We present a case of a primary advanced gastric tumor that was composed of 2 different pathological components: small cell carcinoma and moderately-differentiated adenocarcinoma. The patient was still alive four years after the surgery was performed, without recurrence. A large part of the tumor consisted of a diffuse sheet of small cell carcinoma, which transitioned into another small portion consisting of moderately-differentiated tubular adenocarcinoma components. Therefore, this case raised the possibility that small cell gastric carcinoma may originate from totipotential stem cells of the stomach. Although small cell carcinoma progresses aggressively, and patients with it have an extremely poor prognosis, this patient recovered uneventfully after the surgical resection, and has remained in good health, without any recurrences.</p

Honma, Masanori

Ishizawa, Shin

Masuyama, Kiichi

Nakayama, Yoshihide

Sawataishi, Masaru

Sugiyama, Toshiro

Suzuki, Shuichiro

Takahara, Terumi

Tanaka, Michio

Watanabe, Akiharu

Yamazaki, Kunio

Yata, Yutaka

Okayama University Scientific Achievement Repository

Acta Medica OkayamaVolume 58, Issue 6 2004 Article 4DECEMBER 2004A case of small cell gastric carcinoma with anadenocarcinoma component operatedcuratively.Yutaka Yata, &#xFEFF;Koseiren Itoigawa General HospitalYoshihide Nakayama, &#xFEFF;Koseiren Itoigawa General HospitalTerumi Takahara, &#xFEFF;Toyama Medical and Pharmaceutical UniversityKunio Yamazaki, &#xFEFF;Koseiren Itoigawa General HospitalKiichi Masuyama, &#xFEFF;Koseiren Itoigawa General HospitalMasaru Sawataishi, &#xFEFF;Koseiren Itoigawa General HospitalShuichiro Suzuki, Koseiren Itoigawa General HospitalMasanori Honma, &#xFEFF;Toyama Medical and Pharmaceutical UniversityShin Ishizawa, &#xFEFF;Toyama Medical and Pharmaceutical UniversityMichio Tanaka, &#xFEFF;Toyama Medical and Pharmaceutical UniversityAkiharu Watanabe, Toyama Medical and Pharmaceutical UniversityToshiro Sugiyama, &#xFEFF;Toyama Medical and Pharmaceutical UniversityCopyright c©1999 OKAYAMA UNIVERSITY MEDICAL SCHOOL. All rights reserved.A case of small cell gastric carcinoma with anadenocarcinoma component operatedcuratively.∗Yutaka Yata, Yoshihide Nakayama, Terumi Takahara, Kunio Yamazaki, KiichiMasuyama, Masaru Sawataishi, Shuichiro Suzuki, Masanori Honma, ShinIshizawa, Michio Tanaka, Akiharu Watanabe, and Toshiro SugiyamaAbstractWe present a case of a primary advanced gastric tumor that was composed of 2 differentpathological components: small cell carcinoma and moderately-differentiated adenocarcinoma.The patient was still alive four years after the surgery was performed, without recurrence. A largepart of the tumor consisted of a diffuse sheet of small cell carcinoma, which transitioned into an-other small portion consisting of moderately-differentiated tubular adenocarcinoma components.Therefore, this case raised the possibility that small cell gastric carcinoma may originate fromtotipotential stem cells of the stomach. Although small cell carcinoma progresses aggressively,and patients with it have an extremely poor prognosis, this patient recovered uneventfully after thesurgical resection, and has remained in good health, without any recurrences.KEYWORDS: gastric tumor, small cell carcinoma, adenocarcinoma∗PMID: 15762296 [PubMed - indexed for MEDLINE]Copyright (C) OKAYAMA UNIVERSITY MEDICAL SCHOOL A Case of Small Cell Gastric Carcinoma with an Adenocarcinoma Component Operated Curatively Yutaka Yata???, Yoshihide Nakayama?, Terumi Takahara?,Kunio Yamazaki?, Kiichi Masuyama?, Masaru Sawataishi?,Shuichiro Suzuki?, Masanori Honma?, Shin Ishizawa?,Michio Tanaka?, Akiharu Watanabe?, and Toshiro Sugiyama??Department of Medicine and?Surgery, Koseiren Itoigawa General Hospital, Niigata 941-8502, Japan,?Second Department of Pathology, ?Department of Endoscopy, and?Third Department of Internal Medicine,Toyama Medical and Pharmaceutical University, Toyama 930-0194, Japan We present a case of a primary advanced gastric tumor that was composed of 2 diﬀerent pathological components: small cell carcinoma and moderately-diﬀerentiated adenocarcinoma. The patient was still alive four years after the surgery was performed, without recurrence. A large part of the tumor consisted of a diﬀuse sheet of small cell carcinoma, which transitioned into another small portion consisting of moderately-diﬀerentiated tubular adenocarcinoma components. Therefore,this case raised the possibility that small cell gastric carcinoma may originate from totipotential stem cells of the stomach. Although small cell carcinoma progresses aggressively, and patients with it have an extremely poor prognosis, this patient recovered uneventfully after the surgical resection,and has remained in good health, without any recurrences.Key words: gastric tumor, small cell carcinoma, adenocarcinoma S mall cell gastric carcinoma (SCGC), although rare, is one of the most aggressive cancers found,and patients with this diagnosis have an extremely poor prognosis. There are 2 types of SCGC, a pure-type and a composite-type admixing glandular and/or squamous diﬀerentiation［1］. We report the case of a 78-year-old man who suﬀered from composite-type SCGC, and who was curatively operated on.Case report A 78-year-old Japanese man was admitted to our hospital with hematemesis. The history was notable for epigastric discomfort for 2 weeks before admission. On physical examination, there was no swelling of the lymph nodes, and no abdominal tenderness or mass.Laboratory data on admission were as follows:red blood cell count (RBC)281×10?/μl, hemoglobin(Hb)9.0 g/dl, white blood cell count(WBC)9100/μl with a normal diﬀerential, platelets 192,000/μl, total protein 5.0 g/dl, albumin 3.3 g/dl, LDH 198 IU/l, CEA 1.7 ng/ml.Upper gastrointestinal endoscopy revealed a large ulcerated Borrman type? tumor on the anterior wall near the cardia of the stomach. Although there was no active bleeding upon examination, the source of bleeding was unclear. Biopsies of the tumor demonstrated moderately-diﬀerentiated tubular adenocarcinoma. An upper gastro-Received July 4, 2003;accepted May 10, 2004.?Corresponding author, Phone:＋81-76-434-7301;Fax:＋81-76-434-5027 E-mail:yyata＠toyama-mpu.ac.jp(Y.Yata)http://www.lib.okayama-u.ac.jp/www/acta/Acta Med. Okayama, 2004 Vol. 58, No. 6, pp. 275-278 Case Report Copyright?ｃ2004 by Okayama University Medical School.1Yata et al.: A case of small cell gastric carcinoma with an adenocarcinomProduced by The Berkeley Electronic Press, 2004intestinal radiograph also revealed a large ulcerative tumor on the anterior wall, and segmental narrowing of the upper body of the stomach. Preoperative chest radiogra-phy and whole-body computerized tomography (CT)showed no metastatic lesions. Total gastrectomy with splenectomy and regional lymph node dissection was performed. The surgical ﬁndings were T2, N1, P0, H0,M0, Stage?, PM (－), DM (－), with a curability of A［2］. Surgical pathology revealed a 3.0×4.5 cm ulcer-ated Borrmann type? tumor on the anterior wall near the cardia. In addition, there was a?c lesion on the lesser curvature next to the tumor(Figs. 1a, b). The 2 lesions were contiguous in cut surface sections. There-fore, we classiﬁed this case as a Borrmann type V(unclassiﬁed type)that measured 4.5×7.5 cm in postoper-ative diagnosis. Microscopically, the Borrmann type?tumor was composed of two components. The majority of the tumor consisted of a population of small cells that had hyperchromatic, dark round, and oval or spindle-shaped nuclei with scant cytoplasm (Fig. 2a). These small cells were homogeneous in size and shape, had proliferated diﬀusely, and were arranged in sheets with ﬁne ﬁbrous connective tissue. In addition, numerous abnormal mitotic ﬁgures were present. The other compo-nent of the tumor was composed of moderately-diﬀerentiated tubular adenocarcinoma, which was continu-ous with the IIc lesion. The IIc lesion was also composed of moderately-diﬀerentiated tubular adenocarcinoma(Fig.2b). In the immunohistochemical studies conducted, the small cells were positive for neuron-speciﬁc enolase(NSE) and chromogranin A staining, whereas the adenocarcinoma cells were negative. Grimelius staining and Fontana-Masson staining were negative in both cell populations. Based on these histological and immunohis-tochemical features, we diagnosed this case as a SCGC with adenocarcinoma. Although chemotherapy was not performed, by request of the patient, he recovered uneventfully after surgery, and was in good health,without evidence of recurrence, 4 years after the surgery.Discussion SCGC is rare(0.1  of gastric carcinoma), and its prognosis is extremely poor because it tends to invade local structures and rapidly metastasize［3-5］. We here reported a case of SCGC with an adenocarcinoma compo-nent that was operated curatively.In the lung, it has been reported that small cell carcinoma can be associated with adeno or squamous cell carcinoma;some of these tumors have exhibited multidi-rectional diﬀerentiation［6］. Matsusaka et al. ﬁrst reported on the only 2 cases of SCGC in a review of about 2000 gastric carcinomas, one of which was a mixed tumor composed of small cell carcinoma, well-Yata et al. Acta Med. Okayama Vol. 58, No. 6 276 Fig.1  Macroscopic ﬁndings.(a)A large Borrmann type III tumor in the anterior wall near the cardia, along the lessor curvature and IIc lesion next to the tumor. (b)Schema of the tumor. This tumor consisted of 2 components, small cell carcinoma( )and adenocarcinoma( ). The 2 components were continuous in cut surface sections ( ).2Acta Medica Okayama, Vol. 58 [2004], Iss. 6, Art. 4http://escholarship.lib.okayama-u.ac.jp/amo/vol58/iss6/4diﬀerentiated adenocarcinoma, and mucous cell carcinoma［3］. Although small cell carcinoma is thought to originate from pre-existing neuroectodermal cells, pluripotent epi-thelial stem cells, or adenocarcinoma precursor cells, its origin is still unclear［7］. Some reports suggest that SCGC can be derived from the stem cells, since some cases of SCGC have been accompanied by adenocar-cinoma components［1, 8, 9］. Experimental data has indicated that immature mucous cells (stem cells)of the stomach are capable of diﬀerentiating towards mature mucous, parietal, and chief as well as argyrophilic cells［10］. In addition, in genetic analysis of colorectal tumors, identical genetic alterations, such as a frequent loss of heterozygosity(LOH)for adenomatous polyposis coli(APC), deleted in colorectal carcinoma(DCC)or p53 genes, were found in both composite small cell carcinoma and the associated adenocarcinomas. Therefore, both tumors are considered to have the same cell origin［11］.Our case also supports the idea that neoplastic multidi-rectional diﬀerentiation of totipotential stem cells is pos-sible in the stomach.Since the behavior and growth characteristics of SCGC are similar to pulmonary small cell carcinoma,treatment with regimens speciﬁc for pulmonary small cell carcinoma may be the recommended choice for treatment of this tumor, instead of surgical resection［12, 13］.However, nearly 50 of the patients with SCGC under-went chemotherapy, and favorable clinical eﬀects were not found. Furthermore, the non-small-cell components in the stomach are more resistant to chemotherapy that those same components in the lung［13］. Despite the fact that our patient requested not to receive chemotherapy,recurrence of the tumor has not been seen for the four years since surgery was performed. In light of our experience, earlier surgical resection is the most impor-tant and the followed adjunctive chemotherapy based on the regimen for pulmonary small cell carcinoma should be appropriate for the treatment of SCGC according to the conditions of the each cases.It has also been reported that several endocrine cell tumors, including small cell carcinomas, were found to have originated from amine precursor uptake and decar-boxylation (APUD) cells, and several transcriptional factors are important for the diﬀerentiation of APUD cells［14］. For SCGC, additional studies that include gene expressing proﬁling will be critical to revealing the cellular origin and pattern of diﬀerentiation of this type of tumor.Acknowledgments. We would like to thank Dr. Don C. Rockey(of Duke University Medical Center, NC, USA)for his critical reading of this manuscript, and for his invaluable advice.Small Cell Gastric Carcinoma with Adenocarcinoma December 2004 Fig.2  Histological ﬁndings(HE staining). (a)The Borrmann type III tumor was composed primarily of small cell carcinoma(round or ovoid cells with hyperchromatic nuclei and scant cytoplasm). (b)The IIc lesion was composed of moderately-diﬀerentiated tubular adenocarcinoma.Bars indicate 50μm.2773Yata et al.: A case of small cell gastric carcinoma with an adenocarcinomProduced by The Berkeley Electronic Press, 2004 References 1. Matsui K, Kitagawa M, Miwa A, Kuroda Y and Tsuji M:Small cell carcinoma of the stomach:a clinicopathologic study of 17 cases. Am J Gastroenterol(1988)86:1167-1175.2. Japanese Gastric Cancer Association:Japanese classiﬁcation of gas-tric carcinoma. 2 nd English Edition. Gastric Cancer(1998)1:10-24.3. Matsusaka T, Watanabe H and Enjoji M:Oat cell carcinoma of the stomach. Fukuoka Igaku Zasshi(Fukuoka Acta Med, Fukuoka)(1976)67:65-73(in Japanese).4. Lo Re G, Canzonieri V, Veronesi A, Dal Bo V, Barzan L, Zancanaro C and Trovo M:Extrapulmonary small cell carcinoma:A single-institution experience and review of the literature. Ann Oncol(1994)5:909-913.5. Takaku H, Oka K, Naoi Y, Santoh N, Setsu Y and Mori N:Primary advanced gastric small cell carcinoma. A Case report and review of the literature. Am J Gastroenterol(1999)94:1402-1404.6. McDowell EM and Trump BF:Pulmonary small cell carcinoma showing tripartite diﬀerentiation in individual cells. Human Pathol(1981)12:286-294.7. Jass JR, Sobin LH and Watanabe H:The World Health Organization’s histologic classiﬁcation of gastrointestinal tumors. 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A Case report and review of the literature. Am J Clin Oncol(1998)21:458-461.14. Ito T, Udaka N, Okudela K, Yazawa T and Kitamura H:Mechanisms of neuroendocrine differentiation in pulmonary neuroendocrine cells and small cell carcinoma. Endocr Pathol(2003)14:133-139.Yata et al. Acta Med. Okayama Vol. 58, No. 6 2784Acta Medica Okayama, Vol. 58 [2004], Iss. 6, Art. 4http://escholarship.lib.okayama-u.ac.jp/amo/vol58/iss6/4

A case of small cell gastric carcinoma with an adenocarcinoma component operated curatively.

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A case of small cell gastric carcinoma with an adenocarcinoma component operated curatively.

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