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

SIMPLE SUMMARY: The optimal cut-offs for tumor markers in CNS germ cell tumors (GCTs) to specify non-germinomatous GCTs are under active investigation. This study investigated 162 cases with histopathological confirmation and tumor markers, including 77 cases with robust specimens obtained from tumo...

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Detalles Bibliográficos
Autores principales: Takami, Hirokazu, Graffeo, Christopher S., Perry, Avital, Giannini, Caterina, Nakazato, Yoichi, Saito, Nobuhito, Matsutani, Masao, Nishikawa, Ryo, Ichimura, Koichi, Daniels, David J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8869781/
https://www.ncbi.nlm.nih.gov/pubmed/35205726
http://dx.doi.org/10.3390/cancers14040979
Descripción
Sumario:SIMPLE SUMMARY: The optimal cut-offs for tumor markers in CNS germ cell tumors (GCTs) to specify non-germinomatous GCTs are under active investigation. This study investigated 162 cases with histopathological confirmation and tumor markers, including 77 cases with robust specimens obtained from tumor resection. This study demonstrates that tumor markers are elevated in germinomas and teratomas, especially HCG in germinomas and AFP in immature teratomas, emphasizing the clinical significance of tissue diagnosis. Similarly, some biopsy cases without malignant findings on histopathology demonstrated tumor marker elevations, highlighting the limitations of reliable tissue diagnosis from a diminutive specimen. This study concludes that an integrated diagnosis based on tumor markers and histopathology is the key to precise diagnosis and, therefore, the avoidance of over- or under-treatment. This study also invites novel questions regarding whether marker-positive germinomas or teratomas should be treated as intensively as malignant NGGCTs, as well as the optimal treatment strategy for marker-negative immature teratomas. ABSTRACT: The central nervous system germ cell tumor (CNS GCT) is a rare and incompletely understood disease. A major outstanding question in the 2015 consensus document for CNS GCT management was the utility and interpretation of the tumor markers human chorionic gonadotropin (HCG) and alpha fetoprotein (AFP) in the diagnosis of malignant non-germinomatous GCTs (hereafter NGGCTs) prior to treatment. In the current study, we assembled two geographically and ethnically different clinical cohorts from the Mayo Clinic (1988–2017) and the intracranial GCT Genome Analysis Consortium (iGCT Consortium) in Japan to address this question. Patients with both histopathological diagnosis and tumor markers available were eligible for inclusion (n = 162). Biopsy and surgical resection were performed in 85 and 77 cases, respectively. Among 77 resections, 35 demonstrated positivity for HCG, AFP, or both (45%). Seventeen of the marker-positive cases had no malignant non-germinomatous component identified on histopathology, but they were composed strictly of germinoma, teratoma, or both (49%). One embryonal carcinoma was the only marker-negative NGGCT in the study sample. Among 85 biopsies, 18 were marker positive (21%). Seven of these patients had no malignant non-germinomatous component on histopathology, suggesting the potential limitations of limited tissue sample volumes. Neither histopathological diagnosis nor tumor markers alone reliably diagnose NGGCTs due to the secretion of HCG and AFP by germinomas and teratomas. Treatment planning should incorporate integrated histopathological and laboratory-based diagnosis to optimize diagnostic and treatment strategies for this unusual and histologically heterogeneous tumor.