Patients whose ultrasound exams show multiple thyroid nodules have the same risk of cancer as those with only one nodule, according to a study presented at the 2001 American Institute of Ultrasound in Medicine meeting.
Based on their findings, the researchers from the University of Pennsylvania Medical Center in Philadelphia recommended biopsying all nodules larger than 1 cm in diameter. If three or more nodules are detected, they advocate biopsying only those nodules that look suspicious on an 123-iodine scan -- a nuclear medicine test that detects cancerous nodules based on their failure to absorb the isotope.
The study, led by associate professor of radiology Dr. Jill Langer, could help answer a lingering question in thyroid ultrasonography: What to do with the growing number of small nodules detected only on ultrasound? Currently, the only research-based patient management algorithm concerns palpable nodules. Conventional wisdom holds that because solitary palpable nodules are more likely to be cancerous than multiple nodules, most solitary palpable nodules should be biopsied.
Over the past 15 years, however, more and more patients have been receiving ultrasound of the carotid artery and surrounding tissues. As a result, more and more small nonpalpable nodules are being detected, Langer said. In addition, 60% of patients with one palpable nodule have additional nodules on ultrasound examination, 70% of which are smaller than 1 cm.
"No one really knows what to do when you’re presented with a patient with multiple nodules on ultrasound," Langer said.
This leaves the radiologist in a bind. Which nodules are clinically significant? Which should be biopsied? Further muddying the problem, only 5% of thyroid nodules are cancerous, meaning it isn’t cost effective to biopsy most of them.
Hoping to get a better idea of when to order fine-needle aspirations, Langer, along with endocrinologists Dr. Stephanie Fish and Dr. Susan Mandel, evaluated the risk of thyroid cancer in patients with solitary versus multiple nodules, as detected by ultrasound.
They retrospectively reviewed the records of 399 patients who had undergone ultrasound-guided biopsy for two types of nodules: those larger than 1 cm as seen on ultrasound, or if three or more large nodules were detected, those that looked suspicious on the 123-iodine scan. The cancer risk was virtually the same in both groups: 16% in patients with solitary nodules and 15% in patients with multiple sub-centimeter or red-flagged nodules as per the iodine scan.
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"Our data indicates you have to biopsy both groups, those with multiple [nodules] and the solitary nodules," Langer said. "Some people might think this is a very aggressive management scheme, instead of only biopsying the dominant nodule. But if a patient is sent to you to rule out cancer, you can’t have a false sense of security that because they have a multinodular gland, they don’t have an underlying thyroid cancer."
How to manage nodules that appear ambiguous on the 123-Iodine scan -- meaning nodules that absorb some, but not a lot of the isotope -- is still unclear. Langer said her team follows these patients with serial ultrasound exams about every nine months, and if the nodule enlarges, they biopsy it.
Multiple nodules smaller than 1 cm are another gray area. Langer’s team also follows these nodules with serial ultrasound, and biopsies any that grow larger than 1 cm in diameter -- except in patients who have been exposed to excessive levels of radiation at some point in their lives, she said. Patients from the Ukraine who were exposed to radiation following the 1986 Chernobyl accident are always biopsied, she said.
By Dan KrotzAuntMinnie.com contributing writer
April 17, 2001
Related Reading
FDG-PET influences thyroid treatments, January 18, 2001
Referring physicians in Philadelphia ordering more US-guided procedures, January 8, 2001
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![Examples of ultrasound findings and techniques. (A) Images in a 39-year-old male patient with a mass in the left thigh. The mass is heterogeneous on the B-mode US image (compared with the patient in D) and showed increased microvascularity (superb microvascular imaging [SMI]) and shear-wave elastography (SWE) values. Undifferentiated pleomorphic sarcoma was diagnosed at biopsy (with pleomorphic rhabdomyosarcoma in surgical specimen). (B) Images in an 18-year-old male patient with a mass in the left leg. The mass is hypoechoic on the B-mode image, with no other findings suggestive of malignancy. The lesion is in contact with the cortex of the tibia, which is slightly irregular. CT revealed a doubtful anteromedial tibial erosion. The microvascular study demonstrated high vascularization, suggestive of malignancy. Periosteal Ewing sarcoma was diagnosed with both histologic and immunohistochemical confirmation. (C) Images in a 69-year-old female patient with a lump growing on the outside of the left leg. Multiple SWE examinations were performed (please note the high values obtained in the measurements, whereas the color map highlights the stiffness relative to adjacent tissues). SMI showed areas of increased vascularization to target for sampling. Undifferentiated spindle cell sarcoma was diagnosed at biopsy, with residual leiomyosarcoma in the surgical specimen after neoadjuvant therapy. (D) Images in a 56-year-old female patient with a mass in the right thigh. The mass is heterogeneous at both B-mode ultrasound (similar to patient A) and MRI (coronal T2-weighted spectral attenuated inversion recovery [SPAIR]; T1-weighted pre-contrast and postcontrast imaging), which even shows uptake after the administration of paramagnetic contrast material, which is traditionally suggestive of malignancy. Low values at SMI and elastography are suggestive of benignity. Spindle cell lipoma was diagnosed at biopsy, with atypical spindle cell lipomatous tumor in the surgical specimen.](https://img.auntminnie.com/mindful/smg/workspaces/default/uploads/2026/08/images-radiol250278fig2.APCFLSvX6p.jpg?auto=format%2Ccompress&fit=crop&h=100&q=70&w=100)
![Examples of ultrasound findings and techniques. (A) Images in a 39-year-old male patient with a mass in the left thigh. The mass is heterogeneous on the B-mode US image (compared with the patient in D) and showed increased microvascularity (superb microvascular imaging [SMI]) and shear-wave elastography (SWE) values. Undifferentiated pleomorphic sarcoma was diagnosed at biopsy (with pleomorphic rhabdomyosarcoma in surgical specimen). (B) Images in an 18-year-old male patient with a mass in the left leg. The mass is hypoechoic on the B-mode image, with no other findings suggestive of malignancy. The lesion is in contact with the cortex of the tibia, which is slightly irregular. CT revealed a doubtful anteromedial tibial erosion. The microvascular study demonstrated high vascularization, suggestive of malignancy. Periosteal Ewing sarcoma was diagnosed with both histologic and immunohistochemical confirmation. (C) Images in a 69-year-old female patient with a lump growing on the outside of the left leg. Multiple SWE examinations were performed (please note the high values obtained in the measurements, whereas the color map highlights the stiffness relative to adjacent tissues). SMI showed areas of increased vascularization to target for sampling. Undifferentiated spindle cell sarcoma was diagnosed at biopsy, with residual leiomyosarcoma in the surgical specimen after neoadjuvant therapy. (D) Images in a 56-year-old female patient with a mass in the right thigh. The mass is heterogeneous at both B-mode ultrasound (similar to patient A) and MRI (coronal T2-weighted spectral attenuated inversion recovery [SPAIR]; T1-weighted pre-contrast and postcontrast imaging), which even shows uptake after the administration of paramagnetic contrast material, which is traditionally suggestive of malignancy. Low values at SMI and elastography are suggestive of benignity. Spindle cell lipoma was diagnosed at biopsy, with atypical spindle cell lipomatous tumor in the surgical specimen.](https://img.auntminnie.com/mindful/smg/workspaces/default/uploads/2026/08/images-radiol250278fig2.APCFLSvX6p.jpg?auto=format%2Ccompress&dpr=2&fit=crop&h=167&q=70&w=250)
