337 results on '"Testicular Neoplasms classification"'
Search Results
2. Genomic landscape and distinct molecular subtypes of primary testicular lymphoma.
- Author
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Zhang W, Yang P, Yang Y, Liu S, Xu Y, Wu C, Wang J, Liu C, Liu H, Li S, Huang W, and Jing H
- Subjects
- Humans, Male, Aged, Middle Aged, Lymphoma genetics, Lymphoma pathology, Lymphoma classification, Exome Sequencing, Aged, 80 and over, Adult, Lymphoma, Large B-Cell, Diffuse genetics, Lymphoma, Large B-Cell, Diffuse pathology, Lymphoma, Large B-Cell, Diffuse classification, Testicular Neoplasms genetics, Testicular Neoplasms pathology, Testicular Neoplasms classification, Mutation genetics, DNA Copy Number Variations genetics, Genomics
- Abstract
Primary testicular lymphoma (PTL) is a rare lymphoma predominantly occurring in the elderly male population. It is characterized by a limited response to treatment and a heightened tendency towards relapse. Histologically, approximately 90% of PTL cases are classified as diffuse large B-cell lymphomas (DLBCL). Genetic features of PTL were delineated in a limited scope within several independent studies. Some of the articles which analyzed the genetic characterization of DLBCL have incorporated PTL samples, but these have been constrained by small sample sizes. In addition, there have been an absence of independent molecular typing studies of PTL. This report summarizes the common mutational features, copy number variations (CNVs) and molecular typing of PTL patients, based on whole-exome sequencing (WES) conducted on a cohort of 25 PTL patients. Among them, HLA, CDKN2A and MYD88 had a high mutation frequency. In addition, we found two core mutational characteristics in PTL including mutation in genes linked to genomic instability (TP53 and CDKN2A) and mutation in immune-related genes (HLA, MYD88, CD79B). We performed molecular typing of 25 PTL patients into C1 subtype with predominantly TP53 mutations and C2 subtype with predominantly HLA mutations. Notably, mutations in the TP53 gene predicted a poor outcome in most types of lymphomas. However, the C1 subtype, dominated by TP53 mutations, had a better prognosis compared to the C2 subtype in PTL. C2 subtype exhibited a worse prognosis, aligning with our finding that the mechanism of immune escape in PTL was primarily the deletions of HLA rather than PD-L1/PD-L2 alterations, a contrast to other DLBCLs. Moreover, we calculated the tumor mutation burden (TMB) and identified that TMB can predict prognosis and recurrence rate in PTL. Our study underscores the significance of molecular typing in PTL based on mutational characteristics, which plays a crucial role in prognostication and guiding therapeutic strategies for patients., (© 2024. The Author(s).)
- Published
- 2024
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3. News in the fifth edition of World Health Organization classification of testicular tumors.
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Horák S and Čierna Z
- Subjects
- Humans, Male, Testicular Neoplasms classification
- Abstract
Background: The fifth edition of World Health Organization classification of urinary and male genital tumours also brought news regarding testicular tumours. In contrast to the previous editions' radical alterations, the adjustments in the fifth edition are subtle and mostly impact the terminology, categorization of some of the rare tumours and diagnostic criteria., Purpose: Acquainting with current terms and tumor classification, which is necessary for good clinical practice.
- Published
- 2023
4. "Embryonic-type Neuroectodermal Tumor" Should Replace "Primitive Neuroectodermal Tumor" of the Testis and Gynecologic Tract: A Rationale for New Nomenclature.
- Author
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Flood TA, Ulbright TM, and Hirsch MS
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- Biomarkers, Tumor genetics, Cell Differentiation, Cell Proliferation, Diagnosis, Differential, Female, Genital Neoplasms, Female genetics, Genital Neoplasms, Female pathology, Humans, Male, Neuroectodermal Tumors, Primitive, Peripheral genetics, Neuroectodermal Tumors, Primitive, Peripheral pathology, Predictive Value of Tests, Sarcoma, Ewing genetics, Sarcoma, Ewing pathology, Testicular Neoplasms genetics, Testicular Neoplasms pathology, Genital Neoplasms, Female classification, Neuroectodermal Tumors, Primitive, Peripheral classification, Sarcoma, Ewing classification, Terminology as Topic, Testicular Neoplasms classification
- Abstract
Competing Interests: Conflicts of Interest and Source of Funding: The authors have disclosed that they have no significant relationships with, or financial interest in, any commercial companies pertaining to this article.
- Published
- 2021
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5. Clinical utility of the AJCC 8 th edition pT1 subclassification and impact on practice patterns in stage I seminoma.
- Author
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Badia RR, Woldu S, Patel HD, Singla N, Srivastava A, Cheaib JG, Pierorazio PM, and Bagrodia A
- Subjects
- Humans, Male, Retrospective Studies, Seminoma classification, Testicular Neoplasms classification, Neoplasm Staging standards, Practice Patterns, Physicians', Seminoma pathology, Seminoma therapy, Testicular Neoplasms pathology, Testicular Neoplasms therapy
- Abstract
Background: The American Joint Committee on Cancer 8
th edition staging guidelines for testicular cancer established a 3 cm cutoff to subclassify stage T1 seminomas (<3 cm = pT1a and ≥3 cm = pT1b). The efficacy of this cutoff in predicting metastatic disease and impact on treatment patterns have not been studied., Methods: We retrospectively reviewed patients with pT1 testicular seminoma in the National Cancer Database from 2004 to 2016. Receiver operating curves were used to determine the efficacy of the 3 cm tumor cutoff in identifying metastatic disease, and multivariable regression was used to compute the effect of tumor size on the rate of adjuvant therapy among Stage I patients., Results: A total of 10,134 patients with pT1 seminoma were evaluated. The current size cutoff of 3 cm for subclassification did not exhibit high discrimination in identifying metastatic disease (area under receiver operating curve: 0.546). Surveillance has grown as the preferred treatment after orchiectomy -32.1% in 2004 to 81.2% in 2015. However, the rate of adjuvant therapy for pT1, Stage I seminomas associated positively with tumor size even with adjustment for year of diagnosis. For tumors above 3 cm, the odds ratio stabilized around 1.9. By using the 3 cm cutoff to guide adjuvant therapy, up to 85% of T1b patients may be overtreated., Conclusion: The 3 cm cutoff for subclassification of Stage I seminoma does not predict metastatic recurrence but is associated with increased receipt of adjuvant therapy. A 3 cm cutoff and the pT1a/b classification may therefore contribute to overtreatment in many young patients with a long life expectancy for whom minimizing adverse effects should be prioritized., (Copyright © 2020 Elsevier Inc. All rights reserved.)- Published
- 2021
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6. Management of Germ Cell Tumours of the Testis in Adult Patients. German Clinical Practice Guideline Part I: Epidemiology, Classification, Diagnosis, Prognosis, Fertility Preservation, and Treatment Recommendations for Localized Stages.
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Kliesch S, Schmidt S, Wilborn D, Aigner C, Albrecht W, Bedke J, Beintker M, Beyersdorff D, Bokemeyer C, Busch J, Classen J, de Wit M, Dieckmann KP, Diemer T, Dieing A, Gockel M, Göckel-Beining B, Hakenberg OW, Heidenreich A, Heinzelbecker J, Herkommer K, Hermanns T, Kaufmann S, Kornmann M, Kotzerke J, Krege S, Kristiansen G, Lorch A, Müller AC, Oechsle K, Ohloff T, Oing C, Otto U, Pfister D, Pichler R, Recken H, Rick O, Rudolph Y, Ruf C, Schirren J, Schmelz H, Schmidberger H, Schrader M, Schweyer S, Seeling S, Souchon R, Winter C, Wittekind C, Zengerling F, Zermann DH, Zillmann R, and Albers P
- Subjects
- Adult, Fertility Preservation, Humans, Male, Neoplasm Staging, Practice Guidelines as Topic, Prognosis, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal diagnosis, Neoplasms, Germ Cell and Embryonal epidemiology, Neoplasms, Germ Cell and Embryonal therapy, Testicular Neoplasms classification, Testicular Neoplasms diagnosis, Testicular Neoplasms epidemiology, Testicular Neoplasms therapy
- Abstract
Introduction: This is the first German evidence- and consensus-based clinical guideline on diagnosis, treatment, and follow-up on germ cell tumours (GCTs) of the testis in adult patients. We present the guideline content in two publications. Part I covers the topic's background, methods, epidemiology, classification systems, diagnostics, prognosis, and treatment recommendations for the localized stages., Methods: An interdisciplinary panel of 42 experts including 1 patient representative developed the guideline content. Clinical recommendations and statements were based on scientific evidence and expert consensus. For this purpose, evidence tables for several review questions, which were based on systematic literature searches (last search was in March 2018) were provided. Thirty-one experts entitled to vote, rated the final clinical recommendations and statements., Results: We provide 161 clinical recommendations and statements. We present information on the quality of cancer care and epidemiology and give recommendations for staging and classification as well as for diagnostic procedures. The diagnostic recommendations encompass measures for assessing the primary tumour as well as procedures for the detection of metastases. One chapter addresses prognostic factors. In part I, we separately present the treatment recommendations for germ cell neoplasia in situ, and the organ-confined stages (clinical stage I) of both seminoma and nonseminoma., Conclusion: Although GCT is a rare tumour entity with excellent survival rates for the localized stages, its management requires an interdisciplinary approach, including several clinical experts. Quality of care is highly related to institutional expertise and can be reassured by established online-based second-opinion boards. There are very few studies on diagnostics with good level of evidence. Treatment of metastatic GCTs must be tailored to the risk according to the International Germ Cell Cancer Collaboration Group classification after careful diagnostic evaluation. An interdisciplinary approach as well as the referral of selected patients to centres with proven experience can help achieve favourable clinical outcomes., (© 2021 The Author(s). Published by S. Karger AG, Basel.)
- Published
- 2021
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7. Evidence supporting the existence of testicular mixed germ cell-sex cord stromal tumor Pathol Res Pract.
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Roth LM
- Subjects
- Epigenesis, Genetic, Female, Genetic Variation, Germ Cells pathology, Humans, Male, Ovarian Neoplasms genetics, Ovarian Neoplasms pathology, Sex Cord-Gonadal Stromal Tumors genetics, Sex Cord-Gonadal Stromal Tumors pathology, Testicular Neoplasms genetics, Testicular Neoplasms pathology, Ovarian Neoplasms classification, Sex Cord-Gonadal Stromal Tumors classification, Testicular Neoplasms classification
- Published
- 2021
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8. Borderline serous papillary tumor of the testis.
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Fonseca D, Manasa PL, Sharma R, and Giridhar A
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- Adult, Cystadenoma, Serous pathology, Humans, Immunohistochemistry, Male, Orchiectomy, Precancerous Conditions pathology, Testicular Neoplasms surgery, Testis pathology, Cystadenoma, Serous diagnosis, Precancerous Conditions diagnosis, Testicular Neoplasms classification, Testicular Neoplasms diagnosis
- Abstract
Ovarian epithelial type tumor of the testis is a rare entity. Herein, we report borderline serous papillary tumor of the testis in a 37-year-old male, which was clinically suspected to be a testicular malignancy.
- Published
- 2020
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9. Differential expression of DNA methyltransferases and demethylases among the various testicular germ cell tumor subtypes.
- Author
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Lobo J, Guimarães R, Miranda-Gonçalves V, Monteiro-Reis S, Cantante M, Antunes L, Braga I, Maurício J, Looijenga LH, Jerónimo C, and Henrique R
- Subjects
- Adolescent, Adult, Cell Line, Tumor, Computer Simulation, DNA (Cytosine-5-)-Methyltransferases genetics, DNA Methyltransferase 3A, DNA-Binding Proteins genetics, Dioxygenases, Humans, Male, Middle Aged, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal genetics, Proto-Oncogene Proteins genetics, RNA, Messenger metabolism, Testicular Neoplasms classification, Testicular Neoplasms genetics, Young Adult, DNA Methyltransferase 3B, DNA (Cytosine-5-)-Methyltransferases metabolism, DNA-Binding Proteins metabolism, Neoplasms, Germ Cell and Embryonal enzymology, Proto-Oncogene Proteins metabolism, Testicular Neoplasms enzymology
- Abstract
Aim: Characterize DNA methyltransferases/demethylases expression in testicular germ cell tumors (TGCTs). Methods: In silico analysis of TCGA database, assessment of transcript levels of most relevant enzymes in four TGCT cell lines and validation in patient cohort (real-time quantitative polymerase chain reaction; immunohistochemistry). Results: DNMT3A , DNMT3B and TET2 were the most differentially expressed between seminomas (SEs) and nonseminomas (NSs). DNMT3B was significantly overexpressed in NS-related cell lines, and the opposite was found for TET2 . Significantly higher DNMT3A/B mRNA expression was observed in NS, indicating a role for de novo methylation in reprogramming. Significantly higher TET2 protein expression was observed in SEs, suggesting active demethylation contributes for SE hypomethylated state. More differentiated histologies disclosed distinct expression patterns. Conclusion: DNA-modifying enzymes are differentially expressed between TGCT subtypes, influencing reprogramming and differentiation.
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- 2020
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10. Clinical implications of the American Joint Committee on Cancer (AJCC) 8th edition update in seminoma pT1 subclassification.
- Author
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Fontes-Sousa M, Lobo J, Magalhães H, Cassis J, Malheiro M, Ramos S, Henrique R, Martins A, and Maurício MJ
- Subjects
- Adolescent, Adult, Aged, Humans, Male, Middle Aged, Neoplasm Staging, Retrospective Studies, United States, Young Adult, Seminoma classification, Seminoma pathology, Testicular Neoplasms classification, Testicular Neoplasms pathology
- Abstract
Background: Seminoma accounts for 30-50% of testicular germ cell tumors (TGCT)-the most common solid malignancy in men aged 15-35 years. The American Joint Committee on Cancer (AJCC) 8th edition (2018) created the subclassifications pT1a (tumor size < 3 cm) and pT1b (≥ 3 cm), despite not being universally recognized. Rete testis invasion (RTI) and tumor size > 4 cm are considered features associated with a higher recurrence risk, but not formally used for staging. The authors propose further understanding the subclassification's potential impact in clinical practice, by summarizing current evidence and reviewing clinical cases in their institutions., Methods: All consecutive cases of seminoma stage I, pT1 treated in two institutions between January 2005 and December 2016 were included. Clinical data were retrieved, and variables were analyzed using SPSS. Relevant literature on the topic was reviewed., Results: Seminoma pT1 was identified in 58 patients. By using newly AJCC criteria, 29 (50%) would have been staged as pT1a and 29 (50%) pT1b. Median age at diagnosis was similar (33 in pT1a vs 32 in pT1b). Median follow-up time 5.8 years. Almost half (45%) of pT1b patients had a tumor size < 4 cm. The majority of either pT1a or pT1b were treated with chemotherapy or radiotherapy, reflecting more intensive approaches in the past. Three retroperitoneal recurrences were recorded (two in pT1a, one in pT1b, all under surveillance protocol); no deaths occurred. RTI and extensive necrosis (EN) were associated with pT1b (P < 0.0001 and P = 0.023, respectively), known adverse biological features., Conclusions: In our population, the exploratory analysis of the newly created AJCC criteria showed no significant difference in recurrence or death, although pT1b was associated with adverse biomarkers, such as RTI and EN, but its clinical relevance remains incompletely understood. Our results confirm an excellent prognosis, regardless of subcategorization, thus a larger population and a longer follow-up time are needed to understand prospectively the impact of the recently updated criteria. We would recommend using the latest AJCC staging system, although the individual risk of relapse, long-term toxicities and patient preferences should be taken into account when considering surveillance or active treatment adjuvant options.
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- 2020
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11. A Morphologic and Immunohistochemical Comparison of Nuclear β-Catenin Expressing Testicular Sertoli Cell Tumors and Pancreatic Solid Pseudopapillary Neoplasms Supporting Their Continued Separate Classification.
- Author
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Kao CS and Ulbright TM
- Subjects
- Biopsy, Cell Nucleus pathology, Humans, Male, Pancreatic Neoplasms classification, Pancreatic Neoplasms pathology, Predictive Value of Tests, Sertoli Cell Tumor classification, Sertoli Cell Tumor pathology, Testicular Neoplasms classification, Testicular Neoplasms pathology, Biomarkers, Tumor analysis, Cell Nucleus chemistry, Immunohistochemistry, Pancreatic Neoplasms chemistry, Sertoli Cell Tumor chemistry, Testicular Neoplasms chemistry, beta Catenin analysis
- Abstract
Some recent reports suggested that many Sertoli cell tumors, not otherwise specified (SCTs-NOS) of the testis were analogs of the solid pseudopapillary neoplasm (SPN) of the pancreas. One of the most relied on pieces of information for this assertion was the shared occurrence in both neoplasms of exon 3 mutations of the CTNNB1 gene, which was reflected by nuclear β-catenin expression. We, therefore, compared the morphologic and immunohistochemical features of 18 SCTs-NOS with strong, diffuse nuclear β-catenin expression with 16 SPNs that also showed such positivity. Although there were clear similarities in the light microscopic features of these neoplasms, there were also significant differences that included, in SCT-NOS and SPN, respectively: hollow tubules (53% vs. 0%), sheet-like growth (44% vs. 94%), circumscription (79% vs. 25%), corded or trabecular patterns (81% vs. 31%), formation of papillae or pseudopapillae (24% vs. 69%), growth in nests or clusters (94% vs. 50%), perivascular pseudorosettes (13% vs. 56%), and rhabdoid cytology (6% vs. 50%). Commonly shared morphologic features included signet-ring cells, pale or foamy cytoplasm, myxoid stroma, cyst formation, perivascular hyalinization, and globular or band-like basement membrane deposits. On immunohistochemical study, sex cord markers were frequently positive in SCTs-NOS (steroidogenic factor-1-94%; FOXL2-87%; SOX9-69%; calretinin-60%; Wilms tumor-1-38%; inhibin-29%) whereas all of these markers were negative in the SPNs. We conclude that even though SCT-NOS and SPN share some morphologic features and nuclear immunoreactivity for β-catenin, there remain differences, both morphologically and immunohistochemically, between these neoplasms to the degree that SCT-NOS should not be equated with pancreatic SPN.
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- 2020
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12. Contemporary North-American population-based validation of the International Germ Cell Consensus Classification for metastatic germ cell tumors of the testis.
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Mazzone E, Knipper S, Mistretta FA, Tian Z, Palumbo C, Soulieres D, De Cobelli O, Montorsi F, Shariat SF, Saad F, Briganti A, and Karakiewicz PI
- Subjects
- Adult, Consensus Development Conferences as Topic, Humans, International Cooperation, Male, Middle Aged, Neoplasms, Germ Cell and Embryonal mortality, Prognosis, Retrospective Studies, Seminoma mortality, Survival Rate, Testicular Neoplasms classification, Testicular Neoplasms mortality, Testicular Neoplasms secondary, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal secondary, Seminoma classification, Seminoma secondary, Testicular Neoplasms pathology
- Abstract
Background: The International Germ Cell Consensus Classification (IGCCC) is the recommended stratification scheme for newly diagnosed metastatic seminoma (mSGCT) and non-seminoma germ cell tumor (mNSGCT) patients. However, a contemporary North-American population-based validation has never been completed and represented our focus., Materials and Methods: We identified mSGCT and mNSGCT patients within the SEER database (2004-2015). The IGCCC criteria were used for stratification into prognostic groups. Kaplan-Meier (KM) derived actuarial 5-year overall survival (OS) rates were calculated. In addition, cumulative incidence plots tested cancer-specific (CSM) and other-cause mortality (OCM) rates., Results: Of 321 mSGCT patients, 190 (59.2%) and 131 (40.8%), respectively, fulfilled good and intermediate prognosis criteria. Of 803 mNSGCT patients, 209 (26.1%), 100 (12.4%), and 494 (61.5%), respectively, fulfilled good, intermediate, and poor prognosis criteria. In mSGCT patients, actuarial KM derived 5-year OS was 87% and 78% for, respectively, good and intermediate prognosis groups (p = 0.02). In cumulative incidence analyses, statistically significant differences were recorded for CSM but not for OCM between good versus intermediate prognosis groups. In mNSGCT patients, actuarial KM derived 5-year OS was 89%, 75% and 60% for, respectively, good, intermediate, and poor prognosis groups (p < 0.001). In cumulative incidence analyses, statistically significant differences were recorded for both CSM and OCM between good, intermediate, and poor prognosis groups., Conclusions: Our findings represent the first population-based validation of the IGCCC in contemporary North-American mSGCT and mNSGCT patients. The recorded OM rates closely replicate those of the original publication, except for better survival of poor prognosis mNSGCT patients.
- Published
- 2020
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13. MicroRNA and transcription factor co-regulatory networks and subtype classification of seminoma and non-seminoma in testicular germ cell tumors.
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Qin G, Mallik S, Mitra R, Li A, Jia P, Eischen CM, and Zhao Z
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- Humans, Kruppel-Like Factor 4, Male, Gene Expression Regulation, Neoplastic genetics, Gene Regulatory Networks genetics, MicroRNAs genetics, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal genetics, Seminoma classification, Seminoma genetics, Testicular Neoplasms classification, Testicular Neoplasms genetics, Transcription Factors genetics
- Abstract
Recent studies have revealed that feed-forward loops (FFLs) as regulatory motifs have synergistic roles in cellular systems and their disruption may cause diseases including cancer. FFLs may include two regulators such as transcription factors (TFs) and microRNAs (miRNAs). In this study, we extensively investigated TF and miRNA regulation pairs, their FFLs, and TF-miRNA mediated regulatory networks in two major types of testicular germ cell tumors (TGCT): seminoma (SE) and non-seminoma (NSE). Specifically, we identified differentially expressed mRNA genes and miRNAs in 103 tumors using the transcriptomic data from The Cancer Genome Atlas. Next, we determined significantly correlated TF-gene/miRNA and miRNA-gene/TF pairs with regulation direction. Subsequently, we determined 288 and 664 dysregulated TF-miRNA-gene FFLs in SE and NSE, respectively. By constructing dysregulated FFL networks, we found that many hub nodes (12 out of 30 for SE and 8 out of 32 for NSE) in the top ranked FFLs could predict subtype-classification (Random Forest classifier, average accuracy ≥90%). These hub molecules were validated by an independent dataset. Our network analysis pinpointed several SE-specific dysregulated miRNAs (miR-200c-3p, miR-25-3p, and miR-302a-3p) and genes (EPHA2, JUN, KLF4, PLXDC2, RND3, SPI1, and TIMP3) and NSE-specific dysregulated miRNAs (miR-367-3p, miR-519d-3p, and miR-96-5p) and genes (NR2F1 and NR2F2). This study is the first systematic investigation of TF and miRNA regulation and their co-regulation in two major TGCT subtypes.
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- 2020
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14. Ovarian germ cell tumour classification: views from the testis.
- Author
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Berney DM, Stoneham S, Arora R, Shamash J, and Lockley M
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- Female, Humans, Male, Neoplasms, Germ Cell and Embryonal pathology, Ovarian Neoplasms pathology, Testicular Neoplasms pathology, Neoplasms, Germ Cell and Embryonal classification, Ovarian Neoplasms classification, Ovary pathology, Testicular Neoplasms classification, Testis pathology
- Abstract
The classification of ovarian germ cell tumours has remained unchanged for many years, while there have been considerable changes in the testicular classification. In recent years there has been concern about the overtreatment of clinical stage 1 testicular germ cell tumours with increasing use of surveillance for low-risk disease. We outline here the current classification of germ cell tumours of the ovary with particular regard to treatment and outcome and highlight some areas which may cause confusion, particularly pertaining to immature teratomas and mixed germ cell tumours. We suggest that some minor changes to the classification, evidenced by a recent retrospective series by some of the authors, may lead to less adjuvant chemotherapy for immature teratomas and may obviate the need for the grading of immature teratomas, by aligning with testicular experience in pure post-pubertal teratomas. Adoption of this will require retrospective and prospective re-evaluation, but may avoid long-term patient morbidity., (© 2019 John Wiley & Sons Ltd.)
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- 2020
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15. Testicular Cancer, Version 2.2020, NCCN Clinical Practice Guidelines in Oncology.
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Gilligan T, Lin DW, Aggarwal R, Chism D, Cost N, Derweesh IH, Emamekhoo H, Feldman DR, Geynisman DM, Hancock SL, LaGrange C, Levine EG, Longo T, Lowrance W, McGregor B, Monk P, Picus J, Pierorazio P, Rais-Bahrami S, Saylor P, Sircar K, Smith DC, Tzou K, Vaena D, Vaughn D, Yamoah K, Yamzon J, Johnson-Chilla A, Keller J, and Pluchino LA
- Subjects
- Combined Modality Therapy, Humans, Male, Neoplasm Metastasis, Prognosis, Testicular Neoplasms diagnosis, Practice Guidelines as Topic standards, Testicular Neoplasms classification, Testicular Neoplasms therapy
- Abstract
Testicular cancer is relatively uncommon and accounts for <1% of all male tumors. However, it is the most common solid tumor in men between the ages of 20 and 34 years, and the global incidence has been steadily rising over the past several decades. Several risk factors for testicular cancer have been identified, including personal or family history of testicular cancer and cryptorchidism. Testicular germ cell tumors (GCTs) comprise 95% of malignant tumors arising in the testes and are categorized into 2 main histologic subtypes: seminoma and nonseminoma. Although nonseminoma is the more clinically aggressive tumor subtype, 5-year survival rates exceed 70% with current treatment options, even in patients with advanced or metastatic disease. Radical inguinal orchiectomy is the primary treatment for most patients with testicular GCTs. Postorchiectomy management is dictated by stage, histology, and risk classification; treatment options for nonseminoma include surveillance, systemic therapy, and nerve-sparing retroperitoneal lymph node dissection. Although rarely occurring, prognosis for patients with brain metastases remains poor, with >50% of patients dying within 1 year of diagnosis. This selection from the NCCN Guidelines for Testicular Cancer focuses on recommendations for the management of adult patients with nonseminomatous GCTs.
- Published
- 2019
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16. [Management of metastatic testicular germ cell tumors].
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Lavaud P, Baciarello G, and Fizazi K
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- Antineoplastic Agents therapeutic use, Cisplatin therapeutic use, Combined Modality Therapy methods, Humans, Male, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal pathology, Orchiectomy, Prognosis, Testicular Neoplasms classification, Testicular Neoplasms pathology, Neoplasms, Germ Cell and Embryonal secondary, Neoplasms, Germ Cell and Embryonal therapy, Testicular Neoplasms secondary, Testicular Neoplasms therapy
- Abstract
Metastatic testicular germ cell tumors are rare entities with a high cure rate owing to their major chemosensitivity. Current guidelines should be strictly followed to ensure maximal cure rate. Germ cell tumor treatment requires multidisciplinary skills and is based on cisplatin-based chemotherapy. The current challenge for these patients with favorable prognosis is to limit over- or under-treatment. Centralization of care for patients with these rare cancers is a key point to achieve the best chance of cure., (Copyright © 2019. Published by Elsevier Masson SAS.)
- Published
- 2019
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17. Incidence of testicular tumor subtypes according to the updated WHO classification, North Rhine-Westphalia, Germany, 2008-2013.
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Stang A, Rusner C, Trabert B, Oosterhuis JW, McGlynn KA, and Heidinger O
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- Adolescent, Adult, Aged, Aged, 80 and over, Child, Child, Preschool, Germany epidemiology, Humans, Incidence, Infant, Infant, Newborn, Male, Middle Aged, Testicular Neoplasms classification, World Health Organization, Young Adult, Testicular Neoplasms epidemiology
- Abstract
Background: In 2016, the WHO introduced an updated classification for testicular tumors. The application of this updated classification to cancer registry data requires some recoding of tumors., Objectives: The aim of this study was to provide up-to-date population-based incidence estimates of subtypes of testicular germ cell tumors (TGCT) according to the updated classification., Material and Methods: We reviewed 2251 pathology reports (42.9%) out of 5252 testicular tumors at the cancer registry of North Rhine-Westphalia for the years 2008-2013. We used population counts to estimate age-standardized incidence rates per million person-years (EUROSTAT revised European Standard Population)., Results: The application of the updated WHO classification resulted in a recoding of 8.9% of all testicular tumors. While the recodings have no influence on the incidence of seminomatous and non-seminomatous TGCTs that include mixed TGCTs, they influence the incidence of individual histological types of seminomatous and non-seminomatous TGCTs. Among the 4935 testicular germ cell tumors (TGCT), 23.7% were mixed TGCTs. Overall, 46.9% of all mixed TGCTs included seminoma and age-standardized incidence rates were highest for the combination seminoma plus embryonal carcinoma (5.9 per million person-years) and embryonal carcinoma plus teratoma (4.9 per million person-years). The median age at diagnosis was higher for mixed TGCTs including seminoma (31 years) than those that did not include seminoma (28 years)., Discussion and Conclusions: Population-based incidence time trends for seminomatous and non-seminomatous TGCTs that include mixed TGCTs are not distorted by the introduction of the WHO update. Trend distortions can only be expected if time trends of individual histological subtypes of the seminomatous and non-seminomatous TGCTs are examined., (© 2018 American Society of Andrology and European Academy of Andrology.)
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- 2019
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18. Recently Described and Clinically Important Entities in Testis Tumors: A Selective Review of Changes Incorporated Into the 2016 Classification of the World Health Organization.
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Ulbright TM
- Subjects
- Humans, Male, Testicular Neoplasms pathology, World Health Organization, Testicular Neoplasms classification
- Abstract
Context.—: In 2016 the World Health Organization published a revised classification of testicular neoplasms based upon advances in understanding their pathogenesis and molecular biology. The rationale for this revision and additional clinically relevant observations were the topics of a talk given to the Houston Society of Clinical Pathologists in April 2017. This paper summarizes that talk., Objective.—: To summarize and explain the most important changes to the classification of testicular neoplasms in the World Health Organization 2016 revision., Data Sources.—: Peer-reviewed published literature and contributions by individuals with expertise in this area that were also reviewed by genitourinary pathologists., Conclusions.—: Most changes occurred in the germ cell tumor classification, including replacement of the terms intratubular germ cell neoplasia unclassified and carcinoma in situ by germ cell neoplasia in situ ; subdivision of the tumors into 2 main categories, those derived from germ cell neoplasia in situ and those not derived from germ cell neoplasia in situ; distinction of germ cell neoplasia in situ from germ cells with delayed maturation and pre-germ cell neoplasia in situ; expansion of the trophoblastic tumor category to include epithelioid trophoblastic tumor and cystic trophoblastic tumor; and substitution of spermatocytic tumor for spermatocytic seminoma and its placement in the non-germ cell neoplasia in situ group. Other revisions included eliminating sclerosing Sertoli cell tumor as a distinct entity; the recognition of intratubular hyalinizing Sertoli cell tumor; and acceptance of the role of undifferentiated gonadal tissue in the pathogenesis of gonadoblastoma.
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- 2019
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19. [Testicular germ cell tumors: Histopathological and molecular features].
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Tourne M, Radulescu C, and Allory Y
- Subjects
- Age Factors, Carcinoma, Embryonal classification, Carcinoma, Embryonal genetics, Carcinoma, Embryonal pathology, Choriocarcinoma classification, Choriocarcinoma genetics, Choriocarcinoma pathology, Choriocarcinoma, Non-gestational classification, Choriocarcinoma, Non-gestational genetics, Choriocarcinoma, Non-gestational pathology, Gene Deletion, Humans, Immunohistochemistry, Male, Mutation genetics, Neoplasms, Germ Cell and Embryonal classification, Seminoma classification, Seminoma genetics, Seminoma pathology, Teratoma classification, Teratoma genetics, Teratoma pathology, Terminology as Topic, Testicular Neoplasms classification, Neoplasms, Germ Cell and Embryonal genetics, Neoplasms, Germ Cell and Embryonal pathology, Testicular Neoplasms genetics, Testicular Neoplasms pathology
- Abstract
In 2016, the WHO classification of testicular germ cell tumors was revised considering advances in the understanding of their tumorigenesis and molecular features. This restructuring led to a division into two major groups with, on one hand, prepubertal-type tumors, not derived from germ cell neoplasia in situ (GCNIS), and on the other hand, postpubertal-type tumors, GCNIS-derived, which occur in youg men (seminoma and non seminomatous germ cell tumors - embryonal carcinoma, yolk sac tumor, teratoma and choriocarcinoma essentially). The term germ cell neoplasia in situ is consensually accepted as a new terminology for the precursor lesion. In this new classification, the term "spermatocytic seminoma" is replaced by "spermatocytic tumor", reclassified among non-GCNIS-derived tumors. The purpose of this change of nomenclature is to reflect the usually non-aggressive behaviour of this tumor and to avoid any confusion with usual seminoma. The spectrum of trophoblastic tumors continues to expand with the description of new rare entities such as the cystic trophoblastic tumor, the placental site trophoblastic tumor and the epithelioid trophoblastic tumor. This review aims to provide a focus on testicular germ cell tumors highlighting the new immunohistochemical and molecular features responsible for the restructuring of classification. The TNM staging is presented according to the AJCC 8th edition 2017 update., (Copyright © 2019 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.)
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- 2019
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20. Reclassification of good-risk seminoma: prognostic factors, novel biomarkers and implications for clinical management.
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Casadei C, Schepisi G, Menna C, Chovanec M, Gurioli G, Gallà V, Altavilla A, Marcellini M, Bellia SR, Lolli C, Mego M, Rosti G, and De Giorgi U
- Subjects
- Disease-Free Survival, Humans, Lung Neoplasms secondary, Lung Neoplasms therapy, Male, Neoplasm Staging, Prognosis, Risk Assessment, Seminoma mortality, Seminoma secondary, Seminoma therapy, Testicular Neoplasms mortality, Testicular Neoplasms secondary, Testicular Neoplasms therapy, Testis pathology, Biomarkers, Tumor analysis, Lung Neoplasms mortality, Seminoma classification, Testicular Neoplasms classification
- Abstract
Germ cell tumors represent 11% of the cancers diagnosed in adolescent males and are the most common solid tumors in adult men between the ages of 20 and 35. Pure seminoma accounts for around 50% of all testicular germ cell tumors. The prognostic classification of the International Germ Cell Cancer Collaborative Group for good-prognosis seminoma includes both nodal disease and pulmonary visceral metastases. In this article, we analyzed recent data on prognosis and outcome of good-prognosis seminoma to revise the traditional classification of the disease and improve tailored treatment.
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- 2019
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21. Shared and unique genomic structural variants of different histological components within testicular germ cell tumours identified with mate pair sequencing.
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Bryce AH, Egan JB, Smadbeck JB, Johnson SH, Murphy SJ, Harris FR, Halling GC, Terra SBSP, Cheville J, Pagliaro L, Leibovich B, Costello BA, and Vasmatzis G
- Subjects
- Adolescent, Adult, DNA, Neoplasm genetics, High-Throughput Nucleotide Sequencing, Humans, Middle Aged, Neoplasms, Germ Cell and Embryonal pathology, Testicular Neoplasms pathology, Young Adult, Chromosome Aberrations, DNA, Neoplasm analysis, Genomic Structural Variation, Mutation, Neoplasm Proteins genetics, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal genetics, Testicular Neoplasms classification, Testicular Neoplasms genetics
- Abstract
Post-pubertal testicular germ-cell tumours (TGCTs) can present with a variety of distinct histologies which are nevertheless lineage related and often co-occurring. The exact lineage relationships and developmental pathways leading to the different histologies is debated. In order to investigate the relationship of histologic populations, mate-pair sequencing (MPseq) and exome sequencing (ExomeSeq) were conducted on different histological populations within the same tumour. Ten TGCTs with 1-3 histologic types/tumour were sequenced. Junctions of somatic chromosomal rearrangements were identified on a per genome basis, with germ cell neoplasia in situ possessing the least (median 1, range 0-4) and embryonal carcinoma the most (median 8.5, range 6-12). Copy number variation revealed gains and losses, including isoform 12p (i12p) (10/10 samples), and chromosomes 7, 8, and 21 gains (7/10 samples). Mapping of shared junctions within a tumour revealed lineage relationships, but only i12p was shared between patients. ExomeSeq from two cases demonstrated a high level of copy-neutral loss of heterozygosity. Parallel assessment of separate histologies within a single TGCT demonstrated cumulative and divergent changes, suggesting the importance of parallel sequencing for detection of relevant biomarkers.
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- 2019
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22. Pre-orchiectomy tumor marker levels should not be used for International Germ Cell Consensus Classification (IGCCCG) risk group assignment.
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Fankhauser CD, Gerke TA, Roth L, Sander S, Grossmann NC, Kranzbühler B, Eberli D, Sulser T, Beyer J, and Hermanns T
- Subjects
- Adult, Antineoplastic Agents, Disease-Free Survival, Humans, Male, Neoplasms, Germ Cell and Embryonal pathology, Neoplasms, Germ Cell and Embryonal therapy, Orchiectomy, Prognosis, Testicular Neoplasms pathology, Testicular Neoplasms therapy, Biomarkers, Tumor analysis, Neoplasms, Germ Cell and Embryonal classification, Testicular Neoplasms classification
- Abstract
Purpose: To investigate whether the use of pre-orchiectomy instead of pre-chemotherapy tumor marker (TM) levels has an impact on the International Germ Cell Consensus Classification (IGCCCG) risk group assignment in patients with metastatic germ cell tumors (GCT)., Methods: Demographic and clinical information of all patients treated for primary metastatic testicular non-seminomatous GCT in our tertiary care academic center were extracted from medical charts. IGCCCG risk group assignment was correctly performed with pre-chemotherapy marker levels and additionally with pre-orchiectomy marker levels. Agreement between pre-chemotherapy and pre-orchiectomy risk group assignments was assessed using Cohen's kappa., Results: Our cohort consisted of 83 patients. The use of pre-orchiectomy TMs resulted in an IGCCCG risk group upstaging in 12 patients (16%, 8 patients from good to intermediate risk and 4 patients from intermediate to poor risk) and a downstaging in 1 patient (1.2%, from intermediate- to good-risk). The agreement between pre-orchiectomy and pre-chemotherapy IGCCCG risk groups resulted in a Cohen's kappa of 0.888 (p < 0.001)., Conclusions: Using pre-orchiectomy TMs can result in incorrect IGCCCG risk group assignment, which in turn can impact on the clinical management and follow-up of patients with metastatic GCT. Thus, adherence to the IGCCCG standard using pre-chemotherapy TMs levels is recommended.
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- 2019
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23. Updates in Staging and Reporting of Testicular Cancer.
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Magers MJ and Idrees MT
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- Biomarkers, Tumor blood, Humans, Lymphatic Metastasis, Male, Neoplasm Invasiveness, Neoplasm Metastasis, Neoplasm Staging, Neoplasms, Germ Cell and Embryonal classification, Prognosis, Risk Assessment, Testicular Neoplasms classification, Testis anatomy & histology, Testis pathology, Neoplasms, Germ Cell and Embryonal pathology, Testicular Neoplasms pathology
- Abstract
The American Joint Committee for Cancer eighth edition staging manual incorporated several critical changes regarding staging of testis germ cell tumors, and these changes are summarized and discussed in this article. Further challenges, however, remain, and these are also highlighted., (Copyright © 2018 Elsevier Inc. All rights reserved.)
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- 2018
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24. DNA methylation profiling as a tool for testicular germ cell tumors subtyping.
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Costa AL, Moreira-Barbosa C, Lobo J, Vilela-Salgueiro B, Cantante M, Guimarães R, Lopes P, Braga I, Oliveira J, Antunes L, Henrique R, and Jerónimo C
- Subjects
- Adolescent, Adult, Cytokines genetics, DNA Modification Methylases genetics, DNA Repair Enzymes genetics, GPI-Linked Proteins genetics, Homeodomain Proteins genetics, Humans, Intercellular Signaling Peptides and Proteins genetics, Male, Middle Aged, Neoplasm Proteins genetics, Neoplasms, Germ Cell and Embryonal diagnosis, Neoplasms, Germ Cell and Embryonal genetics, Neoplasms, Germ Cell and Embryonal pathology, Portugal, Prognosis, ROC Curve, Testicular Neoplasms diagnosis, Testicular Neoplasms genetics, Testicular Neoplasms pathology, Tumor Suppressor Proteins genetics, Young Adult, DNA Methylation, Neoplasms, Germ Cell and Embryonal classification, Promoter Regions, Genetic genetics, Testicular Neoplasms classification
- Abstract
Aim: Assess differential patterns of selected five genes' promoter methylation among testicular germ cell tumors (TGCT) subtypes., Materials & Methods: CRIPTO, HOXA9, MGMT, RASSF1A and SCGB3A1 promoter methylation levels were evaluated by quantitative methylation-specific PCR in 161 TGCT and 16 controls. Associations between clinicopathological parameters and promoter methylation levels were assessed, and receiver operating characteristics curve analysis was performed., Results: Promoter methylation of CRIPTO/HOXA9/SCGB3A1 panel and RASSF1A best discriminated between controls and nonseminomatous tumors or seminomas, respectively, whereas HOXA9/RASSF1A panel displayed the best discriminative performance between nonseminomatous tumor and seminomas. Significant differences in CRIPTO, MGMT and RASSF1A methylation levels were depicted between pure forms and matched mixed components of seminomas and embryonal carcinoma. HOXA9, RASSF1A and SCGB3A1 promoter methylation significantly associated with tumor stage., Conclusion: Different combinations of five genes' promoter methylation levels discriminate among TGCT subtypes. Methylation patterns may also assist in identification of more clinically aggressive tumors.
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- 2018
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25. Testicular germ cell tumors: revisiting a series in light of the new WHO classification and AJCC staging systems, focusing on challenges for pathologists.
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Lobo J, Costa AL, Vilela-Salgueiro B, Rodrigues Â, Guimarães R, Cantante M, Lopes P, Antunes L, Jerónimo C, and Henrique R
- Subjects
- Adult, Biopsy, Disease Progression, Humans, Immunohistochemistry, Male, Mitotic Index, Necrosis, Neoplasm Invasiveness, Neoplasm Recurrence, Local, Neoplasms, Germ Cell and Embryonal mortality, Neoplasms, Germ Cell and Embryonal therapy, Predictive Value of Tests, Retrospective Studies, Risk Factors, Testicular Neoplasms mortality, Testicular Neoplasms therapy, Time Factors, Tumor Burden, World Health Organization, Young Adult, Neoplasm Staging methods, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal secondary, Pathologists, Testicular Neoplasms classification, Testicular Neoplasms pathology
- Abstract
Testicular germ cell tumors (TGCTs) are strikingly heterogeneous, reflecting a complex tumor model, posing serious challenges for pathologists. Accurate classification and staging, according to most recent systems, is fundamental. We aimed to revise a series of consecutively diagnosed TGCTs (2005-2016) in light of the new World Health Organization (WHO) classification and American Joint Committee on Cancer (AJCC) staging systems, discussing dilemmas imposed to pathologists. All 164 patients' clinical files/histological slides were reviewed. Follow-up was last updated on November 2017. Statistical analysis was performed with SPSS (v24). P < 0.05 was considered significant. Non-seminomatous tumors (NSTs) showed more frequently cysts, necrosis, hemorrhage, lymphovascular invasion (LVI) and higher stage than seminomas (SEs) (P < .001, P = .015, P < .001, P = .001, P = .007). Embryonal carcinoma (EC), yolk sac tumor (YST) and teratoma (TE) were the most frequent components in mixed tumors (82.5%, 82.5% and 80.7%). SEs with "atypical features" showed more LVI, higher mitotic count and more extensive necrosis (P = .030, P < .001, P = .016). LVI and >50%EC component, but not rete testis invasion, were associated with higher stage (P < .001, P = .009). Regarding SEs, there was an association between tumor size and both stage (P = .004) and LVI (P < .001). Only four patients disclosed altered stage group when AJCC 8th Edition was employed. Disease recurrence/progression occurred in 5.4% of cases. In two cases, tumor components in metastasectomy specimens were not present in the primary TGCT. Overall survival at 5 years was 98.6%. TGCTs are challenging neoplasms, and pathologists and clinicians alike must be aware of recent updates in classification and staging for adequately tailoring treatment strategies., (Copyright © 2018 Elsevier Inc. All rights reserved.)
- Published
- 2018
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26. Integrated Molecular Characterization of Testicular Germ Cell Tumors.
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Shen H, Shih J, Hollern DP, Wang L, Bowlby R, Tickoo SK, Thorsson V, Mungall AJ, Newton Y, Hegde AM, Armenia J, Sánchez-Vega F, Pluta J, Pyle LC, Mehra R, Reuter VE, Godoy G, Jones J, Shelley CS, Feldman DR, Vidal DO, Lessel D, Kulis T, Cárcano FM, Leraas KM, Lichtenberg TM, Brooks D, Cherniack AD, Cho J, Heiman DI, Kasaian K, Liu M, Noble MS, Xi L, Zhang H, Zhou W, ZenKlusen JC, Hutter CM, Felau I, Zhang J, Schultz N, Getz G, Meyerson M, Stuart JM, Akbani R, Wheeler DA, Laird PW, Nathanson KL, Cortessis VK, and Hoadley KA
- Subjects
- DNA Copy Number Variations, DNA Methylation, Gene Expression Regulation, Neoplastic, Humans, Male, MicroRNAs metabolism, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal metabolism, Proto-Oncogene Proteins c-kit genetics, Proto-Oncogene Proteins c-kit metabolism, Seminoma metabolism, Seminoma pathology, Testicular Neoplasms classification, Testicular Neoplasms metabolism, ras Proteins genetics, ras Proteins metabolism, Neoplasms, Germ Cell and Embryonal pathology, Testicular Neoplasms pathology
- Abstract
We studied 137 primary testicular germ cell tumors (TGCTs) using high-dimensional assays of genomic, epigenomic, transcriptomic, and proteomic features. These tumors exhibited high aneuploidy and a paucity of somatic mutations. Somatic mutation of only three genes achieved significance-KIT, KRAS, and NRAS-exclusively in samples with seminoma components. Integrated analyses identified distinct molecular patterns that characterized the major recognized histologic subtypes of TGCT: seminoma, embryonal carcinoma, yolk sac tumor, and teratoma. Striking differences in global DNA methylation and microRNA expression between histology subtypes highlight a likely role of epigenomic processes in determining histologic fates in TGCTs. We also identified a subset of pure seminomas defined by KIT mutations, increased immune infiltration, globally demethylated DNA, and decreased KRAS copy number. We report potential biomarkers for risk stratification, such as miRNA specifically expressed in teratoma, and others with molecular diagnostic potential, such as CpH (CpA/CpC/CpT) methylation identifying embryonal carcinomas., (Copyright © 2018 The Author(s). Published by Elsevier Inc. All rights reserved.)
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- 2018
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27. Germ cell tumour subtypes display differential expression of microRNA371a-3p.
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Vilela-Salgueiro B, Barros-Silva D, Lobo J, Costa AL, Guimarães R, Cantante M, Lopes P, Braga I, Oliveira J, Henrique R, and Jerónimo C
- Subjects
- Adolescent, Adult, Aged, Aged, 80 and over, Humans, Male, MicroRNAs metabolism, Middle Aged, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal metabolism, Portugal, Testicular Neoplasms classification, Testicular Neoplasms metabolism, Young Adult, Gene Expression, MicroRNAs genetics, Neoplasms, Germ Cell and Embryonal genetics, Testicular Neoplasms genetics
- Abstract
Testicular germ cell tumours (TGCTs) are a heterogeneous group of neoplasms, mostly affecting young men. Curability rates are high and adequate treatment relies on careful and accurate pathological and clinical assessment. Indeed, TGCTs' histopathological subtyping is critical for adequate therapeutic decision. Considering the limitation of currently available serum biomarkers, novel candidates have been proposed, most notably miR-371a-3p, which outperformed classical serum markers, but no detailed information concerning TGCT subtype was available. Thus, we carried out evaluation of miR-371a-3p expression levels among TGCT subtypes using a consecutive cohort of tissue samples. MiR-371a-3p discriminated TGCTs from control tissues with high sensitivity and specificity (AUC = 0.99). Furthermore, seminomas displayed higher miR-371a-3p expression levels compared to non-seminomatous TGCTs, which also showed significant differences among them. Nonetheless, prepubertal TGCTs depicted lower miR-371a-3p expression levels than postpubertal TGCTs. Globally, miR-371a-3p expression levels decreased in parallel with progressive cell differentiation. We concluded that miR-371a-3p is TGCTs-specific and it might be clinically useful for early detection and disease monitoring.This article is part of a discussion meeting issue 'Frontiers in epigenetic chemical biology'., (© 2018 The Author(s).)
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- 2018
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28. Recent Advances in New Discovered Molecular Targets in Testicular Germ Cell Tumors.
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Chieffi P
- Subjects
- Animals, Aurora Kinase B antagonists & inhibitors, Biomarkers, Tumor genetics, Humans, Male, MicroRNAs genetics, Molecular Targeted Therapy, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal genetics, Testicular Neoplasms classification, Testicular Neoplasms genetics, Biomarkers, Tumor metabolism, Neoplasms, Germ Cell and Embryonal metabolism, Testicular Neoplasms metabolism
- Abstract
Background: Testicular germ cell tumor (TGCT) is the most common solid malignancy occurring in young men between 20 and 34 years of age, and its incidence has increased significantly over the last decades. TGCTs can be subdivided into seminoma and nonseminoma germ cell tumors (NSGCTs), which includes yolk sac tumor, choriocarcinoma, embryonal cell carcinoma, and teratoma. Seminomas and NSGCTs present significant differences in therapy, prognosis, and both show characteristics of the Primordial Germ Cells (PGCs)., Methods: I undertook a search of bibliographic data from peer-reviewed research literature., Results: Seventy papers were included in the mini-review showing that a large number of new biomarkers have given further advantages to discriminate the different histotypes and could represent useful novel molecular targets for anticancer strategies., Conclusion: A deeper understanding of the pathogenesis of TGCTs is likely to significantly improve not only our knowledge on stem cells and oncogenesis but also the disease management with more selective tumor treatment., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)
- Published
- 2018
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29. Detailed pathologic analysis on the co-occurrence of non-seminomatous germ cell tumor subtypes in matched orchiectomy and retroperitoneal lymph node dissections.
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Spratt DE, Suresh K, Osawa T, Schipper M, Jackson WC, Abugharib A, Lebastchi A, Smith D, Montgomery JS, Palapattu GS, Priya Kunju L, Wu A, Lew M, Tomlins SA, Chinnaiyan AM, Weizer AZ, Hafez KS, Kaffenberger SD, Udager A, and Mehra R
- Subjects
- Adult, Follow-Up Studies, Humans, Male, Middle Aged, Neoplasms, Germ Cell and Embryonal surgery, Prognosis, Retroperitoneal Neoplasms surgery, Retrospective Studies, Survival Rate, Testicular Neoplasms surgery, Lymph Node Excision methods, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal pathology, Orchiectomy methods, Retroperitoneal Neoplasms pathology, Testicular Neoplasms classification, Testicular Neoplasms pathology
- Abstract
The frequency of co-occurrence between germ cell tumor (GCT) components in non-seminomatous germ cell tumor (NSGCT) orchiectomy specimens and their correlation with histologic findings in subsequent retroperitoneal lymph node dissection (RPLND) specimens have not been well characterized. The objective of the study was to report the first detailed clinicopathologic analysis of NSGCT orchiectomy and RPLND samples to determine the likelihood and agreement of the co-occurrence of GCT components. A total of 118 consecutive patients with NSGCT treated between 1988 and 2012 who underwent both orchiectomy and RPLND at a single academic tertiary care center were analyzed. Statistical analysis of co-occurrence likelihood and agreement of GCT components was performed, both within and between orchiectomy and RPLND specimens. Embryonal carcinoma was the most frequent component present in orchiectomy specimens, and there were multiple significant associations between orchiectomy GCT components; seminoma occurred less frequently with embryonal carcinoma (OR 0.29 [95% confidence interval (CI) 0.11-0.75]; p < 0.01), and teratoma more frequently occurred with choriocarcinoma (OR 9.64 [95% CI 1.22-76.12]; p = 0.01). Presence of teratoma in the orchiectomy specimen predicted for a fourfold increase in distant metastasis on multivariate analysis (HR 4.92 [1.14-18.9]; p = 0.02). The only significant association of co-occurrence in the RPLND specimen was between embryonal carcinoma and teratoma (OR 0.01 [95% CI 0-0.07]; p < 0.001), where it was significantly less likely for them to occur together. Our findings are limited by their retrospective nature. The co-occurrence of GCT components within orchiectomy specimens does not appear to be a completely random process. However, there is less agreement and more randomness between the occurrence of the GCT components in matched orchiectomy and RPLND samples. In this report, we look at the co-occurrence of different GCT components within matched orchiectomy and RPLND pathology specimens and show that co-occurrence is not a completely random process.
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- 2018
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30. Incorporating age into International Germ Cell Consensus Classification (IGCCC): a time to move forward?
- Author
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Abdel-Rahman O
- Subjects
- Adult, Age Factors, Biomarkers, Tumor metabolism, Consensus, Databases, Factual, Female, Humans, Internationality, Kaplan-Meier Estimate, Male, Multivariate Analysis, Neoplasm Metastasis, Neoplasms, Germ Cell and Embryonal pathology, Prognosis, SEER Program, Seminoma pathology, Survival Analysis, Testicular Neoplasms pathology, Neoplasms, Germ Cell and Embryonal classification, Seminoma classification, Testicular Neoplasms classification
- Abstract
Background: Older age is a poor prognostic indicator among patients with germ cell tumors. The current study evaluates an age-integrated international germ cell consensus classification (IGCCC) for advanced germ cell tumors., Methods: SEER database (2004-2014) was accessed through SEER*Stat program and both IGCCC and age-integrated IGCCC were calculated based on site of the primary, site of the metastasis and level of tumor markers. Overall survival analyses according to IGCCC and age-integrated IGCCC were conducted through Kaplan-Meier analysis., Results: Overall survival was compared according to IGCCC and age-integrated IGCCC for patients with seminoma and Non-seminomatous germ cell tumors (NSGCTs). P values were significant (P <0.001) for all scenarios. c-index for seminoma for IGCCC was 0.553; c-index for seminoma for age-integrated IGCCC was 0.664;c-index for NSGCTs for IGCCC was 0.729; and c-index for NSGCTs for age-integrated IGCCC was 0.738. A Cox-regression multivariate model of factors affecting cancer-specific survival (adjusted for race and surgical treatment) was conducted. All P values for pair wise comparisons (among different age-integrated IGCCC categories) were significant for both seminoma and NSGCTs (P<0.01)., Conclusion: Compared to traditional IGCCC, age-integrated IGCCC is more discriminatory and the new risk groups introduced within it are prognostically relevant.
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- 2018
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31. Sonographic classification of testicular tumors by tissue harmonic imaging: experience of 58 cases.
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Kawamoto A, Hatano T, Saito K, Inoue R, Nagao T, and Sanada S
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- Adult, Humans, Male, Middle Aged, Retrospective Studies, Testicular Neoplasms pathology, Ultrasonography, Doppler, Color, Young Adult, Testicular Neoplasms classification, Testicular Neoplasms diagnostic imaging
- Abstract
Purpose: To evaluate the relationship between our proposed sonographic classification of testicular tumors by tissue harmonic imaging and histological type., Methods: We retrospectively analyzed 58 testicular tumors and tumor-like lesions [seminomatous germ cell tumor (SGCT): 28; non-seminomatous germ cell tumor (NSGCT): 16; lymphoid and hematopoietic tumor (LHT): 7; Leydig cell tumor: 1; epidermal cyst: 2; and tumor of paratesticular structure (TPS): 4]. We divided a sonographic image into six types for morphological criteria and three types for color Doppler criteria. We examined the relationship between the sonographic classification and histological type., Results: For morphological criteria, there were 21 cases of Type I (36%), 15 Type II (26%), 9 Type III (15%), five Type IV (9%), five Type V (9%), and three Type VI (5%). For color Doppler criteria, there were 47 cases classified as hypervascular (81%), eight as hypovascular (14%), and three as avascular (5%). Most of the SGCTs were divided into types I and II; the NSGCTs into types III, IV, and V; the LHTs into only type II; and the TPSs into type VI., Conclusion: We established a sonographic classification of testicular tumors with various histological types. This sonographic classification is potentially useful for estimating the histological type of testicular tumors.
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- 2018
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32. [Adult type granulosa cell testicular tumor. Case report and bibliographic review.]
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Meilán E, Esquinas C, Romero I, Duarte J, and García-Tello A
- Subjects
- Female, Granulosa Cell Tumor classification, Humans, Male, Middle Aged, Testicular Neoplasms classification, Granulosa Cell Tumor pathology, Testicular Neoplasms pathology
- Abstract
Objetive: To describe the adult type granulosa cell testicular tumors (classified as sex cordstromal tumor) due to their behavior, hardly known with a small number of cases reported., Method: We report a new case of a 59-year-old man presenting an adult type granulosa cell tumor of the testis (AGCTT), painless, with a 3.3 centimeter intratesticular heterogeneous mass on ultrasound, with solid and cystic areas. Serum tumor markers and extension study were negative., Results: Histologic and inmunohistochemical studies confirmed an AGCTT, similar to its ovarian counterpart., Conclusion: AGCTT are rare neoplasms with unpredictable behavior. Their metastatic potential has been described, reason why they need a long follow-up; however, they usually have a good prognosis.
- Published
- 2017
33. Perspectives on testicular sex cord-stromal tumors and those composed of both germ cells and sex cord-stromal derivatives with a comparison to corresponding ovarian neoplasms.
- Author
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Roth LM, Lyu B, and Cheng L
- Subjects
- Biomarkers, Tumor analysis, Biomarkers, Tumor genetics, Cell Differentiation, Cell Lineage, Epigenesis, Genetic, Female, Gene Expression Regulation, Neoplastic, Genetic Predisposition to Disease, Humans, Male, Neoplasms, Complex and Mixed chemistry, Neoplasms, Complex and Mixed classification, Neoplasms, Complex and Mixed genetics, Neoplasms, Germ Cell and Embryonal chemistry, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal genetics, Ovarian Neoplasms chemistry, Ovarian Neoplasms classification, Ovarian Neoplasms genetics, Phenotype, Sex Cord-Gonadal Stromal Tumors chemistry, Sex Cord-Gonadal Stromal Tumors classification, Sex Cord-Gonadal Stromal Tumors genetics, Testicular Neoplasms chemistry, Testicular Neoplasms classification, Testicular Neoplasms genetics, Neoplasms, Complex and Mixed pathology, Neoplasms, Germ Cell and Embryonal pathology, Ovarian Neoplasms pathology, Sex Cord-Gonadal Stromal Tumors pathology, Testicular Neoplasms pathology
- Abstract
Sex cord-stromal tumors (SCSTs) are the second most frequent category of testicular neoplasms, accounting for approximately 2% to 5% of cases. Both genetic and epigenetic factors account for the differences in frequency and histologic composition between testicular and ovarian SCSTs. For example, large cell calcifying Sertoli cell tumor and intratubular large cell hyalinizing Sertoli cell neoplasia occur in the testis but have not been described in the ovary. In this article, we discuss recently described diagnostic entities as well as inconsistencies in nomenclature used in the recent World Health Organization classifications of SCSTs in the testis and ovary. We also thoroughly review the topic of neoplasms composed of both germ cells and sex cord derivatives with an emphasis on controversial aspects. These include "dissecting gonadoblastoma" and testicular mixed germ cell-sex cord stromal tumor (MGC-SCST). The former is a recently described variant of gonadoblastoma that sometimes is an immediate precursor of germinoma in the dysgenetic gonads of patients with a disorder of sex development. Although the relationship of dissecting gonadoblastoma to the previously described undifferentiated gonadal tissue is complex and not entirely resolved, we believe that it is preferable to continue to use the term undifferentiated gonadal tissue for those cases that are not neoplastic and are considered to be the precursor of classical gonadoblastoma. Although the existence of testicular MGC-SCST has been challenged, the most recent evidence supports its existence; however, testicular MGC-SCST differs significantly from ovarian examples due to both genetic and epigenetic factors., (Copyright © 2017 Elsevier Inc. All rights reserved.)
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- 2017
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34. [Updates on diagnosis and classification of testicular germ cell tumors].
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Lyu BJ and Cheng L
- Subjects
- Humans, Male, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal diagnosis, Testicular Neoplasms classification, Testicular Neoplasms diagnosis
- Published
- 2017
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35. [Germ cell and sex cord-stromal tumors of the testis : WHO classification 2016].
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Mikuz G
- Subjects
- Humans, Male, Neoplasms, Germ Cell and Embryonal pathology, Sex Cord-Gonadal Stromal Tumors pathology, Testicular Neoplasms pathology, World Health Organization, Neoplasms, Germ Cell and Embryonal classification, Sex Cord-Gonadal Stromal Tumors classification, Testicular Neoplasms classification
- Abstract
Earlier revisions of the WHO classification of testicular tumors, which was originally published in 1977, contained only minor additions. In the WHO 2016 classification, in contrast, germ cell tumors are split into two major groups based on their distinct pathohistogenesis, i. e., those which derive from an in situ forerunner lesion and those which do not. The latter category includes prepubertal yolk sac tumors and teratomas, as well as spermatocytic seminoma. The classification of yolk sac tumors and teratomas as arising before or after puberty is also of prognostic value. The group of trophoblastic tumors has also been divided into choriocarcinoma and "nonchoriocarcinomatous trophoblastic tumors," which are rare but may also be clinically significant. The changes in the classification of the sex cord-stromal tumors are not particularly important; rare variants without clinical importance of the single well-known tumors have been omitted. A new entity, a kind of "in situ" large cell Sertoli cell neoplasia, has been introduced.
- Published
- 2017
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36. A Suggested Prognostic Reclassification of Intermediate and Poor-Risk Nonseminomatous Germ Cell Tumors.
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Necchi A, Pond GR, Nicolai N, Giannatempo P, Raggi D, Adra N, Hanna NH, Salvioni R, Einhorn LH, and Albany C
- Subjects
- Adolescent, Adult, Age of Onset, Bleomycin therapeutic use, Cisplatin therapeutic use, Etoposide therapeutic use, Humans, Male, Middle Aged, Neoplasm Metastasis, Prognosis, Risk Assessment, Survival Analysis, Treatment Outcome, Young Adult, Antineoplastic Agents therapeutic use, Brain Neoplasms secondary, Lung Neoplasms secondary, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal drug therapy, Testicular Neoplasms classification, Testicular Neoplasms drug therapy
- Abstract
Background: The International Germ Cell Cancer Collaborative Group (IGCCCG) classification has been used since 1997 to allocate metastatic germ cell tumors (GCTs), but its applicability needs an update. We aimed to revisit the outcomes of intermediate and poor risk nonseminomatous GCTs (NSGCTs)., Patients and Methods: Individual patient-level data from the databases of 2 institutions were collected. Outcomes of consecutive patients who received first-line chemotherapy from 1990 to 2014 were used. The Kaplan-Meier method was used to estimate relapse-free (RFS) and overall survival (OS). Cox regression analyses were used to evaluate potential prognostic factors of RFS and OS univariably. Forward stepwise selection was used to construct a multivariable model. A risk factor (RF) model was then constructed and compared with IGCCCG classification using the concordance statistics (CS)., Results: A total of 647 patients were identified. Four RFs for OS in the multivariable model were identified: primary mediastinal NSGCT (P < .001), brain metastases (P < .001), lung metastases (P = .016), and age at the time of diagnosis (P = .003). CS were improved on the basis of the number of RF (0, 1, 2, and 3 or 4) compared with IGCCCG (RFS: 0.63 vs. 0.58; OS: 0.65 vs. 0.59). For intermediate risk, there were no differences between 3 (n = 25) and 4 cycles of cisplatin, etoposide, and bleomycin (BEP; n = 159) or BEP × 3 + etoposide and cisplatin (EP) × 1 (n = 31) for RFS (P = .35) and OS (P = .061)., Conclusion: An improved risk stratification was obtained for intermediate and poor risk GCTs. Our reclassification system might provide an aid for a reclassification attempt of all GCT patients. Our prognostic model might be offered to clinicians to improve their ability to assess patient prognosis, enhance stratification, and inform patients., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2017
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37. The World Health Organization 2016 classification of testicular non-germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel.
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Idrees MT, Ulbright TM, Oliva E, Young RH, Montironi R, Egevad L, Berney D, Srigley JR, Epstein JI, and Tickoo SK
- Subjects
- Humans, Male, World Health Organization, Sex Cord-Gonadal Stromal Tumors classification, Testicular Neoplasms classification
- Abstract
The World Health Organization (WHO) released a new tumour classification for the genitourinary system in early 2016 after consensus by pathologists with expertise in these organs. It utilized the framework of the 2004 classification, and incorporated the most up-to-date information concerning these tumours. In testicular tumours, the majority of the changes occurred in the nomenclature and classification of germ cell tumours; however, several modifications were also made for non-germ cell tumours. Among sex cord-stromal tumours, sclerosing Sertoli cell tumour (SCT) is no longer recognized as a separate entity but as a morphological variant of SCT not otherwise specified (NOS), as CTNNB1 gene mutations have been noted in both neoplasms but not in the other forms of SCT. Similarly, the lipid cell variant is not separately classified, but is considered to be a morphological variant of SCT NOS. Large-cell calcifying SCT is recognized as a distinct entity that occurs either sporadically or in association with Carney complex, with the latter patients having a distinct germline PRKAR1A gene mutation. Intratubular large-cell hyalinizing Sertoli cell neoplasia is also accepted as a separate entity linked with Peutz-Jeghers syndrome. The subcategories of 'mixed' and 'incompletely differentiated' forms of sex cord/gonadal stromal tumours have been replaced by 'mixed and unclassified sex cord-stromal tumours'. New entities introduced in the latest WHO revision include: myoid gonadal stromal tumour and 'undifferentiated gonadal tissue', a putative precursor lesion of gonadoblastoma, whereas juvenile xanthogranuloma and haemangioma are included in the miscellaneous category of tumours., (© 2016 John Wiley & Sons Ltd.)
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- 2017
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38. The epigenetics of testicular germ cell tumors: looking for novel disease biomarkers.
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Costa AL, Lobo J, Jerónimo C, and Henrique R
- Subjects
- Animals, Biomarkers, Epigenesis, Genetic, Humans, Male, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal pathology, Prognosis, Testicular Neoplasms classification, Testicular Neoplasms pathology, Neoplasms, Germ Cell and Embryonal genetics, Testicular Neoplasms genetics
- Abstract
Testicular germ cell tumors (TGCT) are a group of heterogeneous, biologically diverse and clinically challenging neoplasms. Despite the relatively low incidence and mortality rates, a subgroup of patients with disseminated disease relapse after conventional therapy and have a dismal prognosis. Moreover, TGCT afflict mostly young men and have therapeutic peculiarities, with some patients showing resistance to cisplatin-based treatments and others being troubled by irreversible side effects, such as infertility. Most TGCT share a common tumorigenic pathway and are cytogenetically similar, making room for Epigenetics to explain its heterogeneity at pathological and clinical level. In this review, we summarize the foremost epigenetic alterations among TGCT focusing on their clinical potential as diagnostic, prognostic and predictive biomarkers.
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- 2017
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39. The World Health Organization 2016 classification of testicular germ cell tumours: a review and update from the International Society of Urological Pathology Testis Consultation Panel.
- Author
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Williamson SR, Delahunt B, Magi-Galluzzi C, Algaba F, Egevad L, Ulbright TM, Tickoo SK, Srigley JR, Epstein JI, and Berney DM
- Subjects
- Humans, Male, Neoplasms, Germ Cell and Embryonal classification, Testicular Neoplasms classification
- Abstract
Since the last World Health Organization (WHO) classification scheme for tumours of the urinary tract and male genital organs, there have been a number of advances in the understanding, classification, immunohistochemistry and genetics of testicular germ cell tumours. The updated 2016 draft classification was discussed at an International Society of Urological Pathology Consultation on Testicular and Penile Cancer. This review addresses the main updates to germ cell tumour classification. Major changes include a pathogenetically derived classification using germ cell neoplasia in situ (GCNIS) as a new name for the precursor lesion, and the distinction of prepubertal tumours (non-GCNIS-derived) from postpubertal-type tumours (GCNIS-derived), acknowledging the existence of rare benign prepubertal-type teratomas in the postpubertal testis. Spermatocytic tumour is adopted as a replacement for spermatocytic seminoma, to avoid potential confusion with the unrelated usual seminoma. The spectrum of trophoblastic tumours arising in the setting of testicular germ cell tumour continues to expand, to include epithelioid and placental site trophoblastic tumours analogous to those of the gynaecological tract. Currently, reporting of anaplasia (seminoma or spermatocytic tumour) or immaturity (teratoma) is not required, as these do not have demonstrable prognostic importance. In contrast, overgrowth of a teratomatous component (somatic-type malignancy) and sarcomatous change in spermatocytic tumour indicate more aggressive behaviour, and should be reported., (© 2016 John Wiley & Sons Ltd.)
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- 2017
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40. Value of Supraregional Multidisciplinary Review for the Contemporary Management of Testicular Tumors.
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Purshouse K, Watson RA, Church DN, Richardson C, Crane G, Traill Z, Sullivan M, Roberts I, Browning L, Turner G, Parameshwaran V, Johnson J, Chitnis M, Protheroe A, and Verrill C
- Subjects
- Disease Management, Humans, Male, Patient Care Team, Patient-Centered Care, Prognosis, Seminoma pathology, Testicular Neoplasms classification, Testicular Neoplasms pathology
- Abstract
Purpose: Testicular cancers are an uncommon and highly curable group of tumors that are typically managed by specialist multidisciplinary teams (MDTs). Although recent guidelines have emphasized the importance of tumor prognostic factors in predicting recurrence and personalizing therapy in early-stage disease, the role of central pathology review in determining these factors is unclear., Patients and Methods: We compared the referral histopathology reports with those obtained after expert central review for all cases reviewed by the UK Thames Valley Cancer Network testicular tumor MDT from August 2004 to September 2012. For cases in which the findings differed, we recorded the effect of the alteration on the estimates of patient prognosis and predicted clinical management using international (European Society of Medical Oncology [ESMO]) and local guidelines., Results: The histopathology reports were altered after central review in 129 of 465 cases (27.7%) referred to the testicular tumor MDT during the study period. These resulted in changes in the estimation of prognosis for 42 patients (9.0% total), with a predicted affect on management according to the ESMO guidelines in 30 cases (6.5%). These proportions were broadly similar for both seminoma and nonseminoma, although the reasons for the discrepancies differed between the 2 (principally errors in categorization of rete testis invasion in seminoma and of lymphovascular invasion in nonseminoma). Changes to the tumor type were uncommon (2 cases)., Conclusion: Central MDT review results in frequent, clinically relevant alterations to testicular tumor histopathology reports for testicular tumors. The results of our study demonstrate the importance of specialist MDTs to inform patient-centered care and ensure best practice in the management of these uncommon cancers., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2017
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41. Perspectives on testicular germ cell neoplasms.
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Cheng L, Lyu B, and Roth LM
- Subjects
- Biomarkers, Tumor analysis, Biopsy, Gene Amplification, Genetic Predisposition to Disease, Humans, Immunohistochemistry, In Situ Hybridization, Fluorescence, Male, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal pathology, Neoplasms, Germ Cell and Embryonal therapy, Phenotype, Prognosis, Testicular Neoplasms classification, Testicular Neoplasms pathology, Testicular Neoplasms therapy, Biomarkers, Tumor genetics, Chromosomes, Human, Pair 12, Isochromosomes, Neoplasms, Germ Cell and Embryonal genetics, Testicular Neoplasms genetics
- Abstract
Our knowledge of testicular germ cell neoplasms has progressed in the last few decades due to the description of germ cell neoplasia in situ (GCNIS) and a variety of specific forms of intratubular germ cell neoplasia, the discovery of isochromosome 12p and its importance in the development of invasiveness in germ cell tumors (GCTs), the identification of specific transcription factors for GCTs, and the recognition that a teratomatous component in mixed GCT represents terminal differentiation. Isochromosome 12p and 12p overrepresentation, collectively referred to as 12p amplification, are fundamental abnormalities that account for many types of malignant GCTs of the testis. Embryonal carcinoma is common in the testis but rare in the ovary, whereas the converse is true for mature cystic teratoma. Spermatocytic tumor occurs only in the testis; it has not been described in the ovary or extragonadal sites. The origin of ovarian mature cystic teratoma is similar to that of prepubertal-type testicular teratoma and dermoid cyst at any age in that it arises from a nontransformed germ cell, whereas postpubertal-type testicular teratoma arises from a malignant germ cell, most commonly through the intermediary of GCNIS. Somatic neoplasms, often referred to as monodermal teratomas, arise not infrequently from mature cystic teratoma of the ovary, whereas such neoplasms are rare in testicular teratoma with the exception of carcinoid. Integration of classical morphologic observations and emerging novel molecular studies will result in better understanding of the pathogenesis of GCTs and will optimize patient therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)
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- 2017
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42. Germ cell neoplasia in situ (GCNIS): evolution of the current nomenclature for testicular pre-invasive germ cell malignancy.
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Berney DM, Looijenga LH, Idrees M, Oosterhuis JW, Rajpert-De Meyts E, Ulbright TM, and Skakkebaek NE
- Subjects
- Humans, Male, Neoplasms, Germ Cell and Embryonal pathology, Spermatogonia pathology, Testicular Neoplasms pathology, Neoplasms, Germ Cell and Embryonal classification, Terminology as Topic, Testicular Neoplasms classification, Testis pathology
- Abstract
The pre-invasive lesion associated with post-pubertal malignant germ cell tumours of the testis was first recognized in the early 1970s and confirmed by a number of observational and follow-up studies. Until this year, this scientific story has been confused by resistance to the entity and disagreement on its name. Initially termed 'carcinoma in situ' (CIS), it has also been known as 'intratubular germ cell neoplasia, unclassified' (IGCNU) and 'testicular intraepithelial neoplasia' (TIN). In this paper, we review the history of discovery and controversy concerning these names and introduce the reasoning for uniting behind a new name, endorsed unanimously at the World Health Organization (WHO) consensus classification 2016: germ cell neoplasia in situ (GCNIS)., (© 2016 John Wiley & Sons Ltd.)
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- 2016
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43. The 2016 WHO Classification of Tumours of the Urinary System and Male Genital Organs-Part A: Renal, Penile, and Testicular Tumours.
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Moch H, Cubilla AL, Humphrey PA, Reuter VE, and Ulbright TM
- Subjects
- Carcinoma, Renal Cell enzymology, Carcinoma, Renal Cell pathology, Carcinoma, Squamous Cell virology, Humans, Kidney Neoplasms pathology, Leiomyomatosis classification, Leiomyomatosis pathology, Male, Neoplasm Grading, Neoplasm Invasiveness, Neoplasms, Germ Cell and Embryonal pathology, Neoplastic Syndromes, Hereditary classification, Neoplastic Syndromes, Hereditary pathology, Papillomavirus Infections complications, Penile Neoplasms virology, Skin Neoplasms classification, Skin Neoplasms pathology, Succinate Dehydrogenase deficiency, Testicular Neoplasms pathology, Uterine Neoplasms classification, Uterine Neoplasms pathology, World Health Organization, Carcinoma, Renal Cell classification, Carcinoma, Squamous Cell classification, Kidney Neoplasms classification, Neoplasms, Germ Cell and Embryonal classification, Penile Neoplasms classification, Testicular Neoplasms classification
- Abstract
Unlabelled: The fourth edition of the World Health Organization (WHO) classification of urogenital tumours (WHO "blue book"), published in 2016, contains significant revisions. These revisions were performed after consideration by a large international group of pathologists with special expertise in this area. A subgroup of these persons met at the WHO Consensus Conference in Zurich, Switzerland, in 2015 to finalize the revisions. This review summarizes the most significant differences between the newly published classification and the prior version for renal, penile, and testicular tumours. Newly recognized epithelial renal tumours are hereditary leiomyomatosis and renal cell carcinoma (RCC) syndrome-associated RCC, succinate dehydrogenase-deficient RCC, tubulocystic RCC, acquired cystic disease-associated RCC, and clear cell papillary RCC. The WHO/International Society of Urological Pathology renal tumour grading system was recommended, and the definition of renal papillary adenoma was modified. The new WHO classification of penile squamous cell carcinomas is based on the presence of human papillomavirus and defines histologic subtypes accordingly. Germ cell neoplasia in situ (GCNIS) of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours, and testicular germ cell tumours are now separated into two fundamentally different groups: those derived from GCNIS and those unrelated to GCNIS. Spermatocytic seminoma has been designated as a spermatocytic tumour and placed within the group of non-GCNIS-related tumours in the 2016 WHO classification., Patient Summary: The 2016 World Health Organization (WHO) classification contains new renal tumour entities. The classification of penile squamous cell carcinomas is based on the presence of human papillomavirus. Germ cell neoplasia in situ of the testis is the WHO-recommended term for precursor lesions of invasive germ cell tumours., (Copyright © 2016 European Association of Urology. Published by Elsevier B.V. All rights reserved.)
- Published
- 2016
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44. Defining a New Prognostic Index for Stage I Nonseminomatous Germ Cell Tumors Using CXCL12 Expression and Proportion of Embryonal Carcinoma.
- Author
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Gilbert DC, Al-Saadi R, Thway K, Chandler I, Berney D, Gabe R, Stenning SP, Sweet J, Huddart R, and Shipley JM
- Subjects
- Biomarkers, Tumor genetics, Chemokine CXCL12 genetics, Disease-Free Survival, Gene Expression Regulation, Neoplastic, Humans, Male, Neoplasm Invasiveness, Neoplasm Recurrence, Local pathology, Neoplasm Staging, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal pathology, Risk Factors, Testicular Neoplasms classification, Testicular Neoplasms pathology, Biomarkers, Tumor biosynthesis, Chemokine CXCL12 biosynthesis, Neoplasm Recurrence, Local genetics, Neoplasms, Germ Cell and Embryonal genetics, Testicular Neoplasms genetics
- Abstract
Purpose: Up to 50% of patients diagnosed with stage I nonseminomatous germ cell tumors (NSGCTs) harbor occult metastases. Patients are managed by surveillance with chemotherapy at relapse or adjuvant treatment up front. Late toxicities from chemotherapy are increasingly recognized. Based on a potential biologic role in germ cells/tumors and pilot data, our aim was to evaluate tumor expression of the chemokine CXCL12 alongside previously proposed markers as clinically useful biomarkers of relapse., Experimental Design: Immunohistochemistry for tumor expression of CXCL12 was assessed as a biomarker of relapse alongside vascular invasion, histology (percentage embryonal carcinoma), and MIB1 staining for proliferation in formalin-fixed paraffin-embedded orchidectomy samples from patients enrolled in the Medical Research Council's TE08/22 prospective trials of surveillance in stage I NSGCTs., Results: TE08/TE22 trial patients had a 76.4% 2-year relapse-free rate, and both CXCL12 expression and percentage embryonal carcinoma provided prognostic value independently of vascular invasion (stratified log rank test P = 0.006 for both). There was no additional prognostic value for MIB1 staining. A model using CXCL12, percentage embryonal carcinoma, and VI defines three prognostic groups that were independently validated., Conclusions: CXCL12 and percentage embryonal carcinoma both stratify patients' relapse risk over and above vascular invasion alone. This is anticipated to improve the stratification of patients and identify high-risk cases to be considered for adjuvant therapy., (©2015 American Association for Cancer Research.)
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- 2016
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45. The Changing Landscape of Intermediate- and Poor-Risk Germ Cell Tumors: Do We Need to Reclassify Patients With Metastatic Germ Cell Tumors?
- Author
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Necchi A, Nicolai N, Giannatempo P, Raggi D, Miceli R, Mariani L, and Salvioni R
- Subjects
- Humans, Male, Neoplasms, Germ Cell and Embryonal diagnosis, Neoplasms, Germ Cell and Embryonal drug therapy, Neoplasms, Germ Cell and Embryonal secondary, Prognosis, Randomized Controlled Trials as Topic, Risk, Testicular Neoplasms diagnosis, Testicular Neoplasms drug therapy, Testicular Neoplasms pathology, Neoplasms, Germ Cell and Embryonal classification, Testicular Neoplasms classification
- Published
- 2016
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46. Nonchoriocarcinomatous Trophoblastic Tumors of the Testis: The Widening Spectrum of Trophoblastic Neoplasia.
- Author
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Idrees MT, Kao CS, Epstein JI, and Ulbright TM
- Subjects
- Adenocarcinoma chemistry, Adenocarcinoma classification, Adenocarcinoma drug therapy, Adenocarcinoma mortality, Adult, Biomarkers, Tumor analysis, Biopsy, Epithelioid Cells chemistry, Female, Humans, Immunohistochemistry, Male, Neoplasms, Complex and Mixed chemistry, Neoplasms, Complex and Mixed classification, Neoplasms, Complex and Mixed drug therapy, Neoplasms, Complex and Mixed mortality, Neoplasms, Complex and Mixed secondary, Pregnancy, Testicular Neoplasms chemistry, Testicular Neoplasms classification, Testicular Neoplasms drug therapy, Testicular Neoplasms mortality, Time Factors, Treatment Outcome, Trophoblastic Neoplasms chemistry, Trophoblastic Neoplasms classification, Trophoblastic Neoplasms drug therapy, Trophoblastic Neoplasms mortality, Trophoblastic Neoplasms secondary, Trophoblastic Tumor, Placental Site chemistry, Trophoblastic Tumor, Placental Site classification, Trophoblastic Tumor, Placental Site drug therapy, Trophoblastic Tumor, Placental Site mortality, Trophoblastic Tumor, Placental Site secondary, Young Adult, Adenocarcinoma pathology, Epithelioid Cells pathology, Neoplasms, Complex and Mixed pathology, Testicular Neoplasms pathology, Trophoblastic Neoplasms pathology, Trophoblastic Tumor, Placental Site pathology
- Abstract
Tumors of trophoblastic derivation other than choriocarcinoma are very rare in the testis but have been reported on occasion in association with other germ cell tumors. Their morphologic spectrum is analogous to the trophoblastic tumors of the female genital tract including epithelioid trophoblastic tumor (ETT) and placental site trophoblastic tumor (PSTT). Herein we report our experience with 8 cases of trophoblastic tumors of testicular origin that lacked the features of choriocarcinoma; these included 4 ETTs, 1 PSTT, 1 unclassified trophoblastic tumor (UTT), 1 partially regressed choriocarcinoma with a monophasic morphology, and 1 hybrid tumor showing a mixture of adenocarcinoma and a UTT. All tumors occurred in young men 19 to 43 years old. Five arose de novo within the testis (2 ETTs, 1 UTT, 1 regressing choriocarcinoma, and the hybrid tumor) as a component of mixed germ cell tumors, and 3 (2 ETTs and 1 PSTT) were found in metastatic sites after chemotherapy. The trophoblastic component was minor (5% to 10%) in 6 tumors but was 95% of 1 metastatic tumor (ETT) and 50% of the hybrid tumor. Other germ cell tumor elements were identified in all cases, most commonly teratoma. The ETTs consisted of nodules and nests of squamoid trophoblast cells showing abundant eosinophilic cytoplasm, frequent apoptotic cells, extracellular fibrinoid material, and positivity for p63 and negativity for human placental lactogen (HPL). The PSTT showed sheets of discohesive, pleomorphic, mononucleated trophoblast cells that invaded blood vessels with fibrinoid change and were p63 negative and HPL positive. The UTT showed a spectrum of small and large trophoblast cells, some multinucleated but lacking distinct syncytiotrophoblasts, and was patchily positive for both p63 and HPL. The hybrid tumor had ETT-like and adenocarcinomatous areas that coexpressed inhibin and GATA3 but were negative for p63 and HPL, leading to classification of the trophoblastic component as UTT. Seven of the patients were alive and well on follow-up (8 to 96 mo; median, 39 mo), whereas the patient with the hybrid tumor died of liver metastases at 2 years. Our study verifies that trophoblastic neoplasms often having the features of nonchoriocarcinomatous gestational trophoblastic tumors may arise from the testis, occur either in the untreated primary tumor or in metastases after chemotherapy, and should be distinguished from choriocarcinoma given what appears to be a less aggressive clinical course.
- Published
- 2015
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47. Editorial Comment from Dr Beyer to Identification of a subgroup with worse prognosis among patients with poor-risk testicular germ cell tumor.
- Author
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Beyer J
- Subjects
- Humans, Male, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal therapy, Testicular Neoplasms classification, Testicular Neoplasms therapy
- Published
- 2015
- Full Text
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48. Identification of a subgroup with worse prognosis among patients with poor-risk testicular germ cell tumor.
- Author
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Kojima T, Kawai K, Tsuchiya K, Abe T, Shinohara N, Tanaka T, Masumori N, Yamada S, Arai Y, Narita S, Tsuchiya N, Habuchi T, and Nishiyama H
- Subjects
- Adolescent, Adult, Chorionic Gonadotropin blood, Follow-Up Studies, Humans, L-Lactate Dehydrogenase blood, Male, Middle Aged, Neoplasms, Germ Cell and Embryonal mortality, Neoplasms, Germ Cell and Embryonal secondary, Orchiectomy, Prognosis, Retrospective Studies, Risk Factors, Survival Rate, Testicular Neoplasms mortality, Testicular Neoplasms pathology, Testicular Neoplasms secondary, Young Adult, alpha-Fetoproteins metabolism, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal therapy, Testicular Neoplasms classification, Testicular Neoplasms therapy
- Abstract
Objectives: To clarify the significance of the International Germ Cell Cancer Collaborative Group classification in the 2000s, especially in intermediate- and poor-prognosis testicular germ cell tumor in Japan., Methods: We retrospectively analyzed 117 patients with intermediate- and poor-prognosis testicular non-seminomatous germ cell tumor treated at five university hospitals in Japan between 2000 and 2010. Data collected included age, levels of tumor markers, spread to non-pulmonary visceral metastases, treatment details and survival., Results: The median follow-up period of all patients was 57 months. A total of 50 patients (43%) were classified as having intermediate prognosis, and 67 patients (57%) as poor prognosis according to the International Germ Cell Cancer Collaborative Group classification. As first-line chemotherapy, 92 patients (79%) received bleomycin, etoposide and cisplatin. Of all patients, 74 patients (63%) received second-line chemotherapy. The most commonly used second-line chemotherapy regimens were a combination of taxanes, ifosfamide and platinum in 49 cases (66%). Overall, 33 patients (28%) received third-line chemotherapy. A total of 88 patients (75%) underwent post-chemotherapy surgery. The 5-year overall survival for intermediate (n = 50) and poor prognosis (n = 67) was 89% and 83% (P = 0.21), respectively. In poor prognosis patients, patients with two or more risk factors (any of high lactic dehydrogenase, alpha-fetoprotein and human chorionic gonadotropin levels, and presence of non-pulmonary visceral metastases) had significantly worse survival than those with only one risk factor (71% and 91%, respectively, P = 0.01)., Conclusions: The 5-year overall survivals of poor-prognosis testicular non-seminomatous germ cell tumor patients reached 83%. Further stratification of poor-prognosis patients based on a number of risk factors has the potential to further identify those with poorer prognosis., (© 2015 The Japanese Urological Association.)
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- 2015
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49. Editorial Comment from Dr Nakamura to Identification of a subgroup with worse prognosis among patients with poor-risk testicular germ cell tumor.
- Author
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Nakamura T
- Subjects
- Humans, Male, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Neoplasms, Germ Cell and Embryonal classification, Neoplasms, Germ Cell and Embryonal therapy, Testicular Neoplasms classification, Testicular Neoplasms therapy
- Published
- 2015
- Full Text
- View/download PDF
50. Nuclear Localization of β-Catenin in Sertoli Cell Tumors and Other Sex Cord-Stromal Tumors of the Testis: An Immunohistochemical Study of 87 Cases.
- Author
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Zhang C and Ulbright TM
- Subjects
- Cell Nucleus pathology, Humans, Male, Predictive Value of Tests, Sertoli Cell Tumor classification, Sertoli Cell Tumor pathology, Sex Cord-Gonadal Stromal Tumors classification, Sex Cord-Gonadal Stromal Tumors pathology, Testicular Neoplasms classification, Testicular Neoplasms pathology, Biomarkers, Tumor analysis, Cell Nucleus chemistry, Immunohistochemistry, Sertoli Cell Tumor chemistry, Sex Cord-Gonadal Stromal Tumors chemistry, Testicular Neoplasms chemistry, beta Catenin analysis
- Abstract
The diagnosis and subclassification of Sertoli cell tumors (SCT) of the testis are often challenging to general surgical pathologists because of the rarity of the tumors. Immunohistochemical study to date has limited diagnostic value. Nuclear localization of β-catenin, which correlated closely with CTNNB1 gene mutation, was recently reported in SCTs. We investigated the utility of β-catenin nuclear localization in diagnosing SCTs and differentiating them from other testicular sex cord-stromal tumors. Immunohistochemical staining for β-catenin was evaluated in 87 cases of testicular sex cord-stromal tumor: 33 SCTs, not otherwise specified (SCT-NOS) (15 with benign and 18 with malignant features), 10 sclerosing SCTs (SSCT), 5 large cell calcifying SCTs (LCCSCT), 6 Sertoli-stromal cell tumors, 10 Leydig cell tumors, 7 juvenile granulosa cell tumors, 4 adult granulosa cell tumors, and 12 sex cord-stromal tumors, unclassified. Twenty-one of 33 (64%) SCT-NOS, 6 of 10 (60%) SSCTs, and 4 of 6 (67%) Sertoli-stromal cell tumors showed strong, diffuse β-catenin nuclear staining. Nuclear β-catenin positivity was more frequent in SCTs-NOS with benign features than in those with malignant features (93% and 39%, respectively, P=0.13) and, in the Sertoli-stromal cell tumors, occurred only in the Sertoli component. All 5 LCCSCTs and all other types of sex cord-stromal tumor were negative for β-catenin nuclear staining. In conclusion, SCT-NOS and SSCT frequently show β-catenin nuclear localization. Positive nuclear staining of β-catenin is specific for SCT-NOS, SSCT, and Sertoli-stromal cell tumor among testicular sex cord-stromal tumors but has limited sensitivity (63%) in this group. The similar reactivity of SCT-NOS and SSCT provides additional support that these 2 variants are not distinct entities.
- Published
- 2015
- Full Text
- View/download PDF
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