Pedunculated Polyp of Early Sigmoid Colon Cancer with Invasive Micropapillary Carcinoma

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1 Japanese Journal of Clinical Oncology Advance Access published June 26, 2009 Jpn J Clin Oncol 2009 doi: /jjco/hyp051 Case Report Pedunculated Polyp of Early Sigmoid Colon Cancer with Invasive Micropapillary Carcinoma Hiroshi Sonoo 1, Masao Kameyama 1, Naoki Inatugi 2, Akitaka Nonomura 3 and Yasunori Enomoto 3 1 Department of Surgery, Bell Land General Hospital, Osaka, 2 Center of Coloproctology, Dongo Hospital and 3 Department of Diagnostic Pathology, Nara Medical University School of Medicine, Nara, Japan Received June 23, 2008; accepted April 10, 2009 A 64-year-old man was admitted to Dongo Hospital (Nara, Japan) with colonic cancer, following the onset of abdominal pain, diarrhea and fever. A pedunculated polyp was detected in the sigmoid colon by colonoscopy, and laparoscopy-assisted sigmoidectomy with regional lymph node resection was performed. Histopathologically, the tumor exhibited massive invasion of the submucosa, and multiple lymph node metastases were detected. The tumor mainly consisted of a micropapillary component. Immunohistochemically, MUC1 was expressed at the stromal edge of the micropapillary component and showed the characteristic inside-out pattern of a micropapillary carcinoma. The multiple lymph node metastases were predominantly composed of carcinoma with a micropapillary pattern. Our case suggests that when a micropapillary component is identified in a pre-operative biopsy specimen, even for a pedunculated early colorectal cancer, the extent of surgical resection should be carefully considered due to the high potential for nodal metastasis. Key words: micropapillary carcinoma early colonic cancer lymph node metastasis INTRODUCTION Invasive micropapillary carcinoma (MC) is defined as a carcinoma composed of small clusters of tumor cells lying within clear stromal spaces simulating vascular channels (1) and is known to be associated with a high incidence of nodal metastasis (2). MC has been reported in various organs, including the breast (2 8), lung, ovary, urinary bladder, salivary gland (9 12) and colorectum (13 15), but its incidence in early colorectal cancer has not been described. We experienced a patient with pedunculated early sigmoid colon cancer, which had a micropapillary component and multiple nodal metastases. In the present report, we describe the clinicopathological and histochemical features of this early sigmoid colon cancer with a micropapillary component and review some reports in the English medical literature. For reprints and all correspondence: Hiroshi Sonoo, Department of Surgery, Bell Land General Hospital, Higashiyama, Naka-ku, Sakai-city, Osaka , Japan. h_sonoo@seichokai.or.jp CASE REPORT A 64-year-old man was admitted to Dongo Hospital (Nara, Japan) with colonic cancer, following the onset of abdominal pain, diarrhea and fever. A pedunculated polyp of 3 cm in diameter was detected in the sigmoid colon by colonoscopy (Fig. 1). The histological diagnosis of a biopsy specimen was moderately differentiated tubular adenocarcinoma. A barium enema revealed wall deformities in the sigmoid colon (Fig. 2a). Abdominal computed tomography revealed regional lymph node swelling (Fig. 2b). The pre-operative diagnosis was early sigmoid colon cancer with stalk invasion, and laparoscopy-assisted sigmoidectomy and regional lymph node resection were performed. Macroscopically, the tumor was a pedunculated polyp of mm with a flat tumor head that resembled a crown (Fig. 3). Microscopically, massive submucosal invasion of 1500 mm from the muscular layer of the mucosa (Fig. 4), extensive lymphatic invasion (Fig. 5a) and mild venous vessel invasion were observed (Fig. 5b). The tumor was mainly composed of atypical cells arranged in micropapillary structures and tumor cell clusters were observed to # The Author (2009). Published by Oxford University Press. All rights reserved.

2 Page 2 of 5 Pedunculated polyp of early sigmoid colon cancer Figure 1. A pedunculated polyp of 3 cmindiameterisdetectedinthe sigmoid colon by colonoscopy. A color version of this figure is available as supplementary data at Figure 3. Macroscopic findings of the invasive micropapillary carcinoma. The tumor is a pedunculated polyp of mm with a flat tumor head that resembles a crown. A color version of this figure is available as supplementary data at Figure 4. A loupe image shows massive submucosal invasion of 1500 mm from the muscular layer of the mucosa. A color version of this figure is available as supplementary data at oxfordjournals.org. Figure 2. (a) A barium enema shows wall deformities in the sigmoid colon. (b) Abdominal computed tomography shows regional lymph node swelling. float in clear spaces (Fig. 6a and b). Immunohistochemically, MUC1 (Ma695 NCL-MUC-1 Novocastra) expression was observed in a luminal staining pattern in typical adenocarcinoma foci, but at the stromal edges of tumor clusters in the micropapillary structures (Fig. 7). The latter staining represented the characteristic inside-out pattern of MC and we diagnosed the tumor as an MC. The micropapillary structures comprised 80% of the tumor, and the remaining 20% was moderately differentiated tubular adenocarcinoma. Regional lymph node (paracolic lymph node) metastases predominantly composed of carcinoma with a micropapillary pattern were detected (Fig. 8). The final pathological stage was A (TNM classification). At the present time, the patient has received adjuvant chemotherapy for 25 months after the operation without recurrence.

3 Jpn J Clin Oncol 2009 Page 3 of 5 Figure 5. (a) Immunohistochemical staining for D2-40 reveals extensive lymphatic invasion. (b) Immunohistochemical staining for EVG reveals mild venous invasion. A color version of this figure is available as supplementary data at DISCUSSION Since Siriaunkgul and Tavassoli (3) reported that an MC was a rare variant of invasive breast carcinoma and that the micropapillary pattern was maintained in metastatic foci, MC has been reported to be an aggressive variant of breast carcinoma with a high incidence of lymph node metastases and poor clinical outcome (2,4,10,13 15). MC has distinctive histological features characterized by tufts of tumor cells arranged in pseudopapillary structures devoid of fibrovascular cores and surrounded by empty and clear spaces bounded by fibrocollagenous tissue (13). This pseudopapillary structure resembles lymphatic invasion but has been attributed to inversion of cell polarization, meaning that an epithelial membrane is present on the outer surface of the cell clusters. This was confirmed in the present study by immunostaining for MUC1, a glycoprotein normally located on the apical cell surface of normal glandular epithelia, which showed a characteristic inside-out pattern Figure 6. (a) The tumor is mainly composed of micropapillary structures. The proportion of the micropapillary component is 80%, and the remaining 20% is moderately differentiated adenocarcinoma. (b) Papillary cell clusters are surrounded by clear empty spaces. A color version of this figure is available as supplementary data at (16,17). It has been supposed that the reverse polarization of the epithelial cells in an MC is related to their ability to invade vessels (16,17). To the best of our knowledge, there are only three previous reports of a micropapillary colorectal carcinoma, especially early colorectal carcinoma, and no previous reports of colorectal MC. Kim et al. (14) reported that the positive rate for nodal metastasis was higher in MC (74.5%, 41/55 cases) than in conventional adenocarcinoma (33.6%, 40/119 cases, P, 0.001). Haupt et al. (15) showed that the presence of MC is an independent predictor of nodal metastasis. In our case, the presence of MC in the colorectum was closely related with nodal metastasis, similar to the case for MCs in other organs.

4 Page 4 of 5 Pedunculated polyp of early sigmoid colon cancer Figure 7. Immunohistochemical staining for MUC1 reveals that the outer surfaces of the cell clusters are positive, resembling the characteristic inside-out pattern of a micropapillary carcinoma. A color version of this figure is available as supplementary data at Figure 8. Regional lymph node metastases composed predominantly of carcinoma with the micropapillary pattern are detected. A color version of this figure is available as supplementary data at Figure 9. The tumor is mainly composed of micropapillary structures in the biopsy specimen. A color version of this figure is available as supplementary data at was,30% of the tumor volume. Haupt et al. (15) reported that the proportion of the micropapillary component ranged from 5% to 60% of the entire tumor and that the micropapillary component was,10% in the majority (70%) of colorectal carcinomas with an MC component. In our case, the micropapillary component accounted for 80% of the entire tumor and was even detected in the biopsy specimen. Although the histological diagnosis of the biopsy specimen was moderately differentiated tubular adenocarcinoma at first, reviewing it after operation, there were almost MC component in it (Fig. 9). In conclusion, we experienced a patient with a pedunculated early sigmoid colon cancer, which had a micropapillary component and multiple nodal metastases. The presence of an MC in the colorectum seemed to be closely related with nodal metastasis, similar to the case for MCs in other organs. Therefore, if a micropapillary component is identified in a tumor, particularly in a biopsy specimen, even if the pre-operative diagnosis is a pedunculated early colorectal cancer, we should carefully consider the extent of surgical resection due to the high potential for nodal metastasis. In the present case, the pedunculated polyp of early sigmoid colon cancer with a micropapillary component was associated with extensive lymphovascular invasion and multiple lymph node metastases, although pedunculated polyps are generally considered to exhibit few lymph node metastases (18 20). The proportion of the MC component required for a diagnosis of MC has not yet been established. Pure MCs are extremely rare. A micropapillary component is usually associated with conventional carcinoma. Kim et al. (14) reported that the proportion of the MC component ranged from 5% to 80% of the total tumor volumes, and that in most cases (87.3%), the proportion of the MC component Conflict of interest statement None declared. References 1. Ellis IO, Schnitt SJ, Sastre-Garau X. Invasive ductal carcinoma. In: Tavassoli FA, Devilee P, editors. WHO Classification of Tumours: Pathology and Genetics of Tumours of the Breast and Female Genital Organs. Lyon: IARC Press 2003; Zekioglu O, Erhan Y, Ciris M, Bayramoglu H, Ozdemir N. Invasive micropapillary carcinoma of the breast: high incidence of lymph node metastasis with extranodal extension and its immunohistochemical profile compared with invasive ductal carcinoma. Histopathology 2004;44:18 23.

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