Case Report Paraneoplastic limbic encephalitis from esophagogastric squamous cell carcinoma successfully managed by radical gastrectomy Orla Mc Cormack, MD,a,b John M. Cooney, MD,c Colin P. Doherty, MD,d Cian Muldoon, FRCpath, FFacPath, RCPI,e and John V. Reynolds, MD, FRCS,a,b Dublin, Ireland
From the Department of Surgery,a St. James’s Hospital, Trinity College Dublin,b Departments of Psychiatry,c Neurology,d and Histopathology,e St. James’s Hospital, Dublin, Ireland
PARANEOPLASTIC NEUROLOGIC SYNDROMES are relatively uncommon immune-mediated disorders of the nervous system that occur as nonmetastatic complications of cancer. Up to 20 distinct neurologic syndromes are described and typically the neurologic symptoms occur before the cancer is diagnosed.1 Paraneoplastic limbic encephalitis (PLE) is one such syndrome. It is often difficult to diagnose, because it can present with a myriad of symptoms including dementia, memory loss, impaired consciousness, depression, hallucinations, paranoid ideations, and bizarre behavior. As with other paraneoplastic neurologic disorders, effective treatment of the primary malignancy may result in resolution of neurologic symptoms and signs. In this report, we present one such case, owing to a locally advanced squamous cell carcinoma (SCC) occupying most of stomach, but probably arising at the esophagogastric junction. CASE PRESENTATION A 72-year-old man with no prior psychiatric history was admitted to a psychiatric hospital with a 2-month history of progressive agitation, paranoid delusions, and anxiety. His illness began when he was on holidays in Italy 1 month before presentation; he felt a man on the trip was trying
Accepted for publication November 12, 2012. Reprint requests: John V. Reynolds, MD, FRCS, Trinity Centre, St James’s Hospital, Dublin 8, Ireland. E-mail:
[email protected]. Surgery 2013;154:638-40. 0039-6060/$ - see front matter Ó 2013 Mosby, Inc. All rights reserved. http://dx.doi.org/10.1016/j.surg.2012.11.014
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to kill him. On admission, he was started on olanzapine, an antipsychotic. He did not improve with a treatment course, became more agitated, and then cognitively impaired, suggesting a delirium. Computed tomography (CT) of his brain was normal, and magnetic resonance imaging of the brain showed early periventricular white matter change consistent with ischemia only. He was transferred to our center for further assessment. He was agitated, confused, not oriented to place or time, and was prone to wander off the hospital ward prompting instigation of 1:1 nursing care. He had visual hallucinations, stating that he could see animals in his room. He also displayed a fluctuating level of consciousness consistent with a delirium. His medications were changed to haloperidol and lorazepam. An electroencephalogram revealed a burst of slow activity suggestive of bilateral cerebral dysfunction. Cerebrospinal fluid from a lumbar puncture was normal for biochemical analysis and negative for cytology. Serum and cerebrospinal fluid antibodies (anti-Hu, anti-Ro, anti-La, anti-Yo, anti-Ri anti-SM, anti-RNP, anti-Jo-1, anti-Scl-70, and antinuclear antibodies) were all negative. On a broader dimension, he was catabolic and had lost >15% of his body weight in 3 months. His hemoglobin was 10.4 g/dL, and his neutrophil count was 19.7. A septic screen was negative. Endoscopy demonstrated a tumor mass commencing at the esophagogastric junction and occupying most of the proximal stomach. Histology revealed an invasive moderately differentiated SCC. A positron emission tomography (PET)-CT scan showed a bulky, 10-cm, soft tissue mass arising from the lesser curve of the stomach (SUVMax 17.5) with
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Fig 1. PET-CT. Intense tracer uptake in a bulky gastric cancer (SUVMax 17.5). (Color version of figure is available online.)
local subcentimeter nodes but no distant metastases (Fig 1). Cytologic assessment of peritoneal lavage fluid at laparoscopy was negative for malignancy. He underwent open total radical gastrectomy with D2 lymphadenectomy and Roux-en-y jejunal anastomosis. A huge mass filling the lumen of the proximal stomach was found. On opening the specimen, the large friable mass was arising just beyond the esophagogastric junction along the lesser curve and extending into lumen (Fig 2). His neutrophil leukocytosis resolved within 48 hours. On postoperative day 10 he commenced oral fluids and progressed to diet rapidly. As he improved physically, his paranoia resolved. His medications were weaned and he was discharged home on postoperative day 21, with full resolution of his neurologic symptoms. Paraneoplastic neurologic disorders are all nonmetastatic, neurologic complications of cancer where no specific etiology (vascular, infectious, metabolic, or treatment related) can be found. They may affect any level of the nervous system
and include retinopathy, limbic encephalitis, epilepsy, opsoclonus-myoclonus-ataxia, rhomboencephalitis, extrapyramidal symptoms, cerebellar degeneration, myelitis, sensory neuropathy, mononeuropathy, motor neuron syndromes, LambertEaton myasthenic syndrome, myasthenia gravis, polymyositis, neuromyotonia, and stiff-person syndrome.1 PLE was first described by Brierley et al in 1960.2 It is a rare disorder characterized by personality changes, irritability, depression, seizures, memory loss, and sometimes dementia. Diagnosis can be difficult and delayed because there are no known serologic markers and magnetic resonance imaging or electroencephalogram may not be helpful. Gultekin et al3 examined the neurologic symptoms and the causal tumors in 50 patients with PLE. On reviewing the literature they found 137 patients with PLE, the most common tumor type being small cell lung cancer (96 cases), followed by testicular germ cell tumors, thymoma, Hodgkin’s lymphoma, and ovarian teratoma. In their cohort, 50% of cases were associated with lung
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ion channels and surface antigens have also been found in this disorder, including antibodies against the voltage-gated potassium channel complex, NMDA receptor, AMPA receptor, and g-aminobutyric acid b.4 These antibodies are found more frequently in autoimmune encephalitis and those patients usually respond to immunomodulation, whereas PLE patients improve only with treatment of the underlying tumor. Gastric SCC is extremely rare and the pathogenic origin is unclear.5 The bulk of the tumor in this case was in the stomach, but it probably arose from the squamous epithelium at the esophagogastric junction. Although there was no antibody or imaging confirmation of PLE in this case, all symptoms resolved with radical surgery. In addition to PLE, paraneoplastic leukocytosis has been associated with gastric SCC. REFERENCES Fig 2. Stomach has been opened longitudinally to reveal the tumor arising from the lesser curve. The mucosa of the stomach in the antrum and along the greater curve is normal. (Color version of figure is available online.)
cancer, 20% with testicular germ cell tumors, 8% with breast cancer, 4% with Hodgkin’s disease, and 4% with ovarian teratomas.3 Several classes of antibodies have been described in association with PLE. The classical onconeuronal antibodies are directed against intracellular antigens. Recently, antibodies against
1. Voltz R. Paraneoplastic neurological syndromes: an update on diagnosis pathogenesis, and therapy. Lancet Neurol 2002;1:294-305. 2. Brierley JB, Corsellys JAN, Hierons R, Nevin S. Subacute encephalitis of later adult life mainly affecting the limbic areas. Brain 1960;83:357-68. 3. Gultekin SH, Rosenfeld MR, Voltz R, Eichen J, Posner JB, Dalmau J. Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain 2000;123:1481-94. 4. Grisold W, Giometto B, Vitaliani R, Oberndorfer S. Current approaches to the treatment of paraneoplastic encephalitis. Ther Adv Neurol Disord 2011;4:237-48. 5. Amuluru K, Gupta H. Primary squamous cell carcinoma of the stomach: a case report. J Gastrointest Cancer 2010;41:24-6.
