Clinical significance and pitfalls of human chorionic gonadotropin-related tumor markers for intracranial germinomas.

PURPOSE: Measuring serum and cerebrospinal fluid human chorionic gonadotropin (hCG) is essential for the diagnosis of intracranial germ cell tumors. There are three types of hCG-related markers in clinical use: hCGß, intact hCG, and total hCG. The best marker for the diagnosis of intracranial germ cell tumors, especially germinoma, is currently unknown. This study aimed to evaluate the usefulness of these hCG-related markers. METHODS: We investigated 19 serum samples obtained from 6 patients with histologically diagnosed germinoma treated in our institute. Serum hCGß, intact hCG, and total hCG values were measured before, during, and after treatment. Samples with hCG values above the lower limits were considered positive. RESULTS: The positivity rates of serum hCGß, intact hCG, and total hCG were 6% (1/17), 47% (7/15), and 42% (8/19), respectively, with the latter two having significantly higher positivity rates than hCGß (p = 0.041). Both intact and total hCGs showed similar values. The median values of hCGß, intact hCG, and total hCG before treatment were 0.1 ng/mL, 4.6 mIU/mL, and 4.5 mIU/mL, respectively. CONCLUSION: Serum intact and total hCGs have higher detection rates than hCGß in patients with germinoma using available commercial measurement tools.

Induction Chemotherapy Reduces Radiation Therapy Dose and Volume in the Treatment of Intracranial Germinoma: Results of the SMC-G13 Trial.

PURPOSE: We performed a prospective single-arm trial (NCT02782754) to explore the feasibility of reducing radiation therapy (RT) dose when induction chemotherapy is combined in the treatment of intracranial germinoma with beta-human chorionic gonadotropin levels <200 mIU/mL. METHODS AND MATERIALS: All patients aged 3 to 35 years from November 2012 to June 2018 were eligible for this study. Four cycles of induction chemotherapy were given before RT. Carboplatin/etoposide and cyclophosphamide/etoposide regimens were used in alternation every 3 weeks. A dose of 18 Gy of craniospinal RT for metastatic tumors, whole brain RT for basal ganglia tumors, or otherwise whole ventricular RT followed by 12.6 Gy of boost RT to the primary tumor bed was administered after induction chemotherapy. The primary endpoint of this study was progression-free survival. RESULTS: A total of 41 consecutive patients were enrolled (location: suprasellar in 12, pineal in 12, both suprasellar and pineal in 11, and basal ganglia in 6 patients). Eleven patients had leptomeningeal seeding. Toxicity during chemotherapy was mild, except for bone marrow suppression. Tumor status after induction chemotherapy was complete response in 33 patients and partial response in 8. All but 2 patients completed the scheduled treatment. All patients but 1 remained event free during a median follow-up of 3.4 (range, 0.3-7.0) years from diagnosis. The 1 patient experienced relapse and died of tumor bleeding. Late effects were not significant except for neuroendocrine dysfunction already present at diagnosis. Vertical growth and cognitive function were not significantly disturbed by treatment. CONCLUSIONS: This study showed the feasibility of reducing RT dose/volume with induction chemotherapy in pathologically pure germinoma with elevated beta-human chorionic gonadotropin levels up to 200 mIU/mL.

Optimization of Intracranial Germinoma Treatment: Radiotherapy Alone with Reduced Volume and Dose.

PURPOSE: We investigated optimal management for intracranial germinoma, including target volume and dose of radiation therapy (RT) and the combination of RT and chemotherapy (CTx). METHODS AND MATERIALS: We retrospectively evaluated 213 patients with intracranial germinoma treated between 1971 and 2017. Treatment policies changed as diagnostic techniques and clinical experience improved. In the 1980s, trial RT and tumor marker study were performed, and craniospinal irradiation was performed to treat patients with presumed germinoma. CTx was introduced in 1991, and RT volume was reduced in patients showing a complete response. In 2012, the policy was changed to a "reduced volume/dose RT alone" approach, involving a smaller target volume (the whole ventricle/whole brain for localized disease) without CTx. RT doses were gradually reduced to 36 Gy for primary tumors and 18 Gy for neuraxis. RESULTS: The median age was 16 years. In total, 118 and 95 patients had pathologically proven and presumed germinoma, respectively, and 151 and 62 patients had localized and multifocal or metastatic diseases, respectively. With a median follow-up of 141 months, the 10-year disease-free and overall survival rates were 91.6% and 95.6%, respectively. Recurrence rates were similar for patients receiving RT-only (9 of 137, 6.6%) and those receiving CTx + RT (4 of 73, 5.5%); all patients receiving CTx-only experienced recurrences (3 of 3, 100%). Rates were the highest in the focal RT group (10 of 29, 34.5%) but were relatively low in the whole ventricle/whole brain RT (3 of 51, 5.9%) and craniospinal irradiation groups (0 of 130, 0%). Infield failure occurred in 3 patients. Fourteen patients died of recurrence (n = 4), secondary malignancy (n = 4), CTx-related toxicity (n = 2), and others (n = 4). Among the 33 patients who received "reduced volume/dose RT alone" treatment, 2 (6.1%) experienced recurrence in the spinal cord and biopsy tract, respectively. CONCLUSIONS: The additional benefit of CTx in the treatment of intracranial germinoma seems minimal. An RT-only approach with reduced target volume and dose seems reasonable.

Intracranial Germ Cell Tumors in Adolescents and Young Adults: A 40-Year Multi-Institutional Review of Outcomes.

PURPOSE: The aim of this study was to determine the practice patterns and outcomes of intracranial germ cell tumors (IGCT) in adolescents and young adults according to different therapeutic approaches. METHODS AND MATERIALS: One-hundred twelve patients with IGCT aged 15 to 39 years were managed at either XX or the XY center from 1975 to 2015. The charts were retrospectively reviewed and data collected. RESULTS: Median duration of follow-up was 8.3 years. Ninety-four patients had germinomas, and 18 had nongerminomatous germ cell tumors (NGGCT). The primary disease sites were pineal gland (37 of 94 germinoma, 14 of 18 NGGCT) and suprasellar region (23 of 94 germinoma, 2 of 18 NGGCT). Eleven patients with germinoma (12%) and 2 patients with NGGCT (11%) had radiographic spinal metastases or positive lumbar cerebrospinal fluid cytology. Event-free survival (EFS) was 84% and overall survival (OS) was 90% at 10 years for germinoma; EFS was 71% and OS was 86% at 10 years for NGGCT. For patients with germinoma, 10-year EFS was 100% after craniospinal radiation therapy (CSRT) with chemotherapy (N = 10); 100% after whole-ventricular radiation therapy (WVRT), whole-brain radiation therapy (WBRT), or focal radiation therapy (FRT) with chemotherapy (N = 22); 90% after CSRT alone (N = 46); and 41% after WVRT, WBRT, or FRT alone (N = 16) (P < .0005). Ten-year OS was 100%, 100%, 90%, and 72%, respectively (P = .032). For patients with NGGCT, 10-year EFS was 80% after CSRT, WBRT, or WVRT plus chemotherapy (N = 10) versus 58% after FRT plus chemotherapy (N = 8) (P = .31); 10-year OS was 90% versus 58%, respectively (P = .16). CONCLUSIONS: We report excellent overall outcomes according to treatment approach in the largest study of IGCT in adolescents and young adults to our knowledge. EFS and OS were inferior after non-CSRT without chemotherapy in germinoma.

Peripheral Precocious Puberty Caused by Human Chorionic Gonadotropin Producing Pineal Gland Tumor.

BACKGROUND: Pineal gland lesions usually present with central precocious puberty. CASE CHARACTERISTICS: A 3½-yr-old boy presented with precocious puberty. Clinically and biochemically, it was gonadotropin releasing hormone (GnRH) independent. Serum and CSF beta-hCG levels were increased. Thin section magnetic resonance imaging of brain revealed a pineal gland tumor. OUTCOME: He received chemotherapy followed by radiotherapy and responded well. MESSAGE: CSF beta-hCG should be measured in all cases of peripheral precocity, and if CSF beta-hCG is elevated, thin section magnetic resonance imaging of brain should be considered.

An update on the clinical diagnostic value of ß-hCG and αFP for intracranial germ cell tumors.

BACKGROUND: Pathological examination combined with tumor markers has become a standard for the diagnosis of intracranial germ cell tumors (ICGCTs), but the current concept of 'secreting germ cell tumors' and three empirically highly specific diagnostic criteria (ß-hCG ≥ 50 IU/L or αFP ≥ 10 ng/mL; ß-hCG ≥ 100 IU/L or αFP ≥ 50 ng/mL; ß-hCG > 50 IU/L or αFP > 25 ng/mL) are not based upon pathology examination or CSF cytology. Further investigation is needed to re-evaluate their value. METHODS: A multidisciplinary diagnostic team was created. Valid ß-hCG/αFP data were collected from cases of ICGCTs confirmed by pathology and CSF cytology (n = 58) between 1991 and 2012, and from suspected ICGCTs cases (n = 17) between 2011 and 2012 as controls [Langerhans cell histiocytosis (LCH), n = 12; and other intracranial tumor (ICT), n = 5]. The cut-off points for ß-hCG and αFP were calculated using receiver operating characteristic (ROC) curves. RESULTS: This study clarifies the relative rationality of one criteria (ß-hCG > 50 IU/L and αFP > 25 ng/mL); confirms new ß-hCG diagnostic cut-off points: CSF ß-hCG ≥ 8.2 IU/L and serum ß-hCG ≥ 2.5 IU/L (sensitivity of 47 and 34%, respectively, specificity of 100%, both; P < 0.05); and empirically adjusts the criteria for αFP to ≥ 3.8 ng/mL in CSF and to ≥ 25 ng/mL in serum. The total diagnostic sensitivity for ICGCTs finally increased from 34.6 to 65.4% (P < 0.05, diagnostic value of CSF ß-hCG exceeds 90%). Subtype diagnosis improved with αFP in 16.7% of non-geminomatous germ cell tumor cases. CONCLUSION: New evidence-based criteria of ß-hCG and αFP can help improving early and formal diagnosis of ICGCTs, and is of great clinical significance.

Solitary Langerhans cell histiocytosis located in the neurohypophysis with a positive titer HCG-ß in the cerebrospinal fluid.

INTRODUCTION: Beta-human chorionic gonadotropin (HCG-ß) is considered to be a useful tumor marker for germ cell tumors (GCTs); however, various tumors other than GCTs, including cystic pituitary adenomas, Rathke's cleft cysts, and craniopharyngiomas, were reported to express HCG-ß. CASE REPORT: We herein present the case of a 5-year-old boy who presented with polyuria and had a solitary lesion in the neurohypophysis with a positive HCG-ß titer in the cerebrospinal fluid. Under a preoperative diagnosis of germinoma, a biopsy was performed from the posterior pituitary lobe via the transsphenoidal endoscopic approach and the histological diagnosis was revealed to be Langerhans cell histiocytosis (LCH). CONCLUSIONS: The finding of a slightly positive HCG-ß titer in the cerebrospinal fluid (CSF) cannot exclude the possibility of LCH, and we strongly recommend a histological diagnosis for the diagnosis of a solitary neurohypophysial lesion.

Intensive chemotherapy followed by reduced-dose radiotherapy for biopsy-proven CNS germinoma with elevated beta-human chorionic gonadotropin.

In this study, 10 patients with biopsy-proven germinoma with a beta-human chorionic gonadotropin (ß-HCG) level >50 mIU/ml received intensive chemotherapy followed by reduced-dose radiotherapy (RT) to reduce late effects from RT. CSF ß-HCG levels were >200 mIU/ml in five patients. After endoscopic or stereotactic biopsy, four cycles of induction chemotherapy were administered prior to RT. A CEB regimen (carboplatin + etoposide + bleomycin) and a CyEB regimen (cyclophosphamide + etoposide + bleomycin) were alternated. No residual tumor remained after induction chemotherapy in six patients, only cystic lesions were present at the primary tumor site in three, and a small solid residual tumor was observed in the remaining patient; however, all these patients had normal ß-HCG levels. If complete response was achieved before initiation of RT, 19.5 Gy craniospinal RT (CSRT) + 10.8 Gy local RT was administered to the tumor bed. If residual lesion was suspected, the dose of RT was selected according to the presence/absence of tumor dissemination at diagnosis (19.5 Gy CSRT + 19.8 Gy local RT for localized tumors and 24.0 Gy CSRT + 16.2 Gy local RT for disseminated tumors). Eight patients, including four patients with a ß-HCG level >200 mIU/ml, received 19.5 Gy CSRT. All patients remain disease free at a median follow-up of 58 (range 35-94) months from diagnosis. Our data suggest that pathologically pure germinoma with a significantly elevated ß-HCG level might be cured with reduced-dose RT if intensive chemotherapy is provided.

Successful treatment of metastatic ßHCG-secreting germ cell tumor occurring 3 years after total resection of a pineal mature teratoma.

UNLABELLED: Patients diagnosed with intracranial teratoma are at risk for developing a recurrent malignant germ cell tumor. We describe a 14-year-old boy initially diagnosed with a mature teratoma in the pineal region that recurred as a metastatic beta-human chorionic gonadotropin (ßHCG)-secreting germ cell tumor 3 years after gross total resection. A surveillance brain MRI scan during follow-up demonstrated multiple lesions within the ventricular and subependymal area infiltrating the brain parenchyma along with concomitant elevated levels of ßHCG in both the serum and cerebrospinal fluid. The patient underwent chemotherapy with PEI (cis-platinum, etoposide, ifosfamide) followed by radiation therapy according to the SIOP CNS GCT protocol. The patient is currently alive without evidence of disease 35 months after starting therapy. CONCLUSIONS: A careful and long-term follow-up including scheduled tumor markers as well as surveillance MRI scans is required for patients with intracranial teratoma in an effort to detect and diagnose recurrent malignant disease, especially since multimodal therapy provides the potential for long-term cure.

Potential role of ventricular tumor markers in CNS germ cell tumors.

BACKGROUND: There is increasing reliance on oncoprotein assays such as the ß-subunit of human chorionic gonadotropin (ß-hCG) and alpha-fetoprotein (AFP) for diagnosis or confirmation of histology of central nervous system (CNS) germ cell tumors (GCT), but the relative diagnostic sensitivity and reliability of assays from serum (S), lumbar (L), and ventricular (V) cerebrospinal fluid (CSF) are uncertain. PROCEDURE: A total of 86 patients with CNS GCT were identified from our database. Fourteen patients had contemporaneous ß-hCG and/or AFP measurements from serum, ventricular, and lumbar CSF at diagnosis (n = 13) or relapse (n = 1), constituting the subjects for this report. Their primary tumor sites were: pineal (n = 8), suprasellar (n = 1), or both (n = 5). Their mean age at diagnosis was 16.0 years (range 9.1-25.9). The male:female sex ratio was 13:1. RESULTS: For the germinoma-treated patients (n = 8), the median (range) ß-hCG values (S, V, L) were 0 (0-6.9), 7.0 (0-57.4), 8.3 (0-34.0) mIU/ml. For patients managed as mixed malignant GCT (MMGCT) (n = 6), the median (range) ß-hCG values (S, V, L) were 3.9 (0-58.0), 3.6 (0-147.0), 61.8 (0-358.0) mIU/ml. The median (range) AFP values were 7.5 (0-27,400.0), 2.0 (0-2,981.0), 3.0 (0-14,015.0) ng/ml. Lumbar CSF ß-hCG values were equal or greater than those in ventricular CSF or serum in 12 of 13 cases (92.3%). All patients with MMGCT had lumbar AFP equal or greater than the ventricular CSF values, while serum AFP values remained highest. CONCLUSIONS: Ventricular CSF values cannot be considered a replacement for lumbar CSF. Lumbar CSF is the most reliable source of tumor markers to establish baseline and follow-up diagnostic endpoints.

Diagnostic sensitivity of serum and lumbar CSF bHCG in newly diagnosed CNS germinoma.

BACKGROUND: Marked elevations of AFP and bHCG in serum or CSF may serve as surrogate diagnostic markers in lieu of histology for primary CNS mixed, malignant germ cell tumors. There is less information on the diagnostic sensitivity of bHCG assays in germinoma. PROCEDURE: We report baseline serum and lumbar CSF bHCG values in 58 newly diagnosed, histologically confirmed germinoma patients gathered from two prospective clinical trials which required that patients have a normal AFP and bHCG ≤50 mIU/ml in serum and lumbar CSF. RESULTS: The location of the primary tumors was: suprasellar(23); pineal(20); suprasellar/pineal(9); and other sites(6). The mean age of the study population was 13.5 (4.3-25.9) years. A total of 23(40%) patients had elevations of bHCG in either serum or CSF, 20(34.5%) of whom had only bHCG elevations in CSF. The patients' bHCG profiles were divided into four categories: I (normal serum and lumbar CSF bHCG), 35(60%); II (normal serum and elevated CSF bHCG), 20(34.5%); III (elevated serum and CSF bHCG), 2(3.5%); and IV (elevated serum and normal CSF bHCG), 1(2%). The median CSF bHCG level was 7.7(2.5-16) in the 22 patients with abnormal CSF values and the lumbar value was higher than the serum value in 20 of 23(87%) patients with bHCG elevations. CONCLUSIONS: Lumbar CSF was a more informative screen for bHCG than serum but the majority of patients (60%) had normal bHCG values at diagnosis. Until a more sensitive tumor marker for germinoma is devised, histologic confirmation remains the standard of care. Pediatr Blood Cancer 2012; 59: 1180-1182. © 2012 Wiley Periodicals, Inc.

Intracranial germ cell tumours. A review with special reference to endocrine manifestations.

EPIDEMIOLOGY: Intracranial germ cell tumours (icGCTs) represent 3-15% of primary paediatric intracranial neoplasms with a considerable geographical variation in incidence. Ninety percent of patients diagnosed with icGCTs are under 20 years of age. PATHOLOGY: Histologic characteristics and investigation of the tumour markers ß-human chorionic gonadotropin (ß-hCG) and alpha-fetoprotein (AFP) help define the different categories of icGCTs. The tumours are divided into two major groups called germinomas and non-germinomatous GCTs (NGGCTs). CLINICAL PRESENTATION: The clinical symptoms depend on the size and location of tumour in the brain, which is most commonly in the pineal or suprasellar region. Pineal GCTs often present with neurological symptoms because of their tendency to cause increased intracranial pressure. Suprasellar GCTs are often accompanied by endocrine abnormalities such as diabetes insipidus (DI), growth retardation and precocious or delayed puberty. DIAGNOSIS: A combination of clinical findings, endocrine and tumour marker evaluation, spinal fluid cytology, magnetic resonance imaging (MRI) and biopsy helps verifying the diagnosis of an icGCT. A summary of published data (n = 97) revealed that >90% of patients at diagnosis had at least one endocrine abnormality, DI being the most common (>80%). TREATMENT: Classification of tumour is important for choice of treatment and for prognosis. A combination of chemotherapy and radiotherapy is often used, since most icGCTs have a great sensitivity to these treatment modalities. CONCLUSION: Endocrine symptoms are very frequently appearing in patients with icGCTs and they can present long before neuroimaging verification of tumour is possible. It is of the outmost importance to have the diagnosis of icGCTs in mind when children, adolescents and young adults are presenting with endocrine irregularities, because most icGCTs are very sensitive to radiotherapy and chemotherapy, and early onset of treatment is important in order to minimize morbidity and mortality.

Late spinal metastases from an isolated pineal region germinoma mimicking a schwannoma.

A 20-year-old male with a prior history of germinoma presented 8 years after the initial diagnosis with progressive lower back pain. The preoperative diagnosis was schwannoma based on the appearances of a tumor in the lumbosacral region on MRI; however, histologically, a germinoma "drop" metastasis was seen. This report emphasizes the need for long-term follow-up in patients with germinoma. In addition, this patient is unusual in that the preoperative assessment favored schwannoma.

Pineal mixed germ cell tumor with a synchronous sellar lesion in the sixth decade.

Intracranial germ cell tumors (GCTs) typically affect children and adolescents. We here report on a 59-year-old male patient presenting with diplopia, polydipsia and polyuria. On clinical examination, slight restriction of the upward gaze was seen on the left side. Computed tomography demonstrated calcifications in the pineal region and enhanced neurohypophysis. Magnetic resonance imaging displayed a heterogeneous pineal mass of 3-cm diameter, which was multicystic with an enhanced cyst wall, and also swelling of the pituitary stalk. The pineal lesion of the tumor, which included calcifications and keratinaceous components, was totally excised using an occipital transtentorial approach. Histopathological examination showed it to be a mixed GCT with germinoma and mature teratoma components. Postoperative chemoradiotherapy provided complete disappearance of the suprasellar lesion. To our knowledge, this is the first case of mixed bifocal GCT in an older adult reported in the literature, although a few cases of tumors with a single histological component have been reported. Hence, our case further underlines the possibility of the occurrence of GCTs in older adults and advocates the consideration of GCTs in the differential diagnosis of such cases for appropriate management.

Recurrent pure CNS germinoma with markedly elevated serum and cerebrospinal fluid human chorionic gonadotropin-beta (HCGß).

Controversy continues regarding what level of serum and/or cerebrospinal fluid (CSF) human chorionic gonadotrophin-beta (HCGß) is consistent with pure germinoma of the central nervous system (CNS). We report a 10-year female with biopsy-proven pure germinoma and normal serum and CSF HCGß who experienced subsequent biopsy-proven recurrences of germinoma. At recurrence, serum and CSF HCGß levels were 560 and 3,202 mIU/ml, respectively, although final autopsy demonstrated pure germinoma. This case illustrates the need to re-evaluate the assumption that pathologically pure germinomas may be associated with high levels of HCGß which are unrelated to nongerminomatous germ cell tumor (NGGCT)/choriocarcinomatous elements.

[Diagnostic value of serum levels of ß-human chorionic gonadotropin (ß-hcG) combined with ß-hcG in cerebrospinal fluid for determining locations of germinomas in children with precocious puberty].

OBJECTIVE: To study the clinical manifestations of germinoma in children with precocious puberty and to evaluate the diagnostic value of serum levels of ß-human chorionic gonadotropin (ß-hcG) combined with detections of ß-hcG in cerebrospinal fluid (CSF). METHOD: Twelve male children with germinomas confirmed by pathology from Jan. 2005 to Dec. 2009, aged from 4.2 to 10.2 years, were enrolled in this study. Patients were classified into two groups according to tumor locations: intracranial group and non-intracranial group. Levels of ß-hcG in serum as well as in CSF were detected before the initiation of therapy. Age and gender matched 5 children undergoing lumbar puncture for other diseases were set as control group for the determinations of ß-hcG in CSF. Levels of ß-hcG and testosterone in serum and CSF were compared between intracranial group and non-intracranial group, and levels of ß-hcG in CSF were compared between non-intracranial group and control group. RESULT: The 12 children showed elevated serum levels of testosterone: 10.43 (1.70-254.00) µg/L, 11 children had testicular volume > 4 ml, while response to LHRH stimulation tests were low; 6 children had gynecomastia. Serum levels of ß-hcG were elevated in both intracranial and non-intracranial group and no significant differences were found between groups 63.75 (8.50-309.50) IU/L vs. 59.00 (25.10-71.77) IU/L, P = 0.644. No correlations were found between serum levels of ß-hcG and ages, tumor locations, and courses of the patients. Levels of ß-hcG in CSF were significantly higher in intracranial group than that in non-intracranial group 488.99 (17.30-1048.53) IU/L vs. 1.20 (1.20-1.50) IU/L, P = 0.009. Children with non-intracranial germinomas had similar levels of ß-hcG in CSF as that in control group (P = 0.571). CONCLUSION: The main clinical manifestations in boys suffered from germinoma included pseudo-precocious puberty, disproportionate testicular volume and gynecomastia. Detection of serum levels of ß-hcG combined with ß-hcG levels in CSF may be useful for determination of the locations of germinomas in children with precocious puberty.

Germinoma with syncytiotrophoblastic giant cells arising in the corpus callosum.

A previously healthy 31-year-old Japanese man presented with a very rare germinoma of the corpus callosum without other intracranial lesions manifesting as transitory speech disturbance. Magnetic resonance (MR) imaging revealed a heterogeneously enhanced mass in the corpus callosum extending into the cavity of the septum pellucidum. A tumor specimen obtained by stereotactic biopsy revealed a two-cell pattern germinoma containing human chorionic gonadotropin (HCG)-beta-positive giant cells. The cerebrospinal fluid and serum levels of HCG and HCG-beta subunit were measurable. The diagnosis was germinoma with syncytiotrophoblastic giant cells. Three cycles of chemotherapy consisting of ifosfamide, cisplatin, and etoposide, followed by radiation therapy achieved complete remission, and 5 cycles of chemotherapy with carboplatin and etoposide were added. MR imaging performed 40 months after the diagnosis showed a cicatricial cyst in the body of the corpus callosum, the original tumor site. All 11 previously reported cases of germinoma in the corpus callosum were associated with synchronous or metachronous intracranial lesions. These patients tended to be older than patients with general intracranial germinoma. Germinoma should be included in the differential diagnosis of corpus callosum tumors, especially in young adult males.

Metachronous mediastinal seminoma occurring after intracranial germinoma in an adolescent.

We report a case of a mediastinal seminoma occurring 19 months after the resolution of a pineal germinoma. A 15-year-old boy with headaches and visual changes was diagnosed with a pineal germinoma by biopsy and mildly elevated beta-human chorionic gonadatropin (beta-HCG) in serum and cerebral spinal fluid. Radiation therapy leads to the resolution of his pineal germinoma and normalization of the beta-HCG. A mediastinal seminoma (germinoma) was diagnosed nearly 2 years later because of rising serum beta-HCG. There was no evidence of recurrent central nervous system disease. The patient underwent systemic chemotherapy with the complete resolution of the mediastinal seminoma.

The prognostic value of tumor markers in newly diagnosed patients with primary central nervous system germ cell tumors.

BACKGROUND: To determine the impact of diagnostic serum and/or cerebrospinal fluid (CSF) alpha-fetoprotein (AFP) and beta-human chorionic gonadotropin (b-HCG) elevations on survival in newly diagnosed patients with central nervous system germ cell tumors (CNS GCT) treated with chemotherapy with the intent to avoid irradiation. PROCEDURE: Seventy-five patients with newly diagnosed CNS GCT enrolled in two sequential internationally conducted clinical trials with serum and CSF AFP and b-HCG levels available from initial diagnosis were retrospectively analyzed. Subjects received platinum based chemotherapy and were followed with serial imaging and tumor marker evaluations. RESULTS: The 5-year overall survival (OS) and event free survival (EFS) for patients with normal tumor markers compared with those with elevated markers at diagnosis was 78% (95% CI 51-91%) versus 60% (95% CI 46-72%) (P = 0.08) and 22% (95% CI 7-43%) versus 28% (95% CI 16-40%) (P = 0.68). The hazard ratio of death for patients with elevated markers was 1.9 times as high as that for those with normal markers (95% CI 0.58-6.5) after adjusting for other baseline characteristics. There was no observed difference in survival among patients with histologically confirmed germinomas, irrespective of level of b-HCG. CONCLUSIONS: Patients with elevated tumor markers appear to have poorer OS independent of tumor histology, although these differences do not reach statistical significance (P < or = 0.05). No differences were observed in EFS between groups likely due to the poor response of chemotherapy only approach to patients with normal markers. b-HCG elevations in biopsy proven germinomas do not seem to alter a patient's prognosis.