- Case report
- Open Access
- Open Peer Review
Carcinosarcoma of the colon: report of a case with morphological, ultrastructural and molecular analysis
© Ambrosini-Spaltro et al; licensee BioMed Central Ltd. 2006
- Received: 14 February 2006
- Accepted: 12 July 2006
- Published: 12 July 2006
Carcinosarcoma of the colon is a rare histopathological entity with uncertain histogenesis, that shows both epithelial and mesenchymal malignant differentiation. Carcinosarcoma rarely affects the gastrointestinal tract and only few cases are reported in the colon. Herein we describe a carcinosarcoma of the ascending colon, with morphological, ultrastructural and molecular analysis.
An 81-year-old man was hospitalised for asthenia, weight loss and iron-deficiency anaemia. The patient underwent colonoscopy and adenocarcinoma was diagnosed by endoscopic biopsy. A right hemicolectomy was performed and, during surgical operation, liver metastases were detected. Histological examination of the surgical specimen revealed areas of both carcinomatous and sarcomatous differentiation, completely separated by fibrous septae. The sarcomatous component exhibited areas of smooth muscle and osteoblastic differentiation, with focal osteoid material deposition. Molecular analysis conducted separately on the epithelial and mesenchymal components revealed the same p53 gene mutation (R282W in exon 8) and identical polymorphisms in p53 exon 4, in EGFR exons 20 and 21, and in c-kit exon 17. Microsatellite markers analysis revealed a common loss of heterozygosis on 18q. Overall, the data are consistent with a common origin of the two tumor components. The patient was treated with 8 cycles of oral capecitabine (1250 mg/m2 twice a day for 14 days repeated every 28 days) and two years after surgery is alive with liver metastases.
Carcinosarcoma of the colon is a rare tumour with both epithelial and sarcomatous components. Molecular analysis of the current case suggests the histogenesis from a common cell progenitor.
- Carotid Artery Disease
- Sarcomatoid Carcinoma
- Sarcomatous Component
Carcinosarcoma is a rare histopathological entity, exhibiting both epithelial and mesenchymal malignant differentiation, with uncertain histogenesis. Carcinosarcoma has been described in various organs, although head and neck, and female urogenital system are the most frequent sites of occurrence . In the gastrointestinal tract, carcinosarcoma arises predominantly in the oesophagus, in the stomach and in the biliary tract , whereas carcinosarcoma of the large intestine has been reported only rarely. This type of tumour generally displays an aggressive behaviour and poor prognosis. Herein we present a case of carcinosarcoma of the ascending colon.
An 81-year-old man with a past medical history of atherosclerotic heart disease, arterial hypertension, mitral insufficiency, bilateral carotid artery disease and early chronic renal failure was hospitalised for asthenia and weight loss. Laboratory investigation revealed iron-deficiency anaemia, with low haemoglobin (Hb) concentration (7.8 g/dl; normal range: 13–17 g/dL), median cellular volume (MCV) level (67.2 fl; normal range: 80–97 fl) and serum ferritin concentration (3.3 ng/mL; normal range: 30–400 ng/dL). Serum levels of carcinoembryonic antigen (CEA), carbohydrate antigen (CA) 19-9 and alphafoetoprotein (AFP) were within normal limits. Stool guaiac was positive for occult blood. Colonoscopy demonstrated an exophytic mass in the ascending colon and multiple diverticula in the entire colon, especially in the sigmoid region. Endoscopic biopsies were performed and at histological examination, adenocarcinoma was diagnosed. Chest x-ray was negative for metastatic disease. A week later a right hemicolectomy and regional lymph node dissection were performed. During surgery, liver metastases were detected. Computer tomography (CT) scan carried out after surgery identified 3 liver nodules in segment 4, in segment 8 and in segment 5, measuring 15 cm, 10 cm and 10 cm in their greatest dimension, respectively. The patient was subsequently treated with capecitabine at 1250 mg/m2 orally twice a day for 14 days repeated every 28 days for 8 cycles. Capecitabine was chosen for adjuvant therapy in this case since it has been reported to be as effective as 5-fluorouracil but with milder side effects in stage III colon cancer . No specific chemotherapeutic agents have been shown to be effective in carcinosarcoma . Two years after surgical treatment, the patient is alive with liver metastases.
Representative sections of the tumour and all lymph nodes isolated from the surrounding adipose tissue were fixed in 10% buffered neutral formalin, embedded in paraffin and routinely processed. From each block, 5 μm-thick sections were cut and stained with haematoxylin and eosin (H&E).
List of antibodies used
c-kit, CD 117
Smooth Muscle Actin
For ultrastructural examination, small samples were retrieved from paraffin-embedded material, deparaffinised in xylene, rehydrated in ethanol, post-fixed in osmium tetroxyde (OsO4), dehydrated and embedded in epoxy resin. Ultrathin sections were counterstained in uranile acetate and lead citrate and observed in a Jeol JEM 1010 (Tokyo, Japan) electron microscope operating at 80 kV.
Running methods and temperature used for DHPLC mutation detection
Starting Gradient (%B)
The surgical specimen included a 4 cm long ileal segment, a 13.5 cm long colonic segment, and the caecal appendix. At the ileocaecal valve, on the colonic side, an exophytic, centrally ulcerated mass, measuring 7 cm in its greatest dimension, was documented. Twenty-two lymph nodes were isolated from the adipose tissue surrounding the bowel wall.
Cases of carcinosarcoma reported in literature
Weidner, 1986 
DOD 4 years
Staroz F, 1995 
DOD some months later
Roncaroli, 1995 
DOD 6 months
Isimbaldi, 1996 
NED 2 years
Gentile, 1997 
DOD 2 months
Bertram, 1997 
DOD 5 months
Serio, 1997 
NED 6 months
Shoji, 1998 
NED 16 months
Nakao, 1998 
NED 14 months
Takeyoshi, 2000 
DOD 6 months
Shah, 2001 
DOD 5 months
Kim, 2001 
DOD 4 months
Di Vizio, 2001 
DOD 21 months
Ishida, 2003 
DOD 6 months
Aramendi, 2003 
ARF after 4 hours
Macaigne, 2004 
DOD 2 months
Kim, 2005 
AWD 2 years
Herein we report a carcinosarcoma with distinct epithelial and mesenchymal components, at the morphological, immunohistochemical and ultrastructural levels. Moreover, the sarcomatous component was composed of cells reminiscent of smooth muscle differentiation and cells with osteoblastic appearance. Some authors classified as large bowel carcinosarcomas epithelial tumours with areas of sarcomatoid differentiation, weakly immunoreactive for cytokeratins and with no evidence of osteosarcomatous nor chondrosarcomatous differentation [12, 13, 20, 21]. According to Aramendi et al., these cases are not properly carcinosarcomas, but should be considered sarcomatoid poorly differentiated carcinomas . In the present case, the sarcomatous component completely lacked any epithelial signs of differentiation; furthermore, we noted areas of osteosarcomatous differentiation and osteoid material deposition. The topographic distribution was remarkable for the complete separation of the two components. Ultrastructural examination confirmed such distinct separation. Bertram et al. instead reported intermixed epithelial and mesenchymal components . Other authors have classified as carcinosarcomas or sarcomatoid carcinomas tumours with sarcomatous features immunoreactive for cytokeratin and epithelial membrane antigen (EMA), but lacking carcinomatous component [4, 15, 16]. Shoji highlights the difficulty in making the correct diagnosis, since sarcomatous component closely resembles sarcoma, except for cytokeratin-immunoreactivity .
Treatment, as underlined by Bertram et al., should follow guidelines for common colon adenocarcinomas  and the poor prognosis associated with this tumour should require a strict follow-up. Remarkably, the patient reported here is still alive, two years after surgical resection of the primary tumour, despite the presence of liver metastases. Therefore we believe that aggressive therapy may be indicated in these tumours.
The histogenesis of carcinosarcoma is still controversial. Morphologically, the presence of distinct carcinomatous and sarcomatous components suggests a different origin (multiclonal hypothesis). The molecular analysis performed in the current case supports the hypothesis of a common cell precursor (monoclonal hypothesis), since the same mutation R282W in exon 8 of the p53 gene as well as the same allelic status, with the loss of 18q21, were identified in both carcinomatous and sarcomatous components.
Studies conducted on carcinosarcomas of nasopharynx , uterus [26, 27] and breast , documented a large overlap of cytogenetic and molecular alterations in the two tumour components. Furthermore, Van Rees et al.  described an uncommon case of adenosquamous carcinoma raised in a Barrett esophagus where the two malignant components showed loss of the same allele at all informative chromosomal markers tested as well as the same missense mutation in the p53 tumor-suppressor gene. All these findings are consistent with our results suggesting the hypothesis of a common progenitor of both epithelial and mesenchymal components. Therefore morphological divergence, even at the extreme levels displayed by carcinosarcomas, necessarily appears late in tumor progression, well after the initial hits that cause cancer.
Herein we describe a case of carcinosarcoma of the colon, with epithelial and mesenchymal components, completely different and separate at the morphological, immunohistochemical and ultrastructural levels. Molecular analysis revealed the same mutation R282W in exon 8 of the p53 gene and identical LOH for D18S585, D18S35 and D18S51 in both carcinomatous and sarcomatous components, supporting the hypothesis of a common cell progenitor.
We thank Patrizia Doi for immunohistochemical studies and Maria Saponaro for molecular studies. Written consent was obtained from the patient for publication of study.
- Wick MR, Swanson PE: Carcinosarcomas: current perspectives and an histological review of nosological concepts. Semin Diagn Pathol. 1993, 10: 118-127.PubMedGoogle Scholar
- Iezzoni JC, Mills SE: Sarcomatoid carcinomas (carcinosarcomas) of the gastrointestinal tract: a review. Semin Diagn Pathol. 1993, 10: 176-187.PubMedGoogle Scholar
- Twelves C, Wong A, Nowacki MP, Abt M, Burris H, Carrato A, Cassidy J, Cervantes A, Fagerberg J, Georgoulias V, Husseini F, Jodrell D, Koralewski P, Kroning H, Maroun J, Marschner N, McKendrick J, Pawlicki M, Rosso R, Schuller J, Seitz JF, Stabuc B, Tujakowski J, Van Hazel G, Zaluski J, Scheithauer W: Capecitabine as adjuvant treatment for stage III colon cancer. N Engl J Med. 2005, 352: 2696-704. 10.1056/NEJMoa043116.View ArticlePubMedGoogle Scholar
- Kim N, Luchs JS, Halpern D, Davis E, Donovan V, Weston SR, Katz DS: Radiology-pathology conference: carcinosarcoma of the colon. J Clin Imag. 2005, 29: 259-262. 10.1016/j.clinimag.2004.09.002.View ArticleGoogle Scholar
- Lynch TJ, Bell DW, Sordella R, Gurubhagavatula S, Okimoto RA, Brannigan BW, Harris PL, Haserlat SM, Supko JG, Haluska FG, Louis DN, Christiani DC, Settleman J, Haber DA: Activating Mutations in the Epidermal Growth Factor Receptor Underlying Responsiveness of Non-Small-Cell Lung Cancer to Gefitinib. N Engl J Med. 2004, 350: 2129-2139. 10.1056/NEJMoa040938.View ArticlePubMedGoogle Scholar
- Romagnoli S, Graziani D, Bramerio M, Gambacorta M, Colombo P, Roncalli M, Coggi G, Bosari S: Immunohistochemical profile and c-kit mutations in gastrointestinal stromal tumors. Pathol Res Pract. 2005, 201: 71-81. 10.1016/j.prp.2005.01.005.View ArticlePubMedGoogle Scholar
- Marchetti A, Buttitta F, Merlo G, Diella F, Pellegrini S, Pepe S, Macchiarini P, Chella A, Angeletti CA, Callahan R: p53 alterations in non-small cell lung cancers correlate with metastatic involvement of hilar and mediastinal lymph nodes. Cancer Res. 1993, 53: 2846-2851.PubMedGoogle Scholar
- Sobin LH, Wittekind Ch, Eds: TNM classification of malignant tumours. 2002, New York: John Wiley & SonsGoogle Scholar
- Weidner N, Zekan P: Carcinosarcoma of the colon – Report of a unique case with light and immuoistochemical studies. Cancer. 1986, 58: 1126-1130. 10.1002/1097-0142(19860901)58:5<1126::AID-CNCR2820580525>3.0.CO;2-Q.View ArticlePubMedGoogle Scholar
- Staroz F, Botton A, Potet F: Tumeurs malignes du colon a double composante (carcinosarcomes). A propos d'un cas. Ann Pathol. 1995, 15: 457-458.PubMedGoogle Scholar
- Roncaroli F, Montironi R, Feliciotti F, Losi L, Eusebi V: Sarcomatoid carcinoma of the anorectal junction with neuroendocrine and rhabdomyoblastic features. Am J Surg Pathol. 1995, 19: 217-223.View ArticlePubMedGoogle Scholar
- Isimbaldi G, Sironi M, Assi A: Sarcomatoid carcinoma of the colon: report of the second case with immuonohistochemical study. Pathol Res Pract. 1996, 192: 483-487.View ArticlePubMedGoogle Scholar
- Gentile R, Castellaneta A: Carcinosarcoma of the colon, one or two tumors?. Pathologica. 1997, 89: 62-68.PubMedGoogle Scholar
- Bertram P, Treutner KH, Lietze L, Schumpelick V: True carcinosarcoma of the colon. Langenbecks Arch Chir. 1997, 382: 173-174.PubMedGoogle Scholar
- Serio G, Aguzzi A: Spindle and giant cell carcinoma of the colon. Histopathology. 1997, 30: 383-358. 10.1046/j.1365-2559.1997.d01-610.x.View ArticlePubMedGoogle Scholar
- Shoji M, Dobashi Y, Iwabuchi K, Kuwao S, Mikami T, Kameya T: Sarcomatoid carcinoma of the descending colon – A histological, immunoistochemical and ultrastructural analysis. Acta Oncol. 1998, 37: 765-768. 10.1080/028418698430179.View ArticlePubMedGoogle Scholar
- Nakao A, Sakagami K, Uda M, Mitsuoka S, Ito H: Carcinosarcoma of the colon: report of a case and review of the literature. J Gastroenterol. 1998, 33: 276-279. 10.1007/s005350050083.View ArticlePubMedGoogle Scholar
- Takeyoshi I, Yoshida M, Ohwada S, Yamada T, Yanagisawa A, Morishita Y: Skin metastasis from the spindle cell component in rectal carcinosarcoma. Hepatogastroenetrology. 2000, 47: 1611-1614.Google Scholar
- Shah S, Kim DH, Harster G, Hossain A: Carcinosarcoma of the colon and spleen – A fleshy purple mass on colonoscopy. Dig Dis Sci. 2001, 46: 106-108. 10.1023/A:1005682413793.View ArticlePubMedGoogle Scholar
- Kim JH, Moon WS, Kang MJ, Park MJ, Lee DG: Sarcomatoid carcinoma of the colon: a case report. J Korean Med Sci. 2001, 16: 657-660.View ArticlePubMedPubMed CentralGoogle Scholar
- Di Vizio D, Insabato L, Zafonte BT, Ferrara G, Pettinato G: Sarcomatoid carcinoma of the colon: a case reoport with literature review. Tumori. 2001, 87: 431-435.PubMedGoogle Scholar
- Ishida H, Ohsawa T, Nakada H, Hashimoto D, Ohkubo T, Adachi A, Itoyama S: Carcinosarcoma of the rectosigmoid colon: report of a case. Surg Today. 2003, 33: 545-549.PubMedGoogle Scholar
- Aramendi T, Fernández-Aceñero MJ, Villanueva MC: Carcinosarcoma of the colon: report of a rare tumor. Pathol Res Pract. 2003, 199: 345-348. 10.1078/0344-0338-0428.View ArticlePubMedGoogle Scholar
- Macaigne G, Aouad K, Boivin JF, Bellaïche A, Auriault ML, Picard D, Deplus R: Carcinome sarcomatoïde du colon: presentation d'un cas et revue de la littérature. Gastroenterol Clin Biol. 2004, 28: 600-604.View ArticlePubMedGoogle Scholar
- Torenbeek R, Hermsen MAJA, Meijer GA, Baak JPA, Meijer CJLM: Analysis by comparative genomic hybridization of epithelial and spindle cell components in sarcomatoid carcinoma and carcinosarcomas: histogenetic aspects. J Pathol. 1999, 189: 338-343. 10.1002/(SICI)1096-9896(199911)189:3<338::AID-PATH429>3.0.CO;2-Q.View ArticlePubMedGoogle Scholar
- Thompson L, Chang B, Barsky SH: Monoclonal origins of malignant mixed tumors (carcinosarcomas): evidence for a divergent histogenesis. Am J Surg Pathol. 1996, 20: 277-185. 10.1097/00000478-199603000-00003.View ArticlePubMedGoogle Scholar
- Gorai I, Yanagibashi T, Taki A, Udagawa K, Miyagi E, Nakazawa T, Hirahara F, Nagashima Y, Minaguchi : Uterine carcinosarcoma is derived from a single stem cells: an in vitro study. Int J Cancer. 1997, 72: 821-827. 10.1002/(SICI)1097-0215(19970904)72:5<821::AID-IJC19>3.0.CO;2-B.View ArticlePubMedGoogle Scholar
- Wada H, Enomoto T, Tsujimoto M, Nomura T, Murata Y, Shroyer KR: Carcinosarcoma of the breast: molecular-biological study for analysis of histogenesis. Hum Pathol. 1998, 29: 1324-1328. 10.1016/S0046-8177(98)90266-0.View ArticlePubMedGoogle Scholar
- Van Rees B, Rouse R, De Wit M, Van Noesel C, Tytgat G, Lanschot J, Offerhaus G: Molecular evidence for the same clonal origin of both components of an adenosquamous barrett carcinoma. Gastroenterology. 2002, 122: 784-788. 10.1053/gast.2002.31903.View ArticlePubMedGoogle Scholar
- The pre-publication history for this paper can be accessed here:http://0-www.biomedcentral.com.brum.beds.ac.uk/1471-2407/6/185/prepub
This article is published under license to BioMed Central Ltd. This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.