Journal of Medical Cases, ISSN 1923-4155 print, 1923-4163 online, Open Access
Article copyright, the authors; Journal compilation copyright, J Med Cases and Elmer Press Inc
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Case Report

Volume 4, Number 9, September 2013, pages 627-632


Hypercalcemia and Peripheral T-Cell Lymphoma-Type Lymphoproliferative Disorder Associated With Methotrexate in a Rheumatoid Arthritis Patient

Figures

Figure 1.
Figure 1. Enhanced chest and abdominal CT series. a). Chest CT on 3 HD showing enlarged left axillary lymph nodes (open triangle). b). Abdominal CT on 3 HD showing multiple low-contrast nodules in the enlarged spleen (arrow). c). Chest CT on 19 HD showing left axillary lymph nodes (open triangle) were smaller compared to the findings of chest CT on 3 HD. d). Abdominal CT on 19 HD showing low-contrast nodules have disappeared from the spleen (arrow). Abbreviations: HD; hospital day.
Figure 2.
Figure 2. Aspiration cytology of left axillary lymph nodes. Aspiration cytology showing large atypical cells (arrows) with big nuclear body indicative class V. Original magnification, × 400, Papanicolaou stain.
Figure 3.
Figure 3. Pathology of axillary lymph nodes. Histology of biopsy specimens (HE staining) showing angioimmunoblastic lymphadenopathy-type lymphoproliferative disorder (a) including cells that were diffusely positive for T-cell marker (CD3) (b), and a few cells that were weakly positive for B-cell marker (CD20) (c) immunohistochemically and negative for EBV-encoded RNA (EBER-1) by in situ hybridization staining (d). These pathological features mimic peripheral T-cell lymphoma. Original magnification, × 400.
Figure 4.
Figure 4. Proposed pathogenic relationship among RA, MTX-LPD, hypercalcemia and general malaise in our patient. We propose that the immuno-suppressive state induced by MTX treatment for RA reactivated latent EBV and possibly coincidentally was associated with PTCL-type MTX-LPD. Hyperproinflammatory cytokinemia resulting from both high disease activity of RA and PTCL-type MTX-LPD caused hypercalcemia and consequent fatigue. Abbreviations: RA: Rheumatoid arthritis; MTX: Methotrexate; EBV: Epstein-Barr virus; PTCL: peripheral T-cell lymphoma; MTX-LPD: Methotrexate - lymphoproliferative disease.

Table

Table 1. Summary of the Investigations Performed, all Positive and Relevant Negative Results are Shown
 
Urinalysis on admission:Biochemistry on admission:Hormone test on admission:
CBC: complete blood count; ESR: erythrocyte sedimentation rate; EBV: Epstein-Barr virus; EBV-EBNA: anti-EBV associated nuclear antigen; EBV-VCA: anti-EBV capsid antigen; PTHrP: parathyroid hormone-related protein; iPTH: intact parathyroid hormone; HCV: Hepatitis C virus; HTLV-1: Human T-lymphotropic virus Type I.
pH5.0TP5.9g/dL1, 25-dihydroxy vitamin D317pg/dL
Specific Gravity1.020Alb1.9g/dLPTHrP1pmol/L
Protein±AST54U/LiPTH< 5pg/mL
Sugar-ALT52U/L
Acetone-LDH205U/LViral antibody test on admission:
Bilirubin-CK13U/LHCV antibodynegative
Urobilinogen±ALP274U/LHTLV-1 antibodynegative
Occult blood±CRP22.8mg/dL
CBC on admission:Na140mmol/LEBV studies on hospital day 22:
White Blood Cell11,250/µLK3.8mmol/LEBV-VCA IgG1,280times
  Neutrophil93.0%Cl101mmol/LEBV-VCA IgM< 10times
  Lymphocyte2.0%Ca10.2mg/dLEBV-EBNA IgG10times
  Monocyte5.0%P6.0pg/mLEBV DNA1.4 × 103copies/106 cells
Red Blood Cell585 × 104/µLBUN42mg/dL
Hb15.5g/dLCr1.69mg/dLEBV studies on 72 days after discharge:
Platelet39.6 × 104/µLEBV-EBNA IgG40times
ESR135mm/hrEBV DNA1.1 × 102copies/106 cells