Paraneoplastic autoimmune encephalitis associated with pleomorphic lung carcinoma: An autopsy case report.

Abstract

A 64-year-old man was admitted with acute onset disturbed consciousness. Cerebrospinal fluid analysis revealed pleocytosis and elevated protein, with negative cultures and PCR. Serum antibodies for autoimmune encephalitis were also negative. Brain magnetic resonance imaging (MRI) was unremarkable, but whole-body CT scan showed a tumor in the left lower lung lobe. Bronchial brush cytology demonstrated clusters of malignant cells, and 18 F-fluorodeoxyglucose positron emission tomography showed multiple lesions and increased uptake in the lung tumor. Clinically the patient had a stage IV lung carcinoma, graded as T3N3M1b (OSS). Steroid therapy had limited efficacy, but chemotherapy dramatically improved his neurological symptoms. Therefore, he was diagnosed with paraneoplastic autoimmune encephalitis based on the diagnostic criteria for paraneoplastic neurological syndromes. He died due to disease progression 14 months later. Subsequent postmortem examination revealed white ill-defined nodules in the left lung, with similar nodules in other organs. The brain weighed 1500 g before fixation, and a nodule was observed in the right precentral gyrus. Microscopically, the lung tumor was a pleomorphic carcinoma with an adenocarcinoma component. Multiple areas of micro-softening (≤500 μm) were identified in the cerebral cortex, gray-white matter junction and basal ganglia, and were distributed diffusely in both the limbic and non-limbic systems. Mild lymphocytic infiltrates were observed involving few intraparenchymal vessels. Few tumor metastases were observed in the right precentral gyrus. The multiple micro-softenings may reflect a chronic neuropathologic change of paraneoplastic autoimmune encephalitis. They were too small to be detected by brain MRI. However, these lesions may have the potential to cause the neurological symptoms in the acute phase because they were observed in many anatomical regions. We should pay attention to subtle findings such as micro-softenings when estimating the neuropathology of autoimmune encephalitis. Further investigations are needed to understand the characteristic neuropathology of this condition.