-
BMC Cancer Sep 2023Two thirds of patients with germ-cell cancer (GCC) present as clinical stage I (CSI). Following orchiectomy, active surveillance (AS) has become their standard...
BACKGROUND
Two thirds of patients with germ-cell cancer (GCC) present as clinical stage I (CSI). Following orchiectomy, active surveillance (AS) has become their standard management. However, 15-50% of patients eventually relapse with metastatic disease after AS. Relapses need to be detected early in order to achieve cure and avoid overtreatment.
METHODS
We retrospectively analyzed consecutive GCC patients treated at two Swiss academic centers between 2010 and 2020. Patients with stage IS and extragonadal primaries were excluded. We compared disease characteristics and survival outcomes of patients relapsed from initial CSI to patients with de novo metastatic disease. Primary endpoint was the IGCCCG category at the time of relapse. Main secondary endpoints were progression-free survival (PFS) and overall survival (OS).
RESULTS
We identified 360 GCC patients with initial CSI and 245 de novo metastatic patients. After a median follow-up of 47 months, 81 of 360 (22.5%) CSI patients relapsed: 41 seminoma (Sem) and 40 non-seminoma (NSem) patients. All Sems relapsed in the IGCCCG good prognosis group. NSem relapsed with good 29/40 (72.5%) and intermediate 11/40 (27.5%) prognostic features; 95.1% of relapses occurred within five years post-orchiectomy. Only 3 relapsed NSem patients died from metastatic disease. Five-year OS for relapsed CSI patients was 100% for Sem and 87% (95% CI: 61-96%) for NSem patients; five-year PFS was 92% (95% CI: 77-97) and 78% (95% CI: 56-90) for Sem and NSem, respectively. When stratified by IGCCCG prognostic groups, good risk relapsed patients had a trend towards better OS and PFS as compared to de novo metastatic patients.
CONCLUSIONS
GCC patients who relapse after initial CSI can be detected early by active surveillance and have an excellent survival.
Topics: Humans; Male; Testicular Neoplasms; Retrospective Studies; Seminoma; Ethnicity; Neoplasms, Germ Cell and Embryonal; Neoplasms, Second Primary
PubMed: 37715132
DOI: 10.1186/s12885-023-11388-y -
Mediastinum (Hong Kong, China) 2022Germ cell tumors (GCTs) are uncommon malignancies generally originating from gonads. However, about 5% of GCTs arise outside the gonad (extragonadal), of which 80%... (Review)
Review
BACKGROUND AND OBJECTIVE
Germ cell tumors (GCTs) are uncommon malignancies generally originating from gonads. However, about 5% of GCTs arise outside the gonad (extragonadal), of which 80% develop from the mediastinum. While the prognosis of seminomas is not affected by the gonadal or extragonadal primary location, the prognosis of nonseminoma primary mediastinal GCTs (NS-PMGCTs) is poor, compared to its gonadal counterpart with an estimated 5-year overall survival of about 50%. The current treatments are sub-optimal to increase the cure rate of these rare GCTs. Therefore, molecular insights into these tumors would be valuable to develop novel therapies. The main objective of this review is to describe and dissect the genomic features associated with primary mediastinal GCTs (PMGCTs), highlighting the more frequent genomic alterations and their correlation with clinical outcomes.
METHODS
We conducted a narrative review of the English literature available in PubMed and Google Scholar between 1982 and 2021, including meta-analyses, systematic reviews, case series and case reports regarding the genomic and clinical features of PMGCTs. We analyzed the available data to describe the molecular characteristics of PMGCTs compared to testicular GCTs (TGCTs), highlighting the most relevant biological and prognostic factors.
KEY CONTENT AND FINDINGS
The high percentage of platinum resistance, the unique association with hematologic malignancies (HMs) and other malignancies, the higher prevalence of mutations, and a distinct genomic landscape characterize this rare disease.
CONCLUSIONS
Although some studies have unveiled recurrent molecular alterations in PMGCTs, few are particularly suitable for targeted therapy. Due to the rarity of PMGCTs, data sharing and the creation of an international consortium would be helpful to have a better understanding of the molecular drivers of these tumors.
PubMed: 36582975
DOI: 10.21037/med-22-4 -
Neurology(R) Neuroimmunology &... May 2020To report the clinical and oncologic associations of antibodies against Kelch-like protein 11 (KLHL11-ab), recently suggested as biomarkers of a paraneoplastic brainstem...
OBJECTIVE
To report the clinical and oncologic associations of antibodies against Kelch-like protein 11 (KLHL11-ab), recently suggested as biomarkers of a paraneoplastic brainstem cerebellar syndrome associated with testicular seminoma, and to determine the value of immunohistochemistry as a screening technique.
METHODS
Studies included 432 sera or CSF from 329 patients with paraneoplastic (157) or autoimmune neurologic syndromes (172); 63 with neurologic symptoms and benign teratomas; 28 with small-cell lung cancer, and 12 healthy subjects. KLHL11-abs were examined using a cell-based assay (CBA) with HEK293 cells transfected with a human KLHL11 clone. The CBA specificity was confirmed by immunoprecipitation. All positive samples were examined by immunohistochemistry on rat brain sections.
RESULTS
KLHL11-abs were detected in 32 patients by CBA, and patients' antibodies immunoprecipitated KLHL11. Using rat brain immunohistochemistry, only 7 samples (22%) were positive. Patients' median age was 28 years (range 9-76 years), and 16 (50%) were women. Tumors were identified in 23/32 (72%) patients, including 14 teratomas and 7 seminomas or mixed germ cell tumors. Thirteen (41%) patients had cerebellar ataxia (7) or encephalitis with brainstem cerebellar symptoms (6), 7 (22%) anti-NMDA receptor (NMDAR) encephalitis (5 with ovarian teratoma), 5 (16%) opsoclonus-myoclonus, 3 (9%) limbic encephalitis, and 4 (12%) diverse neurologic symptoms (3 with benign teratomas). Concurrent autoantibodies occurred in 14 (44%) patients (7 anti-NMDAR, 6 Ma2, and 1 Hu).
CONCLUSIONS
KLHL11-abs associate with a spectrum of syndromes and tumors wider than those previously reported; 44% of patients have concurrent neuronal antibodies, some of them (anti-NMDAR) pathogenically relevant. Brain immunostaining is not useful for routine screening of KLHL11-abs.
Topics: Adolescent; Adult; Aged; Animals; Autoantibodies; Autoimmune Diseases of the Nervous System; Carrier Proteins; Child; Female; HEK293 Cells; Humans; Male; Middle Aged; Neoplasms; Paraneoplastic Syndromes, Nervous System; Rats; Retrospective Studies; Young Adult
PubMed: 31953318
DOI: 10.1212/NXI.0000000000000666 -
Andrology Jan 2023The comparison of the incidence of gonadal germ cell tumors among males and females can provide insights that cannot be gained by separately studying these tumors.
BACKGROUND & OBJECTIVES
The comparison of the incidence of gonadal germ cell tumors among males and females can provide insights that cannot be gained by separately studying these tumors.
MATERIAL AND METHODS
Incidence data on male and female gonadal germ cell tumors were drawn from the cancer registries of North Rhine-Westphalia, Germany, and the United States Surveillance, Epidemiology and End Results program, for non-Hispanic White persons only, for the years 2008-2016. We estimated age-standardized and age-, and histology-specific incidence rates.
RESULTS
We included 21,840 male and 716 female gonadal germ cell tumors. Incidence rates among males were higher in Germany (95.8 per million, standard error [SE] 1.1) than in the United States (68.0, SE 0.6), while incidence rates among females were lower in Germany (1.9, SE 0.2) than in the United States (2.6, SE 0.1). The characteristic peak of infantile (age 0-4 years) germ cell tumors among males were missing among females. The age peak of ovarian germ cell tumors occurred 15-20 years earlier (Germany: 10-14 years, United States: 15-19 years) than the age peak of testicular germ cell tumors (30-34 years). The three most common testicular germ cell tumors histologies were seminoma, mixed germ cell tumors, and embryonal carcinoma Among females, the three most common ovarian germ cell tumors histologies were teratoma, yolk sac tumor, monodermal teratomas, and somatic-type tumors arising from dermoid cysts in both countries.
DISCUSSION
The characteristic peak of infantile (age 0-4 years) germ cell tumors among males was missing among females. The shapes of the age-specific incidence curves are similar for males and females in Germany and the United States, though with much lower incidence rates in females, suggesting a common pathogenesis.
CONCLUSION
The lower rates among females may be due to the lower number of initiated tumors in the absence of the Y-chromosome, and the earlier peak among females may be due to a younger age at puberty.
Topics: Male; Female; United States; Humans; Infant, Newborn; Infant; Child, Preschool; Adolescent; Young Adult; Adult; Seminoma; Incidence; Testicular Neoplasms; Neoplasms, Germ Cell and Embryonal; Germany; Teratoma
PubMed: 36059277
DOI: 10.1111/andr.13282 -
Medicine Dec 2021To explore the feasibility of using conventional MRI features combined with apparent diffusion coefficient (ADC) values for the differential diagnosis of testicular...
To explore the feasibility of using conventional MRI features combined with apparent diffusion coefficient (ADC) values for the differential diagnosis of testicular tumors.A total of 63 patients with pathologically confirmed testicular tumors were enrolled in this study. In particular, there were 46 cases of malignant lesions and 17 cases of benign lesions. All patients underwent conventional magnetic resonance imaging (MRI) and diffusion weighted imaging. Multivariate logistic regression models and receiver operating characteristic curves were constructed to assess diagnostic accuracies.T2-homogeneity, intratumoral septa, and peritumoral infiltration were more common in the malignant group, and capsule sign was more common in the benign group (P < .05 for all). The mean ADC value of the malignant group was lower than that of the benign group (P < .05). When the ADC value ≤ 0.90 × 10-3 mm2/s, the diagnosis tended to be malignancy. The conventional MRI model could achieve better diagnostic accuracy than ADC values alone (P < .05). Compared with the conventional MRI model, the specificity and accuracy of the full model (ADC and conventional MRI model) increased by 9.8% and 3.2%, respectively. T2-homogeneity and T2-hypointensity were more common in seminoma and lymphoma, cystic changes were more common in nonseminomatous germ cell tumor (NSGCT), and intratumoral septa was more common in seminoma (P < .05 for all). The ADC value of NSGCT was larger than seminoma, and lymphoma was the smallest (P < .05 for all). Cystic changes, T2-hypointensity, intratumoral septa, and ADC value were independent factors for differentiating the seminoma, NSGCT, and lymphoma subgroups.A combination of conventional MRI features and ADC values can improve the diagnostic efficiency for differentiating benign and malignant testicular tumors, and can additionally distinguish different subtypes of malignant testicular tumors.
Topics: Adult; Aged; Diffusion Magnetic Resonance Imaging; Humans; Lymphoma; Magnetic Resonance Imaging; Male; Middle Aged; Neoplasms, Germ Cell and Embryonal; Retrospective Studies; Seminoma; Testicular Neoplasms
PubMed: 35049179
DOI: 10.1097/MD.0000000000027799 -
International Journal of Surgery Case... Jun 2022Burned-out testicular cancer is a rare phenomenon to be taken into account for differential diagnosis in males presenting with retroperitoneal lymphadenopathy.
INTRODUCTION AND IMPORTANCE
Burned-out testicular cancer is a rare phenomenon to be taken into account for differential diagnosis in males presenting with retroperitoneal lymphadenopathy.
CASE PRESENTATION
A 54-years-old male complaining of abdominal pain over the past several months was found on CT to have a large mass adjacent to the inferior vena cava, with the imaging features of a malignant lymphadenopathy.
CLINICAL DISCUSSION
The hematologist who evaluated the case suggested a biopsy of the retroperitoneal mass: a seminoma was diagnosed on pathological examination. Then a testicular US revealed a focal peripheral hypoechoic region with no associated internal vascularization within the right testicle.
CONCLUSION
This case report highlights the need for routine scrotal examination in all men presenting with an abdominal mass in order to rule out the possibility of an intra-abdominal seminoma.
PubMed: 35661496
DOI: 10.1016/j.ijscr.2022.107245 -
Frontiers in Cell and Developmental... 2022Testicular cancer is the most common solid tumor affecting young males. Most testicular cancers are testicular germ cell tumors (TGCTs), which are divided into seminomas... (Review)
Review
Testicular cancer is the most common solid tumor affecting young males. Most testicular cancers are testicular germ cell tumors (TGCTs), which are divided into seminomas (SGCTs) and non-seminomatous testicular germ cell tumors (NSGCTs). During their development, primordial germ cells (PGCs) undergo epigenetic modifications and any disturbances in their pattern might lead to cancer development. The present study provides a comprehensive review of the epigenetic mechanisms-DNA methylation, histone post-translational modifications, bivalent marks, non-coding RNA-associated with TGCT susceptibility, initiation, progression and response to chemotherapy. Another important purpose of this review is to highlight the recent investigations regarding the identification and development of epigenetic biomarkers as powerful tools for the diagnostic, prognostic and especially for epigenetic-based therapy.
PubMed: 35465311
DOI: 10.3389/fcell.2022.861995 -
International Journal of Surgery... Sep 2023The overall prognosis of primary mediastinal germ cell tumors (PMGCTs) is poor and the associated prognostic factors are not fully understood. Our goal was to...
BACKGROUND
The overall prognosis of primary mediastinal germ cell tumors (PMGCTs) is poor and the associated prognostic factors are not fully understood. Our goal was to investigate the prognostic factors of PMGCTs and to develop a validated prognostic prediction model.
MATERIALS AND METHODS
A total of 114 PMGCTs with specific pathological types were included in this study. Clinicopathological characteristics of nonseminomatous PMGCTs and mediastinal seminomas were compared using the χ2 or Fisher's exact test. Independent prognostic factors of nonseminomatous PMGCTs screened using the univariate and multivariate Cox regression analysis were then used to generate a nomogram. The predictive performance of the nomogram was evaluated using the concordance index, decision curve, and the area under the receiver operating characteristic curve (AUC) and validated by bootstrap resampling. The Kaplan-Meier curves of independent prognostic factors were analyzed.
RESULTS
This study included 71 cases of nonseminomatous PMGCTs and 43 cases of mediastinal seminomas. The 3-year overall survival rates for nonseminomatous PMGCTs and mediastinal seminomas patients were 54.5 and 97.4%, respectively. The overall survival prognostic nomogram for nonseminomatous PMGCTs was established by integrating independent prognostic factors, including the Moran-Suster stage, white blood cell, hemoglobin, and platelet-lymphocyte ratio. The nomogram demonstrated good performance with a concordance index of 0.760 and the 1-year and 3-year AUC values of 0.821 and 0.833, respectively. These values were better than those of the Moran-Suster stage system. The bootstrap validation had an AUC of 0.820 (0.724-0.915) and showed a well-fitting calibration curve. Besides, patients with mediastinal seminomas showed favorable clinical outcomes and all the nine patients received neoadjuvant therapy and postoperative surgery achieved pathological complete response.
CONCLUSION
A nomogram based on staging and blood routine examination results was established to accurately and consistently predict the prognosis of patients with nonseminomatous PMGCTs.
Topics: Humans; Male; Prognosis; Seminoma; Mediastinal Neoplasms; Nomograms; Neoplasms, Germ Cell and Embryonal; Testicular Neoplasms
PubMed: 37222675
DOI: 10.1097/JS9.0000000000000507 -
Frontiers in Oncology 2023Testicular cancer is a common malignancy of young males and is believed to be originated from defective embryonic or adult germ cells. Liver kinase B1 (LKB1) is a...
Testicular cancer is a common malignancy of young males and is believed to be originated from defective embryonic or adult germ cells. Liver kinase B1 (LKB1) is a serine/threonine kinase and a tumor suppressor gene. LKB1 is a negative regulator of the mammalian target of rapamycin (mTOR) pathway, often inactivated in many human cancer types. In this study, we investigated the involvement of LKB1 in the pathogenesis of testicular germ cell cancer. We performed immunodetection of LKB1 protein in human seminoma samples. A 3D culture model of human seminoma was developed from TCam-2 cells, and two mTOR inhibitors were tested for their efficacy against these cancer cells. Western blot and mTOR protein arrays were used to show that these inhibitors specifically target the mTOR pathway. Examination of LKB1 showed reduced expression in germ cell neoplasia lesions and seminoma compared to adjacent normal-appearing seminiferous tubules where the expression of this protein was present in the majority of germ cell types. We developed a 3D culture model of seminoma using TCam-2 cells, which also showed reduced levels of LKB1 protein. Treatment of TCam-2 cells in 3D with two well-known mTOR inhibitors resulted in reduced proliferation and survival of TCam-2 cells. Overall, our results support that downregulation or loss of LKB1 marks the early stages of the pathogenesis of seminoma, and the suppression of downstream signaling to LKB1 might be an effective therapeutic strategy against this cancer type.
PubMed: 36969070
DOI: 10.3389/fonc.2023.1081110 -
Medicina (Kaunas, Lithuania) Mar 2024The incidence of testicular cancer (TC) has been rapidly increasing over the past years. Diagnosis and early treatment have shown good oncological control, guaranteeing... (Review)
Review
The incidence of testicular cancer (TC) has been rapidly increasing over the past years. Diagnosis and early treatment have shown good oncological control, guaranteeing the patient different treatment approaches according to histology and tumor stage. Currently, physicians usually prioritize oncological outcomes over sexual outcomes and quality of life, considering as a first aim the overall survival of the patients; however, differently from other neoplasms, quality of life is still strongly affected among TC patients, and sexual outcomes are frequently compromised after each TC treatment. Several studies have suggested that each treatment approach may be associated with sexual dysfunctions, including erectile dysfunction, ejaculatory disorders, fertility issues, and hormonal changes. Since testicular cancer patients are more frequently young men, the subject of this work is substantial and should be analyzed in detail to help specialists in the management of this disease. The aim of the current narrative review is to generally describe every treatment for TC, including surgery, chemotherapy, radiotherapy, and retroperitoneal lymph node dissection, and to establish which sexual dysfunction may be specifically associated with each therapy.
Topics: Humans; Testicular Neoplasms; Male; Sexual Dysfunction, Physiological; Quality of Life; Sexuality; Erectile Dysfunction
PubMed: 38674232
DOI: 10.3390/medicina60040586