Vascular malformations are inborn developmental abnormalities of the blood vessels that are evident at birth and are divided into low flow lesions (capillary, venous, and lymphatic anomalies) and rapid flow lesions (arterial and arterio-venous congenital anomalies) based on the flow pattern. Lymphangiomas, also known as lymphatic malformations, are benign hamartomas that originate abnormally from the primitive lymphatic sacs. They account for 25 percent of benign vascular masses in children and 4 percent of vascular masses. Lymphangiomas present as smooth, homogeneous, nontender, collapsible, solitary masses that can be transilluminated in any part of the body, with 75 percent of the time appearing in the head and neck region, 15 percent in the axilla, and the rest in the thoracic and abdominal regions. Lymphangiomas are evident at birth in 50-60% of patients, and they become visible in 80-91 percent of cases during adolescence and adulthood. Lymphangiomas are made up of dilated lymph vessels filled with proteinaceous material that is normally not related to the lymphatic system. The great majority of lymphangiomas are congenital, although they can also develop as a result of trauma, inflammatory process, or lymphatic blockage in rare situations.
Vascular malformations are vascular defects that occur during development. In the United States, lymphangiomas are uncommon. They account for 4.2% of all vascular tumors in children and 26% of all benign pediatric vascular masses. There is no preference based on race or gender. Lymphangiomas usually appear at birth or within the first few years of life, but cutaneous lymphangioma circumscriptum is more common in adults.
Redenbacher described the lymphangioma for the first time in the 1820s, and Wernher reported the first incidence of cystic hygroma in the 1840s, using this name taken from Greek - "hygro" denotes fluid, and "oma" indicates tumor - for the first time. Landing and Farber categorized lymphatic anomalies for the first time in the 1950s, while Bill and Summer established that cystic hygroma and lymphangioma are variants of the same disorder in the 1960s, and proposed that categorization be based on localization.
Although the cause of congenital lymphangiomas is uncertain, they are caused by an obstruction of the lymphatic vessels during fetal development. Trisomy 13, 18, and 21, as well as Noonan syndrome, Turner syndrome, and Down syndrome, are all linked to cystic lymphangiomas. Acquired lymphangioma circumscriptum is a type of lymphangioma that develops in the presence of prolonged lymphedema and causes disruption of normally functioning lymphatic pathways.
Embryologic Development of Lymphatic System
The lymphatic system is a collection of vessels that is responsible for returning excess fluid from the body to the venous system. The lymphatic system begins to form at the end of the fifth week of pregnancy, two weeks after the recognition of the cardiovascular system's primordia, and one week following the first -coordinated cardiac beats begin to initiate unidirectional blood flow.
The centrifugal hypothesis, proposed by Lewis and fully endorsed by Huntington and McClure, and validated by Kamp-Maier, states that lymph system develops at the same time as those that later combine to form the venous system's network; and the centripetal hypothesis, proposed by Huntington and McClure and validated by Kamp-Maier, states that jugular and posterior lymph vessels are developed in the mesenchymal tissue from the venous endot Eight lymphatic sacs form in the eighth week of pregnancy: two jugular sacs, two iliac sacs, and two retroperitoneal sacs - one at the base of the mesentery and another behind it, the cisterna chyli. The bilateral thoracic ducts connect cysterna chyli to the jugular sacs during the ninth week. To construct the final thoracic duct, a large anastomosis is made between the two thoracic ducts.
Lymphangiomas are caused by congenital or acquired lymphatic system disorders. The congenital type is caused by the incorrect attachment of lymph vessels to the main lymph drainage duct before the age of five years. Any disruption of normally functioning lymphatic drainage, such as surgery, trauma, cancer, or radiation treatment, can result in acquired lymphangiomas.
Histopathologic examination reveals a collection of large lymphatic reservoirs down in the subcutaneous plane that connects via dilated dermal lymph vessels lined with endothelial cells. The overlying epidermis is typically acanthotic or hyperkeratotic, with uneven rete peg elongation. There are usually no aberrant vascular characteristics, nucleus atypia, mitotic activity, or koilocytic alterations. There may be a mild to moderate inflammatory infiltration. Large, irregular vascular areas are lined with a single layer of flattened endothelial cells within fibroblastic or collagenous parenchyma that may contain lymphocytes in cystic or cavernous lymphangiomas. Muscle invasion is possible.
Multiple, clustered or dispersed, transparent or hemorrhagic vesicular papules that resemble frog-spawn present medically as lymphangioma circumscriptum. Purple patches can be detected distributed among the vesicle-like papules because the lesions include a mixture of blood and lymph components. The skin of the vaginal area can be verrucous, and lesions can be misinterpreted for warts. The acquired type is most commonly observed in the axilla, inguinal, and vaginal areas, with lymphedema frequently present. Pruritus, discomfort, burning, lymphatic discharge, infection, and cosmetic issues are all possible symptoms.
Cavernous lymphangioma appears as a painless, poorly-defined subcutaneous protrusion with no alterations in the overlying skin that can be many centimeters in size during childhood. A complete extremity may be impacted in rare circumstances. On deep probing of the area, patients may feel discomfort. In clinical settings, they are frequently misdiagnosed as cysts or lipomas.
Cystic hygromas are lymphatic anomalies that are more medically limited than cavernous lymphangiomas and most commonly appear in the neck, axilla, or groin. They are soft, with various sizes and forms on physical inspection, and will normally expand if not surgically removed. There may be a link between posterior neck lesions and Turner syndrome, hydrops fetalis, or other congenital disorders. Transabdominal or transvaginal ultrasounds can be used to envision these lesions in utero. The degree of structural involvement of cystic or cavernous lymphangiomas can be determined by magnetic resonance imaging (MRI).
Lymphangiomas are categorized into three types by Landing and Faber: lymphangioma simplex, cavernous lymphangioma, and cystic hygroma.
The phrases cavernous lymphangioma and cystic hygroma are frequently used interchangeably. There are four categories, according to a more modern classification:
- Lymphangioma circumscriptum, also known as microcystic lymphangiomas: they constituted of small lymphatic vessels, capillary-size, positioned into the epidermis;
- Cavernous lymphangiomas: they consisted mainly of enlarged lymph vessels invading the surrounding tissues;
- Cystic hygroma: they are also known as macrocystic lymphangiomas
- Hemangiolymphangioma, also known as Vasco-lymphatic malformations: they are lymphatic abnormalities having vascular elements.
However, because all four types have comparable symptoms, distinct varieties may coexist and emerge as a result of the same disease process.
The majority of lymphangiomas are located in the neck region (75%) and the armpit region (15%), with the other lymphangiomas being discovered in the mediastinum, mesentery, retroperitoneum, colon, groin, bone, skin, scrotum, and spleen.
- Lymphangioma circumscriptum, also known as capillary or microcystic lymphangiomas, appears as a bundle of small, transparent bubbles on the skin surface that range in color from pink to deep red. The vesicles are normally visible at birth or shortly after delivery, and they grow steadily in size over time, usually without causing any symptoms. After the lesions break, hemorrhage and clear vesicular liquid leakage may occur. With lymphangiectasia, hemangioma, angiokeratoma, metastatic cancer of the skin, verrucae, molluscum contagiosum, warts, and other skin cancers, a differential diagnosis should be made.
- Cavernous lymphangioma appears as a large, deep mass with no darkening of the underlying skin during birth or during childhood. It comes in a variety of sizes. This lymphangioma grows quickly, and like other hemangiomas, it can spread to a whole extremity. The majority of the time, it's on the neck, tongue, or lips.
- Cystic hygroma is identical to cavernous lymphangioma in that it is characterized by a deep cystic swelling that is somewhat collapsible and coated by the skin. It is most commonly observed on the neck, armpit, and groin area. The tumor will be emptied if it is evacuated. If not surgically eliminated, the cyst quickly fills up with fluid and grows in size. If the lymphangioma is not complicated, the patient's overall health is good. If the lesions get infected, the patient may have a fever, and the lymphangioma may become warm, painful, and erythematous or shine on the underlying skin. Lymphangiomas are usually unilateral, although they can spread to the other side of the body over time.
A clinical diagnosis can usually be designed depending on the patient's history and physical examination. Dermoscopy and biopsy can be used to support the diagnosis if necessary, and imaging may be required to determine the depth and extent of a disease.
Differentiating superficial lymphangioma from other cutaneous lesions can be done with a dermoscopic evaluation. There are two unique dermoscopic patterns: yellow lacunae bordered by light septa with no blood inclusion and yellow to pink lacunae interspersed with dark-red or blue lacunae with blood inclusion. A "hypopyon-like" characteristic, which comprises a color shift from dark to light in some lacunae, is a more recently described dermoscopic finding. This is due to blood sediment, which isolates cellular components at the base from serum at the top of the lacunae.
Ultrasound imaging, computer tomography, and magnetic resonance imaging (MRI) all show cystic tumor tissues masses of varied sizes in the same way. On ultrasonography, anechoic cysts with uniform boundaries and many interior septa can be identified. Only peripherally, a color Doppler analysis showed minimal vascular flow. On computed tomography, cystic masses with homogeneous internal density without contrast enhancement can be seen, whereas lymphangiomas on MRI are seen as hyperintense masses on T2-weighted images, with regular boundaries, thin walls, and internal septa, and increased signal intensity on T1-weighted images - thin walls and septa, but no internal contrast enhancement. All three modalities enable the identification and characterization of the lesion, but ultrasound is the first-line approach for diagnosis and characterization because of its lack of invasiveness, minimal price, and lack of radioactivity.
Computed tomography and Magnetic resonance imaging provide a non-panoramic image as well as more information about the lymphangiomas' local expansion. MRI provides for a more detailed examination of the lesions' morphology and structure, internal septa, and wall thickness, as well as the exclusion of other cystic components such as mucus, adipose tissue, or solid fillings. In lymphangioma of the skin, imaging modalities are critical for diagnosis, differential diagnosis (e.g., excluding malignancy), and precise anatomical localization prior to surgery (relationships with major vessels and neighboring tissues). Plain radiography, especially in the case of thoracic and abdominal lymphangiomas, may be useful in the absence of Computed tomography and magnetic resonance imaging.
In patients who will be treated with sclerosing drugs, needle aspiration and cytological evaluation of the aspirated fluid are critical. The surgery may also be required in cases when there is a danger of abscess formation due to bleeding or infection. If severe compression of the respiratory airways develops, the same approach can be utilized to delay surgical resection. Microbiological cultures and examination of the cells in the aspirated fluid are advised.
If not complicated, lymphangiomas are a harmless disease that does not require treatment unless it is for cosmetic reasons. However, if the situation is severe or there is a high danger of complications, therapy is required. Aspiration, surgical resection, laser ablation, radiofrequency ablation, percutaneous administration of sclerosing chemicals, or combinations including radio-chemotherapy can all be used to treat lymphangiomas, although surgical excision of the cystic lesion remains the gold standard treatment. Aspiration and drainage are not treatment options because the fluid pools quickly after aspiration, although they can be used temporarily in severe airway compressions before operation. This treatment strategy aims for full surgical removal, but it should be noted that surgery removes not just the cystic mass but also some of the normal surrounding tissues. If the lymphangioma is eliminated, recurrence is possible but unlikely. The best time to have surgery varies on the size of the tumor and any potential problems, with very big lymphangiomas necessitating even intrauterine operation. The recurrence rates differ between 10% and 52% if the cyst is not completely removed, which is commonly attributable to challenging excision of the cyst walls. A multidisciplinary approach is required in difficult instances. Lesions of the neighboring structures, infections, recurrence, seroma, pulmonary obstructions, pneumonia, palsies, painful and debilitating scars, and other postsurgical problems can occur in 13 to 34 percent of patients. Injections of sclerosing agents have become more common in recent years, with different outcomes. The lymphangioma becomes infected, shrinks, or disappears altogether once the sclerosing agent is injected - the epithelium of the cystic cavities is damaged, fluid production is reduced, and the cysts collapse. Lymphangioma was treated with a variety of sclerosing agents, including 1 or 3 percent sodium tetradecyl sulfate, doxycycline, bleomycin, 40-50 percent acetic acid, absolute ethanol, hypertonic saline, and OK 432. Hemangiolymphangioma was managed with propranolol. The fundamental issue with sclerosing chemicals is their propensity for spreading further than the injected tumor. Pain, swelling, inflammation, cutaneous necrosis, neurological lesions, irregular heartbeats, cutaneous erosions, infections, baldness, skin discoloration, pulmonary fibrosis, tooth discoloration, and other problems might occur after sclerosing agents are administered. In hemangiomas, radiotherapy and chemical cauterization are ineffective. Dye laser therapy may be used to treat Lymphangioma circumscriptum.
Prenatal Diagnosis and Genetic Counseling
Prenatal diagnosis has advanced significantly in recent years, with prenatal ultrasonography or Magnetic resonance now being able to detect up to 75% of lymphangiomas. A screening ultrasound is usually sufficient for a positive and differential diagnosis, but Magnetic resonance imaging can provide extra details, distinguish between different types of lymphatic malformations, and is especially useful in cases of complicated extension because it allows the neighboring structures to be evaluated. Imagistic approaches can help distinguish between lymphangiomas and nuchal translucency. Lymphangiomas found in the neck may need to be distinguished from cystic teratoma, branchial and thymic cysts, and congenital fibrosarcoma, whereas those found in the abdomen may need to be distinguished from ovarian cysts, renal cystic masses, mesenchymal liver hamartoma, urachal cysts, and congenital fibrosarcoma. Because cystic lymphangioma is closely associated with genetic abnormalities (Noonan syndrome, 13, 18, and 21 trisomies) and cystic hygroma is related to aneuploidies (Turner syndrome and Down syndrome), prenatal detection of a lymphangioma should induce amniocentesis and genetic investigation. Because of the higher risk of recurrence in subsequent pregnancies, chromosomal testing and genetic guidance are indicated at least for cystic hygroma. Because prenatal testing is inaccurate, a detailed evaluation is required in cases requiring intrauterine treatment due to severe intrauterine compression. Imagistic techniques could also aid in determining the best delivery mode.
Lymphangioma circumscriptum and cavernous lymphangioma have relatively good prognoses. Minor hemorrhage, recurrent cellulitis, and lymph fluid leaks are all symptoms of this disease. There have been two examples of lymphangiosarcoma originating from lymphangioma circumscriptum; however, both patients had a preexisting tumor that had been subjected to extensive radiation therapy.
Big cysts in cystic hygroma can induce dysphagia, respiratory difficulties, and infection if they affect the neck. Cystic hygroma patients should have cytogenetic testing to see if they have chromosomal abnormalities, and parents should seek genetic counseling because the problem might return in later pregnancies.
Damage to the tissues in the neck, infection, and the reappearance of cystic hygroma are all risks associated with surgical treatment of cystic hygroma.
As our understanding of lymphangioma grows, a greater focus has been put on personalized therapy, in which distinct treatment regimens are devised based on the location, scope, and categorization of the lesions. For large cystic lymphangiomas, surgery and most sclerotherapy treatments are appropriate, but not for microcystic lymphangioma. While the new medications discussed above are more appropriate for the management of macrocystic lymphangioma, more research is needed because the response of macrocystic lymphangioma to treatments can differ. Only a subset of lymphangioma patients can benefit from the medications, implying that the molecular pathological basis of each type of lymphangioma is likely to be different, necessitating various therapeutic targets. However, the precise molecular pathophysiology of lymphangioma remains unknown at this time. The following research directions should be investigated in order to improve lymphangioma diagnosis and therapy. Initially, a greater understanding of the pathological characteristics of each type of lymphangioma is needed, which will not only aid in improving the diagnostic accuracy of different types of lymphangioma but will also pave the way for a more detailed analysis of their pathophysiology and molecular biochemical properties, a more precise molecular categorization, and successful LM treatment. Second, continued research into drugs that have been used in the treatment of lymphangioma as well as those in clinical studies is required, as is studying the pharmacological mechanisms of these drugs in order to optimize their efficacy and minimize different side effects, as well as determining the particular therapeutic regimen for each categorization. Finally, for those lymphangiomas that are resistant to drug treatment, comprehensive treatments such as surgery, sclerotherapy, and pharmacological therapy should be considered to reduce disease complications and improve patient outcomes.