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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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.2025; 21(1): 200. 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.2025; 16(1): 64. CrossRef
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
Compromiso gástrico por enfermedad relacionada con IgG4
Gilberto Jaramillo Trujillo, Oscar Fernando Ruiz, Melissa González Pabón, Maria Andrea Jaramillo Trujillo
Revista Repertorio de Medicina y Cirugía.2024; 33(3): 319. 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.

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A Perivascular Epithelioid Cell Tumor in the Ascending Colon: A Rare Case Involving a Patient With Tuberous Sclerosis
Kai Seharada, Masato Kitazawa, Satoshi Nakamura, Yuta Yamamoto, Yuji Soejima
Cureus.2025;[Epub] CrossRef
Malignant Perivascular Epithelioid Cell Tumor of Ovary: A Rare Case Report
Anuradha Sharma, Reetika Sharma, Jyoti Bala, Monika Sharma
Journal of Mid-life Health.2025; 16(1): 107. CrossRef
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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Potential of Proliferative Markers in Pancreatic Cancer Management: A Systematic Review
Aryan Salahi‐Niri, Paniz Zarand, Negar Mansouri, Parvaneh Rastgou, Omid Yazdani, Romina Esbati, Fatemeh Shojaeian, Behnaz Jahanbin, Zhaleh Mohsenifar, Hamid Asadzadeh Aghdaei, Farid Azmoudeh Ardalan, Seyed Amir Ahmad Safavi‐Naini
Health Science Reports.2025;[Epub] CrossRef
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.

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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.

Original Article

The Expressions of E2F1 and p53 in Gastrointestinal Stromal Tumors and Their Prognostic Significance.: Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye Rim Park, Hyung Sik Shin, Jong Seok Lee, Chan Heun Park, Woon Geon Shin; Korean J Pathol. 2009;43(3):212-220.; DOI: https://doi.org/10.4132/KoreanJPathol.2009.43.3.212

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Abstract PDF

BACKGROUND
E2F1 plays a critical role in the G1-to-S phase transition by inducing various genes that encode S phase-activating proteins and that modulate such diverse cellular functions as DNA synthesis, mitosis and apoptosis. The purpose of this study was to assess the E2F1 expression in relation to the clinicopathologic parameters and other tumor markers in gastrointestinal stromal tumors.
METHODS
Immunohistochemical stainings for obtaining the E2F1, p53, and Ki-67 labeling indices were performed on a tissue microarray of 72 gastrointestinal stromal tumor specimens. The clinicopathologic parameters that were analyzed including the risk grade system by Miettinen et al. and the disease-free survival (DFS) rate.
RESULTS
1) An E2F1 expression was correlated with a larger tumor size, a p53 expression and a shorter period of DFS (p=0.014, p=0.007, and p=0.039). 2) A p53 expression was significantly associated with a high risk grade, a larger tumor size, high mitotic counts and a shorter period of DFS (p=0.003, p=0.044, p<0.001, and p<0.0001). 3) A high-risk grade and the epithelioid type were significantly associated with a shorter period of DFS (p=0.0006 and p=0.0008).
CONCLUSIONS
E2F1, as well as p53, may be a potentially novel independent prognostic factor for predicting a worse outcome for those patients suffering with Gastrointestinal stromal tumors.

Citations

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Comparison of tissue microarray and full section in immunohistochemistry of gastrointestinal stromal tumors
Mi Jung Kwon, Eun Sook Nam, Seong Jin Cho, Hye Rim Park, Hyung Sik Shin, Jun Ho Park, Chan Heun Park, Won Jae Lee
Pathology International.2009; 59(12): 851. CrossRef

Case Reports

Endoscopic Ultrasound-Guided Fine Needle Aspiration Cytology in the Diagnosis of a Gastrointestinal Stromal Tumor of the Stomach: A Case Report.: Lucia Kim, Hyung Gil Kim, Young Chae Chu, In Suh Park, Suk Jin Choi, Jee Young Han, Sun Hee Kim, Don Haeng Lee, Joon Mee Kim; J Pathol Transl Med. 2008;19(2):178-182.; DOI: https://doi.org/10.3338/kjc.2008.19.2.178

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Abstract PDF: We report here a case of a gastrointestinal stromal tumor (GIST) in the stomach that was diagnosed by endoscopic ultrasound-guided fine needle aspiration cytology (EUS-FNA). A 67 year old male patient underwent regular check-ups for five years due to the presence of a submucosal tumor that was found in the fundus of the stomach incidentally. EUS-FNA was performed to evaluate the tumor, which had increased in size from 1cm to 2.8cm. A cytologic smear revealed cohesive sheets or clusters of spindle cells with elongated nuclei. Immunohistochemical staining revealed a strong positive reaction for c-kit and CD34, without any reaction for smooth muscle actin and Ki-67. Therefore, a diagnosis of GIST was made.

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 Articles

Primary Extragastrointestinal Stromal Tumor (EGIST) of the Greater Omentum.: Kyung Un Choi, Jee Yeun Kim, Do Youn Park, Chang Hun Lee, Mee Young Sol, Kang Suek Suh, Jun Woo Lee; Korean J Pathol. 2001;35(4):347-350.

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Abstract PDF: Gastrointestinal stromal tumors (GISTs) were recently defined as spindle cell, epithelioid, or occasionally, pleomorphic mesenchymal tumors of the gastrointestinal tract that express the CD117 (proto-oncogene c-kit protein, stem cell factor receptor), as detected using immunohistochemistry. And they show a new tendency to include the CD117-positive mesenchymal spindle cell or epithelioid neoplasms primary in the omentum and mesentery, and is so termed extragastrointestinal stromal tumors (EGISTs). Omental EGISTs are very rare and similar to their gastrointestinal counterpart. We present a case of primary EGIST of the greater omentum in a 58-year-old man. The resected tumor mass measured 20X15X5 cm and weighed 1,150 g. The cut surface displayed a central cystic change and partial mural nodules. Microscopically, most parts of the tumor were composed of round or polygonal cells, with many of them containing perinuclear vacuoles. The mitotic count was less than one per 50 high-power-fields. Immunohistochemically, the tumor cells were diffusely positive for CD117 and vimentin, and focally for smooth muscle actin and CD34. Ultrastructurally, partially smooth muscle differentiation was confirmed in this case.

Flow Cytometric DNA Analysis of Gastrointestinal Stromal Tumors .: Mee Yon Cho, Soon Won Hong, Soon Hee Jung, Hogeun Kim, Chanil Park; Korean J Pathol. 1997;31(7):608-616.

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Abstract PDF: To evaluate the correlation between the histologic grade and DNA ploidy or proliferation index/S phase fraction (SPF) of gastrointestinal stromal tumors, we performed the DNA analysis using the flow cytometry. Paraffin embedded tissue samples of 57 gastrointestinal stromal tumors were used. The sites of the tumors were: stomach (28), small intestine (23), and large intestine(6). DNA index, proliferative index, and SPF by the flow cytomery were compared with histologic grade. The histologic grade of the gastric tumors were benign (12), borderline (10), and malignant (6). Those of the small intestinal timors were benign (2), borderline (13), and malignant(8). The large intestine were borderline (2), and malignant (4). In stomach, aneuploidy was found in 25.0% of benign, 40.0% of borderline, and 100% of malignant. And there was statistically significant correlation between the histologic grade and ploidy (p < 0.05). By contrast, small and large intestinal tumors showed more frequent aneuploidy in benign than in malignant. The proliferative index was correlated with the histologic grade in gastric tumors (p<0.05), but the SPF was not. In conclusion, the ploidy and proliferative index of gastric tumors are closely correlated to the histologic grade. However, aneuploidy in tumors of the small and large intestine were difficult to predict the malignancy.

Case Report

Synchronous Development of Gastrointestinal Stromal Tumor and Arteriovenous Malformation in the Jejunum: A Case Report.: Sang Hwa Shim, Yoon Hee Han, Ji Eun Kwak, Sun Hee Chang, Hanseong Kim, Je G Chi, Mee Joo; Korean J Pathol. 2008;42(3):185-188.

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Abstract PDF: Vascular malformations associated with neoplasms are extremely rare. Herein we report an extraordinary coincidence of arteriovenous malformation (AVM) and gastrointestinal stromal tumor (GIST) in the jejunum. A 44-year-old woman presented with melena and anemia. Abdominal computed tomography revealed a highly vascularized, strong early arterial enhancing soft tissue mass in the jejunum, which was confirmed by angiography to be an AVM supplied by the distal jejunal branch of the superior mesenteric artery. An emergency operation was performed due to active gastrointestinal (GI) bleeding. The resected jejunum showed a protruding, mostly solid subserosal mass. The mass was confirmed to be a spindle cell type GIST and was intermingled with the AVM located in the overlying submucosa and muscularis propria. To our knowledge, this is the first reported case of an AVM associated with a GIST. This case masqueraded radiologically as an AVM alone and presented clinically with GI bleeding.

Original Article

CD34 Antigen Expression in Gastrointestinal Stromal Tumors.: Sun Hee Sung, Min Sun Cho, Woon Sup Han; Korean J Pathol. 1997;31(11):1166-1171.

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Abstract: Gastrointestinal stromal tumor (GIST) is known as considerable controversal tumor about it's histogenesis, differentiation and biologic behavior. It is traditionally regarded as smooth muscle tumor. To evaluate and clarify the origin of tumor, we performed immunohistochemical study of 23 cases of GIST on CD34 antigen, alpha-smooth muscle actin, S-100 protein, and compared the result with 4 cases of typical leiomyoma of GI tract. The results were as follows. CD34 antigen expression was noted in 21 cases (91.3%) of GIST, while typical leiomyoma was all negative. There were no difference of CD34 expression according to the biologic behavior. However, it's staining pattern was significantly different (p<0.05). Focal or multifocal expression was dominant in benign GIST (58.3%), while diffuse expression was dominant in malignant GIST (80%). Actin was expressed in 5 cases of benign GIST (38.5%) and 1 of malignant GIST (16.7%) focally. All typical leiomyoma showed diffuse strong positivity on alpha-smooth muscle actin. S-100 protein was expressed in 2 cases of benign GIST (16.7%) only. The pattern of CD34 expression was focal in the actin or S-100 protein positive cases. In conclusion CD34 antigen is useful marker in the separation of GIST, from typical smooth muscle tumor. Also it suggest that most GISTs are histogenetically primitive mesenchymal cell origin. However, CD34 expression was unrelated with biologic behavior of GIST.

Case Reports

Mixed Germ Cell-Sex Cord-Stromal Tumor of Non-Gonadoblastoma Type of Ovary: A Case Report.: Kwangseon Min, Byungha Choi, Kyu Rae Kim; Korean J Pathol. 2002;36(1):62-65.

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Abstract PDF: We described a case of mixed germ cell-sex cord-stromal tumor of non-gonadoblastoma type (GCSCT-NG) of the ovary in a 2-year-old girl and compared its histological, immunohistochemical and ultrastructural findings with those of gonadoblastoma. The germ cell component showed an immunopositivity for cytokeratin and epithelial membrane antigen (EMA), and a negative reaction for -inhibin, alpha-fetoprotein (AFP), placental alkaline phosphatase (PLAP), vimentin and CD99. The sex cord elements showed an immunopositivity for cytokeratin, EMA, vimentin and inhibin, but negativity for AFP, PLAP, and CD99. The ultrastructural features showed desmosome-like cell junctions, suggesting spermatocytic differentiation from the primordial germ cells or gonocytes. Immunohistochemical and ultrastructural findings suggested that GCSCT-NG is probably a more differentiated form of mixed germ cell- sex cord-stromal tumor than gonadoblastoma.

Uterine Tumor Resembling Ovarian Sex-Cord Tumor: A Case Report of the Cytologic Finding.: Insun Kim, Eun Mee Han, Woon Yong Jung, Ju Han Lee, Bum Woo Yeom; J Pathol Transl Med. 2003;14(2):71-75.

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Abstract PDF: Uterine stromal tumors with features of ovarian sex-cord differentiation are relatively rare. The neoplasms composed of sex cord-like components in more than 50% of the tumor are classified as group II. We report the cytologic findings of a case of uterine tumor resembling ovarian sex-cord tumor. The cervical smears of a 62-year-old woman with submucosal tumor showed loose aggregates of spindle cells as well as glandular or tubular structures of round cells with a distinct cell membrane and a prominent small nucleolus. Because uterine stromal tumor can have sex cord differentiation, its possibility should be considered in the interpretation of cervical smears.

Original Articles

Immunohistochemical and Ultrastructural Studies of Gastric Smooth Muscle Tumor.: Hyang Mi Ko, Kyung Soo Kim, Jae Hyuk Lee, Woo Sik Juhng, Sang Woo Juhng; Korean J Pathol. 1996;30(3):245-254.

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Abstract PDF: To evaluate the differentiation status of smooth muscle in gastric stromal tumors which were negative for S-100 protein, immunohistochemistry using desmin, actin, myosin and vimentin was performed in 14 cases of gastric smooth muscle tumors. Ultrastructural Examination was also performed. For comparison a case of leiomyoma of the esophagus, a case of the sigmoid colon, 10 cases of the uterus were also examined. The results obtained were as follows. All gastric smooth muscle tumors showed vimentin-positivity. Six of 14 gastric smooth muscle tumors, (5 of 8 leiomyoma and 1 of 4 leiomyosarcoma) showed positivity for desmin, actin, and myosin(42.9%). All esophageal, colonic, and uterine leiomyomas showed diffuse positive reaction for desmin, actin, and myosin. Vimentin positivity was also noted in leiomyoma of the colon and uterus. Ultrastructurally, a few cells in the gastric stromal tumors had scattered microfilaments with dense bodies, subplasmalemmal dense plaques, and micropinocytic vesicles. However, most of the tumor cells did not have any of the ultrastructural features of smooth muscle differentiation. Leiomyomas of the esophagus and uterus showed many cytoplasmic microfilaments with dense bodies. These results suggest that most of the benign and malignant tumor cells of gastric stromal tumors have features of the undifferentiated cells, immunohistochemically as well as ultrastructurally, although a few cells have. It is speculated that most gastric stromal tumors may have lost their smooth muscle differentiation.

Prognosis of Gastrointestinal Stromal Tumors Arising in the Stomach and Small Intestine: A Retrospective Study of 126 Cases from a Single Institution.: Sang Hee Seok, Jun Mo Kim, Jung Min Bae, Se Won Kim, Sang Woon Kim, Sun Kyo Song, Young Kyung Bae; Korean J Pathol. 2008;42(6):335-343.

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Abstract PDF: BACKGROUND
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal tumor in the gastrointestinal tract. As all GISTs have the potential for aggressive clinical behavior, the guidelines for defining the risk of aggressive behavior have been developed and they have been recently revised to precisely assess these patients' prognosis.
METHODS
We analyzed 94 gastric and 32 small intestinal GISTs to compare the patients' survival with the risk stratification (original and revised). RESULTS: For gastric GISTs, 10 mitoses/50HPF was an important cutoff value for the risk of metastasis (1.3% vs 29.4%, respectively), whereas 16.7% of all the small intestinal GISTs with less than 5 mitoses/50HPF metastasized. The small intestinal GISTs showed higher frequencies of mucosal invasion and coagulation necrosis than did the gastric ones. Gastric GISTs had a significantly lower incidence of metastasis/recurrence than did the small intestinal ones in the same risk group. On multivariate analysis, the anatomic location (small intestine), the tumor size (>10 cm) and the mitotic count (>10/50HPF) were independent prognostic factors for a shorter disease-free survival for patients with GISTs. The mitotic count was more important than tumor size for both gastric and small intestinal GISTs.
CONCLUSION
Small intestinal GIST is a more aggressive tumor than gastric GIST and the mitotic count is the most important prognostic factor for GISTs.

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.

Pathological Predictor for Prognosis in Gastrointestinal Mesenchymal Neoplasms.: Mee Yon Cho, Ho Guen Kim, Chan Il Park, Yoo Bock Lee; Korean J Pathol. 1991;25(6):528-538.

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Abstract PDF: To evaluate the prognostic predictor and clinicopathologic characteristics of the gastrointestinal (GI) mesenchymal neoplasm, we examined 75 cases of GI mesenchymal tumors surgically resected during 8 years from 1983 to 1990. Various histological parameters referrable to the prognosis, including the Ag-NORs count, were analysed. Fifty cases were followed-up for 1 to 7 years. Sixteen out of these fifty cases died during this period. The location of tumor was the stomach in 33 cases, the small intestine in 31 cases and the large intestine in 11 cases, and the tumor size was variable from 2 to 35 cm in diameter. The GI mesenchymal neoplasm appeared as an extraluminal mass in 50 cases, an intramural mass in 17 cases, and an intraluminal mass in 8 cases. Each tumor was composed of spindle or epithelioid cells, the former cell type being more common than the latter (45 vs 30 cases). Mitotic count of the tumor showed the best correlationship with the survival of patients(p<0.05), although the tumor size and necrosis appeared to have some values. The Ag-NORs count was variable and was not significantly correlated with the patient's prognosis(p>0.05). These results indicate that the mitotic count is the most valuable pathological predictor for the prognosis in GI mesenchymal neoplasms.

Case Reports

Gastrointestinal Stromal Tumors associated with Neurofibromatosis Type I: A Report of Two Cases.: Joo Heon Kim, Ock Seong In, Seong Kyu Lee, Haing Woon Baik, Seong Ho Kim, Dong Wook Kang, Kyung Hee Kim, Mee Ja Park, Yong Il Kim; Korean J Pathol. 2006;40(2):137-141.

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Abstract PDF: Gastrointestinal stromal tumor (GIST) is the most common non-epithelial neoplasm arising in the gastrointestinal tract, but this tumor is rarely seen in association with type 1 neurofibromatosis (NF-1). We report here on two cases of multiple GISTs of the small intestine that occurred in NF-1 patients. We also analyzed the mutations of c-kit exons 9, 11, 13 and 17 and the plateletderived growth factor receptor-alpha (PDGFRA) exons 12 and 18 in two GIST patients. Histologically, the NF-1-associated GISTs were similar to those of non-the NF-1 GISTs, but they characteristically revealed hyperplastic interstitial cells of Cajal around the GISTs. Immunohistochemically, these tumors showed strong co-expressions of CD117 and CD34. The molecular genetic analysis of the GISTs showed that all of the c-kit and PDGFRA exons that were analyzed in the GISTs of the two patients were the wild-type, suggesting a limited role for the c-kit and PDGFRA mutations in the tumorigenesis of NF-1-associated GISTs.

Gonadoblastoma Overgrown by Dysgerminoma in Women with 46,XX Karyotype: A Report of Two Cases.: Mi Jung Kim, Hee Jeong Ahn, Ji Young Kim, Kyu Rae Kim; Korean J Pathol. 2003;37(1):66-70.

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Abstract PDF: Gonadoblastoma is a neoplasm containing an intimate mixture of germ cells and elements resembling immature granulosa or Sertoli cells. It has been considered as in situ germ cell malignancy that can be overgrown by more malignant germ cell neoplasms. The tumor has been reported to almost exclusively develop in various types of gonadal maldevelopment syndromes containing the Y chromosome, such as in pure or mixed gonadal dysgenesis and, less commonly, in male hermaphroditism. However, occurrences in phenotypically and chromosomally normal, menstruating women are exceptionally rare. We report two cases of gonadoblastoma overgrown by dysgerminoma occurring in the ovaries of phenotypically and cytogenetically normal menstruating women. One of the two cases showed an area composed of granulosa cell tumor-like elements. This type of combination has been very rarely described, and exemplified that gonadoblastoma may progress to sex cord-stromal tumors as well as to the malignant germ cell tumors.

Original Articles

c-kitMutation and Immunohistochemical Expression in Gastrointestinal Stromal Tumors.: Dong Wook Kang, Joo Heon Kim, Dong Hun Kim, Kung Hee Kim, Mee Ja Park, Dae Young Kang; Korean J Pathol. 2003;37(4):246-254.

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Abstract PDF: BACKGROUND
Gastrointestinal stromal tumor (GIST) is the most common non-epithelial neoplasm arising in the gastrointestinal tract. The aim of this study is to investigate the correlation among the clinicopathologic features, presence of c-kit mutation, and immunohistochemical expression of c-kit in 61 cases of GISTs.
METHODS
We divided the GISTs into three groups as benign, boderline and malignant, according to histologic grade. Exon 11 of the c-kit was amplified by PCR and sequenced. We performed immunohistochemical study for CD117, CD34, vimentin, SMA, desmin, and S-100 protein.
RESULTS
Twenty-one cases were diagnosed as benign GISTs, 14 cases as borderline GISTs, and 26 cases as malignant GISTs. The shape, atypia, cellularity, and necrosis showed good correlations with the histologic grades of the GISTs.Mutations of exon 11 of the c-kit were detected in 3 benign GISTs, 4 borderline GISTs, and 13(%) malignant GISTs. Sequence analysis confirmed the deletion mutation (n=16) and the singlebase pair mutation (n=4). The immunohistochemical stainings showed myogenic differentiation(n=20), neurogenic differentiation (n=15), and neither myogenic or neurogenic differentiation(n=34).
CONCLUSIONS
The GIST is the primitive mesenchymal tumor capable of divergent differentiation, and the mutation of the c-kit is a good parameter for the malignant GIST.

A Clinicopathologic Study of 53 Gastrointestinal Mesenchymal Tumors.: Young Kyung Bae, Dong Sug Kim, Mi Jin Gu, Joon Hyuk Choi, Mi Jin Kim, Young Jin Kim, Won Hee Choi, Sun Kyo Song, Koing Bo Kwun; Korean J Pathol. 2000;34(11):909-918.

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Abstract PDF: The gastrointestinal mesenchymal tumors (GIMTs) form a heterogenous group with controversy centering on both the cell of origin and the prediction of clinical behavior. They include a small group of tumors with mature smooth muscle or Schwann cell differentiation and a larger group with inconsistent or no evidence of differentiation. Tumors in the latter are now referred to as gastrointestinal stromal tumors (GISTs). A clinicopathologic and immunohistochemical study was performed on 53 cases of GIMTs to identify cellular differentiation and predictors of clinical behavior. Fifty three cases of GIMTs could be histologically and immunophenotypically divided into three categories, 6 leiomyomas (11.3%), 4 schwannomas (7.6%), and 43 GISTs (81.1%). All leiomyomas (SMA desmin ) and schwannomas (S-100 ) were located in stomach and negative for CD34 and CD117. Thirty nine cases of GISTs were either CD34 (n=26) or CD117 (n=23) immunoreactive. Of these 39 GISTs, 26 were negative for myoid (SMA, desmin) and neural marker (S-100), 10 SMA desmin-S-100-, two SMA-desmin-S-100 , and one SMA desmin-S-100 . Two out of 4 GISTs, which were negative for CD34 and CD117, were immunohistochemically considered leiomyosarcoma (SMA desmin ). GISTs of small intestine had a tendency to be malignant than those of stomach. Pathologic grade of GISTs was not correlated with cellular differentiation. In 29 GISTs with clinical follow-up information, tumor size, mitotic counts, Ki-67 labelling index, tumor necrosis, mucosal invasion, and CD34 expression were significantly correlated with metastasis/recurrence.

A Study of the Correlation between Cellular Proliferating Activities and Prognosis in Gastrointestinal Stromal Tumors .: Hee Jin Chang, Duck Hwan Kim, Sung Sook Pang, Jin Hee Sohn, Jung Il Suh, In Sun Kim, Jong Sang Choi; Korean J Pathol. 1995;29(2):152-169.

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Abstract PDF: Gastrointestinal stromal tumors are notorious for their unpredictable clinical behavior. To assess the cellular proliferating activities, four different methods were used: mitotic count, nucleolar organizer region(AgNOR) staining, immunostaining of proliferating cell nuclear antigen (PCNA) and DNA ploidy were used on 39 cases of gastrointestinal stromal tumors. Additionally, we analysed cellularity, cellular atypism and necrosis. Among 39 cases of gastrointestinal stromal tumors, 11 cases were diagnosed as benign lesions according to clinicopathologic findings. Malignant lesions were arbitrarily classified into low grade(n=ll) and high grade(n=17) on the basis of absence or presence of recurrence, metastasis or tumor-related death during the follow-up period. Numbers of mitosis, AgNORs, PCNA index and DNA ploidy were correlated with grades of tumor and prognosis. Among them, AgNORs counting appeared to be the most useful in predicting prognosis. Numbers of mitosis, PCNA index and DNA ploidy showed varying degrees of overlap among the 3 groups. Among the histological parameters, cellular atypia showed some relationship with the prognosis that others did not reveal.

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