J Med Cases

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

Journal website http://www.journalmc.org

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. 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. 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. 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. 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.
pH	5.0		TP	5.9	g/dL	1, 25-dihydroxy vitamin D3	17	pg/dL
Specific Gravity	1.020		Alb	1.9	g/dL	PTHrP	1	pmol/L
Protein	±		AST	54	U/L	iPTH	< 5	pg/mL
Sugar	-		ALT	52	U/L
Acetone	-		LDH	205	U/L	Viral antibody test on admission:
Bilirubin	-		CK	13	U/L	HCV antibody	negative
Urobilinogen	±		ALP	274	U/L	HTLV-1 antibody	negative
Occult blood	±		CRP	22.8	mg/dL
CBC on admission:			Na	140	mmol/L	EBV studies on hospital day 22:
White Blood Cell	11,250	/µL	K	3.8	mmol/L	EBV-VCA IgG	1,280	times
Neutrophil	93.0	%	Cl	101	mmol/L	EBV-VCA IgM	< 10	times
Lymphocyte	2.0	%	Ca	10.2	mg/dL	EBV-EBNA IgG	10	times
Monocyte	5.0	%	P	6.0	pg/mL	EBV DNA	1.4 × 10³	copies/10⁶ cells
Red Blood Cell	585 × 10⁴	/µL	BUN	42	mg/dL
Hb	15.5	g/dL	Cr	1.69	mg/dL	EBV studies on 72 days after discharge:
Platelet	39.6 × 10⁴	/µL				EBV-EBNA IgG	40	times
ESR	135	mm/hr				EBV DNA	1.1 × 10²	copies/10⁶ cells