Kaposiform haemangioendothelioma: A radiological dilemma

were palpable. Flexible nasopharnyngolaryngoscope revealed no significant findings other than slight fullness over the left lateral pharyngeal wall and dilated vessels at the posterior pharyngeal wall. On admission, full blood count investigation revealed thrombocytopenia with platelet count of 14 x 10 9 /L, normal total white cell count (11.6 x 10 9 /L) and haemoglobin (9.8 g/dL). Full blood picture showed no abnormal mononuclear or blast cells, which did not


Introduction
Kaposiform haemangioendotheliomas (KHE) is a rare type of locally aggressive vascular tumour with a reported incidence between 0.07 and 0.091 per 100,000 children per year, typically diagnosed in infancy or early childhood [1].KHE is associated with a poorer prognosis than infantile or congenital haemangioma, a disease usually found within the similar age group [1,2].KHE with the presence of severe thrombocytopenia due to platelet trapping within the tumour, sometimes accompanied by haemolytic anaemia, and secondary coagulation abnormalities form the characteristic features of Kasabach-Merritt Syndrome (KMS); a life-threatening condition which according to Zhou J et al has incidence rate of 45.9% and resulting in high mortality rate of up to 30% [3,4].Radiological knowledge of this rare tumour especially in ultrasound and magnetic resonance imaging (MRI) is crucial in reaching the diagnosis and, ultimately in guiding the appropriate management [5].

Case description
A 4-month-old girl presented with progressive left neck swelling for 3 months.It was first observed at day 40 of life as a small non-tender swelling under the chin that gradually enlarged and extended to the left side of the neck.No prior history of trauma or family history of malignancy.The swelling became discoloured from blackish to purplish over the interval of 1 month.Otherwise, the patient was active and exhibited no symptoms of airway compression, fever, or weight loss.
Physical examination revealed a large swelling over the left side of the neck measuring 13.0 x 8.0 cm with upper border at the submental region extending to posterior auricular region and the lower border at the supraclavicular region.The overlying skin appeared purplish to bluish, non-tender, firm in consistency with no bruit on auscultation (Figure 1).No other swelling or neck nodes were palpable.Flexible nasopharnyngolaryngoscope revealed no significant findings other than slight fullness over the left lateral pharyngeal wall and dilated vessels at the posterior pharyngeal wall.
On admission, full blood count investigation revealed thrombocytopenia with platelet count of 14 x 10 9 /L, normal total white cell count (11.6 x 10 9 /L) and haemoglobin (9.8 g/dL).Full blood picture showed no abnormal mononuclear or blast cells, which did not explain the thrombocytopenia; therefore, peripheral consumption or destruction must be considered.The neck ultrasound (US) demonstrated an ill-defined heterogeneously hypoechoic solid mass at the left preauricular region extending to the left submandibular and neck regions measuring 4.5 x 6.3 x 5.3 cm (AP x W x CC).This lesion exhibited minimal low-flow internal vascularity on colour and pulse wave Doppler (Figure 2).No enlarged cervical lymph nodes.
In the subsequent MRI, the mass appeared heterogeneously isointense on T1-weighted image (T1WI), heterogeneously hyperintense on T2weighted image (T2WI) and exhibited heterogeneous enhancement post-contrast.It measures about 4.7 cm x 4.7 x 4.4 cm (AP x W x CC) and was associated with extensive oedema involving underlying subcutaneous tissue, left neck muscles and the adjacent deep spaces (Figure 3).The mass was not suppressed on fat suppression sequence with no blooming artefact in the gradient echo sequences to suggest haemosiderin deposit or calcification.There was no serpiginous flow void to suggest arteriovenous malformation.Feeding vessels from the external carotid artery were identified on magnetic resonance angiography sequence (MRA) (images not shown).In view of the clinical suspicion of KMS based on the patient's age, clinical and haematological findings, the features on MRI could suggest a vascular neoplasm such as KHE.
A trucut biopsy was carried out and revealed positive immunohistochemical and histological morphology results for CD31 & ERG, CD34, and Podoplanin which supported the diagnosis of KHE (Figure 4).
A combination of syrup sirolimus and syrup prednisolone was started according to her body weight as the first line of treatment.After 3 weeks on   medication, the swelling on her left neck has reduced in size which clinically measured 7.0 cm x 6.0 cm (previously 13.0 x 6.0 cm) with minimal bluish discolouration.Syrup prednisolone was tapered off, while syrup sirolimus was continued with a plan to increase dose according to patient's condition.After nearly 4 months on medication, the left neck swelling became much smaller with no bluish discolouration and softer on palpation (Figure 5).Repeated MRI scan done at 10 months after the medication commencement showed significant reduction of the mass size which measures 2.7 cm x 1.8 cm x 2.3 cm (AP x W x CC) with residual lesion seen at the left submandibular space and below the left mandible (Figure 6).The patient remained active, developmental milestone was appropriate to age, and she had no other clinical symptoms.

Discussion
Vascular lesions within the head and neck have a broad pathological spectrum.The most used classification is from the International Society for the Study of Vascular Anomalies (ISSVA), which classifies the lesions into benign, locally aggressive/borderline, and malignant [1].The actual prevalence and incidence of KHE are most likely higher than those reported, as smaller KHE lesions are typically not associated with KMS or other related conditions and can therefore be misdiagnosed as an uncommon variant of infantile haemangioma or other vascular anomalies [6].
To classify the lesion in this patient, radiological knowledge is required.Based on our ultrasound findings, a vascular lesion is suspected due to the illdefined infiltrative pattern, and it exhibits low-flow colour and pulse wave on Doppler [7,8].A welldefined lesion may be a haemangioma, while illdefined lesions may represent KHE, angiosarcoma or another malignant lesion [7][8][9].However, according to Bansal AG et al these lesions can be further differentiated by looking into the pattern of vascularity within the lesion which is divided into high-flow and low-flow [9].In our case, the minimal intralesional vascularity with a slow-flow pattern on ultrasound favours towards lymphatic malformation, mixed venolymphatic or other common non-vascular tumour like rhabdomyosarcoma which can exhibit variable internal vascularity [9].
To further characterise the lesion, MRI is indispensable.In our patient, the mass appeared illdefined, isointense to muscles on T1WI, and heterogeneously hyperintense on T2WI involving multiple planes of soft tissue with heterogenous enhancement post-contrast, features which favoured KHE according to Brambhatt et al. and Navarro et al [1,10].Stranding of the surrounding subcutaneous fat, as observed in our patient, lends additional support to the diagnosis of KHE.However, other indicators of KHE, such as hemosiderin deposits and destructive changes of the adjacent bones, were absent in our patient [10].In contrast, infantile haemangioma, despite having an incidence within the same age group, it is described as a well-defined solid homogenous mass that appears isointense to muscles on T1WI, hyperintense on T2WI, homogenously enhanced post-contrast with fastflow and tumour blush on MRA [11].Angiosarcoma is a malignant tumour that needs to be taken into consideration when encountering such mass.
Typically, this tumour returns intermediate signal on T1WI, appears heterogeneously hyperintense on T2WI, demonstrates avid enhancement postcontrast, and contains flow voids or high-flow serpentine loss of signal on T1WI and T2WI imaging [1].Other non-vascular tumours such as rhabdomyosarcoma are common in children of her age, but this is unlikely in the absence of intralesional haemorrhage or necrosis [12].
Despite the advancements in MRI technology, the role of MRI in characterising soft-tissue tumours remains limited, with only 50% of cases correctly predicting the exact histological features [10].Thus, correlation with patient's history and blood results is essential, as proven in this case where the combination of this information raised the initial clinical suspicion of KMS.The incidence of KMS is 45.9% in KHE patient, with the greatest risk of KMS found at early onset of KHE (≤4.75 months) and large lesion (> 5.35 cm) [3].Our patient's age carries a higher risk of KMS, along with clinical features of progressive engorgement and purpura [13].
According to Mahajan P et al, KMS also can lead to significant pain which is due to engorgement of the mass by blood elements secondary to venous stasis which may lead to thrombosis.However, this symptom was not present in our patient [14].Biopsy is the gold standard for conclusive diagnosis involving immunohistochemical and histological morphology examination [11].
Due to marked heterogeneity and rarity of KHE, there are no definitive treatment guidelines for patients.Instead, the management is based on a review of the evidence, expert opinions, and clinical experience.In children with complex vascular anomalies and tumours, including KHE, Sirolimus has been recommended.Sirolimus, a well-known mTOR inhibitor, is a potent immunosuppressant and is used in conjunction with corticosteroids as a first-line treatment for KHE with KMP.For the management of patients with severe complications or who are at risk of complications, multidisciplinary team involvement is required [13].

Conclusion
Correlation between patient's history, clinical findings, laboratory results and imaging appearance is of paramount importance in diagnosing paediatric masses, especially when they are rare.MRI is an essential imaging tool to characterize vascular lesions.Early diagnosis is vital in preventing life-threatening conditions that result from KMP or due to the nature of KHE.

Figure 1 .
Figure 1.Left side of neck enlargement

Figure 2 .
Figure 2. (a) Ultrasound of neck reveals an ill-defined heterogeneously hypoechoic solid mass in axial and longitudinal views (arrows) (b) Low-flow internal vascularity is demonstrated on colour and pulse wave Doppler.

Figure 4 .
Figure 4. Immunohistochemical and histological morphology results of left neck mass: a. Strip of tumour tissue composed of vague irregular lobules made up of proliferation of rounded capillary-type vessels (circle) and dilated lymphatic vessels (rectangular), embedded within oedematous, fibrous, and haemorrhagic stroma.Peripheral fibrosis and hyalinization of stroma is observed (HE stains 40x magnification).b.ERG immunostaining (brown coloured stain) is positive and highlights the endothelial cells lined the spindled cells and vascular lumina.c.CD31 positive highlights the endothelial cells.Some of the vascular lumina are filled with plateletrich microthrombi, highlighted by CD31 immunostaining (red arrow).d.Podoplanin (brown coloured stain) highlights the lymphatic endothelium.

Figure 5 .
Figure 5.Following 4 months of oral treatment, the left neck swelling has significantly reduced in size with no obvious skin discolouration.

Figure 6 .
Figure 6.Repeated neck MRI in axial (a) and sagittal (b) views showing the heterogenous hyperintense mass has significantly reduced in size with less locoregional tissue involvement (arrows).