Heterogeneous Distribution of ITGCNU in an Adult Testis: Consequences for Biopsy-Based Diagnosis

Casteren, Niels J. van; Boellaard, Willem; Dohle, Gert R.; Weber, R. F. A.; Kuizinga, Marti C.; Stoop, Hans; Oosterhuis, Wolter; Looijenga, Leendert H. J.

doi:10.1177/1066896907306125

Cited by 49 publications

(27 citation statements)

References 13 publications

(11 reference statements)

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“…Testicular biopsy is the current gold standard method for diagnosis, however false negative results can occur because GCNIS cells are not always randomly distributed throughout the entire testis (van Casteren et al, 2008a). It would be vastly preferable to identify and treat GCNIS before neoplasias develop in order to minimise long-term side effects of treatment.…”

Section: New Approachesmentioning

confidence: 99%

Germ cell neoplasia in situ: The precursor cell for invasive germ cell tumors of the testis

Spiller

Bowles

2017

The International Journal of Biochemistry & Cell Biology

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This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. AbstractGerm cell neoplasia in situ is the non-invasive precursor cell of origin for type II testicular germ cell tumors. It has long been postulated that germ cell neoplasia in situ is derived from defective germ cell development during embryonic life, and although it is impossible to trace in vivo the progression from fetal germ cell to germ cell neoplasia in situ to tumor, there is a large volume of evidence supporting this theory. Current studies focus on understanding how germ cell neoplasia in situ forms, how these cells are activated at puberty and how they transform to invasive tumors of various subtypes. Such information is informing novel diagnostic and therapeutic options.

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Section: New Approachesmentioning

confidence: 99%

Germ cell neoplasia in situ: The precursor cell for invasive germ cell tumors of the testis

Spiller

Bowles

2017

The International Journal of Biochemistry & Cell Biology

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“…[9] There is usually a heterogeneous distribution of ITGCN with intervening normal tubules throughout the testicle. [7475] Testicular biopsies should be placed in Bouin's or Stieve's solution, as formalin can make morphologic diagnosis more difficult. As discussed above, a wide variety of markers can be used to identify ITGCN via immunohistochemistry (IHC).…”

Section: Diagnosismentioning

confidence: 99%

“…[2678] PLAP has a sensitivity of 83-98%, [1718] however, Oct 3/4 has reported sensitivity and specificity of 100% in some studies. [267478] Semen analysis for the diagnosis of ITGN has been studied in a number of small trials with a variety of techniques, some of which appear promising; however this is still investigational. [79–81]…”

Section: Diagnosismentioning

confidence: 99%

“…Large series of testicular biopsies performed on the contralateral testicle with unilateral TGCT have demonstrated the false negative rate to be about 0.5% when performed along with IHC for PLAP. [83] The false negatives were thought to be due to the focal nature of ITGCN,[74] and a number of small series and case reports described TGCT despite prior negative biopsies. [168384] Investigations were done to examine the utility of two-site biopsies, which found in a series of 2318 patients a discordance rate of 31%, and an extra yield of 18%.…”

Section: Diagnosismentioning

confidence: 99%

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Intratubular germ cell neoplasms of the testis and bilateral testicular tumors: Clinical significance and management options

Masterson

2010

Indian J Urol

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Objectives:Intratubular germ cell neoplasia (ITGCN) is the precursor lesion for invasive testicular germ cell tumors (TGCTs) of adolescents and young adults. The rising incidence of these tumors has prompted a rigorous investigation of the etiology, diagnosis and management of ITGCN. Bilateral testicular cancer is closely linked with ITGCN, as patients with unilateral testicular cancer are at the highest risk for a future malignancy in the contralateral testicle.Methods:A literature review directed at ITGCN and bilateral testis cancer was performed using the Medline/PubMed database. Our review focused on the pathogenesis, risk factors, diagnosis and treatment regimens utilized.Results:Major advances have been made in the understanding of ITGCN over the past 30 years. There is evidence that TGCTs arise from ITGCN, ITGCN is closely related to fetal gonocytes, and that events in pre- and perinatal period may result in abnormal persistence of fetal gonocytes leading to ITGCN and subsequent TGCT. Controversy exists regarding the need to biopsy men at increased risk of TGCT, as well as the best approach to managing patients with known ITGCN. Bilateral testicular cancer has excellent outcomes in the current era of platinum-based chemotherapy.Conclusion:The optimal management of patients at risk for ITGCN and future TGCT is still a matter of debate. Individualization of management, including biopsy and treatment, should be based on risk factors for TGCT, compliance with potential surveillance, and patient preferences particularly with regard to fertility.

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“…OCT4 (OCT 3/4, POU5F1) is a nuclear transcription factor that is expressed in early embryonic cells and germ cells [13,14]. OCT4 has been detected in neoplastic pluripotent germ cells, specifically those of testicular seminoma, embryonal carcinoma [15], and IGCNU [16]. Antibodies to OCT4 mark the nuclei of these pluripotent cells.…”

Section: Introductionmentioning

confidence: 99%

OCT 4 immunohistochemistry in postpubertal cryptorchidism

et al. 2011

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AbstractPatients with cryptorchidism are at an increased risk for germ cell testicular cancer. OCT 4 has been shown to be a sensitive and specific marker for some types of germ cell testicular cancer. We undertook this study to establish whether OCT 4 immunohistochemistry is a useful tool in the pathohistologic evaluation of postpubertal patients with cryptorchidism. Seventeen postpubertal patients underwent orchidectomy for cryptorchidism at our center since 1997. Immunohistochemical staining with OCT 4 was performed on these samples. Characteristic OCT 4 nuclear staining was positive in two patients. One patient was correctly diagnosed on previous pathohistological evaluation, while OCT4 immunohistochemical staining revealed previously unidentified intratubular germ cell neoplasia in the other patient. OCT 4 immunohistochemistry can be useful in diagnosing a testicular germ cell tumor in patients with cryptorchidism. If we consider a low number of postpubertal patients with cryptorchidism a benefit of immunohistochemical staining with OCT4, this could favor the use of OCT 4 staining in work-up of cryptorchidism.

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Heterogeneous Distribution of ITGCNU in an Adult Testis: Consequences for Biopsy-Based Diagnosis

Cited by 49 publications

References 13 publications

Germ cell neoplasia in situ: The precursor cell for invasive germ cell tumors of the testis

Germ cell neoplasia in situ: The precursor cell for invasive germ cell tumors of the testis

Intratubular germ cell neoplasms of the testis and bilateral testicular tumors: Clinical significance and management options

OCT 4 immunohistochemistry in postpubertal cryptorchidism

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