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Journal of Clinical Oncology, Vol 26, No 26 (September 10), 2008: pp. 4353-4355 © 2008 American Society of Clinical Oncology. DOI: 10.1200/JCO.2008.16.0879
Sudden Psychotic Symptoms in a 28-Year-Old Male With ThymomaDepartment of Bone Marrow Transplantation, Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem, Israel
Department of Psychiatry, Hadassah University Hospital, Jerusalem, Israel
Department of Bone Marrow Transplantation, Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem, Israel
Department of Pathology, Hadassah University Hospital, Jerusalem, Israel
Department of Radiology, Hadassah University Hospital, Jerusalem, Israel
Department of Bone Marrow Transplantation, Cancer Immunotherapy and Immunobiology Research Center, Hadassah University Hospital, Jerusalem, Israel A 28-year-old previously healthy male experienced sudden auditory (hearing music in peoples’ voices) and visual hallucinations along with incoherent speech. Bizarre disorganized movements of the limbs were observed, but no chorea, ataxia, or automatisms were observed. These episodes, which lasted several minutes, recurred during the following days with increasing severity. In our emergency room he was in an acute, fluctuating psychotic state with ideas of self-reference (eg, things he heard on the radio were referring to him) and suspiciousness. His remaining physical examination and all laboratory tests were unremarkable, including toxicity tests, antibody screening, and EEG. He denied the use of drugs, medications, or alcohol. His own and his family's psychiatric histories were unremarkable. Routine chest x-ray showed a small mediastinal shadow compatible, according to the chest computed tomography (CT) scan, with thymoma, which is often associated with paraneoplastic syndrome (PNS). Axial fluid-attenuated inversion recovery magnetic resonance imaging (FLAIR MRI) scan of the brain showed subtle mesial temporal hyperintensity (Fig 1A, chest x-ray shows a suspected mass between the left hilum and the aortic knob [arrow]; Fig 1B, enhanced axial chest CT shows an elongated mass antero-lateral to the main pulmonary artery, compatible with thymoma [arrow]; and Fig 1C, the subtle hyperintensity of the axial cerebral FLAIR MRI through the medial temporal lobes suggests an inflammatory or degenerative process [arrows; more on the left], possibly limbic encephalitis, or PNS). Antipsychotic treatment with oral olanzapine 5 mg/d significantly improved his psychotic symptoms within a few days. Total thymectomy was then performed, which confirmed the diagnosis of thymoma WHO type B2 (Fig 2, type B2 thymoma composed of a mixture of neoplastic epithelial cells and non-neoplastic lymphocytes; Fig 2A, there is a perivascular space [arrows], surrounded by palisaded epithelial cells, typical of B2 thymoma [hematoxylin and eosin; magnification x200]; Fig 2B, the neoplastic epithelial cells are immunoreactive for cytokeratin [membranous stain; magnification x200]; Fig 2C, tdt-positive immature T-cells of thymic cortical origin are seen between neoplastic epithelial cells [nuclear stain; magnification x200]). He recovered fully from his psychotic symptoms after thymectomy, and olanzapine was discontinued 30 days after the operation. Over a follow-up period of more than 2 years, during which the patient received six monthly treatments of intravenous immunoglobulins 30 g, his clinical condition remains unremarkable without any additional treatments.
Sudden onset of repeated episodes of unexplained psychotic symptoms without other complaints may mislead a general practitioner to refer his patient for psychiatric care without further diagnostic investigation. However, other diagnostic etiologies should be investigated, including epilepsy (especially temporal lobe epilepsy), Cushing syndrome, or factitious disorders. Our patient's previous psychiatric history, laboratory tests, EEG, and abdominal CT scan were all normal, while the imaging studies of his chest were indicative of thymoma, a diagnosis later confirmed by biopsy from the mass. PNS fully explained his clinical and radiological condition. This diagnosis was confirmed by the resolution of all symptoms after thymectomy, without other treatments. PNS, an unexplained symptom complex that precedes the diagnosis of underlying malignancies in 60% of cancer-bearing patients, is often found in association with thymoma1,2 and other tumors.3 PNS can present with mucocutaneous,4 hematologic,5 endocrine-metabolic,6 and nephrologic7 symptoms, and with manifold neurological manifestations8-10 including cerebellar degeneration, schizophreniform,11 and, rarely, neuropsychiatric symptoms.12 In the pathogenesis of PNS,13 auto-antibodies against the tumor are produced (Table 1),14,15 which also damage structures of the neural system.16 The underlying tumor is often small, difficult to detect, and clinically inactive in the presence of PNS17—a remarkable effect of the body's endogenous immune function on cancer. The causative auto-antibodies are often not identified, as was the case with our patient. Since fluctuating psychotic symptoms might be associated with a tumor, they should not be explained away as being due to a psychiatric disorder, and the diagnosis of PNS should be considered. In our case, routine chest x-ray provided the clue which finally led to the correct clinical diagnosis. While the concomitant finding of limbic encephalitis by FLAIR MRI was consistent with PNS,18,19 there are no definite diagnostic findings for PNS per se.20 Therefore, the diagnostic work-up should focus on detecting the underlying tumor; testing for tumor markers is a crucial diagnostic tool in this process. In our patient it was difficult to distinguish the fluctuating psychotic symptoms clinically from other disorders, but their sudden onset and the radiological finding of thymoma were indicative of an atypical presentation of neurological PNS,21 and the patient's clinical course indeed supported this diagnosis retrospectively. Early diagnosis of PNS is crucial, as it may allow for prompt curative treatment of the underlying malignancy with—as in our patient—an excellent long-term outcome.
AUTHORS’ DISCLOSURES OF POTENTIAL CONFLICTS OF INTEREST The author(s) indicated no potential conflicts of interest.
ACKNOWLEDGMENTS We thank Jacob Bar and Lilly Schaechter for their help in preparing this manuscript. REFERENCES
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Copyright © 2008 by the American Society of Clinical Oncology, Online ISSN: 1527-7755. Print ISSN: 0732-183X
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