Case Presentation: A 36-year-old man with human immunodeficiency virus (HIV) on antiretroviral therapy presented with an anterior mediastinal mass on computed tomography (CT). A biopsy was not concerning for a malignant or infectious process, and the mass was monitored with routine imaging. Two years later, he presented with neck weakness, diplopia, and dysphagia concerning for myasthenia gravis. Medical workup found a positive anti-acetylcholine receptor antibody, and a biopsy of his mediastinal mass was consistent with thymoma. CT imaging demonstrated implants along the right hemi-diaphragm consistent with pleural metastases. He received a partial course of intravenous immunoglobulin but did not follow-up for radiation or chemotherapy.Four years after initial presentation, he returned with chronic diarrhea and failure to thrive. His stool was watery, non-bloody, and associated with abdominal pain. He had a pruritic rash involving his trunk, buttocks, extremities, palms, and soles. Clinical examination revealed pink papules with scale, coalescing into plaques involving 60% total body surface area. His abdominal examination was benign, and there was no pathologic lymphadenopathy. Laboratory findings were remarkable for a CD4 count of 605 cells/mm3 and an undetectable viral load. The white blood cell count was 11.99 x109/L, and liver enzymes were normal. Antinuclear antibody titer was 1:2560. Anti-SSA, anti-SSB, anti-Smith, anti-SCL-70, anti-Jo-1, anti-RNP, and calcium channel binding antibody were negative. Stool cultures for Salmonella, Shigella, Campylobacter, Clostridium difficile toxin, Cryptosporidium, and ova and parasites were negative. Cultures and serologies for Legionella, Nocardia, Pneumocystis jiroveci, Histoplasma, Aspergillus, Cryptococcus, and acid-fast bacilli were negative. Esophagogastroduodenoscopy and colonoscopy showed gastritis involving oxyntic and antral mucosa and colitis with prominent apoptosis. A skin biopsy revealed vacuolar interface dermatitis with acanthosis and numerous epidermal necrotic keratinocytes. Direct immunofluorescence to evaluate for paraneoplastic pemphigus was negative for IgG, IgA, IgM, and C3 deposits.

Discussion: Paraneoplastic syndromes result from tumor secretion of peptides or hormones or immune cross-reactivity. They most commonly affect the endocrine, neurologic, dermatologic, and rheumatologic systems and may manifest prior to diagnosis of malignancy or with an established malignancy. An estimated 8% of individuals with cancer have a paraneoplastic syndrome. This patient presented with a diffuse rash and chronic diarrhea in the setting of HIV and thymoma. Biopsies demonstrated dermatitis, gastritis, and colitis, consistent with multi-organ autoimmune syndrome. Thymoma-associated multi-organ autoimmunity (TAMA) is a rare paraneoplastic syndrome that mimics graft-versus-host disease (GVHD). It can affect the liver, skin, and gastrointestinal tract and histologically resembles GVHD.

Conclusions: Physicians should maintain a high index of suspicion for TAMA in patients with cutaneous eruptions, chronic diarrhea, and/or abnormal liver enzymes in the setting of thymoma. More broadly, physicians should consider paraneoplastic syndromes to explain a constellation of seemingly disjointed symptoms in the setting of malignancy or prior to a diagnosis.