Liquid biopsy in CNS tumors: Current status & future perspectives

Precise classification of central nervous system (CNS) malignancies is vital for the treatment and prognostication. Identification of noninvasive markers can be of importance to guide treatment decisions and in monitoring treatment response. CNS tumors are classified based on morphology with an essential complement of molecular changes, including mutations, amplifications, and methylation. Neuroimaging is the mainstay for initial diagnosis and monitoring tumor response with obvious limitations of imprecise tumor typing and no information on diagnostic, predictive and prognostic markers. Liquid biopsy has evolved as a diagnostic tool in body fluids and is being investigated as a surrogate for tissue biopsy in managing primary and metastatic brain tumors. Liquid biopsy refers to analyzing biological fluids such as peripheral blood, urine, pleural effusion, ascites, and cerebrospinal fluid (CSF); however, peripheral blood remains the primary source of fluid biopsy. The analytes include cell-free DNA (cfDNA) circulating tumor cells (CTCs), circulating micro RNAs (miRNAs), circulating proteins and extracellular vesicles (EVs). Analysis of these components is actively used for early cancer detection, auxiliary staging, prognosis assessment, detection of minimal residual disease (MRD), and monitoring drug resistance in various solid tumors. In recent years, liquid biopsy has been studied in CNS tumors, and analysis of CTCs and cfDNA have become relevant research topics. In the current review, we have explained the clinical potential of liquid biopsy in CNS tumors to assist in diagnosing and predicting prognosis and response to treatment.

Evaluating neurosurgical biopsies for CNS tumor diagnoses: An algorithmic and pattern based approach

The 2016 and 2021 World Health Organization (WHO) Classifications of Tumors of the Central Nervous System (CNS) reflect the importance of integrating molecular analysis into CNS tumor diagnosis and classification, adding to the complexity of any surgical neuropathology practice. On the other hand, our evolving understanding of genomic alterations across the spectrum of CNS tumors highlights the importance of utilizing traditional histological and immunohistochemical approaches to first establish as accurate a diagnosis as possible. Such an approach is also essential to recognizing the most appropriate ancillary test(s) needed for accurate classification and grading of CNS tumors. Here, we present an algorithmic approach to be considered while evaluating surgical neuropathology biopsies, which includes a recognition of main histological patterns, and incorporates clinical and radiologic features, to assist with accurate diagnosis and optimal selection of subsequent ancillary testing

Miscellaneous newly recognized types of CNS tumors in the WHO CNS5 classification (other than gliomas, glioneuronal and embryonal tumors)

In this review, we describe salient features of a few of the newer entities recognized in the fifth edition of World Health Organization (WHO) classification of central nervous system (CNS) tumors. While most of these have been offshoots of the deoxyribonucleic acid (DNA) methylation profiling of CNS tumors with distinct profiling such as desmoplastic myxoid tumor (DMT) of the pineal region, SMARCB1-mutant, these also demonstrate subtle, distinct morphological features, which should be carefully searched for to diagnose them.

Clinico-pathological and radiological correlation of CNS tumors along with role of Ki 67 proliferative index in grading Astrocytoma and Meningiomas

Background: CNS neoplasms are a heterogenous group contributing to <2% of all the malignant neoplasms. Imaging and histopathology play a great role in diagnosing these lesions. Aim of the study is to correlate radiological findings with that of histopathology and evaluate the role of Ki 67 proliferative index in various grades of Astrocytomas and MeningiomasMethods: This is an observational study for a period 2 years from July 2015 to June 2017 in Department of Pathology Andhra Medical College. The total number of specimens of CNS tumors received during this period were126. The specimens were routinely processed and stained with H&E. The tumors were classified based on WHO 2016 classification. In total 71 cases-45 cases of meningiomas and 26 cases of astrocytomas, the expression of Ki 67 labelling index was recorded in various grades of these tumors and results tabulated.Results: Among 126 cases, tumors predominantly encountered were of meningeal origin accounting to 45 cases (35.71%) followed by tumors of neuroepithelial origin 35 cases (27.78%). Tumors were seen in all age groups, but common was among 41-50 years of age group with metastatic tumors being seen in >60 year group. Tumors were more common in males with male: female ratio being 1.25:1. Ki 67 proliferative index increased as the grade of tumor increased in both astrocytomas and meningiomas.Conclusions: Grading of meningiomas and astrocytomas are very much essential with reference to prognosis and therapy. Histopathology plays a great role in grading these lesions but Ki 67 proliferative index adds as an adjunct and helps in confirmation and predicting the recurrence of these lesions.

Quantification of cerebrospinal fluid ferritin as a biomarker for CNS malignant infiltration / Quantificação de ferritina no líquido cefalorraquidiano como biomarcador para o diagnóstico de infiltração maligna no SNC

Several markers have been studied for their ability to make the CNS infiltration diagnosis earlier and more precise; previous studies showed that CSF ferritin concentrations were higher in patients with malignant invasion of CNS. The objective was to determine the importance of CSF ferritin as a biomarker for the diagnosis of CNS neoplasic infiltration. This study is based on 93 CSF samples, divided into five groups: malignant cells present (n13); malignant cells not present (n26); inflammatory neurological diseases (n16); neurocysticercosis (n20); acute bacterial meningitis (n18). CSF ferritin values were determined by micro particle enzyme immunoassay. CSF ferritin level (mean±SD) in the group with neoplasic cells in the CSF was 42.8±49.7 ng /mL, higher than in the other groups (p<0.0001). We conclude that CSF ferritin with the cut off 20 ng/mL could be an adjuvant biomarker to the diagnosis of CNS malignant infiltration.

Diversos marcadores foram estudados com a finalidade de avaliar sua capacidade de diagnosticar a infiltração neoplásica no SNC precocemente e de forma mais precisa. Estudos anteriores mostraram que as concentrações de ferritina no LCR eram mais elevadas nos pacientes com infiltração neoplásica no SNC. O objetivo foi determinar a importância da ferritina no LCR como biomarcador para o diagnóstico de infiltração neoplásica no SNC. Este estudo é baseado em 93 amostras do LCR, divididas em cinco grupos: células malignas presentes (n13); células malignas ausentes (n26); doenças neurologicas inflamatórias (n16); neurocisticercose (n20); meningites bacterianas agudas (n18). Os valores de ferritina no LCR foram determinados por ELISA de microparticulas. O nível de ferritina no LCR (média±desvio padrão) no grupo com células neoplásicas no LCR foi 42,8±49,7 ng/mL, mais elevado do que nos outros grupos (p<0.0001). Concluímos que a ferritina no LCR com cut off de 20 ng/mL pode ser um biomarcador para o diagnóstico de infiltração maligna no SNC.

Cerebrospinal fluid cytological and biochemical characteristics in the presence of CNS neoplasia

Central nervous system (CNS) infiltration must be ruled out in patients with known neoplastic diseases and neurological symptoms. It was done a retrospective analysis of 1,948 CSF samples from patients with suspected malignant infiltration in the CNS, in order to evaluate the positivity rate of malignant cells in cerebrospinal fluid (CSF) samples and correlate with cytochemical characteristics. Sixty-two percent of subjects had acute lymphocytic leukemia. Malignant cells were found in 24 percent of all CSF samples. Subjects with positive malignant cells had predominance of increased levels of CSF total protein (TP), glucose and total cytology (p<0.05). Mean total cell count in this group was 232 (SD 933) cells/mm³, compared to 9 (SD 93) cells/mm³ in the group without neoplasic cells (p=0.029). CSF TP specificity was 87 percent and negative predictive value (NPV) 96 percent. CSF total cell count specificity 86 percent and NPV 97 percent. Although sensitivity and positive predictive value were low. The presence of inflammatory cells and elevated TP found in patients with malignant cells in the CSF can aid in diagnosing CNS neoplasms.

A infiltração neoplásica no SNC deve ser afastada em pacientes com neoplasia e sintomas neurológicos. Foi realizada uma análise retrospectiva de 1.948 amostras de LCR de pacientes com suspeita de infiltração neoplásica no SNC. Sessenta e dois por cento dos pacientes eram portadores de leucemia linfocitica aguda. Células neoplásicas foram encontradas em 24 por cento de todas as amostras. Houve níveis aumentados no LCR da proteína total (PT), glicose e de citologia global (p<0.05), no grupo com presença de células neoplásicas. A média da contagem global de células no LCR, neste grupo, foi 232±933 cels/mm³, contra 9±93 cells/mm³ no grupo sem células neoplásicas no LCR (p=0,029). O aumento de PT no LCR apresentou especificidade 87 por cento e valor preditivo negativo (VPN) 96 por cento. A contagem global de células no LCR apresentou especificidade 86 por cento e VPN 97 por cento. Porém sensibilidade e valores preditivos positivos foram baixos. A presença de células inflamatórias e PT no LCR elevada em pacientes com neoplasias pode ser um indicador do envolvimento no SNC.

A Case of Neurilemmomatosis Associated with CNS Tumors / 대한피부과학회지

Neurilemmomatosis is a clinical entity clearly distinguished from neurofibromatosis of von Recklinghausen's disease, and characteristically consists of multiple, cutaneuos neurilemmomas, central nervous system tumors, and neurologic disorders. A 52-year-old man, with multiple spinal cord neurilemmomas and unilateral acoutic neurilemmoma, presented with multiple subcutaneous nodules on the flexor parts of the extremities. Histologically, it was diagnosed as neurilemmoma. We report a case of neurilemmomatosis associated with CNS tumors.

Tendencias del tratamiento radiante en los tumores del sistema nervioso central / Trends of the radiant treatment in the central nervous system tumors

Se sabe que el tratamiento de los tumores del sistema nervioso central (SNC) está basado en el empleo de la cirugía y la radioterapia (RT) y que la quimioterapia (QMT) se emplea cada vez más, así como los otros medicamentos. Se hizo una revisión bibliográfica para actualizar los conocimientos sobre las tendencias actuales y perspectivas de la RT aplicada a los tumores del SNC, entre las cuales se hallan: a) combinaciones de RT y QMT; b) radiosensibilizadores incorporados al tratamiento radiante; c) inhibidores de la angiogénesis asociados a la RT; d) la escalada o incremento de las dosis de RT, gracias al desarrollo de nuevas tecnologías como la radioterapia conformacional en tercera dimensión, la radioterapia de intensidad modulada, la cirugía y otros; otro campo de investigación es el constituido por los cambios en el ritmo o fraccionamiento de la RT: hiperfraccionada, acelerada, combinaciones de ambas, etc., lo que permitirá principalmente incrementar el escalado de las dosis.

It is known that the treatment of the central nervous system (CNS) tumors is based on the use of surgery and radiotherapy (RT) and that chemotherapy (QMT) is used even more, as well as the other drugs. A bibliographic review was made to update the knowledge on the current trends and perspectives of RT applied to CNS tumors. The following were found among them: a) combinations of RT and CMT; b) radiosensibilizers incorporated to the radiant treatment; c) angiogenesis inhibitors associated with RT; d) the scale-up or increase of the RT doses thanks to the development of new technologies, such as 3 D conformal radiotherapy, intensity- modulated radiotherapy, surgery and others. Another field of research is that of the changes in the rhythm or fractioning of the RT: hyperfractionated, accelerated, combinations of both, etc., which will allow mainly to increase the dosage scale-up.