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Primary Pediatric Lung TumorsPrimary Pediatric Lung Tumors

Claire Langston, M.D.Department of PathologyTexas Children’s HospitalpBaylor College of Medicine

Houston, TexasUSA

Primary Lung Tumors in ChildhoodPrimary Lung Tumors in Childhood

• Solitary lung lesions in childhood:– Commonest solid parenchymal lesions are:

• Inflammatory, infectious or reactive i h b d diff i l

yprocesses with broad differential– Granulomatous inflammation– Abscess– Pneumonia– Septic embolus– InfarctionHematoma– Hematoma

• Benign developmental lesions– Bronchopulmonary malformations

• Neoplastic lesions– Benign, Borderline, Malignant

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Primary Lung Tumors in ChildhoodPrimary Lung Tumors in Childhood

• Neoplastic lesions of any sort are rare– Metastatic tumors far exceed primary t (5 1)tumors (5:1)• Wilms tumor and osteosarcoma most frequent–Solitary or multiple circumscribed nodules

–Often peripheral–Often involving lower lobe

Primary Lung Tumors in ChildhoodPrimary Lung Tumors in Childhood

• Benign somewhat more common than malignant (1.5:1)g ( )

• Parenchymal commoner than tracheobronchial (1.4:1)

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Primary Lung Tumors in ChildhoodPrimary Lung Tumors in ChildhoodTracheobronchialTracheobronchial

• Benign – Squamous papilloma – commonest; specific

isetting– Hemangioma– Juvenile xanthogranuloma– Inflammatory myofibroblastic tumor– Chondroid Hamartoma

• Malignant– Carcinoid – commonest– Mucoepidermoid tumor

Respiratory Respiratory PapillomaPapilloma Respiratory Respiratory PapillomaPapilloma Intrapulmonary Intrapulmonary PapillomaPapilloma

Intrapulmonary Intrapulmonary PapillomatosisPapillomatosis ChondroidChondroid HamartomaHamartoma Carcinoid TumorIntrapulmonary Intrapulmonary PapillomatosisPapillomatosis ChondroidChondroid HamartomaHamartoma Carcinoid Tumor

CarcinoidCarcinoid TumorTumor MucoepidermoidMucoepidermoid CaCa MucoepidermoidMucoepidermoid CACA

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Primary Lung Tumors in ChildhoodPrimary Lung Tumors in ChildhoodParenchymalParenchymal

• Benign – slightly less common than malignant– Ebstein-Barr associated smooth muscle tumors

most common; specific settingmost common; specific setting– Other include

• Inflammatory myofibroblastic tumor• Lipoblastoma• Lymphangioma• Squamous papilloma• Myofibroma• Fetal lung interstitial tumor• Congenital pulmonary myofibroblastic tumor

Primary Lung Tumors in ChildhoodPrimary Lung Tumors in ChildhoodParenchymalParenchymal

• Malignant– Pleuropulmonary blastoma – commonest

• Familial occurrenceDICER t ti ith f ili l/ d i d • DICER mutations with familial/syndromic and sometimes with sporadic

• Low-grade cystic, type I (may regress)• Partially cystic, type II• Solid, type III – most primary lung high-grade

sarcomas of lung in childhood belong in this group, regardless of histogenesis except:– Leiomyosarcoma (EBV associated) specific setting– Bronchopulmonary fibrosarcoma

– Bronchogenic carcinoma (squamous cell carcinoma) exceedingly rare

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PPB PPB PPBPPB-I PPB-I PPB-I

PPB-II PPBP-III PPB-III

PPB-III PPB-III

Pleuropulmonary BlastomaPleuropulmonary BlastomaAssociated LesionsAssociated Lesions

• Dysplastic/neoplastic diseases in 25% of PPB patient relatives, often siblings

• Multicentric PPB, PPB in siblings/cousins• Germ cell tumors• Wilms’ tumor, cystic nephroma• Lymphoma/leukemia• Various sarcomas….• Ovarian fibrosis

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Lung Tumors in Immunocompromised ChildrenLung Tumors in Immunocompromised Children• EBV driven lymphoproliferative disorder

– Occur commonly with solid organ (heart &/or lung more common) or bone marrow transplantation (PTLD) and with primary immunodeficiency

• Lymphoma – Congenital/acquired immunodeficiency states

HIV i f i lid l b l • HIV infection, solid organ transplant, bone marrow transplant, congenital immunodeficiency

– Typically high/intermediate grade diffuse large B cell lymphoma – Not isolated to lung

• Smooth muscle tumors (leiomyoma/leiomyosarcoma)– HIV infection, solid organ transplant, primary immunodeficiency– EBV associated– Solitary or multifocal– Typically gastrointestinal and respiratory tract involvement– Spectrum from benign to malignant– Potential for regression with modulation of immunosuppression

• Kaposi Sarcoma (associated with HHV8 infection)– HIV infection and solid organ transplant– Cutaneous commoner than visceral; in lung endobronchial or

parenchymal with pulmonary hemorrhage, cough and dyspnea

Lymphoproliferative Disorder Leiomyoma

Leiomyoma In situ hybridization - EBV

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Congenital Lung TumorsCongenital Lung Tumors

• Congenital Peribronchial Myofibroblastic Tumor– Rare, benign, associated with hydrops

• Congenital/Infantile Fibrosarcoma– Rarely presents in lung; analogue of congenital mesoblastic nephroma with t(12;15)(p13;q25) ETV6-NTRK3

• Congenital Pleuropulmonary BlastomaUnc mm n l s l r d c stic– Uncommon, always low-grade cystic

• Fetal Lung Interstitial Tumor (FLIT)– Rare, recently identified

Congenital Peribronchial Congenital Peribronchial Myofibroblastic Tumor Myofibroblastic Tumor -- ClinicalClinical

• Stillborn or newborn infant with hydrops d l (5 7 ) il t l th i and large (5-7 cm) unilateral thoracic

mass• Polyhydramnios, hydrops, immediate

respiratory failure on delivery• High mortality rate for liveborns, 55%• Early resection (pneumonectomy or

lobectomy) may result in long-term survival

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Congenital Peribronchial Myofibroblastic TumorCongenital Peribronchial Myofibroblastic Tumor

Congenital Congenital PeribronchialPeribronchialMyofibroblasticMyofibroblastic Tumor Tumor -- HistologyHistology

• Spindle cell neoplasm –– Peribronchiolar distributionPeribronchiolar distribution– Poorly circumscribed fascicular pattern– Expands periairway, pleural, and other

interstitial compartments; pushing growth pattern

– No atypia, but frequent mitoses, none abnormal

– Immunopositive for vimentin and SMA– Negative for MyoD1, ALK-1, bcl-2, S-100

• Uninvolved lung appropriate for gestational age

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Congenital/Infantile FibrosarcomaCongenital/Infantile Fibrosarcoma

• Rare tumor of infants and young children• Rarely presents in lung• ?Analogue of congenital mesoblastic ?Analogue of congenital mesoblastic

nephroma with t(12;15)(p13;q25) ETV6-NTRK3

• Spindle cell neoplasm with high mitotic rate, infiltrative growth pattern and vimentin (less commonly muscle specific actin) immunopositivity

• Considered “borderline” tumor with better prognosis than adult fibrosarcoma; complete resection may be curative if metastatic disease is not present

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Congenital/Infantile FibrosarcomaCongenital/Infantile Fibrosarcoma

Congenital Pleuropulmonary BlastomaCongenital Pleuropulmonary Blastoma

• Always low-grade cystic (type I)T i ll ll lit ti l i • Typically small solitary cystic lesion identified by in utero ultrasound

• Resection usually curative• May recur or have second primary• DICER mutation for familial tumors

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4 month old male infant with 5 cm cystic lesion in LUL

Low grade cystic PPB

Miniati, et al Prenatal diagnosis and outcome of children with pleuropulmonary blastoma. J Ped Surg, 2006

Second excision, 5 months of age 1cm cystic lesion RLL

Fetal Lung Interstitial TumorFetal Lung Interstitial Tumor

• Recently identified solid to microcystic congenital lung tumor (10 cases)

• All identified by imaging at <3 months of age (7M,3F)– 2 with in utero ultrasound abnormality– others by X-ray in setting of mild to moderate

i ly y g

respiratory symptomatology• RLL – 4, RUL – 2, LLL – 2, RML & LUL 1 each• Lobectomy, complete in 8; chemotherapy in one; no

recurrences or metastasis with follow-up >3 years for 5 including one with incomplete resection, nor in others with lesser follow-up

• Gross– Well circumscribed spongy appearing intraparenchymal

mass 2 6 cm maximum dimensionmass 2-6 cm maximum dimension– Sharp border, incomplete fibrous interface

• Histology– Bland undifferentiated mesenchymal cells with cytoplasmic

glycogen, irregular air-space structures with flattened alveolar epithelium; no significant inflammation, but sometimes areas of necrosis

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Fetal Lung Interstitial Tumor

Fetal Lung Interstitial TumorFetal Lung Interstitial Tumor

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Fetal Lung Interstitial Fetal Lung Interstitial Tumor (FLIT)Tumor (FLIT)

CK Vimentin Ki-67

Primary Pediatric Lung TumorsPrimary Pediatric Lung Tumors

• Although rare, often seen in specific clinical settingsclinical settings

• Should always consider this possibility with isolated lung masses in childhood and handle tissue appropriately for tumor diagnosis (freeze, EM, cytogenetics)

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ReferencesReferences• Yu DC, Grabowski MJ, Kozakewich HP, Perez-Atayde AR,

Voss SD, Shamberger RC, Weldon CB. Primary lung tumors in children and adolescents: a 90 year experience. Journal of Pediatric Surgery, 2010; 45:1090-1095.

• Dishop MK Kuruvilla S Primary and metastatic lung tumor in • Dishop MK, Kuruvilla S. Primary and metastatic lung tumor in the pediatric population: a review and 25 year experience at a large children’s hospital. Archives of Pathology and Laboratory Medicine, 2008; 132:1079-1103.

• Coffin CM, Dehner LP. Fibroblastic-myofibroblastic tumors in children and adolescents: a clinicopathologic study of 108 examples in 103 patients. Pediatric Pathology, 1991; 11:569-588.Di h MK M K EM K i PA P i t JR Willi GA • Dishop MK, McKay EM, Krieger PA, Priest JR, Williams GA, Langston C, Jarzembowski J, Suchi M, Dehner LP, Hill DA. Fetal lung interstitial tumor (FLIT): A newly recognized lung tumor of infancy. American Journal of Surgical Pathology, in press 2010.