Overview

Nowadays, many people are facing difficulties in diagnosing a soft tissue or cystic mass because lymphangioma can resemble a variety of harmless or malignant tumours. The good news is that if you are facing it, it would be much easier to differentiate between them when you have the appropriate clinical, diagnostic and histopathologic approach. To be able to distinguish lymphangioma from other soft tissue masses, one would need to check a few features:

• Imaging, such as ultrasound
• Histology 
• Immunohistochemistry

In this article, clinical presentation, diagnostic errors, and imaging indications will be analysed, as well as the ability to recognise it from its most similar counterparts. 

Diagnosing lymphangiomas among cystic soft tissue masses 

Cystic soft tissue masses are difficult to diagnose, especially when they resemble both benign and malignant conditions. Although they are most prevalent in early childhood, lymphangiomas, sometimes referred to as lymphatic abnormalities, are harmless genetic lesions of the lymphatic system that can appear at any age.¹ Haemangiomas, cystic neoplasms, and developing cysts are just a few of the soft tissue masses whose imaging and clinical characteristics can resemble. A misdiagnosis could result in therapy delays or needless invasive procedures.² 

Accurate identification of lymphangiomas requires accurate knowledge of their distinctive clinical, radiological, and histological characteristics. Patients can avoid harsher treatments by using conservative surgical or sclerotherapy-based methods to treat these tumours after they are appropriately recognised. This article offers a targeted diagnostic approach to distinguish lymphangioma from its similar soft tissue masses, combining imaging and histopathologic details, as well as clinical findings to help doctors approach these lesions confidently.¹

Clinical representation and epidemiology

Up to 90% of cases of lymphangiomas, which are harmless congenital abnormalities of the lymphatic system, are discovered before the age of two. They typically appear in early childhood. About 75% of cases occur in the cervicofacial region (neck and face), with the axilla followed by the mediastinum.¹ While lymphangiomas are more commonly observed in children, as said in Hoang et al. (2023)’s study, they can also develop in adults, especially in deep anatomical sites such as the retroperitoneum, where they may be undetectable until they get large enough to produce an enormous influence. Less than 5% of all cases are retroperitoneal or intra-abdominal lymphangiomas. Patients may exhibit nonspecific symptoms in these areas, such as bloating, stomach pain, or consequences of compression on surrounding organs.² 

Usually, the lesions are slow-growing, mild, and painless. Depending on their size and location, they may result in deformity, dysphagia, or airway impairment in the cervicofacial region. Due to their cystic nature, they have a tendency to transilluminate with light.¹ Bochor and Parshotam (2025) stated that cysts of the branchial cleft, thyroglossal duct, or metastatic cystic lymph nodes are among the most common differential diagnoses in adults. Because adult lymphangiomas are deep and develop slowly, sometimes they can be difficult to diagnose and can be mistaken for other cystic or neoplastic diseases.³

Imaging evaluation 

In order to diagnose lymphangiomas and distinguish them from other soft tissue tumours, imaging is essential. The first imaging technique that is usually used is ultrasound. In contrast with their fluid-filled form, it displays lymphangiomas as multiloculated cystic lesions (multiple connected fluid-filled sacs) with thin septa (walls between the sacs) and anechoic or hypoechoic content (dark or nearly dark areas on the scan, indicating fluid). Crucially, Doppler investigations (a special type of ultrasound that checks blood flow) typically reveal no indication of internal vascular flow (no blood movement inside), which assist in differentiating them from arteriovenous malformations or haemangiomas (other types of growths that contain abnormal blood vessels).¹ 

Magnetic resonance imaging (MRI)

Clearer details of soft tissue and how far the tumour spreads are provided by Magnetic Resonance Imaging (MRI). T1 signals on T2-weighted sequences (different types of MRI scan settings) vary according to haemorrhage (bleeding) or proteinaceous content (thicker or protein-rich fluid), and lymphangiomas present as hyperintense, multilocular masses (bright, multi-chambered lumps). The septa are typically slightly enhanced in post-contrast snapshots, but the cysts themselves are not visible. MRI is essential prior to surgery and particularly useful 

in deep or complicated areas like the retroperitoneum.

Computer tomography (CT) scans

Computer tomography (CT) scans are very helpful for assessing lesions in the abdomen or retroperitoneum. Low-density, non-enhancing cystic masses with internal septations are the typical appearance of these tumours. Other abdominal cystic entities, such as mesenteric cysts (cysts in the abdominal lining), pancreatic pseudocysts (fluid collections near the pancreas), or cystic teratomas (benign tumours that may contain different tissue types), can also be identified by CT.²

Haemangiomas, on the other hand, frequently exhibit significant enhancement and internal vascularity (contain visible blood vessels), making differentiation essential. While epidermoid cysts are typically non-septated (do not have internal walls) and found close to dermal or joint structures, lipomas have a significant fat signal on MRI (appear bright because they are made of fat) and decrease on fat-saturated sequences.³

Histology and immunohistochemistry

According to histopathology, lymphangiomas consist of flattened endothelial cells lining dilated lymphatic channels (widened vessels of the lymph system) that are normally filled with lymph or eosinophilic fluid clear or pinkish protein-rich fluid). Lymphocytes, fibrous tissue, and occasionally bundles of smooth muscle can be found in the surrounding stroma. While microcystic variants (smaller cyst types) display a denser variety of smaller, irregular channels, macrocystic varieties (larger cyst types), previously known as cystic hygromas, exhibit these findings most frequently. 

Essentially, lymphangiomas are free of the necrosis, mitotic patterns (signs of rapid cell division), or cytologic atypia that are characteristics of malignant tumours. When the diagnosis is unreliable, immunohistochemistry is crucial. The lymphatic endothelium-specific markers (proteins found mainly in lymphatic vessels) D2-40 (Podoplanin), LYVE-1, and PROX1 are all detected in positive lymphangioma endothelial cells. Due to their similar expression with blood vessel tumours, they may also exhibit weak production of CD31 and CD34, although these are not identifiable.¹ 

This immunoprofile assists in differentiating vascular tumours from lymphangiomas. Capillary haemangiomas, for instance, have thick endothelial cells, exhibit mitotic activity (active cell division), and have high CD31/CD34 positivity (strong presence of blood vessel markers) but low lymphatic-specific marker levels (markers unique to lymph vessels). Adults may develop cystic neck masses fluid-filled swellings) as a consequence of cystic metastases, such as those from squamous cell tumours or papillary thyroid carcinoma (a common type of thyroid cancer), which are confirmed by cytokeratin testing (test detecting proteins found in skin or glandular cells) to contain malignant epithelial cells.² Additionally, in an unusual case of mesocolic lymphangioma in an adolescent, where imaging alone was insufficient, immunohistochemistry investigation played a critical role in confirming the diagnosis.⁵ This emphasises how important histology and molecular analysis are, especially in deep or unusual areas.

Treatment and management

Lesion size, location, type (macro-, micro-, or mixed), and related symptoms will affect the way in which lymphangiomas are treated. With careful clinical monitoring, many tiny, asymptomatic lesions, particularly in children, can be conservatively handled.¹ 

In the other comparative study, it is stated that lesions that are symptomatic, expanding, or aesthetically problematic, however, usually need to be treated. The most popular first-line treatment, particularly for macrocystic and some mixed tumours, is sclerosing therapy. Under imaging guidance, sclerosant drugs such as OK-432, bleomycin, or doxycycline are injected directly into the lesion, causing fibrosis and a decrease in its volume.² While microcystic lesions, especially those located around the suprahyoid region, present greater treatment challenges and are usually considered to require staged or combination approaches, intralesional sclerotherapy is highly beneficial for macrocystic lymphatic malformations, according to a systematic review by Perkins et al. (2010). 

Additionally, sirolimus, an mTOR inhibitor (a type of medication that blocks a specific cell growth pathway), shows potential for diffuse or ineffective lesions (widespread or non-responsive tumours) by reducing lymphangiogenesis and improving symptoms.⁴ Laparoscopic excision was successful in deep or abdominal cases, as the mesocolic lymphangioma, and there was no further development at monitoring.⁵ To develop individualised strategies, optimise results, and reduce recurrence, a multidisciplinary team including radiologists, interventionalists, surgeons, and pathologists is essential.¹

Diagnostic challenges and differentiation of lymphangiomas

According to Miceli and Stewart (2023), treatment must be guided by the ability to distinguish lymphangiomas from other soft-tissue tumours. Unlike multilocular and infiltrative lymphangiomas, branchial cleft cysts in the neck are often isolated, non-septated, and situated along the sternocleidomastoid.¹ 

Cysts of the thyroglossal duct are in the middle, do not multiloculate, and travel with the protrusion of the oral cavity. Although metastatic cystic lymph nodes from squamous or thyroid carcinoma in adults might resemble lymphangiomas, they are usually distinguished from harmless lymphatic lesions by cytokeratin on small needle aspiration, necrotic centres, and uneven border edges.² 

Lesion subtype has a significant impact on medical treatment. While microcystic forms, particularly suprahyoid, are more resistant to treatment and may require multiple procedures or surgical assistance, macrocystic lymphangiomas typically respond effectively to sclerotherapy.⁴ Mesenteric cysts (fluid-filled sacs in the abdominal membrane) and enteric duplication cysts (rare cysts that mimic parts of the intestine) were among the differential diagnoses in the Feng et al. (2022) mesocolic lymphangioma case. So, only a combination of imaging, histopathology, and immunohistochemical studies allowed for an accurate diagnosis, highlighting the necessity of a multidisciplinary approach in atypical areas.⁵

Summary

Lymphangiomas are mild lymphatic malformations that mostly affect children. Because of their clinical and imaging resemblance to other soft tissue masses, they can be difficult to diagnose. An integrated strategy utilising clinical presentation, imaging modalities such as ultrasonography and MRI, histology, and immunohistochemistry markers is necessary for a precise differential diagnosis. Understanding the unique characteristics of lymphangiomas is essential to avoiding needless intrusive procedures and choosing the most effective therapies, such as sclerotherapy or surgical excision when required. Optimal patient treatment is further guided by knowledge of lesion subtypes and available therapy choices, particularly the differences between macro- and microcystic forms. By ensuring precise diagnosis and individualised treatment strategies, multidisciplinary collaboration reduces recurrence and enhances patient results.