Diagnosis
Diagnosis
Colonic Perineurioma (PN) with Epithelioid Morphology
Discussion
Perineuriomas (PNs) are commonly detected as incidental lesions during screening colonoscopy, typically in adult patients. They usually present as solitary, asymptomatic polyps in the rectosigmoid colon. Histologically, these polyps feature a benign spindle cell proliferation with abundant pale cytoplasm and lack atypia, mitotic figures, or necrosis. PNs are frequently associated with serrated polyps, such as sessile serrated polyps/adenomas or hyperplastic polyps.
On immunohistochemistry, PNs express perineural markers, including epithelial membrane antigen (EMA), GLUT1, and claudin-1; however, EMA staining may be weak and require high magnification for confirmation. This immunoprofile is critical in distinguishing epithelioid PN from other epithelioid or spindle cell neoplasms in the gastrointestinal tract. These include mucosal Schwann cell hamartoma, ganglioneuroma, gastrointestinal stromal tumor (GIST), granular cell tumor, and benign epithelioid nerve sheath tumor.
Schwann cell hamartoma (SCH) is also often detected incidentally on screening colonoscopy in the left colon. Histologically, this lesion presents as a superficial nodular spindle cell proliferation within the lamina propria. It is immunoreactive for S100 and SOX10 but lacks expression of perineural markers such as EMA or GLUT1.
Ganglioneuroma (GN) is another neural lesion distinguishable by the presence of biphasic histology. GN has components of both spindled Schwann cells and scattered ganglion cells. Most colonic ganglioneuromas are sporadic lesions that are single and discovered on screening colonoscopy. However, if they are multiple, they can be associated with multiple endocrine neoplasia type 2b (MEN 2b) and neurofibromatosis type 1 (NF1).
Gastrointestinal stromal tumor (GIST) is the most common mesenchymal neoplasm of the gastrointestinal tract and may exhibit spindle, epithelioid, or mixed spindle-epithelioid morphology. GISTs are extremely rare in the colon and rectum. Unlike PNs, GISTs are typically mural masses involving the wall of the tubular gut and only rarely involve the mucosa or lamina propria. GISTs are positive for CD117 and DOG1.
In 2005, Lewin et al described benign epithelioid nerve sheath tumor (BENST). Similar to PNs these were discovered incidentally on colonoscopy and were seen primarily in the left colon of adults with a mean age of 58.6-years-old. Morphologically, BENST demonstrate epithelioid cells with small bland nuclei, prominent pale pseudonuclear inclusions, and abundant eosinophilic cytoplasm. BENSTs involve the mucosa and submucosa and may extend into the muscularis propria. The cells diffusely express S100 unlike PNs.
Lastly, granular cell tumor (GCT) is a rare, generally benign, neoplasm with probable Schwannian differentiation. Similar to PN, colonic examples of GCT are often discovered as polyps on screening colonoscopy. Histologically, GCT is composed of epithelioid cells with abundant granular eosinophilic cytoplasm, distinct cell borders, and small pyknotic nuclei. The tumor cells may rarely be spindled. The neoplastic cells are highlighted by S100, CD68, and calretinin.
Clinically, colonic PNs are benign with an excellent prognosis post-excision, with no documented risk of malignant transformation or recurrence. The epithelioid variant of PN is not well-described in the literature and may create diagnostic challenges when it mimics other epithelioid mesenchymal subepithelial polyps in the colon. Awareness of this variant’s possible epithelioid morphology, along with careful immunohistochemical assessment, is essential for accurate diagnosis.
References
Ritterhaus AC, et al. Benign gastrointestinal mesenchymal BUMPS: a brief review of some spindle cell polyps with published names. Arch Pathol Lab Med. 2011;135:1311-1319.
Hornick JL, et al. Intestinal perineuriomas: clinicopathological definition of a new anatomic subset in a series of 10 cases. Am J Surg Pathol. 2005;29:859-865.
Hissong E, et al. Epithelial-stromal polyps of the colon are not perineuriomas. Am J Clin Pathol. 2021;1546:109-116.
Salimian KJ, et al. Non-epithelial endoscopic colon polyps: a focus on mesenchymal lesions. Diagnostic Histopathology. 2018;24:493-499.
Papke Jr. DJ, et al. Recent developments in gastroesophageal mesenchyma tumors. Histopathology. 2021;78:171-186.
Lewin MR, et al. Mucosal benign epithelioid nerve sheath tumors. Am J Surg Pathol. 2005;29:1310-1315.
Salimian JK, et al. Non-epithelial endoscopic colon polyps: a focus on mesenchymal lesions. Diagnostic Histopathology. 2018;24:493-499.
Voltaggio L, et al. Polypoid stromal lesions of the intestines. Histopathology. 2015;66:88-101.