Variations in Epithelial Lining of Duplication Cysts Cannot be Explained by Known Theories

Introduction

Duplication cysts are rare congenital malformations of the gastrointestinal (GI) tract. The etiology of duplication cysts is unclear, and several theories have been put forward to explain their etiopathogenesis. ¹ It is present in 0.2% of children and has an incidence of 1:4500 to 1:8200 live births, with a small male predilection.^2–6 They are predominantly localized in the jejunum and ileum but can be found throughout the entire GI tract, from the oropharynx to the anus. ⁷

Duplication cysts are usually symptomatic in the first 2 years of life, but often remain asymptomatic. Prenatal diagnosis is possible on ultrasonography (US) only 20% to 30% of the duplication cysts. ⁵ The variations in location, size, type, and histopathological findings of duplication cysts create a diverse clinical presentation and make the diagnosis challenging. Diagnosis can be based on US, magnetic resonance imaging, and computed tomography.^1,8 Scintigraphy and upper GI series can be also used for diagnosis. ³

Pathological evaluations of duplication cysts have identified three distinct features: a well-defined layer of smooth muscle; an epithelial lining that represents a portion of the GI tract mucosa; and a close anatomic association with a portion of the GI tract. Based on their structure, duplication cysts can be categorized as tubular or cystic. ⁵ The duplication cysts are named for the portion of the GI tract to which they are most closely attached, even though their mucosal lining does not always match the surrounding GI tissue. They might not always have the same epithelial lining as the nearby GI tract, and they might exhibit distinct epithelial. Therefore, a retrospective study was performed to evaluate the variations of epithelial lining of patients with duplication cysts and its impact on clinical findings.

Methods and Patients

Twenty-five patients with a diagnosis of duplication cysts between January 2012 and December 2022 included. The medical records of patients were evaluated for demographic features, clinical findings, radiological methods used for diagnosis, treatment options, localization, size, type, and histopathological findings of duplication cysts. Associated anomalies and postoperative complications were also retrieved from the medical records.

Results

Twenty-five patients enrolled into the study. Sixty percentage (n = 15) of them were male and 40% (n = 10) of them were female. The mean age was 4 years (16 days-14 years). Table 1 displays the clinical features, associated anomalies, diagnostic methods, treatment options, and postoperative complications of the patients.

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Table 1.

Clinical Features, Associated Anomalies, Diagnostic Tools, Treatment Options, and Postoperative Complications.

Parameters	n (%)
Clinical presentations Abdominal pain Prenatal diagnosed Constipation and nausea/vomiting Gastrointestinal bleeding Intestinal obstruction and volvulus	9 (36%) 6 (24%) 5 (20%) 2 (8%) 1 (4%)
Associated anomalies Asthma Epilepsy Hydroureteronephrosis Serebromandibulocostal syndrome Congenital Horner Syndrome Vertebral deformity and scoliosis	1 (4%) 1 (4%) 1 (4%) 1 (4%) 1 (4%) 1 (4%)
Diagnostic approach Ultrasound Magnetic resonance imaging Ultrasound and computed tomography Ultrasound and Magnetic resonance imaging Upper gastrointestinal series and x-ray X-ray + ultrasound and computed tomography	10 (40%) 1 (4%) 3 (12%) 9 (36%) 1 (4%) 1 (4%)
Treatment Laparotomy - Cyst excision - Bowel resection with cyst excision Cyst excision in rectum Endoscopic unroofing	20 (80%) 8 (32%) 12 (48%) 1 (4%) 1 (4)
Postoperative complications Nausea and vomiting	1 (4)

Most common clinical presentation was abdominal pain (36%). Constipation, nausea, and vomiting could often accompany abdominal pain or occur as a single symptom in some patients. GI bleeding with abdominal pain and constipation was observed in patients with rectal localization. One of our patients admitted to hospital with intestinal obstruction and volvulus. Respiratory distress was observed in only one patient. Six of the patients were diagnosed prenatally and two of them were found in thoracoabdominal localization. The clinical presentation of two patients could not be accessed.

Six (24%) of the patients had associated anomalies including asthma, epilepsy, and hydroureteronephrosis with bilateral renal pelviectasis, cerebromandibulocostal syndrome with midgut malrotation, congenital Horner syndrome, and vertebral deformity with scoliosis.

US was performed in 92% (n = 23) of the patients. CT scan (n = 4) and MRI (n = 9) were performed for diagnosis. To have an accurate differential diagnosis and better demonstration of relationship with the cyst and the spinal channel, MRI was the first choice of diagnostic methods in the patient with rectal localization (Figure 1). The patient who developed intestinal obstruction findings and midgut volvulus diagnosed with upper GI series. In this patient, emergency surgery with surgical excision of duplication cysts extending from the duodenum to the jejunum was excised. In one of the patients, active GI bleeding was the only findings and diagnosed with scintigraphy. In that patient, an 18 cm long tubular duplication cyst adjacent to the ileum was detected.

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Figure 1.

Magnetic resonance imaging demonstrating presacral mass (arrow) with the diagnosis of rectal DC.

Laparotomy was performed in 18 of 22 operated patients and two of them converted from laparoscopy. While cyst excision was performed in eight of the patients, bowel resection was performed with cyst excision in the 12 patients. Simple cyst excision was performed in rectal DC. One of the patients with duodenal duplication cysts underwent endoscopic unroofing.

In histopathological evaluations, different epithelial linings were found in different localizations. Table 2 shows the type and histopathological findings of the duplication cysts according to localization in our series. Ileum (n = 12; 48%) was the most common site of duplication cysts in our series. Three patients had duplication cysts in more than one localization. Two of them were extended from the esophagus to the stomach and other one extends from the duodenum to the jejunum. Intestinal and duodenal (n = 12, 48%) and gastric (n = 10, 40%) epithelial layers were the most common finding in our patient series.

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Table 2.

The Type and Histopathological Findings of the Duplication Cyst According to Different Localization.

	Location	Cases (n, %)	Histopathological findings (n)	Type of duplication cysts(Cystic:Tubular)
FOREGUT	Thoracoabdominal	2 (8%)	Respiratory and intestinal (1)	2:0
	Stomach	3 (12%)	Respiratory (1) Gastric (2)	3:0
	Duodenum	4 a (16%)	Gastric and intestinal (1) Gastric (1) Duodenal (1)	3:0
			Duodenal a (1)	0:1 a
MIDGUT	Jejunum	2 a (8%)
			Gastric (1)	1:0
	Ileum	12 (48%)	Gastric (3) Respiratory and gastric (1) Intestinal (6)	9:2
HINDGUT	Colon	2(8%)	Gastric and duodenal (1) Duodenal (1)	1:1
	Rectum	1(4%)	Respiratory	1:0

^a

One patient had cyst extending from the duodenum to the jejunum (patient #3).

Four of the patients had respiratory epithelial lining (16%): two of them were in foregut duplication cysts localized in the thoracoabdominal and gastric DC, one in ileal, and one in rectal duplications. Figure 2 shows the histopathological features of ciliated pseudostratified epithelium lining in the rectal cyst. In a patient with ileal cyst, the gastric epithelial layer accompanied respiratory epithelial layer. Also, two distinct epithelium patterns in duplication cysts were found together in 5 of all of the patients. We could not find any relation between epithelial lining and clinical findings. The clinical findings of the patients mostly depend on the localization of duplication cysts, not on epithelial lining of the cysts.

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Figure 2.

(a) Cyst with fibrous tissue in the wall (Hematoxylin and Eosin, scale bar: 500 µm). (b) Ciliated pseudostratified epithelium lining the cyst (Hematoxylin and Eosin, scale bar: 50 µm).

Discussion

The term duplication cysts, also known as alimentary tract duplications, was proposed to simplify the nomenclature by William E. Ladd in 1937, believing that duplication cysts shared a similar embryological mechanism. ⁹ Although the term widespread used today, we know that no single theory accounts for all duplications, locations, and associated anomalies. Also, the pathogenesis is still not completely understood.

Duplication cysts believed to arise during the early embryonic development of the GI tract between fourth to eighth weeks of gestation.^1,5 Several theories may explain variants that seen in children. There is a slight predominance in male patients and it is similar to our series.^2–5 Most of the patients (80%) are cystic whereas 16% of them are tubular and only 4% of them are mixed. ² Their clinical presentation depends on the adjacent GI tract and most of them asymptomatic. Gastric and pancreatic tissues are usually ectopic in the duplication cysts and may cause clinical findings such as bleeding. Epithelial lining of the duplication cysts is different from the ectopic tissues and their role in the etiology is not known. This is first study that evaluating the role of epithelial lining on clinical findings of duplication cysts.

Although ectopic tissues may have impact on symptoms in patients with duplication cysts, we found no relation between epithelium of cyst and the clinical findings of the patients. The epithelial lining of duplication cysts may not be the same type as the surrounding tissue. Ectopic gastric mucosa is seen in 20-30% of duplication cysts, most often in the esophagus and midgut. ⁵ In our cohort, intestinal and/or duodenal (n = 12, 48%) and gastric (n = 10, 40%) epithelial layers were the most common finding, and there was no ectopic pancreatic mucosa in any of the duplication cysts.

Respiratory epithelia in foregut duplication cysts are not surprising, however, localization of respiratory epithelium in midgut and hindgut arouse curiosity. Therefore, we tried to explain the presence of respiratory epithelium in other parts of GI tract with the known theories. According to the partial or abortive twinning theory, duplication cysts may arise as a result of an incomplete twinning of the GI tract. Although this theory could explain the colorectal duplication cysts associated with doubling anomalies of the genitourinary tract, it falls short of explaining cysts occurring in other areas. ⁵ It also does not explain the respiratory epithelia in midgut and hindgut.

There is a connection between the foregut endoderm and the neural tube ectoderm, which normally separates at the fourth week of intrauterine development. According to the split notochord theory, during this separation, a gap appearance occurs in the notochord through which a diverticulum from the foregut can herniate. This mechanism results in the development of the duplications of tubular outpouchings. This theory could be explaining the dorsal location of duplication cysts in the chest and the occurrence of duplication cysts associated with vertebral anomalies^1,6 but not explain the migration of foregut epithelia to hindgut.

The embryonic diverticula theory is based on the explanation that there exist many diverticula in the growing embryo and they are mostly located in the ileum, that the site of most duplication cysts. Although it seems reasonable that this mechanism contributes to the formation of enteric duplications, this theory fails to explain the cause of cysts with heterotopic mucosa or located in the bowel mesentery. Because most of the diverticula are located on the antimesenteric side of the bowel.^1,5,10

Finally, the recanalization theory of duplication cysts proposes that these cysts form due to errors in the recanalization of the intestine during embryonic development. However, this theory cannot explain why duplication cysts also occur in areas that do not undergo the recanalization. ⁵

It is not clear which of these different theories plays a role in the development of duplications. During embryologic development, environmental stresses on the fetus or disorders in any of the developmental mechanisms may be involved in the formation of duplications. All of these suggest that the origin of duplication cysts may be multifactorial.^8,11,12 And none of these theories explain the presence of respiratory epithelium different from foregut duplications in our series.

Duplication cysts have spectrum of symptoms and non-specific findings often mimic other diseases. Clinical features could be variable depending on the location, size, and mucosal lining of the cyst. ¹⁰ These include such as pain, nausea, vomiting, bleeding, swelling, bloating, dysphagia, dyspepsia, respiratory distress, chronic constipation, and complications including bleeding, perforation, malignancy, and obstruction of the GI tract and vessels. Although studies indicate that due to this wide range of symptoms, most of the duplication cysts will be diagnosed incidentally, especially during surgery. In our series, only one lesion was detected incidentally during surgery and most of the patients were diagnosed with imaging modalities. ¹³ Twenty-four percent of patients were diagnosed prenatally in our series.

Small number of patients is one of the limitations of our study. Since all duplication cysts excised, it is not possible to suggest that different epithelial linings are related with clinical findings and they may have role in transformation to malignancy.

Conclusions

Duplication cysts shows wide variation in epithelial lining. Respiratory epithelium may exist not only in foregut duplications but also in midgut and hindgut ones. Although the presence of respiratory epithelium did not have any impact on clinical findings, none of the previous theories explain the presence of respiratory epithelium different from foregut duplications.