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Poorly Differentiated Small Cell Carcinoma of the Sigmoid Colon Associated With Tubulo Villous Adenoma

Introduction

Small cell carcinoma of the sigmoid colon was considered to be very uncommon as more than 500 cases have been documented so far with 40 % confined to the rectum in origin (Scherwitz, Lindenfelser & Krüger, 2009).There is a controversy regarding the etiopathology of this disorder with some feeble belief on pleuripotent neuroendocrine stem cell. Available reports have described that afflicted individuals would survive upto 10-20 years after resection in contrast to the mean survival period of 5-11 months. There is need to throw light on this abnormal clinical finding keeping in view of the pertinent research literature.

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Case Presentation

A 74-year-old Caucasian female started developing a progressively worsening vague fatigue and abdominal pain from the early 2008.Her pathological findings revealed blood in her stools where as physical examination was normal except for right upper quadrant tenderness and hepatomegaly. On examining the patient with a colonoscopy, a rectal polyp was found at the rectosigmoid junction and its biopsy illustrated small cell carcinoma along with tubulovilousadenomatous features. There were total two stages of cancer identified such as T2NOM1, and grade three carcinoma. Therapy was started with etoposide and carbolatin and she is currently in the second cycle. A continuous follow up with the oncology clinic was recommended to her.

Discussion

Small cell carcinoma although considered rare is the second major disorder in highly developed countries as more than 940,000 cases were reported to occur globally contributing to approximately 500,000 deaths. Epidemiological studies have emphasized on reducing meat and enhancing vegetables and fruit consumption to lessen the incidence of small cell carcinoma episodes. Earlier, only 18 cases were known in the medical literature (Gelas Thomas et al., 2002). But it is reasonable to assume that this estimate could slightly increase. However, there is a need to focus on the pathophysiology of this rare oncogenic disorder. It was reported that a metabolite of cyclooxygenase-2A family such as Prostaglandin E (2) (PGE (2)) has a role in the tumorigenesis and tumor progression of colorectal cancer.

The receptor of PGE (2) known as the EP4 receptor contributes to metastasis in this specific malignancy (Shoji et a., 2002).This was further strengthened by another report that described the significance of PGE (2) receptor subtype EP(3) in suppressing cell growth and its downegulating effect on the improvement of colon carcinogenesis (Shoji et al., 2004).This particular aspect of pathophysiology was believed to occur due to hypermethylation of the EP (3) receptor gene0 (Shoji et al., 2004).Similarly, animal studies have revealed the upregulation of EP(1) and EP(2) subtypes and down regulation of EP(3). EP(1) and EP(4) contribute to aberrant crypt foci(Takahashi & Wakabayashi, 2004). Hence chemically induced colon carcinogenesis in animal models helps in understanding the pathophysioogy of colorectal neoplasia in man (Takahashi & Wakabayashi, 2004). Firstly, blocking EP4 receptor with EP4 antagonist could better help in the management of small cell carcinoma. Neoplasms of the large intestine such as small cell undifferentiated carcinoma (SCUC) was reported to arise from colorectum (Yasuim, Tsukamoto and Kudo,2006).As such, effective adjuvant therapy was reported to play vital role in the management of small cell carcinoma (Yasuim, Tsukamoto and Kudo,2006).It was reported that rare cases of neuroendocrine or small cell cancer (SCC) tumor, with adenocarcinoma were managed with immunocytochemistry positive for synaptophysin and chromogranin (Scherwitz, Lindenfelser & Krüger, 2009). Resection of the rectum with lymphadenectomy when performed could also yield better results as far as management is concerned (Izuishi, et al., 2002). Minimal access approaches such as laparoscopic cancer procedures were found to be beneficial in the management of variety of solid tumors (Greene et al., 2007). This is because patients with cancers of colon have shown improved benefits in contrast to conventional open techniques (Greene et al., 2007). Previously, attempts to treat rare a case of small-cell anaplastic carcinoma of the colon were insignificant as it did not involve a systematic protocol. Hence it may suggest an urgent need for an evidence based management (Villeta Plaza, et al., 1996). Biopsy specimens of the colon could better address the problem if applied in the present as it has produced good outcome for a patient with small cell carcinoma of the lung (Payne et al., 1996).

Further, a type of carcinoma such as oat-cell carcinoma of the rectum was found to be metastasizing to distant organs characterized by cellular polymorphism and hyperchromic nucleus. Hence cytological investigations may be required for the present case to gain better insights on the pathogenesis (Fornaro et al., 1991).It was revealed in study that identification of a spectrum of squamous, endocrine, and glandular features in large bowel tumors found with minimum differentiation was reliable in understanding the small cell carcinoma of large intestine (Burke et al., 1991). Therefore this approach has better implications. In an earlier description, cases of neuroendocrine small cell colorectal carcinoma were managed by identifying immunocytochemical data with the help of epithelial membrane antigen (EMA), carcinoembryonic antigen (CEA), neurofilaments (NF) (Wick, Weatherby & Weiland, 1987). In a much remote and important case, small cell carcinomas of the lung and three tumors of the large intestine with combined adenocarcinomatous were effectively addressed with histologic, histopathologic, and embryologic evidence (Sidhu, 1979).However, recent strategies focusing on small cell cancer of lung with special emphasis on the expression of Bcl-2 oncoprotein as a prognostic marker were reported (Ilievska Poposka et al., 2009). The efficacy of Bcl-2 may need to be explored in small cell carcinoma of colon. In a random study on metastatic tumors it was reported that immunohistochemical stains were reliable for determining the cell type and for making a perfect diagnosis (Plaza et al., 2008).

Conclusion

The present case has adequate pathological signs to support the documentation. More probably, there seems to be an association with the gastric discomfort such as abdominal pain and liver function. These problems could be bettered addressed with immunohistocemical, genomic and proteomic approaches. Further, as carcinomas other than colon and rectum such as lung, bile duct, and urethra have already been managed, there is a need to adopt the methodologies in evidence based manner and tried for the present case. This approach may have better implications in the perfect prognosis of metastatic regions at the earliest.

References

Burke AB, Shekitka KM, Sobin LH.1991. Small cell carcinomas of the large intestine. Am J Clin Pathol 95 (3):315-21.

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Fornaro R, Belcastro E, Lo Presti G, Estienne G, Antoniotti GV, Ferraris R.1991. A case of small-cell carcinoma of the rectum. Chir Ital 43(1-2): 55-60.

Gelas Thomas, PEYRAT Patrice, Francois Yves, Gerard J. Pierre, Baulieux Jacques Gilly F. Noël Vignal Jacques, Glehen Olivier.2002. Diseases of the colon & rectum 45:11, 1535-1540

Greene FL, Kercher KW, Nelson H, Teigland CM, Boller AM.2007. Minimal access cancer management. CA Cancer J Clin 57(5):300.

Ilievska Poposka, B., Smickova, S., Jovanovska Crvenkovska, S., Zafirovska Ivanovska, B., Stefanovski, T., Petrusevska, G.2009.Bcl-2 as a prognostic factor for survival in small-cell lung cancer.Prilozi 29(2):281-94.

Izuishi, K., Arai, T., Ochiai, A., Ono, M., Sugito, M., Tajiri, H., Saito, N. 2002. Long-term survival in advanced small cell carcinoma of the colorectum: report of a case. Surg Today 32(1): 72-74.

Payne, T, Mayfield-Stokes, S, Powers, J, Roy TM. 1994. Gastrointestinal hemorrhage and small cell carcinoma. J Ky Med Assoc 92 (4):140-2.

Plaza JA, Perez-Montiel D, Mayerson, J, Morrison C, Suster, S.2008. Metastases to soft tissue: a review of 118 cases over a 30-year period. Cancer 112(1):193-203.

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Scherwitz, P, Lindenfelser, R, Krüger, I.2002. Localization of primary small cell carcinoma with liver metastasis: a rare combination of colonic adenocarcinoma and undifferentiated small cell carcinoma. Chirurg 73(8):859-61.

Shoji Y, Takahashi M, Kitamura T, Watanabe K, Kawamori T, Maruyama T, Sugimoto Y, Negishi M, Narumiya S, Sugimura T, Wakabayashi K.(2004). Gut 53(8):1151-8.

Sidhu GS.1979. The endodermal origin of digestive and respiratory tract APUD cells. Histopathologic evidence and a review of the literature. Am J Pathol 96,:5-20

Takahashi M and Wakabayashi K. (2004). Gene mutations and altered gene expression in azoxymethane-induced colon carcinogenesis in rodents. Cancer Sci 95(6):475-80.

Villeta Plaza R, Alcalde Escribano J, Rodríguez Dapena S, Sánchez López, D, Ramia Angel, J M, Novo O, Ibarra Peláez A, Morales Gutiérrez C, Abad Barahona, A.1996. Small cell anaplastic carcinoma of the colon. Rev Esp Enferm Dig 88(1):46-8.

Wick MR, Weatherby, RP, Weiland, LH.1987. Small cell neuroendocrine carcinoma of the colon and rectum: clinical, histologic, and ultrastructural study and immunohistochemical comparison with cloacogenic carcinoma. Hum Pathol 18(1):9-21.

Yang L, Huang Y, Porta R, Yanagisawa K, Gonzalez A, Segi E, Johnson DH, Narumiya S, Carbone DP.2006.Host and direct antitumor effects and profound reduction in tumor metastasis with selective EP4 receptor antagonism 2006.Cancer Res 66(19):9665-72.

Yasuim, O, Tsukamoto, F, Kudo, K. 2006. Small cell undifferentiated carcinoma of the ascending colon with rapid enlargement after resection: report of a case and review of the literature.” Tohoku J Exp Med 209 (4):361-7

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