Journal of Pathology and Translational Medicine

Volume 57(6); November 2023

Review

The Asian Thyroid Working Group, from 2017 to 2023: Kennichi Kakudo, Chan Kwon Jung, Zhiyan Liu, Mitsuyoshi Hirokawa, Andrey Bychkov, Huy Gia Vuong, Somboon Keelawat, Radhika Srinivasan, Jen-Fan Hang, Chiung-Ru Lai; J Pathol Transl Med. 2023;57(6):289-304. Published online November 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.04

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Abstract PDF Supplementary Material: The Asian Thyroid Working Group was founded in 2017 at the 12th Asia Oceania Thyroid Association (AOTA) Congress in Busan, Korea. This group activity aims to characterize Asian thyroid nodule practice and establish strict diagnostic criteria for thyroid carcinomas, a reporting system for thyroid fine needle aspiration cytology without the aid of gene panel tests, and new clinical guidelines appropriate to conservative Asian thyroid nodule practice based on scientific evidence obtained from Asian patient cohorts. Asian thyroid nodule practice is usually designed for patient-centered clinical practice, which is based on the Hippocratic Oath, “First do not harm patients,” and an oriental filial piety “Do not harm one’s own body because it is a precious gift from parents,” which is remote from defensive medical practice in the West where physicians, including pathologists, suffer from severe malpractice climate. Furthermore, Asian practice emphasizes the importance of resource management in navigating the overdiagnosis of low-risk thyroid carcinomas. This article summarizes the Asian Thyroid Working Group activities in the past 7 years, from 2017 to 2023, highlighting the diversity of thyroid nodule practice between Asia and the West and the background reasons why Asian clinicians and pathologists modified Western systems significantly.

Original Articles

Senescent tumor cells in colorectal cancer are characterized by elevated enzymatic activity of complexes 1 and 2 in oxidative phosphorylation: Jun Sang Shin, Tae-Gyu Kim, Young Hwa Kim, So Yeong Eom, So Hyun Park, Dong Hyun Lee, Tae Jun Park, Soon Sang Park, Jang-Hee Kim; J Pathol Transl Med. 2023;57(6):305-314. Published online November 7, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.09

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Abstract PDF Supplementary Material: Background
Cellular senescence is defined as an irreversible cell cycle arrest caused by various internal and external insults. While the metabolic dysfunction of senescent cells in normal tissue is relatively well-established, there is a lack of information regarding the metabolic features of senescent tumor cells.
Methods
Publicly available single-cell RNA-sequencing data from the GSE166555 and GSE178341 datasets were utilized to investigate the metabolic features of senescent tumor cells. To validate the single-cell RNA-sequencing data, we performed senescence-associated β-galactosidase (SA-β-Gal) staining to identify senescent tumor cells in fresh frozen colorectal cancer tissue. We also evaluated nicotinamide adenine dinucleotide dehydrogenase–tetrazolium reductase (NADH-TR) and succinate dehydrogenase (SDH) activity using enzyme histochemical methods and compared the staining with SA-β-Gal staining. MTT assay was performed to reveal the complex 1 activity of the respiratory chain in in-vitro senescence model.
Results
Single-cell RNA-sequencing data revealed an upregulation in the activity of complexes 1 and 2 in oxidative phosphorylation, despite overall mitochondrial dysfunction in senescent tumor cells. Both SA-β-Gal and enzyme histochemical staining using fresh frozen colorectal cancer tissues indicated a high correlation between SA-β-Gal positivity and NADH-TR/SDH staining positivity. MTT assay showed that senescent colorectal cancer cells exhibit higher absorbance in 600 nm wavelength.
Conclusions
Senescent tumor cells exhibit distinct metabolic features, characterized by upregulation of complexes 1 and 2 in the oxidative phosphorylation pathway. NADH-TR and SDH staining represent efficient methods for detecting senescent tumor cells in colorectal cancer.

Elevated expression of Axin2 in intestinal metaplasia and gastric cancers: Dong Hui Lee, In Ho Jeong, Bogun Jang; J Pathol Transl Med. 2023;57(6):315-322. Published online November 7, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.12

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Abstract PDF: Background
The Wnt signaling pathway regulates crucial cellular processes, including stem cell development and tissue repair. Dysregulation of this pathway, particularly β-catenin stabilization, is linked to colorectal carcinoma and other tumors. Axin2, a critical component in the pathway, plays a role in β-catenin regulation. This study examines Axin2 expression in normal gastric mucosa and various gastric pathologies.
Methods
Formalin-fixed and paraffin-embedded tissue samples from normal stomach, gastritis, intestinal metaplasia (IM), and gastric carcinoma were collected. Axin2 and β-catenin expression were evaluated using RNA in situ hybridization and immunohistochemistry, respectively. Histo-scores (H-scores) were calculated to quantify expression levels of Axin2. Associations between Axin2 expression and clinicopathological variables were examined.
Results
Axin2 expression was examined in normal stomach, gastritis, and IM tissues. Axin2 expression was mainly observed in the surface and isthmus areas in the normal stomach and gastritis, whereas Axin2 expression was markedly higher at the bases of IM. Axin2 H-scores were significantly elevated in IM (mean ± standard deviation [SD], 87.0 ± 38.9) compared to normal (mean ± SD, 18.0 ± 4.5) and gastritis tissues (mean ± SD, 33.0 ± 18.6). In total, 30% of gastric carcinomas showed higher Axin2 expression. Axin2 expression did not have significant associations with age, sex, Lauren classification, histological differentiation, invasion depth, and lymph node metastasis. However, a strong positive correlation was observed between Axin2 and nuclear β-catenin in gastric carcinomas (p < .001).
Conclusions
Axin2 expression was significantly increased in IM compared to normal and gastritis cases. In addition, Axin2 showed a strong positive association with nuclear β-catenin expression in gastric carcinomas, demonstrating a close relationship with abnormal Wnt/β-catenin signaling pathway.

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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Abstract PDF Supplementary Material: 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.

Case Study

Intravascular NK/T-cell lymphoma: a case report and literature review: Ji Min Na, Wookjae Jung, Minhye Kim, Yun-Hong Cheon, Jong Sil Lee, Dae Hyun Song, Jung Wook Yang; J Pathol Transl Med. 2023;57(6):332-336. Published online November 14, 2023; DOI: https://doi.org/10.4132/jptm.2023.10.30

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1 Web of Science
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Abstract PDF

Intravascular lymphoma is characterized by an exclusively intravascular distribution of tumor cells. Intravascular natural killer/T-cell lymphoma (IVNKTL) is extremely rare, highly aggressive, commonly Epstein-Barr virus (EBV)–positive, and predominantly affects the skin and central nervous system. Here we report a case of IVNKTL diagnosed in a 67-year-old female, presenting with persistent intermittent fever and skin rashes throughout the body. Incisional biopsy of an erythematous lesion on the chest exhibited aggregation of medium to large-sized atypical lymphoid cells confined to the lumen of small vessels that were positive for CD3, granzyme B, and CD56 on immunohistochemistry and EBV-encoded RNA in situ hybridization. EBV DNA was also detected in serum after diagnosis. With a review of 26 cases of IVNKTL to date, we suggest that active biopsy based on EBV DNA detection may facilitate early diagnosis of IVNKTL.

Citations

Citations to this article as recorded by

Cutaneous Intravascular Hematolymphoid Entities: A Review
Emily Hatheway Marshall, Bethany Brumbaugh, Allison Holt, Steven T. Chen, Mai P. Hoang
Diagnostics.2024; 14(7): 679. CrossRef

Newsletter

What’s new in dermatopathology 2023: WHO 5th edition updates: Jonathan Ho, Chico J Collie; J Pathol Transl Med. 2023;57(6):337-340. Published online October 17, 2023; DOI: https://doi.org/10.4132/jptm.2023.09.22

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Abstract PDF: The 5th edition WHO Classification of Skin Tumors (2022) has introduced changes to nomenclature and diagnostics. Important differences are discussed below. Changes in each category of skin tumor have been detailed, with particular emphasis on meaningful advances in our understanding of the molecular pathogenesis of the skin’s diverse tumor landscape.

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