Thoracic Tumors

Thoracic Tumors

Saumini Srinivasan, MD, MS

Introduction

•Primary pulmonary tumors are rare in infants and children and may be either benign or malignant.

•Metastatic tumor involvement is much more common than primary tumors.

•The lungs can be affected by therapies for childhood cancer; these complications may also be seen by the primary practitioner (see Chapter 84, Pulmonary Complications of Cancer Therapy).

•Primary pulmonary and thoracic tumors may arise in the lungs, the mediastinum, or the chest wall.

•These tumors may be diagnosed at any age, including at prenatal ultrasonography and incidentally on chest radiographs.

Airway Tumors

Tracheal Tumors

Papillomas

•Papillomas are proliferative lesions found on the skin or mucous membranes (Figure 83-1). (See also Chapter 49, Papillomatosis.)

•They can involve the larynx, trachea, and bronchi and are frequently multiple.

•Symptoms result from airway obstruction from the tumor.

•Pulmonary seeding has been noted in these tumors, and the human papillomavirus has a role in the pathogenesis.

•Patients present with hoarseness and stridor. Dyspnea results from progressive airway obstruction.

•These tumors are removed because of their tendency for growth and airway obstruction. However, repeat surgical procedures may be required because of their tendency to recur.

Hemangiomas

•Hemangiomas affect girls twice as often as boys.

•Hemangiomas manifest most often between 2 weeks and 2 months of age but can occur at any age.

Figure 83-1. Tracheal papilloma in a 17-year-old girl. Coronal reconstructed computed tomographic image shows a lobulated tracheal papilloma (black arrow) and scattered nodules due to pulmonary seeding (white arrows) that are too numerous to count.

•The skin and the liver are the most common locations for infantile hemangiomas, which are usually treated conservatively because

of their predictable course of early proliferation, followed by spontaneous involution.

•Tracheal cases are usually diagnosed by 6 months of age and manifest as recurrent croup or, less often, clinically significant bleeding.

•Cutaneous hemangiomas—particularly on the face, head, and neck— commonly coexist with tracheal lesions.

•Soft-tissue neck radiography of tracheal hemangiomas shows asymmetrical subglottic narrowing. However, lesions are better diagnosed at bronchoscopy (see Chapter 13, Subglottic Stenosis).

•Hemangiomas typically follow a predictable course of proliferation in the first year of life, followed by spontaneous involution during childhood.

•Vascular malformations have been reclassified in the past decade by the International Society for the Study of Vascular Anomalies. Those involving the chest wall, most often infantile hemangiomas and venous malformations, may manifest at any age.

• β-blockers and steroids are used to hasten the involution of hemangiomas. Rarely, complicated lesions may undergo embolization.

•The head and neck are the most common locations for venous malformations (previously termed cavernous hemangiomas, cystic hygromas, and lymphangiomas). These lesions can now be treated with percutaneous sclerotherapy and, less often, surgery.

Bronchial Adenoma

•Bronchial adenomas arise from the mucous gland of the bronchi.

•On the basis of pathologic findings, there may be 2 types:

—Ninety percent are of the carcinoid type but are rarely associated with the carcinoid syndrome.

—Ten percent are cylindromatous.

•Carcinoid tumors have malignant potential and can spread to local lymph nodes.

•Bronchial carcinoids arise in the Kulchitsky cells in the bronchial mucosa.

•Patients with both types of adenoma may present with recurrent pneumonia, chest pain, and, sometimes, hemoptysis.

•Bronchoscopy (Figure 83-2) with biopsy helps to establish the diagnosis; definitive treatment involves surgical resection.

Figure 83-2. Bronchial adenoma (carcinoid) in a 15-year-old patient who presented with hemoptysis. Bronchoscopy shows a mass obstructing the right bronchus intermedius.

• Localized tumors can be resected by using a “sleeve” resection of the airway, thereby preserving the lung parenchyma.

•These tumors may spread to the surrounding airway, necessitating a lobar resection unless well localized to the airway wall.

Benign Pulmonary (Parenchymal) Tumors

•Hamartomas are tumorlike malformations formed from abnormal mixing of normal organ components.

—Lung hamartomas are usually located in the periphery and are composed of cartilage.

—These tumors are reported more commonly in adults with a solitary pulmonary nodule.

—The rare form reported in infants can be large and necessitate surgical resection.

—Differential diagnosis of hamartomas includes congenital cystic adenomatoid malformation.

•Plasma cell granulomas are also known as inflammatory pseudotumors, due to a polymorphic infiltrate of inflammatory cells at pathologic examination.

—These rare tumors have been reported in patients as young as 6 years old in 1 series, in which 11% of patients were asymptomatic and 86% of the lesions were located in the lung periphery.

—Surgical resection is the therapy of choice.

Malignant Tumors in the Lung

•Primary epithelial malignancies in the lung are rare, with 50 cases reported in the literature, mostly in adolescents and in association with respiratory papillomatosis.

—Most patients are symptomatic, with cough, hemoptysis, and/or chest pain.

—Malignant tumors may be misdiagnosed as pneumonia, which results in a delay in diagnosis.

•Bronchogenic carcinoma is the most frequent pulmonary malignancy in childhood and adolescence, after bronchial carcinoids.

—These tumors have been described with several cell types in the pediatric population, with the exception of alveolar cell carcinoma, giant cell carcinoma, and carcinosarcoma.

—Only 7 cases of squamous cell carcinoma in the pediatric population have been reported in the literature.

—Squamous cell carcinoma is typically reported in adult men with a history of smoking; no risk factors have been identified in the pediatric population.

—The prognosis depends on histologic findings, disease stage, and response to therapy, as in adults.

• Pleuropulmonary blastomas (PPBs) (Figure 83-3) are rare childhood tumors that develop during fetal lung development and contain both epithelial and mesenchymal elements.

—These can be preceded by lung cysts, congenital cystic adenomatoid malformations, and congenital pulmonary airway malformations, especially in familial cases.

—These tumors can be caused by a heterozygous mutation of the DICER1 gene (13q32.13).

—Twenty percent to 25% of affected children have a close relative with other neoplasias or dysplasias.

—Although DICER1 mutations have been reported in several different malignancies, the most common association is with PPB, cystic nephroma, and ovarian Sertoli-Leydig cell tumors.

—PPBs are classified as type I (cystic), type II (cystic and solid), and type III (solid). Type I tumors have the best prognosis. However, transformation from type I to type II or III tumors can occur.

—Clinically, patients with PPB present with nonspecific symptoms, including cough, respiratory distress, fever, chest pain, and anorexia. Type I tumors are seen in younger patients (median age, 9 months) as compared to types II and III (median age, 35 months).

—Radiologically, a pulmonary or pleural mass is noted; 60% of lesions are right sided.

—Rarely, pneumothorax or pneumomediastinum may be noted.

—Treatment is surgical resection and chemotherapy with the use of sarcoma-targeted agents (vincristine, dactinomycin, cyclophosphamide, ifosfamide, doxorubicin, cisplatin), as well as radiation therapy.

—Prognosis is poor, with 50% of patients dying within 2 years of diagnosis. Outcomes are poorer with mediastinal and pleural involvement.

Figure 83-3. Pleuropulmonary blastoma in a 10-year-old girl with a persistent cough. A. Frontal chest radiograph demonstrates near-complete opacification of the right hemithorax, with right-to-left midline shift. B. Axial contrast-enhanced chest computed tomographic image shows a low-attenuation soft-tissue mass filling the right hemithorax.

Systemic Neoplasms Affecting the Lung: Leukemia

•Acute lymphoblastic leukemia (ALL) is the most common childhood malignancy, with an annual incidence of 4,900 cases (2 to 5 cases per 100,000 children).

•T cell ALL is frequently seen in older boys; a mediastinal mass is present in about one-half of patients.

•Acute myeloid leukemia (AML) has an incidence of about 500 new cases each year in children aged 0–14 years.

•Clinically, bone pain results from involvement of the bone marrow and periosteum.

•Painless lymphadenopathy and hepatosplenomegaly result from extramedullary leukemia spread. Laboratory evaluation findings will be clinically significant for anemia, thrombocytopenia, and neutropenia.

•Standard therapy for ALL includes vincristine, steroids, and L-asparaginase; AML is typically treated with a regimen consisting of cytarabine, daunorubicin, and etoposide.

•Both types of malignancies require prophylaxis against Pneumocystis jirovecii pneumonia.

•Patients recovering from prolonged neutropenia may develop invasive pulmonary aspergillosis that can cause massive hemoptysis.

•Patients with AML and hyperleukocytosis (white blood cell [WBC] counts >100 × 10⁹/L) at presentation are at risk for developing pulmonary leukostasis. These patients develop tachypnea, hypoxia, pulmonary edema, or hemorrhage and may progress to respiratory failure. Therapy includes supportive measures, as well as early institution of chemotherapy and leukapheresis to decrease WBC counts.

Metastatic Pulmonary Tumors

•Metastatic pulmonary tumors comprise most malignant lesions in the lung in children. Pulmonary metastases arise from primary tumors from several sources, as summarized in Table 83-1.

•Pulmonary metastases may be solitary or multiple and are present at diagnosis or at evaluation for recurrence.

•Metastases can be diagnosed with computed tomography (CT).

•Surgical resection of metastases is considered after therapy for the primary tumor.

•Radiation therapy of the lung and/or chest may play a role in the management of lung metastases.

Mediastinal Tumors

•The mediastinum is the portion of the thorax that lies in between the lungs. It is divided into the following 4 compartments:

—Superior mediastinum

—Anterior mediastinum (anterior to the anterior plane of the trachea)

Table 83-1. Pediatric Tumors That Metastasize to the Lung
Primary Site	Tumor
Skeletal system	Osteosarcoma Ewing sarcoma Chondrosarcoma Ameloblastoma
Musculoskeletal system	Rhabdomyosarcoma Soft-tissue sarcoma Synovial cell sarcoma Malignant fibrous histiocytoma Chondrosarcoma Fibrosarcoma Liposarcoma Malignant neurilemmoma
Gastrointestinal tract	Hepatoblastoma Hepatocellular carcinoma Embryonal sarcoma of the liver Leiomyosarcoma Adenocarcinoma of the colon
Genitourinary tract	Wilms tumor Malignant rhabdoid tumor of the kidney Clear cell sarcoma of the kidney Gonadal germ cell tumor Trophoblastic choriocarcinoma
Endocrine system	Differentiated thyroid carcinoma Adrenocortical carcinoma

—Middle mediastinum (contains the heart and pericardium, ascending aorta, bifurcation of the pulmonary artery, trachea, the 2 mainstem bronchi, and the lower segment of the inferior vena cava)

—Posterior mediastinum (posterior to the anterior plane of the trachea)

•Anterior mediastinal masses are more likely to be malignant.

•Mediastinal lesions may remain asymptomatic and may be found incidentally on images.

•Respiratory symptoms result from compression of the airway, which causes narrowing of the trachea and bronchi.

•Signs at clinical examination depend on the level of partial obstruction.

—Stridor when the extrathoracic is partially obstructed

—Monophonic wheeze when the intrathoracic large airway is obstructed

•Pressure on the recurrent laryngeal nerve results in a brassy cough and hoarseness.

•Gastrointestinal symptoms can arise from pressure on the esophagus and include dysphagia and regurgitation.

•Tracheal or bronchial obstruction from a mediastinal tumor may result in dyspnea.

• Vascular symptoms may arise with compression of the great vessels, which is usually seen with malignant tumors.

•Although magnetic resonance (MR) imaging is important for evaluating the heart, great vessels, and mediastinum, CT remains the preferred modality for imaging the lungs. However, distinction of an enlarged thymus can be achieved with the use of ultrasonography or MR imaging.

Mediastinal Cysts

•Bronchogenic cysts (Figure 83-4) occur most often in the middle mediastinum (subcarinal) or lung parenchyma. They are rarely seen outside of these locations, in which case they are frequently asymptomatic.

•Subcarinal bronchogenic cysts may cause respiratory distress.

•Esophageal cysts (duplications, Figure 83-5) located in the middle mediastinum are usually right sided and are associated with the esophageal wall

•Frontal radiographs of esophageal cysts may show a well-defined, often subtle retrocardiac mass. Intracystic air is not seen because direct esophageal communication is rare.

•Neurenteric cysts lie in the posterior mediastinum against the vertebrae, free of the esophagus.

•Mediastinal cysts tend to be symptomatic (ie, cough or vomiting), due to pressure on thoracic structures.

•On radiographs, midline defects of the vertebra may occur just caudad to neurenteric cysts. When seen, they are highly suggestive of the diagnosis.

•Boys are affected more commonly than girls.

Thymic Tumors

•The thymus is located in the anterior superior mediastinum and is noted as a widened mediastinum in infants; the normal thymic shadow disappears by 1 year of age.

•Rarely, the enlarged thymus can cause respiratory obstruction.

•Thymomas, which arise from epithelial cells in the thymus, result in an anterior mediastinal mass and are rare (<2%) as a cause of mediastinal masses in children, as well as being associated with myasthenia gravis (MG).

•One-half of patients with cortical thymoma develop MG, while 15% of patients with MG have thymomas.

Teratoid and Germ Cell Tumors

•Teratoid tumors make up one-fifth of all mediastinal neoplasms in the pediatric age group; teratoma is the most common anterior mediastinal tumor in children.

•Teratomas are germ cell tumors that exhibit differentiation to somatic tissues of endodermal, mesodermal, and/or ectodermal tissue.

Figure 83-4. Bronchogenic cyst in a 12-year-old boy discovered incidentally. A. Frontal chest radiograph demonstrates a mass (arrow) overlying the left hilum, which is known as the “hilum overlay sign.” B. Axial contrast-enhanced chest computed tomographic image shows a unilocular, fluid-attenuated, anterior mediastinal mass (arrow) at the level of the aortic arch, adjacent to the thymus.

Figure 83-5. Esophageal duplication cyst in a 10-year-old girl with recurrent pneumonia. A. Frontal chest radiograph shows a well-defined retrocardiac mass (arrow). B. Axial chest computed tomographic image demonstrates a unilocular, fluid-attenuated (cystic), posterior mediastinal mass (arrow).

• Mediastinal teratomas are located in the anterior mediastinum. In the prepubertal age group, the tumor is more common in girls, with predominance in boys after puberty.

•Patients typically present with dyspnea, with evidence of a mediastinal mass on radiographs (Figure 83-6).

•There is an association with Klinefelter syndrome.

•Treatment is surgical resection after chemotherapy.

•Patients are at increased risk for developing hematopoietic malignancies.

Neurogenic Tumors

•Neurogenic tumors make up 25%–35% of all mediastinal tumors. They are generally located in the posterior mediastinum and include rare lesions, such as benign neurofibromas and neurilemmomas, as well as neuroblastomas, which are the most common extracranial solid tumors in children.

•Neuroblastomas arise in the adrenal medulla or from the ganglia of the sympathetic nervous system.

•Although these tumors may regress spontaneously in infants, older children often present with unresectable or metastatic disease.

•Seventy-five percent of neuroblastomas arise in the abdomen.

•The prevalence of thoracic and cervical tumors is higher in infants. These tumors predominantly affect young children, with most receiving diagnoses by 5 years of age.

Figure 83-6. Germ cell tumor in a 16-year-old boy with dyspnea. A. Frontal chest radiograph shows complete opacification of the left hemithorax. B. Axial contrast-enhanced chest computed tomographic image demonstrates a large anterior mediastinal mass encasing the aortic arch and compressing the mediastinal veins. Numerous enhancing collateral veins posterior to the spine are noted, along with a left pleural effusion (arrow).

• Symptoms from thoracic tumors can be caused by superior vena cava syndrome from venous obstruction or from Horner syndrome, but these tumors may be discovered incidentally at chest radiography (Figure 83-7).

•Localized tumors are treated with surgical resection.

•Chemotherapeutic agents used include vincristine, doxorubicin, cyclophosphamide, cisplatin, and etoposide.

•Despite aggressive therapies, 5-year survival continues to be poor (40%) when compared to that for other childhood cancers.

Chest Wall Tumors

•Chondroma and chondrosarcoma are the main bone tumors of the chest wall, with 80% occurring in the ribs or sternum.

•Ewing sarcoma (also termed Askin tumor when involving the chest wall)

is the second most common primary bone tumor after osteosarcoma. Up to 23% of Ewing sarcomas occur in the chest wall (Figure 83-8). Therapy is multimodal and includes chemotherapy, radiation therapy, and surgical resection. Recurrence is common and has a poor prognosis.

•Rhabdomyosarcoma of the chest wall may have metastatic disease at presentation and has a poor prognosis.

•Most chest wall tumors manifest with local pain and swelling.

•Osler-Weber-Rendu syndrome, a disorder of multiple arteriovenous malformations (AVMs), should be considered in patients with AVMs of the lung. Modern treatment of AVMs includes embolization and, less often, surgical resection, chemotherapy, or radiation therapy.