Still divergent but on the way to convergence: clinical practice of CNS germ cell tumors in Europe and North America from the perspectives of the East

Takami, Hirokazu; Nakamura, Hideo; Ichimura, Koichi; Nishikawa, Ryo

doi:10.1093/noajnl/vdac061

Cited by 5 publications

(4 citation statements)

References 7 publications

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“…Little is known about the clinical and histopathological presentations for GCTs at atypical sites, much less for medulla oblongata GCTs, particularly in terms of clinical behaviors. While chemotherapy (CMT) regimens and radiation fields have been historically investigated for GCTs at typical sites in multiple clinical trials worldwide [10,[17][18][19][20][21][22][23][24], the most appropriate treatment strategies, such as optimal radiation field based on relapse patterns, remain poorly characterized [25]. Germinomas at atypical sites outside of these midline structures have been known to show worse prognoses than those at typical sites [8].…”

Section: Introductionmentioning

confidence: 99%

Histopathological, Demographic, and Clinical Signatures of Medulla Oblongata Germ Cell Tumors: A Case Report With the Review of Literature

Sato,

Tanaka,

Takami

et al. 2024

Cureus

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The medulla oblongata is one of the rarest sites of occurrence for germ cell tumors (GCTs) of the central nervous system. As there is scant data regarding epidemiology, clinical presentations, optimal intervention, and long-term prognosis, we aimed to delineate the features of this rare entity by presenting our representative case and performing a quantitative review of the literature. A 24-year-old woman presented to our department with vertigo and swallowing difficulties. Magnetic resonance imaging revealed a homogenously enhanced exophytic lesion arising from the medulla oblongata and extending to the fourth ventricle. Surgical resection was performed and a histological diagnosis of pure germinoma was made. The patient underwent chemotherapy and whole-ventricular irradiation. No recurrence has been experienced for 4 months after the surgery. According to the literature, the prognosis of GCTs at the medulla oblongata seems no worse than those at typical sites. Striking features including occurrence at an older age, female preponderance, and a predominance of germinoma were noteworthy. The pattern of local recurrence suggests extensive radiation coverage is not a prerequisite. Special attention is needed for cardiac and respiratory functions as the main factors eliciting mortality.

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Section: Introductionmentioning

confidence: 99%

Histopathological, Demographic, and Clinical Signatures of Medulla Oblongata Germ Cell Tumors: A Case Report With the Review of Literature

Sato,

Tanaka,

Takami

et al. 2024

Cureus

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“…In tandem, histopathological diagnosis based on a small biopsy specimen predisposes to sampling error and associated under-estimation in the prevalence of malignant components. Collectively, these complexities have yielded a highly heterogenous set of protocols with regard to how tumor markers are incorporated into algorithms for GCT diagnosis and treatment across the world [ 17 ].…”

Section: Introductionmentioning

confidence: 99%

Impact of tumor markers on diagnosis, treatment and prognosis in CNS germ cell tumors: correlations with clinical practice and histopathology

et al. 2023

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Tumor markers in CNS germ cell tumors (GCTs) include human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP), which have significant diagnostic implications, as elevation of either one leads to clinical diagnosis of non-germinomatous GCTs without histopathological confirmation, justifying intensified chemotherapy and irradiation. The current study, based on an international cohort of histopathologically verified GCTs that underwent biopsy (n = 85) or resection (n = 76), sought to better define the clinical role and prognostic significance of tumor markers from serum and CSF in this challenging patient population. We found that HCG was elevated only in cases with a germinoma or choriocarcinoma component, and there existed a clear cut-off HCG value between the two. AFP was often elevated in GCTs without a yolk sac tumor component, especially immature teratoma. HCG was elevated only in CSF in 3-of-52 cases, and AFP was elevated only in serum in 7-of-49 cases, emphasizing the potential utilization of both serum and CSF studies. Immature teratoma demonstrated unfavorable prognosis independent of tumor marker status, with 56% 5-year overall survival; however, co-existent germinoma components indicated a more favorable prognosis. Taken together, the study findings emphasize the importance for routine assessment and guarded interpretation of tumor markers in CNS GCTs.

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“…If tumor markers are elevated, patients are diagnosed with NGGCTs; if not, patients require a biopsy for histopathological diagnosis ( 6 – 10 ). In Japan, treatment stratification is unique in that it is based on three prognostic subgroups (i.e., germinoma, intermediate prognosis, and poor prognosis subgroups) that are determined according to histopathological confirmation ( Table 1 ) ( 11 , 12 ).…”

Section: Introductionmentioning

confidence: 99%

“…If tumor markers are elevated, patients are diagnosed with NGGCTs; if not, patients require a biopsy for histopathological diagnosis (6)(7)(8)(9)(10). In Japan, treatment stratification is unique in that it is based on three prognostic subgroups (i.e., germinoma, intermediate prognosis, and poor prognosis subgroups) that are determined according to histopathological confirmation (Table 1) (11,12). One of the ongoing issues in treatment and patient care is that treatment stratification is currently mostly limited to two or three categories and predictive biomarkers for guiding personalized treatment are presently scarce.…”

Section: Introductionmentioning

confidence: 99%

Biomarkers for risk-based treatment modifications for CNS germ cell tumors: Updates on biological underpinnings, clinical trials, and future directions

Takami

Ichimura

2022

Front. Oncol.

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CNS germ cell tumors (GCTs) preferentially occur in pediatric and adolescent patients. GCTs are located predominantly in the neurohypophysis and the pineal gland. Histopathologically, GCTs are broadly classified into germinomas and non-germinomatous GCTs (NGGCTs). In general, germinoma responds well to chemotherapy and radiation therapy, with a 10-year overall survival (OS) rate of approximately 90%. In contrast, NGGCTs have a less favorable prognosis, with a five-year OS of approximately 70%. Germinomas are typically treated with platinum-based chemotherapy and whole-ventricular radiation therapy, while mature teratomas can be surgically cured. Other NGGCTs require intensive chemotherapy with radiation therapy, including whole brain or craniospinal irradiation, depending on the dissemination status and protocols. Long-term treatment-related sequelae, including secondary neoplasms and cerebrovascular events, have been well recognized. These late effects have a tremendous impact in later life, especially since patients are mostly affected in childhood or young adults. Intending to minimize the treatment burden on patients, the identification of biomarkers for treatment stratification and evaluation of treatment response is of critical importance. Recently, tumor cell content in germinomas has been shown to be closely related to prognosis, suggesting that cases with low tumor cell content may be safely treated with a less intensive regimen. Among the copy number alterations, the 12p gain is the most prominent and has been shown to be a negative prognostic factor in NGGCTs. MicroRNA clusters (mir-371-373) were also revealed to be a hallmark of GCTs, demonstrating the potential for the application of liquid biopsy in the diagnosis and detection of recurrence. Recurrent mutations have been detected in the MAPK or PI3K pathways, most typically in KIT and MTOR and low genome-wide methylation has been demonstrated in germinoma; this most likely reflects the cell-of-origin primordial germ cells for this tumor type. These alterations can also be leveraged for liquid biopsies of cell-free DNA and may potentially be targeted for treatment in the future. Advancements in basic research will be translated into clinical practice and can directly impact patient management. Additional understanding of the biology and pathogenesis of GCTs will lead to the development of better-stratified clinical trials, ultimately resulting in improved treatment outcomes and a reduction in long-term treatment-related adverse effects.

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Still divergent but on the way to convergence: clinical practice of CNS germ cell tumors in Europe and North America from the perspectives of the East

Cited by 5 publications

References 7 publications

Histopathological, Demographic, and Clinical Signatures of Medulla Oblongata Germ Cell Tumors: A Case Report With the Review of Literature

Histopathological, Demographic, and Clinical Signatures of Medulla Oblongata Germ Cell Tumors: A Case Report With the Review of Literature

Impact of tumor markers on diagnosis, treatment and prognosis in CNS germ cell tumors: correlations with clinical practice and histopathology

Biomarkers for risk-based treatment modifications for CNS germ cell tumors: Updates on biological underpinnings, clinical trials, and future directions

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