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Unusual Cancers of Childhood Treatment (PDQ®): Treatment - Health Professional Information [NCI]

This information is produced and provided by the National Cancer Institute (NCI). The information in this topic may have changed since it was written. For the most current information, contact the National Cancer Institute via the Internet web site at http://cancer.gov or call 1-800-4-CANCER.

General Information About Unusual Cancers of Childhood

Introduction

Cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975.[1] Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered for children and adolescents with cancer. This multidisciplinary team approach incorporates the skills of the primary care physician, pediatric surgeons, radiation oncologists, pediatric medical oncologists/hematologists, rehabilitation specialists, pediatric nurse specialists, social workers, and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life. (Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)

Guidelines for pediatric cancer centers and their role in the treatment of pediatric patients with cancer have been outlined by the American Academy of Pediatrics.[2] At these pediatric cancer centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate in these trials is offered to most patients/families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with therapy that is currently accepted as standard. Most of the progress made in identifying curative therapy for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI website.

Dramatic improvements in survival have been achieved for children and adolescents with cancer. Between 1975 and 2010, childhood cancer mortality decreased by more than 50%.[3] Childhood and adolescent cancer survivors require close monitoring because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ summary on Late Effects of Treatment for Childhood Cancer for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)

Childhood cancer is a rare disease with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[4] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 persons and, by definition, all pediatric cancers are considered rare. The designation of a pediatric rare tumor is not uniform among international groups:

  • The Italian cooperative project on rare pediatric tumors (Tumori Rari in Eta Pediatrica [TREP]) defines a pediatric rare tumor as one with an incidence of less than two cases per 1 million population per year and is not included in other clinical trials.[5]
  • The Children's Oncology Group (COG) has opted to define rare pediatric cancers as those listed in the International Classification of Childhood Cancer subgroup XI, which includes thyroid cancer, melanoma and nonmelanoma skin cancers, and multiple types of carcinomas (e.g., adrenocortical carcinoma, nasopharyngeal carcinoma, and most adult-type carcinomas such as breast cancer, colorectal cancer, etc.).[6] These diagnoses account for about 4% of cancers diagnosed in children aged 0 to 14 years, compared with about 20% of cancers diagnosed in adolescents aged 15 to 19 years (refer to Figures 1 and 2).[7] Most cancers within subgroup XI are either melanomas or thyroid cancer, with the remaining subgroup XI cancer types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers in adolescents aged 15 to 19 years.

These rare cancers are extremely challenging to study because of the low incidence of patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the lack of clinical trials for adolescents with rare cancers such as melanoma.

Pie chart showing age-adjusted and age-specific cancer incidence rates for patients aged 0-14 years (SEER 2009-2012).
Figure 1. Age-adjusted and age-specific (0–14 years) Surveillance, Epidemiology, and End Results cancer incidence rates from 2009 to 2012 by International Classification of Childhood Cancer group and subgroup and age at diagnosis, including myelodysplastic syndrome and group III benign brain/central nervous system tumors for all races, males, and females. Pie chart showing age-adjusted and age-specific cancer incidence rates for patients aged 15-19 years (SEER 2009-2012).
Figure 2. Age-adjusted and age-specific (15–19 years) Surveillance, Epidemiology, and End Results cancer incidence rates from 2009 to 2012 by International Classification of Childhood Cancer group and subgroup and age at diagnosis, including myelodysplastic syndrome and group III benign brain/central nervous system tumors for all races, males, and females.

Several initiatives to study rare pediatric cancers have been developed by the COG and other international groups, such as the International Society of Paediatric Oncology (Société Internationale D'Oncologie Pédiatrique [SIOP]). The Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) rare tumor project was founded in Germany in 2006.[8] The Italian cooperative project on rare pediatric tumors (TREP) was launched in 2000,[5] and the Polish Pediatric Rare Tumor Study Group was launched in 2002.[9] In Europe, the rare tumor studies groups from France, Germany, Italy, Poland, and the United Kingdom have joined in the European Cooperative study Group on Pediatric Rare Tumors (EXPeRT), focusing on international collaboration and analyses of specific rare tumor entities.[10] Within the COG, efforts have concentrated on increasing accrual to the COG registry (now known as the Childhood Cancer Research Network/Project Every Child) and the rare tumor bank, developing single-arm clinical trials, and increasing cooperation with adult cooperative group trials.[11] The accomplishments and challenges of this initiative have been described in detail.[6,12]

The tumors discussed in this summary are very diverse; they are arranged in descending anatomic order, from infrequent tumors of the head and neck to rare tumors of the urogenital tract and skin. All of these cancers are rare enough that most pediatric hospitals might see less than a handful of some histologies in several years. The majority of the histologies described here occur more frequently in adults. Information about these tumors may also be found in sources relevant to adults with cancer.

References:

  1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010.
  2. Corrigan JJ, Feig SA; American Academy of Pediatrics: Guidelines for pediatric cancer centers. Pediatrics 113 (6): 1833-5, 2004.
  3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014.
  4. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr.
  5. Ferrari A, Bisogno G, De Salvo GL, et al.: The challenge of very rare tumours in childhood: the Italian TREP project. Eur J Cancer 43 (4): 654-9, 2007.
  6. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children's Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010.
  7. Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2012. Bethesda, Md: National Cancer Institute, 2015. Also available online. Last accessed March 29, 2018.
  8. Brecht IB, Graf N, Schweinitz D, et al.: Networking for children and adolescents with very rare tumors: foundation of the GPOH Pediatric Rare Tumor Group. Klin Padiatr 221 (3): 181-5, 2009 May-Jun.
  9. Balcerska A, Godzinski J, Bien E, et al.: [Rare tumours--are they really rare in the Polish children population?]. Przegl Lek 61 (Suppl 2): 57-61, 2004.
  10. Bisogno G, Ferrari A, Bien E, et al.: Rare cancers in children - The EXPeRT Initiative: a report from the European Cooperative Study Group on Pediatric Rare Tumors. Klin Padiatr 224 (6): 416-20, 2012.
  11. Musselman JR, Spector LG, Krailo MD, et al.: The Children's Oncology Group Childhood Cancer Research Network (CCRN): case catchment in the United States. Cancer 120 (19): 3007-15, 2014.
  12. Pappo AS, Furman WL, Schultz KA, et al.: Rare Tumors in Children: Progress Through Collaboration. J Clin Oncol 33 (27): 3047-54, 2015.

Head and Neck Cancers

Childhood sarcomas often occur in the head and neck area and they are described in other sections. Unusual pediatric head and neck cancers include the following:

  • Nasopharyngeal carcinoma.
  • Esthesioneuroblastoma.
  • Thyroid tumors.
  • Oral cavity cancer.
  • Salivary gland tumors.
  • Laryngeal carcinoma and papillomatosis.
  • Midline tract carcinoma involving the NUT gene.

It must be emphasized that these cancers are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from small case series or cohorts combining pediatric and adult patients.

Nasopharyngeal Carcinoma

Incidence

Nasopharyngeal carcinoma arises in the lining of the nasal cavity and pharynx, and it accounts for about one-third of all cancers of the upper airways in children.[1,2] Nasopharyngeal carcinoma is very uncommon in children younger than 10 years but increases in incidence to 0.8 cases per 1 million per year in children aged 10 to 14 years and 1.3 cases per million per year in children aged 15 to 19 years.[3,4,5]

The incidence of nasopharyngeal carcinoma is characterized by racial and geographic variations, with an endemic distribution among well-defined ethnic groups, such as inhabitants of some areas in North Africa and the Mediterranean basin, and, particularly, Southeast Asia. In the United States, the incidence of nasopharyngeal carcinoma is higher in black children and adolescents younger than 20 years.[4]

Risk Factors

Nasopharyngeal carcinoma is strongly associated with Epstein-Barr virus (EBV) infection. In addition to the serological evidence of infection in more than 98% of patients, EBV DNA is present as a monoclonal episome in the nasopharyngeal carcinoma cells, and tumor cells can have EBV antigens on their cell surface.[6] The circulating levels of EBV DNA and serologic documentation of EBV infection may aid in the diagnosis.[7] Specific HLA subtypes, such as the HLA A2Bsin2 haplotype, are associated with a higher risk of nasopharyngeal carcinoma.[1]

Histology

Three histologic subtypes of nasopharyngeal carcinoma are recognized by the World Health Organization (WHO):

  • Type I is keratinizing squamous cell carcinoma.
  • Type II is nonkeratinizing squamous cell carcinoma. Type II is distinguished into type IIa and IIb depending on the presence of lymphoid infiltration.
  • Type III is undifferentiated carcinoma. Type III is distinguished into type IIIa and IIIb depending on the presence of lymphoid infiltration.

Children with nasopharyngeal carcinoma are more likely to have WHO type II or type III disease.[4]

Clinical Presentation

Signs and symptoms of nasopharyngeal carcinoma include the following:[2,8]

  • Cervical lymphadenopathy.
  • Nosebleeds.
  • Nasal congestion and obstruction.
  • Headache.
  • Otalgia.
  • Otitis media.

Given the rich lymphatic drainage of the nasopharynx, bilateral cervical lymphadenopathy is often the first sign of disease. The tumor spreads locally to adjacent areas of the oropharynx and may invade the skull base, resulting in cranial nerve palsy or difficulty with movements of the jaw (trismus).

Distant metastatic sites may include the bones, lungs, and liver.

Diagnostic and Staging Evaluation

Diagnostic tests will determine the extent of the primary tumor and the presence of metastases. Visualization of the nasopharynx by an ear-nose-throat specialist using nasal endoscopy and magnetic resonance imaging of the head and neck can be used to determine the extent of the primary tumor.

A diagnosis can be made from a biopsy of the primary tumor or enlarged lymph nodes of the neck. Nasopharyngeal carcinomas must be distinguished from all other cancers that can present with enlarged lymph nodes and from other types of cancer in the head and neck area. Thus, diseases such as thyroid cancer, rhabdomyosarcoma, non-Hodgkin lymphoma including Burkitt lymphoma, and Hodgkin lymphoma must be considered, as well as benign conditions such as nasal angiofibroma, which usually presents with epistaxis in adolescent males, infectious lymphadenitis, and Rosai-Dorfman disease.

Evaluation of the chest and abdomen by computed tomography (CT) and bone scan is performed to determine whether there is metastatic disease. Fluorine F 18-fludeoxyglucose positron emission tomography (PET)–CT may also be helpful in the evaluation of potential metastatic lesions.[9]

Stage Information for Childhood Nasopharyngeal Carcinoma

Tumor staging is performed using the tumor-node-metastasis (TNM) classification system of the American Joint Committee on Cancer (AJCC, 8th edition).[10,11]

More than 90% of children and adolescents with nasopharyngeal carcinoma present with advanced disease (stage III/IV or T3/T4).[12,13,14] Metastatic disease (stage IVC) at diagnosis is uncommon. A retrospective analysis of data from the Surveillance, Epidemiology, and End Results program reported that patients younger than 20 years had a higher incidence of advanced-stage disease than did older patients.[4]

Prognosis

The overall survival (OS) of children and adolescents with nasopharyngeal carcinoma has improved over the last four decades; with state-of-the-art multimodal treatment, 5-year survival rates exceed 80%.[4,5,8,13,14,15,16,17] After controlling for stage, children with nasopharyngeal carcinoma have significantly better outcomes than do adults.[4,5] However, the intensive use of chemotherapy and radiation therapy results in significant acute and long-term morbidities, including subsequent neoplasms.[4,13,14,16]

Treatment of Childhood Nasopharyngeal Carcinoma

Treatment of nasopharyngeal carcinoma is multimodal and includes the following:

  1. Combined-modality therapy with chemotherapy and radiation: High-dose radiation therapy alone has a role in the management of nasopharyngeal carcinoma; however, studies in both children and adults show that combined-modality therapy with chemotherapy and radiation is the most effective way to treat nasopharyngeal carcinoma.[17]; [13,14,15,18,19,20,21][Level of evidence: 2A]
    1. Randomized studies have investigated the role of chemotherapy in the treatment of adult nasopharyngeal carcinoma. The use of concomitant chemoradiation therapy was associated with a significant survival benefit, including improved locoregional disease control and reduction in distant metastases.[20,22] The use of neoadjuvant chemotherapy has also resulted in better local and distant control rates, whereas postradiation chemotherapy does not seem to offer any benefit.[22]
    2. In children, four studies used preradiation chemotherapy with different combinations of methotrexate, cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without recombinant interferon-beta.[14,15,23,24][Level of evidence: 2A]
      • These four studies reported response rates of more than 90% and excellent outcomes.
      • Neoadjuvant chemotherapy with cisplatin and 5-FU (with or without leucovorin), followed by chemoradiation with single-agent cisplatin has yielded 5-year overall survival (OS) rates consistently above 80%.[14,15]
      • A preliminary analysis of the NPC-2003-GPOH study, which included a 6-month maintenance therapy phase with interferon-beta, reported a 30-month OS estimate of 97.1%.[15]
    3. While nasopharyngeal carcinoma is a very chemosensitive neoplasm, high radiation doses to the nasopharynx and neck (approximately 60 Gy) are required for optimal locoregional control.[13,14,15,16] The combination of cisplatin-based chemotherapy and high doses of radiation therapy to the nasopharynx and neck are associated with a high probability of hearing loss, hypothyroidism and panhypopituitarism, trismus, xerostomia, dental problems, and chronic sinusitis or otitis.[13,14,16]; [8][Level of evidence: 3iiiA]
    4. A randomized prospective trial compared cisplatin and 5-FU with cisplatin, 5-FU, and docetaxel for the treatment of nasopharyngeal carcinoma in children and adolescents.[25][Level of evidence: 1iiA] The addition of docetaxel was not associated with improved outcome.
    5. Additional drug combinations that have been used in children with nasopharyngeal carcinoma include bleomycin with epirubicin and cisplatin, and cisplatin with methotrexate and bleomycin.[1]
    6. Other approaches to the management of nasopharyngeal carcinoma in children have been evaluated and include the following:
      • Incorporation of high-dose-rate brachytherapy into the chemoradiation therapy approach.[26,27]
      • Following adult studies and data, taxanes have been incorporated into the treatment of childhood nasopharyngeal carcinoma; studies have shown good objective response rates and favorable outcomes with the use of docetaxel in combination with cisplatin.[28][Level of evidence: 3iiiDiv]
  2. Surgery: Surgery has a limited role in the management of nasopharyngeal carcinoma because the disease is usually considered unresectable because of extensive local spread.

The use of Epstein-Barr virus–specific cytotoxic T-lymphocytes has shown to be a very promising approach with minimal toxicity and evidence of significant antitumor activity in patients with relapsed or refractory nasopharyngeal carcinoma.[29]

(Refer to the PDQ summary on Nasopharyngeal Cancer Treatment [Adult] for more information.)

Treatment Options Under Clinical Evaluation for Childhood Nasopharyngeal Carcinoma

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.

The following are examples of national and/or institutional clinical trials that are currently being conducted:

  • H-25145 (NCT00953420) (Carboplatin, Docetaxel, and Laboratory-Treated T Cells in Treating Patients With Refractory or Relapsed Epstein-Barr Virus [EBV]-Positive Nasopharyngeal Cancer): The objective of this trial is to determine the overall response rate in patients with relapsed/refractory, advanced-stage, EBV-positive nasopharyngeal carcinoma after treatment with docetaxel and carboplatin followed by immunotherapy with EBV-specific cytotoxic T lymphocytes. Individuals aged 10 years and older are eligible for this trial.
  • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 3,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.

    Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the ClinicalTrials.gov website for APEC1621 (NCT03155620).

Esthesioneuroblastoma

Incidence

Esthesioneuroblastoma (olfactory neuroblastoma) is a small round-cell tumor arising from the nasal neuroepithelium that is distinct from primitive neuroectodermal tumors.[37,38,39,40] In children, esthesioneuroblastoma is a very rare malignancy, with an estimated incidence of 0.1 cases per 100,000 per year in children younger than 15 years.[41]

Despite its rarity, esthesioneuroblastoma is the most common cancer of the nasal cavity in pediatric patients, accounting for 28% of cases in a Surveillance, Epidemiology, and End Results (SEER) study.[42] In a series of 511 patients from the SEER database, there was a slight male predominance, the mean age at presentation was 53 years, and only 8% of cases were younger than 25 years.[43] Most patients were white (81%) and the most common tumor sites were the nasal cavity (72%) and ethmoid sinus (13%).[43]

Clinical Presentation

Most children present in the second decade of life with symptoms that include the following:

  • Nasal obstruction.
  • Epistaxis.
  • Hyposmia.
  • Exophthalmos.
  • Nasopharyngeal mass, which may have local extension into the orbits, sinuses, or frontal lobe.

Prognostic Factors

Review of multiple case series of mainly adult patients indicate that the following may correlate with adverse prognosis:[44,45,46]

  • Higher histopathologic grade.
  • Positive surgical margin status.
  • Metastases to the cervical lymph nodes.

Stage Information for Childhood Esthesioneuroblastoma

Tumors are staged according to the Kadish system (refer to Table 1). Correlated with Kadish stage, survival ranges from 90% (stage A) to less than 40% (stage D). Most patients present with locally advanced–stage disease (Kadish stages B and C) and almost one-third of patients have tumors at distant sites (Kadish stage D).[41,42] Recent reports suggest that positron emission tomography–computed tomography (PET-CT) may aid in staging the disease.[47]

Table 1. Kadish Staging System
Stage Description
A Tumor confined to the nasal cavity.
B Tumor extending to the nasal sinuses.
C Tumor extending to the nasal sinuses and beyond.
D Tumor metastases present.

Treatment and Outcome of Childhood Esthesioneuroblastoma

The use of multimodal therapy optimizes the chances for survival, with more than 70% of children expected to survive 5 or more years after initial diagnosis.[41,48,49] A multi-institutional review of 24 patients younger than 21 years at diagnosis found a 5-year disease-free survival and overall survival of 73% to 74%.[50][Level of evidence: 3iiiA]

Treatment options according to Kadish stage include the following:[51]

  1. Kadish stage A: Surgery alone with clear margins. Adjuvant radiation therapy is indicated in patients with close and positive margins or with residual disease.
  2. Kadish stage B: Surgery followed by adjuvant radiation therapy. The role of adjuvant chemotherapy is controversial.
  3. Kadish stage C: Neoadjuvant approach with chemotherapy, radiation therapy, or concurrent chemotherapy-radiation therapy followed by surgery.
  4. Kadish stage D: Systemic chemotherapy and palliative radiation therapy to local and metastatic sites. Palliative care is incorporated into the treatment plan to improve quality of life.

The mainstay of treatment is surgery and radiation.[52] Newer techniques such as endoscopic sinus surgery may offer similar short-term outcomes to open craniofacial resection.[43]; [53][Level of evidence: 3iiiDii] Other techniques such as stereotactic radiosurgery and proton-beam therapy (charged-particle radiation therapy) may also play a role in the management of this tumor.[49,54]

Nodal metastases are seen in about 5% of patients. Routine neck dissection and nodal exploration are not indicated in the absence of clinical or radiological evidence of disease.[55] Management of cervical lymph node metastases has been addressed in a review article.[55]

Reports indicate promising results with the increased use of resection and neoadjuvant or adjuvant chemotherapy in patients with advanced-stage disease.[37,48,50,56,57]; [58][Level of evidence: 3iii] Chemotherapy regimens that have been used with efficacy include cisplatin and etoposide with or without ifosfamide;[51,59] vincristine, actinomycin D, and cyclophosphamide with or without doxorubicin; ifosfamide and etoposide; cisplatin plus etoposide or doxorubicin;[48] vincristine, doxorubicin, and cyclophosphamide;[60] and irinotecan plus docetaxel.[61][Level of evidence: 3iiA]

Treatment Options Under Clinical Evaluation for Childhood Esthesioneuroblastoma

Information about National Cancer Institute (NCI)–supported clinical trials can be found on the NCI website. For information about clinical trials sponsored by other organizations, refer to the ClinicalTrials.gov website.

The following is an example of a national and/or institutional clinical trial that is currently being conducted:

  • APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 3,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.

    Tumor tissue from progressive or recurrent disease must be available for molecular characterization. Patients with tumors that have molecular variants addressed by treatment arms included in the trial will be offered treatment on Pediatric MATCH. Additional information can be obtained on the ClinicalTrials.gov website for APEC1621 (NCT03155620).

Thyroid Tumors

Incidence

The annual incidence of thyroid cancers is 2 cases per 1 million people per year in children younger than 15 years, accounting for approximately 1.5% of all cancers in this age group.[3] Thyroid cancer incidence is higher in children aged 15 to 19 years (17.6 cases per 1 million people), and it accounts for approximately 8% of cancers arising in this older age group.[3,62] More thyroid carcinomas occur in females than in males.[63]

A retrospective review of the Surveillance, Epidemiology, and End Results (SEER) database from 1973 to 2011 identified 2,504 cases of papillary thyroid carcinoma in patients aged 20 years and younger.[62] The incidence of papillary thyroid carcinoma increased over this interval by roughly 2% each year. The trend toward larger tumors suggests that diagnostic scrutiny is not the only explanation for the observed results.[64]

An update from the SEER database for the period of 2007 to 2012 identified 1,723 pediatric patients with thyroid cancer.[65] The average age-adjusted incidence of pediatric thyroid cancer was 0.59 cases per 100,000 patients. When the incidence in females was compared with the incidence in males, the ratio of pediatric thyroid cancer was 4.4:1. The papillary subtype was the most common (n = 1,014; 58.8%), followed by the follicular variant subtype (n = 397; 23%), the follicular subtype (n = 173; 10.1%), and the medullary subtype (n = 139; 8.1%). As pediatric patients reached the ages of 15 to 19 years, the incidences of the papillary and follicular variant subtypes increased. An analysis of medullary thyroid cancer data revealed that the incidence was the highest in the age group of 0 to 4 years and declined at older ages (refer to Figure 3).[65]

Chart showing the incidence of pediatric thyroid carcinoma based on most frequent subtype per 100,000 as a percent of total cohort.
Figure 3. Incidence of pediatric thyroid carcinoma based on most frequent subtype per 100,000 as a percent of total cohort. Reprinted from International Journal of Pediatric Otorhinolaryngology, Volume 89, Sarah Dermody, Andrew Walls, Earl H. Harley Jr., Pediatric thyroid cancer: An update from the SEER database 2007–2012, Pages 121–126, Copyright (2016), with permission from Elsevier.

Risk Factors

There is an excessive frequency of thyroid adenoma and carcinoma in patients who previously received radiation to the neck.[66,67] In the decade following the Chernobyl nuclear incident, there was a tenfold increase in the incidence of thyroid cancer compared with the previous and following decades.[68] In this group of patients with exposure to low-dose radiation, tumors commonly show a gain of chromosome band 7q11.[69]

When occurring in patients with the multiple endocrine neoplasia syndromes, thyroid cancer may be associated with the development of other types of malignant tumors. (Refer to the Multiple Endocrine Neoplasia [MEN] Syndromes and Carney Complex section of the PDQ summary on Unusual Cancers of Childhood Treatment for more information.)

Histology

Tumors of the thyroid are classified as adenomas or carcinomas.[70,71,72] Adenomas are benign, well circumscribed and encapsulated nodules that may cause enlargement of all or part of the gland, which extends to both sides of the neck and can be quite large; some tumors may secrete hormones. Transformation to a malignant carcinoma may occur in some cells, which may grow and spread to lymph nodes in the neck or to the lungs. Approximately 20% of thyroid nodules in children are malignant.[70,73]

Various histologies account for the general diagnostic category of carcinoma of the thyroid; papillary and follicular carcinoma are often referred to as differentiated thyroid carcinoma:[67]

  • Papillary carcinoma (60%–75%): Papillary carcinoma often has a multicentric origin and a very high rate of lymph node metastasis (7