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Upper Gastrointestinal Tract

Chapter

Abstract

The application of immunohistochemistry in the diagnostic gastrointestinal pathology is similar to many other organ systems. The most commonly used markers are epithelial cell markers such as cytokeratin AE1/3, cytokeratin 7 and cytokeratin 20, and markers for common mesenchymal tumors such as CD117, CD34, S100, desmin, etc. Tumors of neuroendocrine origin are probably more commonly seen in the digestive and pulmonary systems. A synaptophysin and chromogranin immunostain generally can confirm their ­neuroendocrine nature. Use of immunohistochemical studies to evaluate dysplasia in Barrett’s esophagus is still investigational, although many have found p53 overexpression helpful in confirming dysplasia, particularly in high-grade dysplasia. The use of immunohistochemical studies in nonneoplastic diseases of the gastrointestinal tract is limited. Finally, immunohistochemistry, like GCDFP-15 immunostain, may play a critical role in differentiating certain metastases, such as lobular carcinoma of the breast, from primary tumors, including gastric signet ring cell carcinoma.

Keywords

Dysplasia Carcinoma GIST Neuroendocrine Metastasis Keratin CD117 Synaptophysin 

References

  1. 1.
    Lee MJ, Lee HS, Kim WH, Choi Y, Yang M. Expression of mucins and cytokeratins in primary carcinomas of the digestive system. Mod Pathol. 2003;16(5):403–10.PubMedCrossRefGoogle Scholar
  2. 2.
    Zhou Q, Toivola DM, Feng N, Greenberg HB, Franke WW, Omary MB. Keratin 20 helps maintain intermediate filament organization in intestinal epithelia. Mol Biol Cell. 2003;14(7):2959–71.PubMedCrossRefGoogle Scholar
  3. 3.
    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
  4. 4.
    Kende AI, Carr NJ, Sobin LH. Expression of cytokeratins 7 and 20 in carcinomas of the gastrointestinal tract. Histopathology. 2003;42(2):137–40.PubMedCrossRefGoogle Scholar
  5. 5.
    Chu PG, Weiss LM. Expression of cytokeratin 5/6 in epithelial neoplasms: an immunohistochemical study of 509 cases. Mod Pathol. 2002;15(1):6–10.PubMedCrossRefGoogle Scholar
  6. 6.
    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
  7. 7.
    Portela-Gomes GM, Stridsberg M. Chromogranin A in the human gastrointestinal tract: an immunocytochemical study with region-specific antibodies. J Histochem Cytochem. 2002;50(11):1487–92.PubMedCrossRefGoogle Scholar
  8. 8.
    Yang A, Kaghad M, Wang Y, et al. p63, a p53 homolog at 3q27-29, encodes multiple products with transactivating, death-inducing, and dominant-negative activities. Mol Cell. 1998;2(3):305–16.PubMedCrossRefGoogle Scholar
  9. 9.
    Di Como CJ, Urist MJ, Babayan I, et al. p63 expression profiles in human normal and tumor tissues. Clin Cancer Res. 2002;8(2):494–501.PubMedGoogle Scholar
  10. 10.
    Kaufmann O, Fietze E, Mengs J, Dietel M. Value of p63 and cytokeratin 5/6 as immunohistochemical markers for the differential diagnosis of poorly differentiated and undifferentiated carcinomas. Am J Clin Pathol. 2001;116(6):823–30.PubMedCrossRefGoogle Scholar
  11. 11.
    Willert K, Nusse R. Beta-catenin: a key mediator of Wnt signaling. Curr Opin Genet Dev. 1998;8(1):95–102.PubMedCrossRefGoogle Scholar
  12. 12.
    Krasinskas AM, Goldsmith JD. Immunohistology of the gastrointestinal tract. In: Dabbs DJ, editor. Diagnostic immunohistochemistry. 3rd ed. Philadelphia: Churchill Livingstone Elsevier; 2010. p. 500–40.Google Scholar
  13. 13.
    Bacchi CE, Gown AM. Distribution and pattern of expression of villin, a gastrointestinal-associated cytoskeletal protein, in human carcinomas: a study employing paraffin-embedded tissue. Lab Invest. 1991;64(3):418–24.PubMedGoogle Scholar
  14. 14.
    Dahl J, Greenson JK, Gramlich TL, Petras RE, Fenger C. Histology of small intestine, colon and anal canal. In: Mills SE, editor. Histology for pathologists. 3rd ed. Philadelphia: Lippincott Williams & Williams; 2006. p. 601–83.Google Scholar
  15. 15.
    Goldblum JR, Rice TW, Zuccaro G, Richter JE. Granular cell tumors of the esophagus: a clinical and pathologic study of 13 cases. Ann Thorac Surg. 1996;62(3):860–5.PubMedCrossRefGoogle Scholar
  16. 16.
    John BK, Dang NC, Hussain SA, et al. Multifocal granular cell tumor presenting as an esophageal stricture. J Gastrointest Cancer. 2008;39(1–4):107–13.PubMedCrossRefGoogle Scholar
  17. 17.
    David O, Jakate S. Multifocal granular cell tumor of the esophagus and proximal stomach with infiltrative pattern: a case report and review of the literature. Arch Pathol Lab Med. 1999;123(10):967–73.PubMedGoogle Scholar
  18. 18.
    Yamamoto J, Ohshima K, Ikeda S, Iwashita A, Kikuchi M. Primary esophageal small cell carcinoma with concomitant invasive squamous cell carcinoma or carcinoma in situ. Hum Pathol. 2003;34(11):1108–15.PubMedCrossRefGoogle Scholar
  19. 19.
    Takahashi Y, Noguchi T, Takeno S, Kimura Y, Okubo M, Kawahara K. Reduced expression of p63 has prognostic implications for patients with esophageal squamous cell carcinoma. Oncol Rep. 2006;15(2):323–8.PubMedGoogle Scholar
  20. 20.
    Yun JP, Zhang MF, Hou JH, et al. Primary small cell carcinoma of the esophagus: clinicopathological and immunohistochemical features of 21 cases. BMC Cancer. 2007;7:38.PubMedCrossRefGoogle Scholar
  21. 21.
    Lam KY, Law S, Wong J. Malignant melanoma of the oesophagus: clinicopathological features, lack of p53 expression and steroid receptors and a review of the literature. Eur J Surg Oncol. 1999;25(2):168–72.PubMedCrossRefGoogle Scholar
  22. 22.
    Cheuk W, Chan JK. Thyroid transcription factor-1 is of limited value in practical distinction between pulmonary and extrapulmonary small cell carcinomas. Am J Surg Pathol. 2001;25(4):545–6.PubMedCrossRefGoogle Scholar
  23. 23.
    Takubo K, Nakamura K, Sawabe M, et al. Primary undifferentiated small cell carcinoma of the esophagus. Hum Pathol. 1999;30(2):216–21.PubMedCrossRefGoogle Scholar
  24. 24.
    Lohmann CM, Hwu WJ, Iversen K, Jungbluth AA, Busam KJ. Primary malignant melanoma of the oesophagus: a clinical and pathological study with emphasis on the immunophenotype of the tumours for melanocyte differentiation markers and cancer/testis antigens. Melanoma Res. 2003;13(6):595–601.PubMedCrossRefGoogle Scholar
  25. 25.
    Lu J, Xue LY, Lu N, Zou SM, Liu XY, Wen P. Superficial primary small cell carcinoma of the esophagus: clinicopathological and immunohistochemical analysis of 15 cases. Dis Esophagus. 2010;23(2):153–9.PubMedCrossRefGoogle Scholar
  26. 26.
    Makino T, Yamasaki M, Takeno A, et al. Cytokeratins 18 and 8 are poor prognostic markers in patients with squamous cell carcinoma of the oesophagus. Br J Cancer. 2009;101(8):1298–306.PubMedCrossRefGoogle Scholar
  27. 27.
    Sengpiel C, Konig IR, Rades D, et al. p53 Mutations in carcinoma of the esophagus and gastroesophageal junction. Cancer Invest. 2009;27(1):96–104.PubMedCrossRefGoogle Scholar
  28. 28.
    Brown JG, Familiari U, Papotti M, Rosai J. Thymic basaloid carcinoma: a clinicopathologic study of 12 cases, with a general discussion of basaloid carcinoma and its relationship with adenoid cystic carcinoma. Am J Surg Pathol. 2009;33(8):1113–24.PubMedCrossRefGoogle Scholar
  29. 29.
    Truong LD, Mody DR, Cagle PT, Jackson-York GL, Schwartz MR, Wheeler TM. Thymic carcinoma. A clinicopathologic study of 13 cases. Am J Surg Pathol. 1990;14(2):151–66.PubMedCrossRefGoogle Scholar
  30. 30.
    Suster S. Thymic carcinoma: update of current diagnostic criteria and histologic types. Semin Diagn Pathol. 2005;22(3):198–212.PubMedCrossRefGoogle Scholar
  31. 31.
    Kuo TT, Chan JK. Thymic carcinoma arising in thymoma is associated with alterations in immunohistochemical profile. Am J Surg Pathol. 1998;22(12):1474–81.PubMedCrossRefGoogle Scholar
  32. 32.
    Dorfman DM, Shahsafaei A, Chan JK. Thymic carcinomas, but not thymomas and carcinomas of other sites, show CD5 immunoreactivity. Am J Surg Pathol. 1997;21(8):936–40.PubMedCrossRefGoogle Scholar
  33. 33.
    Tateyama H, Eimoto T, Tada T, Hattori H, Murase T, Takino H. Immunoreactivity of a new CD5 antibody with normal epithelium and malignant tumors including thymic carcinoma. Am J Clin Pathol. 1999;111(2):235–40.PubMedGoogle Scholar
  34. 34.
    Wong NA, Pawade J. Mast cell-rich leiomyomas should not be mistaken for gastrointestinal stromal tumours. Histopathology. 2007;51(2):273–5.PubMedCrossRefGoogle Scholar
  35. 35.
    Zhang X, Rong TH, Wu QL, et al. Differential diagnosis and treatment of esophageal stromal tumors and smooth muscle tumors [in Chinese]. Ai Zheng. 2006;25(7):901–5.PubMedGoogle Scholar
  36. 36.
    Miettinen M, Sarlomo-Rikala M, Sobin LH, Lasota J. Esophageal stromal tumors: a clinicopathologic, immunohistochemical, and molecular genetic study of 17 cases and comparison with esophageal leiomyomas and leiomyosarcomas. Am J Surg Pathol. 2000;24(2):211–22.PubMedCrossRefGoogle Scholar
  37. 37.
    Miettinen M, Sarlomo-Rikala M, Lasota J. Gastrointestinal stromal tumors: recent advances in understanding of their biology. Hum Pathol. 1999;30(10):1213–20.PubMedCrossRefGoogle Scholar
  38. 38.
    Debiec-Rychter M, Sciot R, Le Cesne A, et al. KIT mutations and dose selection for imatinib in patients with advanced gastrointestinal stromal tumours. Eur J Cancer. 2006;42(8):1093–103.PubMedCrossRefGoogle Scholar
  39. 39.
    West RB, Corless CL, Chen X, et al. The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol. 2004;165(1):107–13.PubMedCrossRefGoogle Scholar
  40. 40.
    Espinosa I, Lee CH, Kim MK, et al. A novel monoclonal antibody against DOG1 is a sensitive and specific marker for gastrointestinal stromal tumors. Am J Surg Pathol. 2008;32(2):210–8.PubMedCrossRefGoogle Scholar
  41. 41.
    Li TJ, Zhang YX, Wen J, Cowan DF, Hart J, Xiao SY. Basaloid squamous cell carcinoma of the esophagus with or without adenoid cystic features. Arch Pathol Lab Med. 2004;128(10):1124–30.PubMedGoogle Scholar
  42. 42.
    Sarbia M, Verreet P, Bittinger F, et al. Basaloid squamous cell carcinoma of the esophagus: diagnosis and prognosis. Cancer. 1997;79(10):1871–8.PubMedCrossRefGoogle Scholar
  43. 43.
    Tsubochi H, Suzuki T, Suzuki S, et al. Immunohistochemical study of basaloid squamous cell carcinoma, adenoid cystic and mucoepidermoid carcinoma in the upper aerodigestive tract. Anticancer Res. 2000;20(2B):1205–11.PubMedGoogle Scholar
  44. 44.
    Serrano MF, El-Mofty SK, Gnepp DR, Lewis Jr JS. Utility of high molecular weight cytokeratins, but not p63, in the differential diagnosis of neuroendocrine and basaloid carcinomas of the head and neck. Hum Pathol. 2008;39(4):591–8.PubMedCrossRefGoogle Scholar
  45. 45.
    Emanuel P, Wang B, Wu M, Burstein DE. p63 Immunohistochemistry in the distinction of adenoid cystic carcinoma from basaloid squamous cell carcinoma. Mod Pathol. 2005;18(5):645–50.PubMedCrossRefGoogle Scholar
  46. 46.
    Mino M, Pilch BZ, Faquin WC. Expression of KIT (CD117) in neoplasms of the head and neck: an ancillary marker for adenoid cystic carcinoma. Mod Pathol. 2003;16(12):1224–31.PubMedCrossRefGoogle Scholar
  47. 47.
    Owonikoko T, Loberg C, Gabbert HE, Sarbia M. Comparative analysis of basaloid and typical squamous cell carcinoma of the oesophagus: a molecular biological and immunohistochemical study. J Pathol. 2001;193(2):155–61.PubMedCrossRefGoogle Scholar
  48. 48.
    Chu PG, Jiang Z, Weiss LM. Hepatocyte antigen as a marker of intestinal metaplasia. Am J Surg Pathol. 2003;27(7):952–9.PubMedCrossRefGoogle Scholar
  49. 49.
    Shi XY, Bhagwandeen B, Leong AS. CDX2 and villin are useful markers of intestinal metaplasia in the diagnosis of Barrett esophagus. Am J Clin Pathol. 2008;129(4):571–7.PubMedCrossRefGoogle Scholar
  50. 50.
    Groisman GM, Amar M, Meir A. Expression of the intestinal marker Cdx2 in the columnar-lined esophagus with and without intestinal (Barrett’s) metaplasia. Mod Pathol. 2004;17(10):1282–8.PubMedCrossRefGoogle Scholar
  51. 51.
    Glickman JN, Wang H, Das KM, et al. Phenotype of Barrett’s esophagus and intestinal metaplasia of the distal esophagus and gastroesophageal junction: an immunohistochemical study of cytokeratins 7 and 20, Das-1 and 45 MI. Am J Surg Pathol. 2001;25(1):87–94.PubMedCrossRefGoogle Scholar
  52. 52.
    Sarbia M, Donner A, Franke C, Gabbert HE. Distinction between intestinal metaplasia in the cardia and in Barrett’s esophagus: the role of histology and immunohistochemistry. Hum Pathol. 2004;35(3):371–6.PubMedCrossRefGoogle Scholar
  53. 53.
    Ormsby AH, Goldblum JR, Rice TW, et al. Cytokeratin subsets can reliably distinguish Barrett’s esophagus from intestinal metaplasia of the stomach. Hum Pathol. 1999;30(3):288–94.PubMedCrossRefGoogle Scholar
  54. 54.
    Shearer C, Going J, Neilson L, Mackay C, Stuart RC. Cytokeratin 7 and 20 expression in intestinal metaplasia of the distal oesophagus: relationship to gastro-oesophageal reflux disease. Histopathology. 2005;47(3):268–75.PubMedCrossRefGoogle Scholar
  55. 55.
    Wang J, Qin R, Ma Y, et al. Differential gene expression in normal esophagus and Barrett’s esophagus. J Gastroenterol. 2009;44(9):897–911.PubMedCrossRefGoogle Scholar
  56. 56.
    Flucke U, Steinborn E, Dries V, et al. Immunoreactivity of cytokeratins (CK7, CK20) and mucin peptide core antigens (MUC1, MUC2, MUC5AC) in adenocarcinomas, normal and metaplastic tissues of the distal oesophagus, oesophago-gastric junction and proximal stomach. Histopathology. 2003;43(2):127–34.PubMedCrossRefGoogle Scholar
  57. 57.
    Lu D, Vohra P, Chu PG, Woda B, Rock KL, Jiang Z. An oncofetal protein IMP3: a new molecular marker for the detection of esophageal adenocarcinoma and high-grade dysplasia. Am J Surg Pathol. 2009;33(4):521–5.PubMedCrossRefGoogle Scholar
  58. 58.
    Odze RD. Update on the diagnosis and treatment of Barrett esophagus and related neoplastic precursor lesions. Arch Pathol Lab Med. 2008;132(10):1577–85.PubMedGoogle Scholar
  59. 59.
    Shi XY, Bhagwandeen B, Leong AS. p16, cyclin D1, Ki-67, and AMACR as markers for dysplasia in Barrett esophagus. Appl Immunohistochem Mol Morphol. 2008;16(5):447–52.PubMedCrossRefGoogle Scholar
  60. 60.
    Dorer R, Odze RD. AMACR immunostaining is useful in detecting dysplastic epithelium in Barrett’s esophagus, ulcerative colitis, and Crohn’s disease. Am J Surg Pathol. 2006;30(7):871–7.PubMedCrossRefGoogle Scholar
  61. 61.
    Hanas JS, Lerner MR, Lightfoot SA, et al. Expression of the cyclin-dependent kinase inhibitor p21(WAF1/CIP1) and p53 tumor suppressor in dysplastic progression and adenocarcinoma in Barrett esophagus. Cancer. 1999;86(5):756–63.PubMedCrossRefGoogle Scholar
  62. 62.
    Moskaluk CA, Heitmiller R, Zahurak M, Schwab D, Sidransky D, Hamilton SR. p53 and p21(WAF1/CIP1/SDI1) gene products in Barrett esophagus and adenocarcinoma of the esophagus and esophagogastric junction. Hum Pathol. 1996;27(11):1211–20.PubMedCrossRefGoogle Scholar
  63. 63.
    Ireland AP, Clark GW, DeMeester TR. Barrett’s esophagus. The significance of p53 in clinical practice. Ann Surg. 1997;225(1):17–30.PubMedCrossRefGoogle Scholar
  64. 64.
    Al-Khafaji B, Noffsinger AE, Miller MA, DeVoe G, Stemmermann GN, Fenoglio-Preiser C. Immunohistologic analysis of gastrointestinal and pulmonary carcinoid tumors. Hum Pathol. 1998;29(9):992–9.PubMedCrossRefGoogle Scholar
  65. 65.
    Park SY, Kim BH, Kim JH, Lee S, Kang GH. Panels of immunohistochemical markers help determine primary sites of metastatic adenocarcinoma. Arch Pathol Lab Med. 2007;131(10):1561–7.PubMedGoogle Scholar
  66. 66.
    Kim MA, Lee HS, Yang HK, Kim WH. Cytokeratin expression profile in gastric carcinomas. Hum Pathol. 2004;35(5):576–81.PubMedCrossRefGoogle Scholar
  67. 67.
    Roberts CC, Colby TV, Batts KP. Carcinoma of the stomach with hepatocyte differentiation (hepatoid adenocarcinoma). Mayo Clin Proc. 1997;72(12):1154–60.PubMedCrossRefGoogle Scholar
  68. 68.
    Louhimo J, Nordling S, Alfthan H, von Boguslawski K, Stenman UH, Haglund C. Specific staining of human chorionic gonadotropin beta in benign and malignant gastrointestinal tissues with monoclonal antibodies. Histopathology. 2001;38(5):418–24.PubMedCrossRefGoogle Scholar
  69. 69.
    Plaza JA, Vitellas K, Frankel WL. Hepatoid adenocarcinoma of the stomach. Ann Diagn Pathol. 2004;8(3):137–41.PubMedCrossRefGoogle Scholar
  70. 70.
    Villari D, Caruso R, Grosso M, Vitarelli E, Righi M, Barresi G. Hep Par 1 in gastric and bowel carcinomas: an immunohistochemical study. Pathology. 2002;34(5):423–6.PubMedCrossRefGoogle Scholar
  71. 71.
    Jan YJ, Chen JT, Ho WL, Wu CC, Yeh DC. Primary coexistent adenocarcinoma and choriocarcinoma of the stomach. A case report and review of the literature. J Clin Gastroenterol. 1997;25(3):550–4.PubMedCrossRefGoogle Scholar
  72. 72.
    Saigo PE, Brigati DJ, Sternberg SS, Rosen PP, Turnbull AD. Primary gastric choriocarcinoma. An immunohistological study. Am J Surg Pathol. 1981;5(4):333–42.PubMedCrossRefGoogle Scholar
  73. 73.
    O’Connell FP, Wang HH, Odze RD. Utility of immunohistochemistry in distinguishing primary adenocarcinomas from metastatic breast carcinomas in the gastrointestinal tract. Arch Pathol Lab Med. 2005;129(3):338–47.PubMedGoogle Scholar
  74. 74.
    van Velthuysen ML, Taal BG, van der Hoeven JJ, Peterse JL. Expression of oestrogen receptor and loss of E-cadherin are ­diagnostic for gastric metastasis of breast carcinoma. Histopathology. 2005;46(2):153–7.PubMedCrossRefGoogle Scholar
  75. 75.
    Park DI, Yun JW, Park JH, et al. HER-2/neu amplification is an independent prognostic factor in gastric cancer. Dig Dis Sci. 2006;51(8):1371–9.PubMedCrossRefGoogle Scholar
  76. 76.
    Matsubara J, Yamada Y, Hirashima Y, et al. Impact of insulin-like growth factor type 1 receptor, epidermal growth factor receptor, and HER2 expressions on outcomes of patients with gastric cancer. Clin Cancer Res. 2008;14(10):3022–9.PubMedCrossRefGoogle Scholar
  77. 77.
    Kim JH, Kim MA, Lee HS, Kim WH. Comparative analysis of protein expressions in primary and metastatic gastric carcinomas. Hum Pathol. 2009;40(3):314–22.PubMedCrossRefGoogle Scholar
  78. 78.
    Chen L, Li X, Wang GL, Wang Y, Zhu YY, Zhu J. Clinicopathological significance of overexpression of TSPAN1, Ki67 and CD34 in gastric carcinoma. Tumori. 2008;94(4):531–8.PubMedGoogle Scholar
  79. 79.
    Feakins RM, Nickols CD, Bidd H, Walton SJ. Abnormal expression of pRb, p16, and cyclin D1 in gastric adenocarcinoma and its lymph node metastases: relationship with pathological features and survival. Hum Pathol. 2003;34(12):1276–82.PubMedCrossRefGoogle Scholar
  80. 80.
    Kopp R, Diebold J, Dreier I, et al. Prognostic relevance of p53 and bcl-2 immunoreactivity for early invasive pT1/pT2 gastric carcinomas: indicators for limited gastric resections? Surg Endosc. 2005;19(11):1507–12.PubMedCrossRefGoogle Scholar
  81. 81.
    Chen HC, Chu RY, Hsu PN, et al. Loss of E-cadherin expression correlates with poor differentiation and invasion into adjacent organs in gastric adenocarcinomas. Cancer Lett. 2003;201(1):97–106.PubMedCrossRefGoogle Scholar
  82. 82.
    Mizoshita T, Tsukamoto T, Nakanishi H, et al. Expression of Cdx2 and the phenotype of advanced gastric cancers: relationship with prognosis. J Cancer Res Clin Oncol. 2003;129(12):727–34.PubMedCrossRefGoogle Scholar
  83. 83.
    Lee HS, Lee HK, Kim HS, Yang HK, Kim YI, Kim WH. MUC1, MUC2, MUC5AC, and MUC6 expressions in gastric carcinomas: their roles as prognostic indicators. Cancer. 2001;92(6):1427–34.PubMedCrossRefGoogle Scholar
  84. 84.
    Rubin BP, Singer S, Tsao C, et al. KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res. 2001;61(22):8118–21.PubMedGoogle Scholar
  85. 85.
    Taniguchi M, Nishida T, Hirota S, et al. Effect of c-kit mutation on prognosis of gastrointestinal stromal tumors. Cancer Res. 1999;59(17):4297–300.PubMedGoogle Scholar
  86. 86.
    Kaiserling E, Heinle H, Itabe H, Takano T, Remmele W. Lipid islands in human gastric mucosa: morphological and immunohistochemical findings. Gastroenterology. 1996;110(2):369–74.PubMedCrossRefGoogle Scholar
  87. 87.
    Ludvikova M, Michal M, Datkova D. Gastric xanthelasma associated with diffuse signet ring carcinoma. A potential diagnostic problem. Histopathology. 1994;25(6):581–2.PubMedCrossRefGoogle Scholar
  88. 88.
    Nakasono M, Hirokawa M, Muguruma N, et al. Colorectal xanthomas with polypoid lesion: report of 25 cases. APMIS. 2004;112(1):3–10.PubMedCrossRefGoogle Scholar
  89. 89.
    Lasota J, Wang ZF, Sobin LH, Miettinen M. Gain-of-function mutations, earlier reported in gastrointestinal stromal tumors, are common in small intestinal inflammatory fibroid polyps. A study of 60 cases. Mod Pathol. 2009;22(8):1049–56.PubMedCrossRefGoogle Scholar
  90. 90.
    Pantanowitz L, Antonioli DA, Pinkus GS, Shahsafaei A, Odze RD. Inflammatory fibroid polyps of the gastrointestinal tract: evidence for a dendritic cell origin. Am J Surg Pathol. 2004;28(1):107–14.PubMedCrossRefGoogle Scholar
  91. 91.
    Kim MK, Higgins J, Cho EY, Ko YH, Oh YL. Expression of CD34, bcl-2, and kit in inflammatory fibroid polyps of the gastrointestinal tract. Appl Immunohistochem Mol Morphol. 2000;8(2):147–53.PubMedCrossRefGoogle Scholar
  92. 92.
    Hasegawa T, Yang P, Kagawa N, Hirose T, Sano T. CD34 expression by inflammatory fibroid polyps of the stomach. Mod Pathol. 1997;10(5):451–6.PubMedGoogle Scholar
  93. 93.
    Bluth RF, Carpenter HA, Pittelkow MR, Page DL, Coffey RJ. Immunolocalization of transforming growth factor-alpha in normal and diseased human gastric mucosa. Hum Pathol. 1995;26(12):1333–40.PubMedCrossRefGoogle Scholar
  94. 94.
    Dempsey PJ, Goldenring JR, Soroka CJ, et al. Possible role of transforming growth factor alpha in the pathogenesis of Menetrier’s disease: supportive evidence form humans and transgenic mice. Gastroenterology. 1992;103(6):1950–63.PubMedGoogle Scholar
  95. 95.
    Rimsza LM, Vela EE, Frutiger YM, et al. Rapid automated ­combined in situ hybridization and immunohistochemistry for sensitive detection of cytomegalovirus in paraffin-embedded tissue biopsies. Am J Clin Pathol. 1996;106(4):544–8.PubMedGoogle Scholar
  96. 96.
    Spano LC, Lima Pereira FE, Gomes da Silva Basso N, Mercon-de-Vargas PR. Human cytomegalovirus infection and abortion: an immunohistochemical study. Med Sci Monit. 2002;8(6):BR230–5.PubMedGoogle Scholar
  97. 97.
    Feiden W, Borchard F, Burrig KF, Pfitzer P. Herpes oesophagitis. I. Light microscopical and immunohistochemical investigations. Virchows Arch A Pathol Anat Histopathol. 1984;404(2):167–76.PubMedCrossRefGoogle Scholar
  98. 98.
    Cao J, Li ZQ, Borch K, Petersson F, Mardh S. Detection of spiral and coccoid forms of Helicobacter pylori using a murine monoclonal antibody. Clin Chim Acta. 1997;267(2):183–96.PubMedCrossRefGoogle Scholar
  99. 99.
    Rotimi O, Cairns A, Gray S, Moayyedi P, Dixon MF. Histological identification of Helicobacter pylori: comparison of staining methods. J Clin Pathol. 2000;53(10):756–9.PubMedCrossRefGoogle Scholar
  100. 100.
    Chu PG, Schwarz RE, Lau SK, Yen Y, Weiss LM. Immuno­histochemical staining in the diagnosis of pancreatobiliary and ampulla of Vater adenocarcinoma: application of CDX2, CK17, MUC1, and MUC2. Am J Surg Pathol. 2005;29(3):359–67.PubMedCrossRefGoogle Scholar
  101. 101.
    Goldstein NS, Bassi D. Cytokeratins 7, 17, and 20 reactivity in pancreatic and ampulla of vater adenocarcinomas. Percentage of positivity and distribution is affected by the cut-point threshold. Am J Clin Pathol. 2001;115(5):695–702.PubMedCrossRefGoogle Scholar
  102. 102.
    Zhou H, Schaefer N, Wolff M, Fischer HP. Carcinoma of the ampulla of Vater: comparative histologic/immunohistochemical classification and follow-up. Am J Surg Pathol. 2004;28(7):875–82.PubMedCrossRefGoogle Scholar
  103. 103.
    Sarbia M, Fritze F, Geddert H, von Weyhern C, Rosenberg R, Gellert K. Differentiation between pancreaticobiliary and upper gastrointestinal adenocarcinomas: is analysis of cytokeratin 17 expression helpful? Am J Clin Pathol. 2007;128(2):255–9.PubMedCrossRefGoogle Scholar
  104. 104.
    Vang R, Gown AM, Barry TS, et al. Cytokeratins 7 and 20 in primary and secondary mucinous tumors of the ovary: analysis of coordinate immunohistochemical expression profiles and staining distribution in 179 cases. Am J Surg Pathol. 2006;30(9):1130–9.PubMedCrossRefGoogle Scholar
  105. 105.
    Chen ZM, Ritter JH, Wang HL. Differential expression of alpha-methylacyl coenzyme A racemase in adenocarcinomas of the small and large intestines. Am J Surg Pathol. 2005;29(7):890–6.PubMedCrossRefGoogle Scholar
  106. 106.
    Lin A, Weiser MR, Klimstra DS, et al. Differential expression of alpha-methylacyl-coenzyme A racemase in colorectal carcinoma bears clinical and pathologic significance. Hum Pathol. 2007;38(6):850–6.PubMedCrossRefGoogle Scholar
  107. 107.
    Weinrach DM, Wang KL, Blum MG, Yeldandi AV, Laskin WB. Multifocal presentation of gangliocytic paraganglioma in the mediastinum and esophagus. Hum Pathol. 2004;35(10):1288–91.PubMedCrossRefGoogle Scholar
  108. 108.
    Hironaka M, Fukayama M, Takayashiki N, Saito K, Sohara Y, Funata N. Pulmonary gangliocytic paraganglioma: case report and comparative immunohistochemical study of related neuroendocrine neoplasms. Am J Surg Pathol. 2001;25(5):688–93.PubMedCrossRefGoogle Scholar
  109. 109.
    Burke AP, Helwig EB. Gangliocytic paraganglioma. Am J Clin Pathol. 1989;92(1):1–9.PubMedGoogle Scholar
  110. 110.
    Perrone T, Sibley RK, Rosai J. Duodenal gangliocytic paraganglioma. An immunohistochemical and ultrastructural study and a hypothesis concerning its origin. Am J Surg Pathol. 1985;9(1):31–41.PubMedCrossRefGoogle Scholar
  111. 111.
    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
  112. 112.
    Bornstein-Quevedo L, Gamboa-Dominguez A. Carcinoid tumors of the duodenum and ampulla of vater: a clinicomorphologic, immunohistochemical, and cell kinetic comparison. Hum Pathol. 2001;32(11):1252–6.PubMedCrossRefGoogle Scholar
  113. 113.
    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
  114. 114.
    Capella C, Solcia E, Sobin LH, Arnold R. Endocrine tumors of the small intestine. In: Hamilton SR, Aaltonen LA, editors. WHO classification of tumours, volume 2, Pathology & genetics: tumours of the digestive system. Lyon, France: IARC press; 2000. p. 77–82.Google Scholar
  115. 115.
    Makhlouf HR, Burke AP, Sobin LH. Carcinoid tumors of the ampulla of Vater: a comparison with duodenal carcinoid tumors. Cancer. 1999;85(6):1241–9.PubMedCrossRefGoogle Scholar
  116. 116.
    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
  117. 117.
    Miettinen M, Sobin LH, Sarlomo-Rikala M. Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT). Mod Pathol. 2000;13(10):1134–42.PubMedCrossRefGoogle Scholar
  118. 118.
    Dow N, Giblen G, Sobin LH, Miettinen M. Gastrointestinal stromal tumors: differential diagnosis. Semin Diagn Pathol. 2006;23(2):111–9.PubMedCrossRefGoogle Scholar
  119. 119.
    Sarlomo-Rikala M, Kovatich AJ, Barusevicius A, Miettinen M. CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol. 1998;11(8):728–34.PubMedGoogle Scholar
  120. 120.
    Miettinen M, Virolainen M, Maarit-Sarlomo-Rikala. Gastrointestinal stromal tumors – value of CD34 antigen in their identification and separation from true leiomyomas and schwannomas. Am J Surg Pathol. 1995;19(2):207–16.PubMedCrossRefGoogle Scholar
  121. 121.
    Greenson JK. Gastrointestinal stromal tumors and other mesenchymal lesions of the gut. Mod Pathol. 2003;16(4):366–75.PubMedCrossRefGoogle Scholar
  122. 122.
    Brimo F, Dion D, Huwait H, Turcotte R, Nahal A. The utility of MDM2 and CDK4 immunohistochemistry in needle biopsy interpretation of lipomatous tumours: a study of 21 Tru-Cut biopsy cases. Histopathology. 2008;52(7):892–5.PubMedCrossRefGoogle Scholar
  123. 123.
    Carlson JW, Fletcher CD. Immunohistochemistry for beta-catenin in the differential diagnosis of spindle cell lesions: analysis of a series and review of the literature. Histopathology. 2007;51(4):509–14.PubMedCrossRefGoogle Scholar
  124. 124.
    Montgomery E, Torbenson MS, Kaushal M, Fisher C, Abraham SC. Beta-catenin immunohistochemistry separates mesenteric fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis. Am J Surg Pathol. 2002;26(10):1296–301.PubMedCrossRefGoogle Scholar
  125. 125.
    Bhattacharya B, Dilworth HP, Iacobuzio-Donahue C, et al. Nuclear beta-catenin expression distinguishes deep fibromatosis from other benign and malignant fibroblastic and myofibroblastic lesions. Am J Surg Pathol. 2005;29(5):653–9.PubMedCrossRefGoogle Scholar
  126. 126.
    Ho-Yen C, Chang F, van der Walt J, Mitchell T, Ciclitira P. Recent advances in refractory coeliac disease: a review. Histopathology. 2009;54(7):783–95.PubMedCrossRefGoogle Scholar
  127. 127.
    Robert ME. Gluten sensitive enteropathy and other causes of small intestinal lymphocytosis. Semin Diagn Pathol. 2005;22(4):284–94.PubMedCrossRefGoogle Scholar
  128. 128.
    Groisman GM, Amar M, Livne E. CD10: a valuable tool for the light microscopic diagnosis of microvillous inclusion disease (familial microvillous atrophy). Am J Surg Pathol. 2002;26(7):902–7.PubMedCrossRefGoogle Scholar
  129. 129.
    Groisman GM, Ben-Izhak O, Schwersenz A, Berant M, Fyfe B. The value of polyclonal carcinoembryonic antigen immunostaining in the diagnosis of microvillous inclusion disease. Hum Pathol. 1993;24(11):1232–7.PubMedCrossRefGoogle Scholar
  130. 130.
    Raafat F, Green NJ, Nathavitharana KA, Booth IW. Intestinal microvillous dystrophy: a variant of microvillous inclusion disease or a new entity? Hum Pathol. 1994;25(11):1243–8.PubMedCrossRefGoogle Scholar
  131. 131.
    Russo P. GI tract enteropathies of infancy and childhood. In: Odze RD, Goldblum JR, editors. Surgical pathology of the GI tract, liver, biliary tract and pancreas. Philadelphia, PA: Saunders; 2008. p. 169–83.Google Scholar

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© Springer Science+Business Media, LLC 2011

Authors and Affiliations

  1. 1.Department of Pathology and Laboratory MedicineGeisinger Medical CenterDanvilleUSA

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