Acta Pædiatrica ISSN 0803-5253
REGULAR ARTICLE
An interdisciplinary specialist team leads to improved diagnostics and treatment for paediatric patients with vascular anomalies Katariina A. Mattila ([email protected])1, Kaisa Kervinen1, Teija Kalajoki-Helmi€o2, Kimmo Lappalainen2, Pia Vuola3, Jouko Lohi4, Risto J. Rintala1, Anne Pitk€aranta5,6, P€aivi Salminen1 1.Department 2.Department 3.Department 4.Department 5.Department 6.The College
of of of of of of
Paediatric Surgery, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Radiology, HUS Medical Imaging Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Plastic Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland Pathology, HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Otorhinolaryngology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Medicine, Qatar University, Doha, Qatar
Keywords Diagnostics, Haemangiomas, Interdisciplinary, Paediatric, Vascular anomalies Correspondence Katariina A. Mattila, MD, Children’s Hospital, P.O. Box 281, FIN-00029 HUS, Helsinki, Finland. Tel: +358 50 5377301 | Fax: +358 9 471 75314 | Email: [email protected] Received 8 April 2015; revised 12 May 2015; accepted 8 June 2015. DOI:10.1111/apa.13076
ABSTRACT Aim: Patients with vascular anomalies are often misdiagnosed, leading to delayed or improper treatment. The aim of this study was to evaluate the impact of an interdisciplinary team on the diagnosis and treatment of paediatric patients with vascular anomalies. Methods: We reviewed the paediatric patients evaluated by our interdisciplinary team between 2002 and 2012, analysing the referral diagnosis, final diagnosis, patient age, sex, clinical history, laboratory tests, imaging studies and treatments. Results: Of the 480 patients who were evaluated, 435 (90.6%) had a vascular anomaly: 30.7% of all patients had a tumour and 55.2% had a malformation. Haemangiomas comprised 93.2% of all tumours, while malformations included capillary (9.8%), lymphatic (30.1%), venous (36.8%), arteriovenous (3.8%) and combined slow–flow (7.9%) malformations. Tumours were initially diagnosed correctly in 89.2% of the patients, but only 38.0% of the malformations were diagnosed correctly. Improper treatment was given to 1.4%, due to incorrect diagnoses. Conclusion: This study showed that haemangiomas were likely to be diagnosed correctly, but other tumours and vascular malformations were likely to be misdiagnosed. Misdiagnosis seldom led to improper treatment, but probably led to delayed treatment in many cases. The interdisciplinary approach led to improved diagnostics and treatment.
INTRODUCTION Historically, the treatment of vascular anomalies has been encumbered by inaccurate terminology and incorrect diagnoses. The classification (1,2) proposed by the International Society for the Study of Vascular Anomalies (ISSVA) in 1996 is now widely accepted and has facilitated both clinical work and research, but the terminology and clinical practices used are still not consistent worldwide. Vascular anomalies are a largely heterogeneous group of lesions that often present during childhood or adolescence,
but may appear at any age. They typically involve the skin, but can affect any organ. An interdisciplinary approach was recommended by ISSVA, due to their complexity, and this approach was later endorsed by a number of researchers, including Enjolras et al. (3) and Donnelly et al. (4). Our aim was to evaluate the impact of an interdisciplinary team on the diagnosis and treatment of paediatric patients with vascular anomalies. We also characterised
Key Notes
Abbreviations CLOVES, Congenital lipomatous overgrowth, vascular malformations, epidermal nevi and scoliosis/skeletal and spinal anomalies; ISSVA, International Society for the Study of Vascular Anomalies; LUMBAR, Lower body haemangioma, urogenital anomalies, ulceration, myelopathy, bony deformities, anorectal malformations, arterial anomalies and renal anomalies; MRI, Magnetic resonance imaging; PHACES, Posterior fossa malformations, haemangioma, arterial anomalies, cardiovascular anomalies, eye anomalies, sternal clefting and/or supraumbilical raphe.
©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. 1109–1116
Patients with vascular anomalies are often misdiagnosed, leading to delayed or improper treatment. This study focused on 435 paediatric patients with a vascular anomaly referred to our interdisciplinary team between 2002 and 2012. We found that haemangiomas were likely to be diagnosed correctly, but other tumours and vascular malformations were likely to be misdiagnosed. The interdisciplinary approach led to improved diagnostics and treatment.
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various types of lesions, with regard to their anatomical location, patient sex and age.
MATERIALS AND METHODS We retrospectively reviewed our vascular anomalies registry for paediatric patients evaluated by our interdisciplinary team between December 2002 and December 2012. Patients treated in Helsinki Children’s Hospital and paediatric patients from outside the Hospital District of Helsinki and Uusimaa who were evaluated by the interdisciplinary team were included in this study. The study was approved by the Helsinki University Hospital Ethics Committee. We analysed the patients’ clinical history, laboratory tests, imaging studies and treatments, which included follow-up, pharmacological, interventional radiological, surgical and other, based on their medical records. Furthermore, we recorded the patient’s sex, age and location of the vascular anomaly, including head and neck, trunk, upper limbs, lower limbs, visceral or multiple. The primary diagnoses were compared with the final diagnoses to determine the percentage of patients diagnosed incorrectly. Finally, the recommendations, which included follow-up, imaging, biopsy or treatment, of the interdisciplinary team for each patient, were recorded.
The diagnosis was based on the ISSVA classification, and the updated 2014 classification (5) was used here. The vascular tumours comprised haemangiomas, epithelioid haemangiomas, kaposiform haemangioendotheliomas and infantile haemangiomas associated with other anomalies, including PHACES (posterior fossa malformations, haemangioma, arterial anomalies, cardiovascular anomalies, eye anomalies, sternal clefting and/or supraumbilical raphe) syndrome and LUMBAR (lower body haemangioma, urogenital anomalies, ulceration, myelopathy, bony deformities, anorectal malformations, arterial anomalies and renal anomalies) syndrome. Infantile and congenital haemangiomas could not be differentiated in this study. The vascular malformations comprised capillary malformations, including cutis marmorata telangiectatica congenita and capillary malformations with bone and, or, soft tissue hyperplasia; lymphatic malformations including lymphoedema; venous malformations including glomuvenous malformations; combined slow–flow malformations such as capillary–venous malformations, capillary–lymphatic malformations and lymphatic–venous malformations; arteriovenous malformations; vascular malformations associated with other anomalies, including Sturge–Weber syndrome, Parkes–Weber syndrome, Klippel–Trenaunay syndrome, Bannayan–Riley–Ruvalcaba syndrome, CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi and scoliosis/skeletal and spinal anomalies)
Table 1 Vascular anomalies in this material according to the 2014 ISSVA classification Tumours
Malformations
Unclassified vascular anomalies
Haemangioma Infantile haemangioma
Capillary malformation Capillary malformation
Congenital haemangioma Other tumours
Cutis marmorata telangiectatica congenita Capillary malformation with bone / soft- tissue hyperplasia Lymphatic malformation Lymphatic malformation Lymphoedema Venous malformation Venous malformation Glomuvenous malformation Combined slow–flow Lymphatic–venous malformation Capillary–venous malformation Capillary–lymphatic malformation Arteriovenous malformation Arteriovenous malformation Malformations associated with other anomalies Sturge–Weber syndrome Parkes–Weber syndrome Klippel–Trenaunay syndrome Bannayan–Riley–Ruvalcaba syndrome CLOVES syndrome Maffucci syndrome Spinal arteriovenous metameric syndrome*
Verrucous haemangioma PTEN hamartoma/’angiomatosis’ of soft tissue Angiokeratoma
Epithelioid haemangioma Kaposiform haemangioendothelioma Infantile haemangioma associated with other lesions PHACES syndrome LUMBAR syndrome
*Spinal arteriovenous metameric syndrome is not mentioned in the ISSVA classification.
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Interdisciplinary support for vascular anomalies
syndrome, Maffucci syndrome and spinal arteriovenous metameric syndrome (Table 1).
RESULTS Patient characteristics Our interdisciplinary team evaluated 480 paediatric patients between December 2002 and December 2012. Of these patients, 57 (11.9%) were sent for consultation from outside the Hospital District of Helsinki and Uusimaa. Slightly over half of the patients were evaluated once by the interdisciplinary team (n = 251, 52.3%), while the rest required two or more evaluations (Fig. 1). The total number of evaluations was 943. Of the patients with confirmed diagnoses, 148 (30.7%) had a tumour and 266 (55.2%) a malformation. In addition, 21 patients (4.4%) had an unclassified or unknown vascular anomaly and 45 patients (9.4%) were diagnosed with something other than a vascular anomaly. The tumours included haemangioma (93.2%), epithelioid haemangioma (0.7%), kaposiform haemangioendothelioma (3.4%), other tumours (0.7%) and infantile haemangiomas associated with other lesions (PHACES syndrome 1.3% and LUMBAR syndrome 0.7%). The malformations included capillary malformation (9.8%), lymphatic malformation (30.1%), venous malformation (36.8%), combined slow–flow malformation (7.9%), arteriovenous malformation (3.8%) and malformations associated with other lesions (KlippelTrenaunay 7.1%, Parkes–Weber 1.5%, Sturge–Weber 1.1%, CLOVES 0.8%, spinal arteriovenous metameric 0.4%, Maffucci 0.4% and Bannayan–Riley–Ruvalcaba 0.4% syndrome) (Table 2). The median age of the patients when they were first evaluated was 4 years (range 0–22). Two patients were over 18 years of age at the time of the first evaluation, but they were included in this study because their treatment was begun before they turned 18. Most patients (n = 136, 28.2%) were under 1 year of age at the time of the first evaluation (Fig. 2). Haemangiomas were more common in females (69.6%), capillary malformations (61.5%) and arteriovenous malfor-
Table 2 Confirmed diagnoses of 414 evaluated patients with vascular anomalies Tumour
30.7% (n = 148)
Haemangioma Other tumour
93.2 4.8
Infantile haemangioma associated with other lesions
2.0
55.2% (n = 266)
Malformation Venous malformation Lymphatic malformation Capillary malformation Arteriovenous malformation Combined slow–flow malformation Malformations associated with other lesions
36.8 30.1 9.8 3.8 7.9 11.7
mations (60.0%) were slightly more common in females, but lymphatic malformations were slightly more common in males (60.0%). The sex distribution was equal in venous malformations. Haemangiomas were most often located in the head and neck region (65.2%), as were capillary malformations (38.5%), but capillary malformations also often spanned multiple regions (30.8%). Venous malformations were most common in the lower limbs (48.0%) and arteriovenous malformations in the upper limbs (50.0%). Lymphatic malformations were more evenly divided among the various anatomical locations than the other malformations (Table 3). The median follow-up time for all patients in this study was 2 years and 4 months (range 0–10 years). Clinical follow-up or treatment was ongoing for 56.2% of the patients after 2012. Diagnostic accuracy Of all the patients evaluated by our interdisciplinary team, 57.5% had correct referral diagnoses. Tumours were diagnosed correctly in 89.2% of the cases, but only 38.0% of
175 140 Patients (n)
Patients (n)
251
132
45
105 70
136
30
16
6
0
111 83
35
79
69 2
18
Age (years)
Evaluations (n)
Figure 1 Number of times patients were evaluated by the interdisciplinary team. Patients with eight or more evaluations had complex vascular anomalies.
Figure 2 Age of patients when they were first evaluated by the interdisciplinary team. For the two patients over 18 years of age, treatment was begun before they turned 18.
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Table 3 Location of vascular anomalies
Anomaly (n) Haemangioma (138) Venous malformation (98) Lymphatic malformation (80) Capillary malformation (26) Arteriovenous malformation (10) Combined slow–flow malformation (21)
Head / neck, %
Upper limbs, %
Lower limbs, %
Trunk, %
Visceral, %
65.2
9.4
2.2
12.3
2.2
8.7
7.1
32.7
48.0
5.1
2.0
5.1
33.8
11.3
27.5
22.5
5.0
0.0
38.5
11.5
19.2
0.0
0.0
30.8
10.0
50.0
30.0
10.0
0.0
0.0
4.8
52.4
28.6
4.8
4.8
4.8
Multiple, %
Figure 3 A 12-year-old boy with a lymphatic–venous malformation of the left thigh initially diagnosed as a ‘haemangioma’.
the malformations. Haemangiomas were diagnosed correctly in 92.8% of the cases, capillary malformations in 57.7% and lymphatic malformations in 63.0%, but only 18.6% of the patients with venous malformations and 30.0% of those with arteriovenous malformations were diagnosed correctly, while none of the patients with combined slow– flow malformations were diagnosed correctly (Table 4) (Figs 3–5). In 17 cases (3.5%), the team initially gave an incorrect diagnosis, but corrected it later (Fig. 6). The most common incorrect referral diagnosis was haemangioma, and 40.8% of the venous malformations, 40.0% of the arteriovenous malformations and 33.3% of the combined slow–flow malformations were initially misdiagnosed as haemangiomas. Other incorrect referral diagnoses varied
Table 4 Percentage of patients with correct referral diagnosis Tumour
89.2% (132/148)
Haemangioma
92.8 (128/138)
Other tumour
28.6 (2/7)
Infantile haemangioma associated with other lesions
66.7 (2/3)
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Malformation Venous malformation Lymphatic malformation Capillary malformation Arteriovenous malformation Combined slow– flow malformation Malformations associated with other lesions
38.0% (101/266) 18.4 (18/98) 63.8 (51/80) 57.7 (15/26) 30.0 (3/10) 0.0 (0/21) 45.2 (14/31)
widely, and included, for example, 19.2% of the capillary malformations misdiagnosed as combined slow–flow malformations and 14.3% of the combined slow–flow malformations misdiagnosed as lymphatic malformations. Recommendations and examinations Before being evaluated by the interdisciplinary team for the first time, 81.3% of the patients underwent imaging studies, pathological samples were available from 2.7% of the patients, and 18.5% were only examined clinically. The team recommended additional imaging for 24.1% and biopsies for 7.8% of the patients. The majority (85.7%) of the patients were examined by imaging at some point, most commonly magnetic resonance imaging (MRI) (73.6%) and ultrasound (68.9%). Coagulation parameters were evaluated in 33.5% of all patients, particularly in those with venous malformations (65.3%), arteriovenous malformations (50.0%), combined slow–flow malformations (66.7%) and vascular malformations associated with other anomalies (80.6%). Elevated D-dimer levels (≥0.5 lg/mL) were found in 43.3% of the patients with venous malformations, 20.0% with arteriovenous malformations, 57.1% with combined slow–flow malformations and 54.2% of those with malformations associated with other anomalies. Pathological samples were available from 37.7% of the patients: 40.6% of these were from biopsies and 59.4% from surgical removal of lesions. However, in 21.3% the original report from pathology was incorrect and did not correspond to the clinical diagnosis.
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(a)
(a)
(b)
(b)
Figure 4 (a) A 6-month-old girl with LUMBAR syndrome, referred to us with the diagnosis ‘capillary malformation’. The patient had a segmental infantile haemangioma with ulceration, bladder exstrophy and right renal agenesis. MRI of the spine, pelvis and lower limb was normal. (b) Photograph of the same patient at the age of three years showing involution of the haemangioma. The patient also received pulsed dye laser therapy due to ulceration.
Treatment Before being evaluated by the interdisciplinary team, 21.5% of the patients received some type of treatment: pharmacological treatment was given to 4.6%, interventional radiological treatment to 3.1%, surgical treatment to 7.5% and other treatments to 10.6%. The percentage of patients who received treatment after being evaluated by the team was significantly higher at 61.9%. Of these patients, pharmacological treatment was given to 7.1%, interventional radiological treatment to 25.4%, surgical treatment to 24.8% and other treatment to 27.3% of the patients. Pharmacological treatment most commonly consisted of cortisone and propranolol for haemangiomas, while a few patients with rare and complex vascular anomalies, such as kaposiform haemangioendothelioma, angiolipomatosis and Bannayan–Riley–Ruvalcaba syndrome, were treated with vincristine or thalidomide. Interventional radiological treat-
Figure 5 (a) A boy referred to us at the age of four years with the diagnosis ‘haemangioma’, the actual diagnosis being venous malformation of the right lower limb. (b) T2 weighted fat saturated sagittal MRI of the same patient showing a venous malformation in the anterior right lower limb.
ment was performed with OK-432, doxycycline or bleomycin for lymphatic malformations and 3% sodium tetradecyl sulphate, polidocanol or ethanol for venous malformations. Approximately one-third (32.5%) of all patients received more than one type of treatment. Only 2.1% of the patients received no treatment at all, not even follow-up, while 27.7% received follow-up only. Before referral, improper treatments were given to six patients (1.4%) with vascular anomalies. All these patients were primarily diagnosed incorrectly: three were believed to have arthritis and managed as such, when in reality they had an intra-articular venous malformation, one was considered to have a haemangioma and received pulsed dye laser therapy, when the correct diagnosis was venous
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Figure 6 A girl at the age of seven years, who was initially diagnosed with a parotid haemangioma by the interdisciplinary team, the actual diagnosis being venous malformation of the parotid gland.
malformation and one patient with a lymphatic malformation was believed to have a ganglion that was treated with aspiration. Finally, one patient with a capillary–venous malformation was considered to have a haemangioma and was treated with embolisation.
DISCUSSION An interdisciplinary team for the diagnostics and treatment of vascular anomalies was founded at Helsinki University Hospital in December 2002 and was the first of its kind in Finland. The hospital provides special healthcare services for patients living in the Hospital District of Helsinki and Uusimaa, covering 29.0% of the Finnish population. It also acts as tertiary referral centre and receives patients from other hospital districts. The interdisciplinary team at Helsinki University Hospital consists of specialists from the fields of paediatric surgery, plastic surgery, otorhinolaryngology, ophthalmology, dermatology, radiology and pathology. Other specialists, for example paediatric haematologists or hand surgeons, can be consulted if needed. Patients are referred to the team by specialists, mostly from within the Hospital District of Helsinki and Uusimaa, but the team also replies to nationwide consultations. Followup is carried out by the referring specialist, but in addition some patients require multiple evaluations by the team. Before the interdisciplinary team was founded, patients with vascular anomalies were treated in various clinics, using different specialties, and clinical practices varied widely. When the team was first founded they even handled
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simple cases of vascular tumours and malformations, so that common guidelines for treatment and follow-up could be established. More recently, most of the cases presented to the team have been more complex, requiring the expertise of many specialists. Over the last 10 years, the interdisciplinary team has gained knowledge in vascular anomalies, diagnostics have improved and treatments have evolved. However, some rare vascular anomalies in this material could not be identified, while some patients (3.5%) were misdiagnosed by the team. Typical patients misdiagnosed by the team included those previously considered to have Klippel– Trenaunay syndrome, but who actually had only a capillary malformation with bone and, or, soft tissue hyperplasia. During the follow-up time of this study, advancements were made in the field of vascular anomalies. New treatments became available, most notably propranolol for haemangiomas in 2008 (6). Some new entities, such as fibroadipose vascular anomaly (7) and CLOVES (8,9), were discovered. Consequently, the diagnoses for some of our patients could be further defined, leading to new recommendations regarding treatments. Examples include patients with fibroadipose vascular anomalies, previously considered to have venous malformations, for whom sclerotherapy was no longer recommended for the intramuscular fibrofatty component. Although vascular tumours are much more common than vascular malformations, with an estimated incidence of 1:20 compared to 1:200 (10,11), only one-third of the patients in this study had a vascular tumour. Within this category, most of the patients with haemangiomas were initially diagnosed correctly, while most of the other vascular tumours were often misdiagnosed. This suggests that haemangiomas are well recognised and mainly treated outside tertiary referral centres. Small and asymptomatic haemangiomas may well be evaluated and followed up by single practitioners, whereas large, ulcerated or multiple haemangiomas, as well as haemangiomas causing morbidity, for example amblyopia or airway obstruction, should be referred to regional centres. Vascular malformations, on the other hand, were usually misdiagnosed, suggesting that diagnosing and treating them requires the knowledge of specialists, often from many medical specialties. Lesions appearing after infancy should always raise a suspicion of a vascular malformation, and not be simply labelled as haemangiomas. Vascular malformations should be referred to specialists with knowledge of vascular anomalies. This view is supported by data from a previous study with similar results (12). Most patients underwent imaging studies before being evaluated by the interdisciplinary team, but additional imaging was recommended for one-fourth of this group. Some patients required new MRIs, some of the previous MRIs were performed without contrast media and thus had to be repeated, while some required angiographies or venographies. We were surprised to learn that only about two-thirds of the patients underwent ultrasound scans and speculate that, in reality, the percentage could have been higher, but may have appeared smaller in this material, due
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to the lack of notes in patient records, especially if the scans were performed in other hospitals. Biopsies proved to be helpful in diagnosing vascular anomalies, but only when the pathologist had a thorough knowledge of vascular anomalies and was familiar with their clinical classification, as shown by our results, in which 21.3% of the pathological diagnoses differed from the clinical diagnoses. Biopsies taken in our clinic are evaluated by a single pathologist who is familiar with vascular anomalies. If possible, biopsies taken elsewhere are re-evaluated by our pathologist, especially if there are discrepancies in the pathological reports and clinical diagnoses or if the diagnoses are unclear. Elevated D-dimer levels occur in approximately 40% of patients with venous malformations (13–15), but also in patients with combined slow–flow malformations and Klippel–Trenaunay syndrome (16). In this study, the D-dimer levels in patients with venous malformations, combined slow–flow malformations and malformations associated with other anomalies were similar to those in previous studies. Evaluating the coagulation parameters in patients with venous malformations, arteriovenous malformations, combined slow–flow malformations and Klippel–Trenaunay syndrome is recommended by our interdisciplinary team. In patients with high D-dimer values, low-molecular-weight heparin is recommended in conjunction with procedures such as sclerotherapy. The patients received significantly more treatment, especially interventional radiological and surgical, after they were evaluated by the interdisciplinary team. As many patients with complex vascular anomalies are presented to the team for diagnostic purposes and treatment planning, this is a logical consequence. One-third of the patients received more than one type of treatment. Some of these patients required a combination of different treatment modalities, while some did not respond to the first line treatment. Discussing treatment options and proposing new protocols for patients with complex vascular anomalies has been facilitated by the existence of an interdisciplinary team. Despite the high percentage of incorrect diagnoses, only a few patients (1.4%) in this study received improper treatment. In a previous study from 2009 by Hassanein et al., 20.6% of patients whose vascular anomalies were mislabelled received improper treatment (17). The low percentage of improper treatments in our patients could have been due to several reasons. Firstly, the misdiagnosed vascular anomalies were mostly considered as haemangiomas, and thus, no treatments were given, but instead the lesions were expected to involute with increasing age. Secondly, before the interdisciplinary team was founded, only a few treatments were available for vascular malformations, most commonly surgery and OK-432 for lymphatic malformations. Advanced interventional radiological treatments became widely available only after the team was founded. However, almost two-thirds (62.0%) of the vascular malformations were initially misdiagnosed, most probably leading to delayed treatment in many cases.
Interdisciplinary support for vascular anomalies
Strikingly, almost one-tenth (9.5%) of the patients evaluated by the interdisciplinary team did not have a vascular anomaly. The diagnoses of these patients were mostly benign and included, among others, branchial cleft cyst, epidermal cyst, neurofibroma and giant-cell tumour. Two patients were, however, diagnosed with a malignant disease after biopsies were taken: one with synovial sarcoma and one with dermatofibrosarcoma protuberans. Biopsies proved to be a valuable tool in the diagnostic process when the diagnosis is unclear, and these malignant cases led to biopsies being recommended increasingly. This study is limited to those patients evaluated by the interdisciplinary team and treated at the Helsinki Children’s Hospital, and thus, direct conclusions regarding the prevalence or characteristics of the various vascular anomalies cannot be drawn. Other limitations of this study include its retrospective nature.
CONCLUSION Our study shows that large numbers of patients with vascular anomalies were misdiagnosed. Only a correct diagnosis will ensure that the patients receive proper follow-up and treatment. Our data support the view that only small or asymptomatic haemangiomas may be evaluated by single practitioners, whereas large, symptomatic or multiple haemangiomas, other vascular tumours and vascular malformations should be sent to regional centres with expertise in vascular anomalies. In Helsinki University Hospital, establishing an interdisciplinary team has led to improved knowledge of vascular anomalies and consistent practices regardless of the clinic where the patient is treated. It has also made new treatment modalities more quickly available.
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©2015 Foundation Acta Pædiatrica. Published by John Wiley & Sons Ltd 2015 104, pp. 1109–1116
REGULAR ARTICLE
An interdisciplinary specialist team leads to improved diagnostics and treatment for paediatric patients with vascular anomalies Katariina A. Mattila ([email protected])1, Kaisa Kervinen1, Teija Kalajoki-Helmi€o2, Kimmo Lappalainen2, Pia Vuola3, Jouko Lohi4, Risto J. Rintala1, Anne Pitk€aranta5,6, P€aivi Salminen1 1.Department 2.Department 3.Department 4.Department 5.Department 6.The College
of of of of of of
Paediatric Surgery, Children’s Hospital, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Radiology, HUS Medical Imaging Centre, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Plastic Surgery, Helsinki University Hospital and University of Helsinki, Helsinki, Finland Pathology, HUSLAB, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Otorhinolaryngology, University of Helsinki and Helsinki University Hospital, Helsinki, Finland Medicine, Qatar University, Doha, Qatar
Keywords Diagnostics, Haemangiomas, Interdisciplinary, Paediatric, Vascular anomalies Correspondence Katariina A. Mattila, MD, Children’s Hospital, P.O. Box 281, FIN-00029 HUS, Helsinki, Finland. Tel: +358 50 5377301 | Fax: +358 9 471 75314 | Email: [email protected] Received 8 April 2015; revised 12 May 2015; accepted 8 June 2015. DOI:10.1111/apa.13076
ABSTRACT Aim: Patients with vascular anomalies are often misdiagnosed, leading to delayed or improper treatment. The aim of this study was to evaluate the impact of an interdisciplinary team on the diagnosis and treatment of paediatric patients with vascular anomalies. Methods: We reviewed the paediatric patients evaluated by our interdisciplinary team between 2002 and 2012, analysing the referral diagnosis, final diagnosis, patient age, sex, clinical history, laboratory tests, imaging studies and treatments. Results: Of the 480 patients who were evaluated, 435 (90.6%) had a vascular anomaly: 30.7% of all patients had a tumour and 55.2% had a malformation. Haemangiomas comprised 93.2% of all tumours, while malformations included capillary (9.8%), lymphatic (30.1%), venous (36.8%), arteriovenous (3.8%) and combined slow–flow (7.9%) malformations. Tumours were initially diagnosed correctly in 89.2% of the patients, but only 38.0% of the malformations were diagnosed correctly. Improper treatment was given to 1.4%, due to incorrect diagnoses. Conclusion: This study showed that haemangiomas were likely to be diagnosed correctly, but other tumours and vascular malformations were likely to be misdiagnosed. Misdiagnosis seldom led to improper treatment, but probably led to delayed treatment in many cases. The interdisciplinary approach led to improved diagnostics and treatment.
INTRODUCTION Historically, the treatment of vascular anomalies has been encumbered by inaccurate terminology and incorrect diagnoses. The classification (1,2) proposed by the International Society for the Study of Vascular Anomalies (ISSVA) in 1996 is now widely accepted and has facilitated both clinical work and research, but the terminology and clinical practices used are still not consistent worldwide. Vascular anomalies are a largely heterogeneous group of lesions that often present during childhood or adolescence,
but may appear at any age. They typically involve the skin, but can affect any organ. An interdisciplinary approach was recommended by ISSVA, due to their complexity, and this approach was later endorsed by a number of researchers, including Enjolras et al. (3) and Donnelly et al. (4). Our aim was to evaluate the impact of an interdisciplinary team on the diagnosis and treatment of paediatric patients with vascular anomalies. We also characterised
Key Notes
Abbreviations CLOVES, Congenital lipomatous overgrowth, vascular malformations, epidermal nevi and scoliosis/skeletal and spinal anomalies; ISSVA, International Society for the Study of Vascular Anomalies; LUMBAR, Lower body haemangioma, urogenital anomalies, ulceration, myelopathy, bony deformities, anorectal malformations, arterial anomalies and renal anomalies; MRI, Magnetic resonance imaging; PHACES, Posterior fossa malformations, haemangioma, arterial anomalies, cardiovascular anomalies, eye anomalies, sternal clefting and/or supraumbilical raphe.
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Patients with vascular anomalies are often misdiagnosed, leading to delayed or improper treatment. This study focused on 435 paediatric patients with a vascular anomaly referred to our interdisciplinary team between 2002 and 2012. We found that haemangiomas were likely to be diagnosed correctly, but other tumours and vascular malformations were likely to be misdiagnosed. The interdisciplinary approach led to improved diagnostics and treatment.
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various types of lesions, with regard to their anatomical location, patient sex and age.
MATERIALS AND METHODS We retrospectively reviewed our vascular anomalies registry for paediatric patients evaluated by our interdisciplinary team between December 2002 and December 2012. Patients treated in Helsinki Children’s Hospital and paediatric patients from outside the Hospital District of Helsinki and Uusimaa who were evaluated by the interdisciplinary team were included in this study. The study was approved by the Helsinki University Hospital Ethics Committee. We analysed the patients’ clinical history, laboratory tests, imaging studies and treatments, which included follow-up, pharmacological, interventional radiological, surgical and other, based on their medical records. Furthermore, we recorded the patient’s sex, age and location of the vascular anomaly, including head and neck, trunk, upper limbs, lower limbs, visceral or multiple. The primary diagnoses were compared with the final diagnoses to determine the percentage of patients diagnosed incorrectly. Finally, the recommendations, which included follow-up, imaging, biopsy or treatment, of the interdisciplinary team for each patient, were recorded.
The diagnosis was based on the ISSVA classification, and the updated 2014 classification (5) was used here. The vascular tumours comprised haemangiomas, epithelioid haemangiomas, kaposiform haemangioendotheliomas and infantile haemangiomas associated with other anomalies, including PHACES (posterior fossa malformations, haemangioma, arterial anomalies, cardiovascular anomalies, eye anomalies, sternal clefting and/or supraumbilical raphe) syndrome and LUMBAR (lower body haemangioma, urogenital anomalies, ulceration, myelopathy, bony deformities, anorectal malformations, arterial anomalies and renal anomalies) syndrome. Infantile and congenital haemangiomas could not be differentiated in this study. The vascular malformations comprised capillary malformations, including cutis marmorata telangiectatica congenita and capillary malformations with bone and, or, soft tissue hyperplasia; lymphatic malformations including lymphoedema; venous malformations including glomuvenous malformations; combined slow–flow malformations such as capillary–venous malformations, capillary–lymphatic malformations and lymphatic–venous malformations; arteriovenous malformations; vascular malformations associated with other anomalies, including Sturge–Weber syndrome, Parkes–Weber syndrome, Klippel–Trenaunay syndrome, Bannayan–Riley–Ruvalcaba syndrome, CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi and scoliosis/skeletal and spinal anomalies)
Table 1 Vascular anomalies in this material according to the 2014 ISSVA classification Tumours
Malformations
Unclassified vascular anomalies
Haemangioma Infantile haemangioma
Capillary malformation Capillary malformation
Congenital haemangioma Other tumours
Cutis marmorata telangiectatica congenita Capillary malformation with bone / soft- tissue hyperplasia Lymphatic malformation Lymphatic malformation Lymphoedema Venous malformation Venous malformation Glomuvenous malformation Combined slow–flow Lymphatic–venous malformation Capillary–venous malformation Capillary–lymphatic malformation Arteriovenous malformation Arteriovenous malformation Malformations associated with other anomalies Sturge–Weber syndrome Parkes–Weber syndrome Klippel–Trenaunay syndrome Bannayan–Riley–Ruvalcaba syndrome CLOVES syndrome Maffucci syndrome Spinal arteriovenous metameric syndrome*
Verrucous haemangioma PTEN hamartoma/’angiomatosis’ of soft tissue Angiokeratoma
Epithelioid haemangioma Kaposiform haemangioendothelioma Infantile haemangioma associated with other lesions PHACES syndrome LUMBAR syndrome
*Spinal arteriovenous metameric syndrome is not mentioned in the ISSVA classification.
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syndrome, Maffucci syndrome and spinal arteriovenous metameric syndrome (Table 1).
RESULTS Patient characteristics Our interdisciplinary team evaluated 480 paediatric patients between December 2002 and December 2012. Of these patients, 57 (11.9%) were sent for consultation from outside the Hospital District of Helsinki and Uusimaa. Slightly over half of the patients were evaluated once by the interdisciplinary team (n = 251, 52.3%), while the rest required two or more evaluations (Fig. 1). The total number of evaluations was 943. Of the patients with confirmed diagnoses, 148 (30.7%) had a tumour and 266 (55.2%) a malformation. In addition, 21 patients (4.4%) had an unclassified or unknown vascular anomaly and 45 patients (9.4%) were diagnosed with something other than a vascular anomaly. The tumours included haemangioma (93.2%), epithelioid haemangioma (0.7%), kaposiform haemangioendothelioma (3.4%), other tumours (0.7%) and infantile haemangiomas associated with other lesions (PHACES syndrome 1.3% and LUMBAR syndrome 0.7%). The malformations included capillary malformation (9.8%), lymphatic malformation (30.1%), venous malformation (36.8%), combined slow–flow malformation (7.9%), arteriovenous malformation (3.8%) and malformations associated with other lesions (KlippelTrenaunay 7.1%, Parkes–Weber 1.5%, Sturge–Weber 1.1%, CLOVES 0.8%, spinal arteriovenous metameric 0.4%, Maffucci 0.4% and Bannayan–Riley–Ruvalcaba 0.4% syndrome) (Table 2). The median age of the patients when they were first evaluated was 4 years (range 0–22). Two patients were over 18 years of age at the time of the first evaluation, but they were included in this study because their treatment was begun before they turned 18. Most patients (n = 136, 28.2%) were under 1 year of age at the time of the first evaluation (Fig. 2). Haemangiomas were more common in females (69.6%), capillary malformations (61.5%) and arteriovenous malfor-
Table 2 Confirmed diagnoses of 414 evaluated patients with vascular anomalies Tumour
30.7% (n = 148)
Haemangioma Other tumour
93.2 4.8
Infantile haemangioma associated with other lesions
2.0
55.2% (n = 266)
Malformation Venous malformation Lymphatic malformation Capillary malformation Arteriovenous malformation Combined slow–flow malformation Malformations associated with other lesions
36.8 30.1 9.8 3.8 7.9 11.7
mations (60.0%) were slightly more common in females, but lymphatic malformations were slightly more common in males (60.0%). The sex distribution was equal in venous malformations. Haemangiomas were most often located in the head and neck region (65.2%), as were capillary malformations (38.5%), but capillary malformations also often spanned multiple regions (30.8%). Venous malformations were most common in the lower limbs (48.0%) and arteriovenous malformations in the upper limbs (50.0%). Lymphatic malformations were more evenly divided among the various anatomical locations than the other malformations (Table 3). The median follow-up time for all patients in this study was 2 years and 4 months (range 0–10 years). Clinical follow-up or treatment was ongoing for 56.2% of the patients after 2012. Diagnostic accuracy Of all the patients evaluated by our interdisciplinary team, 57.5% had correct referral diagnoses. Tumours were diagnosed correctly in 89.2% of the cases, but only 38.0% of
175 140 Patients (n)
Patients (n)
251
132
45
105 70
136
30
16
6
0
111 83
35
79
69 2
18
Age (years)
Evaluations (n)
Figure 1 Number of times patients were evaluated by the interdisciplinary team. Patients with eight or more evaluations had complex vascular anomalies.
Figure 2 Age of patients when they were first evaluated by the interdisciplinary team. For the two patients over 18 years of age, treatment was begun before they turned 18.
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Table 3 Location of vascular anomalies
Anomaly (n) Haemangioma (138) Venous malformation (98) Lymphatic malformation (80) Capillary malformation (26) Arteriovenous malformation (10) Combined slow–flow malformation (21)
Head / neck, %
Upper limbs, %
Lower limbs, %
Trunk, %
Visceral, %
65.2
9.4
2.2
12.3
2.2
8.7
7.1
32.7
48.0
5.1
2.0
5.1
33.8
11.3
27.5
22.5
5.0
0.0
38.5
11.5
19.2
0.0
0.0
30.8
10.0
50.0
30.0
10.0
0.0
0.0
4.8
52.4
28.6
4.8
4.8
4.8
Multiple, %
Figure 3 A 12-year-old boy with a lymphatic–venous malformation of the left thigh initially diagnosed as a ‘haemangioma’.
the malformations. Haemangiomas were diagnosed correctly in 92.8% of the cases, capillary malformations in 57.7% and lymphatic malformations in 63.0%, but only 18.6% of the patients with venous malformations and 30.0% of those with arteriovenous malformations were diagnosed correctly, while none of the patients with combined slow– flow malformations were diagnosed correctly (Table 4) (Figs 3–5). In 17 cases (3.5%), the team initially gave an incorrect diagnosis, but corrected it later (Fig. 6). The most common incorrect referral diagnosis was haemangioma, and 40.8% of the venous malformations, 40.0% of the arteriovenous malformations and 33.3% of the combined slow–flow malformations were initially misdiagnosed as haemangiomas. Other incorrect referral diagnoses varied
Table 4 Percentage of patients with correct referral diagnosis Tumour
89.2% (132/148)
Haemangioma
92.8 (128/138)
Other tumour
28.6 (2/7)
Infantile haemangioma associated with other lesions
66.7 (2/3)
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Malformation Venous malformation Lymphatic malformation Capillary malformation Arteriovenous malformation Combined slow– flow malformation Malformations associated with other lesions
38.0% (101/266) 18.4 (18/98) 63.8 (51/80) 57.7 (15/26) 30.0 (3/10) 0.0 (0/21) 45.2 (14/31)
widely, and included, for example, 19.2% of the capillary malformations misdiagnosed as combined slow–flow malformations and 14.3% of the combined slow–flow malformations misdiagnosed as lymphatic malformations. Recommendations and examinations Before being evaluated by the interdisciplinary team for the first time, 81.3% of the patients underwent imaging studies, pathological samples were available from 2.7% of the patients, and 18.5% were only examined clinically. The team recommended additional imaging for 24.1% and biopsies for 7.8% of the patients. The majority (85.7%) of the patients were examined by imaging at some point, most commonly magnetic resonance imaging (MRI) (73.6%) and ultrasound (68.9%). Coagulation parameters were evaluated in 33.5% of all patients, particularly in those with venous malformations (65.3%), arteriovenous malformations (50.0%), combined slow–flow malformations (66.7%) and vascular malformations associated with other anomalies (80.6%). Elevated D-dimer levels (≥0.5 lg/mL) were found in 43.3% of the patients with venous malformations, 20.0% with arteriovenous malformations, 57.1% with combined slow–flow malformations and 54.2% of those with malformations associated with other anomalies. Pathological samples were available from 37.7% of the patients: 40.6% of these were from biopsies and 59.4% from surgical removal of lesions. However, in 21.3% the original report from pathology was incorrect and did not correspond to the clinical diagnosis.
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(a)
(a)
(b)
(b)
Figure 4 (a) A 6-month-old girl with LUMBAR syndrome, referred to us with the diagnosis ‘capillary malformation’. The patient had a segmental infantile haemangioma with ulceration, bladder exstrophy and right renal agenesis. MRI of the spine, pelvis and lower limb was normal. (b) Photograph of the same patient at the age of three years showing involution of the haemangioma. The patient also received pulsed dye laser therapy due to ulceration.
Treatment Before being evaluated by the interdisciplinary team, 21.5% of the patients received some type of treatment: pharmacological treatment was given to 4.6%, interventional radiological treatment to 3.1%, surgical treatment to 7.5% and other treatments to 10.6%. The percentage of patients who received treatment after being evaluated by the team was significantly higher at 61.9%. Of these patients, pharmacological treatment was given to 7.1%, interventional radiological treatment to 25.4%, surgical treatment to 24.8% and other treatment to 27.3% of the patients. Pharmacological treatment most commonly consisted of cortisone and propranolol for haemangiomas, while a few patients with rare and complex vascular anomalies, such as kaposiform haemangioendothelioma, angiolipomatosis and Bannayan–Riley–Ruvalcaba syndrome, were treated with vincristine or thalidomide. Interventional radiological treat-
Figure 5 (a) A boy referred to us at the age of four years with the diagnosis ‘haemangioma’, the actual diagnosis being venous malformation of the right lower limb. (b) T2 weighted fat saturated sagittal MRI of the same patient showing a venous malformation in the anterior right lower limb.
ment was performed with OK-432, doxycycline or bleomycin for lymphatic malformations and 3% sodium tetradecyl sulphate, polidocanol or ethanol for venous malformations. Approximately one-third (32.5%) of all patients received more than one type of treatment. Only 2.1% of the patients received no treatment at all, not even follow-up, while 27.7% received follow-up only. Before referral, improper treatments were given to six patients (1.4%) with vascular anomalies. All these patients were primarily diagnosed incorrectly: three were believed to have arthritis and managed as such, when in reality they had an intra-articular venous malformation, one was considered to have a haemangioma and received pulsed dye laser therapy, when the correct diagnosis was venous
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Figure 6 A girl at the age of seven years, who was initially diagnosed with a parotid haemangioma by the interdisciplinary team, the actual diagnosis being venous malformation of the parotid gland.
malformation and one patient with a lymphatic malformation was believed to have a ganglion that was treated with aspiration. Finally, one patient with a capillary–venous malformation was considered to have a haemangioma and was treated with embolisation.
DISCUSSION An interdisciplinary team for the diagnostics and treatment of vascular anomalies was founded at Helsinki University Hospital in December 2002 and was the first of its kind in Finland. The hospital provides special healthcare services for patients living in the Hospital District of Helsinki and Uusimaa, covering 29.0% of the Finnish population. It also acts as tertiary referral centre and receives patients from other hospital districts. The interdisciplinary team at Helsinki University Hospital consists of specialists from the fields of paediatric surgery, plastic surgery, otorhinolaryngology, ophthalmology, dermatology, radiology and pathology. Other specialists, for example paediatric haematologists or hand surgeons, can be consulted if needed. Patients are referred to the team by specialists, mostly from within the Hospital District of Helsinki and Uusimaa, but the team also replies to nationwide consultations. Followup is carried out by the referring specialist, but in addition some patients require multiple evaluations by the team. Before the interdisciplinary team was founded, patients with vascular anomalies were treated in various clinics, using different specialties, and clinical practices varied widely. When the team was first founded they even handled
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simple cases of vascular tumours and malformations, so that common guidelines for treatment and follow-up could be established. More recently, most of the cases presented to the team have been more complex, requiring the expertise of many specialists. Over the last 10 years, the interdisciplinary team has gained knowledge in vascular anomalies, diagnostics have improved and treatments have evolved. However, some rare vascular anomalies in this material could not be identified, while some patients (3.5%) were misdiagnosed by the team. Typical patients misdiagnosed by the team included those previously considered to have Klippel– Trenaunay syndrome, but who actually had only a capillary malformation with bone and, or, soft tissue hyperplasia. During the follow-up time of this study, advancements were made in the field of vascular anomalies. New treatments became available, most notably propranolol for haemangiomas in 2008 (6). Some new entities, such as fibroadipose vascular anomaly (7) and CLOVES (8,9), were discovered. Consequently, the diagnoses for some of our patients could be further defined, leading to new recommendations regarding treatments. Examples include patients with fibroadipose vascular anomalies, previously considered to have venous malformations, for whom sclerotherapy was no longer recommended for the intramuscular fibrofatty component. Although vascular tumours are much more common than vascular malformations, with an estimated incidence of 1:20 compared to 1:200 (10,11), only one-third of the patients in this study had a vascular tumour. Within this category, most of the patients with haemangiomas were initially diagnosed correctly, while most of the other vascular tumours were often misdiagnosed. This suggests that haemangiomas are well recognised and mainly treated outside tertiary referral centres. Small and asymptomatic haemangiomas may well be evaluated and followed up by single practitioners, whereas large, ulcerated or multiple haemangiomas, as well as haemangiomas causing morbidity, for example amblyopia or airway obstruction, should be referred to regional centres. Vascular malformations, on the other hand, were usually misdiagnosed, suggesting that diagnosing and treating them requires the knowledge of specialists, often from many medical specialties. Lesions appearing after infancy should always raise a suspicion of a vascular malformation, and not be simply labelled as haemangiomas. Vascular malformations should be referred to specialists with knowledge of vascular anomalies. This view is supported by data from a previous study with similar results (12). Most patients underwent imaging studies before being evaluated by the interdisciplinary team, but additional imaging was recommended for one-fourth of this group. Some patients required new MRIs, some of the previous MRIs were performed without contrast media and thus had to be repeated, while some required angiographies or venographies. We were surprised to learn that only about two-thirds of the patients underwent ultrasound scans and speculate that, in reality, the percentage could have been higher, but may have appeared smaller in this material, due
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to the lack of notes in patient records, especially if the scans were performed in other hospitals. Biopsies proved to be helpful in diagnosing vascular anomalies, but only when the pathologist had a thorough knowledge of vascular anomalies and was familiar with their clinical classification, as shown by our results, in which 21.3% of the pathological diagnoses differed from the clinical diagnoses. Biopsies taken in our clinic are evaluated by a single pathologist who is familiar with vascular anomalies. If possible, biopsies taken elsewhere are re-evaluated by our pathologist, especially if there are discrepancies in the pathological reports and clinical diagnoses or if the diagnoses are unclear. Elevated D-dimer levels occur in approximately 40% of patients with venous malformations (13–15), but also in patients with combined slow–flow malformations and Klippel–Trenaunay syndrome (16). In this study, the D-dimer levels in patients with venous malformations, combined slow–flow malformations and malformations associated with other anomalies were similar to those in previous studies. Evaluating the coagulation parameters in patients with venous malformations, arteriovenous malformations, combined slow–flow malformations and Klippel–Trenaunay syndrome is recommended by our interdisciplinary team. In patients with high D-dimer values, low-molecular-weight heparin is recommended in conjunction with procedures such as sclerotherapy. The patients received significantly more treatment, especially interventional radiological and surgical, after they were evaluated by the interdisciplinary team. As many patients with complex vascular anomalies are presented to the team for diagnostic purposes and treatment planning, this is a logical consequence. One-third of the patients received more than one type of treatment. Some of these patients required a combination of different treatment modalities, while some did not respond to the first line treatment. Discussing treatment options and proposing new protocols for patients with complex vascular anomalies has been facilitated by the existence of an interdisciplinary team. Despite the high percentage of incorrect diagnoses, only a few patients (1.4%) in this study received improper treatment. In a previous study from 2009 by Hassanein et al., 20.6% of patients whose vascular anomalies were mislabelled received improper treatment (17). The low percentage of improper treatments in our patients could have been due to several reasons. Firstly, the misdiagnosed vascular anomalies were mostly considered as haemangiomas, and thus, no treatments were given, but instead the lesions were expected to involute with increasing age. Secondly, before the interdisciplinary team was founded, only a few treatments were available for vascular malformations, most commonly surgery and OK-432 for lymphatic malformations. Advanced interventional radiological treatments became widely available only after the team was founded. However, almost two-thirds (62.0%) of the vascular malformations were initially misdiagnosed, most probably leading to delayed treatment in many cases.
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Strikingly, almost one-tenth (9.5%) of the patients evaluated by the interdisciplinary team did not have a vascular anomaly. The diagnoses of these patients were mostly benign and included, among others, branchial cleft cyst, epidermal cyst, neurofibroma and giant-cell tumour. Two patients were, however, diagnosed with a malignant disease after biopsies were taken: one with synovial sarcoma and one with dermatofibrosarcoma protuberans. Biopsies proved to be a valuable tool in the diagnostic process when the diagnosis is unclear, and these malignant cases led to biopsies being recommended increasingly. This study is limited to those patients evaluated by the interdisciplinary team and treated at the Helsinki Children’s Hospital, and thus, direct conclusions regarding the prevalence or characteristics of the various vascular anomalies cannot be drawn. Other limitations of this study include its retrospective nature.
CONCLUSION Our study shows that large numbers of patients with vascular anomalies were misdiagnosed. Only a correct diagnosis will ensure that the patients receive proper follow-up and treatment. Our data support the view that only small or asymptomatic haemangiomas may be evaluated by single practitioners, whereas large, symptomatic or multiple haemangiomas, other vascular tumours and vascular malformations should be sent to regional centres with expertise in vascular anomalies. In Helsinki University Hospital, establishing an interdisciplinary team has led to improved knowledge of vascular anomalies and consistent practices regardless of the clinic where the patient is treated. It has also made new treatment modalities more quickly available.
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