Journal of Pathology and Translational Medicine

Original Article

Reclassification of Mongolian Diffuse Gliomas According to the Revised 2016 World Health Organization Central Nervous System Tumor Classification: Enkhee Ochirjav, Bayarmaa Enkhbat, Tuul Baldandorj, Gheeyoung Choe; J Pathol Transl Med. 2019;53(5):298-307. Published online August 2, 2019; DOI: https://doi.org/10.4132/jptm.2019.07.15

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Background
The 2016 World Health Organization (WHO) classification of central nervous system (CNS) tumors has been modified to incorporate the IDH mutation and 1p/19q co-deletion in the diagnosis of diffuse gliomas. In this study, we aimed to evaluate the feasibility and prognostic significance of the revised 2016 WHO classification of CNS tumors in Mongolian patients with diffuse gliomas.
Methods
A total of 124 cases of diffuse gliomas were collected, and tissue microarray blocks were made. IDH1 mutation was tested using immunohistochemistry, and 1p/19q co-deletion status was examined using fluorescence in situ hybridization analysis.
Results
According to the 2016 WHO classification, 124 cases of diffuse brain glioma were reclassified as follows: 10 oligodendroglioma, IDH^mut and 1p/19q co-deleted; three anaplastic oligodendroglioma, IDH^mut and 1p/19q co-deleted; 35 diffuse astrocytoma, IDH^mut, 11 diffuse astrocytoma, IDH^wt, not otherwise specified (NOS); 22 anaplastic astrocytoma, IDH^mut, eight anaplastic astrocytoma, IDH^wt, NOS; and 35 glioblastoma, IDH^wt, NOS, respectively. The 2016 WHO classification presented better prognostic value for overall survival in patients with grade II tumors than traditional histological classification. Among patients with grade II tumors, those with oligodendroglioma IDH^mut and 1p/19q co-deleted and diffuse astrocytoma IDH^mut showed significantly higher survival than those with diffuse astrocytoma IDH^wt, NOS (p<.01).
Conclusions
Mongolian diffuse gliomas could be reclassified according to the new 2016 WHO classification. Reclassification revealed substantial changes in diagnosis of both oligodendroglial and astrocytic entities. We have confirmed that the revised 2016 WHO CNS tumor classification has prognostic significance in Mongolian patients with diffuse gliomas, especially those with grade II tumors.

Citations

Citations to this article as recorded by

Targeted next‐generation sequencing of adult gliomas for retrospective prognostic evaluation and up‐front diagnostics
J. K. Petersen, H. B. Boldt, M. D. Sørensen, S. Blach, R. H. Dahlrot, S. Hansen, M. Burton, M. Thomassen, T. Kruse, F. R. Poulsen, L. Andreasen, H. Hager, B. P. Ulhøi, S. Lukacova, G. Reifenberger, B. W. Kristensen
Neuropathology and Applied Neurobiology.2021; 47(1): 108. CrossRef

Case Reports

HER2-Positive Breast Carcinomas with Co-amplification or Gain of Chromosome 17 Centromere Locus: Report of Three Cases and an Impact on HER2 Testing.: Hyeong Chan Shin, Young Kyung Bae, Aeri Kim, Seok Ju Park; Korean J Pathol. 2011;45(6):665-669.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.6.665

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Abstract PDF: Recently we experienced three cases of human epidermal growth factor receptor 2 (HER2)-amplified invasive breast carcinomas associated with co-amplification or gain of chromosome 17 centromere (CEP17) in silver-enhanced in situ hybridization (SISH) analysis. These cases revealed 2+ or 3+ staining for HER2 immunohistochemistry and >6 HER2 copies per cell on SISH analyses. However, the calculated HER2/CEP17 ratios were low (<2.2) and did not fit within the HER2-positive category. We interpreted those cases as HER2-positive tumors based on the number of HER2 copies per cell. There is a potential for misinterpretation of SISH analysis in cases showing increased CEP17 copy number, based on the criterion used for HER2 positivity (HER2 copies >6 per cell vs HER2/CEP17 ratio>2.2). We recommend reporting raw SISH or fluorescence in situ hybridization data, including number of cells counted, average numbers of HER2 and CEP17 signals, and the calculated HER2/CEP17 ratio to prevent underreporting of HER2 amplification.

Extramedullary B Lymphoblastic Crisis of CML, Presenting as a Leptomeningeal Tumor: A Case Report.: Hoiseon Jeong, Bongkyung Shin, Sook Young Bae, Sangho Lee, Youngjune Ryu, Hankyeom Kim, Insun Kim; Korean J Pathol. 2009;43(5):482-488.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.5.482

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Abstract PDF: We report here on a rare case of a patient who presented with an extramedullary B lymphoblastic crisis as an initial manifestation of chronic myelogenous leukemia (CML). A 71-year-old man visited the emergency room due to suddenly developed dysarthria and right side weakness. Emergency craniotomy was done under the presumptive diagnosis of subdural hemorrhage. During the operation, a poorly demarcated firm mass was identified in the leptomeningeal space. Microscopically, the majority of the tumor was composed of monotonous immature cells with blast morphology, and these cells were immunoreactive for TdT, CD34, CD10 and CD20, indicating the precursor B-cell phenotype. The peripheral area of the tumor consisted of myeloid cells in various stages of maturation, and these cells were reactive for myeloperoxidase, chloroacetate esterase, CD43 and CD15. FISH analysis using the LSI bcr-abl dual color probe showed gene fusion signals in both the B-lymphoblasts and myeloid cells. The peripheral blood and bone marrow findings were consistent with CML with no evidence of a blast crisis. Cytogenetic study of the bone marrow demonstrated the 46, XY, t(9;22)(q34;q11) chromosome. A diagnosis of extramedullary B lymphoblastic blast crisis in a patient with Philadelphia chromosome-positive CML was made. Despite treatment, the patient died 3 months after he was diagnosed.

Original Articles

Clonality Study in Carcinosarcomas and Malignant Mixed Epithelial Tumors.: Eun Jung Park, Yoo Duk Choi, Jong Hee Nam, Min Cheol Lee, Chang Soo Park, Sang Woo Juhng, In Seon Choi, Kyung Hee Kim, Chan Choi; Korean J Pathol. 2002;36(4):205-211.

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Abstract PDF: BACKGROUND
Tumors are usually considered to be clonal progeny of single transformed cells. Carcinosarcomas and malignant mixed epithelial tumors are examples where controversies exist regarding the singularity or multiplicity of their cell of origin.
METHODS
The authors examined the clonality of carcinosarcomas (7 cases) and malignant mixed epithelial tumor (5 cases) in female patients by X-chromosome inactivation as a marker. Each component of the tumors were picked up by the laser capture microscope. The polymorphic exon 1 CAG trinucleotide repeat in the X-linked human androgen receptor (HUMARA) gene was amplified by a polymerase chain reaction before and after treatment of the methylation-sensitive endonuclease HpaII.
RESULTS
Eleven cases were informative for clonality determination. Six out of seven carcinosarcomas and three out of four malignant mixed epithelial tumors revealed the same patterns of X-chromosome inactivation, which suggests that they are monoclonal. In contrast, the patterns of X-chromosome inactivation were different between the two tumor components in each cases of carcinosarcoma and malignant mixed epithelial tumor, indicating that they are of polyclonal origin.
CONCLUSIONS
These observations show that although most of carcinosarcomas and malignant mixed epithelial tumors are of monoclonal origin, some of them are of polyclonal origin. This finding suggests that these tumors are genuinely polyclonal, and that they originated in the neoplastic transformation of more than one somatic cells

Alterations of 9p21-22 Region Encoding Genes in Primary Glioblastomas.: Hong Jik Doh, Seong Il Suh, Dong Won Kim, Il Man Kim, Man Bin Yim, Eun Ik Son, Kun Young Kwon, Sang Sook Lee, Sang Pyo Kim; Korean J Pathol. 2002;36(6):394-399.

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Abstract PDF: BACKGROUND
Glioblastomas are one of the most common and aggressive malignant glial tumors occuring in the central nervous system. This study analyzed the status of p15INK4b, p14ARF, p16INK4a, MTAP, IFNA, and IFNB genes in 36 primary glioblastomas to investigate whether the inactivation of these genes participate in primary glioblastoma tumorigenesis.
METHODS
We used polymerase chain reaction, polymerase chain reaction/single strand conformational polymorphism (PCR/SSCP) analysis, and methylation-specific PCR.
RESULTS
Homozygous deletions at the p16INK4a gene were detected in 11 cases (30.5%) of 36 primary glioblastomas, and the promoter hypermethylation was found in 3 cases (8.3%) of 36 primary glioblastomas. In mutational analysis for the p16INK4a gene by PCR/SSCP, there was no abnormal mobility-shifted band in 36 cases of primary glioblastomas. The overall frequency of p16INK4a alterations including homozygous deletion and promoter hypermethylation in 36 primary glioblastomas was 38.8% (14 of 36). Deletions of p15INK4b were noted in 4 cases (11.1%), whereas deletions of the p14ARF and MTAP genes were detected in 1 case of 36 cases of primary glioblastomas. But deletions of the INFA and B genes were not found.
CONCLUSIONS
These results suggest that alterations of the p16INK4a gene can be important mechanisms of the tumorigenesis of primary glioblastomas, and the p16INK4a gene is inactivated by mechanisms including homozygous deletion and promoter hypermethylation.

Adequate Microsatellite Markers for 1p/19q Loss of Heterozygosity of Oligodendroglial Tumors in Korean Patients.: Se Hoon Kim, Hoguen Kim, Tai Seung Kim; Korean J Pathol. 2005;39(1):23-33.

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Abstract PDF: BACKGROUND
It is well known that oligodendrogliomas can be divided into two groups according to the 1p/19q or 1p loss of heterozygosity (LOH) status because oligodendrogliomas with the 1p/19q LOH or the 1p LOH have a better prognosis and chemosensitivity. In this study, we investigated the adequate microsatellite markers for 1p/19q LOH of oligodendroglial tumors in Korean patients.
METHODS
We performed PCR that was based on the LOH test with the 1p (D1S508, D1S199, D1S2734, D1S186 & D1S312) and 19q (D19S219, D19S112, D19S412 & D19S596) microsatellite markers; these were the markers that were recommended by other researchers. We performed this PCR on microdissected paraffin embedded tissue blocks of 67 tumors from 56 cases.
RESULTS
The PCR based LOH analysis revealed that 3 microsatellite markers (D1S508, D1S2734 & D1S186) of 1p and 2 markers (D19S219 & D19S412) of 19q had higher heterozygosity scores than other markers. In addition, chromosomal LOH status using these selective markers showed a statistically significant difference of prognosis for oligodendroglial tumors.
CONCLUSIONS
We can suggest that the microsatellite markers with high heterozygosity scores (D1S508, D1S2734, D1S186, D19S219 and D19S412) would be adequate microsatellite markers for a PCR based LOH test of oligodendroglial tumors in Korean patients.

Detection of Chromosome Aberration in Interphase Nuclei of Tumor Cells by Nonradioactive In Situ Hybridization Using Chromosome-specific Probes.: Sang Sook Lee; Korean J Pathol. 1993;27(6):573-580.

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Abstract PDF: An improved protocol for in situ hybridization(ISH) to routinely processed, paraffin-embedded tissue sections from lung carcinoma is presented. For this study, DNA probes for alpha-satellite chromosome 7 and 17 were used. The protocol to detect numerical chromosome aberrations involved treatment of sections with 1 M sodium thiocyanate prior to pepsin digestion, resulting in reproducible ISH reactions. The effect of avidin-biotin detection system. Four layer avidin methods and triple biotin methods, using avidin-PO, goat antiavidin, biotinylated antigoat IgG, avidin-PO or anti-biotin, biotinylated antirabbit IgG, avidin-PO, markedly enhanced the intensity of positive signals. More than 80% of the tumor and stromal cells showed distinct chromosome hybridization signals in 6 micrometer-thick sections. Lung carcinoma cells showed multiple chromosome signals(2~5 spots), contrasted by one or two signals in the stromal cells in the same section. These results suggest that chromosome polysomy can be reliably detected in tissue sections using in situ hybridization. This capability will prove to be an important tool for determining the underlying genetic basis for tumor development, tissue phenotype heterogeneity and progression by allowing genetic determination to be made on paraffin-embedded tissue sections where tumor histologic architecture is preserved.

Detection of Numerical Chromosomal Aberration in Squamous Cell Carcinoma of the Lung by In Situ Hybridization Using #17 Centromeric Probes.: Sang Sook Lee, Seong Beom Han, Soong Kook Park; Korean J Pathol. 1993;27(5):443-458.

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Abstract PDF: This study was carried out to understand the relationship between specific chromosome changes and their phenotypic consequences at the tissue level of human lung cancers. Then paraffin-embedded human lung squamous cell carcinoma samples were investigated for in evidence of genetic alterations, using chromosome 7 and 17-specific repetitive alpha-satellite DNA probes. In situ hybridization procedure with chromosome-specific DNA probes was optimized for use on formalin-fixed paraffin-embedded lung tissue sections. The chromosome index ranged from 1.10 to 1.88(median, 1.49) for chromosome 7 and 1.20 to 1.98(median, 1.69) for chromosome 17. Normal lymphocytes and stromal cells showed one or two chromosome signals per cell in most cases. All tumors showed three or more chromosome signals per cell with range of 16.0% to 80.6% of cancer cells(median, 50.9%) for chromosome 7 and 32.7% to 84.7%(median, 69.9%) for chromosome 17. The chromosome index did not correlate with the DNA content in most cases. Chromosomes 7 and 17 were either overrepresented or underrepresented when they were compared with corresponding DNA index determined by FCM. An increase in copy number, particularly of chromosome 7 was associated with a less favorable phenotype, including high nuclear grade. In addition, chromosome alterations were differentially expressed in the different areas of the same tissue section, correlating with histologic heterogeneity. These results suggest that chromosome polysomy can be reliably detected in tissue sections using in situ hybridization. There is a strong correlation between genotypic abnormalities and tumor phenotype in human lung cancer. This capability will prove to be an important tool for determining the underlying genetic basis for tumor development, tissue phenotype heterogeneity and progression by allowing genetic determination to be made on paraffin-embedded tissue sections where tumor histologic architecture is preserved.

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