Journal of Pathology and Translational Medicine

Volume 55(2); March 2021

Review

Non-conventional dysplastic subtypes in inflammatory bowel disease: a review of their diagnostic characteristics and potential clinical implications: Won-Tak Choi; J Pathol Transl Med. 2021;55(2):83-93. Published online March 9, 2021; DOI: https://doi.org/10.4132/jptm.2021.02.17

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The early detection and grading of dysplasia is the current standard of care to minimize mortality from colorectal cancer (CRC) in patients with inflammatory bowel disease. With the development of advanced endoscopic resection techniques, colectomy is now reserved for patients with invisible/flat dysplasia (either high-grade [HGD] or multifocal low-grade dysplasia) or endoscopically unresectable lesions. Although most pathologists are familiar with the morphologic criteria of conventional (intestinal type) dysplasia, the most well-recognized form of dysplasia, an increasing number of diagnostic material has led to the recognition of several different morphologic patterns of epithelial dysplasia. The term “non-conventional” dysplasia has been coined to describe these changes, but to date, the recognition and full appreciation of these novel forms of dysplasia by practicing pathologists is uneven. The recognition of these non-conventional subtypes is becoming increasingly important, as some of them appear to have a higher risk of developing HGD or CRC than conventional dysplasia or sporadic adenomas. This review describes the morphologic characteristics of all seven non-conventional subtypes that have been reported to date as well as our current understanding of their clinicopathologic and molecular features that distinguish them from conventional dysplasia or sporadic adenomas.

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Morphological subtypes of colorectal low-grade intraepithelial neoplasia: diagnostic reproducibility, frequency and clinical impact
Corinna Lang-Schwarz, Maike Büttner-Herold, Stephan Burian, Ramona Erber, Arndt Hartmann, Moritz Jesinghaus, Kateřina Kamarádová, Carlos A Rubio, Gerhard Seitz, William Sterlacci, Michael Vieth, Simone Bertz
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“Artificial histology” in colonic Neoplasia: A critical approach
Gavino Faa, Matteo Fraschini, Luca Didaci, Luca Saba, Mario Scartozzi, Enrico Orvieto, Massimo Rugge
Digestive and Liver Disease.2025; 57(3): 663. CrossRef
Examination of non-conventional dysplasias adjacent to colorectal adenocarcinoma in patients with IBD
Szintia Almási, Zsófia Balajthy, Bence Baráth, Zsófia Krisztina Török, Panna Szaszák, Tamás Lantos, Bence Kővári, Anita Sejben
Pathology and Oncology Research.2025;[Epub] CrossRef
Clinical Characteristics, Management, and Outcomes of Colitis-Associated Colorectal Cancer and the Comparison With Sporadic Colorectal Cancer in Taiwan
Hsin-Yun Wu, Meng-Tzu Weng, Jen-Wei Chou, Hsu-Heng Yen, Chun-Chi Lin, Feng-Fan Chiang, Chen-Shuan Chung, Wei-Chen Lin, Chen-Wang Chang, Puo-Hsien Le, Chia-Jung Kuo, Ching-Pin Lin, Wen-Hung Hsu, Chiao-Hsiung Chuang, Tzung-Jiun Tsai, I-Che Feng, Shu-Chen We
Clinical and Translational Gastroenterology.2025; 16(2): e00798. CrossRef
Dysplasia in Pediatric Patients with Inflammatory Bowel Disease Shows Distinct Clinicopathologic Features Compared With that in Adult Patients
Dorukhan Bahceci, Shaomin Hu, Xiaoyan Liao, Lindsay Alpert, Hwajeong Lee, Huaibin Mabel Ko, Adam L. Booth, Gregory Y. Lauwers, Won-Tak Choi
Modern Pathology.2025; 38(6): 100735. CrossRef
Nonconventional dysplasia in patients with inflammatory bowel disease and colorectal adenocarcinoma: a case-cohort study
Siri A Urquhart, Namratha Pallipamu, Hima Varsha Voruganti, Bhavana Baraskar, Pratyusha Muddaloor, Arshia K Sethi, Renisha Redij, Keirthana Aedma, Keerthy Gopalakrishnan, Shivaram Poigai Arunachalam, Kelli N Burger, Douglas W Mahoney, Blake A Kassmeyer, R
Journal of Crohn's and Colitis.2025;[Epub] CrossRef
Cutting Edge: A Comprehensive Guide to Colorectal Cancer Surgery in Inflammatory Bowel Diseases
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Inflammatory bowel disease‐associated serrated lesions with dysplasia are frequently associated with advanced neoplasia: supporting a unified classification approach
Dorukhan Bahceci, Anita Sejben, Lindsay Yassan, Gregory Miller, Xiaoyan Liao, Huaibin Mabel Ko, Marcela Salomao, Masato Yozu, Gregory Y. Lauwers, Won‐Tak Choi
Histopathology.2025;[Epub] CrossRef
Recently described types of dysplasia associated with IBD: tips and clues for the practising pathologist
Zahra Alipour, Kristen Stashek
Journal of Clinical Pathology.2024; 77(2): 77. CrossRef
Nonconventional Dysplasia is Frequently Associated With Goblet Cell Deficient and Serrated Variants of Colonic Adenocarcinoma in Inflammatory Bowel Disease
Andrew Xiao, Masato Yozu, Bence P. Kővári, Lindsay Yassan, Xiaoyan Liao, Marcela Salomao, Maria Westerhoff, Anita Sejben, Gregory Y. Lauwers, Won-Tak Choi
American Journal of Surgical Pathology.2024; 48(6): 691. CrossRef
Increased Active Inflammation in the Colon is Not a Reliable Predictor of an Elevated Risk of Dysplasia in Patients With Primary Sclerosing Cholangitis and Ulcerative Colitis
Ruth Zhang, Dongliang Wang, Gregory Y. Lauwers, Won-Tak Choi
American Journal of Surgical Pathology.2024; 48(9): 1154. CrossRef
Dysplasia Detected in Patients With Serrated Epithelial Change Is Frequently Associated With an Invisible or Flat Endoscopic Appearance, Nonconventional Dysplastic Features, and Advanced Neoplasia
Dorukhan Bahceci, Lindsay Alpert, Tanner Storozuk, Xiaoyan Liao, Masato Yozu, Maria Westerhoff, Bence P. Kővári, Gregory Y. Lauwers, Won-Tak Choi
American Journal of Surgical Pathology.2024; 48(10): 1326. CrossRef
Difficulties in diagnosis of non-conventional dysplasia in inflammatory bowel disease
Kh. M. Akhrieva, A. S. Tertychnyy, N. V. Pachuashvili, L. S. Urusova
Bulletin of the Medical Institute "REAVIZ" (REHABILITATION, DOCTOR AND HEALTH).2024; 14(3): 21. CrossRef
Hypermucinosus és kehelysejtszegény, gyulladásos bélbetegséghez társult, non-conventionalis dysplasia colorectalis adenocarcinoma mellett
Szintia Almási, Bence Baráth, Panna Szaszák, Bence Kővári, Anita Sejben
Orvosi Hetilap.2023; 164(51): 2039. CrossRef
DNA content abnormality frequently develops in the right/proximal colon in patients with primary sclerosing cholangitis and inflammatory bowel disease and is highly predictive of subsequent detection of dysplasia
Ruth Zhang, Peter S. Rabinovitch, Aras N. Mattis, Gregory Y. Lauwers, Won‐Tak Choi
Histopathology.2023; 83(1): 116. CrossRef
Non‐conventional dysplasia is frequently associated with low‐grade tubuloglandular and mucinous adenocarcinomas in inflammatory bowel disease
Fahire Goknur Akarca, Masato Yozu, Lindsay Alpert, Bence P Kővári, Lei Zhao, Marcela Salomao, Xiaoyan Liao, Maria Westerhoff, Gregory Y Lauwers, Won‐Tak Choi
Histopathology.2023; 83(2): 276. CrossRef
The yield of dysplasia and serrated lesions in a single-centre tertiary inflammatory bowel disease cohort
Fiona Yeaman, Lena Thin
Therapeutic Advances in Gastroenterology.2023;[Epub] CrossRef
MYC overexpression in inflammatory bowel disease-associated conventional dysplasia and association of subsequent low-grade dysplasia in follow-up biopsies
Yuanxin Liang, Yansheng Hao, Yiqin Xiong, Minghao Zhong, Dhanpat Jain
Pathology - Research and Practice.2023; 248: 154642. CrossRef
Characteristics, Reporting, and Potential Clinical Significance of Nonconventional Dysplasia in Inflammatory Bowel Disease
Won-Tak Choi
Surgical Pathology Clinics.2023; 16(4): 687. CrossRef
Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
Vladislava Stojic, Natasa Zdravkovic, Tamara Nikolic-Turnic, Nebojsa Zdravkovic, Jelena Dimitrijevic, Aleksandra Misic, Kristijan Jovanovic, Stefan Milojevic, Jelena Zivic
Open Medicine.2023;[Epub] CrossRef
And the story goes on: non-conventional dysplasia of the colorectum
Lavisha S. Punjabi, Yi Neng Lai, Anjula Thomas
Journal of Pathology and Translational Medicine.2022; 56(2): 109. CrossRef
Clinicopathologic features of undetected dysplasia found in total colectomy or proctocolectomy specimens of patients with inflammatory bowel disease
Dorukhan Bahceci, Gregory Y Lauwers, Won‐Tak Choi
Histopathology.2022; 81(2): 183. CrossRef
Increased Risk of Non-conventional and Invisible Dysplasias in Patients with Primary Sclerosing Cholangitis and Inflammatory Bowel Disease
Ruth Zhang, Gregory Y Lauwers, Won-Tak Choi
Journal of Crohn's and Colitis.2022; 16(12): 1825. CrossRef
Increased histologic inflammation is an independent risk factor for nonconventional dysplasia in ulcerative colitis
Eric D. Nguyen, Dongliang Wang, Gregory Y. Lauwers, Won‐Tak Choi
Histopathology.2022; 81(5): 644. CrossRef

Original Articles

Histologically confirmed distant metastatic urothelial carcinoma from the urinary bladder: a retrospective review of one institution’s 20-year experience: Youngeun Yoo, Junghye Lee, Heae Surng Park, Min-Sun Cho, Sun Hee Sung, Sanghui Park, Euno Choi; J Pathol Transl Med. 2021;55(2):94-101. Published online December 3, 2020; DOI: https://doi.org/10.4132/jptm.2020.10.19

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Abstract PDF

Background
Urothelial carcinoma (UC) accounts for roughly 90% of bladder cancer, and has a high propensity for diverse differentiation. Recently, certain histologic variants of UC have been recognized to be associated with unfavorable clinical outcomes. Several UC studies have also suggested that tumor budding is a poor prognostic marker. Distant metastasis of UC after radical cystectomy is not uncommon. However, these metastatic lesions are not routinely confirmed with histology.
Methods
We investigated the histopathologic features of 13 cases of UC with biopsy-proven distant metastases, with a special emphasis on histologic variants and tumor budding.
Results
Lymph nodes (6/13, 46%) were the most common metastatic sites, followed by the lung (4/13, 31%), liver (4/13, 31%), and the adrenal gland (2/13, 15%). The histologic variants including squamous (n=1), micropapillary (n=4), and plasmacytoid (n=1) variants in five cases of UC. Most histologic variants (4/5, 80%) of primary UCs appeared in the metastatic lesions. In contrast, high-grade tumor budding was detected in six cases (46%), including one case of non-muscle invasive UC. Our study demonstrates that histologic variants are not uncommonly detected in distant metastatic UCs. Most histologic variants seen in primary UCs persist in the distant metastatic lesions. In addition, high-grade tumor budding, which occurs frequently in primary tumors, may contribute to the development of distant metastasis.
Conclusions
Therefore, assessing the presence or absence of histologic variants and tumor budding in UCs of the urinary bladder, even in non-muscle invasive UCs, may be useful to predict distant metastasis.

Citations

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Do Histology and Primary Tumor Location Influence Metastatic Patterns in Bladder Cancer?
Hyung Kyu Park
Current Oncology.2023; 30(10): 9078. CrossRef

The prognostic significance of p16 expression pattern in diffuse gliomas: Jin Woo Park, Jeongwan Kang, Ka Young Lim, Hyunhee Kim, Seong-Ik Kim, Jae Kyung Won, Chul-Kee Park, Sung-Hye Park; J Pathol Transl Med. 2021;55(2):102-111. Published online December 23, 2020; DOI: https://doi.org/10.4132/jptm.2020.10.22

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Abstract PDF

Background
CDKN2A is a tumor suppressor gene that encodes the cell cycle inhibitor protein p16. Homozygous deletion of the CDKN2A gene has been associated with shortened survival in isocitrate dehydrogenase (IDH)–mutant gliomas. This study aimed to analyze the prognostic value of p16 and to evaluate whether p16 immunohistochemical staining could be used as a prognostic marker to replace CDKN2A genotyping in diffuse gliomas.
Methods
p16 immunohistochemistry was performed on tissue microarrays of 326 diffuse gliomas with diagnoses that reflected IDH-mutations and 1p/19q codeletion status. The results were divided into three groups (negative, focal expression, overexpression) according to the presence and degree of p16 expression. Survival analysis was performed to assess the prognostic value of p16 expression.
Results
A loss of p16 expression predicted a significantly worse outcome in all glioma patients (n=326, p<.001), in the IDH-mutant glioma patients (n=103, p=.010), and in the IDH-mutant astrocytoma patients (n=73, p=.032). However, loss of p16 expression did not predict the outcome in the IDH-wildtype glioma patients (n=223, p=.121) or in the oligodendroglial tumor patients with the IDH-mutation and 1p/19q codeletion (n=30, p=.457). Multivariate analysis showed the association was still significant in the IDH-mutant glioma patients (p=.008; hazard ratio [HR], 2.637; 95% confidence interval [CI], 1.295 to 5.372) and in the IDH-mutant astrocytoma patients (p=.001; HR, 3.586; 95% CI, 1.649 to 7.801). Interestingly, patients who presented with tumors with p16 overexpression also had shorter survival times than did patients with tumors with p16 focal expression in the whole glioma (p< .001) and in IDH-mutant glioma groups. (p=.046).
Conclusions
This study suggests that detection of p16 expression by immunohistochemistry can be used as a useful surrogate test to predict prognosis, especially in IDH-mutant astrocytoma patients.

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Revealing the role of necroptosis microenvironment: FCGBP + tumor-associated macrophages drive primary liver cancer differentiation towards cHCC-CCA or iCCA
Chun Wang, Cuimin Chen, Wenting Hu, Lili Tao, Jiakang Chen
Apoptosis.2024; 29(3-4): 460. CrossRef
FISH analysis reveals CDKN2A and IFNA14 co-deletion is heterogeneous and is a prominent feature of glioblastoma
Sofian Al Shboul, Shelagh Boyle, Ashita Singh, Tareq Saleh, Moath Alrjoub, Ola Abu Al Karsaneh, Amel Mryyian, Rand Dawoud, Sinem Gul, Shaden Abu Baker, Kathryn Ball, Ted Hupp, Paul M. Brennan
Brain Tumor Pathology.2024; 41(1): 4. CrossRef
p16 Expression in Laryngeal Squamous Cell Carcinoma: A Surrogate or Independent Prognostic Marker?
Roberto Gallus, Davide Rizzo, Giorgia Rossi, Luca Mureddu, Jacopo Galli, Alberto Artuso, Francesco Bussu
Pathogens.2024; 13(2): 100. CrossRef
CDKN2A/B deletion in IDH-mutant astrocytomas: An evaluation by Fluorescence in-situ hybridization
Manali Ranade, Sridhar Epari, Omshree Shetty, Sandeep Dhanavade, Sheetal Chavan, Ayushi Sahay, Arpita Sahu, Prakash Shetty, Aliasgar Moiyadi, Vikash Singh, Archya Dasgupta, Abhishek Chatterjee, Sadhana Kannan, Tejpal Gupta
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Molecular prognostication in grade 3 meningiomas and p16/MTAP immunohistochemistry for predicting CDKN2A/B status
Kira Tosefsky, Karina Chornenka Martin, Alexander D Rebchuk, Justin Z Wang, Farshad Nassiri, Amy Lum, Gelareh Zadeh, Serge Makarenko, Stephen Yip
Neuro-Oncology Advances.2024;[Epub] CrossRef
Insights into brain tumor diagnosis: exploring in situ hybridization techniques
E. D. Namiot, G. M. Zembatov, P. P. Tregub
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CDKN2A Homozygous Deletion Is a Stronger Predictor of Outcome than IDH1/2-Mutation in CNS WHO Grade 4 Gliomas
Sang Hyuk Lee, Tae Gyu Kim, Kyeong Hwa Ryu, Seok Hyun Kim, Young Zoon Kim
Biomedicines.2024; 12(10): 2256. CrossRef
Homozygous CDKN2A/B deletions in low- and high-grade glioma: a meta-analysis of individual patient data and predictive values of p16 immunohistochemistry testing
Darius Noack, Johannes Wach, Alonso Barrantes-Freer, Nils H. Nicolay, Erdem Güresir, Clemens Seidel
Acta Neuropathologica Communications.2024;[Epub] CrossRef
p16 Immunohistochemical Expression as a Surrogate Assessment of CDKN2A Alteration in Gliomas Leading to Prognostic Significances
Lucas Geyer, Thibaut Wolf, Marie-Pierre Chenard, Helene Cebula, Roland Schott, Georges Noel, Eric Guerin, Erwan Pencreach, Damien Reita, Natacha Entz-Werlé, Benoît Lhermitte
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P16 immunohistochemistry is a sensitive and specific surrogate marker for CDKN2A homozygous deletion in gliomas
Meenakshi Vij, Benjamin B. Cho, Raquel T. Yokoda, Omid Rashidipour, Melissa Umphlett, Timothy E. Richardson, Nadejda M. Tsankova
Acta Neuropathologica Communications.2023;[Epub] CrossRef
CDKN2A mutations have equivalent prognostic significance to homozygous deletion in IDH-mutant astrocytoma
Raquel T Yokoda, William S Cobb, Raymund L Yong, John F Crary, Mariano S Viapiano, Jamie M Walker, Melissa Umphlett, Nadejda M Tsankova, Timothy E Richardson
Journal of Neuropathology & Experimental Neurology.2023; 82(10): 845. CrossRef
Efficient diagnosis of IDH-mutant gliomas: 1p/19qNET assesses 1p/19q codeletion status using weakly-supervised learning
Gi Jeong Kim, Tonghyun Lee, Sangjeong Ahn, Youngjung Uh, Se Hoon Kim
npj Precision Oncology.2023;[Epub] CrossRef
The Prognostic Significance of P16 Immunohistochemical Expression Pattern in Women with Invasive Ductal Breast Carcinoma
Alireza Rezaei, Navidreza Shayan, Saman Shirazinia, Sara Mollazadeh, Negin Ghiyasi-Moghaddam
Reports of Biochemistry and Molecular Biology.2023; 12(1): 83. CrossRef
Sporadic and Lynch syndrome-associated mismatch repair-deficient brain tumors
Hyunhee Kim, Ka Young Lim, Jin Woo Park, Jeongwan Kang, Jae Kyung Won, Kwanghoon Lee, Yumi Shim, Chul-Kee Park, Seung-Ki Kim, Seung-Hong Choi, Tae Min Kim, Hongseok Yun, Sung-Hye Park
Laboratory Investigation.2022; 102(2): 160. CrossRef
Simple approach for the histomolecular diagnosis of central nervous system gliomas based on 2021 World Health Organization Classification
Maher Kurdi, Rana H Moshref, Yousef Katib, Eyad Faizo, Ahmed A Najjar, Basem Bahakeem, Ahmed K Bamaga
World Journal of Clinical Oncology.2022; 13(7): 567. CrossRef
P16INK4A—More Than a Senescence Marker
Hasan Safwan-Zaiter, Nicole Wagner, Kay-Dietrich Wagner
Life.2022; 12(9): 1332. CrossRef

A study of pathological characteristics and BRAF V600E status in Langerhans cell histiocytosis of Vietnamese children: Thu Dang Anh Phan, Bao Gia Phung, Tu Thanh Duong, Vu Anh Hoang, Dat Quoc Ngo, Nguyen Dinh The Trinh, Tung Thanh Tran; J Pathol Transl Med. 2021;55(2):112-117. Published online January 27, 2021; DOI: https://doi.org/10.4132/jptm.2020.11.30

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Abstract PDF

Background
Langerhans cell histiocytosis (LCH) is more common in children than adults and involves many organs. In children, the BRAF V600E mutation is associated with recurrent and high-risk LCH.
Methods
We collected paraffin blocks of 94 pediatric LCH patients to detect BRAF V600E mutation by sequencing. The relationship between BRAF V600E status and clinicopathological parameters were also critically analyzed.
Results
BRAF V600E mutation exon 15 was detected in 45 cases (47.9%). Multiple systems LCH showed a significantly higher BRAF V600E mutation rate than a single system (p=.001). No statistical significance was evident for other clinical characteristics such as age, sex, location, risk organs involvement, and CD1a expression.
Conclusions
In Vietnamese LCH children, the proportion of BRAF V600E mutational status was relatively high and related to multiple systems.

Citations

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Pathologic characteristics of histiocytic and dendritic cell neoplasms
Sun Och Yoon
Blood Research.2024;[Epub] CrossRef
Sulfur dots/Au@Ag nanorods array-based polarized ECL sensor for the detection of thyroid cancer biomarker
Zixuan Ding, Peilin Wang, Zhenrun Li, Yupeng Guo, Qiang Ma
Talanta.2023; 265: 124925. CrossRef

Deep learning for computer-assisted diagnosis of hereditary diffuse gastric cancer: Sean A. Rasmussen, Thomas Arnason, Weei-Yuarn Huang; J Pathol Transl Med. 2021;55(2):118-124. Published online January 22, 2021; DOI: https://doi.org/10.4132/jptm.2020.12.22

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Abstract PDF

Background
Patients with hereditary diffuse gastric cancer often undergo prophylactic gastrectomy to minimize cancer risk. Because intramucosal poorly cohesive carcinomas in this setting are typically not grossly visible, many pathologists assess the entire gastrectomy specimen microscopically. With 150 or more slides per case, this is a major time burden for pathologists. This study utilizes deep learning methods to analyze digitized slides and detect regions of carcinoma.
Methods
Prophylactic gastrectomy specimens from seven patients with germline CDH1 mutations were analyzed (five for training/validation and two for testing, with a total of 133 tumor foci). All hematoxylin and eosin slides containing cancer foci were digitally scanned, and patches of size 256×256 pixels were randomly extracted from regions of cancer as well as from regions of normal background tissue, resulting in 15,851 images for training/validation and 970 images for testing. A model with DenseNet-169 architecture was trained for 150 epochs, then evaluated on images from the test set. External validation was conducted on 814 images scanned at an outside institution.
Results
On individual patches, the trained model achieved a receiver operating characteristic (ROC) area under the curve (AUC) of 0.9986. This enabled it to maintain a sensitivity of 90% with a false-positive rate of less than 0.1%. On the external validation dataset, the model achieved a similar ROC AUC of 0.9984. On whole slide images, the network detected 100% of tumor foci and correctly eliminated an average of 99.9% of the non-cancer slide area from consideration.
Conclusions
Overall, our model shows encouraging progress towards computer-assisted diagnosis of hereditary diffuse gastric cancer.

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Non-endoscopic Applications of Machine Learning in Gastric Cancer: A Systematic Review
Marianne Linley L. Sy-Janairo, Jose Isagani B. Janairo
Journal of Gastrointestinal Cancer.2024; 55(1): 47. CrossRef
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Guoyang Zhang, Jingjing Song, Zongfeng Feng, Wentao Zhao, Pan Huang, Li Liu, Yang Zhang, Xufeng Su, Yukang Wu, Yi Cao, Zhengrong Li, Zhigang Jie
Frontiers in Oncology.2023;[Epub] CrossRef
Deep learning of endoscopic features for the assessment of neoadjuvant therapy response in locally advanced rectal cancer
Anqi Wang, Jieli Zhou, Gang Wang, Beibei Zhang, Hongyi Xin, Haiyang Zhou
Asian Journal of Surgery.2023; 46(9): 3568. CrossRef
Preparing Data for Artificial Intelligence in Pathology with Clinical-Grade Performance
Yuanqing Yang, Kai Sun, Yanhua Gao, Kuansong Wang, Gang Yu
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Using Deep Learning to Predict Final HER2 Status in Invasive Breast Cancers That are Equivocal (2+) by Immunohistochemistry
Sean A. Rasmussen, Valerie J. Taylor, Alexi P. Surette, Penny J. Barnes, Gillian C. Bethune
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MicroRNA-552 expression in colorectal cancer and its clinicopathological significance: Joon Im, Soo Kyung Nam, Hye Seung Lee; J Pathol Transl Med. 2021;55(2):125-131. Published online February 19, 2021; DOI: https://doi.org/10.4132/jptm.2021.01.17

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Abstract PDF Supplementary Material

Background
MicroRNA-552 (miR-552) has been reported to correlate with the development and progression of various cancers, including colorectal cancer (CRC). This study aimed to investigate miR-552 expression in cancer tissue samples compared to normal mucosal tissue and its role as a diagnostic or prognostic marker in CRC patients.
Methods
Normal mucosal tissues and primary cancer tissues from 80 surgically resected CRC specimens were used. Quantitative real-time polymerase chain reaction was performed for miR-552 and U6 small nuclear RNA to analyze miR-552 expression and its clinicopathological significance. Immunohistochemistry for p53 and phosphatase and tension homolog (PTEN) was performed to evaluate their association with miR-552 expression.
Results
miR-552 expression was significantly higher in primary cancer tissues compared to normal mucosal tissues (p<.001). The expression level of miR552 was inversely correlated with that of PTEN (p=.068) and p53 (p=.004). Survival analysis showed that high miR-552 expression was associated with worse prognosis but this was not statistically significant (p=.255). However, patients with CRC having high miR-552 expression and loss of PTEN expression had significantly worse prognosis than others (p=.029).
Conclusions
Our results suggest that high miR-552 expression might be a potential diagnostic biomarker for CRC, and its combined analysis with PTEN expression can possibly be used as a prognostic marker.

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Blood miRNAs miR-549a, miR-552, and miR-592 serve as potential disease-specific panels to diagnose colorectal cancer
Soroush Akbar, Samaneh Mashreghi, Mohammad Reza Kalani, Akram Valanik, Farzaneh Ahmadi, Mahdi Aalikhani, Zahra Bazi
Heliyon.2024; 10(7): e28492. CrossRef
Integration of TE Induces Cancer Specific Alternative Splicing Events
Woo Ryung Kim, Eun Gyung Park, Yun Ju Lee, Woo Hyeon Bae, Du Hyeong Lee, Heui-Soo Kim
International Journal of Molecular Sciences.2022; 23(18): 10918. CrossRef

Case Studies

Adenocarcinoma of the minor salivary gland with concurrent MAML2 and EWSR1 alterations: Sangjoon Choi, Junhun Cho, Seung Eun Lee, Chung-Hwan Baek, Yi-Kyung Kim, Hyung-Jin Kim, Young Hyeh Ko; J Pathol Transl Med. 2021;55(2):132-138. Published online January 22, 2021; DOI: https://doi.org/10.4132/jptm.2020.12.11

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Abstract PDF

Salivary gland tumors are histologically diverse, and each entity has distinctive histopathological and molecular features. We report two cases of salivary gland tumors with unique histological and molecular findings, which have not been documented previously. The tumors were located in the base of the tongue in both patients. Most tumor cells were arranged in cords and nests, giving a trabecularlike appearance. Focally, glandular structures with intraluminal mucin and perivascular pseudorosette-like configurations were identified. Tumor cells had eosinophilic to clear cytoplasm, and showed mild nuclear atypia. They were positive for pancytokeratin and negative for S-100, p63, c-KIT, androgen receptor, and neuroendocrine markers. Multiple foci of capsular or lymphovascular invasion were identified, but the Ki-67 labeling index was low (< 5%). Fluorescence in situ hybridization revealed concurrent alterations of MAML2 and EWSR1 gene. Further investigations with a larger number of cases with similar histological and molecular features will accurately classify this tumor.

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Salivary Gland Neoplasms With a Unique Trabecular Histology and MAML2 Translocation
Bokyung Ahn, Seung-Ho Choi, Doeun Kim, Deokhoon Kim, Kyung-Ja Cho
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Hyun Hee Koh, Eunhyang Park, Hyun-Soo Kim
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The evolving role of molecular pathology in the diagnosis of salivary gland tumours with potential pitfalls
Kanwalpreet Kaur, Shailee Mehta, Sangita Vanik, Priti Trivedi, Nirmalya Banerjee, Harsh Dhar, Sourav Datta, Subhadeep Karanjai
European Archives of Oto-Rhino-Laryngology.2022; 279(8): 3769. CrossRef
Alveolar Soft Part Sarcoma of the Uterus: Clinicopathological and Molecular Characteristics
Yurimi Lee, Kiyong Na, Ha Young Woo, Hyun-Soo Kim
Diagnostics.2022; 12(5): 1102. CrossRef
Endometrioid Carcinomas of the Ovaries and Endometrium Involving Endocervical Polyps: Comprehensive Clinicopathological Analyses
Jihee Sohn, Yurimi Lee, Hyun-Soo Kim
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Sujin Park, Go Eun Bae, Jiyoung Kim, Hyun-Soo Kim
Diagnostics.2021; 11(8): 1450. CrossRef
Mesonephric-like Adenocarcinoma of the Uterine Corpus: Comprehensive Immunohistochemical Analyses Using Markers for Mesonephric, Endometrioid and Serous Tumors
Hyunjin Kim, Kiyong Na, Go Eun Bae, Hyun-Soo Kim
Diagnostics.2021; 11(11): 2042. CrossRef

A case of concomitant EGFR/ALK alteration against a mutated EGFR background in early-stage lung adenocarcinoma: Ki-Chang Lee, Jiwon Koh, Doo Hyun Chung, Yoon Kyung Jeon; J Pathol Transl Med. 2021;55(2):139-144. Published online January 22, 2021; DOI: https://doi.org/10.4132/jptm.2020.12.16

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Rare cases of lung adenocarcinoma (LUAD) with concomitant epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) translocation have been reported. However, their clonal and evolutional relationship remains unclear. We report a case of early-stage EGFR-mutated LUAD with a focal concomitant EGFR/ALK alteration. A 63-year-old male underwent lobectomy to remove a 1.9-cm-sized lung nodule, which was diagnosed with EGFR-mutated LUAD. ALK immunohistochemistry (IHC) showed focal positivity within the part of the tumor characterized by lepidic pattern, also confirmed by fluorescence in-situ hybridization (FISH). Targeted next-generation sequencing was performed separately on the ALK IHC/FISH-positive and -negative areas. EGFR L833V/L858R mutations were detected in both areas, whereas EML4 (echinoderm microtubule-associated protein-like 4)-ALK translocations was confirmed only in the ALK IHC/FISH-positive area, suggesting the divergence of an EGFR/ALK co-altered subclone from the original EGFR-mutant clone. Our study suggests that concurrent alterations of EGFR and ALK can arise via divergent tumor evolution, even in the relatively early phases of tumorigenesis.

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Malignant rhabdoid tumor of the kidney in an adult with loss of INI1 expression and mutation in the SMARCB1 gene: Eunkyung Han, Jiyoon Kim, Min Jung Jung, Susie Chin, Sang Wook Lee, Ahrim Moon; J Pathol Transl Med. 2021;55(2):145-153. Published online March 9, 2021; DOI: https://doi.org/10.4132/jptm.2021.01.26

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A 57-year-old man with left flank pain was referred to our institute. Computed tomography scans revealed two enhancing masses in the left kidney. The clinical diagnosis was renal cell carcinoma (RCC). He underwent a radical nephrectomy with an adrenalectomy. Two well-circumscribed solid masses in the hilum and the lower pole (4.5 × 3.5 cm and 7.0 × 4.1 cm) were present. Poorly cohesive uniform round to polygonal epithelioid cells making solid sheets accounted for most of the tumor area. The initial diagnosis was RCC, undifferentiated with rhabdoid features. As the tumor showed loss of INI1 expression and a mutation in the SMARCB1 gene on chromosome 22, the revised diagnosis was a malignant rhabdoid tumor (MRT) of the kidney. To date, only a few cases of renal MRT in adults have been reported. To the best of our knowledge, this is the first report of MRT in the native kidney of an adult demonstrating a SMARCB1 gene mutation, a hallmark of MRT.

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Multiple hepatocyte nuclear factor 1A (HNF1A)-inactivated hepatocellular adenomas arising in a background of congenital hepatic fibrosis: Yangkyu Lee, Hyunjin Park, Kyoungbun Lee, Youngeun Lee, Kiryang Lee, Haeryoung Kim; J Pathol Transl Med. 2021;55(2):154-158. Published online December 23, 2020; DOI: https://doi.org/10.4132/jptm.2020.11.12

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What’s New in Pathology Newsletter by PathologyOutlines.com: Nat Pernick; J Pathol Transl Med. 2021;55(2):159-160. Published online March 12, 2021; DOI: https://doi.org/10.4132/jptm.2021.03.08

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What’s new in gynecologic pathology 2021: vulva, cervix, and uterus: Carlos Parra-Herran, Jennifer A. Bennett; J Pathol Transl Med. 2021;55(2):161-162. Published online March 12, 2021; DOI: https://doi.org/10.4132/jptm.2021.03.09

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