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1.
Medicine (Baltimore) ; 103(15): e37688, 2024 Apr 12.
Artículo en Inglés | MEDLINE | ID: mdl-38608099

RESUMEN

Testicular germ cell tumors (TGCT) are the most common testicular malignancies. KLRB1 is considered to influence the development and progression of a number of cancers. However, it is unclear how the KLRB1 gene functions in TGCT. First, it was determined the expression level of KLRB1 in TGCT using The Cancer Genome Atlas (TCGA) (The Cancer Genome Atlas) dataset and GTEx (Genotype-Tissue Expression) dataset. The clinical significance and biological functions of KLRB1 were explored using the TCGA dataset, and we analyzed the correlation of the KLRB1 gene with tumor immunity and infiltrating immune cells using gene set variation analysis and the TIMER database. We found that the expression level of KLRB1 was upregulated in TGCT malignant tissues with the corresponding normal tissues as controls, and KLRB1 expression correlated with clinicopathologic features of TGCT. Functional enrichment analysis suggested that KLRB1 might be involved in immune response and inflammatory response. KLRB1 was highly positively correlated with natural killer cell activation in immune response and positively correlated with tumor-infiltrating immune cells. This study demonstrated for the first time the role of KLRB1 in TGCT, which may serve as a new biomarker associated with immune infiltration and provide a potential therapeutic target for the treatment of TGCT.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Humanos , Masculino , Neoplasias Testiculares/genética , Neoplasias de Células Germinales y Embrionarias/genética , Bases de Datos Factuales , Activación de Linfocitos , Subfamilia B de Receptores Similares a Lectina de Células NK
2.
Curr Opin Oncol ; 36(3): 169-173, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38573206

RESUMEN

PURPOSE OF REVIEW: Despite the remarkable advances in the treatment of germ cell tumors (GCT), several challenges remain. This review aims to highlight some of these challenges and provide guidance on how to navigate through them. RECENT FINDINGS: Patients with International Germ Cell Cancer Collaborative Group poor risk disease have worse prognosis and investigating novel therapeutic interventions are warranted in this population. Patients with brain metastases require a multidisciplinary approach by a group of clinicians experienced in the management of germ cell tumors. Patients with platinum refractory disease have poor prognosis and development of novel treatment options is urgently needed. Conventional tumor markers including alpha fetoprotein and human chorionic gonadotropin remain standard. Development of novel biomarkers to detect minimal residual disease or teratoma is needed. SUMMARY: Management of patients with GCT requires a multidisciplinary approach. Patients should preferably be evaluated at tertiary care centers with expertise in the management of this disease.


Asunto(s)
Neoplasias Encefálicas , Neoplasias de Células Germinales y Embrionarias , Teratoma , Humanos , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/terapia , Biomarcadores de Tumor , Neoplasia Residual
3.
Rev Esp Patol ; 57(2): 146-150, 2024.
Artículo en Español | MEDLINE | ID: mdl-38599737

RESUMEN

Spermatocytic tumor is a very rare germ cell testicular neoplasm that accounts for less than 1% of testicular cancers. It generally affects older men with a mean age of 53.6 years (range 19-92 years). Spermatocytic tumor is classified within the group of germ cell tumors not related to germ cell neoplasia in situ. It presents clinicopathological characteristics different from classic seminoma and is not considered a variant of the latter. Due to a morphologic overlap with classical seminoma, it was called "sperm cell seminoma" in the past. The anaplastic variant of spermatocytic tumor is exceptional, few cases have been described in the literature, it presents an earlier onset compared to spermatocytic tumor and a benign behavior despite showing histological patterns similar to classic seminoma. We present the second case of bilateral synchronous anaplastic spermatocytic tumor, in a young patient treated with orchiectomy and chemotherapy.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Humanos , Masculino , Anciano , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano de 80 o más Años , Seminoma/patología , Semen , Neoplasias Testiculares/patología
4.
Eur J Cancer ; 202: 114042, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38564927

RESUMEN

AIMS: To resolve the ongoing controversy surrounding the impact of teratoma (TER) in the primary among patients with metastatic testicular non-seminomatous germ-cell tumours (NSGCT). PATIENTS AND METHODS: Using the International Germ Cell Cancer Collaborative Group (IGCCCG) Update Consortium database, we compared the survival probabilities of patients with metastatic testicular GCT with TER (TER) or without TER (NTER) in their primaries corrected for known prognostic factors. Progression-free survival (5y-PFS) and overall survival at 5 years (5y-OS) were estimated by the Kaplan-Meier method. RESULTS: Among 6792 patients with metastatic testicular NSGCT, 3224 (47%) had TER in their primary, and 3568 (53%) did not. In the IGCCCG good prognosis group, the 5y-PFS was 87.8% in TER versus 92.0% in NTER patients (p = 0.0001), the respective 5y-OS were 94.5% versus 96.5% (p = 0.0032). The corresponding figures in the intermediate prognosis group were 5y-PFS 76.9% versus 81.6% (p = 0.0432) in TER and NTER and 5y-OS 90.4% versus 90.9% (p = 0.8514), respectively. In the poor prognosis group, there was no difference, neither in 5y-PFS [54.3% in TER patients versus 55.4% (p = 0.7472) in NTER], nor in 5y-OS [69.4% versus 67.7% (p = 0.3841)]. NSGCT patients with TER had more residual masses (65.3% versus 51.7%, p < 0.0001), and therefore received post-chemotherapy surgery more frequently than NTER patients (46.8% versus 32.0%, p < 0.0001). CONCLUSION: Teratoma in the primary tumour of patients with metastatic NSGCT negatively impacts on survival in the good and intermediate, but not in the poor IGCCCG prognostic groups.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Seminoma , Teratoma , Neoplasias Testiculares , Masculino , Humanos , Neoplasias Testiculares/tratamiento farmacológico , Neoplasias de Células Germinales y Embrionarias/terapia , Pronóstico , Teratoma/terapia , Factores de Riesgo , Estudios Retrospectivos
5.
J Cancer Res Clin Oncol ; 150(4): 201, 2024 Apr 17.
Artículo en Inglés | MEDLINE | ID: mdl-38630148

RESUMEN

PURPOSE: We assessed factors that affect the utilization of sperm cryopreservation before 2021, when patients covered expenses, and the influence on quality of life. METHODS: Between 2011 and 2021, testicular cancer survivors (TCS) at our clinic completed a questionnaire, including EORTC QLQ-TC26, covering sperm cryopreservation, sociodemographic details, post-treatment births, and artificial insemination. RESULTS: After 5.7 ± 3.0 years, 279 participants (64%) responded to the questionnaire. Among them, 33% (91/279) of testicular cancer survivors chose sperm cryopreservation prior to treatment, with 11% (10/91) using it for insemination. Conversely, 2% (3/188) without cryopreservation reported unfulfilled desire to have children. Univariate analysis showed TCS with cryopreservation were younger (30.6 ± 7.1 (35 (21-59)) vs. 42.4 ± 10.9 (48 (22-81)) years; p = 0.001), had a lower BMI (24.2 ± 3.3 vs. 26.6 ± 4.6 kg/m2; p = 0.009) and a lower Charlson Score (> 3: 36% vs. 60%; p < 0.001). Multivariate analysis revealed older age (≥ 37 years: OR 13.1 (5.5-31.2), p < 0.001) and lower education (middle school or less: OR 3.3 (1.6-6.9), p = 0.001) as independent factors associated with not undergoing cryopreservation. Regarding quality of life, multivariate analysis identified a lower infertility anxiety score (OR 4.3 (2.0-9.0), p < 0.001) and higher age (≥ 44 years: OR 5.4 (2.6-11.3); p < 0.001) as predictors for the absence of prior cryopreservation. CONCLUSIONS: Age and education seem to impact the choice of undergoing paid sperm cryopreservation. Urologists should inform testicular cancer patients about costs and coverage. Importantly, the occurrence of unmet desires for parenthood is minimal among those who forego cryopreservation.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Niño , Humanos , Masculino , Adulto , Neoplasias Testiculares/terapia , Calidad de Vida , Semen , Criopreservación , Espermatozoides
6.
Environ Health ; 23(1): 42, 2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627679

RESUMEN

BACKGROUND: Per- and polyfluoroalkyl substances (PFAS) are associated with many adverse health conditions. Among the main effects is carcinogenicity in humans, which deserves to be further clarified. An evident association has been reported for kidney cancer and testicular cancer. In 2013, a large episode of surface, ground and drinking water contamination with PFAS was uncovered in three provinces of the Veneto Region (northern Italy) involving 30 municipalities and a population of about 150,000. We report on the temporal evolution of all-cause mortality and selected cause-specific mortality by calendar period and birth cohort in the local population between 1980 and 2018. METHODS: The Italian National Institute of Health pre-processed and made available anonymous data from the Italian National Institute of Statistics death certificate archives for residents of the provinces of Vicenza, Padua and Verona (males, n = 29,629; females, n = 29,518) who died between 1980 and 2018. Calendar period analysis was done by calculating standardised mortality ratios using the total population of the three provinces in the same calendar period as reference. The birth cohort analysis was performed using 20-84 years cumulative standardised mortality ratios. Exposure was defined as being resident in one of the 30 municipalities of the Red area, where the aqueduct supplying drinking water was fed by the contaminated groundwater. RESULTS: During the 34 years between 1985 (assumed as beginning date of water contamination) and 2018 (last year of availability of cause-specific mortality data), in the resident population of the Red area we observed 51,621 deaths vs. 47,731 expected (age- and sex-SMR: 108; 90% CI: 107-109). We found evidence of raised mortality from cardiovascular disease (in particular, heart diseases and ischemic heart disease) and malignant neoplastic diseases, including kidney cancer and testicular cancer. CONCLUSIONS: For the first time, an association of PFAS exposure with mortality from cardiovascular disease was formally demonstrated. The evidence regarding kidney cancer and testicular cancer is consistent with previously reported data.


Asunto(s)
Ácidos Alcanesulfónicos , Enfermedades Cardiovasculares , Agua Potable , Fluorocarburos , Neoplasias Renales , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Femenino , Humanos , Agua Potable/análisis , Italia/epidemiología
7.
BMJ Case Rep ; 17(4)2024 Apr 16.
Artículo en Inglés | MEDLINE | ID: mdl-38627058

RESUMEN

Gliomatosis peritonei (GP) and Growing Teratoma Syndrome (GTS) are rare and clinically significant conditions often associated with ovarian teratomas. GP involves the development of benign glial implants on the peritoneal surface, while GTS is characterised by the growth of benign, yet enlarging peritoneal implants following chemotherapy for malignant germ cell tumours. These implants are typically histologically mature teratomas devoid of malignancy. Our report documents a unique case where both GP and GTS manifested in a patient undergoing treatment for an immature ovarian teratoma. This dual occurrence is scarcely reported in the existing literature. The patient, a nulliparous woman in her 20s, developed a tumour indicative of GTS immediately after completing three cycles of bleomycin, etoposide and cisplatin therapy. This chemotherapy regimen followed fertility-sparing surgery for a stage IIIb ovarian immature teratoma. Given that total tumour resection is pivotal in positively influencing the prognosis of GTS, early minimally invasive surgical intervention before significant tumour growth is essential. This approach is particularly crucial considering that ovarian germ cell tumours are commonly present in younger patients, necessitating a focus on fertility preservation in most cases.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Neoplasias Ováricas , Teratoma , Femenino , Humanos , Pronóstico , Neoplasias Ováricas/patología , Teratoma/complicaciones , Teratoma/cirugía , Teratoma/patología , Neoplasias de Células Germinales y Embrionarias/complicaciones
8.
J Med Case Rep ; 18(1): 170, 2024 Apr 11.
Artículo en Inglés | MEDLINE | ID: mdl-38600580

RESUMEN

INTRODUCTION: Paratesticular cellular angiofibroma is a rare benign mesenchymal tumor. The optimal management is surgical resection due to the difficulty of preoperative accurate diagnosis. CASE PRESENTATION: A 51-year-old Japanese male visited our hospital complaining of asymptomatic left scrotal swelling. Physical examination revealed a nontender elastic paratesticular mass (5.5 cm in diameter). Although testicular germ cell tumor was ruled out clinically, the possibility of malignant potential remained for the tumor. Since the patient consented to complete resection, a transinguinal radical orchiectomy was performed. The pathological diagnosis revealed cellular angiofibroma. The patient recovered without perioperative complications, and no apparent recurrence was observed at 5 years after surgery. CONCLUSION: The pathological findings were compatible for cellular angiofibroma. The tumor was successfully resected, and no apparent recurrence was observed at 5 years after surgery.


Asunto(s)
Angiofibroma , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Humanos , Masculino , Persona de Mediana Edad , Angiofibroma/diagnóstico por imagen , Angiofibroma/cirugía , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/cirugía , Neoplasias Testiculares/patología , Orquiectomía , Neoplasias de Células Germinales y Embrionarias/cirugía
9.
J Cancer Res Ther ; 20(1): 238-242, 2024 Jan 01.
Artículo en Inglés | MEDLINE | ID: mdl-38554327

RESUMEN

BACKGROUND: Small round cell tumors (SRCTs) are a group of malignant neoplasms with minimal or no differentiation, characterized by the presence of round cells with high nuclear-cytoplasmic ratio. Although SRCTs can occur in any part of the body, involvement of central nervous system (CNS) is uncommon. AIM: We aimed to study the clinicopathological spectrum of cranial SRCT diagnosed in our institute over a period of four years (2016-2019). MATERIAL AND METHODS: A retrospective review of medical records (2016-2019) with a morphological diagnosis of cranial SRCT was made. Both intra-axial and extra-axial tumors were included. A total of 60 cases were retrieved, and the clinical and histopathological features were studied. Special cytochemical staining and immunohistochemistry were performed, where needed. RESULTS: The mean age at presentation was 18.4 years (range, 1-60 years), with a male-to-female ratio of 2.5:1. The most common site was posterior fossa of brain (n = 28, 47%), followed by dorso-lumbar spine (n = 9, 15%). The most common type of tumor was medulloblastoma (n = 29, 48.3%), followed by Ewing sarcoma (ES)/peripheral primitive neuroectodermal tumor (pPNET) (n = 11, 18.3%), non-Hodgkin lymphoma (NHL) (n = 9, 15%), neuroblastoma (n = 3, 5%), and CNS embryonal tumor, NOS (n = 2, 3.3%). One case each of atypical teratoid rhabdoid tumor (ATRT), rhabdomyosarcoma, pineoblastoma, melanoma, rhabdomyosarcoma, and undifferentiated pleomorphic sarcoma was also documented. CONCLUSIONS: SRCTs have a variable age of presentation. Their incidence in CNS is low as compared to other organ systems. On light microscopy, the histopathology of these lesions is overlapping, posing a great diagnostic dilemma for the pathologist. The use of ancillary techniques like immunohistochemistry helps in arriving at the correct diagnosis. Treatment strategy and tumor prognosis also vary along the entire spectrum of SRCT, thus making exact characterization essential for proper management.


Asunto(s)
Neoplasias del Sistema Nervioso Central , Neoplasias Cerebelosas , Neoplasias de Células Germinales y Embrionarias , Tumores Neuroectodérmicos Primitivos , Rabdomiosarcoma , Sarcoma , Humanos , Masculino , Femenino , Lactante , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Centros de Atención Terciaria , Sarcoma/patología , Rabdomiosarcoma/patología , Tumores Neuroectodérmicos Primitivos/patología , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/epidemiología
10.
Environ Health ; 23(1): 33, 2024 Mar 28.
Artículo en Inglés | MEDLINE | ID: mdl-38549149

RESUMEN

The largest documented episode of human contamination by PFOA in the world (approximately 150,000 actual residents on 1 January 2020) has occurred in Italy's Veneto Region. In this large, mostly flat plain area, a cluster of testicular cancers has also been observed. Preliminary data are reported, and the most relevant and recent recommendations regarding the health surveillance of exposed individuals are emphasized.


Asunto(s)
Ácidos Alcanesulfónicos , Fluorocarburos , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Contaminantes Químicos del Agua , Masculino , Humanos , Fluorocarburos/análisis , Contaminantes Químicos del Agua/análisis , Italia/epidemiología , Neoplasias Testiculares/inducido químicamente , Neoplasias Testiculares/epidemiología
11.
Adv Anat Pathol ; 31(3): 206-214, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38525515

RESUMEN

The current WHO classification of testicular germ cell tumors is based on the pathogenesis of the tumors driven by different genomic events. The germ cell neoplasia in situ is the precursor lesion for all malignant germ cell tumors. The current understanding of pathogenesis is that the developmental and environmental factors with the erasure of parental genomic imprinting lead to the development of abnormal gonocytes that settle in the "spermatogonial Niche" in seminiferous tubules. The abnormal primordial germ cells in the seminiferous tubules give rise to pre-GCNIS cells under the influence of TPSY and OCT4 genes. The whole genome duplication events give rise to germ cell neoplasia in situ, which further acquires alterations in 12p along with NRAS and KRAS mutations to produce seminoma. A subset of seminomas acquires KIT mutation and does not differentiate further. The remaining KIT-stable seminomas differentiate to nonseminomatous GCTs after obtaining recurrent chromosomal losses, epigenetic modification, and posttranscriptional regulation by multiple genes. Nonseminomatous germ cell tumors also develop directly from differentiated germ cell neoplasia in situ. TP53 pathway with downstream drivers may give rise to somatic-type malignancies of GCT. The GCTs are remarkably sensitive to cisplatin-based combination chemotherapy; however, resistance to cisplatin develops in up to 8% of tumors and appears to be driven by TP53/MDM2 gene mutations. Serum and Plasma miRNAs show promise in diagnosing, managing, and following up on these tumors. The mechanisms underlying the development of most tumors have been elucidated; however, additional studies are required to pinpoint the events directing specific characteristics. Advances in identifying specific molecular markers have been seen recently and may be adopted as gold standards in the future.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Seminoma , Neoplasias Testiculares , Masculino , Humanos , Seminoma/metabolismo , Cisplatino , Neoplasias Testiculares/patología , Neoplasias de Células Germinales y Embrionarias/genética
12.
Handb Clin Neurol ; 200: 431-445, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38494295

RESUMEN

Paraneoplastic neurologic syndromes (PNSs) are a group of diseases affecting the central and/or peripheral nervous system caused by immune-mediated processes directed toward antigens with shared expression in tumor and neural tissue. Germ cell tumors (GCTs) are associated with PNSs with varied clinical phenotypes. Early diagnosis of PNS is vital to potentially uncover and treat underlying tumors, improving the chances of recovery, and preventing permanent neurologic complications. In this chapter, we outline the pathophysiology and epidemiology of PNS. We briefly provide a summary of GCTs in males and females. We review the neural-specific autoantibodies and PNSs associated with GCTs and their clinical and radiologic accompaniments. We also provide an overview of the treatment and prognosis of these disorders.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Enfermedades del Sistema Nervioso , Síndromes Paraneoplásicos del Sistema Nervioso , Masculino , Femenino , Humanos , Autoanticuerpos , Síndromes Paraneoplásicos del Sistema Nervioso/diagnóstico , Enfermedades del Sistema Nervioso/complicaciones , Pronóstico , Neoplasias de Células Germinales y Embrionarias/complicaciones
13.
Cells ; 13(5)2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38474332

RESUMEN

BACKGROUND: Most patients with testicular germ cell tumors (GCTs) are treated with cisplatin (CP)-based chemotherapy. However, some of them may develop CP resistance and therefore represent a clinical challenge. Cyclin-dependent kinase 5 (CDK5) is involved in chemotherapy resistance in different types of cancer. Here, we investigated the possible role of CDK5 and other CDKs targeted by dinaciclib in nonseminoma cell models (both CP-sensitive and CP-resistant), evaluating the potential of the CDK inhibitor dinaciclib as a single/combined agent for the treatment of advanced/metastatic testicular cancer (TC). METHODS: The effects of dinaciclib and CP on sensitive and resistant NT2/D1 and NCCIT cell viability and proliferation were evaluated using MTT assays and direct count methods. Flow cytometry cell-cycle analysis was performed. The protein expression was assessed via Western blotting. The in vivo experiments were conducted in zebrafish embryos xenografted with TC cells. RESULTS: Among all the CDKs analyzed, CDK5 protein expression was significantly higher in CP-resistant models. Dinaciclib reduced the cell viability and proliferation in each cell model, inducing changes in cell-cycle distribution. In drug combination experiments, dinaciclib enhances the CP effect both in vitro and in the zebrafish model. CONCLUSIONS: Dinaciclib, when combined with CP, could be useful for improving nonseminoma TC response to CP.


Asunto(s)
Cisplatino , Óxidos N-Cíclicos , Indolizinas , Neoplasias de Células Germinales y Embrionarias , Compuestos de Piridinio , Neoplasias Testiculares , Masculino , Animales , Humanos , Cisplatino/farmacología , Pez Cebra , Proliferación Celular , Inhibidores de Proteínas Quinasas/farmacología
14.
PeerJ ; 12: e16971, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38495765

RESUMEN

Stem cells are critical for replenishment of cells lost to death, damage or differentiation. Drosophila testes are a key model system for elucidating mechanisms regulating stem cell maintenance and differentiation. An intriguing gene identified through such studies is the transcription factor, chronologically inappropriate morphogenesis (Chinmo). Chinmo is a downstream effector of the Jak-STAT signaling pathway that acts in testis somatic stem cells to ensure maintenance of male stem cell fate and sexual identity. Defects in these processes can lead to infertility and the formation of germ cell tumors. While Chinmo's effect on testis stem cell behavior has been investigated in detail, there is still much to be learned about its structure, function, and interactions with other proteins. Using a two-hybrid screen, we find that Chinmo interacts with itself, the small ubiquitin-like modifier SUMO, the novel protein CG11180, and four other proteins (CG4318, Ova (ovaries absent), Taf3 (TBP-associated factor 3), and CG18269). Since both Chinmo and CG11180 contain sumoylation sites and SUMO-interacting motifs (SIMs), we analyzed their interaction in more detail. Using site-directed mutagenesis of a unique SIM in CG11180, we demonstrate that Chinmo's interaction with CG11180 is SUMO-dependent. Furthermore, to assess the functional relevance of both SUMO and CG11180, we performed RNAi-mediated knockdown of both proteins in somatic cells of the Drosophila testis. Using this approach, we find that CG11180 and SUMO are required in somatic cells of adult testes, and that reduction of either protein causes formation of germ cell tumors. Overall, our work suggests that SUMO may be involved in the interaction of Chinmo and CG11180 and that these genes are required in somatic cells of the adult Drosophila testis. Consistent with the CG11180 knockdown phenotype in male testes, and to underscore its connection to Chinmo, we propose the name Chigno (Childless Gambino) for CG11180.


Asunto(s)
Proteínas de Drosophila , Neoplasias de Células Germinales y Embrionarias , Animales , Masculino , Drosophila/genética , Drosophila melanogaster/genética , Proteínas de Drosophila/genética , Neoplasias de Células Germinales y Embrionarias/metabolismo , Proteínas del Tejido Nervioso/genética , Factores de Transcripción STAT/genética , Testículo , Proteína SUMO-1
15.
Acta Neuropathol Commun ; 12(1): 42, 2024 Mar 18.
Artículo en Inglés | MEDLINE | ID: mdl-38500181

RESUMEN

Central nervous system (CNS) embryonal tumors are a heterogeneous group of high-grade malignancies, and the increasing clinical use of methylation profiling and next-generation sequencing has led to the identification of molecularly distinct subtypes. One proposed tumor type, CNS tumor with BRD4::LEUTX fusion, has been described. As only a few CNS tumors with BRD4::LEUTX fusions have been described, we herein characterize a cohort of 9 such cases (4 new, 5 previously published) to further describe their clinicopathologic and molecular features. We demonstrate that CNS embryonal tumor with BRD4::LEUTX fusion comprises a well-defined methylation class/cluster. We find that patients are young (4 years or younger), with large tumors at variable locations, and frequently with evidence of leptomeningeal/cerebrospinal fluid (CSF) dissemination. Histologically, tumors were highly cellular with high-grade embryonal features. Immunohistochemically, 5/5 cases showed synaptophysin and 4/5 showed OLIG2 expression, thus overlapping with CNS neuroblastoma, FOXR2-activated. DNA copy number profiles were generally flat; however, two tumors had chromosome 1q gains. No recurring genomic changes, besides the presence of the fusion, were found. The LEUTX portion of the fusion transcript was constant in all cases assessed, while the BRD4 portion varied but included a domain with proto-oncogenic activity in all cases. Two patients with clinical follow up available had tumors with excellent response to chemotherapy. Two of our patients were alive without evidence of recurrence or progression after gross total resection and chemotherapy at 16 and 33 months. One patient relapsed, and the last of our four patients died of disease one month after diagnosis. Overall, this case series provides additional evidence for this as a distinct tumor type defined by the presence of a specific fusion as well as a distinct DNA methylation signature. Studies on larger series are required to further characterize these tumors.


Asunto(s)
Neoplasias Encefálicas , Neoplasias del Sistema Nervioso Central , Neoplasias de Células Germinales y Embrionarias , Humanos , Neoplasias Encefálicas/patología , Proteínas Nucleares/genética , Factores de Transcripción/genética , Neoplasias del Sistema Nervioso Central/genética , Neoplasias del Sistema Nervioso Central/patología , Neoplasias de Células Germinales y Embrionarias/genética , Proteínas que Contienen Bromodominio , Proteínas de Ciclo Celular , Factores de Transcripción Forkhead , Proteínas de Homeodominio
16.
Cancer Rep (Hoboken) ; 7(3): e2052, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38507271

RESUMEN

BACKGROUND: Testicular cancer (TC), comprising merely 1% of male neoplasms, holds the distinction of being the most commonly encountered neoplasm among young males. RECENT FINDINGS: Most cases of testicular neoplasms can be classified into two main groups, namely germ cell tumors representing approximately 95% of the cases, and sex cord-stromal tumors accounting for about 5% of the cases. Moreover, its prevalence is on the rise across the globe. TC is a neoplastic condition characterized by a favorable prognosis. The advent of cisplatin-based chemotherapeutic agents in the latter part of the 1970s has led to a significant enhancement in the 5-year survival rate, which presently surpasses 95%. Given that TC is commonly detected before reaching the age of 40, it can be anticipated that these individuals will enjoy an additional 40-50 years of life following successful treatment. The potential causes of TC are multifactorial and related to different pathologies. Accurate identification is imperative to guarantee the utmost efficacious and suitable therapy. To a certain degree, this can be accomplished through the utilization of blood examinations for neoplastic indicators; nonetheless, an unequivocal diagnosis necessitates an evaluation of the histological composition of a specimen via a pathologist. CONCLUSION: TC is multifactorial and has various pathologies, therefore this review aimed to revise the prenatal and postnatal causes as well as novel diagnostic biomarkers and the therapeutic strategies of TC.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Humanos , Masculino , Adulto , Persona de Mediana Edad , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/epidemiología , Neoplasias Testiculares/terapia , Prevalencia , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Neoplasias de Células Germinales y Embrionarias/epidemiología , Neoplasias de Células Germinales y Embrionarias/terapia , Biomarcadores
17.
Appl Neuropsychol Child ; 13(2): 180-189, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38447131

RESUMEN

Survivors of pediatric brain tumors are at high risk for long-term neuropsychological difficulties. In the current case study, we present longitudinal neuropsychological data spanning 10 years (from age 9 to 19 years) of a patient with a rare, very large, bifrontal, embryonal tumor with abundant neuropil and true rosettes (ETANTR), which is typically associated with poor survivorship and significant neurological impact. Results demonstrated that the patient had largely intact cognitive functioning with specific difficulties in executive functioning, fine motor skills, and adaptive functioning at her most recent neuropsychology 10-year follow-up. These results highlight outcomes for a patient with remarkable resiliency in the context of numerous risk factors (a very large tumor size, multi-modal treatment, and seizure history). Patient protective factors (a high level of cognitive reserve, family support, and appropriate comprehensive educational services) likely contributed to the patient's favorable neuropsychological outcome. The patient's age at brain tumor diagnosis (9 years) and associated treatment was at a critical period of development for emerging higher order cognitive functions which likely impacted acquisition of executive functioning skills and secondarily adaptive skill outcomes. Consequently, pediatric brain tumor survivors with ETANTR or other frontal tumors require targeted screening of executive functions and proactive interventions.


Asunto(s)
Neoplasias Encefálicas , Neoplasias de Células Germinales y Embrionarias , Niño , Femenino , Humanos , Adolescente , Adulto Joven , Adulto , Neoplasias Encefálicas/complicaciones , Neurópilo/patología , Función Ejecutiva , Neoplasias de Células Germinales y Embrionarias/patología , Cognición , Pruebas Neuropsicológicas
18.
Ann Clin Lab Sci ; 54(1): 3-8, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38514050

RESUMEN

OBJECTIVE: We hypothesized that reticence to address a groin mass may result in late presentation of testicular/paratesticular malignancy in early puberty through adolescence. METHODS: Malignant testicular and paratesticular tumors (malignant germ cell tumors and rhabdomyosarcomas) diagnosed at our institution from 1994-2023 for patients aged 11-20 were included. Clinicopathologic features were recorded, and statistically analyzed. RESULTS: Eighty-five cases were identified. Patient ages ranged from 11 to 20 years (mean 17 years, median 16 years). The greatest tumor dimension ranged from 0.8 to 18.0 cm (mean 4.4 cm, median 3.5 cm). Ten tumors (11.8% of cases) were ≥10.0 cm. In the 11-13-year-old age group, 100% of tumors (3/3) were ≥10 cm. The proportion of tumors ≥10 cm was significantly higher in the 11-13-year-old age group than in either the 14-16-year-old (P<0.001) or 17-20-year-old (P<0.001) age groups. CONCLUSION: This adolescent cohort with malignant testicular and paratesticular tumors showed a high proportion (11.8%) of very large (≥10 cm) tumors. Although the reasons are unknown and likely multifactorial, this study suggests that adolescents, particularly the 11-13 year age group, are a vulnerable population.


Asunto(s)
Neoplasias de los Genitales Masculinos , Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Adolescente , Niño , Adulto Joven , Adulto , Neoplasias Testiculares/diagnóstico
19.
Psychooncology ; 33(3): e6333, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38520671

RESUMEN

OBJECTIVE: Masculinities have been explored in men with testicular cancer (TC), though limited contemporary research is available on traditional masculine norms important to masculine self-perception. The purpose of this research was to explore the discourse of TC experience in relation to masculine self-perception. METHODS: A qualitative descriptive study was conducted consisting of semi-structured interviews with 21 men. Men were aged between 31 and 47 (Mage = 35.7). Most men were diagnosed with Stage 1 cancer (66.6%), all men had finished active treatment and time since diagnosis ranged from 17.3 to 71.8 months (M = 47.2). Independent coding was conducted by two researchers and was refined in coding meetings with authors. Themes were developed in a predominantly deductive manner, and analysis of themes was undertaken using a reflexive analysis approach. RESULTS: Traditional masculine norms showed differing relationships to masculine self-perception. Two main themes were identified [1] Maintained or enhanced masculine self-perception and [2] threats to masculine self-perception. Subthemes demonstrated that maintaining emotional control, strength and 'winning' was important to men, and reduced physical competencies (i.e., strength, sexual dysfunction, virility) challenged self-perception. Strict adherence to traditional norms in response to threatened self-perception related to psychological distress. CONCLUSION: Leveraging traditionally masculine norms such as physical strength and control and developing flexible adaptations of masculinities should be encouraged with men with TC to retain self-perception and potentially enable better coping. Masculine self-perception of gay/bisexual men may centre around sexual functioning, though further research is required.


Asunto(s)
Neoplasias de Células Germinales y Embrionarias , Neoplasias Testiculares , Masculino , Humanos , Adulto , Persona de Mediana Edad , Masculinidad , Conducta Sexual , Autoimagen
20.
J Pediatr Hematol Oncol ; 46(3): e248-e250, 2024 Apr 01.
Artículo en Inglés | MEDLINE | ID: mdl-38446472

RESUMEN

Germ cell tumors (GCTs) are a heterogeneous group of pediatric cancers. In up to one-third of male patients, a primary mediastinal location is associated with the presence of Klinefelter syndrome (KS). We describe a case of mediastinal GCT in a patient, with unacknowledged KS, that presented a relapse 7 years from diagnosis, that is, 2 years after the end of the follow-up program usually recommended for patients with GCT. There are no recommendations for screening for KS in patients with mediastinal GCT and there are no specific guidelines for surveillance of GCT in KS patients. Our experience suggests that KS should be suspected in patients with mediastinal GCT, and a longer follow-up plan should be implemented when GCT occurs in patients with KS.


Asunto(s)
Síndrome de Klinefelter , Neoplasias del Mediastino , Neoplasias de Células Germinales y Embrionarias , Niño , Humanos , Masculino , Síndrome de Klinefelter/complicaciones , Síndrome de Klinefelter/diagnóstico , Recurrencia Local de Neoplasia , Neoplasias del Mediastino/complicaciones , Neoplasias del Mediastino/diagnóstico , Neoplasias del Mediastino/patología , Neoplasias de Células Germinales y Embrionarias/complicaciones , Neoplasias de Células Germinales y Embrionarias/diagnóstico , Enfermedad Crónica
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