Definition
• Secondary malignant lung tumors in pediatric patients
Clinical features
Epidemiology
• Metastatic tumors account for approximately 80% of all lung tumors in children and more than 95% of malignant tumors
• The ratio of primary malignant to secondary malignant neoplasms is 1:12
• Most common pediatric metastases are from osteosarcoma and Wilms tumor, followed by Ewing/primitive neuroectodermal tumor (PNET), neuroblastoma, malignant peripheral nerve sheath tumor (MPNST), hepatoblastoma, rhabdomyosarcoma, and, rarely, other sarcomas and carcinomas
• With the exception of osteosarcoma, the lung is rarely the initial or only site of metastasis for pediatric tumors
Presentation
• Osteosarcoma: solitary or multiple nodules with cavitation and calcification causing coughing, wheezing, and hemoptysis
• Soft tissue sarcomas: multiple peripherally located sharply outlined nodules with central necrosis or endobronchial masses with asthmalike symptoms
• If nodules are subpleural, they can cause formation of bronchopleural fistula and pneumothorax with severe chest pain/Pancoast syndrome
• The lower lobes are more frequently involved in hematogenous metastases
• A reticular or miliary pattern occurs in tumors spreading via lymphatics
Prognosis and treatment
• Metastasectomy (wedge excision) is the mainstay treatment for osteosarcoma, improving 3-year survival rates from 5% to 45%
• Surgical excisions are also used for diagnosis and staging and for tumors resistant to chemotherapy and radiotherapy such as adrenocortical carcinoma, chondrosarcoma, and alveolar soft part sarcoma
• Wilms, Ewing/PNET, neuroblastoma, rhabdomyosarcoma, and germ-cell tumors are treated with chemotherapy and radiotherapy
• Disease-free survival remains poor, except for Wilms tumor and solitary metastases of osteosarcoma
Pathology
Gross
• Well-circumscribed nodules that are either pleural-based or in lymphatic distribution
• Majority are firm, gray, glistening with “fish-flesh” cut surface
• Osteosarcomas commonly have firm, fleshy, and gritty appearance due to osteoid and chondroid production, as well as cystic hemorrhagic spaces and geographic necrosis
Histology
• Histopathology of metastatic tumors is usually similar to that of the primary site; however, chemosensitive tumors could show cellular maturation phenomenon, necrosis, fibrosis, or hemosiderin deposition
• It is critical to assess the percentage of necrosis as an indicator of treatment efficacy
Immunopathology/special stains
• Virtually all sarcomas are vimentin positive
• The most useful immunohistochemical (IHC) markers for metastatic pediatric tumors are listed in Table 2 in the Appendix
Main differential diagnosis
• Pleuropulmonary blastoma: very rare, always involves pleura, no tendency to entrap normal respiratory epithelium, and no history of prior sarcoma elsewhere
Fig 1 Metastatic pediatric tumors. Metastatic osteosarcoma with malignant osteoid production; pleomorphic polygonal cells with abundant cytoplasm and high grade nuclei (A). Note formation of cystic hemorrhagic spaces characteristic in telangiectatic osteosarcomas (B).
Fig 2 Metastatic pediatric tumors. Ewing sarcoma/PNET lung metastasis: vague lobular pattern of monotonous population of small blue cells (A); higher magnification shows scant cytoplasm, round nuclei, small inconspicuous nucleoli, mitotic figures, and apoptotic bodies (B).
Fig 3 Metastatic pediatric tumors. Another example of metastatic Ewing/PNET seen as a large endobronchial mass: low power (A) and higher magnification (B) demonstrate large atypical cells with irregular nuclear outline, conspicuous nucleoli, high pleomorphism, and spindling consistent with atypical large cell variant.
Fig 4 Metastatic pediatric tumors. Well-circumscribed metastatic nodule of MPNST. A, Low power showing long fascicles of uniform, closely spaced, hyperchromatic spindle cells. B, At higher power one can appreciate nuclear atypia, multinucleation, large vesicular nuclei with macronucleoli, and numerous atypical mitotic figures.