Immunohistochemistry and molecular genetics in the differential diagnostics of mesenchymal lesions of gastrointestinal tract

Download PDF Czech version

Authors: Magdaléna Daumová ^1,2; Bohuslava Vaňková ^1,2; Marián Švajdler ^1,2; Michal Michal ¹; Ondřej Daum ^1,2
Authors‘ workplace: Šiklův ústav patologie LF UK a FN Plzeň ¹; Bioptická laboratoř s. r. o., Plzeň ²
Published in: Čes.-slov. Patol., 56, 2020, No. 4, p. 212-220
Category: Reviews Article

Overview

Although, in routine practice, the differential diagnostics of mesenchymal tumors of the gastrointestinal tract is still focused mainly on the correct diagnosis of gastrointestinal stromal tumor and its further therapeutic management based on predictive diagnostics, recent progress in the development of endoscopic techniques has led to increased detection of other mesenchymal lesions, which were previously commonly neglected due to their small size or absence of symptoms requiring surgical exploration. Diagnosis of some of these lesions may be reached based on their histologic pattern alone, while others may be recognized with the use of tissue specific antibodies related to the probable lineage of differentiation of the neoplastic cells. Finally, a subset of tumors, commonly with uncertain lineage of differentiation, is defined by pathognomonic genetic alterations of neoplastic cells. Recognition of such alterations, based either on methods of molecular genetics or immunohistochemical detection of an altered protein product, enables a precise diagnosis in a growing number of these cases. However, regarding the fact that most of these alterations are not unique to a single tumor type, but are often shared by more neoplastic entities, the diagnosis must still be based on a complex diagnostic attitude, reflecting histological, immunohistochemical and molecular genetic features of the investigated tumor.

Keywords:

Gastrointestinal tract – digestive tract – mesenchymal tumors – differential diagnostics – immunohistochemistry – Molecular genetics

Sources

1. Daimaru Y, Kido H, Hashimoto H, Enjoji M. Benign schwannoma of the gastrointestinal tract: a clinicopathologic and immunohistochemical study. Hum Pathol 1988; 19(3): 257-264.

2. Miettinen M, Shekitka KM, Sobin LH. Schwannomas in the colon and rectum: a clinicopathologic and immunohistochemical study of 20 cases. Am J Surg Pathol 2001; 25(7): 846-855.

3. Zámečník M, Mukenšnabl P, Sokol L, Michal M. Perineurial cells and nerve axons in gastrointestinal schwannomas: a similarity with neurofibromas. An immunohistochemical study of eight cases. Cesk Patol 2004; 40(4): 150-153.

4. Le BH, Boyer PJ, Lewis JE, Kapadia SB. Granular cell tumor: immunohistochemical assessment of inhibin-alpha, protein gene product 9.5, S100 protein, CD68, and Ki-67 proliferative index with clinical correlation. Arch Pathol Lab Med 2004; 128(7): 771-775.

5. Pareja F, Brandes AH, Basili T, et al. Loss-of-function mutations in ATP6AP1 and ATP6AP2 in granular cell tumors. Nature communications 2018; 9(1): 3533.

6. Gibson JA, Hornick JL. Mucosal Schwann cell “hamartoma”: clinicopathologic study of 26 neural colorectal polyps distinct from neurofibromas and mucosal neuromas. Am J Surg Pathol 2009; 33(5): 781-787.

7. Pasquini P, Baiocchini A, Falasca L, et al. Mucosal Schwann cell “hamartoma”: a new entity? World J Gastroenterol 2009; 15(18): 2287-2289.

8. Hechtman JF, Harpaz N. Neurogenic polyps of the gastrointestinal tract: a clinicopathologic review with emphasis on differential diagnosis and syndromic associations. Arch Pathol Lab Med 2015; 139(1): 133-139.

9. Rossi S, Gasparotto D, Cacciatore M, et al. Neurofibromin C terminus-specific antibody (clone NFC) is a valuable tool for the identification of NF1-inactivated GISTs. Mod Pathol 2018; 31(1): 160-168.

10. Green C, Spagnolo DV, Robbins PD, Fermoyle S, Wong DD. Clear cell sarcoma of the gastrointestinal tract and malignant gastrointestinal neuroectodermal tumour: distinct or related entities? A review. Pathology (Phila) 2018; 50(5): 490-498.

11. Hollowood K, Stamp G, Zouvani I, Fletcher CD. Extranodal follicular dendritic cell sarcoma of the gastrointestinal tract. Morphologic, immunohistochemical and ultrastructural analysis of two cases. Am J Clin Pathol 1995; 103(1): 90-97.

12. Griffin GK, Sholl LM, Lindeman NI, Fletcher CD, Hornick JL. Targeted genomic sequencing of follicular dendritic cell sarcoma reveals recurrent alterations in NF-kappaB regulatory genes. Mod Pathol 2016; 29(1): 67-74.

13. Andersen EF, Paxton CN, O’Malley DP, et al. Genomic analysis of follicular dendritic cell sarcoma by molecular inversion probe array reveals tumor suppressor-driven biology. Mod Pathol 2017; 30(9): 1321-1334.

14. Coffin CM, Watterson J, Priest JR, Dehner LP. Extrapulmonary inflammatory myofibroblastic tumor (inflammatory pseudotumor). A clinicopathologic and immunohistochemical study of 84 cases. Am J Surg Pathol 1995; 19(8): 859-872.

15. Coffin CM, Humphrey PA, Dehner LP. Extrapulmonary inflammatory myofibroblastic tumor: a clinical and pathological survey. Sem Diagn Pathol 1998; 15(2): 85-101.

16. Bridge JA, Kanamori M, Ma Z, et al. Fusion of the ALK gene to the clathrin heavy chain gene, CLTC, in inflammatory myofibroblastic tumor. Am J Pathol 2001; 159(2): 411-415.

17. Lawrence B, Perez-Atayde A, Hibbard MK, et al. TPM3-ALK and TPM4-ALK oncogenes in inflammatory myofibroblastic tumors. Am J Pathol 2000; 157(2): 377-384.

18. Milne AN, Sweeney KJ, O’Riordain DS, et al. Inflammatory myofibroblastic tumor with ALK/TPM3 fusion presenting as ileocolic intussusception: an unusual presentation of an unusual neoplasm. Hum Pathol 2006; 37(1): 112-116.

19. Cole B, Zhou H, McAllister N, Afify Z, Coffin CM. Inflammatory myofibroblastic tumor with thrombocytosis and a unique chromosomal translocation with ALK rearrangement. Arch Pathol Lab Med 2006; 130(7): 1042-1045.

20. Ma Z, Hill DA, Collins MH, et al. Fusion of ALK to the Ran-binding protein 2 (RANBP2) gene in inflammatory myofibroblastic tumor. Genes Chromosomes Cancer 2003; 37(1): 98-105.

21. Panagopoulos I, Nilsson T, Domanski HA, et al. Fusion of the SEC31L1 and ALK genes in an inflammatory myofibroblastic tumor. Int J Cancer 2006; 118(5): 1181-1186.

22. Cools J, Wlodarska I, Somers R, et al. Identification of novel fusion partners of ALK, the anaplastic lymphoma kinase, in anaplastic large-cell lymphoma and inflammatory myofibroblastic tumor. Genes Chromosomes Cancer 2002; 34(4): 354-362.

23. Yamamoto H, Yoshida A, Taguchi K, et al. ALK, ROS1 and NTRK3 gene rearrangements in inflammatory myofibroblastic tumours. Histopathology 2016; 69(1): 72-83.

24. Mosquera JM, Sboner A, Zhang L, et al. Novel MIR143-NOTCH fusions in benign and malignant glomus tumors. Genes Chromosomes Cancer 2013; 52(11): 1075-1087.

25. Yoshida A, Tsuta K, Ohno M, et al. STAT6 immunohistochemistry is helpful in the diagnosis of solitary fibrous tumors. Am J Surg Pathol 2014; 38(4): 552-559.

26. McCluggage WG, Sumathi VP, Maxwell P. CD10 is a sensitive and diagnostically useful immunohistochemical marker of normal endometrial stroma and of endometrial stromal neoplasms. Histopathology 2001; 39(3): 273-278.

27. Choi YJ, Jung SH, Kim MS, et al. Genomic landscape of endometrial stromal sarcoma of uterus. Oncotarget 2015; 6(32): 33319-33328.

28. McCluggage WG, Lee CH. YWHAE-NUTM2A/B translocated high-grade endometrial stromal sarcoma commonly expresses CD56 and CD99. Int J Gynecol Pathol 2019; 38(6): 528-532.

29. Mehrad M, LaFramboise WA, Lyons MA, Trejo Bittar HE, Yousem SA. Whole-exome sequencing identifies unique mutations and copy number losses in calcifying fibrous tumor of the pleura: report of 3 cases and review of the literature. Hum Pathol 2018; 78): 36-43.

30. Graham RP, Nair AA, Davila JI, et al. Gastroblastoma harbors a recurrent somatic MALAT1-GLI1 fusion gene. Mod Pathol 2017; 30(10): 1443-1452.

31. Schildhaus HU, Cavlar T, Binot E, et al. Inflammatory fibroid polyps harbour mutations in the platelet-derived growth factor receptor alpha (PDGFRA) gene. J Pathol 2008; 216(2): 176-182.

32. Daum O, Hes O, Vaněček T, et al. Vanek’s tumor (inflammatory fibroid polyp). Report of 18 cases and comparison with three cases of original Vanek’s series. Ann Diagn Pathol 2003; 7(6): 337-347.

33. Daum O, Hatlová J, Mandys V, et al. Comparison of morphological, immunohistochemical, and molecular genetic features of inflammatory fibroid polyps (Vanek’s tumors). Virchows Arch 2010; 456(5): 491-497.

34. Su HA, Yen HH, Chen CJ. An update on clinicopathological and molecular features of plexiform fibromyxoma. Canadian journal of gastroenterology & hepatology 2019; 2019: 3960920.

35. Spans L, Fletcher CD, Antonescu CR, et al. Recurrent MALAT1-GLI1 oncogenic fusion and GLI1 up-regulation define a subset of plexiform fibromyxoma. J Pathol 2016; 239(3): 335-343.

36. Banerjee S, Corless CL, Miettinen MM, et al. Loss of the PTCH1 tumor suppressor defines a new subset of plexiform fibromyxoma. Journal of translational medicine 2019; 17(1): 246.

37. Eslami-Varzaneh F, Washington K, Robert ME, et al. Benign fibroblastic polyps of the colon: a histologic, immunohistochemical, and ultrastructural study. Am J Surg Pathol 2004; 28(3): 374-378.

38. Zámečník M, Chlumská A. Perineurioma versus fibroblastic polyp of the colon. Am J Surg Pathol 2006; 30(10): 1337-1339.

39. Agaimy A, Stoehr R, Vieth M, Hartmann A. Benign serrated colorectal fibroblastic polyps/intramucosal perineuriomas are true mixed epithelial-stromal polyps (hybrid hyperplastic polyp/mucosal perineurioma) with frequent BRAF mutations. Am J Surg Pathol 2010; 34(11): 1663-1671.

40. West RB, Corless CL, Chen X, et al. The novel marker, DOG1, is expressed ubiquitously in gastrointestinal stromal tumors irrespective of KIT or PDGFRA mutation status. Am J Pathol 2004; 165(1): 107-113.

41. Novelli M, Rossi S, Rodriguez-Justo M, et al. DOG1 and CD117 are the antibodies of choice in the diagnosis of gastrointestinal stromal tumours. Histopathology 2010; 57(2): 259-270.

42. Iwata J, Fletcher CD. Immunohistochemical detection of cytokeratin and epithelial membrane antigen in leiomyosarcoma: a systematic study of 100 cases. Pathol Int 2000; 50(1): 7-14.

43. Montgomery E, Torbenson MS, Kaushal M, Fisher C, Abraham SC. Beta-catenin immunohistochemistry separates mesenteric fibromatosis from gastrointestinal stromal tumor and sclerosing mesenteritis. Am J Surg Pathol 2002; 26(10): 1296-1301.

44. Ng TL, Gown AM, Barry TS, et al. Nuclear beta-catenin in mesenchymal tumors. Mod Pathol 2005; 18(1): 68-74.

45. Yantiss RK, Spiro IJ, Compton CC, Rosenberg AE. Gastrointestinal stromal tumor versus intra-abdominal fibromatosis of the bowel wall: a clinically important differential diagnosis. Am J Surg Pathol 2000; 24(7): 947-957.

46. Colombo P, Rahal D, Grizzi F, Quagliuolo V, Roncalli M. Localized intra-abdominal fibromatosis of the small bowel mimicking a gastrointestinal stromal tumor: a case report. World J Gastroenterol 2005; 11(33): 5226-5228.

47. Miyoshi Y, Iwao K, Nawa G, et al. Frequent mutations in the beta-catenin gene in desmoid tumors from patients without familial adenomatous polyposis. Oncol Res 1998; 10(11-12): 591-594.

48. Giarola M, Wells D, Mondini P, et al. Mutations of adenomatous polyposis coli (APC) gene are uncommon in sporadic desmoid tumours. Br J Cancer 1998; 78(5): 582-587.

49. Terry J, Saito T, Subramanian S, et al. TLE1 as a diagnostic immunohistochemical marker for synovial sarcoma emerging from gene expression profiling studies. Am J Surg Pathol 2007; 31(2): 240-246.

50. Yamaguchi U, Hasegawa T, Masuda T, et al. Differential diagnosis of gastrointestinal stromal tumor and other spindle cell tumors in the gastrointestinal tract based on immunohistochemical analysis. Virchows Arch 2004; 445(2): 142-150.

51. Wong NA, Shelley-Fraser G. Specificity of DOG1 (K9 clone) and protein kinase C theta (clone 27) as immunohistochemical markers of gastrointestinal stromal tumour. Histopathology 2010; 57(2): 250-258.

52. Dubová M, Daum O, Švajdler M, et al. Jaká je Vaše diagnóza? Téma: DOG1 imunoexprese v měkkotkáňových nádorech. Cesk Patol 2017; 53(4): 183-184 a 188-189.

53. Guillou L, Coindre J, Gallagher G, et al. Detection of the synovial sarcoma translocation t(X;18) (SYT;SSX) in paraffin-embedded tissues using reverse transcriptase-polymerase chain reaction: a reliable and powerful diagnostic tool for pathologists. A molecular analysis of 221 mesenchymal tumors fixed in different fixatives. Hum Pathol 2001; 32(1): 105-112.

54. Lasota J, Jasinski M, Debiec-Rychter M, et al. Detection of the SYT-SSX fusion transcripts in formaldehyde-fixed, paraffin-embedded tissue: a reverse transcription polymerase chain reaction amplification assay useful in the diagnosis of synovial sarcoma. Mod Pathol 1998; 11(7): 626-633.

55. Makhlouf HR, Ahrens W, Agarwal B, et al. Synovial sarcoma of the stomach: a clinicopathologic, immunohistochemical, and molecular genetic study of 10 cases. Am J Surg Pathol 2008; 32(2): 275-281.

56. Nga ME, Wong AS, Wee A, Salto-Tellez M. Cytokeratin expression in gastrointestinal stromal tumours: a word of caution. Histopathology 2002; 40(5): 480-481.

57. Rossi G, Sartori G, Valli R, et al. The value of c-kit mutational analysis in a cytokeratin positive gastrointestinal stromal tumour. J Clin Pathol 2005; 58(9): 991-993.

58. Martland GT, Goodman AJ, Shepherd NA. CD117 expression in oesophageal carcinosarcoma: a potential diagnostic pitfall. Histopathology 2004; 44(1): 77-80.