effect of the gene on tumorigenicity; indeed, the data2 point to nm23


a tumour

suppressor gene. been recognised that metastasis is a complex, multistep process, and the recent elegant demonstration (in animals) that the process can fail at any one of several stages3 serves to illustrate this. It also underlines the necessity of taking as many factors as possible into consideration when interpreting, and extrapolating from, data from such animal models. Unfortunately, this is something that too many such studies of metastasis patently fail to do. It has



Department Surgery, Royal Infirmary, Glasgow G31 2ER, UK, and CRC Beatson Laboratories,



M, Fiers W, Van Roy F. Genetic manipulation of E cadherin expression by epithelial tumour cells reveals an invasion suppressor role. Cell 1991; 66: 107-19 2. Leone A, Flatow U, Richter King C, et al. Reduced tumour incidence, metastatic potential and cytokine responsiveness of nm23-transfected melanoma cells. Cell 1991; 65: 25-35. 3. Aslakson CJ, Miller FR. Selective events in the metastatic process defined by analysis of the sequential dissemination of subpopulations of a mouse mammary tumour. Cancer Res 1992; 52: 1399-405. 1. Vleminckx K, Vakaet L, Mareel

Paraneoplastic limbic encephalitis presenting as acute viral encephalitis SIR,-We report a paraneoplastic encephalitis that mimicked encephalitis. Limbic encephalitis is a rare non-metastatic complication of various tumours, especially small cell carcinoma of bronchus,l and typically presents as a chronic or subacute encephalopathy with perivascular lymphocytic infiltrates, neuronal drop-out, and gliosis.2 The cerebrospinal fluid (CSF) may be normal, have slightly raised protein, or low-grade lymphocytosis.l Our patient, a woman aged 58, was admitted elsewhere with a 4 day history of headache, myalgia, and pyrexia. She was a heavy smoker. She had become drowsy, incontinent, and confused, and had symmetrically brisk reflexes. Temperature was 38°C. Chest radiography and cerebral computed tomography were normal. CSF was turbid, without malignant cells or organisms. Cryptococcal antigen was negative. CSF leucocytes were 570/ml (94% lymphocytes, 6% neutrophils) and erythrocytes 2/ml; glucose was 3-3 mmol/1 and protein 1-3 g/1. Acute viral encephalitis was diagnosed, and on the basis that herpes simplex virus infection was the only encephalitis for which effective chemotherapy was available, the patient was given intravenous acyclovir 10 mg/kg and dexamethasone 8 mg, both 8 hourly. She was transferred to our unit the next day after deterioration in her conscious state and the development of seizures. The patient was deeply unconscious and she required intubation and mechanical ventilation. Intravenous phenytoin was used to control seizures. An electroencephalogram showed polyrhythmic delta and theta activity, occasional sharp discharges, and seizure activity consistent with a diffuse encephalopathy. She died 13 days later. At necrospy the lungs showed centrilobular emphysema and a tiny small cell carcinoma in the right lower lobe with histological lymph-node metastases. The brain had mild generalised oedema. On microscopy there was prominent perivascular lymphocytic cuffmg around the meningeal and intracerebral vessels, a diffuse increase in microglial numbers, and striking neuronal drop-out in the hippocampus. There were no viral inclusions or metastases. The findings were typical of paraneoplastic encephalitis. Although paraneoplastic encephalitis typically presents as a chronic or subacute encephalopathy, it may be fulminant and be clinically indistinguishable from an acute viral encephalitis. The consideration of paraneoplastic encephalitis in the differential diagnosis of sporadic acute encephalitis is important because the disease may respond to chemotherapy.3 acute viral

Intensive Care Unit, Princess Alexandra Hospital,

Woolloongabba, Brisbane Q4102, Australia 1. Bakheit


AMO, Kennedy PGE, Behan PO. Paraneoplastic limbic encephalitis: dinico-pathological correlations. J Neurol Neurosurg Psych 1990; 53: 1084-88. 2. Brashear HR, Caccamo DV, Heck A, Keeney PM. Localization of antibody in the


central nervous system of a patient with paraneoplastic encephalomyelitis. Neurology 1991; 41: 1583-87. den Hollander AM, van Hulst AM, Meerwaldt JD, Haasjes JG. Limbic encephalitis: a rare presentation of the small cell lung carcinoma. Gen Hosp Psychiatry 1989; 11:

Autoimmune haemolytic anaemia associated with transitional cell carcinoma SIR,—Autoimmune haemolytic anaemia (AIHA) associated with carcinoma, especially with non-ovarian carcinoma, is uncommon. We describe mixed warm and cold AIHA associated with transitional cell carcinoma of the bladder/ureter. The patient, a 70-year-old white man, presented with haematuria in December, 1970, and was diagnosed with stage 0 transitional cell carcinoma of bladder. He was treated with local resection, and was not anaemic. In March, 1982, he presented with weakness, fatigue, and dyspnoea on exertion; AIHA was diagnosed. Laboratory values showed haemoglobin 5-4 g/dl, packed-cell volume 18%, reticulocytes 10-1x 109/1, direct Coombs’ positive (4+) for IgG/ C3/C4, indirect Coombs’ positive ( + ) for anti I, cold agglutinin titre 256, and decreased iron and vitamin B12. Viral titres, rheumatoid factor, and anti-nuclear antibody were not remarkable. Urine, which had been previously negative, showed malignant cells. High-dose prednisone was started for a presumptive diagnosis of idiopathic AIHA and gave a reasonable response. In August, 1983, the patient injured his spleen in a motor vehicle accident requiring splenectomy with some improvement in anaemia. Rapid plasma reagin test became positive but fluorescent treponemal antibody remained negative. In December, 1985, transitional cell carcinoma recurred in the right kidney, ureter, and bladder, and was surgically resected. Preoperatively, haemoglobin was 12 g/dl and packed-cell volume was 40%, while the patient received 10 mg prednisone. By March, 1986, prednisone could be discontinued (13 g/dl, 42%). In October, 1990, computed tomography of the abdomen and pelvis revealed extensive lymphadenopathy, which proved to be positive for transitional cell carcinoma by needle biopsy. High-dose prednisone and methotrexate/vinblastine/doxorubicin/cyclophosphamide were started. Rapid plasma reagin was still positive but the titre became 1 postchemotherapy (16 prechemotherapy). Direct Coombs’ test remained positive while the indirect test became negative by the fourth cycle of chemotherapy. Prednisone was tapered to 5 mg per day. Repeat scan revealed almost complete resolution of lymphadenopathy. AIHA was diagnosed after positive cytologies in 1982 and resolved after resection of tumour. It recurred with relapse of tumour and resolved with resolution of tumour by chemotherapy, which suggests a connection between tumour antigen load and AIHA. Several tumour surface antigens of bladder carcinoma were detected, including A, B, H, and T blood group antigens.l,2 It is conceivable that one of the tumour antigens resulted in development of autoantibodies. AIHA and bladder cancer have been associated, but the case was mediated by cold antibody. In our patient, AIHA was mediated by both warm and cold antibodies.’ AIHA associated with carcinoma has been said to be refractory to corticosteroids.4 Our patient had a moderate response to corticosteroids but had more dramatic improvement (reduction in tumour load), initially after resection and subsequently with chemotherapy. A false positive for syphilis in AIHA has been documented,s as was the case for our patient. Again, high rapid plasma reagin titre seems to be related to tumour antigen load. Department of Medicine, Montefiore University Hospital, University of Pittsburgh, Pittsburgh, PA 15213, USA


1. Limas

C, Lange P, Fraley E, et al. A B H antigens in transitional cell tumor of the urinary bladder. Cancer 1979; 44: 2099-107. 2. Coon JS, Weinstein RS, Summers JL, et al. Blood group precursor T-antigen in human urinary bladder carcinoma. Am J Clin Pathol 1982; 77: 692-99. 3. Sokol RJ, Hewitt S. Autoimmune hemolysis and non-ovarian carcinoma. South Med J 1986; 79: 1466. IA, Branch DR, Petz LD. Autoimmune hemolytic anemia with both cold and warm autoantibodies. JAMA 1985; 253: 1746-48. 5. Conley CL, Savarese DM. Biologic false positive serologic tests for syphilis and other serologic abnormalities in autoimmune hemolytic anemia and thrombocytopenic purpura Medicine 1989; 68: 67-84. 4. Shulman

Paraneoplastic limbic encephalitis presenting as acute viral encephalitis.

373 effect of the gene on tumorigenicity; indeed, the data2 point to nm23 being a tumour suppressor gene. been recognised that metastasis is a com...
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