General Information About Childhood Tracheobronchial Tumors

Primary lung tumors are rare in children and histologically quite diverse.[1 ] When epithelial cancers of the lung occur, they tend to be of advanced stage, with prognosis dependent on both histology and stage.[2 ] Most primary lung tumors are malignant. In a review of 383 primary pulmonary neoplasms in children, 76% were malignant and 24% were benign.[3 ] A review of primary malignant epithelial lung tumors using the National Cancer Data Base found that the most common primary malignant pediatric lung neoplasms were carcinoid tumors (63%) followed by mucoepidermoid carcinoma of the lung (18%).[4 ]

References:

1. Yu DC, Grabowski MJ, Kozakewich HP, et al.: Primary lung tumors in children and adolescents: a 90-year experience. J Pediatr Surg 45 (6): 1090-5, 2010.
2. Lal DR, Clark I, Shalkow J, et al.: Primary epithelial lung malignancies in the pediatric population. Pediatr Blood Cancer 45 (5): 683-6, 2005.
3. Hancock BJ, Di Lorenzo M, Youssef S, et al.: Childhood primary pulmonary neoplasms. J Pediatr Surg 28 (9): 1133-6, 1993.
4. Rojas Y, Shi YX, Zhang W, et al.: Primary malignant pulmonary tumors in children: a review of the national cancer data base. J Pediatr Surg 50 (6): 1004-8, 2015.

Histology

Tracheobronchial tumors are a heterogeneous group of primary endobronchial lesions, and although adenoma implies a benign process, all varieties of tracheobronchial tumors on occasion display malignant behavior. The following histologic types have been identified (refer to Figure 1):[1 ,2 ,3 ,4 ,5 ,6 ,7 ]

• Carcinoid tumor (neuroendocrine tumor of the bronchus). Carcinoid tumors account for 80% to 85% of all tracheobronchial tumors in children.[1 ,2 ,3 ,4 ,5 ]; [8 ][Level of evidence: 3iiA] It is the most common tracheobronchial tumor.
• Mucoepidermoid carcinoma. A slow-growing vascular polypoid mass of the airway that is the second most common (10%) pediatric tracheobronchial tumor.
• Inflammatory myofibroblastic tumors. These low-grade benign tumors account for 1% of pediatric tracheobronchial tumors, are commonly located in the upper trachea, and rarely metastasize.
• Rhabdomyosarcoma.
• Granular cell tumors. Malignant transformation has not been documented in pediatric patients.

Figure 1. The most representative primary tracheobronchial tumors are described with their more frequent location. Reprinted from Seminars in Pediatric Surgery, Volume 25, Issue 3, Patricio Varela, Luca Pio, Michele Torre, Primary tracheobronchial tumors in children, Pages 150–155, Copyright (2016), with permission from Elsevier.

References:

1. 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.
2. Kulke MH, Mayer RJ: Carcinoid tumors. N Engl J Med 340 (11): 858-68, 1999.
3. Oliaro A, Filosso PL, Donati G, et al.: Atypical bronchial carcinoids. Review of 46 patients. J Cardiovasc Surg (Torino) 41 (1): 131-5, 2000.
4. 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.
5. 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.
6. Roby BB, Drehner D, Sidman JD: Pediatric tracheal and endobronchial tumors: an institutional experience. Arch Otolaryngol Head Neck Surg 137 (9): 925-9, 2011.
7. Varela P, Pio L, Torre M: Primary tracheobronchial tumors in children. Semin Pediatr Surg 25 (3): 150-5, 2016.
8. Potter SL, HaDuong J, Okcu F, et al.: Pediatric Bronchial Carcinoid Tumors: A Case Series and Review of the Literature. J Pediatr Hematol Oncol 41 (1): 67-70, 2019.

Prognosis

With the exception of rhabdomyosarcoma, tracheobronchial tumors of all histologic types are associated with an excellent prognosis after surgical resection in children, even in the presence of local invasion.[1 ,2 ]; [3 ][Level of evidence: 2A]

References:

1. 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.
2. Fauroux B, Aynie V, Larroquet M, et al.: Carcinoid and mucoepidermoid bronchial tumours in children. Eur J Pediatr 164 (12): 748-52, 2005.
3. Redlich A, Wechsung K, Boxberger N, et al.: Extra-appendiceal neuroendocrine neoplasms in children - data from the GPOH-MET 97 Study. Klin Padiatr 225 (6): 315-9, 2013.

Clinical Presentation and Diagnostic Evaluation

The presenting symptoms of a tracheobronchial tumor are usually caused by an incomplete tracheobronchial obstruction and include the following:

• Cough.
• Recurrent pneumonitis.
• 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 for as long as 4 to 5 years.[1 ]

Metastatic lesions are reported in approximately 6% of carcinoid tumors, and recurrences are reported in 2% of cases. Atypical carcinoid tumors are rare but more aggressive, with 50% of patients presenting with metastatic disease at diagnosis.[2 ,3 ] There is a single report of a child with a carcinoid tumor and metastatic disease who developed the classic carcinoid syndrome.[4 ] Octreotide nuclear scans may demonstrate uptake of radioactivity by the tumor or lymph nodes, suggesting metastatic spread.

The management of tracheobronchial tumors is somewhat controversial because tracheobronchial tumors are usually visible endoscopically. Biopsy of these lesions may be hazardous because of the risk of hemorrhage. New endoscopic techniques have allowed biopsy to be performed safely;[5 ,6 ] however, endoscopic resection is not recommended except in highly selected cases.[6 ,7 ,8 ] 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.[9 ]

References:

1. Abuzetun JY, Hazin R, Suker M, et al.: Primary squamous cell carcinoma of the lung with bony metastasis in a 13-year-old boy: case report and review of literature. J Pediatr Hematol Oncol 30 (8): 635-7, 2008.
2. Lal DR, Clark I, Shalkow J, et al.: Primary epithelial lung malignancies in the pediatric population. Pediatr Blood Cancer 45 (5): 683-6, 2005.
3. Rizzardi G, Marulli G, Calabrese F, et al.: Bronchial carcinoid tumours in children: surgical treatment and outcome in a single institution. Eur J Pediatr Surg 19 (4): 228-31, 2009.
4. 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.
5. Roby BB, Drehner D, Sidman JD: Pediatric tracheal and endobronchial tumors: an institutional experience. Arch Otolaryngol Head Neck Surg 137 (9): 925-9, 2011.
6. Malkan AD, Sandoval JA: Controversial tumors in pediatric surgical oncology. Curr Probl Surg 51 (12): 478-520, 2014.
7. Luckraz H, Amer K, Thomas L, et al.: Long-term outcome of bronchoscopically resected endobronchial typical carcinoid tumors. J Thorac Cardiovasc Surg 132 (1): 113-5, 2006.
8. Varela P, Pio L, Torre M: Primary tracheobronchial tumors in children. Semin Pediatr Surg 25 (3): 150-5, 2016.
9. 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.

Treatment of Childhood Tracheobronchial Tumors

Conservative pulmonary resection, including sleeve segmental resection, when feasible, with the removal of the involved lymphatics, is the treatment of choice.[1 ,2 ]; [3 ][Level of evidence: 2A] Chemotherapy and radiation therapy are not indicated for tracheobronchial tumors, unless evidence of metastasis is documented or the tumor is the rhabdomyosarcoma histologic type.

Treatment options for tracheobronchial tumors, according to histologic type, are as follows:

1. Carcinoid tumor (neuroendocrine tumor of the bronchus). Surgical resection with lymph node sampling is the treatment of choice. The overall survival rate is 95%.[4 ,5 ]
2. Mucoepidermoid carcinoma. The recommended treatment is open surgical resection and lymph node sampling. Endoscopic resection is not recommended.[6 ,7 ]
3. Inflammatory myofibroblastic tumors. Surgery is the treatment of choice. However, if the tumor is ALK mutation positive, treatment with crizotinib may be effective.[7 ,8 ,9 ,10 ]
4. Rhabdomyosarcoma. Mutilating surgery is not indicated. This tumor is very responsive to chemotherapy and radiation therapy, even with lymph node metastasis.[7 ]
5. Granular cell tumors. Surgical resection is based on morbidity risk.[7 ,11 ,12 ]

(Refer to the PDQ summary on Childhood Gastrointestinal Carcinoid Tumors Treatment for information about other neuroendocrine carcinoid tumors.)

References:

1. 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.
2. 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.
3. Redlich A, Wechsung K, Boxberger N, et al.: Extra-appendiceal neuroendocrine neoplasms in children - data from the GPOH-MET 97 Study. Klin Padiatr 225 (6): 315-9, 2013.
4. Travis WD, Rush W, Flieder DB, et al.: Survival analysis of 200 pulmonary neuroendocrine tumors with clarification of criteria for atypical carcinoid and its separation from typical carcinoid. Am J Surg Pathol 22 (8): 934-44, 1998.
5. McMullan DM, Wood DE: Pulmonary carcinoid tumors. Semin Thorac Cardiovasc Surg 15 (3): 289-300, 2003.
6. Qian X, Sun Z, Pan W, et al.: Childhood bronchial mucoepidermoid tumors: A case report and literature review. Oncol Lett 6 (5): 1409-1412, 2013.
7. Varela P, Pio L, Torre M: Primary tracheobronchial tumors in children. Semin Pediatr Surg 25 (3): 150-5, 2016.
8. Jindal A, Bal A, Agarwal R: Inflammatory myofibroblastic tumor of the trachea in the pediatric age group: case report and systematic review of the literature. J Bronchology Interv Pulmonol 22 (1): 58-65, 2015.
9. Butrynski JE, D'Adamo DR, Hornick JL, et al.: Crizotinib in ALK-rearranged inflammatory myofibroblastic tumor. N Engl J Med 363 (18): 1727-33, 2010.
10. Chavez C, Hoffman MA: Complete remission of ALK-negative plasma cell granuloma (inflammatory myofibroblastic tumor) of the lung induced by celecoxib: A case report and review of the literature. Oncol Lett 5 (5): 1672-1676, 2013.
11. Finck C, Moront M, Newton C, et al.: Pediatric granular cell tumor of the tracheobronchial tree. J Pediatr Surg 43 (3): 568-70, 2008.
12. Pernas FG, Younis RT, Lehman DA, et al.: Management of pediatric airway granular cell tumor: role of laryngotracheal reconstruction. Int J Pediatr Otorhinolaryngol 70 (6): 957-63, 2006.

Treatment Options Under Clinical Evaluation for Childhood Tracheobronchial Tumors

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

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

• APEC1621 (NCT03155620) (Pediatric MATCH: Targeted Therapy Directed by Genetic Testing in Treating Pediatric Patients with Relapsed or Refractory Advanced Solid Tumors, Non-Hodgkin Lymphomas, or Histiocytic Disorders): NCI-COG Pediatric Molecular Analysis for Therapeutic Choice (MATCH), referred to as Pediatric MATCH, will match targeted agents with specific molecular changes identified using a next-generation sequencing targeted assay of more than 4,000 different mutations across more than 160 genes in refractory and recurrent solid tumors. Children and adolescents aged 1 to 21 years are eligible for the trial.

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

Special Considerations for the Treatment of Children With Cancer

Cancer in children and adolescents is rare, although the overall incidence of childhood cancer has been slowly increasing since 1975.[1 ] Referral to medical centers with multidisciplinary teams of cancer specialists experienced in treating cancers that occur in childhood and adolescence should be considered for children and adolescents with cancer. This multidisciplinary team approach incorporates the skills of the following health care professionals and others to ensure that children receive treatment, supportive care, and rehabilitation that will achieve optimal survival and quality of life:

• Primary care physicians.
• Pediatric surgeons.
• Radiation oncologists.
• Pediatric medical oncologists/hematologists.
• Rehabilitation specialists.
• Pediatric nurse specialists.
• Social workers.
• Child-life professionals.
• Psychologists.

(Refer to the PDQ Supportive and Palliative Care summaries for specific information about supportive care for children and adolescents with cancer.)

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

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

Childhood cancer is a rare disease, with about 15,000 cases diagnosed annually in the United States in individuals younger than 20 years.[4 ] The U.S. Rare Diseases Act of 2002 defines a rare disease as one that affects populations smaller than 200,000 persons. Therefore, all pediatric cancers are considered rare.

The designation of a rare tumor is not uniform among pediatric and adult groups. Adult rare cancers are defined as those with an annual incidence of fewer than six cases per 100,000 people, and they are estimated to account for up to 24% of all cancers diagnosed in the European Union and about 20% of all cancers diagnosed in the United States.[5 ,6 ] Also, the designation of a pediatric rare tumor is not uniform among international groups, as follows:

• The Italian cooperative project on rare pediatric tumors (Tumori Rari in Eta Pediatrica [TREP]) defines a pediatric rare tumor as one with an incidence of less than two cases per 1 million population per year and is not included in other clinical trials.[7 ]
• The Children's Oncology Group has opted to define rare pediatric cancers as those listed in the International Classification of Childhood Cancer subgroup XI, which includes thyroid cancer, melanoma and nonmelanoma skin cancers, and multiple types of carcinomas (e.g., adrenocortical carcinoma, nasopharyngeal carcinoma, and most adult-type carcinomas such as breast cancer, colorectal cancer, etc.).[8 ] These diagnoses account for about 4% of cancers diagnosed in children aged 0 to 14 years, compared with about 20% of cancers diagnosed in adolescents aged 15 to 19 years.[9 ]

  Most cancers within subgroup XI are either melanomas or thyroid cancer, with the remaining subgroup XI cancer types accounting for only 1.3% of cancers in children aged 0 to 14 years and 5.3% of cancers in adolescents aged 15 to 19 years.

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

References:

1. Smith MA, Seibel NL, Altekruse SF, et al.: Outcomes for children and adolescents with cancer: challenges for the twenty-first century. J Clin Oncol 28 (15): 2625-34, 2010.
2. Corrigan JJ, Feig SA; American Academy of Pediatrics: Guidelines for pediatric cancer centers. Pediatrics 113 (6): 1833-5, 2004.
3. Smith MA, Altekruse SF, Adamson PC, et al.: Declining childhood and adolescent cancer mortality. Cancer 120 (16): 2497-506, 2014.
4. Ward E, DeSantis C, Robbins A, et al.: Childhood and adolescent cancer statistics, 2014. CA Cancer J Clin 64 (2): 83-103, 2014 Mar-Apr.
5. Gatta G, Capocaccia R, Botta L, et al.: Burden and centralised treatment in Europe of rare tumours: results of RARECAREnet-a population-based study. Lancet Oncol 18 (8): 1022-1039, 2017.
6. DeSantis CE, Kramer JL, Jemal A: The burden of rare cancers in the United States. CA Cancer J Clin 67 (4): 261-272, 2017.
7. Ferrari A, Bisogno G, De Salvo GL, et al.: The challenge of very rare tumours in childhood: the Italian TREP project. Eur J Cancer 43 (4): 654-9, 2007.
8. Pappo AS, Krailo M, Chen Z, et al.: Infrequent tumor initiative of the Children's Oncology Group: initial lessons learned and their impact on future plans. J Clin Oncol 28 (33): 5011-6, 2010.
9. Howlader N, Noone AM, Krapcho M, et al., eds.: SEER Cancer Statistics Review, 1975-2012. Bethesda, Md: National Cancer Institute, 2015. Also available online. Last accessed February 20, 2020.

Changes to This Summary (04 / 17 / 2020)

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

Editorial changes were made to this summary.

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

About This PDQ Summary

Purpose of This Summary

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

Reviewers and Updates

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

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

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

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

The lead reviewers for Childhood Tracheobronchial Tumors Treatment are:

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

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

Levels of Evidence

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

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The preferred citation for this PDQ summary is:

PDQ® Pediatric Treatment Editorial Board. PDQ Childhood Tracheobronchial Tumors Treatment. Bethesda, MD: National Cancer Institute. Updated <MM/DD/YYYY>. Available at: https://www.cancer.gov/types/lung/hp/child-tracheobronchial-treatment-pdq. Accessed <MM/DD/YYYY>.

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Last Revised: 2020-04-17