Diagnosis of primary cerebral lymphomas: possible value of PCR testing in equivocal cases requiring rebiopsy.

INTRODUCTION. Rebiopsy rates as high as 12% have been reported in previous studies of Primary Central Nervous System Lymphoma (PCNSL). This can lead to secondary operations, increasing risks of morbidity to the patient and costs for the NHS. Polymerase Chain Reaction (PCR) testing for clonality in haematological malignancies has been applied to cases of lymphoma outwith the central nervous system (CNS), but is less commonly used in the diagnosis of CNS lymphomas. Clonality in B- and T-cell populations may indicate the presence of malignancy. We aimed to identify factors to reduce the rebiopsy rate in PCNSL. METHODS. We examined a cohort of 102 suspected cerebral lymphoma cases biopsied at Frenchay Hospital, Bristol over a 10-year period (2000-2010). Clinical data, including age, sex, location, pre-biopsy steroid use, the need for rebiopsy and histological diagnosis, were collected. We retrospectively reviewed rebiopsied cases and they subsequently underwent PCR testing for clonality. RESULTS. Overall, 96/102 (94%) cases achieved a histological diagnosis after one or more biopsies. 81/96 (84%) of these were lymphomas involving the brain and 15/96 (16%) were spinal lymphomas. The majority of these were B-cell lymphomas (95/96 (99%)), with one case of peripheral T-cell lymphoma (1/96 (1%)). Due to insufficient histological evidence of PCNSL after the first biopsy, 9/102 (9%) of cases had required rebiopsy. In 7/9 (78%) of these cases, we undertook PCR testing for clonality on tissue from the first biopsy. We found 3/7 (43%) cases were monoclonal for B or T populations, raising the possibility of PCNSL. CONCLUSIONS. We recommend that all CNS lymphoproliferative lesions be assessed by haematopathologists, with the inclusion of PCR testing particularly in equivocal cases. This would reduce the number of patients going for rebiopsy and reduce the patient morbidity and costs for the NHS.

15q overgrowth syndrome: a newly recognized phenotype associated with overgrowth, learning difficulties, characteristic facial appearance, renal anomalies and increased dosage of distal chromosome 15q.

Trisomy and tetrasomy of distal chromosome 15q have rarely been reported. Although most of the described patients have some learning difficulties and are overgrown, the phenotype associated with distal trisomy/tetrasomy 15q is uncertain due to the small numbers of reported cases and the common co-occurrence of additional chromosome deletions in many patients with trisomy 15q. We present five individuals with overgrowth, learning difficulties and increased dosage of distal 15q. Partial trisomy 15q was identified in four of these cases. Two were generated through recombination of a parental pericentric inversion and two were generated through malsegregation of a maternal balanced 14;15 reciprocal translocation. In all four cases the trisomy can be considered "pure" as the 14p and 15p monosomies will exert no phenotypic effect. Partial tetrasomy 15q, as the result of an analphoid supernumerary chromosome derived from an inverted duplication of distal 15q, was identified in the fifth patient. In addition to the overgrowth and learning difficulties, all five had a characteristic facial appearance and three had renal anomalies. The gestalt consists of a long, thin face with a prominent chin and nose. Renal anomalies included renal agenesis, horseshoe kidney, and hydronephrosis. We provide further support for a distinct "15q overgrowth syndrome" caused by either trisomy or tetrasomy resulting in increased dosage of distal 15q. In addition we propose that renal anomalies and a distinctive facial appearance be considered major features of this condition.

Nociceptin/orphanin FQ modulates human T cell function in vitro.

Although nociceptin/orphanin FQ (N/OFQ) and its receptor (ORL-1) are widely distributed throughout the immune system, its role has yet to be elucidated. This study shows that N/OFQ (10(-14)-10(-12) M) modulates T cell activation by up-regulating activation marker expression, e.g. CD28, leading to enhanced proliferation and modulation of TNFalpha secretion. However, on re-stimulated T cells N/OFQ causes inhibition of proliferation, which could be linked with N/OFQ up-regulating CTLA-4 expression. We have also shown that some of these effects are partly prostaglandin-dependent and that N/OFQ induces prostaglandin synthesis. This report suggests that N/OFQ could exert a key modulatory role in human T cell functions.