Journal of Pathology and Translational Medicine

Original Article

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.

Case Report

Solitary Peutz-Jeghers type harmartomatous polyp in duodenum with gastric foveolar epithelium: a case report: Eugene Choi, Junghwan Lee, Youngsoo Park; J Pathol Transl Med. 2023;57(2):128-131. Published online January 10, 2023; DOI: https://doi.org/10.4132/jptm.2022.11.07

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Peutz-Jeghers type hamartomatous polyp is known to be associated with Peutz-Jeghers syndrome, which shows characteristic multiple hamartomatous polyp involvement in the gastrointestinal tract, combined with mucocutaneous symptom, familial history of Peutz- Jeghers syndrome or STK11/LTB1 mutation. However, some cases showing histologic appearance of the polyps discovered in Peutz- Jeghers syndrome while lacking other diagnostic criteria of the syndrome have been reported, and these are called solitary Peutz- Jeghers type polyps. Herein, we report a case of solitary Peutz-Jeghers type polyp covered with heterotopic epithelium. The patient was 47-year-old female without any mucocutaneous symptoms nor familial history of Peutz-Jeghers syndrome. Microscopic examination revealed Peutz-Jeghers type hamartomatous polyp in duodenum covered with gastric type foveolar epithelium. Considering the definition of hamartomatous polyp, which is, the abnormal overgrowth of the indigenous epithelial component, the histological feature of current case is noteworthy in a point that it shows proliferation of heterotopic component, rather than the indigenous component.

Citations

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A Solitary Peutz-Jeghers Hamartomatous Polyp in the Gastric Body: A Case Report
Noelia Madera, Noemí Acevedo, Carmen González-Peralta, Rafael Castro, Vismelis Mezquita-Luna
Cureus.2024;[Epub] CrossRef

Original Article

Identification of PI3K-AKT signaling as the dominant altered pathway in intestinal type ampullary cancers through whole-exome sequencing: Niraj Kumari, Rajneesh K. Singh, Shravan K. Mishra, Narendra Krishnani, Samir Mohindra, Raghvendra L.; J Pathol Transl Med. 2021;55(3):192-201. Published online March 9, 2021; DOI: https://doi.org/10.4132/jptm.2021.01.23

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Abstract PDF Supplementary Material

Background
The genetic landscape of intestinal (INT) and pancreatobiliary (PB) type ampullary cancer (AC) has been evolving with distinct as well as overlapping molecular profiles.
Methods
We performed whole-exome sequencing in 37 cases of AC to identify the targetable molecular profiles of INT and PB tumors. Paired tumor-normal sequencing was performed on the HiSeq 2500 Illumina platform.
Results
There were 22 INT, 13 PB, and two cases of mixed differentiation of AC that exhibited a total of 1,263 somatic variants in 112 genes (2–257 variants/case) with 183 somatic deleterious variants. INT showed variations in 78 genes (1–31/case), while PB showed variations in 51 genes (1–29/case). Targetable mutations involving one or more major pathways were found in 86.5% of all ACs. Mutations in APC, CTNNB1, SMAD4, KMT2, EPHA, ERBB, and Notch genes were more frequent in INT tumors, while chromatin remodeling complex mutations were frequent in PB tumors. In the major signaling pathways, the phosphoinositide 3-kinase (PI3)/AKT and RAS/mitogen-activated protein kinase (MAPK) pathways were significantly mutated in 70% of cases (82% INT, 46% PB, p = .023), with PI3/AKT mutation being more frequent in INT and RAS/MAPK in PB tumors. Tumor mutation burden was low in both differentiation types, with 1.6/Mb in INT and 0.8/Mb in PB types (p =.217).
Conclusions
The exome data suggest that INT types are genetically more unstable than PB and involve mutations in tumor suppressors, oncogenes, transcription factors, and chromatin remodeling genes. The spectra of the genetic profiles of INT and PB types suggested primary targeting of PI3/AKT in INT and RAS/RAF and PI3/AKT pathways in PB carcinomas.

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Molecular aspects of BRAF and HER2 in prognosis of periampullary carcinoma
Apurva, Nimisha, Abhay Kumar Sharma, Arun Kumar, Ejaj Ahmad, Seneha Santoshi, Sundeep Singh Saluja
Pancreatology.2024; 24(7): 1084. CrossRef
Comparison of clinical characteristics and prognostic factors in two site-specific categories of ampullary cancer
Jing-Zhao Zhang, Zhi-Wei Zhang, Xin-Yi Guo, Deng-Sheng Zhu, Xiao-Rui Huang, Ming Cai, Tong Guo, Ya-Hong Yu
World Journal of Gastroenterology.2024; 30(39): 4281. CrossRef
The role of histone post-translational modifications in cancer and cancer immunity: functions, mechanisms and therapeutic implications
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Molecular pathways in periampullary cancer: An overview
Apurva, Real Sumayya Abdul Sattar, Asgar Ali, Nimisha, Abhay Kumar Sharma, Arun Kumar, Seneha Santoshi, Sundeep Singh Saluja
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Histologic subtyping of ampullary carcinoma for targeted therapy
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Journal of Pathology and Translational Medicine.2021; 55(3): 235. CrossRef

Case Study

Gastric IgG4-related disease presenting as a mass lesion and masquerading as a gastrointestinal stromal tumor: Banumathi Ramakrishna, Rohan Yewale, Kavita Vijayakumar, Patta Radhakrishna, Balakrishnan Siddartha Ramakrishna; J Pathol Transl Med. 2020;54(3):258-262. Published online March 4, 2020; DOI: https://doi.org/10.4132/jptm.2020.02.10

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Abstract PDF

IgG4-related disease of the stomach is a rare disorder, and only a few cases have been reported. We present two cases that were identified over a 2-month period in our center. Two male patients aged 52 and 48 years presented with mass lesion in the stomach, which were clinically thought to be gastrointestinal stromal tumor, and they underwent excision of the lesion. Microscopic examination revealed marked fibrosis, which was storiform in one case, associated with diffuse lymphoplasmacytic infiltration and an increase in IgG4-positive plasma cells on immunohistochemistry. Serum IgG4 level was markedly elevated. Although rare, IgG4-related disease should be considered in the differential diagnosis of gastric submucosal mass lesions.

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Systemic diseases affecting the GI tract: A review of clinical and histopathologic manifestations
Maryam K. Pezhouh, Dora Lam-Himlin, Atif Zaheer, Lysandra Voltaggio
Annals of Diagnostic Pathology.2024; 73: 152351. CrossRef
Utilizing Immunoglobulin G4 Immunohistochemistry for Risk Stratification in Patients with Papillary Thyroid Carcinoma Associated with Hashimoto Thyroiditis
Faridul Haq, Gyeongsin Park, Sora Jeon, Mitsuyoshi Hirokawa, Chan Kwon Jung
Endocrinology and Metabolism.2024; 39(3): 468. CrossRef
Isolated IgG4-related disease of terminal ileum: Report of a rare case and review of literature
Subham Bhowmik, Hemanga K. Bhattacharjee, Joyner Abraham, Raju Sharma, Prasenjit Das
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Suvendu Maji, Jayesh kumar Jha, Vikram Chaturvedi
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Bei Ji, Lili Qiao, Wei Zhai
Digestive Diseases and Sciences.2023; 68(3): 791. CrossRef
IgG4-related diseases of the digestive tract
J.-Matthias Löhr, Miroslav Vujasinovic, Jonas Rosendahl, John H. Stone, Ulrich Beuers
Nature Reviews Gastroenterology & Hepatology.2022; 19(3): 185. CrossRef
Clinicopathological characteristics of gastric IgG4‐related disease: Systematic scoping review
Haruki Sawada, Torrey Czech, Krixie Silangcruz, Landon Kozai, Adham Obeidat, Eric Andrew Wien, Midori Filiz Nishimura, Asami Nishikori, Yasuharu Sato, Yoshito Nishimura
Journal of Gastroenterology and Hepatology.2022; 37(10): 1865. CrossRef
Utility of gastric biopsy in diagnosing IgG4‐related gastrointestinal disease
Kaori Uchino, Kenji Notohara, Takeshi Uehara, Yasuhiro Kuraishi, Junya Itakura, Akihiro Matsukawa
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Original Articles

Molecular and Clinicopathological Features of Gastrointestinal Stromal Tumors in Vietnamese Patients: Quoc Dat Ngo, Quoc Thang Pham, Dang Anh Thu Phan, Anh Vu Hoang, Thi Ngoc Ha Hua, Sao Trung Nguyen; J Pathol Transl Med. 2019;53(6):361-368. Published online September 16, 2019; DOI: https://doi.org/10.4132/jptm.2019.08.27

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Abstract PDF Supplementary Material

Background
Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal neoplasms of the gastrointestinal tract. Management of GIST patients is currently based on clinicopathological features and associated genetic changes. However, the detailed characteristics and molecular genetic features of GISTs have not yet been described in the Vietnamese population.
Methods
We first identified 155 patients with primary GIST who underwent surgery with primary curative intent between 2011 and 2014 at University Medical Center at Ho Chi Minh City, Vietnam. We evaluated the clinicopathological features and immunohistochemical reactivity to p53 and Ki-67 in these patients. Additionally, KIT genotyping was performed in 100 cases.
Results
The largest proportion of GISTs was classified as high-risk (43.2%). Of the 155 GISTs, 52 (33.5%) were positive for Ki-67, and 58 (37.4%) were positive for p53. The expression of Ki-67 and p53 were correlated with mitotic rate, tumor size, risk assessment, and tumor stage. Out of 100 GIST cases, KIT mutation was found in 68%, of which 62 (91.2%) were found in exon 11, two (2.9%) in exon 9, and four (5.8%) in exon 17. No mutation in exon 13 was identified. Additionally, KIT mutations did not correlate with any clinicopathological features.
Conclusions
The expression of Ki-67 and p53 were associated with high-risk tumors. Mutations in exon 11 were the most commonly found, followed by exon 17 and exon 9. Additionally, KIT mutation status was not correlated with any recognized clinicopathological features.

Citations

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Ki67 for evaluating the prognosis of gastrointestinal stromal tumors: A systematic review and meta‑analysis
Ji Li, An-Ran Wang, Xiao-Dong Chen, Hong Pan, Shi-Qiang Li
Oncology Letters.2022;[Epub] CrossRef
Endoscopic ultrasound‐guided fine‐needle aspiration cytology in the diagnosis of the gastrointestinal stromal tumor of the stomach
José‐Fernando Val‐Bernal, Elena Yllera, María Moris, Ihab Abdulkader Nallib, Angel Vázquez‐Boquete, María Martino
Diagnostic Cytopathology.2020; 48(9): 833. CrossRef

Prognostic Impact of Fusobacterium nucleatum Depends on Combined Tumor Location and Microsatellite Instability Status in Stage II/III Colorectal Cancers Treated with Adjuvant Chemotherapy: Hyeon Jeong Oh, Jung Ho Kim, Jeong Mo Bae, Hyun Jung Kim, Nam-Yun Cho, Gyeong Hoon Kang; J Pathol Transl Med. 2019;53(1):40-49. Published online December 26, 2018; DOI: https://doi.org/10.4132/jptm.2018.11.29

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Abstract PDF Supplementary Material

Background
This study aimed to investigate the prognostic impact of intratumoral Fusobacterium nucleatum in colorectal cancer (CRC) treated with adjuvant chemotherapy.
Methods
F. nucleatumDNA was quantitatively measured in a total of 593 CRC tissues retrospectively collectedfrom surgically resected specimens of stage III or high-risk stage II CRC patients who had receivedcurative surgery and subsequent oxaliplatin-based adjuvant chemotherapy (either FOLFOXor CAPOX). Each case was classified into one of the three categories: F. nucleatum–high, –low, or –negative.
Results
No significant differences in survival were observed between the F.nucleatum–high and –low/negative groups in the 593 CRCs (p = .671). Subgroup analyses accordingto tumor location demonstrated that disease-free survival was significantly better in F.nucleatum–high than in –low/negative patients with non-sigmoid colon cancer (including cecal,ascending, transverse, and descending colon cancers; n = 219; log-rank p = .026). In multivariateanalysis, F. nucleatum was determined to be an independent prognostic factor in non-sigmoidcolon cancers (hazard ratio, 0.42; 95% confidence interval, 0.18 to 0.97; p = .043). Furthermore,the favorable prognostic effect of F. nucleatum–high was observed only in a non-microsatellite instability-high (non-MSI-high) subset of non-sigmoid colon cancers (log-rank p = 0.014), but not ina MSI-high subset (log-rank p = 0.844), suggesting that the combined status of tumor locationand MSI may be a critical factor for different prognostic impacts of F. nucleatum in CRCs treatedwith adjuvant chemotherapy.
Conclusions
Intratumoral F. nucleatum load is a potential prognosticfactor in a non-MSI-high/non-sigmoid/non-rectal cancer subset of stage II/III CRCs treatedwith oxaliplatin-based adjuvant chemotherapy.

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Case Study

Perivascular Epithelioid Cell Tumor in the Stomach: Sun Ah Shin, Jiwoon Choi, Kyung Chul Moon, Woo Ho Kim; J Pathol Transl Med. 2017;51(4):428-432. Published online April 4, 2017; DOI: https://doi.org/10.4132/jptm.2016.09.16

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Abstract PDF

Perivascular epithelioid cell tumors or PEComas can arise in any location in the body. However, a limited number of cases of gastric PEComa have been reported. We present two cases of gastric PEComas. The first case involved a 62-year-old woman who presented with a 4.2 cm gastric subepithelial mass in the prepyloric antrum, and the second case involved a 67-year-old man with a 5.0 cm mass slightly below the gastroesophageal junction. Microscopic examination revealed that both tumors were composed of perivascular epithelioid cells that were immunoreactive for melanocytic and smooth muscle markers. Prior to surgery, the clinical impression of both tumors was gastrointestinal stromal tumor (GIST), and the second case was erroneously diagnosed as GIST even after microscopic examination. Although gastric PEComa is a very rare neoplasm, it should be considered in the differential diagnosis of gastric submucosal lesions.

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Original Articles

PHH3 as an Ancillary Mitotic Marker in Gastrointestinal Stromal Tumors: Yooju Shin, Jiyeon Hyeon, Boram Lee, Sang Yun Ha, Min Eui Hong, In Gu Do, Kyoung-Mee Kim; J Pathol Transl Med. 2015;49(1):23-29. Published online January 15, 2015; DOI: https://doi.org/10.4132/jptm.2014.10.08

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Abstract PDF

Background
Counting mitoses is subjective and time-consuming. The adjunctive diagnostic utility of a recently reported mitotic marker, phosphohistone H3 (PHH3), was investigated in gastrointestinal stromal tumors (GISTs). Methods: We reviewed 77 GISTs for several proliferative indices. These included the mitotic count per 50 high power fields (HPFs), the immunohistochemical Ki- 67 labeling index and the immunohistochemical PHH3 mitotic index (MI). For comparison, Spearman’s rank correlation and interclass correlation coefficient were used. Results: Mitotic counts ranged from 0–138 (mean, 7.57±2.34) and the PHH3 MI ranged from 0–126 per 50 HPFs (mean, 9.61±2.27). We found a positive correlation between mitotic counts and PHH3 MI (r=0.810, p<.001). The inter-observer correlation coefficient for three participants was 0.975 for mitotic counts and 0.940 for the PHH3 MI. When using the PHH3 MI instead of mitotic counts in the Armed Forces Institute of Pathology (AFIP) stratification criteria, 10 cases were reclassified. In one patient with a mitotic count of 2 and a PHH3 MI of 6 per 50 HPFs, distant metastasis occurred. Conclusions: In GISTs, the PHH3 MI correlated adequately with mitotic counts and can be used as a useful adjunctive to count mitotic figures efficiently.

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A retrospective study on expression and clinical significance of PHH3, Ki67 and P53 in bladder exophytic papillary urothelial neoplasms
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Phosphohistone H3 (PHH3) as a surrogate of mitotic figure count for grading in meningiomas: a comparison of PHH3 (S10) versus PHH3 (S28) antibodies
Napaporn Puripat, Kongsak Loharamtaweethong
Virchows Archiv.2019; 474(1): 87. CrossRef
Gastrointestinal Stromal Tumors Risk Stratification Utilizing Phospho-Histone H3 Evaluated by Manual Counting and Computer-Assisted Image Analysis
Cao Jin, Yan Huang, Mansoor Nasim, Yihe Yang, Lili Lee
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The utility of phosphohistone H3 in early prediction of benign and borderline phyllodes tumor recurrence
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Tumor Digital Masking Allows Precise Patient Triaging: A Study Based on Ki-67 Scoring in Gastrointestinal Stromal Tumors
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The mitosis‐specific marker phosphohistone‐H3 (PHH3) is an independent prognosticator in uterine smooth muscle tumours: an outcome‐based study
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Update on the Proposal for Creating a Guideline for Cancer Registration of the Gastrointestinal Tumors (I-2): Eun Sun Jung, Yun Kyung Kang, Mee-Yon Cho, Joon Mee Kim, Won Ae Lee, Hee Eun Lee, Sunhoo Park, Jin Hee Sohn, So-Young Jin; Korean J Pathol. 2012;46(5):443-453. Published online October 25, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.5.443

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Abstract PDF

Background

Cancer registries play a fundamental role in cancer control and multicenter collaborative research. Recently, the need for reassessment of cancer registry criteria has arisen due to the newly released 2010 World Health Organization (WHO) classification. Accordingly, development of new coding guidelines for cancer is necessary to improve the quality of cancer registries, as well as to prevent conflicts that may arise when seeking medical insurance compensation.

Methods

With funding from the Management Center for Health Promotion, 35 members of the Gastrointestinal Pathology Study Group and the Cancer Registration Committee of the Korean Society of Pathologists (KSP) participated in a second workshop for gastrointestinal tumor registration in Korea.

Results

The topics of gastric epithelial tumor, colonic intramucosal carcinoma, neuroendocrine tumor (NET), gastrointestinal stromal tumor (GIST) and appendiceal mucinous tumor were discussed for new coding guidelines. A survey was then conducted among 208 members of the KSP for a consensus of the guidelines proposed in the workshop.

Conclusions

Although a few issues were set aside for further discussion, such as coding for non-gastric GIST and some types of NET, the members agreed upon most of the proposed guidelines. Therefore, we suggest using the newly revised International Classification of Diseases for Oncology, 3rd edition (ICD-O-3) coding guidelines for registering gastrointestinal tumors in Korea.

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Review

CpG Island Hypermethylation in Gastric Carcinoma and Its Premalignant Lesions: Gyeong Hoon Kang; Korean J Pathol. 2012;46(1):1-9. Published online February 23, 2012; DOI: https://doi.org/10.4132/KoreanJPathol.2012.46.1.1

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Abstract PDF

Gastric cancers arise through a multistep process characterized by the progressive accumulation of molecular alterations in which genetic and epigenetic mechanisms have been implicated. Gastric cancer is one of the human malignancies in which aberrant promoter CpG island hypermethylation is frequently found. Helicobacter pylori and Epstein-Barr virus, which are known carcinogens for gastric cancer, are closely associated with enhanced hypermethylation of CpG island loci in gastric non-neoplastic epithelial cells and cancer cells, respectively. Aberrant CpG island hypermethylation occurs early in the multistep cascade of gastric carcinogenesis and tends to increase with the step-wise progression of the lesion. Approximately 400 genes that are actively expressed in normal gastric epithelial cells are estimated to be inactivated in gastric cancers as a result of promoter CpG island hypermethylation. In this review, a variety of information is summarized regarding CpG island hypermethylation in gastric cancer.

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Original Articles

An Approach to Diagnosing Gastrointestinal Stromal Tumors Using Immunohistochemistry of c-kit and PDGFRA with Molecular Analysis.: Jeong Shik Kim, Jae Hoon Kim, Hyun Jin Oh, In Soo Suh, Jong Gwang Kim, Byung Wook Kang, Wan Sik Yu, Ho Young Chung, Han Ik Bae; Korean J Pathol. 2010;44(2):173-178.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.173

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Abstract PDF: BACKGROUND
Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors in the gastrointestinal tract. Recently, many methods for the diagnosis of GIST have been developed including molecular diagnosis.
METHODS
We selected 90 cases of GIST that had presented at Kyungpook National University Hospital between 1998 and 2007. Tissue microarrays were made using core areas of tumor tissues. Immunohistochemical staining for c-kit, protein kinase C-theta, and platelet-derived growth factor receptor alpha (PDGFRA) was done. Direct sequencing of hot spot exonal areas for c-kit and PDGFRA were done using extracted DNAs of all 90 paraffin block tissues.
RESULTS
Among the 90 cases, 83.3% (75/90) were c-kit positive, 16.6% (15/90) were c-kit negative, 93.3% (84/90) were PDGFRA positive, and 6.6% (6/90) cases were PDGFRA negative. Fifteen cases of c-kit negative GIST included 1 case of PDGFRA negative and 5 cases of PDGFRA negative GIST were ckit positive. The one case in which both c-kit and PDGFRA were negative, showed a c-kit mutation in exon 11.
CONCLUSIONS
Combined immunohistochemical staining of c-kit, discovered on GIST 1 (DOG1) and PDGFRA is helpful for the diagnosis of GIST. When all staining tests are negative for immunoreactivity, c-kit mutation analysis for exon 11, 9 should be done. Genotyping of kit and PDGFRA do not need to be examined initially, if it is only for the diagnosis of GIST.

Histopathological Evaluation of Pediatric Intestinal Pseudo-Obstruction: Quantitative Morphometric Analysis of Pathological Changes in the Enteric Nervous System.: Hyung Kyung Kim, Harin Cheong, Hanna Kang, Ji Yoon Bae, Dong Eun Song, Min Sun Cho, Sun Hee Sung, Woon Sup Han, Heasoo Koo; Korean J Pathol. 2010;44(2):162-172.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.162

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Abstract PDF

BACKGROUND
This study was done to obtain comprehensive data on changes in the structural components of the enteric nervous system in pediatric patients with intestinal pseudo-obstruction (IPO). We evaluated routinely processed, in formalin-fixed tissues by quantitative morphometric analysis. In addition, we used formalin-fixed tissue to explore the possibility of using previously proposed diagnostic criteria to evaluate frozen serial sections for intestinal neuronal dysplasia (IND) type B and hypoganglionosis.
METHODS
We analyzed data for 19 IPO cases. Morphometric analysis for quantification of ganglia and ganglion cells (GCs) was done for the myentric and the submucous plexus. In addition, we determined the presence of immature GCs and the distribution of nerve fibers and interstitial cells of Cajal (ICC).
RESULTS
Nine patients showed combined hypoganglionosis, IND, and decreased ICC; others showed various combinations of these. Several morphometric factors were significantly different between patient groups as well as being different than the control group.
CONCLUSIONS
Our pediatric IPO cases showed extensive overlapping of pathological findings. And the findings suggest the utility of using previously proposed morphometrically measured factors in multiple frozen sections as diagnostic criteria for IND type B and hypoganglionosis in formalin-fixed tissue.

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PTEN Immunohistochemistry
Simone Antunes Terra, Pedro Luiz Toledo de Arruda Lourenção,, Maria Aparecida Marchesan Rodrigues
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Challenges in the diagnosis of intestinal neuronal dysplasia type B: A look beyond the number of ganglion cells
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Usefulness of DOG1 Expression in the Diagnosis of Gastrointestinal Stromal Tumors.: Jun Mo Kim, Aeri Kim, Joon Hyuk Choi, Young Kyung Bae; Korean J Pathol. 2010;44(2):141-148.; DOI: https://doi.org/10.4132/KoreanJPathol.2010.44.2.141

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Abstract PDF

BACKGROUND
Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors in the gastrointestinal tract. Expression of KIT protein (CD117) is an important diagnostic criterion of GIST. However, about 5% of GISTs are CD117 negative. Discovered on GIST 1 (DOG1) was introduced recently as a promising marker for GIST. We tested this new antibody in 105 GISTs tissue specimens, including 6 cases of metastatic GISTs, to determine the usefulness of DOG1 expression in the diagnosis of GISTs.
METHODS
We performed immunohistochemical (IHC) staining for DOG1 and CD117 on tissue microarrays that included 70 gastric GISTs, 29 small intestinal GISTs, 6 metastatic GISTs, 14 gastric leiomyomas and 16 gastric schwannomas.
RESULTS
DOG1 was positive in 98.1% (103/105) of GISTs and CD117 was positive in 97.1% (102/105) of GISTs. Only 1 case was negative for both markers. Two (66.7%) out of 3 GISTs tested CD117 negative were tested DOG1 positive. All leiomyomas and schwannomas were negative for both DOG1 and CD117.
CONCLUSIONS
DOG1 was highly expressed in GIST including CD117 negative cases. Adding DOG1 testing to the IHC panel for diagnosing GIST will help to identify GIST patients who are CD117 negative but may otherwise benefit from targeted therapy.

Citations

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Gastrointestinal tract spindle cell tumors with interstitial cells of Cajal: Prevalence excluding gastrointestinal stromal tumors
So Jung Lee, Chung Su Hwang, Ahrong Kim, Kyungbin Kim, Kyung Un Choi
Oncology Letters.2016; 12(2): 1287. CrossRef

Case Reports

Gastrointestinal Stromal Tumor of the Colon Mimicking Inflammatory Fibroid Polyp with a Novel 63 bp c-kit Deletion Mutation: A Case Report.: In Gu Do, Cheol Keun Park, Sung Hyun Yoon, John Goldblum, Kyoung Mee Kim; Korean J Pathol. 2009;43(4):374-377.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.374

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Abstract PDF: Colonic gastrointestinal stromal tumors (GISTs) are rare and behave aggressively compared to GISTs in other parts of the gastrointestinal tract. Therefore, accurate diagnosis of GISTs and their distinction from other mesenchymal tumors is important for proper patient management and follow-up. Herein, we present an unusual case of a colonic GIST mimicking an inflammatory fibroid polyp with a novel 63 bp deletion mutation in exon 11 of the c-kit gene, which has not previously been reported. The tumor consisted of loosely arranged spindle cells and many inflammatory cells scattered throughout the tumor. Immunohistochemically, the tumor cells were focally and weakly positive for c-kit and diffusely positive for CD34, but were negative for PKC-theta, SMA, S-100 protein, ALK-1, and desmin. Our case re-emphasizes the broad morphologic spectrum of GISTs.

Morphological Features of Metastatic Gastrointestinal Stromal Tumors after Gleevec Treatment: Two Cases Report.: Joon Hyuk Choi, Young Kyung Bae, Sun Kyo Song, Hong Jin Kim, Min Chul Shim, Kyung Hee Lee; Korean J Pathol. 2009;43(4):368-373.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.4.368

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Abstract PDF: We report two patients with metastatic gastrointestinal stromal tumors (GISTs) with a focus on the morphological features related to Gleevec treatment. In case 1, a 50-year-old woman presented with a 1.8 cm metastatic GIST in the liver after resection of a gastric GIST. Majority of the metastatic tumor showed fibrosis and hyalinization after 8 weeks of Gleevec treatment. CD117-positive cells were present in approximately 1% of the overall tumor. In case 2, a 2 cm and 14 cm metastatic liver masses were found in a 54-year-old man who had a rectal GIST. After 4 weeks of Gleevec treatment, metastatic tumors showed a decrease in size on CT scan. The metastatic tumors showed a decrease in number of tumor cells. The hemorrhage, cystic changes, necrosis, and fibrosis made up approximately 90% of the tumor. The morphological features related to Gleevec treatment are important for correct diagnosis and evaluation of tumor response and prognosis.

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