A case series of radiologically misdiagnosed visceral lymphatic malformations

Introduction

Lymphatic malformation (LM) is a cystic lesion arising from lymphatic vessels that do not communicate properly with the drainage lymphatic ducts, and is also called ‘lymphangioma’, or ‘hygromas’ previously. Mulliken and Glowacki (1) first proposed a classification of hemangiomas and vascular malformations based on endothelial cell characteristics, and LM was classified as a slow-flow vascular malformation. This classification system was adopted by the International Society for the Study of Vascular Anomalies (ISSVA). In the most recent version of ISSVA classification (2025), LM was further classified as isolated (macrocystic, microcystic, and mixed subtypes) type, complex type, and lymphedemas (2).

Most (95%) LM occurred in the neck and axilla region; others arose in the mesentery, retroperitoneum, abdominal organs, lungs, and mediastinum (3-6). Many syndromes were reported to be associated with LM, such as Gorham-Stout syndrome and Klippel-Trenaunay syndrome (2,3,6-8). LM occurring in visceral organs such as the lung, liver, spleen, and pancreas was extremely rare, and most were case reports (9-14). In a study of abdominal LM, 107 cases were collected over 22 years in the Armed Forces Institute of Pathology (AFIP), only one occurred in the liver, five in the pancreas, and nine in the spleen (4).

Ultrasound is used for initial screening and is especially valuable for superficial LM (7), but it is insufficient for visualizing the entire lesion (especially massive LM or LM located in a complex anatomic structure). Moreover, it could not penetrate bone and air. Computed tomography (CT) can show phleboliths, calcifications, and bone invasion (6). However, it is limited in soft tissue resolution. Magnetic resonance imaging (MRI) is a valuable and first-line modality for the imaging of vascular malformations; it can demonstrate the anatomical relationship of LM and surrounding vascular structures, vascular nerve bundles, and adjacent organs in detail (6,7).

LM is easily misdiagnosed as other tumors in rare locations, even malignant ones (10). To deepen our knowledge of LM and familiarize its clinicopathological and imaging features, we retrospectively reviewed a series of histologically proven visceral LMs that were radiologically misdiagnosed. We present this article in accordance with the AME Case Series reporting checklist (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-318/rc).

Cases presentation

All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Informed consent was waived for publication of this case series and accompanying images according to the Medical Ethics Committee of Fudan University Shanghai Cancer Center. The clinicopathological and imaging findings of 11 cases with LM in the visceral organs were reviewed retrospectively. These masses were all isolated and classified as macrocystic, microcystic, and mixed subtypes (15,16).

The age of onset, gender, levels of tumor markers [alpha-fetoprotein (AFP), CA 19-9, etc.], locations, and symptoms at presentation were reviewed. They all underwent CT examination; one had an unenhanced CT, and the others underwent both unenhanced and enhanced CT in the venous phase (VP). Six of them underwent T1WI, T2WI, and enhanced MRI of VP examinations (Table 1). The CT and MR images were reviewed by a radiologist with more than 10 years of experience in MR interpretations.

Demographic and clinical findings

Four children and seven adults were included (Table 1). The age ranged from 1 to 67 years, with a median age of 34 years. Six cases were male, and five were female, with a sex ratio of 1.2:1.

One was located in the right lower lung, two in the liver (one in the right posterior lobe, and one in the right anterior and left inner lobe), three in the spleen, and five in the pancreas (one in the head, one in the neck, one in the body, and two in the tail of the pancreas) (Table 1).

Seven masses were found incidentally; two complained of abdominal pain, one complained of epigastric discomfort with the elevation of CA 19-9 (74 U/mL), and one was found with a pulmonary mass (Table 1).

There was no significant correlation between the tumors’ greatest diameter and the presence of clinical symptoms (P>0.05, r=0.18).

CT and MR findings

The tumors’ greatest diameter ranged from 1.2 to 12 cm, with an average of 5.12±3.62 cm. Three were macrocystic, four were microcystic, and the others were mixed LM.

Five masses were slightly heterogeneous, and six were homogeneous. They were well-defined, and two were with the capsule. Eight were lobulated and multicystic, with internal fine and uniform septa (Figures 1-5). Three were solitary, round, and unilocular cysts.

Figure 1 Male, 1-year-old, lymphatic malformation of the liver (in the right anterior lobe and the left inner lobe) mimicking hepatic mesenchymal hamartoma, showed a mainly well-defined multicystic mass with uniform septa and speckled calcification on unenhanced CT (A), and showed moderate enhancement of septa on venous phase (B). CT, computed tomography.

Figure 2 Male, 14 months, lymphatic malformation of the right lower lung mimicking congenital pulmonary airway malformation. On the lung window of unenhanced CT, it showed a lobulated multicystic air attenuation mass with internal fine and uniform septa. CT, computed tomography.

Figure 3 Female, 51 years old, presenting as a lobulated multicystic mass in the tail of the pancreas mimicking serous cystadenoma, showed hypo-attenuation on unenhanced CT (A), and moderate enhancement of septa on venous phase (B). CT, computed tomography.

Figure 4 Male, 54 years old, presenting as a lobulated multicystic mass in the body of the pancreas mimicking mucinous cystadenoma, showed hypo-attenuation on unenhanced CT with speckled calcification (A), and moderate enhancement of septa (B). CT, computed tomography.

Figure 5 Female, 4 years old, a giant lymphatic malformation in the right posterior lobe of the liver mimicking hepatic mesenchymal hamartoma, showed hypo-signal intensity on T1WI relative to muscle tissue (A), and mainly hyper-SI on T2WI with internal hypo-SI septa (B,C), and without discernible enhancement (D). SI, signal intensity.

On CT images, LMs mainly showed fluid attenuation with hypoattenuating internal septa (Figures 1,3,4), but one mass was filled with gas (Figure 2). Speckled calcification was found in two cases.

On MR images, LM showed hypo-signal intensity (SI) on T1WI relative to muscle, hyper-SI on T2WI with internal hypo-SI septa (Figure 5). The septa were thin and uniform without mural nodules, and showed mild to moderate enhancement on enhanced CT and MR of VP (Figures 1,3,4). The cyst wall was found without discernible enhancement. No hemorrhage was found.

These visceral LM were all misdiagnosed preoperatively, including congenital pulmonary airway malformation (CPAM), hepatic mesenchymal hamartoma, splenic cyst, intraductal papillary mucinous neoplasms (IPMN), mucinous cystadenoma, serous cystadenoma, and pancreatic ductal adenocarcinoma (Table 1).

These lesions were all surgically excised. Right lower lobe resection, splenectomy, hepatic lobectomy, resection of the pancreatic body or the tail, and the Whipple were performed for different visceral LM. The hospital stays ranged from one to two weeks. One patient with a pancreatic head lesion suffered a complication of bile leakage; the others recovered rapidly with no complications.

Histopathology and immunohistochemistry results

On gross examination, they were mainly grayish-yellow and showed multiple cystic cavities of various sizes filled with clear fluid. The pathological section showed a large number of lymphatic ducts of various sizes containing lymphatic fluid, which were lined by a single layer of flattened epithelial cells (Figure 6), and intermixed with normal cells and lymphocytes.

Figure 6 HE staining (×100) showed a large number of lymphatic ducts of various sizes, lined by a single layer of flattened epithelial cells and filled with lymphatic fluid.

The positive rates of D2-40, CD31, and F8 were 100%, 100%, and 83.3%, respectively. LM occasionally expressed CAM 5.2, CK, DES, EMA, Ki-67, and Vim.

Discussion

LM of visceral organs were multicystic lesions or unilocular cysts and were mainly well-defined. For its rarity, it was easily misdiagnosed, although it had characteristic imaging features. It mainly showed hypo-attenuation on unenhanced CT with septa, showed hypo-SI on T1WI relative to muscle, and showed hyper-SI on T2WI with internal hypo-SI septa. The septa were thin and uniform and mainly showed mild to moderate enhancement. Calcification and capsules were seen occasionally.

Some scholars adopted 1 cm as the cut-off value to distinguish macrocystic from microcystic LM (15,16). In this group, three were macrocystic, four were microcystic, and four were mixed LM. The clinical presentation of most LM in the visceral organ was nonspecific; most were asymptomatic and found incidentally. Abdominal pain, epigastric discomfort with the elevation of CA19-9, and a pulmonary mass were other manifestations at presentation.

On CT images, LM had a density close to fluid density, and the CT values can be affected by hemorrhage, infection, and microcystic components (6). In this group, three LM were well-defined, round, unilocular liquid-density cysts without enhancement. Eight LM showed lobulated multicysts with internal thin septa; seven of them showed liquid density, but one was filled with gas on CT. The gas density that filled the mass was rather unusual, mimicking CPAM. We speculated that it might be due to the connection of the lesion to the bronchus, resulting in the outflow of intracystic fluid.

Similar to the literature, the LM of our research showed mainly hypo-SI on T1WI relative to muscle and hyper-SI on T2WI with internal hypo-SI septa. The septa were fine and uniform, with mild to moderate enhancement. Compared with CT, MRI was more sensitive in detecting internal septa. LM sometimes showed complex SI due to protein-containing internal hemorrhage or secondary infection. LM was reported to be prone to secondary infection, bleeding, and even rupture (15,17).

LM should be considered in the differential diagnosis of thin-walled cystic masses, with or without fine septa. The differential spectrum differed for LM occurring in different organs. The pulmonary LM of this group was misdiagnosed as CPAM, for its multicyst appearance, filling in gas density with thin septa (without mural nodules) on CT (18). Admittedly, CPAM was more commonly seen than LM in children. Other cystic lesions and pulmonary blastoma should also be considered in the differentiation of pulmonary LM (19). Two hepatic LM were misdiagnosed as mesenchymal hamartoma, given their multi-septated cystic appearance and the patient’s age (20), and hepatic LMs are very rare. Bile duct cysts, biliary cystadenoma, polycystic liver disease, undifferentiated embryonal sarcoma, and echinococcal cysts should also be considered in the differentiation (4,21). Three cases of splenic LM were misdiagnosed as splenic cysts, which can be classified as true and pseudocysts (22), but splenic LM were multicystic with mild internal enhancement, which was a unique feature. The diagnosis of pancreatic LM was difficult, for several pancreatic tumors showed a multicystic appearance. Pancreatic LM was easily misdiagnosed as IPMN, mucinous cystadenoma, serous cystadenoma, and pancreatic ductal adenocarcinoma. Pseudocysts, solid pseudopapillary neoplasm (SPN), and cystic neuroendocrine tumors should also be considered in the differentiation of pancreatic LM (23).

D2-40 staining was a characteristic marker for identifying lymphatic vessels (3,10,24). CD31 and F8 were commonly positive in lymphatic endothelial cells (3). We had similar findings: visceral LM was commonly positive for D2-40, CD31, and F8, which facilitated the final diagnosis.

Surgical excision, sclerotherapy, and radiofrequency ablation were the main methods for the treatment of LM (6,15,17,25). LM that occurred in the visceral organs was usually large but often limited to the organs without extra-organic invasion, and it was easy to excise completely. These eleven LMs were all surgically excised without recurrence. In recent years, sirolimus has been reported as an effective drug in the treatment of complex vascular malformations (26,27). Accurate diagnosis of LM on imaging is crucial, as it can help in avoiding unnecessary surgery. For LM with a relatively small size and limited extent, excellent results can be obtained without clinical intervention; continuous clinical or ultrasound follow-up can be carried out. Observation, sclerotherapy, and even pharmacologic therapy (28,29) can play an important role in the treatment of LM, especially in complex subtypes or LM in complex anatomic sites.

Conclusions

Visceral LM should be considered in the differential diagnosis of cystic masses in vital organs. Although visceral LM was rare, it had characteristic imaging and pathological features and could be accurately diagnosed on imaging. It was multicysts or unilocular cysts with thin uniform septa, and was commonly positive for D2-40, CD31, and F8. Familiarizing with the clinicopathological and imaging features of visceral LM can narrow the differential diagnosis, reduce the chances of misdiagnosis, or even avoid unnecessary surgery.

Acknowledgments

The abstract of this article was previously presented as an electronic poster at the Chinese Congress of Pediatric Radiology (2023).

Footnote

Reporting Checklist: The authors have completed the AME Case Series reporting checklist. Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-318/rc

Peer Review File: Available at https://acr.amegroups.com/article/view/10.21037/acr-2025-318/prf

Funding: This study was supported by the Medical Specialty Construction of Minhang District (No. 2025MWFC06).

Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://acr.amegroups.com/article/view/10.21037/acr-2025-318/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. All procedures performed in this study were in accordance with the ethical standards of the institutional and/or national research committee(s) and with the Declaration of Helsinki and its subsequent amendments. Informed consent was waived for publication of this case series and accompanying images according to the Medical Ethics Committee of Fudan University Shanghai Cancer Center.

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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