Radiation-induced Cavernous Malformations Research Articles

Radiation-induced cavernous malformations in the spine: patient series.

Radiation-induced spinal cord cavernous malformations (RISCCMs) are a rare subset of central nervous system lesions and are more clinically aggressive than congenital cavernous malformations (CMs). The authors assessed the characteristics and outcomes of patients with RISCCM at a single institution and systematically reviewed the pertinent literature using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Among the 146 spinal CMs at the authors' institution, 3 RISCCMs were found. Symptom duration ranged from 0.1 to 8.5 months (mean [standard deviation], 3.2 [4.6] months), and latency ranged from 16 to 29 years (22.4 [9.6] years). All 3 RISCCMs were surgically treated with complete resection; 2 patients had stable outcomes, and 1 improved postoperatively. A review of 1240 articles revealed 20 patients with RISCCMs. Six of these patients were treated with resection, 13 were treated conservatively, and in 1 case, the treatment type was not stated. Five of the 6 patients treated surgically reported improvement postoperatively or at follow-up; 1 was stable, and none reported worsened outcomes. RISCCMs are rare sequelae following radiation that inadvertently affect the spinal cord. Altogether, the frequency of stable and improved outcomes on follow-up suggests that resection could prevent further patient decline caused by symptoms of RISCCM. Therefore, surgical management should be considered primary therapy in patients presenting with RISCCMs.

The development of numerous radiation-induced cavernous malformations in a germ cell tumor patient: A case report

Radiation-induced cavernous malformations (RICMs) are most commonly reported in young patients who have previously received radiotherapy. Here, we report a case of a patient with a germ cell tumor who was treated with whole brain radiotherapy (WBRT) and then incidentally found to have numerous RICMs. A 31-year-old male visited the hospital for a testicular mass. On examination, he was diagnosed with a mixed germ cell tumor with lung/brain metastases. The patient underwent a left orchiectomy and received 4 cycles of chemotherapy. He was then treated with WBRT for residual lesions in the brain and a wedge resection for the lung metastasis. Four years later, approximately 250-300 RICMs were incidentally observed in a follow-up brain image. Because the patient had not noticed any symptoms and the RICMs were small in size, he was not treated. To our knowledge, this is the first reported case of numerous (approximately 250-300) RICMs in a germ cell tumor patient after WBRT. Herein, we report details of this case and discuss the typical clinical features of RICM.

Long-term follow-up of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumor.

OBJECTIVE The authors analyzed the efficacy of intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial germ cell tumors (GCTs) and evaluated the long-term late effects caused by chemoradiotherapy (CRT). METHODS The authors performed a retrospective study. The subjects were 24 patients who received CRT between April 1994 and April 2015. After surgery, intensive chemotherapy followed by reduced-dose and reduced-field irradiation was administered. For those with pure germinoma, who comprised the “good prognosis” group, five courses of conventional-dose chemotherapy (CDC) were administered, and radiotherapy (24 Gy) was applied to the whole ventricle. For all others, defined as the “intermediate and poor prognosis” group, two or three courses of CDC and high-dose chemotherapy were administered with peripheral blood stem cell transplantation and radiotherapy (24–30 Gy) applied to the whole ventricle or a larger field with or without local boost irradiation (20 Gy), which was applied as needed. RESULTS The median period of follow-up was 112.5 months (range 28–261 months), and the 5-/10-year overall and progression-free survival rates were 100%/83.5% and 91.3%/86.5%, respectively. The 5-/10-year overall survival rates determined based on the histological subtypes were 100%/100% for pure germinoma and 93.8%/78.7% for others, respectively. The late toxicities were as follows: endocrine disorder (33% in pure germinoma, 56% in others), involuntary movements (17% in pure germinoma, 39% in others), ear and labyrinth disorders (17% in pure germinoma, 33% in others), and psychiatric disorders (0% in pure germinoma, 33% in others). Nineteen of 24 patients underwent MRI (T2*- or susceptibility-weighted imaging) after radiotherapy, and 16 (84%) of those 19 patients had microbleeds detected, while 2 (10.5%) had radiation-induced cavernous vascular malformations detected. CONCLUSIONS Intensive chemotherapy followed by reduced-dose and reduced-field irradiation for intracranial GCTs had the same outcome as that reported in the literature, but late adverse effects after treatment were observed. Almost all of the complications were relatively mild but had the potential to lead to psychiatric disorders and intracranial hemorrhaging. ABBREVIATIONS AFP = alpha-fetoprotein; CDC = conventional-dose chemotherapy; CMB = cerebral microbleed; CRT = chemoradiotherapy; CSI = craniospinal irradiation; EP = etoposide and cisplatin; GCT = germ cell tumor; HCG = human chorionic gonadotropin; HDC = high-dose chemotherapy; ICE = ifosfamide, cisplatin, and etoposide; NGGCT = nongerminomatous GCT; OS = overall survival; PBSCT = peripheral blood stem cell transplantation; PFS = progression-free survival; RICM = radiation-induced cavernous malformation; STGC = syncytiotrophoblastic giant cell; SWI = susceptibility-weighted imaging.

Radiation-Induced Cavernous Malformations After Single-Fraction Meningioma Radiosurgery.

Stereotactic radiosurgery (SRS) is a commonly performed procedure for patients with intracranial meningiomas. To describe the clinical features of patients with radiation-induced cavernous malformations (RICM) after single-fraction meningioma SRS. Retrospective study of patients having single-fraction SRS for intracranial meningioma at our center from 1990 through 2009, and 1 patient who had single-fraction SRS elsewhere. Patients were excluded if they refused research authorization (n=7), had a World Health Organization Grade II or III meningioma (n=65), had a genetic predisposition for tumor development (n=52), had prior or concurrent radiation therapy (n=49), or had less than 2 yr of magnetic resonance imaging follow-up after SRS (n=77). The median follow-up of the remaining 426 patients was 7.9 yr (range, 2-24.9). Three RICM (0.7%) were identified at 2, 10, and 21 yr after SRS. Two patients were asymptomatic, whereas 1 patient had a brainstem hemorrhage causing facial weakness and numbness. The risk of developing an RICM after SRS was 0.2% at 5 yr and 0.9% at 15 yr. All patients were observed and remained stable without additional bleeding in follow-up of 7, 12.8, and 2 yr, respectively. A fourth patient developed progressive neurological dysfunction starting 7 yr after SRS at another center and was treated for several years with bevacizumab without improvement. Surgical resection was performed 11.5 yr after SRS and histologic examination was consistent with an RICM. The risk of RICM after single-fraction SRS for intracranial meningiomas is very low, but the latency period noted until their detection emphasizes the need for extended imaging follow-up after SRS of benign lesions.

Cranial Cavernous Malformations: Natural History and Treatment.

Cavernous malformations (CMs), also known as cavernous angiomas or cavernomas, are low-flow vascular malformations of the brain and spinal cord that consist of clusters of dilated sinusoidal channels lined with endothelial cells that do not exhibit intervening tight junctions. The involved blood vessels lack muscular and elastic layers, and blood at various stages of thrombosis and organization often fills the thin-walled vascular caverns. CMs are grossly distinct from adjacent brain and have a lobulated appearance sometimes likened to a mulberry, with a characteristic dark red or purple color. Hemosiderin and gliosis often surround CMs of the brain and spinal cord; no neural tissue is present inside the lesion. Except for developmental venous anomalies (DVAs) present in ≈33% of CMs,1 no abnormal vascularity is typically seen on digital subtraction angiography, leading CMs to be termed cryptic or occult vascular malformations (Figure 1). Multiple small hemorrhage events lead to a pathognomonic popcorn appearance on magnetic resonance (MR) imaging because of hemosiderin staining from blood products of various ages. Calcifications may be present on computed tomographic imaging (Figure 2). Figure 1. A 48-year-old woman presented with headaches. A , Magnetic resonance imaging of the brain with T2-weighted imaging demonstrated a 1.1-cm lesion in the cerebellar vermis with mixed signal intensity. B – D , Susceptibility-weighted imaging demonstrated hemosiderin within the lesion’s core and a developmental venous anomaly associated with the cavernous malformation (arrowheads). Figure 2. A 28-year-old woman presented with partial seizures without secondary generalization. A , Noncontrast computed tomography of the head demonstrated a 1.4-cm right posterior cingulate hyperdensity, with evidence of mild hemorrhage and calcification. Magnetic resonance imaging of the brain demonstrated the cavernous malformation to have a core of mixed signal intensity, heterogeneous enhancement, and a rim of hemosiderin consistent with a cavernous malformation, as evidenced on ( B ) susceptibility-weighted imaging, ( C ) T2-weighted …

Natural history of cavernous malformations in children with brain tumors treated with radiotherapy and chemotherapy

Cavernous malformations (CM) are cerebral irradiation-related late complications. Little is known about their natural history and the pathogenetic role of concomitant chemotherapy. We present a retrospective, single-institution study of 108 children affected with medulloblastoma, ependymoma, or germinoma treated with radio- and chemotherapy. The frequency, clinical and radiological presentations, and outcomes were analyzed to investigate the relationship among radiation dose, associated chemotherapy, age, latency and localization of radiation-induced CM. 100 out of 108 children were treated with radiotherapy for primary brain tumor; 34 (27 with medulloblastoma and 7 with other histologies) out of 100 patients developed CM. No significant relationship was found between CM and gender (p=0.70), age (p=0.90), use of specific chemotherapy (standard versus high-dose, p=0.38), methotrexate (p=0.49), and radiation dose (p=0.45). However, CM developed more frequently and earlier when radiotherapy was associated with methotrexate (70% of cases). Radiation-induced CM prevailingly occurred in the cerebral hemispheres (p=0.0001). Only 3 patients (9%) were symptomatic with headache. Three patients underwent surgery for intra- or extra-lesional hemorrhage. CM was confirmed by histopathology for all 3 patients. The vast majority of radiation-induced CM is asymptomatic, and macro-hemorrhagic events occur rarely. Concomitant therapy with methotrexate seems to favor their development. We recommend observation for asymptomatic lesions, while surgery should be reserved to symptomatic growth or hemorrhage.

Letter to the Editor: Radiation-induced cavernous malformations

Letter to the Editor: Radiation-induced cavernous malformations

Radiation‐Induced Cavernous Malformations of the Cauda Equina Mimicking Carcinomatous or Infectious Meningitis. A Case Report

The authors present a case of multiple radiation-induced cavernous malformations of the cauda equina in a patient with a remote history of testicular cancer and extended field radiation therapy. Magnetic resonance imaging (MRI) demonstrated multiple nodular areas of enhancement coating the nerve roots of the cauda equina, mimicking an aggressive leptomeningeal process such as carcinomatous or infectious meningitis. Biopsy of one of these lesions revealed ectatic vascular channels devoid of intervening neuroglial tissue consistent with cavernous malformation.

Cavernous malformation after radiation therapy for astrocytoma in adult patients: report of 2 cases

Radiation-induced cavernous malformations are rarely reported, and most cases have been children. We describe two adult patients with cavernous malformation after irradiation for astrocytoma. Magnetic resonance (MR) imaging, at their ages of 53 years, showed a cavernous malformation in the irradiated field 26 and 10 years after resection and irradiation, respectively. Cavernous malformations were confirmed by the histopathological examination in the both cases. Radiation-induced cavernous malformations are rare in adult patients with astrocytoma. One reason why we found two such cases was that these patients had been successfully treated for astrocytoma and had long follow-up periods.

Multiple Spinal Cavernous Malformations with Atypical Phenotype after Prior Irradiation: Case Report

This is the first reported case of histologically proven multiple spinal cavernous malformations (CMs) associated with previous irradiation. There are only two cases reported in the literature of solitary spinal CM after irradiation. In addition, the lesions in our patient had an atypical magnetic resonance imaging appearance mimicking intraspinal drop metastasis. A 33-year-old man had an incidental finding of multiple enhancing intraspinal lesions as revealed by magnetic resonance imaging during staging tests for hepatocellular carcinoma. He had a history of Wilms' tumor at a young age with irradiation to the abdomen and pelvis. His family history included a paternal cousin with multiple cerebral CMs. The diagnosis of spinal drop metastasis was made, and further intervention was undertaken for confirmation. The patient underwent a lumbar laminectomy with durotomy and excision of two of the lesions. Macroscopic analysis revealed mulberry-like appearance with nerve root involvement, and pathological analysis confirmed the diagnosis of CM. Genetic testing of the patient and his affected cousin was negative for the CCM1 gene. The occurrence of multiple spinal lesions in the context of known neoplasia indicates a diagnosis of metastasis. Spinal CMs were not suspected preoperatively because of the atypical appearance revealed by magnetic resonance imaging scans, with uniform contrast enhancement and absence of hemosiderin rim. This case report is discussed relative to previous literature regarding radiation-induced CMs and other known causes of the disease.