To report a case of thymoma with five paraneoplastic syndromes and nine autoantibodies.

Thymic tumors are commonly associated with various paraneoplastic disorders, however, finding multiple paraneoplastic disorders in a single patient is unusual. We present a case with nine autoantibodies and at least five paraneoplastic syndromes.

A healthy 37-year-old woman presented with two days of generalized weakness, urinary incontinence, and diarrhea. She had a three-month history of recurrent leg paresthesias, truncal rash, and lip swelling in addition to weight loss, anorexia, delayed responses, and progressively flat affect. Over two weeks, she became immobile, nonverbal, not following commands, but tracking with eyes, and required intubation. MRI brain showed symmetric non-enhancing T2 FLAIR hyperintensities in bilateral frontal and parietal parasagittal cortices, basal ganglia, cingulate gyri, and hippocampi. CSF studies revealed 50 white blood cells (0–5/mm³) with lymphocytic predominance, 3 red blood cells (0–1/mm³), 39 mg/dL protein (15–45), and normal glucose. Workup revealed a non-metastatic sclerosing spindle-cell thymoma. Serum antibody panels were positive for acetylcholine receptor binding, blocking, modulating; striational, GAD65, N- and P/Q-type voltage-gated calcium channel, voltage-gated potassium channel, CASPR2, CRMP-5, and AMPA-R autoantibodies. CASPR2, CRMP-5, and AMPA-R autoantibodies were also found in the CSF. The primary diagnosis was thymoma-associated paraneoplastic encephalitis with features of other paraneoplastic syndromes including myasthenia gravis, Lambert Eaton syndrome, stiff person syndrome, and autoimmune hemolytic anemia. The prodromal rash and paresthesias were possible further paraneoplastic manifestations. While serial imaging and labs showed improvement, she remained clinically unchanged after four weeks of high-dose IV steroids, plasma exchange (PLEX), and IV immunoglobulin. She underwent thymectomy and continued maintenance rituximab and PLEX. After four months, she returned to a near baseline cognitive status.  

Thymomas may present with multiple concomitant paraneoplastic disorders and antibodies. Early diagnosis and treatment are crucial for a favorable outcome.