Peritumoral Cysts Research Articles

Defining tumor growth in vestibular schwannomas: a volumetric inter-observer variability study in contrast-enhanced T1-weighted MRI

PurposeFor patients with vestibular schwannomas (VS), a conservative observational approach is increasingly used. Therefore, the need for accurate and reliable volumetric tumor monitoring is important. Currently, a volumetric cutoff of 20% increase in tumor volume is widely used to define tumor growth in VS. The study investigates the tumor volume dependency on the limits of agreement (LoA) for volumetric measurements of VS by means of an inter-observer study.MethodsThis retrospective study included 100 VS patients who underwent contrast-enhanced T1-weighted MRI. Five observers volumetrically annotated the images. Observer agreement and reliability was measured using the LoA, estimated using the limits of agreement with the mean (LOAM) method, and the intraclass correlation coefficient (ICC).ResultsThe 100 patients had a median average tumor volume of 903 mm3 (IQR: 193–3101). Patients were divided into four volumetric size categories based on tumor volume quartile. The smallest tumor volume quartile showed a LOAM relative to the mean of 26.8% (95% CI: 23.7–33.6), whereas for the largest tumor volume quartile this figure was found to be 7.3% (95% CI: 6.5–9.7) and when excluding peritumoral cysts: 4.8% (95% CI: 4.2–6.2).ConclusionAgreement limits within volumetric annotation of VS are affected by tumor volume, since the LoA improves with increasing tumor volume. As a result, for tumors larger than 200 mm3, growth can reliably be detected at an earlier stage, compared to the currently widely used cutoff of 20%. However, for very small tumors, growth should be assessed with higher agreement limits than previously thought.

Massive cystic falcine meningioma presented with slight symptoms: a case report

Introduction and importance: Meningiomas are the most common intracranial tumors while their presence with cysts is relatively low. In general, large ones usually present with severe symptoms and have a high recurrence rate even after total resection which is also difficult. Case presentation: The authors present a case of an elderly patient with a large Falcine meningioma associated with peritumoral cysts. The patient presented with mild symptoms despite the tumor’s significant size. Imaging studies revealed a large mass in the falcine region with peritumoral cysts. The patient underwent surgical resection of the tumor, which was completed without complications. Clinical discussion: The atypical presentation of this large Falcine meningioma with peritumoral cysts highlights the variability in clinical manifestations of these tumors. Despite the tumor’s size and the presence of peritumoral cysts, the patient experienced mild symptoms and recovered after relatively easy surgery challenging conventional expectations. Conclusion: The successful outcome of this case demonstrates that even large meningiomas can present with mild symptoms. Medical practitioners should not always link the tumor size to the severity of symptoms, recurrence rate, and complexity of surgery.

CT radiomics to differentiate between Wilms tumor and clear cell sarcoma of the kidney in children

BackgroundTo investigate the role of CT radiomics in distinguishing Wilms tumor (WT) from clear cell sarcoma of the kidney (CCSK) in pediatric patients.MethodsWe retrospectively enrolled 83 cases of WT and 33 cases of CCSK. These cases were randomly stratified into a training set (n = 81) and a test set (n = 35). Several imaging features from the nephrographic phase were analyzed, including the maximum tumor diameter, the ratio of the maximum CT value of the tumor solid portion to the mean CT value of the contralateral renal vein (CTmax/CT renal vein), and the presence of dilated peritumoral cysts. Radiomics features from corticomedullary phase were extracted, selected, and subsequently integrated into a logistic regression model. We evaluated the model's performance using the area under the curve (AUC), 95% confidence interval (CI), and accuracy.ResultsIn the training set, there were statistically significant differences in the maximum tumor diameter (P = 0.021) and the presence of dilated peritumoral cysts (P = 0.005) between WT and CCSK, whereas in the test set, no statistically significant differences were observed (P > 0.05). The radiomics model, constructed using four radiomics features, demonstrated strong performance in the training set with an AUC of 0.889 (95% CI: 0.811–0.967) and an accuracy of 0.864. Upon evaluation using fivefold cross-validation in the training set, the AUC remained high at 0.863 (95% CI: 0.774–0.952), with an accuracy of 0.852. In the test set, the radiomics model achieved an AUC of 0.792 (95% CI: 0.616–0.968) and an accuracy of 0.857.ConclusionCT radiomics proves to be diagnostically valuable for distinguishing between WT and CCSK in pediatric cases.

Supratentorial hemangioblastoma: correlation between phenotype, gender and vascular territory affected.

Supratentorial hemangioblastomas are rare, vascular lesions. The presence of peri-tumoral cysts and edema has meaningful clinical, diagnostic and therapeutic implications. Nevertheless, the pathogenesis of both cyst and edema formation is not fully understood. This study sought to determine if the radiologic phenotype of supratentorial hemangioblastoma is affected by the different cerebral arterial circulations. Review of the English-language literature from 1973 to 2023 yielded 53 cases of parenchymal supratentorial hemangioblastomas eligible for analysis. Patients were divided by the vascular territorial distribution of the lesions: anterior circulation (n = 36) or posterior circulation (n = 17), and the groups were compared for demographic, clinical, radiologic and molecular variables. Univariate analyses yielded a significant difference between the groups in five variables. Cystic changes and "classic" radiological phenotype were associated with hemangioblastomas of the posterior circulation (OR = 0.19, p = 0.045 and OR = 0.287, p = 0.048, respectively), while female gender, significant peritumoral edema and purely solid phenotype were associated with hemangioblastomas of the anterior circulation (OR = 3.384, p = 0.045 and OR = 5.25, p = 0.05 and OR = 14.0, p = 0.015; respectively). On multivariate analysis, solid phenotype and female gender remained significantly associated with the anterior circulation (OR = 36.04, p = 0.014 and OR = 4.45, p = 0.045). The incidence of von-Hippel Lindau disease was higher in the anterior-circulation group. Cystic tumors were present in all females in the posterior-circulation group compared to 43.4% in the anterior-circulation group (OR = 20.714, 95% CI 1.061 to 404.122; p = 0.045). Based on historical cases of supratentorial hemangioblastoma, this study shows that different tumor phenotypes are associated with the different cerebral circulations. Gender was also associated with differences in tumor distribution and radiologic phenotype. These novel data may improve our understanding of unique vascular diseases of the central nervous system.

α-SMA positive vascular mural cells suppress cyst formation in hemangioblastoma.

Approximately 60% of hemangioblastomas (HBs) have peritumoral cysts adjacent to the tumor, which can cause neurological deficits due to the mass effect, and the management of cyst formation is a clinical challenge. Vascular mural cells surrounding endothelial cells consist of vascular smooth muscle cells (vSMCs) and pericytes, which are essential elements that support blood vessels and regulate permeability. This study investigated the involvement of mural cells in cyst formation. We analyzed the expression of α-smooth muscle actin (α-SMA), platelet-derived growth factor receptor-beta (PDGFRB), and CD31 in 39 consecutive human cerebellar HBs, 20 of cystic and 19 of solid type. Solid type HBs showed stronger diffuse expression of α-SMA in precapillary arterioles and capillaries within the tumor than cystic type HBs (p = 0.001), whereas there was no difference in PDGFRB and CD31 expression. Detailed observation with immunofluorescence demonstrated that α-SMA was expressed in vascular mural cells surrounding capillaries in the solid rather than in the cystic type. Multivariate analysis including various clinical and pathological factors showed that lower α-SMA expression was significantly correlated with cyst formation (p < 0.001). Our data suggested that vascular mural cells from precapillary arterioles to capillaries expressing α-SMA may be pericytes and play a crucial role in HB cystogenesis.

DNA methylation profiling of central nervous system hemangioblastomas identifies two distinct subgroups.

Hemangioblastomas (HBs) of the central nervous system are highly vascular neoplasms that occur sporadically or as a manifestation of von Hippel-Lindau (VHL) disease. Despite their benign nature, HBs are clinically heterogeneous and can be associated with significant morbidity due to mass effects of peritumoral cysts or tumor progression. Underlying molecular factors involved in HB tumor biology remain elusive. We investigated genome-wide DNA methylation profiles and clinical and histopathological features in a series of 47 HBs from 42 patients, including 28 individuals with VHL disease. Thirty tumors occurred in the cerebellum, 8 in the brainstem and 8 HBs were of spinal location, while 1 HB was located in the cerebrum. Histologically, 12 HBs (26%) belonged to the cellular subtype and exclusively occurred in the cerebellum, whereas 35 HBs were reticular (74%). Unsupervised clustering and dimensionality reduction of DNA methylation profiles revealed two distinct subgroups. Methylation cluster 1 comprised 30 HBs of mainly cerebellar location (29/30, 97%), whereas methylation cluster 2 contained 17 HBs predominantly located in non-cerebellar compartments (16/17, 94%). The sum of chromosomal regions being affected by copy-number alterations was significantly higher in methylation cluster 1 compared to cluster 2 (mean 262 vs. 109 Mb, p = 0.001). Of note, loss of chromosome 6 occurred in 9/30 tumors (30%) of methylation cluster 1 and was not observed in cluster 2 tumors (p= 0.01). No relevant methylation differences between sporadic and VHL-related HBs or cystic and non-cystic HBs could be detected. Deconvolution of the bulk DNA methylation profiles revealed four methylation components that were associated with the two methylation clusters suggesting cluster-specific cell-type compositions. In conclusion, methylation profiling of HBs reveals 2 distinct subgroups that mainly associate with anatomical location, cytogenetic profiles and differences in cell type composition, potentially reflecting different cells of origin.

Infantile Choroid Plexus Papilloma with Multiple Peritumoral Cysts

Infantile choroid plexus papilloma (CPP) associated with multiple peritumoral cysts is a rare variant of CPP, and clinical course and optimal management are largely unknown. A 9-month-old boy presented with a large solid tumor in the left lateral ventricle associated with multiple peritumoral cysts, arachnoid cysts, and hydrocephalus containing xanthochromic fluid with high protein content. Shrinkage of these cysts and resolution of hydrocephalus were achieved after total resection of the hypervascular solid part of the tumor. Histological examination confirmed the solid part of the tumor as CPP and showed that the wall of the peritumoral cysts consisted of reactive gliosis without neoplastic cells. Follow-up magnetic resonance imaging 12 months after surgery revealed that these cysts remained stable. CPP with nonenhancing peritumoral cysts can be managed by resection of only the solid part of the tumor without permanent cerebrospinal fluid diversion.

Combined transcriptomic and lipidomic analysis reveals aberrant lipid metabolism in central nervous system hemangioblastomas

Peritumoral cysts are commonly detected in the central nervous system tumors, especially hemangioblastomas (HBs). However, the molecular mechanisms driving their formation and propagation are still unknown. We conducted an integrated lipidomics and transcriptomics analysis on solid and cystic HB samples in order to elucidate the changes in the lipid profile and expression of lipid metabolism-related genes during cyst formation. Transcriptomic analysis revealed differential expression of several genes between the solid and cystic HBs, and those associated with lipid metabolism, such as ADCY4, MGLL, ACOT2, DGKG, SHC1 and LPAR2, were markedly dysregulated in the cystic HBs. The lipidomic analysis further showed a significant reduction in the abundance of triacylglycerol, ceramide, lysophosphatidylcholine and lysophosphatidylethanolamine, and an increase in phosphatidylcholine and phosphatidylethanolamine levels in the cystic HBs. Furthermore, bioinformatics analysis revealed altered lipid biosynthesis, glycerophospholipid metabolism and phospholipase activity in the cystic HBs. Taken together, our findings indicate that cyst formation in HBs is related with aberrant lipid metabolism.

Contrast-Enhanced Ultrasound Assisted Surgery of Intramedullary Spinal Cord Tumors: Analysis of Technical Benefits and Intra-operative Microbubble Distribution Characteristics

Intra-operative contrast-enhanced ultrasound (CEUS) is a relatively standardized procedure in brain neurosurgery, but it is still underused in spinal cord and intramedullary tumor evaluation. We reviewed and analyzed the intra-operative data from a surgical series of patients harboring intramedullary spinal cord tumors who underwent surgery under CEUS guidance. CEUS was performed in 12 patients (age range: 13–55 y); all lesions had ill-defined boundaries or peritumoral cysts at preliminary intra-operative B-mode ultrasound. CEUS highlighted the tumors in all cases. The contrast agent's spinal distribution revealed different phases (arterial, peak, washout), as observed in the brain, but these appeared to be slower and less intense. In our experience, intra-operative CEUS allows surgeons to assess spinal cord perfusion and highlight intramedullary tumors in real time. As for other imaging modalities, ultrasound contrast agents add valuable information over baseline imaging, and their use should be fostered to better understand microbubble distribution dynamics.

Outcomes of Fractionated Radiosurgery in Cystic Vestibular Schwannoma

Evaluate outcomes of fractionated SRS in predominantly cystic vestibular schwannoma. Patients undergoing fractionated Radiosurgery for VS were retrospectively reviewed. Patients with cystic tumors were considered candidates for SRS only if they did not have symptomatic or significant radiologic brainstem compression. VSs containing dominant intra-tumoral or peri-tumoral cyst(s) > 50% of the total tumor diameter by greatest linear axial CPA dimension, single or multicystic, were included for study. Pre-treatment clinical and radiographic features, including AAO-HNS hearing class, history of facial weakness, current facial and trigeminal nerve function, AAO-HNS tumor size, and intratumoral vs peritumoral cysts were captured. All Patients underwent treatment on C-Arm Linac with CBCT image guidance to a dose of 25gy/5#. Patients underwent MRI surveillance every 6 months for the first year, annually thereafter for the subsequent 2 years, and then every other year. 15 patients (12 women; median age at treatment, 53 years; range, 36-85 years) with cystic VS met inclusion criteria. The median radiologic follow-up within the cystic group was 48 months (range, 17-100 months), and the median change in tumor size was − 4.3mm. 12 tumors (80%) shrank, 2 (13%) remained stable (experienced significant cyst enlargement within 1 year after treatment, followed by spontaneous cyst shrinkage back to the original pretreatment size), and 1 patient (7%) experienced cyst enlargement of 9 mm over 21 months and underwent retrolabyrinthine subtotal tumor removal and cyst decompression enlarged. Tumor control rate in cystic group of 93%. The median radiologic follow-up in the non-cystic control group, comprising of 53 pts. was 67 months (range, 6-141 months), and the median change in size was −2.0 mm. Tumor control in the solid group was 94%. Comparing only those tumors that decreased in size showed that there was a trend toward a greater reduction within the cystic group, intratumoral being better than peri-tumoral cystic VSs (P = .05). The present study demonstrates that tumor control after fractionated SRS for dominant intratumoral cystic VS may not differ from that of noncystic VS in properly selected cases suggesting that intratumoral cysts have a different behavior compared with those with peripheral cystic components, latter may result from trapped arachnoid or a hemorrhage-related process making them, thus, more susceptible to growth despite control of the solid portion of the tumor.

Cystic Meningioma, an Uncommon Entity: A Case Report

Cystic meningioma refers to meningothelial neoplasms or meningiomas associated with cyst formation. Clinical features depend on the tumors’ size and location, and include symptoms of increased intracranial pressure, seizures, and focal neurological deficit. Four types of cystic meningiomas are described in the literature, suggested by Nauta et al., based on radiologic findings: Type I: Intratumoral cysts in which the tumor, macroscopically visible on all sides of the cyst, surrounds the cavity; Type II: Intratumoral cysts, lying at the periphery of the tumor and surrounded by a row of neoplastic cells, detectable microscopically; Type III: Peritumoral cysts, whose walls consisted partly of adjacent parenchyma and partly of the tumor; and Type IV: Peritumoral cysts, whose walls are formed by the arachnoid (arachnoid cyst), separated from the tumor by a distinct capsule. Theories proposed to explain cyst formation include degeneration or necrosis, direct secretion by meningioma, and reactive changes (peripheral arachnoid cysts). The tumor itself has features similar to non-cystic meningiomas. The cysts are usually of variable size and can be entirely surrounded by tumor (types I or II), clearly between the tumor and the brain (type IV), or within the adjacent brain (type III). On imaging, it is sometimes difficult to distinguish between these types. We herewith present two cases of cystic meningiomas.

Long-Term Outcomes of Gamma Knife Radiosurgery for Cystic Vestibular Schwannomas

Vestibular schwannomas (VSs) can either be solid or contain variable amounts of cystic components. It has been established that gamma knife radiosurgery (GKRS) is an effective treatment modality for solid VSs. However, in the case of cystic VS, given the somewhat unpredictable growth of the cystic portion of these tumors, microsurgery has often been preferred to GKRS in the management of cystic VS. However, to date, a relative paucity of data evaluating the outcomes after GKRS for cystic VS has been available. In the present study, we reviewed our experience treating cystic VSs with GKRS and evaluated the results. The data from patients with a diagnosis of cystic VS who had undergone GKRS from 1999 to 2018 were analyzed. Only those patients who had undergone GKRS as the initial treatment of cystic VSs were included in the present study. Patients who had undergone previous surgical treatment were excluded. The cystic VSs were divided into intratumoral and peritumoral cysts. A total of 24 patients were enrolled in the present study. The mean age was 60.8 ± 2.4 years (range, 38-82 years). The mean follow-up period was 55.8 ± 8.1 months (range, 8-145 months). Of the 24 patients, 11 were men. The control rate after GKRS for cystic VSs was 75%. The 5-year progression-free rate was 70%. Six patients had presented with an increasing lesion size after GKS. Of these 6 patients, 2 underwent surgical treatment and 1 underwent repeat GKRS. No statistically significant differences were found between the control rate and cystic type (P= 0.093). The results from the present study have demonstrated that GKRS is an effective treatment modality for cystic VSs.

Sporadic hemangioblastoma of the film terminale with peritumoral cyst

Background:Spinal hemangioblastoma originating from the film terminale are rare tumors. Here, we present a film terminale hemangioblastoma and review the appropriate literature.Case Description:A 37-year-old female presented with bilateral lower extremity pain without a focal neurological deficit. The magnetic resonance (MR) image demonstrated an intradural spinal tumor at the L1 level, which was accompanied by peritumoral cysts. In addition, there were multiple surpentine flow voids (e.g., consistent with torturous and convoluted vessels), which is typical for hemangioblastoma. At surgery, a spinal hemangioblastoma originating from the film terminale with peritumoral cysts at the L1 level was fully excised without producing a focal postoperative neurological deficit. Histological examination revealed stromal cells with vacuolated cytoplasm and small nuclei in a rich capillary network accompanied by several enlarged vessels. These finding were compatible with a hemangioblastoma.Conclusions:We reported a rare case of a hemangioblastoma originating from the conus presenting at the L1 level. Complete surgical resection was accomplished without any motor deficit.

Expression of angiopoietins in central nervous system hemangioblastomas is associated with cyst formation

PurposeThis study aimed to determine the expression of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), and endothelial tyrosine kinase receptor (Tie-2) in central nervous system (CNS) hemangioblastomas (HBs) and explore the correlation with peritumoral cyst formation. MethodA total of 22 paraffin-embedded specimens derived from 11 cyst-associated and 11 solid solitary CNS HBs were collected for streptavidin-peroxidase immunohistochemical staining. The expression levels of Ang-1, Ang-2 and Tie-2 in cystic and solid HBs were estimated and compared according to the integrated optical density (IOD) of staining in the sections. To further confirm the differential expression of Ang-1 and Ang-2 between cystic and solid HBs, an additional 9 frozen specimens from 5 cyst-associated and 4 solid solitary HBs were collected for Western blot analysis. Clinical histories and radiological records of the patients were reviewed retrospectively. ResultsCompared to normal cerebellum tissue, Ang-1, Ang-2 and Tie-2 were prominently overexpressed in both the stromal cells and endothelial cells of CNS HBs. The expression of Ang-2 and the ratio of Ang-2/Ang-1 in the cystic group were significantly higher than those in the solid group. The intensity of Ang-2 expression in the cystic group was negatively correlated with age. There was no correlation between the expression level of the proteins and sex, tumor location, tumor volume or cyst volume. ConclusionsAng/Tie signaling is upregulated in HBs and is likely associated with the process of intense vascularization and cyst formation. Higher Ang-2 levels and a higher Ang-2/Ang-1 ratio may contribute to cyst formation by increasing the vascular permeability. The decrease in Ang-2 expression with advanced age in cystic-associated HBs may be associated with the reduced growth rate of peritumoral cysts among elderly patients. Ang-2 shows great potential as an effective therapeutic target of symptomatic CNS HBs associated with cysts.

Choroid Plexus Papillomas of the Cerebellopontine Angle

Choroid plexus papillomas (CPPs) of the cerebellopontine angle (CPA) are extremely rare. We present a series of 21 cases operated on in the last 7 years at our institution. During the period from January 2008 to October 2015, we encountered 102 histologically established cases of CPPs, of which 21 were located in the CPA region. Clinical profiles, radiologic features, surgical procedures, intraoperative findings, and outcomes were extracted from the patient records and neuroimaging data. The 21 CPPs in the CPA region accounted for 20.5% of all CPPs. Two of the tumors occurred in pediatric patients. Tumor size was 2.5-4.7 cm. The rate of calcification was higher in the CPPs in the CPA region. Peritumoral cysts and cysts with small nodules were observed in our cases. A far lateral suboccipital approach was chosen for CPPs protruding inferiorly into the foramen magnum region (n= 14), and a suboccipital retrosigmoid approach was chosen for the other tumors. Total resection was achieved in 18 patients, and subtotal resection was achieved in 3 patients. During the follow-up period, only 1 patient experienced recurrence 32 months after the first operation. The recurrence turned out to be an atypical CPP. CPPs in the CPA region cannot be easily differentiated from other tumors preoperatively. Cysts and calcifications appear on neuroimaging. CPPs in the CPA region usually protrude inferiorly into the foramen magnum region. As much tumor should be removed as possible to avoid recurrence and malignant transition.

Biological and clinical impact of hemangioblastoma-associated peritumoral cysts in von Hippel-Lindau disease.

Peritumoral cysts are frequently associated with CNS hemangioblastomas and often underlie neurological morbidity and mortality. To determine their natural history and clinical impact, the authors prospectively analyzed hemangioblastoma-associated peritumoral cysts in patients with von Hippel-Lindau (VHL) disease. Patients with VHL disease who had 2 or more years of follow-up and who were enrolled in a prospective study at the National Institutes of Health were included. Serial prospectively acquired laboratory, genetic, imaging, and clinical data were analyzed. One hundred thirty-two patients (of 225 in the VHL study with at least 2 years of follow-up) had peritumoral cysts that were followed for more than 2 years (total of 292 CNS peritumoral cysts). The mean age at study entrance was 37.4 ± 13.1 years ([mean ± SD], median 37.9, range 12.3-65.1 years). The mean follow-up was 7.0 ± 1.7 years (median 7.3, range 2.1-9.0 years). Over the study period, 121 of the 292 peritumoral cysts (41.4%) became symptomatic. Development of new cysts was associated with a larger number cysts at study enrollment (p = 0.002) and younger age (p < 0.0001). Cyst growth rate was associated with anatomical location (cerebellum cysts grew faster than spine and brainstem cysts; p = 0.0002 and p = 0.0008), younger age (< 35 years of age; p = 0.0006), and development of new neurological symptoms (p < 0.0001). Cyst size at symptom production depended on anatomical location (p < 0.0001; largest to smallest were found, successively, in the cerebellum, spinal cord, and brainstem). The most common location for peritumoral cysts was the cerebellum (184 cysts [63%]; p < 0.0001). Peritumoral cysts frequently underlie symptom formation that requires surgical intervention in patients with VHL disease. Development of new cysts was associated with a larger number of cysts at study enrollment and younger age. Total peritumoral cyst burden was associated with germline partial deletion of the VHL gene.

Discrete or diffuse intramedullary tumor? Contrast-enhanced intraoperative ultrasound in a case of intramedullary cervicothoracic hemangioblastomas mimicking a diffuse infiltrative glioma: technical note and case report

Hemangioblastomas are benign, highly vascularized intramedullary lesions that may also extend into the intradural space. Surgery represents the standard therapy, with the goal of obtaining complete resection even at the risk of neurological morbidity. MRI is the gold standard for diagnosis and assessment of intramedullary tumors. Nevertheless, sometimes MRI may not accurately differentiate between different types of intramedullary tumors, in particular if they are associated with syringes or intra- and peritumoral cysts. This could subsequently affect surgical strategies. Intraoperative ultrasound (ioUS) has become in the last few years a very useful tool for use during neurosurgical procedures. Various ioUS modalities such as B-mode and Doppler have been applied during neurosurgical procedures. On the other hand, the use of contrast-enhanced ultrasound (CEUS) is not yet well defined and standardized in this field. We report a case of a young patient harboring a cervicothoracic intramedullary tumor, for which the preoperative neuroradiologi-cal diagnosis was in favor of a diffuse astrocytoma with nodular components whereas ioUS demonstrated 3 distinct intramedullary nodules. CEUS showed highly vascularized lesions, compatible with hemangioblastomas. These findings, particularly those obtained with CEUS, allowed better definition of the lesions for diagnosis, enhanced understanding of the physiopathological aspects, and permitted the localization of all 3 nodules, thus limiting spinal cord manipulation and allowing complete resection of the lesions, with an uneventful postoperative neurological course. To the best of our knowledge, this is the first report of the use of intraoperative CEUS in a case of intramedullary hemangioblastoma.

Peritumoral cysts associated with pituitary macroadenoma.

Peritumoral cysts are benign nonneoplastic cysts that are found adjacent to extraaxial brain tumors such as meningiomas, schwannomas, craniopharyngiomas, and esthesioneuroblastomas. Peritumoral cysts associated with pituitary macroadenomas have not been previously described in the literature. The authors report 6 cases of giant macroadenoma-associated peritumoral cysts and delineate their imaging spectrum. The authors retrospectively reviewed the records of 179 patients diagnosed with pituitary macroadenomas who underwent tumor resection at their institution and had preoperative MRI scans available for review. The patients were evaluated for the presence of associated peritumoral cysts. Clinical presentation, histopathology, follow-up time, tumor and peritumoral cyst dimensions were recorded. Signal intensity on T1-weighted, T2-weighted, diffusion-weighted, and FLAIR sequences, as well as pre- and postcontrast appearance, were determined. Six patients (3.4%) with associated peritumoral cysts were identified in our cohort of 179 patients with pituitary macroadenoma. Twelve patients in the cohort had giant macroadenomas (≥ 4.0 cm), and 50% of these tumors had associated peritumoral cysts with significant extrasellar extension of the macroadenoma. Only tumors with craniocaudal, transverse, and anteroposterior diameters of 3.6 × 3.4 × 4.2 cm to 7.0 × 7.4 × 6.8 cm (mean 5.3 × 5.1 × 5.6 cm), respectively, had associated peritumoral cysts. The growth pattern in all tumors was suprasellar, with predominant anterior and lateral extension. Cysts showed T1-weighted, T2-weighted, and FLAIR hyperintensity in 67%, 67%, and 60% of patients, respectively. There was no contrast enhancement of the cyst wall or fluid contents in any patient. Postoperatively, cysts had completely resolved (4 of 5) or significantly decreased in size (1 of 5). One patient was lost to follow-up. Macroadenoma-associated peritumoral cysts are rare, benign, and likely nonneoplastic fluid collections that do not represent neoplasm. These cysts display a predictable pattern of hyperintensity on T1-weighted, T2-weighted, and FLAIR sequences and do not enhance. They most likely represent proteinaceous CSF in a sulcus or cistern that becomes trapped (encysted) by anterolateral extension of unusually large macroadenomas. Peritumoral cysts may facilitate resection of the associated macroadenoma by providing a cleavage plane.

Effect of pregnancy on hemangioblastoma development and progression in von Hippel-Lindau disease

Prior cases suggest that pregnancy increases the development and progression of CNS hemangioblastomas and/or peritumoral cysts. To determine the effect of pregnancy on CNS hemangioblastomas and peritumoral cysts, the authors prospectively evaluated serial clinical and imaging findings in patients with von Hippel-Lindau (VHL) disease who became pregnant and compared findings during pregnancy to findings in the same patients when they were not pregnant as well as to findings from a cohort of VHL patients who did not become pregnant. Female VHL disease patients enrolled in a prospective natural history study who were of reproductive age (16-35 years at study entrance) were included. Analysis of serial clinical and imaging findings was performed. Thirty-six consecutive female VHL disease patients harboring 177 hemangioblastomas were included (mean follow-up [± SD] 7.5 ± 2.3 years). Nine patients (25%) became pregnant (pregnancy cohort). The mean rates of development of new hemangioblastomas and peritumoral cysts in these women during pregnancy (0.4 ± 0.4 tumors/year; 0.1 ± 0.2 cysts/year) did not differ significantly (p > 0.05) from the mean rates in the same group during nonpregnant periods (0.3 ± 0.4 tumors/year; 0.1 ± -0.1 cysts/year) or from the rate in the 27 patients who did not become pregnant (the no-pregnancy cohort: 0.3 ± 0.5 tumors/year; 0.1 ± 0.2 cysts/year). Hemangioblastoma growth rates were similar (p > 0.05) during pregnancy (mean 29.8% ± 42.7% increase in volume per year) compared with during nonpregnant periods (41.4% ± 51.4%) in the pregnancy cohort and the no-pregnancy cohort (34.3% ± 55.3%). Peritumoral cyst growth rates during pregnancy (571.0% ± 887.4%) were similar (p > 0.05) to those of the no-pregnancy cohort (483.9% ± 493.9%), but the rates were significantly higher for women in the pregnancy cohort during nonpregnant periods (2373.6% ± 3392.9%; p < 0.05 for comparison with no-pregnancy cohort). There was no significant difference (p > 0.05) in the need for resection or the mean age at resection between the pregnancy (28% of hemangioblastomas in cohort; mean patient age at resection 30.2 ± 2.6 years) and no-pregnancy cohorts (19%; 32.3 ± 5.6 years). Pregnancy is not associated with increased hemangioblastoma or peritumoral cyst development or progression in patients with VHL disease.

Differential diagnosis of frontal lobe dilated perivascular spaces

We read with great interest the article by Cerase et al. [1] on the regression of dilated perivascular spaces (DPVS) of the brain. They reported that the most common location of such spaces is along lenticulostriate arteries and that their differential diagnosis includes an extensive list of diseases such as lacunar infarctions, fungal and parasitic infections, and cystic neoplasms [1]. They successfully noted that some cases reported as ‘‘cysts’’ might have been DPVS [1]. We agree and we would like to comment on the differential diagnosis of such spaces, based on a case from our experience where DPVS appeared as cysts within the frontal lobe. Carrying out a neuroanatomical study in our Department, we found (in a coronally sectioned middle-aged male brain) a cystic cavity placed into the lateral putamen (Fig. 1) and a few small cysts in the white matter above the striatum. The cavity, full of a transparent fluid, appeared as an oval hole with a 9 mm diameter. The putamen around the cavity appeared discoloured, probably because of the space-occupying effect of the cystic lesion. This discolouration extended medially to the internal capsule. Other cysts appeared in the white matter above the striatum. Inside the inferior part of the larger cavity there was a diaphragm forming a vesicle. Maximum dimensions of the main lateral putamen lesion were 15 9 14 9 8 mm. All the observed cysts appeared in the left middle cerebral artery territory. Micropathological examination confirmed the DPVS diagnosis. Cysts are common findings at brain imaging [4]. The commonest causes include vascular diseases, infections and tumours [2–5]. Neurocysticercosis occurs in 75% of all cases of systemic cysticercosis [4] and is the commonest worldwide parasitic brain infection. It causes mainly parenchymal cysts with transparent liquid [2]. Cysts may be multiple but do not typically occur in clusters [4]. Toxoplasmosis forms multiple brain abscesses especially in basal ganglia [2]. Echinococcus granulosus forms hydatid cysts in several organs involving the brain [2, 4]. Primary multiple cerebral hydatid cysts are extremely rare, often found in the middle cerebral artery territory. Typically large cysts may contain daughter cysts [4]. Fungal infections, especially in patients with immunodeficiency [5], include cerebral cryptococcosis and aspergillosis. Lowgrade astrocytomas are frequently seen in the frontal lobe and can be located in basal ganglia, oft containing cysts with smooth internal surface and transparent liquid [3]. Metastatic carcinomas are a usual cause for intracerebral cystic lesions, although having a much lower incidence of associated cysts compared to gliomas [2]. There are also neoplasm-associated benign peritumoral cysts, true arachnoid cysts [4], lacunes (usually located in basal ganglia [5]) and beneign congenital neuroglial (glioependymal) cysts, typically located within the frontal lobe [4]. To conclude, there are numerous causes of multiple intracerebral cystic lesions involving both the basal ganglia and frontal lobe white matter and have to be differentiated from DPVS. A location-based approach to intracranial cysts is helpful in establishing an appropriate differential diagnosis [4]. Lesions following a vessel territory could be due to either vascular or infectious disease [4].