A solitary hyperfunctioning thyroid nodule harboring thyroid carcinoma: review of the literature

Abstract

Hyperfunctioning nodules of the thyroid are thought to only rarely harbor thyroid cancer, and thus are infrequently biopsied. Here, we present the case of a patient with a hyperfunctioning thyroid nodule harboring thyroid carcinoma and, using MEDLINE literature searches, set out to determine the prevalence of and characteristics of malignant “hot” nodules as a group. Historical, biochemical and radiologic characteristics of the case subjects and their nodules were compared to those in cases of benign hyperfunctioning nodules. A literature review of surgical patients with solitary hyperfunctioning thyroid nodules managed by thyroid resection revealed an estimated 3.1% prevalence of malignancy. A separate literature search uncovered 76 cases of reported malignant hot thyroid nodules, besides the present case. Of these, 78% were female and mean age at time of diagnosis was 47 years. Mean nodule size was 4.13 ± 1.68 cm. Laboratory assessment revealed T3 elevation in 76.5%, T4 elevation in 51.9%, and subclinical hyperthyroidism in 13% of patients. Histological diagnosis was papillary thyroid carcinoma (PTC) in 57.1%, follicular thyroid carcinoma (FTC) in 36.4%, and Hurthle cell carcinoma in 7.8% of patients. Thus, hot thyroid nodules harbor a low but non-trivial rate of malignancy. Compared to individuals with benign hyperfunctioning thyroid nodules, those with malignant hyperfunctioning nodules are younger and more predominantly female. Also, FTC and Hurthle cell carcinoma are found more frequently in hot nodules than in general. We were unable to find any specific characteristics that could be used to distinguish between malignant and benign hot nodules.

Hot and malignant – a case of invasive papillary carcinoma in hyperthyroid patient with hot nodules

“…The subsequent excisional biopsy of the lymph node and thyroidectomy proved the presence of invasive papillary carcinoma of thyroid. Multiple other cases of hyper-functioning malignant thyroid nodules have been reported [4,6–8]. In a review by Mirfakhraee et al, the prevalence of intra-nodular thyroid malignancy among hyper-functioning ‘hot’ nodules ranged from 0% to 12.5% in different case series with the weighted prevalence rate being 3.1% [6].…”

“…Multiple other cases of hyper-functioning malignant thyroid nodules have been reported [4,6–8]. In a review by Mirfakhraee et al, the prevalence of intra-nodular thyroid malignancy among hyper-functioning ‘hot’ nodules ranged from 0% to 12.5% in different case series with the weighted prevalence rate being 3.1% [6]. Similarly, there are increasing number of reports of co-existence of thyroid malignancy and hyperthyroidism [9–12].…”

“…In a review by Gabriele et al, the prevalence of thyroid malignancy in hyperthyroid patients was 1.65% [11]. Most of these malignancies were of the papillary carcinoma type [6]. While the exact pathophysiological mechanism has not been elucidated, mutations in TSH receptors and Ki-RAS play an important role in the hyper-functioning of the thyroid tumor and its carcinogenetic process [13,14].…”

Marine-Lenhart syndrome in two adolescents, including one with thyroid cancer: a case series and review of the literature

“…In a recent study, Mirfakhraee et al [34] reviewed 14 case series and 77 individual patients with hyperfunctioning thyroid nodules and thyroid cancer. Intranodular carcinoma rates ranged from 0% to 12.5%, with a weighted average of 3.1%.…”

“…Based on the available literature, the prevalence of thyroid cancer in hot nodules appears to be at least twofold higher in children than in adults (7% vs. 3%) [32][33][34]. While the mechanistic driving force behind the increased prevalence of thyroid cancer in pediatric hot nodules remains unclear, sequencing analyses of such nodules in children suggest that neither mutations in RAS and BRAF or rearrangements in PAX8/PPARG or RET/PTC, which are detectable in approximately two-thirds of adult patients with PTCs or FTCs, are likely to be responsible for this phenomenon [38].…”