis, and the presence and type of variant morphology for each case were evaluated. Variant morphology was identified in 5 biopsy specimens (7.2%) and 42 resection specimens (13.4%). The most common variant morphologic pattern was squamous differentiation (16 cases, 4.5%) followed by an inverted growth pattern (8 cases, 2.2%). The presence of variant morphology in resection specimens had a significant association with higher tumor grade, higher pT stage, and non-papillary configuration. Out of 69 patients with biopsies, 31 had a subsequent resection. In comparison, 181 consultation cases from 168 patients showed variant morphology in six biopsies (7.1%) and twenty-seven resections (28.1%). In conclusion, the frequency of recognizing variant morphology in biopsies is about one-half of that in resections. The inclusion of consultation cases can inflate the incidence of variant morphology. As a result, the frequency of variant morphology in our in-house cases is lower than the percentage reported in the literature, most likely secondary to a consultation bias.

  View details for DOI 10.1016/j.humpath.2017.05.001

  View details for PubMedID 28506733

• Immunohistochemical Assessment of 23 Immature Ovarian Teratomas Charville, G., Longacre, T., Vogel, H., Ulbright, T. M., Kao, C. NATURE PUBLISHING GROUP. 2017: 279A–280A

  View details for Web of Science ID 000394467301400

• Plasmacytoid Urothelial Carcinoma: A Single Institution Immunohistochemical and Molecular Study of 26 Cases Perrino, C., Cheng, L., Idrees, M., Eble, J. N., Kao, C., Grignon, D. NATURE PUBLISHING GROUP. 2017: 248A

  View details for Web of Science ID 000393724401277

• A Comparative Study of pT3 versus pT2 Testicular Germ Cell Tumors, Including Evaluation of Lymphovascular Invasion (LVI) in the Spermatic Cord Sanfrancesco, J., Trevino, K., Osunkoya, A., Xiao, G. Q., Kao, C., Gordetsky, J., Unger, P., Ulbright, T. M., Idrees, M. NATURE PUBLISHING GROUP. 2017: 255A–256A

  View details for Web of Science ID 000393724401306

• A Clinicopathologic and Molecular Analysis of 34 Mediastinal Germ Cell Tumors (GCT) Supporting a Dual Histogenesis for Teratomas Kao, C., Bangs, D., Ulbright, T. M. NATURE PUBLISHING GROUP. 2017: 482A

  View details for Web of Science ID 000393724402420

• Plasmacytoid Urothelial Carcinoma: A Single Institution Immunohistochemical and Molecular Study of 26 Cases Perrino, C., Cheng, L., Idrees, M., Eble, J. N., Kao, C., Grignon, D. NATURE PUBLISHING GROUP. 2017: 248A

  View details for Web of Science ID 000394467301277

• Adrenal Gland Myelolipomas with Plasma Cell Neoplasms Levy, D., Lin, C., Higgins, J. P., Kunder, C. A., Kao, C. NATURE PUBLISHING GROUP. 2017: 149A

  View details for Web of Science ID 000393724400587

• Adrenal Gland Myelolipomas with Plasma Cell Neoplasms Levy, D., Lin, C., Higgins, J. P., Kunder, C. A., Kao, C. NATURE PUBLISHING GROUP. 2017: 149A

  View details for Web of Science ID 000394467300588

• A Comparative Study of pT3 versus pT2 Testicular Germ Cell Tumors, Including Sanfrancesco, J., Trevino, K., Osunkoya, A., Xiao, G. Q., Kao, C., Gordetsky, J., Unger, P., Ulbright, T. M., Idrees, M. NATURE PUBLISHING GROUP. 2017: 255A–256A

  View details for Web of Science ID 000394467301306

• A Clinicopathologic and Molecular Analysis of 34 Mediastinal Germ Cell Tumors (GCT) Supporting a Dual Histogenesis for Teratomas Kao, C., Bangs, D., Ulbright, T. M. NATURE PUBLISHING GROUP. 2017: 482A

  View details for Web of Science ID 000394467302511

• Immunohistochemical Assessment of 23 Immature Ovarian Teratomas Charville, G., Longacre, T., Vogel, H., Ulbright, T. M., Kao, C. NATURE PUBLISHING GROUP. 2017: 279A–280A

  View details for Web of Science ID 000393724401400

• Evidence of a dual histogenetic pathway of sacrococcygeal teratomas HISTOPATHOLOGY Emerson, R. E., Kao, C., Eble, J. N., Grignon, D. J., Wang, M., Zhang, S., Wang, X., Fan, R., Masterson, T. A., Roth, L. M., Cheng, L. 2017; 70 (2): 290-300

  Abstract

  Sacrococcygeal teratomas are rare tumours that occur most frequently in neonates, although adult cases also occur. The molecular pathogenesis of these tumours and their long-term prognosis is uncertain. We investigated the i(12p) status of a large number of primary sacrococcygeal teratomas in both children and adults, including cases with malignant germ cell tumour elements.Fifty-four sacrococcygeal teratoma specimens from 52 patients were identified, and available follow-up information was obtained. Fluorescence in-situ hybridization analysis was performed to identify isochromosome 12p [i(12p)] abnormalities on paraffin blocks of the tumours. Among the 48 paediatric patients, there were 44 teratomas and four tumours with combined teratoma and yolk sac tumour (one of whom also had primitive neuroectodermal tumour). The teratomas included 37 mature teratomas and 11 immature teratomas (four grade 1, two grade 2, and five grade 3). The 44 teratomas lacking a yolk sac tumour component were all negative for i(12p). The four tumours with a yolk sac tumour component were all positive for i(12p). The four adult cases all lacked non-teratomatous germ cell tumour components, immature elements, and i(12p). Follow-up information was available for 32 patients. Two patients with teratoma had recurrence, but were alive with no evidence of disease after long-term follow-up. One patient with combined teratoma and yolk sac tumour had recurrence 7 months after resection. The other patients were alive with no evidence of disease at last follow-up.Our data suggest that paediatric sacrococcygeal teratomas should be considered as two distinct groups with divergent histogenetic pathways. The prognosis of these tumours is excellent, despite rare recurrence.

  View details for DOI 10.1111/his.13062

  View details for Web of Science ID 000394982000017

• "Dissecting Gonadoblastoma" of Scully: A Morphologic Variant That Often Mimics Germinoma. American journal of surgical pathology Kao, C., Idrees, M. T., Young, R. H., Ulbright, T. M. 2016; 40 (10): 1417-1423

  Abstract

  Dr Robert E. Scully, who recognized and defined gonadoblastoma (GB), used the term "dissecting gonadoblastoma" (DGB) to describe variants with either an infiltrative type or diffuse pattern instead of the usual small nested arrangement. These patterns have not been emphasized in the literature. To investigate the features of DGB we examined 50 GBs microscopically and performed immunohistochemistry (IHC) in some. DGB was found in 38 (76%) GBs and was represented by 3 patterns. The most frequent was solid/expansile (n=26), consisting of large coalescent nests of germ cells, often (92%) interrupted by fibrovascular septa, with usually minor numbers of sex cord cells. Less frequent were small anastomosing nests (n=24) and cord-like arrangements (n=22) of germ cells irregularly distributed in a prominent stroma and with mostly inconspicuous sex cord cells. Most DGBs (24) showed >1 pattern and demonstrated the characteristic globular deposits of basement membrane, although these were often subtle. The germ cells in all patterns varied from spermatogonium-like to seminoma-like; OCT3/4 was positive only in the latter (7/7). The sex cord cells were small with dense, oval or angulated nuclei, inconspicuous nucleoli, and positivity for inhibin (9/9, strong), FOXL2 (9/9, strong), SF1 (8/9, strong), SOX9 (9/9, weak and focal), WT1 (5/7, variable), and calretinin (3/7, variable). Granulomas were present in 84% of germinoma foci, 13% of DGB foci, and 8% of classic GB foci. Twenty two of 38 DGBs had associated germinoma; 3 also had embryonal carcinoma, yolk sac tumor, and choriocarcinoma, respectively. Follow-up of 2 cases lacking an invasive tumor showed that both patients were disease free at 13 and 4.8 years after bilateral gonadectomy. We conclude that DGB is commonly seen with classic GB and displays identical IHC features, supporting it as a morphologic variant of GB. It appears likely that cord-like DGB is the earliest phase in a GB developmental continuum that may proceed successively into anastomosing, nested (classic GB), and solid/expansile patterns. DGB often mimics germinoma because of the large size of the nests, pseudoinfiltrative pattern of some cases, and inconspicuous sex cord cells. The presence of sex cord cells (identification aided by IHC for sex cord markers), the heterogenous morphology of the germ cells, and globules of basement membrane are useful differential features. The lack of a granulomatous reaction also favors DGB over germinoma. Mistaking DGB for GB with invasive germinoma may result in more aggressive therapy than warranted. The likely relationship of DGB to the relatively recently described concept of so-called "undifferentiated gonadal tissue" is discussed herein.

  View details for DOI 10.1097/PAS.0000000000000704

  View details for PubMedID 27454939