Alpha-fetoprotein-producing early rectal carcinoma: a rare case report and review
- Hiroyuki Anzai1Email author,
- Shinsuke Kazama1,
- Tomomichi Kiyomatsu1,
- Takeshi Nishikawa1,
- Toshiaki Tanaka1,
- Junichiro Tanaka1,
- Keisuke Hata1,
- Kazushige Kawai1,
- Hironori Yamaguchi1,
- Hiroaki Nozawa1,
- Takamitsu Kanazawa1,
- Tetsuo Ushiku2,
- Soichiro Ishihara1,
- Eiji Sunami1,
- Masashi Fukayama2 and
- Toshiaki Watanabe1
© Anzai et al.; licensee BioMed Central. 2015
Received: 1 November 2014
Accepted: 24 April 2015
Published: 12 May 2015
Alpha-fetoprotein (AFP)-producing rectal cancer is very rare, and this type of cancer frequently metastasizes to the liver with a poor prognosis. To date, only 11 cases of AFP-producing colorectal cancer have been reported.
A 41-year-old woman was first presented to the hospital for anal bleeding. An elevated tumor with a central shallow depression in the lower rectum was detected by colonoscopy. Transanal excision was performed, and the histology revealed adenocarcinoma. Further immunohistopathological examination revealed that the tumor was an AFP-producing adenocarcinoma of the rectum. Although local resection was performed 2 months before the diagnosis of AFP tumor, the serum AFP level was normal. The depth of the submucosal invasion was 5,000 μm, and there was venous invasion. Also, no lymphatic invasion was detected. Therefore, additional surgical resection with lymph node dissection was conducted, and the patient underwent laparoscopic intersphincteric resection. No residual cancer was identified in the surgical specimens, and there was no evidence of lymph node metastasis. The patient was discharged 18 days postoperatively, and 12 months after the operation, there are no signs of recurrence.
To the best of our knowledge, this is the first case of an AFP-producing rectal cancer that was diagnosed at an early stage.
Alpha-fetoprotein (AFP), a serum glycoprotein with a molecular weight of approximately 70 kDa, develops during gestation and is produced from fetal liver and yolk sac . It was first described in 1963 by Abeleb et al. . Immediately after birth, serum AFP levels are high, approximately 10,000 ng/mL but decrease rapidly, and by the second year of life and thereafter are less than 10 ng/mL. Some tumors produce AFP and lead to an increase in serum AFP levels. Therefore, AFP is a useful tumor marker in the diagnosis of tumors, such as hepatocellular carcinomas, hepatoblastoma, and yolk sac tumors [3-5]. AFP-producing tumors have mainly been reported in organs originating from the foregut endoderm . The majority of AFP-producing cancers originate from the stomach, bile duct, and pancreas. However, AFP-producing colorectal cancer is extremely rare because the colorectum originates from the hindgut endoderm. Only 11 cases of AFP-producing colorectal cancer have been reported in English literature to date. Here, we report a case with early rectal cancer diagnosed as an AFP-producing tumor by immunohistochemistry. AFP-producing tumors have been reported to frequently metastasize to the liver and have a poor prognosis. However, the tumor in the present case was diagnosed at an early stage and no distant metastases were detected simultaneously [7-17]. To the best of our knowledge, this is the first case of an early diagnosis of an AFP-producing rectal cancer reported in English literature.
We report on a patient with AFP-producing rectal cancer diagnosed at an early stage. Although local resection was performed 2 months before the diagnosis of AFP tumor, the serum AFP levels of 2 months after the initial operation were normal. In Japanese literature, there are only two reported cases of AFP-producing colorectal disease detected in the early stages, which were T1 N0 and T2 N0 colorectal cancer, respectively[18,19]. AFP-producing cancer is defined by positively stained tumor of anti-AFP monoclonal antibody. Several reports describe that AFP-producing gastric cancer (AFP-GC) has an aggressive clinical course and poorer prognosis than AFP-negative GC. Interestingly, there are similarities with AFP-producing colorectal cancer and AFP-GC that it rapidly progresses and frequently metastasizes into the liver and show poor prognosis.
Clinical features of reported cases of AFP-producing colorectal carcinomas
Pretherapy AFP level (ng/ml)
Depth of invasion
Lymph node metastasis
Nakajima et al. 
Yu et al. 
Sato et al. 
Hocking et al. 
Kato et al. 
Taguchi et al. 
Kurihara et al. 
Ishikura et al. 
Lattes et al. 
Yachida et al. 
Fu et al. 
Several studies have demonstrated the histopathological factors that predict lymph node metastasis of T1 stage colorectal cancer. The rate of lymph node metastasis of submucosal cancer has been reported to be 6% to 12% . The risk factors for lymph node metastasis in submucosal colorectal cancers include poor differentiation, lymphatic invasion, vascular invasion, deep submucosal invasion, or a positive resection margin [22-24]. In the present case, the risk factors of massive invasion and vascular invasion were detected, which led us to perform the additional surgery.
In conclusion, we report on an AFP-producing colon cancer diagnosed at an early stage, whereby early detection enabled a complete resection of the carcinoma. It is important to note that management of a patient with an elevated tumor with a shallow depression, even when no malignancy is detected, should include local excision for immunohistopathological analysis. Although serum AFP levels have been high in all previously reported cases, it is important to remember that serum AFP levels may not rise in the early stages of AFP-producing cancer. Further accumulation of data and investigation of AFP-producing colon cancer is necessary.
Written informed consent was obtained from the patient for publication of this case report and accompanying images.
The authors wish to thank Tetsuo Ushiku for pathological diagnosis.
- Bergstrand CG, Czar B. Demonstration of a new protein fraction in serum from the human fetus. Scand J Clin Lab Invest. 1956;8:174.View ArticlePubMedGoogle Scholar
- Abelev GI, Perova SD, Khramkova NI, Postnikova ZA, Irlin IS. Production of embryonal alpha-globulin by transplantable mouse hepatomas. Transplantation. 1963;1:174–80.View ArticlePubMedGoogle Scholar
- Norgaard-Pedersen B, Albrechtsen R, Teilum G. Serum alpha-foetoprotein as a marker for endodermal sinus tumour (yolk sac tumour) or a vitelline component of “teratocarcinoma”. Acta Pathol Microbiol Scand A. 1975;83:573–89.PubMedGoogle Scholar
- O'Conor GT, Tatarinov YS, Abelev GI, Uriel J. A collaborative study for the evaluation of a serologic test for primary liver cancer. Cancer. 1970;25:1091–8.View ArticlePubMedGoogle Scholar
- Smith CJ, Ajdukiewicz A, Kelleher PC. Concanavalin-A-affinity molecular heterogeneity of human hepatoma AFP and cord-serum AFP. Ann N Y Acad Sci. 1983;417:69–74.View ArticlePubMedGoogle Scholar
- McIntire KR, Waldmann TA, Moertel CG, Go VL. Serum alpha-fetoprotein in patients with neoplasms of the gastrointestinal tract. Cancer Res. 1975;35:991–6.PubMedGoogle Scholar
- Nakajima T, Okazaki N, Morinaga S, Tsumuraya M, Shimosato Y, Saiki S. A case of alpha-fetoprotein-producing rectal carcinoma. Jpn J Clin Oncol. 1985;15:679–85.PubMedGoogle Scholar
- Yu YY, Ogino T, Okada S. An alpha-fetoprotein-producing carcinoma of the rectum. Acta Pathol Jpn. 1992;42:684–7.PubMedGoogle Scholar
- Sato Y, Sekine T, Ohwada S. Alpha-fetoprotein-producing rectal cancer: calculated tumor marker doubling time. J Surg Oncol. 1994;55:265–8.View ArticlePubMedGoogle Scholar
- Hocking GR, Shembrey M, Hay D, Ostor AG. Alpha-fetoprotein-producing adenocarcinoma of the sigmoid colon with possible hepatoid differentiation. Pathology. 1995;27:277–9.View ArticlePubMedGoogle Scholar
- Kato K, Matsuda M, Ingu A, Imai M, Kasai S, Mito M, et al. Colon cancer with a high serum alpha-fetoprotein level. Am J Gastroenterol. 1996;91:1045–6.PubMedGoogle Scholar
- Taguchi J, Yano H, Sueda J, Yamaguchi R, Kojiro M, Shirouzu G, et al. alpha-Fetoprotein-producing rectal carcinoma - a case report. Kurume Med J. 1997;44:339–48.Google Scholar
- Kurihara K, Konishi F, Kanazawa K, Fujii T, Saito K. Alpha-fetoprotein-producing carcinoma of the colon: report of a case. Surg Today. 1997;27:453–6.View ArticlePubMedGoogle Scholar
- Ishikura H, Kishimoto T, Andachi H, Kakuta Y, Yoshiki T. Gastrointestinal hepatoid adenocarcinoma: venous permeation and mimicry of hepatocellular carcinoma, a report of four cases. Histopathology. 1997;31:47–54.View ArticlePubMedGoogle Scholar
- Lattes C, Carella R, Faggioli S, Gabusi E, Grigioni WF. Hepatoid adenocarcinoma of the rectum arising in ulcerative colitis: report of a case. Dis Colon Rectum. 2000;43:105–8.View ArticlePubMedGoogle Scholar
- Yachida S, Fukushima N, Nakanishi Y, Akasu T, Kitamura H, Sakamoto M, et al. Alpha-fetoprotein-producing carcinoma of the colon: report of a case and review of the literature. Dis Colon Rectum. 2003;46:826–31.View ArticlePubMedGoogle Scholar
- Fu K, Kobayashi A, Saito N, Sano Y, Kato S, Ikematsu H, et al. Alpha-fetoprotein-producing colon cancer with atypical bulky lymph node metastasis. World J Gastroenterol. 2006;12:7715–6.PubMed CentralPubMedGoogle Scholar
- Nakagawa K, Koike S, Matsumura H, Yokoi K. Kitamura H [alpha-fetoprotein producing rectal cancer]. Gan To Kagaku Ryoho. 2012;39:671–4.PubMedGoogle Scholar
- Shiwaku H. Alpha-fetoprotein producing carcinoma of sigmoid colon; [article in Japanese]. Jpn Gastroenterol Surg. 2007;40:134–40.View ArticleGoogle Scholar
- Hishinuma M, Ohashi KI, Yamauchi N, Kashima T, Uozaki H, Ota S, et al. Hepatocellular oncofetal protein, glypican 3 is a sensitive marker for alpha-fetoprotein-producing gastric carcinoma. Histopathology. 2006;49:479–86.View ArticlePubMedGoogle Scholar
- Kitajima K, Fujimori T, Fujii S, Takeda J, Ohkura Y, Kawamata H, et al. Correlations between lymph node metastasis and depth of submucosal invasion in submucosal invasive colorectal carcinoma: a Japanese collaborative study. J Gastroenterol. 2004;39:534–43.View ArticlePubMedGoogle Scholar
- Netzer P, Forster C, Biral R, Ruchti C, Neuweiler J, Stauffer E, et al. Risk factor assessment of endoscopically removed malignant colorectal polyps. Gut. 1998;43:669–74.View ArticlePubMed CentralPubMedGoogle Scholar
- Seitz U, Bohnacker S, Seewald S, Thonke F, Brand B, Braiutigam T, et al. Is endoscopic polypectomy an adequate therapy for malignant colorectal adenomas? Presentation of 114 patients and review of the literature. Dis Colon Rectum. 2004;47:1789–96. discussion 1796–1787.View ArticlePubMedGoogle Scholar
- Yasuda K, Inomata M, Shiromizu A, Shiraishi N, Higashi H, Kitano S. Risk factors for occult lymph node metastasis of colorectal cancer invading the submucosa and indications for endoscopic mucosal resection. Dis Colon Rectum. 2007;50:1370–6.View ArticlePubMedGoogle Scholar
This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.