National Cancer Institute National Cancer Institute
U.S. National Institutes of Health National Cancer Institute
Send to Printer
Unusual Cancers of Childhood Treatment (PDQ®)     
Last Modified: 09/05/2008
Health Professional Version
Table of Contents

Purpose of This PDQ Summary
General Information
Head and Neck Cancers
Nasopharyngeal Carcinoma
        Treatment options under clinical evaluation
Esthesioneuroblastoma
Thyroid Tumors
Oral Cancers
Salivary Gland Tumors
Laryngeal Cancer and Papillomatosis
Respiratory Tract Carcinoma Involving the NUT Gene on Chromosome 15
Thoracic Cancers
Breast Cancer
Bronchial Tumors
Pleuropulmonary Blastoma
Esophageal Tumors
Thymoma and Thymic Carcinoma
Tumors of the Heart
Mesothelioma
Abdominal Cancers
Carcinoma of the Adrenal Cortex
        Treatment options under clinical evaluation
Carcinoma of the Stomach
Cancer of the Pancreas
Colorectal Carcinoma
Carcinoid Tumors
Gastrointestinal Stromal Cell Tumor
Genital/Urinary Tumors
Carcinoma of the Bladder
Ovarian Cancer
Carcinoma of the Cervix and Vagina
Other Rare Childhood Cancers
Multiple Endocrine Neoplasia Syndrome
        Treatment options under clinical evaluation
Skin Cancer (Melanoma, Basal Cell, and Squamous Cell Carcinoma)
        Treatment options under clinical evaluation
Chordoma
Cancer of Unknown Primary Site
Get More Information From NCI
Changes to This Summary (09/05/2008)
More Information

Purpose of This PDQ Summary

This PDQ cancer information summary for health professionals provides comprehensive, peer-reviewed, evidence-based information about the treatment of unusual cancers of childhood. This summary is reviewed regularly and updated as necessary by the PDQ Pediatric Treatment Editorial Board 1.

Information about the following is included in this summary:

  • Incidence of unusual childhood cancers.
  • Treatment options for unusual childhood cancers.

This summary is intended as a resource to inform and assist clinicians and other health professionals who care for pediatric cancer patients. It does not provide formal guidelines or recommendations for making health care decisions.

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 and Adult Treatment Editorial Boards use a formal evidence ranking system 2 in developing their level-of-evidence designations. Based on the strength of the available evidence, treatment options are described as either “standard” or “under clinical evaluation.” These classifications should not be used as a basis for reimbursement determinations.

This summary is also available in a patient version 3, which is written in less-technical language, and in Spanish 4.

General Information

The National Cancer Institute (NCI) provides the PDQ pediatric cancer treatment information summaries as a public service to increase the availability of evidence-based cancer information to health professionals, patients, and the public.

Cancer in children and adolescents is rare. 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 the primary care physician, pediatric surgical subspecialists, 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 Care 5 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.[1] 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 therapies for childhood cancers has been achieved through clinical trials. Information about ongoing clinical trials is available from the NCI Web site 6.

In recent decades, dramatic improvements in survival have been achieved for children and adolescents with cancer. Childhood and adolescent cancer survivors require close follow-up because cancer therapy side effects may persist or develop months or years after treatment. (Refer to the PDQ Late Effects of Treatment for Childhood Cancer 7 summary for specific information about the incidence, type, and monitoring of late effects in childhood and adolescent cancer survivors.)

The tumors discussed in this summary are diverse; the discussion is 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 fewer than two in a year. Most of these tumors are more frequent in adults with cancer; thus, much of the information about these tumors may also be sought through sources relevant to adults with cancer.

References

  1. Guidelines for the pediatric cancer center and role of such centers in diagnosis and treatment. American Academy of Pediatrics Section Statement Section on Hematology/Oncology. Pediatrics 99 (1): 139-41, 1997.  [PUBMED Abstract]

Head and Neck Cancers

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence 2 for more information.)

Head and neck cancers include nasopharyngeal carcinoma, esthesioneuroblastoma, thyroid tumors, mouth cancer, salivary gland cancer, laryngeal carcinoma, papillomatosis, and respiratory tract carcinoma involving the NUT gene on chromosome 15. The prognosis, diagnosis, classification, and treatment of these head and neck cancers are discussed below.

Nasopharyngeal Carcinoma

Nasopharyngeal cancer arises in the lining of the nasal cavity and pharynx.[1,2] This tumor accounts for about one-third of all cancers of the upper airways. The incidence of this tumor is approximately 1 in 100,000 persons younger than 20 years in the United States.[3] There is a higher frequency of this tumor in North Africa and Southeast Asia.

Nasopharyngeal carcinoma occurs in association with Epstein-Barr virus (EBV), the virus associated with infectious mononucleosis.[4] The virus can be detected in biopsy specimens of these cancers, and tumor cells can have EBV antigens on their cell surface. Three histologic subtypes are recognized by the World Health Organization. Type 1 is squamous cell carcinoma, type 2 is nonkeratinizing carcinoma, and type 3 is undifferentiated carcinoma.

This cancer most frequently spreads to lymph nodes in the neck, which may alert the patient, parent, or physician to the presence of this tumor. The tumor may also spread to the nose, mouth, and pharynx, causing snoring, epistaxis, obstruction of the eustachian tubes, or hearing loss; it may also invade the base of the skull, causing cranial nerve palsy or difficulty with movements of the jaw (trismus). Distant metastatic sites may include the bones, lungs, and liver. The location of the primary tumor can be made by direct inspection of the nasopharynx. A diagnosis can be made from a biopsy of the primary tumor or of 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, Hodgkin lymphoma, and Burkitt lymphoma must be considered, as should benign conditions such as nasal angiofibroma, which presents with epistaxis, and infections draining into the lymph nodes of the neck.

Diagnostic tests should determine the extent of the primary tumor and whether there are metastases. Visualization of the nasopharynx by an ear-nose-throat specialist using a mirror, examination by a neurologist, and magnetic resonance imaging of the head and neck can be used to determine the extent of the primary tumor. Evaluation of the chest and abdomen by computed tomography and bone scan should also be performed to determine whether there is metastatic disease. The levels of EBV and antibody to EBV should also be measured.[1,5]

Tumor staging is performed utilizing the tumor-node-metastasis (TNM) classification system of the American Joint Committee on Cancer (AJCC).[6] The majority (>90%) of children and adolescents with nasopharyngeal carcinoma present with advanced disease (stage III/IV or T3/T4).[7] Metastatic disease at diagnosis is uncommon (stage IVC). Outcome is directly related to the stage of the disease, with overall survival ranging from 80% for stage I and stage II to 40% for stage III.[8] Other factors associated with an inferior outcome include node size larger than 6 cm, radiation dose less than 60 Gy, and poor response to chemotherapy.[8]

Surgery has a limited role in the management of nasopharyngeal carcinoma since the disease is usually considered unresectable because of extensive local spread. High-dose radiation therapy alone may have a role in the management of low-stage nasopharyngeal carcinoma; however, studies in both children and adults have shown that combined modality therapy with chemotherapy and radiation is the most effective way to treat nasopharyngeal carcinoma.[8-11] In a meta-analysis of studies adding chemotherapy to radiation therapy in adults with nasopharyngeal carcinoma, concomitant chemotherapy plus radiation therapy offered a significant benefit for survival, locoregional disease control, and reduction in distant metastases.[11] Neoadjuvant chemotherapy resulted in a significant reduction in locoregional recurrence only, while postradiation chemotherapy did not offer any benefit. In children, two studies utilizing preradiation chemotherapy with methotrexate, cisplatin, 5-fluorouracil (5-FU), and leucovorin with or without recombinant interferon-beta reported response rates of more than 90%.[12,13] Radiation therapy doses utilized in both studies were approximately 60 Gy. Additional drug combinations that have been used in children with nasopharyngeal carcinoma include bleomycin, epirubicin, and cisplatin (BEP), cisplatin and fluorouracil (PF), and cisplatin, methotrexate, and bleomycin (PMB).[2] Incorporation of high-dose-rate brachytherapy into the chemoradiotherapy approach has been reported, but its role in the management of nasopharyngeal carcinoma in children is unknown.[14,15]

A preliminary report of the use of EBV-specific cytotoxic T-lymphocytes revealed minimal toxicity and evidence of significant anti-tumor activity in patients with relapsed or refractory nasopharyngeal carcinoma.[16] (Refer to the PDQ summary on Nasopharyngeal Cancer Treatment 8 for more information.)

Treatment options under clinical evaluation
  • ARAR0331: This Children's Oncology Group (COG) trial (COG-ARAR0331 9) is evaluating the efficacy of induction chemotherapy with cisplatin plus 5-FU followed by concomitant chemotherapy (cisplatin) plus radiation therapy with amifostine as a radioprotectant in patients with AJCC stages IIB to IV nasopharyngeal carcinoma. Patients with stages I to IIA disease will receive only radiation therapy with amifostine.
Esthesioneuroblastoma

Esthesioneuroblastoma (olfactory neuroblastoma) is a very rare, small round-cell tumor arising from the nasal neuroepithelium that is distinct from primitive neuroectodermal tumors.[17-19] Most children present with a nasopharyngeal mass, which may have local extension into the orbits, sinuses, or frontal lobe, with associated symptoms. There appears to be a male predominance, and the average age of presentation is in adolescence. The youngest child reported with this diagnosis was aged 2 years. Metastatic disease is uncommon. The mainstay of treatment has been surgery and radiation. Newer techniques such as endoscopic sinus surgery, radiosurgery, and proton-beam therapy may play a role in the management of this tumor.[20] A retrospective analysis of data from the Surveillance, Epidemiology, and End Results program identified 311 patients with esthesioneuroblastoma.[21] Patients were staged by the extent of the tumor. Disease limited to the nasal cavity was considered the lowest stage and involvement of regional lymph nodes or metastasis was considered the highest stage. This staging system correlated well with outcome. A meta-analysis of 26 studies with a total of 390 patients, largely adults, with esthesioneuroblastoma indicates that higher histopathologic grade and metastases to the cervical lymph nodes may correlate with adverse prognostic factors.[22] Recent reports indicate increasing use of neoadjuvant chemotherapy.[17,18,23,24] Chemotherapy regimens that have been used with efficacy include etoposide (VP-16), ifosfamide, and cisplatin (Platinol) (VIP),[25] vincristine, actinomycin D and cyclophosphamide (VAC) without doxorubicin (Adriamycin), ifosfamide/etoposide, and cisplatin plus etoposide or doxorubicin.[23] The long-term survival rate appears to be approximately 60% to 80%. Local recurrences may occur later in life.

Thyroid Tumors

Tumors of the thyroid are classified as adenomas or carcinomas.[26-30] Adenomas are benign growths 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 of these tumors may secrete hormones. Transformation to a malignant carcinoma may occur in some cells, which then may grow and spread to lymph nodes in the neck or to the lungs.

Although rare, thyroid cancers represent about 1.5% of all tumors seen in the pediatric age group. Most thyroid carcinomas occur in girls.[31] Patients with thyroid cancer usually present with a thyroid mass with or without cervical adenopathy.[32-34] There is an excessive frequency of thyroid adenoma and carcinoma in patients who previously received radiation to the neck.[35,36] 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 Syndrome 10 section of this summary for more information.) The American Thyroid Association Taskforce [37] has developed guidelines for management of thyroid nodules in older adolescents and adults, but it is not yet known how to apply these guidelines to thyroid nodules in children.[26]

Initial evaluation of a child or adolescent with a thyroid nodule should include an ultrasound of the thyroid. Tests of thyroid function are usually normal, but thyroglobulin can be elevated. Fine needle aspiration (FNA) is the initial diagnostic approach, though experience in FNA in pediatric hospitals may be limited, in which case open biopsy or lobe resection should be considered.[38,39] Open biopsy or resection may be preferable for young children as well.

Various histologies account for the general diagnostic category of carcinoma of the thyroid,[40] but the vast majority of tumors are differentiated. These tumors comprise papillary carcinoma (60%–75%),[36] follicular carcinoma (10%–20%), medullary carcinoma (5%–10%), and anaplastic carcinoma (<1%). Follicular carcinoma may be sporadic or familial and medullary carcinoma is usually familial.[41] Papillary carcinoma often has multicentric origins and a very high rate of lymph node metastasis (70%–90%).[40] Follicular carcinoma is usually encapsulated and has a higher incidence of bone and lung metastasis. Follicular carcinoma and papillary carcinoma generally have a benign course, with a 10-year survival rate of more than 95%.[42] Fifty percent of medullary thyroid carcinomas in adults and children have hematogenous metastases at diagnosis.[43] Patients with medullary carcinoma of the thyroid have a guarded prognosis, unless they have very small tumors (microcarcinoma, defined as <1.0 cm in diameter), which carry a good prognosis.[44]

Surgery by an experienced thyroid surgeon is the treatment required for all thyroid neoplasms.[42] Total or near-total thyroidectomy plus cervical lymph node dissection, when indicated, is the most common surgical approach.[32] For patients with obvious metastatic disease or heavy nodal invasion, total thyroidectomy and treatment with radioactive idodine is indicated. For patients with an isolated nodule in the thyroid, treatment may involve only a lobectomy.[32,45] During the 4- to 6-week period following surgery, patients who received a total thyroidectomy may develop hypothyroidism. A radioactive iodine (I-131) scan is then performed to search for residual, functionally active neoplasms. If there is no disease outside of the thyroid bed, an ablative dose of I-131 (approximately 29 mCi) is administered for total thyroid destruction. If there is evidence of nodal or disseminated disease, higher doses (100–200 mCi) of I-131 are required. After surgery and radioactive iodine therapy, hormone replacement therapy must be given to compensate for the lost thyroid hormone and to suppress thyrotropin (TSH) production.[46]

Initial treatment (defined as surgery plus one radioactive iodine ablation plus thyroid replacement) is effective in inducing remission for 70% of patients. Extensive disease at diagnosis and larger tumor size predict failure to remit. With additional treatment, 89% of patients achieve remission.[47] Periodic evaluations are required to determine whether there is metastatic disease involving the lungs. Lifelong follow-up is necessary.[48] Thyroglobulin, T4, and TSH levels should be evaluated periodically to determine whether replacement hormone is appropriately dosed.

Patients with differentiated thyroid cancer generally have an excellent survival with relatively few side effects.[48-50] Recurrence is common (35%–45%), however, and is seen more often in children younger than 10 years and in those with palpable cervical lymph nodes at diagnosis.[28,51,52] Of note, the sodium-iodide symporter (a membrane-bound glycoprotein cotransporter) essential for uptake of iodide and thyroid hormone synthesis, is expressed in 35% to 45% of thyroid cancers in children and adolescents. Patients with expression of the sodium-iodide symporter have a lower risk of recurrence.[53] Recurrent papillary thyroid cancer is usually responsive to treatment with radioactive iodine ablation.[54] Even patients with a tumor that has spread to the lungs may expect to have no decrease in life span after appropriate treatment. (Refer to the PDQ summary on adult Thyroid Cancer Treatment 11 for more information.)

Oral Cancers

Cancer of the oral cavity is extremely rare in children and adolescents.[3,55] The vast majority (>90%) of tumors and tumor-like lesions in the oral cavity are benign.[56-59] Benign odontogenic neoplasms include odontoma and ameloblastoma. The most common nonodontogenic neoplasms are fibromas, hemangiomas, and papillomas. Tumor-like lesions include lymphangiomas, granulomas, and eosinophilic granuloma (Langerhans cell histiocytoma [LCH]). Malignant tumors are found in 0.1% to 2% of a series of oral biopsies performed in children [56,57] and 3% to 13% of oral tumor biopsies.[58,59] Malignant tumor types include lymphomas (especially Burkitt) and sarcomas (including rhabdomyosarcoma and fibrosarcoma). The most common type of primary oral cancer in adults, squamous cell carcinoma (SCC), is extremely rare in children. Only occasional case reports are found in the literature.[60,61] Adolescents with an oral SCC should be screened for Fanconi anemia.[62,63]

Treatment of benign oral tumors is surgical. Management of malignant tumors is dependent on histology and may include surgery, chemotherapy, and radiation.[64] LCH may require other treatment besides surgery. (Refer to the PDQ summaries on adult Oropharyngeal Cancer Treatment 12 and Lip and Oral Cavity Cancer Treatment 13 for more information.)

Salivary Gland Tumors

Most salivary gland neoplasms arise in the parotid gland.[65-69] About 15% of these tumors may arise in the submandibular glands or in the minor salivary glands under the tongue and jaw. These tumors are most frequently benign, but on very rare occasions, may be malignant. Sialoblastomas are usually benign tumors presenting in the neonatal period, but can rarely metastasize.[70] A chemotherapy regimen of carboplatin, epirubicin, vincristine, etoposide, ifosfamide, and dactinomycin has been used in the treatment of metastatic sialoblastoma and has produced a response in one child.[71][Level of evidence: 3iiiDiv] The malignant lesions include mucoepidermoid carcinoma,[72] acinic cell carcinoma, rhabdomyosarcoma, adenocarcinoma, and undifferentiated carcinoma. These tumors may occur after radiation therapy and chemotherapy are given for treatment of primary leukemia or solid tumors.[73,74] Radical surgical removal is the treatment of choice, whenever possible, with additional use of radiation therapy and chemotherapy for high-grade tumors or tumors that have spread from their site of origin.[72,75,76] Prognosis for patients with these tumors is generally good.[68,77-79] (Refer to the PDQ summary on adult Salivary Gland Cancer Treatment 14 for more information.)

Laryngeal Cancer and Papillomatosis

Benign tumors of the larynx are rare. Malignant tumors, which are especially rare, may be associated with benign tumors such as polyps and papillomas.[80,81] These tumors may cause hoarseness, difficulty swallowing, and enlargement of the lymph nodes of the neck. Rhabdomyosarcoma is the most common malignant tumor of the larynx in the pediatric age group. SCC of the larynx should be managed in the same manner as in adults with carcinoma at this site, with surgery and radiation.[82] Laser surgery may be the first type of treatment utilized for these lesions.

Papillomatosis of the larynx is a benign overgrowth of tissues lining the larynx and is associated with the human papillomavirus (HPV), most commonly HPV-6 and HPV-11.[83] The presence of HPV-11 appears to correlate with a more aggressive clinical course than HPV-6.[84] This condition is not cancerous, and primary treatment is surgical ablation with laser vaporization.[85] Frequent recurrences are common. If a patient requires more than four surgical procedures per year, treatment with interferon should be considered.[86] A pilot study of immunotherapy with HspE7, a recombinant fusion protein that has shown activity in other HPV-related diseases, has suggested a marked increase in the amount of time between surgeries.[87] These results, however, must be confirmed in a larger randomized trial. These tumors can cause hoarseness because of their association with wart-like nodules on the vocal cords and may rarely extend into the lung, producing significant morbidity. Malignant degeneration may occur, with development of cancer in the larynx and squamous cell lung cancer. (Refer to the PDQ summary on adult Laryngeal Cancer Treatment 15 for more information.)

Respiratory Tract Carcinoma Involving the NUT Gene on Chromosome 15

Researchers have described a group of young patients with midline carcinomas with a very poor prognosis. The tumors arise in midline epithelial structures including the thymus, mediastinum, airway structures, and bladder. They exhibit squamous differentiation. Tumors from 8 of 11 patients exhibited a balanced chromosomal translocation t(15;19) involving the BRD4 and the NUT genes. These patients had no response to chemotherapy and died very quickly. Tumors from the remaining three patients had a chromosomal break in the NUT gene on chromosome 15 but had normal chromosome 19. These patients were older and had a slightly longer survival than the eight patients exhibiting t(15;19).[88]

References

  1. Vasef MA, Ferlito A, Weiss LM: Nasopharyngeal carcinoma, with emphasis on its relationship to Epstein-Barr virus. Ann Otol Rhinol Laryngol 106 (4): 348-56, 1997.  [PUBMED Abstract]

  2. Ayan I, Kaytan E, Ayan N: Childhood nasopharyngeal carcinoma: from biology to treatment. Lancet Oncol 4 (1): 13-21, 2003.  [PUBMED Abstract]

  3. Young JL Jr, Miller RW: Incidence of malignant tumors in U. S. children. J Pediatr 86 (2): 254-8, 1975.  [PUBMED Abstract]

  4. Bar-Sela G, Ben Arush MW, Sabo E, et al.: Pediatric nasopharyngeal carcinoma: better prognosis and increased c-Kit expression as compared to adults. Pediatr Blood Cancer 45 (3): 291-7, 2005.  [PUBMED Abstract]

  5. Naegele RF, Champion J, Murphy S, et al.: Nasopharyngeal carcinoma in American Children: Epstein-Barr virus-specific antibody titers and prognosis. Int J Cancer 29 (2): 209-12, 1982.  [PUBMED Abstract]

  6. American Joint Committee on Cancer.: AJCC Cancer Staging Manual. 6th ed. New York, NY: Springer, 2002. 

  7. Casanova M, Ferrari A, Gandola L, et al.: Undifferentiated nasopharyngeal carcinoma in children and adolescents: comparison between staging systems. Ann Oncol 12 (8): 1157-62, 2001.  [PUBMED Abstract]

  8. Laskar S, Sanghavi V, Muckaden MA, et al.: Nasopharyngeal carcinoma in children: ten years' experience at the Tata Memorial Hospital, Mumbai. Int J Radiat Oncol Biol Phys 58 (1): 189-95, 2004.  [PUBMED Abstract]

  9. Al-Sarraf M, LeBlanc M, Giri PG, et al.: Chemoradiotherapy versus radiotherapy in patients with advanced nasopharyngeal cancer: phase III randomized Intergroup study 0099. J Clin Oncol 16 (4): 1310-7, 1998.  [PUBMED Abstract]

  10. Wolden SL, Steinherz PG, Kraus DH, et al.: Improved long-term survival with combined modality therapy for pediatric nasopharynx cancer. Int J Radiat Oncol Biol Phys 46 (4): 859-64, 2000.  [PUBMED Abstract]

  11. Langendijk JA, Leemans ChR, Buter J, et al.: The additional value of chemotherapy to radiotherapy in locally advanced nasopharyngeal carcinoma: a meta-analysis of the published literature. J Clin Oncol 22 (22): 4604-12, 2004.  [PUBMED Abstract]

  12. Mertens R, Granzen B, Lassay L, et al.: Treatment of nasopharyngeal carcinoma in children and adolescents: definitive results of a multicenter study (NPC-91-GPOH). Cancer 104 (5): 1083-9, 2005.  [PUBMED Abstract]

  13. Rodriguez-Galindo C, Wofford M, Castleberry RP, et al.: Preradiation chemotherapy with methotrexate, cisplatin, 5-fluorouracil, and leucovorin for pediatric nasopharyngeal carcinoma. Cancer 103 (4): 850-7, 2005.  [PUBMED Abstract]

  14. Nakamura RA, Novaes PE, Antoneli CB, et al.: High-dose-rate brachytherapy as part of a multidisciplinary treatment of nasopharyngeal lymphoepithelioma in childhood. Cancer 104 (3): 525-31, 2005.  [PUBMED Abstract]

  15. Louis CU, Paulino AC, Gottschalk S, et al.: A single institution experience with pediatric nasopharyngeal carcinoma: high incidence of toxicity associated with platinum-based chemotherapy plus IMRT. J Pediatr Hematol Oncol 29 (7): 500-5, 2007.  [PUBMED Abstract]

  16. Straathof KC, Bollard CM, Popat U, et al.: Treatment of nasopharyngeal carcinoma with Epstein-Barr virus--specific T lymphocytes. Blood 105 (5): 1898-904, 2005.  [PUBMED Abstract]

  17. Kumar M, Fallon RJ, Hill JS, et al.: Esthesioneuroblastoma in children. J Pediatr Hematol Oncol 24 (6): 482-7, 2002 Aug-Sep.  [PUBMED Abstract]

  18. Theilgaard SA, Buchwald C, Ingeholm P, et al.: Esthesioneuroblastoma: a Danish demographic study of 40 patients registered between 1978 and 2000. Acta Otolaryngol 123 (3): 433-9, 2003.  [PUBMED Abstract]

  19. Dias FL, Sa GM, Lima RA, et al.: Patterns of failure and outcome in esthesioneuroblastoma. Arch Otolaryngol Head Neck Surg 129 (11): 1186-92, 2003.  [PUBMED Abstract]

  20. Unger F, Haselsberger K, Walch C, et al.: Combined endoscopic surgery and radiosurgery as treatment modality for olfactory neuroblastoma (esthesioneuroblastoma). Acta Neurochir (Wien) 147 (6): 595-601; discussion 601-2, 2005.  [PUBMED Abstract]

  21. Jethanamest D, Morris LG, Sikora AG, et al.: Esthesioneuroblastoma: a population-based analysis of survival and prognostic factors. Arch Otolaryngol Head Neck Surg 133 (3): 276-80, 2007.  [PUBMED Abstract]

  22. Dulguerov P, Allal AS, Calcaterra TC: Esthesioneuroblastoma: a meta-analysis and review. Lancet Oncol 2 (11): 683-90, 2001.  [PUBMED Abstract]

  23. Eich HT, Müller RP, Micke O, et al.: Esthesioneuroblastoma in childhood and adolescence. Better prognosis with multimodal treatment? Strahlenther Onkol 181 (6): 378-84, 2005.  [PUBMED Abstract]

  24. Loy AH, Reibel JF, Read PW, et al.: Esthesioneuroblastoma: continued follow-up of a single institution's experience. Arch Otolaryngol Head Neck Surg 132 (2): 134-8, 2006.  [PUBMED Abstract]

  25. Kim DW, Jo YH, Kim JH, et al.: Neoadjuvant etoposide, ifosfamide, and cisplatin for the treatment of olfactory neuroblastoma. Cancer 101 (10): 2257-60, 2004.  [PUBMED Abstract]

  26. Dinauer C, Francis GL: Thyroid cancer in children. Endocrinol Metab Clin North Am 36 (3): 779-806, vii, 2007.  [PUBMED Abstract]

  27. Vasko V, Bauer AJ, Tuttle RM, et al.: Papillary and follicular thyroid cancers in children. Endocr Dev 10: 140-72, 2007.  [PUBMED Abstract]

  28. Grigsby PW, Gal-or A, Michalski JM, et al.: Childhood and adolescent thyroid carcinoma. Cancer 95 (4): 724-9, 2002.  [PUBMED Abstract]

  29. Skinner MA: Cancer of the thyroid gland in infants and children. Semin Pediatr Surg 10 (3): 119-26, 2001.  [PUBMED Abstract]

  30. Halac I, Zimmerman D: Thyroid nodules and cancers in children. Endocrinol Metab Clin North Am 34 (3): 725-44, x, 2005.  [PUBMED Abstract]

  31. Shapiro NL, Bhattacharyya N: Population-based outcomes for pediatric thyroid carcinoma. Laryngoscope 115 (2): 337-40, 2005.  [PUBMED Abstract]

  32. Thompson GB, Hay ID: Current strategies for surgical management and adjuvant treatment of childhood papillary thyroid carcinoma. World J Surg 28 (12): 1187-98, 2004.  [PUBMED Abstract]

  33. Harness JK, Sahar DE, et al.: Childhood thyroid carcinoma. In: Clark O, Duh Q-Y, Kebebew E, eds.: Textbook of Endocrine Surgery. 2nd ed. Philadelphia, PA: Elsevier Saunders Company, 2005., pp 93-101. 

  34. Rachmiel M, Charron M, Gupta A, et al.: Evidence-based review of treatment and follow up of pediatric patients with differentiated thyroid carcinoma. J Pediatr Endocrinol Metab 19 (12): 1377-93, 2006.  [PUBMED Abstract]

  35. 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 37 (8): 1020-6, 2001.  [PUBMED Abstract]

  36. Kaplan MM, Garnick MB, Gelber R, et al.: Risk factors for thyroid abnormalities after neck irradiation for childhood cancer. Am J Med 74 (2): 272-80, 1983.  [PUBMED Abstract]

  37. Cooper DS, Doherty GM, Haugen BR, et al.: Management guidelines for patients with thyroid nodules and differentiated thyroid cancer. Thyroid 16 (2): 109-42, 2006.  [PUBMED Abstract]

  38. Flannery TK, Kirkland JL, Copeland KC, et al.: Papillary thyroid cancer: a pediatric perspective. Pediatrics 98 (3 Pt 1): 464-6, 1996.  [PUBMED Abstract]

  39. Willgerodt H, Keller E, Bennek J, et al.: Diagnostic value of fine-needle aspiration biopsy of thyroid nodules in children and adolescents. J Pediatr Endocrinol Metab 19 (4): 507-15, 2006.  [PUBMED Abstract]

  40. Feinmesser R, Lubin E, Segal K, et al.: Carcinoma of the thyroid in children--a review. J Pediatr Endocrinol Metab 10 (6): 561-8, 1997 Nov-Dec.  [PUBMED Abstract]

  41. Skinner MA: Management of hereditary thyroid cancer in children. Surg Oncol 12 (2): 101-4, 2003.  [PUBMED Abstract]

  42. Hung W, Sarlis NJ: Current controversies in the management of pediatric patients with well-differentiated nonmedullary thyroid cancer: a review. Thyroid 12 (8): 683-702, 2002.  [PUBMED Abstract]

  43. Hill CS, Ibanez ML, Samaan NA, et al.: Medullary (solid) carcinoma of the thyroid gland: an analysis of the M.D. Anderson Hospital experience with patients with the tumor, its special features, and its histogenesis. Medicine 52(2): 141-171, 1973. 

  44. Krueger JE, Maitra A, Albores-Saavedra J: Inherited medullary microcarcinoma of the thyroid: a study of 11 cases. Am J Surg Pathol 24 (6): 853-8, 2000.  [PUBMED Abstract]

  45. Newman KD, Black T, Heller G, et al.: Differentiated thyroid cancer: determinants of disease progression in patients <21 years of age at diagnosis: a report from the Surgical Discipline Committee of the Children's Cancer Group. Ann Surg 227 (4): 533-41, 1998.  [PUBMED Abstract]

  46. Yeh SD, La Quaglia MP: 131I therapy for pediatric thyroid cancer. Semin Pediatr Surg 6 (3): 128-33, 1997.  [PUBMED Abstract]

  47. Powers PA, Dinauer CA, Tuttle RM, et al.: Tumor size and extent of disease at diagnosis predict the response to initial therapy for papillary thyroid carcinoma in children and adolescents. J Pediatr Endocrinol Metab 16 (5): 693-702, 2003.  [PUBMED Abstract]

  48. Vassilopoulou-Sellin R, Goepfert H, Raney B, et al.: Differentiated thyroid cancer in children and adolescents: clinical outcome and mortality after long-term follow-up. Head Neck 20 (6): 549-55, 1998.  [PUBMED Abstract]

  49. Wiersinga WM: Thyroid cancer in children and adolescents--consequences in later life. J Pediatr Endocrinol Metab 14 (Suppl 5): 1289-96; discussion 1297-8, 2001.  [PUBMED Abstract]

  50. Jarzab B, Handkiewicz-Junak D, Wloch J: Juvenile differentiated thyroid carcinoma and the role of radioiodine in its treatment: a qualitative review. Endocr Relat Cancer 12 (4): 773-803, 2005.  [PUBMED Abstract]

  51. Alessandri AJ, Goddard KJ, Blair GK, et al.: Age is the major determinant of recurrence in pediatric differentiated thyroid carcinoma. Med Pediatr Oncol 35 (1): 41-6, 2000.  [PUBMED Abstract]

  52. Borson-Chazot F, Causeret S, Lifante JC, et al.: Predictive factors for recurrence from a series of 74 children and adolescents with differentiated thyroid cancer. World J Surg 28 (11): 1088-92, 2004.  [PUBMED Abstract]

  53. Patel A, Jhiang S, Dogra S, et al.: Differentiated thyroid carcinoma that express sodium-iodide symporter have a lower risk of recurrence for children and adolescents. Pediatr Res 52 (5): 737-44, 2002.  [PUBMED Abstract]

  54. Powers PA, Dinauer CA, Tuttle RM, et al.: Treatment of recurrent papillary thyroid carcinoma in children and adolescents. J Pediatr Endocrinol Metab 16 (7): 1033-40, 2003.  [PUBMED Abstract]

  55. Berstein L, Gurney JG: Carcinomas and other malignant epithelial neoplasms. In: Ries LA, Smith MA, Gurney JG, et al., eds.: Cancer incidence and survival among children and adolescents: United States SEER Program 1975-1995. Bethesda, Md: National Cancer Institute, SEER Program, 1999. NIH Pub.No. 99-4649., Chapter 11, pp 139-148. Also available online. 16 Last accessed April 19, 2007. 

  56. Das S, Das AK: A review of pediatric oral biopsies from a surgical pathology service in a dental school. Pediatr Dent 15 (3): 208-11, 1993 May-Jun.  [PUBMED Abstract]

  57. Ulmansky M, Lustmann J, Balkin N: Tumors and tumor-like lesions of the oral cavity and related structures in Israeli children. Int J Oral Maxillofac Surg 28 (4): 291-4, 1999.  [PUBMED Abstract]

  58. Tröbs RB, Mader E, Friedrich T, et al.: Oral tumors and tumor-like lesions in infants and children. Pediatr Surg Int 19 (9-10): 639-45, 2003.  [PUBMED Abstract]

  59. Tanaka N, Murata A, Yamaguchi A, et al.: Clinical features and management of oral and maxillofacial tumors in children. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 88 (1): 11-5, 1999.  [PUBMED Abstract]

  60. Torossian JM, Beziat JL, Philip T, et al.: Squamous cell carcinoma of the tongue in a 13-year-old boy. J Oral Maxillofac Surg 58 (12): 1407-10, 2000.  [PUBMED Abstract]

  61. Bill TJ, Reddy VR, Ries KL, et al.: Adolescent gingival squamous cell carcinoma: Report of a case and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 91 (6): 682-5, 2001.  [PUBMED Abstract]

  62. Oksüzoğlu B, Yalçin S: Squamous cell carcinoma of the tongue in a patient with Fanconi's anemia: a case report and review of the literature. Ann Hematol 81 (5): 294-8, 2002.  [PUBMED Abstract]

  63. Reinhard H, Peters I, Gottschling S, et al.: Squamous cell carcinoma of the tongue in a 13-year-old girl with Fanconi anemia. J Pediatr Hematol Oncol 29 (7): 488-91, 2007.  [PUBMED Abstract]

  64. Sturgis EM, Moore BA, Glisson BS, et al.: Neoadjuvant chemotherapy for squamous cell carcinoma of the oral tongue in young adults: a case series. Head Neck 27 (9): 748-56, 2005.  [PUBMED Abstract]

  65. Johns ME, Goldsmith MM: Incidence, diagnosis, and classification of salivary gland tumors. Part 1. Oncology (Huntingt) 3 (2): 47-56; discussion 56, 58, 62, 1989.  [PUBMED Abstract]

  66. Ethunandan M, Ethunandan A, Macpherson D, et al.: Parotid neoplasms in children: experience of diagnosis and management in a district general hospital. Int J Oral Maxillofac Surg 32 (4): 373-7, 2003.  [PUBMED Abstract]

  67. da Cruz Perez DE, Pires FR, Alves FA, et al.: Salivary gland tumors in children and adolescents: a clinicopathologic and immunohistochemical study of fifty-three cases. Int J Pediatr Otorhinolaryngol 68 (7): 895-902, 2004.  [PUBMED Abstract]

  68. Shapiro NL, Bhattacharyya N: Clinical characteristics and survival for major salivary gland malignancies in children. Otolaryngol Head Neck Surg 134 (4): 631-4, 2006.  [PUBMED Abstract]

  69. Ellies M, Schaffranietz F, Arglebe C, et al.: Tumors of the salivary glands in childhood and adolescence. J Oral Maxillofac Surg 64 (7): 1049-58, 2006.  [PUBMED Abstract]

  70. Williams SB, Ellis GL, Warnock GR: Sialoblastoma: a clinicopathologic and immunohistochemical study of 7 cases. Ann Diagn Pathol 10 (6): 320-6, 2006.  [PUBMED Abstract]

  71. Scott JX, Krishnan S, Bourne AJ, et al.: Treatment of metastatic sialoblastoma with chemotherapy and surgery. Pediatr Blood Cancer 50 (1): 134-7, 2008.  [PUBMED Abstract]

  72. Rahbar R, Grimmer JF, Vargas SO, et al.: Mucoepidermoid carcinoma of the parotid gland in children: A 10-year experience. Arch Otolaryngol Head Neck Surg 132 (4): 375-80, 2006.  [PUBMED Abstract]

  73. Kaste SC, Hedlund G, Pratt CB: Malignant parotid tumors in patients previously treated for childhood cancer: clinical and imaging findings in eight cases. AJR Am J Roentgenol 162 (3): 655-9, 1994.  [PUBMED Abstract]

  74. Whatley WS, Thompson JW, Rao B: Salivary gland tumors in survivors of childhood cancer. Otolaryngol Head Neck Surg 134 (3): 385-8, 2006.  [PUBMED Abstract]

  75. Kamal SA, Othman EO: Diagnosis and treatment of parotid tumours. J Laryngol Otol 111 (4): 316-21, 1997.  [PUBMED Abstract]

  76. Rogers DA, Rao BN, Bowman L, et al.: Primary malignancy of the salivary gland in children. J Pediatr Surg 29 (1): 44-7, 1994.  [PUBMED Abstract]

  77. Bentz BG, Hughes CA, Lüdemann JP, et al.: Masses of the salivary gland region in children. Arch Otolaryngol Head Neck Surg 126 (12): 1435-9, 2000.  [PUBMED Abstract]

  78. Ribeiro Kde C, Kowalski LP, Saba LM, et al.: Epithelial salivary glands neoplasms in children and adolescents: a forty-four-year experience. Med Pediatr Oncol 39 (6): 594-600, 2002.  [PUBMED Abstract]

  79. Guzzo M, Ferrari A, Marcon I, et al.: Salivary gland neoplasms in children: the experience of the Istituto Nazionale Tumori of Milan. Pediatr Blood Cancer 47 (6): 806-10, 2006.  [PUBMED Abstract]

  80. McGuirt WF Jr, Little JP: Laryngeal cancer in children and adolescents. Otolaryngol Clin North Am 30 (2): 207-14, 1997.  [PUBMED Abstract]

  81. Bauman NM, Smith RJ: Recurrent respiratory papillomatosis. Pediatr Clin North Am 43 (6): 1385-401, 1996.  [PUBMED Abstract]

  82. Siddiqui F, Sarin R, Agarwal JP, et al.: Squamous carcinoma of the larynx and hypopharynx in children: a distinct clinical entity? Med Pediatr Oncol 40 (5): 322-4, 2003.  [PUBMED Abstract]

  83. Kashima HK, Mounts P, Shah K: Recurrent respiratory papillomatosis. Obstet Gynecol Clin North Am 23 (3): 699-706, 1996.  [PUBMED Abstract]

  84. Maloney EM, Unger ER, Tucker RA, et al.: Longitudinal measures of human papillomavirus 6 and 11 viral loads and antibody response in children with recurrent respiratory papillomatosis. Arch Otolaryngol Head Neck Surg 132 (7): 711-5, 2006.  [PUBMED Abstract]

  85. Andrus JG, Shapshay SM: Contemporary management of laryngeal papilloma in adults and children. Otolaryngol Clin North Am 39 (1): 135-58, 2006.  [PUBMED Abstract]

  86. Avidano MA, Singleton GT: Adjuvant drug strategies in the treatment of recurrent respiratory papillomatosis. Otolaryngol Head Neck Surg 112 (2): 197-202, 1995.  [PUBMED Abstract]

  87. Derkay CS, Smith RJ, McClay J, et al.: HspE7 treatment of pediatric recurrent respiratory papillomatosis: final results of an open-label trial. Ann Otol Rhinol Laryngol 114 (9): 730-7, 2005.  [PUBMED Abstract]

  88. French CA, Kutok JL, Faquin WC, et al.: Midline carcinoma of children and young adults with NUT rearrangement. J Clin Oncol 22 (20): 4135-9, 2004.  [PUBMED Abstract]

Thoracic Cancers

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence 2 for more information.)

Thoracic cancers include breast cancer, bronchial adenomas, bronchial carcinoid tumors, pleuropulmonary blastoma, esophageal tumors, thymomas, thymic carcinomas, tumors of the heart, and mesothelioma. The prognosis, diagnosis, classification, and treatment of these thoracic cancers are discussed below.

Breast Cancer

The most frequent breast tumor seen in children is a fibroadenoma.[1] These tumors can be observed and many will regress without a need for biopsy. However, rare malignant transformation leading to phyllodes tumors has been reported.[2] Sudden rapid enlargement of a suspected fibroadenoma is an indication for needle biopsy or excision. Phyllodes tumors can be managed by wide local excision without mastectomy.[2]

Carcinomas have been reported in both males and females younger than 21 years.[3-8] There is an increased lifetime risk of breast cancer in female survivors of Hodgkin lymphoma who were treated with radiation to the chest area, however, breast cancer is also seen in patients who were treated for any cancer that was treated with chest irradiation.[7,9-11] (Refer to the PDQ summary on the Late Effects of Treatment for Childhood Cancer 7 for more information about secondary breast cancers.) Carcinomas are more frequent than sarcomas. Mammograms should start at age 25 years or 10 years postexposure to radiation therapy (whichever came last). Treatment options for children and adolescents with breast cancer include radiation, chemotherapy, and surgery. Breast tumors may also occur as metastatic deposits from leukemia, rhabdomyosarcoma, other sarcomas, or lymphoma (particularly in patients who are infected with the human immunodeficiency virus). (Refer to the PDQ summary on adult Breast Cancer Treatment 17 for more information.)

Bronchial Tumors

Bronchial tumors are a heterogeneous group of primary endobronchial lesions, and though adenoma implies a benign process, all varieties of bronchial tumors on occasion display a malignant behavior. There are three histologic types. The most frequent type is a carcinoid tumor; this is followed by mucoepidermoid carcinoma and adenoid cystic carcinoma. Carcinoid tumors account for 80% to 85% of all bronchial tumors in children.[12-16] The presenting symptoms are usually because of an incomplete bronchial obstruction with a cough, recurrent pneumonitis, and hemoptysis. Because of difficulties in diagnosis, symptoms are frequently present for months and occasionally children with wheezing have been treated for asthma with delays in diagnosis as long as 4 to 5 years. Metastatic lesions are reported in approximately 6% of cases and recurrences occur in 2% of cases. Atypical carcinoid tumors are rare but more aggressive with 50% of patients presenting with metastatic disease at diagnosis.[17] There is a single report of a child with a carcinoid tumor and metastatic disease who developed the classic carcinoid syndrome.[18] Octreotide nuclear scans may demonstrate uptake of radioactivity by the tumor or lymph nodes, suggesting metastatic spread. Bronchial tumors of all histologic types are associated with an excellent prognosis in children, even in the presence of local invasion.[19,20] The management of bronchial tumors is somewhat controversial because all bronchial tumors are usually visible endoscopically. Biopsy in these lesions may be hazardous because of hemorrhage, and endoscopic resection is not recommended. Bronchography or computed tomography scan may be helpful to determine the degree of bronchiectasis distal to the obstruction since the degree of pulmonary destruction may influence surgical therapy.[21] Epithelial cancers of the lung are rare in children. When they do occur, they tend to be of advanced stage with prognosis dependent on both histology and stage.[17]

Conservative pulmonary resection with the removal of the involved lymphatics is the treatment of choice. Sleeve segmental bronchial resection is possible in children and when feasible, is the treatment of choice.[22,23] Adenoid cystic carcinomas (cylindroma) have a tendency to spread submucosally, and late local recurrence or dissemination has been reported. In addition to en bloc resection with hilar lymphadenectomy, a frozen section examination of the bronchial margins should be carried out in children with this lesion. Neither chemotherapy nor radiation therapy is indicated for bronchial tumors, unless evidence of metastasis is documented.

Pleuropulmonary Blastoma

Pleuropulmonary blastoma is a rare and highly aggressive pulmonary malignancy in children. Pleuropulmonary blastoma appears to progress through stages with the earliest stage (type I) being a purely lung cystic neoplasm with subtle malignant changes, typically occurring in the first 2 years of life with a good prognosis, followed by the more aggressive stages: type II (cystic and solid neoplasm) and type III (purely solid neoplasm).[24,25] There have been reports of type I transitioning directly to type III.[26] Cerebral metastasis occurs in up to 50% of patients with type III tumors.[27] An independent group of researchers has established a registry and resource Web site for this rare tumor.[28] An association between congenital lung cysts and pleuropulmonary blastoma has been reported, although cytogenetic and molecular studies can help distinguish the nonneoplastic congenital cystic adenomatoid malformation from pleuropulmonary blastoma.[29-33] The tumor is usually located in the lung periphery, but it may be extrapulmonary with involvement of the mediastinum, diaphragm, and/or pleura.[32,34] The tumors may recur or metastasize, in spite of primary resection.[25,35] Responses to chemotherapy have been reported with agents similar to those used for the treatment of rhabdomyosarcoma, and adjuvant chemotherapy may benefit patients with type I pleuropulmonary blastoma by reducing the risk of recurrence.[24,36] Achieving total resection of the tumor at any time during treatment is associated with improved prognosis.[32] Chemotherapeutic agents may include vincristine, cyclophosphamide, dactinomycin, and doxorubicin. High-dose chemotherapy with stem cell rescue has been used without success.[37] Radiation, either external beam or P-32, may be used when the tumor cannot be surgically removed. A family history of cancer in close relatives has been noted for many young patients affected by this tumor.[38] In addition, there has been a reported association between pleuropulmonary blastoma and cystic nephroma.[39,40] Data from the International Pleuropulmonary Blastoma Registry suggest that adjuvant chemotherapy may reduce the risk of recurrence.[24]

Esophageal Tumors

Esophageal cancer is rare in the pediatric age group, though it is relatively common in older adults.[41] Symptoms are related to difficulty in swallowing and associated weight loss. Most of these tumors are squamous cell carcinomas, though sarcomas can also arise in the esophagus. The most common benign tumor is leiomyoma. Diagnosis is made by histologic examination of biopsy tissue.

Treatment options for esophageal carcinoma include either external-beam intracavitary radiation therapy or chemotherapy agents commonly used to treat carcinomas: platinum derivatives, paclitaxel, and etoposide. Prognosis generally is poor for this cancer, which rarely can be completely resected. (Refer to the PDQ summary on adult Esophageal Cancer Treatment 18 for more information.)

Thymoma and Thymic Carcinoma

A cancer of the thymus is not considered a thymoma or a thymic carcinoma unless there are neoplastic changes of the epithelial cells that cover the organ.[42,43] The term thymoma is customarily used to describe neoplasms that show no overt atypia of the epithelial component. A thymic epithelial tumor that exhibits clear-cut cytologic atypia and histologic features no longer specific to the thymus is known as thymic carcinoma, also known as type C thymoma. Other tumors that involve the thymus gland include lymphomas, germ cell tumors, carcinomas, carcinoids, and thymomas. Hodgkin lymphoma and non-Hodgkin lymphoma may also involve the thymus and must be differentiated from true thymomas and thymic carcinomas.

Thymoma and thymic carcinomas are rare in adults and children.[44,45] Various diseases and syndromes are associated with thymoma, including myasthenia gravis, polymyositis, systemic lupus erythematosus, rheumatoid arthritis, thyroiditis, Isaacs syndrome, and pure red-cell aplasia.[46,47] Endocrine (hormonal) disorders including hyperthyroidism, Addison disease, and panhypopituitarism can also be associated with a diagnosis of thymoma.[48]

These neoplasms are usually located in the front part of the chest and are usually discovered during a routine chest x-ray. Symptoms can include cough, difficulty with swallowing, tightness of the chest, chest pain, and shortness of breath, though nonspecific symptoms may occur. These tumors generally are slow growing but are potentially invasive, with metastases to distant organs or lymph nodes. Staging is related to invasiveness. Surgery is performed with the goal of a complete resection.

Radiation therapy is necessary for patients with invasive thymoma or thymic carcinoma, even with a complete resection.[48] Chemotherapy is usually reserved for patients with advanced-stage disease who have not responded to radiation therapy or corticosteroids. Agents that have been effective include doxorubicin, cisplatin, and paclitaxel.[48-50] The prognosis for patients with invasive thymoma or thymic carcinoma usually is poor, though significantly higher rates of survival have been reported for patients with tumors that are not locally invasive. (Refer to the PDQ summary on adult Thymoma and Thymic Carcinoma Treatment 19 for more information.)

Researchers have described a group of young patients with midline carcinomas with a very poor prognosis. The tumors arise in midline epithelial structures including the thymus, mediastinum, airway structures, and bladder. They exhibit squamous differentiation. Tumors from 8 of 11 patients exhibited a balanced chromosomal translocation t(15;19) involving the BRD4 and NUT genes. These patients had no response to chemotherapy and died very quickly. Tumors from the remaining three patients had a chromosomal break in the NUT gene on chromosome 15 but had normal chromosome 19. These patients were older and had a slightly longer survival than the eight patients exhibiting t(15;19).[51]

Tumors of the Heart

The most common tumors of the heart are benign and include myxomas, rhabdomyomas, and neurofibromas (i.e., tumors of the nerves that innervate the muscles).[52-54] Primary tumors of the heart may include benign and malignant teratomas, rhabdomyosarcomas, hemangiomas, and chondrosarcomas. Multiple cardiac tumors noted in the fetal or neonatal period are highly associated with a diagnosis of tuberous sclerosis.[52] In a retrospective review of 94 patients with cardiac tumors detected by prenatal or neonatal echocardiography, 68% of the patients exhibited features of tuberous sclerosis.[55] In another study, 79% (15/19) of patients with rhabdomyomas discovered prenatally had tuberous sclerosis, while 96% of those diagnosed postnatally had tuberous sclerosis. Most rhabdomyomas, whether diagnosed prenatally or postnatally, will spontaneously regress.[56] Other tumors of the heart can include metastatic spread of rhabdomyosarcoma, melanoma, leukemia, and carcinoma of other sites. Symptoms include abnormalities of heart rhythm, enlargement of the heart, fluid in the pericardial sac, and congestive heart failure. Successful treatment may require surgery, which may include transplantation, and chemotherapy appropriate for the type of cancer that is present.[57,58]

Mesothelioma

Mesothelioma is extremely rare in childhood with only 2% to 5% of patients presenting during the first two decades of life.[59]

This tumor can involve the membranous coverings of the lung, the heart, or the abdominal organs.[60] These tumors can spread over the surface of organs, without invading far into the underlying tissue, and may spread to regional or distant lymph nodes. Mesothelioma may develop after successful treatment of an earlier cancer, especially after treatment with radiation.[61,62] In adults, these tumors have been associated with exposure to asbestos, which was used as building insulation.[63] The amount of exposure required to develop cancer is unknown, and there is no information about the risk for children exposed to asbestos.

Benign and malignant mesotheliomas cannot be differentiated using histologic criteria. A poor prognosis is associated with lesions that are diffuse and invasive or for those that recur. In general, the course of the disease is slow, and long-term survival is common. Diagnostic thoracoscopy should be considered in suspicious cases to confirm diagnosis.[59] Radical surgical resection has been attempted with mixed results.[64] Treatment with various chemotherapeutic agents used for carcinomas or sarcomas may result in partial responses.[65] Pain is an infrequent symptom; however, radiation therapy may be used for palliation of pain.

Papillary serous carcinoma of the peritoneum is sometimes mistaken for mesothelioma.[66] This tumor generally involves all surfaces lining the abdominal organs, including the surfaces of the ovary. Treatment includes surgical resection whenever possible and use of chemotherapy with agents such as cisplatin, carboplatin, and paclitaxel. (Refer to the PDQ summary on adult Malignant Mesothelioma Treatment 20 for more information.)

References

  1. Santen RJ, Mansel R: Benign breast disorders. N Engl J Med 353 (3): 275-85, 2005.  [PUBMED Abstract]

  2. Valdes EK, Boolbol SK, Cohen JM, et al.: Malignant transformation of a breast fibroadenoma to cystosarcoma phyllodes: case report and review of the literature. Am Surg 71 (4): 348-53, 2005.  [PUBMED Abstract]

  3. Serour F, Gilad A, Kopolovic J, et al.: Secretory breast cancer in childhood and adolescence: report of a case and review of the literature. Med Pediatr Oncol 20 (4): 341-4, 1992.  [PUBMED Abstract]

  4. Drukker BH: Breast disease: a primer on diagnosis and management. Int J Fertil Womens Med 42 (5): 278-87, 1997 Sep-Oct.  [PUBMED Abstract]

  5. Rogers DA, Lobe TE, Rao BN, et al.: Breast malignancy in children. J Pediatr Surg 29 (1): 48-51, 1994.  [PUBMED Abstract]

  6. Rivera-Hueto F, Hevia-Vázquez A, Utrilla-Alcolea JC, et al.: Long-term prognosis of teenagers with breast cancer. Int J Surg Pathol 10 (4): 273-9, 2002.  [PUBMED Abstract]

  7. Kaste SC, Hudson MM, Jones DJ, et al.: Breast masses in women treated for childhood cancer: incidence and screening guidelines. Cancer 82 (4): 784-92, 1998.  [PUBMED Abstract]

  8. Costa NM, Rodrigues H, Pereira H, et al.: Secretory breast carcinoma--case report and review of the medical literature. Breast 13 (4): 353-5, 2004.  [PUBMED Abstract]

  9. 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 18 (12): 2435-43, 2000.  [PUBMED Abstract]

  10. Swerdlow AJ, Barber JA, Hudson GV, et al.: Risk of second malignancy after Hodgkin's disease in a collaborative British cohort: the relation to age at treatment. J Clin Oncol 18 (3): 498-509, 2000.  [PUBMED Abstract]

  11. van Leeuwen FE, Klokman WJ, Veer MB, et al.: Long-term risk of second malignancy in survivors of Hodgkin's disease treated during adolescence or young adulthood. J Clin Oncol 18 (3): 487-97, 2000.  [PUBMED Abstract]

  12. Vadasz P, Palffy G, Egervary M, et al.: Diagnosis and treatment of bronchial carcinoid tumors: clinical and pathological review of 120 operated patients. Eur J Cardiothorac Surg 7 (1): 8-11, 1993.  [PUBMED Abstract]

  13. Kulke MH, Mayer RJ: Carcinoid tumors. N Engl J Med 340 (11): 858-68, 1999.  [PUBMED Abstract]

  14. Oliaro A, Filosso PL, Donati G, et al.: Atypical bronchial carcinoids. Review of 46 patients. J Cardiovasc Surg (Torino) 41 (1): 131-5, 2000.  [PUBMED Abstract]

  15. Moraes TJ, Langer JC, Forte V, et al.: Pediatric pulmonary carcinoid: a case report and review of the literature. Pediatr Pulmonol 35 (4): 318-22, 2003.  [PUBMED Abstract]

  16. Al-Qahtani AR, Di Lorenzo M, Yazbeck S: Endobronchial tumors in children: Institutional experience and literature review. J Pediatr Surg 38 (5): 733-6, 2003.  [PUBMED Abstract]

  17. Lal DR, Clark I, Shalkow J, et al.: Primary epithelial lung malignancies in the pediatric population. Pediatr Blood Cancer 45 (5): 683-6, 2005.  [PUBMED Abstract]

  18. Lack EE, Harris GB, Eraklis AJ, et al.: Primary bronchial tumors in childhood. A clinicopathologic study of six cases. Cancer 51 (3): 492-7, 1983.  [PUBMED Abstract]

  19. Soga J, Yakuwa Y: Bronchopulmonary carcinoids: An analysis of 1,875 reported cases with special reference to a comparison between typical carcinoids and atypical varieties. Ann Thorac Cardiovasc Surg 5 (4): 211-9, 1999.  [PUBMED Abstract]

  20. Fauroux B, Aynie V, Larroquet M, et al.: Carcinoid and mucoepidermoid bronchial tumours in children. Eur J Pediatr 164 (12): 748-52, 2005.  [PUBMED Abstract]

  21. Ahel V, Zubovic I, Rozmanic V: Bronchial adenoid cystic carcinoma with saccular bronchiectasis as a cause of recurrent pneumonia in children. Pediatr Pulmonol 12 (4): 260-2, 1992.  [PUBMED Abstract]

  22. Gaissert HA, Mathisen DJ, Grillo HC, et al.: Tracheobronchial sleeve resection in children and adolescents. J Pediatr Surg 29 (2): 192-7; discussion 197-8, 1994.  [PUBMED Abstract]

  23. Jalal A, Jeyasingham K: Bronchoplasty for malignant and benign conditions: a retrospective study of 44 cases. Eur J Cardiothorac Surg 17 (4): 370-6, 2000.  [PUBMED Abstract]

  24. Priest JR, Hill DA, Williams GM, et al.: Type I pleuropulmonary blastoma: a report from the International Pleuropulmonary Blastoma Registry. J Clin Oncol 24 (27): 4492-8, 2006.  [PUBMED Abstract]

  25. Miniati DN, Chintagumpala M, Langston C, et al.: Prenatal presentation and outcome of children with pleuropulmonary blastoma. J Pediatr Surg 41 (1): 66-71, 2006.  [PUBMED Abstract]

  26. Shivastava R, Saha A, Mehera B, et al.: Pleuropulmonary blastoma: transition from type I (cystic) to type III (solid). Singapore Med J 48 (7): e190-2, 2007.  [PUBMED Abstract]

  27. Priest JR, Magnuson J, Williams GM, et al.: Cerebral metastasis and other central nervous system complications of pleuropulmonary blastoma. Pediatr Blood Cancer 49 (3): 266-73, 2007.  [PUBMED Abstract]

  28. Pleuropulmonary Blastoma Registry. St. Paul, Minn: Children's Hospitals and Clinics of St. Paul. Available online 21. Last accessed November 6, 2008. 

  29. Hasiotou M, Polyviou P, Strantzia CM, et al.: Pleuropulmonary blastoma in the area of a previously diagnosed congenital lung cyst: report of two cases. Acta Radiol 45 (3): 289-92, 2004.  [PUBMED Abstract]

  30. Dosios T, Stinios J, Nicolaides P, et al.: Pleuropulmonary blastoma in childhood. A malignant degeneration of pulmonary cysts. Pediatr Surg Int 20 (11-12): 863-5, 2004.  [PUBMED Abstract]

  31. Vargas SO, Korpershoek E, Kozakewich HP, et al.: Cytogenetic and p53 profiles in congenital cystic adenomatoid malformation: insights into its relationship with pleuropulmonary blastoma. Pediatr Dev Pathol 9 (3): 190-5, 2006 May-Jun.  [PUBMED Abstract]

  32. Indolfi P, Bisogno G, Casale F, et al.: Prognostic factors in pleuro-pulmonary blastoma. Pediatr Blood Cancer 48 (3): 318-23, 2007.  [PUBMED Abstract]

  33. Taube JM, Griffin CA, Yonescu R, et al.: Pleuropulmonary blastoma: cytogenetic and spectral karyotype analysis. Pediatr Dev Pathol 9 (6): 453-61, 2006 Nov-Dec.  [PUBMED Abstract]

  34. Indolfi P, Casale F, Carli M, et al.: Pleuropulmonary blastoma: management and prognosis of 11 cases. Cancer 89 (6): 1396-401, 2000.  [PUBMED Abstract]

  35. Wright JR Jr: Pleuropulmonary blastoma: A case report documenting transition from type I (cystic) to type III (solid). Cancer 88 (12): 2853-8, 2000.  [PUBMED Abstract]

  36. Schmaltz C, Sauter S, Opitz O, et al.: Pleuro-pulmonary blastoma: a case report and review of the literature. Med Pediatr Oncol 25 (6): 479-84, 1995.  [PUBMED Abstract]

  37. de Castro CG Jr, de Almeida SG, Gregianin LJ, et al.: High-dose chemotherapy and autologous peripheral blood stem cell rescue in a patient with pleuropulmonary blastoma. J Pediatr Hematol Oncol 25 (1): 78-81, 2003.  [PUBMED Abstract]

  38. Priest JR, McDermott MB, Bhatia S, et al.: Pleuropulmonary blastoma: a clinicopathologic study of 50 cases. Cancer 80 (1): 147-61, 1997.  [PUBMED Abstract]

  39. Bouron-Dal Soglio D, Harvey I, Yazbeck S, et al.: An association of pleuropulmonary blastoma and cystic nephroma: possible genetic association. Pediatr Dev Pathol 9 (1): 61-4, 2006 Jan-Feb.  [PUBMED Abstract]

  40. Boman F, Hill DA, Williams GM, et al.: Familial association of pleuropulmonary blastoma with cystic nephroma and other renal tumors: a report from the International Pleuropulmonary Blastoma Registry. J Pediatr 149 (6): 850-854, 2006.  [PUBMED Abstract]

  41. Gangopadhyay AN, Mohanty PK, Gopal SC, et al.: Adenocarcinoma of the esophagus in an 8-year-old boy. J Pediatr Surg 32 (8): 1259-60, 1997.  [PUBMED Abstract]

  42. Verley JM, Hollmann KH: Thymoma. A comparative study of clinical stages, histologic features, and survival in 200 cases. Cancer 55 (5): 1074-86, 1985.  [PUBMED Abstract]

  43. Hsueh C, Kuo TT, Tsang NM, et al.: Thymic lymphoepitheliomalike carcinoma in children: clinicopathologic features and molecular analysis. J Pediatr Hematol Oncol 28 (12): 785-90, 2006.  [PUBMED Abstract]

  44. Furman WL, Buckley PJ, Green AA, et al.: Thymoma and myasthenia gravis in a 4-year-old child. Case report and review of the literature. Cancer 56 (11): 2703-6, 1985.  [PUBMED Abstract]

  45. Yaris N, Nas Y, Cobanoglu U, et al.: Thymic carcinoma in children. Pediatr Blood Cancer 47 (2): 224-7, 2006.  [PUBMED Abstract]

  46. Souadjian JV, Enriquez P, Silverstein MN, et al.: The spectrum of diseases associated with thymoma. Coincidence or syndrome? Arch Intern Med 134 (2): 374-9, 1974.  [PUBMED Abstract]

  47. Coulter D, Gold S: Thymoma in the offspring of a patient with Isaacs syndrome. J Pediatr Hematol Oncol 29 (11): 797-8, 2007.  [PUBMED Abstract]

  48. Cowen D, Richaud P, Mornex F, et al.: Thymoma: results of a multicentric retrospective series of 149 non-metastatic irradiated patients and review of the literature. FNCLCC trialists. Fédération Nationale des Centres de Lutte Contre le Cancer. Radiother Oncol 34 (1): 9-16, 1995.  [PUBMED Abstract]

  49. Carlson RW, Dorfman RF, Sikic BI: Successful treatment of metastatic thymic carcinoma with cisplatin, vinblastine, bleomycin, and etoposide chemotherapy. Cancer 66 (10): 2092-4, 1990.  [PUBMED Abstract]

  50. Niehues T, Harms D, Jürgens H, et al.: Treatment of pediatric malignant thymoma: long-term remission in a 14-year-old boy with EBV-associated thymic carcinoma by aggressive, combined modality treatment. Med Pediatr Oncol 26 (6): 419-24, 1996.  [PUBMED Abstract]

  51. French CA, Kutok JL, Faquin WC, et al.: Midline carcinoma of children and young adults with NUT rearrangement. J Clin Oncol 22 (20): 4135-9, 2004.  [PUBMED Abstract]

  52. Isaacs H Jr: Fetal and neonatal cardiac tumors. Pediatr Cardiol 25 (3): 252-73, 2004 May-Jun.  [PUBMED Abstract]

  53. Elderkin RA, Radford DJ: Primary cardiac tumours in a paediatric population. J Paediatr Child Health 38 (2): 173-7, 2002.  [PUBMED Abstract]

  54. Uzun O, Wilson DG, Vujanic GM, et al.: Cardiac tumours in children. Orphanet J Rare Dis 2: 11, 2007.  [PUBMED Abstract]

  55. Tworetzky W, McElhinney DB, Margossian R, et al.: Association between cardiac tumors and tuberous sclerosis in the fetus and neonate. Am J Cardiol 92 (4): 487-9, 2003.  [PUBMED Abstract]

  56. Bader RS, Chitayat D, Kelly E, et al.: Fetal rhabdomyoma: prenatal diagnosis, clinical outcome, and incidence of associated tuberous sclerosis complex. J Pediatr 143 (5): 620-4, 2003.  [PUBMED Abstract]

  57. Michler RE, Goldstein DJ: Treatment of cardiac tumors by orthotopic cardiac transplantation. Semin Oncol 24 (5): 534-9, 1997.  [PUBMED Abstract]

  58. Stiller B, Hetzer R, Meyer R, et al.: Primary cardiac tumours: when is surgery necessary? Eur J Cardiothorac Surg 20 (5): 1002-6, 2001.  [PUBMED Abstract]

  59. Nagata S, Nakanishi R: Malignant pleural mesothelioma with cavity formation in a 16-year-old boy. Chest 127 (2): 655-7, 2005.  [PUBMED Abstract]

  60. Kelsey A: Mesothelioma in childhood. Pediatr Hematol Oncol 11 (5): 461-2, 1994 Sep-Oct.  [PUBMED Abstract]

  61. Hofmann J, Mintzer D, Warhol MJ: Malignant mesothelioma following radiation therapy. Am J Med 97 (4): 379-82, 1994.  [PUBMED Abstract]

  62. Pappo AS, Santana VM, Furman WL, et al.: Post-irradiation malignant mesothelioma. Cancer 79 (1): 192-3, 1997.  [PUBMED Abstract]

  63. Hyers TM, Ohar JM, Crim C: Clinical controversies in asbestos-induced lung diseases. Semin Diagn Pathol 9 (2): 97-101, 1992.  [PUBMED Abstract]

  64. Maziak DE, Gagliardi A, Haynes AE, et al.: Surgical management of malignant pleural mesothelioma: a systematic review and evidence summary. Lung Cancer 48 (2): 157-69, 2005.  [PUBMED Abstract]

  65. Milano E, Pourroy B, Rome A, et al.: Efficacy of a combination of pemetrexed and multiple redo-surgery in an 11-year-old girl with a recurrent multifocal abdominal mesothelioma. Anticancer Drugs 17 (10): 1231-4, 2006.  [PUBMED Abstract]

  66. Wall JE, Mandrell BN, Jenkins JJ 3rd, et al.: Effectiveness of paclitaxel in treating papillary serous carcinoma of the peritoneum in an adolescent. Am J Obstet Gynecol 172 (3): 1049-52, 1995.  [PUBMED Abstract]

Abdominal Cancers

Note: Some citations in the text of this section are followed by a level of evidence. The PDQ editorial boards use a formal ranking system to help the reader judge the strength of evidence linked to the reported results of a therapeutic strategy. (Refer to the PDQ summary on Levels of Evidence 2 for more information.)

Abdominal cancers include adrenocortical tumors, carcinomas of the stomach, cancer of the pancreas, colorectal carcinomas, carcinoid tumors, and gastrointestinal stromal cell tumors. The prognosis, diagnosis, classification, and treatment of these abdominal cancers are discussed below.  [Note: Refer to the Renal Cell Carcinoma section in the PDQ summary on Wilms Tumor and Other Childhood Kidney Tumors 22 for more information.]

Carcinoma of the Adrenal Cortex

Adrenocortical tumors are classified as carcinomas and adenomas.[1-5] Adrenocortical tumors may be hormonally active or inactive. Adenomas are generally benign, whereas adrenocortical carcinomas frequently secrete hormones and may cause the patient to develop masculine traits, irrespective of the patient’s gender. Pediatric patients with adrenocortical carcinoma often have Li-Fraumeni syndrome, which is an inherited condition that predisposes family members to multiple cancers, including breast cancer, rhabdomyosarcoma, and osteosarcoma.[6] A variety of p53 mutations associated with Li-Fraumeni syndrome have been observed in North American children with adrenocortical carcinoma, whereas in a southern Brazilian population, a distinctive p53 mutation predisposes to this disease.[1,7] Children with Beckwith-Wiedemann syndrome [8] or hemihypertrophy [9] are at an increased risk of developing carcinoma of the adrenal cortex (as well as Wilms tumor, hepatoblastoma, and other rare cancers) in the first several years of life.

These tumors spread locally to the lymph nodes and can also involve the kidneys, lungs, bones, and brain.[10] Surgical removal should be attempted but may not always be possible if the tumor has spread widely. Additional treatment may include the use of an artificial hormone that blocks the masculinizing effects of the tumor [11] or chemotherapy using cisplatin, 5-fluorouracil (5-FU), and etoposide.[4,12] A retrospective analysis in Italy and Germany identified 177 patients with adrenocortical carcinoma. Recurrence-free survival was significantly prolonged by the use of adjuvant mitotane. Benefit was present with 1 to 3 g/