Journal of Pathology and Translational Medicine

Brief Case Report

Vascular Ehlers-Danlos syndrome with distinct histopathologic features: Hee Sang Hwang, Jin Woo Song, Se Jin Jang; J Pathol Transl Med. 2022;56(3):167-169. Published online May 11, 2021; DOI: https://doi.org/10.4132/jptm.2021.03.24

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Variante no descrita previamente en el gen COL3A1: causalidad del Síndrome de Ehlers-Danlos tipo Vascular
Estrella Gutiérrez Romero, Nuria Padilla Apuntate, Silvia Izquierdo Álvarez
Advances in Laboratory Medicine / Avances en Medicina de Laboratorio.2025; 6(4): 504. CrossRef
A de novo variant of the COL3A1 gene: causality of vascular Ehlers-Danlos syndrome
Estrella Gutiérrez Romero, Nuria Padilla Apuntate, Silvia Izquierdo Álvarez
Advances in Laboratory Medicine / Avances en Medicina de Laboratorio.2025; 6(4): 500. CrossRef
Uncommon association between vascular Ehlers–Danlos syndrome and ocular complications
Matei Popa Cherecheanu, Mihaela Oana Romanitan, Ruxandra Pirvulescu, Raluca Iancu, Gerhard Garhöfer, George Iancu, Alina Popa Cherecheanu, Mihail Zemba, Victor Vasile, Andrei Simonov, Daniel Branisteanu
Frontiers in Medicine.2023;[Epub] CrossRef

Original Articles

Sarcoma metastasis to the pancreas: experience at a single institution: Miseon Lee, Joon Seon Song, Seung-Mo Hong, Se Jin Jang, Jihun Kim, Ki Byung Song, Jae Hoon Lee, Kyung-Ja Cho; J Pathol Transl Med. 2020;54(3):220-227. Published online April 22, 2020; DOI: https://doi.org/10.4132/jptm.2020.03.04

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Abstract PDF

Background
Reports of metastatic sarcoma to the pancreas are limited. We reviewed the clinicopathologic characteristics of such cases.
Methods
We reviewed 124 cases of metastatic tumors to the pancreas diagnosed at Asan Medical Center between 2000 and 2017.
Results
Metastatic tumors to the pancreas consisted of 111 carcinomas (89.5%), 12 sarcomas (9.6%), and one melanoma (0.8%). Primary sarcoma sites were bone (n = 4); brain, lung, and soft tissue (n = 2 for each); and the uterus and pulmonary vein (n = 1 for each). Pathologically, the 12 sarcomas comprised 2 World Health Organization grade III solitary fibrous tumors/hemangiopericytomas, and one case each of synovial sarcoma, malignant solitary fibrous tumor, undifferentiated pleomorphic sarcoma, osteosarcoma, mesenchymal chondrosarcoma, intimal sarcoma, myxofibrosarcoma, myxoid liposarcoma, rhabdomyosarcoma, subtype uncertain, and high-grade spindle-cell sarcoma of uncertain type. The median interval between primary cancer diagnosis and pancreatic metastasis was 28.5 months. One case manifested as a solitary pancreatic osteosarcoma metastasis 15 months prior to detection of osteosarcoma in the femur and was initially misdiagnosed as sarcomatoid carcinoma of the pancreas.
Conclusions
The metastatic sarcoma should remain a differential diagnosis when spindle-cell malignancy is found in the pancreas, even for solitary lesions or in patients without prior history.

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Visceral Metastases of Osteosarcoma in the Hepatopancreatobiliary System
Anna Hohensteiner, Lars Kowalscheck, Kevin Döring, Gerhard Martin Hobusch, Raphael Johannes Tanios, Oliver Strobel, Reinhard Windhager, Philipp Theodor Funovics
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Interobserver Reproducibility of PD-L1 Biomarker in Non-small Cell Lung Cancer: A Multi-Institutional Study by 27 Pathologists: Sunhee Chang, Hyung Kyu Park, Yoon-La Choi, Se Jin Jang; J Pathol Transl Med. 2019;53(6):347-353. Published online October 28, 2019; DOI: https://doi.org/10.4132/jptm.2019.09.29

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Abstract PDF

Background
Assessment of programmed cell death-ligand 1 (PD-L1) immunohistochemical staining is used for treatment decisions in non-small cell lung cancer (NSCLC) regarding use of PD-L1/programmed cell death protein 1 (PD-1) immunotherapy. The reliability of the PD-L1 22C3 pharmDx assay is critical in guiding clinical practice. The Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists investigated the interobserver reproducibility of PD-L1 staining with 22C3 pharmDx in NSCLC samples.
Methods
Twenty-seven pathologists individually assessed the tumor proportion score (TPS) for 107 NSCLC samples. Each case was divided into three levels based on TPS: <1%, 1%–49%, and ≥50%.
Results
The intraclass correlation coefficient for TPS was 0.902±0.058. Weighted κ coefficient for 3-step assessment was 0.748±0.093. The κ coefficients for 1% and 50% cut-offs were 0.633 and 0.834, respectively. There was a significant association between interobserver reproducibility and experience (formal PD-L1 training, more experience for PD-L1 assessment, and longer practice duration on surgical pathology), histologic subtype, and specimen type.
Conclusions
Our results indicate that PD-L1 immunohistochemical staining provides a reproducible basis for decisions on anti–PD-1 therapy in NSCLC.

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Clinical Utility of a Fully Automated Microsatellite Instability Test with Minimal Hands-on Time: Miseon Lee, Sung-Min Chun, Chang Ohk Sung, Sun Y. Kim, Tae W. Kim, Se Jin Jang, Jihun Kim; J Pathol Transl Med. 2019;53(6):386-392. Published online October 11, 2019; DOI: https://doi.org/10.4132/jptm.2019.09.25

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Abstract PDF Supplementary Material

Background
Microsatellite instability (MSI) analysis is becoming increasingly important in many types of tumor including colorectal cancer (CRC). The commonly used MSI tests are either time-consuming or labor-intensive. A fully automated MSI test, the Idylla MSI assay, has recently been introduced. However, its diagnostic performance has not been extensively validated in clinical CRC samples.
Methods
We evaluated 133 samples whose MSI status had been rigorously validated by standard polymerase chain reaction (PCR), clinical nextgeneration sequencing (NGS) cancer panel test, or both. We evaluated the diagnostic performance of the Idylla MSI assay in terms of sensitivity, specificity, and positive and negative predictive values, as well as various sample requirements, such as minimum tumor purity and the quality of paraffin blocks.
Results
Compared with the gold standard results confirmed through both PCR MSI test and NGS, the Idylla MSI assay showed 99.05% accuracy (104/105), 100% sensitivity (11/11), 98.94% specificity (93/94), 91.67% positive predictive value (11/12), and 100% negative predictive value (93/93). In addition, the Idylla MSI assay did not require macro-dissection in most samples and reliably detected MSI-high in samples with approximately 10% tumor purity. The total turnaround time was about 150 minutes and the hands-on time was less than 2 minutes.
Conclusions
The Idylla MSI assay shows good diagnostic performance that is sufficient for its implementation in the clinic to determine the MSI status of at least the CRC samples. In addition, the fully automated procedure requires only a few slices of formalin-fixed paraffin-embedded tissue and might greatly save time and labor.

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Review

Provisional Guideline Recommendation for EGFR Gene Mutation Testing in Liquid Samples of Lung Cancer Patients: A Proposal by the Korean Cardiopulmonary Pathology Study Group: Dong Hoon Shin, Hyo Sup Shim, Tae Jung Kim, Heae Surng Park, Yun La Choi, Wan Seop Kim, Lucia Kim, Sun Hee Chang, Joon Seon Song, Hyo jin Kim, Jung Ho Han, Chang Hun Lee, Geon Kook Lee, Se Jin Jang; J Pathol Transl Med. 2019;53(3):153-158. Published online February 28, 2019; DOI: https://doi.org/10.4132/jptm.2019.02.22

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Abstract PDF

Liquid biopsy for detection of mutation from circulating tumor DNA is a new technology which is attractive in that it is non-invasive. Epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKI) is an effective first line drug for advanced non-small cell lung cancer patients who harbor activating EGFR mutation. During the course of treatment, resistance against TKI arises which can be contributed to EGFR T790M mutation in about 50–60% of patients. Third generation TKI may overcome the resistance. In patients who cannot undergo tissue biopsy due to variable reasons, liquid biopsy is an excellent alternative for the detection of EGFR T790M mutation. However, this relatively novel method requires standardization and vigorous quality insurance. Thus, a standard set of guideline recommendations for liquid biopsy for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of provisional guideline recommendations that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

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Molecular biomarker testing for non–small cell lung cancer: consensus statement of the Korean Cardiopulmonary Pathology Study Group
Sunhee Chang, Hyo Sup Shim, Tae Jung Kim, Yoon-La Choi, Wan Seop Kim, Dong Hoon Shin, Lucia Kim, Heae Surng Park, Geon Kook Lee, Chang Hun Lee
Journal of Pathology and Translational Medicine.2021; 55(3): 181. CrossRef
Current status and future perspectives of liquid biopsy in non-small cell lung cancer
Sunhee Chang, Jae Young Hur, Yoon-La Choi, Chang Hun Lee, Wan Seop Kim
Journal of Pathology and Translational Medicine.2020; 54(3): 204. CrossRef
Prevalence of T790M mutation among TKI-therapy resistant Lebanese lung cancer patients based on liquid biopsy analysis: a first report from a major tertiary care center
Hazem Assi, Arafat Tfayli, Nada Assaf, Sarah Abou Daya, Aram H. Bidikian, Dima Kawsarani, Puzant Fermanian, Ghazi Zaatari, Rami Mahfouz
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Original Articles

Guanabenz Acetate Induces Endoplasmic Reticulum Stress–Related Cell Death in Hepatocellular Carcinoma Cells: Hyo Jeong Kang, Hyang Sook Seol, Sang Eun Lee, Young-Ah Suh, Jihun Kim, Se Jin Jang, Eunsil Yu; J Pathol Transl Med. 2019;53(2):94-103. Published online January 16, 2019; DOI: https://doi.org/10.4132/jptm.2019.01.14

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Abstract PDF Supplementary Material

Background
Development of chemotherapeutics for the treatment of advanced hepatocellular carcinoma (HCC) has been lagging. Screening of candidate therapeutic agents by using patient-derived preclinical models may facilitate drug discovery for HCC patients.
Methods
Four primary cultured HCC cells from surgically resected tumor tissues and six HCC cell lines were used for high-throughput screening of 252 drugs from the Prestwick Chemical Library. The efficacy and mechanisms of action of the candidate anti-cancer drug were analyzed via cell viability, cell cycle assays, and western blotting.
Results
Guanabenz acetate, which has been used as an antihypertensive drug, was screened as a candidate anti-cancer agent for HCC through a drug sensitivity assay by using the primary cultured HCC cells and HCC cell lines. Guanabenz acetate reduced HCC cell viability through apoptosis and autophagy. This occurred via inhibition of growth arrest and DNA damage-inducible protein 34, increased phosphorylation of eukaryotic initiation factor 2α, increased activating transcription factor 4, and cell cycle arrest.
Conclusions
Guanabenz acetate induces endoplasmic reticulum stress–related cell death in HCC and may be repositioned as an anti-cancer therapeutic agent for HCC patients.

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Guanabenz acetate, an antihypertensive drug repurposed as an inhibitor of Escherichia coli biofilm
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WITHDRAWN:A Clinicopathologic Study of 220 Cases of Pulmonary Sclerosing Pneumocytoma in Korea: A Nationwide Survey: Myunghee Kang, Seung Yeon Ha, Joung Ho Han, Mee Sook Roh, Se Jin Jang, Hee Jin Lee, Heae Surng Park, Geon Kook Lee, Kyo Young Lee, Jin-Haeng Chung, Yoo Duk Choi, Chang Hun Lee, Lucia Kim, Myoung Ja Chung, Soon Hee Jung, Gou Young Kim, Wan-Seop Kim; Received April 4, 2018 Accepted July 9, 2018 Published online July 16, 2018; DOI: https://doi.org/10.4132/jptm.2018.07.10 [Accepted]

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Reviews

Good Laboratory Standards for Clinical Next-Generation Sequencing Cancer Panel Tests: Jihun Kim, Woong-Yang Park, Nayoung K. D. Kim, Se Jin Jang, Sung-Min Chun, Chang-Ohk Sung, Jene Choi, Young-Hyeh Ko, Yoon-La Choi, Hyo Sup Shim, Jae-Kyung Won; J Pathol Transl Med. 2017;51(3):191-204. Published online May 10, 2017; DOI: https://doi.org/10.4132/jptm.2017.03.14

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1,118 Download
36 Web of Science
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Abstract PDF

Next-generation sequencing (NGS) has recently emerged as an essential component of personalized cancer medicine due to its high throughput and low per-base cost. However, no sufficient guidelines for implementing NGS as a clinical molecular pathology test are established in Korea. To ensure clinical grade quality without inhibiting adoption of NGS, a taskforce team assembled by the Korean Society of Pathologists developed laboratory guidelines for NGS cancer panel testing procedures and requirements for clinical implementation of NGS. This consensus standard proposal consists of two parts: laboratory guidelines and requirements for clinical NGS laboratories. The laboratory guidelines part addressed several important issues across multistep NGS cancer panel tests including choice of gene panel and platform, sample handling, nucleic acid management, sample identity tracking, library preparation, sequencing, analysis and reporting. Requirements for clinical NGS tests were summarized in terms of documentation, validation, quality management, and other required written policies. Together with appropriate pathologist training and international laboratory standards, these laboratory standards would help molecular pathology laboratories to successfully implement NGS cancer panel tests in clinic. In this way, the oncology community would be able to help patients to benefit more from personalized cancer medicine.

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Molecular Testing of Lung Cancers: Hyo Sup Shim, Yoon-La Choi, Lucia Kim, Sunhee Chang, Wan-Seop Kim, Mee Sook Roh, Tae-Jung Kim, Seung Yeon Ha, Jin-Haeng Chung, Se Jin Jang, Geon Kook Lee; J Pathol Transl Med. 2017;51(3):242-254. Published online April 21, 2017; DOI: https://doi.org/10.4132/jptm.2017.04.10

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Abstract PDF

Targeted therapies guided by molecular diagnostics have become a standard treatment of lung cancer. Epidermal growth factor receptor (EGFR) mutations and anaplastic lymphoma kinase (ALK) rearrangements are currently used as the best predictive biomarkers for EGFR tyrosine kinase inhibitors and ALK inhibitors, respectively. Besides EGFR and ALK, the list of druggable genetic alterations has been growing, including ROS1 rearrangements, RET rearrangements, and MET alterations. In this situation, pathologists should carefully manage clinical samples for molecular testing and should do their best to quickly and accurately identify patients who will benefit from precision therapeutics. Here, we grouped molecular biomarkers of lung cancers into three categories—mutations, gene rearrangements, and amplifications—and propose expanded guidelines on molecular testing of lung cancers.

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Original Article

Analysis of Mutations in Epidermal Growth Factor Receptor Gene in Korean Patients with Non-small Cell Lung Cancer: Summary of a Nationwide Survey: Sang Hwa Lee, Wan Seop Kim, Yoo Duk Choi, Jeong Wook Seo, Joung Ho Han, Mi Jin Kim, Lucia Kim, Geon Kook Lee, Chang Hun Lee, Mee Hye Oh, Gou Young Kim, Sun Hee Sung, Kyo Young Lee, Sun Hee Chang, Mee Sook Rho, Han Kyeom Kim, Soon Hee Jung, Se Jin Jang, The Cardiopulmonary Pathology Study Group of Korean Society of Pathologists; J Pathol Transl Med. 2015;49(6):481-488. Published online October 13, 2015; DOI: https://doi.org/10.4132/jptm.2015.09.14

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Abstract PDF

Background
Analysis of mutations in the epidermal growth factor receptor gene (EGFR) is important for predicting response to EGFR tyrosine kinase inhibitors. The overall rate of EGFR mutations in Korean patients is variable. To obtain comprehensive data on the status of EGFR mutations in Korean patients with lung cancer, the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists initiated a nationwide survey. Methods: We obtained 1,753 reports on EGFR mutations in patients with lung cancer from 15 hospitals between January and December 2009. We compared EGFR mutations with patient age, sex, history of smoking, histologic diagnosis, specimen type, procurement site, tumor cell dissection, and laboratory status. Results: The overall EGFR mutation rate was 34.3% in patients with non-small cell lung cancer (NSCLC) and 43.3% in patients with adenocarcinoma. EGFR mutation rate was significantly higher in women, never smokers, patients with adenocarcinoma, and patients who had undergone excisional biopsy. EGFR mutation rates did not differ with respect to patient age or procurement site among patients with NSCLC. Conclusions: EGFR mutation rates and statuses were similar to those in published data from other East Asian countries.

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Brief Case Report

Adenocarcinoma Arising in Gastric Duplication Cyst: Hyo Jeong Kang, Se Jin Jang, Young Soo Park; Korean J Pathol. 2014;48(2):159-161. Published online April 28, 2014; DOI: https://doi.org/10.4132/KoreanJPathol.2014.48.2.159

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PDF

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Review & Perspective

Guideline Recommendations for EGFR Mutation Testing in Lung Cancer: Proposal of the Korean Cardiopulmonary Pathology Study Group: Hyo Sup Shim, Jin-Haeng Chung, Lucia Kim, Sunhee Chang, Wan-Seop Kim, Geon Kook Lee, Soon-Hee Jung, Se Jin Jang; Korean J Pathol. 2013;47(2):100-106. Published online April 24, 2013; DOI: https://doi.org/10.4132/KoreanJPathol.2013.47.2.100

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Abstract PDF

Mutations of the epidermal growth factor receptor (EGFR) are the strongest predictive factor for response to EGFR tyrosine kinase inhibitors (TKIs), such as gefitinib and erlotinib. EGFR TKIs are approved in Korea as a first-line treatment for lung cancer patients with mutated EGFR. Rapid and accurate EGFR mutation testing is essential for patient selection and establishing targeted therapies with EGFR TKIs. Thus, a standard set of guideline recommendations for EGFR mutation testing suitable for the Korean medical community is necessary. In this article, we propose a set of guideline recommendations for EGFR mutation testing that was discussed and approved by the Cardiopulmonary Pathology Study Group of the Korean Society of Pathologists.

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Journal of Pathology and Translational Medicine.2017; 51(3): 242. CrossRef
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Original Article

Cytologic Study of Thymoma.: Gu Kong, Se Jin Jang, Jung Dal Lee; J Pathol Transl Med. 1990;1(1):36-42.

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Abstract PDF: The fluoroscopy-guided fine needle aspiration biopsy has been gaining widespread acceptance as a rapid and effective method to make a pre-operative diagnosis of mediastinal tumors including thymoma, malignant lymphoma, and metastatic carcinoma. Although thymoma is a most common tumor of the superior mediastinum, most cytopathologists are not experted in cytologic diagnosis of this tumor because of limited experience. In order to define the diagnostic cytologic features of thymoma, we have retrospectively reviewed imprinting smears and corresponding tissue sections from four cases of this tumor. All cases revealed an apparent biphasic pattern of epithelial cell clusters and lymphocytes with occasional branching capillary fronds extending from three dimensional epithelial cell clusters. Epithelial cell clusters predominated in one case and lymphocytes in two cases. Mixed epithelial cell and lymphocyte type represented in one of four cases. In the lymphocyte predominant type, the presence of epithelial cell clusters and small mature lymphocytes are helpful features to differentiate from a malignent lymphoma.

Case Report

Clinicopathologic Analysis of the Liver Explant with Severe Hepatitis A Virus Infection.: Joo Young Kim, Sung Gyu Lee, Shin Hwang, Ji Hoon Kim, Se Jin Jang, Eunsil Yu; Korean J Pathol. 2011;45:S48-S52.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.S1.S48

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Abstract PDF: The incidence of severe hepatitis A virus (HAV) infection has been increasing. However, clinicopathologic features of severe HAV infection that lead to liver transplantation (LT) have not been reported in Korea. We retrieved 16 LT cases with HAV infection during the last 3 years at Asan Medical Center, Seoul, Korea. Fifteen cases progressed to hepatic encephalopathy. Thirteen cases survived with or without complications, and three patients died of sepsis. The explanted liver showed massive or zonal necrosis with moderate to severe cholestasis. The zonal distribution of necrosis was frequently associated with endothelialitis of portal and/or central veins. Degenerative changes of hepatocytes were various in degree and distribution. Viral inclusions were suspected in two cases. Although HAV infection is usually confirmed by serological tests, significant venulitis of central and/or portal veins and viral inclusions, which are rarely observed, can suggest an HAV infection as a cause of massive hepatic necrosis of unknown mechanism.

Original Articles

Histologic Parameters Predicting Survival of Patients with Multiple Non-small Cell Lung Cancers.: Joo Young Kim, Hee Jin Lee, Jun Kang, Se Jin Jang; Korean J Pathol. 2011;45(5):506-515.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.5.506

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Abstract PDF: BACKGROUND
In multiple lung cancers (MLCs), distinction between intrapulmonary metastases and multiple primary tumors is important for staging and prognosis. In this study, we have investigated histopathologic prognostic factors of patients with MLCs.
METHODS
Histologic subtype, size differences, lobar location, lymphovascular invasion (LVI), size of the largest tumor, nodal status, number of tumors, morphology of tumor periphery, and immunohistochemical profiles using eight antibodies, were analyzed in 65 patients with MLCs.
RESULTS
There was no significant difference in the survivals of patients with multiple primary tumors and intrapulmonary metastases, as determined by the Martini-Melamed criteria (p=0.654). Risk grouping by four histologic parameters, LVI, margin morphology, size differences, and lobar locations of paired tumors were prognostic. The patients with one or two of aforementioned parameters had significantly longer survival than those with three or four parameters (p=0.017). In patients with largest mass (< or =5 cm), the risk grouping was found to be an independent prognostic factor (p=0.022). However, differences in immunohistochemical staining were not related to patients' survival.
CONCLUSIONS
A risk grouping of MLC patients by using combinations of histologic parameters can be a useful tool in evaluating the survival of patients with MLCs, and may indicate clonal relationship between multiple tumors.

The Histone Acetyltransferase hMOF is Overexpressed in Non-small Cell Lung Carcinoma.: Joon Seon Song, Sung Min Chun, Ji Young Lee, Dong Kwan Kim, Yong Hee Kim, Se Jin Jang; Korean J Pathol. 2011;45(4):386-396.; DOI: https://doi.org/10.4132/KoreanJPathol.2011.45.4.386

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Abstract PDF

BACKGROUND
One of the histone acetyltransferases (HATs) family of proteins, human MOF (hMOF, MYST1), is involved in histone H4 acetylation, particularly at lysine 16 (H4K16Ac), an epigenetic mark of active genes. Dysregulation of the epigenetic mark influences cellular biology and possibly leads to oncogenesis. We examined the involvement of hMOF and H4K16Ac in primary non-small cell lung cancer (NSCLC).
METHODS
Reverse transcription polymerase chain reaction using fresh-frozen lung cancer tissues and lung cancer cell lines and immunohistochemistry for hMOF and H4K16Ac via tissue microarray of 551 formalin-fixed paraffin-embedded NSCLC tissue blocks were conducted.
RESULTS
hMOF mRNA was frequently overexpressed in lung cancer tissues, compared with normal lung tissues (10/20, 50%). NSCLC tissues were positive for hMOF in 37.6% (184/489) and H4K16Ac in 24.7% (122/493) of cases. hMOF protein expression was tightly correlated with the H4K16Ac level in tumors (p<0.001). Knockdown of hMOF mRNA with siRNA led to a significant inhibition of growth in the Calu-6 cell line.
CONCLUSIONS
hMOF was frequently expressed in NSCLC and was correlated with H4K16Ac. To our knowledge, this is the first study that has focused on the expression status of HATs and hMOF in NSCLC. Our results clearly suggest a potential oncogenic role of the gene and support its utility as a potential therapeutic target.

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Arsenic Trioxide Reduces Global Histone H4 Acetylation at Lysine 16 through Direct Binding to Histone Acetyltransferase hMOF in Human Cells
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Jin Zhang, Hui Liu, Hao Pan, Yuan Yang, Gang Huang, Yun Yang, Wei-Ping Zhou, Ze-Ya Pan
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Regulation and function of histone acetyltransferase MOF
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The Clinicopathological Parameters for Making the Differential Diagnosis of Neonatal Cholestasis.: Heejin Lee, Jun Kang, Kyung Mo Kim, Joo Young Jang, Se Jin Jang, Eunsil Yu; Korean J Pathol. 2009;43(1):43-47.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.1.43

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Abstract PDF

BACKGROUND
The diseases that cause neonatal cholestasis display several overlapping clinical feature. Making the differential diagnosis using liver biopsy specimens from infants with neonatal cholestasis is important for delivering the proper treatment.
METHODS
We assessed the clinical manifestations, laboratory data, and histopathologic features of the pretreatment liver biopsy specimens from patients suffering with biliary atresia (n=66), intrahepatic bile duct paucity (n=15), and neonatal hepatitis (n=21).
RESULTS
The gender distribution was nearly equal for the patients with biliary atresia and intrahepatic bile duct paucity, whereas males predominated for the cases of neonatal hepatitis. Only the gamma-glutamyl transferase level differed significantly amongst the groups. The diagnostic features for making the differential diagnosis of bile duct lesions included marked bile ductular proliferation, severe fibrosis, and bile duct loss. The difference of the average percentage of portal tracts with bile duct loss was statistically significant between the patients with intrahepatic bile duct paucity (73.9%) and those patients with neonatal hepatitis (39.1%) (p<0.001).
CONCLUSIONS
Bile ductular proliferation, bile duct loss, and advanced fibrosis are useful for the differential diagnosis of neonatal cholestasis. Moreover, stricter diagnostic criteria for bile duct loss (more than 2/3 of bile ducts) should be applied for the definitive diagnosis of intrahepatic bile duct paucity, because bile duct loss also frequently occurs in infants suffering with neonatal hepatitis.

Citations

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False-negative Hepatobiliary Scintigraphy for Biliary Atresia
Hyunji Kim, Sujin Park, Sejin Ha, Jae Seung Kim, Dae Yeon Kim, Minyoung Oh
Nuclear Medicine and Molecular Imaging.2019; 53(5): 356. CrossRef
Morphometric assessment of liver fibrosis may enhance early diagnosis of biliary atresia
Ahmed F. Abdalla, Abeer Fathy, Khaled R. Zalata, Ahmed Megahed, Ahmed Abo-Alyazeed, Mohammed Ezz El regal
World Journal of Pediatrics.2013; 9(4): 330. CrossRef
Differential hepatic expression of CD56 can discriminate biliary atresia from other neonatal cholestatic disorders
Mostafa Mohamed Sira, Mohamed Abdel-Salam El-Guindi, Magdy Anwar Saber, Nermin Ahmad Ehsan, Marwa Sabry Rizk
European Journal of Gastroenterology & Hepatology.2012; 24(10): 1227. CrossRef
Biliary Atresia: A Multidisciplinary Approach to Diagnosis and Management
Roger Klein Moreira, Rodrigo Cabral, Robert A. Cowles, Steven J. Lobritto
Archives of Pathology & Laboratory Medicine.2012; 136(7): 746. CrossRef
Tentative Proposal of Optimal Timing of Kasai Operation for Biliary Atresia Based on Fibroscan Results
Hwa Young Lee, Young A Park, Seok Joo Han, Hong Koh
Korean Journal of Pediatric Gastroenterology and Nutrition.2011; 14(1): 74. CrossRef

Methylation Abnormality in Body Fluid Cytology: A Supplemental Molecular Marker for the Diagnosis of Malignant Mesothelioma.: Joon Seon Song, Jin Kyung Jung, Ji Hye Kang, Ilseon Hwang, Se Jin Jang; J Pathol Transl Med. 2008;19(2):126-135.; DOI: https://doi.org/10.3338/kjc.2008.19.2.126

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Abstract PDF

Malignant mesothelioma (MM) is a highly lethal neoplasm arising in pleura and the peritoneum and a rapid and accurate diagnosis is crucial for treatment of the disease. However, the sensitivity of cytological analysis using pleural or ascitic fluid is relatively low, yielding an accurate diagnosis in only 32~79% of cases. We tested the diagnostic value of epigenetic alterations in body fluid cytology as a supplement to conventional methods. Paraffin-embedded tissue blocks from 21 MM patients and associated body fluid cytology slides considered no evidence of malignancy were used to test for epigenetic alteration. Using methylation-specific PCR, we detected methylation of RASSF1A and p16 in 47.6% (10/21) of both surgically resected tumor samples, respectively. Body fluid samples of MM also showed abnormal methylation of RASSF1A and p16INK4a genes in 38.1% (8/21) and 33.3% (7/21) of cases. The concordance in the rates of RASSF1A and p16INK4a gene-methylation abnormalities determined from cytology samples and tissue samples were 61.9% (13/21) and 66.7% (14/21), respectively. Combining both genes increases the sensitivity of the test to 57.1% (12 of 21) of cases. Our results suggest that testing for methylation abnormalities in selected individual genes or gene combinations has diagnostic value as an alternative or adjunct method to conventional cytological diagnosis.

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Utility of Promoter Hypermethylation for Differentiating Malignant and Benign Effusions in Liquid-Based Cytology Specimens
Ga-Eon Kim, Jo-Heon Kim, Yeong-Hui Kim, Chan Choi, Ji Shin Lee
The Korean Journal of Pathology.2010; 44(3): 315. CrossRef

Clinicopathologic Analysis of Lymphocytic Gastritis.: Jeong Eun Hwang, Young Ok Hong, Dong Eun Song, Se Jin Jang, Eunsil Yu; Korean J Pathol. 2007;41(5):289-295.

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Abstract PDF: BACKGROUND
Lymphocytic gastritis (LG) is defined as an infiltration of more than 25 intraepithelial lymphocytes (IELs) per 100 surface epithelial cells, and the histological differential diagnosis of LG and residual mucosa associated lymphoid tissue (MALT) lymphoma can be difficult. Helicobacter pylori (H. pylori) is regarded as one of the possible causes of LG, but its clinicopathologic features of LG have not been clarified in Korea, which has a much higher prevalence of H. pylori infection than Western countries. We analyzed the clinicopathologic findings of LG in Korean patients and compared the cytologic findings of IELs of LG with those of MALT lymphoma.
METHODS
Sixty six cases of LG and 59 cases of MALT lymphoma were selected and clinicopathologic features were analyzed.
RESULTS
Eighteen cases (27.3%) of LG were found to be associated with H. pylori infection. The IELs in LG were found to diffusely and regularly infiltrate in the epithelium, but MALT lymphoma showed patchy IELs. IELs in LG and MALT lymphoma were CD 8+T lymphocytes and CD20+B lymphocytes, respectively. The mean nuclear size of IELs in LG was 4.37 micrometer, which was significantly smaller than those in MALT lymphoma (5.19 micrometer).
CONCLUSION
LG, a rare variant of chronic gastritis is partly associated with H. pylori infection and more complex unknown causative factors. In addition to the immunophenotyping, the nuclear sizes of IELs can be helpful in the differential diagnosis of LG and residual MALT lymphoma.

Clinicopathologic Analysis of Epidermal Growth Factor Receptor Status in Non-small Cell Lung Cancer: Protein Expression, Gene Amplification and Survival Analysis.: Seungkoo Lee, Jene Choi, Se Jin Jang; Korean J Pathol. 2007;41(6):387-392.

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Abstract PDF: BACKGROUND
Abnormal over-expression or gene amplification of epidermal growth factor receptor (EGFR) is important in the prognosis of non-small cell lung cancer (NSCLC). We investigated the frequency of EGFR protein expression and gene amplification, and the correlation between EGFR status and survival in NSCLC.
METHODS
We examined 360 cases of microarrayed NSCLC tissues for the EGFR protein expression and EGFR gene amplification using immunohistochemistry and fluorescent in situ hybridization.
RESULTS
EGFR protein expression and EGFR gene amplification occurred in 110 cases (30.6%) and 24 cases (6.7%), respectively. EGFR protein expression and gene amplification were more frequent in squamous cell carcinoma than in adenocarcinoma. Differences in EGFR protein expression did not dramatically affect survival curves (p=0.740), but differences in gene amplification did (p<0.05): EGFR gene amplification was associated with a lower 5-year survival rate.
CONCLUSION
EGFR protein expression and gene amplification showed moderate correlation with each other. EGFR gene amplification predicted a poor prognosis, whereas EGFR protein expression did not.

Correlation between Histologic Differentiation and Prognosis of Prostate Adenocarcinoma.: Se Jin Jang, Jung Dal Lee; Korean J Pathol. 1990;24(3):243-253.

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Abstract PDF: The authors reviewed clinical data and 50 pathologic specimens from 41 patients of prostate adenocarcinoma filed in the Department of Pathology, Hanyang University school of Medicine, in order to evaluate correlation between clinical stages and histopathologic grades of prostate adenocarcinoma. Each of five currently used grading systems were compared with clinical stages of prostate adenocarcinomas. The followings results were obtained: All of the grading systems were relatively well correlated with clinical progression of the tumon. Histologic grading systems including Gleason's grading system, Gleasons scoring system and M.D. Anderson system showed better correlation than cytologic grading system of Mostofi. Gaeta gradings system regarding both histologic and cytologic aspects of the carcinoma showed good correlation to clinical stage with correlation coefficient of 0.654. Combined scoring system of cytologic and histologic grades (Mostofi-M.D. Anderson combined scoring system) showed better correlation to the clinical stage than single individual grading s system. The author conclued that Gleasons histologic grading system with cytologic characteristics of tumor cells would represent best parameter of clinical progression of the prostate adenocarcinoma.

Case Reports

Sarcoidosis Associated with Adenocarcinoma of the Lung: A Case Report.: Joon Seon Song, Seungkoo Lee, Yong Hee Kim, Se Jin Jang; Korean J Pathol. 2008;42(2):108-112.

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Abstract PDF: Sarcoidosis and malignant neoplasm are frequently encountered pulmonary diseases, but their combined existence in the same patient is rare. As sarcoidosis usually presents as mediastinal lymphadenopathy, its concurrence in lung cancer patient radiologically mimics mediastinal metastasis and this can be possibly interpreted as unresectable disease. We report here on a case of lung adenocarcinoma associated with sarcoidosis that developed in a 64 year-old male who underwent surgical resection. Radiological examinations revealed 5.7 cm-sized mass in the right upper lobe with an enlargement of the bilateral supraclavicular, highest mediastinal, subcarinal and the upper and lower paratracheal lymph nodes. Histologic examination showed a well differentiated adenocarcinoma with non-caseating epithelioid granulomas in the lung. The enlarged peribronchial and mediastinal lymph nodes also revealed sarcoid granulomas without cancer metastasis. A good prognosis may be expected for those cases of lung cancers with non-caseating granulomas in the regional lymph nodes. The patient presently has no symptoms or signs of tumor, without further treatment since his surgery.

Cytologic Findings of Parathyroid Carcinoma: Report of Two Cases.: Yun Hee Jin, Yong Wook Park, Mi Sheon Jin, Seung Sam Paik, Se Jin Jang, Moon Hyang Park; J Pathol Transl Med. 2003;14(1):1-6.

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Abstract PDF: Parathyroid carcinoma is a rare disorder accounting for 0.5% to 5% of parathyroid neoplasia. Diagnosis of parathyroid carcinoma in fine needle aspiration cytology(FNAC) is difficult because all characteristic features of parathyroid carcinoma can be recognized in parathyroid adenoma or hyperplasia. Cellular atypism cannot be used for the diagnostic criteria of parathyroid carcinoma as malignancies of most other organs. We experienced two cases of cytologic features of parathyroid carcinoma confirmed by histologic examination. The majority of tumor cells formed large cohesive clusters, although individual tumor cells were also present. The tumor cells displayed rather pleomorphic round to oval nuclei, occasional prominent nucleoli, and distinct cytoplasmic margin. Occasionally karyolysis, anuclear cells, and nonepithelial cell clusters were noted. The histologic findings showed a partially lobulated architecture, with admixture of sheets of chief cells, oxyphil cells, and occasional water clear cells. The tumor infiltrated into the thyroid parenchyme and perithyroidal soft tissue. The electron microscopic study of case 1 disclosed typical findings of parathyroid neoplasm; clusters of secretory chief cells with centrally located round to ovoid nuclei, moderately clumped heterochromatins and one or two nucleoli. The tumor cells showed conspicous interdigitation of contiguous cell membrane and intercellular microvilli.

Cardiac Fibroma of the Ventricular Septum: A case report.: Byung Tae Park, Se Jin Jang, Moon Hyang Park, Jung Dal Lee, Hyo Jin Lee; Korean J Pathol. 1991;25(1):37-41.

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Abstract PDF: This is an autopsy case of a 6 month old girl who suddenly died of respiratory distress during sleep. She had suffered from mild but frequent episodes of common cold and was treated for eczema for several days. At autopsy, the heart was enlarged and weighed 100 gm. A firm and gray-white tumor, measuring 4.5 x 3.8 x 2.8 cm, was located in the interventricular septum and encroached upon the wall of left ventricle. The mass was well demarcated but was not encapsulated. Neither necrosis nor calcification was present. Microscopically the tumor was composed of haphazardly arranged bundles of collagen fibers and fibroblasts. Myocardial cells are intermingled with the fibroblasts at the margin of the tumor. Massive edema of the lung and congestion of the liver and spleen were pronounced.

Original Articles

Association of CXCR4 Expression with Metastasis and Survival among Patients with Non-small Cell Lung Cancer.: Joon Seon Song, Jin Kyung Jung, Jong Chul Park, Dong Kwan Kim, Se Jin Jang; Korean J Pathol. 2008;42(6):358-364.

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Abstract PDF: BACKGROUND
Expression of CXCR4 chemokine receptor, initially described to be involved in the homing of lymphocytes in inflammatory tissue, on breast cancer cell lines is associated with the development of lung metastases. In the present study, we evaluated CXCR4 expression in patients with non-small cell lung cancer (NSCLC). METHODS: Tissue microarray blocks were constructed from 408 formalin-fixed, paraffin-embedded NSCLC samples and analyzed via immunohistochemical staining. RESULTS: We observed CXCR4 expression in 214 (66.3%) of the 323 tumors with cytoplasmic or nuclear staining patterns. These tumors were then divided into 109 negative, 166 weak-positive and 48 strong-positive expression groups. Strong expression of CXCR4 correlated with NSCLC recurrence (p=0.047) and distant metastasis (p=0.035). However, lymph node metastasis (p=0.683) and locoregional recurrence (p=0.856) were not associated with CXCR4 expression. Interestingly, the median overall survival times relative to CXCR4 expression were 71 months in the CXCR4-negative group, 43 months in the weakly positive CXCR4 group and 23 months in the strongly positive CXCR4 group. Strongly positive CXCR4 staining was associated with significantly worse outcomes (p=0.005, log-rank test).
CONCLUSIONS
Expression of CXCR4 was associated with distant NSCLC metastases and shorter survival times.

Expression of the 14-3-3 sigma Protein and Methylation Status of the 14-3-3 sigma gene in Biliary Neoplasms.: Dong Eun Song, Se Jin Jang, Jung Sun Kim, Sang Soo Lee, Myung Hwan Kim, Seung Gyu Lee, Young Joo Lee, Hae Joung Park, Yhong Hee Shim, Eunsil Yu; Korean J Pathol. 2006;40(1):9-16.

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Abstract PDF: BACKGROUND
The 14-3-3 sigma (sigma) protein has a negative regulatory role in the cell cycle progression of the. Down-regulation or overexpression of the 14-3-3 sigma protein has been reported in various human cancers.
METHODS
Immunohistochemistry for the 14-3-3 sigma protein was performed in non-neoplastic bile duct cells, intraductal papillary neoplasms of the liver (IPNL), mass-forming intrahepatic cholangiocarcinomas (ICC) and non-papillary extrahepatic cholangiocarcinomas (ECC). We investigated the methylation status of the 14-3-3 sigma gene in 45 cases of these 3 tumor groups.
RESULTS
The non-neoplastic bile duct cells demonstrated negative or weakly positive cytoplasmic immunoreactivity for the 14-3-3 sigma protein and no methylation of the 14-3-3 sigma gene. Overexpression as well as negative immunoreactivity associated with hypermethylation of the 14-3-3 sigma protein was observed in 16 (69.6%) of 23 cases of IPNL, in 21 (63.6%) of 33 cases of mass-forming ICC and in 27 (71.1%) of 38 cases of non-papillary ECC. Negative immunoreactivity was increased in the invasive IPNL (4/6, 66.7%), as well as in the poorly differentiated cases of mass-forming ICC (8/12, 66.7%) and the non-papillary ECC (5/8, 62.5%).
CONCLUSIONS
The similar rates for the abnormal expression of the 14-3-3 sigma protein among the three groups of biliary neoplasms indicate its general association with biliary carcinogenesis. Furthermore, the loss of the 14-3-3 sigma protein may be involved in the tumor progression and differentiation in the biliary carcinogenesis.

Case Reports

Cytologic Features of Glassy Cell Carcinoma of the Uterine Cervix: Three Cases Report.: Seok Hoon Jeon, Seung Sam Paik, Won Mi Lee, Se Jin Jang, Yong Wook Park, Moon Hyang Park, Jung Dal Lee; J Pathol Transl Med. 1996;7(2):197-201.

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Abstract PDF: Glassy cell carcinoma is an unusual neoplasm of the uterine cervix that accounts for 1~2% of all cervical malignancy. It is a rapidly progressive and biologically aggressive disease with poor response to therapy. This tumor is considered to be a poorly differentiated mixed adenosquamous carcinoma. The cytologic findings are characterized by tumor cells arranged predominantly in syncytial like aggregates and an inflammatory background. The tumor cells have moderate amounts of eosinophilic or amphophilic cytoplasm, which is often finely granular. The nuclei are relatively large and have fine chromatin with prominent eosinophilic nucleoli. Cytologically, glassy cell carcinoma is most likely to be confused with large cell nonkeratinizing squamous cell carcinoma and with atypical reparative cells. Herein, we report three cases of glassy cell carcinoma of the uterine cervix diagnosed by cervicovaginal smear and confirmed by histologic section with review of literatures.

Extrapulmonary Silicosis: A case report.: Won Mi Lee, Se Jin Jang, Eun Kyung Hong, Jung Dal Lee; Korean J Pathol. 1998;32(7):540-542.

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Abstract: A case of extrapulmonary silicosis involving abdominal lymph nodes in a 62-year-old man is presented. The patient underwent subtotal gastrectomy and regional lymph nodes dissection for gastric adenocarcinoma of clinical stage III. On gross examination, two separate gastric adenocarcinomas and multiple enlarged lymph nodes mimicking metastatic lesion were noted. Microscopic examination of the enlaged lymph nodes revealed characteristic sclerohyaline silicotic nodules without metastatic adenocarcinoma. Chest roentgenogram showed diffusely scattered multiple tiny nodular lesions in the entire lung fields, particularly the posterior side of both upper lung fields. He had worked in a mine for 18 years and had been exposed to silica for 5 of those years. We report incidentally found, unusual case of extrapulmonary silicosis.

Original Articles

The Significance of AgNOR Count in Body Fluid: Differential between reactive mesothelial cells & malignant cells.: Seung Sam Paik, Eun Kyung Hong, Se Jin Jang, Moon Hyang Park, Jung Dal Lee; J Pathol Transl Med. 1997;8(2):129-134.

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Abstract PDF: To distinguish reactive mesothelial cells from malignant cells in body fluid, we applied silver staining of nucleolar organizer regions(AgNORs) to ethanol fixed cytologic preparations. Fifty aspirated samples of benign(22 cases) and malignant(26 cases) body fluids were studied using the one step silver staining method. Two cytologically atypical samples were also included in the study. In malignant cases the mean AgNOR count was 3.56+/-0.81, while in benign cases the mean AgNOR count was 2.02+/-0.33. The difference of AgNOR counts between these two groups were statistically significant(p<0.001). The mean of atypical cases was 2.91. Both were diagnosed as malignant in follow-up cytology. In malignant effusions, there is statistically significant difference in AgNOR counts between cells forming complex papillae or clusters and singly scattered cells(p<0.05), 3.29+/-0.95 and 3.83+/-0.55, respectively. We concluded that AgNOR count appears to be useful as a diagnostic tool especially when the cytologic differentiation is difficult.

Fine Needle Aspiration Cytology of Pilomatrixoma.: Seung Sam Paik, Dong Hoon Kim, How Jin Lee, Se Jin Jang, Moon Hyang Park, Jung Dal Lee; J Pathol Transl Med. 1997;8(2):155-159.

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Abstract PDF: Pilomatrixoma is a benign skin appendage tumor of hair matrix cell origin. The cytological appearance of this tumor may cause problems when attempting to establish a differential diagnosis with other neoplasms. Herein we report the aspiration cytology findings of two cases of pilomatrixoma. One case was diagnosed as atypical cell clusters initially and the other was diagnosed as pilomatrixoma. On cytologic examination, both cases showed clusters of tightly arranged basaloid cells with an uniform appearance, scanty cytoplasm and round hyperchromatic nuclei. There were histiocytes and multinucleated foreign body giant cells merged with the amorphous opaque orangeophilic materials of "ghost cells". The differential diagnosis with other neoplasms is discussed.

Case Report

Inflammatory Myofibroblastic Tumor in Posterior Mediastinum.: Seung Sam Paik, Seok Hoon Jeon, Se Jin Jang, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1997;31(1):63-67.

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Abstract PDF: Inflammatory myofibroblastic tumor(IMT) or inflammatory pseudotumor is a rare, solid tumor that most often affects children. This tumor is characterized by a spindle cell proliferation admixed with a variety of inflammatory cells. Although it has disputed nosology, a distinctive fibroinflammatory and even pseudosarcomatous appearance have been well appreciated. Herein, we report a case of IMT in the posterior mediastinum in a 19-year-old girl with clinical findings. The immunohistochemical and ultrastructural studies on the tumor cells are reported, and their distinctive characteristics are discussed in details.

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