Abstract
To confirm the usefulness of an immunohistochemical panel of antibodies for KIT (c-kit/CD117), CD34, desmin, smooth-muscle actin (SMA), h-caldesmon (HCD), S-100 protein, neuron-specific enolase (NSE), and beta-catenin, 297 mesenchymal and peripheral nerve-sheath tumors of the gastrointestinal tract and intra-abdominal locations including 211 gastrointestinal stromal tumors (GISTs), 12 leiomyomas, 18 leiomyosarcomas, 17 solitary fibrous tumors (SFTs), 14 schwannomas, and 25 desmoid-type fibromatoses (DTFs) were analyzed immunohistochemically. Consistent (100%) immunoreactivity for KIT, CD34, desmin and S-100, and nuclear accumulation of beta-catenin were detected in GISTs, SFTs, smooth-muscle tumors, schwannomas, and DTFs, respectively. Immunoreactivity for SMA, HCD, and NSE was observed in a wide range of these tumors. In addition, 418 bone and soft tissue tumors were enrolled in this study for KIT immunostaining. As a result, a limited number of these tumors were KIT positive, including synovial sarcoma that showed morphological similarity to GISTs. These findings suggest that KIT, CD34, desmin, S-100, and beta-catenin are key markers for clinical diagnosis of GISTs and other spindle cell tumors that may involve the gastrointestinal tract, whereas SMA, HCD, and NSE have only limited value.
Similar content being viewed by others
References
Alman BA, Li C, Pajerski ME, Diaz-Cano S, Wolfe HJ (1997) Increased beta-catenin protein and somatic APC mutations in sporadic aggressive fibromatoses (desmoid tumor). Am J Pathol 151:329–334
Antonioli DA (1989) Gastrointestinal autonomic nerve tumors. Expanding the spectrum of gastrointestinal tumors. Arch Pathol Lab Med 113:831–833
Appelman HD (1990) Mesenchymal tumors of the gut: histological perspectives, new approaches, new results, and does it make any difference. Monogr Pathol 31:220–246
Barisella M, Andreola S, Rosai J (2002) CD117 in soft tissue sarcomas. Am J Clin Pathol 118:470–471
Brabletz T, Herrmann K, Jung A, Faller G, Kirchner T (2000) Expression of nuclear beta-catenin and c-myc is correlated with tumor size but not with proliferative activity of colorectal adenomas. Am J Pathol 156:865–870
Daimaru Y, Kido H, Hashimoto H, Enjoji M (1988) Benign schwannoma of the gastrointestinal tract: a clinicopathologic and immunohistochemical study. Hum Pathol 19:257–264
Dhimes P, Lopez-Carreira M, Ortega-Serrano MP, Garcia-Munoz H, Martinez-Gonzalez MA, Ballestin C (1995) Gastrointestinal autonomic nerve tumors and their separation from other gastrointestinal stromal tumors: an ultrastructural and immunohistochemical study of seven cases. Virchows Arch 426:27–35
Fletcher CDM, Berman JJ, Corless C, Gorstein F, Lasota J, Longley BJ, Miettinen M, O’Leary TJ, Remotti H, Rubin BP, Shmookler B, Sobin LH, Weiss SW (2002) Diagnosis of gastrointestinal stromal tumors: a consensus approach. Hum Pathol 33:459–465
Giarola M, Wells D, Mondini P, Pilotti S, Sala P, Azzarelli A, Bertario L, Pierotti MA, Delhanty JD, Radice P (1998) Mutations of adenomatous polyposis coli (APC) gene are uncommon in sporadic desmoid tumors. Br J Cancer 78:582–587
Graadt van Roggen JF, van Velthuysen MLF, Hogendoorn PCW (2001) The histopathological differential diagnosis of gastrointestinal stromal tumors. J Clin Pathol 54:96–103
Greenson JK (2003) Gastrointestinal stromal tumors and other mesenchymal lesions of the gut. Mod Pathol 16:366–375
Hasegawa T, Yokoyama R, Matsuno Y, Shimoda T, Hirohashi S (2001) Prognostic significance of histologic grade and nuclear expression of beta-catenin in synovial sarcoma. Hum Pathol 32:257–263
Hasegawa T, Matsuno Y, Shimoda T, Hirohashi S (2002) Gastrointestinal stromal tumor: consistent CD117 immunostaining for diagnosis, and prognostic classification based on tumor size and MIB-1 grade. Hum Pathol 33:669–676
Heinrich MC, Corless CL, Duensing A, McGreevey L, Chen CJ, Joseph N, Singer S, Griffith DJ, Haley A, Town A, Demetri GD, Fletcher CD, Fletcher JA (2003) PDGFRA activating mutations in gastrointestinal stromal tumors. Science 299:708–710
Hirohashi S (1998) Inactivation of the E-cadherin-mediated cell adhesion system in human cancers. Am J Pathol 153:333–339
Hirose T, Tani T, Shimada T, Ishizawa K, Shimada S, Sano T (2003) Immunohistochemical demonstration of EMA/Glut1-positive perineurial cells and CD34-positive fibroblastic cells in peripheral nerve sheath tumors. Mod Pathol 16:293–298
Hirota S, Isozaki k, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, Kawano K, Hanada M, Kurata A, Takeda M, Muhammad Tunio G, Matsuzawa Y, Kanakura Y, Shinomura Y, Kitamura Y (1998) Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 279:577–580
Hirota S, Ohashi A, Nishida T, Isozaki K, Kinoshita K, Shinomura Y, Kitamura Y (2003) Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumors. Gastroenterology 125:660–667
Hornick JL, Fletcher CDM (2002) Immunohistochemical staining for KIT (CD117) in soft tissue sarcomas is very limited in distribution. Am J Clin Pathol 117:188–193
Hurlimann J, Gardiol D (1991) Gastrointestinal stromal tumors. An immunohistochemical study of 165 cases. Histopathology 19:311–320
Joensuu H, Roberts PJ, Sarlomo-Rikara M, Andersson LC, Tervahartiala P, Tuveson D, Silberman SL, Capdeville R, Dimitrijevic S, Druker B, Demetri GD (2001) Effect of tyrosine kinase inhibitor STI-571 in a patient with a metastatic gastrointestinal stromal tumor. N Engl J Med 344:1052–1056
Kindblom L, Remotti HE, Aldenborg F, Meis-Kindblom JM (1998) Gastrointestinal pacemaker cell tumor (GIPACT): gastrointestinal stromal tumors show phenotypic characteristics of the interstitial cells of Cajal. Am J Pathol 152:1259–1269
Kitamura Y, Hirota S, Nishita T (1998) Molecular pathology of c-kit proto-oncogene and development of gastrointestinal stromal tumors. Ann Chir Gynaecol 87:282–286
Kuhnen C, Herter P, Muller O, Muehlberger T, Krause L, Homann H, Steinau HU, Muller KM (2000) Beta-catenin in soft tissue sarcomas: expression is related to proliferative activity in high-grade sarcomas. Mod Pathol 13:1005–1013
Lasota J, Jasinski M, Sarlomo-Rikara M, Miettinen M (1999) C-kit mutations occur preferentially in malignant versus benign GISTs and do not occur in leiomyomas and leiomyosarcomas. Am J Pathol 154:53–60
Lasota J, Wozniak A, Sarlomo-Rikara M, Rys J, Kordek R, Nassar A, Sobin LH, Miettinen M (2000) Mutations in exons 9 and 13 of KIT gene are rare events in gastrointestinal stromal tumors: a study of two hundred cases. Am J Pathol 157:1091–1095
Lauwers GY, Erlandson RA, Casper ES, Brennan MF, Woodruff JM (1993) Gastrointestinal autonomic nerve tumors. A clinicopathological, immunohistochemical, and ultrastructural study of 12 cases. Am J Surg Pathol 17:887–897
Lee JR, Joshi V, Griffin JW Jr, Lasota J, Miettinen M (2001) Gastrointestinal autonomic tumors: immunohistochemical and molecular identity with gastrointestinal stromal tumor. Am J Surg Pathol 25:979–987
Li C, Bapat B, Alman BA (1998) Adenomatous polyposis coli gene mutation alters proliferation through its beta-catenin-regulatory function in aggressive fibromatosis (desmoid tumor). Am J Pathol 153:709–714
Lucas DR, Al-Abbadi M, Tabaczka P, Hamre MR, Weaver DW, Mott MJ (2003) c-Kit expression in desmoid fibromatosis. Am J Clin Pathol 119:339–345
Lux M, Rubin BP, Biase TL, Chen CJ, Maclure T, Demetri G, Xiao S, Singer S, Fletcher CD, Fletcher JA (2000) KIT extracellular and kinase domain mutations in gastrointestinal stromal tumors. Am J Pathol 156:791–795
Ma CK, Amin MB, Kintanar E, Linden MD, Zarbo RJ (1993) Immunohistologic characterization of gastrointestinal stromal tumors: a study of 82 cases compared with 11 cases of leiomyomas. Mod Pathol 6:139–144
Martin JF, Bazin P, Feroldi J (1960) Tumeurs myoides intra-murales de lestomac; consideration microscopiques a propos de 6 cas. Ann Anat Pathol 5:484–497
Mazur MT, Clark HB (1983) Gastric stromal tumors: reappraisal of histogenesis. Am J Surg Pathol 7:507–519
Miettinen M, Lasota J (2001) Gastrointestinal stromal tumors: definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch 438:1–12
Miettinen M, Virolainen M, Sarlomo-Rikara M (1995) Gastrointestinal stromal tumors: value of CD34 antigen in their identification and separation from true leiomyomas and schwannomas. Am J Surg Pathol 19:207–216
Miettinen M, Sarlomo-Rikara M, Sobin LH, Lasota J (2000) Gastrointestinal stromal tumors and leiomyosarcomas in the colon: a clinicopathologic, immunohistochemical, and molecular genetic study of 44 cases. Am J Surg Pathol 24:1339–1352
Miettinen M, Sobin LH, Sarlomo-Rikara M (2000) Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT). Mod Pathol 13:1134–1142
Miettinen M, Furlong M, Sarlomo-Rikala M, Burke A, Sobin LH, Lasota J (2001) Gastrointestinal tumors, intramural leiomyomas, and leiomyosarcomas in the rectum and anus: a clinicopathologic, immunohistochemical, and molecular genetic study of 144 cases. Am J Surg Pathol 25:1121–1133
Miettinen M, Majidi M, Lasota J (2002) Pathology and diagnostic criteria of gastrointestinal stromal tumors (GISTs): a review. Eur J Cancer 38[Suppl]:S39–S51
Miettinen M, Kopczynski J, Makhiouf HR, Sarlomo-Rkala M, Gyorffy H, Burke A, Sobin LH, Lasota J (2003) Gastrointestinal stromal tumors, intramural leiomyomas, and leiomyosarcomas in the duodenum: a clinicopathologic, immunohistochemical, and molecular genetic study of 167 cases. Am J Surg Pathol 27:625–641
Miyoshi K, Iwao K, Nawa G, Yoshikawa H, Ochi T, Nakamura Y (1998) Frequent mutation in the beta-catenin gene in desmoid tumors from patients without familial adenomatous polyposis. Oncol Res 10:591–594
Montgomery E, Torbenson MS, Kaushal M, Fisher C, Abraham SC (2002) Beta-catenin immunohistochemistry separates mesenteric fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis. Am J Surg Pathol 26:1296–1301
Moskaluk CR, Tian Q, Marshall CR, Rumpel CA, Franquemont DW, Frierson HF Jr (1999) Mutation of c-kit JM domain are found in a minority of human gastrointestinal stromal tumors. Oncogene 18:1897–1902
Polakis P (1999) The oncogenetic activation of beta-catenin. Curr Opin Genet Dev 9:15–21
Rubin BP, Fletcher JA, Fletcher CD (2000) Molecular insights into the histogenesis and pathogenesis of gastrointestinal tumors. Int J Surg Pathol 8:5–10
Rubin BP, Singer S, Tsao C, Duensing A, Lux ML, Ruiz R, Hibbard MK, Chen CJ, Xiao S, Tuveson DA, Demetri GD, Fletcher CD, Fletcher JA (2001) KIT activation is a ubiquitous feature of gastrointestinal stromal tumors. Cancer Res 61:8118–8121
Sabah M, Leader M, Kay E (2003) The problem with KIT: clinical implications and practical difficulties with CD117 immunostaining. Appl Immunohistochem Mol Morphol 11:56–61
Sarlomo-Rikala M, Kovatich AJ, Barusevicius A, Miettinen M (1998) CD117: a sensitive marker for gastrointestinal stromal tumors that is more specific than CD34. Mod Pathol 11:728–734
Shidham VB, Chivukula M, Gupta D, Rao RN, Komorowski R (2002) Immunohistochemical comparison of gastrointestinal stromal tumor and solitary fibrous tumor. Arch Pathol Lab Med 126:1189–1192
Shitoh K, Konishi F, Iijima T, Ohdaira T, Sakai K, Kanazawa K, Miyaki M (1999) A novel case of a sporadic desmoid tumor with mutation of the beta-catenin gene. J Clin Pathol 52:695–696
Smithey BE, Pappo AS, Hill DA (2002) c-kit expression in pediatric solid tumor: a comparative immunohistochemical study. Am J Surg Pathol 26:486–492
Stout AP (1962) Bizarre smooth muscle tumors of the stomach. Cancer 15:400–409
Tejpar S, Nollet F, Li C, Wunder JS, Michils G, dal Cin P, Van Cutsem E, Bapat B, van Roy F, Cassiman JJ, Alman BA (1999) Predominance of beta-catenin mutations and beta-catenin dysregulation in sporadic aggressive fibromatosis (desmoid tumor). Oncogene 18:6615–6620
Ueyama T, Guo KJ, Hashimoto H, Daimaru Y, Enjoji M (1992) A clinicopathologic and immunohistochemical study of gastrointestinal stromal tumors. Cancer 69:947–955
van Oosterom AT, Judson I, Verweij J, Stroobants S, Donato di Paola E, Dimitrijevic S, Martens M, Webb A, Sciot R, Van Glabbeke M, Silverman S, Nielsen OS (2001) Safety and efficacy of imatinib (STI-571) in metastatic gastrointestinal stromal tumors: a phase I study. Lancet 358:1421–1423
Walker P, Dvorak AM (1986) Gastrointestinal autonomic nerve (GAN) tumor: ultrastructural evidence for a newly recognized entity. Arch Pathol Lab Med 110:309–316
Wieczorek TJ, Faquin WC, Rubin BP, Cibas ES (2001) Cytologic diagnosis of gastrointestinal stromal tumor with emphasis on the differential diagnosis with leiomyosarcoma. Cancer (Cancer Cytopathol) 93:276–287
Yantiss RK, Spiro IJ, Compton CC, Rosenberg AE (2000) Gastrointestinal stromal tumor versus intra-abdominal fibromatosis of the bowel wall: a clinically important differential diagnosis. Am J Surg Pathol 24:947–957
Zambrano E, Reyes-Mugica M, Franchi A, Rosai J (2003) An osteoclast-rich tumor of the gastrointestinal tract with features resembling clear cell sarcoma of soft parts: reports of 6 cases of a GIST simulator. Int J Surg Pathol 11:75–81
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Yamaguchi, U., Hasegawa, T., Masuda, T. et al. Differential diagnosis of gastrointestinal stromal tumor and other spindle cell tumors in the gastrointestinal tract based on immunohistochemical analysis. Virchows Arch 445, 142–150 (2004). https://doi.org/10.1007/s00428-004-1055-8
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00428-004-1055-8