A case of methotrexate-related lymphoproliferative disease showing multiple liver lesions in a patient with rheumatoid arthritis

Abstract

A 66-year-old woman with rheumatoid arthritis (RA) who had been receiving methotrexate (MTX) for 2 years presented with tarry stools. Contrast-enhanced computed tomography (CT) of the abdomen revealed irregular wall thickening in the ileocecal region and multiple low-contrast masses in both lobes of the liver. Lower gastrointestinal endoscopy revealed a type 2 tumor in the ileocecal region with a semi-peripheral ulcer. Histological examination of liver and colon biopsies showed other iatrogenic immunodeficiency-associated lymphoproliferative disorder (Oi-LPD), diffuse large B-cell lymphoma type, with positivity for Epstein-Barr virus DNA. After withdrawal of MTX, the LPD lesions disappeared and the patient achieved remission. We considered this to be a sporadic case of Oi-LPD, diffuse large B-cell lymphoma type, in the liver and colon due to treatment with MTX. There has been no previous report of this condition with simultaneous hepatic and colonic lesions, and the present case is thought to be highly informative in relation to the pathogenesis.

Keywords: Colon; Diffuse large B-cell lymphoma; Liver; Methotrexate-related lymphoproliferative disease; Rheumatoid arthritis.

Fig. 1

Abdominal imaging modalities. Contrast-enhanced computed tomography (CT) showed a mass with enhancement in the ileocecal region (A, arrow), and multiple nodular masses without enhancement in the liver (B) and para-aortic region (C, arrow). Penetrating vessels running through the tumor were detected in the liver (B, arrow). Contrast-enhanced magnetic resonance imaging (MRI) with gadolinium-ethoxybenzyl diethylenetriamine-penta-acetic acid (Gd-EOB-DTPA) showed that multiple tumors in the liver were lower contrast than the liver parenchyma in portal phase (D). T1-weighted images showed low signal in all lesions (E). The coarse lesion was centrally high signal on T2-weighted images (F) and low signal on DWI images (G)

Fig. 2

Lower gastrointestinal endoscopy. Lower gastrointestinal endoscopy revealed a mass in the ileocecal region which was suspected malignant tumor

Fig. 3

Histological findings in the liver and colon specimens. Histological examination showed diffuse proliferation of mostly large lymphoid cells with necrosis (A, B). Immunohistochemically, the liver specimens revealed CD20 ( +) (C), CD30 ( +) (D), CD10 ( +) (E), CD 23 (−) (F), BCL2 (−) (G), BCL6 (−) (H), MUM1 (−) (I), and Ki-67 labeling index 80% (J). EBV encoding RNA (EBER) positivity was detected by in situ hybridization (ISH) (K). Similarly, histology of the colon specimens also revealed CD20 ( +) (L) and EBER-ISH positivity (M)

Fig. 4

Imaging of the abdomen after methotrexate withdrawal. CT of the abdomen four months later revealed spontaneous shrinkage of most of the tumors (A). There has been no sign of recurrence for eight months (B)

Fig. 5

Lower gastrointestinal endoscopy after methotrexate withdrawal. The tumor in the ileocecal region disappeared 8 months later