Angiomatous Malformation Research Articles

A comprehensive review on the development of sporadic cerebral arteriovenous malformations: from Padget to next-generation sequencing.

Cerebral arteriovenous malformations (AVMs) are a leading cause of intracerebral hemorrhage in both children and young adults. With the continued advancement of science and technology, the understanding of the pathophysiology behind the development of these lesions has evolved. From early theory published by Harvey Cushing and Percival Bailey in 1928, Tumors Arising from the Blood-vessels of the Brain: Angiomatous Malformations and Hemangioblastoma, which regarded AVMs as tumors arising from blood vessels, to the meticulous artistry of Dorcas Padget's embryological cataloguing of the cerebral vasculature in 1948, to the proliferative capillaropathy theory of Yaşargil in 1987, to Ramey's 2014 hierarchical model of vascular development, there have been multiple hypotheses of congenital, developmental, and genetic two-hit theories in the pathogenesis of AVMs. Most recent evidence implicates somatic KRAS mutations in the cerebral endothelium, producing an important understanding of the pathogenesis of this disease, which is critical to the development of targeted therapeutics. The authors present the historical progression of their understanding of AVM pathogenesis. They focus on the foundation laid by early pioneers, discussing embryological anatomy and vasculogenesis, the prominent theories of AVM development that have emerged over time, and culminate in an overview of the most current understanding of the pathogenesis of these complex vascular lesions and the clinical implications of our scientific progress.

“Sturge – Weber Syndrome: A Case Report and Review of Literature”

Sturge-Weber syndrome is a rare, sporadically occurring neurocutaneous syndrome characterized by port wine stain (facial nevus flammeus), congenital glaucoma, and anomalous leptomeningeal angiomatous malformation. Port wine stain is usually the first component of the syndrome. Seizures of the side contralateral to the port wine stain occur early in infancy and worsen with age. Radiological investigations, like computed tomography and magnetic resonance imaging are most useful, playing a pivotal role in demonstrating the cerebral changes. We report the case of a three year old child presenting with port wine stain over left half of the body, weakness of right upper and lower limb with an episode of seizure. The child was known to have seizures from 6 months of age and was on irregular anticonvulsant treatment. This case highlights the various neurological manifestations of Sturge-Weber syndrome and how imaging helps to characterize each.

Outcome of Colonoscopic Screening in Potential Liver Transplant Candidates

BackgroundScreening for neoplastic lesions is mandatory as a part of the evaluation process of potential candidates for liver transplant (LT). This work aimed at identifying the main findings in screening colonoscopy and their risk factors. MethodsEndoscopic and pathologic findings of the biopsied lesions of 311 potential candidates for living donor liver transplant were collected and analyzed. ResultsColorectal polyps (8.7%) were the most common colonoscopic finding, of which 4.18% were diagnosed as adenomas. Other findings included hemorrhoids (7.7%), portal hypertensive colopathies (3.5%), angiomatous malformations (2.6%), rectal varices (1.6%), and diverticulosis (1.6%). The univariate analysis revealed that the prevalence of colonic adenoma was significant in patients 50 years and older (P = .03; odds ratio, 1.178; 95% CI, 1.016-1.365) and in patients who had hepatocellular carcinoma (P = .043; odds ratio, 6.5; 95% CI, 1.002-42.172). In the multivariate analysis, age was found to be the single best predictor of the presence of adenoma (P = .044; odds ratio, 1.178; 95% CI, 1.005-1.382). ConclusionWe can conclude that a screening colonoscopy prior to liver donor liver transplant should be performed at least in every LT candidate 50 years or older. Colonic polyps were the most common findings on screening colonoscopy prior to LT.

Adgrf5 contributes to patterning of the endothelial deep layer in retina

Neovascularization of the inner retinal space is a major cause of vision loss. In retinal angiomatous proliferation (RAP) syndrome, newly formed vessels originate from the retinal plexus and invade the inner retinal space. However, the molecular pathways preventing subretinal vascularization remain largely unknown. In most murine models of RAP, pathological neovascularization occurs concomitantly with the development of the retinal vasculature. Here, we demonstrate that disturbing the sequence of morphogenetic events that shape the three-layered retinal vascular network leads to subretinal vascularization. Sprouts emerging from the perivenous region after the first postnatal week extended toward the retinal space where they merged into the deep layer. The small GTPase Rac1 was required for the formation of these vascular extensions and the vascular inner plexus is formed coaxially to the overarching veins. The adhesion receptor Adgrf5 was highly expressed in the endothelium of the central nervous system, where it regulates blood–brain barrier formation. The vascular superficial plexus of Adgrf5 mutant mouse retinae exhibited an increased vascular density in the perivenous areas with increased projections toward the inner plexus where they subsequently created hyper-dense endothelial cells (EC) clusters. Disturbing the perivenous pool of EC thus significantly altered the inner plexus formation. These abnormalities culminated in transient vascular protrusions in the inner retinal space. Taken together, these results reveal a previously unobserved vascular morphogenetic defect in Adgrf5 knockout mice, implicating a role for ADGRF5 in the initiation of subretinal vascularization. Our findings also illustrate how vein-derived EC shape the inner retinal layer formation and could control the appearance of angiomatous malformations.

Double balloon enteroscopy in children: diagnosis, treatment, and safety.

To assess the feasibility and utility of double balloon enteroscopy (DBE) in the management of small bowel diseases in children. Fourteen patients (10 males) with a median age of 12.9 years (range 8.1-16.7) underwent DBE; 5 for Peutz-Jeghers syndrome (PJ syndrome), 2 for chronic abdominal pain, 4 for obscure gastrointestinal (GI) bleeding, 2 with angiomatous malformations (1 blue rubber bleb nevus syndrome) having persistent GI bleeding, and 1 with Cowden's syndrome with multiple polyps and previous intussusception. Eleven procedures were performed under general anesthesia and 3 with deep sedation. The entire small bowel was examined in 6 patients, and a length between 200 cm and 320 cm distal to pylorus in the remaining 8. Seven patients had both antegrade (trans-oral) and retrograde (trans-anal and via ileostomy) examinations. One patient underwent DBE with planned laparoscopic assistance. The remaining 6 had trans-oral examination only. The median examination time was 118 min (range 95-195). No complications were encountered. Polyps were detected and successfully removed in all 5 patients with PJ syndrome, in a patient with tubulo-villous adenoma of the duodenum, in a patient with significant anemia and occult bleeding, and in a patient with Cowden's syndrome. A diagnosis was made in a patient with multiple angiomata not amenable to endotherapy, and in 1 with a discrete angioma which was treated with argon plasma coagulation. The source of bleeding was identified in a further patient with varices. DBE was normal or revealed minor mucosal friability in the remaining 3 patients. Hence a diagnostic yield of 11/14 with therapeutic success in 9/14 was achieved. Double balloon enteroscopy can be a useful diagnostic and therapeutic tool for small bowel disease in children, allowing endo-therapeutic intervention beyond the reach of the conventional endoscope.

Lymphangiomatosis with Extensive Skeletal Involvement

Aim : To review a case presentation of systemic lymphangiomatosis- an uncommon medical condition that can be easily misdiagnosed in the clinical setting Abstract : Generalized lymphangiomatosis is a rare condition with characteristic multi-centric angiomatous malformations of the skeletal system, with involvement of surrounding soft tissues and skin. It results from a congenital anomaly and presents predominantly in the paediatric age group. Systemic involvement includes not only the skeletal system, but also the pulmonary and gastrointestinal systems. Its diagnosis can be difficult to ascertain but is hinged on clinical presentation, imaging and histological confirmation. The condition carries a variable prognosis as treatment options are very limited. Pulmonary involvement is usually terminal, however. A case is presented to highlight the difficulties in diagnosing and managing this condition. Conclusion : The diagnosis of lymphangiomatosis involving the skeletal system is highly reliant on imaging studies; that depict well defined osteolytic changes of the bone. Management is supportive and no cure currently exists. Keywords : lymphangiomatosis, systemic, skeletal involvement

Cystic angiomatosis: a rare cause of osteolytic lesions and pathological fracture - a case report

Cystic angiomatosis is an uncommon benign multifocal disorder in which there is proliferation of endothelial lined vessels in bone. Angiomatous malformation results in progressive loss of bone. Bony cystic lesion affects the axial and proximal appendicular skeleton. Patients usually presents with pain. We report a case of 58 year old man who presented with pain and pathological fracture. X-Ray imagery showed multicystic lesions involving the whole length of multiple ribs. Rib biopsy showed the proliferating capillary network growing in to the bone marrow spaces associated with destruction of bone. Cystic angiomatosis should be kept as one of the rare differential diagnosis in a case presenting with multiple lytic lesions of bone.

Lymphangiomatosis with Extensive Skeletal Involvement

Aim : To review a case presentation of systemic lymphangiomatosis- an uncommon medical condition that can be easily misdiagnosed in the clinical setting Abstract : Generalized lymphangiomatosis is a rare condition with characteristic multi-centric angiomatous malformations of the skeletal system, with involvement of surrounding soft tissues and skin. It results from a congenital anomaly and presents predominantly in the paediatric age group. Systemic involvement includes not only the skeletal system, but also the pulmonary and gastrointestinal systems. Its diagnosis can be difficult to ascertain but is hinged on clinical presentation, imaging and histological confirmation. The condition carries a variable prognosis as treatment options are very limited. Pulmonary involvement is usually terminal, however. A case is presented to highlight the difficulties in diagnosing and managing this condition. Conclusion : The diagnosis of lymphangiomatosis involving the skeletal system is highly reliant on imaging studies; that depict well defined osteolytic changes of the bone. Management is supportive and no cure currently exists. Keywords : lymphangiomatosis, systemic, skeletal involvement

Spectrum of CT and MR findings in Sturge-Weber syndrome: A case report

Sturge-Weber syndrome is an uncommon, sporadically occurring neurocutaneous syndrome characterized by port wine stain (facial nevus flammeus), congenital glaucoma, and anomalous leptomeningeal angiomatous malformation. Port wine stain is usually the first component of the syndrome. Seizures of the side contralateral to the port wine stain occur early in infancy and worsen with age. Radiological investigations, like computed tomography and magnetic resonance imaging are most useful, playing a pivotal role in demonstrating the cerebral changes. We report the case of a 10-month-old infant presenting with port wine stain over face, trunk, and extremities, hemiparesis of the left side of the body, and new onset of seizure. This case highlights the various neurological manifestations of Sturge-Weber syndrome and how imaging helps to characterize each.

Periodontal Manifestations and Ambulatorial Management in a Patient With Sturge Weber Syndrome

Sturge-Weber syndrome is a nonhereditary congenital condition characterized by leptomeningeal and facial skin angiomatous malformation following the trigeminal nerve path. The intraoral angiomatosis are presented in 40% of cases and results in an important periodontal alteration, increasing the risk of bleeding during dental procedures. A 43-year-old male patient presented with port wine stain on the right side of the face, the entire hard and soft palates, the alveolar ridge, and buccal mucosa, and had an excessive accumulation of calcified masses in both supragingival and subgingival sites, with swelling and generalized inflammation throughout the gingiva and alveolar mucosa. He reported not having sanitized the area for years for fear of bleeding. Periodontal management, to remove calculus and to control gingivitis initiated in the supragingival region and gradually reaching the subgingival region to control oral microbiota, was performed with mild bleeding. The redness of the staining greatly diminished with time and the extreme halitosis of the patient also improved sharply leading to a dramatic improvement in quality of life. Ambulatory care is a feasible alternative for periodontal management that within safety limits for bleeding risks reduces the operational cost.

Intraoperative localization of vascular malformation of small bowel by selective intra-arterial dye injection

Angiomatous malformation is the most common vascular abnormality, accounting for 30-40% cases of obscure GI bleeding from small bowel. Surgical resection is the treatment of choice in severe or recurrent hemorrhage requiring multiple blood transfusions. However, the diffuse nature of the lesions poses a challenge to localize them accurately preoperatively, for exact resection. We present a case in which we have used selective mesenteric angiography with selective cannulation and exact localization of the lesion by injecting dye such as methylene blue, indigo carmine, and fluorescein, to localize the angiomatous malformation before surgical resection and also to determine the exact resection to be done.

Prevalence of Celiac Disease, Helicobacter pylori and Gastroesophageal Reflux in Patients with Refractory Iron Deficiency Anemia

The aim of this article is to determine the prevalence of celiac disease (CD), Helicobacter pylori (H. pylori) and gastroesophageal reflux (GER) in patients with resistant iron deficiency anemia (IDA). The study included 25 patients <18 years of age with refractory IDA (not responding to iron therapy for 3 months in a dose of 6 mg elemental iron/kg/day). All patients included in the study were subjected to careful history taking and thorough clinical examination. Blood sample was taken for analysis of antibodies for CD including: antigliadin antibody (AGA), antiendomysial antibody (EMA), antireticulin antibody (ARA) and antitissue Transglutaminase (tTg) IgG antibody. Anti-H. pylori IgG antibodies and a (13)C-urea breath test (UBT) was done to all patients to diagnose H. pylori. Upper gastrointestinal tract endoscopy was done for all patients to evaluate for the presence of some etiologies of intractable anemia as chronic blood loss. These included: CD, H. pylori infection and GER. The upper gastrointestinal tract endoscopy was also done to evaluate the presence of bleeding spots, ulcers or angiomatous malformations. In addition, gastric antral biopsies were taken for diagnosis of H. pylori infection by the following tests: rapid urease test, histopathological examination and culture. CD was positive in 11 out of 25 patients (44%), H. pylori infection in 12 out of 25 patients (48%), while GER was diagnosed in 11 out of 25 patients (44%). Patients with CD had age of presentation < or =2 years in two patients (18.2%) while the remaining nine patients (81.8%) had age of presentation >2 years and it was statistically significant (p = 0.05*). Also patients with H. pylori had age of presentation < or =4 years in five patients (41.7%) and the remaining seven patients (81.8%) had age of presentation >4 years and it was statistically significant (p = 0.03*). Logistic regression analysis demonstrated that the risk factors for severity of anemia were age of patients and duration of anemia. On the other hand, other parameters have no significant influence on the severity of anemia. Also risk factors of short stature were age of presentation of anemia, degree of anemia and H. pylori infection. AGA had the highest sensitivity (100%) followed by antiendomysium antibody (81.8%) while the tTG antibody had the highest specificity (85.7%) for diagnosis of CD. UBT and histopathology had the highest sensitivity (100%) for diagnosis of H. pylori while rapid urease test, culture, H. pylori stool antigen and anti-H. pylori IgG antibody had the highest specificity (100%). In conclusion, refractory IDA may be due to clinically unapparent H. pylori gastritis and CD. CD is one of the most common causes of intestinal malabsorption during childhood which leads to impairment of iron absorption. Apart from offering them gluten-free diet rich in iron, early detection and treatment of IDA and prophylactic iron and folic acid supplementation will go a long way to optimize their mental and psychological functions. Eradication of H. pylori infection with concomitant iron therapy should correct the anemia.

Deviated nasal septum in case of Klippel-Trenaunay-Weber Syndrome

Klippel-Trenaunay-Weber Syndrome (KTWS) is a rare entity. It includes cutaneous hemangioma (Port-wine stains) of the face and extremities with associated varicosities and hypertrophy of underlying soft tissue and bone. Craniofacial involvement is rare in this syndrome. We report a case of Klippel-Trenaunay-Weber Syndrome who presented with craniofacial deformity leading to deviated nasal septum, nasal obstruction and intermittent nasal bleed. These patients can have involvement of oral cavity and nasal mucosa with angiomatous malformation, which can give rise to epistaxis and excessive bleeding during oral and nasal surgeries. We discuss the review and management of such cases from Otolaryngologists point of view.

Ileoscopy in 39 hematochezia patients with normal colonoscopy

To assess the role of retrograde terminal ileoscopy in hematochezia patients with normal colonoscopy. Between January 1997 and March 2005, 39 hematochezia patients (males 36, females 3, mean age 44.7 years) with a reported normal colonoscopy underwent a repeat colonoscopy. After reaching the cecum, attempt was made to localize the ileocecal valve and intubate the terminal ileum. Any abnormality in the mucosa of the terminal ileum was carefully recorded and biopsies were obtained from suspicious-looking lesions. During the study period there were 39 patients admitted for hematochezia in whom colonoscopy till cecum did not reveal any abnormality. Full-length colonoscopy till the cecum could be performed in all the patients. The terminal ileum could be intubated in 36 patients. No abnormality was noted in 31 patients. Ileal ulcers were noted in two patients. Nodularity along with ulceration of the ileal mucosa, a Dieulafoy's lesion, and an angiomatous malformation were noted in one patient each. Histological examination of the biopsies obtained from the ulcers revealed typical tuberculous lesion in the patient with nodularity and ulceration. One of the patients had typhoid ulcers and another had non-specific ulcers. Retrograde terminal ileoscopy gives limited but valuable information, in patients with hematochezia and should be attempted in all such patients.

Partial hydatidiform mole: clinicopathological features, differential diagnosis, ploidy and molecular studies, and gold standards for diagnosis.

Partial hydatidiform mole is optimally diagnosed histopathologically when four microscopic features coexist: 1) two populations of villi, 2) enlarged villi (> or = 3-4 mm) with central captivation, 3) irregular villi with geographic, scalloped borders with trophoblast inclusions, and 4) trophoblast hyperplasia (usually focal and involving syncytiotrophoblast). Pathologic mimics of partial mole include Beckwith-Wiedemann syndrome, placental angiomatous malformation, twin gestation with complete mole and existing fetus, early complete hydatidiform mole, and hydropic spontaneous abortion. Because partial hydatidiform mole results from diandric triploidy, flow cytometry (or another method to assess ploidy) can be utilized by pathologists for supporting diagnostic classification of problematic specimens, or for educational or quality assurance purposes. Confirmation of the histopathologic diagnosis by ploidy or molecular studies is important for scientific reports of partial hydatidiform mole, especially when unusual or aggressive outcomes (such as choriocarcinoma) are reported.

Sturge-Weber syndrome without facial nevus

An 11-month-old patient with Sturge-Weber syndrome with the absence of facial angioma and normal mental development is presented. Noncontrast computed tomography revealed left parieto-occipital atrophy with heavy gyriform calcifications. Axial T 2-weighed magnetic resonance imaging confirmed the presence of low-signal areas corresponding to the gyral calcifications evident on computed tomography. Contrast-enhanced T 1-weighted axial and coronal images exhibited high signals in the left parieto-occipital cortical and subcortical areas, representing angiomatous malformations. The clinical appearance and pathologic features of the reported patient were compared with those of similar patients described in published reports.

Excerpts from “Tumors Arising from the Blood-vessels of the Brain: Angiomatous Malformations and Hemangioblastomas”

Excerpts from “Tumors Arising from the Blood-vessels of the Brain: Angiomatous Malformations and Hemangioblastomas”

Angiomatous malformation of the floor of the mouth associated with fluctuating macroglossia in an adult: an unusual case report

We report an unusual case of a large vascular lesion of the floor of the mouth of rapid onset in a 50-year-old man who presented with an external swelling in the submental region and a history of fluctuating swelling of the tongue. The clinical features, investigations, treatment and course of this rare condition are discussed.

Angiomatosis at the Saphenofemoral Junction

Objective: To describe 12 patients with a vascular malformation found at the saphenofemoral junction during dissection of the inguinal region for surgery of varicose veins. Design: Retrospective study of cases found during the period from 1986 to 1991. Setting: University Hospital of the Military School of Medicine, Bogota, Colombia. Patients: Twelve patients, 11 unilateral and one bilateral, representing 0.5% of our total experience in surgery of varicose veins in 5 years. Interventions: Surgical resection of the angiomatous malformation. Main outcome measures: Clinical assessment of patients and histological examination of excised tissue. Results: The excised angiomatous tissue was found to contain irregular venous vessels, associated with lymphatic nodular structures and surrounded by adipose tissue. A satisfactory clinical outcome was obtained in patients where the angiomatous tissue could be excised. Conclusions: Vascular surgeons treating varicose veins should be aware of the possibility of finding vascular angiomatous malformation of the saphenofemoral junction. Surgical resection of these benign lesions results in a satisfactory clinical outcome.

The Sturge-Weber syndrome: correlation between the clinical status and radiological CT and MRI findings.

In the Sturge-Weber syndrome facial venous and leptomeningeal angiomas are associated. We studied 14 consecutive cases with clinical and radiological evaluations [computed tomography (CT) and magnetic resonance imaging (MRI)]. Radiological studies demonstrated the extent and patency of the leptomeningeal angiomatous malformation, the degree of parenchymal atrophy, the presumed ischemic changes affecting the gray and white matter, the presence and extent of cortical calcifications, the prominence of the choroid plexus, the parenchymal venous anomalies, and the diploic prominence in the affected side. The white matter alterations, being greater, the extent of lobar involvement, and the degree of parenchymal atrophy all correlated with the patient's clinical status being poorer. MRI is more efficient in the detection of the radiological findings related to the clinical status: seizure control, degree of psychomotor development and hemiparesis. Therefore, MRI is the imaging modality of choice in the diagnosis of these patients.