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Archives of Pathology & Laboratory... Apr 2008The histopathology of testicular tumors is presented, emphasizing new, unusual, or underemphasized aspects. Within the category of seminoma of the usual type, the recent... (Review)
Review
The histopathology of testicular tumors is presented, emphasizing new, unusual, or underemphasized aspects. Within the category of seminoma of the usual type, the recent literature has drawn attention to the presence in occasional tumors of solid or hollow tubules or spaces of varying sizes and shape that may result in cribriform or microcystic patterns, causing potential confusion with other neoplasms, most notably Sertoli cell tumor or yolk sac tumor. Although regions of typical neoplasia and awareness of this phenomenon usually will be diagnostic, immunohistochemistry may play a role in excluding Sertoli cell tumor or yolk sac tumor. Although immunohistochemistry can play an undoubted helpful role in this and selected other areas of testicular tumor evaluation, careful evaluation of the gross and routine microscopic features will solve the vast majority of diagnostic problems. An excellent review of immunohistochemistry in this area by R. E. Emerson, MD, and T. M. Ulbright, MD, is cited herein. Spermatocytic seminoma remains a crucial pitfall in diagnosis, and the pathologist must always be alert to the possible diagnosis when looking at a seminomatous neoplasm, particularly in an older patient, although about one third of these tumors occur in the usual seminoma age range. The embryonal carcinoma has a great diversity of patterns, which are briefly noted. The enigmatic and picturesque tumor, polyembryoma, which virtually never occurs in pure form but may be a confusing component of a variety of mixed germ cell tumors, is discussed and illustrated. The phenomenon of burnt-out germ cell neoplasia is also briefly noted and an excellent recent contribution is referred to. Within the sex cord-stromal family of neoplasms, recent contributions and elaborations of unusual morphologic features of Leydig cell tumors and Sertoli cell tumors are presented. Within the Leydig cell family, cyst formation, adipose metaplasia, calcification or ossification, and spindle cell patterns may be particularly confusing, and in the Sertoli cell family, a great array of patterns caused by differing admixtures of tubular, solid, and stromal components occur. The peculiar lesion, intratubular large cell hyalinizing Sertoli cell tumor, of young boys with Peutz-Jeghers syndrome, is briefly discussed. Some of the problems in the family of hematopoietic neoplasms are reviewed, these processes posing diverse problems in differential diagnosis and their correct recognition having crucial therapeutic implications. Although secondary tumors to the testis have not received the same attention in the literature as the similar phenomenon in the female gonad, remarkable examples of testicular spread of diverse neoplasms, usually carcinoma but rarely melanoma, are seen, and the pathologist should be alert to this possibility, particularly when examining an unusual morphology in an older patient. Finally, a few comments are made on the common paratesticular neoplasm, the adenomatoid tumor, highlighting its varied patterns and recent description of some of the issues that may arise when they undergo total or subtotal infarction.
Topics: Carcinoma, Embryonal; Diagnosis, Differential; Endodermal Sinus Tumor; Humans; Male; Neoplasms, Germ Cell and Embryonal; Pathology; Seminoma; Teratoma; Testicular Neoplasms
PubMed: 18384207
DOI: 10.5858/2008-132-548-TTNAAF -
International Journal of Molecular... Dec 2019Endocannabinoids are natural lipid molecules whose levels are regulated by specific biosynthetic and degradative enzymes. They bind to and activate two main cannabinoid... (Review)
Review
Endocannabinoids are natural lipid molecules whose levels are regulated by specific biosynthetic and degradative enzymes. They bind to and activate two main cannabinoid receptors type 1 (CB) and type 2 (CB), and together with their metabolizing enzymes form the "endocannabinoid system" (ECS). In the last years, the relevance of endocannabinoids (eCBs) as critical modulators in various aspects of male reproduction has been pointed out. Mammalian male germ cells, from mitotic to haploid stage, have a complete ECS which is modulated during spermatogenesis. Compelling evidence indicate that in the testis an appropriate "eCBs tone", associated to a balanced CB receptors signaling, is critical for spermatogenesis and for the formation of mature and fertilizing spermatozoa. Any alteration of this system negatively affects male reproduction, from germ cell differentiation to sperm functions, and might have also an impact on testicular tumours. Indeed, most of testicular tumours develop during early germ-cell development in which a maturation arrest is thought to be the first key event leading to malignant transformation. Considering the ever-growing number and complexity of the data on ECS, this review focuses on the role of cannabinoid receptors CB and CB signaling in male germ cells development from gonocyte up to mature spermatozoa and in the induction of epigenetic alterations in these cells which might be transmitted to the progeny. Furthermore, we present new evidence on their relevance in testicular cancer.
Topics: Animals; Biomarkers; Disease Susceptibility; Epigenesis, Genetic; Gene Expression Regulation, Neoplastic; Humans; Male; Neoplasms, Germ Cell and Embryonal; Receptors, Cannabinoid; Reproduction; Signal Transduction; Spermatogenesis; Testicular Neoplasms
PubMed: 31861494
DOI: 10.3390/ijms21010025 -
Journal of the National Medical... Aug 1980Precise localization, detection, and recognition of minor changes in testicular lesions are important because teratocarcinoma is notorious for manifesting as secondaries...
Precise localization, detection, and recognition of minor changes in testicular lesions are important because teratocarcinoma is notorious for manifesting as secondaries at the time the primary site is obvious to the clinician. In the past, questionable enlargement of the testis due to significant pathology required numerous radiographic invasive special procedures to provide a correct diagnosis. Due to the advent of the sophisticated digital ultrasound imager with high frequency quarter wave transducer, it is possible to detect minor changes in the tissue character of the testis, thus enabling the physician to tackle primary neoplasms prior to distant spread.In our case we were able to detect the abnormality in the testis, but unfortunately a large secondary abnormal mass was present. Even at that stage we were able to map out the extent of the lesion which was beneficial to the surgeon and the patient. Ultrasound studies were utilized in serial follow-up studies.
Topics: Adult; Humans; Male; Teratoma; Testicular Neoplasms; Ultrasonography
PubMed: 7401191
DOI: No ID Found -
British Journal of Cancer Aug 2016Cancer/testis-antigens (CTAs) are specifically expressed in human malignancies and testis tissue, but their molecular functions are poorly understood. CTAs serve as...
BACKGROUND
Cancer/testis-antigens (CTAs) are specifically expressed in human malignancies and testis tissue, but their molecular functions are poorly understood. CTAs serve as regulators of gene expression, cell cycle and spermatogenesis, as well as targets for immune-based therapies. The CTA PRAME is expressed in various cancers, antagonises retinoic acid signalling and is regulated by DNA methylation and histone acetylation.
METHODS
We analysed the molecular function of the CTA PRAME in primordial germ cells (PGC) and testicular germ cell cancers (GCC). GCCs arise from a common precursor lesion termed germ cell neoplasia in situ (GCNIS), which itself is thought to originate from a defective PGC. GCNIS cells eventually develop into unipotent seminomas or totipotent embryonal carcinomas (ECs), which are capable of differentiation into teratomas, yolk-sac tumours and choriocarcinomas.
RESULTS
PRAME is, like the master regulator of PGCs SOX17 expressed in human PGCs, GCNIS and seminomas but absent in ECs. shRNA-mediated knockdown of PRAME in seminomatous TCam-2 cells left SOX17 levels unchanged, but resulted in downregulation of pluripotency- and PGC-related genes (LIN28, PRDM14, ZSCAN10), whereas somatic and germ cell differentiation markers were upregulated. So, PRAME seems to act downstream of SOX17 by mediating the regulation of the germ cell differentiation and pluripotency programme. Endoderm differentiation is triggered in somatic cells by SOX17, suggesting that in PGCs, PRAME represses this programme and modulates SOX17 to function as a PGC-master regulator. Surprisingly, knockdown of PRAME in TCam-2 cells did not render the cells sensitive towards retinoic acid, despite the fact that PRAME has been described to antagonise retinoic acid signalling. Finally, we demonstrate that in non-seminomas PRAME expression is silenced by DNA methylation, which can be activated by formation of euchromatin via histone-deacetylase-inhibitors.
CONCLUSIONS
We identified the CTA PRAME as a downstream factor of SOX17 and LIN28 in regulating pluripotency and suppressing somatic/germ cell differentiation in PGC, GCNIS and seminomas.
Topics: Antigens, Neoplasm; Blotting, Western; Cell Differentiation; Cell Line, Tumor; Cells, Cultured; Gene Knockdown Techniques; Germ Cells; Humans; Immunohistochemistry; Male; RNA, Messenger; RNA, Small Interfering; Real-Time Polymerase Chain Reaction; Seminoma; Testicular Neoplasms; Testis
PubMed: 27441500
DOI: 10.1038/bjc.2016.187 -
Anales de Pediatria (Barcelona, Spain :... May 2014
Topics: Humans; Infant, Newborn; Male; Testicular Neoplasms
PubMed: 24103251
DOI: 10.1016/j.anpedi.2013.06.027 -
Frontiers in Endocrinology 2020
Topics: Cell Transformation, Neoplastic; Fertility; Health Status; Humans; Male; Neoplasms, Germ Cell and Embryonal; Quality of Life; Sexual Behavior; Testicular Neoplasms
PubMed: 32117067
DOI: 10.3389/fendo.2020.00041 -
Andrology Jul 2019The insulin-like growth factor (IGF) axis plays key roles in normal tissue growth and development as well as in the progression of several tumour types and their... (Review)
Review
The insulin-like growth factor (IGF) axis plays key roles in normal tissue growth and development as well as in the progression of several tumour types and their subsequent growth and progression to a metastatic phenotype. This review explores the role of IGF system in normal germ cell development and function in addition to examining the evidence for deregulation of IGF signalling in cancer, with particular relevance to evidence supporting a role in testicular germ cell tumours (TGCTs). Despite the clear preclinical rationale for targeting the IGF axis in cancer, there has been a lack of progress in identifying which patients may benefit from such therapy. Future employment of agents targeting the IGF pathway is expected to concentrate on their use in combination with other treatments to prevent resistance and exploit their potential as chemo- and radiosensitizers.
Topics: Animals; Carcinogenesis; Drug Resistance, Neoplasm; Germ Cells; Humans; Molecular Targeted Therapy; Neoplasms, Germ Cell and Embryonal; Receptor, IGF Type 1; Somatomedins; Testicular Neoplasms
PubMed: 31179642
DOI: 10.1111/andr.12658 -
Journal of the American Veterinary... Jul 2020
Topics: Animals; Camelids, New World; Male; Seminoma; Testicular Neoplasms
PubMed: 32538695
DOI: 10.2460/javma.257.1.45 -
PloS One 2017Innovative therapies for solid tumors are urgently needed. Recently, therapies that harness the host immune system to fight cancer cells have successfully treated a...
Innovative therapies for solid tumors are urgently needed. Recently, therapies that harness the host immune system to fight cancer cells have successfully treated a subset of patients with solid tumors. These responses have been strong and durable but observed in subsets of patients. Work from our group and others has shown that epigenetic therapy, specifically inhibiting the silencing DNA methylation mark, activates immune signaling in tumor cells and can sensitize to immune therapy in murine models. Here we show that colon and ovarian cancer cell lines exhibit lower expression of transcripts involved in antigen processing and presentation to immune cells compared to normal tissues. In addition, treatment with clinically relevant low doses of DNMT inhibitors (that remove DNA methylation) increases expression of both antigen processing and presentation and Cancer Testis Antigens in these cell lines. We confirm that treatment with DNMT inhibitors upregulates expression of the antigen processing and presentation molecules B2M, CALR, CD58, PSMB8, PSMB9 at the RNA and protein level in a wider range of colon and ovarian cancer cell lines and treatment time points than had been described previously. In addition, we show that DNMTi treatment upregulates many Cancer Testis Antigens common to both colon and ovarian cancer. This increase of both antigens and antigen presentation by epigenetic therapy may be one mechanism to sensitize patients to immune therapies.
Topics: Animals; Antigen Presentation; Antigens, Neoplasm; Caco-2 Cells; Colonic Neoplasms; DNA Methylation; DNA, Neoplasm; Female; Humans; Male; Mice; Ovarian Neoplasms; Testicular Neoplasms
PubMed: 28622390
DOI: 10.1371/journal.pone.0179501 -
Journal of Epidemiology and Community... Sep 1986
Topics: Humans; Male; Testicular Neoplasms
PubMed: 3772291
DOI: 10.1136/jech.40.3.279-a