Journal of Pathology and Translational Medicine

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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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
Journal of Cancer Research and Therapeutics.2024;[Epub] CrossRef
Great Mimics in Oncology: A Retrospective Study from a Tertiary Care Centre of Eastern India
Suvendu Maji, Jayesh kumar Jha, Vikram Chaturvedi
Indian Journal of Surgical Oncology.2024;[Epub] CrossRef
CGB5, INHBA and TRAJ19 Hold Prognostic Potential as Immune Genes for Patients with Gastric Cancer
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
Pathology International.2021; 71(2): 124. CrossRef

Original Article

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.

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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

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.

Citations

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Unusual paediatric sigmoid perivascular epithelioid cell tumour with regional lymph node metastasis treated using gemcitabine and docetaxel: a case report and literature review
Hsiu-Chung Cheng, Chia-Yu Kuo, Ching-Wen Huang, Hsiang-Hung Shih, Chih-Hung Lin, Jaw-Yuan Wang
Journal of International Medical Research.2021;[Epub] CrossRef
Gastric Perivascular Epithelioid Cell Tumor (PEComa)
Jinghong Xu, Yu Yan, Xueping Xiang, Peter Jiang, Xiangrong Hu, Wenjun Yang
American Journal of Clinical Pathology.2019; 152(2): 221. CrossRef
Robotic wedge resection of a rare gastric perivascular epithelioid cell tumor: A case report
Alessandra Marano, Francesca Maione, Yanghee Woo, Luca Pellegrino, Paolo Geretto, Diego Sasia, Mirella Fortunato, Giulio Fraternali Orcioni, Roberto Priotto, Renato Fasoli, Felice Borghi
World Journal of Clinical Cases.2019; 7(23): 4011. CrossRef

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
Gaoxiu Qi, Jinmeng Liu, Shuqi Tao, Wenyuan Fan, Haoning Zheng, Meihong Wang, Hanchao Yang, Yongting Liu, Huancai Liu, Fenghua Zhou
PeerJ.2023; 11: e15675. CrossRef
Loss of Slfn3 induces a sex-dependent repair vulnerability after 50% bowel resection
Emilie E. Vomhof-DeKrey, Jack T. Lansing, Diane C. Darland, Josey Umthun, Allie D. Stover, Christopher Brown, Marc D. Basson
American Journal of Physiology-Gastrointestinal and Liver Physiology.2021; 320(2): G136. CrossRef
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
International Journal of Surgical Pathology.2019; 27(7): 706. CrossRef
The utility of phosphohistone H3 in early prediction of benign and borderline phyllodes tumor recurrence
AymenM El-Saka, MohamedA Mlees, YomnaA Zamzam
Egyptian Journal of Pathology.2019; 39(2): 402. CrossRef
Identification of Phosphohistone H3 Cutoff Values Corresponding to Original WHO Grades but Distinguishable in Well-Differentiated Gastrointestinal Neuroendocrine Tumors
Min Jeong Kim, Mi Jung Kwon, Ho Suk Kang, Kyung Chan Choi, Eun Sook Nam, Seong Jin Cho, Hye-Rim Park, Soo Kee Min, Jinwon Seo, Ji-Young Choe, Hyoung-Chul Park
BioMed Research International.2018; 2018: 1. CrossRef
Tumor Digital Masking Allows Precise Patient Triaging: A Study Based on Ki-67 Scoring in Gastrointestinal Stromal Tumors
Piotr Lewitowicz, Jaroslaw Matykiewicz, Magdalena Chrapek, Dorota Koziel, Agata Horecka-Lewitowicz, Martyna Gluszek-Osuch, Iwona Wawrzycka, Stanisław Gluszek
Scanning.2018; 2018: 1. CrossRef
The mitosis‐specific marker phosphohistone‐H3 (PHH3) is an independent prognosticator in uterine smooth muscle tumours: an outcome‐based study
Kin‐Long Chow, Ka‐Yu Tse, Ching‐Lung Cheung, Ka‐Wing Wong, Annie N Y Cheung, Richard W C Wong, Alice N H Chan, Nancy W F Yuen, Hextan Y S Ngan, Philip P C Ip
Histopathology.2017; 70(5): 746. CrossRef

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.

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

Citations to this article as recorded by

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.

Malignant Gastrointestinal Stromal Tumor of the Esophagus: A Case Report.: Hae Joung Sul, Kyeong Hee Kim, Dae Young Kang; Korean J Pathol. 2001;35(3):252-255.

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Abstract PDF: Gastrointestinal stromal tumors (GISTs) predominate in the stomach and small intestine but have rarely been documented in the esophagus. We report a rare case of GIST of the esophagus in a 47-year-old woman. Histologically, the tumors showed a combination of solid, myxoid, and perivascular collar-like patterns, with spindle and epithelioid cells. The tumor cells were positive for CD117, CD34, and S-100 protein and negative for desmin and -smooth muscle actin.

Original Article

The Loss of Expression of Caveolin-1 in Gastrointestinal Stromal Tumors.: Eo Jin Kim, Jin Hee Sohn, Min Kyung Kim, Seoung Wan Chae, Hye Seung Lee, Eun Yoon Cho, Woo Ho Kim; Korean J Pathol. 2005;39(5):338-344.

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Abstract PDF: BACKGROUND
The down-regulation of caveolin-1, a putative tumor suppressor gene, has been demonstrated in several types of sarcomas. However, it's not known whether or not the gastrointestinal stromal tumors (GISTs) express caveolin-1. We carried out this study to investigate the caveolin-1 expression in GISTs and to determine the correlation between the clinicopathologic profiles of GISTs and the expression of caveolin-1.
METHODS
One hundred eight cases of formalin-fixed and paraffin-embedded tissues of GISTs were immunohistochemically evaluated for the expression of caveolin-1 by using the tissue-array method. Survival data of 98 cases of primary GISTs was analysed according to the expression status of caveolin-1.
RESULTS
Ninety three cases (86.1%) of 108 GISTs did not express caveolin-1 protein. There was no correlation between the caveolin-1 expression status and any of the clinicopathologic variables, including mitosis (p=0.948) and tumor grade (p=0.334). The expression of caveolin-1 was not correlated with other immunohistochemical marker proteins including, c-kit (p=0.373), CD34 (p=0.437) and SMA (p=0.831). On the univariate analysis, the caveolin-1 expression status (p=0.635) was not a significant predictor of the disease-free survival for GIST patients.
CONCLUSIONS
The results of this study suggest that caveolin-1 might act as a tumor suppressor gene in the GIST oncogenesis, but it has no function as a prognostic marker for disease free survival.

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