Journal of Pathology and Translational Medicine

Review

Recommendations for pathologic practice using digital pathology: consensus report of the Korean Society of Pathologists: Yosep Chong, Dae Cheol Kim, Chan Kwon Jung, Dong-chul Kim, Sang Yong Song, Hee Jae Joo, Sang-Yeop Yi; J Pathol Transl Med. 2020;54(6):437-452. Published online October 8, 2020; DOI: https://doi.org/10.4132/jptm.2020.08.27

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Digital pathology (DP) using whole slide imaging (WSI) is becoming a fundamental issue in pathology with recent advances and the rapid development of associated technologies. However, the available evidence on its diagnostic uses and practical advice for pathologists on implementing DP remains insufficient, particularly in light of the exponential growth of this industry. To inform DP implementation in Korea, we developed relevant and timely recommendations. We first performed a literature review of DP guidelines, recommendations, and position papers from major countries, as well as a review of relevant studies validating WSI. Based on that information, we prepared a draft. After several revisions, we released this draft to the public and the members of the Korean Society of Pathologists through our homepage and held an open forum for interested parties. Through that process, this final manuscript has been prepared. This recommendation contains an overview describing the background, objectives, scope of application, and basic terminology; guidelines and considerations for the hardware and software used in DP systems and the validation required for DP implementation; conclusions; and references and appendices, including literature on DP from major countries and WSI validation studies.

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Original Articles

Frequency of BRAF Mutation and Clinical Relevance for Primary Melanomas: Hyoun Wook Lee, Ki Hoon Song, Jin Woo Hong, Su Young Jeon, Dong Yeob Ko, Ki Ho Kim, Hyuk Chan Kwon, Suee Lee, Sung Hyun Kim, Dae Cheol Kim; Korean J Pathol. 2012;46(3):246-252. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.246

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Abstract PDF

Background

This study was conducted to clarify the frequency of the BRAF mutation in primary melanomas and its correlation with clinicopathologic parameters.

Methods

We analyzed the frequency of BRAF mutation in patients with primary cutaneous melanoma (n=58) or non-cutaneous one (n=27) by performing dual priming oligonucleotide-based multiplex real-time polymerase chain reaction to isolate and to purify the DNA from the formalin-fixed and paraffin-embedded tumors.

Results

The BRAF mutation was found in 17.2% (10/58) of patients with primary cutaneous melanoma and 11.1% (3/27) of those with non-cutaneous melanoma. The frequency of BRAF mutation was not correlated with any clinicopathologic parameters with the exception of the patient age. The frequency of the BRAF mutation was significantly higher in patients younger than 60 years as compared with those older than 60 years (p=0.005).

Conclusions

Compared with previous reports, our results showed that the frequency of the BRAF mutation was relatively lower in patients with primary cutaneous melanoma. Besides, our results also showed that the frequency of the BRAF mutation had an inverse correlation with the age. Further studies are warranted to exclude methodological bias, to elucidate the difference in the frequency of the BRAF mutation from the previous reports from a Caucasian population and to provide an improved understanding of the molecular pathogenesis of malignant melanoma.

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OSMANGAZİ JOURNAL OF MEDICINE.2023;[Epub] CrossRef
Genetic characteristics and response to systemic therapies of acral lentiginous melanoma at a tertiary care center—a retrospective review
Taylor Jamerson, Vito W. Rebecca, Crystal Aguh
Journal of the National Medical Association.2022; 114(1): 7. CrossRef
Comparative study of cutaneous melanoma and its associated issues between people of African decent and Caucasians
Ehiaghe L. Anaba
Dermatologic Therapy.2021;[Epub] CrossRef
BRAF, KIT, and NRAS Mutations of Acral Melanoma in White Patients
Emi Dika, Giulia Veronesi, Annalisa Altimari, Mattia Riefolo, Giulia Maria Ravaioli, Bianca Maria Piraccini, Martina Lambertini, Elena Campione, Elisa Gruppioni, Michelangelo Fiorentino, Barbara Melotti, Manuela Ferracin, Annalisa Patrizi
American Journal of Clinical Pathology.2020; 153(5): 664. CrossRef
Clinical Application of Next-Generation Sequencing–Based Panel to BRAF Wild-Type Advanced Melanoma Identifies Key Oncogenic Alterations and Therapeutic Strategies
Changhee Park, Miso Kim, Min Jung Kim, Hyeongmin Kim, Chan-Young Ock, Bhumsuk Keam, Tae Min Kim, Dong-Wan Kim, Jong-Il Kim, Dae Seog Heo
Molecular Cancer Therapeutics.2020; 19(3): 937. CrossRef
BRAF and NRAS mutations and antitumor immunity in Korean malignant melanomas and their prognostic relevance: Gene set enrichment analysis and CIBERSORT analysis
Kyueng-Whan Min, Ji-Young Choe, Mi Jung Kwon, Hye Kyung Lee, Ho Suk Kang, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Yun Joong Kim, Nan Young Kim, Ho Young Kim
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MGMT Gene Promoter Methylation Analysis by Pyrosequencing of Brain Tumour.: Young Zoon Kim, Young Jin Song, Ki Uk Kim, Dae Cheol Kim; Korean J Pathol. 2011;45(5):455-462.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.455

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Abstract PDF

BACKGROUND
The aim of this study was to determine whether pyrosequencing (PSQ) might be useful to achieve O6-methyl guanine methyltransferase (MGMT) promoter methylation using 1- to 13-year-old archival tissues as a clinical biomarker in routine practice.
METHODS
The study included 141 formalin-fixed paraffin-embedded (FFPE) glial tumors from the archives of the Pathology Department from 1997-2010.
RESULTS
The average percentage of methylation (MP) of the 141 cases was 14.0+/-16.8%, and methylated cases were 32.3+/-14.9%. The average MP of each year did not show a linear increasing or decreasing pattern according to the age of the FFPE block (p=0.771). The average MP of methylated glioblastomas was 35.8+/-14.7%, 31.8+/-15.5% for anaplastic astrocytomas, and 22.4+/-15.1% for astrocytoma. A tendency was observed toward an increasing pattern of average MP with World Health Organization (WHO) grade (p=0.063) in astrocytic tumors. A correlation was observed between average MP and WHO grade (p=0.038) and a bimodal distribution was observed between the methylated and unmethylated cases, using a 9% cut-off value (p<0.001).
CONCLUSIONS
The results showed that a quantitative approach for MGMT promoter methylation yielded a 100% success rate for FFPE tissues from archives. PSQ can be used in a retrospective trial, but the cut-off value and calculation method should be further validated.

Citations

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Immunohistochemical Classification of Primary and Secondary Glioblastomas
Kyu Sang Lee, Gheeyoung Choe, Kyung Han Nam, An Na Seo, Sumi Yun, Kyung Ju Kim, Hwa Jin Cho, Sung Hye Park
Korean Journal of Pathology.2013; 47(6): 541. CrossRef

Case Report

Malignant Rhabdoid Tumor of the Kidney in an Adult: A case report.: Sang Yong Lee, Dae Cheol Kim, Seo Hee Rha, Sook Hee Hong; Korean J Pathol. 1996;30(6):539-543.

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Abstract PDF: Malignant rhabdoid tumor is a distinct renal tumor in pediatric age group and extremely rare in adults. It was originally described as a rhabdomyosarcomatoid variant of Wilms' tumor. But subsequent studies failed to confirm myogenous differentiation, so the rhabdoid tumor is now considered to be a distinct and unique disease type of highly malignant renal tumor, histogenetically unrelated to Wilms' tumor. However the histogenesis have not been clearly defined until now. We report a case of malignant rhabdoid tumor of the kidney in a 34-year-old man who represented with a left abdominal mass. Grossly, a large mass occupying most of the left kidney except for a part of upper pole was invading beyond renal capsule and the perirenal soft tissue. It measured 18x14 cm in dimension and was soft, lobulated and yellowish gray with large areas of hemorrhage and necroses. Microscopically, the tumor mass was composed of sheets of round or polygonal neoplastic cells growing in a solid pattern. These tumor cells were medium to large in size with ample cytoplasm containing recognizable eosinophilic inclusion and had an eccentrically located, large nucleus with one or a few prominent nucleoli. Mitotic figures were frequently observed. Ultrastructurally, the tumor cells contained whorled filamentous inclusions corresponding to vimentin, epithelial membrane antigen and cytokeratin in immunostaining.

Original Article

Expression Pattern of Tumor Progression and Metastasis-related Gene Proteins - CD44H, CD44v6, erbB-2, and p53 -in Gastric Carcinoma.: Sung Woo Joo, Young Jhoon Chin, Dae Cheol Kim, Gi Yeoung Huh, Sook Hee Hong; Korean J Pathol. 1996;30(9):751-763.

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Abstract PDF: Immunohistochemical studies of the molecules associated with gastric tumor progression and metastasis were done to evaluate their relationship with known prognostic factors and their usefulness in assessment of the progression of gastric carcinoma in 127 gastric carcinoma tissues. The 4 antibodies used in this study were CD44H, CD44v6, erbB-2, and p53. The CD44H expression was detected in 76 (59.8%), CD44v6 in 63 (49.6%), erbB-2 in 18 (14.2%), and mutant p53 in 98 (77.2%) out of 127 cases of gastric carcinomas. There was no significant correlation between the expression rates of each four proteins. The expression rates of all 4 proteins were not significantly correlated with age and sex of the patients and lymph node metastasis, but the correlation between CD44v6 expression and the depth of tumor invasion and tumor stage was significant (p<0.05). These results suggest that CD44v6 is closely associated with tumor invasion, and high levels of CD44H, erbB-2 and p53 are associated with tumorigenesis of the stomach as they are highly expressed in early as well as in advanced gastric carcinomas. The findings also support the conclusion that the loss of control of alternative CD44 mRNA splicing resulted in production of CD44v6 splicing variant in tumor cell facilitates tissue invasion by increased adherence of the tumor cell to an extracellular matrix or by tumor cell migration. It can be expected that CD44v6 overexpression in tumor cells appears to be an important prognostic indicator for gastric tumor progression.

Case Report

Adenomyoepithelioma of the Breast.: Sang Yong Lee, Hea Kyoung Hur, Dae Cheol Kim, Seo Hee Rha, Sook Hee Hong; Korean J Pathol. 1997;31(1):83-86.

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Abstract PDF: Adenomyoepithelioma is a rare benign tumor which occurs mainly in the skin, salivary gland and very rarely in the breast. Histologically this tumor demonstrates biphasic differentiation of luminal epithelial cells and myoepithelial cells. We report a case of adenomyoepithelioma occuring in the outer lower quadrant of the right breast of a 56-year-old female, confirmed histologically with an aid of immunohistochemistry. This is the first documented report in Korean literature.

Original Article

Expression of Cell Adhesion Molecules -CD44H and CD44v6- in Colorectal Carcinoma.: Dae Cheol Kim, Seo Hee Rha, Jin Sook Jeong, Sook Hee Hong; Korean J Pathol. 1998;32(9):655-662.

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Abstract: During tumor progression, a subset of cells acquires metastatic properties, presumably through a series of genetic alterations. As the result, cells detach from the primary tumor, penetrate the basement membrane and invade the adjacent structures including lymph and blood vessels. Loss of adhesive functions and gain of new adhesive functions are thought to play a crucial role in this metastatic cascade. Since tumor metastasis is the principle cause of death for cancer patients including colon cancer, there is a consensus that a search for tools that allow effective assessment of the metastatic potential of tumors is a prime goal for cancer research. An immunohistochemical study of cell adhesion molecules, CD44H and its variant CD44v6, was done to evaluate their relationship with known prognostic factors related to the progression and metastasis of colorectal carcinoma in 94 cases of colorectal carcinoma tissues. The results were as follows. The CD44H expression was detected in 90 (95.7%) and CD44v6 in 53 (56.4%) out of 94 cases of colorectal carcinoma, and the CD44H was overexpressed in tumor tissue more than in normal mucosa in 62% of the cases. The expression rates of both protein were not significantly correlated with age and sex of the patients, invasion depth, lymph node metastasis, tumor differentiation, and tumor site. The coexpression of CD44H and CD44v6 in tumor was significant (p<0.05). The above results suggest that overexpression of CD44H and loss of function to control the alternative splicing of CD44 mRNA resulting in CD44v6 expression and alteration of adhesive function are closely associated with tumorigenesis of the colorectum.

Case Reports

Extrarenal Malignant Rhabdoid tumor: A Case Report.: Sang Yong Lee, Dae Cheol Kim, Seo Hee Rha, Sook Hee Hong, Tae Hun Kang, Young Ho Lee, Kyoung Jin Nam, Jin Sook Jeong; Korean J Cytopathol. 1996;7(1):69-74.

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Abstract PDF: Malignant rhabdoid tumor is a distinct renal tumor in the pediatric age group. It was originally described as a rhabdomyosarcomatoid variant of Wilms tumor. However, subsequent studies failed to confirm myogenous differentiation, so it is now considered to be a distinct and unique type of highly malignant tumor, histogenetically unrelated. Although extrarenal forms of this tumor are rare, several examples have been described in other sites, especially the liver, prostate, paravertebral area, urinary bladder and soft tissue. We experienced a case of malignant rhabdiod tumor located in the intraabdominal cavity in a 10 month-old boy. Smear of peritoneal fluid showed round, polygonal and irregular shaped cells with large nuclei, ample cytoplasm containing Jight pink "to purple cytoplasmic inclusions, and one or a few prominent nucleoli. Immunocytochemistry revealed positivity to cytokeratin, epithelial membrane antigen and vimentin, and negativity to desmin and neuron-specific enolase. These distinct cytologic appearance and immunophenotypes were most consistent with a diagnosis of extrarenal malignant rhabdoid tumor. The cytoplasmic inclusions were correlated with eosinophilic inclusions seen in histologic section and electron microscopy confirmed this interpretation, showing filamentous aggregations in the cytoplasms of the tumor cells.

Glial Choristoma of the Middle Ear: A Case Report.: Su Jin Kim, Dae Cheol Kim; Korean J Pathol. 2007;41(5):362-365.

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Abstract PDF: Glial choristoma is defined as a mass that is composed of mature, normal brain tissue, isolated from the cranial cavity or spinal canal. The involvement of an extracranial non-midline location, especially the middle ear or mastoid region, is quite exceptional. We report here on a case of glial choristoma of the middle ear in a 2-year-old boy. He presented with otalgia and otorrhea that had lasted for 6 months, and radiological studies revealed a mass-like lesion with soft tissue density in the middle ear cavity. The patient underwent simple mastoidectomy and tympanoplasty. Histologically, the mass was composed of disorganized but mature, normal glial tissue with immunoreactivity for glial fibrillary acidic protein. The patient had no previous history of head trauma or surgery, and no evidence of central nervous system connection was noted on the radiological or operative findings. This mass was regarded as a primary glial heterotopia rather than an acquired encephalocele.

Original Article

p53, Heat Shock Protein 70 and Topoisomerase II Expression in Gallbladder Carcinoma.: Dae Cheol Kim, Mee Sook Roh, Jin Sook Jeong; Korean J Pathol. 2006;40(6):432-438.

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Abstract PDF: BACKGROUND
The present study was designed to investigate the expression of p53, Heat Shock Protein 70 (HSP70), and Topoisomerase (Topo) II alpha in the preneoplastic lesions and carcinomas of the gallbladder (GB) and to assess the correlation between the expression of these proteins and the clinicopathologic parameters by performing immunohistochemistry.
METHODS
The immunohistochemical expressions of p53, HSP70 and Topo II alpha were evaluated in 38 gallbladder carcinomas and 3 adenomas. Fifteen CIS(s) and 8 dysplasias that were located adjacent to invasive carcinomas were also studied.
RESULTS
A p53 expression was identified in 22 (57.9%) of the 38 GB carcinomas, in 9 (64.3%) of 14 CISs, and in none of the 8 dysplasias and 3 adenomas. A HSP70 expression was found in 11 (29%) of the 38 carcinomas, in 11 (78.6%) of 14 CIS(s), and in 4 (57.2%) of 7 dysplasias. A Topo II alpha expression was present in 36 (94.7%) of the 38 carcinomas, in 13 (92.9%) of 14 CIS(s), in 7 (100%) of 7 dysplasias and in 3 (100%) of 3 adenomas. p53 overexpression was related to the T stage of the primary tumor, while HSP70 and Topo II alpha were not related to any of the clinicopathologic parameters.
CONCLUSION
p53 may be involved in GB carcinogenesis and in the progression of cancer. p53 may be also helpful for making the differential diagnosis between dysplasia and CIS. A further large study is needed to better elucidate the roles of HSP70 and Topo II alpha in GB carcinogenesis.

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