General Information About Rare Cancers of Childhood

Introduction

Cancer in children and adolescents is rare, although the overall incidence has slowly increased since 1975.[1] Children and adolescents with cancer should be referred to medical centers that have a multidisciplinary team of cancer specialists with experience treating the cancers that occur during childhood and adolescence. This multidisciplinary team approach incorporates the skills of primary care physicians, pediatric surgeons, pathologists, pediatric radiation oncologists, pediatric medical oncologists and hematologists, rehabilitation specialists, pediatric oncology nurses, social workers, child-life professionals, psychologists, nutritionists, and others to ensure that children receive treatment, supportive care, and rehabilitation to achieve optimal survival and quality of life. For specific information about supportive care for children and adolescents with cancer, see the summaries on Supportive and Palliative Care.

The American Academy of Pediatrics has outlined guidelines for pediatric cancer centers and their role in the treatment of children and adolescents with cancer.[2] At these centers, clinical trials are available for most types of cancer that occur in children and adolescents, and the opportunity to participate is offered to most patients and their families. Clinical trials for children and adolescents diagnosed with cancer are generally designed to compare potentially better therapy with current standard therapy. Other types of clinical trials test novel therapies when there is no standard therapy for a cancer diagnosis. Most of the progress in identifying curative therapies 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 2020, childhood cancer mortality decreased by more than 50%.[3,4,5] Childhood and adolescent cancer survivors require close monitoring because side effects of cancer therapy may persist or develop months or years after treatment. For information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors, see Late Effects of Treatment for Childhood Cancer.

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[6] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 people. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. In adults, rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people. They account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[7,8] In children and adolescents, the designation of a rare tumor is not uniform among international groups, as follows:

• A consensus effort between the European Union Joint Action on Rare Cancers and the European Cooperative Study Group for Rare Pediatric Cancers (EXPeRT) estimated that 11% of all cancers in patients younger than 20 years could be categorized as very rare. This consensus group defined very rare cancers as those with annual incidences of fewer than 2 cases per 1 million people. However, three additional histologies (thyroid carcinoma, melanoma, and testicular cancer) with incidences of more than 2 cases per 1 million people were also included in the very rare group due to a lack of knowledge and expertise in the management of these tumors.[9]
• The Children's Oncology Group (COG) defines rare pediatric cancers as those listed in the International Classification of Childhood Cancer subgroup XI, which includes thyroid cancers, melanomas and nonmelanoma skin cancers, and multiple types of carcinomas (e.g., adrenocortical carcinomas, nasopharyngeal carcinomas, and most adult-type carcinomas such as breast cancers and colorectal cancers).[10] These diagnoses account for about 5% of the cancers diagnosed in children aged 0 to 14 years and about 27% of the cancers diagnosed in adolescents aged 15 to 19 years.[4]

  Most cancers in subgroup XI are either melanomas or thyroid cancers, with other cancer types accounting for only 2% of the cancers in children aged 0 to 14 years and 9.3% of the cancers in adolescents aged 15 to 19 years.

These rare cancers are extremely challenging to study because of the relatively few patients with any individual diagnosis, the predominance of rare cancers in the adolescent population, and the small number of clinical trials for adolescents with rare cancers.

Some investigators have used large databases, such as the Surveillance, Epidemiology, and End Results (SEER) Program and the National Cancer Database, to gain more insight into these rare childhood cancers. However, these database studies are limited. Several initiatives to study rare pediatric cancers have been developed by the COG and other international groups, including the Société Internationale D'Oncologie Pédiatrique (SIOP). The Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH) rare tumor project was founded in Germany in 2006.[11] The Italian Tumori Rari in Eta Pediatrica (TREP) group was launched in 2000,[12] and the Polish Pediatric Rare Tumor Study Group was launched in 2002.[13] In Europe, the rare tumor study groups from France, Germany, Italy, Poland, and the United Kingdom joined to become the EXPeRT group, focusing on international collaboration and analyses of specific rare tumor entities.[14] Within the COG, efforts have concentrated on increasing accrual to COG registries (Project Every Child) and tumor banking protocols, developing single-arm clinical trials, and increasing cooperation with adult cooperative group trials.[15] The accomplishments and challenges of this initiative have been described in detail.[10,16]

The tumors listed 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 pediatric hospitals might see less than a handful of some histologies in several years. Most of the histologies listed here occur more frequently in adults. Information about these tumors may also be found in sources relevant to adults with cancer.

The Rare Cancers of Childhood Treatment summary has been separated into individual summaries for each topic. Please use the lists below or the following link to find the individual summaries: PDQ Cancer Information Summaries: Pediatric Treatment.

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. American Academy of Pediatrics: Standards for pediatric cancer centers. Pediatrics 134 (2): 410-4, 2014. Also available online. Last accessed August 23, 2024.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014.
4. National Cancer Institute: NCCR*Explorer: An interactive website for NCCR cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed August 23, 2024.
5. Surveillance Research Program, National Cancer Institute: SEER*Explorer: An interactive website for SEER cancer statistics. Bethesda, MD: National Cancer Institute. Available online. Last accessed September 5, 2024.
6. 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.
7. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017.
8. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017.
9. Ferrari A, Brecht IB, Gatta G, et al.: Defining and listing very rare cancers of paediatric age: consensus of the Joint Action on Rare Cancers in cooperation with the European Cooperative Study Group for Pediatric Rare Tumors. Eur J Cancer 110: 120-126, 2019.
10. 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.
11. 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.
12. 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.
13. Balcerska A, Godziński J, Bień E, et al.: [Rare tumours--are they really rare in the Polish children population?]. Przegl Lek 61 (Suppl 2): 57-61, 2004.
14. 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.
15. 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.
16. 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

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.

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

Nasopharyngeal Carcinoma

For more information, see Childhood Nasopharyngeal Cancer Treatment.

Esthesioneuroblastoma

For more information, see Childhood Esthesioneuroblastoma Treatment.

Thyroid Tumors

For more information, see Childhood Thyroid Cancer Treatment.

Oral Cavity Cancer

For more information, see Childhood Oral Cavity Cancer Treatment.

Salivary Gland Tumors

For more information, see Childhood Salivary Gland Tumors Treatment.

Laryngeal Cancer and Papillomatosis

For more information, see Childhood Laryngeal Tumors Treatment.

NUT Carcinoma

For more information, see Childhood NUT Carcinoma Treatment.

Thoracic Cancers

The prognosis, diagnosis, classification, and treatment of pediatric thoracic cancers are discussed below. These cancers are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series.

Rare pediatric thoracic cancers include the following:

Breast Cancer

For more information, see Childhood Breast Tumors Treatment.

Lung Cancer

Most pulmonary malignant neoplasms in children result from metastatic disease. The approximate ratio of primary malignant tumors to metastatic disease is 1:5.[1]

The most common malignant primary tumors of the lung include the following:

• Pulmonary inflammatory myofibroblastic tumors.
• Tracheobronchial tumors.
• Pleuropulmonary blastoma.

Pulmonary Inflammatory Myofibroblastic Tumors

For more information, see Childhood Pulmonary Inflammatory Myofibroblastic Tumors Treatment.

Tracheobronchial Tumors

For more information, see Childhood Tracheobronchial Tumors Treatment.

Pleuropulmonary Blastoma

For more information, see Childhood Pleuropulmonary Blastoma Treatment.

Esophageal Cancer

For more information, see Childhood Esophageal Cancer Treatment.

Thymoma and Thymic Carcinoma

For more information, see Childhood Thymoma and Thymic Carcinoma Treatment.

Cardiac Tumors

For more information, see Childhood Cardiac Tumors Treatment.

References:

1. Weldon CB, Shamberger RC: Pediatric pulmonary tumors: primary and metastatic. Semin Pediatr Surg 17 (1): 17-29, 2008.

Abdominal Cancers

The prognosis, diagnosis, classification, and treatment of pediatric abdominal cancers are discussed below. These cancers are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series. For information about kidney tumors, see Wilms Tumor and Other Childhood Kidney Tumors Treatment.

Rare pediatric abdominal cancers include the following:

Adrenocortical Carcinoma

For more information, see Childhood Adrenocortical Carcinoma Treatment.

Gastric Cancer

For more information, see Pediatric Gastric Cancer Treatment.

Pancreatic Cancer

For more information, see Childhood Pancreatic Cancer Treatment.

Colorectal Cancer

For more information, see Childhood Colorectal Cancer Treatment.

Gastrointestinal Neuroendocrine Tumors

For more information, see Pediatric Gastrointestinal Neuroendocrine Tumors Treatment.

Gastrointestinal Stromal Tumors (GIST)

For more information, see Childhood Gastrointestinal Stromal Tumors Treatment.

Genital / Urinary Tumors

The prognosis, diagnosis, classification, and treatment of pediatric genital/urinary tumors are discussed below. These tumors are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series.

Rare pediatric genital/urinary tumors include the following:

Bladder Cancer

For more information, see Childhood Bladder Cancer Treatment.

Testicular Cancer (Non–Germ Cell)

For more information, see Childhood Testicular Cancer Treatment.

Ovarian Cancer (Non–Germ Cell)

For more information, see Childhood Ovarian Cancer Treatment.

Cervical and Vaginal Cancer

For more information, see Childhood Cervical and Vaginal Cancer Treatment.

Other Rare Childhood Cancers

The prognosis, diagnosis, classification, and treatment of other rare childhood cancers are discussed below. These cancers are seen very infrequently in patients younger than 15 years, and most of the evidence is derived from case series.

Other rare childhood cancers include the following:

Mesothelioma

For more information, see Childhood Mesothelioma Treatment.

Multiple Endocrine Neoplasia (MEN) Syndromes

For more information, see Childhood Multiple Endocrine Neoplasia (MEN) Syndromes Treatment.

Pheochromocytoma and Paraganglioma

For more information, see Childhood Pheochromocytoma and Paraganglioma Treatment.

Skin Cancer (Melanoma, Basal Cell Carcinoma [BCC], and Squamous Cell Carcinoma [SCC])

For more information about specific genetic variants and related hereditary skin cancer syndromes, see Genetics of Skin Cancer. For information about uveal melanoma in children, see Childhood Intraocular (Uveal) Melanoma Treatment.

Melanoma

For more information, see Childhood Melanoma Treatment.

BCC and SCC

For more information, see Childhood Basal Cell Carcinoma and Squamous Cell Carcinoma of the Skin Treatment.

Intraocular (Uveal) Melanoma

For more information, see Childhood Intraocular (Uveal) Melanoma Treatment.

Chordoma

For more information, see Childhood Chordoma Treatment.

Cancer of Unknown Primary (CUP) Site

For more information, see Childhood Cancer of Unknown Primary (CUP) Treatment.

Latest Updates to This Summary (09 / 27 / 2024)

The PDQ cancer information summaries are reviewed regularly and updated as new information becomes available. This section describes the latest changes made to this summary as of the date above.

This summary was comprehensively reviewed.

This summary is written and maintained by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of NCI. The summary reflects an independent review of the literature and does not represent a policy statement of NCI or NIH. More information about summary policies and the role of the PDQ Editorial Boards in maintaining the PDQ summaries can be found on the About This PDQ Summary and PDQ® Cancer Information for Health Professionals pages.

About This PDQ Summary

Purpose of This Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of rare cancers of childhood. It is intended as a resource to inform and assist clinicians in the care of their patients. It does not provide formal guidelines or recommendations for making health care decisions.

Reviewers and Updates

This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board, which is editorially independent of the National Cancer Institute (NCI). The summary reflects an independent review of the literature and does not represent a policy statement of NCI or the National Institutes of Health (NIH).

Board members review recently published articles each month to determine whether an article should:

• be discussed at a meeting,
• be cited with text, or
• replace or update an existing article that is already cited.

Changes to the summaries are made through a consensus process in which Board members evaluate the strength of the evidence in the published articles and determine how the article should be included in the summary.

The lead reviewers for Rare Cancers of Childhood Treatment are:

• Denise Adams, MD (Children's Hospital Boston)
• Sally J. Cohen-Cutler, MD, MS (Children's Hospital of Philadelphia)
• Karen J. Marcus, MD, FACR (Dana-Farber Cancer Institute/Boston Children's Hospital)
• William H. Meyer, MD
• Paul A. Meyers, MD (Memorial Sloan-Kettering Cancer Center)
• Thomas A. Olson, MD (Aflac Cancer and Blood Disorders Center of Children's Healthcare of Atlanta - Egleston Campus)
• Alberto S. Pappo, MD (St. Jude Children's Research Hospital)
• D. Williams Parsons, MD, PhD (Texas Children's Hospital)
• Arthur Kim Ritchey, MD (Children's Hospital of Pittsburgh of UPMC)
• Carlos Rodriguez-Galindo, MD (St. Jude Children's Research Hospital)
• Stephen J. Shochat, MD (St. Jude Children's Research Hospital)

Any comments or questions about the summary content should be submitted to Cancer.gov through the NCI website's Email Us. Do not contact the individual Board Members with questions or comments about the summaries. Board members will not respond to individual inquiries.

Levels of Evidence

Some of the reference citations in this summary are accompanied by a level-of-evidence designation. These designations are intended to help readers assess the strength of the evidence supporting the use of specific interventions or approaches. The PDQ Pediatric Treatment Editorial Board uses a formal evidence ranking system in developing its level-of-evidence designations.

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The preferred citation for this PDQ summary is:

PDQ® Pediatric Treatment Editorial Board. PDQ Rare Cancers of Childhood Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/childhood-cancers/hp/rare-childhood-cancers-pdq. Accessed <MM/DD/YYYY>. [PMID: 26389315]

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Last Revised: 2024-09-27