Abstract
Foregut duplication cyst is most commonly seen in the posterior mediastinum without communication with adjacent organs or presence of other malformations and typically shows ectopic gastric or respiratory epithelium. The finding of ectopic pancreatic tissue is extremely rare. A 15-year-old female patient presented with elevated blood pressure, intermittent right flank pain for 18 months. An abdominal MRI revealed a 4 cm right cystic retroperitoneal mass, initially thought to arise from the right adrenal gland. Intraoperatively, the mass was centered in the retroperitoneum between the right adrenal gland and kidney, without attachments to these organs and no communication with other structures, and it was completely excised. Gross examination revealed a 3.5 cm well-circumscribed solid and cystic mass with orange–white cut surface and cloudy fluid surrounded by variable amounts of adipose tissue. On microscopic examination, the cysts were lined by respiratory and gastric antral/oxyntic-type mucosa, surrounded by muscularis mucosae, submucosal tissue, muscularis propria, and perienteric tissue. Within the muscular propria, exocrine pancreatic tissue was also noted. The patient is well with 7-months of follow up. This case is the first one reporting gastric, respiratory, and pancreatic epithelia.
Introduction
Malformations during the embryologic development and differentiation may result in foregut duplication cysts, with approximately 150 cases reported up to date. 1 Enteric duplication cysts are classified by location as foregut, midgut, or hindgut types. Foregut duplication cysts more commonly show epithelium similar to adjacent normal digestive mucosa, 2 with less than 20 cases containing respiratory epithelium 1 and only 92–10 with ectopic pancreatic tissue reported in the English literature.
Herein, we report the 10th case of foregut duplication cyst containing ectopic pancreatic tissue, and the first one with the three types of epithelia: gastric, respiratory, and pancreatic in a very unusual location (retroperitoneum)2,11 and perform a systematic literature review in the English literature.
Case Report
A 15-year-old female patient presented with elevated blood pressure and intermittent right flank pain for 18 months. Her past medical history was remarkable for obesity and hepatic steatosis. An abdominal ultrasound showed a 3 cm cyst in right upper quadrant without evident origin. An abdominal magnetic resonance imaging (MRI) with contrast performed at our institution showed a 4 cm non-enhancing T2-hyperintense right upper quadrant lesion with internal septations and layering debris, initially interpreted to be a cyst arising from the right adrenal gland with mass effect on the right upper renal pole (Figure 1). A decision to perform surgery was made. Intraoperatively, the cystic lesion was found to be densely adherent posteriorly along the retroperitoneum, between the right adrenal gland and kidney without attachment to these organs. No communication with other structures was seen. Excision of the lesion was performed.
Coronal T2-weighted (A) and post-contrast T1 (B) MRI show a 4 cm well-defined non-enhancing T2 hyperintense cystic lesion with thin septations in the right upper retroperitoneum (arrow) initially misinterpreted as a right adrenal mass given the mass effect on the right upper renal pole and lack of clear visualization of the right adrenal gland.
Gross examination revealed a 3.5 × 3.4 × 1.9 cm well-circumscribed mass with a solid and cystic, orange-white cut surface with the cysts containing tan-white cloudy fluid.
On microscopic examination, the cysts were lined by respiratory epithelium and gastric antral/oxyntic-type mucosa with associated muscularis mucosae and submucosal tissue. The respiratory epithelium showed tall cells with pseudostratified nuclei and apical cilia admixed with goblet cells and focal squamous metaplasia, and rare Paneth-like cells without associated salivary-type glands or cartilage (Figure 2). The gastric mucosa recapitulated antral/oxyntic-type mucosa with abundant apical cytoplasmic mucin cap and basally oriented nuclei lining acini (Figure 3). The gastric epithelium was focally continuous with the ciliated respiratory epithelium (Figure 2). The respiratory and gastric-type mucosa were associated with scattered lymphoid aggregates. Focal ulceration was seen associated with chronic inflammation, histiocytes, and underlying fibrosis. A thick coat of smooth muscle with both circular and longitudinal layers (Figure 2) containing numerous nerves and ganglionic plexuses, adipose tissue, blood vessels, and a lymph node was seen at the outer layer of the cysts wall. Scattered throughout the muscular layers there were variable-sized islands of exocrine pancreatic tissue composed of small acini containing columnar to pyramidal-type cells with a tubuloalveolar arrangement with abundant granules surrounding sparse pancreatic ducts lined by cuboidal epithelium (Figure 4). Islets of Langerhans were absent.
Cyst lined by respiratory epithelium surrounded by lamina propria, muscularis mucosae, submucosa, and longitudinal (A, ×100) and circular (B, ×100) layers of smooth muscle. Pseudostratified ciliated epithelium alternates with scattered goblet cells (C, ×400). Transition from gastric (left) to respiratory-type epithelium with squamous metaplasia (right) (D, ×400).
Cyst lined by gastric foveolar epithelium with abundant apical cytoplasmic mucin cap and basally oriented nuclei, underlying antral (A) and oxyntic (B) glands, and muscular layers (A, ×100; B, ×200).
Islands of exocrine pancreas composed of acini with tubuloalveolar arrangement, and sparse pancreatic ducts lined with cuboidal epithelium present within muscular wall (A, ×100; B, ×200; C and D, ×400).
The postoperative course of the patient was uneventful, and she remains well at 7-month follow-up.
Discussion
Enteric duplication cysts, also designated as alimentary tract duplication cysts, are rare congenital malformations that can occur anywhere along the gastrointestinal tract; they are most common in the small intestine, particularly the ileum, and are classified as foregut, midgut, or hindgut. 12 Enteric duplication cysts of either type are extremely rare in the retroperitoneum, with only 14 such cases reported in the literature. 7 They are commonly located in the left suprarenal region or behind the right mesocolon. Thirteen did not share a common muscular wall with the native bowel, and only one communicated with the adjacent colon, 13 with intestinal-type epithelium being the most common lining.
In the current case, the right retroperitoneal duplication cyst was initially considered to arise from the right adrenal gland as MRI failed to clearly visualize this organ, and there was secondary mass effect on the right kidney. Imaging interpretation can be very challenging in this location. Retroperitoneal duplication cysts with a significant size can cause mass effect on adjacent organs, such as kidney and adrenal gland, and may show poorly demarcated borders, leading to misinterpretation of its anatomic origin. Similarly, inflammatory changes and adhesions can decrease anatomic delineation between the cyst and other organs with lesions initially misinterpreted as renal and adrenal masses.7,14
The embryologic development of foregut duplication cysts remains unclear. Theories have been proposed with the split notochord syndrome theory as the most widely accepted. 15 According to this theory, foregut duplication cysts may occur when the foregut endoderm and the notochord are not completely separated, forming a traction diverticulum that later on develops into a cyst. The incomplete separation may prevent the fusion of vertebral bodies, leading to anomalies in the vertebral column which explains the coexistence of foregut duplication cysts with vertebral malformations in some cases. Foregut cysts appear before the development of the laryngotracheal tube during where the cranial part of the foregut is partitioned, which may explain the possible presence of respiratory epithelium in these cysts. As the esophagus grows caudally, foregut duplication cysts may grow into intraabdominal/retroperitoneal locations.
Criteria to establish the diagnosis of foregut duplication cyst include the finding of a cyst lined by gastrointestinal-type epithelium, sharing a common blood supply with its neighboring alimentary tract, and the presence of a muscular wall with both circular and longitudinal layers, recapitulating the normal foregut. 16 In the current case, the cysts were lined by respiratory and antral/oxyntic gastric-type epithelium, surrounded by circular and longitudinal layers of smooth muscle containing exocrine pancreas, recapitulating foregut.
Up to date, only nine foregut duplication cysts containing ectopic pancreatic tissue have been reported in the English literature (Table 1).2–10 Patients had a mean age of 13 (range: 0–52) years with similar male-to-female ratio. Four of nine patients were neonates, all presenting with respiratory distress. Cysts were located in the posterior mediastinum in 3, and in the lung in 1. Among the other five patients, two had chest pain with cysts in the posterior mediastinum, two had abdominal pain with cysts in the left retroperitoneum, and one had rectal pain with the cyst centered in the presacral region. 2 The presacral foregut duplication cyst reported by Seydafkan et al., 2 although not explicitly described in the retroperitoneum, the location between rectum and sacrum makes it likely the cyst to be in that location. Three of nine patients also presented with other malformations, all neonates. One had communicating hydrocephalus and bilateral floppy upper limbs; another had Tetralogy of Fallot; and the last one had T3–T4 hemivertebrae. The mean dimension of these foregut duplication cysts was 4.4 (range: 0.5–8.6) cm, and only three out of nine communicated with adjacent organs (esophagus in two and lung in one (neonate)). Most of the lesions were solid and cystic, with brownish fluid noted in three on gross exam. Besides pancreatic tissue (mixed exocrine and endocrine in five; exclusively exocrine in four) seen in all nine cysts, four had gastric epithelium (fundic type in two; cardiac type in one; unknown in two; and one with immature squamous epithelium), four had respiratory epithelium (cartilage only present in the lung lesion; bronchial glands absent in four; one with mature squamous epithelium), and two had intestinal-type epithelium. Eight of nine patients underwent excision of the cysts, with one patient having been followed for 14 years before surgery. One neonate had a lobectomy as the cyst was within the lung parenchyma. She also presented with Tetralogy of Fallot and died 3 days after surgery due to severe hypoxemia. The other four patients with follow-up (range: 8 months–3.0 years) are alive without any further complications. In the case reported by Emoto K et al., 8 it is stated in the “histological findings” that “…. positive Muc5AC glycoprotein and Muc6 glycoprotein indicated some functional gastric mucosa besides the presence of respiratory and pancreatic tissue.” This statement is based only on immunohistochemical, without morphologic description of gastric mucosa. Therefore, the findings are relatively different from the current case.
Summary of clinical and pathological features of foregut duplication cysts with ectopic pancreatic tissue
Abbreviations: AWOD: alive without disease; DOD: dead of disease; F: female; H: Hispanic; IHC: immunohistochemistry; M, male; N, neonate; NA, not available; W: White; y: years.
* “Functional gastric mucosa” is based only on immunohistochemical, without morphologic description of gastric mucosa.
** Although retroperitoneum is not explicitly described, the location between rectum and sacrum makes it likely that that duplication cyst was in the retroperitoneum.
In conclusion, herein we report the 10th case of foregut duplication cyst containing ectopic pancreatic tissue, and the first with respiratory, gastric, and pancreatic tissues.
Footnotes
Declaration of Conflicting Interests
The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
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