Journal of Pathology and Translational Medicine

Original Article

Reclassification of Mixed Oligoastrocytic Tumors Using a Genetically Integrated Diagnostic Approach: Seong-Ik Kim, Yujin Lee, Jae-Kyung Won, Chul-Kee Park, Seung Hong Choi, Sung-Hye Park; J Pathol Transl Med. 2018;52(1):28-36. Published online September 29, 2017; DOI: https://doi.org/10.4132/jptm.2017.09.25

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Background
Mixed gliomas, such as oligoastrocytomas (OA), anaplastic oligoastrocytomas, and glioblastomas (GBMs) with an oligodendroglial component (GBMO) are defined as tumors composed of a mixture of two distinct neoplastic cell types, astrocytic and oligodendroglial. Recently, mutations ATRX and TP53, and codeletion of 1p/19q are shown to be genetic hallmarks of astrocytic and oligodendroglial tumors, respectively. Subsequent molecular analyses of mixed gliomas preferred the reclassification to either oligodendroglioma or astrocytoma. This study was designed to apply genetically integrated diagnostic criteria to mixed gliomas and determine usefulness and prognostic value of new classification in Korean patients.
Methods
Fifty-eight cases of mixed OAs and GBMOs were retrieved from the pathology archives of Seoul National University Hospital from 2004 to 2015. Reclassification was performed according to genetic and immunohistochemical properties. Clinicopathological characteristics of each subgroup were evaluated. Overall survival was assessed and compared between subgroups.
Results
We could reclassify all mixed OAs and GBMOs into either astrocytic or oligodendroglial tumors. Notably, 29 GBMOs could be reclassified into 11 cases of GBM, IDH-mutant, 16 cases of GBM, IDH-wildtype, and two cases of anaplastic oligodendroglioma, IDH mutant. Overall survival was significantly different among these new groups (p<.001). Overall survival and progression-free survival were statistically better in gliomas with IDH mutation, ATRX mutation, no microscopic necrosis, and young patient age (cut off, 45 years old).
Conclusions
Our results strongly suggest that a genetically integrated diagnosis of glioma better reflects prognosis than former morphology-based methods.

Citations

Citations to this article as recorded by

The prognostic significance of p16 expression pattern in diffuse gliomas
Jin Woo Park, Jeongwan Kang, Ka Young Lim, Hyunhee Kim, Seong-Ik Kim, Jae Kyung Won, Chul-Kee Park, Sung-Hye Park
Journal of Pathology and Translational Medicine.2021; 55(2): 102. CrossRef
Dynamic susceptibility contrast and diffusion MR imaging identify oligodendroglioma as defined by the 2016 WHO classification for brain tumors: histogram analysis approach
Anna Latysheva, Kyrre Eeg Emblem, Petter Brandal, Einar Osland Vik-Mo, Jens Pahnke, Kjetil Røysland, John K. Hald, Andrés Server
Neuroradiology.2019; 61(5): 545. CrossRef

Case Report

Granular Cell Astrocytoma: Report of a Case: Kyu Ho Kim, Ju Young Song, Chang Hwan Choi, Lucia Kim, Suk Jin Choi, Jee Young Han, Joon Mee Kim, Young Chae Chu, In Suh Park; Korean J Pathol. 2012;46(4):370-372. Published online August 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.4.370

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Abstract PDF

We report here a rare case of granular cell astrocytoma. A 75-year-old man was admitted to Inha University Hospital with a three-month history of language deterioration. In a magnetic resonance imaging, a 6.5 cm-sized heterogeneous enhancing mass was seen in both the frontal lobes and the anterior genu of the corpus callosum. A stereotactic biopsy was performed. The tumor was composed of large and small round cells with abundant intracytoplasmic granules. The nuclei were bland, round to oval, and often eccentrically located. The cytoplasm of the tumor cells was positive for glial fibrillary acidic protein and S-100 protein.

Citations

Citations to this article as recorded by

Cytopathological findings of granular cell glioblastoma in intraoperative squash smear preparations: A case report
Samuel López‐Muñoz, Borja Sánchez‐Cordon, Mario Taravilla‐Loma, Isabel Esteban‐Rodríguez
Cytopathology.2024;[Epub] CrossRef
Granular cell tumor of the brain: case report and review of literature
Shyam Duvuru, Vivek Sanker, Deepak Pandit, Sheezah Khan, Sara Alebrahim, Tirth Dave
Journal of Surgical Case Reports.2023;[Epub] CrossRef
Granular cell astrocytoma: Case report
Rohan Gupta, Supriya Gupta, Nathaniel Shapiro, Scott Rahimi, Suash Sharma
Human Pathology: Case Reports.2018; 14: 4. CrossRef
Unusual presentation of a granular cell astrocytoma
Alan A George, Gregory N Fuller, Lauren A Langford, Clayton D Simon, Amy A Zingalis, Derek A Mathis
Histopathology.2013; 63(6): 883. CrossRef

Original Articles

CD44 and MMP14 Expression Associated with WHO Grade of the Astrocytoma and the Prognostic Implications.: Jaekyung Myung, Bogun Jang, Heae Surng Park, Woongjae Yon, Hyun Ju Lee, Sung Hye Park; Korean J Pathol. 2010;44(1):35-41.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.1.35

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Abstract PDF: BACKGROUND
CD44 is a cell surface receptor that has been implicated in tumor cell invasion and metastasis in a range of tumors of various organs, including breast, ovary, colon, lung, and brain. CD44 stimulates the invasive ability by interacting with matrix metalloproteinase 14 (MMP14). The expression of MMP14 on the cell surface is thought to trigger multiple proteinase cascades and to stimulate cell migration.
METHODS
A total 54 astrocytoma patients were eligible for this study. We performed a retrospective clinicopathological review and CD44 and MMP14 immunohistochemistry.
RESULTS
The expressions of CD44 and MMP14 were significantly correlated with the World Health Organization (WHO) grade. On univariate analysis, the WHO grade and the expression of CD44 were the significant prognostic factors affecting overall survival (OS) and disease progression free survival (DPFS). On the multivariate analysis by the Cox regression model, the only WHO grade was shown to be a significant independent prognostic factor for predicting the DPFS and OS.
CONCLUSIONS
In this study, the CD44 and MMP14 expressions were related to the WHO grade of astrocytoma. The CD44 expression status was a prognostic factor for DPFS and OS on univariate analysis, but it was not an independent prognostic factor on the multivariate analysis.

Angiogenensis and Overexpression of p53 Gene Produc in Brain Tumor.: Jeong Yun Shim, Ho Guen Kim, Tai Seung Kim; Korean J Pathol. 1997;31(1):23-33.

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Abstract PDF: Angiogenesis depends on the net balance between positive and negative angiogenic factors. Tumor cells are angiogenic resulting from increased production of positive factors and decreased production of negative factors. Among these, vascular endothelial growth factor and glioma- derived angiogenesis inhibiting factor are related to glioblastoma multiforme. The p53 gene is more frequently mutated than any other known oncogene or tumor suppressor gene in human tumors including glioblastoma multiforme. Angiogenesis is reported to be controlled by p53 regulation in recent studies. To examine the effect of p53 overexpression on angiogenesis in glioblastoma multiforme, we performed immunohistochemical staining in 51 cases of glioblastoma multiforme, using monoclonal antibodies to p53 protein and factor VIII. 20 cases of low grade astrocytoma were used as control. p53 overexpression was present in 15(75%) of 20 cases of low grade astrocytoma and the mean vessel count was 37.7+/-9.9 at x200 field and 17.5+/-5.8 at x400 field. p53 overexpression was present in 35(68%) of 51 cases of glioblastoma multiforme and the mean vessel count was 91.9 45.8 at x200 field and 40.7 19.1 at x400 field. Mean vessel count in low grade astrocytoma with p53 overexpression was 39.4 10.2 at x200 field and 18.9 5.7 at x400 field, while in cases without p53 overexpression it was 32.4+/-7.6 at x200 field and 13.2 3.5 at x400 field. Mean vessel count in glioblastoma multiforme with p53 overexpression was 94.5+/-51.8 at x200 field and 42.1+/-16.8 at x400 field, while in cases without p53 overexpression it was 86.1+/-29.5 at x200 field and 37.1+/-16.8 at x400 field. The mean survival time was 12.4 months in the 39 cases of glioblastoma multiforme in which follow-up studies were possible. Significant prognostic factors were age, p53 overexpression and adjuvant therapy. These results show that p53 gene mutation is one of the many contributing factors to angiogenesis in glioblastoma multiforme. In addition, other oncogenes and tumor suppressor genes, as well as growth factors may be involved. Age, p53 overexpression and adjuvant therapy proved to be significant prognostic factors, while microvessel density was not.

The Relationship of Ki-67, Proliferating Cell Nuclear Antigen, AgNORs and p53 Protein Expression in Astrocytoma.: Dong Ja Kim, Jae Weon Lim, Yoon Kyung Sohn; Korean J Pathol. 1999;33(1):25-31.

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Abstract PDF: The grading of astrocytoma has traditionally relied on histological assessment, but there are some differences in their parameters, application, and reproducibility. Recently, numerous studies have attempted to correlate biological aggresiveness with tumor proliferation index using new immunohistochemical methods. The purpose of this study is to correlate the histopathological grades of astrocytoma with the expression of Ki-67, PCNA, p53 protein and AgNORs. The paraffin sections of 41 consecutive cases of astrocytomas were examined. Histologically the tumors were graded as three groups under the St. Anne-Mayo system and showed 14 cases in grade II, 15 cases in grade III and 12 cases in grade IV (glioblastoma multiforme). As a result, the Ki-67 labelling index and p53 protein expression tended to increase with increasing grade of malignancy. But the univariate analysis showed that there was no significant difference between the tumor grades (p>0.05). The PCNA labelling index and number of AgNORs revealed striking differences between the grade II and grade III astrocytomas (p<0.05). We concluded that the PCNA labelling index and AgNORs counting are useful markers for differentiation between grade II and III astrocytomas.

Loss of Heterozygosity on Chromosome 9p21, 17p13 and 3p in Human Astrocytic Tumor.: Youn Soo Lee, Chang Suk Kang, Seung Myung Dong, Jung Yong Lee, Sang In Shim, Byung Kee Kim; Korean J Pathol. 2001;35(4):330-337.

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Abstract PDF: BACKGROUND
The purpose of this study was to determine the genetic abnormalities of chromosomes 9p21, 17p13.1, 3p25 and 3p14.2 in the development and progression of astrocytic tumors.
METHODS
We performed loss of heterozygosity (LOH) analysis in 41 astrocytic tumors, including 20 astrocytomas, 11 anaplastic astrocytomas and 10 glioblastomas, and correlated the results of LOH at different histopathologic grades. LOH was determined by multiplex polymerase chain reaction analysis of the DNA, which was extracted by microdissection.
RESULTS
LOH of 9p21 was found in 55.6% of astrocytomas, 54.6% of anaplastic astrocytomas and 100.0% of glioblastomas. LOH of 17p13.1 was found in 21.4% of astrocytomas, 28.6% of anaplastic astrocytomas, and 66.7% of glioblastomas. LOH of 3p25 was found in 37.5% of astrocytomas, 16.7% of anaplastic astrocytomas, and 14.3% of glioblastomas. LOH of 3p14.2 was found in 16.7% of astrocytomas, 40.0% of anaplastic astrocytomas, and 42.9% of glioblastomas. LOH on chromosome 9p21 and 17p13.1 was closely related with the histopathologic grades.
CONCLUSIONS
These results may suggest that LOH of 9p21, 17p13.1, 3p25 and 3p14.2 involves an early event of astrocytoma development and accumulates during progression. LOH of 3p25 may be involved in the tumorigenesis of astrocytoma. Identification of these LOH may illuminate the stepwise pathogenesis of astrocytic tumors and predict the possibility of malignant transformation.

Case Reports

Cerebellar Pleomorphic Xanthoastrocytoma: A Case Report.: Seung Baik Han, Suk Jin Choi, Lucia Kim, Jee Young Han, Joon Mee Kim, Young Chae Chu, In Suh Park; Korean J Pathol. 2006;40(3):231-234.

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Abstract PDF: Cerebellar pleomorphic xanthoastrocytoma (PXA) is a rare tumor. The most common manifestation of PXA is a seizure, as opposed to the headache and dizziness that were present in our reported case; these atypical symptoms were related to the development of tumor in cerebellum. We describe here a case of PXA in the cerebellum of a 49-year-old female and we discuss the radiological, histological and immunohistochemical findings of PXA that occurred in the cerebellum.

Pleomorphic Xanthoastrocytoma in a 58-year-old Woman: A case report.: Joo Heon Kim, Myoung Jae Kang, Dong Geun Lee, Ho Yeul Choi, Sang Ho Kim, Min Cheol Lee; Korean J Pathol. 1995;29(1):122-125.

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Abstract: A case of left parietal pleomorphic xanthoastrocytoma that occurred in a 58-year-old woman is reported clinicopathologically. Histopathologic diagnosis of pleomorphic xanthoastrocytoma was made because of the unique pleomorphic histologic features, positive glial fibrillary acidic protein in immunohistochemical staining. The flow cytometric analysis reveals DNA aneuploidy and relatively high S-phase fraction. The pleomorphic xanthoastrocytoma is considered as a special subgroup of glioma on the basis of superficial cortical location, GFAP expression, marked cellular atypia, xanthomatous cells, and relatively favorable prognosis.

Original Articles

Overexpression of Mutant p53 in Human Anaplastic Astrocytoma and Glioblastoma Multiforme.: Sang Sook Lee, Kam Rae Cho, Cheoul Hee Yun, Sang Pyo Kim, Kwan Kyu Park, Eun Sook Chang, Eun Ik Sohn; Korean J Pathol. 1994;28(4):376-380.

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Abstract PDF: A total of 30 cases of cerebral gliomas, including 6 cases of low grade astrocytomas, 6 anaplasticastrocytoomas and l8 glioblastomas multiforme, was examined immunohistochemically to demonstrate the overexpression of mutant forms of p53 protein and to evaluate their relationships with histological subtypes. A p53 monoclonal antibody was applied to the routine formalin fixed, paraffin-embedded tissues for this study using microwave-assisted avidin-biotin method. Overexpression of p53 protein was identified in 4 out of 6 anaplastic astrocytomas (66.7%) and in l3 out of l8 glioblastomas multiforme (72.2%). No immunohistochemical positivity of p53 was found in adjacent normal brain tissue, gliosis and 6 cases of astrocytoma. These results suggest that overexpression of mutant p53 may be an important step in the development and progression of malignant astrocytoma, especially of the aggressive subtypes of glioma, including glioblastoma multiforme.

Histologic Grading of Astrocytic Neoplasms in Conjunction with Evaluation of Proliferative Activity Using Ag-NORs Count PCNA Expression, and Flow CYtometric DNA Analysis.: Mee Yon Cho, Soon Hee Jung, Tal Seung Kim, Yong Pyo Han; Korean J Pathol. 1994;28(1):49-55.

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Abstract PDF: Although the histologic grade of astrocytic neoplasms of the brain have been used as a prognostic factor, the lack of an objective criteria is possible to create the disagreement of classification. We evaluated 25 cases of astrocytic neoplasms of brain to document the usefulness of prolifera-tive potential of tumor as a prognostic indicator and the correlation with histologic grade by Nils Ringertz. The Ringertz's classification was relatively simple in an application among the variable systems and easy to define the differentiate from grade to grade. The examined cases were com-prised of 7 astrocytomas, 9 anaplastic astrocytomas and 9 glioblastoma multif6rmes. The prolife-rative potential of tumors were measured by Ag-NORs count, PCNA labeling index and flow cytometric analysis. The mean numbers of Ag-NORs per cell and PCNA labeling index were sig-nificantly differ among each histologic grade. In addition, abnormal DNA content and high prolif-erative index were frequently identified in anaplastic astrocytoma and glioblastoma multiforme. Therefore, the Ag-NORs counts, PCNA labeling index, DNA index and proliferative index were well correlated with the histologic grade.

Case Reports

Pleomorphic Xanthoastrocytoma: A Case Report.: Seong Ki Min, Dong Wook Kang, Kyu Sang Song, Dae Young Kang, Seong Ho Kim; Korean J Pathol. 1993;27(6):666-669.

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Abstract PDF: Pleomorphic xanthoastrocytoma is histologically characterized by marked cellular pleomorphism of lipid-laden neoplastic astrocytes and bizarre giant cells showing mitotic figures and high cellularity. Inspite of its ominous-looking microscopic features, howerver, the prognosis is usually favorable. This tumor develops mainly in the supratentorial area of young people and frequently involves the leptomeninges. We experienced a case of pleomorphic xanthoastrocytoma in 18 year-old-male. In addition to the cellular pleomophism, the prominent reticulin fibers surround the individual tumor cells or the tumor cells nests. Immunohistochemical staining and electron microscopy revealed glial fibrillary acidic protein(GFAP) expression and pericytoplasmic basal lamina in the tumor cells.

Pleomorphic Xanthoastrocytoma: A case report.: Soon Ae Oak, Hee Kyung Chang, Man Ha Huh; Korean J Pathol. 1993;27(3):287-289.

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Abstract PDF: The Pleomorphic xanthoastrocytoma(PXA) is considered as a special subgroup of gliomas because of its distinctive characteristics: onset in young subject; predilection for the temopral or parietal lobe and a superficial location; frequent appearance as a yellow encapsulated mass with a grossly visible tumor-associated cyst; marked histological pleomorphism; little or no mitosis and no necrosis; presence of a rich reticulin network; and demonstrable GFAP in many of the fusiform and giant cells; most importantly, the relatively favorable prognosis despite plemorphism and bizzare giant cells in the microscopic picture. The objective of this report is to add one more case of pleomorphic xanthoastrocytoma to the medical literature.

Original Article

Spinal Pleomorphic Xanthoastrocytoma.: Tae Jin Kim, Je G Chi; Korean J Pathol. 1993;27(2):184-186.

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Abstract PDF: Pleomorphic xanthoastrocytoma is a rare tumor, presenting superficially over the cerebral hemispheres of young subjects. We report a case of Pleomorphic xanthoastrocytoma of the cervical cord in view of its unusual location. The patient is a 20-year-old female, presenting with left neck pain radiating to the left shoulder one month before the admission. Magnetic resonance imaging revealed a high signal lesion in the upper cervical cord lower brainstem in T2 weighted image. On operation, intramedullary tumor was present and it was relatively well delineated. Near-total removal of the spinal cord mass was done. Microscopically, the tumor was composed of pleomorphic astrocytes, which were spindle-shaped with cytoplasmic processes and hyperchromatic nuclei. Other cells were round with vesicular nuclei and abundant eosinophilic cytoplasm. A few giant cells were seen. Despite the marked pleomorphism, mitosis or necrosis was not encountered. Scattered foamy cells were also seen, which showed negative staining in GFAP immunostaining in contrast to other GFAP-positive tumors cells.

Case Reports

Brain Stem Glioma (An autopsy case).: Doo Hyun Chung, Soong Deok Lee, Hee Jin Yang, Dae Hee Han, Je G Chi; Korean J Pathol. 1991;25(6):607-610.

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Abstract PDF: We report an autopsy case of the brain stem glioma that extended extensively in the brain stem itself and cephalad. This 18-year-old boy first presented with dizziness, vomiting and left side weakness with left facial palsy. Brain MRI revealed a diffusely infiltrative tumor involving whole medulla, pons and lower midbrain. A total of 4000 R was given with some alleviation of respiratory difficulty. He died one year after the onset. Autopsy revealed the tumor involving pons, a portion of medulla oblongata, and cerebellum. The tumor showed diffusely infiltrative pattern and extended along the periventricular area to the thalamus and corpus callosum. The cut surface was grayish white and solid. It also showed areas of myxoid degeneration and necrosis probably related to radiation therapy. Microscopically the tumor was a cellular and pleomorphic glioma that showed some astrocytic differentiation. It was diffuse without geographic necrosis.

Delayed Radionecrosis of the Brain: A case simulating recurrent glioma.: Shin Kwang Khang, Jun Ho Song, Kyu Ho Lee, In Wook Choo, Je G Chi; Korean J Pathol. 1988;22(3):360-366.

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Abstract PDF: An appreciation of the radiation changes in the brain adjacent to radiated glioma is of considerable importance from both clinical and pathological standpoint because the alteration in the brain parenchyma may result in a picture that mimics recurrence of the neoplasm. A 35 years old woman was admitted because of deterioration of consciousness which has started about 20 days ago. Past history revealed removal of left frontal brain tumor 4 years earlier and the diagnosis was grade II astroma. Postoperative radiation was done at that time. Sine then, she has been doing well. Computerized tomogram showed an ill defined huge low density mass at right frontal and left posterior parietal areas, which was irregularly enhanced in postcontrast study. Unlikely to the usual brain tumors, there was no mass effect on adjacent structures. Histologically acellular necrotic zone was alternating with hypercellular zone and most striking changes were vascular and glial reaction. Most of the vessels showed acellular hyliane thickening of their wall and some vessels were almost completely occluded. There was marked glial proliferation with considerable cellular and nuclear irregularities. Gemistocytic astrocytes were frequently seen and some were multinucleated.

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