A pathologist’s view on the testis biopsy

Oosterhuis, J. Wolter; Stoop, Hans; Dohle, Gert R.; Boellaard, Willem; Casteren, Niels van; Wolffenbuttel, KP; Looijenga, Leendert H. J.

doi:10.1111/j.1365-2605.2011.01204.x

Cited by 45 publications

(26 citation statements)

References 31 publications

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“…KITLG may be expressed in testes containing pre-intratubular germ cell neoplasia. 14,25 Immunohistochemistry Tissue samples from 36 gonads (22 gonads from patients with expected no AR activity; 9 gonads from patients with expected residual AR activity; 5 gonads from patients with uncertain AR activity) were available for immunohistochemical staining. After antigen retrieval (120 1C, 0.9 Bar), 4-mm-thick …”

Section: Gonadal Histology Assessmentmentioning

confidence: 99%

Complete androgen insensitivity syndrome: factors influencing gonadal histology including germ cell pathology

et al. 2014

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Patients with complete androgen insensitivity syndrome are at an increased risk for the development of gonadal germ cell cancer. Residual androgen receptor (AR) activity and abnormal gonadal location may influence the survival of atypical germ cells and the development of other histopathological features. To assess this, we evaluated 37 gonads from 19 patients with complete androgen insensitivity (ranging in age from 3 months to 18 years). Histological abnormalities were examined using hematoxylin and eosin-stained sections and sections stained for POU5F1 and KITLG, markers of early changes in germ cells at risk for malignant transformation. Hamartomatous nodules (HNs), Leydig cell hyperplasia (LCH), decreased germ cells, tubular atrophy and stromal fibrosis were more pronounced as age increased (Po0.001). Expected residual AR activity acted as a positive predictor only for non-malignant germ cell survival in (post)pubertal patients (Po0.05). Immunohistochemical studies indicated that delayed maturation of germ cells was present in three patients, whereas intermediate changes that occurred between delayed maturation and intratubular germ cell neoplasia, designated pre-intratubular germ cell neoplasia, were identified in four cases. Intratubular germ cell neoplasia was observed in one patient. Neither POU5F1 nor KITLG expression was dependent on expected residual AR activity. An independent effect of inguinal versus abdominal position of the gonads was difficult to assess because inguinal gonads were present primarily in the youngest individuals. In conclusion, many histological changes occur increasingly with age. Expected residual AR activity contributes to better survival of the general germ cell population in (post)pubertal age; however, it did not seem to have an important role in the survival of the germ cells at risk for malignant transformation (defined by POU5F1 positivity and KITLG overexpression) in complete androgen insensitivity. Comparison of the high percentage of patients in our study that were carrying germ cells with delayed maturation or pre-intratubular germ cell neoplasia with previously reported cumulative risk of tumor development in adult patients indicates that not all such precursor lesions in complete androgen insensitivity will progress to invasive germ cell cancer.

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Section: Gonadal Histology Assessmentmentioning

confidence: 99%

Complete androgen insensitivity syndrome: factors influencing gonadal histology including germ cell pathology

et al. 2014

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“…144, [168][169][170][171] Malignant transformation from GCNIS to both seminomatous GCTs and NSGCTs results from the accumulation of additional genomic alterations. Believed to be critical to this transformation is the acquisition of the testicular GCT-specific isochromosome 12p, which is of uniparental origin in most cases, and is present in the vast majority of both seminomatous GCTs and NSGCTs.…”

Section: Molecular Pathogenesis Of Gcnis and Progression Tomentioning

confidence: 99%

Precursor Lesions of Urologic Malignancies

Khani¹,

Robinson²

2017

Archives of Pathology &Amp; Laboratory Medicine

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Context.— Precursor lesions of urologic malignancies are established histopathologic entities, which are important not only to recognize for clinical purposes, but also to further investigate at the molecular level in order to gain a better understanding of the pathogenesis of these malignancies. Objective.— To provide a brief overview of precursor lesions to the most common malignancies that develop within the genitourinary tract with a focus on their clinical implications, histologic features, and molecular characteristics. Data Sources.— Literature review from PubMed, urologic pathology textbooks, and the 4th edition of the World Health Organization Classification of Tumours of the Urinary System and Male Genital Organs. All photomicrographs were taken from cases seen at Weill Cornell Medicine or from the authors' personal slide collections. Conclusions.— The clinical importance and histologic criteria are well established for the known precursor lesions of the most common malignancies throughout the genitourinary tract, but further investigation is warranted at the molecular level to better understand the pathogenesis of these lesions. Such investigation may lead to better risk stratification of patients and potentially novel treatments.

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“…The markers that are useful in clinical practice and research are listed in Table 1. Immunohistochemistry is very helpful for the detection of GCNIS in testicular biopsies [59][60][61] and we suggest using at least two different markers for each tissue specimen, e.g. PLAP and OCT4 or PDPN (Figure 2).…”

Section: Immunohistochemical Markers Useful For Gct Diagnosis In Tissmentioning

confidence: 99%

Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs

Meyts

Nielsen

Skakkebæk

et al. 2015

Folia Histochem Cytobiol.

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This concise review summarises tissue and serum markers useful for differential diagnosis of germ cell tumours (GCT), with focus on the most common testicular GCT (TGCT). GCT are characterised by phenotypic heterogeneity due to largely retained embryonic pluripotency and aberrant somatic differentiation. TGCT that occur in young men are divided into two main types, seminoma and nonseminoma, both derived from a pre-invasive germ cell neoplasia in situ (GCNIS), which originates from transformed foetal gonocytes. In severely dysgenetic gonads, a GCNIS-resembling lesion is called gonadoblastoma. GCT occur rarely in young children (infantile GCT) in whom the pathogenesis is different (no GCNIS/gonadoblastoma stage) but the histopathological features are similar to the adult GCT. The rare spermatocytic tumour of older men is derived from post-pubertal spermatogonia that clonally expand due to gain-of function mutations in survival-promoting genes (e.g. FGFR3, HRAS), thus this tumour has a different expression profile than GCNIS-derived TGCT. Clinically most informative immunohistochemical markers for GCT, except teratoma, are genes expressed in primordial germ cells/gonocytes and embryonic pluripotency-related factors, such as placental-like alkaline phosphatase (PLAP), OCT4 (POU5F1), NANOG, AP-2γ (TFAP2C) and LIN28, which are not expressed in normal adult germ cells. Some of these markers can also be used for immunocytochemistry to detect GCNIS or incipient tumours in semen samples. Gene expression in GCT is regulated in part by DNA and histone modifications, and the epigenetic profile of these tumours is characterised by genome-wide demethylation, except nonseminomas. In addition, a recently discovered mechanism of post-genomic gene expression regulation involves small non-coding RNAs, predominantly micro-RNA (miR). Testicular GCT display micro-RNA profiles similar to embryonic stem cells. Targeted miRNA-based blood tests for miR-371-3 and miR-367 clusters are currently under development and hold a great promise for the future. In some patients miR-based tests may be even more sensitive than the classical serum tumour markers, b-chorio-gonadotrophin (b-hCG), a-fetoprotein (AFP) and lactate dehydrogenase (LDH), which are currently used in the clinic. In summary, research advances have provided clinicians with a panel of molecular markers, which allow specific diagnosis of various subtypes of GCT and are very useful for early detection at the precursor stage and for monitoring of patients during the follow-up.

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A pathologist’s view on the testis biopsy

Cited by 45 publications

References 31 publications

Complete androgen insensitivity syndrome: factors influencing gonadal histology including germ cell pathology

Complete androgen insensitivity syndrome: factors influencing gonadal histology including germ cell pathology

Precursor Lesions of Urologic Malignancies

Diagnostic markers for germ cell neoplasms: from placental-like alkaline phosphatase to micro-RNAs

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