Hemangioma

Overview

A hemangioma is a benign vascular tumor that develops from blood vessel cell types. The most frequent benign tumor in babies is a hemangioma. The terms tumor and cancer should not be used interchangeably. A hemangioma is not a kind of cancer. Vascular lesions include hemangioma and vascular abnormalities. Many vascular abnormalities are incorrectly referred to as hemangiomas. 

What is a Hemangioma?

Hemangiomas are the most frequent benign tumor of infancy. They are also known as hemangiomas of infancy or infantile hemangiomas (IH). Because of their clinical look, they are sometimes referred to as "strawberry markings." Hemangiomas are caused by endothelial cell growth. Hemangiomas are classified into several categories. Congenital hemangiomas can be seen at birth, whereas infantile hemangiomas develop later in childhood. Infantile angiomas are distinguished by fast development that is followed by spontaneous involution.

Hemangioma strawberry (Infantile hemangiomas)

Infantile hemangiomas are benign vascular neoplasms with a distinct clinical history characterized by early growth and spontaneous involution. Hemangiomas are the most frequent pediatric tumors and are typically medically inconsequential. 

Epidemiology

Infantile hemangioma is the most common benign vascular tumor of infancy, affecting around 4% to 5% of babies. It arises as a result of an aberrant cluster of tiny blood arteries during the first year of life. Infantile hemangiomas are more common in Caucasian newborns than in other ethnic groups.

There is also a feminine predominance, with up to a 5:1 female to male ratio. Hemangiomas are also more common in premature newborns, kids born with low birth weights, and babies born with prenatal hypoxia. Infantile hemangiomas are frequent in babies born to elderly moms.

The condition is frequently observed during post-chorionic villus sampling or in multiple deliveries including twins or triplets. The majority of instances are sporadic, however infantile hemangiomas have been shown to run in families. They have been linked to an autosomal dominant pattern of inheritance, albeit no particular genes have been identified.

Etiology 

The etiology of infantile hemangiomas is unknown, however various possibilities exist. The most plausible explanation is that hypoxic stress increases the production of GLUT 1 and VEGF, resulting in the mobilization of endothelial progenitor cells. The progenitor cells express CD133 and CD31. Another theory proposes that placental trophoblasts are the source of stem cells for hemangiomas.

A third theory proposes that IH development involves both de novo vessel production from progenitor cells and the generation of new vessels from existing ones (angiogenesis). It has been proposed that angiogenic factors operate on endothelial cells and pericytes to induce the creation of a capillary network.

Pathophysiology

Endothelial cells proliferate and plump up in infantile hemangiomas. The cells are disorganized early in proliferation, but during development, they create vascular niches and channels brimming with blood cells.

These seemingly harmless endothelial cells create only a few basement membrane structures. As growth slows and eventually stops, hemangiomas develop a lobular morphology. Mast cells appear to influence this process by promoting the feeding arterioles and veins that supply each lobule. They have also been discovered in significant amounts during involution.

Immature endothelial cells cohabit alongside immature pericytes during the third trimester of fetal development, and they retain their proliferative ability for a brief time after birth. Angiogenic peptides such as beta-fibroblast growth factor, vascular endothelial growth factor (VEGF), and proliferating cell nuclear antigen stimulate the proliferation of these immature cells, resulting in the formation of hemangioma.

An influx of mast cells, diverse myeloid cells, and tissue inhibitors of metalloproteinases (TIMPs) occurs when endothelial cells develop. TIMPs, together with interferon and transforming growth factors generated by mast cells, inhibit endothelial cell proliferation and passively cause endothelial cell senescence.

Clinical presentation

Infantile hemangioma is generally absent at birth, however, it can manifest as a variety of precursor lesions. A pale region of vasoconstriction, an erythematous macule, a telangiectatic red macule, or blue bruise-like patches are examples of these. Infantile hemangiomas manifest clinically at 1 to 4 weeks.

The localization is widespread, and it can appear on the skin and mucosal surfaces. The majority of infantile hemangiomas show as a single localized cutaneous hemangioma, however, they can be multifocal or segmental. Hemangiomas are most frequent on the head and neck, accounting for 60% of all occurrences. This is followed by lesions on the trunk in 25% of patients and, less typically, on the extremities in 15% of cases.

Hemangiomas can be superficial, deep, or a combination of both superficial and deep layers. The superficial dermis is involved in superficial lesions, which are elevated, lobulated, and brilliant red. Deep hemangiomas, also known as subcutaneous hemangiomas, are bluish-colored nodules, plaques, or tumors that emerge from the reticular dermis and/or the subcutis layer. Mixed hemangiomas have characteristics of both sites.

The natural history of infantile hemangioma has a triphasic evolution:

• Early proliferative or growth phase: Typically, fast development occurs during the first three months of life, followed by steady growth from months five to eight. Deep infantile hemangiomas multiply over a prolonged length of time, often until the ninth or twelfth month of life.
• Plateau phase: The lesion remains stable and quiescent for a period of months (between 6 and 12 months of life).
• Involution phase: This can start as early as the first year of life and last for several years. Regressive infantile hemangiomas soften and become more compressible, changing color from brilliant red to purple or gray. The skin may return to normal, although there are frequently lasting abnormalities (excessive fibrofatty tissue, telangiectasia, skin laxity)

Diagnosis

After a comprehensive history and physical examination, a skin biopsy might be conducted if the diagnosis is in doubt. Glucose transporter 1 (GLUT-1) staining is universally positive in infantile hemangiomas during both the proliferation and involution stages. The following laboratory investigations have been conducted to look for potential indicators of hemangioma proliferation and differentiation:

• Serum and urinary vascular endothelial growth factor (VEGF)
• Urinary beta-fibroblast growth factor
• Urinary matrix metalloproteinases (MMPs)

Magnetic resonance imaging (MRI) has the following uses:

• Delineate the location and extent of cutaneous and visceral hemangiomas
• Differentiate proliferating hemangiomas from other high-flow vascular lesions (eg, arteriovenous malformations)

Features of ultrasonography are as follows:

• Can aid in distinguishing hemangiomas from other deep dermal or subcutaneous structures (eg, cysts, lymph nodes)
• It is impossible to accurately assess the size and extent of the hemangioma.
• When compared to other soft tissue masses, high vessel density (>5 vessels/cm2) and high peak arterial Doppler shift (>2 kHz) are sensitive and specific for infantile hemangiomas.

Management

Most juvenile hemangiomas cure on their own and do not require treatment. Treatment is required for complicated infantile hemangiomas. The great majority of infantile hemangiomas do not necessitate medical or surgical treatment. The following are treatment options for clinically severe hemangiomas:

• Medication
• Laser surgery
• Surgical excision

Beta-blockers, such as oral propranolol (2mg/kg/day), have recently been demonstrated to be useful as first-line treatment. Propanolol's adverse effect profile, on the other hand, includes bradycardia, hypotension, bronchospasm, and hypoglycemia.

An alternate treatment that can be employed is oral prednisone (2-4mg/kg/day). The high prednisone dose would have to be gradually decreased over weeks to months. Irritability, sleep disruption, hypertension, bone demineralization, cardiomyopathy, and growth retardation are all possible side effects of prednisone. Timolol, a topical beta blocker, is used to treat infantile hemangiomas that are tiny, superficial, and simple.

Small localized lesions can be treated with intralesional and topical corticosteroids. Otherwise, surgical excision to avoid problems may be considered. Surgical excision removes the remaining fibrofatty tissue, which enhances treatment results.

Features of laser surgery treatment are as follows:

• The most common type of pulsed-dye laser is the flashlamp-pumped pulsed-dye laser.
• Laser surgery using pulsed dyes It is useful in the treatment of ulcerated hemangiomas and thin superficial hemangiomas.
• Lasers should be utilized with caution in places where they are likely to have a major functional or psychological impact (eg, fingers, eyes, lips, nasal tip, ears, face)
• Many ulcerated hemangiomas react to therapy with decreased discomfort (sometimes as soon as a few days), quick reepithelialization, and accelerated involution.
• Laser treatments are typically administered every 2-4 weeks until full recovery occurs.
• Scarring or persistent skin changes are possible.
• Laser therapy may aggravate ulceration, especially in deep or mixed superficial and deep lesions.

Features of surgical excision are as follows:

• It is not rare for it to be used to treat cutaneous abnormalities caused by involuted hemangiomas.
• Because of the risk of bleeding and injury to important tissues, surgical excision of proliferating hemangiomas requires specially educated surgeons.
• Early excision may save a person's life, preserve vision, or remove a visually unappealing lesion.

Differential Diagnosis

When considering hemangiomas, there are various differentials that fall into this category. It is important to consider each of them to obtain the accurate diagnosis.  

• Congenital hemangioma 
• Pyogenic granuloma
• Kaposiform hemangioendothelioma
• Tufted hemangioma
• Venous malformation
• Capillary malformation: port wine stain
• Macrocystic lymphatic malformation
• Malignant tumors: sarcoma, a cutaneous location of neuroblastoma or lymphoma

Congenital hemangiomas

Congenital hemangiomas are uncommon solitary vascular tumors that do not grow after birth. Congenital hemangiomas are characterized based on whether they shrink and disappear, do not shrink and disappear, or partially shrink. Rapidly involuting congenital hemangiomas (RICH) are those that diminish and disappear fast. Noninvoluting congenital hemangiomas are those that do not shrink and stay (NICH).

Hemangioma on liver

Hepatic hemangiomas are benign venous hypervascular abnormalities of the liver. They are the most prevalent benign mesenchymal liver tumors. Endothelial cells line hemangiomas, which are surrounded by a thin fibrous stroma. They are also known as cavernous hepatic hemangiomas or capillary hepatic hemangiomas. They are usually asymptomatic and only discovered by chance on imaging. Usually observed as a single lesion, however numerous lesions may be present. They are classified according to their size. Small hemangiomas are 1 cm to 2 cm in size, normal hemangiomas are 2 cm to 10 cm in size, and enormous hemangiomas are larger than 10 cm in size.

Hepatic hemangiomas' genesis is not well known. They arise infrequently and without any identified risk factors. Giant hemangiomas are hemangiomas that are larger than 10 cm in diameter. Because they are vascular abnormalities, they expand by ectasia rather than hyperplasia or hypertrophy. The hemangioma may grow as a result of the rise in hormones (estrogen and progesterone) during pregnancy; however, estrogen receptors have not been demonstrated in all tumors. Some cancers may even develop if estrogen treatment is not used.

Hepatic hemangiomas are often asymptomatic and discovered via imaging examinations for other reasons, such as laparotomy or autopsy. Hemangiomas larger than 4 cm, on the other hand, frequently induce stomach pain and discomfort.

Right upper quadrant discomfort, widespread abdominal pain, or abdominal fullness are the most prevalent symptoms. If there is bleeding within the lesion, it might cause Glisson's capsule to expand and inflame, resulting in intense abdominal discomfort. When a hemangioma grows in size, the symptomatology is caused by compression of neighboring tissues (i.e., early satiety from gastric compression).

Drug-induced hemangioma

Some medicines have been linked to the development of hemangiomas in nonclinical toxicological animal models used to research carcinogenesis. In male rats, for example, hemangiomas of the mesenteric lymph node were significantly elevated at 700 mg/kg/day of Empagliflozin, or nearly 42 times the exposure from a 25 mg therapeutic dosage. Nonclinical animal studies indicate that some medications can cause hemangiomas in humans, and cautious dosage during therapeutic drug design can assure their safe usage.

Prognosis

Most simple infantile hemangiomas have a very excellent prognosis, with full involution occurring in 50% of cases by age 5 years, 70% by age 7 years, and 90% by age 9 years. Despite the resolution of the vascular component, persistent skin abnormalities are noted in around half of the cases. By the age of six years, 38 percent of hemangiomas that had involuted still had residual signs, such as scar development, telangiectasia, or redundant or anetodermic skin.

Permanent cutaneous residua is more common in hemangiomas that take longer to involute. Eighty percent of lesions that finish involution beyond the age of six years may have serious aesthetic abnormalities. When the lip, nasal tip, eyelid, and ear are implicated, the risk of persistent residua increases.

Complications

The complications depend on the patient's age and on the hemangioma's size and location. The complications of Hemangioma are listed below. 

• Ulceration is the most common consequence, occurring in up to 10% of patients. Ulcers are more likely to form in the anogenital region, lower lip, axilla, and neck.
• Amblyopia, astigmatism, myopia, retrobulbar involvement, and tear duct blockage are examples of ophthalmologic problems.
• Nasal, subglottic, and laryngeal passageways can all be obstructed.
• Feeding difficulties might occur as a result of perioral or lip hemangiomas.
• Visceral hemangiomatosis, particularly multifocal hemangiomas (five or more skin lesions), has been linked to the liver or gastrointestinal dysfunction.
• Large face area involvement or involvement of the nasal tip (called Cyrano nose), ears, and perioral region can result in cosmetic deformity.
• PHACES syndrome is characterized by a massive segmental face hemangioma (greater than or equal to 5 cm). The abbreviation PHACES stands for posterior fossa malformations, cervicofacial hemangioma, arterial anomalies, cardiac abnormalities, ocular anomalies, and sternal or abdominal clefting.
• LUMBAR syndrome is characterized by lumbosacral hemangiomas and may be connected with underlying developmental defects. The abbreviation LUMBAR stands for lumbosacral hemangioma, urogenital abnormalities, myelopathy, bone deformities, anorectal or arterial anomalies, and renal anomalies.

Conclusion 

Hemangiomas are the most frequent pediatric tumors, and the majority of infantile hemangiomas are medically unimportant. Infantile hemangiomas can occasionally encroach on important tissues, ulcerate, hemorrhage, and induce high-output heart failure, as well as substantial morphological defects or deformity. A cutaneous infantile hemangioma is occasionally accompanied with one or more underlying congenital abnormalities.

Infantile hemangiomas are benign vascular neoplasms with a distinct clinical history characterized by early growth and spontaneous involution. Infantile hemangiomas expand during the proliferative phase in the neonatal period or early infancy due to rapidly dividing endothelial cell proliferation. Finally, an involutional phase begins, during which most infantile hemangiomas are clinically cleared by the age of 9 years.