Pediatric Thyroid Cancer Workup
- Author: Mark E Gerber, MD; Chief Editor: Arlen D Meyers, MD, MBA more...
See the list below:
- Levels of serum triiodothyronine (T3), thyroxine (T4), and thyroid-stimulating hormone (TSH) are usually within reference ranges in malignancy. Therefore, although these blood studies have no predictive value for thyroid cancer, they help shape the differential diagnosis of a child's thyroid mass.
- Antithyroid antibodies are helpful in diagnosing chronic lymphocytic thyroiditis. Thyroglobulin levels may be elevated in differentiated thyroid carcinoma and may help in postoperative monitoring. The thyroglobulin level should not be measured until at least 14 days after fine-needle aspiration (FNA) to prevent an artificial level elevation from the needle instrumentation.
- Traditional screening for both medullary thyroid cancer (MTC) and thyroid C-cell hyperplasia is performed by measuring calcitonin levels before and after pentagastrin stimulation. Screening for multiple endocrine neoplasia 2 (MEN2) is now possible with DNA analysis for specific mutations in the ret protooncogene.
- Serum carcinoembryonic antigen (CEA) should be measured in those in whom MTC is suspected. Unfortunately, a negative value may be found in advanced stages of the disease.
- Obtain a 24-hour urine collection to screen for catecholamines metabolites, as a pheochromocytoma or paraganglioma should be surgically removed before thyroidectomy to avoid a hypertension crisis during surgery.
- Obtain genetic testing at birth in children at risk for MEN2B and no later than age one year in children at risk for MEN2A.[29, 42]
Imaging studies reveal the malignant potential and the extent of disease, and they provide an anatomical roadmap for surgical planning. The following are the imaging studies with the highest yield.
- Ultrasonography, a safe and widely available technique, is the first-line screening diagnostic test in all pediatric patients with thyroid nodules.
- In particular, children with a history of radiation exposure should be observed with serial ultrasonography. Nodules that enlarge even a few millimeters should undergo FNAB.
- Ultrasonography is useful in differentiating solid from cystic lesions and in revealing nonpalpable lesions. Many investigators consider cystic lesions to be benign lesions that represent hemorrhage into or degeneration of an adenomatous nodular goiter.
- A solid nodule is more likely to be malignant; however, up to 50% of malignant lesions may have a cystic component, and approximately 8% of cystic lesions represent malignancies.[43, 23]
- Ultrasonography reveals critical information regarding the risk of benign versus malignant disease. Benign features on ultrasound include multiple, solid isoechogenic or nonechogenic lesions and a uniform peripheral halo. Malignant features include a thick irregular halo.
- Color-Doppler sonography may aid in the diagnosis in patients with hyperfunctioning nodules (hot on scintigraphy [SC] and usually benign histologically), indicating an intensive vascular flow within a highly vascularized lesion and no visible flow through the remaining suppressed thyroid gland. Color-Doppler sonography is also valuable in distinguishing a cystic lesion (with no vascular flow) from a solid neoplasm (with intranodular flow).
- One of the most helpful capabilities of ultrasonography is guidance of percutaneous needle biopsy.[10, 11]
- Radionucleotide scan (scintigraphy)
- Thyroid scintigraphy is most useful in revealing tissue function in thyroglossal duct cysts (eg, ensuring that thyroid tissue in the normal location is functioning) and in diagnosing ectopic thyroid. However, thyroid scintigraphy has not proven worthwhile in distinguishing malignant from benign disease.
- Classic hot nodules show uptake only in the nodule area of the thyroid and are associated with about a 6% incidence of malignancy.
- Harach et al (2002) wrote that untreated hot nodules can progress to carcinoma. Surgical treatment is advisable for all children and adolescents with autonomously functioning thyroid nodules because of the risks of hyperthyroidism and thyroid carcinoma.[47, 7]
- Cold nodules are usually benign adenomas, although, in children, a larger number of them are carcinomas. Solid lesions that are cold on scintigraphy are malignant in about 30% of children.
- Total-body radioactive iodine (RAI) scans often reveal pulmonary nodal metastases, which are missed on radiography.
- CT scan
- Noncontrast CT scans can be helpful in patients with substernal extension, local invasion, or lymph node metastasis.
- At initial evaluation, approximately 20% of children have pulmonary metastasis that can be revealed by either chest radiography or CT scan.
- Children have a much higher incidence of pulmonary involvement than adults.
- The CT lung findings, which usually consist of diffuse miliary spots and, less often, infiltrating nodules, are often also best noted with RAI scans.
See the list below:
- Fine-needle aspiration biopsy
- FNAB is the criterion standard in the diagnostic workup of adult thyroid nodules. Several studies report efficacy in the pediatric population.
- High diagnostic accuracy with experienced pathologists improves the selection of pediatric patients for surgery and is an adjunct to guide further management.[50, 15, 16, 51]
- Ultrasonography can be a useful guide for percutaneous needle biopsy when the lesion is difficult to identify with palpation.[10, 11]
- FNAB is often not practical in children younger than 10 years; excisional biopsy under general anesthesia is recommended in this population.
- Using molecular polymerase chain reaction (PCR) studies on FNAB aspirate is mostly beneficial in the clinical research setting. It can be used in a very small number of patients for diagnostic purposes, but it remains expensive.
Follicular adenoma is the most common cause of solitary nodules of the thyroid in the pediatric population. Adenomas are solitary, well circumscribed, and well encapsulated and are composed of glandular epithelium. Most are histologically follicular but are occasionally papillary.
- Most thyroid cancers (papillary, follicular, anaplastic) originate from follicular cells. Medullary thyroid cancers (25% hereditary vs 75% sporadic) are of C-cell (calcitonin-producing) origin.
- Thyroid malignancies in children are usually well-differentiated papillary or papillary-follicular subtypes, but all histologic types have been observed. Papillary carcinoma lesions, which comprise an estimated 72% of pediatric thyroid cancers, are irregular, solid, or cystic masses that arise from follicular epithelium.
- Microscopically, these masses have fronds of epithelium and distinct uniform cells with rare mitoses. Most contain both papillary and follicular components. The cells contain pink, finely granular cytoplasm with large pale nuclei (Orphan Annie eyes) and nuclear grooves. Psammoma bodies are rounded calcified deposits and can be found in approximately 50% of the lesions. Papillary carcinoma has frequent lymphatic and pulmonary metastases.
- Follicular carcinoma lesions, which comprise 18% of pediatric thyroid cancers, are usually encapsulated and have highly cellular follicles and microfollicles with compact dark-staining nuclei of fairly uniform size, shape, and location. Pathologic diagnosis can be made only when invasion of the capsule, adjacent glands, lymphatics, or blood vessels is seen. Follicular carcinoma metastasizes intravascularly to the lungs, brain, and bones. When a portion of the cells in the tumor are found to be oxyphilic (Hürthle cells), it is called a Hürthle cell tumor. These lesions tend to have a less favorable prognosis.
- MTC arises from the thyroid parafollicular or C cells, which secrete calcitonin and are derived from the neural crest and ultimobranchial body. Hyperplasia of the C cells is thought to represent a precancerous state. Histologically, MTC is composed of columns of epithelial cells and dense stroma that typically stain for amyloid and collagen. The nuclei are hyperchromatic, and mitoses are common. The cells have a fusiform shape and may form a whirling pattern. Calcifications are observed in 50% of these lesions.
The American Joint Committee on Cancer (AJCC) created the following staging system:[54, 55]
- T1 - Tumor diameter 2 cm or smaller
- T2 - Primary tumor diameter greater than 2-4 cm
- T3 - Primary tumor diameter greater than 4 cm limited to the thyroid or with minimal extrathyroidal extension
- T4a - Tumor of any size extending beyond the thyroid capsule to invade subcutaneous soft tissues, larynx, trachea, esophagus, or recurrent laryngeal nerve
- T4b - Tumor invades prevertebral fascia or encases carotid artery or mediastinal vessels
- TX - Primary tumor size unknown, but without extrathyroidal invasion
- NO - No metastatic nodes
- N1a - Metastases to level VI (pretracheal, paratracheal, and prelaryngeal/Delphian lymph nodes)
- N1b - Metastasis to unilateral, bilateral, contralateral cervical, or superior mediastinal mode metastases
- NX - Nodes not assessed at surgery
- MO - No distant metastases
- M1 - Distant metastases
- MX - Distant metastases not assessed
Stage I (any T, any N, M0)
Stage II (any T, any N, M1)
See Thyroid Cancer Staging for information on stage groupings.
[Guideline] Francis G, Waguespack SG, Bauer AJ, et al. Management Guidelines for Children with Thyroid Nodules and Differentiated Thyroid Cancer The American Thyroid Association Guidelines Task Force on Pediatric Thyroid Cancer. Thyroid. 2015 Apr 21. [Medline]. [Full Text].
Busko M. ATA Issues First Advice for Thyroid Nodules, Cancer in Children. Medscape Medical News. Apr 27 2015. [Full Text].
Albright JT, Topham AK, Reilly JS. Pediatric head and neck malignancies: US incidence and trends over 2 decades. Arch Otolaryngol Head Neck Surg. 2002 Jun. 128(6):655-9. [Medline].
Corrias A, Mussa A. Thyroid Nodules in Pediatrics: Which Ones Can Be Left Alone, Which Ones Must be Investigated, When and How. J Clin Res Pediatr Endocrinol. 2013 March. 5(Suppl 1):57–69. [Medline].
Silverman SH, Nussbaum M, Rausen AR. Thyroid nodules in children: a ten year experience at one institution. Mt Sinai J Med. 1979 Sep-Oct. 46(5):460-3. [Medline].
Ridgway EC. Clinician Evaluation of a Solitary Thyroid Nodules. Journal of Clinical Endocrinology and Metaoblism. 1992. Vol. 74, No. 2:231-235.
Niedziela M, Korman E. Thyroid carcinoma in a fourteen-year-old boy with Graves disease. Med Pediatr Oncol. 2002 Apr. 38(4):290-1. [Medline].
Halac I, Zimmerman D. Thyroid nodules and cancers in children. Endocrinol Metab Clin North Am. 2005 Sep. 34(3):725-44, x. [Medline].
Festen C, Otten BJ, van de Kaa CA. Follicular adenoma of the thyroid gland in children. Eur J Pediatr Surg. 1995 Oct. 5(5):262-4. [Medline].
Schneider K. Sonographic imaging of the thyroid in children. Prog Pediatr Surg. 1991. 26:1-14. [Medline].
Sherman NH, Rosenberg HK, Heyman S, et al. Ultrasound evaluation of neck masses in children. J Ultrasound Med. 1985 Mar. 4(3):127-34. [Medline].
Dinauer CA, Breuer C, Rivkees SA. Differentiated thyroid cancer in children: diagnosis and management. Curr Opin Oncol. 2008 Jan. 20(1):59-65. [Medline].
Garcia CJ, Daneman A, Thorner P, et al. Sonography of multinodular thyroid gland in children and adolescents. Am J Dis Child. 1992 Jul. 146(7):811-6. [Medline].
Rapkin L, Pashankar FD. Management of thyroid carcinoma in children and young adults. J Pediatr Hematol Oncol. 2012 May. 34 Suppl 2.:S39-46. [Medline].
Khurana KK, Labrador E, Izquierdo R, et al. The role of fine-needle aspiration biopsy in the management of thyroid nodules in children, adolescents, and young adults: a multi-institutional study. Thyroid. 1999 Apr. 9(4):383-6. [Medline].
Lugo-Vicente H, Ortiz VN, Irizarry H, et al. Pediatric thyroid nodules: management in the era of fine needle aspiration. J Pediatr Surg. 1998 Aug. 33(8):1302-5. [Medline].
Niedziela M. Pathogenesis, diagnosis and management of thyroid nodules in children. Endocr Relat Cancer. 2006 Jun. 13(2):427-53. [Medline].
Corrias A, Cassio A, Weber G, et al. Thyroid nodules and cancer in children and adolescents affected by autoimmune thyroiditis. Arch Pediatr Adolesc Med. 2008 Jun. 162(6):526-31. [Medline].
Zimmerman, D. Thyroid Carcinoma in Children and Adolescents: diagnostic implications of analysis of the tumor genome. Curr Opin Pediatr. 25:[Medline].
Miccoli P, Minuto MN, Ugolini C, et al. Papillary thyroid cancer: pathological parameters as prognostic factors in different classes of age. Otolaryngol Head Neck Surg. 2008 Feb. 138(2):200-3. [Medline].
Williams ED, Abrosimov A, Bogdanova T, et al. Thyroid carcinoma after Chernobyl latent period, morphology and aggressiveness. Br J Cancer. 2004 Jun 1. 90(11):2219-24. [Medline].
Ron E. Thyroid cancer incidence among people living in areas contaminated by radiation from the Chernobyl accident. Health Phys. 2007 Nov. 93(5):502-11. [Medline].
Yoskovitch A, Laberge JM, Rodd C, et al. Cystic thyroid lesions in children. J Pediatr Surg. 1998 Jun. 33(6):866-70. [Medline].
Alessandri AJ, Goddard KJ, Blair GK, et al. Age is the major determinant of recurrence in pediatric differentiated thyroid carcinoma. Med Pediatr Oncol. 2000 Jul. 35(1):41-6. [Medline].
La Quaglia MP, Telander RL. Differentiated and medullary thyroid cancer in childhood and adolescence. Semin Pediatr Surg. 1997 Feb. 6(1):42-9. [Medline].
Attie JA. Carcinoma of the thyroid in children and adolescents. F Lifshitz. Pediatric Endocrinology. 3. New York: Marcel Dekker; 1996. 423-432.
Estevao-Costa J, Gil-Da-Costa MJ, Medina AM, et al. Thyroid carcinoma in a newborn: clinical challenges in managing the first recorded case. Med Pediatr Oncol. 2000 Apr. 34(4):290-2. [Medline].
Yip FW, Reeve TS, Poole AG, et al. Thyroid nodules in childhood and adolescence. Aust N Z J Surg. 1994 Oct. 64(10):676-8. [Medline].
Skinner MA, Wells SA Jr. Medullary carcinoma of the thyroid gland and the MEN 2 syndromes. Semin Pediatr Surg. 1997 Aug. 6(3):134-40. [Medline].
Cotterill SJ, Pearce MS, Parker L. Thyroid cancer in children and young adults in the North of England. Is increasing incidence related to the Chernobyl accident?. Eur J Cancer. 2001 May. 37(8):1020-6. [Medline].
Gawrysiak W, Niedziela M. Suppurative thyroiditis. Endokrynologia Pediatryczna (Pediatric Endocrinology). 2005. 4:65-69.
Bhatia S, Ramsay NK, Bantle JP, et al. Thyroid Abnormalities after Therapy for Hodgkin's Disease in Childhood. Oncologist. 1996. 1(1 & 2):62-67. [Medline].
Jensen MO, Antonenko D. Thyroid and thymic malignancy following childhood irradiation. J Surg Oncol. 1992 Jul. 50(3):206-8. [Medline].
Metayer C, Lynch CF, Clarke EA, et al. Second cancers among long-term survivors of Hodgkin's disease diagnosed in childhood and adolescence. J Clin Oncol. 2000 Jun. 18(12):2435-43. [Medline].
Nikiforov Y, Gnepp DR. Pediatric thyroid cancer after the Chernobyl disaster. Pathomorphologic study of 84 cases (1991-1992) from the Republic of Belarus. Cancer. 1994 Jul 15. 74(2):748-66. [Medline].
Vane D, King DR, Boles ET Jr. Secondary thyroid neoplasms in pediatric cancer patients: increased risk with improved survival. J Pediatr Surg. 1984 Dec. 19(6):855-60. [Medline].
Thomas GA, Bunnell H, Cook HA, et al. High prevalence of RET/PTC rearrangements in Ukrainian and Belarussian post-Chernobyl thyroid papillary carcinomas: a strong correlation between RET/PTC3 and the solid-follicular variant. J Clin Endocrinol Metab. 1999 Nov. 84(11):4232-8. [Medline].
Sklar C, Whitton J, Mertens A, et al. Abnormalities of the thyroid in survivors of Hodgkin's disease: data from the Childhood Cancer Survivor Study. J Clin Endocrinol Metab. 2000 Sep. 85(9):3227-32. [Medline].
Patti G, Ragni G, Calisti A. Papillary thyroid carcinoma in a thyroglossal duct cyst in a child. Med Pediatr Oncol. 2000 Jan. 34(1):67-9. [Medline].
Luboshitzky R, Lavi I, Ishay A. Serum thyroglobulin levels after fine-needle aspiration of thyroid nodules. Endocr Pract. 2006 May-Jun. 12(3):264-9. [Medline].
Bockhorn M, Frilling A, Rewerk S, et al. Lack of elevated serum carcinoembryonic antigen and calcitonin in medullary thyroid carcinoma. Thyroid. 2004 Jun. 14(6):468-70. [Medline].
Telander RL, Moir CR. Medullary thyroid carcinoma in children. Semin Pediatr Surg. 1994 Aug. 3(3):188-93. [Medline].
Bajpai M, Ramaswamy S, Gupta DK, et al. Solitary thyroid nodule. Indian Pediatr. 1992 Jan. 29(1):116-8. [Medline].
Solbiati L, Cioffi V, Ballarati E. Ultrasonography of the neck. Radiol Clin North Am. 1992 Sep. 30(5):941-54. [Medline].
Hegedüs L, Bonnema SJ, Bennedbaek FN. Management of simple nodular goiter: current status and future perspectives. Endocr Rev. 2003 Feb. 24(1):102-32. [Medline].
Harach HR, Sanchez SS, Williams ED. Pathology of the autonomously functioning (hot) thyroid nodule. Ann Diagn Pathol. 2002 Feb. 6(1):10-9. [Medline].
Croom RD 3rd, Thomas CG Jr, Reddick RL, et al. Autonomously functioning thyroid nodules in childhood and adolescence. Surgery. 1987 Dec. 102(6):1101-8. [Medline].
Geiger JD, Thompson NW. Thyroid tumors in children. Otolaryngol Clin North Am. 1996 Aug. 29(4):711-9. [Medline].
Desjardins JG, Khan AH, Montupet P, et al. Management of thyroid nodules in children: a 20-year experience. J Pediatr Surg. 1987 Aug. 22(8):736-9. [Medline].
Eisenhut CC, King DE, Nelson WA, et al. Fine-needle biopsy of pediatric lesions: a three-year study in an outpatient biopsy clinic. Diagn Cytopathol. 1996 Feb. 14(1):43-50. [Medline].
Raab SS, Silverman JF, Elsheikh TM, et al. Pediatric thyroid nodules: disease demographics and clinical management as determined by fine needle aspiration biopsy. Pediatrics. 1995 Jan. 95(1):46-9. [Medline].
Bettendorf M. Thyroid disorders in children from birth to adolescence. Eur J Nucl Med Mol Imaging. 2002 Aug. 29 Suppl 2:S439-46. [Medline].
Gimm O, Sutter T, Dralle H. Diagnosis and therapy of sporadic and familial medullary thyroid carcinoma. J Cancer Res Clin Oncol. 2001. 127(3):156-65. [Medline].
Dinauer CA, Breuer C, Rivkees SA. Differentiated thyroid cancer in children: diagnosis and management. Curr Opin Oncol. 2008 Jan. 20(1):59-65. [Medline].
AJCC Cancer Staging Manual. Sixth Edition. New York: Springer-Verlag, , Inc; 2002.
Yeh SD, La Quaglia MP. 131I therapy for pediatric thyroid cancer. Semin Pediatr Surg. 1997 Aug. 6(3):128-33. [Medline].
Bryarly RC, Shockley WW, Stucker FJ. The method and management of thyroid surgery in the pediatric patient. Laryngoscope. 1985 Sep. 95(9 Pt 1):1025-8. [Medline].
Herzog B. Thyroid gland diseases and tumours. Surgical aspects. Prog Pediatr Surg. 1983. 16:15-22. [Medline].
Lallier M, St-Vil D, Giroux M, et al. Prophylactic thyroidectomy for medullary thyroid carcinoma in gene carriers of MEN2 syndrome. J Pediatr Surg. 1998 Jun. 33(6):846-8. [Medline].
Newman KD, Black T, Heller G, et al. Differentiated thyroid cancer: determinants of disease progression in patients 1111111111111111Ann Surg</i>. 1998 Apr. 227(4):533-41. [Medline].
Ben Arush MW, Stein ME, Perez Nahum M, et al. Pediatric thyroid carcinoma: 22 years of experience at the Northern Israel Oncology Center (1973-1995). Pediatr Hematol Oncol. 2000 Jan-Feb. 17(1):85-92. [Medline].
Amrikachi M, Ponder TB, Wheeler TM, et al. Thyroid fine-needle aspiration biopsy in children and adolescents: experience with 218 aspirates. Diagn Cytopathol. 2005 Apr. 32(4):189-92. [Medline].
Belfiore A, Giuffrida D, La Rosa GL, et al. High frequency of cancer in cold thyroid nodules occurring at young age. Acta Endocrinol (Copenh). 1989 Aug. 121(2):197-202. [Medline].
Hughes CJ, Shaha AR, Shah JP, et al. Impact of lymph node metastasis in differentiated carcinoma of the thyroid: a matched-pair analysis. Head Neck. 1996 Mar-Apr. 18(2):127-32. [Medline].
Millman B, Pellitteri PK. Nodular thyroid disease in children and adolescents. Otolaryngol Head Neck Surg. 1997 Jun. 116(6 Pt 1):604-9. [Medline].
Salas M. Thyroid nodules in children and adolescents. Ed. F Lifshitz. In Pediatric Endocrinology, edn 3. New York: Marcel Dekker; 1995. pp 415-422.