Unusual Cancers of Childhood

Summary Type: Treatment
Summary Audience: Health professionals
Summary Language: English
Summary Description: Expert-reviewed information summary about the treatment of unusual cancers of childhood.


Unusual Cancers of Childhood

General Information

This cancer treatment information summary provides an overview of the treatment of unusual cancers of childhood.

The National Cancer Institute 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. These summaries are updated regularly according to the latest published research findings by an Editorial Board of pediatric oncology specialists.

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 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.

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 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.



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.

Head and Neck Cancers

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, the lungs, and the 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’s lymphoma, Hodgkin’s lymphoma, and Burkitt’s 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 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. Outcome is directly related to the stage of the disease, with overall survival ranging from 80% for stage I/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.8,9,10,11 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, 2 studies utilizing preradiation chemotherapy with methotrexate, cisplatin, 5-fluorouracil, and leucovorin with or without recombinant interferon-β 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 BEP (bleomycin, epirubicin, and cisplatin), PF (cisplatin, fluorouracil), and PMB (cisplatin, methotrexate, and bleomycin).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 (Refer to the PDQ summary on Nasopharyngeal Cancer Treatment for more information.)

Treatment Options Under Clinical Evaluation

  • ARAR0331: 15 This Children's Oncology Group trial is evaluating the efficacy of induction chemotherapy with cisplatin plus 5-fluorouracil followed by concomitant chemotherapy (cisplatin) plus radiation therapy with amifostine as a radioprotectant in patients with AJCC stages IIB–IV nasopharyngeal carcinoma. Patients with stages I–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.16,17,18 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 and radiosurgery may play a role in the management of this tumor.19 Recent reports indicate increasing use of neoadjuvant chemotherapy.16,17,20,21 Chemotherapy regimens that have been used with efficacy include VIP (etoposide [VP-16], ifosfamide, and cisplatin [Platinol]),22 VAC (vincristine + actinomycin D + cyclophosphamide) without doxorubicin [Adriamycin], ifosfamide/etoposide, and cisplatin plus etoposide or doxorubicin.20 The long-term survival rate appears to be approximately 60% to 80%. Local recurrences may occur late.

Thyroid Tumors

Tumors of the thyroid are classified as adenomas or carcinomas.23 24,25,26 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.27 Patients with thyroid cancer usually present with a thyroid mass with or without cervical adenopathy.28,29 There is an excessive frequency of thyroid adenoma and carcinoma in patients who previously received radiation to the neck.30,31 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 section of this summary for more information.)

Initial evaluation of a child or adolescent with a thyroid nodule should include an ultrasound of the thyroid and a radionuclide scan. Most thyroid nodules are cold or hypofunctional. 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.32,33 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,34 but the vast majority of tumors are differentiated. Papillary carcinoma represents 60% to 75% of these tumors,31 follicular carcinoma 10% to 20%, medullary carcinoma 5% to 10%, and anaplastic carcinoma less than 1%. Follicular carcinoma may be sporadic or familial and medullary carcinoma is usually familial.35 Papillary carcinoma often has multicentric origins and a very high rate of lymph node metastasis (70% to 90%).34 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 more than 95% 10-year survival rate.36 Fifty percent of medullary thyroid carcinomas in adults and children have hematogenous metastases at diagnosis.37 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.38,

Surgery by an experienced thyroid surgeon is the treatment required for all thyroid neoplasms.36 Total or near-total thyroidectomy plus cervical lymph node dissection, when indicated, is the most common surgical approach.28 During the 4- to 6-week period following surgery, patients will develop hypothyroidism. A radioactive iodine, or (I-131) scan is then performed to search for residual neoplasm in the functioning thyroid tissue. 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 TSH production.39

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.40 Periodic evaluations are required to determine whether there is metastatic disease involving the lungs. Lifelong follow-up is necessary.41 Thyroglobulin, T4, and thyrotropin (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.41,42,43 Recurrence is common (35% to 45%), however, and is seen more often in children younger than 10 years and in those with palpable cervical lymph nodes at diagnosis.24,44,45 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.46 Recurrent papillary thyroid cancer is usually responsive to treatment with radioactive iodine ablation.47 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 for more information.)

Oral Cancers

Cancer of the oral cavity is extremely rare in children or in adolescents.3,48 The vast majority (>90%) of tumors and tumor-like lesions in the oral cavity are benign.49,50,51,52 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 49,50 and 3% to 13% of oral tumor biopsies.51,52 Malignant tumor types include lymphomas (especially Burkitt’s) 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.53,54 Adolescents with an oral SCC should be screened for Fanconi anemia.55

Treatment of benign oral tumors is surgical. Management of malignant tumors is dependent on histology and may include surgery, chemotherapy, and radiation.56 LCH may require other treatment besides surgery. (Refer to the PDQ summaries on adult Oropharyngeal Cancer Treatment and Lip and Oral Cavity Cancer Treatment for more information.)

Salivary Gland Tumors

Most salivary gland neoplasms arise in the parotid gland.57,58,59,60,61 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. The malignant lesions include mucoepidermoid carcinoma,62 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.63,64 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.62,65,66 Prognosis for patients with these tumors is generally good.60,67,68 (Refer to the PDQ summary on adult Salivary Gland Cancer Treatment for more information.)

Laryngeal Cancer and Papillomatosis

Benign and especially malignant tumors of the larynx are rare. Malignant tumors may be associated with benign tumors such as polyps and papillomas.69,70 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.71 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-11.72 The presence of HPV-11 appears to correlate with a more aggressive clinical course than HPV-6.73 This condition is not cancerous, and primary treatment is surgical ablation with laser vaporization.74 Frequent recurrences are common. If a patient requires more than four surgical procedures per year, treatment with interferon should be considered.75 A pilot study of immunotherapy with HspE7, a recombinant fusion protein that has shown activity in other human papilloma virus–related diseases, has suggested a marked increase in the amount of time between surgeries.76 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 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).77,



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77 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.

Thoracic Cancers

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.3,4,5,6,7,8 There is an increased lifetime risk of breast cancer in female survivors of Hodgkin’s 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.7,9,10,11 (Refer to the PDQ summary on the Late Effects of Treatment for Childhood Cancer for more information about secondary breast cancers.) Carcinomas are more frequent than sarcomas. Mammograms should start at age 25 or 10 years postexposure to radiation therapy (whichever came last). Treatment options include radiation, chemotherapy, and surgery for children and adolescents with breast cancer. 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 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 3 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.12,13,14,15,16 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. An independent group of researchers has established a registry and resource web site for this rare tumor.24 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.25,26,27 The tumor is usually located in the lung periphery, but it may be extrapulmonary with involvement of the mediastinum, diaphragm, and/or pleura.28 The tumors may recur or metastasize, in spite of primary resection.29,30 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.31,32 Chemotherapeutic agents may include vincristine, cyclophosphamide, dactinomycin, and doxorubicin. High-dose chemotherapy with stem cell rescue has been used without success.33 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.34 In addition, there has been a reported association between pleuropulmonary blastoma and cystic nephroma.35 Data from the International Pleuropulmonary Blastoma Registry suggest that adjuvant chemotherapy may reduce the risk of recurrence.32,

Esophageal Tumors

Esophageal cancer is rare in the pediatric age group, though it is relatively common in older adults.36 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 with the platinum derivatives, paclitaxel, and etoposide, agents commonly used to treat carcinomas. Prognosis generally is poor for this cancer, which rarely can be completely resected. (Refer to the PDQ summary on adult Esophageal Cancer Treatment 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.37 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’s lymphoma and non-Hodgkin’s 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.38,39 Various diseases and syndromes are associated with thymoma, including myasthenia gravis, polymyositis, systemic lupus erythematosus, rheumatoid arthritis, thyroiditis, and pure red-cell aplasia.40 Endocrine (hormonal) disorders including hyperthyroidism, Addison’s disease, and panhypopituitarism can also be associated with a diagnosis of thymoma.41,

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.

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 3 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 8 patients exhibiting t(15;19).42,

Radiation therapy is necessary for patients with invasive thymoma or thymic carcinoma, even with a complete resection.41 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.41,43,44 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 for more information.)

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).45,46 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.45 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.47 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.48 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.49,50,

Mesothelioma

Mesothelioma is extremely rare in childhood with only 2% to 5% of patients presenting during the first two decades of life.51

This tumor can involve the membranous coverings of the lung, the heart, or the abdominal organs.52 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.53,54 In adults, these tumors have been associated with exposure to asbestos, which was used as building insulation.55 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.51 Radical surgical resection has been attempted with mixed results.56 Treatment with various chemotherapeutic agents used for carcinomas or sarcomas may result in partial responses. 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.57 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 for more information.)



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

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.

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.

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

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

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.

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

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.

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.

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.

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

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.

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.

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.

24 Pleuropulmonary Blastoma Registry. St. Paul, Minn: Children's Hospitals and Clinics of St. Paul. Available online. Last accessed April 19, 2007.

25 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.

26 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.

27 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.

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

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

30 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.

31 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.

32 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.

33 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.

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

35 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.

36 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.

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

38 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.

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

40 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.

41 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.

42 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.

43 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.

44 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.

45 Isaacs H Jr: Fetal and neonatal cardiac tumors. Pediatr Cardiol 25 (3): 252-73, 2004 May-Jun.

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

47 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.

48 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.

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

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

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

52 Kelsey A: Mesothelioma in childhood. Pediatr Hematol Oncol 11 (5): 461-2, 1994 Sep-Oct.

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

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

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

56 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.

57 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.

Abdominal Cancers

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. Refer to the Renal Cell Carcinoma section in the PDQ summary on Wilms' Tumor and Other Childhood Kidney Tumors for more information.

Carcinoma of the Adrenal Cortex

Adrenocortical tumors are classified as carcinomas and adenomas.1,2,3,4 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.5 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.1,6 Children with Beckwith-Wiedemann Syndrome 7 or hemihypertrophy 8 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.9 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 10 or chemotherapy using cisplatin, 5-fluorouracil (5-FU), and etoposide.4,11 The prognosis for patients who have small, completely resected tumors generally is excellent, but prognosis can be poor for patients who have large primary tumors or metastatic disease at diagnosis.3,12 Tumor stage has been identified as a significant prognostic factor in chi