Methotrexate-related lymphoproliferative disorders in the liver: Case presentation and mini-review

Table 1 Laboratory data on admission of a patient with methotrexate-associated lymphoproliferative liver tumors

Item	Data	Item	Data	Item	Data
White blood cells	13900 /μL	Total protein	7.1 g/dL	Sodium	134 mEq/L
Neutrophils	82.9%	Albumin	3.6 g/dL	Potassium	4.3 mEq/L
Lymphocytes	8.6%	AST	316 IU/L	Chloride	97 mEq/L
Monocytes	8.4%	ALT	370 IU/L	CRP	18.74 mg/dL
Eosinophils	0%	ALP	2006 IU/L	CEA	1.5 ng/mL
Basophils	0.1%	LDH	2844 IU/L	CA19-9	4.0 U/mL
Red blood cells	389 × 104 /μL	γ-GTP	1300 IU/L	AFP	2.0 ng/mL
Hemoglobin	12.6 g/dL	T. Bil	2.51 mg/dL	PIVKA-II	16 mAU/mL
Platelet count	25.8 × 104 /μL	D. Bil	0.82 mg/dL	sIL2R	2120 U/mL
PT	84.7%	BUN	25.6 mg/dL
APTT	30.4 s	Creatinine	0.63 mg/dL

PT: Prothrombin time activity; APTT: Activated partial thromboplastin time; AST: Aspartate aminotransferase; ALT: Alanine aminotransferase; ALP: Alkaline phosphatase; γ-GTP: γ-glutamyltransferase; T. Bil: Total bilirubin; D. Bil: Direct bilirubin; BUN: Blood urea nitrogen; CRP: C-reactive protein; CEA: Carcinoembryonic antigen; CA19-9: Carbohydrate antigen 19-9; AFP: α-fetoprotein; PIVKA-II: Protein induced by vitamin K absence or antagonist II; sIL2R: Soluble interleukin-2 receptor.

Table 2 Summary of 10 reported cases of methotrexate-associated lymphoproliferative liver tumors

Ca-se	Ref.	Age	Sex	Sym-ptom	MTX peri-od (yr)	Num-ber of tu-mors	CT	MRI	PET	US	CE-US	Ti-ssue Colle-ction	Path-ology	Immunohisto-chemistry	Treat-ment	Re-spon-se	Re-currence	On-set pa-ttern	Prog-nosis
1	9	68	F	Ma-laise	8	Mul-tiple	Low den-sity hypovas-cular	N/A	N/A	Hypo-echoic	N/A	US-gui-ded	Hodg-kin lym-pho-ma	CD15+, CD20-, CD30+	Un-trea-ted	No re-spon-se	None	Persis-tent	Death
2	10	76	M	None	4.5	Single	Low den-sity hypovas-cular		N/A	Hypo-echoic	N/A	Sur-gery	B cell	CD10-, CD20+, CD79a+	Resec-tion, cessa-tion	Effec-tive	None	Re-gre-ssive	Alive (10 mo)
3	11	67	F	Abdo-minal pain, fever	6	Mul-tiple	Low den-sity hypovas-cular	N/A	High up-take	N/A	N/A	US-gui-ded	B cell	CD10-, CD20+, CD5-, EBER+	R-THP-COP	Effec-tive	None	Persis-tent	Alive (1 yr)
4	12	56	F	Weig-ht loss, fever	7	Mul-tiple	Iso den-sity hypovas-cular	N/A	High up-take	N/A	N/A	US-gui-ded	B cell	CD10+, CD20+, CD5-	R-CH-OP	Effec-tive	None	Persis-tent	Alive (6 mo)
5	13	64	M	Abdo-minal pain, fever	2	Mul-tiple	Low den-sity hypovas-cular	N/A	N/A	N/A	N/A	US-gui-ded	B cell	CD10+, CD79a+, CD20+; Bcl-2-, CD3-, EBER-	R-CH-OP	Effec-tive	None	Persis-tent	Alive (2 yr)
6	14	65	F	None	7	Single	Low den-sity mild enhance-ment	T1: low, T2: high, diffu-sion: high	N/A	Hypo-echoic	N/A	Sur-gery	B cell	CD10-, CD15-, CD20+, CD30+, CD79a+, EBER+	Resec-tion, cessa-tion	Effec-tive	None	Re-gre-ssive	Alive (1 yr)
7	15	70	F	Abdo-minal pain	10	Single	Low den-sity hypovas-cular	T1: low, T2: high, diffu-sion: high	N/A	N/A	N/A	Surgery	T cell	CD10-, CD20-, CD79a-, CD3+, CD45RO+, CD5+, bcl-2-, EBER-	Resec-tion, cessa-tion	Effec-tive	None	Re-gre-ssive	Alive (1 yr)
8	16	76	F	Ano-rexia	9	Mul-tiple	Low den-sity	N/A	N/A	N/A	N/A	US-gui-ded	T and B cell	N/A	Cessa-tion	Effec-tive	None	Re-gre-ssive	Alive (N/A)
9	17	63	M	Abdo-minal pain	10	Mul-tiple	Low den-sity	N/A	High up-take	Hypo-echoic	Hypovas-cular	US-gui-ded	B cell	N/A	Cessa-tion	Effec-tive	None	Re-gre-ssive	Alive (7 mo)
10	Our case	70	F	Abdo-minal pain, fever	5	Mul-tiple	Low den-sity hypovas-cular	T1: low, T2: high	N/A	Hypo-echoic	Hypovas-cular	US-gui-ded	T and B cell	CD3+, CD4+, CD8+, CD56-, CD20-, CD79a+, EBER-	Cessa-tion	Effec-tive	None	Re-gre-ssive	Alive (2 yr)

N/A: Information not applicable; CD: Cluster of differentiation; EBER: Epstein-Barr virus-encoded small RNA; R-THP-COP: Rituximab–Pirarubicin-Cyclophosphamide–Oncovin-Prednisolone; R-CHOP: Rituximab–Cyclophosphamide–Doxorubicin Hydrochloride–Oncovin-Prednisolone.

Table 3 Characteristic of methotrexate related lymphoproliferative disorder

Characteristic of MTX-LPD
Potential association of EB virus
Treatment includes stopping the MTX and administering chemotherapy or performing surgery in some cases
By stopping MTX, about 30% of cases show improvement within a month
Chemotherapy includes R-CHP, R-THP-COP, etc. depending on the histological pattern

MTX-LPD: Methotrexate related lymphoproliferative disorder; EB: Epstein-Barr.

Table 4 Characteristic of the image of methotrexate related lymphoproliferative disorder in the liver

Characteristic of the image of MTX-LPD in the liver
CT: Low density, poor enhancement effect
MRI: Low signal intensity in T1-weighted image
High signal intensity in T2-weighted image
US: Low echoic pattern
CE-US: Poor enhancement, low echoic area in the Kupffer phase

MTX-LPD: Methotrexate related lymphoproliferative disorder; CT: Computed tomography; MRI: Magnetic resonance imaging; US: Ultrasound; CE-US: Contrast-enhanced ultrasound.