Somatic STAT3 mutations in large granular lymphocytic leukemia.
Large granular lymphocyte leukaemia (LGL) is a rare lymphoproliferative T-cell disorder characterised by abnormal CD3?CD8?CD57? lymphocyte infiltration of blood, bone marrow, spleen and liver . It is associated with autoimmune diseases like rheumatoid arthritis (RA) and immune-mediated cytopenias. However, the clinical course is mostly indolent . Treatment is indicated, if patients suffer from symptomatic anaemia, neutropenia or RA. Due to the rarity of the disease therapy remains nonstandardised. Mostly, immunosuppressants like low-dose methotrexate and cyclophosphamide are recommended . Leptomeningeal or CNS involvement of LGL has never been reported in the literature so far. A 63-year-old man with LGL diagnosed 5 years ago suffered from progressive auditory loss until complete deafness since 2 years. Strong visual impairment of the right eye was also noticed at that time. He was intermittently treated for neutropenia with corticosteroids, cyclosporine and cyclophosphamide. On admission, he presented with progressive visual loss of the left eye. No symptoms or clinical signs of the spinal cord were present. Laboratory work-up disclosed anaemia (haemoglobin 83 g/l), but normal leucocytes and thrombocytes. The MRI of the brain showed predominant dural contrast enhancement with no further structural abnormalities (Fig. 1a, b). CSF examination including immunophenotyping revealed T-cell pleocytosis (204 cells/ll; 96 % lymphocytes with characteristic granulation). A clonal rearrangement of the T-cell receptor gamma of the cells derived from the CSF confirmed leptomeningeal LGL infiltration. In the absence of an established therapeutic option with regard to the CNS manifestation the patient underwent cerebral irradiation to a cumulative dose of 30 Gray in 10 fractions. Intrathecal chemotherapy was rejected as the CSF compartment of the optical nerve sheath was found to be less accessible by this treatment modality. Symptoms partially resolved after whole brain radiotherapy and the patient was prevented from becoming blind. After 1 year of follow-up the patient clinically relapsed but was successfully treated with intrathecal liposomal cytarabine for 9 months. Afterwards, treatment was stopped according to further neurological deterioration. 33 months after diagnosis of leptomeningeal manifestation of LGL the patient is still alive, but suffers from progressive neurological symptoms. He is currently treated with best supportive care. T. Hundsberger (&) Department of Neurology, Cantonal Hospital, Rorschacherstr. 95, 9007 St. Gallen, Switzerland e-mail: email@example.com