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Molecular Pathology of Pediatric Tumors of the Lung

  • Josefine M. Heim-Hall
Part of the Molecular Pathology Library book series (MPLB, volume 1)

Abstract

Primary lung tumors, both benign and malignant, are overall rare in the pediatric population. Among 166 cases seen at the Armed Forces Institute between 1950 and 1989, malignant tumors were more frequent than benign tumors, with a ratio of 1 : 1.68. Inflammatory myofibroblastic tumor, also known as inflammatory pseudotumor or plasma cell granuloma, is the most common benign pediatric lung tumor and is discussed later. Epithelial lung malignancies are rare in childhood. Although histologic subtypes are similar to those that occur in adults, the frequencies of types differ, with carcinoid tumors being the most common.1 There is no known association of environmental or genetic factors and the development of epithelial malignancies in children. Pleuropulmonary blastoma, discussed later, is truly a tumor of childhood and never occurs in adults. Thoracopulmonary small round cell tumor, also called Askin’s tumor, is not restricted to childhood but is most common in adolescents and young adults and will therefore be discussed here as well.

Keywords

Anaplastic Lymphoma Kinase Malignant Peripheral Nerve Sheath Tumor Anaplastic Large Cell Lymphoma Congenital Cystic Adenomatoid Malformation Small Round Cell Tumor 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

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References

  1. 1.
    Lal DR, Clark I, Shalkow J, et al. Primary epithelial lung malignancies in the pediatric population. Pediatr Blood Cancer 2005;45(5):683–686.CrossRefPubMedGoogle Scholar
  2. 2.
    Priest JR, Watterson J, Strong L, et al. Pleuropulmonary blastoma: a marker for familial disease. J Pediatr 1996;128(2):220–224.CrossRefPubMedGoogle Scholar
  3. 3.
    Manivel CJ, Priest JR, Watterson J, et al. Pleuropulmonary blastoma: the so-called pulmonary blastoma of childhood. Cancer 1988;62(8):1516–1526.CrossRefPubMedGoogle Scholar
  4. 4.
    Priest JR, McDermott MB, Bhatia S, et al. Pleuropulmonary blastoma: a clinicopathologic study of 50 cases. Cancer 1997;80(1):147–161.CrossRefPubMedGoogle Scholar
  5. 5.
    Hill DA. USCAP Specialty Conference: case 1-type I pleuropulmonary blastoma. Pediatr Dev Pathol 2005;8(1):77–84.CrossRefPubMedGoogle Scholar
  6. 6.
    Dehner LP, Watterson J, Priest J. Pleuropulmonary blastoma. A unique intrathoracic neoplasm of childhood. Perspect Pediatr Pathol 1995;18:214–226.Google Scholar
  7. 7.
    Quilichini B, Andre N, Bouvier C, et al. Hidden chromosomal abnormalities in pleuropulmonary blastomas identified by multiplex FISH. BMC Cancer 2006;6:4.CrossRefPubMedGoogle Scholar
  8. 8.
    Kelsey AM, McNally K, Birch J, et al. Case of extra pulmonary, pleuro-pulmonary blastoma in a child: pathological and cytogenetic findings. Med Pediatr Oncol 1997;29(1):61–64.CrossRefPubMedGoogle Scholar
  9. 9.
    Barnard M, Bayani J, Grant R, et al. Use of multicolor spectral karyotyping in genetic analysis of pleuropulmonary blastoma. Pediatr Dev Pathol 2000;3(5):479–486.CrossRefPubMedGoogle Scholar
  10. 10.
    Roque L, Rodrigues R, Martins C, et al. Comparative genomic hybridization analysis of a pleuropulmonary blastoma. Cancer Genet Cytogenet 2004;149(1):58–62.CrossRefPubMedGoogle Scholar
  11. 11.
    Bridge JA, Liu J, Qualman SJ, et al. Genomic gains and losses are similar in genetic and histologic subsets of rhabdomyosarcomas, whereas amplification predominates in embryonal with anaplasia and alveolar subtypes. Genes Chromosomes Cancer 2002;33(3):310–321.CrossRefPubMedGoogle Scholar
  12. 12.
    Vargas SO, Nose V, Fletcher JA, et al. Gains of chromosome 8 are confined to mesenchymal components in pleuropulmonary blastoma. 8 are confined to mesenchymal components in pleuropulmonary blastoma. Pediatr Dev Pathol 2001;4(5):434–445.CrossRefPubMedGoogle Scholar
  13. 13.
    Stocker JT. Congenital and developmental diseases. In Dail DH, Hammar SP, eds. Pulmonary Pathology. Berlin: Springer-Verlag; 1994:155–181.Google Scholar
  14. 14.
    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 2006;9:190–195.CrossRefPubMedGoogle Scholar
  15. 15.
    Griffin CA, Hawkins AL, Dvorak C, et al. Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors. Cancer Res 1999;59(12):2776–2780.PubMedGoogle Scholar
  16. 16.
    Cessna MH, Zhou H, Sanger WG, et al. Expression of ALK1 and p80 in inflammatory myofibroblastic tumor and its mesenchymal mimics: a study of 135 cases. Mod Pathol 2002;15(9):931–938.CrossRefPubMedGoogle Scholar
  17. 17.
    Pulford K, Morris SW, Turturro F. Anaplastic lymphoma kinase proteins in growth control and cancer. J Cell Physiol 2004;199(3):330–358.CrossRefPubMedGoogle Scholar
  18. 18.
    Falini B, Bigerna B, Fizzotti M, et al. ALK expression defines a distinct group of T/null lymphomas (“ALK lymphomas”) with a wide morphological spectrum. Am J Pathol 1998;153(3):857–886.Google Scholar
  19. 19.
    Nakamura S, Shiota M, Nakagawa A, et al. Anaplastic large cell lymphoma: a distinct molecular pathologic entity: a reappraisal with special reference to p80(NPM/ALK) expression. Am J Surg Pathol 1997;21(12):1420–1432.CrossRefPubMedGoogle Scholar
  20. 20.
    Shiota M, Fujimoto J, Takenaga M, et al. Diagnosis of t(2;5)(p23;q35)-associated Ki-1 lymphoma with immunohisto-chemistry. Blood 1994;84(11):3648–3652.PubMedGoogle Scholar
  21. 21.
    Pittaluga S, Wiodarska I, Pulford K, et al. The monoclonal antibody ALKI identifies a distinct morphological subtype of anaplastic large cell lymphoma associated with 2p23/ALK rearrangements. Am J Pathol 1997;151(2):343–51.PubMedGoogle Scholar
  22. 22.
    Pulford K, Lamant L, Morris SW, et al. Detection of anaplastic lymphoma kinase (ALK) and nucleolar protein nucleo-phosmin (NPM)-ALK proteins in normal and neoplastic cells with the monoclonal antibody ALKI. Blood 1997;89(4):1394–1404.PubMedGoogle Scholar
  23. 23.
    Falini B, Bigerna B, Fizzotti M, et al. ALK expression defines a distinct group of T/null lymphomas (“ALK lymphomas”) with a wide morphological spectrum. Am J Pathol 1998;153:875–886.PubMedGoogle Scholar
  24. 24.
    Cataldo KA, Jalal SM, Law ME, et al. Detection of t(2;5) in anaplastic large cell lymphoma: comparison of immunohistochemical studies, FISH, and RT-PCR in paraffin-embedded tissue. Am J Surg Pathol 1999;23(11):1386–1392.CrossRefPubMedGoogle Scholar
  25. 25.
    Lamant L, Pulford K, Bischof D, et al. Expression of the ALK tyrosine kinase gene in neuroblastoma. Am J Pathol 2000;156(5):1711–1721.PubMedGoogle Scholar
  26. 26.
    Coffin CM, Patel A, Perkins S, et al. ALK1 and p80 expression and chromosomal rearrangements involving 2p23 in inflammatory myofibroblastic tumor. Mod Pathol 2001;14(6):569–576.CrossRefPubMedGoogle Scholar
  27. 27.
    Cook JR, Dehner LP, Collins M, et al. Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study. Am J Surg Pathol 2001;25(11):1364–1371.CrossRefPubMedGoogle Scholar
  28. 28.
    Coffin CM, Patel A, Perkins S, et al. ALK1 and p80 expression and chromosomal rearrangements involving 2p23 in inflammatory myofibroblastic tumor. Mod Pathol 2001;14(6):569–576.CrossRefPubMedGoogle Scholar
  29. 29.
    Lawrence B, Perez-Atavde A, Hibbard MK, et al. TPM3-ALK and TPMA4-ALK oncogenes in inflammatory myofi-broblastic tumors. Am J Pathol 2000;157(2):377–384.PubMedGoogle Scholar
  30. 30.
    Debiec-Rychter M, Marynen P, Hagemeijer A, et al. ALKATIC fusion in urinary bladder inflammatory myofibroblastic tumor. Genes Chromosomes Cancer 2003;38(2):187–190.CrossRefPubMedGoogle Scholar
  31. 31.
    Debelenko LV, Arthur DC, Pack SD, et al. Identification of CARS-ALK fusion in primary and metastatic lesions of an inflammatory myofibroblastic tumor. Lab Invest 2003;83(9):1255–1265.CrossRefPubMedGoogle Scholar
  32. 32.
    Bridge JA, Kanamori M, Ma Z, et al. Fusion of the ALK gene to the clathrin heavy chain gene. CLTC, in inflammatory myofibroblastic tumor. Am J Pathol 200l;159(2):411–415.Google Scholar
  33. 33.
    Ma Z, Hill DA, Collins MH, et al. Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor. Genes Chromosomes Cancer 2003;37(1):98–105.CrossRefPubMedGoogle Scholar
  34. 34.
    Panagopoulos I, Nilsson T, Domanski HA, et al. Fusion of the SEC31L1 and ALK genes in an inflammatory myofibroblastic tumor. Int J Cancer 2006;118(5):1181–1186.CrossRefPubMedGoogle Scholar
  35. 35.
    Lamant L, Pulford K, Bischof D, et al. Expression of the ALK tyrosine kinase gene in neuroblastoma. Am J Pathol 2000;156(5):1711–1721.PubMedGoogle Scholar
  36. 36.
    Mergan F, Jaubert F, Sauvat F, et al. Inflammatory myofibroblastic tumor in children: clinical review with anaplastic lymphoma kinase, Epstein-Barr virus, and human herpesvirus 8 detection analysis. 8 detection analysis. J Pediatr Surg 2005;40(10):1581–1586.CrossRefPubMedGoogle Scholar
  37. 37.
    Chan JK, Cheuk W, Shimizu M. Anaplastic lymphoma kinase expression in inflammatory pseudotumors. Am J Surg Pathol 2001;25(6):761–768.CrossRefPubMedGoogle Scholar
  38. 38.
    Coffin CM, Watterson J, Priest JR, et al. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol 1995;19(8):859–872.PubMedCrossRefGoogle Scholar
  39. 39.
    Gomez-Roman JJ, Ocejo-Vinyals G, Sanchez-Velasco P, et al. Presence of human herpesvirus-8 DNA sequences and overexpression of human II-6 and cyclin D1 in inflammatory myofibroblastic tumor (inflammatory pseudotumor). Lab Invest 2000;80(7):1121–1126.PubMedGoogle Scholar
  40. 40.
    Arber DA, Kamel OW, van de Rijn M, et al. Frequent presence of the Epstein-Barr virus in inflammatory pseudotumor. Hum Pathol 1995;26(10):1093–1098.CrossRefPubMedGoogle Scholar
  41. 41.
    Neuhauser TS, Derringer GA, Thompson LD, et al. Splenic inflammatory myofibroblastic tumor (inflammatory pseudotumor): a clinicopathologic and immunophenotypic study of 12 cases. Arch Pathol Lab Med 2001;125(3):379–885.PubMedGoogle Scholar
  42. 42.
    Askin FB, Rosai J, Sibley RK, et al. Malignant small cell tumor of the thoracopulmonary region in childhood: a distinctive clinicopathological entity of uncertain histogenesis. Cancer 1997;43:2438–2451.CrossRefGoogle Scholar
  43. 43.
    Arvand A, Denny CT. Biology of EWS/ETS fusions in Ewing’s family tumors. Oncogene 2001;20(40):5747–5754.CrossRefPubMedGoogle Scholar
  44. 44.
    Delattre O, Zucman J, Melot T, et al. The Ewing family of tumors a subgroup of small-round-cell tumors defined by specific chimeric transcripts. N Engl J Med 1994;331(5):294–299.CrossRefPubMedGoogle Scholar
  45. 45.
    Ohno T, Ouchida M, Lee L, et al. The EWS gene, involved in Ewing family of tumors, malignant melanoma of soft parts and desmoplastic small round cell tumors, codes for an RNA binding protein with novel regulatory domains. Oncogene 1994;9(10):3087–3097.PubMedGoogle Scholar
  46. 46.
    Yang L, Embree LJ, Tsai S, et al. Oncoprotein TLS interacts with serine-arginine proteins involved in RNA splicing. J Biol Chem 1998;273(43):27761–27764.CrossRefPubMedGoogle Scholar
  47. 47.
    Sementchenko VI, Watson DK. Ets target genes: past, present and future. Oncogene 2000;19(55):6533–6548.CrossRefPubMedGoogle Scholar
  48. 48.
    Khoury J. Ewing sarcoma family of tumors. Adv Anat Pathol 2005;12(4):212–220.CrossRefPubMedGoogle Scholar
  49. 49.
    Zoubek A, Dockhorn-Dworniczak B, Delattre O, et al. Does expression of different EWS chimeric transcripts define clinically distinct risk groups of Ewing tumor patients? J Clin Oncol 1996;14(4):1245–1251.PubMedGoogle Scholar
  50. 50.
    Zoubek A, Pfleiderer C, Salzer-Kuntschik M, et al. Variability of EWS chimaeric transcripts in Ewing tumours: a comparison of clinical and molecular data. Br J Cancer 1994;70(5):908–913.PubMedGoogle Scholar
  51. 51.
    Zucman J, Melot T, Desmaze C, et al. Combinatorial generation of variable fusion proteins in the Ewing family of tumours. EMBO J 1993;12(12):4481–4487.PubMedGoogle Scholar
  52. 52.
    De Alava E, Kawai A, Healey JH, et al. EWS-FLI1 fusion transcript structure is an independent determinant of prognosis in Ewing’s sarcoma. J Clin Oncol 1998;16(4):1248–1255.PubMedGoogle Scholar
  53. 53.
    Hu-Lieskovan S, Zhang J, Wu L, et al. EWS-FL11 Fusion protein up-regulates critical genes in neural crest development and is responsible for the observed phenotype of Ewing’s family of tumors. Cancer Res 2005;65(11):4633–4644.CrossRefPubMedGoogle Scholar
  54. 54.
    Delattre O, Zucman J, Plougastel B, et al. Gene fusion with an ETS DNA-binding domain caused by chromosome translocation in human tumours. Nature 1992;359(6391):162–165.CrossRefPubMedGoogle Scholar
  55. 55.
    May WA, Gishizky ML, Lessnick SL, et al. Ewing sarcoma 11;22 translocation produces a chimeric transcription factor that requires the DNA-binding domain encoded by FL11 for transformation. Proc Natl Acad Sci USA 1993;90(12):5752–5756.CrossRefPubMedGoogle Scholar
  56. 56.
    Sorensen PH, Lessnick SL, Lopez-Terrada D, et al. A second Ewing’s sarcoma translocation, t(21:22), fuses the EWS gene to another ETS-family transcription factor, ERG. Nat Genet 1994;6(2):146–151.CrossRefPubMedGoogle Scholar
  57. 57.
    Jeon IS, Davis JN, Braun BS, et al. A variant Ewing’s sarcoma translocation (7;22) fuses EWS gene to the ETS gene ETV1. Oncogene 1995;10(6):1229–1234.PubMedGoogle Scholar
  58. 58.
    Kaneko Y, Yoshida K, Handa M, et al. Fusion of an ETS-family gene, E1AF, to EWS by t(17;22)(q12;q12) chromosome translocation in an undifferentiated sarcoma of infancy. Genes Chromosomes Cancer 1996;15(2):115–121.CrossRefPubMedGoogle Scholar
  59. 59.
    Urano F, Umezawa A, Hong W, et al. A novel chimera gene between EWS and E1A-F, encoding the adenovirus E1A enhancer-binding protein in extraosseous Ewing’s sarcoma. Biochem Biophys Res Commun 1996;219(2):608–612.CrossRefPubMedGoogle Scholar
  60. 60.
    Peter M, Couturier J, Pacquement H, et al. A new member of the ETS family fused t EWS in Ewing tumors. Oncogene 1997;14(10):1159–1164.CrossRefPubMedGoogle Scholar
  61. 61.
    Mastrangelo T, Modena P, Tornielli S, et al. A novel zinc finger gene is fused to EWS in small round cell tumor. Oncogene 2000;19(33):3799–3804.CrossRefPubMedGoogle Scholar
  62. 62.
    Bridge RS, Rajaram V, Dehner LP, et al. Molecular diagnosis of Ewing sarcoma/primitive neuroectodermal tumor in routinely processed tissue: a comparison of two FISH strategies and RT-PCR in malignant round cell tumors. Mod Pathol 2006;19(1):1–8.CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC. 2008

Authors and Affiliations

  • Josefine M. Heim-Hall
    • 1
  1. 1.Department of PathologyUniversity of Texas Health Science Center at San AntonioSan AntonioUSA

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