Discussion
Schwannomas are benign peripheral nerve sheath tumors derived from Schwann cells which rarely arise in the soft tissues of the gastrointestinal tract. Schwann cells, discovered by Theodore Ambrose Hubert Schwann almost two centuries ago, are specialized cells dedicated to axon myelinization and nerve trauma repair (7). Schwannomas can arise sporadically or in the context of a few congenital conditions associated with multiple schwannomas, such as familial schwannomatosis, Carney complex syndrome and neurofibromatosis type 2 (8). The tumorigenesis of these soft tissue tumors in type 2 neurofibromatosis, is associated with the loss of the suppressor gene NF2 function, located on chromosome 22q12, which encodes Merlin (moezin-ezrin- radixin like protein, also known as schwannomina) (9). Merlin acts as a scaffold protein indirectly linking F-actin, modulating cell signals that promote cell survival and proliferation through, among others, tyrosine kinase receptors, cell adhesion, small GTPases, mammalian target of rapamycin (mTOR) and PI3K/Akt (10).
Within the gastrointestinal tract, schwannomas are usually found in the gastric corpus and in the right colon. There is a wide age range with peak incidence in the seventh decade and a female predominance for gastric schwannomas (11). Colonic schwannomas have no gender predominance, they are usually located on the cecum, and the macroscopic features vary from polypoid masses to bulging over the serosal surface. Schwann cells are associated with the Auerbach´s and Meissner´s plexus (12). We therefore, hypothesized that if the tumorigenic Schwann cell is in the submucosal plexus the tumor configuration could be polypoid or intraluminal. Additionally, if the tumorigenic Schwann cell is in the myenteric plexus the tumor configuration could be non-luminal.
The presentation of symptoms depends on the location and macroscopic configuration of the tumor. Clinical presentation of schwannoma as a polypoid intraluminal mass is rare, and this macroscopic configuration tends to produce lower gastrointestinal bleeding, or obstruction symptoms (13). Other symptoms such as vague abdominal pain or even the clinical presentation of an incidentally gastrointestinal mass detected by radiological imaging, have also been reported in gastrointestinal schwannoma cases (14,15). Presurgical diagnosis is the exception and not the rule, and just a few cases have been diagnosed in pre-surgical specimens. The rarity of the tumor in the gastrointestinal tract, the depth of the tissue obtained through the endoscopic procedure, submucosal location and confounding biopsy factors such as ulceration and severe inflammatory infiltrate hinder a precise diagnosis in biopsy specimens. In the diagnostic work-up of a mesenchymal mucosal-submucosal gastrointestinal lesion, there is a wide differential diagnosis (16). There were not histopathological criteria for malignancy, gastrointestinal stromal tumor (GIST), was ruled out with the negativity of KIT, DOG1 and CD34, as well as muscular tumors due to negativity of Desmin and SMA. The strong nuclear and cytoplasmic positivity for S100 protein, narrowed the differential diagnosis in this case. The morphology was not typical for Clear Cell Sarcoma Like Gastrointestinal Tumor, usually these kinds of tumors are negative for GFAP (17), and positive for neuroendocrine markers (18). The benign morphology, the combined positivity for S100, SOX10 and GFAP after ruling out other mesenchymal tumors, favored the diagnosis of schwannoma.
Bibliography
1. Bai Y, Peng J, Gao J, Zou D-W, Li Z-S. Epidemiology of lower gastrointestinal bleeding in China: single-center series and systematic analysis of Chinese literature with 53,951 patients. J Gastroenterol Hepatol. 2011;26(4):678–82. doi: 10.1111/j.1440-1746.2010.06586.x.
2. Gustafsson BI, Siddique L, Chan A, Dong M, Drozdov I, Kidd M, et al. Uncommon cancers of the small intestine, appendix and colon: an analysis of SEER 1973-2004, and current diagnosis and therapy. Int J Oncol. 2008;33(6):1121–31. PMID: 19020744
3. Charville GW, Longacre TA. Surgical Pathology of Gastrointestinal Stromal Tumors: Practical Implications of Morphologic and Molecular Heterogeneity for Precision Medicine. Adv Anat Pathol. 2017;24(6):336–53. doi: 10.1097/PAP.0000000000000166.
4. Chintanaboina J, Clarke K. Case of colonic mucosal Schwann cell hamartoma and review of literature on unusual colonic polyps. BMJ Case Rep. 2018; bcr2018224931.
5. van Wyk AC, van Zyl H, Rigby J. Colonic perineurioma (benign fibroblastic polyp): case report and review of the literature. Diagn Pathol. 2018;13(1):16. doi: 10.1136/bcr-2018-224931.
6. Rawal G, Zaheer S, Ahluwalia C, Dhawan I. Malignant peripheral nerve sheath tumor of the transverse colon with peritoneal metastasis: a case report. J Med Case Reports. 2019;13(1):15. doi: 10.1186/s13256-018-1896-4.
7. Sonig A, Gandhi V, Nanda A. From the cell of Schwann to schwannoma–a century’s fruition. World Neurosurg. 2014;82(5):906–11. doi: 10.1016/j.wneu.2014.05.038.
8. Carroll SL, Ratner N. How does the Schwann cell lineage form tumors in NF1?. Glia. 2008;56(14):1590–605. doi: 10.1002/glia.20776.
9. Petrilli AM, Fernández-Valle C. Role of Merlin/NF2 inactivation in tumor biology. Oncogene. 2016;35(5):537–48. doi: 10.1038/onc.2015.125.
10. Stamenkovic I, Yu Q. Merlin, a “magic” linker between extracellular cues and intracellular signaling pathways that regulate cell motility, proliferation, and survival. Curr Protein Pept Sci. 2010;11(6):471–84. doi: 10.2174/138920310791824011.
11. Bohlok A, El Khoury M, Bormans A, Galdon MG, Vouche M, El Nakadi I, et al. Schwannoma of the colon and rectum: a systematic literature review. World J Surg Oncol. 2018;16(1):125. doi: 10.1186/s12957-018-1427-1.
12. Tsunoda C, Kato H, Sakamoto T, Yamada R, Mitsumaru A, Yokomizo H, et al. A Case of Benign Schwannoma of the Transverse Colon with Granulation Tissue. Case Rep Gastroenterol. 2009;3(1):116–20. doi: 10.1159/000214837.
13. 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):846–55. doi: 10.1097/00000478-200107000-00002.
14. Goh BKP, Chow PKH, Kesavan S, Yap W-M, Ong H-S, Song I-C, et al. Intraabdominal schwannomas: a single institution experience. J Gastrointest Surg Off J Soc Surg Aliment Tract. 2008;12(4):756–60. doi: 10.1007/s11605-007-0441-3.
15. Uhr A, Singh AP, Munoz J, Aka A, Sion M, Jiang W, et al. Colonic Schwannoma: A Case Study and Literature Review of a Rare Entity and Diagnostic Dilemma. Am Surg. 2016;82(12):1183–6. PMID: 28234182
16. Hirota S. Differential diagnosis of gastrointestinal stromal tumor by histopathology and immunohistochemistry. Transl Gastroenterol Hepatol. 2018;3:27. doi: 10.21037/tgh.2018.04.01.
17. Doyle LA, Hornick JL. Mesenchymal Tumors of the Gastrointestinal Tract Other than GIST. Surg Pathol Clin. 2013;6(3):425–73. doi: 10.1016/j.path.2013.05.003.
18. Wang J, Thway K. Clear cell sarcoma-like tumor of the gastrointestinal tract: an evolving entity. Arch Pathol Lab Med. 2015;139(3):407–12. doi: 10.5858/arpa.2013-0547-RS.