Lung, Pleura, and Mediastinum

  • Kai Zhang
  • Phillip Cagle
Chapter

Abstract

The chapter contains 51 frequently asked ­immunohistochemical questions with answers addressed with tables and concise note and representative pictures in the diagnosis of common and uncommon pleuropulmonary and mediastinal tumors. The questions and selected frequently used antibodies or antibody panels come from a review of numerous published literatures, books, and book chapters incorporated with authors’ own practicing experience, which reflects up to date information in practicing immunohistochemistry in the field. Many of the antibodies have been tested, evaluated, and verified in author’s institution on tissue microarray and tissue sections. In lights of recent progress in diagnosing and treating nonsmall cell lung carcinomas (NSCLC), the most useful diagnostic antibody panels have been highlighted in the chapter. For example, to differentiate pulmonary adenocarcinoma from squamous cell carcinoma, a panel of antibodies including (CK7, CK20, CK5/6, p63, TTF-1) has been recommended. Napsin A has been increasingly used together with TTF-1 to confirm NSCLC since a small subset of NSCLC may be only positive for Napsin A while being negative for TTF-1. Furthermore, immunophenotypes of various cell types of normal lung tissue have been described.

Keywords

Nonsmall cell lung carcinoma Adenocarcinoma Squamous cell carcinoma Small cell lung carcinoma TTF-1 (thyroid transcription factor-1) Napsin A CK5/6 and p63 

References

  1. 1.
    Abutaily AS, Addis BJ, Roche WR. Immunohistochemistry in the distinction between malignant mesothelioma and pulmonary adenocarcinoma: a critical evaluation of new antibodies. J Clin Pathol. 2002;55(9):662–8.PubMedCrossRefGoogle Scholar
  2. 2.
    Agoff SN, Lamps LW, Philip AT, et al. Thyroid transcription factor-1 is expressed in extrapulmonary small cell carcinomas but not in other extrapulmonary neuroendocrine tumors. Mod Pathol. 2000;13(3):238–42.PubMedCrossRefGoogle Scholar
  3. 3.
    Alijo Serrano F, Sanchez-Mora N, Angel Arranz J, Hernandez C, Alvarez-Fernandez E. Large cell and small cell neuroendocrine bladder carcinoma: immunohistochemical and outcome study in a single institution. Am J Clin Pathol. 2007;128(5):733–9.PubMedCrossRefGoogle Scholar
  4. 4.
    Allen TC, Cagle PT, Churg AM, et al. Localized malignant mesothelioma. Am J Surg Pathol. 2005;29(7):866–73.PubMedCrossRefGoogle Scholar
  5. 5.
    Amin MB, Tamboli P, Merchant SH, et al. Micropapillary component in lung adenocarcinoma: a distinctive histologic feature with possible prognostic significance. Am J Surg Pathol. 2002;26(3):358–64.PubMedCrossRefGoogle Scholar
  6. 6.
    Andrion A, Mazzucco G, Gugliotta P, Monga G. Benign clear cell (sugar) tumor of the lung. A light microscopic, histochemical, and ultrastructural study with a review of the literature. Cancer. 1985;56(11):2657–63.PubMedCrossRefGoogle Scholar
  7. 7.
    Attanoos RL, Papagiannis A, Suttinont P, Goddard H, Papotti M, Gibbs AR. Pulmonary giant cell carcinoma: pathological entity or morphological phenotype? Histopathology. 1998;32(3):225–31.PubMedCrossRefGoogle Scholar
  8. 8.
    Bakir K, Kocer NE, Deniz H, Guldur ME. TTF-1 and surfactant-B as co-adjuvants in the diagnosis of lung adenocarcinoma and pleural mesothelioma. Ann Diagn Pathol. 2004;8(6):337–41.PubMedCrossRefGoogle Scholar
  9. 9.
    Barbareschi M, Ferrero S, Aldovini D, et al. Inflammatory pseudotumour of the lung. Immunohistochemical analysis on four new cases. Histol Histopathol. 1990;5(2):205–11.PubMedGoogle Scholar
  10. 10.
    Barbareschi M, Roldo C, Zamboni G, et al. CDX-2 homeobox gene product expression in neuroendocrine tumors: its role as a marker of intestinal neuroendocrine tumors. Am J Surg Pathol. 2004;28(9):1169–76.PubMedCrossRefGoogle Scholar
  11. 11.
    Beasley MB. Immunohistochemistry of pulmonary and pleural neoplasia. Arch Pathol Lab Med. 2008;132(7):1062–72 [erratum appears in Arch Pathol Lab Med 2008;132(9):1384].PubMedGoogle Scholar
  12. 12.
    Bejarano PA, Baughman RP, Biddinger PW, et al. Surfactant proteins and thyroid transcription factor-1 in pulmonary and breast carcinomas. Mod Pathol. 1996;9(4):445–52.PubMedGoogle Scholar
  13. 13.
    Bejarano PA, Nikiforov YE, Swenson ES, Biddinger PW. Thyroid transcription factor-1, thyroglobulin, cytokeratin 7, and cytokeratin 20 in thyroid neoplasms. Appl Immunohistochem Mol Morphol. 2000;8(3):189–94.PubMedCrossRefGoogle Scholar
  14. 14.
    Berger U, Khaghani A, Pomerance A, Yacoub MH, Coombes RC. Pulmonary lymphangioleiomyomatosis and steroid receptors. An immunocytochemical study. Am J Clin Pathol. 1990;93(5):609–14.PubMedGoogle Scholar
  15. 15.
    Bobos M, Hytiroglou P, Kostopoulos I, Karkavelas G, Papadimitriou CS. Immunohistochemical distinction between Merkel cell carcinoma and small cell carcinoma of the lung. Am J Dermatopathol. 2006;28(2):99–104.PubMedCrossRefGoogle Scholar
  16. 16.
    Bonetti F, Chiodera PL, Pea M, et al. Transbronchial biopsy in lymphangiomyomatosis of the lung. HMB45 for diagnosis. Am J Surg Pathol. 1993;17(11):1092–102.PubMedCrossRefGoogle Scholar
  17. 17.
    Butnor KJ, Nicholson AG, Allred DC, et al. Expression of renal cell carcinoma-associated markers erythropoietin, CD10, and renal cell carcinoma marker in diffuse malignant mesothelioma and metastatic renal cell carcinoma. Arch Pathol Lab Med. 2006;130(6):823–7.PubMedGoogle Scholar
  18. 18.
    Byrd-Gloster AL, Khoor A, Glass LF, et al. Differential expression of thyroid transcription factor 1 in small cell lung carcinoma and Merkel cell tumor. Hum Pathol. 2000;31(1):58–62.PubMedCrossRefGoogle Scholar
  19. 19.
    Cagle PT, Truong LD, Roggli VL, Greenberg SD. Immunohisto­­chemical differentiation of sarcomatoid mesotheliomas from other spindle cell neoplasms. Am J Clin Pathol. 1989;92(5):566–71.PubMedGoogle Scholar
  20. 20.
    Castro CY, Moran CA, Flieder DG, Suster S. Primary signet ring cell adenocarcinomas of the lung: a clinicopathological study of 15 cases. Histopathology. 2001;39(4):397–401.PubMedCrossRefGoogle Scholar
  21. 21.
    Cerfolio RJ, Allen MS, Nascimento AG, et al. Inflammatory pseudotumors of the lung. Ann Thorac Surg. 1999;67(4):933–6.PubMedCrossRefGoogle Scholar
  22. 22.
    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):931–8.PubMedCrossRefGoogle Scholar
  23. 23.
    Chan JK, Cheuk W, Shimizu M. Anaplastic lymphoma kinase expression in inflammatory pseudotumors. Am J Surg Pathol. 2001;25(6):761–8.PubMedCrossRefGoogle Scholar
  24. 24.
    Chejfec G, Candel A, Jansson DS, et al. Immunohistochemical features of giant cell carcinoma of the lung: patterns of expression of cytokeratins, vimentin, and the mucinous glycoprotein recognized by monoclonal antibody A-80. Ultrastruct Pathol. 1991;15(2):131–8.PubMedCrossRefGoogle Scholar
  25. 25.
    Choi SJ, Kim JM, Han JY, et al. Extrapulmonary small cell carcinoma of the liver: clinicopathological and immunohistochemical findings. Yonsei Med J. 2007;48(6):1066–71.PubMedCrossRefGoogle Scholar
  26. 26.
    Chu P, Wu E, Weiss LM. Cytokeratin 7 and cytokeratin 20 expression in epithelial neoplasms: a survey of 435 cases. Mod Pathol. 2000;13(9):962–72.PubMedCrossRefGoogle Scholar
  27. 27.
    Coffin CM, Patel A, Perkins S, Elenitoba-Johnson KS, Perlman E, Griffin CA. ALK1 and p80 expression and chromosomal rearrangements involving 2p23 in inflammatory myofibroblastic tumor. Mod Pathol. 2001;14(6):569–76.PubMedCrossRefGoogle Scholar
  28. 28.
    Coffin CM, Watterson J, Priest JR, Dehner LP. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol. 1995;19(8):859–72.PubMedCrossRefGoogle Scholar
  29. 29.
    Colley MH, Geppert E, Franklin WA. Immunohistochemical detection of steroid receptors in a case of pulmonary lymphangioleiomyomatosis. Am J Surg Pathol. 1989;13(9):803–7.PubMedCrossRefGoogle Scholar
  30. 30.
    Cook JR, Dehner LP, Collins MH, et al. Anaplastic lymphoma kinase (ALK) expression in the inflammatory myofibroblastic tumor: a comparative immunohistochemical study. Am J Surg Pathol. 2001;25(11):1364–71.PubMedCrossRefGoogle Scholar
  31. 31.
    Copin MC, Buisine MP, Leteurtre E, et al. Mucinous bronchioloalveolar carcinomas display a specific pattern of mucin gene expression among primary lung adenocarcinomas. Hum Pathol. 2001;32(3):274–81.PubMedCrossRefGoogle Scholar
  32. 32.
    Corson JM, Weiss LM, Banks-Schlegel SP, Pinkus GS. Keratin proteins and carcinoembryonic antigen in synovial sarcomas: an immunohistochemical study of 24 cases. Hum Pathol. 1984;15(7):615–21.PubMedCrossRefGoogle Scholar
  33. 33.
    Dabbs DJ, Bhargava R, Chivukula M. Lobular versus ductal breast neoplasms: the diagnostic utility of p120 catenin. Am J Surg Pathol. 2007;31(3):427–37.PubMedCrossRefGoogle Scholar
  34. 34.
    Dabbs DJ, Landreneau RJ, Liu Y, et al. Detection of estrogen receptor by immunohistochemistry in pulmonary adenocarcinoma. Ann Thorac Surg. 2002;73(2):403–5.PubMedCrossRefGoogle Scholar
  35. 35.
    de Leval L, Ferry JA, Falini B, Shipp M, Harris NL. Expression of bcl-6 and CD10 in primary mediastinal large B-cell lymphoma: evidence for derivation from germinal center B cells? Am J Surg Pathol. 2001;25(10):1277–82.PubMedCrossRefGoogle Scholar
  36. 36.
    Devouassoux-Shisheboran M, Hayashi T, Linnoila RI, Koss MN, Travis WD. A clinicopathologic study of 100 cases of pulmonary sclerosing hemangioma with immunohistochemical studies: TTF-1 is expressed in both round and surface cells, suggesting an origin from primitive respiratory epithelium. Am J Surg Pathol. 2000;24(7):906–16.PubMedCrossRefGoogle Scholar
  37. 37.
    Dixon AY, Moran JF, Wesselius LJ, McGregor DH. Pulmonary mucinous cystic tumor. Case report with review of the literature. Am J Surg Pathol. 1993;17(7):722–8.PubMedCrossRefGoogle Scholar
  38. 38.
    Doglioni C, Dei Tos AP, Laurino L, et al. Calretinin: a novel immunocytochemical marker for mesothelioma. Am J Surg Pathol. 1996;20(9):1037–46.PubMedCrossRefGoogle Scholar
  39. 39.
    Du EZ, Goldstraw P, Zacharias J, et al. TTF-1 expression is specific for lung primary in typical and atypical carcinoids: TTF-1-positive carcinoids are predominantly in peripheral location. Hum Pathol. 2004;35(7):825–31.PubMedCrossRefGoogle Scholar
  40. 40.
    Erickson LA, Papouchado B, Dimashkieh H, Zhang S, Nakamura N, Lloyd RV. Cdx2 as a marker for neuroendocrine tumors of unknown primary sites. Endocr Pathol. 2004;15(3):247–52.PubMedCrossRefGoogle Scholar
  41. 41.
    Fishback NF, Travis WD, Moran CA, Guinee Jr DG, McCarthy WF, Koss MN. Pleomorphic (spindle/giant cell) carcinoma of the lung. A clinicopathologic correlation of 78 cases. Cancer. 1994;73(12):2936–45.PubMedCrossRefGoogle Scholar
  42. 42.
    Folpe AL, Chand EM, Goldblum JR, Weiss SW. Expression of ­Fli-1, a nuclear transcription factor, distinguishes vascular neoplasms from potential mimics. Am J Surg Pathol. 2001;25(8):1061–6.PubMedCrossRefGoogle Scholar
  43. 43.
    Folpe AL, Gown AM, Lamps LW, et al. Thyroid transcription factor-1: immunohistochemical evaluation in pulmonary neuroendocrine tumors. Mod Pathol. 1999;12(1):5–8.PubMedGoogle Scholar
  44. 44.
    Gaffey MJ, Mills SE, Askin FB, et al. Clear cell tumor of the lung. A clinicopathologic, immunohistochemical, and ultrastructural study of eight cases. Am J Surg Pathol. 1990;14(3):248–59.PubMedCrossRefGoogle Scholar
  45. 45.
    Gaffey MJ, Mills SE, Zarbo RJ, Weiss LM, Gown AM. Clear cell tumor of the lung. Immunohistochemical and ultrastructural evidence of melanogenesis. Am J Surg Pathol. 1991;15(7):644–53.PubMedCrossRefGoogle Scholar
  46. 46.
    Gal AA, Koss MN, Hochholzer L, Chejfec G. An immunohistochemical study of benign clear cell (‘sugar’) tumor of the lung. Arch Pathol Lab Med. 1991;115(10):1034–8.PubMedGoogle Scholar
  47. 47.
    Griffin CA, Hawkins AL, Dvorak C, Henkle C, Ellingham T, Perlman EJ. Recurrent involvement of 2p23 in inflammatory myofibroblastic tumors. Cancer Res. 1999;59(12):2776–80.PubMedGoogle Scholar
  48. 48.
    Han AJ, Xiong M, Gu YY, Lin SX, Xiong M. Lymphoepithelioma-like carcinoma of the lung with a better prognosis. A clinicopathologic study of 32 cases. Am J Clin Pathol. 2001;115(6):841–50.PubMedCrossRefGoogle Scholar
  49. 49.
    Hayashi H, Kitamura H, Nakatani Y, Inayama Y, Ito T, Kitamura H. Primary signet-ring cell carcinoma of the lung: histochemical and immunohistochemical characterization. Hum Pathol. 1999;30(4):378–83.PubMedCrossRefGoogle Scholar
  50. 50.
    Higashiyama M, Doi O, Kodama K, Yokouchi H, Tateishi R. Cystic mucinous adenocarcinoma of the lung. Two cases of cystic variant of mucus-producing lung adenocarcinoma. Chest. 1992;101(3):763–6.PubMedCrossRefGoogle Scholar
  51. 51.
    Hiroshima K, Iyoda A, Shida T, et al. Distinction of pulmonary large cell neuroendocrine carcinoma from small cell lung carcinoma: a morphological, immunohistochemical, and molecular analysis. Mod Pathol. 2006;19(10):1358–68.PubMedCrossRefGoogle Scholar
  52. 52.
    Honda T, Ota H, Ishii K, Nakamura N, Kubo K, Katsuyama T. Mucinous bronchioloalveolar carcinoma with organoid differentiation simulating the pyloric mucosa of the stomach: clinicopathologic, histochemical, and immunohistochemical analysis. Am J Clin Pathol. 1998;109(4):423–30.PubMedGoogle Scholar
  53. 53.
    Hussong JW, Brown M, Perkins SL, Dehner LP, Coffin CM. Comparison of DNA ploidy, histologic, and immunohistochemical findings with clinical outcome in inflammatory myofibroblastic tumors. Mod Pathol. 1999;12(3):279–86.PubMedGoogle Scholar
  54. 54.
    Ionescu DN, Treaba D, Gilks CB, et al. Nonsmall cell lung carcinoma with neuroendocrine differentiation – an entity of no clinical or prognostic significance. Am J Surg Pathol. 2007;31(1):26–32.PubMedCrossRefGoogle Scholar
  55. 55.
    Jaffee IM, Rahmani M, Singhal MG, Younes M. Expression of the intestinal transcription factor CDX2 in carcinoid tumors is a marker of midgut origin. Arch Pathol Lab Med. 2006;130(10):1522–6.PubMedGoogle Scholar
  56. 56.
    Jerome Marson V, Mazieres J, Groussard O, et al. Expression of TTF-1 and cytokeratins in primary and secondary epithelial lung tumours: correlation with histological type and grade. Histopathology. 2004;45(2):125–34.PubMedCrossRefGoogle Scholar
  57. 57.
    Kaufmann O, Dietel M. Thyroid transcription factor-1 is the superior immunohistochemical marker for pulmonary adenocarcinomas and large cell carcinomas compared to surfactant proteins A and B. Histopathology. 2000;36(1):8–16.PubMedCrossRefGoogle Scholar
  58. 58.
    Koss MN, Hochholzer L, O’Leary T. Pulmonary blastomas. Cancer. 1991;67(9):2368–81.PubMedCrossRefGoogle Scholar
  59. 59.
    Kuhnen C, Harms D, Niessen KH, Diehm T, Müller KM. Congenital pulmonary fibrosarcoma. Differential diagnosis of infantile pulmonary spindle cell tumors. Pathologe. 2001;22(2): 151–6 [in German].PubMedCrossRefGoogle Scholar
  60. 60.
    Lantuejoul S, Isaac S, Pinel N, Negoescu A, Guibert B, Brambilla E. Clear cell tumor of the lung: an immunohistochemical and ultrastructural study supporting a pericytic differentiation. Mod Pathol. 1997;10(10):1001–8.PubMedGoogle Scholar
  61. 61.
    Lantuejoul S, Moro D, Michalides RJ, Brambilla C, Brambilla E. Neural cell adhesion molecules (NCAM) and NCAM-PSA expression in neuroendocrine lung tumors. Am J Surg Pathol. 1998;22(10):1267–76.PubMedCrossRefGoogle Scholar
  62. 62.
    Lau SK, Chu PG, Weiss LM. Immunohistochemical expression of estrogen receptor in pulmonary adenocarcinoma. Appl Immunohistochem Mol Morphol. 2006;14(1):83–7.PubMedCrossRefGoogle Scholar
  63. 63.
    Lee WJ, Kim CH, Chang SE, et al. Cutaneous metastasis from large-cell neuroendocrine carcinoma of the urinary bladder expressing CK20 and TTF-1. Am J Dermatopathol. 2009;31(2):166–9.PubMedCrossRefGoogle Scholar
  64. 64.
    Lin BT, Colby T, Gown AM, et al. Malignant vascular tumors of the serous membranes mimicking mesothelioma. A report of 14 cases. Am J Surg Pathol. 1996;20(12):1431–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Lin X, Saad RS, Luckasevic TM, Silverman JF, Liu Y. Diagnostic value of CDX-2 and TTF-1 expressions in separating metastatic neuroendocrine neoplasms of unknown origin. Appl Immunohistochem Mol Morphol. 2007;15(4):407–14.PubMedCrossRefGoogle Scholar
  66. 66.
    Loy TS, Calaluce RD. Utility of cytokeratin immunostaining in separating pulmonary adenocarcinomas from colonic adenocarcinomas. Am J Clin Pathol. 1994;102(6):764–7.PubMedGoogle Scholar
  67. 67.
    Lucas DR, Pass HI, Madan SK, et al. Sarcomatoid mesothelioma and its histological mimics: a comparative immunohistochemical study. Histopathology. 2003;42(3):270–9.PubMedCrossRefGoogle Scholar
  68. 68.
    Mai KT, Perkins DG, Zhang J, Mackenzie CR. ES1, a new lung carcinoma antibody – an immunohistochemical study. Histopathology. 2006;49(5):515–22.PubMedCrossRefGoogle Scholar
  69. 69.
    Miettinen M. Keratin subsets in spindle cell sarcomas. Keratins are widespread but synovial sarcoma contains a distinctive keratin polypeptide pattern and desmoplakins. Am J Pathol. 1991; 138(2):505–13.PubMedGoogle Scholar
  70. 70.
    Miettinen M, Fetsch JF. Distribution of keratins in normal endothelial cells and a spectrum of vascular tumors: implications in tumor diagnosis. Hum Pathol. 2000;31(9):1062–7.PubMedCrossRefGoogle Scholar
  71. 71.
    Nakamura N, Miyagi E, Murata S, Kawaoi A, Katoh R. Expression of thyroid transcription factor-1 in normal and neoplastic lung tissues. Mod Pathol. 2002;15(10):1058–67.PubMedCrossRefGoogle Scholar
  72. 72.
    Nakatani Y, Dickersin GR, Mark EJ. Pulmonary endodermal tumor resembling fetal lung: a clinicopathologic study of five cases with immunohistochemical and ultrastructural characterization. Hum Pathol. 1990;21(11):1097–107.PubMedCrossRefGoogle Scholar
  73. 73.
    Oliveira AM, Tazelaar HD, Myers JL, Erickson LA, Lloyd RV. Thyroid transcription factor-1 distinguishes metastatic pulmonary from well-differentiated neuroendocrine tumors of other sites. Am J Surg Pathol. 2001;25(6):815–9.PubMedCrossRefGoogle Scholar
  74. 74.
    Ordonez NG. The diagnostic utility of immunohistochemistry in distinguishing between mesothelioma and renal cell carcinoma: a comparative study. Hum Pathol. 2004;35(6):697–710.PubMedCrossRefGoogle Scholar
  75. 75.
    Ordonez NG. Application of mesothelin immunostaining in tumor diagnosis. Am J Surg Pathol. 2003;27(11):1418–28.PubMedCrossRefGoogle Scholar
  76. 76.
    Ordonez NG. Value of thyroid transcription factor-1 immunostaining in distinguishing small cell lung carcinomas from other small cell carcinomas. Am J Surg Pathol. 2000;24(9):1217–23.PubMedCrossRefGoogle Scholar
  77. 77.
    Ordonez NG. Value of calretinin immunostaining in differentiating epithelial mesothelioma from lung adenocarcinoma. Mod Pathol. 1998;11(10):929–33.PubMedGoogle Scholar
  78. 78.
    Pelosi G, Pasini F, Olsen Stenholm C, et al. p63 Immunoreactivity in lung cancer: yet another player in the development of squamous cell carcinomas? J Pathol. 2002;198(1):100–9.PubMedCrossRefGoogle Scholar
  79. 79.
    Pettinato G, Manivel JC, Wick MR, Dehner LP. Classical and cellular (atypical) congenital mesoblastic nephroma: a clinicopathologic, ultrastructural, immunohistochemical, and flow cytometric study. Hum Pathol. 1989;20(7):682–90.PubMedCrossRefGoogle Scholar
  80. 80.
    Purdy LJ, Colby TV, Yousem SA, Battifora H. Pulmonary Kaposi’s sarcoma. Premortem histologic diagnosis. Am J Surg Pathol. 1986;10(5):301–11.PubMedCrossRefGoogle Scholar
  81. 81.
    Ralston J, Chiriboga L, Nonaka D. MASH1: a useful marker in differentiating pulmonary small cell carcinoma from Merkel cell carcinoma. Mod Pathol. 2008;21(11):1357–62.PubMedCrossRefGoogle Scholar
  82. 82.
    Ramachandra S, Hollowood K, Bisceglia M, Fletcher CD. Inflammatory pseudotumour of soft tissues: a clinicopathological and immunohistochemical analysis of 18 cases. Histopathology. 1995;27(4):313–23.PubMedCrossRefGoogle Scholar
  83. 83.
    Rdzanek M, Fresco R, Pass HI, Carbone M. Spindle cell tumors of the pleura: differential diagnosis. Semin Diagn Pathol. 2006;23(1):44–55.PubMedCrossRefGoogle Scholar
  84. 84.
    Roberts F, McCall AE, Burnett RA. Malignant mesothelioma: a comparison of biopsy and postmortem material by light microscopy and immunohistochemistry. J Clin Pathol. 2001;54(10):766–70.PubMedCrossRefGoogle Scholar
  85. 85.
    Rodig SJ, Savage KJ, LaCasce AS, et al. Expression of TRAF1 and nuclear c-Rel distinguishes primary mediastinal large cell lymphoma from other types of diffuse large B-cell lymphoma. Am J Surg Pathol. 2007;31(1):106–12.PubMedCrossRefGoogle Scholar
  86. 86.
    Rossi G, Cavazza A, Sturm N, et al. Pulmonary carcinomas with pleomorphic, sarcomatoid, or sarcomatous elements: a clinicopathologic and immunohistochemical study of 75 cases. Am J Surg Pathol. 2003;27(3):311–24.PubMedCrossRefGoogle Scholar
  87. 87.
    Rossi G, Murer B, Cavazza A, et al. Primary mucinous (so-called colloid) carcinomas of the lung: a clinicopathologic and immunohistochemical study with special reference to CDX-2 homeobox gene and MUC2 expression. Am J Surg Pathol. 2004;28(4):442–52.PubMedCrossRefGoogle Scholar
  88. 88.
    Saqi A, Alexis D, Remotti F, Bhagat G. Usefulness of CDX2 and TTF-1 in differentiating gastrointestinal from pulmonary carcinoids. Am J Clin Pathol. 2005;123(3):394–404.PubMedCrossRefGoogle Scholar
  89. 89.
    Sasaki E, Tsunoda N, Hatanaka Y, Mori N, Iwata H, Yatabe Y. Breast-specific expression of MGB1/mammaglobin: an examination of 480 tumors from various organs and clinicopathological analysis of MGB1-positive breast cancers. Mod Pathol. 2007;20(2):208–14.PubMedCrossRefGoogle Scholar
  90. 90.
    Shah RN, Badve S, Papreddy K, Schindler S, Laskin WB, Yeldandi AV. Expression of cytokeratin 20 in mucinous bronchioloalveolar carcinoma. Hum Pathol. 2002;33(9):915–20.PubMedCrossRefGoogle Scholar
  91. 91.
    Sholl LM, Hornick JL, Pinkus JL, Pinkus GS, Padera RF. Immunohistochemical analysis of langerin in langerhans cell histiocytosis and pulmonary inflammatory and infectious diseases. Am J Surg Pathol. 2007;31(6):947–52.PubMedCrossRefGoogle Scholar
  92. 92.
    Siami K, McCluggage WG, Ordonez NG, et al. Thyroid transcription factor-1 expression in endometrial and endocervical adenocarcinomas. Am J Surg Pathol. 2007;31(11):1759–63.PubMedCrossRefGoogle Scholar
  93. 93.
    Sica G, Wagner PL, Altorki N, et al. Immunohistochemical expression of estrogen and progesterone receptors in primary pulmonary neuroendocrine tumors. Arch Pathol Lab Med. 2008;132(12):1889–95.PubMedGoogle Scholar
  94. 94.
    Smith TA, Machen SK, Fisher C, Goldblum JR. Usefulness of cytokeratin subsets for distinguishing monophasic synovial sarcoma from malignant peripheral nerve sheath tumor. Am J Clin Pathol. 1999;112(5):641–8.PubMedGoogle Scholar
  95. 95.
    Srivastava A, Hornick JL. Immunohistochemical staining for CDX-2, PDX-1, NESP-55, and TTF-1 can help distinguish gastrointestinal carcinoid tumors from pancreatic endocrine and pulmonary carcinoid tumors. Am J Surg Pathol. 2009;33(4):626–32.PubMedCrossRefGoogle Scholar
  96. 96.
    Striebel JM, Dacic S, Yousem SA. Gross cystic disease fluid protein-(GCDFP-15): expression in primary lung adenocarcinoma. Am J Surg Pathol. 2008;32(3):426–32.PubMedCrossRefGoogle Scholar
  97. 97.
    Sturm N, Rossi G, Lantuejoul S, et al. 34BetaE12 expression along the whole spectrum of neuroendocrine proliferations of the lung, from neuroendocrine cell hyperplasia to small cell carcinoma. Histopathology. 2003;42(2):156–66.PubMedCrossRefGoogle Scholar
  98. 98.
    Suster S, Fisher C, Moran CA. Expression of bcl-2 oncoprotein in benign and malignant spindle cell tumors of soft tissue, skin, serosal surfaces, and gastrointestinal tract. Am J Surg Pathol. 1998;22(7):863–72.PubMedCrossRefGoogle Scholar
  99. 99.
    Swerdlow SH, Campo E, Harris N, et al. WHO classification of tumours of haematopoietic and lymphoid tissues. 4th ed. Lyon, France: International Agency for Research on Cancer (IARC); 2008. p. 439.Google Scholar
  100. 100.
    Tan D, Li Q, Deeb G, et al. Thyroid transcription factor-1 expression prevalence and its clinical implications in non-small cell lung cancer: a high-throughput tissue microarray and immunohistochemistry study. Hum Pathol. 2003;34(6):597–604.PubMedCrossRefGoogle Scholar
  101. 101.
    Tan D, Zander DS. Immunohistochemistry for assessment of pulmonary and pleural neoplasms: a review and update. Int J Clin Exp Pathol. 2008;1(1):19–31.PubMedGoogle Scholar
  102. 102.
    Tan J, Sidhu G, Greco MA, Ballard H, Wieczorek R. Villin, cytokeratin 7, and cytokeratin 20 expression in pulmonary adenocarcinoma with ultrastructural evidence of microvilli with rootlets. Hum Pathol. 1998;29(4):390–6.PubMedCrossRefGoogle Scholar
  103. 103.
    Tot T. Cytokeratins 20 and 7 as biomarkers: usefulness in discriminating primary from metastatic adenocarcinoma. Eur J Cancer. 2002;38(6):758–63.PubMedCrossRefGoogle Scholar
  104. 104.
    Tot T. The value of cytokeratins 20 and 7 in discriminating metastatic adenocarcinomas from pleural mesotheliomas. Cancer. 2001;92(10):2727–32.PubMedCrossRefGoogle Scholar
  105. 105.
    Traverse-Glehen A, Pittaluga S, Gaulard P, et al. Mediastinal gray zone lymphoma: the missing link between classic Hodgkin’s lymphoma and mediastinal large B-cell lymphoma. Am J Surg Pathol. 2005;29(11):1411–21.PubMedCrossRefGoogle Scholar
  106. 106.
    Travis WD, Brambilla E, Muller-Hermelink HK, Harris CC. Tumours of the lung, pleura, thymus and heart. Lyon, France: IARC Press; 2004. p. 341.Google Scholar
  107. 107.
    Uzaslan E, Stuempel T, Ebsen M, et al. Surfactant protein A detection in primary pulmonary adenocarcinoma without bronchioloalveolar pattern. Respiration. 2005;72(3):249–53.PubMedCrossRefGoogle Scholar
  108. 108.
    Wang BY, Gil J, Kaufman D, Gan L, Kohtz DS, Burstein DE. P63 in pulmonary epithelium, pulmonary squamous neoplasms, and other pulmonary tumors. Hum Pathol. 2002;33(9):921–6.PubMedCrossRefGoogle Scholar
  109. 109.
    Wang J, Weiss LM, Hu B, et al. Usefulness of immunohistochemistry in delineating renal spindle cell tumours. A retrospective study of 31 cases. Histopathology. 2004;44(5):462–71.PubMedCrossRefGoogle Scholar
  110. 110.
    Warson C, Van De Bovenkamp JH, Korteland-Van Male AM, et al. Barrett’s esophagus is characterized by expression of gastric-type mucins (MUC5AC, MUC6) and TFF peptides (TFF1 and TFF2), but the risk of carcinoma development may be indicated by the intestinal-type mucin, MUC2. Hum Pathol. 2002;33(6):660–8.PubMedCrossRefGoogle Scholar
  111. 111.
    Werling RW, Yaziji H, Bacchi CE, Gown AM. CDX2, a highly sensitive and specific marker of adenocarcinomas of intestinal origin: an immunohistochemical survey of 476 primary and metastatic carcinomas. Am J Surg Pathol. 2003;27(3):303–10.PubMedCrossRefGoogle Scholar
  112. 112.
    Wu M, Wang B, Gil J, et al. p63 and TTF-1 immunostaining. A useful marker panel for distinguishing small cell carcinoma of lung from poorly differentiated squamous cell carcinoma of lung. Am J Clin Pathol. 2003;119(5):696–702.PubMedCrossRefGoogle Scholar
  113. 113.
    Yamamoto H, Bai YQ, Yuasa Y. Homeodomain protein CDX2 regulates goblet-specific MUC2 gene expression. Biochem Biophys Res Commun. 2003;300(4):813–8.PubMedCrossRefGoogle Scholar
  114. 114.
    Yao JL, Madeb R, Bourne P, et al. Small cell carcinoma of the prostate: an immunohistochemical study. Am J Surg Pathol. 2006;30(6):705–12.PubMedCrossRefGoogle Scholar
  115. 115.
    Yatabe Y, Mitsudomi T, Takahashi T. TTF-1 expression in pulmonary adenocarcinomas. Am J Surg Pathol. 2002;26(6):767–73.PubMedCrossRefGoogle Scholar
  116. 116.
    Yousem SA, Shaw H, Cieply K. Involvement of 2p23 in pulmonary inflammatory pseudotumors. Hum Pathol. 2001;32(4):428–33.PubMedCrossRefGoogle Scholar
  117. 117.
    Yousem SA, Wick MR, Randhawa P, Manivel JC. Pulmonary blastoma. An immunohistochemical analysis with comparison with fetal lung in its pseudoglandular stage. Am J Clin Pathol. 1990;93(2):167–75.PubMedGoogle Scholar
  118. 118.
    Zamecnik J, Kodet R. Value of thyroid transcription factor-1 and surfactant apoprotein A in the differential diagnosis of pulmonary carcinomas: a study of 109 cases. Virchows Arch. 2002;440(4):353–61.PubMedCrossRefGoogle Scholar
  119. 119.
    Zhang H, Liu J, Cagle PT, Allen TC, Laga AC, Zander DS. Distinction of pulmonary small cell carcinoma from poorly ­differentiated squamous cell carcinoma: an immunohistochemical approach. Mod Pathol. 2005;18(1):111–8.PubMedCrossRefGoogle Scholar
  120. 120.
    Zhu LC, Yim J, Chiriboga L, Cassai ND, Sidhu GS, Moreira AL. DC-LAMP stains pulmonary adenocarcinoma with bronchiolar Clara cell differentiation. Hum Pathol. 2007;38(2):260–8.PubMedCrossRefGoogle Scholar
  121. 121.
    Chu PG, Weiss LM. Modern immunohistochemistry. New York, NY: Cambridge University Press; 2009.Google Scholar
  122. 122.
    Dabbs DJ. Diagnostic immunohistochemistry. 3rd ed. Philadelphia, PA: Churchill Livingstone Elsevier; 2010.Google Scholar
  123. 123.
    Taylor C, Cote R. Immunomicroscopy a diagnostic tool for the surgical pathologist, Major problems in pathology, vol. 19. 3rd ed. Philadelphia, PA: Saunders Elsevier; 2006.Google Scholar
  124. 124.
    Chilosi M, Murer B. Mixed adenocarcinomas of the lung: place in new proposals in classification, mandatory for target therapy. Arch Pathol Lab Med. 2010;134(1):55–65.PubMedGoogle Scholar
  125. 125.
    Gerald WL, Ladanyi M, de Alava E, et al. Clinical, pathologic, and molecular spectrum of tumors associated with t(11;22)(p13;q12): desmoplastic small round-cell tumor and its variants. J Clin Oncol. 1998;16(9):3028–36.PubMedGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  • Kai Zhang
    • 1
  • Phillip Cagle
  1. 1.Department of Pathology and Laboratory MedicineGeisinger Medical CenterDanvilleUSA

Personalised recommendations