Rapidly involuting congenital haemangioma: diagnostic and therapeutic approach regarding two case reports

Abstract

Two unrelated neonates were born with a large purplish congenital mass of the thigh and forearm. Both showed signs of heart dysfunction, and one of them had anaemia and thrombocytopenia. The imaging assessment of the lesions showed well-defined subcutaneous solid masses with an exuberant vascular component. Both were kept under surveillance and maintenance therapy. A progressive dimensional reduction of the lesions supported the diagnosis of rapidly involuting congenital haemangioma (RICH). RICH is a rare vascular tumour that presents as a congenital purplish bulky mass. The diagnosis depends on the clinical evaluation of the lesion and the imaging characterisation of its solid components and vascular network. RICH may be complicated by high-output heart failure, anaemia and thrombocytopenia. Despite its exuberant presentation, it undergoes involution in the first year of life; therefore, early invasive therapies should be avoided. It is essential to detect any dimensional increase, suggesting more aggressive diagnoses, such as kaposiform haemangioendothelioma.

Background

Rapidly involuting congenital haemangioma (RICH) is a rare congenital vascular tumour. Its presentation in neonates impresses relatives and professionals, but its approach is expectant, contrary to its aggressive differential diagnosis. The two cases described here are intended to present the main characteristics of the disease and the difficulties experienced in its approach, showing how important it is to recognise this entity in the first assessment of newborns.

Case presentation

On the first day of life, two unrelated Caucasian newborns were transferred to the neonatal intensive care unit, presenting unique large masses of the thigh and forearm, respectively.

Case 1

Clinical data

The first case was a preterm female infant with a large and highly vascularised soft tissue thigh lesion discovered during a routine obstetric ultrasound assessment at the 31st week of gestation. Concomitant prenatal cardiac examination suggested cardiac overload. The girl was delivered at 32 weeks of gestation, with an Apgar score of 7–8−9 and a weight of 1955 g.

Neonatal examination of the thigh revealed a well-defined bulky mass, measuring approximately 15 cm in maximal diameter, with a smooth surface and a purplish/reddish colour, along with a desquamative aspect of the adjacent skin (figure 1A). Additionally, the surrounding area of the limb exhibited oedema and ecchymosis.

Figure 1.

(A,B) Clinical pictures of the reported lesions ((A) inferior limb of the female patient; (B) the forearm of the male patient) show large purplish and greyish lesions of the thigh and forearm, respectively, with a smooth surface and visible superficial veins (A). Note the desquamative aspect of the skin of the inferior limb (A).

The newborn was markedly hypotensive and tachycardic, with diffuse body oedema. The evaluation of neonatal cardiac ultrasound showed dilated heart chambers with high systolic ejection flow, supporting the hypothesis of high-output heart failure.

She also had persistent jaundice, with reduced haemoglobin (87 g/L) and platelet counts (55×10⁹/L) and increased total bilirubin (8.45 mg/dL) suggesting a rapid haematological turnover. In addition, the increase in prothrombin time (16 s) and international normalised ratio (1.31) reflected an increased risk of coagulation disturbance.

Imaging characterisation

Ultrasound and colour Doppler study of the thigh on the first day of age showed a thick subcutaneous lesion with a high density of intralesional vessels (>5 vessels/cm²), including fast arterial flow with high peak systolic velocity (maximal velocity of 70 cm/s), and significantly dilated slow venous flows. There were no apparent venous lakes.

Contrast-enhanced CT angiography (CTA) of the thigh performed on the 19th day of age showed a large heterogeneous soft tissue lesion, measuring 15 cm on the longest axis, with solid constitution and diffuse vascularisation (figure 2A,B). Segmental branches of the deep femoral artery ensured the arterial blood supply of the lesion. The contralateral arterial system was significantly thinner, suggesting an arterial steal phenomenon (figure 3A,B). An extremely dilated and tortuous venous network involving the internal saphenous and deep femoral veins was responsible for the drainage of the lesion. The early venous opacification insinuated the presence of an intralesional arteriovenous shunt. There were no intralesional calcifications.

Figure 2.

(A,B) CT angiography images of the right thigh of the female patient which were acquired on the 19th day of life ((A) axial view; (B) three-dimensional reconstruction). CT imaging showed a large exophytic lesion localised in the anterior compartment of the thigh, predominantly located in the subcutaneous tissue, with diffuse contrast enhancement, reflecting solid constitution and hypervascularisation. The three-dimensional reconstruction (B) shows the exuberant vascular network that supplies the lesion.

Figure 3.

(A,B) CT angiography images of the right thigh of the female patient which were acquired on the 19th day of life (simple coronal view), showing the calibre discrepancy between the right (A, arrow) and the left (B, arrow) primary iliac arteries, as a likely result of the arterial steal phenomenon in the right thigh.

Case 2

Clinical data

The second case was a full-term male infant, born after 37 weeks of gestation, with an overall good condition, who was transferred to a tertiary care centre to investigate a vascularised soft tissue lesion in the forearm identified on prenatal ultrasound performed at 32 weeks of gestation.

Neonatal examination revealed a well-defined greyish lesion (figure 1B), which later demonstrated many dilated veins visible through the skin. In addition, there was a halo of pale-coloured skin around its edges. The maximum diameter of the lesion was 10 cm at birth.

In the first days of life, the boy developed persistent hypotension and tachycardia; therefore, an echocardiographic evaluation was performed, revealing suggestive findings of high-output heart failure.

The laboratory assessment was unremarkable.

Imaging characterisation

Ultrasound examination showed a thick subcutaneous lesion with an exuberant intralesional vascular component, including arterial vessels with fast systolic flow rates and largely dilated veins.

MRI of the forearm performed on the 10th day of age showed a notable soft tissue mass, measuring 10 cm on the longest axis, with a homogeneous intermediate T1 and T2 signal (figure 4A–C), denoting a solid component. An important vascular component was present, with multiple tortuous and dilated intralesional vessels, including numerous flow voids, corresponding to rapid-flow and slow-flow vessels (figure 4A and C). There were no apparent venous lakes or signs of aggressive or sarcomatous nature, such as perilesional oedema or deep tissue invasion.

Figure 4.

(A–C) MRI of the forearm of the male patient which were acquired on the 10th day of life ((A) axial T2; (B) coronal T1; (C) coronal fat suppressed proton density), showing a homogeneous intermediate signal lesion in both ponderations, suggesting a solid component. Note the important vascular component, with multiple tortuous and dilated intralesional vessels extending superiorly through the arm. There is a predominance of rapid-flow vessels in the internal strand of the arm, with low luminal signal (asterisks) and slow-flow vessels in the external strand of the arm, with high luminal signals (arrows).

Treatment

In both cases, a conservative approach was favoured, with close monitoring of the dimensional variations of the lesion.

Both patients underwent medical therapy with furosemide to reduce cardiac overload, and the female patient received multiple transfusions of red blood cell concentrate, plasma, platelets and fibrinogen.

Therapy with sirolimus, an angiogenesis inhibitor, was also started for the female patient, the application of which is controversial in highly vascularised tumours.

Outcome and follow-up

Both cases demonstrated overall good outcomes.

The female infant was discharged after 110 days of hospitalisation and the male infant was discharged after 31 days, both with a well-stabilised haemodynamic profile. Regarding the female infant, there was a progressive resolution of almost all laboratory alterations, with normalisation of haemoglobin levels (12 g/dL), platelet counts (252×10⁹/L) and coagulation parameters (prothrombin time of 11.2 s and international normalised ratio of 1.01). Only total bilirubin remained slightly increased (1.80 mg/dL) at the time of discharge, with normalisation a few months later.

Both patients were followed up for dimensional evaluation of the lesions. It revealed a dimensional involution, with a progressively lighter colour and associated skin retraction (figure 5A–D). None of the cases reported episodes of bleeding during follow-up.

Figure 5.

(A–D) Clinical pictures of the forearm of the male patient acquired at the time of birth and sequentially throughout the follow-up time ((A) initial presentation; (B) 3 months of follow-up; (C) 6 months of follow-up; (D) 9 months of follow-up), demonstrating marked dimensional involution, with progressively lighter colour and skin retraction. Note that the lesion is almost not discernible at 9 months of follow-up.

Differential diagnosis

The differential diagnosis of a congenital soft tissue tumour depends on the age of presentation and clinical aspects of the lesion, coagulation and haematological profile, and cardiac function. Imaging characterisation plays a complementary role in better delineating the constituents of the lesion and excluding aggressive signs.¹

Furthermore, the presence of a congenital soft tissue tumour generates a vital opportunity to diagnose associated genetic syndromes that result from mutations of tumourigenic genes. The main examples include syndromes related to vascular tumours or malformations, such as the Proteus syndrome, that is characterised by partial gigantism, connective tissue nevi, soft tissue hamartomas and low-flow vascular malformations; or the Maffucci syndrome, which is associated with enchondromatosis and multiple low-flow vascular malformations (see the Discussion section).² Early exclusion of associated skeletal or cutaneous anomalies is fundamental.

In front of such enormous congenital lesions with associated consumptive coagulopathy, the three principal diagnoses to consider are the following: (a) congenital haemangioma and kaposiform haemangioendothelioma (both vascular tumours); (b) infantile fibrosarcoma (non-vascular tumour).³

The described lesions have an exuberant vascular component, with cardiac and haematological repercussions and imaging findings of venous ectasia, flow voids and arteriovenous shunts. Concomitantly, they present a significant solid component. The coalition of these two aspects highly suggests a solid vascular tumour.³

Concerning solid vascular tumours, the characteristics of these lesions, namely, their large dimension and age of occurrence, more likely suggest the following diagnoses: (a) congenital haemangioma, a benign entity that arises in utero and is fully developed at birth; (b) kaposiform haemangioendothelioma, an aggressive tumour that is less prevalent but must be considered, as it is also present at birth.³ Infantile haemangiomas are less likely to correspond to the described lesions, as they appear and develop in the first days or weeks of life and then stabilise and spontaneously regress by the age of 3–5 years.⁴

Usually, congenital haemangiomas have better defined margins than kaposiform haemangioendotheliomas, which can involve several tissues, including the surrounding bone.^{5 6} Both congenital haemangiomas and kaposiform haemangioendotheliomas have an enormous blood supply and, consequently, may originate high-output heart failure and consumption of blood-derived products, such as erythrocytes and platelets. This last aspect is characteristic of kaposiform haemangioendotheliomas, and it is known as the ‘Kasabach-Merritt phenomenon’, a term frequently transposed to congenital haemangiomas.³ The most critical point in the distinction of these two entities is that, in most cases, congenital haemangiomas involute with adipose substitution in the first year of life, being called ‘RICH’.⁵ This phenomenon was verified in the reported cases. Meanwhile, kaposiform haemangioendotheliomas behave similar to malignant neoplasms with rapid and infiltrative growth and potential for locoregional spread.^{5 6}

Finally, infantile fibrosarcoma is a non-vascular tumour that must also be considered due to the large size of the lesions. One-third of infantile fibrosarcoma cases are congenital. Limb localisation is the most frequent, and purplish colouration of the surrounding skin is common.⁷ CTA and MRI effectively distinguish between infantile fibrosarcoma and vascular tumours since the first is a homogeneous and well-defined lesion, with few intralesional vessels and a heterogeneous enhancement. Perilesional oedema is common, resulting from its aggressive nature.⁷ These aspects were not present in the illustrated cases, making this a less likely diagnosis.

Discussion

Congenital haemangiomas are rare vascular tumours (<3% of all haemangiomas), fully developed at birth, frequently affecting the limbs, head, neck and organs, such as the liver.¹

They are included in the category of benign vascular tumours of the International Society for the Study of Vascular Anomalies (last revised in 2018), which comprises one of the most frequent soft tissue tumours in paediatric age (ie, infantile haemangioma).⁸ They are also included in the section of vascular lesions of the fifth edition of the ‘WHO Classification of Tumours of Soft Tissue and Bone’.⁹

There are no established risk factors or racial predispositions for isolated congenital haemangiomas, unlike infantile haemangiomas, where female sex, white non-Hispanic ethnicity, prematurity and low birth weight are known risk factors. Meanwhile, in congenital haemangiomas linked to genetic syndromes, a familial predisposition is expected.¹⁰

Unlike vascular malformations, vascular tumours represent neoplastic growth of vascular endothelial cells, not just vascular structural anomalies.¹

Three types of congenital haemangioma have been described: involutive, partially involutive and non-involutive. The first type is the most common, having its maximum dimension at birth, with progressive lipomatous transformation and dimensional regression starting at 4 weeks of life. It resolves within 8–14 months, which is why they are called ‘RICH’.¹ One-third of those initially called RICH undergo incomplete involution, making them partially involuting congenital haemangiomas.¹ The third type is less common, and it occurs in haemangiomas that present with an early abundant lipidic component and a progressive increase in size.⁵

The distinction between congenital haemangioma and its locally aggressive differential diagnosis is essential to the therapeutic decision (see the Differential diagnosis section).¹

Clinically, congenital haemangioma presents as a solitary exophytic non-pulsatile red/purple lesion, located in the subcutaneous fat and covered by a smooth skin surface, with visible superficial dilated vessels, similar to telangiectasia. Most lesions have diameters between 2 and 5 cm at birth. More than 50% of the lesions are surrounded by a peripheral pale halo, resulting from reactive vasoconstriction.¹ The surrounding area of the limbs may present a desquamative aspect, and there may be associated oedema of the respective limb.⁶

Several known syndromes result from mutations of tumourigenic genes and course with the development of vascular tumours, more commonly infantile haemangioma, but rarely congenital haemangioma. These include Proteus syndrome, Von Hippel-Lindau syndrome, Maffucci syndrome and Klippel-Trenaunay syndrome. Vascular lesions associated with these syndromes are difficult to treat and require long-term treatment strategies; therefore, it is essential to exclude them at an early phase of the diagnostic approach.² Meanwhile, early diagnosis of these syndromes may provide a critical social compensation opportunity and prevent severe complications.

As the lesions are superficial, the diagnosis is largely based on the clinical aspect. However, congenital haemangioma is usually detected by antenatal ultrasound or MRI.¹ After birth, imaging assessment is helpful in characterising the constituents of the lesion and vascular network, and excluding suggestive aspects of aggressiveness.⁵

Postnatal imaging assessment includes ultrasound, MRI and CTA.⁵

Greyscale and Doppler ultrasound imaging characteristics suggest the constitution of the lesion and its degree of vascularisation.⁶ The lesions are thick, well defined and predominantly hypoechogenic.¹ They present prominently visible vessels with high vessel density (more than 5 vessels/cm²), high-velocity arterial systolic flows (>2 kHz) and slow venous flows.¹¹ The presence of venous lakes and venous ectasia is exclusive of congenital haemangiomas.¹¹ Arteriovenous shunts may be present. The vascular resistance index increases as the tumour suffers involution.¹ Ultrasound can play an essential role in stratifying the risk of complications in these lesions.

MRI is the modality of choice in the initial characterisation and reassessment of these lesions due to its high resolution and absence of ionising radiation. T1 and T2 sequences characterise the anatomy and extension of the lesion. The first may detect the intralesional lipidic component, and the second demonstrates any liquid content. The administration of contrast allows the characterisation of the vessels and facilitates the distinction of cystic or necrotic intralesional components.^{5 6}

Early RICH MRI studies show well-defined solid lesions with low T1 and T2 signals. They appear highly heterogeneous because of the coexistence of intralesional rapid-flow and slow-flow vessels responsible for signal voids and hyperintense water-like signal regions, respectively.⁶ Later, during involution, there is a signal increase in T1, with progressive substitution of adipose tissue.¹²

CT imaging after administration of iodine contrast, acquired in an early arterial phase, allows the detailed study of the vasculature of the lesion.

RICH appears as a lobulated mass with the same density as the surrounding muscles and an early homogeneous enhancement by contrast. The lesion has a vast vascular supply, with dilated intralesional and peripheral vessels. CTA can often demonstrate the feeding arteries of the lesion and the intralesional arteriovenous shunts responsible for the prominent venous network around the lesion.¹²

In case of sustained doubts about the nature of the lesion, a histological examination is essential, although biopsies are not always performed.

Congenital haemangiomas are located in the dermis and hypodermis, and the three subtypes of congenital haemangioma have similar histopathological features. They comprise capillary lobules with variable histopathological patterns and large extralobular vessels. Most of these extralobular vessels are abnormal veins and lymphatic vessels.¹³ Therefore, the presence of long and narrow lymphatic vessels is important for diagnosis.¹³

Intralobular expression of podoplanin may be found in RICH, especially in the case of concomitant thrombocytopenia. This aspect, along with the lobular architecture, could lead to a misdiagnosis of kaposiform haemangioendothelioma.¹³

Glucose transporter (GLUT) 1 staining is negative, contrary to infantile haemangioma.¹³

RICH may be complicated with high-output heart failure, sometimes in utero, due to the presence of intralesional high blood flow rates and arteriovenous shunts.¹ This aspect is usually transitory, but the mortality rate reaches 30% in large congenital haemangiomas.¹⁴ Waelti et al suggested the association between the presence of venous lakes in the ultrasound evaluation and the increased risk of cardiac failure.¹¹

Consumption of blood-derived components may occur, resembling the Kasabach-Merritt phenomenon. Contrary to kaposiform haemangioendotheliomas, in RICH, this phenomenon occurs in a transitory and mild manner.¹²

Finally, ulceration is also a potential complication of RICH, usually occurring in the involuting phase. When ulceration involves a large vessel, massive and life-threatening bleeding may occur.^{15 16} Waelti et al reported an association between ultrasonographic evidence of venous ectasia or venous lakes and the increased risk of bleeding.¹¹

These complications may require invasive therapeutic measures and threaten caregivers, who must be constantly informed about the patient’s condition. In this sense, it is essential to clarify the parents' doubts, support them in psychological and social aspects, and assure them that all the therapeutic procedures are performed to improve survival and quality of life.

Commonly, expectant management is undertaken, with close monitoring of the lesion. The prognosis is good when there is dimensional regression of the lesion in the first year of life.¹ The main indications for non-expectant therapy are consumptive coagulopathy, high-output heart failure, mass effect, lesion haemorrhage or ulceration, and aesthetic compromise.⁵

Given the predicted spontaneous dimensional regression, lesion-aimed therapy is controversial and optional. The use of beta-blockers, corticosteroid therapy or inhibitors of vascular endothelial growth factors is of questionable value.¹ After spontaneous resolution, large lesions often leave behind aesthetical problems, with residual scars, redundant skin or telangiectasia. Advances in medical and surgical methods allow safe treatment to prevent children from suffering the psychological impact of having a congenital haemangioma. If substantial deformity is evident, surgical therapy is offered for atrophic skin or fibrofatty residuum. Pulsed-dye laser therapy may be an option for residual telangiectasia. In late involution haemangiomas, surgical excision or laser treatment is offered at approximately 2 years of age.¹⁷

In case of life-threatening complications, urgent endovascular embolisation or surgical recession may be necessary. Treatment should always include haematological and cardiovascular support, and antifibrinolytic drugs may be helpful in minimising the risk of bleeding.^{5 11}

Ultimately, limb amputation is indicated if cardiovascular and haematological complications are refractory.¹² Family members are often resistant to this course of action, making it essential to discuss all prosthetic replacement hypotheses for an amputated limb and provide prompt psychological support.

Learning points.

• Rapidly involuting congenital haemangiomas are rare vascular tumours, with an eccentric presentation in neonates but an overall good prognosis with spontaneous involution.

• The diagnosis is based primarily on the clinical appearance, with bulky and purplish congenital masses that usually affect the limbs.

• Imaging assessment demonstrates large solid tumours with an important intralesional vascular component and marked dilation of the vascular network.

• The therapeutic approach is usually expectant, with a close monitor of the dimensions of the lesion.

• Complications include high-output heart failure, consumptive coagulopathy and severe haemorrhage, which constitute the main indications for non-conservative therapies.

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