Pediatric mediastinal lymphatic malformation: misdiagnosis analysis and literature review

Abstract

Objectives

Mediastinal cystic lymphatic malformation (MCLM) in children is prone to misdiagnosis as cystic teratoma. We compared the clinical and radiologic features between the two diseases and performed a cross-comparison with previous research on adult cases. This study aims to identify characteristic pediatric manifestations to improve diagnostic accuracy.

Methods

A retrospective study of clinical and radiologic data was conducted on 12 MCLM and 20 cases of cystic teratomas confirmed by pathology or intervention biopsy. Clinical characters and radiology features (mass location and morphology, density, component, secondary complication) were recorded and compared. We reviewed clinical studies on MCLM published in the past decades, analyzing radiological differences and comparing pediatric MCLM cases at our hospital with those in the literature.

Results

Group comparison in pediatrics between MCLM and cystic teratomas: There were significant age differences (p = 0.036), shape (p = 0.003), CT difference value (p < 0.001), CT difference ratio (p < 0.001), calcification (p < 0.001), fat (p < 0.001), and typing (p < 0.001) between the two diseases. An analysis of literature data on MCLM cases involved 16 studies.

Conclusion

The absence of internal fat or irregular morphology, along with a minimal CT difference value, may suggest the diagnosis of MCLM. In pediatric cases, anterior mediastinal diseases tend to extend toward the neck, and the presence of the thymus can complicate the component analysis, thereby increasing the risk of misdiagnosis. Clinical diagnosis and differential diagnosis of pediatric MCLM rely heavily on imaging evaluation.

Introduction

Mediastinal cystic lymphatic malformation (MCLM) is a benign congenital malformation characterized by the proliferation of well-differentiated lymphatic vessels, typically presenting as polycystic or spongy aggregates. However, the incidence rate of MCLM is extremely low, accounting for only 1% [1]. The anterior superior mediastinum of children contains thymus and adipose tissue. When cystic lymphangioma develops in this area, it can easily be misdiagnosed as a teratoma. Radiologists usually misinterpreted adipose tissue as a fat component of teratoma [1, 2]. The treatment strategies for these two tumors differ, with MCLM usually managed through a combination of interventional therapy and surgery, while teratomas are typically treated with surgery alone [3]. Hence, the accuracy of preoperative diagnosis is crucial for clinical surgical decision-making.

Due to its extremely low incidence, most research on MCLM is confined to case reports. These studies predominantly focus on clinical aspects [4], with only a few examining radiologic findings and even fewer addressing pediatric cases [5,6,7,8,9]. In this study, we conducted a retrospective analysis of clinical and imaging features of MCLM and mediastinal teratomas, confirmed by pathology or interventional biopsy, to identify key diagnostic factors for pediatric MCLM. Additionally, a literature review was performed to compare the radiological characteristics of MCLM between adult and pediatric cohorts. This research aims to enhance disease differentiation, reduce misdiagnosis rates, and support surgical decision-making.

Methods

Patient selection

A retrospective study of clinical and radiological data was conducted on patients with mediastinal masses who underwent surgical resection or interventional treatment at Shenzhen Children’s Hospital between January 2011 and December 2023. Cases were selected based on the following criteria: [1] diagnosed as MCLM or cystic teratoma; [2] pre- and post-contrast chest CT scans conducted before surgical treatment. Patients with concurrent lung diseases or other types of mediastinal mass lesions were excluded. Thirty-two patients were ultimately included, comprising 12 MCLM cases and 20 cystic teratomas. This study was approved by the local institutional review board.

CT image acquisition

An Optima CT 680 Quantum scanner from GE (USA) was used for the CT procedure. We utilized automatic exposure control (Care KV) and automatic tube current modulation (Care Dose 4D), setting a reference tube voltage of 100 kV and tube current of 250 mAs. The gantry rotation time was 280 ms with a pitch of 0.984. Following the plain scan, all patients received nonionic contrast material (Iopamiron from Bayer Schering Pharma, Osaka, Japan; or Omnipaque from Daiichi Sankyo, Tokyo, Japan) with an iodine concentration of 300 mgI/mL. The contrast material was administered at 2 mL/kg body weight, with injection speed and scanning duration personalized based on the child’s age, body weight, vein condition, and overall health. The scan slice thickness was 5 mm, the reconstruction slice thickness was 0.625 mm, and the reconstruction matrix was 512 × 512.

Imaging review

Two senior chest radiologists with at least 7 years of working experience evaluated all images. The radiologists were blinded to the clinical diagnosis and pathologic outcomes. When two radiologists disagreed, the third one with 20 years of experience gave the final opinion and reached a consensus. The detailed qualitative and quantitative CT indicators were as follows: mass location and morphology (location, short-axis/long-axis ratio, contact surface with heart, shape, margin), density (pre and post-contrast CT value), the difference value (DV) and the difference ratio (DR) between two CT sequences (using the thymus as reference), component (calcification, fat, cystic variation, septum), classification (sunken, flattened, convex, perfusion) [10], secondary complication (pleural effusion, pericardial effusion). The typical CT characteristics of the MCLM and cystic teratoma are exemplified in Figs. 1 and 2.

Fig. 1

CT and pathologic picture of a patient with MCLM. The patient, a 5-year-old male, presented with a mediastinal lymphangioma mass. CT scans revealed uniform density within the mass with multiloculated cystic lesions (Figure A). The enhanced CT scan showed no intensification in the cystic part, with evidence of septal-like alterations and mild enhancement in the septa (Figure B). Pathological examination displayed cystic walls composed of proliferated fibrous tissue, focal hemorrhage, and a single layer of flat epithelial overlay in local foci (Figure C)

Fig. 2

CT and pathologic picture of a patient with mediastinal teratoma. The patient, an 11-year-old male, presented with a mediastinal teratoma. CT scans revealed uneven density within the mass, with evidence of fat and calcification (Figure A). The enhanced CT scan showed no enhancement in the cystic part, with segmentation-like changes and mild enhancement in the septum (Figure B). Pathological examination displayed matured tissues of three germinal origins, including keratinized compound squamous epithelium, hair follicles, and sebaceous glands in the ectodermal layer; fibrofatty tissue in the mesoderm; and ciliated columnar epithelium in the endodermal layer (Figure C)

Literature review

We searched published clinical studies on MCLM, from PubMed, EMBASE, and Web of Science, between January 2014 and January 2024. Keywords were set as bellowing: ((“Lymphangioma/diagnostic imaging“[Mesh]) AND (“Mediastinal Neoplasms“[Mesh])) OR ((Lymphangiomas[Title/Abstract]) OR (cystic hygroma[Title/Abstract]) OR (Lymphatic cyst[Title/Abstract]) ). A search of the lists of references from included studies was also performed.

We screened and checked the articles retrieved respectively, according to the predefined inclusion and exclusion criteria. Firstly, the title and abstract of the study were reviewed. Then the full text of potentially eligible studies was scanned swiftly. A full-text review was performed later on to identify the eligible studies. Eligibility criteria were set as follows: [1] Whether or not an MRI was performed; [2] Whether it spreads to the neck. Disagreement was resolved by discussion, and finally reaching a consensus.

Statistical methods

SPSS 18.0 (IBM, New York, USA) statistical analysis software was used for data analysis. Since all continuous variables were non-normally distributed, they were described as median (interquartile range, IQR), and the Mann-Whitney U test was used for analysis. Categorical variables are presented as frequencies (%) and Fisher’s exact test was utilized for inter-group comparisons, given the small sample size (< 40). A p-value of < 0.05 was considered to be statistically significant.

Results

Results of clinical data

Table 1 shows a comparison of the clinical characteristics between the two diseases. In this study, 32 patients were included, with 12 MCLM and 20 mediastinal teratomas. The MCLM dataset consisted of 7 boys and 5 girls, while the median age was 1.46 years (IQR, 0.10–5.29). The cystic teratomas dataset consisted of 13 male and 7 female patients, and the median age was 4.96 years (IQR, 1.52–11.13). Patients diagnosed with MCLM were younger than teratomas (median age of years 1.46 vs. 4.96, p = 0.036).

Table 1 Clinical baseline data on mediastinal lymphangiomas and teratomas in children

Results of CT features

Qualitative factors

The location of MCLM (5 were in the left anterior mediastinum, 5 in the right anterior mediastinum, and 2 in the posterior mediastinum) was not significantly different from that of teratoma. The shape was considered irregular in ten patients (83.3%) in the group with MCLM outcomes vs. five patients (25%) in those with teratoma outcomes (p = 0.033). Calcification is suggestive of a teratoma, but not present in all teratoma (p < 0.001). About the classification, MCLM is mostly perfusion (41.67%), while teratoma tends to be convex (35%), and the difference between the two groups is statistically significant (p < 0.001). The detailed statistical results are shown in Table 2.

Table 2 CT signs of MCLM and teratomas in children

Quantitative factors

The post-contrast CT value difference of mediastinal lesions with the MCLM was lower than that with the teratoma group, and the difference was statistically significant (mean value of 3.73 vs. 12.31, p < 0.001). The post-contrast CT value difference ratio of mediastinal lesions with the MCLM was lower than that with the teratoma group, and the difference was statistically significant (mean value of 0.08 vs. 0.25, p < 0.001). The detailed statistical results are shown in Table 2.

Results of the literature review

A total of 1284 articles met the retrieval requirements Fig. 3, followed by the removal of 468 duplicate articles. After reviewing the titles and abstracts, 23 articles remained. A full-text review excluded seven articles for the following reasons: four included only clinical analysis, and three mentioned CT examination without detailing its features. Finally, a total of 16 studies were included in the literature review. Of these, only five focused on children (31%), with the majority (14/16) being case reports. It was found that among the MLCM cases analyzed, only one exhibited calcification [11] and one contained fat [8]. Five of the studies included MRI analysis and six cases described neck involvement feature (Table 3).

Fig. 3

Literature search and inclusion-exclusion flowchart

Table 3 Imaging features of mediastinal cystic lymphangioma

Discussion

MCLM is a rare benign disease of the lymphatic system that primarily affects the configuration and function of lymphatic vessels. The development of lymphangiomas is associated with abnormal proliferation of lymphatic tissue, leading to the expansion of lymphatic vessels and local tumor formation. Among primary mediastinal tumors in children, distinguishing teratomas undergoing cystic transformation from solitary MCLMs can be challenging. Enhanced CT is the preferred imaging modality for assessing and characterizing most mediastinal lesions [12]. While the definitive clinical diagnosis depends on pathological findings or interventional diagnostic procedures, enhanced CT is essential for analyzing lesion characteristics and evaluating the relationship with adjacent vascular structures.

Statistical analysis of clinical data reveals that patients with MCLM tend to present at a younger age compared to those with teratomas. This outcome may be attributed to the greater propensity of MCLM to infiltrate and grow, potentially invading adjacent blood vessels and thereby increasing the likelihood of clinical symptoms [13].

The literature review revealed that eight studies reported anterior mediastinal masses, while four described lesions in both the anterior and middle mediastinum, consistent with our findings. In terms of staging, MCLM typically exhibits perfusion-type growths, spreading through the lax interstitial spaces with a “creeping” pattern and causing plastic changes in the surrounding tissue. In contrast, teratomas usually present as protruding masses that compress adjacent tissues inwardly. Previous research indicated that convex MLCMs were more common in children (3/5), whereas flattened MLCMs were more prevalent in adults (4/11). Our results suggest the trend was notably pronounced in teratomas, implying that a single morphological analysis might not always be sufficient for accurate cancer differentiation. The imaging features of MLCM varied significantly with age, further complicating diagnosis. In children, it extends to the neck or anterior mediastinum with vascular malformations, while in adults, it is typically confined to the middle or posterior mediastinum with fluid cysts [14, 15].

Component analysis proved more specific. The presence of intertumoral fat in the anterior mediastinal mass (measured at -40 HU to -120 HU on CT) was highly indicative of a benign teratoma [16, 17], while MLCMs typically appeared as pure cysts without fat or calcification. Although fat-fluid levels and the presence of bone or teeth within the tumor are highly specific for teratoma diagnosis, these signs are rare and not particularly valuable for daily clinical use. To better analyze the internal structure of the lesion, we proposed the difference ratio, using the thymus as a reference. This method revealed a statistically significant difference between the two tumor types, with teratomas showing a higher difference ratio due to their complex and densely packed composition. Studies utilizing MRI were also conducted to better analyze the internal composition of lesions, as MRI provides superior detail in component imaging.

However, this study has several potential limitations: (1) Retrospective studies are inherently limited by the quality and completeness of past records, which can affect the reliability and accuracy of the data. This limitation is significant as it might skew the results, leading to biased conclusions that could misinform clinical practices. (2) The small number of cases reduces the statistical power of the study, making it challenging to draw definitive conclusions or detect subtle differences. It also limits the ability to apply the findings to the wider population, necessitating further research with larger cohorts to validate the results. (3) The absence of comprehensive MRI data limits the study’s ability to fully characterize the lesions, as MRI offers superior soft tissue contrast compared to CT. This gap restricts a complete understanding of the morphological differences between MCLM and teratomas, potentially leading to diagnostic inaccuracies. (4) Inter-observer variability in manual measurements can affect the reproducibility and consistency of the results. This variability might lead to discrepancies in the evaluation of imaging characteristics, undermining the study’s reliability. (5) While it limits the diversity of the study population, this issue is less critical than the methodological concerns. However, multi-center studies would provide a more comprehensive overview and enhance the applicability of the findings across different healthcare settings. These issues need to be further explored in the future.

Conclusion

In conclusion, the absence of internal fat or irregular morphology with minimal CT difference value suggests a diagnosis of MCLM. Children with anterior mediastinal diseases often extend towards the neck, which complicates component analysis, resulting in misdiagnoses. The contrast-enhanced CT examination and certain quantitative indicators contribute to the clinical diagnosis and surgical decision-making process in pediatric MCLM.