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1/225. Implantation metastasis of primary central nervous system lymphoma complicating radiotherapy outcome.

    Computed tomography-guided stereotactic biopsy is commonly used in the diagnosis of brain lesions. An uncommonly reported risk of the procedure is the potential of implantation metastasis. This phenomenon has been reported in central nervous system malignancies. Although the role of prophylactic local radiotherapy at biopsy sites is well recognized in solid tumors, it has not been reported to occur after stereotactic biopsy of a brain tumor. The authors report a case of locally progressive primary central nervous system lymphoma at an unsuspiciously underdosed biopsy site complicating radiotherapy outcome. ( info)

2/225. Exclusive CNS involvement by lymphomatoid granulomatosis in a 12-year-old boy: a case report.

    BACKGROUND: lymphomatoid granulomatosis [LYG] is an angiocentric, angiodestructive disease at the higher grade end of the spectrum of angiocentric immunoproliferative lesions. It primarily involves the lungs, but it may also involve several extrapulmonary sites including the central nervous system (CNS), skin, and kidneys. CASE DESCRIPTION: Clinical presentation, radiology and treatment of LYG in a 12-year-old male child with multiple intracranial extraaxial lesions is described. A 12-year-old boy presented with sudden onset of left focal motor seizures with associated history of headache and vomiting. Computerized tomographic scan of the brain suggested high-density, bilateral, parietal extraaxial lesions. On magnetic resonance imaging, the lesions were iso- to hyperintense on T1-weighted images and hyperintense on T2-weighted images. The lesions were excised in two stages and histopathological examination confirmed the diagnosis. CONCLUSION: LYG seldom involves the CNS exclusively. The present case demonstrates exclusive CNS involvement by LYG in a young boy. ( info)

3/225. Chronic lymphocytic leukaemia with symptomatic diffuse central nervous system infiltration responding to therapy with systemic fludarabine.

    B-cell chronic lymphocytic leukaemia is an indolent disease characterized by the insidious accumulation of small mature-appearing lymphocytes in the peripheral blood, bone marrow and lymphoid tissues. Direct symptomatic invasion of the central nervous system is exceedingly rare and, to our knowledge, only three cases histologically confirmed as true chronic lymphocytic leukaemia have been reported in the literature. We describe the first case of early Rai stage B-cell chronic lymphocytic leukaemia presenting with symptomatic infiltration of the brain and spinal cord which could be demonstrated radiographically by magnetic resonance imaging. The diagnosis was confirmed by examination of peripheral blood, cerebrospinal fluid, brain and bone marrow biopsies, both morphologically and immunophenotypically by means of flow cytometric analysis. The patient demonstrated a complete response to therapy with standard-dose systemic fludarabine and remains in complete remission 6 months after completion of therapy. ( info)

4/225. central nervous system involvement in patients with mantle cell lymphoma.

    In small cell lymphomas, central nervous system (CNS) involvement has been considered to be very rare. Mantle cell lymphoma (MCL) is a distinct subtype of non-Hodgkin's lymphomas consisting of small or intermediate lymphatic B-cells. It has a poorer prognosis than the other small cell lymphomas. Only a few MCL patients with CNS involvement have been reported in the literature to date. We analyzed retrospectively the incidence, clinical characteristics, and outcome of CNS involvement in 94 patients with confirmed MCL treated at one center from 1980 to 1997. Four of the 94 patients (4%) developed CNS lymphoma during the median follow-up of 51 months. The diagnosis was based on clinical, cytological and radiological findings. CNS involvement appeared at 4.6, 56, 66, or 86 months from the diagnosis of MCL. All patients had neurological symptoms and a leukemic disease; two cases were seen with a blastoid morphology. Malignant lymphatic cells were detected in spinal fluid in all cases and parenchymal infiltrations in brain in two. All patients were treated with intrathecal chemotherapy, without response. survival time after diagnosis of CNS lymphoma ranged from 18 to 55 days. At diagnosis, no adverse prognostic factors predictive of CNS lymphoma were found. CNS involvement was associated with a progressive leukemic disease as a late event or a blastoid transformation. The prognosis of MCL patients with CNS involvement is poor. ( info)

5/225. Extramedullary disease in acute promyelocytic leukemia.

    All-trans retinoic acid (ATRA) is currently recommended as standard treatment for acute promyelocytic leukemia (APL). However there has been increasing concern that ATRA is associated with unusual sites of relapse. Although there is insufficient evidence so far to substantiate this, we review the potential mechanisms by which ATRA may increase the incidence of extramedullary and, in particular, central nervous system (CNS) relapse. ( info)

6/225. Atypical teratoid/rhabdoid tumor of the CNS: cytopathology and immunohistochemistry of insulin-like growth factor-II, insulin-like growth factor receptor type 1, cathepsin d, and Ki-67.

    insulin-like growth factor (IGF)-II is a potent growth factor, normally controlled by a number of other factors, including IGF binding proteins and IGF binding protein proteases. In general, the latter increase the bioavailability of IGF by cleaving IGF binding proteins. cathepsin d (an IGF binding protein protease) was also implicated in tumor invasion. Although IGF-II was implicated in the pathogeneses of various childhood neoplasms, its significance in the pathogenesis of atypical teratoid/rhabdoid tumor of the central nervous system (ATRT-CNS) was not studied to date. We present clinicopathologic features of two cases of ATRT-CNS. In addition, formalin-fixed, paraffin-embedded tissue sections were stained immunohistochemically for IGF-II, IGF receptor type 1, cathepsin d, and Ki-67. Both tumors demonstrated diffuse strong cytoplasmic positivity for IGF-II, diffuse cytoplasmic and focal membranous positivity for IGF receptor type I, and diffuse cytoplasmic positivity for cathepsin d. The Ki-67 labeling indices were 10.0% and 1.4%. We conclude that ATRT-CNS cells express both IGF-II and IGF receptor type 1, supporting the hypothesis that autocrine/paracrine stimulation of cell growth by IGF-II might be one mechanism involved in ATRT-CNS tumorigenesis. cathepsin d expressed by the tumor cells might also be involved in both tumor cell invasion and growth. The exact pathogenesis of ATRT-CNS remains to be elucidated. ( info)

7/225. Germline hMSH2 and differential somatic mutations in patients with Turcot's syndrome.

    Turcot's syndrome is characterized clinically by the occurrence of primary brain tumor and colorectal tumor and has in previous reports been shown to be associated with germline mutations in the genes APC, hMLH1, and hPMS2. Here we describe three patients with Turcot's syndrome, each having colorectal adenocarcinoma and malignant glioma. All the colorectal and brain tumors from these patients showed replication errors in most of the microsatellite loci investigated. Search for underlying germline mutations in the nucleotide mismatch repair genes revealed three different hMSH2 mutations. All colorectal tumors showed a frameshift in the A(10) tract in the coding sequence of the transforming growth factor beta type II receptor (TGFBRII) gene, but no such change was detected in any of the brain tumors. frameshift mutation in the BAX gene was found in one colon carcinoma and mutations in insulin-like growth factor type II receptor (IGFIIR) gene in one glioma. Our data have broadened the possible mutation spectrum of patients with Turcot's syndrome. The difference in the mutation spectrum of TGFBRII, BAX, and IGFIIR between brain and colorectal tumors in these individuals suggests that the mutator phenotype may target different pathogenic pathways in the oncogenic process of the two organs. ( info)

8/225. Chronic lymphocytic leukaemia presenting with central nervous system involvement.

    A 68-year-old man presented with hemiparesis, lymphocytosis, and cerebral lesions on MRI. flow cytometry of blood, bone marrow and cerebrospinal fluid showed B-CLL lymphocytes with bright CD20 expression, sIg, and absence of CD23 antigen. fluorescence in situ hybridisation showed trisomy 12 in 50% of analysed peripheral mononuclear cells. The patient died 6 months after the diagnosis. Rapidly progressive and fatal course of the disease was consistent with known bad prognostic significance of CD20 bright expression and trisomy 12. ( info)

9/225. Gliomatosis cerebri: cytologic and autopsy findings in a case involving the entire neuraxis.

    We describe the case of a 7-year-old girl who was clinically diagnosed as having a pontine glioma based on magnetic resonance imaging studies. Neoplastic cells were identified upon cytologic examination of cerebrospinal fluid. autopsy studies revealed an anaplastic astrocytoma (WHO grade III) diffusely infiltrating the cerebral hemispheres, brain stem, cerebellum, leptomeninges, and spinal cord to the level of the conus medullaris. The Ki-67 labeling index focally approached 30%. Although many of the neoplastic cells displayed elongated twisted nuclei reminiscent of microglia, these cells stained intensely for glial fibrillary acidic protein, supporting an astrocytic origin. Unusual features of this case of gliomatosis cerebri include involvement of the entire central neuraxis, correlation with pre-mortem lumbar puncture cytology, and a markedly elevated Ki-67 labeling index. ( info)

10/225. Primary anaplastic large cell lymphoma of the central nervous system.

    central nervous system (CNS) involvement is extremely rare in anaplastic large cell lymphoma (ALCL), and in children only isolated cases have been reported, mainly as secondary CNS involvement. A case of fatal primary ALCL of the brain in a 13-year-old white boy is reported. magnetic resonance imaging of the brain showed decreased absorption in T1- and T2-weighted image showed a hyperintense signal in the right parietal lobe and 2 masses in the right frontal lobe. A frontal lobe biopsy showed a pleomorphic neoplasm diffusely infiltrating the brain parenchyma and composed of large cells with bizarre, often polylobated or horseshoe-shaped nuclei. Immunohistochemical stains showed diffuse strong positivity for CD30, anaplastic lymphoma kinase protein (ALK-1), p80, leucocyte common antigen, CD45RO (UCHL1), and focal staining for epithelial membrane antigen. Immunostainings for cytokeratins, monocyte-macrophage, and B-cell markers were negative. Epstein-Barr virus latent membrane protein was not detected. To the best of our knowledge, there is only 1 case of primary ALCL of the brain in childhood previously reported in the literature. Before the biopsy, both cases were clinically misdiagnosed as mycobacterial CNS infection. Therefore, primary ALCL should also be included in the differential diagnosis when a mycobacterial CNS infection is suspected in pediatric patients; a careful cytological evaluation of the cerebrospinal fluid or cerebral biopsy are essential for an accurate diagnosis. ( info)
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