Cerebral Spinal Fluid Cytology Research Articles

CSF cytology of common primary CNS neoplasms categorized by CNS WHO 2021.

The detection of neoplastic cells in cerebral spinal fluid (CSF) is pivotal for the management of patients with central nervous system (CNS) tumours. This article delves into the CSF cytological characteristics of common CNS neoplasms, aligning with the 2021 World Health Organization (WHO) classification of CNS tumours. A retrospective review of CSF specimens positive for primary CNS neoplasms was performed at three tertiary medical centres. Only cases that had histopathologic confirmation and/or molecular workup were included. Common primary CNS neoplasms seen in CSF cytology specimens include medulloblastoma, (non-WNT/non-SHH as well as SHH-activated and TP53 mutant), pineoblastoma, atypical teratoid/rhabdoid tumour (AT/RT), IDH-wildtype glioblastoma, and primary diffuse large B-cell lymphoma of the CNS. Ependymomas and germinomas can also have CSF involvement but are less common. Although the typical histologic architecture of these tumours may not be preserved in the CSF, unique cytomorphologic features such as nuclear moulding, nuclear pleomorphism, rhabdoid cells, prominent nucleoli and rosette formation can still be appreciated. Adopting the updated terminology and correlating cytologic observations with molecular findings will streamline the diagnostic process, reducing the complexities and ambiguities pathologists often encounter when analysing CSF specimens for potential primary CNS neoplasms.

Response assessment in paediatric intracranial ependymoma: recommendations from the Response Assessment in Pediatric Neuro-Oncology (RAPNO) working group.

Response criteria for paediatric intracranial ependymoma vary historically and across different international cooperative groups. The Response Assessment in the Pediatric Neuro-Oncology (RAPNO) working group, consisting of an international panel of paediatric and adult neuro-oncologists, neuro-radiologists, radiation oncologists, and neurosurgeons, was established to address both the issues and the unique challenges in assessing the response in children with CNS tumours. We established a subcommittee to develop response assessment criteria for paediatric ependymoma. Current practice and literature were reviewed to identify major challenges in assessing the response of paediatric ependymoma to clinical trial therapy. For areas in which data were scarce or unavailable, consensus was reached through an iterative process. RAPNO response assessment recommendations include assessing disease response on the basis of changes in tumour volume, and using event-free survival as a study endpoint for patients entering clinical trials without bulky disease. Our recommendations for response assessment include the use of brain and spine MRI, cerebral spinal fluid cytology, neurological examination, and steroid use. Baseline postoperative imaging to assess for residual tumour should be obtained 24-48 h after surgery. Our consensus recommendations and response definitions should be prospectively validated in clinical trials.

Case Report: Predominant brain superficial location of Epstein-Barr virus-related primary central nervous system diffuse large B cell lymphoma in a young woman with primary Sjögren’s syndrome

Epstein-Barr virus (EBV)- related primary central nervous system (CNS) diffuse large B cell lymphoma (DLBCL) is very rare in young patients without immunodeficiency.  The predominant brain superficial location of EBV-related primary CNS DLBCL, and its’ concurrence with EBV-related lumbar-sacral radiculitis are special and have not been described previously. A young female patient presented with multiple cranial neuropathies, radiculopathy of lower limbs, and urinary retention. Her series brain magnetic resonance imaging (MRI) revealed dynamic changes, starting from lesions mainly in cranial nerves to mammillary body, pineal body, meninges, and finally in the bilateral cerebellum and cerebral lobes. Lumber spinal MRI showed enhancement in meninges and cauda equine roots. 18-fluorodeoxyglucose PET-CT revealed remarkably increased glucose metabolism in the lesions shown on the aforementioned brain MRI and lumbar spinal MRI, as well as right axillary lymph nodes. The biopsy of a whole axillary node on right side indicated EBV-related lymphoproliferation. Lumbar meninges and cauda nerves biopsy revealed chronic inflammation. By cerebral spinal fluid cytology and in situ hybridization, EBV-encoded small RNA (EBER) positive large B cell lymphoma was identified. The patient also had primary Sjögren’s syndrome (PSS). The patient died two weeks after treatment with rituximab, lenalidomide and methylprednisolone. She had survived for four and a half months since symptom onset. The patient presented with several stages of EBV-related complications in the nervous system, chronic EBV infection of lumbar-sacral radiculitis, and primary CNS DLBCL, indicating the process from chronic EBV infection to DLBCL in nervous system. Intracranial acute bacterium infection probably exacerbated the progression of CNS DLBCL. The concomitant sufferings of PSS reflected immune-dysfunction might have increased the risk of EBV-related CNS DLBCL in this young patient.

Journey of choroidal tubercle to choroidal granuloma

Choroidal tubercles may be unilateral or bilateral and appear as a polymorphic yellowish lesion with discrete borders. Tubercles can arise early in the stages of progression of tuberculosis (TB) and are indicative of hematogenous dissemination seen in acute military TB. Choroidal granuloma is seen in chronic TB in response to antitubercular treatment. We report a case of a 14-year old girl who presented with fever, altered sensorium, and irritability for 1 week. Fundus examination revealed bilateral multiple choroidal tubercles. Antitubercular treatment was started after magnetic resonance imaging head and cerebral spinal fluid cytology confirmed the diagnosis of disseminated TB. Enhanced depth imaging optical coherence tomography was done on follow-up visits to see the stages of progression or regression of choroidal tubercle after the treatment. This is a rare case, reporting the transition of choroidal tubercle into choroidal granuloma, which is demonstrated with serial imaging using various modalities.

Clinical-MRI radiomics enables the prediction of preoperative cerebral spinal fluid dissemination in children with medulloblastoma

BackgroundMedulloblastoma (MB) is the most common pediatric embryonal tumor. Accurate identification of cerebral spinal fluid (CSF) dissemination is important in prognosis prediction. Both MRI of the central nervous system (CNS) and CSF cytology will appear false positive and negative. Our objective was to investigate the added value of preoperative-enhanced T1-weighted image-based radiomic features to clinical characteristics in predicting preoperative CSF dissemination for children with MB.Materials and methodsThis retrospective study included 84 children with histopathologically confirmed MB between November 2006 and November 2018 (training cohort, n=60; internal validation cohort, n=24). A set of cases between December 2018 and February 2020 were used for external validation (n=40). The children with normal head and spine magnetic resonance images (MRI) and no subsequent dissemination in 1 year were diagnosed as non-CSF dissemination. The CSF dissemination was manifested as intracranial or intraspinal nodular-enhanced lesions. Clinical features were collected, and conventional MRI features of preoperative head MRI examinations were evaluated. A total of 385 radiomic features were extracted from preoperative-enhanced T1-weighted images. Minimum redundancy, maximum correlation, and least absolute shrinkage and selection operator were performed to select the features with the best performance in predicting preoperative CSF dissemination. A combined clinical-MRI radiomic prediction model was developed using multivariable logistic regression. Receiver operating curve analysis (ROC) was used to validate the predictive performance. Nomogram and decision curve analysis (DCA) were developed to evaluate the clinical utility of the combined model.ResultsOne clinical and nine radiomic features were selected for predicting preoperative CSF dissemination. The combined model incorporating clinical and radiomic features had the best predictive performance in the training cohort with an AUC of 0.89. This was validated in the internal and external cohorts with AUCs of 0.87 and 0.73. The clinical utility of the model was confirmed by a clinical-MRI radiomic nomogram and DCA.ConclusionsThe combined model incorporating clinical, conventional MRI, and radiomic features could be applied to predict preoperative CSF dissemination for children with MB as a noninvasive biomarker, which could aid in risk evaluation.

Lymphomatosis cerebri with cauda equina lymphoma

Purpose/aim Lymphomatosis cerebri (LC) and cauda equina lymphoma are both rare forms of primary central nervous system lymphoma (PCNSL). LC is characterized by diffuse bilateral non-enhancing (or partially enhancing) inltrative lesions without mass effect, which can be easily confused with other forms of leukoencephalopathy and, thus, lead to delays in diagnosis. Case report For the first time, a case of LC concomitant with cauda equina involvement confirmed by brain stereotactic biopsy is presented. Conclusions This case highlights the necessity of using a multimodal strategy in diagnosing PCNSL, including multimodal magnetic resonance, cerebral spinal fluid cytology, flow cytometry and fluorodeoxyglucose positron emission tomography/computed tomography.

RARE-33. LEPTOMENINGEAL DISEASE IN PATIENTS WITH MIDLINE GLIOMAS HARBORING HISTONE H3 K27M MUTATIONS

Abstract INTRODUCTION The 2016 WHO classification describes a specific subtype of midline gliomas harboring histone 3 (H3) K27M mutations which compromise 15–40% of gliomas in children and young adults. Since we began to perform molecular profiling at Memorial Sloan Kettering Cancer Center (MSKCC) we have observed an increased prevalence of leptomeningeal disease (LMD) in this population. However, the true incidence and the clinical behavior of this group has not been well-defined. METHODS This is a retrospective study of patients with H3K27M/I diffuse midline gliomas at MSKCC from 01/2012 to 01/2019. Mutations were identified through next-generation sequencing (NGS). RESULTS We identified 24 patients. Median age was 21 (6–70) and 13 were male. Thirteen tumors were in the thalamus, 6 in the brainstem, 4 in the spinal cord, and 1 in the pineal region. H3K27M mutations were detected by NGS from tumor tissue in 21 patients, from cerebral spinal fluid (CSF) circulating tumor DNA (ctDNA) in 2 and from tissue and CSF ctDNA in one. LMD was diagnosed in 17/24 (71%) patients radiographically. Of these, 8 underwent LP: CSF cytology was positive in 2/8 and CSF ctDNA was detected in 3/3. All patients received RT and one or more lines of chemotherapy. At analysis, thirteen patients remain alive. Median time to last follow up for all patients was 14.2 months. Median time from diagnosis to LMD was 13.2 months (0–45.1), with median OS of 6.5 months (0.3–27) after diagnosis of LMD. CONCLUSION Our study showed that more than two-thirds of the patients with H3 K27M diffuse midline developed LMD. Neuroaxis imaging should be performed in conjunction with CSF studies to diagnose LMD. Besides, CSF ctDNA represents an important tool to identify molecular profile of tumors when biopsy is not feasible or limited for the analysis.

Leptomeningeal metastasis of pulmonary large-cell neuroendocrine carcinoma: A case report and review of the literature.

Pulmonary large-cell neuroendocrine carcinoma (LCNEC) is a rare and malignant form of lung cancer with a poor prognosis for patients. The common sites of metastases are the liver, adrenal glands, bone and brain. LCNEC rarely metastasizes to the small intestine, ovaries, tonsils, mandible, vulva or spine. To the best of our knowledge, there have been no reports of leptomeningeal metastasis of LCNEC to date. The present case report describes an unusual case of leptomeningeal metastasis from pulmonary LCNEC alongside a review of the literature. Biopsies of pulmonary lesions and cervical lymph nodes confirmed the diagnosis of LCNEC in a 39-year-old male patient. At 2 months after chemotherapy, the patient began to experience hoarseness, epileptic seizures and blurred vision. Furthermore, the patient presented with radiating pain and numbness in his lower left limb. Imaging findings and cytological examination of cerebral spinal fluid supported the diagnosis of leptomeningeal metastasis. The patient's neurological symptoms were markedly alleviated following receipt of radiation and intrathecal chemotherapy. The patient survived for 4.9 months after diagnosis with leptomeningeal metastasis. To the best of our knowledge, the present case report is the first to describe leptomeningeal metastasis from pulmonary LCNEC confirmed by neuroimaging and cerebral spinal fluid cytology. It suggests that leptomeningeal metastasis does occur in this rare disease, and aggressive treatment may result in improved symptoms and possibly survival times.

A revisit of the devastating outcome of leptomeningeal disease.

e13504 Background: Leptomeningeal metastasis (LM) represents a devastating complication of malignancies by forming tumor deposits on the leptomeninges at about 5% to 8% of cancer patients (Pts). Standard therapies include radiotherapy (RT) to focal involved areas, systemic and/or intrathecal (IT) chemotherapies which have been recommended for palliation but with unclear benefit toward survival. This study is to review the pattern of the clinical practice and outcomes on Pts with LM who have received care at Henry Ford Hospital between 2004 and 2014 Methods: A retrospective study targeted all Pts of LM (icd-9 code 198.4) between 01/01/2004 and 01/01/2014. Pts with primary brain, orbital and spinal lesions as well as Pts with cord compressions were excluded from this study. LM Pts were included based on MRI images, cerebral spinal fluid (CSF) cytology and/or dural biopsy. Data from onset of primary tumor, therapeutic interventions, methods of LM diagnosis, duration (days) from initial cancer onset to LM diagnosis, then from LM diagnosis to death were collected and analyzed as shown Results: 328 Pts with LM (icd-9: 198.4) were identified, but 58 Pts fulfilled inclusions. Of 58 Pts, 22 (38%) had breast cancer (38%), 12 (21%) NSCLC. LM was diagnosed in 34 Pts (59%) based on MRI findings, 4 (6%) by CSF cytology and 19 (33%) by both. Majority (37 Pts, 64%) received therapy after LM diagnosis: 16 (27%) received IT chemotherapy, 15 (26%) received RT while 6 (10%) received both. Twenty-one of LM Pts (36%) received no treatment under various circumstances. Of 58 Pts, the median time from cancer onset to LM diagnosis was 686 days while median overall survival (OS) was 1038 days, and median OS from LM to death was 95 days. Survival difference was observed for Pts (37, 64%) received LM-directed treatment as 113 days but only 61 days for those received no therapies Conclusions: LM is a prognostic complication in malignancies. It poses a grave challenge due to limited therapeutics that only carry modest survival benefit. Data from these 58 Pts shown a benchmarks of survival from LM diagnosis was 4 months with treatment, and 2 months without. These are consistent with published data over last decades without improvement. Therefore, more clinical researches in LM diagnosis and therapies are needed

Leptomeningeal metastases in pediatrics: magnetic resonance image manifestations and correlation with cerebral spinal fluid cytology

Detection of leptomeningeal metastases is fundamental to a complete evaluation of central nervous system (CNS) or non-CNS tumor with suspected involvement of the neuroaxis. Our purpose was to assess the appearances of different magnetic resonance (MR) sequences in the diagnosis of leptomeningeal metastases and correlate those positive findings with the cerebral spinal fluid (CSF) cytology results. The authors reviewed the medical records and MR image manifestations of leptomeningeal metastases from 18 children who had positive MR findings and retrospectively correlated them with CSF cytologic results. There was a uniform MR protocol and the patients were examined with the same sequences. The abnormalities included pial-arachnoid disease (n = 16), disease coating the nerves (n = 12), hydrocephalus (n = 3) and subependymal metastases (n = 2). Enhanced T1 images were better than unenhanced fluid attenuated inversion recovery (FLAIR) and T2 to delineate cranial and spinal leptomeningeal metastases. In our sample, seven out of 18 cases were cytologically negative on a single lumbar puncture. Contrast-enhanced MR imaging can be invaluable, detecting the false-negative lumbar punctures. FLAIR and diffusion images can be helpful in diagnosing leptomeningeal metastases of non-enhancing primary tumors. Prognosis was more related to the primary tumor type than to the leptomeningeal enhancement MR pattern.

Clinical characteristics of Burkitt's lymphoma from three regions in Kenya

To describe the clinical characteristics of Burkitt's lymphoma (BL) from three regions in Kenya at different altitudes with a view towards understanding the contribution of local environmental factors. Prospective cross-sectional study. Kenyatta National Hospital and seven provincial hospitals in Kenya. Histologically proven cases of Burkitt's lymphoma in patients less than 16 years of age were clinically examined and investigated. For every case the following parameters were documented: chief complaint(s); physical examination, specifically pallor, jaundice, oedema, lymphadenopathy, presence of masses, splenomegaly and hepatomegaly. Reports of evaluation of chest radiograph, abdominal ultrasound/scan, bone marrow aspiration, cerebral spinal fluid cytology, liver and kidney function tests, urinalysis, stool occult blood and full blood count results. Stage of disease was assigned A, B, C or D. Cases of BL from three provinces of Kenya with diverse geographical features were analysed: Central, Coast, and Western. This study documented 471 BL cases distributed as follows: Central 61 (males 39 and 22 females), M:F ratio 1.8:1; Coast 169 (111 males and 58 females), M:F ratio 1.9:1; and Western 241 (140 males and 101 females), M:F ratio 1.4:1. The major presenting complaints were: abdominal swelling--Central 36%, Coast 4% and Western 26%; swelling on the face--Central 31%, Coast 81% and Western 64%; and proptosis--Central 3%, Coast 1% and Western 9%. The mean duration of these complaints in weeks were Central 6.9, Coast 6.08, and Western 5.05. The initial physical finding was a tumour mass in 39%, 72% and 54% of cases for Central, Coast and Western respectively. Tumour stage at diagnosis was: stage A--Central 21%, Coast 43% and Western 34%; stage B--Central 10%, Coast 5% and Western 10%; stage C--Central 41%, Coast 34% and Western 30%; and stage D--Central 28%, Coast 17% and Western 26%. For the age and sex matched cases the results show that commonly involved sites were: abdomen--Central 35%, Coast 9% and Western 14%; jaw (mandible)--Central 24%, Coast 22% and Western 31%; maxilla--Central 6%, Coast 24% and Western 11%; and lymph nodes--Central 10%, Coast 4% and Western 8%. The disease stage was A--Central 33%, Coast 44% and Western 36%; stage B--Central 11%, Coast 10% and Western 27%; stage C--Central 39%, Coast 34% and Western 27%; and stage D--Central 21%, Coast 13% and Western 37%. This study shows that clinical features of childhood BL vary with geographical region. The variations are documented in proportion of jaw, maxilla, abdominal and lymph nodal sites involvement. The differences observed are potentially due to the local environmental factors within these provinces. BL cases from Western province had features, intermediate between endemic and sporadic. Coastal province BL cases were similar to endemic BL, while BL cases from Central province resembled more or less sporadic BL subtypes. Strategies to explain and investigate the local environmental factors associated with the observed differences may certainly contribute towards improved understanding and clinical management of BL.

A randomized phase III/IV study to determine benefit and safety of cytarabine liposome injection for treatment of neoplastic meningitis

1528 Background: Cytarabine liposome injection (CLI) maintains cytotoxic concentrations in the cerebral spinal fluid (CSF) for >14 days with a single 50 mg dose. This study compared patient benefit and safety of intrathecal CLI with methotrexate (MTX) or nonliposomal cytarabine (Cyt) against solid tumor neoplastic meningitis (STNM) and lymphomatous neoplastic meningitis (LNM), respectively. Methods: This multicenter, randomized, open-label, active-controlled study was powered to detect a 50% hazard ratio for progression-free survival (PFS; i.e., days from randomization to neurological progression or death) in STNM patients. STNM patients (n=103) were randomized to CLI or MTX and LNM patients (n=25) to CLI or Cyt. Patients had either histologically documented STNM or LNM confirmed by ventricular or lumbar CSF cytology or symptomatic meningeal tumor verified by magnetic resonance imaging or computed tomography. CLI treatment consisted of 6 Induction Cycles (2 weeks per cycle) and 4 Maintenance Cycles (4 weeks per cycle). Results: By per-protocol Cox regression analysis, CLI (STNM and LNM combined) was noninferior to MTX and Cyt combined (Control Group). The median PFS was 35 days and 43 days (p=0.7321), respectively; the hazard ratio (95% CI) was 0.98 (0.65, 1.46). CLI was also noninferior to MTX in the STNM group, where the hazard ratio was 0.94 (0.58; 1.53). In the LNM group, superiority of CLI over Cyt was demonstrated a hazard ratio of 0.12 (0.02, 0.77). Median PFS was 34 and 50 days, respectively. More LNM patients had complete response (clearance of tumor cells from CSF) with CLI (33.3%) than with Cyt (16.7%; p=0.3640). All patients experienced AEs; 48% and 60% of the patients in CLI and Control Group, respectively, experienced drug-related AEs. The incidence of serious AEs was 86% and 77%, respectively. Conclusions: These results demonstrate at least comparable patient benefit between CLI and control treatments for STNM and improved benefit for CLI in LNM patients. Intrathecal CLI provides patients with the added convenience of bimonthly treatment. [Table: see text]

Is early recognition of radiologically silent brain metastasis from breast cancer beneficial? A retrospective study of 22 cases

Over a period of 10 years, twenty-two patients with T2-3N2Mx breast cancer presented with symptoms of increased intracranial pressure (ICP), but brain CT scan and/or MRI did not reveal any signs of a space occupying lesion. A brain CT scan and an MRI study were performed every 15 days. Ten patients refused this close follow up. Thus, two groups were formed group A (n = 12) included the patients who were close's followed and group B (n = 10) consisted of those patients who were not. Therefore, Group A, being under careful follow-up, initiated radiotherapy were quickly. The median time from the presentation of increased ICP symptoms until the appearance of metastases on CT and/or MRI directly followed by brain irradiation was 48 days (SE = 6.1) for group A and 72 days (SE = 0.7) for group B (p = 0.0085, log-rank test). In group A, median Overall Survival (OS) was 171.0 (SE = 21.5) days, and was 99.0 (SE = 6.3) days (p = 0.014) for group B. Volumetric analysis of the secondary brain lesions at the initiation of radiotherapy showed a total volume of metastatic lesions of 19.5 +/- 13.9 cm3 versus 65.3 +/- 20.7 cm3 for groups A and B, respectively (p < 0.001, Mann-Whitney test). Post-radiotherapy, Karnofsky Performance Status and Visual Analogue Score were also improved for group A versus B (p = 0.002). Group A appeared to benefit from close follow-up since the metastases were detected and irradiation was given sooner compared with group B, thus achieving better performance status and prolonged survival. Radiologically silent brain metastases from breast cancer should not be ignored because timely whole brain irradiation should be the goal of clinicians. Clinical suspicion should lead to close follow-up with multiple CT/MRI studies and cerebral spinal fluid cytology until the final diagnosis.

Aspects of epidemiological and clinical features of patients with central nervous system Burkitt's lymphoma in Kenya

Establishing characteristics of Central nervous System (CNS) Burkitt's lymphoma (BL) is essential as CNS disease is associated with poor treatment outcome. To document the characteristics of those cases of Burkitt's who had CNS disease at the time of presentation. Prospective study of the clinical details of paediatric patients admitted and treated for Burkitt's lymphoma from January 1986 to December 1997. Kenyatta National Hospital and seven provincial hospitals in Kenya. For every histologically proven Burkitt's case, the following were documented; Age, sex, geographical area (province in Kenya), complaints, physical findings, Cerebral Spinal Fluid (CSF) cytology results, Human Immunodeficiencies Virus screening test result and anatomical sites of the disease at the time of starting therapy. A total of 1005 BL cases were studied and 961(95.6%) were aged between two and 15.4 years median age of six years consisting of males 587(61%) and females 374 (39%) while 44 (4.4%) cases between 16 and 57 years consisting of males 23 (52%) and females 21 (43%). The main complaints; headache, swelling mainly facial, abdominal distension and proptosis. Peak duration at presentation 4 and 8 weeks, range 1 to 26 weeks. Clinical evaluation demonstrated CNS in 5.6%, presenting as headache, blurring of vision and difficulties in walking. Physical examination noted para-paresis, ophthalmoplegia and cranial nerve palsies, while CSF demonstrated BL cells in 158 (18.4%). Overall CNS BL was found in 161 (16.8%), children and 39% adults. All were systemic and no primary CNS BL detected. Peak age was 11 to 15 years for children. Their provinces Eastern; 24.5%, Central 21.3%, and Rift Valley 23.4%, ethnic origins, Meru 29.5%, Kikuyu 23.9% and Kamba 23.7%. The sites of tumour for CNS cases were abdominal, combined sites, and skeletal while least in maxilla and jaw. Seventy one per cent of adults had both CSF BL and HIV infection. CNS-BL children cases were older, reduced M:F ratio; had skeletal/abdominal presentation and were from the Central province, Kikuyu tribe and a positive CSF cytology for malignant cells found in almost all cases with CNS disease at presentation. No primary CNS BL detected. Geographically, cases were from mainly the highlands of Kenya. High CNS disease in adults coincided with HIV positive serostatus.

Intracranial germinoma: The case for lower dose radiation therapy

To determine the optimal dose and treatment outcome of patients treated with radiation for intracranial germinoma. Between 1975 and 1995, 40 patients with the diagnosis of intracranial germinoma were treated with radiation (RT) to the central nervous system. All patients received whole-brain (WB) RT (median dose: 32.4 Gy, range: 15-44.37 Gy) and a boost to the tumor volume (median total tumor volume dose: 52 Gy, range: 45-59.5 Gy). Thirty patients received RT to the spine (median dose: 26 Gy, range: 18.75-37.5 Gy). Four patients were treated with cisplatin-based chemotherapy and WB RT with a boost to the tumor volume (dose range: 51-54 Gy). A low-dose RT only group was defined as < or = 25.5 Gy to the WB (9 patients); < 50 Gy to the primary site (14 patients); and < 22 Gy to the spine (9 patients). Seventeen tumors were biopsy-proven germinoma, and 17 patients presented with multiple midline germinomas (MMG). Among 26 patients who had tumor markers measured, 27% had elevation of beta-human chorionic gonadotropin and by definition, no patient had an elevation of AFP. Twenty-four percent of 26 patients who had spine imaging or cerebral spinal fluid cytology had evidence of tumor seeding at diagnosis. The male to female ratio was 1.9:1. Median age at diagnosis was 14 years for male patients and 9.5 years for female patients (p = 0.02), (overall age ranges: 0.5-31 years). Median follow-up was 62 months (range: 3-226 months). Late effects of 29 patients with follow-up of > or = 20 months and adequate documentation in their medical records were analyzed. The 5-year actuarial rate of disease-free survival (DFS) and overall survival (OS) for biopsy-proven germinomas and presumed germinomas was 97%. No patient died of germinoma. There were no local failures regardless of the dose of RT, elevation of HCG tumor marker, or CSF dissemination at presentation. At presentation 22 patients had evidence of at least one endocrine abnormality. At follow-up there were no new patients diagnosed with an endocrine abnormality; however, 13 out of 22 patients had an increase in the number of endocrine deficiencies requiring hormone replacement. At presentation, 14 patients showed evidence of growth retardation. At follow-up there were no new cases of growth failure in the remaining patients. Germinomas are highly curable with RT alone. Lower doses of RT to the craniospinal axis without chemotherapy appear to produce equally effective DFS and OS as do higher doses of RT or combination chemotherapy and RT. Craniospinal RT may be indicated for patients with MMG or patients with evidence of spinal seeding. Long-term effects of growth retardation, and other endocrine deficiencies appear to be correlated with disease at presentation rather than solely with treatment.

Brain tumours in children. A plea for an interdisciplinary working group.

A considerable number of high risk brain tumours require an interdisciplinary approach with surgery, radiation and chemotherapy rather than one single therapeutic regimen. Children with a medulloblastoma must be subdivided into four different risk groups depending on the size of the tumour, on the age of the child and on cerebral spinal fluid cytology findings. The treatment protocol for ependymomas depends on the location of the tumour and on histological grading. Pineal region tumours can be successfully removed; further therapy depends on the type of the tumour. Children with hemispheric high grade astrocytomas gain substantially from local radiation therapy. The GPO (Gesellschaft für Pädiatrische Onkologie) has most recently taken the initiative to found a pediatric neuro-oncology working group in order to establish and to evaluate different treatment modalities.