Discussion and conclusions
Vascular anomalies are congenital abnormalities of vascular development. The International Society for the Study of Vascular Anomalies (ISSVA) [
6] classified these conditions into vascular malformations and proliferative vascular lesions, like hemangiomas. Most hemangiomas are of the infantile type, which is characterized by excessive proliferation in the first year of life, followed by spontaneous subsequent regression. Vascular malformations are collections of enlarged aberrant and ecstatic vessels, with normal non-proliferative endothelium. They are present at birth and increase in size in parallel with child’s growth [
7,
8].
In most literature reports, vascular abnormalities of the joints are named synovial hemangiomas, but in the majority of cases the microscopic features of these lesions are typical of a vascular venous malformation. In some studies, only intra-articular/intra-synovial lesions were comprised in the group of synovial hemangiomas [
1], whereas other reports also included intra-articular/extra-synovial forms [
2], which raises confusion in their classification. Mattila et al. [
9] stated that they had never seen a real synovial hemangioma of the knee in their experience in tertiary referral center for vascular anomalies in children.
The knee is the most frequent reported location of IAVM, accounting for 60 % of all cases [
1,
5]. In a large cohort of non-syndromic lower extremity IAVM, knee involvement was observed in 97/156 (62 %) patients [
10]. IAVMs seem overall rare, as this lesion was found in only one of 4682 knee arthroscopies [
11]. A variety of other joints can be affected, beside the knee, including the temporomandibular joint [
12].
The typical patient with an IAVM is a child or young adult who presents with swollen and painful knee [
1,
3]. Pain is always reported at the time of the first evaluation [
2,
3,
13]. It can be acute, secondary to intra-lesional thrombosis or hemarthrosis, or chronic, secondary to chondropathy or muscle impairment [
4]. The intra-lesional thrombosis of an IAVM is related to a local intravascular coagulopathy that can manifest as an increase in D-dimer blood level. This complication is more frequent in larger IAVM [
3,
14,
15]. In our case 2 the low level of fibrinogen led the clinicians to misdiagnose of coagulation defect and to prescribe an erroneous treatment.
Another frequent symptom is limitation of the range of motion [
2], that can be useful to differentiate isolated soft tissue vascular malformations from IAVM [
4]. Cutaneous changes suggesting a vascular malformation, such as prominent veins or superficial venous dilation, can occasionally be observed in proximity of the affected joint, which helps to make an early diagnosis [
3,
4,
16]. Occasionally, a tender spongy or firm mass may be palpable [
1,
17]. In all our patients, the lesion was not recognizable clinically on physical examination.
Limb overgrowth is frequently observed in certain disorders with vascular malformations, as Klippel-Trénaunay syndrome [
7]. In non-syndromic IAVM, the majority of the patients have either a normal limb length or a slight undergrowth or overgrowth of the affected extremity [
16‐
18].
A previous trauma is reported in literature in a minority of cases of IAVMs [
1,
2,
13]. Unlike these experiences, in our patients the episodes of knee pain and swelling were frequently heralded by a minor trauma. However, it is often difficult to establish reliably the cause-effect relationship with a trauma because children are exposed to frequent trauma during play and sport.
According to Moon et al., the average age of onset of IAVM is 10.9 years in girls and 12.5 years in boys, with the start of symptoms in 75 % of patients before the age of 16 [
5], but no sex predilection can be defined [
1,
5]. There has been a report in a 4-month-old boy [
2]. The diagnosis of IAVM is often delayed, as preoperative diagnosis is difficult [
5]. In our patients, the average age at first symptom was 3.9 years (range 18 months-7 years), and the average time to diagnosis was 3.1 years (range 1.5 – 7 years). This time lag is in the range of that reported in the literature, which varies from 2.2 to 6.7 years [
2‐
4,
9,
19]. Late diagnosis is associated with worse prognosis after surgical treatment, with the possible development of structural joint changes leading to functional impairment [
20], which may require additional orthopedic surgical treatment to restore mobility [
15].
The course of IAVM is often chronic and is marked by alternance of relapses and remissions. Exacerbation of joint swelling is typically to intra-articular bleeding. In case of intra-synovial lesions, the synovia may become inflamed and hypertrophic, and progressive damage of cartilage and bone may ensue [
1,
16,
21]. Intermittent reappearance of swelling with partial regression over time, as detected in all our cases, is a useful clinical feature to raise the diagnostic suspicion.
The differential diagnosis of IAVM include several causes of monoarthritis in childhood, including JIA, pigmented villonodular synovitis (PVNS), lipoma arborescens, juxta-articular mixoma, bursitis, malignant tumours [
22], posttraumatic organizing hemorrhage, tuberculosis, sarcoidosis and bleeding disorders [
1,
3]. Tuberculosis is often forgotten in the differential diagnosis of knee monoarthritis. It is good clinical practice to rule out tuberculous arthritis before diagnosing JIA. The presenting clinical features of monoarticular JIA can be very similar to those of IAVM, and both conditions may favorably to NSAID therapy in their initial stage. However, the aspiration of bloody fluid from the joint serves to distinguish these two disorders. Misdiagnoses in our patients included JIA, bleeding disorder, and traumatic arthropathy.
Imaging findings play a fundamental role in distinguishing IAVM from JIA and whenever possible, it is advisable to complete the diagnostic workup for persistent or recurrent monoarthritis with an MRI before attributing a diagnosis of JIA [
4,
9,
23‐
26]. Plain radiographs are of limited value, as they are normal in at least half of the patients. On ultrasonography, the IAVM is seen as an iso- or hyperechogenic mass with a posterior reinforcement, accompanied with enhanced venous vascularization [
27]. Abnormal venous drainage around the joint can also be detected [
15]. This technique may allow the definition of the size and location of the lesion, but images may be misleading and misinterpreted, as in our first case, as prominent synovial hypertrophy. Phleboliths, when present, are seen as brightly echogenic foci within the lesion [
23].
Angiography and computed tomography (CT) scan are generally not necessary if MRI is employed [
23,
26]. Indeed, as shown in our patients, the nature and extent of the lesion is more accurately judged by MRI. The mass appears isointense-to-hypointense in comparison to the muscle on T1-weighted images, and hyperintense on T2-weighted images, with a grade of heterogeneity related to recurrent intralesional thrombotic or hemorrhagic episodes. In comparison with fat, the lesions tend to appear much brighter on T2-weighted images. Contrast enhancement largely depends on the gradient of lymphatic or vascular composition [
9,
24,
26].
As highlighted by Kan et al. [
28], certain synovial lesions, such as IAVM, synovial sarcoma, and pigmented villonodular synovitis, display peculiar MRI features that may facilitate their distinction from other conditions containing blood products. In particular, IAVM can be diagnosed by identifying tubular structures within both the intra- and extra-articular spaces, and often extending to the extra-articular soft tissue and bone structures. These lesions may lack extra-articular edema [
9,
28]. The degree of contrast enhancement may help to differentiate IAVM from cystic synovial hyperplasia [
29].
IAVM can extend to fat tissue and muscles, but very rarely invade the bone [
1,
30]. Intra-capsular and intra-synovial lesions are associated with a higher risk of chondral damage [
16], but the size seems not to correlate with the risk of erosive arthropathy [
31]. In our patients, the lesions were located in different knee areas, but all involved the synovium.
Although MRI may precise well the size of the mass, it may not be entirely accurate, and sometimes the exact extension can be defined only at surgery [
9,
15].
Diagnostic arthroscopy can be helpful to confirm the nature of the lesion through the histopathologic assessment, as happened in our cases. However, nowadays arthroscopy is generally indicated only for cases in which the imaging specialist is not certain regarding the MRI findings, or if the findings are atypical. MRI is considered the modality of choice to make the diagnosis.
The histopathologic features of IAVM are in line with their definition as vascular malformations [
8]. At microscopy, a synovium infiltrate composed by a mixture of medium-sized and large-sized vessels with a muscular wall of variable thickness, and thin-walled medium-sized vascular spaces is observed [
1,
3].
Resection of knee IAVM by open surgery is considered the treatment of choice, as it can lead to long-term improvement of pain and joint mobility [
3,
15]. In addition, the complete removal of the lesion is fundamental in order to avoid recurrence of intra-articular bleeding [
3,
15,
17,
18]. It is unclear if treating asymptomatic patients can prevent chondropathy [
15,
18,
32]. None our patients experienced recurrence of bleeding after surgery, even after many years. Another proposed treatment is based on sclerotherapy. This procedure may be helpful as a bridge therapy before open surgery or in case of extensive intra-articular lesions, but it is most frequently applied in soft tissue venous malformations. Sclerotherapy may reduce pain, but its effect is often transient [
15,
18,
33].
Radiotherapy has been proposed in the management of IAVM, but is not used routinely. It might have a role in diffuse IAVM, when complete surgical removal is difficult and the growth plates are closed [
13,
17].
In summary, our report highlights the challenges that may be posed by the detection of knee IAVM and the frequent long delay between the onset of symptoms and the correct diagnosis. A careful assessment of patient history, the demonstration of a bloody fluid upon arthrocentesis, and the proper interpretation of the MRI scanning may facilitate the recognition and early treatment of this lesion, and avoid the need for a diagnostic arthroscopy before surgical removal.
Publisher’s Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.