Version May 2024
INTRODUCTION — Infantile hemangiomas are benign tumors of vascular endothelium and the most common tumors of childhood [1]. Despite their benign and self-limited nature, some hemangiomas can cause complications, such as ulceration or life-altering disfigurement. Occasionally, hemangiomas may compromise vital organ function or may occur in association with developmental anomalies.
The evaluation of infantile hemangiomas will be discussed here. The epidemiology, pathogenesis, clinical features, complications, and management of infantile hemangiomas are discussed separately. PHACE (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, and eye anomalies) syndrome is also discussed separately.
●(See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications".)
●(See "Infantile hemangiomas: Management".)
●(See "PHACE syndrome".)
DIAGNOSIS — In the vast majority of cases, the diagnosis of a hemangioma can be established clinically, based upon the history and physical examination [2]. However, deeper, subcutaneous lesions without the characteristic overlying skin changes and hepatic lesions (especially in the absence of a cutaneous hemangioma) may be very difficult to distinguish from vascular malformations or other tumors. Although imaging studies can be helpful [3-6], tissue biopsy is generally needed for definitive diagnosis in cases that are atypical in appearance or behavior.
History — Important aspects of the history for a child with a vascular lesion include [7]:
●Age at which the lesion was first noted and subsequent behavior of the lesion.
●Presence of ulceration, pain, bleeding, and/or evidence of secondary infection.
●Whether any imaging studies, biopsies, or other prior evaluations (including subspecialty) have been performed.
●Previous treatment and response.
●History of progressive respiratory difficulty in the first several months of life, particularly if a hemangioma is in a cervicofacial or mandibular ("beard") distribution (picture 1) (may indicate the simultaneous presence of airway hemangioma).
●Signs of high-output cardiac failure during early infancy in the presence of multiple (five or more) cutaneous hemangiomas (may indicate the presence of hepatic hemangiomas). (See 'Multiple cutaneous hemangiomas' below and 'Hepatic hemangiomas' below.)
●Rapid growth, along with tenseness, purpuric appearance, or widespread telangiectasias, in the presence of a very low platelet count (may indicate the Kasabach-Merritt phenomenon in the case of a kaposiform hemangioendothelioma or tufted angioma [vascular tumors distinct from infantile hemangiomas]). (See "Tufted angioma, kaposiform hemangioendothelioma (KHE), and Kasabach-Merritt phenomenon (KMP)".)
●Any parental preconceptions: What have they already learned about the potential diagnosis and treatment options? What concerns them the most about their child's lesion(s)?
Examination — The physical examination should include [7]:
●Careful examination of the skin and mucous membranes
●Documentation of lesion morphology, location, and approximate size
●Documentation of the presence and severity of ulceration and whether there is clinical evidence of secondary infection
●Palpation of the abdomen for hepatomegaly and evaluation for abdominal bruit if clinically indicated, including evaluation for signs of high-output heart failure (eg, tachycardia, wide pulse pressure, bounding pulses, midsystolic murmur, and/or a third heart sound caused by the increased rate of ventricular filling) (see "The pediatric physical examination: Chest and abdomen")
Imaging studies — Most hemangiomas can be diagnosed clinically without additional studies. In the minority of cases where the diagnosis is in question, imaging (ultrasonography, computed tomography [CT], or magnetic resonance imaging [MRI]) can be helpful but should not be relied upon if there is any question of malignancy, in which case tissue biopsy is generally necessary. Clinical findings that may raise suspicion of malignancy include lesion present at birth, firm texture on palpation, tenderness (unless ulcerated), and rapid enlargement.
Imaging may also be useful in evaluating the extent of a complicated hemangioma, evaluating for other potential anomalies when clinically indicated (eg, PHACE [posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, and eye anomalies] syndrome, LUMBAR [lower-body hemangioma and other cutaneous defects, urogenital anomalies, ulceration, myelopathy, bony deformities, anorectal malformations, arterial anomalies, and renal anomalies] syndrome), or following response to therapy, particularly in the case of hepatic hemangiomas. (See 'Additional evaluation' below and 'Differential diagnosis' below.)
ADDITIONAL EVALUATION — Depending upon the location and morphology of the hemangioma, additional evaluation and/or referral to an appropriate and experienced vascular anomalies specialist may be necessary for children in whom the diagnosis of infantile hemangioma is in question and for those who have actual or potential organ complications, particularly when the lesion is segmental. Early referral, ideally between four and six weeks of life, is also indicated for infants with high-risk hemangiomas for whom systemic therapy is being considered [8]. (See "Infantile hemangiomas: Management".)
Infantile hemangiomas with minimal or arrested growth — Infantile hemangiomas with minimal or arrested growth (IH-MAGs) are an uncommon variant of infantile hemangiomas, presenting as sharply demarcated, erythematous or bluish patches with one or multiple fine and coarse telangiectasias, venules, and perilesional blanching. Small, proliferative components most commonly develop at the lesion edge, providing a clue to the diagnosis of infantile hemangiomas (picture 2) [9-11].
In contrast with typical infantile hemangiomas, IH-MAGs exhibit minimal growth after birth. They preferentially affect the distal limbs but can also occur on the face and lumbosacral area and may be mistaken for port wine stains. On immunohistochemistry, they stain positive for glucose transporter 1 (GLUT-1), supporting their diagnosis as true infantile hemangiomas that simply lack a significant proliferative phase [12]. IH-MAGs will also involute the same as classic infantile hemangiomas.
Large, segmental IH-MAGs may warrant further investigation for internal organ involvement. Segmental forms located on the face have been described in infants with PHACE (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, and eye anomalies) syndrome and LUMBAR (lower-body hemangioma and other cutaneous defects, urogenital anomalies, ulceration, myelopathy, bony deformities, anorectal malformations, arterial anomalies, and renal anomalies) syndrome [13,14] (see "PHACE syndrome" and 'LUMBAR syndrome' below). Moreover, segmental IH-MAGs involving the extremities have also been associated with persisting underlying soft tissue hypertrophy [15].
Periorbital hemangiomas — Periorbital hemangiomas may compromise normal visual development (picture 3). In concerning cases (eg, hemangiomas obstructing vision), early examination by an ophthalmologist familiar with the evaluation and treatment of periorbital hemangiomas is mandatory [16]. Hemangiomas that are located on the upper eyelid, greater than 1 cm, and have a deep component are at greatest risk of astigmatism and amblyopia [17].
Patients with large, segmental hemangiomas of the face may also be at risk for PHACE syndrome and require further evaluation. (See 'Segmental hemangiomas' below and "PHACE syndrome".)
The management of periorbital hemangiomas is discussed separately. (See "Infantile hemangiomas: Management".)
Segmental hemangiomas — Segmental hemangiomas are usually plaque-like and demonstrate linear and/or geographic patterning (picture 4) [18,19]. Segmental hemangiomas of the face or scalp may be associated with PHACE syndrome, and those overlying the lumbosacral spine, pelvis, and/or lower extremities may be associated with LUMBAR syndrome and should be evaluated accordingly. (See "PHACE syndrome".)
Similar to multiple (≥5) cutaneous hemangiomas, segmental hemangiomas may also be associated with visceral hemangiomatosis [20,21]. The locations of visceral lesions often correlate regionally with the sites of cutaneous lesions. Visceral hemangiomas undergo spontaneous involution, as do their cutaneous counterparts, probably most often without sequelae, and are rarely clinically symptomatic. For this reason, evaluation of infants with segmental hemangiomas depends upon the anatomic location and, most importantly, the presence of clinical signs and symptoms [21]. Imaging of asymptomatic infants with segmental hemangiomas for visceral hemangiomatosis is not recommended because of the expense and usual need for general anesthesia in young infants.
Beard distribution — Infants with segmental, bilateral, cervicofacial or mandibular hemangiomas in a "beard" distribution (picture 1) should be clinically monitored for signs of airway involvement (eg, progressive hoarseness, stridor) [22]. The possibility of PHACE syndrome should also be considered in these patients. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications", section on 'Complications'.)
PHACE syndrome — Infants with large (>5 cm in diameter), segmental hemangiomas, particularly when located on the face or scalp, are at risk for PHACE (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, and eye anomalies) syndrome (table 1 and picture 5) [23-25]. These infants should undergo careful cutaneous, ophthalmologic, cardiovascular, neurovascular, and neurologic evaluations [26,27]. The clinical features, diagnosis, evaluation, and management of PHACE syndrome are discussed separately. (See "PHACE syndrome".)
LUMBAR syndrome — LUMBAR (lower-body hemangioma and other cutaneous defects, urogenital anomalies, ulceration, myelopathy, bony deformities, anorectal malformations, arterial anomalies, and renal anomalies) syndrome defines the association of segmental hemangiomas over the lower half of the body (picture 6) with several underlying anomalies, including tethered spinal cord, lipomyelomeningocele, bony anomalies of the sacrum, abnormal genitalia, imperforate anus with fistula formation, or renal abnormalities [28-36].
LUMBAR syndrome is considered the "lower half of the body" counterpart to PHACE syndrome. MRI is the most sensitive means of definitive diagnosis of spinal anomalies and should be performed in all infants or older children with a segmental hemangioma over the lumbosacral spine. Screening for additional anomalies associated with LUMBAR syndrome is determined on a case-by-case basis as clinically indicated.
Screening of patients with midline hemangiomas in the lumbosacral area is supported by the results of a multicenter, prospective, cohort study [37]. In this study, MRI detected spinal anomalies in 21 out of 41 children (51 percent) with localized or segmental, lumbosacral hemangiomas that were greater than or equal to 2.5 cm in size (risk ratio [RR] 640, 95% CI 404-954). The study did not evaluate imaging in patients with smaller lesions, and it is unclear whether these results translate to patients with small, localized hemangiomas. A retrospective study evaluated the types of spinal dysraphism in children with lumbosacral hemangioma [34]. Among 20 children with lumbosacral hemangioma and spinal dysraphism, 12 had tethered cord, 10 had spinal lipoma or lipomyelomeningocele, 9 had intraspinal hemangiomas, and 8 had sinus tract [34].
Unlike MRI, ultrasonographic examination does not require sedation in infants. Some authors have suggested that ultrasonography can be performed instead of MRI in infants younger than four months of age if expertise in pediatric ultrasonography is available [29,30,32]. However, ultrasounds may miss some spinal abnormalities. In the cohort study described above, 5 out of 12 patients (42 percent) with normal ultrasound examinations were subsequently noted to have spinal anomalies on MRI [37]. The average age of patients who received ultrasounds in the study was two months. The sensitivity and specificity of ultrasonography were 50 percent (95% CI 19-81) and 78 percent (95% CI 40-97), respectively. Another prospective study also found that ultrasounds failed to detect spinal dysraphism in some patients; the diagnosis was missed in 15 percent of infants under the age of six months who had hemangiomas or lipomas overlying the involved area [38].
Therefore, MRI remains the gold standard for evaluating patients with lumbosacral hemangiomas for underlying spinal disorders. In young infants, ultrasonography can be used as an initial test, and MRI can be delayed until the age of four to six months if there are no clinical findings that indicate the need for earlier evaluation (patent sinus tracts, ulceration, or neurologic signs or symptoms) [37].
Multiple cutaneous hemangiomas — Approximately 30 percent of infants have more than one hemangioma, but only 3 percent have six or more lesions [39]. Multifocal cutaneous hemangiomas at risk for concomitant visceral hemangiomas (ie, diffuse neonatal hemangiomatosis) are defined as ≥5 small, localized lesions.
Hepatic hemangiomas
Overview — In infants with multiple cutaneous hemangiomas, the liver is the extracutaneous site most frequently involved, whereas involvement of other sites, such as the gastrointestinal tract or the brain, is rare. Hepatic hemangiomas most often occur as multifocal or, rarely, diffuse lesions [40,41]:
●Focal lesions are most often not true infantile hemangiomas but instead represent rapidly involuting congenital hemangiomas, which are fully developed at birth and are occasionally detected prenatally by routine ultrasound [40,41]. Like their cutaneous counterpart, they typically rapidly involute after birth, with their size reduced by approximately 80 percent by the age of 12 or 13 months [41]. (See "Congenital hemangiomas: Rapidly involuting congenital hemangioma (RICH), noninvoluting congenital hemangioma (NICH), and partially involuting congenital hemangioma (PICH)", section on 'Hepatic rapidly involuting congenital hemangiomas'.)
●Multifocal hepatic hemangiomas are usually associated with multiple cutaneous hemangiomas and are generally detected by screening or routine abdominal ultrasound examination (see 'Screening' below). Multifocal lesions increase in size throughout the proliferative phase (between the neonatal period and the age of approximately six months) and then gradually involute. Also similar to cutaneous infantile hemangiomas, involution is often complete by the age of four to five years, on average. During the proliferative phase, due to increased arteriovenous shunting, infants may develop signs of high-output cardiac failure and consumptive hypothyroidism, due to increased expression of type 3 iodothyronine deiodinase, which inactivates the thyroid hormone.
●Diffuse lesions are characterized by a nearly complete replacement of the liver parenchyma with hemangioma tissue, leading to serious complications with increased mortality risk, including [42]:
•High volume arteriovenous shunting and cardiac failure
•Bleeding and abdominal compartment syndrome
•Liver failure
Screening — There is general consensus among experts that infants presenting with multiple cutaneous hemangiomas should undergo imaging evaluation for hepatic hemangiomas [41]. Doppler ultrasound of the liver is the preferred imaging at initial presentation. Small hepatic hemangiomas (<3 cm) typically appear as a uniformly, hypo- or hyperechoic mass, while larger lesions may contain calcifications, cystic spaces, and sclerotic areas [41]. If the diagnosis is unclear, liver MRI study with contrast and dynamic acquisition pattern can be considered:
●It is generally recommended that infants <6 months with ≥5 cutaneous hemangiomas undergo early evaluation with abdominal ultrasound and be monitored clinically [43-45].
This recommendation is supported by a multicenter study of 151 infants with ≥5 hemangiomas in which 24 (16 percent) had solitary or multiple hepatic hemangiomas and 2 (1.3 percent) had airway or gastrointestinal hemangiomas, while none of the children with ≤4 cutaneous hemangiomas had visceral lesions [46]. Only one child with hepatic hemangioma was symptomatic with hepatomegaly and high-output congestive heart failure and required treatment with propranolol and oral corticosteroids.
●Infants with <5 cutaneous hemangiomas do not require further visceral evaluation or monitoring if findings on physical examination are otherwise normal [47].
●Infants with <5 cutaneous hemangiomas who present with hepatomegaly and/or symptoms of cardiac failure (eg, tachypnea, poor feeding, lethargy) should be evaluated for hepatic hemangiomas regardless.
In a retrospective, single-center, tertiary, referral study including 843 infants (median age six months) with multiple (83 percent) or solitary cutaneous hemangiomas, 71 of 381 infants who were screened by ultrasound (19 percent) had hepatic hemangiomas [48]. Of patients with hepatic hemangioma, approximately one-third had <5 cutaneous hemangiomas. Eight of 843 patients (<1 percent) required treatment for cardiac failure, and six required treatment for hypothyroidism. Six of these 13 patients requiring treatment had <5 cutaneous hemangiomas. All infants treated for cardiac failure were symptomatic at first presentation.
●Infants >6 months who are otherwise healthy do not require additional evaluation and monitoring.
●Infants with diffuse hepatic hemangiomas or with multiple hepatic hemangiomas who show signs or symptoms of hypothyroidism should also be screened for hypothyroidism. Hepatic hemangiomas can cause consumption hypothyroidism through the production of type 3 iodothyronine deiodinase, which is a thyroid-deactivating enzyme [49,50].
Monitoring — Expert consensus-based guidelines for monitoring infantile hepatic hemangiomas recommend [41,42]:
●Liver ultrasound at progressively longer intervals, with an initial two-week interval, adding two weeks to the interval after each stable evaluation. However, the frequency of monitoring may be individualized, based on the degree of liver involvement and whether treatment is implemented.
●Continue monitoring until hemangioma involution is complete.
●Diffuse, hepatic infantile hemangiomas at higher risk of complications and mortality require more frequent monitoring and a longer follow-up period.
●Thyroid function tests (thyroid-stimulating hormone [TSH] and free thyroxine [T4]) should be obtained at the time of diagnosis and then repeated monthly in diffuse disease at least until the age of six months (approximately end of proliferation period).
●Echocardiogram should be considered if there are signs of cardiac failure or ultrasonographic evidence of shunting or massive flow (enlarged hepatic veins).
Large hemangiomas — An increased risk for hepatic hemangiomas in infants with large hemangiomas has been suggested in two, small, retrospective studies [21,51]. In contrast, a prospective study found no hepatic hemangiomas in 60 infants with at least one hemangioma >30 cm2 [52].
Infants with large hemangiomas do not need to be routinely screened for hepatic hemangiomas with ultrasonography purely based upon lesion size. However, if signs or symptoms that suggest hepatic hemangiomas (poor growth or feeding, tachypnea, cardiac murmur, abdominal distension, or hepatomegaly) are present, referral for evaluation and monitoring is indicated [41]. (See 'Hepatic hemangiomas' above.)
DIFFERENTIAL DIAGNOSIS — As mentioned above, the diagnosis of infantile hemangiomas can be made on the basis of history and physical examination in the vast majority of cases (see 'Diagnosis' above). Cases in which the differential diagnosis may be difficult include [53]:
●Cutaneous hemangiomas:
•Capillary malformation – In approximately one-third of cases, infantile hemangioma is present at birth as a macular, telangiectatic patch (picture 7) similar in appearance to a capillary malformation (ie, port wine stain) [28]. Hemangiomas with this presentation often have surrounding pallor representing vasoconstriction, which can help to differentiate them from capillary malformations early on. In addition, in contrast with capillary malformations, hemangiomas quickly begin to develop small, vascular blebs and become raised. Early arteriovenous malformations of the skin can also present as a cutaneous "blush" that is sometimes initially misdiagnosed as an infantile hemangioma. (See "Capillary malformations (port wine birthmarks) and associated syndromes".)
•Congenital hemangiomas and vascular malformations – Large, vascular lesions that are congenital (ie, "fully developed" at birth) are very unlikely to be true infantile hemangiomas, which are characterized by proliferation after birth. These include rapidly involuting or noninvoluting congenital "hemangiomas" (picture 8A-B), other benign and malignant vascular tumors, and vascular malformations, diagnoses that can often be made clinically by a specialist familiar with such entities [28,54,55]. (See "Congenital hemangiomas: Rapidly involuting congenital hemangioma (RICH), noninvoluting congenital hemangioma (NICH), and partially involuting congenital hemangioma (PICH)" and "Venous malformations".)
•Kaposiform hemangioendothelioma and tufted hemangioma – Rapidly proliferating, violaceous tumors in the setting of the Kasabach-Merritt phenomenon are not infantile hemangiomas but one of two other histologically benign, but sometimes aggressive, vascular tumors: kaposiform hemangioendothelioma (most commonly (picture 9)) or tufted angioma (picture 10). (See "Tufted angioma, kaposiform hemangioendothelioma (KHE), and Kasabach-Merritt phenomenon (KMP)".)
•Subcutaneous tumors – Deep, subcutaneous tumors, particularly when no overlying skin changes are present to assist with diagnosis, should be suspect, as should any vascular lesion with an atypical clinical appearance or unusual behavior. Although imaging may be helpful, tissue biopsy is generally necessary in concerning cases in order to exclude malignancy. (See "Skin nodules in newborns and infants".)
•Pyogenic granuloma – Pyogenic granuloma is a small (often less than 1 cm), benign vascular tumor of skin and mucosa characterized by rapid growth and a friable surface that easily bleeds (picture 11). Pyogenic granuloma typically develops on the face or upper trunk in preschool- or school-aged children but is rare in infants [56,57]. Multiple grouped pyogenic granuloma-like lesions may develop in infants and young children over a pre-existing vascular malformation, particularly capillary or arteriovenous malformations [58]. (See "Pyogenic granuloma (lobular capillary hemangioma)".)
•Other cutaneous lesions that can occasionally mimic infantile hemangiomas include plexiform neurofibroma, infantile fibrosarcoma, dermatofibrosarcoma protuberans, rhabdomyosarcoma, nasal glioma, dermoid cysts, and infantile myofibroma [7,53,59]. These lesions generally have a distinct clinical and histologic appearance. (See "Skin nodules in newborns and infants".)
●Hepatic infantile hemangiomas:
•Congenital hemangiomas – Focal hepatic hemangiomas are most often rapidly involuting congenital hemangiomas (RICHs) or, rarely, noninvoluting congenital hemangiomas (NICHs). They do not have associated skin lesions, are generally asymptomatic (except hepatomegaly for large lesions), and show no signs of enlargement after birth. Hepatic RICHs, like their cutaneous counterpart, tend to spontaneously regress in the first 12 to 14 months of life, while NICHs do not change significantly in size over time [41]. (See "Congenital hemangiomas: Rapidly involuting congenital hemangioma (RICH), noninvoluting congenital hemangioma (NICH), and partially involuting congenital hemangioma (PICH)", section on 'Hepatic rapidly involuting congenital hemangiomas'.)
•Other tumors – Hepatic hemangiomas may be very difficult to distinguish from vascular malformations and other benign and malignant infantile liver tumors, including mesenchymal hamartoma, hepatoblastoma, and metastatic neuroblastoma, especially in infants without cutaneous hemangiomas [40,60]. Imaging studies and biopsy for histopathologic examination are required for accurate diagnosis. (See "Fetal abdomen: Differential diagnosis of abnormal echogenicity and calcification", section on 'Mesenchymal hamartoma' and "Overview of hepatoblastoma" and "Clinical presentation, diagnosis, and staging evaluation of neuroblastoma".)
ONLINE RESOURCES — Information for patients and families on infantile hemangioma can be found online at The Society for Pediatric Dermatology and the Hemangioma Investigator Group.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Infantile hemangiomas and PHACE syndrome".)
SUMMARY AND RECOMMENDATIONS
●Diagnosis – In most cases, the diagnosis of a hemangioma can be established clinically, based on history and physical examination. Deeper, subcutaneous lesions may be difficult to distinguish from vascular malformations or other tumors and may require imaging studies and/or a biopsy for histopathologic examination. (See 'Diagnosis' above.)
●Referral – Referral to an appropriate and experienced vascular anomalies specialist is indicated for children in whom the diagnosis is in question and those who have actual or potential organ complications, particularly when the lesion is segmental. Early referral, ideally between four and six weeks of life, is also indicated for infants for whom systemic therapy is being considered (see 'Additional evaluation' above and "Infantile hemangiomas: Management"):
•Periorbital hemangiomas – Infants with periorbital hemangiomas at risk for visual compromise (picture 3) should be referred to an ophthalmologist familiar with the evaluation and treatment of periorbital hemangiomas. (See 'Periorbital hemangiomas' above.)
•Segmental hemangiomas:
-Face and scalp – Infants with large (>5 cm in diameter), segmental hemangiomas, particularly when located on the face, scalp, or posterior neck (picture 5), are at risk for PHACE (posterior fossa anomalies, hemangioma, arterial anomalies, cardiac anomalies, and eye anomalies) syndrome (table 1) and should undergo careful cutaneous, ophthalmologic, cardiac, and neurologic evaluations. (See "PHACE syndrome".)
-Lower body – Infants with segmental hemangiomas over the lower half of the body (picture 6) should be evaluated with MRI for underlying spinal dysraphism and other anomalies that define the LUMBAR (lower-body hemangioma and other cutaneous defects, urogenital anomalies, ulceration, myelopathy, bony deformities, anorectal malformations, arterial anomalies, and renal anomalies) syndrome. (See 'LUMBAR syndrome' above.)
•Multiple hemangiomas – Infants younger than six months with ≥5 small cutaneous hemangiomas should undergo ultrasonography of the abdomen for potential liver hemangiomas and be monitored clinically. Older infants who are otherwise healthy do not require monitoring. (See 'Multiple cutaneous hemangiomas' above and 'Hepatic hemangiomas' above.)
آیا می خواهید مدیلیب را به صفحه اصلی خود اضافه کنید؟
