Primary leptomeningeal T-cell lymphoblastic lymphoma: a rare cause of chronic meningitis.

Primary leptomeningeal lymphomatosis is a rare disease with only a few hundred cases reported. We present a patient with a relatively short history of 25 days of headache followed by diplopia who was found to have primary leptomeningeal T-cell lymphoma without evidence of systemic lymphoma. The patient responded well to chemotherapy along with intrathecal medication and cranial irradiation and returned to a completely normal state of health. Not all chronic meningitis is due to infection or self-limiting inflammatory causes. It is important to consider lymphoma as a differential even in the absence of constitutional features such as loss of weight, appetite, night sweats, lymphadenopathy or hepatosplenomegaly. T-cell lymphoma with only Central Nervous system (CNS) involvement is a rare cause of chronic meningitis, which is eminently amenable to treatment and is fatal if missed.

Eosinophilic meningomyelitis associated with T-cell lymphoma in a cat.

A 12-year-old cat was presented for evaluation of progressive tetraparesis. Magnetic resonance imaging of the cervical spine demonstrated T2-hyperintensity, and contrast enhancement within the C4-C7 spinal cord, with marked meningeal contrast enhancement and segmental nerve root thickening. Lumbar cerebrospinal fluid contained 407 total nucleated cells/µL, with 99% eosinophils. The cat transiently improved with prednisolone, clindamycin, and ivermectin therapy, but subsequently worsened and was euthanized. Necropsy revealed an asymmetric infiltration predominantly of the white matter, meninges, and nerve roots of the C4-C6 spinal cord segments by an unencapsulated, poorly demarcated neoplasm composed of atypical lymphocytes admixed with eosinophils, causing perivascular hemorrhage and lytic necrosis. The neoplastic cells were immunoreactive for CD3, ultimately confirming T-cell lymphoma.

Cytomorphologic and Flow Cytometric Analysis of Cerebrospinal Fluid with T-Cell Lymphoma Involvement: A Retrospective Study of Rare Cases.

OBJECTIVE: To compare the efficacy of conventional cytomorphologic analysis and flow cytometry (FC) in the diagnosis of T-cell lymphoma in the cerebrospinal fluid (CSF). STUDY DESIGN: We performed a retrospective review of CSF samples from 2002 to 2012 that showed involvement of a T-cell lymphoma, either by cytomorphologic analysis and/or FC. Patients' demographics, clinical history and follow-up were assessed. RESULTS: Thirty-nine CSF samples were identified from 9 patients. A definitive diagnosis of T-cell lymphoma involvement was made by cytomorphologic analysis and FC in 6 (15.4%) and 39 (100.0%) specimens, respectively. In specimens with definitive cytopathologic diagnoses, the cytomorphologic features included increased cellularity, a monotonous lymphoid population and large, atypical lymphoid cells. Considering cytomorphologic features only, 9 specimens demonstrated atypical lymphocytes not fulfilling the criteria for malignancy, and 24 specimens were negative for malignancy. CONCLUSIONS: CSF with T-cell lymphoma involvement may yield paucicellular or acellular specimens depending on the volume of the CSF, the time interval between specimen collection and specimen processing and the application of preservative to CSF. The rate of detection of T-cell lymphoma in the CSF by FC is unequivocally higher than by cytomorphologic analysis. Careful attention to clinical history is crucial, as FC testing may be tailored to evaluate for T-cell lymphoproliferative disorders in limited samples.

Flow cytometric immunophenotypic assessment of T-cell clonality by vß repertoire analysis in fine-needle aspirates and cerebrospinal fluid.

Flow cytometric T-cell receptor V(ß) repertoire analysis (TCR-V(ß)-R) is a sensitive method to detect T-cell clonality; however, its implementation in low-cellularity specimens has not been established. We developed a strategy to use TCR-V(ß)-R in cerebrospinal fluid (CSF) and fine-needle aspirate (FNA) specimens. Initially, full TCR-V(ß)-R was evaluated in diagnostic/screening specimens from 8 patients with T-cell neoplasia to determine tumor-specific TCR-V(ß) protein expression. Subsequently, an abbreviated, patient-specific TCR-V(ß)-R evaluation was performed in 17 paucicellular specimens from the patients (8 CSF, 9 FNA) for staging and monitoring of minimal residual disease (MRD). A single cocktail containing 3 anti-V(ß) antibodies (1 tumor-specific and 2 negative controls) in combination with other antibodies chosen to help gate on atypical T cells is highly sensitive and specific for detecting low-level neoplastic T-cell involvement in paucicellular specimens. This TCR-V(ß)-R strategy is valuable in staging and evaluating MRD in patients with T-cell non-Hodgkin lymphoma.

Clinical features and treatment outcomes of isolated secondary central nervous system lymphomas in Miyazaki Prefecture.

BACKGROUND: Secondary central nervous system lymphoma (SCNSL) without extra-central nervous system (CNS) involvement is characterized by isolated secondary CNS relapse in malignant lymphoma patients. SCNSL is a rare disease, and no standard treatment has yet been established. PATIENTS AND METHODS: To elucidate the clinical characteristics and outcomes of SCNSL, we retrospectively analyzed 12 patients (median age 67 years) in Miyazaki prefecture for the last 5 years. RESULTS: The initial histological diagnoses of the patients were diffuse large B-cell lymphoma (DLBCL), mantle-cell lymphoma, and adult T-cell lymphoma in 9, 2, and 1 patient, respectively. We focused on analysis of the 9 SCNSL cases originating from DLBCL. The locations of CNS relapse were the cerebral hemisphere, basal ganglia, and cerebellum in 7, 1, and 1 patient, respectively. Three patients were treated with high-dose methotrexate (HD-MTX) therapy; 4 with whole-brain radiation therapy (WBRTX); and 1 with both HD-MTX and WBRTX. The remaining patients were treated with rituximab. Partial remission was achieved in 6 out of 9 patients (67%); the other 3 patients (33%) did not respond to therapy. Median survival of the 9 patients with CNS relapse was 253 days; 6 of the 9 patients survived for more than 6 months. As of March 2011, 2 HD-MTX group patients but none of the WBRTX group patients were alive. CONCLUSIONS: In this retrospective study, 6 of 9 patients with SCNSL originating from DLBCL survived for more than 6 months. Both HD-MTX and WBRTX had clinical benefits in the treatment of SCNSL.

Flow cytometric immunophenotyping of cerebrospinal fluid specimens.

Flow cytometric immunophenotyping (FCI) is recommended in the evaluation of cerebrospinal fluid (CSF) specimens for hematologic neoplasms. This study reviewed FCI of CSF specimens collected for primary diagnosis (n = 77) and follow-up for known malignancy (n = 153). FCI was positive in 11 (4.8%) of 230 specimens: acute myeloid leukemia, 6; precursor B-acute lymphoblastic leukemia, 2; B-cell lymphoma, 2; and T-cell lymphoma, 1. Positive results were obtained in low-cellularity specimens, including 2 with fewer than 100 events in the population of interest. FCI was indeterminate in 19 (8.3%) of 230 specimens, including 3 with only sparse events, 8 with possible artifact (apparent lack of staining, nonspecific or background staining, and aspirated air), and 8 with phenotypic findings considered insufficient for diagnosis. Indeterminate specimens were often limited by low cellularity and lacked normal cell populations to evaluate for appropriate staining. FCI may be of value in low-cellularity CSF specimens, although the results should be interpreted with caution.

Persistent non-neoplastic gammadelta-T cells in cerebrospinal fluid of a patient with hepatosplenic (gammadelta) T cell lymphoma: a case report with 6 years of flow cytometry follow-up.

Hepatosplenic (gammadelta) T-cell lymphoma (HSTCL) is an uncommon T-cell lymphoma with an aggressive clinical course and poor prognosis. Bone marrow and peripheral blood are frequently involved, with central nervous system involvement less common. We describe a case of a 31-year old man diagnosed with a gammadelta HSTCL in 2003, successfully treated with chemotherapy and allogeneic stem cell transplantation, and followed from 2003 to present. Four-color flow cytometry (FC) was performed on a BD FACSCalibur and data analyzed with CellQuest Pro and FCS Express software. For cerebrospinal fluid (CSF), all cells were acquired due to limited material. Cytological correlation was available on all specimens. Molecular studies for T-cell gene rearrangement were non-contributory. By FC, the diagnostic HSTCL immunophenotype was CD3 (+), CD7 (+), CD2 (+), CD5 (-), CD4 (-), CD8 (-), TCR gammadelta (+). Subsequent CSF FC analysis revealed a distinct population of gammadelta T-cells in all specimens, ranging from <1% to 13% of lymphocytes. Consistently, the gammadelta T-cells exhibited a different immunophenotypic profile from the reported diagnostic immunophenotype; they expressed CD5, and exhibited a heterogeneous pattern of CD8 expression. Comparison to in-house cases from patients with hairy cell leukemia and concomitant increases in non-neoplastic gammadelta T-cells was performed. The persistent gammadelta T-cells from the CSF of the patient with HSTCL were immunophenotypically consistent with non-neoplastic gammadelta T-cells. We describe an unusual case of persistent gammadelta T-cells in the CSF of a patient during 6 years of flow cytometric follow-up after treatment for gammadelta HSTCL. By cytology, non-neoplastic and malignant gammadelta T-cells are often difficult to distinguish. FC analysis helps to make this distinction, even with a limited panel. By FC, the gammadelta-T cells in the CSF of this patient are immunophenotypically consistent with non-neoplastic gammadelta T-cells. Remarkably, this finding is underscored by the patient's unusual clinical picture; he remains well and disease free.

Adrenal extranodal NK/T-cell lymphoma diagnosed by fine-needle aspiration and cerebrospinal fluid cytology and immunophenotyping: a case report.

The cytologic findings of an extranodal NK/T-cell lymphoma (NKTCL) presenting as a large adrenal mass with leptomeningeal involvement diagnosed by CT-guided fine-needle aspiration and cerebrospinal fluid (CSF) cytology are described. The 65-year-old Caucasian patient presented with progressive headache and multiple cranial nerve neuropathies. Magnetic resonance imaging showed leptomeningeal enhancement surrounding the conus medullaris and cauda equine, and a subsequent PET/CT demonstrated a large right adrenal gland mass. Fine-needle aspiration of the adrenal mass showed occasional large pleomorphic cells with prominent nucleoli, moderate amounts of cytoplasm, and rare large cells with sparse cytoplasmic granules admixed with numerous small lymphocytes. Initial flow cytometry from this sample showed no clonal B-cell population. Immunoperoxidase stains performed on the cell block/core specimen showed that the large atypical cells were positive for CD2, CD30, CD43 and CD56, TIA-1, granzyme, and perforin, but for none of the other T-cell markers used (CD3, CD4, CD5, CD8, CD45RO), which stained the abundant background lymphocytes. A CSF specimen showed similar neoplastic cells and flow cytometry showed an NK-cell population with aberrant immunophenotype. The cytologic findings of the neoplastic cells and the extensive panel of immunoperoxidase stains allowed the diagnosis of NKTCL, which was confirmed by the subsequent flow-cytometric immunophenotyping performed on the CSF. This is, to the best of our knowledge, the first case of NKTCL diagnosed by FNA of the adrenal gland and by CSF cytology.

The clinical value of follow-up examinations in childhood T-cell acute lymphoblastic leukemia and T-cell non-Hodgkin's lymphoma.

BACKGROUND: The aim of this study was to evaluate the value of follow-up investigations of T-cell acute lymphoblastic leukemia (T-ALL) and T-cell non-Hodgkin's lymphoma (T-NHL), including cerebrospinal fluid (CSF) examination, bone marrow (BM) aspiration, peripheral blood (PB) count, serum lactate dehydrogenase (LDH) and chest X-rays in patients with an initial mediastinal enlargement. PROCEDURE: We reviewed clinical records of all T-ALL patients from 1987 to 2002 and all T-NHL patients from 1977 to 2002, seen at a single institution. RESULTS: Of 48 T-ALL patients, 15 suffered from a relapse, 6 (40%) were asymptomatic at the time of relapse. T-ALL (13/30) with mediastinal enlargement at first diagnosis relapsed versus 2/16 of those without mediastinal enlargement. However, at relapse, only one patient had a mediastinal mass, which in addition was symptomatic. Of 39 T-NHL patients, 6 patients relapsed. Forty percent of relapsed T-ALL and 17% of relapsed T-NHL were asymptomatic. The seven asymptomatic relapses were detected by CSF (n = 4), BM (n = 2) or blood count (n = 1) examinations. All T-ALL and T-NHL patients with a mediastinal relapse were symptomatic. CONCLUSIONS: This study suggests that routine CSF examinations during treatment can detect relapses of T-ALL and T-NHL before onset of symptoms, which might be of clinical value. Relapses are rarely detected by BM or blood examinations and whether this translates in a clinical benefit is unlikely. Routine chest X-rays are not useful.

Primary central nervous system lymphomas in immunocompetent patients.

Primary Central nervous system lymphoma is a rare non-Hodgkin's tumor of the brain that has been traditionally found in patients with immunodeficiency syndromes. However, there are several immunocompetent patients that have also been reported with this neoplasm. In this group of patients, the mean age of diagnosis is around 60-year old, with a very slight predominance in women. Macroscopically, most of the tumors are unique and mainly located in the supratentorial region in the proximity of the cerebrospinal fluid circulation. The typical histological pattern is a perivascular distribution of tumor cells, within a network of reticulin fibers. Even though they are usually well defined masses, it is not rare to find tumor invasion beyond the macroscopic margin. Coagulative necrosis is not as common as in immunodeficiency-related cases. Immunohistochemistry has demonstrated that most of the tumor cells are B-lymphocytes and the electron microscopic findings do not differ from those reported in systemic non-Hodgkin's lymphomas. There are several histological classifications of these tumors, some of them with recent modifications to facilitate the analysis, but unfortunately, up now with a little or no clinical significance. The diagnosis is based on the histological study of the specimen obtained mainly through a Stereotactic biopsy. The treatment is based on a combination of chemotherapy followed by radiotherapy, but the mortality rate is still high.

[Paraneoplastic opsoclonus-myoclonus syndrome revealing T-cell lymphoma]. / Syndrome opsoclonus-myoclonus paranéoplasique révélateur d'un lymphome T.

BACKGROUND: Nonrhythmic involuntary ocular oscillations and axial and segmentary myoclonia are associated in the opsoclonus-myoclonus syndrome. In adults, a paraneoplastic origin is generally found. We report the first of opsoclonus-myoclonus associated with non-Hodgkin's lymphoma. CASE REPORT: A 66-year-old woman rapidly developed a typical opsoclonus-myoclonus syndrome within a few hours, presenting vertigo, cerebellous ataxia, multidirectional involuntary ocular movements and non-rhythmic axial and segmentary myoclonia. Brain computed tomography and magnetic resonance imaging demonstrated discrete diffuse anomalies of the white substance predominating in the pons. The cerebrospinal fluid showed discrete lymphocytosis. Antineuron antibodies were negative. No cause could be identified until the development 11 months later of pleomorphic T-cell mediastino-cervical lymphoma. The patient responded moderately to a CHOP regimen which had no effect on the opsoclonus-myoclonus syndrome. Death occurred after a 16-month course due to pulmonary complications. DISCUSSION: Neuroblastoma and infectious causes predominate in opsoclonus-myoclonus syndromes observed in children; in adults, the predominant cause is cancer. Antineuron, anti-Ri and anti-Hu antibodies can be evidenced in some cases, arguing in favor of a paraneoplastic mechanism. Recent reports have evidenced MRI anomalies in the pons and the cerebellum, anatomically well correlated with the opsoclonus-myoclonus syndrome. Besides small-cell bronchogenic anaplastic cancer, the possibility of cancer of the breast and uterus, and both non-Hodgkin and Hodgkin lymphoma should be explored, knowing the cancer develops several month after the opsoclonus-myoclonus syndrome.

Primary T cell leptomeningeal lymphoma--successful treatment with systemic chemotherapy.

Primary central nervous system lymphoma (PCNSL) is rare, accounting for only 1-2% of non-Hodgkin's lymphoma, and primary isolated leptomeningeal lymphoma is even rarer. It may create a diagnostic problem, particularly when the tumor cells are of T cell lineage. We herein report a patient with primary T cell leptomeningeal lymphoma. The final diagnosis was confirmed by the cytogenetic study which revealed clonal aberration, isochromosome of long arm of chromosome 7, in the lymphoid cells from CSF. She was treated with a novel protocol of systemic chemotherapy specifically designed for the CNS lymphoma. The regimen consisted of carmustine, vincristine, high-dose methotrexate, etoposide, and methylprednisolone. A total of 5 courses were given and she was still in complete remission at the time of reporting, 21 months after the establishment of diagnosis.

Immunocytological diagnosis of primary cerebral non-Hodgkin's lymphoma.

Four men with primary cerebral non-Hodgkin's lymphoma diagnosed by immunocytological analysis of cerebrospinal fluid (CSF) presented with cranial nerve palsies. All had CSF lymphocytoses and low CSF glucose. The cell phenotypes were two T cell tumours, one B cell, and one null. A review of 13 previously recorded cases of immunocytologically diagnosed CNS non-Hodgkin's lymphoma showed that there were 10 B cell, two T cell, and one null tumour. Overall (17 cases) the cell phenotype distribution was 65% B cell, 24% T cell, and 11% null. High CSF lymphocyte counts were found in 94%, proteinosis in 85%, and low CSF glucose in 87%. In contrast to the B cell tumours, all of the T cell tumours were diagnosed by CSF cytology before being visualised radiologically. It is suggested that all CSF lymphocytes (greater than 5 x 10(6)/ml) should be immunohistochemically typed to permit earlier diagnosis of CNS non-Hodgkin's lymphoma.