Browsing by Subject "testis"

Now showing 1 - 6 of 6
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    Classical gonadoblastoma: its relationship to the “dissecting” variant and undifferentiated gonadal tissue
    (Wiley, 2017) Roth, Lawrence M.; Cheng, Liang; Department of Pathology and Laboratory Medicine, School of Medicine
    Classical gonadoblastoma occurs almost entirely in the dysgenetic gonads of an individual who has a disorder of sex development. Approximately 40% of such neoplasms are bilateral. Almost all gonadoblastomas occur in patients who have a Y chromosome or part thereof; testis specific protein Y-encoded 1 (TSPY1) is the putative gene. If a gonad in a patient who has a disorder of sex development contains germ cells with delayed maturation and also harbors the TSPY1 gene, the cells can undergo transformation to classical gonadoblastoma. The latter consists of rounded islands composed of germ cells, sex cord elements, and hyaline basement membrane material surrounded by a variably cellular gonadal stroma that sometimes contains steroid cells. Classical gonadoblastoma can be interpreted as a noninvasive neoplasm that is the precursor of germinoma, and, indirectly, other more aggressive germ cell neoplasms. Undifferentiated gonadal tissue is the precursor of classical gonadoblastoma and contains germ cells with delayed maturation that express octamer-binding transcription factor 4 (OCT4); however, other germ cells show normal maturation and express TSPY1. If all germ cells in a patient with undifferentiated gonadal tissue involute, the result is a secondary streak. Undifferentiated gonadal tissue is a non-neoplastic condition that should be clearly distinguished from “dissecting gonadoblastoma,” a neoplasm derived from classical gonadoblastoma that is the precursor of some germinomas. “Dissecting gonadoblastoma” is a variant of classical gonadoblastoma that has unusual growth patterns and contains both sex cord and germ cell elements. Clonal expansion of germ cells is a characteristic of the late stage of “dissecting gonadoblastoma”.
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    Evidence of a dual histogenetic pathway of sacrococcygeal teratomas
    (Wiley, 2017-01) Emerson, Robert E.; Kao, Chia-Sui; Eble, John N.; Grignon, David J.; Wang, Mingsheng; Zhang, Shaobo; Wang, Xiaoyan; Fan, Rong; Masterson, Timothy A.; Roth, Lawrence M.; Cheng, Liang; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Aims Sacrococcygeal teratomas are rare tumours that occur most frequently in neonates, although adult cases also occur. The molecular pathogenesis of these tumours and their long-term prognosis is uncertain. We investigated the i(12p) status of a large number of primary sacrococcygeal teratomas in both children and adults, including cases with malignant germ cell tumour elements. Methods and results Fifty-four sacrococcygeal teratoma specimens from 52 patients were identified, and available follow-up information was obtained. Fluorescence in-situ hybridization analysis was performed to identify isochromosome 12p [i(12p)] abnormalities on paraffin blocks of the tumours. Among the 48 paediatric patients, there were 44 teratomas and four tumours with combined teratoma and yolk sac tumour (one of whom also had primitive neuroectodermal tumour). The teratomas included 37 mature teratomas and 11 immature teratomas (four grade 1, two grade 2, and five grade 3). The 44 teratomas lacking a yolk sac tumour component were all negative for i(12p). The four tumours with a yolk sac tumour component were all positive for i(12p). The four adult cases all lacked non-teratomatous germ cell tumour components, immature elements, and i(12p). Follow-up information was available for 32 patients. Two patients with teratoma had recurrence, but were alive with no evidence of disease after long-term follow-up. One patient with combined teratoma and yolk sac tumour had recurrence 7 months after resection. The other patients were alive with no evidence of disease at last follow-up. Conclusions Our data suggest that paediatric sacrococcygeal teratomas should be considered as two distinct groups with divergent histogenetic pathways. The prognosis of these tumours is excellent, despite rare recurrence.
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    Juvenile Granulosa Cell Tumors of the Testis: A Clinicopathologic Study of 70 Cases with Emphasis on Its Wide Morphologic Spectrum
    (Wolters Kluwer, 2015-09) Kao, Chia-Sui; Cornejo, Kristine M.; Ulbright, Thomas M.; Young, Robert H.; Department of Pathology & Laboratory Medicine, IU School of Medicine
    The clinical and pathologic features of 70 juvenile granulosa cell tumors (JGCTs) of the testis are presented. The patients were from 30 weeks gestational age to 10 years old; 60 of 67 (90%) whose ages are known to us were 6 months old or younger. Sixty-two underwent gonadectomy, 6 wedge excision, and 2 only biopsy. Twenty-six tumors were left sided and 22 right sided. Six occurred in an undescended testis and 2 in dysgenetic gonads. The most common presentation was a testicular mass (65%), followed by an “enlarging testis” (25%). Six of 14 patients in whom it was measured had “elevated” serum α-fetoprotein (AFP), likely physiologically, and 1 had gynecomastia. The tumors measured 0.5 to 5 cm (mean, 1.7 cm; median, 1.5 cm) and were most commonly well circumscribed and typically yellow-tan; approximately 2/3 had a cystic component, whereas 1/3 were entirely solid. Microscopic examination typically showed a lobular growth, punctuated in 67 cases by variably sized and shaped follicles containing material that was basophilic (21%), eosinophilic (44%), or of both characters (35%); 3 lacked follicles. In nonfollicular areas, the tumor cells typically grew diffusely but occasionally had a corded arrangement (26%) or reticular appearance (29%). The stroma was either fibrous or fibromyxoid; hemorrhage associated with hemosiderin-laden macrophages was focally seen in 16%. The tumor cells were mostly small to medium sized with round to oval nuclei containing inconspicuous nucleoli and moderate to abundant, but occasionally scant, pale to lightly eosinophilic, sometimes vacuolated, cytoplasm; nuclear grooves were infrequent (6%). Focal columnar morphology was seen in 27% of the tumors. Mitoses were plentiful in 37%, and apoptosis was prominent in 46%. Intratubular tumor was seen in 43% and entrapped seminiferous tubules in 70%. Lymphovascular invasion was present in 2 cases, rete testis involvement in 4, and necrosis in 1. Rare features/patterns included: regressed tumor with hyalinization and prominent blood vessels (13%), papillary growth (4%), basaloid morphology (1%), spindle cell predominance (1%), microcystic foci (1%), adult granulosa cell–like (1%) patterns, and hyaline globules (1%). Inhibin (16/18), calretinin (8/9), WT1 (6/7), FOXL2 (12/12), SF-1 (12/12), and SOX9 (6/11) were positive, whereas SALL4 and glypican-3 were consistently negative in the neoplastic granulosa cells. Only 1 of 10 tumors was focally positive for α-fetoprotein. JGCT is a rare neoplasm with a wide morphologic spectrum that also occurs rarely in undescended testes and dysgenetic gonads. The solid and reticular patterns may pose diagnostic challenges, but the lobular appearance and follicular differentiation are characteristic. Immunohistochemical stains may aid in its distinction from other tumors of young male individuals, particularly yolk sac tumor, a neoplasm that peaks at a somewhat later age. Twenty-four patients with follow-up, including 4 of 6 patients treated with wedge resection/biopsy, had no evidence of disease (2 to 348 mo; mean, 83 mo; median, 61 mo). One additional patient was alive at 260 months, but the disease status is unknown. The benign clinical course of all cases of JGCT with follow-up, despite often frequent mitotic activity, supports testis sparing surgery when technically feasible.
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    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
    (Elsevier, 2017) Roth, Lawrence M.; Lyu, Bingjian; Cheng, Liang; Department of Pathology and Laboratory Medicine, IU School of Medicine
    Sex cord-stromal tumors (SCSTs) are the second most frequent category of testicular neoplasms, accounting for approximately 2–5% 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.
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    Protein expression of the transcription factors DMRT1, TCLF5, and OCT4 in selected germ cell neoplasms of the testis
    (Elsevier, 2018) Roth, Lawrence M.; Michal, Michal; Michal, Michael, Jr.; Cheng, Liang; Pathology and Laboratory Medicine, School of Medicine
    In the present study, we investigated protein expression of the transcription factors mammalian doublesex and mab-3 related transcription factor 1 (DMRT1), basic helix–loop–helix transcription factor-like 5 (TCLF5), and octamer-binding transcription factor 4 (OCT4) in normal human spermatogenesis, testicular mixed germ cell-sex cord stromal tumor (MGC-SCST), spermatocytic tumor, and seminoma. In normal human spermatogenesis, DMRT1 is expressed in the nuclei of spermatogonia, but not in those of more mature germ cells. By way of contrast, TCLF5 is expressed in the nuclei of some clusters of primary spermatocytes that have entered meiosis 1, in secondary spermatocytes, and in round (early) spermatids in the seminiferous tubules of adults during the reproductive years. OCT4 is expressed in primordial germ cells, but not in the seminiferous tubules of the normal adult testis during the reproductive years. DMRT1 is expressed in the germ cells of both testicular MGC-SCST and spermatocytic tumor, whereas TCLF5 is not expressed in either neoplasm. These low-grade neoplasms, however, differ histologically in that all the germ cell nuclei of testicular MGC-SCST resemble spermatogonia, whereas in spermatocytic tumor the nuclei of the medium-sized and large cells resemble those of primary spermatocytes. Both neoplasms lack expression of OCT4. By way of contrast, in seminoma, a fully malignant testicular germ cell tumor, the germ cell nuclei express OCT4, but do not express either DMRT1 or TCLF5.
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    Report From the International Society of Urological Pathology (ISUP) Consultation Conference on Molecular Pathology of Urogenital Cancers: IV: Current and Future Utilization of Molecular-Genetic Tests for Testicular Germ Cell Tumors
    (Wolters Kluwer, 2020-03-20) Looijenga, Leendert H. J.; Van der Kwast, Theodorus H.; Grignon, David; Egevad, Lars; Kristiansen, Glen; Kao, Chia-Sui; Idrees, Muhammad T.; Pathology and Laboratory Medicine, School of Medicine
    The International Society of Urological Pathology (ISUP) organized a Consultation Conference in March 2019 dealing with applications of molecular pathology in Urogenital Pathology, including testicular tumors (with a focus on germ cell tumors [GCTs]), preceded by a survey among its members to get insight into current practices in testicular germ cell tumor (TGCT) diagnostics and adoption of the ISUP immunohistochemical guidelines published in 2014. On the basis of the premeeting survey, the most commonly used immunomarker panel includes OCT3/4, placental alkaline phosphate, D2-40, SALL4, CD117, and CD30 for GCTs and the documentation of germ cell neoplasia in situ (GCNIS). Molecular testing, specifically 12p copy gain, is informative to distinguish non-GCNIS versus GCNIS related GCTs, and establishing germ cell origin of tumors both in the context of primary and metastatic lesions. Other molecular methodologies currently available but not widely utilized for TGCTs include genome-wide and targeted approaches for specific genetic anomalies, P53 mutations, genomic MDM2 amplification, and detection of the p53 inactivating miR-371a-3p. The latter also holds promise as a serum marker for malignant TGCTs. This manuscript provides an update on the classification of TGCTs, and describes the current and future role of molecular-genetic testing. The following recommendations are made: (1) Presence of GCNIS should be documented in all cases along with extent of spermatogenesis; (2) Immunohistochemical staining is optional in the following scenarios: identification of GCNIS, distinguishing embryonal carcinoma from seminoma, confirming presence of yolk sac tumor and/or choriocarcinoma, and differentiating spermatocytic tumor from potential mimics; (3) Detection of gain of the short arm of chromosome 12 is diagnostic to differentiate between non-GCNIS versus GCNIS related GCTs and supportive to the germ cell origin of both primary and metastatic tumors.