Nadia J., et al. Surg Chron 2021; 26(3): 323-324.
323
Granuloma Mimicking Recurrence of Papillary Thyroid Cancer with Positive FDG-PET SCAN
Nadia Jamaludina, Rohaizak Mb, Nani Harlina MLb , Shahrun Niza ASb, Suraya Ac, Yahaya Ad, Lai YMd
aDept of Surgery, Faculty of Medicine & Health Sciences, Universiti Sains Islam Malaysia, Persiaran Ilmu, Putra Nilai, 71800 Nilai, N Sembilan.
bDept of Surgery, cDept of Radiology, dDept of Pathology, Universiti Kebangsaan Malaysia, Jalan Yaakub Latif, 56000 Cheras, Kuala Lumpur
Abstract
Papillary thyroid cancer (PTC) is the commonest thyroid cancer. It accounts for 85% of thyroid malignancy yet still highly curable.
It carries only 5% of disease recurrence with appropriate surgery and nodal dissection. Disease relapse can occur as lymph node metastasis, true soft tissue local recurrence or systemically as a distant metastasis. High resolution neck ultrasound (US) and highly sensitive serum thyroglobulin (Tg) are being used as the standard surveillance tool. There were only a few documented granuloma mimicking recurrences of a well differentiated thyroid cancer in the literature, with positive uptake on FDG PET scan.
A 40 year old lady presented with right neck swelling which developed two years after total thyroidectomy and bilateral lymph node dissection for papillary thyroid cancer. She was treated with radioactive iodide ablation once and subsequently showed no uptake on diagnostic WBS. She was asymptomatic throughout surveillance until serum anti thyroglobulin(anti-Tg) was detected to be elevated with normal serum thyroglobulin(Tg). Neck ultrasound identified a lesion at the right thyroid bed with atypical cell seen on ultrasound-guided fine needle aspiration cytology. Whole body scan was negative. Further FDG-PET scan showed positive uptake only in the right thyroid bed. She underwent excision of the lesion using continuous intraoperative nerve monitoring (c- IONM) but complicated with right recurrent laryngeal nerve palsy as detected by reduction of the amplitude. However, histopathology revealed the presence of only granuloma tissue without malignancy cell. Fortunately, her vocal cord function recovers after three months and subsequent serum Tg still normal with persistent slightly elevated anti Tg. Neck ultrasound showed no new lesion detected.
Granuloma may mimic the recurrence of papillary thyroid cancer with a positive anti thyroglobulin and false positive FDG-PET scan. The diagnosis of granuloma instead of well differentiated thyroid cancer recurrence might be challenging in the absence of adequate tissue diagnosis. This is important as the need for redo surgery and the risk of unnecessary morbidity is avoidable.
It is challenging to differentiate a granuloma from a well differentiated thyroid cancer recurrence in the presence of raised anti Tg and positive PDG-PET scan. Thorough investigation need to be done to avoid unnecessary morbidity of re-do surgery.
Keyword: papillary thyroid cancer, recurrence, granuloma, thyroglobulin,
Introduction
Papillary thyroid cancer (PTC) is a well differentiated thyroid cancer and is the commonest of all thyroid malignancy.
Accurate diagnosis, treatment and long term follow up through a multidisciplinary approach are essential to achieve and maintain survival rates. The 10 year overall relative survival rates for PTC in USA are 93-95%. Tumour recurrence is the primary concern in patients undergone total thyroidectomy with or without lymph node dissection for thyroid malignancy1. The immediate surgical complications of the procedure are recurrent laryngeal nerve injury, haemorrhage, infection and hypocalcaemia 1-3. Those risks are increased in a redo surgery for recurrent or persistent disease.
Case Presentation
A 40-year old female patient was referred for a recurrent right neck swelling. She was diagnosed with a cervical metastatic PTC two years ago and underwent total thyroidectomy with bilateral central lymph node dissection at the previous hospital. It was confirmed as a PTC with pathological staging of T2N1aM0. She was treated with radioactive iodide ablation post operatively and subsequent diagnostic whole body scan (WBS) showed no uptake. The ablation dose was 100 millicuries. She has no other significant medical illness. She is well throughout the
surveillance for two years post surgery until she developed painless right neck swelling.
There was no hoarseness of voice and absence of both local and systemic symptoms. Clinical assessment of the neck did not reveal any obvious neck swelling. Her thyroid status was normal.
Serum Tg was low (0.308 ng/mL) but anti-Tg was raised (130 IU/mL). Neck ultrasound identified right thyroid bed lesion measures 1x2cm. Ultrasound guided FNAC showed presence of atypical cells. FDG-PET scan showed a positive uptake in the similar right thyroid bed with no uptake elsewhere. Since the serum anti-Tg were high with positive FDG-PET, she underwent redo surgery of the right bed thyroid lesion. Intraoperatively, the lesion was densely adhered to the right RLN. The nerve was preserved using sharp dissection but unfortunately, she was complicated with right recurrent laryngeal nerve palsy as detected by presence of double events during c-IONM. Histopathology confirmed the presence of only granuloma tissue without any malignancy cell.
Post operatively, her serum Tg is normal, with anti Tg still elevated with 120 IU/mL. Neck ultrasound showed no new lesion detected. Her vocal cord function returns after three months of surgery. No WBS was done for her after excision of the right thyroid bed lesion since the WBS was negative.
Nadia J., et al. Surg Chron 2021; 26(3): 323-324.
324 Figure 1 : Illustrates FDG-PET scan uptake in the right thyroid bed
Figure 2: Photomicrograph showing multiple granuloma formation composed of aggregates of epitheliod histiocytes surrounded by lymphocytes with presence of Langhan giant cells.
Granuloma with lymphocytes (red arrow), epitheliod histiocytes (green circle) and Langhan giant cells (yellow square), H&E stain.
Discussion
High resolution ultrasonography (US) is the standard evaluation tool used in detection of local recurrence of thyroid cancer either in the thyroid bed, true soft tissue or regional lymph nodes5,6. It is specifically very useful in patients with hemithyroidectomy or lobectomy since Tg alone is not helpful in detecting tumour recurrence. Benign lymph nodes and suture granuloma may mimic tumour recurrence on US 7.
It is challenging to differentiate between a granuloma or a true local recurrence of well differentiated thyroid cancer.
In this case, only the anti Tg is elevated than the upper normal limit with low serum Tg .US showed a right thyroid bed lesion which is concordant with the FDG-PET scan findings; a positive uptake on the similar site with negative
WBS. Besides, USG FNAC of the right thyroid bed lesion itself confirmed presence of atypical cells. Since this lesion is a non-avid iodine (negative WBS) in a symptomatic right neck swelling, she warranted a redo surgery with all those positive findings from pre-operative investigations that suggested of local recurrence.
Yong Eun et al 7 reported a suture granuloma mimicking recurrences of a well differentiated thyroid cancer in the literature. This recurrent thyroid lesion detected on high resolution neck ultrasound and FDG-PET scan but its diagnosis was confirmed by US-guided FNA biopsy. No serum Tg was done in view of the patient did not undergo total thyroidectomy. With that tissue confirmation, unnecessary operations are avoided. In the case presented, the FNA shows presence of atypical cells which is confirmed by positive FDG PET scan, which raised the suspicion of cancer recurrence. Final histopathology report of this patient revealed the presence of only granuloma tissue without any malignant or atypical cell, which explained the positive uptake by FDG PET.
Suture granuloma is a rare complication of thyroid surgery. It may occur anywhere after a variety of surgeries.
It was reported that almost all suture granulomas developed within two years of the surgery, which is similar to our patient. However, the time interval can be varied from several months to years. It occurs because of the use of non- absorbable suture materials within the skin. Thus, in this patient the FDG-PET scan was positive because of the tissue’s inflammatory reactions occurs.
A study by Rettenbacher et al8 mentioned that there are a few characteristic US findings of suture granulomas like a well-defined, hypoechoic lesion but in our case there was no characteristic of US findings of such, instead of only appearance of suspicious lesion. Thus, we proceed with US guided fine needle cytology of the lesion for confirmation prior to surgery.
Khan et al9 reported that PET scan was useful in detecting recurrent differentiated thyroid cancer. However, the specificity was relatively less than sensitivity because of inflammatory lesions which show hot uptake in FDG PET, which is similar in our patient. This will give rise to a false positive result.
False-positive 18F-FDG uptake in the neck was often caused by several sources including muscle, brown fat, salivary glands, vocal cords, tonsils, and other lymphoid tissues. Reactive hyperplasia lesions, inflammatory lesions and benign tumors can also lead to FDG uptake10. Ozkan et al.11 reportedthis false-positive uptake were located in the neck. It was reported in the literature that the 18F-FDG PET/CT scanning had a good diagnostic performance in the selected PTC patients with negative Tg, negative 131I-WBS at first post-ablation and progressively increased Anti Tg level.
Positive 18F-FDG PET/CT findings is closely associated with the progressive increasing Anti Tg level at diagnosis. 18F-FDG PET/CT scanning could be performed routinely for PTC patients with negative Tg, negative 131I-WBS at first post- ablation ablation and progressively increased Anti Tg level, especially for those whose span for progressively increased
Nadia J., et al. Surg Chron 2021; 26(3): 323-324.
325 Anti Tg level more than 3 years and/or progressively
increased Anti Tg value up to 150 IU/mL11.
However, only her anti Tg was high with normal serum Tg. Generally, serum Tg has been used as a standard surveillance tool as it is highly sensitive, but in this case, Tg was normal. Generally, high anti Tg could cause Tg to be undetectable in the circulating blood. Thus, surveillance of anti Tg is useful for detecting persistent or recurrence DTC after total thyroidectomy and radioiodine remnant ablation therapy 12. The rising of anti Tg after initial treatment is evaluated as ‘biochemical incomplete response’ and these patients should be carefully investigated and monitored 12. In this case, thorough investigations have showed positive result from the neck ultrasound, FDG PET scan and USG FNA thus the decision to excise the lesion was justified.
Anti Tg levels may transiently rise post-operatively and after radioactive iodine as an apparent immune reaction 13. Its median disappearance time is reported to be about 3 years 13,14. However, the persistent rise of anti Tg for more than 1 year with undetectable serum Tg should be investigated thoroughly for recurrence or metastatic disease
14.
Conclusion
Granuloma may mimic the recurrence of papillary thyroid cancer with a positive serum thyroglobulin, anti- thyroglobulin and also a false positive FDG-PET scan.
Ultrasound guided core biopsy of the lesion is strongly recommended to avoid unnecessary surgery. FDG PET/CT scan has a good diagnostic result in selected DTC with negative Tg, negative 131I -WBS and progressively increased anti Tg level with low risk of false negative thus thorough investigations are strongly recommended to avoid the unnecessary morbidity of redo surgery.
Reference
1. Jill E Langer, Erika Luster, Steven C Horii. Chronic Granulomatous Lesion After Thyroidectomy: Imaging Findings. Head and Neck Imaging. AJR 2005;185:1350-1354.
2. Bhattacharyya, Fried M. Assessment of the Morbidity and Complications of Total Thyroidectomy. Arch Otolaryngeal Head and Neck Surg 2002;128:389-392.
3. Cheah WK, Arici C, Ituarte P, Siperstein AE, Duh Q, Clark O.
Complications of Neck Dissection for Thyroid Cancer. World J Surg.
2002;26:1013-1016.
4. Yeow K, Liao C, Hao S.US-Guided Needle Aspiration and Catheter Drainage as an Alternative to Open Surgical Drainage for Uniloculated Neck Abscess. J Vasc Inter Radio 2001;12:589-594.
5. Frasoldati A, Pesenti M, Diagnosis of neck recurrences in patients with differentiated thyroid carcinoma. Cancer 2003;97:90-96.
6. Antonelli A,Miccoli P, Ferdeghini M, et al. Role of neck ultrasonography in the follow up of patients operated on for thyroid cancer. Thyroid 1995; 5:25-28.
7. Young Eun Chung, Eun Kyung Kim. Yonsei Medical Journal 2006;47:748-751.
8. Rettenbacher T, Macheiner P, Hollerweger A. Suture granuloma:
sonography enables a correct preoperative diagnosis. Ultrasound Med Biol. 2001;27:343-350.
9. Khan N, Oriuchi N, Higuchi T, Zhang H, Endo K. PET in the follow-up of differentiated thyroid cancer. Br J Radiol. 2003;76:690–695.
10. Nakamoto, Y. et al. Normal FDG distribution patterns in the head and neck: PET/CT evaluation. Radiology 2005; 234, 879–885.
11. Ozkan, E., Aras, G. & Kucuk, N. O. Correlation of 18F-FDG PET/CT findings with histopathological results in differentiated thyroid cancer patients who have increased thyroglobulin or antithyroglobulin antibody levels and negative 131I whole-body scan results. Clin Nucl Med 2013; 38, 326–331.
12. Haugen BR, Alexander EK, Bible KC, et al. 2015 American Thyroid Association management guidelines for adult patients with thyroid nodules and differentiated thyroid cancer: the American Thyroid Association Guidelines task force on thyroid nodules and differentiated thyroid cancer. Thyroid 2016;26:1-133.
13. Gorges R, Maniecki M, Jentzen W, et al. Development and clinical impact of thyroglobulin antibodies in patients with differentiated thyroid carcinoma during the first 3 years after thyroidectomy. Eur J Endocrinol 2005;153:49- 55.
14. Chiovato L, Latrofa F, Braverman LE, et al. Disappearance of humoral thyroid autoimmunity after complete removal of thyroid antigens.
Ann Intern Med 2003;139(5 Pt 1):346-351.
15. Liu SH, Chang JT, Ng SH, Chan SC, Yen TC. False positive fluorine-18 fluorodeoxy-D-glucose positron emission tomography finding caused by osteoradionecrosis in a nasopharyngeal carcinoma patient. Br J Radiol. 2004;77:257–260.
16. Holder WD, Jr, White RL, Jr, Zuger JH, Easton EJ, Jr, Greene FL.
Effectiveness of positron emission tomography for the detection of melanoma metastases. Ann Surg. 1998;227:764–771.
17. Abdul Hamid MF, Yu -Lin NB, Maharani Hassan T, Suture granuloma post thyroidectomy masquerading TB presented with a sinus tract.
Eurasian J Med.2018;50(2):122-124.
Corresponding Author:
Prof Dr Rohaizak Muhammad
Faculty of Medicine, Universiti Kebangsaan Malaysia, JalanYaacob Latif, Bandar Tun Razak,
56000, Cheras, Kuala Lumpur, Malaysia Email : [email protected]
