Cerebral dural arteriovenous fistulas in patients with PTEN-related hamartoma tumor syndrome.

Central nervous system (CNS) dural arteriovenous fistulas (DAVF) have been reported in PTEN-related hamartoma tumor syndrome (PHTS). However, PHTS-associated DAVF remain an underexplored field of the PHTS clinical landscape. Here, we studied cases with a PTEN pathogenic variant identified between 2007 and 2020 in our laboratory (n = 58), and for whom brain imaging was available. Two patients had DAVF (2/58, 3.4%), both presenting at advanced stages: a 34-year-old man with a left lateral sinus DAVF at immediate risk of hemorrhage, and a 21-year-old woman with acute intracranial hypertension due to a torcular DAVF. Interestingly, not all patients had 3D TOF/MRA, the optimal sequences to detect DAVF. Early diagnosis of DAVF can be lifesaving, and is easier to treat compared to developed, proliferative, or complex lesions. As a result, one should consider brain MRI with 3D TOF/MRA in PHTS patients at genetic diagnosis, with subsequent surveillance on a case-by-case basis.

Intramuscular capillary-type hemangioma: Diagnosis, treatment, and outcomes. A French multicentric retrospective study of 66 cases.

PURPOSE: Intramuscular capillary-type hemangiomas (ICTHs) are rare entities, belonging to the group of intramuscular "hemangiomas." The diagnosis remains challenging. We aimed to assess the diagnostic criteria, treatments and outcomes of ICTHs. METHODS: This retrospective study collected all cases of ICTH followed up in 9 French hospital centers, reviewed by an adjudication expert group. RESULTS: Among 133 patients screened, 66 with ICTH were included. The median age of patients at diagnosis was 28.0 years, interquartile range (21.0---36.0). The lesion, mainly presenting as a gradually increasing mass (83.9%), was painless (88.9%) and was located in the head and neck (42.4%). MRI (available in all cases) mainly revealed a well-delineated lesion, isointense to the muscle on T1-weighted images, with enhancement after contrast injection; hyperintense on T2-weighted images; and containing flow voids. Among the 66 cases, 59 exhibited typical ICTH features and 7 shared some imaging features with arteriovenous malformations. These latter were larger than typical ICTHs and more painful and appeared on imaging as less well delimited and more heterogeneous tissue masses, with larger tortuous afferent arteries, earlier draining vein opacification and mild arteriovenous shunting. We propose to name these lesions arteriovenous malformation (AVM)-like ICTH. Pathological reports were similar in typical and AVM-like ICTH, showing capillary proliferation with mainly small-size vessels, negative for GLUT-1 and positive for ERG, AML, CD31 and CD34, with low Ki67 proliferation index (<10%), and adipose tissue. The most frequent treatment for ICTH was complete surgical resection (17/47, 36.2%), preceded in some cases by embolization, which led to complete remission. CONCLUSIONS: ICTH can be diagnosed on MRI when it is typical. Biopsy or angiography are required for atypical forms.

Characteristics, Natural Course and Treatment of Intramuscular Capillary-type Haemangioma: A Systematic Literature Review.

Intramuscular capillary-type haemangiomas (ICTH) are rare vascular anomalies that can easily be misdiagnosed as other entities. A systematic review was performed of all cases of ICTH in the literature since its first description in 1972. An adjudication committee reviewed cases to include only ICTHs. Among 1,143 reports screened, 43 were included, involving 75 patients. The most frequent differential diagnosis was intramuscular venous malformations. The mean age of patients at diagnosis was 21.2 years. ICTH was mainly described as a gradually increasing mass (81.8%), painless (73.9%), that could occur anywhere in the body but most frequently on the head and neck (44.0%). Magnetic resonance imaging (MRI) was mainly used for diagnosis (69.1%) and displayed specific features. The most frequent treatment was complete surgical removal (73.9%), which could be preceded by embolization, and led to complete remission without recurrence in all but 1 case.

French national diagnosis and care protocol (PNDS, protocole national de diagnostic et de soins): cystic lymphatic malformations.

Cystic lymphatic malformations (LMs) are rare chronic conditions which management differs according to the type (macrocystic LMs, microcystic LMs or both). Studies are lacking due to rarity of the pathology. We aimed to establish a French National Diagnosis and Care Protocol (PNDS: Protocole National de Diagnostic et de Soins), to provide health professionals with free open access synthesis on optimal management and care of patients with LMs ( https://www.has-sante.fr/upload/docs/application/pdf/2021-03/malformations_lymphatiques_kystiques_-_pnds.pdf ). The process included a critical review of the literature and multidisciplinary expert consensus. LMs are congenital but are not always discovered at birth. Nearly 75% of them are located in the head and neck because of the highly dense lymphatic system in this region. Physical examination (showing painless masses with normal skin color and depressible consistency, or cutaneous/mucosal lymphangiectasia) and color Doppler ultrasonography, usually allow for diagnosis. MRI (involving T2 sequences with fat saturation in at least two spatial planes) is the tool of choice for evaluating anatomical extension, characterizing lesions (microcystic and macrocystic), and before considering therapeutic management. A biopsy, coupled to a blood sample, can also be used for molecular biology analyses, to search for activating mutations of the PIK3CA gene, particularly with LM integrating in a syndromic form (CLOVES or Klippel-Trenaunay syndrome) but also in certain isolated (or common) LMs. The spontaneous evolution of LMs, in particular microcystic forms, is often toward progressive aggravation, with an increase in the number of vesicles, thickening, increased oozing and bleeding, while pure macrocystic LMs may regress due to "natural sclerosis", i.e. fibrosis secondary to an inflammatory reorganization after common infantile infections. In case of voluminous LMs or syndromic forms, functional and psychological repercussions can be major, deteriorating the patient's quality of life. LMs must be treated by physicians integrated in multidisciplinary teams, and be personalized. Management is a life-long process that involves one or several of these therapies: conservative management, physical therapy (compression), sclerotherapy, surgery, drugs such as mTOR inhibitors (sirolimus), that has shown efficacy in decreasing the volume of LMs, and, more recently, PI3K-inhibitors in syndromic forms. Psychological and social support is necessary, taking into account the patient and his family.

Surgical resection of venous malformations of the forearm.

We retrospectively reviewed 35 patients with venous malformations located in the forearm and treated by surgery in a single institution during the period 2010-19. The common complaints were pain and swelling (34 patients) and impaired function with contractures of fingers (15 patients). Twenty-four had complete resection and 11 had an incomplete resection. Associated procedures were reconstruction or lengthening of tendons in 17 patients. At the last follow-up (mean 61 months), 32 of the 35 had no residual pain and 27 had no functional sequelae. On MRI follow-up exams, 27 had no residual venous malformations. Venous malformations in the anterior compartment of the forearm can impair the function of the hand. They are developed almost exclusively in the connective tissue around tendons and muscles, deforming the musculotendinous structures and involving nerves. Surgery seems an appropriate option for the condition in this area.Level of evidence: IV.

Surgical treatment of vulvar venous malformations without preoperative sclerotherapy: Outcomes of 18 patients.

BACKGROUND: Our aim was to evaluate the benefit of surgical resection of the venous malformations (VMs) of the external female genitalia. METHODS: Over the period of 2009-2019, 18 consecutive females underwent surgical resection for vulvar VM. Evaluations included preoperative Doppler ultrasound, MRI, and pre-and postoperative photographic imaging. The main outcomes were: residual pain, cosmetic distortion, residual VM, and quality of life. RESULTS: Over a 10 year periods, 18 females, mean age 35 years (range 9-71) were included in this study. All patients were symptomatic: 16 had intermittent pain or discomfort, 1 had bleeding and 2 requested cosmetic treatment. Of these cases, there were 5 isolated vulvar VM, 12 associated VM: 3 of the clitoral hood, 3 troncular pelvic vein insufficiency and 12 of the lower limb. Eight patients had undergone previous procedures: 2 sclerotherapy treatments (1-3 sessions), 4 partial surgical resections. There were 18 single resections in the vulva (7 focal, 11 complete), 2 partial resections in clitoral hood and 2 had resection of a VM in the perirtoneovaginal canal at the same time. The mean follow-up was 42. 9 months (range 6-120). Two patients were lost to followup at 6 months. For all patients, elimination of pain and soft tissue redundancy was achieved. Two patients had persistent discomfort and 2 requested cosmetic treatment. CONCLUSION: Surgical resection of vulvar VM can be the best approach with few postoperative complications, good functional and cosmetic results. Appropriate preoperative evaluation is required to identify isolated VM or VM associated with ovarian vein or internal iliac vein insufficiency requiring to be treated before surgery.

Intramuscular venous malformations of the calf: Surgical treatment outcomes of 57 patients.

OBJECTIVES: To report the outcomes of surgical treatment of calf intramuscular venous malformations (IMVMs) on pain, functional limitation, and quality of life. METHODS: We retrospectively reviewed 57 consecutive patients who had surgery for IMVM of the posterior compartment of the leg between 2010 and 2015. Treatments were all done at a single institution. RESULTS: Patients presented with pain (52), muscle contracture (14), or pulmonary embolism (4). Muscle involvement included the soleus muscle (n = 28, 49%), the gastrocnemius muscle (n = 25, 43%), and deep muscles (n = 4, 7%). Complete excision was possible in 52 patients (91%) and partial excision in 5 (9%). Thirty-five of 46 patients who had an MRI follow-up at six months had no residual venous malformation. At the final follow-up (mean 39 months), 32 of 40 patients seen had no residual pain and 37 had no residual functional impairment. CONCLUSION: In cases where IMVM is located in one muscle in the leg, we demonstrated that surgery yielded improvement in pain, function, and quality of life.

Surgical Treatment of Venous Malformations of the Knee: Treatment Outcomes for 35 Patients.

BACKGROUND: The place of open surgery in venous malformations (VMs) of knee joint is still discussed. The aim of this study was to evaluate the benefits of surgery in terms of pain, function, and quality of life. DESIGN: This was a retrospective observational study. METHODS: Thirty-five consecutive young patients undergoing surgery for VMs of the knee between 2011 and 2014 were included. Data collection was performed using a prospective database by reviewing patient records. Pain, mobility of the joint, residual VMs as seen by magnetic resonance imaging, and quality of life were the main outcome endpoints for this study. RESULTS: Thirty-five patients (22 females and 13 males, with a median age of 15 y, range of 5 to 20 y) were included. Twenty-seven VMs were localized in and around the knee joint, of which 8 were extensive. Indication for surgery was intermittent or permanent pain.Details of the surgical excisions of the VM are as follows: suprapatellar area in 57%, suprapatellar and infrapatellar area in 29%, infrapatellar area in 2%, limited in the femoropatellar area in 12%. Partial resection of a vastus muscle or patellar retinaculum was necessary for 19 patients.The median duration of the surgery was 4 hours (range: 2 to 7 h). The median hospital stay was 5 days; full-time physiotherapy was systematic for 2 to 3 weeks.After 6 months, 74% had no longer pain, the mobility of the joint was normal for 60%. Of the 33 patients who had a magnetic resonance imaging at 6 months, 86% (28 patients) had no residual intra-articular VMs, and 14% had focal residual VMs.At the last follow-up, 77% (27 patients) had no longer pain, 23% experienced intermittent pain with unusual activities, and 91% (32 patients) had normal mobility of the joint. Quality of life was increased significantly due to the pronounced impact on pain. CONCLUSION: Extensive surgical excision of knee VMs is a safe procedure with good outcomes in terms of pain, function, and quality of life. LEVEL OF EVIDENCE: Level II-retrospective observational monocentric study.

Germline Loss-of-Function Mutations in EPHB4 Cause a Second Form of Capillary Malformation-Arteriovenous Malformation (CM-AVM2) Deregulating RAS-MAPK Signaling.

BACKGROUND: Most arteriovenous malformations (AVMs) are localized and occur sporadically. However, they also can be multifocal in autosomal-dominant disorders, such as hereditary hemorrhagic telangiectasia and capillary malformation (CM)-AVM. Previously, we identified RASA1 mutations in 50% of patients with CM-AVM. Herein we studied non-RASA1 patients to further elucidate the pathogenicity of CMs and AVMs. METHODS: We conducted a genome-wide linkage study on a CM-AVM family. Whole-exome sequencing was also performed on 9 unrelated CM-AVM families. We identified a candidate gene and screened it in a large series of patients. The influence of several missense variants on protein function was also studied in vitro. RESULTS: We found evidence for linkage in 2 loci. Whole-exome sequencing data unraveled 4 distinct damaging variants in EPHB4 in 5 families that cosegregated with CM-AVM. Overall, screening of EPHB4 detected 47 distinct mutations in 54 index patients: 27 led to a premature stop codon or splice-site alteration, suggesting loss of function. The other 20 are nonsynonymous variants that result in amino acid substitutions. In vitro expression of several mutations confirmed loss of function of EPHB4. The clinical features included multifocal CMs, telangiectasias, and AVMs. CONCLUSIONS: We found EPHB4 mutations in patients with multifocal CMs associated with AVMs. The phenotype, CM-AVM2, mimics RASA1-related CM-AVM1 and also hereditary hemorrhagic telangiectasia. RASA1-encoded p120RASGAP is a direct effector of EPHB4. Our data highlight the pathogenetic importance of this interaction and indicts EPHB4-RAS-ERK signaling pathway as a major cause for AVMs.

Diode endovascular laser treatment in venous malformations of the upper aerodigestive tract.

PURPOSE: Venous malformations of the upper aerodigestive tract can cause pain, dysphagia, obstructive sleep apnea, and rarely bleeding. We studied 980-nm diode endovenous laser therapy. MATERIAL AND METHODS: This is a 2007-2014 retrospective study in our vascular anomalies center. Data on patients' clinical history, polysomnography, magnetic resonance imaging, and treatment were collected. Patients were contacted for Epworth Sleepiness Scale and Eating Assessment Tool (EAT-10) scores to evaluate sleepiness and dysphagia before and after laser therapy. RESULTS: We included 32 patients (mean age 41 years) presenting with obstructive sleep apnea (n = 18) and dysphagia (n = 13). With a mean follow-up of 39 months, average Epworth Sleepiness Scale score fell from 17.3 to 10.4 (p = 0.015), EAT-10 score from 8.2 to 3.5 (p = 0.002) and apnea-hypopnea index from 47.5 to 24.7 (p = 0.01). Of the sleep apnea patients, 89% required continuous positive airway pressure before and 50% afterward (p = 0.016). CONCLUSIONS: Diode endovascular laser treatment seems to be a safe and effective treatment option in venous malformations of the upper airways.

Ethanol threshold doses for systemic complications during sclerotherapy of superficial venous malformations: a retrospective study.

INTRODUCTION: Ethanol has been used for many years for superficial venous malformations (VM) sclerotherapy. Although ethanol is well-tolerated in most of the cases, systemic side effects have been reported in some patients, including cardiac collapse and death. Systemic toxic side effects have been suspected to be proportional to the ratio of ethanol dose divided by the patient's body weight (dose/weight ratio in millilitre per kilogram). No extensive study has yet been conducted to determine the toxic threshold, and no consensus exists on this point. METHODS: We retrospectively studied the systemic effects of ethanol sclerotherapy in a consecutive series of 71 patients with VM. RESULTS: Seventy-one consecutive patients with VMs were treated by ethanol sclerotherapy and 162 procedures were performed. The only factor significantly associated with a systemic adverse event was the ethanol dose/weight ratio per intervention. The ethanol dose/weight ratio superior to 0.24 ml/kg was predictive of systemic toxic effects, suggesting a limit dose for ethanol sclerotherapy of VM. Systematic complications were not related to repetitive sclerotherapy sessions. CONCLUSION: Based on our findings, a maximal ethanol dose/weight ratio of 0.2 ml/kg could be considered as acceptable in VM treatment indications.

Coagulation disorders in patients with venous malformation of the limbs and trunk: a case series of 118 patients.

OBJECTIVE: To investigate the clinical characteristics of venous malformation of the limbs and trunk and known but poorly appraised associated coagulation disorders. Venous malformations are ubiquitous, slow-flow vascular anomalies known to be occasionally painful because of thrombotic episodes inside the lesion. DESIGN: Large case series, with screening of accepted standard coagulation tests. SETTING: Ambulatory multidisciplinary clinics for vascular anomalies. PATIENTS: This 2-year study (2003-2005) included 118 patients with clinical, radiological, and biological features informative for better defining venous malformation and associated coagulation abnormalities. MAIN OUTCOME MEASURES: The primary outcome was coagulation disorders associated with VM. Secondary measures include anatomic location, extent of lesion, localized pain, and impaired motion. RESULTS: The mean age of patients was 27 years, and there was a female preponderance of 64%. The venous malformation involved the upper extremity, lower extremity, and trunk in 30%, 58%, and 36% of patients, respectively; it was plurifocal in 22%. Intralesional pain (in 92% of patients) had a higher frequency in female (63%) than in male (47%) patients. Tissular involvement concerned the skin (65%), muscle (73%), bone (13%), joints (12%), and viscera (9%). According to our severity scoring system, cases of less gravity had a score of 2 or 3 (52%), cases of intermediate severity had a score of 4 or 5 (32%), and cases of major severity had a score of 6 to 9 (10%). The most frequent blood coagulation abnormality was a high plasma D-dimer level (> 0.5 microg/mL) (58% of patients), which was correlated with muscle involvement and high severity score and was more frequent in women. The factor VIII-von Willebrand factor complex was documented in 84 patients, and plasma von Willebrand factor level was decreased (<60%) in 23 (27%) of them; 10 of the 84 patients (12%) had more notably decreased levels (<50%). CONCLUSIONS: This study of a large case series of patients with pure venous malformation in the limbs and/or trunk highlights muscle involvement and frequency of pain. It validates that coagulation disorders, present in 58% of our patients, create thrombotic painful events. Under certain circumstances, these disorders entail a risk of hemorrhage because of the progression of localized intravascular coagulopathy to disseminated intravascular coagulopathy.

Fatal peritoneal bleeding following embolization of a carotid-cavernous fistula in Ehlers-Danlos syndrome type IV.

We report the case of a 25-year-old woman treated for a spontaneous carotid-cavernous fistula in a context of Ehlers-Danlos syndrome type IV. Embolization with a transvenous approach was achieved without complications; however, the patient died 72 hr later of massive intraperitoneal bleeding. At autopsy, no lesion of the digestive arteries was identified. Possible causes of this bleeding are discussed.

Auricular arteriovenous malformation: evaluation, management, and outcome.

BACKGROUND: The external ear is the second most common site for extracranial arteriovenous malformation in the head and neck. METHODS: This retrospective review of 41 patients with auricular arteriovenous malformation was based on medical records, imaging studies, and photographs. Data were collected on natural history, progression, and outcome; patients were questioned about quality of life after treatment. RESULTS: The median age at initial presentation was 26 years (range, 1 to 55 years), and Schobinger stage was I in two patients, II in 19 patients, and III in 20 patients. No patients had a Schobinger stage of IV. Expansion occurred during childhood in seven patients, adolescence in 14 patients, pregnancy in 10 patients, and adulthood in 10 patients. Distribution of auricular and extra-auricular arteriovenous malformation was not limited to "watershed" areas between vascular territories (angiosomes). Twelve patients were untreated (follow-up, 0.5 to 6 years). Mean follow-up time for the 29 treated patients was 5.19 years (range, 1 to 18.75 years). Proximal ligation in nine patients caused progression: eight of them underwent amputation and one had embolization. Fifteen patients had embolization only: the arteriovenous malformation worsened and amputation was necessary in six patients; in the remaining nine patients, two improved, four persisted, and three worsened. Of 20 patients who had auricular amputation, 16 (80 percent) were controlled, three (15 percent) improved, and one had unresectable, residual cervicofacial arteriovenous malformation. Of 22 of 29 treated patients surveyed, 81 percent were satisfied with their management. Hearing was either unaffected (n = 15) or diminished (n = 5); two patients noted decreased sound localization. CONCLUSIONS: The authors recommend periodic evaluation for stage I to II auricular arteriovenous malformation and intervention if there is evolution to stage III. Preoperative embolization and partial or total amputation effectively control auricular and para-auricular arteriovenous malformation. Embolization can be palliative in children or in patients who are not psychologically prepared for amputation. Extensive extra-auricular arteriovenous malformation requires individualized endovascular therapy and resection.

Computed tomographic features of peritoneal carcinomatosis treated by intraperitoneal chemohyperthermia.

PURPOSE: The purpose of this work was to describe the computed tomography (CT) features of peritoneal carcinomatosis after surgery combined with intraperitoneal chemohyperthermia (IPCH). METHOD: Between 1999 and 2001, 51 consecutive patients (33 women and 18 men, with a mean age 45 years) were treated in our institution with IPCH for peritoneal carcinomatosis. Patients that were symptomatic (33 patients) underwent contrast enhanced helical CT of the abdomen and the pelvis during the first 15 postoperative days. The CT scans were reviewed retrospectively by two blinded observers. Computed tomography abnormalities were compared with surgical, biochemical, and clinical findings. RESULTS: None of the CT scans were completely normal. Most postsurgical CT findings, including bowel and peritoneal thickening (14 and 13 cases, respectively), increased intraperitoneal fat density (13 cases), and compartmentalized ascites (8 cases), resulted from an inflammatory mesenteric reaction or inflammation of the small bowel or the peritoneum and did not require specific treatment. Major complications requiring appropriate treatment were intra-abdominal abscesses (5 cases), hemoperitoneum (5 cases), urinary fistula (2 cases), acute pancreatitis (1 case) and abdominal wall abscesses (2 cases). CONCLUSION: Knowledge of early CT findings after therapy with surgery combined with IPCH for peritoneal carcinomatosis is useful for accurate posttreatment management of these patients.

Venous variations of the brain and cranial vault.

Vascular anomalies involving both intra- and extra-cranial structures are more common than previously thought. It is important to evaluate the brain and its coverings carefully when imaging cervicofacial vascular malformations. Scientific knowledge regarding developmental mechanisms responsible for blood vessel formation is increasing rapidly and, hopefully, will contribute to better understanding of these clinical and imaging "patterns."