Journal of Pathology and Translational Medicine

Volume 57(3); May 2023

Review

Trouble-makers in cytologic interpretation of the uterine cervix: Eunah Shin, Jaeeun Yu, Soon Won Hong; J Pathol Transl Med. 2023;57(3):139-146. Published online May 15, 2023; DOI: https://doi.org/10.4132/jptm.2023.04.25

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The development and standardization of cytologic screening of the uterine cervix has dramatically decreased the prevalence of squamous cell carcinoma of the uterine cervix. Advances in the understanding of biology of human papillomavirus have contributed to upgrading the histologic diagnosis of the uterine cervix; however, cytologic screening that should triage those that need further management still poses several difficulties in interpretation. Cytologic features of high grade intraepithelial squamous lesion (HSIL) mimics including atrophy, immature metaplasia, and transitional metaplasia, and glandular lesion masquerades including tubal metaplasia and HSIL with glandular involvement are described with accentuation mainly on the differential points. When the cytologic features lie in a gray zone between the differentials, the most important key to the more accurate interpretation is sticking to the very basics of cytology; screening the background and cellular architecture, and then scrutinizing the nuclear and cytoplasmic details.

Citations

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Pitfalls in Gynecological Cytology: Review of the Common and Less Frequent Entities in Pap Test
Danijela Vrdoljak-Mozetič, Snježana Štemberger-Papić, Damjana Verša Ostojić, Roberta Rubeša, Marko Klarić, Senija Eminović
Acta Cytologica.2024; 68(3): 281. CrossRef
Cytological features of human papillomavirus‐infected immature squamous metaplastic cells from cervical intraepithelial neoplasia grade 2
Mitsuaki Okodo, Kaori Okayama, Koji Teruya, Ruku Shinohara, Shuichi Mizuno, Rei Settsu, Yasuyoshi Ishii, Masahiko Fujii, Hirokazu Kimura, Mizue Oda
Journal of Medical Virology.2023;[Epub] CrossRef

Original Articles

Expression of specific microRNAs in tissue and plasma in colorectal cancer: Allan Fellizar, Vivencio Refuerzo, John Donnie Ramos, Pia Marie Albano; J Pathol Transl Med. 2023;57(3):147-157. Published online May 3, 2022; DOI: https://doi.org/10.4132/jptm.2022.02.19

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Abstract PDF

Background
MicroRNAs (miRNA/miR) play significant roles in the regulation of cell differentiation, cell cycle progression, and apoptosis. They become dysregulated during carcinogenesis and are eventually released into the circulation, enabling their detection in body fluids. Thus, this study compared the miRNA expression in tissue and plasma samples of colorectal cancer (CRC) patients and clinically healthy controls and determined miRNA expression as a potential CRC biomarker.
Methods
Using quantitative reverse transcription polymerase chain reaction (RT-qPCR), miR-21-5p, miR-29a-3p, miR-92a-3p, miR-135b-5p, miR-196b-5p, and miR-197-3p, expression was analyzed and compared between the malignant (n = 41) and the adjacent neoplasm free mucosal tissues (n = 41) of CRC patients. The findings were validated in plasma samples (n = 36) collected from the same CRC patients prior to surgery or any form of treatment and compared to plasma from their age and sex-matched controls (n = 36).
Results
MiR-21-5p, miR-29a-3p, miR-92a-3p, and miR- 196b-5p were upregulated and miR-135b-5p was downregulated in CRC malignant tissues compared to their expression in adjacent neoplasm-free tissue. This was further observed in the plasma of the same CRC cases compared to controls. MiR-92a-3p showed itself the most sensitive (0.93; p < .001) and most specific (0.95; p < .001) in detecting CRC in tissue. In plasma, miR-196b-5p was the most sensitive (0.97; p < .001) and specific (0.94; p < .001) in detecting CRC. Plasma miR-92a-3p and miR-196b-5p were the most sensitive (0.95; p < .001) and specific (0.94; p < .001) in the early detection of CRC.
Conclusions
Results show that specific miRNAs dysregulated in malignant tissues are released and can be detected in the circulation, supporting their potential as non-invasive biomarkers of CRC.

Citations

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Except for Robust Outliers, Rapamycin Increases Lesion Burden in a Murine Model of Cerebral Cavernous Malformations
Roberto J. Alcazar-Felix, Robert Shenkar, Christian R. Benavides, Akash Bindal, Abhinav Srinath, Ying Li, Serena Kinkade, Tatiana Terranova, Evon DeBose-Scarlett, Rhonda Lightle, Dorothy DeBiasse, Hanadi Almazroue, Diana Vera Cruz, Sharbel Romanos, Aditya
Translational Stroke Research.2024;[Epub] CrossRef
Identification of miRNAs Present in Cell- and Plasma-Derived Extracellular Vesicles—Possible Biomarkers of Colorectal Cancer
Marzena Lenart, Izabela Siemińska, Rafał Szatanek, Anna Mordel, Antoni Szczepanik, Mateusz Rubinkiewicz, Maciej Siedlar, Monika Baj-Krzyworzeka
Cancers.2024; 16(13): 2464. CrossRef
The Role of Extracellular Vesicles in Colorectal Cancer
Yujian Xia, Chaoran Yu, Ernest Johann Helwig, Yousheng Li
Technology in Cancer Research & Treatment.2023;[Epub] CrossRef
HNRNPA2B1-Mediated MicroRNA-92a Upregulation and Section Acts as a Promising Noninvasive Diagnostic Biomarker in Colorectal Cancer
Yiling Li, Kexin Li, Xiaoying Lou, Yue Wu, Samuel Seery, Danfei Xu, Yuqing Pei, Benheng Qian, Yuxin Wu, Shuang Liang, Kui Wu, Wei Cui
Cancers.2023; 15(4): 1367. CrossRef
Role of salivary miRNAs in the diagnosis of gastrointestinal disorders: a mini-review of available evidence
Maria Oana Săsăran, Claudia Bănescu
Frontiers in Genetics.2023;[Epub] CrossRef
Exploring the Role of Circulating Cell-Free RNA in the Development of Colorectal Cancer
Chau-Ming Kan, Xiao Meng Pei, Martin Ho Yin Yeung, Nana Jin, Simon Siu Man Ng, Hin Fung Tsang, William Chi Shing Cho, Aldrin Kay-Yuen Yim, Allen Chi-Shing Yu, Sze Chuen Cesar Wong
International Journal of Molecular Sciences.2023; 24(13): 11026. CrossRef
Lynch Syndrome Biopathology and Treatment: The Potential Role of microRNAs in Clinical Practice
Serena Ascrizzi, Grazia Maria Arillotta, Katia Grillone, Giulio Caridà, Stefania Signorelli, Asad Ali, Caterina Romeo, Pierfrancesco Tassone, Pierosandro Tagliaferri
Cancers.2023; 15(15): 3930. CrossRef

Frequent apocrine changes in pleomorphic adenoma with malignant transformation: a possible pre-malignant step in ductal carcinoma ex pleomorphic adenoma: Joon Seon Song, Yeseul Kim, Yoon-Se Lee, Seung-Ho Choi, Soon Yuhl Nam, Sang Yoon Kim, Kyung-Ja Cho; J Pathol Transl Med. 2023;57(3):158-165. Published online May 10, 2023; DOI: https://doi.org/10.4132/jptm.2023.03.13

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Abstract PDF

Background
The most common type of carcinoma ex pleomorphic adenoma (CPA) is histologically equivalent to salivary duct carcinoma, which has an apocrine phenotype. Invasive CPA is often accompanied by non-invasive or in situ carcinoma, an observation that suggests the presence of precursor lesions. The aim of this study was to identify candidate precursor lesions of CPA within pleomorphic adenoma (PA).
Methods
Eleven resected cases of CPA with residual PA and 17 cases of PA with atypical changes were subjected to immunohistochemistry (IHC) for p53, human epidermal growth factor receptor 2 (HER2), androgen receptor (AR), pleomorphic adenoma gene 1, gross cystic disease fluid protein-15 (GCDFP-15), and anti-mitochondrial antibody.
Results
Invasive or in situ carcinoma cells in all CPAs were positive for AR, GCDFP-15, and HER2. Atypical foci in PAs corresponded to either apocrine or oncocytic changes on the basis of their reactivity to AR, GCDFP-15, and anti-mitochondrial antibody. Atypical cells in PAs surrounding CPAs had an apocrine phenotype without HER2 expression.
Conclusions
Our study identified frequent apocrine changes in residual PAs in CPA cases, suggesting a possible precursor role of apocrine changes. We recommend the use of HER2 IHC in atypical PAs, and that clinicians take HER2 positivity into serious consideration.

Citations

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Characterization of a Molecularly Distinct Subset of Oncocytic Pleomorphic Adenomas/Myoepitheliomas Harboring Recurrent ZBTB47-AS1::PLAG1 Gene Fusion
Ziyad Alsugair, Jimmy Perrot, Françoise Descotes, Jonathan Lopez, Anne Champagnac, Daniel Pissaloux, Claire Castain, Mihaela Onea, Philippe Céruse, Pierre Philouze, Charles Lépine, Marie-Delphine Lanic, Marick Laé, Valérie Costes-Martineau, Nazim Benzerdj
American Journal of Surgical Pathology.2024; 48(5): 551. CrossRef

Clinicopathologic characterization of cervical metastasis from an unknown primary tumor: a multicenter study in Korea: Miseon Lee, Uiree Jo, Joon Seon Song, Youn Soo Lee, Chang Gok Woo, Dong-Hoon Kim, Jung Yeon Kim, Sun Och Yoon, Kyung-Ja Cho; J Pathol Transl Med. 2023;57(3):166-177. Published online May 10, 2023; DOI: https://doi.org/10.4132/jptm.2023.04.12

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Abstract PDF Supplementary Material

Background
Research regarding cervical metastasis from an unknown primary tumor (CUP) according to human papillomavirus (HPV) and Epstein-Barr virus (EBV) status in Korea has been sporadic and small-scale. This study aims to analyze and understand the characteristics of CUP in Korea according to viral and p16 and p53 status through a multicenter study.
Methods
Ninety-five cases of CUP retrieved from six hospitals in Korea between January 2006 and December 2016 were subjected to high-risk HPV detection (DNA in situ hybridization [ISH] or real-time polymerase chain reaction), EBV detection (ISH), and immunohistochemistry for p16 and p53.
Results
CUP was HPV-related in 37 cases (38.9%), EBV-related in five cases (5.3%), and unrelated to HPV or EBV in 46 cases (48.4%). HPV-related CUP cases had the best overall survival (OS) (p = .004). According to the multivariate analysis, virus-unrelated disease (p = .023) and longer smoking duration (p < .005) were prognostic factors for poor OS. Cystic change (p = .016) and basaloid pattern (p < .001) were more frequent in HPV-related cases, and lymphoepithelial lesion was frequent in EBV-related cases (p = .010). There was no significant association between viral status and p53 positivity (p = .341), smoking status (p = .728), or smoking duration (p = .187). Korean data differ from Western data in the absence of an association among HPV, p53 positivity, and smoking history.
Conclusions
Virus-unrelated CUP in Korea had the highest frequency among all CUP cases. HPV-related CUP is similar to HPV-mediated oropharyngeal cancer and EBVrelated CUP is similar to nasopharyngeal cancer in terms of characteristics, respectively.

Citations

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Expansion of tumor-infiltrating lymphocytes from head and neck squamous cell carcinoma to assess the potential of adoptive cell therapy
Sangjoon Choi, Mofazzal Hossain, Hyun Lee, Jina Baek, Hye Seon Park, Chae-Lyul Lim, DoYeon Han, Taehyun Park, Jong Hyeok Kim, Gyungyub Gong, Mi-Na Kweon, Hee Jin Lee
Cancer Immunology, Immunotherapy.2024;[Epub] CrossRef

Case Study

Thyroid pathology, a clue to PTEN hamartoma tumor syndrome: Yurimi Lee, Young Lyun Oh; J Pathol Transl Med. 2023;57(3):178-183. Published online March 30, 2023; DOI: https://doi.org/10.4132/jptm.2023.03.04

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Abstract PDF

Phosphatase and tensin homolog (PTEN) hamartoma tumor syndrome (PHTS) is a hereditary disorder caused by germline inactivating mutations in the PTEN tumor suppressor gene. As a type of PHTS, Cowden syndrome is associated with abnormalities of the thyroid, breast, uterus, and gastrointestinal tract. A 52-year-old-woman visited the outpatient clinic of our endocrinology clinic with multiple thyroid nodules and Hashimoto's thyroiditis. Computed tomography imaging revealed a multinodular mass measuring up to 3.5 cm in the left thyroid lobe, causing laryngotracheal airway displacement. The total thyroidectomy specimen revealed multiple follicular adenomas and adenomatous nodules with lymphocytic thyroiditis and lipomatous metaplasia in the background. The patient was suspected of PTHS based on her thyroid pathology, family history, and numerous hamartomatous lesions of the breast, uterus, and skin. Her diagnosis was confirmed through molecular testing. This case demonstrates that pathologists must be well acquainted with thyroid pathology in PHTS.

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Dedifferentiated Leiomyosarcoma of the Uterine Corpus with Heterologous Component: Clinicopathological Analysis of Five Consecutive Cases from a Single Institution and Comprehensive Literature Review
Suyeon Kim, Hyunsik Bae, Hyun-Soo Kim
Diagnostics.2024; 14(2): 160. CrossRef
Case report: Rare oral manifestations in Cowden syndrome with PTEN mutation
Wei Yuan, Yanbin Liu, Haibin Sun, Ming Su, Lizheng Qin, Xin Huang
Frontiers in Oncology.2024;[Epub] CrossRef
Can thyroid histomorphology identify patients with PTEN hamartoma tumour syndrome?
Melad N Dababneh, Laura Rabinowitz, Gilman Plitt, Charis Eng, Christopher C Griffith
Histopathology.2024; 85(6): 929. CrossRef
A novel mutation in PTEN in anaplastic thyroid carcinoma: A case report
Yanli Zhao
Biomedical Reports.2024;[Epub] CrossRef

Newsletter

What’s new in bone and soft tissue pathology 2023: guidelines for molecular testing: Farres Obeidin; J Pathol Transl Med. 2023;57(3):184-187. Published online April 5, 2023; DOI: https://doi.org/10.4132/jptm.2023.03.20

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Abstract PDF

Our understanding of bone and soft tissue tumors has thoroughly evolved as a consequence of modern molecular techniques. DNA and RNA sequencing methods play an important diagnostic and therapeutic role in sarcoma pathology. Herein, we discuss current guidelines and best practices for molecular testing in bone and soft tissue tumors.

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RB1: governor of the cell cycle in health and disease—a primer for the practising pathologist
Fleur Cordier, David Creytens
Journal of Clinical Pathology.2024; 77(7): 435. CrossRef

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