Clin J Gastroenterol (2012) 5:234–238 DOI 10.1007/s12328-012-0308-3
CASE REPORT
Lymphatic invasion in small differentiated-type mucosal gastric cancer Fumi Hasegawa • Hirokazu Kiyozaki • Osamu Takata Koichi Tokai • Takeshi Uehara • Yukio Yoshida • Mitsuhiro Nokubi • Fumio Konishi
•
Received: 5 January 2012 / Accepted: 22 April 2012 / Published online: 21 May 2012 Ó Springer 2012
Abstract Endoscopic resection for early gastric cancer is indicated for patients who are at negligible risk of lymph node metastasis. A 71-year-old female underwent endoscopic resection for a 15-mm differentiated-type mucosal gastric tumor, as recommended in the Japanese treatment guidelines. A histological examination revealed lymphatic invasion. Therefore, we performed laparoscopy-assisted distal gastrectomy and D1? lymph node dissection. A histological examination detected no.3 lymph node metastasis, but no residual cancer cells were observed at the site of the endoscopic resection. This case is rare as lymphatic invasion and lymph node metastasis are highly unusual in small differentiated-type mucosal gastric cancer. Having experienced this case, we consider that en-bloc endoscopic resection of such lesions is extremely important, as it allows precise histological examinations to be performed, which can determine the necessity of additional treatment. Keywords Mucosal gastric cancer Lymph node metastasis Lymphatic invasion En-bloc resection
F. Hasegawa (&) H. Kiyozaki O. Takata F. Konishi Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama, Saitama 330-8503, Japan e-mail: [email protected] K. Tokai T. Uehara Y. Yoshida Department of Gastroenterology, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama, Saitama 330-8503, Japan M. Nokubi Department of Pathology, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama, Saitama 330-8503, Japan
123
Introduction Recently, endoscopic resection for early gastric cancer (EGC) has become accepted as a minimally invasive treatment modality. According to the Japanese treatment guidelines for gastric cancer, endoscopic resection is indicated for differentiated-type mucosal gastric cancers (MGCs) measuring\20 mm in diameter without ulceration [1]. The guidelines also state that differentiated-type MGCs \30 mm in diameter without lymphovascular invasion regardless of the presence or absence of ulcers, those without ulcers regardless of their size, and undifferentiatedtype MGCs \20 mm in diameter without ulcers are included in the extended indications for endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). Gotoda et al. [2] reported that none of the former criteria are associated with nodal metastasis. Furthermore, the guidelines indicate that additional treatment is unnecessary if the invasion extends no deeper than the SM1 level and if there is no lymphovascular invasion. Lymphovascular invasion is rare in differentiated-type MGCs \20 mm in diameter without ulceration [3]. Here, we report the case of a 15-mm differentiated-type MGC involving lymphatic invasion and lymph node metastasis (LNM).
Case report A 71-year-old female underwent periodical check-ups at her local clinic. During one of these examinations, esophagogastroduodenoscopy showed a slightly depressed lesion measuring 15 mm in diameter on the lesser curvature of the middle part of the stomach with a background of intestinal metaplasia (Fig. 1). There was no ulceration or
Clin J Gastroenterol (2012) 5:234–238
inflammation. A biopsy specimen revealed well-differentiated adenocarcinoma without Helicobacter pylori infection. She was referred to our hospital for treatment. She had a history of appendectomy. Her sister had breast cancer. Computed tomography did not detect LNM or distant metastasis. Her laboratory data including tumor marker levels were all within normal limits. A diagnosis of small differentiated-type MGC was made. Based on the Japanese treatment guidelines for gastric cancer, we performed ESD.
235
A histopathological examination revealed a well-differentiated-type MGC of 15 mm in diameter that was confined to the mucosa. The tumor had invaded the lower third of the mucosa, but not the muscularis mucosa (Fig. 2b, c). Lymphatic invasion was also observed in the mucosal layer (Fig. 2d), but no ulcerative components were detected. Immunohistochemical staining with D2-40 confirmed that lymphatic invasion was present in the deep part of the mucosa, adjacent to the muscularis mucosa (Fig. 2e). Both
Fig. 1 a Esophagogastroduodenoscopy showed a slightly depressed lesion measuring 15 mm in diameter on the lesser curvature of the middle gastric body. There was no ulceration. b The tumor border became clearer after it had been sprayed with indigo carmine dye
Fig. 2 a Histological mapping of the ESD specimen. The line indicates the tumor border. The tumor measured 15 9 10 mm. b Cancer cells confined to the mucosa, but in contact with the muscularis mucosa (H&E). c The depth of the mucosal cancer invasion is depicted on highly magnified images. d, e Histological
examination. d Cancer cells in the lymphatic vessels adjacent to the muscularis mucosa (H&E). e Immunohistochemical staining with D240 confirmed that lymphatic invasion had occurred in the deep mucosa
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236
Clin J Gastroenterol (2012) 5:234–238
Fig. 3 a Macroscopic findings of the resected stomach. There were no residual cancer cells or ulceration after ESD. b The microscopic findings of the metastatic lymph node site. The cancer tissue in the involved lymph node measured 1 mm in diameter (H&E)
the lateral and vertical margins were negative (Fig. 2b). The Japanese treatment guidelines describe the criteria for curative endoscopic resection for mucosal cancer as no lymphovascular infiltration and recommend additional surgery after non-curative endoscopic resection. Therefore, we decided that there was a risk of nodal metastasis and decided to perform laparoscopy-assisted distal gastrectomy and D1? lymph node dissection. The entire specimen was cut into 5-mm serial slices and stained with hematoxylin– eosin (H&E) staining. Lymph node metastasis was only evaluated in one central slice of the resected lymph nodes with H&E staining. A histopathological examination revealed ulceration after ESD and no residual cancer cells in the resected stomach (Fig. 3a). One (no. 3) of the 24 lymph nodes removed was positive (Fig. 3b). The cancer tissue in the involved lymph node measured 1 mm in diameter; therefore, this was a micrometastasis. No additional immunohistological staining was performed because metastasis was clearly demonstrated with H&E staining. The patient’s postoperative course was uneventful, and she is currently free of recurrence.
Discussion Recently, endoscopic resection for EGC has become well accepted as a minimally invasive treatment modality, not only because it preserves gastric function but also because it allows the patient to maintain a good quality of life, provided a complete cure can be achieved. The Japanese treatment guidelines [1] include extended indications for endoscopic resection similar to reports from other countries [4, 5]. However, the criteria used can vary from hospital to hospital and tend to be based on retrospective studies and databases of EGC patients that have undergone lymphadenectomy [2, 4–7]. For example, Chung et al. [4] reported that all differentiated MGCs (i.e., irrespective of their size and whether they contain ulcerative tissue) can be included in the expanded indications for endoscopic resection
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because this group is associated with a \1 % risk of LNM. Yamamoto et al. [8] reported that ESD is technically feasible in cases of undifferentiated-type EGC with expanded indications for endoscopic resection. Recently, data for long-term survival after ESD have been widely reported. Okada et al. [9] stated that ESD for undifferentiated-type EGC might yield good long-term outcomes. As many investigators have reported, when determining the criteria for endoscopic resection the most important issue is the incidence of LNM, as LNM was found to be the most significant risk factor for recurrence [10–12]. In some studies, the depth of tumor invasion, tumor size, and lymphovascular invasion were found to be correlated with LNM [7, 10, 12–15]. Naoko et al. reported that mixed histology in MGC was an independent predictor of LNM [16, 17]; however, this case was rare because it involved pure differentiated-type mucosal gastric cancer combined with LNM. Some studies have suggested that the use of endoscopic resection for tumors that have invaded the lower third of the mucosa and undifferentiated-type tumors is inadequate due to the risk of LNM [14, 18]. In our case, based on the patient’s endoscopic findings and the histopathological findings of her biopsy specimens, we considered that no LNM was present; however, unexpectedly, both lymphatic invasion and LNM were detected. In general, the diagnosis of LNM before resection is not easy. It is difficult to evaluate lymph node status preoperatively using endoscopic ultrasonography or computed tomography because the size of the lymph nodes is not a reliable parameter for detecting metastasis [19–23]. It is necessary to determine how localized cancer spreads to the regional lymph nodes. Histological studies have revealed the presence of lymphatic vessels in the deeper third of the mucosa adjacent to and within the muscularis mucosa, while the upper and middle thirds of the mucosa contain no such lymphatic vessels [24, 25]. Therefore, Sako et al. [25] reported that cancer cells are most likely to penetrate the lymphatic system in the muscularis mucosa. Therefore, the risk of LNM might be predictable in cases displaying
Clin J Gastroenterol (2012) 5:234–238
lymphovascular involvement in the deeper third of the mucosal layer. The lymphatic vessels in the gastric wall can be clearly and selectively identified by immunostaining with D2-40 molecules. The area and length of the section of the muscularis mucosa that has been invaded by the tumor might also be important factors for predicting the risk of LNM in EGC [25, 26]. This case was consistent with the indications for endoscopic resection, but lymphovascular invasion was detected in the deeper third of the mucosa adjacent to the muscularis mucosa (Fig. 2d, e), and LNM was present in the resected stomach specimen. Cai et al. [27] reported that micrometastasis was detected in the lymph nodes of well-differentiated-type MGC tumors of 1–2 cm in diameter. Aoyagi et al. [3] reported the case of a differentiated-type MGC\20 mm in diameter without ulceration that displayed lymphovascular invasion. However, some previous studies have detected no LNM from differentiated-type MGC tumors\30 mm in diameter without ulceration (95 % CI 0–0.3 %) [2, 4]. Lymphatic invasion by differentiated-type MGCs measuring B20 mm has only been reported in a small number of cases. Therefore, the frequency of LNM in such cases is unclear. However, taking all the various factors in the present case into consideration, the risk of LNM might have been predictable after ESD, so we think that surgical resection with lymphadenectomy might be necessary because only radical gastrectomy is considered to have a chance of curing the patient if there is any possibility of LNM. The minimally invasive nature of endoscopic resection is important, but excellent disease-related survival is important. This case is rare as lymphatic invasion is highly unusual in small differentiated-type MGC. Tumors with lymphatic invasion carry a risk of LNM regardless of their size. We consider that en-bloc endoscopic resection of such lesions is important for precise histological assessment and the appropriate determination of additional treatment requirements.
Conclusion We experienced a rare case of a 15-mm differentiated-type MGC with lymphatic invasion and LNM. Having experienced such a case, we consider that en-bloc endoscopic resection of such lesions is important for precise histological assessment, and gastrectomy might be necessary in cases of differentiated-type MGC displaying lymphatic invasion, regardless of the size of the tumor, based on the Japanese treatment guidelines. Conflict of interest We have no conflict of interest about this paper.
237
References 1. Japanese Gastric Cancer Association. Guidelines for diagnosis and treatment of carcinoma of the stomach. 3rd ed. Kanehara: Tokyo; 2010. 2. Gotoda T, Yanagisawa A, Sasako M, Ono H, Nakanishi Y, Shimoda T, et al. Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers. Gastric Cancer. 2000;3:219–25. 3. Aoyagi K, Koufuji K, Yano S, Miyagi M, Koga A, et al. A case of small mucosal gastric carcinoma with lymph node metastasis: a case report. Kurume Med J. 2003;50:49–51. 4. Chung JW, Jung HY, Choi KD, Song HJ, Lee GH, Jang SJ, et al. Extended indication of endoscopic resection for mucosal early gastric cancer: analysis of a single center experience. J Gastroenterol Hepatol. 2011;26:884–7. 5. Gotoda T. Endoscopic resection of early gastric cancer. Gastric Cancer. 2007;10:1–11. 6. Novotny AR, Schuhmacher C. Predicting lymph node metastases in early gastric cancer: radical resection or organ-sparing therapy? Gastric Cancer. 2008;11:131–3. 7. Kim H, Kim JH, Park JC, Lee YC, Noh SH, Kim H. Lymphovascular invasion is an important predictor of lymph node metastasis in endoscopically resected early gastric cancers. Oncol Rep. 2011;25:1589–95. 8. Yamamoto Y, Fujisaki J, Hirasawa T, Ishiyama A, Yoshimoto K, Ueki N, et al. Therapeutic outcomes of endoscopic submucosal dissection of undifferentiated-type intramucosal gastric cancer without ulceration and preoperatively diagnosed as 20 millimetres or less in diameter. Dig Endosc. 2010;22:112–8. 9. Okada K, Fujisaki J, Yoshida T, Ishikawa H, Suganuma T, Kasuga A, et al. Long-term outcomes of endoscopic submucosal dissection for undifferentiated-type early gastric cancer. Endoscopy. 2012;44:122–7. 10. Otsuji E, Kuriu Y, Ichikawa D, Ochiai T, Okamoto K, Yamagishi H. Prediction of lymph node metastasis by size of early gastric carcinoma. Hepatogastroenterology. 2007;54:602–5. 11. Roviello F, Rossi S, Marrelli D, Pedrazzani C, Corso G, Vindigni C, et al. Number of lymph node metastases and its prognostic significance in early gastric cancer: a multicenter Italian study. J Surg Oncol. 2006;94:275–80. 12. Lo SS, Wu CW, Chen JH, Li AF, Hsieh MC, Shen KH, et al. Surgical results of early gastric cancer and proposing a treatment strategy. Ann Surg Oncol. 2007;14:340–7. 13. Yoshikawa K, Hiki N, Fukunaga T, Tokunaga M, Yamamoto Y, Miki A, et al. Increased risk of lymph node metastasis in mucosal gastric cancer with extra indication for endoscopic mucosal resection. J Am Coll Surg. 2009;208:1045–50. 14. Sung CM, Hsu CM, Hsu JT, Yeh TS, Lin CJ, Chen TC, et al. Predictive factors for lymph node metastasis in early gastric cancer. World J Gastroenterol. 2010;16:5252–6. 15. Wu CY, Chen JT, Chen GH, Yeh HZ. Lymph node metastasis in early gastric cancer: a clinicopathological analysis. Hepatogastroenterology. 2002;49:1465–8. 16. Naoko T, Shingo I, Yasuko U, Masatoshi K. Mixed intestinaland diffuse-type histology is a risk factor for lymph node metastasis of submucosal invasive gastric cancer. Dig Endosc. 2008;20:17–21. 17. Naoko T, Shingo I, Noriko S. Risk factors for lymph node metastases of intramucosal gastric cancer: a case–control study. Gastroenterol Endosc. 1999;41:1059–65. 18. Ho¨lscher AH, Drebber U, Mo¨nig SP, Schulte C, Vallbo¨hmer D, Bollschweiler E. Early gastric cancer: lymph node metastasis starts with deep mucosal infiltration. Ann Surg. 2009;250:791–7.
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238 19. Maehara Y, Orita H, Okuyama T, Moriguchi S, Tsujitani S, Korenaga D, et al. Predictors of lymph node metastasis in early gastric cancer. Br J Surg. 1992;79:245–7. 20. Mo¨nig SP, Zirbes TK, Schro¨der W, Baldus SE, Lindemann DG, Dienes HP, et al. Staging of gastric cancer: correlation of lymph node size and metastatic infiltration. Am J Roentgenol. 1999;173:365–7. 21. Akahoshi K, Chijiiwa Y, Hamada S, Sasaki I, Maruoka A, Kabemura T, et al. Endoscopic ultrasonography: a promising method for assessing the prospects of endoscopic mucosal resection in early gastric cancer. Endoscopy. 1997;29:614–9. 22. Polkowski M, Palucki J, Wronska E. Endosonography versus helical computed tomography for locoregional staging of gastric cancer. Endoscopy. 2004;36:617–23. 23. Tsendsuren T, Jun SM, Mian XH. Usefulness of endoscopic ultrasonography in preoperative TNM staging of gastric cancer. World J Gastroenterol. 2006;12:43–7.
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Clin J Gastroenterol (2012) 5:234–238 24. Listrom MB, Fenoglio-Preiser CM. Lymphatic distribution of the stomach in normal, inflammatory, hyperplastic, and neoplastic tissue. Gastroenterology. 1987;93:506–14. 25. Sako A, Kitayama J, Ishikawa M, Yamashita H, Nagawa H. Impact of immunohistochemically identified lymphatic invasion on nodal metastasis in early gastric cancer. Gastric Cancer. 2006;9:295–302. 26. Hirasawa T, Fujisaki J, Fukunaga T, Yamamoto Y, Yamaguchi T, Katori M, et al. Lymph node metastasis from undifferentiatedtype mucosal gastric cancer satisfying the expanded criteria for endoscopic resection based on routine histological examination. Gastric Cancer. 2010;13:267–70. 27. Cai J, Ikeguchi M, Tsujitani S, Maeta M, Kaibara N. Micrometastasis in lymph nodes of mucosal gastric cancer. Gastric Cancer. 2000;3:91–6.
CASE REPORT
Lymphatic invasion in small differentiated-type mucosal gastric cancer Fumi Hasegawa • Hirokazu Kiyozaki • Osamu Takata Koichi Tokai • Takeshi Uehara • Yukio Yoshida • Mitsuhiro Nokubi • Fumio Konishi
•
Received: 5 January 2012 / Accepted: 22 April 2012 / Published online: 21 May 2012 Ó Springer 2012
Abstract Endoscopic resection for early gastric cancer is indicated for patients who are at negligible risk of lymph node metastasis. A 71-year-old female underwent endoscopic resection for a 15-mm differentiated-type mucosal gastric tumor, as recommended in the Japanese treatment guidelines. A histological examination revealed lymphatic invasion. Therefore, we performed laparoscopy-assisted distal gastrectomy and D1? lymph node dissection. A histological examination detected no.3 lymph node metastasis, but no residual cancer cells were observed at the site of the endoscopic resection. This case is rare as lymphatic invasion and lymph node metastasis are highly unusual in small differentiated-type mucosal gastric cancer. Having experienced this case, we consider that en-bloc endoscopic resection of such lesions is extremely important, as it allows precise histological examinations to be performed, which can determine the necessity of additional treatment. Keywords Mucosal gastric cancer Lymph node metastasis Lymphatic invasion En-bloc resection
F. Hasegawa (&) H. Kiyozaki O. Takata F. Konishi Department of Surgery, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama, Saitama 330-8503, Japan e-mail: [email protected] K. Tokai T. Uehara Y. Yoshida Department of Gastroenterology, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama, Saitama 330-8503, Japan M. Nokubi Department of Pathology, Saitama Medical Center, Jichi Medical University, 1-847 Amanuma-cho, Omiya-ku, Saitama, Saitama 330-8503, Japan
123
Introduction Recently, endoscopic resection for early gastric cancer (EGC) has become accepted as a minimally invasive treatment modality. According to the Japanese treatment guidelines for gastric cancer, endoscopic resection is indicated for differentiated-type mucosal gastric cancers (MGCs) measuring\20 mm in diameter without ulceration [1]. The guidelines also state that differentiated-type MGCs \30 mm in diameter without lymphovascular invasion regardless of the presence or absence of ulcers, those without ulcers regardless of their size, and undifferentiatedtype MGCs \20 mm in diameter without ulcers are included in the extended indications for endoscopic mucosal resection (EMR) or endoscopic submucosal dissection (ESD). Gotoda et al. [2] reported that none of the former criteria are associated with nodal metastasis. Furthermore, the guidelines indicate that additional treatment is unnecessary if the invasion extends no deeper than the SM1 level and if there is no lymphovascular invasion. Lymphovascular invasion is rare in differentiated-type MGCs \20 mm in diameter without ulceration [3]. Here, we report the case of a 15-mm differentiated-type MGC involving lymphatic invasion and lymph node metastasis (LNM).
Case report A 71-year-old female underwent periodical check-ups at her local clinic. During one of these examinations, esophagogastroduodenoscopy showed a slightly depressed lesion measuring 15 mm in diameter on the lesser curvature of the middle part of the stomach with a background of intestinal metaplasia (Fig. 1). There was no ulceration or
Clin J Gastroenterol (2012) 5:234–238
inflammation. A biopsy specimen revealed well-differentiated adenocarcinoma without Helicobacter pylori infection. She was referred to our hospital for treatment. She had a history of appendectomy. Her sister had breast cancer. Computed tomography did not detect LNM or distant metastasis. Her laboratory data including tumor marker levels were all within normal limits. A diagnosis of small differentiated-type MGC was made. Based on the Japanese treatment guidelines for gastric cancer, we performed ESD.
235
A histopathological examination revealed a well-differentiated-type MGC of 15 mm in diameter that was confined to the mucosa. The tumor had invaded the lower third of the mucosa, but not the muscularis mucosa (Fig. 2b, c). Lymphatic invasion was also observed in the mucosal layer (Fig. 2d), but no ulcerative components were detected. Immunohistochemical staining with D2-40 confirmed that lymphatic invasion was present in the deep part of the mucosa, adjacent to the muscularis mucosa (Fig. 2e). Both
Fig. 1 a Esophagogastroduodenoscopy showed a slightly depressed lesion measuring 15 mm in diameter on the lesser curvature of the middle gastric body. There was no ulceration. b The tumor border became clearer after it had been sprayed with indigo carmine dye
Fig. 2 a Histological mapping of the ESD specimen. The line indicates the tumor border. The tumor measured 15 9 10 mm. b Cancer cells confined to the mucosa, but in contact with the muscularis mucosa (H&E). c The depth of the mucosal cancer invasion is depicted on highly magnified images. d, e Histological
examination. d Cancer cells in the lymphatic vessels adjacent to the muscularis mucosa (H&E). e Immunohistochemical staining with D240 confirmed that lymphatic invasion had occurred in the deep mucosa
123
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Clin J Gastroenterol (2012) 5:234–238
Fig. 3 a Macroscopic findings of the resected stomach. There were no residual cancer cells or ulceration after ESD. b The microscopic findings of the metastatic lymph node site. The cancer tissue in the involved lymph node measured 1 mm in diameter (H&E)
the lateral and vertical margins were negative (Fig. 2b). The Japanese treatment guidelines describe the criteria for curative endoscopic resection for mucosal cancer as no lymphovascular infiltration and recommend additional surgery after non-curative endoscopic resection. Therefore, we decided that there was a risk of nodal metastasis and decided to perform laparoscopy-assisted distal gastrectomy and D1? lymph node dissection. The entire specimen was cut into 5-mm serial slices and stained with hematoxylin– eosin (H&E) staining. Lymph node metastasis was only evaluated in one central slice of the resected lymph nodes with H&E staining. A histopathological examination revealed ulceration after ESD and no residual cancer cells in the resected stomach (Fig. 3a). One (no. 3) of the 24 lymph nodes removed was positive (Fig. 3b). The cancer tissue in the involved lymph node measured 1 mm in diameter; therefore, this was a micrometastasis. No additional immunohistological staining was performed because metastasis was clearly demonstrated with H&E staining. The patient’s postoperative course was uneventful, and she is currently free of recurrence.
Discussion Recently, endoscopic resection for EGC has become well accepted as a minimally invasive treatment modality, not only because it preserves gastric function but also because it allows the patient to maintain a good quality of life, provided a complete cure can be achieved. The Japanese treatment guidelines [1] include extended indications for endoscopic resection similar to reports from other countries [4, 5]. However, the criteria used can vary from hospital to hospital and tend to be based on retrospective studies and databases of EGC patients that have undergone lymphadenectomy [2, 4–7]. For example, Chung et al. [4] reported that all differentiated MGCs (i.e., irrespective of their size and whether they contain ulcerative tissue) can be included in the expanded indications for endoscopic resection
123
because this group is associated with a \1 % risk of LNM. Yamamoto et al. [8] reported that ESD is technically feasible in cases of undifferentiated-type EGC with expanded indications for endoscopic resection. Recently, data for long-term survival after ESD have been widely reported. Okada et al. [9] stated that ESD for undifferentiated-type EGC might yield good long-term outcomes. As many investigators have reported, when determining the criteria for endoscopic resection the most important issue is the incidence of LNM, as LNM was found to be the most significant risk factor for recurrence [10–12]. In some studies, the depth of tumor invasion, tumor size, and lymphovascular invasion were found to be correlated with LNM [7, 10, 12–15]. Naoko et al. reported that mixed histology in MGC was an independent predictor of LNM [16, 17]; however, this case was rare because it involved pure differentiated-type mucosal gastric cancer combined with LNM. Some studies have suggested that the use of endoscopic resection for tumors that have invaded the lower third of the mucosa and undifferentiated-type tumors is inadequate due to the risk of LNM [14, 18]. In our case, based on the patient’s endoscopic findings and the histopathological findings of her biopsy specimens, we considered that no LNM was present; however, unexpectedly, both lymphatic invasion and LNM were detected. In general, the diagnosis of LNM before resection is not easy. It is difficult to evaluate lymph node status preoperatively using endoscopic ultrasonography or computed tomography because the size of the lymph nodes is not a reliable parameter for detecting metastasis [19–23]. It is necessary to determine how localized cancer spreads to the regional lymph nodes. Histological studies have revealed the presence of lymphatic vessels in the deeper third of the mucosa adjacent to and within the muscularis mucosa, while the upper and middle thirds of the mucosa contain no such lymphatic vessels [24, 25]. Therefore, Sako et al. [25] reported that cancer cells are most likely to penetrate the lymphatic system in the muscularis mucosa. Therefore, the risk of LNM might be predictable in cases displaying
Clin J Gastroenterol (2012) 5:234–238
lymphovascular involvement in the deeper third of the mucosal layer. The lymphatic vessels in the gastric wall can be clearly and selectively identified by immunostaining with D2-40 molecules. The area and length of the section of the muscularis mucosa that has been invaded by the tumor might also be important factors for predicting the risk of LNM in EGC [25, 26]. This case was consistent with the indications for endoscopic resection, but lymphovascular invasion was detected in the deeper third of the mucosa adjacent to the muscularis mucosa (Fig. 2d, e), and LNM was present in the resected stomach specimen. Cai et al. [27] reported that micrometastasis was detected in the lymph nodes of well-differentiated-type MGC tumors of 1–2 cm in diameter. Aoyagi et al. [3] reported the case of a differentiated-type MGC\20 mm in diameter without ulceration that displayed lymphovascular invasion. However, some previous studies have detected no LNM from differentiated-type MGC tumors\30 mm in diameter without ulceration (95 % CI 0–0.3 %) [2, 4]. Lymphatic invasion by differentiated-type MGCs measuring B20 mm has only been reported in a small number of cases. Therefore, the frequency of LNM in such cases is unclear. However, taking all the various factors in the present case into consideration, the risk of LNM might have been predictable after ESD, so we think that surgical resection with lymphadenectomy might be necessary because only radical gastrectomy is considered to have a chance of curing the patient if there is any possibility of LNM. The minimally invasive nature of endoscopic resection is important, but excellent disease-related survival is important. This case is rare as lymphatic invasion is highly unusual in small differentiated-type MGC. Tumors with lymphatic invasion carry a risk of LNM regardless of their size. We consider that en-bloc endoscopic resection of such lesions is important for precise histological assessment and the appropriate determination of additional treatment requirements.
Conclusion We experienced a rare case of a 15-mm differentiated-type MGC with lymphatic invasion and LNM. Having experienced such a case, we consider that en-bloc endoscopic resection of such lesions is important for precise histological assessment, and gastrectomy might be necessary in cases of differentiated-type MGC displaying lymphatic invasion, regardless of the size of the tumor, based on the Japanese treatment guidelines. Conflict of interest We have no conflict of interest about this paper.
237
References 1. Japanese Gastric Cancer Association. Guidelines for diagnosis and treatment of carcinoma of the stomach. 3rd ed. Kanehara: Tokyo; 2010. 2. Gotoda T, Yanagisawa A, Sasako M, Ono H, Nakanishi Y, Shimoda T, et al. Incidence of lymph node metastasis from early gastric cancer: estimation with a large number of cases at two large centers. Gastric Cancer. 2000;3:219–25. 3. Aoyagi K, Koufuji K, Yano S, Miyagi M, Koga A, et al. A case of small mucosal gastric carcinoma with lymph node metastasis: a case report. Kurume Med J. 2003;50:49–51. 4. Chung JW, Jung HY, Choi KD, Song HJ, Lee GH, Jang SJ, et al. Extended indication of endoscopic resection for mucosal early gastric cancer: analysis of a single center experience. J Gastroenterol Hepatol. 2011;26:884–7. 5. Gotoda T. Endoscopic resection of early gastric cancer. Gastric Cancer. 2007;10:1–11. 6. Novotny AR, Schuhmacher C. Predicting lymph node metastases in early gastric cancer: radical resection or organ-sparing therapy? Gastric Cancer. 2008;11:131–3. 7. Kim H, Kim JH, Park JC, Lee YC, Noh SH, Kim H. Lymphovascular invasion is an important predictor of lymph node metastasis in endoscopically resected early gastric cancers. Oncol Rep. 2011;25:1589–95. 8. Yamamoto Y, Fujisaki J, Hirasawa T, Ishiyama A, Yoshimoto K, Ueki N, et al. Therapeutic outcomes of endoscopic submucosal dissection of undifferentiated-type intramucosal gastric cancer without ulceration and preoperatively diagnosed as 20 millimetres or less in diameter. Dig Endosc. 2010;22:112–8. 9. Okada K, Fujisaki J, Yoshida T, Ishikawa H, Suganuma T, Kasuga A, et al. Long-term outcomes of endoscopic submucosal dissection for undifferentiated-type early gastric cancer. Endoscopy. 2012;44:122–7. 10. Otsuji E, Kuriu Y, Ichikawa D, Ochiai T, Okamoto K, Yamagishi H. Prediction of lymph node metastasis by size of early gastric carcinoma. Hepatogastroenterology. 2007;54:602–5. 11. Roviello F, Rossi S, Marrelli D, Pedrazzani C, Corso G, Vindigni C, et al. Number of lymph node metastases and its prognostic significance in early gastric cancer: a multicenter Italian study. J Surg Oncol. 2006;94:275–80. 12. Lo SS, Wu CW, Chen JH, Li AF, Hsieh MC, Shen KH, et al. Surgical results of early gastric cancer and proposing a treatment strategy. Ann Surg Oncol. 2007;14:340–7. 13. Yoshikawa K, Hiki N, Fukunaga T, Tokunaga M, Yamamoto Y, Miki A, et al. Increased risk of lymph node metastasis in mucosal gastric cancer with extra indication for endoscopic mucosal resection. J Am Coll Surg. 2009;208:1045–50. 14. Sung CM, Hsu CM, Hsu JT, Yeh TS, Lin CJ, Chen TC, et al. Predictive factors for lymph node metastasis in early gastric cancer. World J Gastroenterol. 2010;16:5252–6. 15. Wu CY, Chen JT, Chen GH, Yeh HZ. Lymph node metastasis in early gastric cancer: a clinicopathological analysis. Hepatogastroenterology. 2002;49:1465–8. 16. Naoko T, Shingo I, Yasuko U, Masatoshi K. Mixed intestinaland diffuse-type histology is a risk factor for lymph node metastasis of submucosal invasive gastric cancer. Dig Endosc. 2008;20:17–21. 17. Naoko T, Shingo I, Noriko S. Risk factors for lymph node metastases of intramucosal gastric cancer: a case–control study. Gastroenterol Endosc. 1999;41:1059–65. 18. Ho¨lscher AH, Drebber U, Mo¨nig SP, Schulte C, Vallbo¨hmer D, Bollschweiler E. Early gastric cancer: lymph node metastasis starts with deep mucosal infiltration. Ann Surg. 2009;250:791–7.
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238 19. Maehara Y, Orita H, Okuyama T, Moriguchi S, Tsujitani S, Korenaga D, et al. Predictors of lymph node metastasis in early gastric cancer. Br J Surg. 1992;79:245–7. 20. Mo¨nig SP, Zirbes TK, Schro¨der W, Baldus SE, Lindemann DG, Dienes HP, et al. Staging of gastric cancer: correlation of lymph node size and metastatic infiltration. Am J Roentgenol. 1999;173:365–7. 21. Akahoshi K, Chijiiwa Y, Hamada S, Sasaki I, Maruoka A, Kabemura T, et al. Endoscopic ultrasonography: a promising method for assessing the prospects of endoscopic mucosal resection in early gastric cancer. Endoscopy. 1997;29:614–9. 22. Polkowski M, Palucki J, Wronska E. Endosonography versus helical computed tomography for locoregional staging of gastric cancer. Endoscopy. 2004;36:617–23. 23. Tsendsuren T, Jun SM, Mian XH. Usefulness of endoscopic ultrasonography in preoperative TNM staging of gastric cancer. World J Gastroenterol. 2006;12:43–7.
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