Glomuvenous Malformations Research Articles

Musculoskeletal glomus tumor: a review of 218 lesions in 176 patients.

To review the spectrum of clinical and imaging features of glomus tumor involving the musculoskeletal system including the typically solitary forms as well as the rarer multifocal forms (glomuvenous malformation and glomangiomatosis). A retrospective review of our institutional pathology database from 1996 to 2023 identified 176 patients with 218 confirmed glomus tumors. Primary imaging studies included MRI (125), radiographs (100), clinical/intraoperative photos (77), and ultrasound (36). Lesions were divided into two groups: those that are typically solitary involving specific anatomic areas (finger, toe, soft tissue, coccyx, and bone), and those that are multifocal (glomuvenous malformation and glomangiomatosis). The finger was the most frequently involved anatomic location for the classic (sporadic) glomus tumor occurring in 51% of patients, 77% of which were women, with the nail plate involved in more of the 75% of cases. Sporadic lesions involving the skin, subcutaneous adipose tissue, and deep soft tissue were termed "soft tissue," and were identified in 39% of patients, 90% of which were in the extremities and in men in 81% of cases. The multifocal syndromic forms of glomus disease occurred in younger individuals and involved less than 6% of the study group. Patients with glomuvenous malformation presented early with predominantly cutaneous involvement, while those with glomangiomatosis present later, often with both superficial and deep involvement, and a high rate of local tumor recurrence. While glomus tumor is generally uncommon, it frequently involves the musculoskeletal extremities. Knowledge of the spectrum of characteristic locations and appearances will facilitate definitive diagnosis.

PA23 Glomuvenous malformation or blue rubber bleb naevus syndrome: a case highlighting how a genetic diagnosis can avoid invasive testing and the need for long-term follow-up

PA23 Glomuvenous malformation or blue rubber bleb naevus syndrome: a case highlighting how a genetic diagnosis can avoid invasive testing and the need for long-term follow-up

Loss-of-function variants in GLMN are associated with generalized skin hyperpigmentation with or without glomuvenous malformation.

Inherited hyperpigmented skin disorders comprise a group of entities with considerable clinical and genetic heterogenicity. The genetic basis of a majority of these disorders remains to be elucidated. This study aimed to identify the underlying gene for an unclarified disorder of autosomal-dominant generalized skin hyperpigmentation with or without glomuvenous malformation. Whole-exome sequencing was performed in five unrelated families with autosomal-dominant generalized skin hyperpigmentation. Variants were confirmed using Sanger sequencing and a minigene assay was employed to evaluate the splicing alteration. Immunofluorescence and transmission electron microscopy (TEM) were used to determine the quantity of melanocytes and melanosomes in hyperpigmented skin lesions. GLMN knockdown by small interfering RNA assays was performed in human MNT-1 cells to examine melanin concentration and the underlying molecular mechanism. We identified five variants in GLMN in five unrelated families, including c.995_996insAACA(p.Ser333Thrfs*11), c.632 + 4delA, c.1470_1473dup(p.Thr492fs*12), c.1319G > A(p.Trp440*) and c.1613_1614insTA(Thr540*). The minigene assay confirmed that the c.632 + 4delA mutant resulted in abolishment of the canonical donor splice site. Although the number of melanocytes remained unchanged in skin lesions, as demonstrated by immunofluorescent staining of tyrosinase and premelanosome protein, TEM revealed an increased number of melanosomes in the skin lesion of a patient. The GLMN knockdown MNT-1 cells demonstrated a higher melanin concentration, a higher proportion of stage III and IV melanosomes, upregulation of microphthalmia-associated transcription factor and tyrosinase, and downregulation of phosphorylated p70S6 K vs. mock-transfected cells. We found that loss-of-function variants in GLMN are associated with generalized skin hyperpigmentation with or without glomuvenous malformation. Our study implicates a potential role of glomulin in human skin melanogenesis, in addition to vascular morphogenesis.

Ultrasonography-guided radiofrequency ablation of vascular malformations-The moving shot technique.

To describe a novel ultrasound-guided technique for percutaneous radiofrequency ablation of vascular malformations-the "moving shot technique." Preliminary observational cohort study, conducted from June 1, 2019, to January 31, 2021, including all consecutive patients diagnosed with vascular malformations who were treated with ultrasound-guided radiofrequency ablation using the moving shot technique. Only patients who had undergone at least one unsuccessful previous treatment were included (sclerotherapy with ethanol/aethoxysklerol or embolization/surgery). Eight patients with a median age of 22 years (interquartile range, 13-31) were included. Patients had different vascular malformations consisting of 1 arteriovenous malformation, 4 venous malformations, and 1 each a mixed venous-lymphatic malformation, a glomuvenous malformation and a FAVA (fibroadipose vascular anomaly). Malformations were located at the limbs in 5 patients (62.5%), the subcutaneous/intramuscular tissue of the body in 2 patients (25%) and at the chin in 1 patient (12.5%). Clinical symptoms were pain in 8 patients (100%), swelling in 6 patients (75%), and partial immobility in 4 patients (50%). All patients showed an improvement of clinical symptoms after treatment with 7 (87.5%) being completely asymptomatic and 1 (12.5%) showing improvement of immobility and pain. No procedural complications, such as nerve damage or skin burns occurred. The moving shot technique using ultrasonography-guided radiofrequency ablation is a promising technique for the interventional treatment of vascular malformations and should be validated in multicenter-approaches.

Glomuvenous malformation: a clinicopathological analysis of 31 cases

Objective: To investigate the clinicopathological features of glomuvenous malformation (GVM). Methods: Thirty-one cases of GVM diagnosed at the Henan Provincial People's Hospital from January 2011 to December 2021 were collected. Their clinical and pathological features were analyzed. The expression of relevant markers was examined using immunohistochemistry. The patients were also followed up. Results: There were 16 males and 15 females in this study, with an average age of 11 years (range, 1-52 years). The locations of the disease included 13 cases in the limbs (8 cases in the upper limbs, 5 cases in the lower limbs), 9 cases in the trunks, and 9 cases in the foot (toes or subungual area). Twenty-seven of the cases were solitary and 4 were multifocal. The lesions were characterized by blue-purple papules or plaques on the skin surface, which grew slowly. The lumps became larger and appeared to be conspicuous. Microscopically, GVM mainly involved the dermis and subcutaneous tissue, with an overall ill-defined border. There were scattered or clustered irregular dilated vein-like lumens, with thin walls and various sizes. A single or multiple layers of relatively uniform cubic/glomus cells were present at the abnormal wall, with scattered small nests of the glomus cells. The endothelial cells in the wall of abnormal lumen were flat or absent. Immunohistochemistry showed that glomus cells strongly expressed SMA, h-caldesmon, and collagen IV. Malformed vascular endothelial cells expressed CD31, CD34 and ERG. No postoperative recurrence was found in the 12 cases. Conclusions: GVM is an uncommon type of simple venous malformation in the superficial soft tissue and different from the classical glomus tumor. Morphologically, one or more layers of glomus cells grow around the dilated venous malformation-like lumen, which can be combined with common venous malformations.

Estimate of the Prevalence of Vascular Malformations

Objectives: To estimate the prevalence of vascular malformations using retrospective data collected from 1999 to 2020 in a specialty vascular anomalies service. Methods: The vascular anomalies service associated with the Royal Children’s Hospital provides a reference service to both adults and children, covering the entire state of Victoria, Australia, which has a population of 6.7 million and around 70,000 births per year. A database of patients was interrogated to identify those treated by the service over the study period with a diagnosis of vascular malformation, excluding capillary malformations. A total of 1501 patients were identified, including 1233 with slow-flow malformations and 147 with arteriovenous malformations. Prevalence was calculated as the number of cases born per year who attended the service plus those estimated as yet to attend for assessment, divided by the average number of live births each year. This was calculated for a selected period comprising the years when the numbers were expected to be most stable. Results: The prevalence of slow-flow malformations is estimated to be 1 case per thousand livebirths. Approximate estimates of cases per 100,000 births for individual lesions are: venous malformation 45, lymphatic malformation 35, intramuscular slow-flow malformation 10, complex malformations (Klippel-Trenaunay and CLOVES) 4, glomuvenous malformation 5, and verrucous venous malformation 2. The prevalence of extracranial arteriovenous malformation is estimated to be around one case per 10,000 population. Conclusions: An updated estimate, more accurate than those previously published, of the prevalence of vascular malformations has been obtained.

About an Observation of Glomuvenous Malformation of the Thumb

Abstract The glomuvenous malformation is a venous and cutaneous malformation that develops from a thermoregulatory unit called the glomus body. Our objective in this work is to clarify the latest terminologies of this pathology based on clinical, radiological, and histological criteria specific to this malformation; we report an exceptional case of a glomuvenous malformation in the thumb of a 41-year-old female patient, which undertook a surgical treatment with a simple postoperatory follow-up.

Glomus Venous malformation of the skin of the left ankle-foot joint: a clinical case and review of the literature

Annotation. The work presents a clinical and histological description of a case of glomuvenous malformation and a review of modern data on the diagnosis and treatment of this disease. A case of diagnosis of glomuvenous malformation on the foot of the right lower limb in a 46-year-old man was analysed. The case was characterized by an uncertain dermatological status with the need to exclude malignant neoplasia of the skin. Considering doubts about the benign nature of the skin lesion, the patient was recommended to undergo a therapeutic and diagnostic biopsy. After a medical-diagnostic biopsy, histological sections showed skin with moderate hyperparakeratosis of the epidermis and a clearly delineated, non-encapsulated formation in the dermis. The tumour is represented by numerous vascular channels of the venous type of small and medium caliber, some of which have an enlarged lumen and a thickened wall, filled with erythrocytes. Clusters, chains, and fields of monomorphic glomus cells with weakly expressed eosinophilic cytoplasm and rounded nuclei with finely dispersed chromatin are located perivascularly, without atypia. Mitotic figures are absent. The intercellular stroma is sclerosed with focal oedema. Considering the results obtained by us and the data of modern studies, we can state the ambiguity of views on the diagnosis of glomuvenous malformation with the need for more aggressive diagnostic and therapeutic tactics in adults. The development of an algorithm for the management of adult patients with glomuvenous malformation of the skin is a prospect for further research.

Dermoscopic Analysis of Vascular Malformations and Tumors Based Upon Dominant Vascular Dermoscopic Features: A Retrospective Analysis From a Tertiary Care Center of East India.

BackgroundCutaneous vascular malformations and tumors comprise a vast group of conditions with variable clinical presentations. It is imperative to differentiate them from nonvascular lesions and from each other as their management and prognosis differ significantly. There is only sparse literature on dermoscopic features of various vascular malformations and tumors, especially from India.AimWe aimed to retrospectively study the dermoscopic findings of various vascular malformations and tumors based on their dominant vascular dermoscopic feature.MethodAll the vascular malformations and tumors for which clinical details and clinical and dermoscopic images were available were included in the analysis. The dominant vascular feature(s) was defined as a single or combination of two or more vascular features (in case a single vascular feature does not satisfy the criteria) that constitute more than 75% of the lesions’ vascular features. These included red, purple, blue, black (or any combination) dots, globules, lacunae, structureless area, linear, linear irregular, hairpin, comma, and arborizing vessels.ResultsA total of 52 patients with 68 vascular lesions (22 vascular malformations and 46 vascular tumors) were analyzed. Port-wine stain showed linear irregular vessels with sharp border with or without intervening white structureless area; unilateral nevoid telangiectasia had red dots and globules; angiokeratoma displayed red, reddish-purple to brown lacunae; blue color was seen in venous and glomuvenous malformation and venous lake; a mixed pattern was noted in infantile hemangioma and verrucous hemangioma; a red to reddish-white structureless area was observed in pyogenic granuloma and cherry angioma, and a subungual ill-defined pink structureless area was spotted in subungual glomus tumor.ConclusionThe dermoscopic features observed in various vascular lesions may overlap; however, the dominant dermoscopic feature along with its color may point to the diagnosis.

Polidocanol: A Review of Off-Label Dermatologic Uses.

Polidocanol is an FDA-approved treatment of incompetent great saphenous veins, accessory saphenous veins, and visible varicosities of the great saphenous vein system, but numerous other off-label dermatological applications have been reported. To describe the various off-label dermatological clinical uses of polidocanol, as well as efficacy and adverse effects. The review of studies searchable on PubMed from 2004 to 2021 describing clinical uses of polidocanol to determine efficacy and adverse effects associated with various dermatologic applications. Polidocanol has shown efficacy in the treatment of mucocele of minor salivary gland, hemangioma, upper extremity veins, reticular veins of the chest, facial veins, pyogenic granuloma, lymphangioma circumscriptum, digital mucous cyst, mixed skin ulcers, cutaneous focal mucinosis, seromas, glomuvenous malformations, acne cysts, lymphocele, and dissecting cellulitis. Commonly reported side effects include pain, erythema, swelling, ecchymosis, and ulceration. Most sources were case reports and small prospective studies, as such the strength of data supporting many uses is limited by small sample sizes and lack of controls. Although polidocanol is currently only FDA approved for incompetent great saphenous veins, accessory saphenous veins, and visible varicosities of the great saphenous vein system, the use of polidocanol has been selected for a variety of off-label clinical applications.

Venous Malformations in Childhood: Clinical, Histopathological and Genetics Update.

Our knowledge in vascular anomalies has grown tremendously in the past decade with the identification of key molecular pathways and genetic mutations that drive the development of vascular tumors and vascular malformations. This has led us to better understand the pathogenesis of vascular lesions, refine their diagnosis and update their classification while also exploring the opportunity for a targeted molecular treatment. This paper aims to provide an overview of venous malformations (VM) in childhood. Specific entities include common VMs, cutaneo-mucosal VM, blue rubber bleb nevus syndrome or Bean syndrome, glomuvenous malformation, cerebral cavernous malformation, familial intraosseous vascular malformation and verrucous venous malformation. The clinicopathological features and the molecular basis of each entity are reviewed.

Surgical and non-surgical treatment modalities for glomuvenous malformations

Surgical and non-surgical treatment modalities for glomuvenous malformations

27933 A rare case of familial generalized multiple glomangiomas in an 11-year-old boy

Glomus tumors are benign vascular neoplasms made up of specialized perivascular modified smooth muscle cells, glomus cells, that present clinically as violaceous-to-blue papules and nodules often on the distal fingers and toes, including the nail bed. Glomus tumors can be histologically classified into 3 variants: solid glomus tumors, glomangiomas, also known as glomuvenous malformations, and glomangiomyomas. We present the case of an 11-year-old boy who presented with multiple blueish lesions on the bilateral arms, trunk, and buttocks, present for 2-3 years. Of note, the patient’s brother reportedly has many similar lesions that developed around the same age. Physical exam revealed solitary and clustered tender, blue, nonblanching vascular papulonodules on the trunk, arms, and back. Biopsy of a lesion on the right arm was performed and histopathology revealed many dilated vascular channels surrounded by sheets of uniform round-to-cuboidal cells with oval nuclei, consistent with a diagnosis of glomangioma. Given the patient’s clinical presentation with multiple glomangiomas and a first degree relative with similar lesions, a diagnosis of familial generalized multiple glomangiomas (FGMG) was made. FGMG is a rare clinical variant present in less than 10% of all glomus tumor cases. FGMG is thought to be caused by mutations in Glomulin (GLMN) and exhibits autosomal dominant inheritance with incomplete penetrance and variable expressivity. Though glomus tumors are benign, they are typically persistent and may be tender. When desired, treatments with reported efficacy include sclerotherapy, local excision and electron beam radiation.

Sclerotherapy in the Treatment of Familial Disseminated Cutaneous Glomuvenous Malformations: Case Report

Glomuvenous malformations usually present as soft bluish-purple dermal or subcutaneous papules, nodules or plaques, and can occur as sporadic or inherited lesions. We present the case of a 41-year-old female, referred for evaluation of disseminated bluish lesions developing since puberty. Histopathology was consistent with the diagnosis of glomuvenous malformations. The history of a sister with similar lesions justified a genetic study of the glomulin gene that revealed a pathogenic mutational variant allowing thediagnosis of familial disseminated cutaneous glomuvenous malformations. Whereas surgical management is often used for symptomatic solitary lesions of glomuvenous malformations, other treatment modalities have been reported for treatment of multiple lesions, with variable results. The patient underwent sclerotherapy with polidocanol and there were significant symptomatic and cosmetic improvements after six sessions, with no adverse effects and no recurrence after 6 months.

FKBP51 and FKBP12.6-Novel and tight interactors of Glomulin.

The protein factor Glomulin (Glmn) is a regulator of the SCF (Skp1-CUL1-F-box protein) E3 ubiquitin-protein ligase complex. Mutations of Glmn lead to glomuvenous malformations. Glmn has been reported to be associated with FK506-binding proteins (FKBP). Here we present in vitro binding analyses of the FKBP—Glmn interaction. Interestingly, the previously described interaction of Glmn and FKBP12 was found to be comparatively weak. Instead, the closely related FKBP12.6 and FKBP51 emerged as novel binding partners. We show different binding affinities of full length and truncated FKBP51 and FKBP52 mutants. Using FKBP51 as a model system, we show that two amino acids lining the FK506-binding site are essential for binding Glmn and that the FKBP51-Glmn interaction is blocked by FKBP ligands. This data suggest FKBP inhibition as a pharmacological approach to regulate Glmn and Glmn-controlled processes.

Solitary extradigital glomangioma with thrombus presenting as a painful nodule

Glomangioma, currently termed as glomuvenous malformation, is a rare type of venous malformation (VM) with a rim of glomus cells around the dilated vessels. This glomus cell lesion is not usually as painful as solid glomus tumor. Rarely, thrombus may be seen in the vessels like other VMs. A male with adult-onset extradigital glomangioma presented with a painful nodule with thrombus seen on histopathology. The thrombus was responsible for the tenderness of the lesion, and its presence confirms it to be a malformation than a tumor.

Glomuvenous malformations: dual PDL-Nd:YAG laser approach.

Glomuvenous malformations are uncommon simple vascular malformations that might be present at birth or appear during childhood that have been classically classified as a subtype of venous malformations. Sclerotherapy and surgery have been used in the past as treatments for this condition although with disappointing results in large glomangiomas. The treatment of these lesions has still not been standardized. We conducted a retrospective study of 17 patients treated with dual wavelength PDL-Nd:YAG. The majority of the patients experience a reduction of at least a 60% in their glomuvenous malformations. Treatment was well-tolerated, and adverse effects were rare.

Glomuvenous malformations in a young man

A young man presented with blue nodules on the trunk, face, and extremities that gradually increased in number and size. His mother had similar lesions. Initially, blue rubber bleb nevus syndrome was suspected, but histological findings confirmed the diagnosis of hereditary glomuvenous malformations. Making the correct diagnosis spares the patient unnecessary evaluation for the arteriovenous malformations of the gastrointestinal tract associated with the former diagnosis.

Post-traumatic, sporadic, patch-type glomuvenous malformations: A case report

Post-traumatic, sporadic, patch-type glomuvenous malformations: A case report

Smoothelin and WT-1 expression in glomus tumors and glomuvenous malformations.

Smoothelin is a specific marker for smooth muscle cells with contractile capacity which has not been widely studied in glomus lesions. In the same way, the expression for Wilms tumor 1 (WT1) has only been studied occasionally in the endothelial cells of glomovenous malformations and in the glomus cells of glomus tumours. We studied the significance of immunohistochemical expression of smoothelin and WT1 in 25 glomus lesions. We assessed 9 cases of solid glomus tumors (SGT), 8 cases of glomus tumors with vascular ectasia (VEGT), 2 cases of glomangiomyomas (GMM) and 6 cases of glomuvenous malformation (GM). Immunohistochemistry was performed, evaluating the expression of WT1, smoothelin, smooth muscle actin (SMA), smooth muscle myosin (SMM), h-caldesmon and desmin. Glomic cells showed cytoplasmic positivity for smoothelin, and WT1 expression was present in all studied cases. SGT showed WT1 positivity in all endothelia. However, in regarding VEGT and GMM, WT1 endothelial expression was positive in some areas, but not in others. GM did not show endothelial cell positivity for WT1. Smoothelin expression in glomic cells indicates that they are contractile smooth muscle cells, and thus its role in routine diagnosis should be considered. The absence of WT1 expression in the endothelium of the vascular structures of the GM is a differential characteristic between SGT, VEGT and GMM.