Paediatric foregut duplication cysts of the head and neck: a retrospective case series, systematic review and meta-analysis

Introduction

Foregut duplication cysts (FDCs) are rare congenital abnormalities that may appear at any site along the upper gastrointestinal tract. They are derived from heterotopic rests of foregut derived epithelium, which deposit in the first trimester, resulting in cysts in foregut-derived tissue (1). This gives rise to the alimentary tract from the oropharynx to the second part of the duodenum, as well as the lower respiratory tract, the pancreas and liver. Therefore, FDCs may comprise epithelium resembling each of these sites. There are several theories proposed to explain the formation of these cysts. One theory postulates that these arise from formation of diverticula in the foregut in embryogenesis in the 4th week of life, leaving cystic structures which do not undergo metaplasia to form their target organ, but remain attached (2). Another theory is that they form from faulty recanalization of the foregut lumen in the 4th–8th weeks of life (3).

Diagnosis of an FDC is confirmed histopathologically, with the traditional definition needing to satisfy three requirements: the presence of a smooth muscle coat, presence of epithelium from the alimentary tract, and being intimately related to one part of the alimentary tract (4). These are most commonly found in the thorax and abdomen, but are less commonly found in the head and neck (5). Often identified prenatally or at birth, the differential diagnosis for head and neck FDCs is extensive, including ranula, sialocoele, lymphatic malformations and mucocoeles.

Reports of head and neck FDCs are rare, and the optimal diagnosis, investigation and management in paediatric populations has not been elucidated, with only few case reports and case series identified in the literature. We describe our experience of head and neck FDCs at a paediatric tertiary centre, and perform a systematic review and meta-analysis of cases in the literature. As well as adding further cases to the literature, this is the first systematic review and meta-analysis to our knowledge on FDCs in the head and neck, providing robust evidence for the appropriate investigation and management, as well as details on imaging and histopathological diagnosis of this rare differential for a cystic neck mass in a paediatric patient.

Methods

This study is reported according to the AME Case Series and PRISMA reporting guidelines (available at https://www.theajo.com/article/view/10.21037/ajo-25-33/rc).

Case series

A retrospective keyword search of FDCs was undertaken through the anatomical pathology database and through the European Prospective Investigation into Cancer and Nutrition (EPIC) electronic medical record (EMR) of the Royal Children’s Hospital (RCH), Melbourne, from 2014 to 2024. Head and neck cases were identified, and data on age at presentation, investigations, management, histopathology and follow-up outcomes were collected and tabulated in Microsoft Excel (v16.92), and means, range and percentage proportions of this data were produced in Excel. The trial was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. Ethics approval was provided by the Royal Children’s Hospital (MCC DERP, reference No. 4429). Because of the retrospective nature of this case series, the requirement for informed consent was waived.

Systematic review

A systematic review of the literature was performed. A search of EMBASE, PubMed and MEDLINE databases was performed on the 17th of November 2024. Two search domains were used, which were combined with the Boolean operator “AND”, and search terms in each domain were combined with “OR”. The first search domain was: “head and neck” (all fields) OR “oral” (all fields), and the second domain was “duplication cyst” (all fields). All articles from 1948 to 2024 were included in the screening process. Article references were also examined to identify further articles for inclusion. This study was not registered with PROSPERO.

Inclusion criteria: (I) case reports/complete case series; (II) paediatric human population; (III) histopathological diagnosis of FDCs; (IV) FDC of the head and neck. Exclusion criteria: (I) non-English articles; (II) adult population; (III) animal studies; (IV) non-FDC cyst; (V) other site of FDC (non-head and neck); (VI) incomplete case report.

Papers identified were imported into the Covidence online software (6). This automatically removed duplicate records. Reviewers F.D. and S.A. independently performed a title and abstract review, and full text review, using inclusion and exclusion criteria as above. All discrepancies were discussed between both reviewers to come to a mutual decision, with assistance from author E.L. as needed. Demographic data (age at presentation and gender), location of cyst, imaging, management, histopathology (including type of epithelium identified), and outcomes were tabulated in Microsoft Excel (v16.92) and statistical analysis was run within Excel to produce mean, range and percentage proportions of this data. Risk of bias and quality assessment was performed using the Joanna Briggs Institute (JBI) Appraisal Checklist for Case Reports (7) (Figure S1).

Further statistical analysis was run using R Statistical Software (version 4.5.1; R Core Team 2025). A P value of <0.05 was used to identify statistical significance and confidence intervals (CIs) of 95% were used. Forest plots were created for pooled proportions of recurrence rates (with recurrence being treated as true recurrence and residual disease for dichotomous analysis) for various management strategies and for airway compromise for various anatomical subsites [with airway compromise being categorised as intubation, ex utero intrapartum treatment (EXIT) procedures or evidence of stridor at birth]. This was performed using the inverse variance method with a random-effects model.

Results

Case series

A total of five cases of head and neck FDCs were identified in the last 10 years at RCH. These are identified in Table 1. The mean age at diagnosis was 8.2 months. Two were female and three were male. Two cases were found in the floor of mouth (FOM), two in the base of tongue (BOT) and one in the uvula. Magnetic resonance imaging (MRI) was utilised in two cases (Figure 1), ultrasound (US) in one and two had no imaging. Four cases were treated with primary excision (Figure 2). One case in the FOM had attempts at excision, aspirations and sclerotherapy with definitive excision following. This patient had two previous attempts at sublingual gland excision at another site after initial presentation at four months of age. Following recurrence after attempted aspiration, he was referred to the RCH for further management. A multi-disciplinary meeting suggested possible lymphovascular malformation and so a decision for sclerotherapy was made. The cyst was injected with 100 mg of doxycycline under US guidance at 6 months of age. Despite this, the cyst recurred and definitive transcervical excision was performed at 8 months of age. Four cases had enteric epithelium found on histopathology, and one respiratory alone. Following excision, there was no reported recurrence of FDC, with three of five cases having a follow-up of over two years. Two cases did not report follow-up in the EMR as they were followed up privately.

Figure 1 Coronal T2 contrast MRI of BOT FDC. BOT, base of tongue; FDC, foregut duplication cyst; MRI, magnetic resonance imaging.

Figure 2 Intraoperative image of BOT FDC. BOT, base of tongue; FDC, foregut duplication cyst.

Systematic review and meta-analysis

A total of 43 cases from 39 reports were found of paediatric FDCs in the literature. A summary of these cases is found in Table 2. A PRISMA flow diagram of cases identified is shown in Figure 3. At both abstract review and full text review, common reasons for exclusion included different sites for FDCs, non-FDC cysts and adult populations. The specific exclusion at the full text review stage is included in the PRISMA diagram in Figure 3.

Figure 3 PRISMA flowchart of identification of studies.

Demographics

Fifteen were prenatal at age of diagnosis (34.8%) and 14 were neonatal (32.5%). In cases identified postnatally, the ages ranged from two months to 10 years old. Twenty were reported in females (46.5%), 18 in males (41.8%), with five unreported genders.

Location

The most common location was the FOM with 17 cases (39.5%), followed by tongue with 15 cases (34.8%). There were three reports in the neck (6.7%), two in the pyriform sinus (4.7%), and two in the pharyngeal walls (4.7%).

Presenting symptoms

Presenting symptoms varied, but 27.9% were asymptomatic (n=12), and 20.9% presented with poor feeding (n=9). There were a few case reports of respiratory distress and stridor at birth (n=6). There were a few reports of EXIT procedures (n=3), and planned intubation at birth (n=3) without known symptomatology at birth. The pooled proportions of airway involvement for BOT were 0.37 (95% CI: 0.00–1, P=0.0919), FOM 0.13 (95% CI: 0.00–0.39, P=0.8011) and tongue 0.02 (95% CI: 0.00–0.13, P=0.9980). The one report in the uvula and three in the neck did not have airway compromise, so the pooled proportion was 0. The cases in the pharyngeal wall and pyriforms all had airway compromise, so their pooled proportions were 1. The forest plot for this data is shown in Figure 4.

Figure 4 Forest plot of pooled proportions of airway involvement for cases against anatomical sites of BOT, uvula, FOM, tongue, oesophagus, neck, pharyngeal wall and pyriform using a random effects model. BOT, base of tongue; CI, confidence interval; FOM, floor of mouth; RCH, Royal Children’s Hospital.

Imaging, management and recurrence

Most of these cases were evaluated by MRI alone (53.4%, n=23), with the remainder by computed tomography (CT) alone (13.9%, n=6), US (11.6%, n=5) and CT and MRI (7%, n=3). 11.6% did not perform any imaging at diagnosis (n=5). These were largely found to be cystic, unilocular or bilocular lesions which were T1 hypointense and T2 hyperintense on MRI without significant contrast enhancement. A total of 65% excised the lesion transorally as initial management (n=28), with varying other management strategies utilised, including marsupialisation (n=5), aspiration (n=3), sclerotherapy (n=1), and potassium titanyl phosphate (KTP) laser (n=1). Eight cases (18.6%) reported residual/recurrent cyst formation, with an average follow-up time of 8.9 months; however, 21 cases (48.8%) did not report any follow-up. Two cases reported long-term complications with a persistent oral defect (n=1) and open mouth posturing ongoing (n=1). Pooled proportions of recurrence for excision were 0.15 (95% CI: 0.02–0.34, P=0.9227) and marsupialisation 0.72 (95% CI: 0.00–1, P=0.2912). KTP laser, sclerotherapy and aspiration cases all had recurrence, so their pooled proportions were 1. This is shown in the forest plot in Figure 5.

Figure 5 Forest plot of pooled proportions of recurrence for cases treated with marsupialisation, excision, KTP laser, sclerotherapy and aspiration using a random effects model. CI, confidence interval; KTP, potassium titanyl phosphate; RCH, Royal Children’s Hospital.

Histopathology

There was a wide range of combinations of foregut-derived epithelium found on histopathology, but the most common was respiratory alone (23.2%, n=10), followed by gastric and respiratory (18.6%, n=8) and gastric alone (14%, n=6).

Discussion

Alimentary tract duplication cysts arise in 1:4,500 live births (46), and FDCs account for approximately 1/3 of these cases (47,48). While they are mostly found in the chest and abdomen (49-51), reports in the head and neck region are rare. To our knowledge, this is the first systematic review and meta-analysis to investigate this rare clinical entity and to elucidate the appropriate investigation and management of these cases. We identified 43 cases of FDCs in paediatric patients in the head and neck in the literature, with a further five identified from the retrospective case series. Most of these cases were identified prenatally or in the neonatal period. There appears to be a largely equal distribution of presentations with FDCs in the head and neck region between males and females, both in the literature and case series. While most cases were asymptomatic, owing to their location mainly in the FOM and tongue, some caused issues with feeding. To our knowledge, we also report the only case reported in the literature of FDC in the uvula, which also caused feeding difficulties. The management of the airway in cases of head and neck FDCs identified prenatally was variable. Very few cases caused respiratory distress at birth. The cases that did cause respiratory distress were exclusively found in the pyriform sinus, cervical oesophagus and lateral pharyngeal walls. Owing largely to size at prenatal diagnosis, there are few case reports of EXIT procedures being performed, or planned intubation at birth, with concern for potential compromise of the airway. MRI was utilised in most cases, with MRI findings of cystic, T1 hypointense and T2 hyperintense lesions. CT and US were also reported to be used either as additional imaging modalities or on their own. Most cases elected to proceed to primary excision of the lesion, with good results and low recurrence rates. Aspiration and marsupialisation produced poor outcomes, with many requiring formal excision following this. Additionally, sclerotherapy and KTP laser have not been shown to be successful. Despite the large size of some of these FDCs, only few cases of oral defects and issues with mouth posture following excision have been reported, with no other long-term complications reported. There is no clear predilection for epithelial subtype identified in head and neck FDCs. Interestingly, we report the first case of a mixed histological diagnosis of a dermoid cyst and FDC in the head and neck.

Demographic data of FDCs in the head and neck reflect those of FDCs at other sites with similar age at diagnosis (52,53), and gender distribution(3,54). Investigation of FDCs with MRI in the head and neck does not reflect that at other sites, where endoscopic US (EUS) is utilised more commonly (55-57) with MRI as an adjunct (58). Due to their anatomical location in the alimentary canal distal to the oesophagus, EUS provides information regarding solid or cystic nature of the lesion, as well as relationship to the layers within the wall of the lumen. With a narrower differential of cystic lesions at these sites, this makes EUS a sensitive and specific test for FDCs (55). The role of fine needle aspirates is controversial, but it is also utilised at other sites (55). This has not been reported in the head and neck region, which reflects common practice for congenital head and neck cystic masses, due to low diagnostic yield and unlikely overlay with malignancy (59). The consideration of airway management is unique to the head and neck in FDCs, and so this is not well discussed in the literature. Similarly, the presenting symptoms are different, where gastrointestinal symptoms predominate at other sites (54,60). Management with definitive primary surgical excision is the mainstay of treatment (3,60). The theories of the embryological origin of FDCs do not support any certain region of the foregut being more likely involved in the formation of these cysts, without a clear predilection for a certain type of epithelium found in the FDCs reported. Despite this, only one case of pancreatic epithelium-derived head and neck FDC has been reported.

This paper has highlighted unique differences in the investigation and management of FDCs in the head and neck compared to other sites, providing clearer evidence for the optimal management at this site. With a broader differential list of congenital cystic head and neck masses compared to cystic masses distally in the alimentary canal, US (including EUS) does not provide sufficient information for diagnosis. MRI has been shown to be highly sensitive in characterising congenital head and neck cystic lesions (61-63), and this was reflected in the study with FDCs. Dermoid or epidermoid cysts are often T1 hyperintense and T2 variable intensity (64) and so this becomes unlikely given consistent MRI findings. Ranulas and lymphovascular malformations, however, may have similar appearances, and this may change the treatment algorithm. Ranulas, particularly plunging ranulas, may have extension into the neck on imaging, while FDCs generally are confined to one subsite (65). Lymphovascular malformations are generally multilocular despite similar signal intensity, while FDCs are generally unilocular or bilobed structures (61). Anterior midline neck FDCs have not been reported, but there is potential for appearances to be similar to a thyroglossal duct cyst pre-operatively. With appearances of unilocular or bilobed cystic structures which are T2 hyperintense and T1 hypointense in the FOM or tongue, an FDC should be considered high in the differential list. With few reports of FDCs in the pyriform sinus, this needs to be differentiated from pyriform sinus tracts. Similar to FDCs, pyriform sinus tracts also demonstrate T2 hyperintensity on MRI. However, they usually contain air pockets and are intimately related to the thyroid gland (66). FDCs in the pyriform sinus identified in the review do not show this characteristic. The possibility of a dual diagnosis is not excluded. The dual dermoid cyst and FDC identified in the case series produced a diagnostic and management dilemma with delay to complete excision, as imaging findings of a T1 and T2 hyperintense lesion were not consistent with FDC. Embryologically, dermoid cysts in the head and neck are thought to form from failure of fusion of first and second brachial arches in the third and fourth weeks in utero (67). While the timeline for genesis of both of these structures aligns, it does not appear that they have a similar embryological origin. To our knowledge, no other reports of a dual dermoid cyst and FDC have been reported at any other site.

Airway management is an important consideration for head and neck FDCs. The complex decision-making required to assess the need for an EXIT procedure is reflected in the International Pediatric Otolaryngology Group (IPOG) guidelines (68). While the tracheoesophageal displacement index is identified as one potential metric to identify foetuses at risk of airway compromise, the importance of referral to a centre with access to a multi-disciplinary team to reach a consensus is highlighted as an important factor in identifying patients at risk. There is no clear guidance in the IPOG guidelines for head and neck FDCs as a rare clinical entity. As there have been no adverse airway-related complications with head and neck FDCs in the most common sites of the tongue or FOM, with patency of nasopharyngeal airways in these cases, this paper provides some guidance regarding safe delivery of these infants. Higher risk locations for airway compromise, as demonstrated by the meta-analysis, were identified in cases of the lateral pharyngeal walls, pyriform sinuses and cervical oesophagus, and so these patients may need consideration of EXIT procedures as per the IPOG guidelines. Management by primary excision has been demonstrated to be highly effective in reducing risk of recurrence or residual disease, in line with management of other subsites. With similar clinical and radiological findings to lymphovascular malformations, sclerotherapy has been attempted with FDCs, but has not produced good outcomes. Similarly, reports of aspiration/marsupialisation (usually reserved for dermoid cysts) and KTP laser (for vascular anomalies), largely required formal excision following this to produce good long-term outcomes, highlighting the importance of accurate and timely diagnosis.

Limitations and future directions

FDCs in the head and neck are rare and as such, there are few reports in the literature identified, in addition to the five cases identified in this retrospective case series. As identified by the JBI checklist (Figure S1), some of these case reports were missing data, in particular with regard to follow-up. Very few detailed long-term complications and outcomes, with only short-term follow-up regarding recurrence in the majority of cases. Selection bias was reduced with selection of all case reports with adequate data. However, non-English articles were excluded which may skew management. Publication bias was difficult to avoid, as only cases with adequate outcomes from excision would be published as case reports, and with a lack of data from larger studies. The meta-analysis was limited due to significant case report heterogeneity, and low case report numbers. None of the data reached statistical significance in the meta-analysis. With publication of the first systematic review of the literature of head and neck FDCs, further mutli-centre retrospective analyses can overcome these limitations related to case numbers and heterogeneity.

Conclusions

FDCs are rarely found in the head and neck region. At this site, they are generally diagnosed prenatally or at birth, and are most commonly found in the tongue or FOM. Due to the most common location, these generally are asymptomatic or cause feeding difficulty, with only cysts in pyriforms, pharyngeal walls or in the cervical oesophagus causing respiratory distress. These can be adequately evaluated with MRI, with formal excision following, producing good outcomes with low recurrence rates. Histopathologically, FDCs in the head and neck region can be derived from a wide range of foregut-derived epithelium.

Acknowledgments

This paper was presented as a poster presentation at the ASOHNS ASM which took place in March 2025.

Footnote

Reporting Checklist: The authors have completed the AME Case Series and PRISMA reporting checklists. Available at https://www.theajo.com/article/view/10.21037/ajo-25-33/rc

Data Sharing Statement: Available at https://www.theajo.com/article/view/10.21037/ajo-25-33/dss

Peer Review File: Available at https://www.theajo.com/article/view/10.21037/ajo-25-33/prf

Funding: None.

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://www.theajo.com/article/view/10.21037/ajo-25-33/coif). The authors have no conflicts of interest to declare.

Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved. The study was conducted in accordance with the Declaration of Helsinki and its subsequent amendments. The study was approved by the Royal Children’s Hospital (MCC DERP, reference No. 4429). Because of the retrospective nature of this case series, the requirement for informed consent was waived.

Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.

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