“Thyroid flare” phenomenon on FDG-PET/CT after radiotherapy for extranodal mucosa-associated lympoid tissue lymphoma in the thyroid.

Objectives: The original purpose of this study was to evaluate the time course of FDG-PET/CT findings in patients with extranodal mucosa-associated lymphoid tissue (MALT) lymphoma in the thyroid who underwent external radiation therapy (RT). In the process of this study, we noticed that spurious and temporary increase in the thyroidal FDG uptake could occur on the follow up FDG-PET/CT scan after RT in a subset of patients. We named the finding “thyroid flare” phenomenon.

Methods: We include 35 patients (M/F 7/28, age 45-77yrs.) with pathologically confirmed primary MALT lymphoma of the thyroid with clinical stage of IE(n=25) or IIE(n=10), who were treated by RT alone. None of the patients were associated with diabetes. Either TgAb or TPOAb or both were positive in all. The dose of RT was 40Gy/20f (30Gy to the whole neck with an additional boost of 10 Gy to the thyroid gland ). Follow up period ranged 23-95 mos (median 55mos.). PET/CT scans were imaged using a dedicated scanner Discovery PET/CT 610 QSV(GE) or Aquiduo (Toshiba), and were repeatedly performed as follows: before RT (PET/CTpre, n=35), 3-7mos. after RT (PET/CT1,n=35), 15-28mos. after RT (PET/CT2,n=35), 33-48mos. after RT (PET/CT3,n=30), and 58-76 mos. after RT (PET/CT4,n=24). Both visual interpretation and semi-quantitative analysis with SUVmax were performed by 2 independent nuclear medicine physicians. Visual assessment was done according to five-point scale in the Lugano Classification(5-PS). Negative FDG uptake, which was considered as a sign for absence of viable tumor, was defined as thyroidal FDG uptake less intensive than that of the liver (score 3, 2, or 1). Therapeutic outcome was confirmed by biopsy in 19 pts. or by clinical examination and other imaging modalities in the remaining 16 pts.

Results: In visual assessment of PET/CT pre, 5-PS score was 4 or 5 in all patients but one. FDG uptake in the thyroid was focal in 12 (34%) and was diffuse in 23 (67%). After RT, CR was achieved in 34 out of 35 pts (97%). On PET/CT1, the 5-PS score was decreased to 3 in all 12 patients with focal thyroidal FDG uptake. Of the patients with diffuse FDG uptake, 5-PS score remained 4 or 5 in 78% (18/23) on PET/CT1, 70%(16/23) on PET/CT2, 60%(12/20) on PET/CT3, and 50%(8/16) on PET/CT4, respectively. There was no significant difference in SUV max between PET/CTpre and PET/CT1 (9.10 vs.8.11,p=0.28) in those patients. We defined flare phenomenon as increase in 5-PS score and/or more than 25% increase in SUVmax on PET/CT1 compared with PET/CTpre. Flare was observed in 9 of 23 patients (39%) with diffuse thyroidal FDG uptake on PET/CTpre. Serum TSH levels at the time of PET/CT1 was within normal range in all 9 patents. On PET/CT2, a spontaneous decrease in SUVmax with shrinkage of goiter were observed in 8 out of 9 patients, who were confirmed to be free from viable tumor by further follow up . In one patient who showed persistence of flare on PET/CT2, viable tumor was confirmed by biopsy.

Conclusions: "Thyroid flare" on FDG-PET/CT1 were observed in about a 40% of patients with diffuse FDG uptake on pretreatment PET/CT. Persistence of flare phenomenon on PET/CT2 may be a sign of residual tumor. On the contrary to previous reports in hematopoietic malignant lymphoma, PET/CT obtained 3-6 months after completion of radiotherapy has a limited value in accurate response assessment of primary MALT lymphoma of the thyroid.