The Japan Society for Neuro-Oncology guideline on the diagnosis and treatment of central nervous system germ cell tumors

Abstract

Primary CNS germ cell tumors (GCTs) are rare neoplasms predominantly observed in the pediatric and young adult populations. In line with the hypothesis that the primordial germ cell is the cell-of-origin, histopathological examinations for this pathology involve a diverse range of components mirroring the embryogenic developmental dimensions. Chemotherapy and radiotherapy are the mainstays of treatment, with surgery having a limited role for diagnosis and debulking of residual tissue after treatment. While better management has been achieved over recent decades by modifying radiation coverage and selecting appropriate chemotherapy, standardization of treatment remains challenging, partly due to the low volume of cases encountered in each institution. As the incidence is higher in East Asia, including Japan, the Japan Society for Neuro-Oncology established a multidisciplinary task force to create an evidence-based guideline for CNS GCTs. This guideline provides recommendations for multiple dimensions of clinical management for CNS GCTs, with particular focus on diagnostic measures including serum markers, treatment algorithms including surgery, radiotherapy and chemotherapy, and under-investigated but important areas such as treatment for recurrent cases, long-term follow-up protocols and long-term sequelae. This guideline serves the purpose of helping healthcare professionals keep up to date with current knowledge and standards of management for patients with this rare disease in daily clinical practice, as well as driving future translational and clinical research by recognizing unmet needs concerning this tumor.

Roles of Tumor Markers in Central Nervous System Germ Cell Tumors Revisited with Histopathology-Proven Cases in a Large International Cohort

“…Although tissue diagnosis is considered the gold standard at most centers, numerous reports have highlighted the vulnerability of histopathologic analysis to error, occasionally including cases with a large specimen from intraoperative resection. Geographically speaking, histopathological diagnosis is more emphasized in Japan, even among marker-positive cases [ 15 ], while higher tumor marker levels are routinely considered diagnostically sufficient for treatment in western countries—including enrollment in a variety of clinical trials [ 16 , 17 ]. Accordingly, a true gold-standard diagnostic paradigm integrating tumor markers and histopathological data has not been defined and validated.…”

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

“…In Europe/North America, NGGCT is defined according to a case presentation in which tumor markers are elevated or according to histopathological confirmation of NGGCTs when tumor markers are normal ( 10 ). In Japan, NGGCT is further subdivided into two classes: an intermediate prognosis group and a poor prognosis group ( 3 , 11 )., The intermediate prognosis group includes immature teratomas, teratomas with somatic-type malignancy, and mixed tumors (mainly composed of germinomas and teratomas). The poor prognosis group mainly includes patients with yolk sac tumors, choriocarcinomas, and embryonal carcinomas.…”

“…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 ).…”

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

“…The Japan Society of Neuro-Oncology guideline appears in the same issue. 2 Neuro-Oncology should be congratulated on providing an excellent opportunity to review the longstanding paradigm toward convergence.…”

“…Therefore, we specifically addressed the advantages and disadvantages of histopathological diagnosis. 2 Notably, direct comparison of treatment outcomes among Japan/E/NA proves difficult. While highly secreting tumors such as yolk sac tumor and choriocarcinoma are rightly diagnosed as NGGCTs in any criteria across countries, germinoma and teratoma with elevated TMs can be heterogeneously diagnosed and treated among different protocols.…”