A 64-year-old right handed male with a university degree in arts presented to the neurology service with the chief medical complaint of behavioral changes slowly progressing over the course of the past seven years. Initially the patient experienced an insidious onset of decline in work productivity and gradually stopped working within the space of a year. Meanwhile, his family also noticed a short-term memory deficit primarily evidenced by difficulty remembering messages he was supposed to give to his wife, as well as not being able to name some specific objects. In the ensuing years the symptoms kept worsening while new behavioral and motor changes such as apathy, irritability, aggressiveness, delusional thoughts, psychomotor and gait slowing were contributing to progressive cognitive impairment. There were also reports of paroxysmal events characterized by self-limited episodes of experiencing unpleasant smells that lasted for seconds to a few minutes. 
The patient had consulted several physicians during the course of the disease. He was diagnosed with bipolar disorder by a psychiatrist with the report of accelerated thinking at the time, and was treated with olanzapine and valproate without any significant improvement. A neurosurgeon diagnosed normal pressure hydrocephalus and performed a ventriculoperitoneal shunt with no apparent symptomatic relief.
At a later stage, he presented to the Neurology Department of the University of Sao Paulo with the main complaint of worsening delusional thoughts. The patient stated that his wife had been substituted by a perfect copy of herself, that the house he was living in only resembled his original property, and the city's most famous avenue had been duplicated in two identical copies. 
Past medical history was relevant for Pulmonary Abscess, Hypertension, Depression, Diabetes and former tobacco and alcohol abuse. He had an unremarkable family history. Prescribed medications were Carbamazepine, Olanzapine, Sertraline and Clonazepam.
Neurological examination was remarkable for a cognitive impairment characterized by dysexecutive syndrome (inappropriate digit span, low fluency verbal test, impairment of abstract thinking and problem solving, inadequate clock drawing test), psychomotor slowing and inappropriate behavior. The Mini-Mental State Examination test score was 26 out of 30 (dropped 1 point in spatial orientation and 3 in recall). Glabellar and palmomental primitive reflexes were markedly present as well as inhibitory paratonia, demonstrating frontal release signs. 
Based on initial impressions, the clinical presentation was attributed to LE (short-term memory impairment, temporal lobe seizures and behavioral abnormalities) of protracted course associated with a delusional misidentification syndrome (Capgras Syndrome concomitant to Reduplicative Paramnesia).
The patient was then admitted to the neurology ward for extensive investigation. General laboratory tests were unremarkable, serology for common infectious diseases were negative (HIV, Syphilis, Lyme, Cytomegalovirus, Herpes Simplex), Antinuclear Antibodies (ANA) were positive in high titers (1:2560) but the remaining rheumatologic panel was unrevealing (AntiSm, Anti-Ro, Anti-La, Anti-dsDNA). Brain Magnetic Resonance Imaging (MRI) revealed high signal intensity on T2/ FLAIR in the left temporal pole and left mesial temporal region. Cerebral spinal fluid (CSF) was relevant for moderate lymphocytic pleocytosis (85 cells/mm3), elevated protein levels (116mg/dl), normal glucose levels (56 mg/dl), negative flow cytometry for malignant cells, and negative infectious markers (cultures for bacteria and fungi, Syphilis, Tuberculosis, Herpes Simplex, Varicella Zoster, Cytomegalovirus, Epstein Barr Virus). Positron Emission Tomography (PET) with fluorodeoxyglucose (FDG) disclosed hypermetabolism in the left mesial temporal region and peri-insular cortex, as well as severe and diffuse hypometabolism in frontal, parietal and lateral temporal cortices. Electroencephalography showed diffuse slow waves (theta and delta) without epileptiform activity. 
While the aforementioned initial work-up was being performed, the patient was started empirically on acyclovir, ampicillin and fluconazole for 14 days. Following the negative results for infectious agents associated with the clinical picture, temporal lobe abnormalities on advanced neuroimaging studies and poor response to antimicrobials, the hypothetical diagnosis of Autoimmune LE was strengthened. The patient received methylprednisolone 1 gram daily for five days without significant improvement and investigation for a paraneoplastic syndrome was continued. Tests for autoantibodies associated with neurological paraneoplastic syndromes in serum and CSF were negative (Anti-Hu, Anti-Ri, Anti-Yo, Anti-Ma2, Anti-NMDAR, Anti-VGKC, Anti-GAD, Anti-TPO, Anti-TG). Computed Tomography (CT) of the neck, thorax, abdomen and pelvis disclosed no significant findings. Ultrasound of the testicles was also normal. However, whole-body FDG-PET revealed an anomalous increase in glycolytic metabolism in cervical external inguinal and iliac portacaval lymph nodes. A cervical lymph node biopsy was performed but anatomopathological study showed nonspecific neutrophilic inflammatory reaction and absence of signs suggestive of malignancy. The patient was then discharged for clinical follow-up scheduled over the next few months.
Two months following previous hospital admission, the patient exhibited progressive worsening of cognitive and behavioral symptoms and therefore another work-up for occult malignancy was undertaken. The repeat whole-body CT scan disclosed enlarged mediastinal, hilar, cardiophrenic and axillary lymph nodes. The hypothesis of lymphoproliferative disease was proposed and the patient was admitted to the hematology ward for fine-needle aspiration of the axillary lymph node. Papanicolaou and Giemsa-stained cytology slides, and the cell block preparation from the sample material, showed morphologic features of a large cell lymphoma: intermediate-to-large sized cells, nuclei of different sizes and shapes, clumping artifact of naked nuclei, frequent mitosis and apoptotic bodies. Immunophenotyping showed a B-cell phenotype with a high Ki-67 labelling index (Figure 3). The tumor cells were negative for CD 3, CD 30 and pan-cytokeratin AE1/AE3. In light of these immunohistochemical results and morphologic features, the diagnosis of diffuse large B-cell lymphoma was reached. After the procedure, the patient acquired a nosocomial respiratory infection followed by septic shock and evolved to death.