Second surgery for relapsed glioblastoma: an observational study on criteria for patient selection in real life.

Aim: There is little consensus on salvage management of glioblastoma after recurrence, for lack of evidence. Materials & methods: A retrospective study of treatments in patients with recurrent glioblastoma. Results: Surgery at recurrence was related to better overall survival (OS) and progression-free survival (PFS). Surgery at recurrence, Karnofsky index, MGMT methylation status, younger age at diagnosis and number of chemotherapy cycles were positive factors for OS and PFS. The benefit of OS was relevant for a second surgery performed at least 9 months after the first one. Systemic treatments after the second surgery were linked to an improved PFS. Conclusion: Younger age, Karnofsky index, MGMT methylation status and a median time between surgeries ≥9 months may be criteria for eligibility for surgery at recurrence.

[Box: see text].

The Glioma-IRE project - Molecular profiling in patients with glioma: steps toward an individualized diagnostic and therapeutic approach.

BACKGROUND: This study aimed to characterize the genetic profile of patients with glioma and discuss the impact of next-generation sequencing in glioma diagnosis and treatment. METHODS: Between 2019 and 2022, we analyzed the genetic profile of 99 patients with glioma through the Oncomine Focus Assay. The assay enables the detection of mutations in 52 driver genes, including single nucleotide variants (SNVs), copy number variants (CNVs), and gene fusions. We also collected and analyzed patients' clinic characteristics and treatment outcomes. RESULTS: Over a period of 35 months, 700 patients with glioma followed by our neuro-oncology unit were screened, and 99 were enrolled in the study; most of the patients were excluded for inadequate non-morphological MRI or lack/inadequacy of the tissue samples. Based on our findings, most patients with glioma present mutations, such as SNVs, CNVs or gene fusions. Our data were similar to those reported by The Cancer Genome Atlas Program in terms of frequency of SNVs and CNVs, while we observed more cases of gene fusions. Median overall survival, progression-free survival, and time to progression were significantly lower for patients with grade VI glioblastoma than those with other gliomas. Only four patients were offered a targeted treatment based on the mutation detected; however, only one received treatment, the others could not receive the selected treatment because of worsening clinical status. CONCLUSION: Routine timely molecular profiling in patients with glioma should be implemented to offer patients an individualized diagnostic approach and provide them with advanced targeted therapy options if available.

Multidomain and long-term cognitive evaluation in malignant glioma patients.

Aim: We performed longitudinal evaluations of the neurocognitive status in glioma patients to describe possible variations over the course of illness. Materials and methods: Glioma patients underwent a complete battery of standardized neuropsychological tests pre-radiotherapy at 6, 12 and 24 months. Results: We enrolled 130 patients, 67.7% of whom had a deficit in at least one cognitive domain. The most affected domains included executive function (n = 68, 52.3%), long-term memory (n = 46, 35.3%) and short-term memory (n = 39, 30%). At follow-up, cognitive status worsened in 31.5%, remained unchanged in 38.4% and improved in 30.1% of patients. Conclusion: This is one of few studies investigating longitudinal neurocognitive status in a wide sample of patients to monitor neuropsychological changes due to tumor progression and treatment administration.

Malignant gliomas are brain tumors with dismal prognosis that can affect patients' neurocognitive status. We performed longitudinal neuropsychological assessments to describe variations due to illness progression and treatment administration. Patients underwent a battery of standardized neuropsychological tests tapping into different cognitive domains (memory, attention, abstract reasoning, executive functions, learning), pre-radiotherapy and at 6, 12 and 24 month follow-up. We enrolled 130 patients, and almost 70% of them had at least one cognitive deficit. The most affected domains were executive function and long- and short-term memory. At follow-up assessments, cognitive status worsened in one-third of patients, whereas it remained unchanged or improved in two-thirds of patients. This is one of few longitudinal studies investigating cognitive function in a large sample of patients to monitor changes along the illness course.

Recurrent glioblastoma: which treatment? A real-world study from the Neuro-oncology Unit "Regina Elena" National Cancer Institute.

BACKGROUND: The majority of patients with glioblastoma (GBM) experience disease progression. At recurrence, treatment options have limited efficacy. Many studies report a limited and short duration response rate. Although clinical trials represent the "gold standard" for providing evidence on efficacy of specific treatment strategies, real-world data can be considered more representative of the "real" GBM population. OBJECTIVE: To describe the management of GBM recurrence in a large real-world sample. METHODS: We analysed retrospectively the data stored in the database of the Neuro-oncology Unit, IRCCS "Regina Elena" National Cancer Institute, Rome, Italy. We considered only data of patients with histological diagnosis of GBM and disease recurrence during their follow-up. We excluded patients who did not receive treatment after the diagnosis. RESULTS: We analysed 422 patients (64% males, 36% females) with a mean age of 59.6 (range 16-87) years. At GBM recurrence, 135 (32.0%) patients underwent palliative care, and 287 (68.0%) underwent other treatments. Patients on palliative care were older, had a worse performance status, and a shorter time between GBM diagnosis and its recurrence. Patients who received chemotherapy in combination with other treatments (surgery and/or radiation therapy) at GBM recurrence had a longer survival than those in palliative care (p < 0.001). Surgery or radiation therapy alone did not have any effect on survival as compared with palliative care (p < 0.001). CONCLUSION: This study confirms the importance of a multidisciplinary approach even at GBM recurrence, suggesting that combination treatments play a key role in management of disease.

Surgical treatment of solitary intradural extramedullary spinal cord metastases from solid cancers of non-neurogenic origin. A multicenter study.

PURPOSE: Intradural extramedullary spinal metastases (IESM) represent an extremely rare manifestation of systemic cancer. We evaluated the surgical indications, complications and outcome in a series of 43 patients with solitary intradural extramedullary metastases originating from solid cancer of non-neurogenic origin. METHODS: Patients' age, histopathological diagnoses of primary cancer, tumor size, spinal location, and extramedullary tumor dissemination were collected. Preoperative functional status, pre- and post-operative neurological status, extent of the tumor resection were also analyzed. RESULTS: The majority of IEMS occurred in the thoracic area, with the most common presenting symptoms ranging from motor (76.7%) to sensory (72%) deficits. Gross total resection was achieved in 55.8% of cases, while In 44.2% of patients a subtotal resection was performed due to strong adherence between the tumor and neural tissue. After surgery, 72.1% of patients exhibited improvement of symptoms in terms of pain relief and partial recovery of motor and/or sensory deficits, while neurologic functional status was severely affected postoperatively in 3 patients. CONCLUSION: Although there was no statistical significance between the different parameters and overall survival, KPS and the presence of other metastases were the strongest prognostic factors for overall survival and postoperative neurologic outcome.

Eribulin in brain metastases of breast cancer: outcomes of the EBRAIM prospective observational trial.

Background: Eribulin shows some activity in controlling brain metastasis in breast cancer. Methods: This observational, multicenter study evaluated brain disease control rates, survival and safety in patients with brain metastatic breast cancer treated with eribulin in clinical practice. Results: A total of 34 patients were enrolled (mean age 49 years, 91% with visceral metastases) and 29 were evaluable for brain disease. Fourteen achieved disease control and showed a longer time without progression: 10 months (95% CI: 2.3-17.7) versus 4 months (95% CI: 3.3-4.7) in the control group (p = 0.029). Patients with clinical benefits at 6 months had longer survival. Leukopenia and neutropenia were the most frequent grade 3-4 toxicities. Conclusion: Eribulin confirms its effectiveness in patients with brain metastatic breast cancer. Further studies on larger cohorts are needed to confirm the results.

Surgical treatment of intramedullary spinal cord metastases: functional outcome and complications-a multicenter study.

Intramedullary spinal cord metastasis (ISCM) is a rare event in the course of advanced malignancy. Management of these lesions remains controversial. Recently, surgery for ISCM has been advocated for selected patients. We performed a retrospective analysis of the clinical course, complications, and outcome of 30 patients surgically treated for ISCM. Patients' age, histopathological diagnoses of primary cancer, tumor size, spinal location, and extramedullary tumor dissemination were collected. Preoperative functional status, pre- and postoperative neurological status, and extent of the tumor resection were also analyzed. Predominant tumor location was thoracic, followed by cervical and conus medullaris. Lung cancer constituted the majority of primary malignancies. In 9 cases, one of the indications for spinal surgery was to obtain a histopathological diagnosis. On admission, all patients presented with neurological symptoms suggestive of myelopathy. After surgery, 18 patients exhibited improvement of symptoms in terms of pain relief and partial recovery of motor and/or sensory deficits; 6 patients were unchanged, while 6 patients exhibited postoperative deterioration. Median survival time after surgery was 9.9 months. Age > 70 years old, presence of systemic metastases, preoperative neurological non functional status, and lung cancer as primary tumor were all factors associated with a worse survival prognosis. This study did not show a clear survival difference between gross total and subtotal ISCM tumor resection. Patients who underwent gross total resection had a worse functional outcome with respect to patients with only partial resection. Gross total resection with low morbidity must be the surgical target, but when not possible, subtotal resection and adjuvant therapy are a valid therapeutic option.

Oblique Lateral Retroperitoneal Lumbar Pre-Psoas Approach for Vertebrectomy in Cancer Patients: Surgical Technique.

Due to the longer survival of cancer patients secondary to improved systemic treatments, there has been a recent increase in the incidence of spinal metastases. Metastatic disease involves the anterior vertebral body in 80% of cases. Progressive osseous invasion may result in pathologic vertebral fractures and neural structure compression. Surgical indications are spinal cord and cauda equina compression or spinal instability in patients with an expected survival of at least 6 months. Tumor resection and spine reconstruction in the lumbar region are technically demanding. Several approaches have recently been developed to access the lumbar spine: anterior lumbar approach (ALIF), lateral and extreme lateral transpsoas lumbar approach (LLIF, XLIF, DLIF), and oblique retroperitoneal lumbar pre-psoas approach (OLIF). Each technique has its advantages and drawbacks. OLIF is an emerging procedure that has progressively been used by spine surgeons. The retroperitoneal space allows direct access to the vertebra, thus avoiding injury to the paraspinal muscles, psoas muscle, and lumbar plexus. Between 2005 and 2017, 14 patients underwent somatectomy and spinal reconstruction using an oblique retroperitoneal lumbar pre-psoas approach at our institution. All were affected by lumbar vertebral metastases from solid and hematological tumors, and all presented a Tokuhashi score ≥ 12. L3 vertebral body was involved in 7 cases, L1 was involved in 3, L2 was involved in 2, and L4 was involved in 2. All patients underwent a lateral retroperitoneal approach to achieve vertebrectomy and spinal reconstruction with a cage. Spinal fixation was completed with pedicle screws and rods in 4 cases. No neurological worsening was noted except in one patient who presented a transitory deficit of the left ileopsoas muscle. The oblique retroperitoneal lumbar pre-psoas approach may be a valuable and feasible technique that is potentially able to significantly reduce tissue trauma in patients while still making it possible to achieve corpectomy and solid reconstruction of lumbar vertebral bodies. To our knowledge, this is the first reported series of patients with lumbar spinal metastases treated with the oblique retroperitoneal lumbar pre-psoas approach.

Comorbidities in elderly patients with glioblastoma: a field-practice study.

AIM: This single-center study evaluated the effect of comorbidities on progression-free and overall survival in elderly patients with glioblastoma multiforme (GBM). PATIENTS & METHODS: Comorbid conditions were identified in each patient with the modified version of the cumulative illness rating scale (CIRS). RESULTS:  Total of 118 patients with GBM were enrolled. An age of >75 years at diagnosis, high CIRS, comorbidity index and performance status play a predictive role on survival. CONCLUSION: Comorbidities play an important prognostic role in elderly patients with GBM, a factor too often neglected in clinical practice. If the prognostic role of comorbidity measured by CIRS on outcome will be confirmed, it would be interesting to add it in the algorithm for treatment choice in elderly GBM patients.

A multicenter real-world study of bevacizumab in heavily pretreated malignant gliomas: clinical benefit is a plausible end point?

Aim: This multicenter, retrospective study evaluates the clinical benefit (CB) of bevacizumab, alone or in combination, in recurrent gliomas (RG). Patients & methods: The CB was measured as a reduction of corticosteroid dosage and an improvement ≥20 points in the Karnofsky Performance Status lasting ≥3 months. Results: We collected data of 197 RG patients. A CB was observed in 120, patients without significant differences between patients treated with bevacizumab alone or in combination. The rate of patients who achieved a CB and free from progression at 1 year was 21.5 versus 1.4% in patients who did not report CB. Conclusion: The majority of RG patients treated with bevacizumab reported CB. Moreover, patients with CB showed improved survival.

MicroRNA-128-3p-mediated depletion of Drosha promotes lung cancer cell migration.

Alteration in microRNAs (miRNAs) expression is a frequent finding in human cancers. In particular, widespread miRNAs down-regulation is a hallmark of malignant transformation. In the present report, we showed that the miR-128-3p, which is up-regulated in lung cancer tissues, has Drosha and Dicer, two key enzymes of miRNAs processing, as the main modulation targets leading to the widespread down-regulation of miRNA expression. We observed that the miRNAs downregulation induced by miR-128-3p contributed to the tumorigenic properties of lung cancer cells. In particular, miR-128-3p-mediated miRNAs down-regulation contributed to aberrant SNAIL and ZEB1 expression thereby promoting the epithelial-to-mesenchymal transition (EMT) program. Drosha also resulted to be implicated in the control of migratory phenotype as its expression counteracted miR-128-3p functional effects. Our study provides mechanistic insights into the function of miR-128-3p as a key regulator of the malignant phenotype of lung cancer cells. This also enforces the remarkable impact of Drosha and Dicer alteration in cancer, and in particular it highlights a role for Drosha in non-small-cell lung cancer cells migration.

Home palliative care and end of life issues in glioblastoma multiforme: results and comments from a homogeneous cohort of patients.

OBJECT: Glioblastoma multiforme (GBM) is a rare tumor whose prognosis has remained poor over the years despite innovative radio- and chemotherapies, and important technical advances in neurosurgery such as intraoperative imaging, fluorescence, Cavitron ultrasonic surgical aspirator, and neuronavigation. Particular attention has been dedicated in the last years to the end of life (EOL) period in cancer patients for both ethical and socioeconomic issues. Good palliative care at home avoids improper and expensive hospitalizations, and helps and trains families, caregivers, and patients in facing a difficult situation. METHODS: In 2012-2013 the authors' group cared for 197 patients with brain tumors. Of these there were 122 with GBMs: 64 died and 58 are still receiving assistance. The clinical conditions are periodically evaluated with the following scales: Barthel Index, Karnofsky Performance Scale, and Mini-Mental State Examination. Home care staff includes 2 neurologists, 5 nurses, 2 psychologists, 3 rehabilitation therapists, and 1 social worker. The intensity of care changes at the different stages of disease, ranging from low to medium levels of intensity at the progression stage (more than 1 access weekly) to high levels of intensity at the EOL stage (at least 3 accesses weekly). Control MRI studies are obtained every 3 months before terminal progression. RESULTS: Overall in this sample of patients there were 2838 home visits and 11,714 days of assistance. Thirty-four patients (14 female and 20 male) died at home (53.1%); 22 (13 female and 9 male) at the hospice (34.4%); and 8 (4 female and 4 male) at the hospital (12.5%). A positive impact on caregivers for home assistance was recorded in 97% of cases, for nursing in 95%, communication in 90%, rehabilitation at home in 92%, and social work help in 85%. Also, 72% had an improvement in their quality of life scores due to rehabilitation. End of life palliative sedation with midazolam was necessary in 11% of cases to obtain good control of symptoms such as uncontrolled delirium, agitation, death rattle, or refractory seizures. Intramuscular phenobarbital is the authors' drug of choice for the severe seizures that occurred in 30% of cases. The reduction of steroid dosage is also used to decrease wakefulness. Steroids were withdrawn in 45% of patients dying at home, mild hydration was done in 87%, and tube feeding in 13%. The decision-making process at the EOL stage is time consuming, but the degree of distress of the family is inversely proportional to the extent of the preparatory period. CONCLUSIONS: A previous paper showed the positive cost-effectiveness of home assistance for a larger group of patients dealing with any kind of malignant brain tumors. The same is enhanced for patients with GBM. This requires a well-trained neuro-oncology team that manages neurological deterioration, clinical complications, rehabilitation, and psychosocial problems with a multidisciplinary approach.

Radionecrosis induced by stereotactic radiosurgery of brain metastases: results of surgery and outcome of disease.

Sterotactic radiosurgery (SRS) is an effective and commonly employed therapy for metastatic brain tumors. Among complication of this treatment, symptomatic focal cerebral radionecrosis (RN) occurs in 2-10 % of cases. The large diffusion of combined therapies as SRS followed by WBRT and/or CHT, has significantly amplified the number of patients who potentially might be affected by this pathology and neurosurgeons are increasingly called to treat suspected area of RN. Results of surgery of RN in patients with brain metastases are rarely reported in literature, a standardization of diagnostic work-up to correctly identify RN is still lacking and the timing and indications in favour of surgical therapy over medical treatments are not clear as well. In this retrospective study, we review current concept related to RN and analyze the outcome of surgical treatment in a series of 15 patients previously submitted to SRS for brain metastases and affected by suspected radionecrotic lesions. After surgery, all patients except one neurologically improved. No intra-operative complications occurred. Brain edema improved in all patients allowing a reduction or even suspension of corticosteroid therapy. Pure RN was histologically determined in 7 cases; RN and tumor recurrence in the other 8. Overall median survival was 19 months. An aggressive surgical attitude may be advisable in symptomatic patients with suspected cerebral RN, to have histologic confirmation of the lesion, to obtain a long-lasting relief from the mass effect and brain edema and to improve the overall quality of life, sparing a prolonged corticosteroid therapy.

Prognostic scoring system for surgical treatment of intramedullary spinal cord metastases.

Although rare, intramedullary spinal cord metastases (ISCMs) are on the rise, most likely due to prolonged survival and improved outcomes as a result of the advances in cancer treatment for cancer patients. While the management of these lesions remains controversial, surgery for ISCM has recently been advocated for selected patients. We performed a retrospective analysis on 30 patients who were surgically treated for intramedullary spinal cord metastases in order to determine a preoperative prognostic scoring system to guide patient selection for surgical interventions. The scoring system was designed to decide between surgery or other therapeutic procedures. The five parameters selected and employed in the assessment system were: 1) patient's general condition, 2) age, 3) primary site of the cancer, 4) number of other extramedullary metastases and 5) severity of neurologic symptoms. Prognosis could not be predicted from a single parameter. These five factors were added together to give a prognostic score between 1 and 10. The average survival period of patients with a prognostic score between 1 and 3 points was 3 months; 11 patients with a score of 4 and 5 points had a mean survival of 7.63 months, while patients with a prognostic score between 6 and 10 was 14.8 months. According to our prognostic scoring system for surgical treatment of ISCM, surgery should be performed in those patients who score above 6 points, while radiotherapy/chemotherapy or palliative care is recommended for those who score between 1 and 3 points. A prognostic score of 4 and 5 represents a grey area where surgeons must use their judgment on whether to intervene either medically or surgically. This scoring system could facilitate decision-making in the management of patients with intramedullary spinal cord metastases.

Surgical treatment of cerebellar metastases in elderly patients: A threshold that moves forward?

The impact of surgery for cerebellar brain metastases in elderly population has been the object of limited studies in literature. Given the increasing burden of their chronic illnesses, the decision to recommend surgery remains difficult. All patients aged ≥65 years, who underwent surgical resection of a cerebellar brain metastasis from May 2000 and May 2021 at IRCCS National Cancer Institute "Regina Elena", were analyzed. The study cohort includes 48 patients with a mean age of 70.8 years. 7 patients belonged to the II Class according to the RPA classification, 41 to the III Class; the median GPA classification was 1.5. Median pre-operative and post-operative KPS was 60. Median Charlson Comorbidity Index (CCI) was 11; median 5-variable modified Frailty Index was 2. Overall, 14 patients (29%) presented perioperative neurologic and systemic complications. 34 patients (71%) were able to perform adjuvant therapies as RT and/or CHT after surgery. A higher CCI predicted complications occurrence (p = 0.044), while significant factors for a post-operative KPS ≥70, were i) hemispheric location of the metastasis, ii) higher pre-operative KPS, iii) RPA II classification. Median Overall Survival was 7 months. A post-operative KPS <70 (p = 0.004) and a short time interval between diagnosis of the primary tumor and cerebellar metastasis appearance, were predictive for a worse outcome (p = 0.012). Our study suggests that selected elderly patients with cerebellar metastases may benefit from microsurgery to continue their adjuvant therapies, although a high complications rate should be taken in account.

Supraorbital keyhole approach for removal of midline anterior cranial fossa meningiomas: a series of 20 consecutive cases.

The paper describes a retrospective study of a consecutive series of 20 midline anterior cranial fossa meningiomas (five of the olfactory groove, 14 of the tuberculum sellae, and one clinoidal), which were operated on via a supraorbital keyhole approach between 2002 and 2008. The series includes three males and 17 females (mean age 57 years, mean size of the tumors 3.5 × 3 cm, and mean follow-up 48 months). Gross total excision was achieved in 18 cases and subtotal resection in two. Out of 14 patients with visual deficits, nine patients improved, one remained stable, and three deteriorated. Two patients presented a recurrence 3 years after surgery. One peri-operative death was recorded. The subgroup of patients with tuberculum sellae meningiomas was analyzed in details. A meta-analysis of the major series of such meningiomas in the last 20 years has been performed in order to compare results of different surgical techniques. With regard to primary outcomes of these tumors, gross total removal, restoration of visual function, morbidity, mortality, and recurrence rates, the supraorbital approach, for selected cases, seems to offer valuable results, comparable with those reported in conventional and endoscopic approaches and with very low surgical aggressiveness. However, statistical data available from the literature, particularly on visual function, are still too limited to draw definitive conclusions. The best surgical option for the individual patient cannot yet be standardized and should be chosen on the basis of tumor anatomy, pre-operative clinical symptoms, and surgeon's experience.

Breast cancer metastasis: Is it a matter of OMICS and proper ex-vivo models?

Genomics has greatly increased the understanding of the study of breast cancer (BC) and has shaped the concept of intra-tumor heterogeneity, currently recognized as a propelling force for cancer progression. In this context, knowledge and understanding of metastatic breast cancer (mBC) has somehow lagged behind that of primary breast cancer. This may be explained by the relative scarcity of matched mBC samples, however it is possible that the mutation spectrum obtained from primary BC does not capture the full complexity of the metastatic disease. Here, we provide a few examples supporting this possibility, from public databases. We evoke the need to perform an integrated multi-OMICS characterization of mBC, to obtain a broad understanding of this complex disease, whose evolution cannot be explained solely by genomics. Pertinent to this, we suggest that rather an infrequent use of Patient-Derived -Tumor-Organoids (PDTOs) may be influenced by assuming that the metastatic conditions of PDTOs growth (mPDTOs) should be similar to those of the tissue of origin. We challenge this view by suggesting that the use of "target-organ inspired" growth conditions for mPDTOs, may better fit the emerging knowledge of metastatic disease. Thus, the integrated use of multi-OMICS and of clinically relevant mPDTOs may allow a further understanding of such disease and foster therapeutically relevant advances. We believe that our points may be valid for other solid cancers.

Surgery of malignant gliomas: advances and perspectives.

PURPOSE OF REVIEW: One of the most controversial issues in the combined treatment of malignant gliomas is the role of surgical resection, even though the relevance of surgery in obtaining tissue diagnosis and alleviating clinical symptoms is well defined; more debated is the importance of radical surgery in improving the patient final outcome. This review aims to present an overview of the recommendations for surgical treatment of malignant gliomas, and to describe the potential role of locoregional treatments. RECENT FINDINGS: An increasing series of data are being collected in favour of radical surgical removal, with the support of intraoperative imaging and fluorescence guide. More controversial, but theoretically relevant, are the experiences of locoregional treatments, mainly in the contest of present combined modality treatments; different interesting approaches are being studied, without any significant therapeutical advantage in phase III studies, and only biodegradable carmustine wafers entered in the clinical practice. SUMMARY: The gold standard of surgical treatment of malignant gliomas has to include well tolerated and radical tumour removal, taking advantage of the introduction of new technological tools. The future role of neurosurgical treatment of malignant glioma is linked to intratumoural administration of antiblastic agents and the development of more efficient delivery systems; localized therapies have to be considered in a well defined multistep therapeutic strategy.

Hemorrhagic Attitude in Frameless and Frame-Based Stereotactic Biopsy for Deep-Seated Primary Central Nervous System Lymphomas in Immunocompetent Patients: A Multicentric Analysis of the Last Twenty Years.

BACKGROUND: Primary central nervous system lymphoma (PCNSL) is a rare manifestation of aggressive extranodal non-Hodgkin lymphoma. In patients with deep-seated lesions, stereotactic brain biopsy (SBB) is an accepted diagnostic procedure to obtain histopathologic confirmation. OBJECTIVE: The aim of this study was to assess the feasibility, diagnostic yield, safety, and complications of stereotactic procedures in midline and deep-seated PCNSLs. METHODS: Patients selected had received a histopathologic diagnosis of PCNSL localized in deep-seated midline structures, obtained by SBB. The intraoperative frozen section was executed as an integral part of the procedure. Computed tomography scan was performed after surgery. RESULTS: A total of 476 SBBs were performed between January 2000 and December 2019 . Of these SBBs, 91 deep-seated lesions had a histologic diagnosis of PCNSL. A significant increase of the incidence of PCNSL compared with all other diseases was observed (P < 0.0001). Eight patients (8.7%) showed a symptomatic hemorrhage, 4 of whom required craniotomy. There were 4 deaths and 2 cases of permanent morbidity. The hemorrhage risk in the PCNSL group was statistically significant (P = 0.0003) compared with other histotypes. CONCLUSIONS: In suspected cases of PCNSL, a histopathologic diagnosis is necessary to distinguish it from glioblastoma or other, nonmalignant conditions. Deep-seated PCNSLs present a higher risk of biopsy-related morbidity and mortality. Intraoperative frozen section increases the diagnostic yield and reduces the number of sampling procedures. Postoperative computed tomography seems to be warranted in patients with suspected PCNSL.