Congenital hemangiomas: Rapidly involuting congenital hemangioma (RICH), noninvoluting congenital hemangioma (NICH), and partially involuting congenital hemangioma (PICH)

INTRODUCTION — Congenital hemangiomas (CHs) are rare, benign vascular tumors that are present and fully grown at birth. They present as bossed plaques or exophytic masses located on the head, neck, or limbs (picture 1A-B). Based on their natural history, three major clinical subtypes of CH have been recognized: rapidly involuting congenital hemangioma (RICH); noninvoluting congenital hemangioma (NICH); and partially involuting congenital hemangioma (PICH), which shows overlapping features and clinical behavior of RICH and NICH [1-3].

CH will be discussed in this topic. Infantile hemangiomas, other vascular tumors of childhood, and capillary malformations are discussed separately.

●(See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications".)

●(See "Infantile hemangiomas: Evaluation and diagnosis".)

●(See "Infantile hemangiomas: Management".)

●(See "Tufted angioma, kaposiform hemangioendothelioma (KHE), and Kasabach-Merritt phenomenon (KMP)".)

●(See "Pyogenic granuloma (lobular capillary hemangioma)".)

●(See "Capillary malformations (port wine birthmarks) and associated syndromes".)

EPIDEMIOLOGY — The precise incidence of congenital hemangioma (CH) is unknown. In a prospective study, RICH occurred in 2 of 594 newborns (0.3 percent) [4]. In a retrospective review of 6459 children with vascular anomalies seen in a vascular anomalies center, CHs were diagnosed in 14 percent, infantile hemangiomas were diagnosed in 43 percent, and capillary malformations were diagnosed in 30 percent [5]. There are no known risk factors for CH. In contrast with infantile hemangioma, there is no association between CH and premature birth or multiple gestation [6].

PATHOGENESIS — There is increasing evidence that most, if not all, congenital hemangiomas (CHs), whether rapidly involuting, noninvoluting, or partially involuting, are due to somatic activating mutations in GNAQ and its paralog GNA11 [7,8]. This suggests that RICH, NICH, and PICH represent a disease spectrum rather than separate entities.

Pathogenic variants that alter glutamine at amino acid 209 (Gln209) in GNAQ or GNA11 were found in all tested frozen-tissue samples from eight CHs collected during a clinically indicated procedure at frequencies ranging from 3 to 33 percent [7]. The same variants were found in three out of seven paraffin-embedded samples. The authors noted that since the same variants are found in both NICH and RICH, other factors must account for the differing clinical presentations and postnatal behaviors. Mutations in GNA11/14 have been shown to constitutively activate mitogen-activated protein kinase (MAPK) signaling pathway [9].

Variants in GNAQ and GNA11 are a common cause of port wine stains, but they are typically found in other alleles, such as R183Q. In one case report, an infant with a very large CH, as well as innumerable small vascular tumors, was found to have the same somatic variant in GNA11 in both the large tumor and in two of the smaller tumors [8]. Two other types of hemangiomas have also been described as being due to Gln209 GNAQ variants: congenital hepatic hemangiomas [7] and anastomosing hemangiomas, a type of vascular tumor with adult onset that mostly occurs in the genitourinary tract and paravertebral soft tissues [10].

These genomic findings, together with immunohistochemical differences between CHs and infantile hemangiomas as well as differing biomarker expression, confirm that they are distinct entities rather than variants of the same vascular tumor [11-13]. At the same time, they link together RICH, NICH, and PICH as related entities, but the reasons they differ in clinical behavior are not well understood.

CLINICAL PRESENTATION

Clinical subtypes — Congenital hemangiomas (CHs) are present and fully grown at birth. They usually present as solitary, plaque-like or exophytic lesions varying from a few centimeters to >10 cm in size (picture 1A-D).

Based on their natural history, three major clinical subtypes of CH have been recognized [1-3]:

●Rapidly involuting congenital hemangioma (RICH)

●Noninvoluting congenital hemangioma (NICH)

●Partially involuting congenital hemangioma (PICH)

In most cases, RICH start rapidly regressing in the few weeks after birth and involute completely or nearly completely by the age of 14 months. NICH do not involute but typically grow in proportion with somatic growth [14]. PICH show clinical and behavioral features of both RICH and NICH; they undergo a phase of rapid involution and then stabilize without regressing completely [1]. Several reports have added another dimension to the natural history of CHs: those that continue to expand and progress over time [15-19].

Rapidly involuting congenital hemangiomas

●Clinical features – RICH are most often located in the head and neck region (picture 1A) or lower extremities [2,20,21]. They vary in size from a few centimeters to >10 cm and are nearly always solitary, although rare examples of multifocal lesions have been reported [22,23]. Several morphologic variants have been described, including:

•A raised, violaceous soft tissue mass with prominent peripheral veins (picture 1A)

•A soft tissue mass with overlying, prominent, coarse telangiectasias admixed with a blanched skin, including a halo of blanched skin at the periphery of the tumor (picture 1C)

•A pink to violaceous tumor with a deeper dermal or subcutaneous infiltration

•Exophytic vascular tumor with central ulceration [24]

•A vascular tumor with overlying pustules [25]

On palpation, lesions are typically warmer than the surrounding skin. Occasionally, a bruit can be heard or a thrill can be felt.

●Clinical course and sequelae – The involution of RICH typically starts a few days to a few weeks after birth and, in most cases, is complete in 6 to 14 months. In rare instances, involution may occur in utero [26]. Involution leaves areas of skin redundancy with dermal or subcutaneous atrophy, textural and color changes, and persistent telangiectasias or scattered veins (picture 2). Other local sequelae include permanent alopecia, superficial scarring, and milia formation [2,27,28].

In a small proportion of patients with RICH, involution is incomplete and leaves a vascular plaque with coarse telangiectasias on the surface and a peripheral, bluish-white border indistinguishable from NICH [3]. (See 'Partially involuting congenital hemangiomas' below.)

Hepatic rapidly involuting congenital hemangiomas — RICH can also occur in the liver [29-31]. They present as an abdominal mass in an otherwise healthy infant. Transient thrombocytopenia, hypofibrinogenemia, and anemia are observed in some infants, presumably due to intralesional thrombosis. Arteriovenous shunting may result in heart failure and pulmonary hypertension [32]. Although rare, these lesions can lead to instability in some neonates, with progressive liver failure and death.

Significant bleeding can occur in some lesions thought to be secondary to the central areas of necrosis. There are reports of infants developing significant ascites needing surgical intervention after the start of regression [33,34]. Ultrasonography demonstrates a well-circumscribed vascular mass with large feeding and draining vessels; coarse subcapsular calcifications can be seen after involution. On magnetic resonance imaging (MRI), the lesions are hyperintense on T2 imaging and hypointense on T1 imaging, with postcontrast imaging demonstrating early peripheral enhancement with eventual diffuse enhancement.

Noninvoluting congenital hemangiomas

●Clinical features – NICH are well-circumscribed, round to oval, plaque-like or bossed soft tissue masses; pink to blue-red or purple in color; and most often located on the head and limbs [3]. Overlying telangiectasias and a rim of pallor are characteristic. NICH are typically flatter than RICH. Two morphologic variants have been described: a patch type, characterized by a flat or slightly atrophic surface resembling a vascular stain (picture 3), and a nodular/plaque type, associated with prominent tissue swelling (picture 1B, 1D) [14].

The tumor size ranges from a few centimeters to >10 cm. In many cases, peripheral, enlarged draining veins can be seen in the surrounding skin (picture 3). Ulceration, scarring, and atrophy are uncommon. On palpation, lesions are typically warm and may have areas of induration with well-circumscribed borders. Nearly one-half of patients in two retrospective case series reported some degree of pain within their lesions [14,35].

●Clinical course – NICH do not resolve spontaneously but tend to enlarge proportionately with the child's growth (picture 4). Doppler examination shows persistent fast flow. Although classically thought of as static in size, some do expand over time. In one case series, 9 of 80 NICHs (11 percent) had postnatal growth, after an initial stable period, at ages 2 to 10 years (mean 5.3 years) [15]. Other reports have described expansion of NICH lesions usually during childhood [16-18] but, in rare cases, even during adolescence or early adulthood [18,19]. Surface changes (eg, development of papules or pyogenic granuloma), bleeding, and pain from focal ulceration have also been described [15,16].

Partially involuting congenital hemangiomas — At birth, PICH are indistinguishable from RICH. They undergo a phase of rapid regression during the first year of life, thus fulfilling the criteria for RICH, but fail to regress completely (picture 5). The residual tumor has the clinical, ultrasonographic, and histologic features of NICH [1,36]. In a series of eight patients followed up for 2.5 to 10 years, the hemangiomas decreased in size and thickness in 12 to 30 months and then stabilized [1]. The residual lesions appeared as red-purple patches or plaques with telangiectasias, prominent veins, and a pale rim. Doppler ultrasound imaging revealed low-resistance, high-velocity arterial flow.

COMPLICATIONS

●Ulceration and bleeding – Ulceration with minor bleeding is a frequent complication of large congenital hemangiomas (CHs), particularly during the involution phase. Severe, life-threatening bleeding due to ulceration involving large feeding vessels or trauma is a rare occurrence and may require early surgical excision [24,37-39]. Liver CHs can have life-threatening bleeding.

●Thrombocytopenia and coagulopathy – Transient thrombocytopenia and coagulopathy with hypofibrinogenemia and anemia are potential complications of RICH, especially in liver lesions. The thrombocytopenia is usually mild and typically resolves without treatment in a few weeks [40,41]. In a case series of seven patients with large RICH presenting with thrombocytopenia, low fibrinogen, and high fibrin split products, only one developed petechiae [40]. In all cases, thrombocytopenia and coagulopathy resolved in two weeks.

Occasionally, transient thrombocytopenia in combination with coagulopathy and hypofibrinogenemia mimics the Kasabach-Merritt phenomenon, a life-threatening complication of other rare congenital vascular tumors (eg, tufted angioma, kaposiform hemangioendothelioma) characterized by profound and protracted thrombocytopenia and disseminated intravascular coagulation [40,42,43]. (See "Tufted angioma, kaposiform hemangioendothelioma (KHE), and Kasabach-Merritt phenomenon (KMP)".)

●Heart failure – High-output heart failure from arteriovenous shunting and cardiac overload has been reported in a small number of infants with large CH (>7 cm) [41,44]. Heart failure is present at birth or develops in the first days of life. There are rare reports of prenatal diagnosis of heart failure in association with a CH [41]. (See "Heart failure in children: Etiology, clinical manifestations, and diagnosis", section on 'Diagnostic evaluation'.)

●Pain – A minority of NICH cause local pain, occasionally to the point where treatment is needed [14,15].

DIAGNOSIS — The diagnosis of congenital hemangioma (CH) is based upon history and physical examination in most cases. Imaging studies (eg, ultrasonography and, less commonly, MRI and arteriography) may be helpful to confirm the diagnosis in uncertain cases. A biopsy for histologic examination is necessary if a malignant lesion is suspected. Additional evaluation, including laboratory and cardiac evaluation, may be needed in infants with suspected coagulopathy or congestive heart failure.

Clinical examination — In most cases, the diagnosis of CH is made clinically in a newborn presenting with a fully grown soft tissue mass with overlying telangiectasias and peripheral vasoconstriction (picture 1A-D). The presence of the tumor at the time of birth is an important clue to the diagnosis and an important criterion for differentiating CH from infantile hemangiomas, which are usually not clinically evident at the time of delivery [2,45]. The observation of a rapid involution starting a few days after birth is usually sufficient to differentiate RICH from NICH.

Imaging studies — Imaging studies (eg, ultrasonography, MRI, arteriography) may be needed when the diagnosis is unclear. Ultrasonography is useful as first-level imaging modality to differentiate a CH from other soft tissue tumors. If there is any question of the diagnosis, MRI is indicated [46].

●On ultrasonography, both RICH and NICH show a predominantly heterogeneous sonographic structure, diffuse vascularity, high vessel density, and, occasionally, calcifications [47]. Doppler examination reveals a high-flow vascular lesion [14]. In involuting lesions, long, tortuous, and compressible channels with a venous flow signal become a dominant feature [48]. In patients with RICH, the presence on B-mode and Doppler ultrasound of visible vessels, venous ectasia, venous lakes, and arteriovenous shunting suggest increased risk of ulceration, bleeding, and, in the case of arteriovenous shunting, high-output congestive heart failure [49].

●On MRI, RICH and NICH show heterogeneous enhancement, hyperintensity on T2-weighted sequences, flow voids, and absence of peripheral edema. Less-defined borders and more fat stranding help distinguish CH from infantile hemangioma [47].

●Angiography reveals heterogeneous parenchyma; large, irregular feeding arteries; venous ectasia; and, in some cases, microshunting [50]. Arterial aneurysms and arteriovenous shunts can also be seen. Angiography is only needed for control of bleeding or to assess anatomic variants if surgical excision is needed.

Prenatal diagnosis — Because of their volume and vascularity, RICH are increasingly detected during prenatal ultrasound investigations, usually during the third trimester of pregnancy [51]. Sonographic features include a solid appearance with a homogeneous or slightly heterogeneous pattern isoechoic with the placenta, venous lakes mimicking a cystic component, hemosiderin deposits, and small calcifications [52].

If RICH is noted on prenatal ultrasound, an antenatal MRI is recommended to better define the characteristics of the tumor. On fetal MRI, the signal of the lesion is slightly hyperintense or hypointense on T2-weighted sequences [52].

Biopsy and histopathology — A biopsy for histopathologic examination is not routinely performed. However, it is warranted if there is a clinical and/or radiologic suspicion of malignant tumor (firmness on palpation, rapid growth, ulceration, and fixation to the fascia).

●Routine staining – RICH, NICH, and PICH show similar histopathologic findings, consisting of small to large lobules of capillary proliferations lined by endothelial cells, with variably shaped lumen (round, slit shaped, or indistinct) (picture 6). In some cases, admixed fibrosis or sheets of compact endothelial cells and pericytes can be seen. Many of the endothelial cells show "hobnailed" features. Virtually all have extralobular vessels, which are usually large, tortuous, and irregular [11,14,53]. Focal thromboses and calcifications may be seen. Stromal hemosiderin deposits are common.

●Immunohistochemistry – Immunohistochemical staining for glucose transporter protein-1 (GLUT-1) is negative. This finding helps distinguish CHs from infantile hemangiomas, whose endothelial cells uniformly express GLUT-1 [12]. The lobular components of NICH and RICH stain for Wilms tumor 1 (WT1) protein, a transcription factor activated during angiogenesis, but the larger dysplastic vessels are WT1 negative [3,11,14,28,54,55]. There are no significant correlations between CH subtype and histopathology [53].

Genetic tumor testing — Gene testing on frozen or paraffin-embedded tissue for GNAQ or GNA11 mutations can help to confirm the diagnosis in uncertain cases [7,8].

Laboratory testing — Laboratory blood tests are not routinely performed in infants with small, uncomplicated CH. However, a complete blood cell count with platelet count and evaluation of the coagulation status (eg, fibrinogen concentration, fibrin split products [D-dimer]) may be warranted in newborns with large tumors at risk of thrombocytopenia and coagulopathy, especially tumors of the liver. (See "Neonatal thrombocytopenia: Clinical manifestations, evaluation, and management", section on 'Diagnostic evaluation to identify underlying cause'.)

DIFFERENTIAL DIAGNOSIS — The differential diagnosis of congenital hemangioma (CH) includes other benign vascular tumors, vascular malformations, and benign and malignant nonvascular tumors [45]:

●Infantile hemangioma – A diagnostic dilemma often arises when the patient's parents/caregivers report that a certain vascular growth "has been there since birth." It is particularly important to ascertain whether a palpable mass (suggesting CH) or just a flat area of discoloration was present at birth, since the latter could represent a premonitory mark of infantile hemangioma (picture 7). A history of rapid postnatal growth is typical of infantile hemangioma and usually differentiates infantile hemangioma from CH. When the diagnosis is uncertain, a tissue biopsy for immunohistochemical staining for glucose transporter protein-1 (GLUT-1) can clarify the diagnosis, as infantile hemangioma always stains positive for GLUT-1. (See "Infantile hemangiomas: Epidemiology, pathogenesis, clinical features, and complications", section on 'Clinical presentation'.)

●Tufted angioma – Tufted angioma is an uncommon, benign vascular tumor that usually develops in early infancy but may be present at birth. It presents as an infiltrated, firm, dusky, red to violaceous plaque or nodule with typical, overlying hypertrichosis (picture 8). Histology shows vascular tufts of tightly packed capillaries randomly dispersed throughout the dermis in a typical "cannonball distribution." Tufted angioma is GLUT-1 negative. (See "Tufted angioma, kaposiform hemangioendothelioma (KHE), and Kasabach-Merritt phenomenon (KMP)", section on 'Tufted angioma'.)

●Kaposiform hemangioendothelioma – Kaposiform hemangioendothelioma is a rare vascular tumor that can be present at birth. Kaposiform hemangioendothelioma appears as a slightly raised, subcutaneous, firm mass with a purpuric, bruised appearance (picture 9). It is often associated with the Kasabach-Merritt phenomenon (severe thrombocytopenia and coagulopathy). Histologically, kaposiform hemangioendothelioma is characterized by spindle cells with minimal atypia and infrequent mitoses lining slit-like or crescentic vessels containing hemosiderin. The tumor is GLUT-1 negative. MRI can be helpful in differentiating CHs and kaposiform hemangioendotheliomas, as the latter present as highly infiltrative and heterogeneous masses with uneven and high signal intensity on T2-weighted imaging [56]. (See "Tufted angioma, kaposiform hemangioendothelioma (KHE), and Kasabach-Merritt phenomenon (KMP)", section on 'Kaposiform hemangioendothelioma'.)

●Vascular malformations – Venous malformations are often present at birth as soft, compressible, blue soft tissue masses or plaques (picture 10). Doppler ultrasonography demonstrates a slow-flow, ill-defined vascular lesion that is compressible on palpation. Histology shows ectatic, venous-like channels with anomalies in mural cells. Some arteriovenous malformations can present as purple-red, swollen lesions resembling CH (picture 11). However, in contrast to CH, venous malformations and combined vascular malformations do not stain for cytoplasmic Wilms tumor 1 (WT1) [55]. (See "Venous malformations" and "Vascular lesions in the newborn", section on 'Arteriovenous malformations'.)

●Infantile myofibromatosis/hemangiopericytoma – Infantile myofibromatosis is a rare fibrous tissue tumor of infancy. In most cases, it presents at birth as solitary or multiple nodules 0.5 cm to several centimeters in diameter that are firm or rubbery in consistency and appear in variable colors (brown, blue, purple, or red) (picture 12) [57]. A biopsy is necessary to differentiate infantile myofibromatosis from CH. Histopathology shows a biphasic pattern of peripheral smooth muscle-like fascicles of spindle cells and central areas resembling hemangiopericytoma with rounded pericytes. Given their considerable clinical and histologic overlap, infantile myofibromatosis and infantile hemangiopericytoma are thought to be related entities or identical conditions in different maturation stages [58-60]. (See "Skin nodules in newborns and infants", section on 'Infantile myofibromatosis'.)

●Lipoblastoma and lipoblastomatosis – Lipoblastoma is a rare, benign infantile tumor that may be present at birth [61]. It presents as a well-circumscribed soft tissue mass located in the subcutaneous tissue on the extremities, trunk, and head and neck area. Histology shows an admixture of mature and immature adipocytes.

●Malignant tumors – Highly vascular malignant tumors (eg, infantile fibrosarcoma, rhabdomyosarcoma, dermatofibrosarcoma protuberans, metastatic neuroblastoma, angiosarcoma) may be present at birth and mimic CH [57]. Clinical signs that raise the suspicion of a malignant lesion and prompt a biopsy for histopathologic examination include firmness on palpation, rapid growth, ulceration, fixation to the fascia, and an atypical appearance on imaging. (See "Skin nodules in newborns and infants", section on 'Malignant tumors'.)

MANAGEMENT

Approach — The approach to the management of congenital hemangioma (CH) must be individualized based on:

●Tumor size and location

●Tendency for spontaneous involution

●Presence of local or systemic complications

For newborns with uncomplicated CH, a wait and watch approach is indicated in the first weeks of life to assess for signs of spontaneous regression (algorithm 1). Consultation with a specialist or multidisciplinary group with special expertise in vascular anomalies for close monitoring and early treatment is warranted in the following situations:

●Large CH that is at increased risk of complications (eg, ulceration, bleeding, thrombocytopenia, high-output cardiac failure)

●CH associated with function impairment

●Large, complicated liver CH

It is important to educate the family/caregivers about the natural history of CH; potential complications; and treatment options for NICH, PICH, or residual skin changes after involution.

Observation and monitoring — Observation and monitoring is the preferred approach for most newborns with CH that are noncomplicated and do not impair function. Serial observation in the first few weeks of life allows the clinician to determine whether the tumor shows a tendency to regress and to monitor for occurrence of complications.

●RICH – It is our practice to examine infants with RICH for at least 12 to 18 months (usually at monthly intervals) to monitor for the occurrence of unexpected complications (eg, ulceration, infection, persistent pain) and whether involution is complete or partial. Evidence from small case series and case reports indicates that most RICH undergo complete regression in 12 to 14 months [2,6,20].

We do not recommend routine laboratory monitoring, unless hematologic abnormalities (eg, thrombocytopenia, hypofibrinogenemia, anemia) were previously noted. However, once hematologic abnormalities resolve, laboratory testing is no longer necessary unless there are changes in clinical status that suggest worsening (eg, increased pain, ulceration with bleeding).

During the rapid involution phase, the regular application of petrolatum to the lesion surface multiple times per day may be helpful in preventing ulceration [6]. Persistently ulcerated lesions or lesions with a history of repeated bleeding may require early surgical excision. (See 'Surgery' below.)

●NICH and PICH – NICH and PICH do not resolve over time, but treatment may not be necessary if they remain asymptomatic and do not bother the patient [3]. We typically continue to see these patients periodically to evaluate for expansion in size or development of surface changes. The frequency of follow-up visits varies depending upon the age of the patient, with young infants and toddlers being seen every four to six months. For most patients with NICH, annual or biennial visits are sufficient. However, individuals should be re-evaluated if there are new or increased symptoms or concerns about expanding size. Serial photographs taken at each visit are helpful for comparison.

Surgery — Early surgical excision with or without preoperative arterial embolization is the treatment of choice in the following situations [15,41,62-65]:

●Large CH associated with heart failure and/or coagulopathy

●CH complicated by life-threatening bleeding, persistent ulceration, repeated bleeding

●CH that has increased in size and is causing systemic symptoms (pain, ascites, infection)

●Large NICH that impairs function (eg, vision obstruction)

Delayed surgical excision and reconstruction is the treatment of choice for:

●NICH or PICH that cause cosmetic concern

●NICH or PICH that show slow volume expansion over time

●Correction of residual skin changes after complete involution of RICH

The optimal timing for surgical excision has not been determined. Most experts recommend surgical excision during the preschool age, when the child begins to manifest a facial or body image [62].

In a series of 53 patients with NICH (age 2 to 30 years), 28 underwent surgical excision [3]. Preoperative arterial embolization was performed in seven patients. No intraoperative or postoperative complications were reported. In another series of 57 patients, 12 patients (1 with RICH, 5 with NICH, and 6 with PICH) underwent surgical excision because of bleeding, esthetic concerns, or pain [35].

Endovascular embolization — Data on the use of percutaneous endovascular embolization for the treatment of problematic CH are limited. In most cases, embolization has been used preoperatively to control bleeding or reduce the tumor mass before surgery [64-67].

●In one report, arterial embolization was successfully used to treat a newborn with a large CH associated with coagulopathy [63]. The tumor subsequently underwent spontaneous regression, fulfilling the diagnosis of RICH.

●Embolization with N-butyl-2-cyanoacrylate (NBCA) and/or percutaneous sclerotherapy has been described in a series of 10 patients with NICH [67]. There are a few reports of percutaneous cryoablation for the management of symptomatic NICH [68]. Indications for treatment included cosmetic deformity, location not amenable to primary surgical resection, and need to reduce the tumor volume before resection. Direct percutaneous sclerotherapy with 98% ethanol was used alone or in combination with endovascular embolization. Two patients underwent subsequent surgical resection.

Laser therapy — Pulsed dye laser treatment may be helpful in reducing the appearance of superficial telangiectasias [62]. (See "Laser and light therapy for cutaneous vascular lesions", section on 'Involuting and resolved lesions'.)

Treatment of complications

●Ulceration – Superficial ulcerations can be treated conservatively with meticulous wound care, which involves the use of topical antibiotics (eg, mupirocin 2% cream), barrier creams (eg, petrolatum), and nonadherent dressings [69]. Crusting should be debrided with diluted hydrogen peroxide or saline soaks two to three times daily since crusting prevents re-epithelization and favors infection. Pulsed dye laser treatment may be a treatment option for ulcerations that do not respond to topical therapy.

Pain associated with ulceration may be severe. Appropriate analgesia with oral acetaminophen or a topical anesthetic agent (ie, lidocaine hydrochloride 2% ointment) may be warranted. (See "Management and prevention of pain in neonates".)

●Bleeding – Minor bleeding can be controlled with compression. Persistent or major bleeding from ulceration or trauma may require arterial embolization and/or surgical excision of the tumor [24,38,39]. In two reported cases, control of minor bleeding from superficial ulcerations was successfully achieved with topical tranexamic acid and compression [37].

●Thrombocytopenia and coagulopathy – The thrombocytopenia associated with CH is transient and usually resolves in a few weeks without treatment. Systemic corticosteroids have been used in a small number of infants with RICH and thrombocytopenia, but their role in the normalization of the platelet count remains uncertain [40].

●Heart failure – For infants who develop CH-induced heart failure, embolization and/or surgical excision of the tumor in addition to medical treatment is required in most cases [41]. The medical management of congestive heart failure in infants and children is discussed separately. (See "Heart failure in children: Management".)

PROGNOSIS — Infants with uncomplicated RICH have a favorable prognosis. The prognosis is guarded for infants with severe bleeding and infants who develop heart failure. In a review of 17 patients with large congenital hemangioma (CH) and heart failure, four died in the first weeks of life despite embolization or excision of the tumor and medical treatment of heart failure [41].

The prognosis of NICH is generally favorable. Lesions that are not excised most often grow in proportion with the child and persist unchanged throughout adulthood [3]. However, a subset expand over time, albeit slowly, and recurrent discomfort or pain can occur in some cases [18].

SUMMARY AND RECOMMENDATIONS

●Clinical subtypes and pathogenesis – Congenital hemangiomas (CHs) are rare, benign vascular tumors that are present and fully grown at birth. Based upon their natural history, three major subtypes have been recognized: rapidly involuting congenital hemangioma (RICH), noninvoluting congenital hemangioma (NICH), and an intermediate subtype called partially involuting congenital hemangioma (PICH). There is increasing evidence that all types of CH are due to somatic activating mutations in GNAQ and GNA11. (See 'Clinical subtypes' above and 'Pathogenesis' above.)

●Clinical presentation:

•RICH – RICH usually present as solitary, violaceous soft tissue masses with coarse telangiectasias and prominent peripheral veins, most often located on the head, neck, or lower extremities (picture 1A, 1C). Involution typically starts a few days to weeks after birth and, in most cases, is complete in 6 to 14 months (picture 2). (See 'Rapidly involuting congenital hemangiomas' above.)

•PICH – At birth, PICH are indistinguishable from RICH. They undergo a phase of rapid regression and then stabilize (picture 5). The residual lesion is identical to NICH. (See 'Rapidly involuting congenital hemangiomas' above and 'Partially involuting congenital hemangiomas' above.)

•NICH – NICH present as well-circumscribed, plaque-like or bossed soft tissue masses with overlying telangiectasias and a characteristic rim of pallor (picture 1B, 1D). NICH do not resolve spontaneously but tend to grow proportionately with the child's somatic growth. In a minority of cases, NICH can slowly expand over time. (See 'Noninvoluting congenital hemangiomas' above.)

●Diagnosis – The diagnosis of CH is made clinically in a newborn presenting with a fully grown soft tissue mass with overlying telangiectasias and peripheral vasoconstriction (picture 1A-D). The rapid involution starting in the first few weeks after birth differentiates RICH from NICH. Imaging studies (eg, ultrasonography, MRI, arteriography) and/or a biopsy for histopathologic examination may be warranted if the diagnosis is unclear or a malignant tumor is suspected. (See 'Diagnosis' above.)

●Management – The approach to the management of CH must be individualized based on tumor size and location, tendency for spontaneous involution, and presence of local or systemic complications (algorithm 1):

•Observation and monitoring – For most newborns with uncomplicated CH, we suggest serial observation rather than surgery (Grade 2C) in order to determine whether the tumor shows a tendency to regress and monitor for occurrence of complications. (See 'Observation and monitoring' above.)

-RICH – We typically examine infants with RICH at monthly intervals until complete involution. All RICH undergo complete regression, typically within 12 to 14 months. Of note, RICH involving the liver require serial evaluations until a marked decrease in size (or disappearance) has been documented with imaging. If there is an increase in size or change in symptomatology, possible causes (eg, intratumoral bleeding) should be investigated.

-NICH/PICH – Observation is a reasonable approach for NICH and PICH if they remain asymptomatic and do not bother the patient. We typically see these patients every four to six months until stabilization and for one to two years thereafter. Serial evaluations every year or two are often sufficient in teens and adults unless symptoms, complications (eg, pain, infection), or progression develop. Serial photographs are helpful for comparison.

•Surgery and endovascular embolization – For large CH complicated by life-threatening or repeated bleeding, heart failure and/or coagulopathy, persistent ulceration, or function impairment, we suggest early surgical excision with or without preoperative endovascular embolization rather than embolization alone or other interventions (Grade 2C). Preoperative endovascular embolization may be used on a case-by-case basis to reduce tumor volume and control bleeding before resection. For patients with a CH in a location not amenable to primary surgical resection, endovascular embolization is an acceptable option.

For NICH and PICH that cause cosmetic concern or expand over time and for correction of residual skin changes after RICH involution, we suggest delayed (rather than immediate) surgical excision (Grade 2C). Most experts recommend surgical excision during the preschool age, when the child begins to manifest a facial or body image. (See 'Surgery' above.)

●Prognosis – Infants with uncomplicated RICH and NICH have a favorable prognosis. The prognosis is guarded for infants with severe bleeding and for infants who develop heart failure. (See 'Prognosis' above.)