Cystic Lymphatic Malformation

Cystic lymphatic malformation (CLM) is a rare congenital disorder characterized by the abnormal growth of lymphatic vessels. This condition typically affects the head and neck regions, although it can also occur in other parts of the body. CLM is also known as lymphangioma, lymphatic cyst, or lymphatic malformation. In this article, we will discuss the various definitions and types of CLM.

Definition: Cystic lymphatic malformation (CLM) is a type of lymphatic malformation in which the lymphatic vessels become abnormally enlarged and form cystic spaces filled with lymphatic fluid. This disorder is caused by the abnormal development of the lymphatic system during fetal development. The lymphatic system is responsible for maintaining the fluid balance in the body and plays a vital role in the immune system.

Types: There are various types of CLM, which are categorized based on their location, size, and extent. The following are the most common types of CLM:

  1. Macrocystic lymphatic malformation: Macrocystic lymphatic malformation is the most common type of CLM, accounting for about 95% of cases. This type of malformation is characterized by the presence of large cysts that can grow up to several centimeters in size. Macrocystic lymphatic malformation is typically located in the neck, armpit, groin, or chest.
  2. Microcystic lymphatic malformation: Microcystic lymphatic malformation is a less common type of CLM, accounting for about 5% of cases. This type of malformation is characterized by the presence of small cysts that are less than 2 centimeters in size. A microcystic lymphatic malformation is typically located in the skin or mucous membranes of the mouth, lips, or tongue.
  3. Mixed lymphatic malformation: Mixed lymphatic malformation is a rare type of CLM that combines features of both macro cystic and microcystic lymphatic malformation. This type of malformation is characterized by the presence of both large and small cysts. The mixed lymphatic malformation can occur anywhere in the body, but it is most commonly found in the neck, armpit, groin, or chest.
  4. Cystic hygroma: Cystic hygroma is a type of CLM that affects the head and neck regions. This type of malformation is characterized by the presence of large cysts that can grow rapidly and become infiltrated with blood vessels. Cystic hygroma can be life-threatening if it compresses vital structures such as the airway or major blood vessels.
  5. Lymphangiectasia: Lymphangiectasia is a type of CLM that affects the intestinal tract. This type of malformation is characterized by the presence of abnormally dilated lymphatic vessels in the walls of the intestine. Lymphangiectasia can lead to malabsorption and malnutrition due to the impaired absorption of nutrients.
  6. Lymphangiomatosis: Lymphangiomatosis is a rare type of CLM that affects multiple organs throughout the body. This type of malformation is characterized by the presence of multiple cysts in the lymphatic vessels of the lungs, bones, liver, and spleen. Lymphangiomatosis can cause a range of symptoms, including shortness of breath, chest pain, bone pain, and abdominal swelling.

Causes

The lymphatic system is responsible for draining excess fluid and waste from tissues and organs, and any disruption in its normal function can lead to the development of CLM. In this article, we will discuss 20 causes of CLM and their respective details.

  1. Congenital: CLM can occur as a result of a congenital abnormality, meaning it is present at birth. This is often due to genetic mutations or environmental factors that affect the development of the lymphatic system during fetal development.
  2. Genetics: Certain genetic mutations have been linked to the development of CLM, such as mutations in the genes responsible for the development and function of the lymphatic system.
  3. Infection: Infections can cause inflammation and damage to the lymphatic vessels, leading to the formation of CLM. For example, lymphatic filariasis is a parasitic infection that can cause lymphatic damage and lead to the development of CLM.
  4. Trauma: Trauma to the lymphatic vessels can cause damage and blockages, leading to the accumulation of fluid and the development of CLM.
  5. Surgery: Surgery can cause damage to the lymphatic vessels, leading to the formation of CLM. This is more likely to occur in surgeries that involve the lymph nodes or lymphatic vessels.
  6. Radiation therapy: Radiation therapy can cause damage to the lymphatic vessels, leading to the formation of CLM. This is more likely to occur in radiation therapy for cancer treatment.
  7. Lymphatic obstruction: Anything that blocks or restricts the flow of lymphatic fluid can lead to the development of CLM. This can include tumors, scar tissue, or other blockages.
  8. Abnormal lymphatic development: In some cases, the lymphatic vessels may not develop properly during fetal development, leading to the formation of CLM.
  9. Autoimmune disorders: Some autoimmune disorders can cause inflammation and damage to the lymphatic vessels, leading to the formation of CLM. Examples include lupus and rheumatoid arthritis.
  10. Hormonal changes: Hormonal changes can affect the lymphatic system, leading to the formation of CLM. This is more likely to occur during puberty, pregnancy, or menopause.
  11. Obesity: Obesity can increase the risk of developing CLM by putting extra pressure on the lymphatic vessels and impairing their function.
  12. Chronic inflammation: Chronic inflammation can cause damage to the lymphatic vessels, leading to the formation of CLM. This can occur in conditions such as inflammatory bowel disease or chronic infections.
  13. Environmental factors: Exposure to certain environmental toxins or pollutants can increase the risk of developing CLM.
  14. Immune system dysfunction: Dysfunction of the immune system can cause inflammation and damage to the lymphatic vessels, leading to the formation of CLM.
  15. Medications: Certain medications can cause damage to the lymphatic vessels, leading to the formation of CLM. Examples include tamoxifen and chemotherapy drugs.
  16. Nutritional deficiencies: Nutritional deficiencies can impair the function of the lymphatic system, leading to the formation of CLM.
  17. Age: The risk of developing CLM increases with age, as the lymphatic system may become less efficient with time.
  18. Hereditary lymphedema: Some forms of hereditary lymphedema are associated with the development of CLM.
  19. Connective tissue disorders: Connective tissue disorders such as Ehlers-Danlos syndrome can affect the development and function of the lymphatic system, leading to the formation of CLM.
  20. Other medical conditions: Certain medical conditions such as Down

Symptoms

Common symptoms and manifestations of CLM:

  1. Swelling: Swelling is the most common symptom of CLM, and it can occur in any part of the body. The swelling can range from mild to severe and can be painless or associated with pain and discomfort.
  2. Discoloration: CLM can cause the skin over the affected area to become discolored or darker in color. This is due to the abnormal accumulation of lymph fluid in the tissue.
  3. Mass or lump: CLM can form a mass or lump under the skin, which may be palpable and visible.
  4. Cystic lesions: CLM can create fluid-filled cystic lesions that can be seen on imaging studies, such as ultrasound, CT scan, or MRI.
  5. Soft tissue swelling: CLM can cause swelling and enlargement of the soft tissue, which can affect the function of nearby organs and structures.
  6. Enlarged lymph nodes: CLM can cause the lymph nodes to become enlarged, which can be felt as lumps in the neck, axilla, or groin.
  7. Pain: CLM can cause pain in the affected area, which can be intermittent or continuous.
  8. Bleeding: CLM can bleed spontaneously or with minor trauma, leading to bruising and discoloration of the skin.
  9. Infection: CLM can become infected, causing redness, warmth, and swelling in the affected area.
  10. Respiratory symptoms: CLM in the neck and chest region can cause respiratory symptoms, such as coughing, wheezing, and shortness of breath.
  11. Dysphagia: CLM in the neck and chest region can cause difficulty swallowing or dysphagia, which can lead to malnutrition and weight loss.
  12. Obstructive symptoms: CLM in the abdominal and pelvic region can cause obstructive symptoms, such as constipation, urinary retention, and pain during defecation.
  13. Gastrointestinal symptoms: CLM in the abdomen can cause gastrointestinal symptoms, such as nausea, vomiting, and abdominal pain.
  14. Bone deformities: CLM in the bone can cause bone deformities, such as scoliosis and limb-length discrepancy.
  15. Neurological symptoms: CLM in the central nervous system can cause neurological symptoms, such as seizures, headaches, and visual disturbances.
  16. Facial asymmetry: CLM in the face can cause facial asymmetry, which can affect the appearance and function of the eyes, nose, and mouth.
  17. Hearing loss: CLM in the ear can cause hearing loss, which can affect the ability to communicate and learn.
  18. Speech difficulties: CLM in the mouth and throat can cause speech difficulties, such as hoarseness, stuttering, and difficulty articulating words.
  19. Dental abnormalities: CLM in the jaw can cause dental abnormalities, such as delayed eruption of teeth and malocclusion.
  20. Skin ulcers: CLM in the skin can cause skin ulcers, which can be painful and prone to infection.
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The clinical presentation of CLM can vary widely depending on the location, size, and extent of the lesion. Some CLMs may be small and asymptomatic, while others can be large and cause significant morbidity and mortality

Diagnosis

The diagnosis of cystic lymphatic malformation can be challenging as it often presents with nonspecific symptoms and can be mistaken for other conditions. In this article, we will discuss the diagnosis and tests for cystic lymphatic malformation and explain the details of each.

  1. Physical examination – The initial step in the diagnosis of cystic lymphatic malformation is a thorough physical examination by a healthcare professional. The presence of a cystic mass, often soft and fluctuant, in the neck, face, or axilla is a common finding. These masses may also be present at birth or become evident later in life. A physical examination can also reveal other associated symptoms, such as difficulty breathing or swallowing, depending on the location of the cystic mass.
  2. Ultrasound – Ultrasound is a noninvasive diagnostic imaging modality that uses sound waves to create images of internal organs and tissues. It is often used as the first-line imaging modality for the diagnosis of cystic lymphatic malformation. Ultrasound can reveal the size, location, and characteristics of the cystic mass, such as its contents, thickness of the wall, and vascularity.
  3. Magnetic resonance imaging (MRI) – MRI is another noninvasive diagnostic imaging modality that uses a magnetic field and radio waves to create detailed images of the internal organs and tissues. It is often used when ultrasound is inconclusive or when further characterization of the cystic mass is needed. MRI can reveal the size, location, and extent of the cystic mass, as well as its relationship to adjacent structures.
  4. Computed tomography (CT) scan – CT scan is a diagnostic imaging modality that uses X-rays and computer processing to create detailed images of internal organs and tissues. It is often used when MRI is contraindicated or when further characterization of the cystic mass is needed. A CT scan can reveal the size, location, and extent of the cystic mass, as well as its relationship to adjacent structures.
  5. Lymphangiography – Lymphangiography is a diagnostic imaging modality that uses a contrast agent injected into the lymphatic system to create images of the lymphatic vessels and their abnormalities. It is often used when ultrasound and MRI are inconclusive or when surgical planning is needed. Lymphangiography can reveal the size, location, and extent of the cystic malformation, as well as its communication with the lymphatic system.
  6. Fine-needle aspiration (FNA) biopsy – FNA biopsy is a diagnostic procedure that involves the insertion of a thin needle into the cystic mass to obtain a sample of its contents for microscopic examination. It is often used when the diagnosis is uncertain or when malignancy is suspected. FNA biopsy can reveal the presence of lymphocytes, lymphatic endothelial cells, and proteinaceous material in the cystic fluid, which are consistent with the diagnosis of cystic lymphatic malformation.
  7. Core needle biopsy – Core needle biopsy is a diagnostic procedure that involves the insertion of a larger needle into the cystic mass to obtain a larger sample of tissue for microscopic examination. It is often used when FNA biopsy is inconclusive or when further characterization of the cystic mass is needed. A core needle biopsy can reveal the presence of lymphatic endothelial cells and connective tissue in the cystic wall, which are consistent with the diagnosis of cystic lymphatic malformation.
  8. Excisional biopsy: Excisional biopsy is a surgical procedure that involves the removal of the entire cystic lesion for histological analysis. It is useful for confirming the diagnosis and determining the extent of the CLM.
  9. Blood tests: Blood tests, such as complete blood count (CBC) and liver function tests, can help identify any abnormalities that may be associated with CLM or its complications.
  10. Genetic testing: Genetic testing can help identify any genetic mutations that may be associated with CLM, such as the PIK3CA mutation, which is a common cause of CLM.
  11. Lymphoscintigraphy: Lymphoscintigraphy is an imaging technique that involves the injection of a radioactive tracer into the lymphatic vessels to visualize the lymphatic system’s function. It can help identify any lymphatic abnormalities associated with CLM.
  12. Chest X-ray: A chest X-ray can help detect any abnormalities in the lungs or mediastinum that may be associated with CLM.
  13. Electrocardiogram (ECG): An ECG can help detect any abnormalities in the heart or its function that may be associated with CLM.

Treatment

drugs that are used in the management of CLMs.

  1. Doxycycline – Doxycycline is a tetracycline antibiotic that has been used for the treatment of CLMs. It has been shown to have sclerosing properties, meaning that it can cause cystic structures to shrink and collapse. Doxycycline can be administered orally or injected directly into the cyst.
  2. Bleomycin – Bleomycin is a chemotherapeutic agent that has been used for the treatment of CLMs. It has sclerosing properties and can be injected directly into the cyst. However, its use is limited due to its potential for systemic toxicity.
  3. OK-432 – OK-432 is a lyophilized preparation of Streptococcus pyogenes that has been used for the treatment of CLMs. It is administered by injection into the cyst and causes an inflammatory response that leads to the formation of fibrous tissue and subsequent shrinkage of the cyst.
  4. Ethanol – Ethanol can be injected directly into the cyst to cause sclerosis. It has been used in the treatment of CLMs in combination with other agents such as doxycycline or bleomycin.
  5. Sodium tetradecyl sulfate – Sodium tetradecyl sulfate is a sclerosing agent that can be injected directly into the cyst to cause sclerosis. It has been used in the treatment of CLMs in combination with other agents such as doxycycline or bleomycin.
  6. Polidocanol – Polidocanol is a sclerosing agent that can be injected directly into the cyst to cause sclerosis. It has been used in the treatment of CLMs in combination with other agents such as doxycycline or bleomycin.
  7. Picibanil – Picibanil is a lyophilized preparation of Streptococcus pyogenes that has been used for the treatment of CLMs. It is administered by injection into the cyst and causes an inflammatory response that leads to the formation of fibrous tissue and subsequent shrinkage of the cyst.
  8. Interferon alpha – Interferon alpha is a type of cytokine that has antiviral and antitumor properties. It has been used for the treatment of CLMs, but its use is limited due to its potential for systemic toxicity.
  9. Sirolimus – Sirolimus is an immunosuppressive agent that has been used for the treatment of CLMs. It works by inhibiting the proliferation of lymphatic endothelial cells. It can be administered orally or topically.
  10. Everolimus – Everolimus is another immunosuppressive agent that has been used for the treatment of CLMs. It works by inhibiting the proliferation of lymphatic endothelial cells. It can be administered orally or topically.
  11. Bevacizumab -Bevacizumab is a monoclonal antibody that targets vascular endothelial growth factor (VEGF). It has been used for the treatment of CLMs, but its use is limited due to its potential for systemic toxicity
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Non Pharmacological treatments for cystic lymphatic malformation in detail.

  1. Observation and Monitoring: In some cases, small cysts may not require any treatment and can be observed and monitored for any changes or growth. Regular imaging studies such as ultrasound or MRI can be performed to assess the size and location of the cysts.
  2. Sclerotherapy: Sclerotherapy is a minimally invasive procedure that involves injecting a sclerosing agent, such as ethanol or sodium tetradecyl sulfate, into the cyst to cause it to collapse and shrink. Sclerotherapy is often used as a first-line treatment for cystic lymphatic malformation and can be repeated as necessary.
  3. Surgery: Surgery may be necessary to remove large cysts or cysts that are causing compression of nearby structures. The surgical approach depends on the location and size of the cysts and may involve open surgery or endoscopic surgery.
  4. Laser Therapy: Laser therapy is a non-invasive treatment that uses a high-intensity laser to heat and destroy the cysts. Laser therapy is often used in combination with other treatments, such as sclerotherapy or surgery.
  5. Radiofrequency Ablation: Radiofrequency ablation is a minimally invasive procedure that uses heat generated by radio waves to destroy the cysts. Radiofrequency ablation is often used in combination with other treatments, such as sclerotherapy or surgery.
  6. Aspiration: Aspiration involves using a needle to remove the fluid from the cyst. Aspiration is often used as a temporary measure to relieve symptoms, but it does not prevent the cyst from refilling with fluid.
  7. Drainage: Drainage involves surgically placing a catheter or tube into the cyst to allow the fluid to drain continuously. Drainage is often used as a temporary measure to relieve symptoms, but it does not prevent the cyst from refilling with fluid.
  8. Chemotherapy: Chemotherapy involves the use of drugs to shrink the cysts. Chemotherapy may be used in combination with other treatments, such as sclerotherapy or surgery.
  9. Radiation Therapy: Radiation therapy involves the use of high-energy radiation to destroy the cysts. Radiation therapy is often used in combination with other treatments, such as sclerotherapy or surgery.
  10. Hormonal Therapy: Hormonal therapy involves the use of hormones to shrink the cysts. Hormonal therapy may be used in combination with other treatments, such as sclerotherapy or surgery.
  11. Immunotherapy: Immunotherapy involves the use of drugs that stimulate the immune system to shrink the cysts. Immunotherapy may be used in combination with other treatments, such as sclerotherapy or surgery.
  12. Cryotherapy: Cryotherapy involves the use of extreme cold to destroy the cysts. Cryotherapy is often used in combination with other treatments, such as sclerotherapy or surgery.
  13. Photodynamic Therapy: Photodynamic therapy involves the use of a photosensitizing agent that is activated by a specific wavelength of light to destroy the cysts. Photodynamic therapy is often used in combination with other treatments, such as sclerotherapy or surgery.
  14. High-Intensity Focused Ultrasound (HIFU): HIFU involves the use of high-intensity ultrasound waves to heat and destroy the cysts. HIFU is often used in combination with other treatments, such as sclerotherapy or surgery.
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