Medical Oncology

, 26:247

Primary small cell carcinoma of the mediastinum: a case report with immunohistochemical and molecular genetic analyses of KIT and PDGFRA genes

Case Report

Abstract

The author reports herein an extremely rare case of primary small cell carcinoma of the mediastinum with an emphasis on KIT and PDGFRA genes. A 66-year-old man was found to have a mediastinal tumor on a routine chest X-ray examination, and was admitted to our hospital. Imaging modalities revealed a 5 × 4 cm tumor in the middle mediastinum near the bronchial carina. No other tumors were detected in the body including the lungs. Video-assisted thoracoscopy confirmed the mediastinal tumor, and a large incisional biopsy was performed. The tumor was histologically small cell carcinoma. An immunohistochemical study revealed positive reactions for cytokeratins (AE1/3, polyclonal), synaptophysin, neuron-specific enolase, CD56, KIT, and PDGFRA, and negative reactions for chromogranin, CEA, CD45, CD20, and CD3. Ki-67 labeling showed a value of 80%. A molecular genetic analysis using PCR-direct sequencing identified no mutations of KIT (exons 9, 11, 13, and 17) and PDGFRA (exons 12 and 18) genes. The patient received radiation and chemotherapy, and the tumor was fully resolved. The patient has remained free of recurrence for 6 years after the first presentation. The present case is the first reported case of primary small cell carcinoma of the mediastinum with an examination of KIT and PDGFRA expressions and KIT and PDFGRA gene mutations.

Keywords

Small cell carcinoma Mediastinum KIT PDGFRA 

References

  1. 1.
    Hirota S, Isozaki K. Pathology of gastrointestinal stromal tumor. Pathol Int. 2006;56:1–9. doi:10.1111/j.1440-1827.2006.02036.x.PubMedCrossRefGoogle Scholar
  2. 2.
    Losota J, Miettinen M. KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin Diang Pathol. 2006;23:91–101. doi:10.1053/j.semdp.2006.08.006.CrossRefGoogle Scholar
  3. 3.
    Miettinen M, Lasota J. Gastrointestinal stromal tumor: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med. 2006;130:1466–78.PubMedGoogle Scholar
  4. 4.
    Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S, et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumor. Science. 1998;279:577–80. doi:10.1126/science.279.5350.577.PubMedCrossRefGoogle Scholar
  5. 5.
    Hirota S, Ohashi A, Nishida T, Isozaki K, Kinoshita K, Shinomura Y, et al. Gain-of-function mutations of platelet-derived growth factor receptor alpha gene in gastrointestinal stromal tumor. Gastroenterology. 2003;125:660–7. doi:10.1016/S0016-5085(03)01046-1.PubMedCrossRefGoogle Scholar
  6. 6.
    Miettinen M, Lasota J. KIT (CD117): a review on expression in normal and neoplastic tissue, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol. 2005;13:205–20. doi:10.1097/01.pai.0000173054.83414.22.PubMedCrossRefGoogle Scholar
  7. 7.
    Takanami I, Imamura T, Yamamoto Y, Yamamoto T, Kodaira S. Long survival in small-cell (neuroendocrine) carcinoma of the mediastinum. Scand J Thorac Cardiovasc Surg. 1966;30:179–80.Google Scholar
  8. 8.
    Yang CC, Lee HS, Chen CC, Cheng CJ, Lin SH. Syndrome of inappropriate antidiuretic secretion in a patient with cryptcoccal meningoencepharltis a hidden mediastinal small cell carcinoma. Am J Med Sci. 2006;331:288–91. doi:10.1097/00000441-200605000-00012.PubMedCrossRefGoogle Scholar
  9. 9.
    LaPoint RJ, Bourne PA, Wang HL, Xu H. Coexpression of c-kit and bcl-2 in small cell carcinoma and large cell neuroendocrine carcinoma of the lung. Appl Immunohistochem Mol Morphol. 2007;15:401–6.PubMedCrossRefGoogle Scholar
  10. 10.
    Lopes-Martin A, Ballenstin C, Garcia-Carbonero R, Castano A, Lopez-Rios F, Lopes-Encuentra A, et al. Prognostic value of KIT expression in small cell lung carcinoma. Lung Cancer. 2007;56:405–13. doi:10.1016/j.lungcan.2007.01.029.CrossRefGoogle Scholar
  11. 11.
    Micke P, Basral M, Faldum A, Bittinger F, Ronnstrand L, Blaukat A, et al. Characterization of c-kit expression in small cell lung carcinoma: prognostic and therapeutic implications. Clin Cancer Res. 2003;9:188–94.PubMedGoogle Scholar
  12. 12.
    Camps C, Sirera R, Bremnes RM, Garde J, Safont MJ, Blasco A, et al. Analysis of c-kit expression in small cell lung carcinoma: prevalence and prognostic implications. Lung Cancer. 2006;52:343–7. doi:10.1016/j.lungcan.2006.02.003.PubMedCrossRefGoogle Scholar
  13. 13.
    Rossi G, Cavazza A, Marchioni A, Miggaldi M, Bavierli M, Fracciolongo N, et al. KIT expression in small cell carcinoma of the lung: effects of chemotherapy. Mod Pathol. 2003;16:1041–7. doi:10.1097/01.MP.0000089780.30006.DE.PubMedCrossRefGoogle Scholar
  14. 14.
    Naeem M, Dahiya M, Clark JI, Creech SD, Alkin S. Analysis of c-kit protein expression in small-cell lung carcinoma and its implications for prognosis. Hum Pathol. 2002;33:1182–7. doi:10.1053/hupa.2002.129199.PubMedCrossRefGoogle Scholar
  15. 15.
    Mojica WD, Saxena R, Starostik P, Cheney RT. CD117+ small cell lung cancer lacks the asp 816 val point mutation in exon 17. Histopathology. 2005;47:517–22. doi:10.1111/j.1365-2559.2005.02259.x.PubMedCrossRefGoogle Scholar
  16. 16.
    Boldrini L, Ursino S, Gisfredi S, Faviana P, Donati V, Camcci T, et al. Expression and mutational status of c-kit in small-cell lung cancer: prognostic relevance. Clin Cancer Res. 2004;15:4101–8. doi:10.1158/1078-0432.CCR-03-0664.CrossRefGoogle Scholar
  17. 17.
    Burger H, Den Bakker MA, Stoter G, Verweij J, Nooter K. Lack of c-kit exon 11 activating mutations in c-kit/CD117-positive SCLC tumor specimens. Eur J Cancer. 2003;39:793–9. doi:10.1016/S0959-8049(03)00026-1.PubMedCrossRefGoogle Scholar
  18. 18.
    Sihto H, Sarlomo-Rikara M, Tynnienen O, Tanner M, Andersson LC, Franssila K, et al. KIT and platelet-derived growth factor receptor alpha tyrosine kinase gene mutations and KIT amplifications in human solid tumors. J Clin Oncol. 2005;23:49–57. doi:10.1200/JCO.2005.02.093.PubMedCrossRefGoogle Scholar
  19. 19.
    Terada T, Kawaguchi M, Furukawa K, Sekido Y, Osamura Y. Minute mixed ductal-endocrine carcinoma of the pancreas with predominant intraductal growth. Pathol Int. 2002;52:740–6. doi:10.1046/j.1440-1827.2002.01416.x.PubMedCrossRefGoogle Scholar
  20. 20.
    Terada T, Kawaguchi M. Primary clear cell adenocarcinoma of the peritoneum. Tohoku J Exp Med. 2005;271:271–5. doi:10.1620/tjem.206.271.CrossRefGoogle Scholar
  21. 21.
    Terada T. Gastrointestinal stromal tumor of the uterus: a case report with genetic analyses of c-kit and PDGFRA genes. Int J Gynecol Oncol. (in press).Google Scholar
  22. 22.
    Terada T. Primary extragastrointestinal stromal tumors of the transverse mesocolon without c-kit mutations but with PDGFRA mutations. Med Oncol. (in press).Google Scholar

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  1. 1.Department of PathologyShizuoka City Shimizu HospitalShizuokaJapan

Personalised recommendations