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Table of Contents
ORIGINAL ARTICLE
Year : 2020  |  Volume : 3  |  Issue : 2  |  Page : 67-70

Tumor growth patterns in central nervous system tumors with astrocytic differentiation


1 Student, Faculty of Medicine, Medical University of Varna Prof. Dr. Paraskev Stoyanov, Varna, Bulgaria
2 Department of General and Clinical Pathology, Forensic Medicine and Deontology, Faculty of Medicine, Medical University of Varna Prof. Dr. Paraskev Stoyanov, Varna, Bulgaria

Date of Submission23-Apr-2020
Date of Acceptance25-May-2020
Date of Web Publication27-Jun-2020

Correspondence Address:
Emran Myumyun Lyutfi
Marin Drinov 55, 9002 Varna
Bulgaria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/glioma.glioma_8_20

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  Abstract 

Background and Aim: Glial tumors with astrocytic differentiation are the most common primary malignant brain tumors. Hans Joachim Scherer established histological criteria based on hematoxylin and eosin (H&E) staining, which form the basis of the World Health Organization (WHO) glial tumor grades. The aim of this study was to investigate the incidence of Scherer structures across different classes of WHO grade tumors with astrocytic differentiation and determine whether secondary structures can be used as a grade-defining tool. Materials and Methods: Tumor samples were obtained from 36 patients with central nervous system (CNS) tumors with astrocytic differentiation between February 2018 and March 2019. The study was approved by the Committee on Ethics for Scientific Research, Medical University—Varna “Prof. Dr. Paraskev Stoyanov,” Protocol no. 20 [1] on April 26, 2012. The presence or absence of primary Scherer structures (pseudopalisading necrosis, glomeruloid vascular proliferation) and secondary Scherer structures (subpial palisading, fascicular aggregation, satellitosis around neurons, and blood vessels) was analyzed in H&E stained samples. Results: The samples were divided into two groups: 28 glioblastoma multiforme (GBM) cases and 8 lower grade astrocytoma cases. All 28 GBM cases exhibited pseudopalisading necrosis. Glomeruloid vascular proliferation was present only in 89.3% of the GBM cases. The GBM group also showed 67.9% subpial palisading, 78.5% fascicular aggregation of tumor cells, 96.4% perineuronal, and 100% perivascular satellitosis. The lower grade astrocytoma group had 0% pseudopalisading necrosis and glomeruloid vascular proliferation. Among all cases of lower grade gliomas, 50.0% showed subpial palisading, 87.5% fascicular aggregation, 100% perineuronal, and 100% perivascular satellitosis. Conclusions: Secondary Scherer structures can be considered as natural phenomena in glial tumors but cannot be used as features for grading.

Keywords: Central nervous system tumors, glioma, pathology, Scherer structure


How to cite this article:
Lyutfi EM, Georgieva R, Stoyanov GS, Dzhenkov D. Tumor growth patterns in central nervous system tumors with astrocytic differentiation. Glioma 2020;3:67-70

How to cite this URL:
Lyutfi EM, Georgieva R, Stoyanov GS, Dzhenkov D. Tumor growth patterns in central nervous system tumors with astrocytic differentiation. Glioma [serial online] 2020 [cited 2022 Dec 8];3:67-70. Available from: http://www.jglioma.com/text.asp?2020/3/2/67/288182


  Introduction Top


Glioma is a general term that describes primary tumors of the central nervous system (CNS), originating from glial progenitors.[1] According to the cell of origin, glial tumors can be classified as astrocytomas, oligodendrogliomas, ependymomas, and mixed gliomas. They account for approximately 80% of all CNS malignant primary tumors.[1],[2] Approximately, 55.4% of the malignant tumors occur in men, and the most common malignant CNS tumor is glioblastoma (48.3%).[1]

Tumors with astrocytic differentiation are the most common primary malignant brain tumors, with an annual incidence of 5.26 per 100,000 capita. These tumors are typically associated with poor prognosis and poor quality of the remaining life.[3]

The gross descriptions of glial tumors can be traced back to the beginning of the 1800s in the English, French, and German scientific literature.[4] The first comprehensive histological depiction of glial tumors is credited to the German pathologist Rudolph Virchow. According to his description, glial tumors are malignant neoplastic formations originating from the glial cells of the CNS; they show clear tissue and cellular structural contrast with healthy brain tissue and invade neighboring structures.[5] He also described the precursor cells and proposed the first classification for glial tumors. The American neuropathologist Percival Bailey and prolific neurosurgeon Harvey Cushing made the next step in glial tumor research and set the basis of the modern World Health Organization (WHO) classification of CNS tumors.[4],[5],[6]

The most under-credited researcher in the field of CNS tumor pathology was the German neuropathologist Hans Joachim Scherer. He was responsible for some of the most important observations and researched glial tumors, especially glioblastoma multiforme (GBM). He established a wide set of histological criteria, based on hematoxylin and eosin (H&E) staining, which form the basis of the WHO grading of glial tumors. In his honor, these criteria are named after him—primary and secondary Scherer structures.[7],[8],[9]

The primary Scherer structures are foci of pseudopalisading necrosis and are pathognomonic for GBM. Such necroses have a specific cellular arrangement around them (pseudopalisadic) because the tumor cells in GBM attempt to escape from the ischemic area to the more richly supplied areas of the tumor.[10]

Neovascular proliferation is a hallmark of tumor growth and in GBM samples can resemble the kidney glomeruli, which is called the glomerulation phenomenon.[11]

The patterns of glioma cell infiltration have since been referred to as the secondary Scherer structures. They are histopathological patterns based on the spread, growth, and biological potential of glial tumors. These glioma cells migrate through the normal parenchyma, assemble just below the pial margin (subpial spread), surround neurons and vessels (perineuronal and perivascular satellitosis), and migrate through the white matter tracks (intrafascicular spread).[5],[9],[12]

The aim of this study was to investigate the incidence of Scherer structures across different classes of WHO grade tumors with astrocytic differentiation and determine whether the secondary structures can be used as a grade-defining tool.


  Materials and Methods Top


Materials

A retrospective nonclinical approach for patient selection was chosen for the study. A total of 36 patients diagnosed with CNS tumors with astrocytic differentiation for a period of one calendar year from February 2018 to March 2019 were included. All patients provided informed consent for providing tumor samples. The study was approved by the Committee on Ethics for Scientific Research, Medical University—Varna “Prof. Dr. Paraskev Stoyanov,” — Protocol no. 20[1]

on April 26, 2012.

Sample staining and observation

Slides stained with H&E are the gold standard that allow visualization of the specific histological characteristics and patterns of different glioma grades. A total of 36 patient tumor samples stained with H&E were scanned and digitalized for observation later using the default presents of the Leica Aperio AT2 automated scanner system. The digital slides were imported to the freeware program Aperio ImageScope v. 12.4.0.5043.

The tumor samples were manually observed, one by one, for the presence or absence of primary Scherer structures—pseudopalisadic necrosis, glomeruloid vascular proliferation, and secondary Scherer structures—subpial palisading, fascicular aggregation, satellitosis around neurons and blood vessels. The observation results were compared using a descriptive statistical approach.


  Results Top


The samples were divided into two groups—GBM and lower grade astrocytoma. After careful observation, 28 cases diagnosed with GBM and eight cases diagnosed with lower grade astrocytoma were analyzed for the presence of primary and secondary Scherer structures and glomeruloid vascular proliferation [Figure 1].
Figure 1: Distribution of primary and secondary Scherer structures in the GBM and lower grade astrocytoma groups. GBM: Glioblastoma multiforme

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Primary Scherer structures — pseudopalisadic necrosis are pathognomonic for GBM. Because this feature is pathognomic, all 28 cases of GBM exhibited it [Figure 2].
Figure 2: Primary Scherer structure (pseudopalisading necrosis; arrows) (hematoxylin and eosin staining; original magnification, 100×)

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Glomeruloid vascular proliferation is another pathognomic histological hallmark for GBM; however, it was observed in only 89.3% of all GBM cases [Figure 3].
Figure 3: Glomeruloid vascular proliferation (arrows) (hematoxylin and eosin staining; original magnification, 200×)

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The results for the GBM group also showed the presence of 67.9% subpial palisading [Figure 4], 78.54% fascicular aggregation of tumor cells [Figure 5], 96.4% perineuronal satellitosis [Figure 6], and 100.0% perivascular satellitosis [Figure 7]. These findings however strongly depend on the amount of tissue examined histologically.
Figure 4: Subpial aggregation (palisading; arrows) (hematoxylin and eosin staining; original magnification, 400×)

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Figure 5: Intrafascicular aggregation (arrows) (hematoxylin and eosin staining; original magnification, 200×)

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Figure 6: Perineural satellitosis (arrows) (hematoxylin and eosin staining; original magnification, 400×)

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Figure 7: Vascular satellitosis (arrows) (hematoxylin and eosin staining; original magnification, 400×)

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In the lower grade astrocytoma, no pseudopalisading necrosis and glomeruloid vascular proliferation as seen in the histological features of a higher-grade neoplasm were found. Secondary Scherer structures were present; however, 50.0% of cases showed subpial palisading tumor cells, 87.5% fascicular aggregation of tumor cells, 100.0% perineuronal satellitosis, and 100.0% perivascular satellitosis.


  Discussion Top


The current 2016 WHO guidelines classify CNS tumors with astrocytic differentiation into four malignant groups based on their histopathological hallmarks: grade I astrocytoma, with the best patient prognosis and the least aggressive course of progression; grade II astrocytoma, with slow progression but recurring as higher-grade tumors; grade III astrocytoma, with anaplasia and mitotic activity; and grade IV astrocytoma, referred to as GBM, with highly atypical cells with rapid progression and the worst patient prognosis of the IV classes. These tumors show anaplasia, mitotic activity with microvascular proliferation, and/or necrosis.[13],[14]

These tumor entries present with late-onset and are larger as compared to metastatic disease, largely due to their growth patterns. Primary and secondary Scherer structures are the natural patterns of growth of glial neoplasm. Although aggressive in their growth and clinical course, these tumors largely grow through the physiological pathways of the brain, using reactivated stem cell migration mechanisms. Therefore, they take a long time to destroy the normal brain structures and lead to the development of neurological deficits or ectopic activity.


  Conclusions Top


The reported features are hallmarks of tumor growth, and apart from the well-established primary Scherer structures and glomeruloid vascular proliferation, these can be considered as natural phenomena of the glial tumor growth.

Financial support and sponsorship

Nil.

Institution review board statement

The study was approved by the Committee on Ethics for Scientific Research, Medical University – Varna “Prof. Dr. Paraskev Stoyanov,” Protocol no. 20 [1] on April 26, 2012 and conducted in concordance with the principles of the Declaration of Helsinki.

Declaration of patient consent

The authors certify that they have obtained the appropriate patient consent forms. In the forms, the patients have given their consent for their images and other clinical information to be reported in journal. The patients understand that their names and initials will not be published, and due efforts will be made to conceal his identity.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, et al. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2012-2016. Neuro Oncol 2019;21:v1-100.  Back to cited text no. 1
    
2.
Hanif F, Muzaffar K, Perveen K, Malhi SM, Simjee SU. Glioblastoma multiforme: A review of its epidemiology and pathogenesis through clinical presentation and treatment. Asian Pac J Cancer Prev 2017;18:3-9.  Back to cited text no. 2
    
3.
Omuro A, DeAngelis LM. Glioblastoma and other malignant gliomas: A clinical review. JAMA 2013;310:1842-50.  Back to cited text no. 3
    
4.
DeAngelis LM, Mellinghoff IK. Virchow 2011 or how to ID(H) human glioblastoma. J Clin Oncol 2011;29:4473-4.  Back to cited text no. 4
    
5.
Scherer HJ. A critical review: The pathology of cerebral gliomas. J Neurol Psychiatry 1940;3:147-77.  Back to cited text no. 5
    
6.
Ferguson S, Lesniak MS. Percival Bailey and the classification of brain tumors. Neurosurg Focus 2005;18:e7.  Back to cited text no. 6
    
7.
Scherer HJ. The forms of growth in gliomas and their practical significance. Brain 1940;63:1-35.  Back to cited text no. 7
    
8.
Peiffer J, Kleihues P. Hans-Joachim Scherer (1906-1945), pioneer in glioma research. Brain Pathol 1999;9:241-5.  Back to cited text no. 8
    
9.
Hara A, Kanayama T, Noguchi K, Niwa A, Miyai M, Kawaguchi M, et al. Treatment strategies based on histological targets against invasive and resistant glioblastoma. J Oncol 2019;2019:2964783.  Back to cited text no. 9
    
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International Agency for Research on Cancer. WHO Classification of Tumours of the Central Nervous System (IARC WHO Classification of Tumours). World Health Organization; 2016.  Back to cited text no. 10
    
11.
Plate KH, Mennel HD. Vascular morphology and angiogenesis in glial tumors. Exp Toxicol Pathol 1995;47:89-94.  Back to cited text no. 11
    
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Scherer HJ. Structural development in gliomas. Cancer 1938;34:333-51.  Back to cited text no. 12
    
13.
Gupta A, Dwivedi T. A simplified overview of World Health Organization classification update of central nervous system tumors 2016. J Neurosci Rural Pract 2017;8:629-41.  Back to cited text no. 13
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14.
Louis DN, Perry A, Reifenberger G, von Deimling A, Figarella-Branger D, Cavenee WK, et al. The 2016 World Health Organization classification of tumors of the central nervous system: A summary. Acta Neuropathol 2016;131:803-20.  Back to cited text no. 14
    


    Figures

  [Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5], [Figure 6], [Figure 7]



 

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