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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
Thyroid cancer is the most common malignancy of the endocrine system[1,2] and the twelfth most common cancer in the United States.[3] The incidence of thyroid cancer has been increasing over the last several decades.[1] Thyroid cancer occurs nearly three times more often in women than men.[3,4]
The gross cross-section of a thyroidectomy specimen shown here reveals multiple bilateral nodules.
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Risk Factors
Historical image of the first patient treated with linear accelerator radiation therapy. [Public domain.] Via Wikimedia Commons.
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
Risk Factors
Radiation exposure in childhood significantly increases the risk of developing thyroid cancer and other thyroid gland anomalies.[1,4] Thyroid malignancies can manifest as early as 5 years or as late as 20 or more years following radiation therapy.[1] In addition, exposure to nuclear fallout has been associated with a high risk of thyroid cancer.[1,4]
The following are also known risk factors for the development of thyroid cancer[1,4]:
Age 25 to 65 years
Female sex
Low dietary iodine intake
Family history of thyroid disease, such as familial medullary thyroid cancer (FMTC)
Mendocrine neoplasia type 2 (MEN 2)
History of goiter
Asian race
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Presentation
Image of an enlarged thyroid presenting as a midline neck mass courtesy of Wikimedia Commons | Drahreg01.
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
Presentation
Thyroid cancer commonly presents as a solitary, painless, nonfunctioning ("cold") thyroid nodule.[1] Patients or clinicians often discover the nodules incidentally during routine palpation of the neck.[4]
Although the overall incidence of cancer in a cold nodule is 12-15%, it is higher in people younger than 40 years and in individuals whose preoperative ultrasonographic studies show the presence of calcifications.[1]
Features associated with malignancy in thyroid nodules include the following[4,5]:
Solitary nodules - Malignancy is more common in patients older than 60 years and those younger than 30 years
Nodular growth
Hard and fixed nodules
Rapid growth
Painless mass (usually) - Sudden onset of pain is more commonly associated with benign disease (eg, hemorrhage into a benign cyst, subacute viral thyroiditis)
Persistent hoarseness or other voice changes
Persistent cough
Dysphagia
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Workup
Images courtesy of Ali Ahmad, MD, (left) and Medscape (right).
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
Workup
The evaluation of the solitary thyroid nodule involves differentiating malignant from benign disease and, therefore, determining whether the patient requires intervention or may be monitored.[5,6]
The following is recommended for the workup of a suspicious thyroid nodule[5,6]:
A detailed medical history, including previous radiation exposure and relevant family medical history, if available
A comprehensive physical examination, including a thorough head-and-neck evaluation (particularly of the thyroid gland and cervical soft tissues), as well as indirect laryngoscopy
Laboratory studies
Fine-needle aspiration (FNA) biopsy
Imaging studies
Firm, fixed, new, and/or rapidly growing cervical masses are highly suggestive of malignancy (regional lymph node metastases).[5,6]
The images depict a left-lobe "cold" nodule on a thyroid uptake scan. FNA biopsy should be considered in light of relevant clinical suspicion of a malignancy.
5 of 15Image courtesy of Welker L, Akkan R, Holz O, Schultz H, Magnussen H. Diagn Pathol. 2007;2:31. [Open access.] PMID: 17716363, PMCID: PMC2063495.
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
FNA biopsy
FNA biopsy is the procedure of choice for evaluating thyroid nodules, and it should be the first intervention.[4,5,6,7] Papillary and medullary thyroid carcinomas are often positively identified on the basis of FNA biopsy results alone.[8]
The image shows different types of fine needles that may be used in FNA biopsy procedures.
Repeat biopsies result in a definitive diagnosis in up to 50% of cases, and in up to 90% when ultrasound guidance is added.[9] Patients with high clinical suspicion for malignancy whose findings are indeterminate or nondiagnostic on FNA despite repeat biopsy can undergo surgery for tissue diagnosis.[4,5,7,8] However, nondiagnostic cases can be monitored clinically if suspicion of malignancy is low.[8]
6 of 15Images courtesy of Dr Ravi Kadasne.
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
Imaging studies
Selective imaging studies, such as the following, are used to evaluate patients with suspected thyroid cancer (including recurrent disease)[4,5,8,10,11]:
Neck ultrasonography
Thyroid radioiodine imaging
Neck computed tomography (CT) scanning or magnetic resonance imaging (MRI)
Positron emission tomography (PET) scanning
The color-flow Doppler ultrasound of the thyroid shown here demonstrates a complex nodule with increased vascularity. Radioiodine scans can be useful for determining the functional status of the thyroid nodule, because most hyperfunctioning nodules are benign.[10]
The 2015 American Thyroid Association consensus statement on preoperative imaging for thyroid cancer surgery noted the following[10]:
Ultrasonography remains the most important imaging modality in the evaluation of thyroid cancer and should be used routinely to preoperatively assess the primary tumor and all associated cervical lymph node basins
Ultrasound-guided FNA of suspicious lymph nodes may provide guidance on the extent of surgical intervention
Selectively consider cross-sectional imaging (CT scanning with contrast or MRI) for better characterization of tumor invasion and bulky, inferiorly or posteriorly located lymph nodes, or when ultrasonographic expertise is not available
PET scanning may be used to assess recurrent disease
7 of 15Image courtesy of Dreamstime.
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
Laboratory studies
Laboratory studies that may be used to assess patients with suspected thyroid cancer include the following[1,4,5,6,8]:
Serum calcitonin/pentagastrin-stimulated calcitonin levels - Elevated levels are highly suggestive for medullary thyroid carcinoma; these measurements may also be used in posttreatment monitoring for recurrent disease
Polymerase chain reaction (PCR) assay for germline mutations in the RET proto-oncogene - May aid in the diagnosis of FMTC, as well as MEN 2 syndromes
Serum thyroglobulin levels (postoperative) - Elevated levels are a strong indicator of tumor recurrence in patients with differentiated thyroid cancer; these findings are most sensitive in the presence of hypothyroidism and elevated TSH levels; for long-term monitoring, measurements of thyroglobulin and antithyroglobulin antibodies should be obtained
Molecular diagnostic testing - May be used for detection/identification of specific genetic mutations, such as RET/PTC and BRAF V600E, among others; these mutations may occur in papillary and/or follicular tumors
Molecular pattern recognition studies with molecular classifiers - May help to guide treatment decisions when FNA biopsy findings are indeterminate
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Papillary Thyroid Carcinoma
Images of papillary thyroid cancer (A,B), including visualization of the papillary structures at high magnification (B), courtesy of Beier F, Moleda L, Guralnik V, et al. J Med Case Rep. 2010;4:110. [Open access.] PMID: 20409321, PMCID: PMC2873447.
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
Papillary Thyroid Carcinoma
Papillary carcinoma is the most common type of thyroid cancer.[4,12]
Under light microscopy, papillary thyroid carcinomas have characteristic "Orphan Annie eye" nuclear inclusions (ie, nuclei with uniform staining that appear empty), which are useful in identifying the follicular variant of papillary thyroid carcinomas, and psammoma bodies.[13]
Papillary thyroid cancers are slow-growing tumors that arise from the thyroxine (T4)- and thyroglobulin-producing follicular cells and are often multifocal.[4] The tumor cells are sensitive to TSH and take up iodine.[5] Lymphatic spread is more common than hematogenous spread.[5]
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Follicular Thyroid Carcinoma
Image of well-differentiated follicular thyroid carcinoma courtesy of Flickr | Yale Rosen.
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
Follicular Thyroid Carcinoma
Follicular carcinoma is the second most common thyroid malignancy and represents an increased percentage of thyroid cancers in regions where dietary intake of iodine is low.[4] Like papillary carcinomas, follicular carcinomas arise from the follicular cells of the thyroid. The neoplastic cells are also TSH sensitive, taking up iodine and producing thyroglobulin; this feature aids in diagnosis and therapy.[5]
Histologically, the neoplastic follicular cells can have a solid, trabecular, or microfollicular growth pattern.[5] Thyroid follicular carcinoma can resemble thyroid follicular adenoma; the two lesions are generally differentiated by the carcinoma invading the tumor capsule and/or blood vessels.[4,8]
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Hürthle Cell Carcinoma
Images courtesy of Medscape (left) and Wikimedia Commons | Nephron (right).
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
Hürthle Cell Carcinoma
Hürthle cell, or oncocytic, carcinoma is a rare thyroid malignancy that the World Health Organization (WHO) and American Joint Committee on Cancer (AJCC) consider a variant of follicular carcinoma.[8] This malignancy may be aggressive, particularly with large tumors or vascular involvement in older individuals.
Histologically, Hürthle cells are large, polygonal follicular cells with well-defined borders that contain abundant granular acidophilic cytoplasm.
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Medullary Thyroid Carcinoma
High-magnification histologic image of medullary thyroid carcinoma (hematoxylin and eosin [HE] stain) courtesy of Wikimedia Commons | Nephron.
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
Medullary Thyroid Carcinoma
Medullary thyroid malignancies arise from the parafollicular C cells of the thyroid gland;[8,14] these neural-crest derivative cells produce calcitonin.[4,14,15] About 75-80% of medullary thyroid cancers occur sporadically, with the remainder belonging to familial or inherited tumor syndromes. Unlike the sporadic cases, which generally manifest in a single thyroid lobe and in people in their 50s and 60s, the familial cases commonly present earlier and are often multifocal, occurring throughout the thyroid gland.[4,8] Metastasis takes place hematogenously and via the lymphatic system.[8,16]
The histologic appearance of medullary thyroid carcinomas may be variable, typically having a lobular, trabecular, insular, or sheetlike growth pattern separated by a fibrovascular stroma.[5,16] The tumor cells may appear round, polygonal, or spindle shaped, and amyloid deposits may be present.[5]
Patients may present with clinical evidence of medullary thyroid disease, or they may present before the tumors develop if their family has a known history of FMTC syndrome.[5] Medullary thyroid cancer is also associated with MEN 2 syndromes. In pediatric patients with MEN syndrome, early childhood screening for medullary thyroid malignancies and prophylactic thyroidectomy are offered.[5,8]
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Anaplastic Thyroid Carcinoma
Image courtesy of Wikimedia Commons | Nephron.
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
Anaplastic Thyroid Carcinoma
Anaplastic, or undifferentiated, carcinoma is rare, but it has the most aggressive biologic behavior of all the thyroid cancers, as well as one of the worst survival rates of all malignancies (mortality approaches 100%).[5,8] Affected individuals typically present later than those with other thyroid malignancies, usually in their 60s and 70s.[5,8]
Histologically, anaplastic tumor cells have a varied appearance and may have mixed morphologies; the most commonly seen variants are biphasic spindles and giant cells.[5,8]
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Treatment
Image courtesy of Wikimedia Commons | Haitham Alfalah.
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
Treatment
Treatment of patients with thyroid malignancy requires a multidisciplinary approach involving an endocrinologist, a thyroid surgeon, a radiologist, and, on occasion, medical and radiation oncologists.
The prognosis and treatment options depend on the following factors[1,8]:
The patient's age (most important) and general health - Thyroid cancer carries a significantly worse prognosis in those older than 60 years of age
Well-differentiated thyroid cancers generally have a good prognosis; poorly differentiated tumors (eg, medullary, anaplastic) are typically aggressive and highly metastatic and have a significantly worse prognosis[1]
Lesions of greater size tend to have a worse prognosis
The presence of MEN 2 syndromes is generally a poor prognostic indicator
Surgery (thyroidectomy) remains the mainstay of treatment. Newer minimally invasive techniques such as robotic thyroidectomy offer promise in minimizing morbidity; however, more research is needed.
The image depicts a video-assisted thyroidectomy.
14 of 15Image courtesy of Flickr | Yale Rosen.
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
Postoperative radiation therapy
Postoperative radiation therapy may be considered in select patients to destroy any remaining thyroid cancer cells.[1,4,8]
Radioactive iodine (RAI) accumulates in any thyroid tissue that is left, including residual cells with metastatic disease. Because only thyroid tissue takes up iodine, RAI therapy destroys thyroid tissue and thyroid cancer cells with an acceptable side effect profile. Before a full treatment dose of RAI is administered, a small test dose is given to determine whether the tumor takes up the iodine.
External beam radiation therapy (EBRT) is rarely used for locoregional control of thyroid disease, although it may be employed for symptomatic management of local tumor recurrences.[1,4] EBRT is not considered first-line therapy, but it may be used in the treatment of medullary and anaplastic thyroid carcinomas.[1,4,8]
The axial CT scan of the lung shown here demonstrates bilateral pulmonary nodules that are consistent with metastatic thyroid carcinoma. [A] = anterior, [L] = left side, and [R] = right side.
15 of 15Image courtesy of the NCI | Bill Branson.
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A Lump in the Throat: Thyroid Cancer
Ali Ahmad, MD | April 25, 2023 | Contributor Information
In general, chemotherapy for thyroid carcinomas is considered only for very advanced disease or for tumors that are not responsive to radioiodine therapy.[8]
The US Food and Drug Administration has approved the following drugs for treatment of thyroid cancer[17]:
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Contributor Information
Ali Ahmad, MD
Surgical Oncologist
University of Kansas School of Medicine - Wichita
Disclosure: Ali Ahmad, MD has received compensation from Intuitive Surgical USA for proctoring surgeons and lectures.
National Cancer Institute. Surveillance, Epidemiology, and End Results (SEER) Program. SEER stat fact sheets: thyroid cancer. Available at: http://seer.cancer.gov/statfacts/html/thyro.html. Accessed March 28, 2023.
Nikiforova MN, Nikiforov YE. Molecular testing of thyroid FNA samples. In: Nikiforov YE, Biddinger PW, Thompson LDR, eds. Diagnostic Pathology and Molecular Genetics of the Thyroid: A Comprehensive Guide for Practicing Thyroid Pathology. 2nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2012: chapter 21.
Saad RS, Silverman JF, Khalbuss WE. Thyroid fine-needle aspiration. In: Khalbuss WE, Li QK, eds. Diagnostic Cytopathology Board Review and Self-Assessment. New York, NY: Springer Science; 2015: chapter 4.
Yeh MW, Bauer AJ, Bernet VA, et al, for the American Thyroid Association Surgical Affairs Committee Writing Task Force. American Thyroid Association statement on preoperative imaging for thyroid cancer surgery. Thyroid. 2015 Jan;25(1):3-14. PMID: 25188202
Gharib H, Papini E, Paschke R, et al, for the AACE/AME/ETA Task Force on Thyroid Nodules. American Association of Clinical Endocrinologists, Associazione Medici Endocrinologi, and European Thyroid Association Medical guidelines for clinical practice for the diagnosis and management of thyroid nodules. Endocr Pract. 2010 May-Jun;16 (suppl 1):1-43. PMID: 20497938
Kumar V, Abbas AK, Fausto N, Mitchell R. The endocrine system. Robbins Basic Pathology. 8th ed. Philadelphia, Pa: Saunders Elsevier; 2007: chapter 20.
Anderson C, McLaren KM. Tumors of the thyroid glands. In: Al-Nafussi A, ed. Tumor Diagnosis: Practical Approach and Pattern Analysis. 2nd ed. Boca Raton, Fla: CRC Press; 2005.
DeLellis RA. Tumors of the thyroid gland (C-cells). In: Khan A, ed. Surgical Pathology of Endocrine and Neuroendocrine Tumors. New York, NY: Humana Press; 2009.
Biddinger PW. Medullary carcinoma. In: Nikiforov YE, Biddinger PW, Thompson LDR, eds. Diagnostic Pathology and Molecular Genetics of the Thyroid: A Comprehensive Guide for Practicing Thyroid Pathology. 2nd ed. Philadelphia, Pa: Lippincott Williams & Wilkins; 2012: chapter 14.
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