Abstract and Introduction
Abstract
Background: Clinically inapparent thyroid nodules discovered serendipitously on imaging for nonthyroid indications are termed as thyroid incidentalomas. It is unclear whether these incidentalomas have a lower prevalence of malignancy or slower tumour progression compared to symptomatic nodules. The aims of this systematic review were to determine the impact of incidental detection of thyroid nodules on both the risk of malignancy and on prognosis in patients with thyroid cancer.
Method: PubMed and MEDLINE® on Web of Science databases were searched from inception to March 2020 for English language articles reporting on human studies of thyroid cancer risk and/or prognosis in incidental and nonincidental nodules.
Results: Eighteen observational studies published between 1998 and 2020 were eligible for analysis; four studies reported on risk, nine on prognosis and five studies reported on both risk and prognosis. When comparing the incidental and nonincidental groups in the risk study, the odds of incidental detection in the cancer and benign groups ranged from 0.16 to 0.5 and 0.06 to 0.38, respectively (odds ratio [OR] = 0.64–2.86) in case-control studies (n = 6); the risk of malignancy for thyroid nodules ranged from 4% to 23.5% in the incidental and 3.8% to 28.7% in the nonincidental groups (relative risk = 0.13–6.27) in the cohort studies (n = 3). A meta-analysis of the eligible case-control studies (n = 3) showed a nonsignificant summated OR of 1.04 (95% confidence interval = 0.63–1.70; p = .88). In the prognosis study, five direct and thirteen indirect markers of prognosis were compared between the incidental and nonincidental groups. A meta-analysis was not possible but incidentally detected thyroid cancer had better progression-free and overall survival.
Conclusion: Current evidence suggests that investigation and management of thyroid nodules should not be influenced by the mode of detection.
Introduction
Thyroid cancer is the most common endocrine cancer worldwide and its incidence has doubled since the early 1990s. It predominantly affects females and incidence increases with age.[1,2] Patients may present with a palpable lump or local compressive symptoms (hoarse voice, difficulty swallowing, difficulty breathing). Thyroid cancer could also be discovered during investigation for benign thyroid disease or incidentally detected on imaging for nonthyroid illness.
Thyroid nodules exist more frequently than they are clinically detected. Autopsy studies[3–6] showed that 50%–60% of individuals with no clinical suspicion of thyroid pathology had thyroid nodules; 13% of which were malignant on histology. Another autopsy study[7] showed that one-third of the individuals without previous thyroid disease had at least one papillary carcinoma detected at autopsy. This suggests that some patients with thyroid cancer have an indolent course that may not become clinically apparent and does not affect life expectancy.
The proportion of patients with thyroid cancer presenting with incidentally detected nodules has increased in recent decades.[8,9] This increase (particularly of small [<2 cm] papillary thyroid cancer [PTC]) has been attributed to the widespread use of diagnostic imaging and the increase in sensitivity and resolution of these modalities.[10,11] Thyroid incidentaloma is defined as a clinically unsuspected, asymptomatic thyroid lesion, that is, detected serendipitously on imaging for indications unrelated to the thyroid gland.[2,9]
Up to two-thirds of thyroid incidentalomas are detected on ultrasound performed to examine the parathyroid glands (46%), carotid arteries (9%–13%) or lymph nodes.[12] Computed tomography and magnetic resonance imaging performed to evaluate the lungs, ‘non-thyroid’ neck or cervical spine disease also contribute (16%) to the detection of asymptomatic thyroid lesions.[6] Positron emission tomography imaging detected thyroid incidentalomas in 2%–3% of patients; the risk of malignancy in these patients ranges from 33% to 55%.[13–15]
While these incidentalomas exist in over 50% of individuals over the age of 50, the clinical and oncological implications remain unclear.[16] Ultrasound is widely accepted as an imaging of choice to evaluate thyroid nodules because it is noninvasive, readily available and its sensitivity in identifying carcinomas ranges from 87% to 95%.[2] Thyroid nodules with suspicious characteristics on ultrasound or patients with risk factors should undergo cytological assessment; and if required, surgery for definitive diagnosis and treatment.[16]
There is a lack of clarity in the risk of cancer and progression of thyroid incidentalomas compared to symptomatic nodules; and therefore, uncertainty over whether incidentally detected nodules should be managed differently.
The aims of this systematic review were to determine (i) the risk of malignancy in incidentally detected thyroid nodules and (ii) the impact of incidental detection on the prognosis of patients with thyroid cancer.