Last March I published a post about this same issue. The conclusion was that indication for thyroidectomy in large Bethesda II thyroid nodules (≥4cm) should be based on compression symptoms and increase in nodule size. Additionally, fine needle aspiration biopsy (FNAB) had a false-negative rate not high enough to promote surgery in all Bethesda II nodules ≥4cm. However, in that time I finished the post with my own idea: "I will keep operating large nodules, I think!" However, more papers are coming out and today I wonder if I really should. This post aims at giving more data to help in decision making.
Since the widespread of thyroid ultrasonography, unsuspected nodules are being diagnosed more often. Thyroid nodules are incidentally found in 17-67% of adult population submitted to neck ultrasonography. However, only 5% will harbour a cancer. FNAB has become the gold standard of care, and decision is based on Bethesda classification. Although benign nodules on FNAB (Bethesda II) are traditionally followed in a surveillance program, doubts still exist for large nodules (≥4cm). Why? Because there are some papers reporting high false-negative rates for FNAB in patients with large nodules (7,3% - 53%), meaning that they are more likely to harbour an undiagnosed cancer, indicating thyroidectomy for Bethesda II nodules ≥4cm. Even though, other studies report a false negative rate for large nodules similar to small ones.
"... it remains unclear if patients with thyroid nodules ≥4cm and a benign FNAB have a higher rate of malignancy and should be managed differently than patients with smaller nodules."
Hellen Shi et al. in The American Journal of Surgery
In 2017, a retrospective study from Hellen Shi et al from the Case Western Reserve School of Medicine and the Department of Surgery from both University Hospitals Case Medical Center and MertroHealth Medical Center, Cleveland, USA, published in "The American Journal of Surgery", analysed and compared data from FNAB and pathology for benign nodules <4cm and ≥ 4 cm. The objective was to determine if large nodules with benign FNAB are more likely to harbour a cancer.
The authors studied 337 patients with benign thyroid nodules on FNAB submitted to thyroidectomy because of: compressive symptoms, tracheal and/or oesophageal displacement, substernal extension, thyrotoxicosis, cosmetic concerns, patient's fear of malignancy. Data from FNAB (size and location) were correlated with size and site of nodule in pathology.
Only 2,1 % had malignant disease in pathology. For patients with nodules <4cm two of them (2/99) had a malignancy (2,0%), and for patients with nodules ≥4cm only five (5/238) had a cancer (2,1%). There was no significant difference between the two groups (p=0,966). A higher number of patients with nodules ≥4cm had tracheal and/or esophageal displacement, compressive symptoms, progressive nodule enlargement, and substernal extension.
Hellen Shi et al point out some drawbacks of this study. The majority of patients were operated because of signs and symptoms related to large size, reason why the majority of patients had nodules ≥4cm (238 ≥4cm vs 99 <4cm). In fact, patients with smaller nodules were submitted to thyroidectomy because of personal reasons, namely cosmetic concerns, mild neck discomfort, and fear of malignancy. So, the major drawback is that not all patients with thyroid nodule and a benign FNAB were submitted to thyroidectomy, meaning this is a high selected population.
In resume, the false negative rate for benign FNAB was 2,1%, and no difference was found in malignancy rate between nodules <4cm and ≥4cm. Following these results the authors concluded the "thyroidectomy should not be recommended based solely on nodule size".
“And the first one now
Will later be the last
For the times they are a-changin”
Bob Dylan
Additionally do not forget that ultrasonographic features suspicious of malignancy (microcalcifications, halo presence, margin irregularity, texture) cannot accurately differenciate malignancy form benignity for nodules ≥4cm. From now on I will probably base my decision to operate on clinical evaluation and nodule growth during surveilance program.
Link to PubMed:
Dr. Carlos Eduardo Costa Almeida
General Surgeon