Subcutaneous Cavernous Haemangioma in a Patient with Klippel-Trenaunay Syndrome: A Case Report.

Background: Klippel-Trenaunay syndrome (KTS) is a rare congenital disease that mainly involves blood vessels and is characterized by the presence of capillary malformations (port wine stains), varicose veins, soft tissue and/or bone hypertrophy. Case Presentation: We report a 28-year-old man who was diagnosed 20 years ago with Klippel-Trenaunay syndrome. Approximately 3 years ago, he found enlarged masses on both upper extremities and a new dark red mass that was pathologically diagnosed as cavernous haemangioma appeared on the right index finger. Conclusion: KTS is a rare and potentially multisystem disease requiring multidisciplinary management for which imaging examination is an important auxiliary diagnostic method. Various complications may occur during its development, so regular follow-up is required to prevent serious accidents.

The Prospective Natural History Study of Patients with Intractable Venous Malformation and Klippel-Trenaunay Syndrome to Guide Designing a Proof-of-Concept Clinical Trial for Novel Therapeutic Intervention.

Background: The natural history of venous malformation (VM) and Klippel-Trenaunay Syndrome (KTS) has not been quantitatively studied. To obtain benchmarks to guide designing clinical trials to assess safety and efficacy of novel drug candidates, the clinical course of the patients was followed for 6 months. Methods and Results: This is a multicenter prospective observational study evaluating the change rate in lesion volume from baseline with magnetic resonance images, as the primary endpoint. In addition, disease severities, performance status (PS), pain visual analog scale (VAS) score, quality of life (QoL), infections, and coagulation markers were also evaluated. Thirty-four patients (VM = 17, KTS = 17, 1-53 of age; median 15.9 years) with measurable lesion volume were analyzed. There was no statistically significant difference in the lesion volume between baseline and day 180, and the mean change rate (standard deviation) was 1.06 (0.28). There were no baseline characteristics that affected the change in lesion volume over 6 months. However, there were patients who showed more than 20% volume change and it was suggested that the lesion volume was largely impacted by local infection. There were no statistically significant changes in pain VAS score, severity, PS, QoL score, D-dimer, and platelet count over 6 months within all patients analyzed. Conclusion: The results showed the representative natural course of VM and KTS for a 6-month period with objective change of lesion volume and other factors, suggesting that it is scientifically reasonable to conduct a Phase 2 proof-of-concept study without a placebo arm, using the results of this study as the control. Clinical Trial Registration: NCT04285723, NCT04589650.

Value of the short time inversion recovery sequence of magnetic resonance imaging in the staging of Klippel-Trenaunay syndrome complicated with lymphedema.

OBJECTIVE: Currently, the focus on limb lymphedema (LE) is on classification and staging. However, few scholars have conducted staging for Klippel-Trenaunay syndrome complicated LE (KTS-LE). This study aimed to investigate the value of the short time inversion recovery sequence of magnetic resonance imaging (MRI) in the staging of KTS-LE. METHODS: Forty-six patients who were diagnosed with KTS-LE were recruited for this retrospective study from July 2011 to November 2022. Referring to the clinical staging standard of lower extremity LE of the International Society of Lymphology in 2020, all patients were divided into three groups: stages I, II, and III. The MRI indicators of the three groups were recorded and statistically compared: LE range (unilateral bilateral, lower limbs, only thighs, only calves and ankles), abnormal parts (skin thickening, abnormal subcutaneous fat signal, abnormal muscle signal, muscle hypertrophy or contraction, abnormal bone signal, hyperostosis), and subcutaneous soft tissue signs (parallel line sign, grid sign, band sign, honeycomb sign, lymph lake sign, crescent sign, and nebula sign). RESULTS: There was a significant difference in the honeycomb sign among the three periods (P = .028). There was a significant difference between stage II and stage I disease (P < .05). There was a significant difference between stage II and stage III disease (P < .05). The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the honeycomb sign in diagnosing KTS-LE of stage II were 87.5%, 63.2%, 33.3%, 96.0%, and 67.4%, respectively. In contrast, the other signs were not statistically significant among the three periods. CONCLUSIONS: The short time inversion recovery sequence of MRI is of great value in KTS-LE. The honeycomb sign is an important imaging indicator for the diagnosis of stage II disease. It is necessary to evaluate the severity of edema with MRI for KTS-LE, which is very important for therapeutic options.

Vascular Anomaly Syndromes in the ISSVA Classification System: Imaging Findings and Role of Interventional Radiology in Management.

Vascular anomalies encompass a spectrum of tumors and malformations that can cause significant morbidity and mortality in children and adults. Use of the International Society for the Study of Vascular Anomalies (ISSVA) classification system is strongly recommended for consistency. Vascular anomalies can occur in isolation or in association with clinical syndromes that involve complex multifocal lesions affecting different organ systems. Thus, it is critical to be familiar with the differences and similarities among vascular anomalies to guide selection of the appropriate imaging studies and possible interventions. Syndromes associated with simple vascular malformations include hereditary hemorrhagic telangiectasia, blue rubber bleb nevus syndrome, Gorham-Stout disease, and primary lymphedema. Syndromes categorized as vascular malformations associated with other anomalies include Klippel-Trenaunay-Weber syndrome, Parkes Weber syndrome, Servelle-Martorell syndrome, Maffucci syndrome, macrocephaly-capillary malformation, CLOVES (congenital lipomatous overgrowth, vascular malformations, epidermal nevi, and scoliosis, skeletal, and spinal anomalies) syndrome, Proteus syndrome, Bannayan-Riley-Ruvalcaba syndrome, and CLAPO (capillary malformations of the lower lip, lymphatic malformations of the face and neck, asymmetry of the face and limbs, and partial or generalized overgrowth) syndrome. With PHACES (posterior fossa malformations, hemangiomas, arterial anomalies, cardiac defects and/or coarctation of the aorta, eye abnormalities, and sternal clefting or supraumbilical raphe) syndrome, infantile hemangiomas associated with other lesions occur. Diagnostic and interventional radiologists have important roles in diagnosing these conditions and administering image-guided therapies-embolization and sclerotherapy, and different ablation procedures in particular. The key imaging features of vascular anomaly syndromes based on the 2018 ISSVA classification system and the role of interventional radiology in the management of these syndromes are reviewed. Online supplemental material is available for this article. ©RSNA, 2022.

Options in the treatment of superficial and deep venous disease in patients with Klippel-Trenaunay syndrome.

OBJECTIVE: Klippel-Trenaunay syndrome (KTS) is a congenital mixed mesenchymal malformation syndrome that includes varicose veins, capillary and venous malformations, lymphatic abnormalities, and hypertrophy of various connective tissue elements. The purpose of the present study was to describe the clinical characteristics and outcomes in a subset of patients with KTS in whom venous interventions, including iliofemoral venous stenting, were performed after failure of conservative therapy. METHODS: A single-center retrospective data review of 34 patients with KTS who had undergone interventions for venous disease between January 2000 and December 2020 was performed. RESULTS: Their mean age was 38.4 ± 17.5 years (range, 12-80 years). No gender predilection was found. Of the 34 patients, 61% had had all three features of the classic triad for KTS. Varicose veins were present in all 34 patients (100%), and 30% had had a history of bleeding varicosities. Most patients (79%) had CEAP (Clinical, Etiology, Anatomy, and Pathophysiology) class ≥C4. Of the 34 patients, 30% had a history of deep vein thrombosis and/or pulmonary embolism. Factor VIII elevation was the most common thrombophilia condition (12%). The venous filling index was elevated at baseline (5.9 ± 5.1 mL/s) and did not normalize despite intervention (3.5 ± 2.3 mL/s; P = .04). The superficial venous interventions (n = 35) included endovenous laser therapy; stripping of the great saphenous vein, small saphenous vein, anterior thigh vein, or marginal vein; ultrasound-guided sclerotherapy; and stab avulsion of varicose veins. One coil embolization of a perforator vein was performed. Deep interventions (n = 19) included endovenous stenting (n = 15), popliteal vein release (n = 3), and valvuloplasty (n = 1). The venous clinical severity score had improved from 9.4 ± 4.5 to 6.2 ± 5.6 (P = .04). The visual analog scale for pain score had improved from 5.5 ± 2.7 to 2.5 ± 3.3 (P = .008). Healing of ulceration was noted in 75% of the patients. Significant improvements in the total pain (P = .04) and total psychological (P = .03) domains were noted in the 20-item chronic venous disease quality of life questionnaire. CONCLUSIONS: Superficial and deep venous interventions are safe and effective in patients with KTS when conservative therapy has failed. Iliofemoral venous stenting is a newer option that should be considered in the treatment of chronic deep venous obstructive disease in patients with KTS in the appropriate clinical context. An aggressive perioperative deep vein thrombosis prophylaxis protocol should be in place to reduce thromboembolic complications in these patients.

Breast Hemangioma: Unique Presentation in a Patient with Klippel- Trenaunay-syndrome.

BACKGROUND: Klippel-Trénaunay-Syndrome (KTS) is characterized by a triad of varicose veins, port-wine stain and soft tissue or bony hypertrophy, and the diagnosis of KTS can be made if any two of these three features are present. Hemangiomas in various locations, e.g., skull, brain, epidural and vertebral hemangioma, mediastinal, colonic hemangioma, intraneural/intramuscular hemangiomas, are reported with KTS. CASE PRESENTATION: Benign vascular tumors may rarely develop malignant transformation as Bugarin- Estrada et al. reported breast angiosarcoma in a patient diagnosed as Klippel-Trenaunay-Syndrome. We reported a case of a 40-year-old female with a known case of Klipple-Trenaunay-Syndrome with left leg varicosities, cutaneous nevus, as well as unfortunate development of deep venous thrombosis and markedly enlarged right breast hemangioma. Due to low incidence or lack of early detection of breast hemangioma, its diagnosis is challenging. CONCLUSION: The history of the patient and multi-modality imaging utilization can help in early and accurate diagnosis of diseases leading to better prognosis.

A neonate with Klippel-Trénaunay syndrome: a case report.

BACKGROUND: Klippel-Trénaunay syndrome is a rare congenital capillary-lymphatic-venous condition characterized by the clinical triad of capillary malformations (port wine stains), varicose veins with or without venous malformations, and bony and/or soft-tissue hypertrophy. It has a very low incidence of about 1:100,000. CASE PRESENTATION: We report the case of 21-day-old neonate Black African female (born in Uganda) with Klippel-Trénaunay syndrome who presented with macrodactyly and ectrodactyly on the left foot, as well as numerous port wine stains on the left thoracoabdominal region and anteroposterior left lower limb. Color Doppler ultrasound examination of the left lower limb and abdomen revealed varicose veins without signs of arteriovenous fistula. CONCLUSION: The report presents the case of a neonate with a rare congenital vascular disorder type Klippel-Trénaunay syndrome.

Case Series of Concomitant Klippel-Trenaunay Syndrome and May-Thurner Syndrome.

Klippel-Trenaunay syndrome is a rare vascular disorder which includes leg swelling, or lower extremity deep venous reflux/thrombosis as a presenting symptom. May-Thurner syndrome is also a rare pathology involving compression of the left common iliac vein, usually by the right common iliac artery. The incidence of concomitant occurrence of these entities is unknown and not well reported. This case series describes 3 patients who underwent evaluation of symptomatic left lower extremity venous disease. All 3 suffered symptomatic Klippel-Trenaunay initially, and were subsequently diagnosed with concomitant May-Thurner Syndrome. They were successfully treated with left common iliac vein stents with symptomatic improvement.

Prevalence and inventory of venous anatomical abnormalities in the arms of patients with combined capillary, venous and lymphatic malformations (Klippel-Trénaunay syndrome).

OBJECTIVES: To investigate the prevalence of arm-involvement in Klippel-Trénaunay syndrome (KTS)-patients and to describe the venous anatomy and/or venous aberrations present in the arm, and if possible, their relationship to complaints (pain, congestion and thromboembolic events). METHODS: A retrospective cohort-study was performed with data from medical records of a large KTS-cohort (n = 173) from a tertiary referral center. Within this cohort, a descriptive study (n = 12) was performed on the KTS-patients with arm involvement and who had been examined with Colour Duplex Ultrasonography (CDU). RESULTS: Our KTS-cohort (n = 173) comprised 43 patients (24.9%) with arm-involvement; in nineteen patients (11.0%) the arm was the only affected limb. Of those KTS patients investigated with CDU, 9 out of 12 (75%) had an aberrant venous anatomy. CONCLUSION: Future research needs to clarity whether the complaints of KTS-patients in general are caused by an aberrant venous anatomy, coagulation alterations and/or other factors. Herein, the KTS-arms may play an important role.

Chiari I malformation with Klippel-Trenaunay syndrome: case report and review of the literature.

We present a rare case of an 8-year-old male with Klippel-Trenaunay syndrome (KTS) and a Chiari I malformation (CIM). Magnetic resonance imaging (MRI) to investigate facial asymmetry and speech delay at age two revealed CIM with cerebellar tonsils 1.3 cm below the foramen magnum without syringomyelia. The patient underwent a craniectomy and posterior fossa decompression with C1 laminectomy. While gene sequencing determined the patient was negative for the PIK3CA gene mutation, the patient's clinical history strongly suggests KTS. He has hemihypertrophy, leg length discrepancy, hemangiomas and pigmentary mosaicism along the upper and lower extremities, heart murmur, chronic low heart rate, recurrent hip pain, and mild scoliosis. Neurodevelopmental concerns include difficulty reading, attention deficit hyperactivity disorder (ADHD), anxiety, and difficulty running and going downstairs. His most recent MRI shows good decompression at the cervicomedullary junction, global cerebrospinal fluid (CSF) flow, and less peg-like cerebellar tonsils. Also noted were two intravertebral hemangiomas at T5 and T6. While the patient's speech has improved, there is still difficulty with the expressive language. He still has mild delays, runs slowly, and does not alternate feet when climbing stairs. The patient is being followed by multiple specialists including neurology, hematology-oncology, genetics, orthopedic surgery, and developmental pediatrics.

Spinal Neurovascular Malformations in Klippel-Trenaunay Syndrome: A Single Center Study.

BACKGROUND: A number of studies have demonstrated spinal anomalies associated with Klippel-Trenaunay syndrome (KTS). To date, there are no large consecutive series examining the prevalence and subtype distribution of spinal neurovascular malformations in patients with KTS. OBJECTIVE: To report the spectrum and incidence of spinal neurovascular manifestations in the KTS population. METHODS: This was a cross-sectional study. Consecutive patients with definite KTS as defined by International Society for the Study of Vascular Anomalies criteria who underwent spinal neuroimaging at our institution were included. All studies were evaluated by a staff neuroradiologist and a senior radiology resident for the presence of developmental venous anomalies, cavernous malformations (CMs), and arteriovenous shunts (AVS). RESULTS: A total of 116 patients with definite KTS who underwent spinal neuroimaging were included. A total of 23 neurovascular anomalies were found in 19 patients (16.4%), including 4 patients with multiple anomalies. These included 5 patients with spinal cord CMs (4.3%), 14 patients with a paraspinal or epidural venous malformation (12.1%), and 4 patients with an AVS (3.4%). Of the AVS, 3 were epidural arteriovenous fistulas, 1 of which likely formed de novo in an epidural venous malformation. One was a conus medullaris arteriovenous malformation. CONCLUSION: Our study cohort of 116 KTS patients demonstrated a wide spectrum of spinal neurovascular anomalies with a relatively high prevalence. Potential phenotypic descriptions of KTS should include the possibility for spinal neurovascular anomalies.