Journal of Pathology and Translational Medicine

Original Articles

BRCA-mutated gastric adenocarcinomas are associated with chromosomal instability and responsiveness to platinum-based chemotherapy: Ji Hyun Oh, Chang Ohk Sung, Hyung-Don Kim, Sung-Min Chun, Jihun Kim; J Pathol Transl Med. 2023;57(6):323-331. Published online November 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.22

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Background
Homologous recombination defect is an important biomarker of chemotherapy in certain tumor types, and the presence of pathogenic or likely pathogenic mutations involving BRCA1 or BRCA2 (p-BRCA) mutations is the most well-established marker for the homologous recombination defect. Gastric cancer, one of the most prevalent tumor types in Asia, also harbors p-BRCA mutations.
Methods
To investigate the clinical significance of p-BRCA mutations, we analyzed 366 gastric cancer cases through next-generation sequencing. We determined the zygosity of p-BRCA mutations based on the calculated tumor purity through variant allelic fraction patterns and investigated whether the presence of p-BRCA mutations is associated with platinum-based chemotherapy and a certain molecular subtype.
Results
Biallelic p-BRCA mutation was associated with better response to platinum-based chemotherapy than heterozygous p-BRCA mutation or wild type BRCA genes. The biallelic p-BRCA mutations was observed only in the chromosomal instability subtype, while all p-BRCA mutations were heterozygous in microsatellite instability subtype.
Conclusions
In conclusion, patients with gastric cancer harboring biallelic p-BRCA mutations were associated with a good initial response to platinum-based chemotherapy and those tumors were exclusively chromosomal instability subtype. Further investigation for potential association with homologous recombination defect is warranted.

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Artificial intelligence algorithm for neoplastic cell percentage estimation and its application to copy number variation in urinary tract cancer
Jinahn Jeong, Deokhoon Kim, Yeon-Mi Ryu, Ja-Min Park, Sun Young Yoon, Bokyung Ahn, Gi Hwan Kim, Se Un Jeong, Hyun-Jung Sung, Yong Il Lee, Sang-Yeob Kim, Yong Mee Cho
Journal of Pathology and Translational Medicine.2024; 58(5): 229. CrossRef

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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Molecular Profiling of H-MSI/dMMR/for Endometrial Cancer Patients: “New Challenges in Diagnostic Routine Practice”
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Enhanced Commendable Sensitivity and Specificity for MSI in Colorectal Cancer by a New PCR‐HRM Based 8‐Loci MSI Assay
Xueping Xiang, Xiaojing Ma, Linlin Ying, Hong Zou
Journal of Clinical Laboratory Analysis.2024;[Epub] CrossRef
Endometriumkarzinom: molekulare Klassifikation in der Routinepathologie
Udo Siebolts, Birgid Schömig-Markiefka, Janna Siemanowski-Hrach, Sabine Merkelbach-Bruse
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Integration of rapid PCR testing as an adjunct to NGS in diagnostic pathology services within the UK: evidence from a case series of non-squamous, non-small cell lung cancer (NSCLC) patients with follow-up
Alison Finall, Gareth Davies, Trevor Jones, Gwion Emlyn, Pearl Huey, Anna Mullard
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Analytical Validation and Clinical Utilization of the Oncomine Comprehensive Assay Plus Panel for Comprehensive Genomic Profiling in Solid Tumors
Catherine I. Dumur, Ramakrishnan Krishnan, Jorge A. Almenara, Kathleen E. Brown, Kailyn R. Dugan, Christiana Farni, Fatima Z. Ibrahim, Naomi A. Sanchez, Sumra Rathore, Dinesh Pradhan, Jonathan H. Hughes
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Performance of Immunohistochemical and Molecular Methods in Detecting Microsatellite Instability in Gastric Cancer: A Multicenter Study
Diogo Sousa Marques, Irene Gullo, Luís Mascarenhas-Lemos, João Ricardo Silva, Catarina Neto do Nascimento, Patrícia Pontes, Lídia Pinho, Luis Cirnes, Xiaogang Wen, Marília Cravo, Fátima Carneiro
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Comparison of the Idylla™ MSI assay with the Promega™ MSI Analysis System and immunohistochemistry on formalin-fixed paraffin-embedded tissue of endometrial carcinoma: results from an international, multicenter study
Sonia Gatius, Ana Velasco, Mar Varela, Miriam Cuatrecasas, Pedro Jares, Lisa Setaffy, Benjamin Bonhomme, Almudena Santon, Kristina Lindemann, Sabrina Croce, Ben Davidson, Sigurd Lax, Jose Palacios, Xavier Matias-Guiu
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Idylla MSI test combined with immunohistochemistry is a valuable and cost effective strategy to search for microsatellite instable tumors of noncolorectal origin
Laura Samaison, Arnaud Uguen
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Detection of microsatellite instability in a panel of solid tumours with the Idylla MSI Test using extracted DNA
Adrien Pécriaux, Loetitia Favre, Julien Calderaro, Cécile Charpy, Jonathan Derman, Anaïs Pujals
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Idylla microsatellite instability assay versus mismatch repair immunohistochemistry: a retrospective comparison in gastric adenocarcinoma
Luke Farmkiss, Ilona Hopkins, Mary Jones
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Multi-center real-world comparison of the fully automated Idylla™ microsatellite instability assay with routine molecular methods and immunohistochemistry on formalin-fixed paraffin-embedded tissue of colorectal cancer
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Evaluation of 3 molecular-based assays for microsatellite instability detection in formalin-fixed tissues of patients with endometrial and colorectal cancers
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Overexpression of C-reactive Protein as a Poor Prognostic Marker of Resectable Hepatocellular Carcinomas: Jin Ho Shin, Chong Jai Kim, Eun Jeong Jeon, Chang Ohk Sung, Hwa Jeong Shin, Jene Choi, Eunsil Yu; J Pathol Transl Med. 2015;49(2):105-111. Published online March 12, 2015; DOI: https://doi.org/10.4132/jptm.2015.01.19

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Abstract PDF

Background
C-reactive protein (CRP) is an acute phase reactant synthesized in the liver. CRP immunoreactivity is a feature of inflammatory hepatocellular adenomas with a higher risk of malignant transformation. A high serum CRP level denotes poor prognosis in hepatocellular carcinoma (HCC) patients. This study was conducted to determine whether CRP is produced in HCC and to assess the clinicopathologic significance of CRP expression in cancer cells. Methods: CRP immunoreactivity was examined in treatment-naïve HCCs (n=224) using tissue microarrays and was correlated with clinicopathologic parameters. The expression of CRP mRNA and protein was also assessed in 12 HCC cases by quantitative real-time polymerase chain reaction and immunoblotting. Hep3B and SNU-449 HCC cell lines were used for the analysis of CRP mRNA regulation by interleukin 6 (IL-6). Results: CRP was expressed in 133 of 224 HCCs (59.4%) with a variable degree of immunoreactivity (grade 1 in 25.9%; grade 2 in 20.1%; grade 3 in 13.4%). There was an inverse relationship between grade 3 CRP immunoreactivity and cancer-specific survival (p=.0047), while no associations were found with other parameters, including recurrence-free survival. The CRP mRNA expression level was significantly higher in CRP immunopositive cases than in immunonegative cases (p<.05). CRP mRNA expression was increased in Hep3B cells, but was not detected in SNU-449 cells even after IL-6 treatment. Conclusions: We report the expression of CRP in HCC for the first time. CRP expression was associated with poor cancer-specific survival in patients with resectable HCC.

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Accuracy of Core Needle Biopsy Versus Fine Needle Aspiration Cytology for Diagnosing Salivary Gland Tumors: In Hye Song, Joon Seon Song, Chang Ohk Sung, Jong-Lyel Roh, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Jeong Hyun Lee, Jung Hwan Baek, Kyung-Ja Cho; J Pathol Transl Med. 2015;49(2):136-143. Published online March 12, 2015; DOI: https://doi.org/10.4132/jptm.2015.01.03

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Abstract PDF

Background
Core needle biopsy is a relatively new technique used to diagnose salivary gland lesions, and its role in comparison with fine needle aspiration cytology needs to be refined. Methods: We compared the results of 228 ultrasound-guided core needle biopsy and 371 fine needle aspiration procedures performed on major salivary gland tumors with their postoperative histological diagnoses. Results: Core needle biopsy resulted in significantly higher sensitivity and more accurate tumor subtyping, especially for malignant tumors, than fine needle aspiration. No patient developed major complications after core needle biopsy. Conclusions: We recommend ultrasoundguided core needle biopsy as the primary diagnostic tool for the preoperative evaluation of patients with salivary gland lesions, especially when malignancy is suspected.

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Brief Case Reports

Mixed Carcinoid-Mucinous Adenocarcinoma Arising in Mature Teratoma of Mesentery: Su-Jin Shin, Eun-Mi Son, Chang Ohk Sung, Kyu-Rae Kim; J Pathol Transl Med. 2015;49(1):61-65. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.09.17

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Original Article

Clinicopathological Analysis of 21 Thymic Neuroendocrine Tumors: Soomin Ahn, Jae Jun Lee, Sang Yun Ha, Chang Ohk Sung, Jhingook Kim, Joungho Han; Korean J Pathol. 2012;46(3):221-225. Published online June 22, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.3.221

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Abstract PDF

Background

Thymic neuroendocrine carcinomas (NECs) are uncommon, for which there is no established information available because of a limited number of epidemiological study in Asia.

Methods

We reviewed 21 cases of surgically resected thymic NECs, and evaluated their pathological and clinical features.

Results

It showed male predominance (male/female ratio, 15/6) with wide age range from 20 to 72 years (mean age, 49 years). All 21 cases were divided into two types according to the World Health Organization criteria: atypical carcinoid (n=18) and large cell NEC (n=3). Three cases of atypical carcinoid (AC) were associated with ectopic Cushing's syndrome. All the patients (3/3) with large cell NEC (3/3) and 16.7% (3/18) of those with AC died of tumor progression. Common sites of metastasis included lung, lymph node, brain, lumbar spine, mediastinum, bone, and liver.

Conclusions

In conclusion, thymic neuroendocrine tumors carry a poor prognosis. Regarding the tumor classification, our results showed that a vast majority of carcinoids in the thymus correspond to ACs. In addition, our results also indicate that typical carcinoid is a very rare entity. Some cases of AC exhibited a large size, solid pattern and they showed aggressive clinical behavior, which highlights the spectrum of histologic appearances of thymic NECs.

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Case Report

Mucinous Bronchioloalveolar Carcinoma Associated with Bronchiectatic Cyst: A Brief Case Report.: Chang Ohk Sung, Joungho Han, Sang Won Um, Chin A Yi, Young Mog Shim; Korean J Pathol. 2010;44(5):540-542.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.5.540

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Abstract PDF: Herein we report a rare case of mucinous bronchioloalveolar carcinoma (BAC) associated with a solitary bronchiectatic cyst in a 29-year-old man. The patient presented with hemoptysis and had a history of pulmonary tuberculosis. Chest radiographs and computed tomography revealed a well-circumscribed, thin-walled cavitary lesion in the right upper pulmonary lobe. Gross examination of a lobectomy specimen showed a bronchiectatic cavity and a fungus ball within it. There were also several ill-defined small gray-white nodules around the cyst, nodules that were mucinous BAC. On microscopy, they were composed of columnar tumor cells along the intact alveolar walls in a single layer.

Short Case Report

Squamous Cell Carcinoma Arising in a Thymic Cyst : A Brief Case Report.: Chang Ohk Sung, Joungho Han, Ji Yeon Kim, Young Mog Shim, Tae Sung Kim; Korean J Pathol. 2009;43(3):260-262.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.260

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Abstract PDF

We present here the case of a 73-year-old man with squamous cell carcinoma that arose in a thymic cyst, and this was incidentally found by chest radiography. Computed tomography revealed a 3.6 cm-sized predominantly cystic lesion with a mural nodule at the antero-superior mediastinum. The resected specimen was a well demarcated cystic mass with a solid mural nodule. Microscopically, the nodule was determined to be invasive squamous cell carcinoma that had originated from the benign squamous epithelium lining the thymic cyst.

Citations

Citations to this article as recorded by

Multilocular Thymic Cyst with Prominent Lymphoid Follicular Hyperplasia: A Case Report
Na-Ra Yoon, Ji Yun Jeong, Joungho Han, Jhingook Kim, Chin A Yi
Journal of Lung Cancer.2012; 11(1): 45. CrossRef

Original Article

Clinicopathologic Features of Early Hepatocellular Carcinoma.: Chang Ohk Sung, Suk Jin Choi, Cheol Keun Park; Korean J Pathol. 2004;38(3):138-144.

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Abstract PDF: BACKGROUND
Early hepatocellular carcinoma (HCC) is an early stage HCC, and it is sometimes difficult to identify the margins of the cancer nodules in the resected specimens.
METHODS
We studied 22 cases of early HCC to investigate the clinicopathologic features of early stage HCC.
RESULTS
Seven of 22 cases were single HCC, and 15 were multicentric HCC. The average tumor size was 1.34 cm (0.4-2.7 cm). Early HCCs didn't destroy the basic architecture of the liver lobules or pseudolobules and the lesions had an indistinct margin. Most tumors were uniformly composed of well-differentiated cancer tissue that was characterized by an increased cell density and an irregular thin-trabecular pattern. The tumor retained a varying number of portal tracts. There was a replacing growth pattern at the tumor-nontumor boundary without tumor capsule. Three of 22 cases had a "nodule-in-nodule" lesion, and the inner nodules consisted of moderately differentiated HCC without portal tracts. All 22 cases showed no vascular invasion. All 7 patients with single early HCC have survived for the past 11-54 months without any local recurrence. But in one patient with single early HCC, multicentric HCC developed 20 months after surgery.
CONCLUSION
The clinicopathologic features of early HCCs are quite different from those of advanced HCCs. The increased recognition of early HCC during routine clinical practice will contribute to improved patient survival.

Case Report

Giant Multilocular Cystadenoma of the Prostate: A Case Report.: Chang Ohk Sung, Jinwon Seo, Sang Yong Song; Korean J Pathol. 2004;38(2):106-108.

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Abstract PDF: Large multilocular cysts and cystic neoplasms of the prostate are very rare. A healthy 52-year-old man presented with acute urinary retension. Physical examination revealed a large abdominal mass. Pelvic MRI showed a 15x10x9 cm, lobulated, and multiseptated cystic mass in the pelvic cavity. Exploration laparotomy revealed a large cytic mass that compressd and displaced the urinary bladder antero-laterally, and adhered to the prostate and the sigmoid colon. Macroscopically, the mass was grayish white colored, multilocular cysts containing reddish-brown serous fluid. Microscopically, the tumor was composed of glands and cysts lined by the prostatic-type epithelium in the fibrous stroma. The prostatic nature of the lesion was confirmed by the lining epithelium expressing prostate-specific antigen.

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