What is capillary lymphangioma? 

Capillary Lymphangioma is a rare condition in which non-cancerous growths, also known as benign tumours, form in the lymphatic system.^1,2 The lymphatic system is a complex network of vessels that carry lymph throughout the body, much like blood vessels carry blood. Lymph is a clear fluid that has the ability to collect fluids across different tissues and contribute to maintaining fluid balance, facilitating lipid transport, and supporting immune surveillance. 

In capillary lymphangioma, these lymphatic vessels do not develop properly, and as a result, cause the formation of disorganized clusters of fluid-filled sacs that form under the skin or in deeper tissues.¹ This condition typically presents at birth as it is considered a congenital disease, or it can become apparent early in childhood, typically by the age of 2. Despite their benign nature, these growths can vary in size and location, leading to functional problems and disfigurement. This can, in turn, significantly affect the person’s body image and also cause serious health complications.²

Addressing the confusing terminology

In the medical field, capillary lymphangioma is described using various terms, which may cause confusion.¹ You might encounter names like:

• Lymphangioma circumscriptum
• Microcystic lymphatic malformation
• Lymphangioma simplex
• Or simply, lymphatic malformation 

These terms are often used to describe the same or similar non-cancerous malformations that involve abnormal clusters of lymphatic vessels.

That’s because capillary lymphangioma falls under a larger category of disorders, known as lymphatic malformations.² This term describes conditions where the lymphatic system fails to properly form before birth, where it would normally develop. These conditions present in different ways on the skin and are categorised based on the cyst size and depth.

• Macrocystic lymphatic malformations: larger (over 2cm) fluid-filled sacs, typically superficial (under the skin)
• Microcystic lymphatic malformations: many small (less than 2cm) cysts that appear in clusters of sponge-looking, clear or red sacs on the skin’s surface
• Mixed lymphatic malformations: where both forms manifest within the same lesion. 

When describing capillary lymphangioma specifically, the terms microcystic lymphangioma, lymphangioma simplex and lymphangioma circumscriptum are often used interchangeably. 

Characteristics

Genetic basis?

As stated above, capillary lymphangioma is considered a congenital condition, developing before birth, during embryonic development. The condition results from the abnormal formation of the lymphatic system. In healthy individuals, the lymphatic vessels across the body form a network that eventually connects with the rest of the vascular system. In capillary lymphangioma, the newly formed lymphatic vessels fail to connect with the vascular system, resulting in clusters of abnormal, dilated vessels that are isolated from the normal process of lymphatic drainage. The exact genetic mutations or inheritance patterns contributing to the condition remain unclear.² However, lymphangioma is common in children with genetic conditions, including:¹¹

• Trisomy 13
• Trisomy 18
• Trisomy 21
• Down syndrome
• Turner syndrome
• Noonan syndrome

Appearance

The visual appearance of capillary lymphangiomas, particularly those presenting superficially on the skin, is quite distinctive. The condition typically manifests as clusters of small and firm blisters on the skin surface, often described as spongy. The bubbly and clustered nature of superficial capillary lymphangioma has led to its cysts being compared to “frog-spawn”, as they resemble frog eggs clustered in jelly-like clumps.³ 

Cyst appearance may vary between individuals. They can present as:

• Clear, translucent or pale yellow- when filled with lymphatic fluid
• Pink, red or purple-brown- when lymph is mixed with blood due to rupture and leakage

The depth of the lesion can also vary, as superficial cysts show more colour in contrast with the skin, and deeper ones may cause swelling or skin thickening. 

Common sites

Capillary lymphangiomas can present anywhere in the body. However, the head and neck area is predominantly affected, making up approximately 70% of reported cases.² Cysts are also reported in the axilla (armpit area), the limbs, and in the oral cavity involving the mouth and tongue.⁴

While capillary lymphangioma is most commonly found on or under the skin, it can occur internally as well. The most common manifestation includes the tongue, while cases have been reported involving the gums, genital and chest area.^5,6,7,8 Internal manifestations are especially noteworthy as they usually do not cause any visible external symptoms and may incidentally be seen during imaging or surgical practices for unrelated factors. This observation highlights the importance of advanced imaging techniques for conditions like capillary lymphangioma, as the cysts can become enlarged and cause serious and sudden symptoms, leading to pain and obstruction. 

Size and growth patterns

The condition is defined by small clusters of cysts that are no bigger than 2 centimetres in diameter. However, capillary lymphangiomas are not static in size. Sometimes the cysts may experience periods of slow, progressive growth when triggered by specific factors.^9,10

Triggers for capillary lymphangioma include:

• Trauma, Surgery & Radiation: Interruptions to the normal lymphatic flow in the body as a result of these factors can lead to chronic lymphatic obstruction, which can cause new lesions to form in previously healthy tissue
• Infection & Chronic Inflammation: Conditions that cause chronic inflammation are also likely to affect lymphatic flow and, therefore, contribute to capillary lymphangioma
• Hormonal Changes: Periods of hormonal shifts or hormonal imbalances, such as puberty or pregnancy, can cause the emergence or exacerbation of capillary lymphangioma

This characteristic suggests that while capillary lymphangioma is mostly congenital, certain triggers can promote its progression, or even its emergence. For this reason, lesions can sometimes extend and become locally invasive to the affected tissue. In rare cases, these triggers can develop later, which describes acquired lymphangiomas. 

Symptoms

Beyond the presence of the characteristic clusters of clear blisters, or “frog-spawn” appearance, common symptoms include pain and swelling at the site, itching and burning sensations and, sometimes, drainage of lymph from the cysts.² 

Symptoms that are more specific to the location of the lymphangioma include:

• Head and neck: problems with speech, eating and swallowing, restricted neck movement and in progressed cases, airway obstruction
• Limbs: swelling and disproportionate growth, possible disfigurement
• Chest: wheezing, chest pain, dyspnea (trouble breathing)

Diagnosis

Physical Exam

A patient presenting with symptoms that fit into the capillary lymphangioma profile will initially receive a physical exam. The healthcare provider will observe the cysts and identify the distinct translucent, soft-to-touch, clustered vesicles, or other presentations that indicate the condition.

Imaging

In cases where the cysts have formed beyond the skin surface or appear abnormally large, healthcare providers may proceed with imaging technology. This includes the use of ultrasounds, where the depth and nature of the cyst are evaluated, or MRI examinations, where the bigger picture of the cyst’s location and characteristics can be built.

Biopsy under the microscope

When capillary lymphangioma is suspected, a small sample of the affected tissue may be taken for examination. This process is called a biopsy, and it is a significantly important part of the diagnostic process for most conditions. A biopsy usually confirms the diagnosis and eliminates suspicion of other conditions that mimic or look similar to capillary lymphangiomas, such as hemangiomas, certain skin cancers and warts. 

The microscopic analysis of tissue affected by capillary lymphangioma typically shows numerous, thin-walled, enlarged vesicles filled with lymph. These spaces are usually lined by normal lymphatic cells, which appear flat and thin, and surrounded by thickened skin. Additionally, where infections or bleeding have occurred, the vesicles contain blood or immune cells.

Immunohistochemistry (IHC) 

For further confirmation, a laboratory technique called immunohistochemistry (IHC) may be performed. This method uses specialised stains and applies them to the biopsied sample. These stains, which are monoclonal antibodies, can only stick to certain target proteins, called markers, and confirm the presence of the suspected condition if they stain the sample. 

The proteins that are present in tissue affected by capillary lymphangioma, also known as the diagnostic markers for the condition, are:

• D2-40 (podoplanin): protein found in lymphatic endothelial cells, used to clarify that lymphatic fluid is inside the cysts and make them visible under the microscope⁴
• LYVE-1 (Lymphatic Vessel Endothelial Hyaluronan Receptor-1): protein found in lymphatic vessel cells, also used to paint a clear picture of cysts of lymphatic nature
• CD31: protein present in all endothelial cells, used in combination with lymphatic-specific markers like D2-40 and LYVE-1, helps confirm the distinct endothelial lining of capillary lymphangioma clusters

Summary

Capillary lymphangioma is a rare congenital condition that causes clusters of fluid-filled cysts, due to malformed lymphatic vessels during embryonic development. These lesions may be benign, but they can cause severe discomfort and health complications. Characterised by their distinct cluster of clear blisters, resembling “frog-spawn”, the cysts usually remain small in size unless triggered by trauma, chronic inflammation or hormonal changes. Diagnosing capillary lymphangioma combines physical examinations, imaging when necessary, biopsy and IHC to provide a precise diagnosis. Early detection is vital in order to manage potential health complications and ensure that appropriate care and treatment is chosen.