Keywords benign tenosynovial giant cell tumor -
18 F-FDG-PET/CT - benign bone tumor - radioiodine refractory thyroid cancer - thyroglobulin
elevated negative iodine scintigraphy - differentiated thyroid carcinoma
Introduction
Patients with radioactive-iodine refractory (RAIR) thyroid cancer and thyroglobulin
elevated negative iodine scintigraphy (TENIS) are considered as therapeutic challenges
and possess guarded prognosis compared to their DTC counterparts. FDG-PET/CT has become
a pivotal imaging tool in these cases, its sensitivity and is positively correlated
with serum thyroglobulin (Tg) levels and plays a prognostic indicator in this patient
subset.[1 ]
[2 ] The false-positive uptake of FDG in multiple other neoplastic as well as non-neoplastic
forms warrants careful interpretation, which may also be observed in benign bone neoplasms.
Additionally, DTCs have been incidentally detected with other malignancies and vice
versa, the most common being breast cancers.[3 ] These facts warrant clinical correlation and cautiousness while labeling FDG uptake
as part of metastatic disease involvement in such cases. Here we discuss a case of
RAIR thyroid cancer, which was imaged using an FDG-PET/CT scan and found to have FDG-avid
benign tenosynovial giant cell tumor (BTSGCT) of the foot.
Case Report
A 50-year-old male patient, diagnosed with differentiated papillary thyroid carcinoma
(classical type), with extensive capsular invasion and extra-thyroidal extension and
bilateral neck lymph node, and lung metastasis (on preoperative evaluation with regional
CT scan), had undergone total thyroidectomy with bilateral central compartment clearance
with bilateral modified neck dissection. The strap muscles also showed metastatic
deposits, and multiple resected nodes were positive for metastases and showed extra-nodal
extension. His RAI scan ([Fig. 1A ]) showed only a small focus of uptake in the neck, following which he received high-dose
RAI therapy with the traditional protocol of TSH elevation following thyroid hormone
withdrawal (the pre-treatment TSH level was 36 µIU/mL). He received a therapeutic
dose of 7,326 MBq of 131 I as per the institutional protocol, and the post-RAI therapy scan ([Fig. 1B ]) showed neck uptake and faint bilateral chest uptake. The TSH stimulated serum Tg
was 432.21 ng/mL before therapy and he was considered for whole-body FDG-PET/CT, especially
in view of that preoperatively noted lesions were not well visualized on RAI scan.
FDG-PET/CT showed multiple nodular lesions in bilateral lungs, many of which showed
intense FDG concentration ([Fig. 2A ], left column of C and D). One FDG avid subcutaneous soft tissue lesion was noted
in the right ankle region, just superior to the calcaneus measuring 3.4 × 3.0 cm with
an SUVmax value of 12.07; subtle cortical erosion of the underlying calcaneus bone
was also noted ([Fig. 2A ], right columns of C and D).
Fig. 1 1-mCi radioactive iodine planar scan (A ) showing tracer uptake in the midline neck region (thyroid bed), and (B ) post-radioiodine therapy scan showing focal tracer concentration in the neck, chest,
and low-grade diffuse chest uptake.
Fig. 2 FDG-PET/CT at baseline (A ) and 2 years of treatment (B ) showing FDG concentrating tiny multiple bilateral lung nodules, increased in number
(dotted arrow ). FDG avid subcutaneous soft tissue density lesion at the right ankle (solid arrow ). On the right panel, the lung and foot lesions are demonstrated with their enlarged
coronal views, at pre-treatment and at 2 years following sorafenib therapy. Of these,
the left column shows CT chest images (lung window) coronal section (C ) and (E ); PET/CT coronal chest fused images (D ) and (F ). Right column CT images coronal section at foot level (C ) and (E ); and corresponding fused PET/CT images (D ) and (F ) at baseline and 2 years of treatment are also illustrated.
The patient was asymptomatic except for some local swelling; on local examination,
there was soft to firm swelling without skin fixity over the Achilles tendon of the
right ankle, which, according to the patient, was stable over last 18 months and was
non-tender. A local ultrasonographic examination done showed a heterogeneous soft
tissue lesion in the subcutaneous plane superficial to the Achilles tendon in the
dorsal aspect of the right ankle measuring 2.9 × 2 × 0.6 cm. The lesion was further
elucidated with a local MRI done after RAI therapy ([Fig. 3 ]). This revealed irregular soft tissue lesion in subcutaneous region of the posterior
aspect of foot, just superior to the calcaneus, encasing the tendon Achilles without
infiltration. It was seen abutting the cortex of the calcaneum with no appreciable
erosion. MR characteristics of lesion were isointense on T1, intermediate on T2, and
hyperintense on STIR, with minimal restricted diffusion and homogenous post-contrast
enhancement. Though these MRI characteristics were not typical for metastasis, considering
the diagnosis of malignancy in the patient, FNAC was planned. The FNAC showed scattered
osteoclastic giant cells, numerous histiocytes, and lymphocytes and was labeled as
a BGCTS. Retrospectively, post-therapy whole body RAI scans ([Fig. 1B ]) also did not reveal any radioiodine concentration in this lesion. This lesion was
followed up clinically and local MRI every 12 months.
Fig. 3 MR image of the right foot and ankle showing (A ) T1-weighted sagittal section image demonstrating T1 isointense soft tissue lesion
in the subcutaneous region of the posterior aspect of the foot superior to the calcaneum,
encasing the Achilles tendon without infiltration. (B ) T2-weighted sagittal section image showing intermediate intensity of the lesion
with no obvious erosions; (C and D ) dynamic post (gadolinium) contrast T1-weighted images showing homogenous post-contrast
enhancement in the lesion.
In his further course, he developed non-radioiodine concentrating disease and elevated
serum Tg with FDG concentrating multiple bilateral lung nodules and started on tyrosine
kinase inhibitor (lenvatinib) therapy. At nearly 2 years down the line, follow-up
FDG-PET/CT study ([Fig. 2B, E, F ]) demonstrated some increase in his metabolically active lung metastatic lung lesions
but almost stable metabolically active right-sided ankle lesion.
Discussion
BTSGCT is one of the rare benign bone tumors usually affecting adults and are limited
to specific joint areas. A few case reports have reported this to be FDG avid, and
FDG-PET/CT along with MRI is useful in evaluating its local extent and the response
to CSF1-targeting therapies. Nervo et al recently performed an extensive study on
bone disease in thyroid cancer and suggested the rare possibility of benign bone tumors
in such setting and the utility of MRI, especially the DWI sequence, in their diagnosis.[4 ] The same is evidenced in the present case, differentiating it from the metastatic
spread, and confirmed on minimally invasive FNAC technique and follow-up scans. To
the best of our knowledge, this is the first such case reported in a patient having
metastatic DTC. Pallas et al have reported similar such FDG avid BGCTS tumor mimicking
melanoma metastases.[5 ]
In the literature, there are descriptions of benign tumors concentrating radioiodine.
This includes (1) parotid tumors such as Warthin's tumor or oncocytoma, (2) meningioma,
(3) cavernous angioma, (4) cystic mesothelioma, (5) hepatic hemangioma, (6) breast
fibroadenoma, (7) uterine myoma, (8) struma cordis and struma ovarii along with other
types of ovarian tumors and teratoma. These findings have been related to NIS-dependent
uptake or other mechanisms[6 ] and potentially may cause false-positive results in routine RAI scans. There are
other reports of incidental findings of various types of BTSGCT showing uptake on
FDG-PET/CT acquired for other indications, mostly in oncology patients. This case
uniqueness was in the incidence of this benign tumor in a patient with thyroid cancer
imaged and treated with radioactive iodine. Despite the known uptake of RAI in certain
other benign tumors, this lesion was cold on the RAI scan and hence underscored the
non-radioiodine concentrating property of BTSGCT. A confounding scenario in this patient
was high serum Tg values, which could be explained by FDG-avid extensive bilateral
pulmonary metastases.
