Cavernous Hemangioma Research Articles

Cavernous Hemangioma of the Palatine Tonsil: A Case Report and Review of the Literature

Cavernous Hemangioma of the Palatine Tonsil: A Case Report and Review of the Literature

Case report: A second case of cerebral cavernous malformation after high-dose chemotherapy for medulloblastoma

The development of cerebral cavernous malformations (CCMs) is a well-recognized sequela of irradiation to the brain in pediatric tumors, particularly in medulloblastoma, glioma, and acute lymphoblastic leukaemia. So far, only one case of cerebral cavernoma after chemotherapy with autologous hematopoietic stem cell transplantation (HSCT) has been described. We describe a case of a patient with medulloblastoma aged 18 months at the time of oncological diagnosis who was treated with high-dose chemotherapy followed by HSCT and who developed CCM two years later. The patient was not treated for vascular malformation since he remained asymptomatic until now and is regularly followed with neuro-radiological check-ups. This represents the second case of acquired cavernoma developed in a patient who has not received radiation therapy.

Lesions of the Palm – Mimickers of Dupuytren’s Disease

Background and Aims: Dupuytren’s contracture is a prevalent, hereditary fibroproliferative disorder affecting the palmar aponeurosis, which can resemble various neoplastic and non-neoplastic disorders of the hand. This resemblance poses a diagnostic challenge for healthcare professionals. This observational study aims to evaluate the range of conditions that can be mistaken for Dupuytren’s contracture over a 12-year period (2008–2020) at a specialised orthopaedic oncology centre. Materials and Methods: A retrospective analysis of palmar lesions referred to our tertiary orthopaedic oncology hospital was conducted. Data were gathered from oncology, radiology and histopathology databases. We specifically examined lesions located solely on the palmar aponeurosis, excluding the thenar and hypothenar regions. Patient demographics, clinical features, imaging results and clinical management outcomes were documented for descriptive analysis. Results: A total of 21 palmar lesions meeting the inclusion criteria were identified. The average age of the participants was 48 years (ranging from 3 to 69 years). There was no significant difference in gender distribution, with 11 females and 10 males represented in the cohort. The majority of the identified lesions were benign tumours (16), with one case of malignant rhabdomyosarcoma. Among the benign tumours, lipomas were the most common ( n = 5). Other benign tumours included three neurofibromas, a schwannoma, a granuloma, a ganglion cyst, a giant cell tumour (GCT), an angiomyxoma, a myofibroma, a cavernous haemangioma, a non-specific fibrovascular lesion and four additional non-neoplastic lesions. Conclusion: A variety of benign, malignant or neoplastic conditions of the hand can closely resemble Dupuytren’s contracture, particularly in the initial stages of their development. A thorough clinical examination, combined with a high level of suspicion, along with supplementary investigations and histopathological analysis, is essential for accurate diagnosis and effective management of patients.

Stereotactic radiosurgery (SRS) for patients with brainstem cerebral cavernous malformations (CCMs): an international, multicentric study

Brainstem cerebral cavernous malformations (CCM) are clinically more aggressive compared to superficial CCMs. Due to their location, resection can be challenging, making stereotactic radiosurgery (SRS) an attractive alternative for symptomatic patient. Brainstem CCM patients (n = 170) were treated with Gamma Knife SRS at 11 radiosurgical centers. Hemorrhagic risk reduction, risk factors of post-SRS hemorrhage, and clinical outcomes were retrospectively analyzed. Most patients had a single (165/170 patients) brainstem CCMs treated; the majority of CCMs (165/181) presented with bleeding. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM (HR: 0.17, p < 0.001) using recurrent multivariate analysis. The annual hemorrhage rate decreased from 14.8 per 100 CCM-years before SRS to 2.3 after treatment. Using univariate Cox-analysis, the probability of a new hemorrhages after SRS was reduced for patient older than 35 years (HR = 0.21, p = 0.002) and increased with a margin dose > 13 Gy (HR = 2.57, p = 0.044). Adverse radiation effect (ARE) occurred in 9 patients (5.3%) and was symptomatic in four (2.4%). At a median follow-up of 3.4 years (Inter-quartile range: 5.4), 13 patients (8.0%) had a worsened clinical status, with the treated CCM being the cause in 5.6% (10) of the patients. Single-session SRS decreased the risk of repeat hemorrhage in patients with hemorrhagic brainstem CCM and conveyed this benefit with a low risk of advrse radiation effects (ARE) and worsening clinical status.

In toto resection of a rare intradural extramedullary cavernous malformation on the S1 nerve root: illustrative case.

Cavernous malformations (CMs) are vascular malformations that usually occur in the brain and occasionally in the spine. Most CMs are sporadic, but they can also be caused by heterozygous cerebral cavernous malformation (CCM) gene mutations. This case describes an intradural extramedullary CM in a unique location, within a fascicle of the S1 nerve root. This tumor was found to have a CCM2 mutation. An operative video demonstrates the surgical procedure used to remove this S1 intradural extramedullary CM. A 61-year-old male with an intradural extramedullary CM, located within a fascicle of the S1 nerve root, presented with pain and neurological symptoms. Additional imaging revealed two CCMs. The S1 CM was removed in toto. Subsequently, genetic screening revealed a CCM2 mutation. Given the rarity of a radicular CM, diagnosis can be challenging. CMs should be considered in patients with radicular pain and corresponding nerve root thickening. When a CM is suspected, imaging of the complete neuraxis should be performed. If multiple CMs are found, genetic screening is indicated. Complete resection of the CM yields good clinical results. The operative video in this case might help surgeons encountering this rare pathology to prepare for surgery. https://thejns.org/doi/10.3171/CASE24270.

Multimodality imaging of right ventricular apical atypical cavernous hemangioma.

Multimodality imaging of right ventricular apical atypical cavernous hemangioma.

Radiosurgery versus observation for brainstem cavernous malformations: a 5-year multicentre cohort study.

The role of radiosurgery in preventing haemorrhage in brainstem cavernous malformations remains a subject of debate. This study aims to evaluate whether radiosurgery provides a protective benefit against haemorrhage in these patients. This multicentre, prospective observational study was conducted in 17 centres and enrolled eligible patients with brainstem cavernous malformations consecutively. Data collected included clinical baseline information, radiosurgery planning details, periodic follow-up evaluations, and any adverse radiation effects. The primary outcome of the study was the incidence of first prospective haemorrhage, while the secondary outcome was the development of new or worsening neurological dysfunctions. The impact of radiosurgery was assessed using multivariate Cox regression analysis. From March 2016 to August 2018, the study enrolled 377 patients: 280 in the observation group receiving standard care alone and 97 in the radiosurgery group receiving both radiosurgery and standard care. The overall cohort consisted of 173 females (45.9%) with a mean age of 40.5 years (range, 18-68 years), and there were no significant differences in baseline characteristics between the two groups. After a median follow-up period of 70 months, haemorrhage occurred in 25.0% (n = 70) of patients in the observation group and 10.3% (n = 10) of patients in the radiosurgery group. Multivariate Cox regression analysis identified radiosurgery as an independent protective factor against haemorrhage (hazard ratio 0.379, 95% confidence interval 0.195-0.738, P = 0.004). Following 1:2 propensity score matching, the incidence of prospective haemorrhage were 24.9% (45/181) in the observation group compared to 10.3% (10/97) in the radiosurgery group (hazard ratio 0.379, 95% confidence interval 0.190-0.755, P = 0.006). Adverse radiation effects were observed in 12 patients (12.4%), with none were permanent. Additionally, new or worsening neurological dysfunctions were significantly more common in the observation group (28.9%) compared to the radiosurgery group (16.5%) (P = 0.016). These results suggest that radiosurgery is associated with a low rate of haemorrhage in patients with brainstem cavernous malformations and could provide a benefit in selected patients. However, further research is required to confirm these findings.

Tailored management of cavernous malformations in women: considerations and strategies—a review

Tailored management of cavernous malformations in women: considerations and strategies—a review

Pure Spinal Epidural Cavernous Hemangioma: A Rare Cause of Thoracic Myelopathy

Cavernous hemangiomas mostly occur in intracranial structures but they also may occur in the spine very rarely. Even if found, spinal hemangiomas are commonly vertebral origin and solely epidural hemangiomas not originating from the vertebral bone are very rare. Our case is a 65-year-old man presented to us with progressive paraparesis from six months with motor power 3/5 in both lower extremities. The pathology was total epidural spinal hemangioma at D9-10 vertebral level with typical myelopathy like presentation. Bang. J Neurosurgery 2024; 13(2): 149-151

On Vascular Lesions of the Thyroid Gland with Emphasis on Intrathyroidal Hemangioma: Clinicopathologic Characterization of Two Cases and Review of the Literature

Mesenchymal neoplasms of the thyroid gland are exceptionally rare accounting for less than 0.5% of all intrathyroidal tumors with hemangiomas comprising merely 6% of them. The clinicopathologic characteristics of two additional examples of thyroid hemangioma together with a thorough review of the pertinent literature are presented. A 62-year-old man and an 18-year-old woman presented with asymptomatic, soft-to-palpation, mobile nodules of the right thyroid lobe classified as TI-RADS 5 and TI-RADS 4, respectively, on ultrasound imaging. Microscopically, lesions featured a circumscribed, unencapsulated, lobular proliferation of variably-sized, congested, vascular channels lined by a single layer of flattened, cytologically bland endothelial cells, together with interspersed residual follicles. Vascular endothelial cells were strongly positive for CD31, CD34 and ERG, and negative for pancytokeratin AE1/AE3, TTF1, and PAX8. A diagnosis of cavernous hemangioma was rendered in the clinical setting of Hashimoto thyroiditis and follicular adenoma, respectively. Following inclusion of the current cases, a total of 53 intrathyroidal hemangiomas were identified in the literature with a patient mean age of 48.9 years (range = 0.17-84) and a slight female predilection (F:M = 1.4:1). A proclivity for the right thyroid lobe (59.6%) was noted with the striking majority of cases exhibiting features of cavernous hemangioma (95.2%). Prognosis is favorable and surgical resection is considered curative. The occasionally alarming clinical presentation in conjunction with absence of pathognomonic imaging features and limited diagnostic accuracy of FNA cytopathology for such lesions renders surgical intervention necessary for definitive diagnosis of intrathyroidal hemangiomas and exclusion of other epithelial and non-epithelial pathologic entities.

Intraoperative changes in electrophysiological monitoring can be used to predict clinical outcomes in patients with spinal cavernous malformation.

The study aimed to evaluate the sensitivity and specificity of these monitoring parameters in predicting postoperative neurological dysfunction. In this study, a total of 85 patients with spinal cavernous malformations (SCMs) treated at Xuanwu Hospital, Capital Medical University, from November 2012 to August 2017 were included. During the surgical procedures, all patients underwent monitoring of motor evoked potentials (MEP) and somatosensory evoked potentials (SEP). The criteria for warning included a reduction of ≥80% in MEP amplitude and ≥50% in SEP amplitude. Among 85 patients, 40 (47.1%) had SCMs located in the thoracic segment, 35 (41.2%) in the cervical segment, 6 (7.1%) in the cervical thoracic segment, and 4 (4.7%) in the lumbar segment. MEP recordings were obtained from 81 patients, and the preoperative McCormick score was 1.53 ± 0.69. The sensitivity of multimodal monitoring combined with the criteria of 80% reduction in MEP amplitude and SEP was 83.9%, with a specificity of 69%, a positive predictive value of 69%, and a negative predictive value of 90.4%. This study emphasizes the crucial role of electrophysiological monitoring, particularly MEP and SEP, during the surgical resection of SCMs. The findings demonstrate that this approach is effective in predicting and preventing postoperative neurological dysfunction, thereby improving patient outcomes.

Efficacy of endoscopic submucosal tunnel dissection in the management of a large esophageal cavernous hemangioma.

Efficacy of endoscopic submucosal tunnel dissection in the management of a large esophageal cavernous hemangioma.

Rare Co-occurrence of Spinal Cord Hemorrhage from Radiation-induced Cavernous Hemangioma and Classical Hodgkin Lymphoma Post-transplant Lymphoproliferative Disorder.

Post-transplant lymphoproliferative disorders (PTLDs) are lymphoproliferative diseases that occur after solid organ transplantation or hematopoietic stem cell transplantation (HSCT). The development of PTLD is often associated with reactivation of Epstein-Barr virus (EBV). A 26-year-old woman with a history of HSCT and total-body irradiation developed spinal cord hemorrhage from a radiation-induced cavernous hemangioma (RICH) shortly after the development of classical Hodgkin lymphoma PTLD with EBV reactivation. Although little is known about the factors leading to hemorrhagic events from spinal cord RICH, we suspect that EBV reactivation may have been a factor contributing to the hemorrhage in the present case.

A Rare Case Report of Cervical Hemangiomatous Polyp.

The uterine cervix is a rare site for cavernous hemangiomas. Cervical hemangiomas are slow-growing tumors with characteristic histological findings, including dilated vessels with increased endothelial cells. Although their pathophysiology remains unclear, hormones are believed to play an important role in the development of these vascular tumors. They may be asymptomatic due to their small size, but they can cause gynecological and obstetrical complications, including abnormal uterine bleeding and impaired fertility. Due to their small size, conservative treatment is the first line of management. Hysterectomy is considered for refractory cases or for patients who are not of childbearing age. We present a case report of a 62-year-old postmenopausal female with postmenopausal bleeding and a polypoid mass hanging over the anterior cervical wall through its stalk. The surgical biopsy revealed no signs of neoplastic changes, with the only notable finding being a polypoidal lesion representing a cavernous hemangiomatous cervical polyp.

Epigenetic regulation by polycomb repressive complex 1 promotes cerebral cavernous malformations.

Cerebral cavernous malformations (CCMs) are anomalies of the cerebral vasculature. Loss of the CCM proteins CCM1/KRIT1, CCM2, or CCM3/PDCD10 trigger a MAPK-Krüppel-like factor 2 (KLF2) signaling cascade, which induces a pathophysiological pattern of gene expression. The downstream target genes that are activated by KLF2 are mostly unknown. Here we show that Chromobox Protein Homolog 7 (CBX7), component of the Polycomb Repressive Complex 1, contributes to pathophysiological KLF2 signaling during zebrafish cardiovascular development. CBX7/cbx7a mRNA is strongly upregulated in lesions of CCM patients, and in human, mouse, and zebrafish CCM-deficient endothelial cells. The silencing or pharmacological inhibition of CBX7/Cbx7a suppresses pathological CCM phenotypes in ccm2 zebrafish, CCM2-deficient HUVECs, and in a pre-clinical murine CCM3 disease model. Whole-transcriptome datasets from zebrafish cardiovascular tissues and human endothelial cells reveal a role of CBX7/Cbx7a in the activation of KLF2 target genes including TEK, ANGPT1, WNT9, and endoMT-associated genes. Our findings uncover an intricate interplay in the regulation of Klf2-dependent biomechanical signaling by CBX7 in CCM. This work also provides insights for therapeutic strategies in the pathogenesis of CCM.

Force-mediated recruitment and reprogramming of healthy endothelial cells drive vascular lesion growth

Force-driven cellular interactions are crucial for cancer cell invasion but remain underexplored in vascular abnormalities. Cerebral cavernous malformations (CCM), a vascular abnormality characterized by leaky vessels, involves CCM mutant cells recruiting wild-type endothelial cells to form and expand mosaic lesions. The mechanisms behind this recruitment remain poorly understood. Here, we use an in-vitro model of angiogenic invasion with traction force microscopy to reveal that hyper-angiogenic Ccm2-silenced endothelial cells enhance angiogenic invasion of neighboring wild-type cells through force and extracellular matrix-guided mechanisms. We demonstrate that mechanically hyperactive CCM2-silenced tips guide wild-type cells by transmitting pulling forces and by creating paths in the matrix, in a ROCKs-dependent manner. This is associated with reinforcement of β1 integrin and actin cytoskeleton in wild-type cells. Further, wild-type cells are reprogrammed into stalk cells and activate matrisome and DNA replication programs, thereby initiating proliferation. Our findings reveal how CCM2 mutants hijack wild-type cell functions to fuel lesion growth, providing insight into the etiology of vascular malformations. By integrating biophysical and molecular techniques, we offer tools for studying cell mechanics in tissue heterogeneity and disease progression.

7328 A case of Adrenal Calcifications in a Patient with Familial Cerebral Cavernous Malformations

Abstract Disclosure: R.I. Dorin: None. L.E. Aguirre: None. M. Bomgardner: None. Background: Familial syndromes of cerebral cavernous malformation (fCCM) having autosomal dominant inheritance and variable penetrance and expression have been linked to loss of function mutations at three genetic loci. The association of small focal adrenal calcifications with fCCM was only recently recognized in a New Mexican cohort of subjects predominately carrying the founder common Hispanic mutation in the CCM1 locus (stop codon Q455X in the Krev1 interaction trapped gene 1 [KRIT1]). We report a case of bilateral, focal adrenal calcifications in a patient affected by fCCM. Clinical Case: A 72-year-old Hispanic male with past medical history of intracranial CCM was referred for osteoporosis and hyperthyroidism due to multinodular goiter. Small focal calcifications of the adrenal glands were incidentally noted on prior imaging studies. There was no history of anticoagulant use, adrenal hemorrhage, or systemic/adrenal infection. The patient was without clinical manifestations of adrenal insufficiency, morning cortisol and plasma ACTH concentrations were normal, and exam was negative for hyperpigmentation or cutaneous vascular malformations. Brain MRI revealed the presence of over 100 parenchymal CCM lesions. A family history of CCM was reported in multiple family members, including 7/10 siblings. Conclusion: In addition to cutaneous malformations, small focal adrenal calcifications are now recognized as one of the extra-neurological manifestations of fCCM, particularly in patients harboring the common Hispanic CCM1/KRIT1 mutation. Whether adrenal calcifications are observed in fCCM patients having other mutations of KRIT1 or other genetic loci of fCCM (CCM2 or PDCD10) remains to be determined. The focal adrenal calcifications are believed to be result of dyssynchronous, subclinical hemorrhagic events related to vascular malformations in the adrenal gland. These findings implicate a role for KRIT1 in endothelial development in the adrenal gland in addition to established role in CNS, spinal cord, and skin. Our patient appeared had normal adrenocortical function, as expected for the focal nature of the adrenal lesions. Though adrenal function has not been evaluated in fCCM patients, there are no reports of primary adrenal insufficiency in fCCM in the literature. Adrenal calcifications may be considered to represent an imaging biomarker for fCCM, and fCCM should be included in the differential diagnosis of adrenal calcifications. The incidental recognition of characteristic small, focal adrenal calcifications in either bilateral or unilateral adrenal glands should prompt evaluation for fCCM.

Clinical case of an atypical variant of Labbe's vein structure in a patient with pharmacoresistant temporal epilepsy

Among the commonly recognised structural lesions that cause drug-resistant temporal lobe epilepsy, such as mesial temporal sclerosis, focal cortical dysplasia, benign intracerebral tumors, arteriovenous malformations and cavernous angiomas, researchers have recently noted other pathologies, such as, encephalocele. There are a number of publications on the connection between epilepsy and cerebral venous angiomas. However, there are no published cases of the influence of the abnormal structure and location of normal cerebral vessels on the development of epilepsy. This article presents a case of an atypically large and unusually located vein of Labbe that may have been involved in epileptogenesis and also complicated an anteromedial temporal lobectomy. Forced coagulation and excision of the Labbe vein during surgery did not lead to venous infarction and neurological deficit.

Presurgical Use of Cenobamate for Adult and Pediatric Patients Referred for Epilepsy Surgery: Expert Panel Recommendations.

Cenobamate has demonstrated efficacy in patients with treatment-resistant epilepsy, including patients who continued to have seizures after epilepsy surgery. This article provides recommendations for cenobamate use in patients referred for epilepsy surgery evaluation. A panel of six senior epileptologists from the United States and Europe with experience in presurgical evaluation of patients with epilepsy and in the use of antiseizure medications (ASMs) was convened to provide consensus recommendations for the use of cenobamate in patients referred for epilepsy surgery evaluation. Many patients referred for surgical evaluation may benefit from ASM optimization; both ASM and surgical treatment should be individualized. Based on previous clinical studies and the authors' clinical experience with cenobamate, a substantial proportion of patients with treatment-resistant epilepsy can become seizure-free with cenobamate. We recommend a cenobamate trial and ASM optimization in parallel with presurgical evaluations. Cenobamate can be started before phase two monitoring, especially in patients who are found to be suboptimal surgery candidates. As neurostimulation therapies are generally palliative, we recommend trying cenobamate before vagus nerve stimulation (VNS), deep brain stimulation, or responsive neurostimulation (RNS). In surgically remediable cases (mesial temporal sclerosis, benign discrete lesion in non-eloquent cortex, cavernous angioma, etc.), cenobamate use should not delay imminent surgery; however, a patient may decide to defer or even cancel surgery should they achieve sustained seizure freedom with cenobamate. This decision should be made on an individual, case-by-case basis based on seizure etiology, patient preferences, potential surgical risks (mortality and morbidity), and likely surgical outcome. The addition of cenobamate after unsuccessful surgery or palliative neuromodulation may also be associated with better outcomes.

Endoscopic transorbital approach for resection of mediobasal temporal lesions using an optic radiation-sparing strategy.

The endoscopic transorbital approach (ETOA) has emerged as a promising minimally invasive technique for resection of lesions in the mediobasal temporal region (MTR) due to its potential to preserve the integrity of the optic radiation (OR). This study evaluated the safety and efficacy of ETOA using an OR-sparing surgical strategy for mediobasal temporal lesions. A retrospective review was conducted of the medical records of 15 patients (7 females and 8 males) who underwent ETOA for lesions in the MTR between November 2017 and November 2022. Preoperative diffusion tensor imaging (DTI) tractography of the OR was utilized in all cases for surgical planning to visualize the spatial relations between the OR and the target mediobasal temporal lesion. The median age of the treated patients was 43 years (range 22-76 years), with a median follow-up duration of 12 months (range 6-35 months). Eleven lesions (73.3%) involved only the anterior segment of the MTR, while 4 lesions (26.7%) affected both the anterior and middle segments. Gross-total resection was achieved in 13 patients (86.7%) and subtotal resection in 2 (13.3%). The final pathologies included low-grade glioma (n = 5), cavernous malformation (n = 3), glioblastoma multiforme (n = 2), multinodular and vacuolating neuronal tumor (n = 1), pleomorphic xanthoastrocytoma (n = 1), anaplastic oligodendroglioma (n = 1), adenoid cystic carcinoma (n = 1), and metastatic renal cell carcinoma (n = 1). Postoperative neuro-ophthalmological examinations revealed that all patients maintained their previous visual function. Follow-up DTI tractography further confirmed the preservation of the preoperative ORs in the treated patients. No postoperative CSF leaks, infections, or cosmetic problems occurred in this series. The combined use of ETOA and OR tractography appears to be a feasible approach for resecting lesions involving the MTR, especially in the anterior segment. In the authors' experience, this surgical strategy enables maximal safe resection while minimizing the risk of postoperative visual dysfunction. Further studies with larger sample sizes are warranted to validate these findings and assess long-term outcomes.