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.

A Case of a 4-Year-Old Female with a Primary Spinal Malignancy Presenting with Froin's Syndrome.

We report the case of a 4-year-old female with a primary extradural intramedullary atypical teratoid/rhabdoid tumor (AT/RT) leading to a middle cerebral artery (MCA) infarct and Froin's syndrome. She presented with a 6-pound weight loss over the previous week, as well as a decreased urinary output and an altered mental status. She underwent a brain MRI that revealed a left MCA infarct, mild ventriculomegaly, and bilateral internal carotid artery, M1, and A1 stenosis. An external ventricular drain (EVD) was placed due to increased intracranial pressure. Cerebrospinal fluid (CSF) was analyzed via lumbar puncture that revealed extremely elevated protein. However, CSF sampled from the EVD was completely normal, a phenomenon called Froin's syndrome. The following day, she developed a right MCA infarct. Her grim prognosis was discussed with her family and care was eventually withdrawn. The patient underwent an autopsy which confirmed a spinal AT/RT. To our knowledge, this is the first reported case of stroke and Froin's syndrome as the initial manifestations of a primary spinal AT/RT with a late onset of spinal cord compression due to tumor obstruction.

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.

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.

Establishment of atypical-teratoid/rhabdoid tumor (AT/RT) cell cultures from disseminated CSF cells: a model to elucidate biology and potential targeted therapeutics.

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system neoplasm that usually affects infants and young children. In this report, we describe culture conditions that enabled the sustained growth of tumor cells obtained from the cerebrospinal fluid (CSF) of an infant with AT/RT. These cells retained the morphological and biomarker characteristics of the original tumor. A screening of receptor tyrosine kinases identified the presence of phosphorylated ErbB4, Insulin-R, PDGFR and IGF-IR, which appear to depend on Hsp90 to maintain their active form. IGF-IR activity is consistent with data from other established AT/RT cell lines. Inhibition of IGF-IR by the small molecular weight inhibitor AEW541 led to growth suppression of cultured AT/RT cells. In addition, neutralizing antibodies to IGF-II also inhibited the growth of these cells suggesting a potential autocrine function for this cytokine. We also compared cultured AT/RT cells to established cell lines to identify consistent drug sensitivity patterns among these cells. In addition to previously described cell lines and xenograft models, continuous culture of CSF derived cells may also provide an effective way to study the biology of AT/RT and to identify potential targets for future therapeutics for this tumor.

Rhabdoid meningioma: cytopathologic findings in cerebrospinal fluid.

Rhabdoid meningioma is a recently described, rare, WHO Grade III intracranial tumor with an aggressive growth pattern and increased risk of recurrence. We describe the cytopathologic findings on cerebrospinal fluid of one such case in a 26-yr-old female who underwent resection of a left temporo-parietal mass. Cerebrospinal fluid contained abundant malignant cells with a prominent "rhabdoid" phenotype, i.e., large cells, eccentric nuclei, single prominent nucleoli, and dense eosinophilic cytoplasm. Although rhabdoid meningioma has a characteristic cytomorphology, the differential diagnosis of this tumor would involve metastatic adenocarcinoma, metastatic malignant melanoma, and other tumors with "rhabdoid" features (such as an atypical teratoid/rhabdoid tumor).

Evidence of recurrent atypical meningioma with rhabdoid transformation and expression of pyrogenic cytokines in a child presenting with a marked acute-phase response: case report and review of the literature.

Children presenting with acute systemic illnesses that lack specific clinical or serological defining features may be diagnosed as having a chronic infection, an atypical systemic vasculitis or a connective tissue disease, but often turn out to have occult neoplasias. Cytokines have been implicated in causing many of the systemic effects in such cases. In this study, we describe the case of a 9-year-old boy presenting at an interval of 18 months with a marked acute-phase response due to a recurrent atypical meningioma with rhabdoid transformation of the tentorium cerebelli. Resection of the recurrent tumor was curative. We evaluated in detail the local and systemic production of cytokines released by the primary and the recurrent tumor. Blood and CSF samples were taken pre-, intra-, and postoperatively, and the production of IL-6, IL-1beta, and TNF-alpha was measured by enzyme-linked immunosorbent assays (ELISA). The level of IL-6 in CSF was about 150-fold increased before tumor resection, normalizing postoperatively. On the contrary, the levels of IL-1beta and TNF-alpha in CSF and of IL-6, IL-1beta, and TNF-alpha in serum were pre-, intra-, and postoperatively within normal limits. Cytokine production was also evaluated immunohistochemically, and confirmed strong IL-6 and TNF-alpha expression in the primary and the recurrent tumor, while expression of IL-1beta was lacking. The scattered MHC class II- and leukocyte common antigen (LCA)-expressing inflammatory cells, which were infiltrating exclusively the tumoral stroma, had no detectable cytokine immunoreactivity. We conclude that chronic IL-6 and TNF-alpha production by the tumor cells in this patient was responsible for the severe systemic illness with which he presented.

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.