Cerebrospinal fluid cytology in a toddler with a posterior fossa space-occupying lesion.

An atypical teratoid rhabdoid tumour (AT/RT) is an extremely rare malignant neoplasm. Cerebrospinal fluid (CSF) involvement at presentation indicates intracranial dissemination and is associated with an aggressive course and worse outcomes. We present the characteristic cytomorphological features of AT/RT in the cerebrospinal fluid from a toddler presenting with a posterior fossa space-occupying lesion.

Neoadjuvant chemotherapy for atypical teratoid rhabdoid tumors: case report.

Atypical teratoid rhabdoid tumors (ATRTs) are a rare pediatric brain tumor with high mortality rate. Several large series have reported achieving gross-total resection (GTR) in less than 50% of patients due to the lesions' large size, vascularity, and limited blood volume in young patients. While neoadjuvant chemotherapy for choroid plexus carcinomas in pediatric patients has become widely accepted, it has not been used as widely for other pediatric brain tumors. To the best of the authors' knowledge, there are only 3 published cases of neoadjuvant chemotherapy for ATRTs. In the present report, the authors present a fourth case of neoadjuvant chemotherapy for ATRT and review the available literature on this strategy. A 17-month-old child presented with a left ventricular ATRT for which imaging raised concern for a highly vascularized tumor. The authors undertook neoadjuvant chemotherapy with 2 cycles of Head Start II therapy, which reduced the size of the ventricular tumor by 35% and decreased the vascularity of the lesion on imaging. The estimated blood loss during resection was 425 ml and GTR was achieved. The patient continued with postoperative chemotherapy but suffered an on-therapy recurrence. While higher-quality data are necessary, available evidence suggests that neoadjuvant chemotherapy can reduce the size and vascularity of ATRTs and facilitate a surgical avenue for large or "inoperable" tumors.

Cytologic characterization of atypical teratoid/rhabdoid tumor in cerebrospinal fluid.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare and highly aggressive intracranial malignancy with a predilection to spread along the cerebrospinal fluid (CSF) pathways. To the authors' knowledge, the cytopathologic characteristics of this tumor have not been extensively studied in CSF. Herein the authors report CSF cytomorphology from a series of patients with histologically documented AT/RT. METHODS: A retrospective review of 40 malignant CSF specimens from 10 patients with histologically confirmed AT/RT was conducted. All the patients were female and ranged in age from 0.8 to 19.6 years at the time of the initial diagnosis (median age, 1.3 years). Cytospin preparations were reviewed. In the majority of cases, at least 2 slides were prepared with the Wright-Giemsa and/or Papanicolaou stains. RESULTS: The CSF samples were predominantly moderately to highly cellular (80%). The 3 most common features were eccentrically placed nuclei (72.5%), prominent nucleoli (70%), and large tumor cells (67.5%). Two principal malignant cell types were noted; the most striking and recognizable form was a large, usually rhabdoid cell with an eccentrically placed nucleus, prominent nucleolus, and abundant cytoplasm, which was observed in 47.5% of the cases. The second type had a small cell appearance and was noted in 57.5% of the cases. Both large rhabdoid and small malignant cells were reported in 25% of the cases. CONCLUSIONS: A significant percentage of CSF AT/RT cases consist of only the small cell component, without the characteristic large rhabdoid cells. Familiarity with this pattern of spread is imperative in differentiating AT/RT from other small cell malignancies such as medulloblastoma, because the clinical behavior and therapeutic regimens differ.

A multimodal approach including craniospinal irradiation improves the treatment outcome of high-risk intracranial nongerminomatous germ cell tumors.

PURPOSE: To evaluate whether a multimodal approach including craniospinal irradiation (CSI) improves treatment outcome in nongerminomatous germ cell tumor (NGGCT) patients. METHODS AND MATERIALS: We reviewed the records of 32 patients with NGGCTs. Fourteen patients belonged to the intermediate prognosis group (immature teratoma, teratoma with malignant transformation, and mixed tumors mainly composed of germinoma or teratoma), and 18 patients belonged to the poor prognosis group (other highly malignant tumors). Patients with pure germinoma or mature teratoma were excluded from this study. Nineteen patients were treated with a combination of surgery, chemotherapy, and radiotherapy (RT); 9 patients received chemotherapy plus RT; 3 patients received surgery plus RT; and 1 patient received RT alone. Twenty-seven patients received CSI with a median of 36 Gy (range, 20-41 Gy) plus focal boost of 18-30.6 Gy, and 5 patients received whole-brain RT (WBRT) (20-36 Gy) or focal RT (50.4-54 Gy). The rate of total and subtotal resection was 71.9%. The median follow-up for surviving patients was 121 months. RESULTS: Treatment failed in 7 patients. Three of the 5 patients who received focal RT or WBRT had local failure. Four cerebrospinal fluid (CSF) failures occurred after CSI. No failure occurred in the intermediate prognosis group. Ten-year recurrence-free survival (RFS) and overall survival (OS) for all patients were 77.6% and 74.6%, respectively. Ten-year RFS for the intermediate and poor prognosis groups were 100% and 61.1%, respectively (p = 0.012). OS for the two groups were 85.1% and 66.7%, respectively (p = 0.215). Tumor histology and CSI were significant prognostic factors for RFS, and CSI was significantly associated with OS. CONCLUSIONS: A multimodal approach was effective for treating NGGCTs. CSI should be considered for patients with poor prognostic histology.

Atypical teratoid/rhabdoid tumor: analysis of cytomorphologic features in CSF, focused on the differential diagnosis from mimickers.

Atypical teratoid and rhabdoid tumor (AT/RT) is a rare tumor with fatal clinical consequences, usually affecting young children. A significant portion of patients present with dissemination to cerebrobspinal fluid (CSF). However, a limited number of studies are available regarding the cytomorphologic findings of AT/RT in CSF. We collected eight cases of CSF cytology of AT/RT and describe the cytomorphologic features of AT/RT in CSF. Typical rhabdoid cells are found in most cases and they are characterized by eccentric nuclei, abundant cytoplasm, and clustering of the tumor cells. The presence of these cells in CSF indicates disseminated diseases and aggressive therapeutic consideration for patient management is required.

Atypical teratoid/rhabdoid tumor involving cerebrospinal fluid: a case report.

BACKGROUND: Atypical teratoid/rhabdoid tumor (AT/RT) is a rare, aggressive tumor of the central nervous system. It is primarily seen in younger age-groups, and the cytomorphology has only been infrequently described. CASE: We present a case of AT/RT arising in the cervical spine of a 6-month-old boy. The cerebrospinal fluid (CSF) cytology and correlating findings are described. The CSF cytomorphologic findings of the AT/RT cells are most notably large cells, eccentrically placed pleomorphic nuclei, prominent nucleoli and, commonly, cytoplasmic inclusions, as well as a second population of smaller mononuclear cells with minimal cytoplasm. CONCLUSION: The cervical spine is a rare site for AT/RT to arise. It is important for pathologists to recognize the cytomorphologic features of AT/RT in the CSF of patients with this tumor to help determine prognosis and disease progression.

EFA6A-like antibodies in paraneoplastic encephalitis associated with immature ovarian teratoma: a case report.

We describe a 19-year-old patient with paraneoplastic encephalitis associated with immature ovarian teratoma (OT), who presented with psychiatric symptoms, prolonged disturbance of consciousness, refractory status epilepticus, central hypoventilation, and various abnormal involuntary movements. Immunological characterization of the patient's serum and cerebrospinal fluid (CSF) demonstrated the presence of an autoantibody that colocalized with EFA6A, a brain-specific protein involved in the regulation of dendritic development of hippocampal neurons. Despite the severity of the symptoms, the patient showed significant neurological improvement following removal of the tumor and chemotherapy. This case suggests that physicians should rule out an OT in young women with encephalitis who present with the subacute-onset of psychiatric symptoms. Antibodies that colocalize with EFA6A are a valuable marker for early diagnosis of a potentially reversible paraneoplastic encephalitis associated with OT.

Pineal region teratoma with high serum and CSF alpha-fetoprotein levels.

We report a patient with an immature teratoma of the pineal region with high levels of alpha-fetoprotein (AFP) in serum and cerebrospinal fluid. This is very rare and to the best our knowledge, the second case reported in the literature.

CSF cytology of atypical teratoid/rhabdoid tumor of the brain in a two-year-old girl: a case report.

Atypical teratoma/rhabdoid tumor (AT/RT) of the central nervous system is a highly malignant neoplasm in infants and early childhood. Approximately one third of patients develop intracranial dissemination with involvement of cerebral spinal fluid (CSF). The clinical, radiological, and pathological features have been described, but cytology of the tumor cells in CSF has not. Multiple CSF samples were examined in a case of AT/RT in a 2-yr-old girl. The most consistent cytologic features of AT/RT are the large size of the tumor cells, eccentricity of the nuclei, and prominent nucleoli. The differential diagnosis includes medulloblastoma/primitive neuroectodermal tumor (PNET) of the brain. Because AT/RT often contains PNET-like regions, the differential diagnosis mainly relies on the presence or absence of large rhabdoid tumor cells. Cytological examination of CSF from a patient with AT/RT is important in the early diagnosis, disease progression analysis, and therapy modulation.

The role of cerebrospinal fluid cytology in radiotherapy planning for intracranial germinoma.

PURPOSE: The association between the cerebrospinal fluid cytology findings and the clinical features of patients with intracranial germinoma was investigated to determine whether cerebrospinal fluid cytology could be helpful in determining the optimal radiation treatment volume. METHODS AND MATERIALS: Between 1976 and 1992, cerebrospinal fluid cytology was performed in 42 germinoma patients using a cytocentrifugation method. Forty patients received irradiation and 2 received chemotherapy with cisplatin and etoposide. RESULTS: Cerebrospinal fluid cytology was positive in 22 of the 42 patients (52%). Dissemination via cerebrospinal fluid (intraventricular or spinal) was present at the initial diagnosis in eight (36%) of the 22 cytology-positive patients and none of the 20 negative patients. After treatment, cerebrospinal fluid dissemination developed in four (18%) of the cytology-positive patients and one (5%) of the negative patients. Two of the former four patients had received chemotherapy alone as initial treatment. Five patients with positive cytology received irradiation to a smaller volume than the cerebrospinal axis (primary tumor site plus spinal axis in three and whole brain in two), but they have not developed recurrence in the 4 to 14 years since therapy. The 5-year survival rate was 93% for the cytology-positive patients and 94% for the negative patients. CONCLUSION: Cerebrospinal fluid cytology-positive patients have a higher risk of cerebrospinal fluid dissemination and it seems reasonable to give them low-dose (20-24 Gy) prophylactic craniospinal irradiation. When properly irradiated, the prognosis of cytology-positive patients is as good as that of negative patients.

Cerebrospinal fluid cytology in immature teratoma of the central nervous system. A case report.

The present case shows the usefulness of cerebrospinal fluid (CSF) cytology in the diagnosis of leptomeningeal dissemination by immature teratoma. The tumor arose in the thoracolumbar spinal cord of a 14-year-old male. The initial histopathologic diagnosis was made on the tumor tissue taken at laminectomy. Postoperatively, CSF cytology revealed epithelial cell clusters, scattered squamous epithelial cells and small bundles of striated muscle fibers in the background of many histiocytes and inflammatory cells. Although these cells showed only slight cytologic atypia, their presence in the subarachnoid space suggested the leptomeningeal spread of well-differentiated portions of the immature teratoma. The postmortem examination revealed the primary tumor in the spinal cord and multiple metastatic nodules in the brain.

Evaluation of polyamine levels in cerebrospinal fluid of children with brain tumors.

Cerebrospinal fluid (CSF) polyamine levels were analyzed retrospectively in 21 pediatric patients with different types of intracranial malignant tumors to determine the benefit of following these markers during the clinical management of brain tumors. The tumors included 16 medulloblastomas and 1 each of germinoma, ependymoma, primitive neuroectodermal tumor, astrocytoma, and malignant teratoma. The clinical course of each patient was followed by neurologic examination, cranial computed tomography, CSF cell count, and cytology after cytocentrifugation. The correlation of CSF putrescine and spermidine levels with the clinical course of the brain tumors was analyzed. The following results were obtained: (1) A significant increase in CSF putrescine levels was observed in children with medulloblastoma when there was recurrent or metastatic disease in the sites close to the CSF pathway compared with the children whose disease status was stable after successful treatment (P less than 0.005). (2) The increase of CSF putrescine levels was the earliest predictor of recurrence or metastasis near the CSF pathway. (3) In tumors other than medulloblastoma, the levels of polyamines were not predictive of disease activity with the possible exception of germinoma. (4) Spermidine levels in the CSF were of limited clinical importance for patients with brain tumors. CSF putrescine levels may be the earliest and most sensitive quantitative marker of the progression of medulloblastoma, and their evaluation should be included in the diagnostic work-up and follow-up examination of children with medulloblastoma.

Concentration of human chorionic gonadotropin in the cerebrospinal fluid of patients with germinal cell hypothalamic tumors.

Plasma and cerebrospinal fluid (CSF) specimens were measured simultaneously for human chorionic gonadotropin (HCG) in two patients with HCG-secreting choriocarcinoma. In the patients with hypothalamic tumors, the CSF HCG levels were higher than the plasma HCG concentrations. In the patient with gestational choriocarcinoma with no known cerebral metastases, the plasma HCG level greatly exceeded the CSF HCG concentration. The finding of a CSF HCG concentration that approaches or exceeds the plasma value would be a useful screening procedure in localizing a pathologic source of HCG secretion in patients with a suspected hypothalamic tumor. An unexpected finding in the patient who also had a hypothalamic embryonal cell carcinoma and hypocortisolism was an extremely high concentration of a biologically inactive adrenocorticotropic like substance in the CSF.

Alphafetoprotein and human chorionic gonadotropin determination in cerebrospinal fluid. An aid to the diagnosis and management of intracranial germ-cell tumors.

The cerebrospinal fluid (CSF) and serum of six patients with histologically verified intracranial germ-cell tumors were assayed serially for the presence of alphafetoprotein (AFP) and the beta subunit of human chorionic gonadotropin (HCG). Two patients had embryonal carcinomas, two had choriocarcinomas, and two had dysgerminomas. The marker profile for a given tumor in either CSF or serum correlated with the histological diagnosis; that is, embryonal carcinoma produced AFP and HCG, choriocarcinoma produced HCG, and dysgerminoma produced no markers. The marker levels in serum and CSF declined with therapy and rose usually prior to the development of overt clinical symptoms if the patient's tumor recurred. A CSF-to-serum gradient of the marker levels was present in three of four patients, and the serum levels were often normal when the CSF values were elevated. Ventricular marker levels were lower than the lumbar levels in two of two patients. The assay of these biological markers is a sensitive indicator of the success of therapy, and the presence of a CSF-to-serum gradient suggests that the major portion of the neoplasm rests within the central nervous system. A histological diagnosis can be inferred without the necessity of surgery in appropriate clinical contexts.

Cerebrospinal fluid markers in central nervous system metastases from testicular carcinoma.

Serum values of alpha-fetoprotein (AFP) and human chorionic gonadotrophin (HCG) have been used to monitor disseminated testicular carcinoma. Serial measurements of these markers have been used to monitor the response to therapy, to follow the progress of disease, and to detect subclinical recurrences. With increasingly effective chemotherapy for systemic disease, central nervous system (CNS) metastases in testicular carcinoma are becoming increasingly important as a cause of treatment failure. Cerebrospinal fluid (CSF) values of AFP and HCG seem to be important ancillary acids in the neurosurgical management of CNS metastases from testicular cancer. Our preliminary experience with three cases suggests that these CSF markers (plus computerized tomograhic scanning) should be evaluated in patients with this disease.

Brain metastases in malignant teratoma: a review of four years' experience and an assessment of the role of tumour markers.

Between 1973 and 1977, 247 patients with malignant teratoma have been treated in two units in London. Seventeen have developed brain metastases, an overall incidence of 6.2%. The median survival from diagnosis of cerebral metastases is 6 weeks and all patients except one have died. The survivor is disease-free 12 months after completing treatment, which included extensive use of chemotherapy, surgery and radiotherapy. Serum gonadotrophin (HCG) and alpha-foetoprotein (AFP) estimations have been performed in 264 patients as a means of monitoring the effects of therapy. In 42 patients (37 of whom had Stage IV disease) the peak HCG level was greater than 10(4) iu/l, and the incidence of brain metastases in this group was 26%, significantly higher than in the group with HCG levels below 10(4) iu/l, for which the incidence of cerebral deposits was 1.8% (P less than 0.0001). No significant correlation was seen between peak AFP levels and the incidence of brain metastasis. With the aim of improving results by earlier diagnosis, cerebrospinal fluid (CSF) specimens have been examined for HCG and AFP levels in 56 subjects, 9 of whom had brain metastases. A serum: CSF HCG ratio less than 40 is an accurate indication of the presence of brain metastases, and may have considerable predictive value. However, false-negative serum: CSF HCG rations (greater than 40) frequently occur in patients with proven brain deposits. Estimation of AFP in spinal fluid has not contributed to the early diagnosis of brain metastases in malignant teratoma.

Cerebrospinal fluid hormone concentration in the evaluation of pituitary tumors.

Cerebrospinal fluid (CSF) concentrations of corticotropin, growth hormone, thyrotropin, prolactin, luteinizing hormone, and follicle stimulating hormone were measured in 28 patients with various neurologic disorders, in 49 patients with pituitary tumors of whom 22 had suprasellar extension, and in 6 patients with craniopharyngiomas. With the exception of 1 patient with pseudotumor cerebri, CSF adenohypophyseal hormone concentrations were low in patients with neurologic disease and in patients with pituitary tumor without suprasellar extension. In marked contrast, 21 to 22 patients with suprasellar extension of a pituitary tumor and 2 of 6 patients with a craniopharyngioma had elevations of one or more CSF adenohypophyseal hormones. Posttreatment CSF adenohypophyseal hormone levels fell from previously elevated levels in 4 of 5 patients. These data suggest that an elevated CSF adenohypophyseal hormone concentration is a sensitive indicator of suprasellar extension of a pituitary tumor, and posttreatment measurements are useful in determining efficacy of therapy.

Increased polyamine concentrations in the cerebrospinal fluid of patients with brain tumors.

An automated method for the quantitative analysis of the polyamines putrescine, spermidine and spermine in cerebrospinal fluid (CSF) was used to analyze CSF samples from 37 patients with central nervous system (CNS) tumors and from 13 patients without tumors. The putrescine and spermidine concentrations in the CSF of most patients in tumors, particularly those with glioblastomas or medulloblastomas, were elevated when compared with those of non-tumor-bearing patients.