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Adenocarcinoma arising from a gastric duplication cyst
Surgical Oncology 21 (2012) e97ee101
Contents lists available at SciVerse ScienceDirect
Surgical Oncology journal homepage: www.elsevier.com/locate/suronc
Review
Adenocarcinoma arising from a gastric duplication cyst Jinfeng Zheng, Hongbiao Jing* Department of Pathology, The General Hospital, Jinan Military Command, Shifan Road 25, Jinan, Shandong Province 250031, PR China
a r t i c l e i n f o
a b s t r a c t
Article history: Accepted 7 March 2012
Malignant transformation in a gastric duplication cyst (GDC) is extremely rare, with only eight reported cases to date. An additional case of an adenocarcinoma arising from a GDC in a 25-year-old male is reported here. Ultrasonography and computed tomography (CT) scans detected a well-defined cyst arising from the greater curvature of the stomach. The patient was submitted to en-bloc resection of the mass with total gastrectomy and regional lymphadenectomy. At the time of laparotomy, the unilocular cyst was full of a thick substance and had no association with the gastric lumen. Microscopic examination revealed that the cystic mass had a well-formed cyst wall with an inner mucosal lining, submucosal layer, muscularis propria, and outer serosal layer. The inner cyst was lined by gastric mucosa. A mediated differentiated adenocarcinoma was found in the duplication cyst, which had invaded the serosa of the cyst wall and the gastric muscular wall. To our knowledge, this is the youngest and only asymptomatic patient in whom neoplastic GDC changes have been reported. Ó 2012 Elsevier Ltd. All rights reserved.
Keywords: Adenocarcinoma Duplication cyst Stomach
Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e97 Case report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e97 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e98 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e100 Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e100 Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e100 Authorship statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e100 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e100 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e100
Introduction
Case report
Gastrointestinal tract duplications are uncommon congenital abnormalities found anywhere along the alimentary tract from the tongue to the anus. By definition, they are located in or adjacent to the wall of the gastrointestinal tract, have smooth muscle in their walls, and are lined by alimentary tract mucosa. Gastric duplication cysts (GDCs) are quite rare, and most have been reported in children [1]. Neoplastic change within GDCs is extremely rare, with only eight previously documented cases in the English-language literature to date (Table 1) [2e6]. In this study, we report the clinicopathological features of an additional case of adenocarcinoma arising from the GDC; furthermore, we review the available literature regarding carcinomas within the GDCs.
A 25-year-old male presented with an abdominal cystic mass that had been found incidentally on ultrasonography during a health check-up. There was no history of nausea, vomiting, weight loss, or colicky abdominal pain. His medical history and family history were unremarkable. On physical examination, there was no evidence of a palpable abdominal mass. The laboratory test results were normal except for an elevated CEA level of 80 mg/l (normal range: 0e5 mg/l). Ultrasonography showed the presence of an 8-cm ovoid cystic mass of heterogeneous density, centered in the region of the gastrosplenic ligament. A computed tomography (CT) scan also detected a well-defined cyst, which measured 8 cm 6 cm, in contact with the greater curvature of the stomach. After endovenous administration of contrast medium, there was contrast enhancement in the cystic wall (Fig. 1). No lymphadenopathy, ascites, or liver metastases were found.
* Corresponding author. Tel.: þ86 531 51666857; fax: þ86 531 51666284. E-mail address: [email protected] (H. Jing). 0960-7404/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.suronc.2012.03.002
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J. Zheng, H. Jing / Surgical Oncology 21 (2012) e97ee101
Table 1 Clinicopathological data for reported cases of carcinoma arising from a GDC. Reference
Sex/age (yr)
Symptoms
Size of cyst (cm)
Histology
Invision
Outcome (mo)
Mayo et al. [2]
F/64
Weakness, anorexia, weight loss
6
ADC
NED/12
Coit and Mies [3]
M/50
Vomiting, weight loss
17
F/72
3.2
Epithelial malignancy ADC
Wall of the stomach and cyst NA
10 8 7
ADC ADC ADC NEC Mixed ADC and SCC ADC
Kuraoka et al. [4]
M/56 F/71 M/40
Abdominal pain and fullness, weight loss Vomiting, weight loss Abdominal pain, appetite loss Fever, back pain
Horne et al. [5] Barussaud et al. [6]
M/40 F/67
Abdominal pain Abdominal mass, weight loss
12 NA
Present case
M/25
Asytomptomatic
8
Wall of the and cyst Wall of the Wall of the Wall of the and cyst Wall of the Wall of the
NA
stomach
NED/72
cyst cyst stomach
NED/28 NED/1 Liver metastasis/7
cyst stomach and cyst
Multiple metastasis/14 DFD/6
Wall of the stomach and cyst
NED/13
GDC: gastric duplication cyst; yr: year; mo: month; F: female; ADC: adenocarcinoma; NED: no evidence of disease; NA: not available; M: male; NEC: neuroendocrine carcinoma; SCC: squamous cell carcinoma.
At laparotomy, the cystic mass adhered strongly to the greater curvature of the stomach. Opening the cyst revealed that it was full of a thick, gelatinous, greenish-yellow substance. Intraoperative frozen-section analysis of the mass was performed and yielded the diagnosis of an adenocarcinoma. Based on the diagnosis of a malignancy, the ensuing operation involved en-bloc resection of the mass with total gastrectomy and regional lymphadenectomy. The patient had an uneventful recovery and, under treatment with adjuvant chemotherapy, is well and free of disease 13 months postoperatively. Gross pathology revealed that the operative specimen was a total stomach bearing an 8 8 6-cm cyst adjacent to the greater curvature. The unilocular cyst had a smooth, external surface and was not associated with the gastric lumen. The elastic-hard wall of the cyst was granular and had variable thickness (approximately 0.5e1.0 cm), except where a 3.0 2.0 1.5-cm nodule, with a friable tan and partially necrotic cut surface, projected into the cystic lumen. Microscopic examination revealed that the cystic mass had a well-formed cystic wall with an inner mucosal lining, a submucosal layer, muscularis propria with inner and outer smooth muscle layers, corresponding to the muscularis propria of the stomach, and
Figure 1. Abdominal CT scan during the arterial phase after injection revealed a cystic mass in contact with the greater curvature of stomach.
an outer serosal layer. The submucosa was absent and the duplication mucosa rested on a smooth muscle coat in some regions of the cystic wall. The inner cyst was lined predominantly by fundictype gastric mucosa in which parietal, chief and mucinous cells were observed (Fig. 2A, B). Focal areas of the cystic wall were lined by simple columnar epithelium (Fig. 2C). These findings were compatible with a GDC. The distinctive and unusual feature of the cyst was that some areas of lining epithelium revealed widespectrum degeneration from low-grade dysplasia to high-grade dysplasia, intramucosal adenocarcinoma, as well as infiltrative adenocarcinoma, which demonstrated nuclear pleomorphism and frequent mitoses (Fig. 2D, E). The carcinoma had invaded the serosa of the cyst wall and the gastric muscular wall adjacent to the duplication cyst. The grossly identified nodular area likewise contained an infiltrative, moderately differentiated tubular carcinoma. The mucosa of the gastric wall abutting the cyst was intact. No epithelial dysplasia, atrophic gastritis, or intestinal metaplasia was observed in gastric mucosa.
Discussion Alimentary tract duplications represent uncommon developmental malformations and most frequently affect the ileum (35%), the esophagus (19%), the jejunum (10%), the stomach (9%) and the colon (7%) [7e9]. Several theories have been proposed to explain the embryologic basis for gastrointestinal tract duplications, but abnormal recanalization after the solid epithelial stage of embryonic bowel development is thought by most to underlie these lesions [1,10]. Strict morphological criteria have been established for the correct diagnosis of alimentary tract duplications: grossly, they are spheric cysts or tubular structures located in, or immediately adjacent to, part of the gastrointestinal tract; they are surrounded by at least one coat of smooth muscle, fusing with the muscularis propria of the alimentary canal (usually all three muscle layers are present, without a plane of cleavage between the cyst and the alimentary canal); and they are lined by typical gastrointestinal mucosa [7]. The pathological features of the cystic mass found in our patient fulfilled the diagnostic criteria for cystic duplication of the stomach. Clinically, GDCs are usually found during the first year of life, being rarely diagnosed in adults. In review of 83 recorded cases of gastric duplication, Pruksapong et al. found that approximately 77% of patients were younger than 12 years of age [11]. Kremer et al. described 9 cases, with only one adult patient [12].
J. Zheng, H. Jing / Surgical Oncology 21 (2012) e97ee101
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Figure 2. Microscopic appearance of the adenocarcinoma within the GDC by hematoxylin and eosin stains. A: The inner cyst was covered mainly by fundic-type gastric mucosa (original magnification, 40). B: The parietal (arrows) and chief cells (arrowheads) were observed in the lining cystic mucosa (original magnification, 100). C: A few parts of the cystic wall was lined by monolayered columnar epithelium (original magnification, 100). D: Transition from epithelium with dysplasia to adenocarcinoma (arrow) (original magnification, 100). E: Transition from intramucosal carcinoma to infiltrative carcinoma (arrow) (original magnification, 100).
GDCs have been noticed twice as frequently in females but no striking racial or geographic differences have been noted [13]. A wide range of symptoms and signs have been reported and vary from asymptomatic to non disease-specific presentations, e.g. vague abdominal complaints, nausea, vomiting, epigastric fullness, weight loss, anemia, dysphagia, dyspepsia, etc [14]. Vomiting usually occurs due to partial or complete gastric outlet obstruction, while even more emergent cases have been reported such as pancreatitis, hemoptysis and gastrointestinal hemorrhage[15e17]. GDCs are associated with other anomalies in one third of cases: esophageal and duodenal diverticula, duplication cysts elsewhere in the digestive tract, annular and ectopic pancreas, and spinal abnormalitis such as hemivertebra and spina bifida [18,19]. Although GDCs are found anywhere in the stomach, the greater curvature is the most common site, followed by posterior wall,
lesser curvature, anterior wall, and pylorus [20,21]. GDCs may have a cystic or tubular configuration and may or may not communicate with the gastric lumen. The noncommunicating duplications are by far more common and, on radiographic examination, show intramural filling defect indenting the gastric contour [9,22]. Communicating gastric duplications are extremely rare and have been described to be mainly of the tubular type. They are easily diagnosed on barium examination, because both gastric lumina can be readily visualized [21e23]. In the present case, adenocarcinoma in the duplication cyst invaded the serosa of the cyst and the stomach wall. Neither adenocarcinoma in situ nor potentially precancerous lesions, such as epithelial dysplasia, atrophic gastritis, or intestinal metaplasia, were detected in the stomach. These findings suggest that the carcinoma arose from a GDC that invaded the stomach. Malignant
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J. Zheng, H. Jing / Surgical Oncology 21 (2012) e97ee101
changes of the gastric duplication are exceptional events with only nine cases reported in the English-language literature to date, including our case (Table 1) [2e6]. As documented in Table 1, gastric carcinomas within GDCs generally occurred in middle-aged adults (age range: 25e71 years; mean: 54 years). The sex ratio was five males to four females, demonstrating no gender predilection despite the limited sample size. The size of the duplication cyst ranged from 3.2 to 17.0 cm (mean, 8.9 cm). Overall, one of seven patients with available followup data died due to a tumor. Of the remaining patients, two presented with the recurrence of metastatic disease, suggesting the tumor’s poor prognosis. The main symptoms were abdominal pain, weight loss, and vomiting. However, our patient was asymptomatic, and the cystic lesion was found by preoperative ultrasonography. Five of these tumors were reported as adenocarcinomas, suggesting that the adenocarcinoma was the most common histologic type of malignant change associated with GDC. Thus, the types of primary neoplasms that may arise in duplications seem to parallel those of the adjacent gastrointestinal tract. Three tumors were located within the duplication cyst and five tumors invaded the stomach, as in our case. The present case highlights three unusual aspects of this rare malignancy from GDC. Firstly, it is unusual for such malignancies to remain asymptomatic. The first eight cases of carcinoma within GDC were all symptomatic with presentations as described in Table 1. Notably, the mass in our patient was found incidentally during a health check-up. There was no history of nausea, vomiting, weight loss, or abdominal pain. Secondly, all the previously reported patients with carcinoma within the GDC were aged 40 or older. To our knowledge, our patient, who was 25 years old, is the youngest to be reported with a diagnosis of a carcinoma within the GDC. Finally, neither chief nor parietal cells were observed in the duplication mucosa of the eight reported cases of GDC with malignant transformation. However, there were chief and parietal cells in the inner cyst of the present tumor. To our knowledge, this is the first reported case with chief and parietal cells in the mucosa. It is recommended that once a duplication cyst has been diagnosed, even an asymptomatic one, it should be removed because of the risk of malignant changes. Complete resection of the duplication should be the procedure of choice. When a cancer is detected, as in our case, a subtotal or total gastrectomy with reconstruction is unfortunately the only solution. This approach is associated with a poor prognosis [6,22,24]. The pathologic differential diagnosis includes gastrointestinal stromal tumor (GIST) and malignant transformation arising within a gastric teratoma. The stomach is the most common location for GIST, with 60e70% of tumors occurring in this location [25]. The wall of a duplication cyst is typically composed of a well-ordered arrangement of tissues that are native to the stomach, a fact which rules out a diagnosis of GIST. Primary gastric teratomas have been reported but are extremely rare, occurring almost exclusively in the pediatric population [26]. The absence of a disordered arrangement of ectodermal, mesodermal, and endodermal tissues in the present tumor excludes the possibility of a teratoma.
Conclusion In conclusion, we have reported a case of adenocarcinoma arising within a GDC in a 25-year-old man. To our knowledge, this is the youngest and only asymptomatic patient to be reported as presenting with a carcinoma within a GDC. This case adds to a small body of literature on such tumors and widens the spectrum of reported clinical features. More cases of carcinomas within the GDC
must be studied to draw definitive conclusions about the tumor’s distinct behavior and its appropriate management. Conflict of interest statement The authors have no conflicts of interest to declare. Funding This work was supported by the President Fund (Grant No. 2011M02) from the General Hospital, Jinan Military Command, China. Authorship statement Guarantor of the integrity of the study: [Hongbiao Jing, Jinfeng Zheng] Study concepts: [Hongbiao Jing, Jinfeng Zheng] Study design: [Hongbiao Jing] Definition of intellectual content: [Hongbiao Jing] Literature research: [Hongbiao Jing] Clinical studies: [Jinfeng Zheng] Data acquisition: [Jinfeng Zheng] Data analysis: [Hongbiao Jing] Manuscript preparation: [Hongbiao Jing, Jinfeng Zheng] Manuscript editing: [Hongbiao Jing] Manuscript review: [Hongbiao Jing] Acknowledgments The authors thank Michele A and Rachel D (American Journal Experts) for editing the present paper. References [1] Macpherson RI. Gastrointestinal tract duplications: clinical, pathologic, etiologic, and considerations. Radiographics 1993;13:1063e80. [2] Mayo HW, McKee EE, Anderson RM. Carcinoma arising in reduplication of the stomach (gastrogenous cyst): a case report. Ann Surg 1955;141:550e5. [3] Coit DG, Mies C. Adenocarcinoma arising within a gastric duplication cyst. J Surg Oncol 1992;50:274e7. [4] Kuraoka K, Nakayama H, Kagawa T, Ichikawa T, Yasui W. Adenocarcinoma arising from a gastric duplication cyst with invasion to the stomach: a case report with literature review. J Clin Pathol 2004;57:428e31. [5] Horne G, Ming-Lum C, Kirkpatrick AW, Parker R. High-grade neuroendocrine carcinoma arising in a gastric duplication cyst: a case report with literature review. Int J Surg Pathol 2007;15:187e91. [6] Barussauda ML, Meurettea G, Cassagnaub E, Dupasc B, Borgnea JL. Mixed adenocarcinoma and squamous cell carcinoma arising in a gastric duplication cyst. Gastroenterol Clin Biol 2008;32:188e91. [7] Rowling JT. Some observations on gastric cysts. Br J Surg 1959;46:441e5. [8] Bisset GS, Towbin RB. Pediatric case of the day. Radiographics 1986;6:917e20. [9] Scatizzi M, Calistri M, Feroci F, Girardi LR, Moraldi L, Rubio CA, et al. Gastric duplication cyst in an adult: case report. In Vivo 2005;19:975e8. [10] Gross RE, Holcomb JW, Farber S. Duplication of the alimentary tract. Pediatrics 1952;9:449e67. [11] Pruksapong C, Donovan RJ, Pinit A, Heidreth FJ. Gastric duplication. J Pediatr Surg 1979;14:83e5. [12] Kremer RM, Lepoff RB, Izant RJ. Duplication of the stomach. J Pediatr Surg 1970;5:360e4. [13] Bartels RF. Duplication of the stomach. Am J Surg 1967;33:747. [14] Theodosopoulos T, Marinis A, Karapanos K, Vassilikostas G, Dafnios N, Samanides L, et al. Foregut duplication cysts of the stomach with respiratory epithelium. World J Gastroenterol 2007;13:1279e81. [15] Katz W, Annessa G, Read RC. Gastric duplication with pancreatic communication. Presenting as pancreatitis. Minn Med 1967;50:1175e9. [16] Menon P, Rao KL, Saxena AK. Duplication cyst of the stomach presenting as hemoptysis. Eur J Pediatr Surg 2004;14:429e31. [17] Stephen TC, Bendon RW, Nagaraj HS, Sachdeva R. Antral duplication cyst: a cause of hypergastrinemia, recurrent peptic ulceration, and hemorrhage. J Pediatr Gastroenterol Nutr 1998;26:216e8. [18] Veekehlhas GMH. Pathogenesis of intrathoracic gastrogenous cyst. Am J Dis Child 1952;83:500e7. [19] Torma MJ. Of double stomachs. Arch Surg 1974;109:555e7.
J. Zheng, H. Jing / Surgical Oncology 21 (2012) e97ee101 [20] Lewis PL, Holder T, Feldman M. Duplication of the stomach: report of a case and review of the English literature. Arch Surg 1961;82:634e40. [21] Agha FP, Gabriele OF, Abdulla FH. Complete gastric duplication. AJR 1981;137: 406e7. [22] Blinder G, Hiller N, Adler SN. A double stomach in an adult. Am J Gastroenterol 1999;94:1100e2. [23] Bower RJ, Sieber WK, Kiesewetter WB. Alimentary tract duplications in children. Ann Surg 1978;188:669e74.
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[24] Etienne S, Pilette C, Prophette B, Serra-Maudet V. Gastric duplication in the adult: a case report presenting as recurring acute edematous pancreatitis. Ann Chir 2002;127:641e4. [25] Negreanu LM, Assor P, Mateescu B, Cirstoiu C. Interstitial cells of Cajal in the gut e a gastroenterologist’s point of view. World J Gastroenterol 2008;14: 6285e8. [26] Ratan KN, Mathur SK, Marwah N, Purwar P, Rohilla S, Balasubramaniam G. Gastric teratoma. Indian J Pediatr 2004;71:171e2.
Contents lists available at SciVerse ScienceDirect
Surgical Oncology journal homepage: www.elsevier.com/locate/suronc
Review
Adenocarcinoma arising from a gastric duplication cyst Jinfeng Zheng, Hongbiao Jing* Department of Pathology, The General Hospital, Jinan Military Command, Shifan Road 25, Jinan, Shandong Province 250031, PR China
a r t i c l e i n f o
a b s t r a c t
Article history: Accepted 7 March 2012
Malignant transformation in a gastric duplication cyst (GDC) is extremely rare, with only eight reported cases to date. An additional case of an adenocarcinoma arising from a GDC in a 25-year-old male is reported here. Ultrasonography and computed tomography (CT) scans detected a well-defined cyst arising from the greater curvature of the stomach. The patient was submitted to en-bloc resection of the mass with total gastrectomy and regional lymphadenectomy. At the time of laparotomy, the unilocular cyst was full of a thick substance and had no association with the gastric lumen. Microscopic examination revealed that the cystic mass had a well-formed cyst wall with an inner mucosal lining, submucosal layer, muscularis propria, and outer serosal layer. The inner cyst was lined by gastric mucosa. A mediated differentiated adenocarcinoma was found in the duplication cyst, which had invaded the serosa of the cyst wall and the gastric muscular wall. To our knowledge, this is the youngest and only asymptomatic patient in whom neoplastic GDC changes have been reported. Ó 2012 Elsevier Ltd. All rights reserved.
Keywords: Adenocarcinoma Duplication cyst Stomach
Contents Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e97 Case report . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e97 Discussion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e98 Conclusion . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e100 Conflict of interest statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e100 Funding . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e100 Authorship statement . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . .e100 Acknowledgments . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e100 References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . e100
Introduction
Case report
Gastrointestinal tract duplications are uncommon congenital abnormalities found anywhere along the alimentary tract from the tongue to the anus. By definition, they are located in or adjacent to the wall of the gastrointestinal tract, have smooth muscle in their walls, and are lined by alimentary tract mucosa. Gastric duplication cysts (GDCs) are quite rare, and most have been reported in children [1]. Neoplastic change within GDCs is extremely rare, with only eight previously documented cases in the English-language literature to date (Table 1) [2e6]. In this study, we report the clinicopathological features of an additional case of adenocarcinoma arising from the GDC; furthermore, we review the available literature regarding carcinomas within the GDCs.
A 25-year-old male presented with an abdominal cystic mass that had been found incidentally on ultrasonography during a health check-up. There was no history of nausea, vomiting, weight loss, or colicky abdominal pain. His medical history and family history were unremarkable. On physical examination, there was no evidence of a palpable abdominal mass. The laboratory test results were normal except for an elevated CEA level of 80 mg/l (normal range: 0e5 mg/l). Ultrasonography showed the presence of an 8-cm ovoid cystic mass of heterogeneous density, centered in the region of the gastrosplenic ligament. A computed tomography (CT) scan also detected a well-defined cyst, which measured 8 cm 6 cm, in contact with the greater curvature of the stomach. After endovenous administration of contrast medium, there was contrast enhancement in the cystic wall (Fig. 1). No lymphadenopathy, ascites, or liver metastases were found.
* Corresponding author. Tel.: þ86 531 51666857; fax: þ86 531 51666284. E-mail address: [email protected] (H. Jing). 0960-7404/$ e see front matter Ó 2012 Elsevier Ltd. All rights reserved. doi:10.1016/j.suronc.2012.03.002
e98
J. Zheng, H. Jing / Surgical Oncology 21 (2012) e97ee101
Table 1 Clinicopathological data for reported cases of carcinoma arising from a GDC. Reference
Sex/age (yr)
Symptoms
Size of cyst (cm)
Histology
Invision
Outcome (mo)
Mayo et al. [2]
F/64
Weakness, anorexia, weight loss
6
ADC
NED/12
Coit and Mies [3]
M/50
Vomiting, weight loss
17
F/72
3.2
Epithelial malignancy ADC
Wall of the stomach and cyst NA
10 8 7
ADC ADC ADC NEC Mixed ADC and SCC ADC
Kuraoka et al. [4]
M/56 F/71 M/40
Abdominal pain and fullness, weight loss Vomiting, weight loss Abdominal pain, appetite loss Fever, back pain
Horne et al. [5] Barussaud et al. [6]
M/40 F/67
Abdominal pain Abdominal mass, weight loss
12 NA
Present case
M/25
Asytomptomatic
8
Wall of the and cyst Wall of the Wall of the Wall of the and cyst Wall of the Wall of the
NA
stomach
NED/72
cyst cyst stomach
NED/28 NED/1 Liver metastasis/7
cyst stomach and cyst
Multiple metastasis/14 DFD/6
Wall of the stomach and cyst
NED/13
GDC: gastric duplication cyst; yr: year; mo: month; F: female; ADC: adenocarcinoma; NED: no evidence of disease; NA: not available; M: male; NEC: neuroendocrine carcinoma; SCC: squamous cell carcinoma.
At laparotomy, the cystic mass adhered strongly to the greater curvature of the stomach. Opening the cyst revealed that it was full of a thick, gelatinous, greenish-yellow substance. Intraoperative frozen-section analysis of the mass was performed and yielded the diagnosis of an adenocarcinoma. Based on the diagnosis of a malignancy, the ensuing operation involved en-bloc resection of the mass with total gastrectomy and regional lymphadenectomy. The patient had an uneventful recovery and, under treatment with adjuvant chemotherapy, is well and free of disease 13 months postoperatively. Gross pathology revealed that the operative specimen was a total stomach bearing an 8 8 6-cm cyst adjacent to the greater curvature. The unilocular cyst had a smooth, external surface and was not associated with the gastric lumen. The elastic-hard wall of the cyst was granular and had variable thickness (approximately 0.5e1.0 cm), except where a 3.0 2.0 1.5-cm nodule, with a friable tan and partially necrotic cut surface, projected into the cystic lumen. Microscopic examination revealed that the cystic mass had a well-formed cystic wall with an inner mucosal lining, a submucosal layer, muscularis propria with inner and outer smooth muscle layers, corresponding to the muscularis propria of the stomach, and
Figure 1. Abdominal CT scan during the arterial phase after injection revealed a cystic mass in contact with the greater curvature of stomach.
an outer serosal layer. The submucosa was absent and the duplication mucosa rested on a smooth muscle coat in some regions of the cystic wall. The inner cyst was lined predominantly by fundictype gastric mucosa in which parietal, chief and mucinous cells were observed (Fig. 2A, B). Focal areas of the cystic wall were lined by simple columnar epithelium (Fig. 2C). These findings were compatible with a GDC. The distinctive and unusual feature of the cyst was that some areas of lining epithelium revealed widespectrum degeneration from low-grade dysplasia to high-grade dysplasia, intramucosal adenocarcinoma, as well as infiltrative adenocarcinoma, which demonstrated nuclear pleomorphism and frequent mitoses (Fig. 2D, E). The carcinoma had invaded the serosa of the cyst wall and the gastric muscular wall adjacent to the duplication cyst. The grossly identified nodular area likewise contained an infiltrative, moderately differentiated tubular carcinoma. The mucosa of the gastric wall abutting the cyst was intact. No epithelial dysplasia, atrophic gastritis, or intestinal metaplasia was observed in gastric mucosa.
Discussion Alimentary tract duplications represent uncommon developmental malformations and most frequently affect the ileum (35%), the esophagus (19%), the jejunum (10%), the stomach (9%) and the colon (7%) [7e9]. Several theories have been proposed to explain the embryologic basis for gastrointestinal tract duplications, but abnormal recanalization after the solid epithelial stage of embryonic bowel development is thought by most to underlie these lesions [1,10]. Strict morphological criteria have been established for the correct diagnosis of alimentary tract duplications: grossly, they are spheric cysts or tubular structures located in, or immediately adjacent to, part of the gastrointestinal tract; they are surrounded by at least one coat of smooth muscle, fusing with the muscularis propria of the alimentary canal (usually all three muscle layers are present, without a plane of cleavage between the cyst and the alimentary canal); and they are lined by typical gastrointestinal mucosa [7]. The pathological features of the cystic mass found in our patient fulfilled the diagnostic criteria for cystic duplication of the stomach. Clinically, GDCs are usually found during the first year of life, being rarely diagnosed in adults. In review of 83 recorded cases of gastric duplication, Pruksapong et al. found that approximately 77% of patients were younger than 12 years of age [11]. Kremer et al. described 9 cases, with only one adult patient [12].
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Figure 2. Microscopic appearance of the adenocarcinoma within the GDC by hematoxylin and eosin stains. A: The inner cyst was covered mainly by fundic-type gastric mucosa (original magnification, 40). B: The parietal (arrows) and chief cells (arrowheads) were observed in the lining cystic mucosa (original magnification, 100). C: A few parts of the cystic wall was lined by monolayered columnar epithelium (original magnification, 100). D: Transition from epithelium with dysplasia to adenocarcinoma (arrow) (original magnification, 100). E: Transition from intramucosal carcinoma to infiltrative carcinoma (arrow) (original magnification, 100).
GDCs have been noticed twice as frequently in females but no striking racial or geographic differences have been noted [13]. A wide range of symptoms and signs have been reported and vary from asymptomatic to non disease-specific presentations, e.g. vague abdominal complaints, nausea, vomiting, epigastric fullness, weight loss, anemia, dysphagia, dyspepsia, etc [14]. Vomiting usually occurs due to partial or complete gastric outlet obstruction, while even more emergent cases have been reported such as pancreatitis, hemoptysis and gastrointestinal hemorrhage[15e17]. GDCs are associated with other anomalies in one third of cases: esophageal and duodenal diverticula, duplication cysts elsewhere in the digestive tract, annular and ectopic pancreas, and spinal abnormalitis such as hemivertebra and spina bifida [18,19]. Although GDCs are found anywhere in the stomach, the greater curvature is the most common site, followed by posterior wall,
lesser curvature, anterior wall, and pylorus [20,21]. GDCs may have a cystic or tubular configuration and may or may not communicate with the gastric lumen. The noncommunicating duplications are by far more common and, on radiographic examination, show intramural filling defect indenting the gastric contour [9,22]. Communicating gastric duplications are extremely rare and have been described to be mainly of the tubular type. They are easily diagnosed on barium examination, because both gastric lumina can be readily visualized [21e23]. In the present case, adenocarcinoma in the duplication cyst invaded the serosa of the cyst and the stomach wall. Neither adenocarcinoma in situ nor potentially precancerous lesions, such as epithelial dysplasia, atrophic gastritis, or intestinal metaplasia, were detected in the stomach. These findings suggest that the carcinoma arose from a GDC that invaded the stomach. Malignant
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changes of the gastric duplication are exceptional events with only nine cases reported in the English-language literature to date, including our case (Table 1) [2e6]. As documented in Table 1, gastric carcinomas within GDCs generally occurred in middle-aged adults (age range: 25e71 years; mean: 54 years). The sex ratio was five males to four females, demonstrating no gender predilection despite the limited sample size. The size of the duplication cyst ranged from 3.2 to 17.0 cm (mean, 8.9 cm). Overall, one of seven patients with available followup data died due to a tumor. Of the remaining patients, two presented with the recurrence of metastatic disease, suggesting the tumor’s poor prognosis. The main symptoms were abdominal pain, weight loss, and vomiting. However, our patient was asymptomatic, and the cystic lesion was found by preoperative ultrasonography. Five of these tumors were reported as adenocarcinomas, suggesting that the adenocarcinoma was the most common histologic type of malignant change associated with GDC. Thus, the types of primary neoplasms that may arise in duplications seem to parallel those of the adjacent gastrointestinal tract. Three tumors were located within the duplication cyst and five tumors invaded the stomach, as in our case. The present case highlights three unusual aspects of this rare malignancy from GDC. Firstly, it is unusual for such malignancies to remain asymptomatic. The first eight cases of carcinoma within GDC were all symptomatic with presentations as described in Table 1. Notably, the mass in our patient was found incidentally during a health check-up. There was no history of nausea, vomiting, weight loss, or abdominal pain. Secondly, all the previously reported patients with carcinoma within the GDC were aged 40 or older. To our knowledge, our patient, who was 25 years old, is the youngest to be reported with a diagnosis of a carcinoma within the GDC. Finally, neither chief nor parietal cells were observed in the duplication mucosa of the eight reported cases of GDC with malignant transformation. However, there were chief and parietal cells in the inner cyst of the present tumor. To our knowledge, this is the first reported case with chief and parietal cells in the mucosa. It is recommended that once a duplication cyst has been diagnosed, even an asymptomatic one, it should be removed because of the risk of malignant changes. Complete resection of the duplication should be the procedure of choice. When a cancer is detected, as in our case, a subtotal or total gastrectomy with reconstruction is unfortunately the only solution. This approach is associated with a poor prognosis [6,22,24]. The pathologic differential diagnosis includes gastrointestinal stromal tumor (GIST) and malignant transformation arising within a gastric teratoma. The stomach is the most common location for GIST, with 60e70% of tumors occurring in this location [25]. The wall of a duplication cyst is typically composed of a well-ordered arrangement of tissues that are native to the stomach, a fact which rules out a diagnosis of GIST. Primary gastric teratomas have been reported but are extremely rare, occurring almost exclusively in the pediatric population [26]. The absence of a disordered arrangement of ectodermal, mesodermal, and endodermal tissues in the present tumor excludes the possibility of a teratoma.
Conclusion In conclusion, we have reported a case of adenocarcinoma arising within a GDC in a 25-year-old man. To our knowledge, this is the youngest and only asymptomatic patient to be reported as presenting with a carcinoma within a GDC. This case adds to a small body of literature on such tumors and widens the spectrum of reported clinical features. More cases of carcinomas within the GDC
must be studied to draw definitive conclusions about the tumor’s distinct behavior and its appropriate management. Conflict of interest statement The authors have no conflicts of interest to declare. Funding This work was supported by the President Fund (Grant No. 2011M02) from the General Hospital, Jinan Military Command, China. Authorship statement Guarantor of the integrity of the study: [Hongbiao Jing, Jinfeng Zheng] Study concepts: [Hongbiao Jing, Jinfeng Zheng] Study design: [Hongbiao Jing] Definition of intellectual content: [Hongbiao Jing] Literature research: [Hongbiao Jing] Clinical studies: [Jinfeng Zheng] Data acquisition: [Jinfeng Zheng] Data analysis: [Hongbiao Jing] Manuscript preparation: [Hongbiao Jing, Jinfeng Zheng] Manuscript editing: [Hongbiao Jing] Manuscript review: [Hongbiao Jing] Acknowledgments The authors thank Michele A and Rachel D (American Journal Experts) for editing the present paper. References [1] Macpherson RI. Gastrointestinal tract duplications: clinical, pathologic, etiologic, and considerations. Radiographics 1993;13:1063e80. [2] Mayo HW, McKee EE, Anderson RM. Carcinoma arising in reduplication of the stomach (gastrogenous cyst): a case report. Ann Surg 1955;141:550e5. [3] Coit DG, Mies C. Adenocarcinoma arising within a gastric duplication cyst. J Surg Oncol 1992;50:274e7. [4] Kuraoka K, Nakayama H, Kagawa T, Ichikawa T, Yasui W. Adenocarcinoma arising from a gastric duplication cyst with invasion to the stomach: a case report with literature review. J Clin Pathol 2004;57:428e31. [5] Horne G, Ming-Lum C, Kirkpatrick AW, Parker R. High-grade neuroendocrine carcinoma arising in a gastric duplication cyst: a case report with literature review. Int J Surg Pathol 2007;15:187e91. [6] Barussauda ML, Meurettea G, Cassagnaub E, Dupasc B, Borgnea JL. Mixed adenocarcinoma and squamous cell carcinoma arising in a gastric duplication cyst. Gastroenterol Clin Biol 2008;32:188e91. [7] Rowling JT. Some observations on gastric cysts. Br J Surg 1959;46:441e5. [8] Bisset GS, Towbin RB. Pediatric case of the day. Radiographics 1986;6:917e20. [9] Scatizzi M, Calistri M, Feroci F, Girardi LR, Moraldi L, Rubio CA, et al. Gastric duplication cyst in an adult: case report. In Vivo 2005;19:975e8. [10] Gross RE, Holcomb JW, Farber S. Duplication of the alimentary tract. Pediatrics 1952;9:449e67. [11] Pruksapong C, Donovan RJ, Pinit A, Heidreth FJ. Gastric duplication. J Pediatr Surg 1979;14:83e5. [12] Kremer RM, Lepoff RB, Izant RJ. Duplication of the stomach. J Pediatr Surg 1970;5:360e4. [13] Bartels RF. Duplication of the stomach. Am J Surg 1967;33:747. [14] Theodosopoulos T, Marinis A, Karapanos K, Vassilikostas G, Dafnios N, Samanides L, et al. Foregut duplication cysts of the stomach with respiratory epithelium. World J Gastroenterol 2007;13:1279e81. [15] Katz W, Annessa G, Read RC. Gastric duplication with pancreatic communication. Presenting as pancreatitis. Minn Med 1967;50:1175e9. [16] Menon P, Rao KL, Saxena AK. Duplication cyst of the stomach presenting as hemoptysis. Eur J Pediatr Surg 2004;14:429e31. [17] Stephen TC, Bendon RW, Nagaraj HS, Sachdeva R. Antral duplication cyst: a cause of hypergastrinemia, recurrent peptic ulceration, and hemorrhage. J Pediatr Gastroenterol Nutr 1998;26:216e8. [18] Veekehlhas GMH. Pathogenesis of intrathoracic gastrogenous cyst. Am J Dis Child 1952;83:500e7. [19] Torma MJ. Of double stomachs. Arch Surg 1974;109:555e7.
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[24] Etienne S, Pilette C, Prophette B, Serra-Maudet V. Gastric duplication in the adult: a case report presenting as recurring acute edematous pancreatitis. Ann Chir 2002;127:641e4. [25] Negreanu LM, Assor P, Mateescu B, Cirstoiu C. Interstitial cells of Cajal in the gut e a gastroenterologist’s point of view. World J Gastroenterol 2008;14: 6285e8. [26] Ratan KN, Mathur SK, Marwah N, Purwar P, Rohilla S, Balasubramaniam G. Gastric teratoma. Indian J Pediatr 2004;71:171e2.