Adenosquamous Carcinoma of the Stomach

Transcription

1 GASTROENTEROLOGY 1987;92: Adenosquamous Carcinoma of the Stomach Histogenetic and Ultrastructural Studies MASAKI MORI, TOSHIRO FUKUDA, and MUNETOMO ENJOJI Secopd Department of Pathology. Faculty of Medicine. Kyushu University. Fukuoka. Japan Adenosquamous carcinoma of the stomach in a 45-yr-old Japanese woman was studied ultrastructurally and light microscopically. The tumor consisted of combined areas of poorly and moderately differentiated adenocarcinoma and squamous cell car(:inoma, with keratinization. Noteworthy was the demonstration of individual cells containing both tonofibrils and mucous vacuoles. The frequencies of this type of tumor in early and advanced gastric carcinomas are given attention and the pathogenesis is discussed with respect to our own observations and to data in the literature. Adenosquamous carcinoma (ASC), a rare tumor of the stomach, is characterized by two different cell components, one adenomatous and the other squamous. Ultrastructurally, individual cells presenting two different characteristics have been noted in a carcinoma occurring in organs other than the stomach (1-7). When examining ASC of the stomach, light and electron microscopically, we noted the concomitant presence of these particular cells. We describe herein our findings, and the frequencies of ASC in early and advanced gastric carcinomas are given attention. Case Report A 45-yr-old Japanese woman was admitted with a 1-mo history of epigastric pain, anorexia, and a 4-kg weight loss. Physical examination revealed epigastric tenderness without any palpable mass. Although the labora- Received March Accepted June Address requests for reprints to: Dr. M. MorL Second Department of Pathology. Faculty of Medicine. Kyushu University Maidashi. Higashi-ku. Fukuoka 812. Japan. The authors thank Dr. Y. Shibata (First Department of Anatomy. Faculty of Medicine, Kyushu University) for advice on the electron microscopy and M. Ohara (Kyushu University) for comments on the manuscript by the American Gastroenterological Association /87/$3.50 tory studies were unremarkable, upper gastrointestinal roentgenograms disclosed a tumor with an irregular ulceration in the posterior wall subjacent to the gastric cardia. Endoscopic biopsies revealed that the lesion was a poorly differentiated adenocarcinoma with areas of squamous cell differentiation. No evidence of a primary tumor was detected elsewhere. Exploration of the abdomen revealed a 6-cm tumor near the gastric cardia and involving the serosal surface. There was no direct invasion to any surrounding organ. The peri gastric lymph nodes were enlarged and metastasis was suspected. The liver appeared free of any metastasis. Total gastrectomy with splenectomy and dissection of the perigastric lymph nodes were immediately performed, but clinical deterioration was rapid and the patient died on the 43rd postoperative day. Permission for autopsy could not be obtained. Materials and Methods Tissues for light microscopy were processed and cut in the usual manner after fixation in formalin. Sections were stained with hematoxylin and eosin. Special stains included the periodic acid-schiff and Alcian blue stains. For electron microscopy. fresh samples from the primary tumor were fixed in 3% glutaraldehyde solution (buffered at ph 7.4) and postfixed in 1 % phosphate-buffered osmium tetroxide. After dehydration, the tissue blocks were embedded in Epon 812 and were cut on an LKB Ultrotome III (LKB Instruments, Gaithersburg. Md.). Ultrathin sections were stained with uranyl acetate and lead acetate, and examined under a JEM 100C electron microscope. To determine the frequencies of ASC in advanced and early carcinomas of the stomach, one of us (M.M.) reappraised microscopically 976 cases of advanced carcinoma and 1028 cases of early carcinoma which had been consecutively examined in our institution from 1979 to Cases of advanced carcinoma included herein, were all those where the cancerous invasion had reached or exceeded the muscularis propria of the gastric wall, and cases of early carcinoma represented those with cancerous invasion restricted to within the mucosa or submucosa Abbreviation used in this paper: ASC. adenosquamous carcinoma.

2 April 1987 GASTRIC ADENOSQUAMOUS CARCINOMA 1079 Figure 1. Adenomatous area of ASC. A. Malignant cells forming glands are evident (H&E, X200). B. Signet-ring cell carcinoma (H&E, X290). without involvement of the muscularis propria (8). The criteria used to identify the component as squamous were the presence of keratinizing cell masses with pearl formation or of intercellular bridges, or both (9). Results Gross Findings The specimen consisted,of a totally resected stomach, measuring 17 cm along the lesser curvature and 25 cm along the greater curvature, ' the spleen, and 11 peri gastric lymph nodes. A 6.5 x 6-cm tumor with a 2 x 2-cm irregularly shaped ulcer at its center was present on the posterior wall near the gastric cardia. The cardioesophageal junction appeared to be free from tumor invasion. The cut surface presented an ill-defined! solid, grayish-white tumor involving the entire thickness of the gastric wall. Whereas spleen was grossly free of the tumor, most of the swollen lymph nodes showed evidence of metastases. Light Microscopic Findings The tumor showed mixed histologic types of adenocarcinoma and squamous cell carcinoma. The former component consisted of smaller areas forming small but distinct tubules and of larger areas containing signet-ring cells stained positive with the periodic acid-schiff reagent and negative or weakly positive with the Alcian blue reagent (Figure 1). The squamous component was characterized by keratin pearl, individual cell keratinization, and intercellular bridges (Figure 2). The adenomatous and squamous components were intermingled and there was no distinct demarcation. In some areas, the mucincontaining cells that stained positive with both periodic acid-schiff and Alcian blue were present in the nests of squamous cells (Figure 3). The spleen was not invaded by the tumor, but 7 of the 11 lymph nodes showed a metastases containing both the adenomatous and squamous components. Electron Microscopic Findings Three cell types were identified: adenomatous, squamous, and those that were intermediate between adenomatous and squamous. The adenomatous cells were round or oval and had mucous vacuoles with a delicate flocculent appearance in the cytoplasm, which compressed the nucleus to the periphery. Some of the cells formed small intercellular acini fringed by numerous microvilli. The

3 1080 MORl ET AL. GASTROENTEROLOGY Vol. 92, No.4 Figure 2. Squamous cell area of ASC. Moderately differentiated squamous cell nests with horny pearls (arrow) (H&E, x290). Inset demonstrates intercellular bridges between the tumor cells (H&E, x 1260). squamous cells with irregular nuclei and prominent nucleoli appeared polygonal. They had numerous cell processes connected to those of the adjacent cells by apical desmosomes, and were rich in electron-dense tonofibrils in the cytoplasm, some converging onto the desmosomes. The intermediate cells also had numerous cell processes, some of which leaving wide intercellular spaces, adjoined the neighboring cells with apical desmosomes. Both large electron-lucent vacuoles. and tonofibrils were present in the cytoplasm (Figure 4). Asthe vacuoles lacked any observable cristae or ribosomes, they did not seem to be swollen mitochondria or endoplasmic reticulas but rather, secretory vacuoles. Light microscopic observations of the same area also demonstrated internal or external periodic acid-schiff- and Alcian blue-positive material (Figure 3). These cells showed a spectrum of changes, ranging from predominantly squamous to predominantly adenomatous types. This intermediate cell type sometimes formed intercellular crypts (Figure 4). Frequency of Adenosquamous Carcinoma in the Stomach In reviewing cases of gastric carcinoma filed in our institution, 9 cases (0.9%) of ASC were found among the 976 cases of advanced carcinoma but there were none among the 1028 cases of early carcinoma. Discussion Although 1 case of gastric ASC was studied ultrastructurally (10), the current report may be the first to ultrastructurally demonstrate both adenomatous and squamous components in an individual cell. In previous ultrastructural studies, an individual cell simultaneously expressing characteristics of two different cell types was noted in carcinomas of the digestive tract other than the stomach. An individual cell with both squamous and adenomatous components was reported in the case of mucoepidermoid carcinoma of the esophagus (2) and also in the case of ASC of the colon (3). An individual cell with tonofibrils and electron-dense neurosecretory granules was also noted in carcinomas of the colon with additional squamous cell and carcinoid features (4-6). In addition, an individual cell with mucous globules and neurosecretory-type granules was detected in the goblet cell carcinoid of the vermiform appendix (7). Clear ultrastructural identification of a cell containing two different characteristics supports the

4 April 1987 GASTRIC ADENOSQUAMOUS CARCINOMA 1081 Figure 3. Mucin-containing cells that stained positive with both periodic acid-schiff and Alcian blue are present in the nests of squamous cells (Periodic acid-schiff and Alcian blue. x 190). Figure 4. Cells containing both mucous vacuoles and tonofibrils (arrow) in electron-dense cytoplasm. Many cell processes and wide intercellular spaces are shown. Some of these processes are attached to those of adjacent cells by desmosomes (X13,500). Tonofibrils and desmosomes are shown in the insets (X77,OOO).

5 1082 MORI ET AL. GASTROENTEROLOGY Vol. 92, No.4 multipotential stem cell OrIgm of these mixed tumors (2-7). There are at least two main explanations for the dual adenosquamous differentiation in this and similar tumors: (a) that there is a stem cell capable of differentiating in both directions simultaneously, and (b) that such stem cells differentiate first into an adenomatous type and that some of the tumor cells later express a squamous phenotype. As this combination is unusual in early gastric carcinomas, but is found in advanced gastric carcinomas, we favor the second hypothesis. Our finding (9) that the clinicopathologic characteristics of ASC are governed basically by the adenocarcinomatous component supports this hypothesis. Studies by Steele and Nettesheim (11) on adenosquamous carcinomas of the lung also confirm this hypothesis. Their studies disclosed that the tumor cells were able to differentiate into adenomatous or squamous cells and, in future generations, to change back from one type to another, thereby suggesting that the appearance of these mixed tumors is not due to proliferation of more than one stem cell with different phenotypes but rather to an unstable differentiation of a single stem cell. References 1. Woodard BH, Brinkhous AD, McCarty KS, McCarty KS Jr. Adenosquamous differentiation in mammary carcinoma: an ultrastructural and steroid receptor study. Arch Pathol Lab Med 1980;104: Woodard BH, Shelburne JD, Vollmer RT, Postlethwait RW. Mucoepidermoid carcinoma of the esophagus. Hum Pathol 1978;9: Cerezo L, Alvarez M, Edwards 0, Price G. Adenosquamous carcinoma of the colon. Dis Colon Rectum 1985;28: Petrelli M. Tetangco E, Reid J. Carcinoma of the colon with undifferentiated, carcinoid, and squamous cell features. Am J Clin PathoI1981;75: Damjanov I, Amenta PS, Bosman FT. Undifferentiated carcinoma of the colon containing exocrine, neuroendocrine and squamous cells. Virchows Arch (pathol Anat) 1983;401: Peonim V, Thakerngpol K, Pacharee p, Stitnimankarn T. Adenosquamous carcinoma and carcinoidal differentiation of the colon. Cancer 1983;52: Warner TFCS, Seo IS. Goblet cell carcinoid of appendix: ultrastructural features and histogenetic aspects. Cancer 1979;44: Japanese Research Society for Gastric Cancer. The general rules for gastric cancer study in surgery and pathology. Jpn J Surg 1981;11: Mori M, Iwashita A, Enjoji M. Adenosquamous carcinoma of the stomach: a clinicopathologic analysis of 28 cases. Cancer 1986;57: Mingazzini PL, Barsotti P, Malchiodialbedi F. Adenosquamous carcinoma of the stomach: histological, histochemical and ultrastructural observations. Histopathology 1983;7: Steele V, Nettesheim P. Unstable cellular differentiation in adenosquamous cell carcinoma. J Natl Cancer Inst 1981; 67: