Combined Vascular Malformations Research Articles

Rare case of combined vascular malformation of the face: a successful surgical management.

Combined vascular malformation affecting the facial region is an extremely rare clinical entity that is debilitating both functionally and emotionally. Treatment warrants a multidisciplinary approach with the aim of removing the vascular anomalies and ameliorating any functional facial disfigurement. Here, we present a case of a 40-year-old female with combined vascular malformation of the face who was treated successfully with surgical intervention accompanying significant resolution of facial disfigurement.

Clinical Values of Whole-Body Blood Pool Scans and SPECT for Evaluation of Congenital Vascular Malformation.

This study examines the diagnostic potential of whole-body blood pool scintigraphy (WBBPS) using technetium-99m-labeled red blood cells to detect congenital vascular malformations (CVMs). It aims to compare its efficacy with traditional imaging techniques such as magnetic resonance imaging (MRI) and ultrasonography (USG), emphasizing its potential advantages in terms of characterization of lesions and capacity for whole-body assessment. The efficacy of WBBPS and single-photon emission computed tomography (SPECT)/computed tomography (CT) imaging in diagnosing CVMs, comparing them with USG and MRI results, was evaluated in this retrospective study. Of the 38 patients, 21 were evaluated using these diagnostic methods, with CVMs classified according to the International Society for the Study of Vascular Anomalies guidelines. Also, this study aimed to elucidate the characteristics between WBBPS, SPECT/CT, USG, or MRI findings and their consistency with the final diagnosis. A total of 21 participants were included in this study, with an average age of 17.7 years old, with female predominance (57.1%). The most common diagnosis was vascular malformations (VMs) (71.4%), followed by combined vascular malformations (14.3%) and lymphatic malformations (9.5%). WBBPS demonstrated positive results in 95.2% of cases. Distinct imaging patterns for each condition were observed, with WBBPS being crucial in locating lesions. The study findings suggested that WBBPS with SPECT/CT could be helpful in detecting occult VM lesions and ruling out a lymphatic malformation diagnosis. Thus, it can be employed in the evaluation of CVMs.

Targeted next-generation sequencing for detection of PIK3CA mutations in archival tissues from patients with Klippel–Trenaunay syndrome in an Asian population

BackgroundKlippel–Trenaunay syndrome (KTS) is a rare slow-flow combined vascular malformation with limb hypertrophy. KTS is thought to lie on the PIK3CA-related overgrowth spectrum, but reports are limited. PIK3CA encodes p110α, a catalytic subunit of phosphatidylinositol 3-kinase (PI3K) that plays an essential role in the PI3K/AKT/mammalian target of rapamycin (mTOR) signaling pathway. We aimed to demonstrate the clinical utility of targeted next-generation sequencing (NGS) in identifying PIK3CA mosaicism in archival formalin-fixed paraffin-embedded (FFPE) tissues from patients with KTS.ResultsParticipants were 9 female and 5 male patients with KTS diagnosed as capillaro-venous malformation (CVM) or capillaro-lymphatico-venous malformation (CLVM). Median age at resection was 14 years (range, 5–57 years). Median archival period before DNA extraction from FFPE tissues was 5.4 years (range, 3–7 years). NGS-based sequencing of PIK3CA achieved an amplicon mean coverage of 119,000x. PIK3CA missense mutations were found in 12 of 14 patients (85.7%; 6/8 CVM and 6/6 CLVM), with 8 patients showing the hotspot variants E542K, E545K, H1047R, and H1047L. The non-hotspot PIK3CA variants C420R, Q546K, and Q546R were identified in 4 patients. Overall, the mean variant allele frequency for identified PIK3CA variants was 6.9% (range, 1.6–17.4%). All patients with geographic capillary malformation, histopathological lymphatic malformation or macrodactyly of the foot had PIK3CA variants. No genotype–phenotype association between hotspot and non-hotspot PIK3CA variants was found. Histologically, the vessels and adipose tissues of the lesions showed phosphorylation of the proteins in the PI3K/AKT/mTOR signaling pathway, including p-AKT, p-mTOR, and p-4EBP1.ConclusionsThe PI3K/AKT/mTOR pathway in mesenchymal tissues was activated in patients with KTS. Amplicon-based targeted NGS could identify low-level mosaicism from low-input DNA extracted from FFPE tissues, potentially providing a diagnostic option for personalized medicine with inhibitors of the PI3K/AKT/mTOR signaling pathway.

Interdisciplinary management of a combined vascular malformation of the orbit

Interdisciplinary management of a combined vascular malformation of the orbit

Occurrence of Rhabdomyosarcoma After Surgery Combined with oral Sirolimus for Mixed Vascular Malformation of the Tongue.

Vascular malformation is the general term of a kind of lesions originated from lymphatic vessels and vascular tissues, which contains a variety of components called mixed vascular malformation. Rhabdomyosarcoma (RMS) is a kind of soft tissue sarcoma, originating from striated muscle cells or mesenchymal cells. RMS and vascular malformation mostly occur in children, and common in the head and neck, but their simultaneous occurrence is rare. A 9-year-old boy who was hospitalized for a second attack of combined vascular malformation: hemolymphangioma. The child experienced severe upper airway obstruction and tongue bleeding. Postoperative pathology demonstrated hemolymphangioma combined with RMS. Subsequently, he was transferred to the oncology department for chemotherapy and lately died of RMS with lung metastasis. The secondary RMS may be related to the usage of sirolimus. Because of its uncertain border, vascular malformation in the oral and maxillofacial region is difficult to completely remove by surgical resection, and local recurrence could be often observed. Due to its rapid progress and continuous bleeding, the possibility of malignant tumor should be considered and multidisciplinary comprehensive treatment should be actively taken. Besides, family history of related malignant tumors and immune function should be investigated in detail before choosing the application of oral sirolimus.

Unusual case of Parkes-Weber syndrome in a patient with spontaneous subarachnoid hemorrhage

Introduction. Parkes-Weber syndrome (PWS) is a complex and rare genetic disease of combined vascular malformations that primarily occur in the extremities and can involve the pelvic blood vessels. In extremely rare cases, the disease is manifested by endocranial and spinal involvement. The treatment of such patients represents a challenge for neurosurgical centers and requires a multidisciplinary approach. Case report. We present the case of a 46-year-old male patient admitted to the emergency department due to spontaneous subarachnoid hemorrhage (SAH), moderate flaccid paraparesis, and urinary incontinence. The patient was previously diagnosed with PWS, while the genetic evaluation proved the RASA1 gene mutation. Furthermore, he experienced a spontaneous SAH and was hospitalized 26 years ago, while six years ago, he underwent a right nephrectomy due to multiple hilar aneurysms of the right renal artery and its branches. Digital subtraction angiography of the endocranium was performed, which detected no aneurysmal dilatations or arteriovenous malformations (AVM). The magnetic resonance imaging recorded spinal intradural AVM in the vertebral levels between T12 and L3, which completely filled the dural sac. After the conservative treatment, there was a significant improvement in the patient?s neurological and clinical condition. Conclusion. To the best of our knowledge, this is the only case report of a patient with PWS who had a spinal intradural AVM and spontaneous SAH without high-output heart failure and with a history of a previous nephrectomy.

Chronic Recalcitrant Lesions of an Enlarged Limb: Consider Parkes Weber Syndrome

Parkes Weber syndrome represents a very rare combined congenital vascular malformation that can lead to chronic leg ulcers in young age groups [1]. We report the case of a patient with dragging leg ulcerations treated as venous ulcers in adulthood.

Retrospective Study of Hematologic Complications in Vascular Malformation Patients with Localized Intravascular Coagulopathy Undergoing Surgical Intervention

BACKGROUNDSlow-flow vascular malformations such as multifocal or extensive venous (VM), venous-lymphatic (VLM), capillary-venous (CVM) and capillary-lymphatic-venous malformations (CLVM), are commonly associated with spontaneous thrombosis and thrombolysis, a phenomenon termed localized intravascular coagulopathy (LIC). LIC is characterized by elevated D-dimer, low fibrinogen, and/or mild thrombocytopenia and may progress to disseminated intravascular coagulopathy. Individuals with LIC are at an increased risk for hematological complications, particularly when undergoing surgical procedures on or near the vascular malformation. The pathogenesis of this coagulopathy is unknown but thought to be secondary to slow blood flow, consumption of coagulation factors, abnormal endothelium and loss of protective anticoagulant factors. The exact mechanism of dysregulation of the coagulation pathway and the resultant hematologic complications remains largely unstudied. Furthermore, many institutions are empirically using peri-procedural LMWH in attempt to decrease morbidity in individuals with LIC despite supportive evidence. This work will be the largest retrospective study investigating post-procedural hematologic complications in children and young adults with vascular malformations as only case reports and series have been published to date. METHODRetrospective chart review was conducted of medical records of adult and pediatric patients with slow-flow vascular malformations with LIC who underwent a surgical intervention and/or sclerotherapy procedure at Cincinnati Children's Hospital Medical Center from 7/1/2008 to 12/31/2016. LIC was defined by high D-dimer (5 times upper limit of normal), fibrinogen <150mg/dL and/or platelet count <150K/mcL. Hematologic complications included any clinically relevant bleeding or clotting abnormality that occurred intra-operatively, 2 weeks post-procedure and/or while on LMWH prophylaxis, up to 2 weeks, prior to surgery. Use of LMWH including dose, frequency and course length was evaluated. RESULTSThirty-nine patients with slow-flow vascular malformations with associated LIC (24 with extensive VM/VLM, 9 with multiple VM/VLM, 4 with CLVM, 2 with localized VM/VLM) underwent a total of 236 sclerotherapy procedures with 86% occurring in individuals under 18 years of age. At our institution, LMWH was administered at 0.5mg/kg/dose once daily for 2 weeks before and after sclerotherapy in 87% of sclerotherapy cases. No thrombotic complications occurred in children. One adult patient on LMWH at treatment dosing developed pulmonary emboli (PE), presumably from deep vein thrombosis (DVT) of the treated extremity; the patient was a known smoker with a history of DVT/PE. In 5 patients fibrinogen levels dropped below 100 mg/dL post-sclerotherapy for which cryoprecipitate was administered and no bleeding complications occurred. No intra-op bleeding or thrombotic events occurred.Total of 104 patients with slow flow malformations underwent 265 procedures represented by all major surgical subspecialties, excluding sclerotherapy. Twenty-seven (26%) of these patients had evidence of LIC prior to surgery. Eight significant bleeding episodes and 3 thrombotic events occurred; seven (64%) of which occurred in patients with known LIC. Two patients had both a clotting and hemorrhagic event. Although complications occurred similarly in both children and adults, 100% of the hematogic complications occurred in patients with extensive combined vascular malformations , most with venous ectasias. The dosing, course length and frequency of LMWH use was highly variable among patients undergoing surgery. CONCLUSIONSProphylactic LMWH use was common in this patient population and did not appear to increase the risk of significant bleeding before, during or after sclerotherapy. Thrombotic events after sclerotherapy appear rare but may still occur. In patients with known LIC, attempts to correct coagulation abnormalities should be made prior to undergoing major surgical interventions. Further studies evaluating peri-procedural LMWH are needed to determine benefit and optimal dosing. Collaborative plans exist to combine data with Boston Children's Hospital so that future studies will allow for comparative effectiveness analysis of LMWH use at different doses in this patient population. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Nosological Consideration of Arterial Aneurysms Associated with Klippel-Trenaunay Syndrome.

Klippel–Trenaunay syndrome (KTS) is a rare slow-flow combined vascular malformation characterized by capillary-lymphatic-venous lesions with soft tissue overgrowth of the limbs. We report the case of a 37-year-old female KTS patient with a deep femoral arterial aneurysm. We finally diagnosed that the aneurysm had resulted from a fundamental defect in the arterial wall structure. We discuss whether the use of “aneurysm associated with KTS” is accurate and how to better classify this type of capillary-venous lesion in 17 reported KTS patients with arterial aneurysms. In this review, we describe nosological problems of arterial aneurysms associated with KTS.

Treatment of superficial vascular anomalies with topical sirolimus: A multicenter case series.

Systemic sirolimus (rapamycin) has recently been found effective in treating complex vascular anomalies by reducing the size and associated complications. Many vascular anomalies have a cutaneous component, and thus, we sought to determine whether topical administration of sirolimus may be an effective therapy, as data on the use of topical sirolimus are limited. We reviewed the efficacy and tolerability of topical formulations of sirolimus in the treatment of various simple and combined vascular malformations and tumors. Eighteen patients with any vascular anomaly treated exclusively with topical sirolimus were retrospectively reviewed. Eleven patients had combined venous lymphatic malformations, three had tufted angiomas, two had a lymphatic malformation, one had a venous malformation, and one had a verrucous venous malformation. All (100%) patients reported some degree of improvement and 50% of patients reported marked improvement in one or more symptoms, most commonly blebs and lymphatic drainage, and bleeding. The retrospective nature, small number of patients, and differences in topical preparations limit the broad application of the results. Topical sirolimus appears to be a safe and useful non-invasive therapy that is well-tolerated in the treatment of the cutaneous portion of a variety of vascular anomalies.

Orthopaedic diagnoses in patients with Klippel-Trenaunay syndrome.

PurposeKlippel-Trenaunay syndrome (KTS) is a rare combined vascular malformation composed of capillary malformation, lymphatic and/or venous malformation and limb overgrowth, which commonly affects the extremities. Due to limb involvement, it is not uncommon for these patients to require referral to an orthopaedic surgeon. Herein we reviewed the prevalence of orthopaedic diagnoses in a large cohort of KTS patients and described the associated surgical interventions.MethodsBetween 1976 and 2012, 410 patients fulfilling strict criteria for KTS were evaluated at a single institution. Patient charts were reviewed for demographic information, details of the clinical evaluation, orthopaedic consultation and surgical interventions.ResultsA total of 264 of 410 patients (64%) with confirmed KTS required orthopaedic evaluation. Of these 264 patients, 84% had documented limb-length discrepancy. Other common diagnoses included: angular deformities (10%), scoliosis (9%), osteopenia/osteoporosis (7%), pathological fractures (6%), joint contracture (5%), degenerative joint disease (4%) and limb/joint pain (4%). Of the 264 patients evaluated by orthopaedic surgery, 133 patients (50.4%) underwent 169 surgeries. Surgery was most commonly performed for limb-length discrepancy (62%). Multivariable analysis confirmed an orthopaedic condition was more likely in patients with lymphatic malformation (odds ratio (OR) 3.78; p < 0.001), as well as in those with bone and/or soft-tissue hypertrophy of the lower extremity (OR 7.51; p < 0.001) or foot (OR 3.23; p < 0.001).ConclusionOrthopaedic conditions are common in patients with KTS and approximately 50% require surgical intervention. Those with a lymphatic malformation and/or soft-tissue hypertrophy of the lower extremity are more likely to need surgery.Level of EvidenceLevel IV, Descriptive Case Series

Effect of sirolimus on coagulopathy of slow-flow vascular malformations.

Stagnant blood flow present in slow-flow vascular malformations can lead to localized intravascular coagulopathy (LIC), measured by elevated D-dimer levels, low fibrinogen, and/or thrombocytopenia. LIC can lead to localized thrombosis and/or bleeding, resulting in pain, swelling, and functional limitations. Patients with complex vascular malformations treated with sirolimus show clinical improvement in these symptoms. We hypothesized that the clinical benefits of sirolimus may correlate with improvements in coexisting LIC. A retrospective chart review was performed, including D-dimer, fibrinogen, and platelet count, in patients with slow-flow vascular malformations treated with sirolimus. Laboratory values were assessed at three time points (presirolimus, 1-3 months postsirolimus, and last clinic visit). Clinical response, as defined by decreased pain and swelling, was extracted from the record. Thirty-five patients at our vascular anomalies center had been prescribed sirolimus between 2014 and 2017. Fifteen patients (12 combined slow-flow vascular malformations and three pure venous malformations) remained after excluding patients that did not have adequate records or a venous component to their vascular malformation. Patients who did not adhere to the treatment were also excluded. All 15 had elevated D-dimer levels prior to treatment and there was a statistically significant decrease in D-dimer levels following treatment with sirolimus. Symptomatic improvement of pain and swelling was reported after 3 months of starting sirolimus in 13/15 patients. This study suggests that sirolimus improves coagulopathy in slow-flow vascular malformations, as evidenced by reduced D-dimer levels. Improvement in LIC symptoms also correlates with sirolimus-corrected coagulopathy.

Wound-Healing Problems Associated with Combined Vascular Malformations in Klippel-Trenaunay Syndrome.

Significance: In Klippel-Trenaunay syndrome (KTS), management of a wound in the affected limb can be difficult because of the underlying vascular malformations present. This review describes the characteristics of KTS with wound complications in light of the genetic and molecular mechanisms of the disease. Recent Advances: KTS is a slow-flow combined vascular malformation characterized by the triad of capillary malformation, venous malformation with or without lymphatic malformation, and limb overgrowth. KTS is encompassed within the phosphatidylinositol-4,5-bisphosphate3-kinase catalytic subunit alpha (PIK3CA)-related overgrowth spectrum (PROS), having recently been linked to activating mutations in the PIK3CA gene. This clearly has implications for both molecular diagnosis and potential treatment strategies for the disease. Critical Issues: KTS should be distinguished from Parkes Weber syndrome, a fast-flow-type combined vascular malformation with limb overgrowth. Individualized management is needed for KTS and should be focused on the treatment of symptoms. Future Directions: Targeted therapies that inhibit the phosphoinositide 3-kinase signaling pathway are a potential treatment option for PROS.

Combined surgical and medical treatment of a retroperitoneal lymphatic-venous malformation presenting with significant haemorrhage

Abstract Lymphatic-venous malformations are rare congenital defects resulting from the abnormal communication between lymphatic vessels and systemic circulation, integrating the group of combined vascular malformations, with low-flow. They affect both genders equally and present preferably in the head and neck (>90%), rarely in retroperitoneal location. Clinical diagnosis can be challenging since presentation is highly variable. Surgical resection is the gold standard but, in complex malformations or when facing incomplete surgical resection due to inaccessible location, combined medical and surgical approaches can improve the prognosis. The authors report a case concerning a three-month-old infant with a retroperitoneal lymphatic-venous malformation, with an uncommon life-threatening presentation and a successful combined medical and surgical approach. In the light of this case report, a specific literature review is discussed.

Fingertip Capillary Malformation and Associated Disorders: Report of 9 Cases.

Although capillary malformations (CMs) are not usually serious health problems in themselves, they can occasionally be warning signs for syndromes with more serious or aggressive vascular malformations not readily apparent at birth or on initial examination. We describe a series of 9 patients with a common phenotype: (1) CM on the fingertips; (2) associated combined vascular (lymphatic-venous) malformations on the trunk and/or extremities; and (3) in some cases, partial overgrowth and asymmetry of the extremities. Data were collected retrospectively for patients with CM on the fingertips who were treated at 2 Vascular Anomalies Centers from January 2006 to January 2016. All the patients presented CM and other associated vascular abnormalities from birth. CMs were centripetal in their distribution. The greater the centripetal progression of the CM, the greater the associated vascular malformation observed. Some patients also presented varying degrees of overgrowth and asymmetry. At present, we have not found a patient with CM of the fingertip without associated anomalies. In conclusion, we present a series of patients with a particular morphology of CM located on the fingertips. All cases were associated with lymphatic-venous malformations at other sites. These data lead us to recommend these patients be referred from birth to a multidisciplinary unit of vascular anomalies.

A rare association of angiokeratoma circumscriptum with Klippel Trenaunay syndrome

&lt;p class="abstract"&gt;&lt;span lang="EN-IN"&gt;Klippel-Trenaunay syndrome (KTS) is a rare congenital disorder of blood and lymphatic vessels that is characterised by a combined vascular malformation of the capillaries, veins and lymphatics, congenital abnormalities, and associated limb hypertrophy. It may also involve gastrointestinal tract which can lead to life threatening bleeding. This syndrome presents since birth to early infancy or childhood with equal distribution in both genders. An adolescent female presented with right lower limb hypertrophy with port wine stain and overlying hemorrhagic vesiclessince birth. Histopathology of these hemorrhagic vesicles angiokeratoma. On the basis of history and classical clinical triad patient was diagnosed as KTS with angiokeratoma, an association rarely reported in literature.&lt;/span&gt;&lt;/p&gt;

Venous anastomosis procedure for treatment of lymphatic malformation in Klippel-Trenaunay syndrome

Abstract Klippel-Trenaunay syndrome (KTS) is a congenital vascular anomaly in children, which requires treatment but challenging. The characteristics of KTS include disproportionality of the affected limbs, usually with enlargement due to lymphatic malformation (LM) [1]. Sometimes the condition is accompanied by pain that is difficult to treat. Compression therapy is one option for reducing the swelling; however, this has limitations [2]. We previously reported that lymphatic venous anastomosis (LVA) may be a safe and effective procedure for reducing the size of micro cystic type LM by decreasing the intra cystic lymph [3]. We treated a case of KTS in a 9-year-old boy who had improvement of lower abdominal swelling and penile pain after a single LVA. The method involved is to make a bypass, from the afferent lymph-collecting vessel to subcutaneous veins. However, to apply LVA to LM, it is sometimes problematic to detect the afferent flow in combined vascular malformations, such as KTS. Therefore, we performed VA making a bypass directly from LM, instead. We classify two types of LVA methods for LM: afferent lymph vessel LMVA (A-LMVA), and sidewall LMVA (S-LMVA). S-LMVA has more merits than the previously reported A-LMVA.

Combined and complex vascular malformations

The correct diagnosis of vascular malformations is obtainable by clinical assessment and patient history in the majority of cases. Nonetheless, confusion in nomenclature, existence of multiple classifications and rarity of these lesions leads to misdiagnosis and related wrong treatment. This is especially the case in combined or complex vascular malformations or vascular malformations that are part of syndromes as these have overlapping clinical and imaging features. New entities in the field of vascular anomalies have been described recently like fibro-adipose vascular anomaly or central conducting lymphatic anomalies.

Differential Diagnosis of Lower Extremity Enlargement in Pediatric Patients Referred with a Diagnosis of Lymphedema

There are many causes for a large lower limb in the pediatric age group. These children are often mislabeled as having lymphedema, and incorrect diagnosis can lead to improper treatment. The purpose of this study was to determine the differential diagnosis in pediatric patients referred for lower extremity "lymphedema" and to clarify management. The authors' Vascular Anomalies Center database was reviewed between 1999 and 2010 for patients referred with a diagnosis of lymphedema of the lower extremity. Records were studied to determine the correct cause for the enlarged extremity. Alternative diagnoses, sex, age of onset, and imaging studies were also analyzed. A referral diagnosis of lower extremity lymphedema was given to 170 children; however, the condition was confirmed in only 72.9 percent of patients. Forty-six children (27.1 percent) had another disorder: microcystic/macrocystic lymphatic malformation (19.6 percent), noneponymous combined vascular malformation (13.0 percent), capillary malformation (10.9 percent), Klippel-Trenaunay syndrome (10.9 percent), hemihypertrophy (8.7 percent), posttraumatic swelling (8.7 percent), Parkes Weber syndrome (6.5 percent), lipedema (6.5 percent), venous malformation (4.3 percent), rheumatologic disorder (4.3 percent), infantile hemangioma (2.2 percent), kaposiform hemangioendothelioma (2.2 percent), or lipofibromatosis (2.2 percent). Age of onset in children with lymphedema was older than in patients with another diagnosis (p = 0.027). "Lymphedema" is not a generic term. Approximately one-fourth of pediatric patients with a large lower extremity are misdiagnosed as having lymphedema; the most commonly confused causes are other types of vascular anomalies. History, physical examination, and often radiographic studies are required to differentiate lymphedema from other conditions to ensure the child is managed appropriately.

Late-Onset Eccrine Angiomatous Hamartoma Associated with a Ganglion Cyst on the Sole of the Foot

Eccrine angiomatous hamartoma (EAH) is a benign, uncommon, combined vascular and eccrine malformation. Most cases of this disorder have been single or multiple nodules or plaques that appear red, yellow, blue, violaceous, or skin colored. EAH may be congenital or appear later in childhood; it rarely arises during puberty or adulthood. A 52-year-old female patient visited our department for tender subcutaneous cystic tumor on the right sole with a one month history. Histopathologic examination confirmed EAH. During excisional biopsy procedure, mucinous discharges were observed which were histopathologically diagnosed as ganglion.