Methotrexate- induced rheumatoid nodules in the liver and spleen masquerading metastatic malignancy: a case report Maria Kosmidou 1, Paraskeyi Kotsi 1, Georgios. Glantzunis 2, Anna Goussia 3, Leonidas Christu 1, Epameinondas Tsianos University of Ioannina of Ioannina, Medical School, Internal medicine Department 2 University of Ioannina, Medical School, Department of Surgery 3 University of Ioannina, Medical School, Pathology Department

2 Background Methotrexate for rheumatoid arthritis has been shown to exacerbate the growth of rheumatoid nodules. They occur most commonly at pressure points, but have also been reported to occur in unusual locations including CNS, heart and lungs. We report the unusual case of rheumatoid nodules in the liver and spleen masquerading as metastatic malignancy due to a longstanding treatment with methotrexate. Case presentation Αn 80 year old woman with a known history of seronegative rheumatoid arthritis and longstanding treatment with methotrexate and low dose of cortisone, was admitted due to anorexia, fatigue and fever. The radiological assessment using computed tomography (as an outpatient clinic) showed multiple hypodense liver and spleen lesions compatible with metastases and the presence of a mass, inhomogeneously located posterior to the head of the pancreas and portal vein and anterior to the inferior vena cava with concomitant abdominal lymphadenopathy. A.CT scan axial plane after iv contrast media administration, demonstrate several hypotense lesions of different size of the liver and spleen parenchyma B.Same CT scan, different level, reveals the presence of a mass, inhomogeneously located posterior to the head of the pancreas and portal vein and anterior to the inferior vena cava. A B

3 Case presentation Clinical examination revealed only mild arthritis in left wrist and laboratory indices tenfold increase of CRP. Methotrexate was discontinued following by doubling the dose of cortisone (from 4mg/d to 8 mg/d). The patient underwent an extensive diagnostic workup, including gastrointestinal endoscopy, excluding any underlying infection, blood malignancy.Due to a non-diagnostic percutaneous liver biopsy, further investigation was necessary and the patient underwent laparoscopic removal of hypodense liver lesions. Microscopically the liver tissue was occupied by rheumatoid-like nodules with necrotic center impregnated with fibrin and surrounded by lymphocytes and histiocytes arranged in a palisading manner.

4 Case presentation The discontinuation of methotrexate showed complete remission of symptoms and the repeat CT scan after two months showed a significant decrease of the size of the liver and spleen lesion, as well as of the mass and complete disappearance of intra-abdominal lymph nodes. Conclusion We suggest that awareness of longstanding treatment with methotrexate can induce rheumatoid nodules in the liver and spleen with intra- abdominal lymph nodes and thus should be included in the differential diagnosis of patients with RA. References 1.Nakamura T, Inaba M, Yoshinaga T, Takaoka H, Iyama KI. Nodules in patients with rheumatoid arthritis and methotrexate treatment. Mod Rheumatol Jan 25: Chakraborty PP. Methotrexate-induced accelerated nodulosis in seropositive rheumatoid arthritis. J Assoc Physicians India Apr;61(4): Takahashi M, Yamamoto J, Idei M, Nakano Y, Soejima Y, Saito T, Akiba D, Nishizawa S. Multiple intracranial nodules associated with rheumatoid arthritis: case report. Neurol Med Chir (Tokyo). 2014;54(4): C. & D. CT scan, axial planes, after iv contrast media administration, reveal the significant decrease of the size of the liver and spleen lesion,as well as the mass and complete disappearance of intra-abdominal lymph nodes. C D