The usefulness of (18)F-FDG PET/CT for assessing methotrexate-associated lymphoproliferative disorder (MTX-LPD)

BMC Cancer. 2016 Aug 15;16:635. doi: 10.1186/s12885-016-2672-8.


Background: Methotrexate-associated lymphoproliferative disorder (MTX-LPD) is a benign lymphoid proliferation or malignant lymphoma in patients who have been treated with MTX. MTX withdrawal and observation for a short period should be considered in the initial management of patients who develop LPD while on MTX therapy. Here we evaluated the diagnostic accuracy and predictive value of (18)F-fluorodeoxyglucose positron emission tomography/computed tomography ((18)F-FDG PET/CT) for MTX-LPD.

Methods: We retrospectively investigated the cases of 15 patients clinically suspected of having MTX-LPD. A total of 324 anatomic regions (207 nodal and 117 extranodal regions) were assessed by (18)F-FDG PET/CT and by multi-detector row CT (MDCT). Each anatomic region was classified as either malignant or benign. The uptake of (18)F-FDG was assessed semi-quantitatively with the standardized uptake value maximum (SUVmax), the whole-body metabolic tumor volume (WBMTV), and the whole-body total lesion glycolysis (WBTLG) in order to investigate predictive factors of spontaneous regression after the withdrawal of MTX.

Results: MTX-LPD lesions were observed in 92/324 (28.4 %) regions. (18)F-FDG PET/CT showed 90.2 % sensitivity, 97.4 % specificity, and 95.4 % accuracy, values which were significantly higher than those of MDCT (59.8, 94.8, and 84.9 %, respectively. p < 0.002). After the withdrawal of MTX, 9/15 patients (60.0 %) achieved complete response (CR). The SUVmax, WBMTV and WBTLG values of the CR patients were 9.2 (range 2.8-47.1), 44.3 (range 0-362.6) ml, 181.8 (range 0-2180.9) ml, respectively, which were not significantly different from those of the non-CR patients: 10.6 (range 0-24.9), 15.7 (range 0-250.1) ml, and 97.4 (range 0-1052.1) ml.

Conclusions: Although (18)F-FDG PET/CT was a useful tool to detect MTX-LPD lesions, none of the (18)F-FDG PET parameters before the withdrawal of MTX could be used to predict CR after the withdrawal of MTX.

Keywords: FDG; Metabolic tumor volume; Methotrexate-associated lymphoproliferative disorder; PET; Total lesion glycolysis.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Fluorodeoxyglucose F18 / metabolism*
  • Glycolysis
  • Humans
  • Lymphoproliferative Disorders / chemically induced
  • Lymphoproliferative Disorders / diagnostic imaging*
  • Lymphoproliferative Disorders / metabolism
  • Male
  • Methotrexate / adverse effects*
  • Middle Aged
  • Positron Emission Tomography Computed Tomography / methods*
  • Radiopharmaceuticals / metabolism*
  • Retrospective Studies
  • Sensitivity and Specificity
  • Tomography, X-Ray Computed / methods
  • Tumor Burden


  • Radiopharmaceuticals
  • Fluorodeoxyglucose F18
  • Methotrexate