Clinicopathological features of Gastrointestinal Stromal Tumors and review of the literature

Abstract

Objective: Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal neoplasias of the gastrointestinal system (GIS). The malignancy potential of GISTs may vary ranging from indolent tumors to progressive malignant tumors. This study aims to define clinicopathological and immunohistochemical features of GISTs diagnosed in our institute with a review of the literature. Method: A total of 28 GIST cases were included in the study. The Hematoxylin&Eosin stained slides of surgical resection materials and cell blocks and immunohistochemistry performed slides were reviewed by a pathologist. The immunohistochemical expression with CD117, DOG-1, CD34, SMA, and S100 was scored between 0 and 3 points according to staining intensity. Descriptive statistics were used in the study. The demographic data, prognostic histopathological, and immunohistochemical findings are evaluated with the literature indications. Result: Eleven of the cases were male and seventeen were female. The age range was 18-88. The most common site of GISTs was the stomach, followed by the small intestine, colorectal region, and, esophagus. Twenty of the tumors were resected surgically, four were endoscopic biopsy material and four were fine-needle aspiration biopsies. The tumor size in measurable materials ranged from 0,2 to 22 cm. The mitotic count in 50 HPF ranges from 0 to 10. Seven of the GISTs were high grade and the remaining 21 were low grade. The majority of the cases were composed of spindle cells, 3 were epithelioid and 3 were the mixed type with spindle and epitheloid cells. Conclusion: A variety of criteria has been proposed to estimate the malignancy potential of GISTs and predict prognosis but definite prognostic criteria remain uncertain. Further studies with larger series of GISTs consisting of different types of biopsy materials may help define criteria to predict prognosis precisely.

Keywords

• gastrointestinal stromal tumors
• CD117
• DOG-1
• CD34
• prognosis

Gastrointestinal Stromal Tümörlerin Klinikopatolojik Özellikleri ve Literatürün Gözden Geçirilmesi: Tek Merkez Deneyimi

Abstract

Amaç: Gastrointestinal stromal tümörler (GİST) gastrointestinal sistemin en sık görülen mezenşimal neoplazileridir. GİST’lerin malignite potansiyeli indolen tümörlerden progresif malign tümörlere kadar değişken olabilir. Bu çalışmada merkezimizde tanı almış GİST’lerin klinikopatolojik ve immünohistokimyasal özelliklerini literatür eşliğinde gözden geçirmek amaçlanmıştır. Gereç ve Yöntem: Toplam 28 GİST olgusu çalışmaya dahil edilmiştir. Cerrahi rezeksiyon materyalleri ile hücre bloklarından hazırlanan Hematoksilen&Eozin boyalı preparatlar ile immünohistokimya uygulanmış preparatlar patoloji uzmanı tarafından değerlendirilmiştir. CD117, DOG-1, CD34, SMA ve S100 immünohistokimyasal ekspresyonları boyanma yoğunluğuna göre 0-3 puan arasında skorlanmıştır. Çalışmada deskriptif istatistikler kullanılmıştır. Demografik bulgular, prognostik histopatolojik ve immünohistokimyasal sonuçlar literatür eşliğinde değerlendirilmiştir. Bulgular: Olguların 11’i erkek, 7’si kadındı. Yaş aralığı 18-88 arasındaydı. GİST’ler için en sık görülen lokasyon mide olup bunu ince barsak, kolorektal bölge ve özofagus takip etmekteydi. Tümörlerin 20’si cerrahi olarak çıkarılmış olup, 4’ü endoskopik biyopsi, kalan 4’ü ince iğne aspirasyon biyopsi materyaliydi. Tümör çapı ölçülebilen materyallerde tümör çapı 0,2 ile 22 cm arasındaydı. 50 büyük büyütme alanında mitoz sayısı 0 ile 10 arasındaydı. GİST’lerin 7’si yüksek dereceli, 21’i düşük dereceliydi. Olguların çoğunluğu iğsi hücrelerden oluşmakta olup, 3’ü epiteloid, 3’ü mikst tipteydi. Sonuç: GİST’lerin malignite potansiyelini tahmin etmek için çeşitli kriterler öne sürülmüş olsa da kesin prognostik kriterler belirlenmemiştir. Çeşitli biyopsi materyallerinden oluşan daha büyük vaka serilerinde yapılacak çalışmalar prognozu daha kesin öngörebilecek kriterlerin belirlenmesine yardımcı olacaktır.

Keywords

• Gastrointestinal Stromal Tümör
• CD17
• DOG-1
• CD34
• Prognoz

References

1. 1. Wang MX, Devine C, Segaran N, Ganeshan D. Current update on molecular cytogenetics, diagnosis and management of gastrointestinal stromal tumors. World J Gastroenterol. 2021; 27(41): 7125-7133.
2. 2. Lokuhetty D, White VA, Watanabe R, Cree IA. WHO Classification of Digestive System Tumors. IARC: Lyon,2019.
3. 3. Chantharasamee J, Adashek JJ, Wong K, Eckardt MA, Chmielowski B, Dry S et al. Translating Knowledge About the Immune Microenvironment of Gastrointestinal Stromal Tumors into Effective Clinical Strategies. Curr Treat Options Oncol. 2021;22(1):9.
4. 4. Mantese G. Gastrointestinal stromal tumor: epidemiology, diagnosis, and treatment. Curr Opin Gastroenterol. 2019;35(6):555-559.
5. 5. Ogun GO, Adegoke OO, Rahman A, Egbo OH. Gastrointestinal Stromal Tumours (GIST): A Review of Cases from Nigeria. J Gastrointest Cancer. 2020;51(3):729-737.
6. 6. Landi B, Blay JY, Bonvalot S, Brasseur M, Coindre JM, Emile JF et al. Gastrointestinal stromal tumours (GISTs): French Intergroup Clinical Practice Guidelines for diagnosis, treatments and follow-up (SNFGE, FFCD, GERCOR, UNICANCER, SFCD, SFED, SFRO). Dig Liver Dis. 2019;51(9):1223-1231.
7. 7. Huss s, Pasternack H, Ihle MA, Merkelbach-Bruse S, Heitkötter B, Hartmann W et al. Clinicopathological and molecular features of a large cohort of gastrointestinal stromal tumors (GISTs) and review of the literature: BRAF mutations in KIT/PDGFRA wild-type GISTs are rare events. Hum Pathol. 2017;62:206-214.
8. 8. Hirota S, Isozaki K, Moriyama Y, Hashimoto K, Nishida T, Ishiguro S et al. Gain-of-function mutations of c-kit in human gastrointestinal stromal tumors. Science 1998;279:577-580.

9. 9. Minhas S, Bhalla S, Jauhri M, Ganvir M, Aggarwal S. Clinico-Pathological Characteristics and Mutational Analysis of Gastrointestinal Stromal Tumors from India: A Single Institution Experience. Asian Pac J Cancer Prev. 2019;20(10):3051-3055.
10. 10. Mehren M, Joensuu H. Gastrointestinal Stromal Tumors. J Clin Oncol. 2018;36(2):136-143.
11. 11. Hwang DG, Qian X, Hornick JL. DOG1 antibody is a highly sensitive and specific marker for gastrointestinal stromal tumors in cytology cell blocks. Am J Clin Pathol. 2011;135(3):448-53.
12. 12. Jansen K, Farahi N, Büscheck F, Lennartz M, Luebke AM, Burandt E et al. DOG1 expression is common in human tumors: A tissue microarray study on more than 15,000 tissue samples. Pathol Res Pract. 2021;228:153663.
13. 13. Hirota S, Isozaki K. Pathology of gastrointestinal stromal tumors. Pathol Int . 2006;56(1):1-9.
14. 14. Miettinen M, Lasota J. Gastrointestinal stromal tumors--definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch. 2001;438(1):1-12.
15. 15. Waidhauser J, Bornemann A, Trepel M, Märkl B. Frequency, localization, and types of gastrointestinal stromal tumor-associated neoplasia. World J Gastroenterol. 2019;25(30):4261-4277.
16. 16. Liu X, Qiu H, Zhang P, Feng X, Chen T, Li Y et al. Prognostic role of tumor necrosis in patients undergoing curative resection for gastric gastrointestinal stromal tumor: a multicenter analysis of 740 cases in China. Cancer Med. 2017;6(12):2796-2803.
17. 17. González-Cámpora R, Delgado MD, Amate AH, Gallardo SP, León MS, Beltrán AL. Old and new immunohistochemical markers for the diagnosis of gastrointestinal stromal tumors. Anal Quant Cytol Histol. 2011;33(1):1-11.
18. 18. Wu CE, Tzen CY, Wang SY, Yeh CN. Clinical Diagnosis of Gastrointestinal Stromal Tumor (GIST): From the Molecular Genetic Point of View. Cancers (Basel). 2019;11(5):679.
19. 19. Yi M, Xia L, Zhou Y, Wu X, Zhuang W, Chen Y et al. Prognostic value of tumor necrosis in gastrointestinal stromal tumor: A meta-analysis. Medicine (Baltimore). 2019;98(17):e15338.
20. 20. Costa J, Wesley RA, Glatstein E, Rosenberg SA. The grading of soft tissue sarcomas. Results of a clinicohistopathologic correlation in a series of 163 cases. Cancer. 1984;53(3):530-41.
21. 21. Trojani M, Contesso G, Coindre JM, Rouesse J, Bui NB, Mascarel A et al. Soft-tissue sarcomas of adults; study of pathological prognostic variables and definition of a histopathological grading system. Int J Cancer. 1984;33(1):37-42.
22. 22. Goh B, Chow PKH, Yap WM, Kesavan SM, Song IC, Paul PG et al. Which is the optimal risk stratification system for surgically treated localized primary GIST? Comparison of three contemporary prognostic criteria in 171 tumors and a proposal for a modified Armed Forces Institute of Pathology risk criteria. Ann Surg Oncol. 2008;15(8):2153-63.
23. 23. Bucher P, Taylor S, Villiger P, Morel P, Brundler MA. Are there any prognostic factors for small intestinal stromal tumors? Am J Surg. 2004;187(6):761-6.
24. 24. Yokoi K, Tanaka N, Shoji K, Ishikawa N, Seya T, Horiba K. A study of histopathological assessment criteria for assessing malignancy of gastrointestinal stromal tumor, from a clinical standpoint. J Gastroenterol. 2005;40(5):467-73.
25. 25. Amin MB, Ma CK, Linden MD, Kubus JJ, Zarbo RJ. Prognostic value of proliferating cell nuclear antigen index in gastric stromal tumors. Correlation with mitotic count and clinical outcome. Am J Clin Pathol. 1993;100(4):428-32.
26. 26. Miettinen M, El-Rifai W, Sobin LHL, Lasota J. Evaluation of malignancy and prognosis of gastrointestinal stromal tumors: a review. Hum Pathol. 2002;33(5):478-83.
27. 27. Zhou Y, Hu W, Chen P, Abe M, Shi L, Tan SY et al. Ki67 is a biological marker of malignant risk of gastrointestinal stromal tumors: A systematic review and meta-analysis. Medicine (Baltimore). 2017;96(34):e7911.
28. 28. Ito H, Inoue H, Ryozawa S, Ikeda H, Odaka N, Eleftheriadis N et al. Fine-needle aspiration biopsy and endoscopic ultrasound for pretreatment pathological diagnosis of gastric gastrointestinal stromal tumors. Gastroenterol Res Pract. 2012;2012:139083.
29. 29. Gómez-Peregrina D, García-Valverde A, Pilco-Janeta D, Serrano C. Liquid Biopsy in Gastrointestinal Stromal Tumors: Ready for Prime Time? Curr Treat Options Oncol. 2021;22(4):32.
30. 30. Trindade AJ, Benias PC, Alshelleh M, Bazarbashi AN, Tharian B, Inamdar S et al. Fine-needle biopsy is superior to fine-needle aspiration of suspected gastrointestinal stromal tumors: a large multicenter study. Endosc Int Open. 2019;7(7):E931-E936.