Central nervous system embryonal tumor with PLAGL1 amplification: a case report of a novel entity focusing on imaging findings.

The embryonal central nervous system (CNS) tumor with PLAGL1 (pleomorphic adenoma gene-like) amplification is a novel type of pediatric neoplasm with a distinct methylation profile, described for the first time in 2022. It may be located anywhere in the neuroaxis and, as its name implies, it is driven by the amplification and overexpression of one of the PLAG family genes. Although the associated clinical, immunohistopathological, and molecular characteristics are well characterized in the seminal report of this entity, data on the radiological features is still lacking. Here, we present a case report of a 4-year-old girl with a biopsy-proven PLAGL1-amplified brainstem tumor and provide a detailed description of the corresponding conventional neuroimaging characteristics, aiming to better delineate this entity and to increase the awareness of this pathology in the radiological community.

Impact of histological diagnosis on the treatment of atypical brainstem lesions.

For atypical brainstem lesions, histological diagnosis can have an impact on treatment, especially in cases where diffuse glioma is not found. Since radiotherapy is the only therapeutic modality that has shown clinical and radiographic improvement in patients with diffuse glioma, the misdiagnosis of diffuse glioma can have drastic consequences, particularly in patients with nontumorous lesions. Thus, the purpose of this study was to evaluate the impact of histological diagnosis on the treatment of atypical brainstem lesions. This was a retrospective study of 31 patients who underwent biopsy of atypical brainstem lesions. The procedures were performed between January 2008 and December 2018 at the Life Center Hospital and Santa Casa de Belo Horizonte, MG, Brazil. A diagnosis was obtained in 26 (83.9%) cases. Three patients presented complications: one presented bleeding with no clinical repercussions and two showed worsening of neurological deficit, only one of which was definitive. No mortality occurred due to the procedure. The histological diagnosis was diffuse glioma in seven cases (22.6%) and not diffuse glioma in 19 cases (61.3%). Thus, the histological diagnosis had an impact on the treatment of 19 patients (treatment impact rate: 61.3%). The histological diagnosis of intrinsic brainstem lesions is a safe, efficient procedure with a high diagnosis rate, and as such, it should be considered in the management of atypical lesions.

Dorsally exophytic glioblastoma of the pons.

Brainstem gliomas are rare tumours in adults, accounting for only 1%-2% of all intracranial gliomas. They are recognised as a heterogeneous group, in which most are malignant tumours. Brainstem gliomas are classified into four major groups according to the growth pattern on imaging, namely diffuse, focal, exophytic and cervicomedullary. Such a classification system is also useful for surgical decision making. The exophytic variant is extremely rare having anecdoctal reports in the literature. We report the case of an adult patient affected by an exophytic glioblastoma of the pons, which was submitted to subtotal resection followed by radiation therapy and chemotherapy with a longer overall survival. To the best of our knowledge, this is the seventh adult patient reported of an exophytic brainstem glioblastoma.

[Relevance of histopathological diagnosis in the treatment of brainstem lesions in adults]. / Importancia del diagnóstico histopatológico en el tratamiento de las lesiones del tronco cerebral en adultos.

Brainstem tumors are uncommon beyond childhood. Controversies arise regarding the need of histological diagnosis in this eloquent area of the brain, weighting the benefits of a reliable diagnosis against the disadvantages of invasive procedures. There are scant publications about the surgical management of brainstem tumors in adults, all of them involving small retrospective cohorts. We are reporting our experience with the aim of contributing to the decision making process. Out of a series of 13 patients, 10 were approached surgically. According to Guillamo's classification the lesions were: focal (n:7), diffuse infiltrative (n:1), tectal (n:1), and exophytic (n:1). According to the Karnofsky Performance Status scale, the neurological status was = 70 in 6 cases and < 70 in 7. Histopathology was confirmed in all 10 treated cases and the samples were obtained by a direct microsurgical approach or by stereotactic biopsy. Histopathological findings were: pilocytic astrocytoma (n:1), low grade glioma (n:1), glioblastoma (n:1), cellular haemangioblastoma (n:1), subependimoma (n:1), pseudotumoral lesions (n:4; 3 cavernomas, 1 inflammatory pseudotumor), and disgerminoma (n:1). As a broad variety of pathologies could be found in this brain localization, an accurate histopathological definition can not only determine the adequate therapy, but also avoid the disastrous consequences of empiric treatments.

Importancia del diagnóstico histopatológico en el tratamiento de las lesiones del tronco cerebral en adultos / Relevance of histopathological diagnosis in the treatment of brainstem lesions in adults

Los tumores del tronco cerebral son infrecuentes en la población adulta. Las controversias surgen cuando se considera la necesidad de confirmar el diagnóstico histopatológico en esta área elocuente del cerebro, balanceando los beneficios de obtener un diagnóstico certero y las desventajas de los procedimientos invasivos. Existen escasas publicaciones acerca de su tratamiento quirúrgico en adultos, todas series pequeñas analizadas retrospectivamente. Presentamos nuestra experiencia con el propósito de contribuir al proceso de toma de decisiones. Diez de 13 pacientes fueron intervenidos. Las lesiones se clasificaron en focales (n:7), infiltrativa difusa (n:1), tectal (1) y exofítica (1). El estado neurológico según la escala Karnofsky Performance Status fue ≥ 70 en 6 casos y < 70 en 7. Las muestras fueron obtenidas mediante abordaje microquirúrgico directo o por biopsia estereotáctica. Los hallazgos histopatológicos fueron confirmados en todos los casos: astrocitoma pilocítico (n:1), glioma de bajo grado (n:1), glioblastoma (n:1), hemangioblastoma celular (n:1), subependimoma (n:1), disgerminoma (n:1), y lesiones pseudotumorales (n:4, 3 cavernomas, 1 pseudotumor inflamatorio). La amplia variedad de hallazgos patológicos en esta localización en adultos exige una precisa definición histopatológica, que no solo determina la terapéutica adecuada sino que también previene las consecuencias potencialmente catastróficoas de los tratamientos empíricos.

Brainstem tumors are uncommon beyond childhood. Controversies arise regarding the need of histological diagnosis in this eloquent area of the brain, weighting the benefits of a reliable diagnosis against the disadvantages of invasive procedures. There are scant publications about the surgical management of brainstem tumors in adults, all of them involving small retrospective cohorts. We are reporting our experience with the aim of contributing to the decision making process. Out of a series of 13 patients, 10 were approached surgically. According to Guillamo´s classification the lesions were: focal (n:7), diffuse infiltrative (n:1), tectal (n:1), and exophytic (n:1). According to the Karnofsky Performance Status scale, the neurological status was ≥ 70 in 6 cases and < 70 in 7. Histopathology was confirmed in all 10 treated cases and the samples were obtained by a direct microsurgical approach or by stereotactic biopsy. Histopathological findings were: pilocytic astrocytoma (n:1), low grade glioma (n:1), glioblastoma (n:1), cellular haemangioblastoma (n:1), subependimoma (n:1), pseudotumoral lesions (n:4; 3 cavernomas, 1 inflammatory pseudotumor), and disgerminoma (n:1). As a broad variety of pathologies could be found in this brain localization, an accurate histopathological definition can not only determine the adequate therapy, but also avoid the disastrous consequences of empiric treatments.

Risk Factors for Unfavorable Outcomes in Surgically Treated Brainstem Cavernous Malformations.

OBJECTIVE: Brainstem cavernous malformations (BSCMs) account for up to 18% of all intracranial cavernous malformations. Due to their complex anatomic location, they represent a significant challenge for neurosurgeons. As such, the identification of risk factors associated with negative outcomes is of significant importance. We analyze a series of 50 cases of BSCMs treated surgically in order to identify risk factors for unfavorable outcomes. METHODS: Patients who underwent surgical resection of BSCM at our institution between 2000 and 2015 were retrospectively reviewed. Univariate and multivariable logistic regression models were used to identify predictors of unfavorable outcomes, defined as those with a modified Rankin score (mRs) of >2. RESULTS: Fifty Latin American patients, with a mean age of 35.85 ± 13.06 years, consisting of 29 females (58%) and 21 males (42%), underwent surgical resection. Mean modified Rankin Scale (mRs) score at admission was 2.6 ± 1.05, and the mean BCSM size was 18.00 ± 7.19 mm. The rate of gross total resection was 92%. Overall, 80% of patients showed improved or unchanged clinical status at the last follow-up period; however, only 58% of patients had a favorable outcome with a mean mRs of 2.33 ± 1.136. Multivariable logistic binary regression identified hemorrhagic recurrence (P = 0.040), lower cranial nerve deficit (P = 0.019), and BSCMs >15 mm in diameter (P = 0.006) as predictive factors for unfavorable surgical outcomes. CONCLUSION: BSCM size, compromise of lower cranial nerves, and hemorrhagic recurrence before surgery were identified as risk factors associated with unfavorable outcomes of surgically treated BSCMs in this cohort.

Surgical approaches for brainstem tumors in pediatric patients.

PURPOSE: To analyze the pathways to brainstem tumors in childhood, as well as safe entry zones. METHOD: We conducted a retrospective study of 207 patients less than 18 years old who underwent brainstem tumor resection by the first author (Cavalheiro, S.) at the Neurosurgical Service and Pediatric Oncology Institute of the São Paulo Federal University from 1991 to 2011. RESULTS: Brainstem tumors corresponded to 9.1 % of all pediatric tumors operated in that same period. Eleven previously described "safe entry zones" were used. We describe a new safe zone located in the superior ventral pons, which we named supratrigeminal approach. The operative mortality seen in the first 2 months after surgery was 1.9 % (four patients), and the morbidity rate was 21.2 %. CONCLUSIONS: Anatomic knowledge of intrinsic and extrinsic brainstem structures, in association with a refined neurosurgical technique assisted by intraoperative monitoring, and surgical planning based on magnetic resonance imaging (MRI) and tractography have allowed for wide resection of brainstem lesions with low mortality and acceptable morbidity rates.

Biopsy of Brainstem Gliomas Using Flexible Endoscopes.

OBJECTIVES: To describe our experience and the results obtained in performing transventricular brainstem biopsy with the use of flexible neuroendoscops. METHODS: We identified patients who underwent a neuroendoscopic procedure with brainstem lesion biopsy to obtain histopathologic diagnosis and to treat obstructive hydrocephalus. All patients had follow-up examinations at months 1, 3, 6, and 12 postsurgery and then annually. RESULTS: Seven patients had a transventricular biopsy of the brainstem performed. Of those, five were pediatric patients. The median age was 10 years (range: 3-26 years). Five of them were female and two male. Four patients presented with secondary obstructive hydrocephalus. The main clinical presentations were intracranial hypertension syndrome in four patients, motor neuron disease in four patients, two with decreased state of alertness, two with gait ataxia, and one with Parinaud syndrome. The types of tumors found in the histopathology and their location were one ventral (pons) and one aqueductal anaplastic astrocytoma, two ventral, one aqueductal, and one attached to the floor of the fourth ventricle pilocytic astrocytoma and one ventral low-grade astrocytoma. The route taken to approach the ventral tumors was made through premammillary fenestration. The tumors of the aqueduct and floor of the fourth ventricle were approached transaqueductally. CONCLUSION: The use of flexible endoscops for biopsy of ventral, dorsal (tectum lamina quadrigemina), and diffuse brainstem tumors is a useful, effective, and safe procedure that also allows to treat obstructive hydrocephalus secondary to the tumors.

[Radiation therapy in the treatment of brain-stem tumors in children]. / Tumores de tronco cerebral en niños tratados con radioterapia.

INTRODUCTION: Due to their location, tumors of the trunk (TT) present a high surgical risk and the diagnosis is usually made by imaging. In Chile, these cases are treated according to the PINDA Program (national treatment guide for pediatric tumors). All patients receive radiotherapy (RT) after diagnosis. The aim of this study is to evaluate the treatment results for TT at the National Cancer Institute (NCI) between 1993 and 2011. PATIENTS AND METHOD: A retrospective review of patients diagnosed with TT at NCI was conducted. Patient population, symptoms, treatment received and overall survival are described. Prognostic factors were analyzed. RESULTS: From November 1993 to December 2011, 70 children were referred for possible RT, 68 of them actually received it. The median age at diagnosis was 7 years old. In June 2012, out of 70 patients, 60 were deceased, all due to disease progression. The median survival of patients who received RT (68 patients) was 8.5 months from the end of treatment; the survival rates at 1, 2 and 3 years was 31.5 %, 14.3 % and 12.8% respectively. Univariate analysis showed that survival was affected by the MRN high resolution imaging (p = 0.07) and by the diffuse tumor pattern (p = 0.025). Multivariate analysis showed survival is affected by the MRN high resolution imaging (p = 0.011) and a higher dose of RT protector (p = 0.015). CONCLUSIONS: The poor results obtained in the treatment of TT with RT at the INC are similar to those reported by other centers. Further explorations regarding other treatment options based on combined therapy using RT are needed.

Tumores de tronco cerebral en niños tratados con radioterapia / Radiation therapy in the treatment of brain-stem tumors in children

Introduction: Due to their location, tumors of the trunk (TT) present a high surgical risk and the diagnosis is usually made by imaging. In Chile, these cases are treated according to the PINDA Program (national treatment guide for pediatric tumors). All patients receive radiotherapy (RT) after diagnosis. The aim of this study is to evaluate the treatment results for TT at the National Cancer Institute (NCI) between 1993 and 2011. Patients and Method: A retrospective review of patients diagnosed with TT at NCI was conducted. Patient population, symptoms, treatment received and overall survival are described. Prognostic factors were analyzed. Results: From November 1993 to December 2011, 70 children were referred for possible RT, 68 of them actually received it. The median age at diagnosis was 7 years old. In June 2012, out of 70 patients, 60 were deceased, all due to disease progression. The median survival of patients who received RT (68 patients) was 8.5 months from the end of treatment; the survival rates at 1, 2 and 3 years was 31.5 percent 14.3 percent and 12.8 percent respectively. Univariate analysis showed that survival was affected by the MRN high resolution imaging (p = 0.07) and by the diffuse tumor pattern (p = 0.025). Multivariate analysis showed survival is affected by the MRN high resolution imaging (p = 0.011) and a higher dose of RT protector (p = 0.015). Conclusions: The poor results obtained in the treatment of TT with RT at the INC are similar to those reported by other centers. Further explorations regarding other treatment options based on combined therapy using RT are needed.

Introducción: Los tumores de tronco (TT), por su ubicación, conllevan un alto riesgo quirúrgico, por lo que generalmente el diagnóstico se realiza por imágenes. En Chile se tratan según el programa PINDA (guía para tratamiento de tumores pediátricos nacional). Todos reciben radioterapia (RT) luego del diagnóstico. El objetivo de esta publicación es evaluar los resultados de tratamiento de los TT en el Instituto Nacional del Cáncer (INC) en el período 1993-2011. Pacientes y Método: Revisión retrospectiva de los pacientes tratados con el diagnóstico de TT en el INC. Se describe la población de pacientes, síntomas de presentación, tratamientos recibidos y sobrevida global. Se exploraron factores pronósticos. Resultados: Desde noviembre de 1993 hasta diciembre de 2011 fueron derivados para consideración de RT 70 niños, de ellos 68 la recibieron. La mediana de edad al diagnóstico fue de 7 años. A junio de 2012, del total de 70 pacientes, 60 se encontraban fallecidos, todos por progresión de enfermedad. La mediana de sobrevida, de los pacientes que recibieron RT (68 pacientes), fue de 8,5 meses desde el fin de esta; la sobrevida a 1, 2 y 3 años fue de 31,5 por ciento, 14,3 por ciento, 12,8 por ciento respectivamente. Al análisis univariado, fue peor para la sobrevida, el alto grado a la imagen de RNM (p = 0,07) y el patrón tumoral difuso (p = 0,025). Al análisis multivariado, es peor para la sobrevida el alto grado a la imagen de RNM (p = 0,011) y protector una mayor dosis de RT (p = 0,015). Conclusiones: Los pobres resultados obtenidos en el tratamiento con RT de TT en el INC son similares a los reportados por los otros centros. Sería sin duda interesante explorar otras alternativas de tratamiento en base a tratamientos combinados con RT.

Pediatric brainstem gangliogliomas show BRAF(V600E) mutation in a high percentage of cases.

Brainstem gangliogliomas (GGs), often cannot be resected, have a much poorer prognosis than those located in more common supratentorial sites and may benefit from novel therapeutic approaches. Therapeutically targetable BRAF c.1799T>A (p.V600E) (BRAF(V600E) ) mutations are harbored in roughly 50% of collective GGs taken from all anatomical sites. Large numbers of pediatric brainstem GGs, however, have not been specifically assessed and anatomic-and age-restricted assessment of genetic and biological factors are becoming increasingly important. Pediatric brainstem GGs (n = 13), non-brainstem GGs (n = 11) and brainstem pilocytic astrocytomas (PAs) (n = 8) were screened by standard Sanger DNA sequencing of BRAF exon 15. Five of 13 (38%) pediatric GG harbored a definitive BRAF(V600E) mutation, with two others exhibiting an equivocal result by this method. BRAF(V600E) was also seen in five of 11 (45%) non-brainstem GGs and one of eight (13%) brainstem PAs. VE1 immunostaining for BRAF(V600E) showed concordance with sequencing in nine of nine brainstem GGs including the two cases equivocal by Sanger. The equivocal brainstem GGs were subsequently shown to harbor BRAF(V600E) using a novel, more sensitive, RNA-sequencing approach, yielding a final BRAF(V600E) mutation frequency of 54% (seven of 13) in brainstem GGs. BRAF(V600E) -targeted therapeutics should be a consideration for the high percentage of pediatric brainstem GGs refractory to conventional therapies.

Diffuse intrinsic brainstem tumor in an infant: a case of therapeutic efficacy with vinorelbine.

Brainstem gliomas constitute 10% to 20% of all pediatric tumors of the central nervous system, and diffusely infiltrative brainstem gliomas are the most common brainstem tumors associated with a poor prognosis. A small subset of these tumors is benign, showing low-grade features on histology. The role of chemotherapy in the management of these tumors is ill defined, especially in the neonates. There are anecdotal reports of spontaneous remission, but the natural history of these tumors does not support a wait-and-see approach. Thus, we report a successful experience of chemotherapy in a 4-month-old girl with a diffuse brainstem fibrillary astrocytoma, treated with vinorelbine (30 mg/m/d on days 0, 8, and 22), a vinca alkaloid that has shown activity against glioma. Our experience suggests that vinorelbine may be effective in pediatric low-grade gliomas as this patient showed significant clinical improvement over a short period of time.

Stereotactic biopsy for brainstem tumors in pediatric patients.

OBJECTIVE: Our aim is to describe clinical and paraclinical features in patients who underwent stereotactic-guided biopsy for brainstem tumors. METHODS: A study of case series was made by reviewing the records of patients who underwent stereotactic biopsy for brainstem tumors. RESULTS: Stereotactic biopsy for brainstem tumors was performed (between 2000 and 2008) in 20 children (11 girls, and 9 boys), mean age 7.95 +/- 3.12 years at the time of diagnosis. The mean time from onset of symptoms to diagnosis was 6.59 +/- 13.58 months (0.50-60 months). The most frequent symptoms and signs at onset were related to disturbance of cerebellar function and cranial nerve nuclei. Location was pontomesencephalic (35%), pontine (30%), pontomedullar (25%), and in the whole brainstem (10%). The most common type of image was intrinsic-diffused (55%). The histopathology was anaplastic astrocytoma (30%), followed by fibrillary and pilocytic types (25% each), low-grade astrocytoma (5%), high-grade astrocytoma (5%), and normal tissue (10%). Mild complications were observed in only two cases. CONCLUSIONS: Stereotactic biopsy done for clarifiying a diagnostic imaging in brainstem tumors is important in obtaining a definitive diagnosis with a low rate of complications.

"La obstrucción estaba abajo": tumores de la médula espinal e hipertensión intracraneal

Aumento de la presión intracraneal, hidrocéfalo y papiledema son observados ocasionalmente en pacientes portadores de tumores medulares en la región cervical o en la unión craneocervical, y entre otros, la obstrucción mecánica de la circulación del líquido cefalorraquídeo es asumida como responsable para tales síntomas y signos. No obstante, la hipertensión intracraneal es un raro fenómeno en tumores espinales de localización tóracolumbar. Los autores describen dos pacientes en quienes un tumor en tal localización (schwannoma benigno y paraganglioma) se asoció a síntomas de hipertensión intracraneal, hidrocefalia y papiledema. Se piensa que este tipo de lesiones puede interferir activamente en la dinámica del flujo del líquido cefalorraquídeo en razón de que la ocupación de espacio impide la expansión del saco dural y espacio subaracnoideo espinal que se piensa juegan algún papel en la compensación de los cambios de volumen y la presión intracraneal

Increased intracranial pressure, hydrocephalus and papilledema are occasionally observed in patients harboring spinal tumors in the cervical region or at the craniocervical junction, and among others, the mechanical obstruction to the cerebrospinal fluid circulation is assumed to be responsible for such symptoms and signs. However, increased intracranial pressure is very rare in spinal tumors located in the thoraco-lumbar region. Two patients are described by the authors in whom a benign thoracolumbar tumor (benign schwannoma and paraganglioma) was associated with symptoms of increased intracranial pressure, hydrocephalus and papiledema. It has been suggested that this kind of lesions could actively interfere with cerebrospinal fluid dynamics by their mass effect, especially by preventing the expansion of the dural sac and spinal subarachnoid space which may play some roce in compensating for volume changes and intracranial pressure

Stereotactically-guided biopsies of brainstem tumors.

INTRODUCTION: More than 10 years ago, the goal of our work had been to obtain a tissue sample of infiltrating lesions of the brainstem that had been diagnosed using computerized axial tomography (CAT). At that time, biopsies were believed to be indispensable when starting treatment of tumors. With time our objectives changed. Biopsies remained necessary, since until 1 year before the writing of this article we had not had the benefits of magnetic resonance imaging (MRI) at our Hospital. We also decided that carrying out sound statistics, confirmed by biopsies, was in itself a good procedure, especially in a country in which, to date, no serial studies of brainstem tumors had been undertaken. METHODS: We analyzed all of the patients diagnosed with posterior fossa tumors between March 1989 and March 2002 at the Hospital Infantil de México Federico Gómez (HIM). A preoperative TAC of the cranium was performed on every patient. Stereotactically-guided biopsies during tomography allowed precise control of penetration. Material obtained was sent to the Department of Pathology for analysis. RESULTS: Fifty patients were diagnosed with infiltrating tumors of the brainstem: 30 cases of low-grade astrocytomas, 13 cases of high-grade astrocytomas, 2 cases of primitive neuroectodermic tumors, 2 cases of rhabdoid tumors, 1 case of ependymoma, and 2 patients had non-specified tumors. The most frequent symptoms and signs were ataxia and disturbances of the cranial nerves. There was no mortality caused by penetration, and follow-up studies of more than 5 years were carried out. DISCUSSION: The results from our series were similar to those in the literature. In our case, follow-up studies were undertaken for longer periods. In the first section of our work, we suggest the need for stereotactic biopsies in order to arrive at a precise diagnosis in environments in which MRI may be unavailable. CONCLUSION: At present, presumptive diagnosis of infiltrating brainstem lesions may be adequately undertaken with imaging methods, such as MRI. However, we believe that a stereotactically-guided biopsy provides an accurate method for diagnosing lesions of the brainstem. In our case, this procedure has been carried out entirely in the tomography room, without any complications of disease or mortality.