Skip to main content
Top
Published in: Archives of Gynecology and Obstetrics 4/2010

01-10-2010 | Gynecologic Oncology

KIT-positive primary small cell carcinoma of the endometrium: a case report with immunohistochemical and molecular genetic analysis of KIT and PDGFRA genes

Author: Tadashi Terada

Published in: Archives of Gynecology and Obstetrics | Issue 4/2010

Login to get access

Abstract

Background

Primary small cell carcinoma of the endometrium is very rare, and there have been no reports on KIT and PDGFRA in endometrial small cell carcinoma.

Case report

An 87-year-old woman was admitted to our hospital because of genital bleeding. Endometrial cytology and biopsy revealed small cell carcinoma. Scrutiny of the body showed stage III endometrial carcinoma with metastases. An immunohistochemical study of the biopsy specimens revealed positive reactions for synaptophysin, CD56, KIT, and PDGFRA, and negative reactions for cytokeratins, neuron-specific enolase, and chromogranin. 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 chemotherapy and radiation, but showed a downhill course, and died of carcinomatosis 6 months after the initial presentation.

Conclusion

The present case is the first reported case of primary small cell carcinoma of the endometrium with an examination of KIT and PDGFRA expressions and KIT and PDFGRA gene mutations.
Literature
1.
go back to reference Huntsman DG, Clements PB, Gilks CB, Scully RE (1994) Small-cell carcinoma of the endometrium. A clinicopathological study of sixteen cases. Am J Surg Pathol 18:364–375CrossRefPubMed Huntsman DG, Clements PB, Gilks CB, Scully RE (1994) Small-cell carcinoma of the endometrium. A clinicopathological study of sixteen cases. Am J Surg Pathol 18:364–375CrossRefPubMed
2.
go back to reference van Hoeven KH, Hudock JA, Woodruff JM, Suhrland MJ (1995) Small cell neuroendocrine carcinoma of the endometrium. Int J Gynecol Pathol 14:21–29CrossRefPubMed van Hoeven KH, Hudock JA, Woodruff JM, Suhrland MJ (1995) Small cell neuroendocrine carcinoma of the endometrium. Int J Gynecol Pathol 14:21–29CrossRefPubMed
3.
go back to reference Varras M, Akrivis Ch, Demou A, Hadjopoulos S, Antoniou N (2002) Primary small-cell carcinoma of the endometrium: clinicopathologic study of a case and review of the literature. Eur J Gynecol Oncol 23:577–581 Varras M, Akrivis Ch, Demou A, Hadjopoulos S, Antoniou N (2002) Primary small-cell carcinoma of the endometrium: clinicopathologic study of a case and review of the literature. Eur J Gynecol Oncol 23:577–581
4.
go back to reference Albores-Saavedra J, Martinez-Benitez B, Luevano E (2008) Small cell carcinomas and large cell neuroendocrine carcinomas of the endometrium and cervix: polypoid tumors and those arising in polyps may have a favorable prognosis. Int J Gynecol Pathol 27:333–339CrossRefPubMed Albores-Saavedra J, Martinez-Benitez B, Luevano E (2008) Small cell carcinomas and large cell neuroendocrine carcinomas of the endometrium and cervix: polypoid tumors and those arising in polyps may have a favorable prognosis. Int J Gynecol Pathol 27:333–339CrossRefPubMed
5.
go back to reference LaPoint RJ, Bourne PA, Wang HL, Xu H (2007) Coexpression of c-kit and bcl-2 in small cell carcinoma and large cell neuroendocrine carcinoma of the lung. Appl Immunohistochem Mol Morphol 15:401–406CrossRefPubMed LaPoint RJ, Bourne PA, Wang HL, Xu H (2007) Coexpression of c-kit and bcl-2 in small cell carcinoma and large cell neuroendocrine carcinoma of the lung. Appl Immunohistochem Mol Morphol 15:401–406CrossRefPubMed
6.
go back to reference Lopes-Martin A, Ballenstin C, Garcia-Carbonero R, Castano A, Lopez-Rios F, Lopes-Encuentra A, Sanchez-Cespedes M, Castellano D, Bartolomes A, Cortes Funes H, Paz-Ares L (2007) Prognostic value of KIT expression in small cell lung carcinoma. Lung Cancer 56:405–413CrossRef Lopes-Martin A, Ballenstin C, Garcia-Carbonero R, Castano A, Lopez-Rios F, Lopes-Encuentra A, Sanchez-Cespedes M, Castellano D, Bartolomes A, Cortes Funes H, Paz-Ares L (2007) Prognostic value of KIT expression in small cell lung carcinoma. Lung Cancer 56:405–413CrossRef
7.
go back to reference Micke P, Basral M, Faldum A, Bittinger F, Ronnstrand L, Blaukat A, Beeh KM, Oesch F, Fischer B, Buhl R, Hengstler JG (2003) Characterization of c-kit expression in small cell lung carcinoma: prognostic and therapeutic implications. Clin Cancer Res 9:188–194PubMed Micke P, Basral M, Faldum A, Bittinger F, Ronnstrand L, Blaukat A, Beeh KM, Oesch F, Fischer B, Buhl R, Hengstler JG (2003) Characterization of c-kit expression in small cell lung carcinoma: prognostic and therapeutic implications. Clin Cancer Res 9:188–194PubMed
8.
go back to reference Camps C, Sirera R, Bremnes RM, Garde J, Safont MJ, Blasco A, Berrocal A, Sanchez JJ, Calabuig C, Marrorell M (2006) Analysis of c-kit expression in small cell lung carcinoma: prevalence and prognostic implications. Lung Cancer 52:343–347CrossRefPubMed Camps C, Sirera R, Bremnes RM, Garde J, Safont MJ, Blasco A, Berrocal A, Sanchez JJ, Calabuig C, Marrorell M (2006) Analysis of c-kit expression in small cell lung carcinoma: prevalence and prognostic implications. Lung Cancer 52:343–347CrossRefPubMed
9.
go back to reference Rossi G, Cavazza A, Marchioni A, Miggaldi M, Bavierli M, Fracciolongo N, Petruzzelli S, Longo L, Tamberi S, Crino L (2003) KIT expression in small cell carcinoma of the lung: effects of chemotherapy. Mod Pathol 16:1041–1047CrossRefPubMed Rossi G, Cavazza A, Marchioni A, Miggaldi M, Bavierli M, Fracciolongo N, Petruzzelli S, Longo L, Tamberi S, Crino L (2003) KIT expression in small cell carcinoma of the lung: effects of chemotherapy. Mod Pathol 16:1041–1047CrossRefPubMed
10.
go back to reference Naeem M, Dahiya M, Clark JI, Creech SD, Alkin S (2002) Analysis of c-kit protein expression in small-cell lung carcinoma and its implications for prognosis. Hum Pathol 33:1182–1187CrossRefPubMed Naeem M, Dahiya M, Clark JI, Creech SD, Alkin S (2002) Analysis of c-kit protein expression in small-cell lung carcinoma and its implications for prognosis. Hum Pathol 33:1182–1187CrossRefPubMed
11.
go back to reference Mojica WD, Saxena R, Starostik P, Cheney RT (2005) CD117+ small cell lung cancer lacks the asp 816 val point mutation in exon 17. Histopathology 47:517–522CrossRefPubMed Mojica WD, Saxena R, Starostik P, Cheney RT (2005) CD117+ small cell lung cancer lacks the asp 816 val point mutation in exon 17. Histopathology 47:517–522CrossRefPubMed
12.
go back to reference Boldrini L, Ursino S, Gisfredi S, Faviana P, Donati V, Camcci T, Lucchi M, Mussi A, Basolo F, Pingitore R, Fontanini G (2004) Expression and mutational status of c-kit in small-cell lung cancer: prognostic relevance. Clin Cancer Res 15:4101–4108CrossRef Boldrini L, Ursino S, Gisfredi S, Faviana P, Donati V, Camcci T, Lucchi M, Mussi A, Basolo F, Pingitore R, Fontanini G (2004) Expression and mutational status of c-kit in small-cell lung cancer: prognostic relevance. Clin Cancer Res 15:4101–4108CrossRef
13.
go back to reference Burger H, Den Bakker MA, Stoter G, Verweij J, Nooter K (2003) Lack of c-kit exon 11 activating mutations in c-kit/CD117-positive SCLC tumor specimens. Eur J Cancer 39:793–799CrossRefPubMed Burger H, Den Bakker MA, Stoter G, Verweij J, Nooter K (2003) Lack of c-kit exon 11 activating mutations in c-kit/CD117-positive SCLC tumor specimens. Eur J Cancer 39:793–799CrossRefPubMed
14.
go back to reference Sihto H, Sarlomo-Rikara M, Tynnienen O, Tanner M, Andersson LC, Franssila K, Nupponen NN, Joensuu H (2005) KIT and platelet-derived growth factor receptor alpha tyrosine kinase gene mutations and KIT amplifications in human solid tumors. J Clin Oncol 23:49–57CrossRefPubMed Sihto H, Sarlomo-Rikara M, Tynnienen O, Tanner M, Andersson LC, Franssila K, Nupponen NN, Joensuu H (2005) KIT and platelet-derived growth factor receptor alpha tyrosine kinase gene mutations and KIT amplifications in human solid tumors. J Clin Oncol 23:49–57CrossRefPubMed
15.
16.
go back to reference Losota J, Miettinen M (2006) KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin Diang Pathol 23:91–101CrossRef Losota J, Miettinen M (2006) KIT and PDGFRA mutations in gastrointestinal stromal tumors (GISTs). Semin Diang Pathol 23:91–101CrossRef
17.
go back to reference Miettinen M, Lasota J (2006) Gastrointestinal stromal tumor: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med 130:1466–1478PubMed Miettinen M, Lasota J (2006) Gastrointestinal stromal tumor: review on morphology, molecular pathology, prognosis, and differential diagnosis. Arch Pathol Lab Med 130:1466–1478PubMed
18.
go back to reference 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, Shimomura Y, Kitamura Y (1998) Gain-of-function mutations of c-kit in human gastrointestinal stromal tumor. Science 279:577–580CrossRefPubMed 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, Shimomura Y, Kitamura Y (1998) Gain-of-function mutations of c-kit in human gastrointestinal stromal tumor. Science 279:577–580CrossRefPubMed
19.
go back to reference 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 tumor. Gastroenterology 125:660–667CrossRefPubMed 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 tumor. Gastroenterology 125:660–667CrossRefPubMed
20.
go back to reference Miettinen M, Lasota J (2005) KIT (CD117): a review on expression in normal and neoplastic tissue, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol 13:205–220CrossRefPubMed Miettinen M, Lasota J (2005) KIT (CD117): a review on expression in normal and neoplastic tissue, and mutations and their clinicopathologic correlation. Appl Immunohistochem Mol Morphol 13:205–220CrossRefPubMed
21.
go back to reference Terada T, Kawaguchi M, Furukawa K, Sekido Y, Osamura Y (2002) Minute mixed ductal-endocrine carcinoma of the pancreas with predominant intraductal growth. Pathol Int 52:740–746CrossRefPubMed Terada T, Kawaguchi M, Furukawa K, Sekido Y, Osamura Y (2002) Minute mixed ductal-endocrine carcinoma of the pancreas with predominant intraductal growth. Pathol Int 52:740–746CrossRefPubMed
22.
go back to reference Terada T, Kawaguchi M (2005) Primary clear cell adenocarcinoma of the peritoneum. Tohoku J Exp Med 271:271–275CrossRef Terada T, Kawaguchi M (2005) Primary clear cell adenocarcinoma of the peritoneum. Tohoku J Exp Med 271:271–275CrossRef
23.
go back to reference Terada T (2009) Gastrointestinal stromal tumor of the uterus: a case report with genetic analyses of c-kit and PDGFRA genes. Int J Gynecol Oncol 28:29–34 Terada T (2009) Gastrointestinal stromal tumor of the uterus: a case report with genetic analyses of c-kit and PDGFRA genes. Int J Gynecol Oncol 28:29–34
24.
go back to reference Terada T (2009) Primary extragastrointestinal stromal tumor of the transverse mesocolon without c-kit mutations but with PDGFRA mutations. Med Oncol 26:233–237CrossRefPubMed Terada T (2009) Primary extragastrointestinal stromal tumor of the transverse mesocolon without c-kit mutations but with PDGFRA mutations. Med Oncol 26:233–237CrossRefPubMed
25.
go back to reference Terada T (2008) Primary multiple extragastrointestinal stromal tumors of the omentum with different mutations of c-kit gene. Would J Gastroenterol 14:7256–7259CrossRef Terada T (2008) Primary multiple extragastrointestinal stromal tumors of the omentum with different mutations of c-kit gene. Would J Gastroenterol 14:7256–7259CrossRef
26.
27.
go back to reference Slomovitz BM, Broaddus RR, Schmandt R, Wu W, Oh JC, Ramondetta LM, Burke TW, Gershenson DM, Lu KH (2004) Expression of imatinib mesylate-targeted kinase in endometrial carcinoma. Gynecol Oncol 95:32–36CrossRefPubMed Slomovitz BM, Broaddus RR, Schmandt R, Wu W, Oh JC, Ramondetta LM, Burke TW, Gershenson DM, Lu KH (2004) Expression of imatinib mesylate-targeted kinase in endometrial carcinoma. Gynecol Oncol 95:32–36CrossRefPubMed
28.
go back to reference Scobie JV, Acs G, Bandera CA, Blank SV, Wheeler JE, Pasha TL, Salscheider M, Zhang PJ (2003) C-kit immunoreactivity in endometrial adenocarcinoma and its clinicopathologic significance. Int J Gynecol Pathol 22:149–155CrossRefPubMed Scobie JV, Acs G, Bandera CA, Blank SV, Wheeler JE, Pasha TL, Salscheider M, Zhang PJ (2003) C-kit immunoreactivity in endometrial adenocarcinoma and its clinicopathologic significance. Int J Gynecol Pathol 22:149–155CrossRefPubMed
Metadata
Title
KIT-positive primary small cell carcinoma of the endometrium: a case report with immunohistochemical and molecular genetic analysis of KIT and PDGFRA genes
Author
Tadashi Terada
Publication date
01-10-2010
Publisher
Springer-Verlag
Published in
Archives of Gynecology and Obstetrics / Issue 4/2010
Print ISSN: 0932-0067
Electronic ISSN: 1432-0711
DOI
https://doi.org/10.1007/s00404-009-1324-5

Other articles of this Issue 4/2010

Archives of Gynecology and Obstetrics 4/2010 Go to the issue