Clin J Gastroenterol (2012) 5:307–311 DOI 10.1007/s12328-012-0320-7
CASE REPORT
Synchronous occurrence of early neuroendocrine carcinoma and tubular adenocarcinoma in the stomach Yoshifumi Nakayama • Aiichirou Higure Kazunori Shibao • Nagahiro Sato • Nobutaka Matayoshi • Koji Yamaguchi
•
Received: 5 April 2012 / Accepted: 27 June 2012 / Published online: 18 July 2012 Ó Springer 2012
Abstract This report describes a patient with early neuroendocrine carcinoma (NEC) and tubular adenocarcinoma in the stomach. A 74-year-old Japanese male experienced epigastralgia. Endoscopic examination revealed two small lesions; one was an elevated lesion with ulceration at the posterior wall of the pre-pylorus and the other was a depressed lesion at the greater curvature of the antrum. Pathological diagnosis of the biopsies indicated poorly differentiated adenocarcinoma from the lesion on the prepylorus and well differentiated adenocarcinoma from the lesion on the antrum. He was referred to the surgical outpatient clinic with early double cancer of the stomach. A distal partial gastrectomy with lymph node dissection was performed. A histopathological examination revealed NEC at the lesion on the pre-pylorus and well differentiated tubular adenocarcinoma at the lesion on the antrum. These two lesions were completely separate from each other. Therefore, this case is thought to demonstrate the synchronous occurrence of early NEC and tubular adenocarcinoma in the stomach.
Introduction
Keywords Neuroendocrine carcinoma Synchronous Tubular adenocarcinoma Early gastric cancer Stomach
Case report
Y. Nakayama (&) A. Higure K. Shibao N. Sato N. Matayoshi K. Yamaguchi Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555, Japan e-mail: [email protected] Y. Nakayama N. Sato Department of Gastroenterological and General Surgery, Wakamatsu Hospital of University of Occupational and Environmental Health, 1-17-1 Hamamachi, Wakamatsu-ku, Kitakyushu 808-0024, Japan
Neuroendocrine carcinoma (NEC) of the gastrointestinal tract is a very rare and aggressive disease. NECs of the stomach account for 7.8 % of all NECs of the gastrointestinal tract [1] and represent less than 0.1 % of all primary gastric carcinomas [2]. Early gastric cancer is defined as gastric carcinoma confined to the mucosa and/or submucosa irrespective of lymph node involvement and tumor size, according to the Japanese Classification of Gastric Carcinoma [3]. Early NEC of the stomach confined to the mucosa and/or submucosa is especially rare [4, 5]. NEC of the stomach occasionally has another component, such as adenocarcinoma, in one tumor [5–10]. However, the concurrent occurrence of NEC and tubular adenocarcinoma in the stomach is extremely rare. This report presents a surgical case of a synchronous occurrence of early NEC and tubular adenocarcinoma in the stomach.
A 74-year-old Japanese male experiencing epigastralgia underwent endoscopic examination to reveal two small lesions. One was a small elevated lesion with ulceration at the posterior wall of the pre-pylorus (Fig. 1a) and the other was a small depressed lesion at the greater curvature of the antrum (Fig. 1b). An upper gastrointestinal series also indicated these two lesions (data not shown). The pathological diagnosis of the biopsies indicated poorly differentiated adenocarcinoma from the lesion on the pre-pylorus and well differentiated adenocarcinoma from the lesion on the antrum. He was referred to the surgical outpatient clinic with early double cancer of the stomach.
123
308
Clin J Gastroenterol (2012) 5:307–311
Fig. 1 Upper endoscopy revealed a small elevated lesion with ulceration at the posterior wall of the pre-pylorus (arrows) (a) and a small depressed lesion at the greater curvature of the antrum (arrow heads) (b)
A physical examination revealed no conjunctival pallor, and there was no muscular rigidity or rebound tenderness on abdominal palpation. Laboratory data showed that he had a white blood cell count of 7,600/mm3, hemoglobin of 12.4 g/dl, hematocrit of 37.9 %, platelets count of 194,000/ mm3, normal electrolytes, as well as normal blood urea nitrogen levels and liver function. Coagulation studies revealed that the prothrombin time was 12.9 s and the activated partial thromboplastin time was 31.8 s. CEA was 3.4 ng/ml and CA19-9 was 10.4 U/ml. Computed tomography revealed no distant metastasis. Marking clips were placed at the oral side of these lesions, and a distal partial gastrectomy with lymph node dissection was performed. The resected specimen indicated a small elevated lesion with ulceration at the posterior wall of the pre-pylorus (Fig. 2a) and a small depressed lesion at the greater curvature of the antrum (Fig. 2b). The carcinoma cells in the lesion on the pre-pylorus were limited to the submucosa (Fig. 3) as were those in the lesion on the antrum. Some lymphatic and venous invasion of the carcinoma cells was found in both lesions. There was no lymph node metastasis. A histopathological examination with hematoxylin and eosin staining revealed NEC in the lesion on the pre-pylorus (Fig. 4a) and well differentiated tubular adenocarcinoma in the lesion on the antrum (Fig. 4d). Immunohistochemical analyses indicated that many NEC cells were positive for synaptophysin (Fig. 4b) and CD56 (Fig. 4c). The serum NSE at the time after operation was 6.1 ng/ml. The patient had an uneventful recovery and was discharged from the hospital on the 14th day after surgery; he received follow-up care in the outpatient clinic. He did not receive adjuvant chemotherapy because he had severe
123
ischemic heart disease and refused adjuvant chemotherapy. He developed hepatic metastasis two years later and died suddenly of acute myocardial infarction.
Discussion Neuroendocrine carcinoma is occasionally accompanied by adenocarcinoma in one tumor of the gastrointestinal tract [6, 7]. Gastrointestinal NECs are morphologically classified into two subgroups: composite-type tumor, in which both components appear to be mixed haphazardly [7], and collision-type tumors, which are considered to be double tumors with a ‘‘side by side’’ or ‘‘one upon another’’ pattern [11, 12]. However, a case with the synchronous occurrence of early NEC and tubular adenocarcinoma at different sites of the stomach is extremely rare. In the current patient, the NEC mass did not have the other component. He had completely separated lesions of NEC and tubular adenocarcinoma. Two hypotheses have arisen regarding the mechanism for the association of adenocarcinoma and NEC [13, 14]. One is that both are derived from a common multipotential epithelial stem cell, the NEC component resulting from differentiation from the adenocarcinoma to the NEC phenotype during tumor progression [13]. This hypothesis is consistent with the structure of the composite type. The other hypothesis is that adenocarcinoma and NEC arise from a multipotential epithelial stem cell and a primitive NEC, respectively, and that they exist next to each other coincidentally [14]. This hypothesis is consistent with the structure of the collision-type in one tumor and the synchronous occurrence-type at different sites from each other.
Clin J Gastroenterol (2012) 5:307–311
309
Fig. 2 The surgical specimen revealed a small elevated lesion with ulceration at the posterior wall of the pre-pylorus (arrows) (a) and a small depressed lesion at the greater curvature of the antrum (arrow heads) (b)
Fig. 3 The histopathological examination of the pre-pyloric lesion reveled that the cancer cells were limited to the submucosa (cross section, hematoxylin and eosin staining, 910)
Indeed, some cases in the Japanese literature report the synchronous occurrence of NEC and adenocarcinoma in the stomach [15–18] (Table 1). However, we found only one other case of synchronous occurrence of early NEC and early adenocarcinoma in the stomach aside from our case [17]. Therefore, the present case is thought to be extremely rare. The prognosis of gastric NEC is generally poor. The overall median survival time is only 7–9 months [4, 5, 19, 20]. Gastric NEC has significantly more frequent invasion to lymphatic and vascular lumens and more frequent metastasis to the lymph nodes and the liver in comparison to typical gastric carcinoma [21]. Brenner et al. [1] reported that a univariate analysis showed that several factors such as performance status, weight loss, T stage, N
and M status, TNM stage and extent of disease (limited disease vs. extended disease) were significant prognostic factors. The 1-year survival rate of the extended disease (29 %) was significantly worse in comparison to that of the limited disease (72 %) [1]. No standard treatment has been established for gastric NEC. Multidisciplinary therapy might be needed for gastric NEC because of its own serious malignant potential. Chemotherapy for gastric NEC has been performed using many regimens such as cisplatin and etoposide [22], topotecan [23], amurubicin [24], paclitaxel [25], gemcitabine [26] and S-1 and cisplatin [27]. Though many chemotherapeutic agents have been used, no conclusions can be made regarding which regimen is most effective because patient numbers are lacking; however, there have been reports of complete
123
310
Clin J Gastroenterol (2012) 5:307–311
Fig. 4 The histopathological examination confirmed two lesions at the pre-pylorus (a, b, c) and the antrum (d). a Hematoxylin and eosin staining (9400). The specimen at the pre-pylorus shows many small cells and a high level of nuclear/columnar rate. b Synaptophysin stained
(9400). Synaptophysin staining in cancer cells is strongly positive. c CD56 stained (9400). CD56 staining in cancer cells is strongly positive. d Hematoxylin and eosin staining (9400). The specimen at the antrum shows well differentiated tubular adenocarcinoma
Table 1 Summary of the synchronous occurrence of NEC and adenocarcinoma in the stomach Case
1
Author
Matsuda
References
[15]
Age/sex
64/M
Neuroendocrine carcinoma
Adenocarcinoma
Prognosis
Macro. type
Depth/LN
Macro. type
Hist. type
Depth/LN
Type 2
T4a/N1
Type 0
tub1
T1a/N0
Dead 27D
tub2
T1b/N0
Alive 18 M
IIa 2
Sakatoku
[16]
79/F
SMT
T1b/N1
Type 0 I
3
Yasuda
[17]
74/F
Type 2
T4a/N2
Type 2
por
T2/N0
Dead 22 M
4
Takahashi
[18]
71/M
SMT
T2/N1
Type 0
tub2
T1b/N0
Alive 18 M
T1b/N0
IIc ? III Type 0
tub1
T1b/N0
Dead 24 M
5
Our case
74/M
Type 0 IIa ? IIc
clinical remission with SCLC chemotherapeutic regimens [28]. The adjuvant chemotherapy was not administered in the current case because the patient had severe angina pectoris and refused to receive adjuvant chemotherapy. Normally, early NEC of the stomach should be treated with adjuvant
123
IIc
chemotherapy because of the chance for early metastasis following surgery [19, 20]. In conclusion, this report presented a rare surgical case of a synchronous occurrence of early NEC and tubular adenocarcinoma in the stomach.
Clin J Gastroenterol (2012) 5:307–311
311
References 1. Brenner B, Shah MA, Gonen M, Klimstra DS. Shia J, Kelsen DP. Small-cell carcinoma of the gastrointestinal tract: a retrospective study of 64 cases. British J Cancer. 2004; 90: 1720–26. 2. Matsusaka T, Watanabe H, Enjoji M. Oat-cell carcinoma of the stomach. Fukuoka Acta Med. 1976;67:65–73. 3. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma. 2nd English edition. Gastric Cancer. 1998;1: 10–24. 4. Iwamuro M, Tanaka S, Bessho A, Takahashi H, Ohta T, Takada R, et al. Two cases of primary small cell carcinoma of the stomach. Acta Med Okayama. 2009;63:293–8. 5. Richards D, Davis D, Yan P, Guha S. Unusual case of small cell gastric carcinoma: case report and review. Dig Dis Sci. 2011;56: 951–7. 6. Chejfec G, Falkmar S, Askenstein U, Grimelius L, Gould VE. Neuroendocrine tumors of the gastrointestinal tract. Pathol Res Pract. 1988;183:143–54. 7. Roger LW, Murphy RC. Gastric carcinoids and carcinomas: morphologic correlates of survival. Am J Surg Pathol. 1979;3: 195–202. 8. Takeuchi H, Futamata K, Maeshima A, Hirose S, Shimada A, Kawaguchi Y, et al. A case of primary gastric small cell carcinoma with rare pattern of lymph node metastasis. Int J Gastrointest Cancer. 2005;36:99–104. 9. Namikawa T, Kobayashi M, Okabayashi T, Okabayashi T, Ozaki S, Nakamura S, et al. Primary gastric small cell carcinoma: report of a case and review of the literature. Med Mol Morphol. 2005;38:256–61. 10. Hirano Y, Hara T, Nozawa H, Oyama K, Ohta N, Omura K, et al. Combined choriocarcinoma, neuroendocrine cell carcinoma and tubular adenocarcinoma in the stomach. World J Gastroenterol. 2008;14:3269–72. 11. Yamashina M, Flinner RA. Concurrent occurrence of adenocarcinoma and carcinoid tumour in the stomach: a composite tumour or collision tumours? Am J Clin Pathol. 1985;83:233–6. 12. Corsi A, Bosman C. Adenocarcinoma and atypical carcinoid: morphological study of a gastric collision type tumor in the carcinoma-carcinoid spectrum. Ital J Gastroenterol. 1995;27: 303–8. 13. Lattes R, Grossi C. Carcinoid tumors of the stomach. Cancer. 1956;9:698–711. 14. De Lellis RA, Dayal Y. Neuroendocrine system. In: Sternberg SS, editor. Histology for pathologists. New York: Raven Press; 1992. p. 359. 15. Matsuda M, Satoh H, Watanabe Y, Yamazaki M, Nabeya M, Tohnosu N. A case of small cell carcinoma of the stomach with a tubular adenocarcinoma (in Japanese with English abstract). Nihon Rinsho Geka Gakkai Zasshi (JJSA). 1998;59:392–6. 16. Sakatoku M, Ietsugu K, Nakashima H, Kiyohara K, Kosugi M, Terahata S. A case of early gastric endocrine cell carcinoma,
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
gastric lymphoma and early gastric cancer (in Japanese with English abstract). Nihon Rinsho Geka Gakkai Zasshi (JJSA). 2001;62:2913–7. Yasuda K, Fujiwara H, Nomura H, Soga Y, Sakai K, Twramura K. A case of neuroendocrine cell carcinoma and poorly differentiated adenocarcinoma of the stomach in synchronous multiple cancer (in Japanese with English abstract). Jpn J Gastroenterol Surg (JSGS). 2006;39:446–51. Takahashi T, Fujisawa M, Hirahata S, Maeda D, Tokura H, Ohyama T, et al. A case of endocrine cell carcinoma and adenocarcinoma of the stomach (in Japanese with English abstract). Jpn J Gastroenterol Surg (JSGS). 2009;42:372–6. Fukuda T, Ohnishi Y, Nishimaki T, Ohtani H, Tachikawa S. Early gastric cancer of the small cell type. Am J Gastroenterol. 1988;83:1176–9. Matsui K, Kitagawa M, Miwa A, Kuroda Y, Tsuji M. Small cell carcinoma of the stomach: a clinicopathologic study of 17 cases. Am J Gastroenterol. 1991;86:1167–75. Chiba N, Suwa T, Hori M, Sakuma M, Kitajima M. Advanced gastric endocrine cell carcinoma with distant lymph node metastasis: a case report and clinicopathological characteristics of the disease. Gastric Cancer. 2004;7:122–7. Okamoto H, Watanabe K, Nishiwaki Y, Mori K, Kurita Y, Hayashi I, et al. Phase II study of area under the plasma-concentration-versus-time curve-based carboplatin plus standarddose intravenous etoposide in elderly patients with small-cell lung cancer. J Clin Oncol. 1999;17:3540–5. von Pawel J, Schiller JH, Shepherd FA, Fields SZ, Kleisbauer JP, Chrysson NG, et al. Topotecan versus cyclophosphamide, doxorubicin, and vincristine for the treatment of recurrent smallcell lung cancer. J Clin Oncol. 1999;17:658–67. Onoda S, Masuda N, Seto T, Eguchi K, Takiguchi Y, Isobe H, et al. Phase II trial of amrubicin for treatment of refractory of relapsed small-cell lung cancer: thoracic Oncology Research Group Study 0301. J Clin Oncol. 2006;24:5448–53. Smit EF, Fokkema E, Biesma B, Groen HJ, Snoek W, Postmus PE. A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer. Br J Cancer. 1998;77:347–51. Masters GA, Declerck L, Blanke C, Sandler A, DeVore R, Miller K, et al. Eastern Cooperative Oncology Group: Phase II trial of gemcitabine in refractory or relapsed small-cell lung cancer: Eastern Cooperative Oncology Group Trial 1597. J Clin Oncol. 2003;21:1550–5. Shimada M, Iwase H, Iyo T, Nakarai K, Kaida S, Indo T, et al. A case of complete response in a primary lesion treated by combined chemotherapy of TS-1 and CDDP for small cell carcinoma of the stomach with liver metastasis (in Japanese with English abstract). Jpn J Cancer Chemother. 2004;31:593–6. O’Byrne KJ, Cherukuri AK, Khan MI, Farrell RJ, Daly PA, Sweeney EC, et al. Extrapulmonary small cell carcinoma. A case report and review of the literature. Acta Oncol. 1997;36:78–80.
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CASE REPORT
Synchronous occurrence of early neuroendocrine carcinoma and tubular adenocarcinoma in the stomach Yoshifumi Nakayama • Aiichirou Higure Kazunori Shibao • Nagahiro Sato • Nobutaka Matayoshi • Koji Yamaguchi
•
Received: 5 April 2012 / Accepted: 27 June 2012 / Published online: 18 July 2012 Ó Springer 2012
Abstract This report describes a patient with early neuroendocrine carcinoma (NEC) and tubular adenocarcinoma in the stomach. A 74-year-old Japanese male experienced epigastralgia. Endoscopic examination revealed two small lesions; one was an elevated lesion with ulceration at the posterior wall of the pre-pylorus and the other was a depressed lesion at the greater curvature of the antrum. Pathological diagnosis of the biopsies indicated poorly differentiated adenocarcinoma from the lesion on the prepylorus and well differentiated adenocarcinoma from the lesion on the antrum. He was referred to the surgical outpatient clinic with early double cancer of the stomach. A distal partial gastrectomy with lymph node dissection was performed. A histopathological examination revealed NEC at the lesion on the pre-pylorus and well differentiated tubular adenocarcinoma at the lesion on the antrum. These two lesions were completely separate from each other. Therefore, this case is thought to demonstrate the synchronous occurrence of early NEC and tubular adenocarcinoma in the stomach.
Introduction
Keywords Neuroendocrine carcinoma Synchronous Tubular adenocarcinoma Early gastric cancer Stomach
Case report
Y. Nakayama (&) A. Higure K. Shibao N. Sato N. Matayoshi K. Yamaguchi Department of Surgery 1, School of Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahata-nishi-ku, Kitakyushu 807-8555, Japan e-mail: [email protected] Y. Nakayama N. Sato Department of Gastroenterological and General Surgery, Wakamatsu Hospital of University of Occupational and Environmental Health, 1-17-1 Hamamachi, Wakamatsu-ku, Kitakyushu 808-0024, Japan
Neuroendocrine carcinoma (NEC) of the gastrointestinal tract is a very rare and aggressive disease. NECs of the stomach account for 7.8 % of all NECs of the gastrointestinal tract [1] and represent less than 0.1 % of all primary gastric carcinomas [2]. Early gastric cancer is defined as gastric carcinoma confined to the mucosa and/or submucosa irrespective of lymph node involvement and tumor size, according to the Japanese Classification of Gastric Carcinoma [3]. Early NEC of the stomach confined to the mucosa and/or submucosa is especially rare [4, 5]. NEC of the stomach occasionally has another component, such as adenocarcinoma, in one tumor [5–10]. However, the concurrent occurrence of NEC and tubular adenocarcinoma in the stomach is extremely rare. This report presents a surgical case of a synchronous occurrence of early NEC and tubular adenocarcinoma in the stomach.
A 74-year-old Japanese male experiencing epigastralgia underwent endoscopic examination to reveal two small lesions. One was a small elevated lesion with ulceration at the posterior wall of the pre-pylorus (Fig. 1a) and the other was a small depressed lesion at the greater curvature of the antrum (Fig. 1b). An upper gastrointestinal series also indicated these two lesions (data not shown). The pathological diagnosis of the biopsies indicated poorly differentiated adenocarcinoma from the lesion on the pre-pylorus and well differentiated adenocarcinoma from the lesion on the antrum. He was referred to the surgical outpatient clinic with early double cancer of the stomach.
123
308
Clin J Gastroenterol (2012) 5:307–311
Fig. 1 Upper endoscopy revealed a small elevated lesion with ulceration at the posterior wall of the pre-pylorus (arrows) (a) and a small depressed lesion at the greater curvature of the antrum (arrow heads) (b)
A physical examination revealed no conjunctival pallor, and there was no muscular rigidity or rebound tenderness on abdominal palpation. Laboratory data showed that he had a white blood cell count of 7,600/mm3, hemoglobin of 12.4 g/dl, hematocrit of 37.9 %, platelets count of 194,000/ mm3, normal electrolytes, as well as normal blood urea nitrogen levels and liver function. Coagulation studies revealed that the prothrombin time was 12.9 s and the activated partial thromboplastin time was 31.8 s. CEA was 3.4 ng/ml and CA19-9 was 10.4 U/ml. Computed tomography revealed no distant metastasis. Marking clips were placed at the oral side of these lesions, and a distal partial gastrectomy with lymph node dissection was performed. The resected specimen indicated a small elevated lesion with ulceration at the posterior wall of the pre-pylorus (Fig. 2a) and a small depressed lesion at the greater curvature of the antrum (Fig. 2b). The carcinoma cells in the lesion on the pre-pylorus were limited to the submucosa (Fig. 3) as were those in the lesion on the antrum. Some lymphatic and venous invasion of the carcinoma cells was found in both lesions. There was no lymph node metastasis. A histopathological examination with hematoxylin and eosin staining revealed NEC in the lesion on the pre-pylorus (Fig. 4a) and well differentiated tubular adenocarcinoma in the lesion on the antrum (Fig. 4d). Immunohistochemical analyses indicated that many NEC cells were positive for synaptophysin (Fig. 4b) and CD56 (Fig. 4c). The serum NSE at the time after operation was 6.1 ng/ml. The patient had an uneventful recovery and was discharged from the hospital on the 14th day after surgery; he received follow-up care in the outpatient clinic. He did not receive adjuvant chemotherapy because he had severe
123
ischemic heart disease and refused adjuvant chemotherapy. He developed hepatic metastasis two years later and died suddenly of acute myocardial infarction.
Discussion Neuroendocrine carcinoma is occasionally accompanied by adenocarcinoma in one tumor of the gastrointestinal tract [6, 7]. Gastrointestinal NECs are morphologically classified into two subgroups: composite-type tumor, in which both components appear to be mixed haphazardly [7], and collision-type tumors, which are considered to be double tumors with a ‘‘side by side’’ or ‘‘one upon another’’ pattern [11, 12]. However, a case with the synchronous occurrence of early NEC and tubular adenocarcinoma at different sites of the stomach is extremely rare. In the current patient, the NEC mass did not have the other component. He had completely separated lesions of NEC and tubular adenocarcinoma. Two hypotheses have arisen regarding the mechanism for the association of adenocarcinoma and NEC [13, 14]. One is that both are derived from a common multipotential epithelial stem cell, the NEC component resulting from differentiation from the adenocarcinoma to the NEC phenotype during tumor progression [13]. This hypothesis is consistent with the structure of the composite type. The other hypothesis is that adenocarcinoma and NEC arise from a multipotential epithelial stem cell and a primitive NEC, respectively, and that they exist next to each other coincidentally [14]. This hypothesis is consistent with the structure of the collision-type in one tumor and the synchronous occurrence-type at different sites from each other.
Clin J Gastroenterol (2012) 5:307–311
309
Fig. 2 The surgical specimen revealed a small elevated lesion with ulceration at the posterior wall of the pre-pylorus (arrows) (a) and a small depressed lesion at the greater curvature of the antrum (arrow heads) (b)
Fig. 3 The histopathological examination of the pre-pyloric lesion reveled that the cancer cells were limited to the submucosa (cross section, hematoxylin and eosin staining, 910)
Indeed, some cases in the Japanese literature report the synchronous occurrence of NEC and adenocarcinoma in the stomach [15–18] (Table 1). However, we found only one other case of synchronous occurrence of early NEC and early adenocarcinoma in the stomach aside from our case [17]. Therefore, the present case is thought to be extremely rare. The prognosis of gastric NEC is generally poor. The overall median survival time is only 7–9 months [4, 5, 19, 20]. Gastric NEC has significantly more frequent invasion to lymphatic and vascular lumens and more frequent metastasis to the lymph nodes and the liver in comparison to typical gastric carcinoma [21]. Brenner et al. [1] reported that a univariate analysis showed that several factors such as performance status, weight loss, T stage, N
and M status, TNM stage and extent of disease (limited disease vs. extended disease) were significant prognostic factors. The 1-year survival rate of the extended disease (29 %) was significantly worse in comparison to that of the limited disease (72 %) [1]. No standard treatment has been established for gastric NEC. Multidisciplinary therapy might be needed for gastric NEC because of its own serious malignant potential. Chemotherapy for gastric NEC has been performed using many regimens such as cisplatin and etoposide [22], topotecan [23], amurubicin [24], paclitaxel [25], gemcitabine [26] and S-1 and cisplatin [27]. Though many chemotherapeutic agents have been used, no conclusions can be made regarding which regimen is most effective because patient numbers are lacking; however, there have been reports of complete
123
310
Clin J Gastroenterol (2012) 5:307–311
Fig. 4 The histopathological examination confirmed two lesions at the pre-pylorus (a, b, c) and the antrum (d). a Hematoxylin and eosin staining (9400). The specimen at the pre-pylorus shows many small cells and a high level of nuclear/columnar rate. b Synaptophysin stained
(9400). Synaptophysin staining in cancer cells is strongly positive. c CD56 stained (9400). CD56 staining in cancer cells is strongly positive. d Hematoxylin and eosin staining (9400). The specimen at the antrum shows well differentiated tubular adenocarcinoma
Table 1 Summary of the synchronous occurrence of NEC and adenocarcinoma in the stomach Case
1
Author
Matsuda
References
[15]
Age/sex
64/M
Neuroendocrine carcinoma
Adenocarcinoma
Prognosis
Macro. type
Depth/LN
Macro. type
Hist. type
Depth/LN
Type 2
T4a/N1
Type 0
tub1
T1a/N0
Dead 27D
tub2
T1b/N0
Alive 18 M
IIa 2
Sakatoku
[16]
79/F
SMT
T1b/N1
Type 0 I
3
Yasuda
[17]
74/F
Type 2
T4a/N2
Type 2
por
T2/N0
Dead 22 M
4
Takahashi
[18]
71/M
SMT
T2/N1
Type 0
tub2
T1b/N0
Alive 18 M
T1b/N0
IIc ? III Type 0
tub1
T1b/N0
Dead 24 M
5
Our case
74/M
Type 0 IIa ? IIc
clinical remission with SCLC chemotherapeutic regimens [28]. The adjuvant chemotherapy was not administered in the current case because the patient had severe angina pectoris and refused to receive adjuvant chemotherapy. Normally, early NEC of the stomach should be treated with adjuvant
123
IIc
chemotherapy because of the chance for early metastasis following surgery [19, 20]. In conclusion, this report presented a rare surgical case of a synchronous occurrence of early NEC and tubular adenocarcinoma in the stomach.
Clin J Gastroenterol (2012) 5:307–311
311
References 1. Brenner B, Shah MA, Gonen M, Klimstra DS. Shia J, Kelsen DP. Small-cell carcinoma of the gastrointestinal tract: a retrospective study of 64 cases. British J Cancer. 2004; 90: 1720–26. 2. Matsusaka T, Watanabe H, Enjoji M. Oat-cell carcinoma of the stomach. Fukuoka Acta Med. 1976;67:65–73. 3. Japanese Gastric Cancer Association. Japanese classification of gastric carcinoma. 2nd English edition. Gastric Cancer. 1998;1: 10–24. 4. Iwamuro M, Tanaka S, Bessho A, Takahashi H, Ohta T, Takada R, et al. Two cases of primary small cell carcinoma of the stomach. Acta Med Okayama. 2009;63:293–8. 5. Richards D, Davis D, Yan P, Guha S. Unusual case of small cell gastric carcinoma: case report and review. Dig Dis Sci. 2011;56: 951–7. 6. Chejfec G, Falkmar S, Askenstein U, Grimelius L, Gould VE. Neuroendocrine tumors of the gastrointestinal tract. Pathol Res Pract. 1988;183:143–54. 7. Roger LW, Murphy RC. Gastric carcinoids and carcinomas: morphologic correlates of survival. Am J Surg Pathol. 1979;3: 195–202. 8. Takeuchi H, Futamata K, Maeshima A, Hirose S, Shimada A, Kawaguchi Y, et al. A case of primary gastric small cell carcinoma with rare pattern of lymph node metastasis. Int J Gastrointest Cancer. 2005;36:99–104. 9. Namikawa T, Kobayashi M, Okabayashi T, Okabayashi T, Ozaki S, Nakamura S, et al. Primary gastric small cell carcinoma: report of a case and review of the literature. Med Mol Morphol. 2005;38:256–61. 10. Hirano Y, Hara T, Nozawa H, Oyama K, Ohta N, Omura K, et al. Combined choriocarcinoma, neuroendocrine cell carcinoma and tubular adenocarcinoma in the stomach. World J Gastroenterol. 2008;14:3269–72. 11. Yamashina M, Flinner RA. Concurrent occurrence of adenocarcinoma and carcinoid tumour in the stomach: a composite tumour or collision tumours? Am J Clin Pathol. 1985;83:233–6. 12. Corsi A, Bosman C. Adenocarcinoma and atypical carcinoid: morphological study of a gastric collision type tumor in the carcinoma-carcinoid spectrum. Ital J Gastroenterol. 1995;27: 303–8. 13. Lattes R, Grossi C. Carcinoid tumors of the stomach. Cancer. 1956;9:698–711. 14. De Lellis RA, Dayal Y. Neuroendocrine system. In: Sternberg SS, editor. Histology for pathologists. New York: Raven Press; 1992. p. 359. 15. Matsuda M, Satoh H, Watanabe Y, Yamazaki M, Nabeya M, Tohnosu N. A case of small cell carcinoma of the stomach with a tubular adenocarcinoma (in Japanese with English abstract). Nihon Rinsho Geka Gakkai Zasshi (JJSA). 1998;59:392–6. 16. Sakatoku M, Ietsugu K, Nakashima H, Kiyohara K, Kosugi M, Terahata S. A case of early gastric endocrine cell carcinoma,
17.
18.
19.
20.
21.
22.
23.
24.
25.
26.
27.
28.
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