Abstract
Cervical and mediastinal lymph nodes represent the most common site (74%) for the The development of metastatic disease in recurrent/persistent differentiated thyroid carcinoma (DTC). Although lymph node metastases are common in DTC, death is not, and the lack of clear data on the prognostic implications of small loco-regional nodal disease has led to controversy in their management. Recently, it has been suggested that small, stable cervical lymph nodes, even when sonographically suspicious, may be followed in selected circumstances to document growth before proceeding with therapeutic intervention. Suspicious lymph nodes typically have a low potential for progression. Furthermore, surgical resection at the time of structural disease progression is generally successful, suggesting that selected patients with small-volume nodal disease can be offered a strategy of frequent monitoring with serial serum thyroglobulin measurements and neck ultrasonography.
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The Case
A19-year-old woman underwent a total thyroidectomy in 2014 for a suspicious nodule; final pathology described a 1.4 cm papillary cancer, classical variant, with no extrathyroidal extension. No central neck dissection was performed. After surgery, 30 mCi of radioiodine was administered. The first follow-up visit documented absence of residual disease with undetectable serum thyroglobulin (Tg) and normal neck ultrasound.
During a subsequent follow-up visit (5 years after initial treatment), neck ultrasound showed a 7×7×9 mm thyroid bed nodule suspicious for recurrent disease; fine-needle aspiration (FNA) biopsy confirmed the presence of a lymph node metastasis from papillary thyroid cancer. At that time, basal Tg was 1.1 ng/ml, rising to 3.4 ng/ml after recombinant human TSH stimulation. A second course of radioiodine was administered at a dose of 150 mCi of 131I. The post-therapy scan showed no uptake in the neck. Her endocrinologist recommended surgery in the near future, and she came to our center to discuss whether this was necessary.
Assessment and Literature Review
In differentiated thyroid cancer, structural tumor recurrences in the post-surgery follow-up occur in about 1–2% of cases with an excellent response to initial therapy regardless of their initial risk stratification [1,2,3,4,5,6].
In the case of cervical lymph node recurrences, the management may include no therapy, compartmental lymph node dissection, radioiodine therapy, ethanol injection and radiofrequency or laser ablation. The final decision should be made after discussions involving the endocrinologist, the surgeon and the patient [7].
Roughly two-thirds of neck lymph nodes classified as indeterminate on ultrasound will spontaneously disappear after several months, so watchful waiting is appropriate for small indeterminate nodes. Overall, only a small proportion of these lymph nodes will grow over time, but no complication due to size increase has been reported during follow-up [8,9,10].
In particular, in a retrospective review of 191 patients with at least 1 thyroid bed nodule (≤11mm) over a median follow-up of 5 years, only 9% of patients had an increase in size of at least 1 nodule, with a low rate of growth (median 1.3 mm/year) [8]. Suspicious cervical lymph nodes left untreated also revealed a low rate of growth. After a median follow-up of 3.5 years, only 9% of them (15/166) grew at least 5 mm in the longest diameter, with a rate of growth of 1.5 mm/year with no associated disease-related mortality. Among the 15 patients, 7 underwent FNA biopsy, and cytology was consistent with papillary thyroid cancer in 5 cases [9]. In the most recent series a total of 113 lesions were followed up (18 thyroid bed masses, 95 lymph nodes). During surveillance (median 3.7 y), group with indeterminate lesions only had significantly lower rates than group with one or more lesions classified as suspicious of lesion growth, defined as >3 mm in the largest diameter (8% vs. 36%, P = .01) and persistence (64% vs. 97%, P = .014) [10].
Unfortunately, no prospective and randomized trials with longer follow-up have compared the outcome of recurrent lymph node metastases treated by surgery or untreated.
Based on the most recent studies and reviews, the 2015 ATA guidelines stated that smaller lesions (<8 mm in the smallest diameter for central neck nodes and <10 mm for lateral neck nodes) probably can be best managed with active surveillance with serial ultrasound complemented by neck CT scans, reserving FNA and subsequent surgical intervention for documented structural disease progression [7].
Apart from size, other factors such as the patient’s emotional status, lymph node location (near or not to vital structure), the functional status of vocal cords, the patient’s comorbidities, histology of primary tumor, and Tg doubling time should be taken into account in the decision to operate. In selected cases, metastatic nodes greater than 8–10 mm in the shortest diameter may be followed without intervention, selecting for surgery those patients in whom there is disease progression during follow-up. This is probably mainly feasible in case of indeterminate rather than suspicious neck lesions, where there is the possibility of a disappearance of abnormalities during follow-up [10].
In the case of larger lymph nodes, surgery is the preferred approach. The experience of the surgeon and the risks associated with a second surgery (mostly when the lymph node is localized in a compartment previously dissected) should be taken into account. Compartmental surgery is recommended over “berry picking”, due to the high risk of recurrence and higher morbidity in case of re-operative surgery. Careful neck dissection in experienced hands has been associated with short-term decreases in serum Tg levels in 60–90% of patients, while undetectable serum Tg was obtained in only 30–50% [11,12,13]. However, most series suggest that surgery results in the disappearance of structural disease in over 90% of patients [14]. Recently a retrospective study, analyzing efficacy, safety and prognostic factor of first neck re-operation in differentiated thyroid cancer, demonstrated that only age >45 years, aggressive histology and >10 N1 at re-operation were independent risk factors of secondary relapse [15].
Back to the Patient
The patient was reassured that her thyroid bed nodules could be closely monitored until there was evidence of progression. Serial neck ultrasound was then performed with a gradual increase in size of the thyroid bed nodule (9×11×17 mm vs. 7×7×9 mm). After 5 years, it was decided to perform a compartmental level VI dissection. Final pathology was consistent with a lymph node metastasis from a papillary thyroid cancer. Six months after the surgery, serum Tg was undetectable and neck ultrasound was negative. She was considered to be in clinical remission and has been followed with annual Tg and neck ultrasound.
Clinical Pearls
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In differentiated thyroid cancer, structural tumor recurrences in the post-surgery follow-up period occur in about 1–2% of patients with an excellent response to initial therapy regardless of their initial risk stratification.
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Suspicious central neck nodes ≥8 mm and lateral neck nodes ≥10mm in the smallest diameter should be considered for surgical removal while indeterminate neck lesions in selected cases could be managed with follow-up.
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Suspicious, but small, stable cervical lymph nodes may be followed with serial ultrasound without intervention.
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Brilli, L., Pilli, T., Pacini, F., Castagna, M.G. (2021). A Case of Papillary Thyroid Cancer Without Aggressive Histological Features with a Nodal Metastasis Detected During Follow-Up in a Young Patient. In: Grani, G., Cooper, D.S., Durante, C. (eds) Thyroid Cancer. Springer, Cham. https://doi.org/10.1007/978-3-030-61919-0_20
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