A Colonic Perineurioma

Abstract

Perineurioma is a mesenchymal neoplasm best known in soft-tissue pathology. A colonic perineurioma is a relatively recently described entity and sometimes encountered in specimens from the large intestine, especially distal colon. Without its recognition, a perineurioma can be misdiagnosed as other more common gastrointestinal spindle cell neoplasms. Here, we describe a case of colonic perineurioma with polypoid growth extruding into the intestinal lumen. Case. A woman in her seventh decade of life underwent a follow-up colonoscopy after an uneventful resection of a benign colonic polyp. A previously undetected 6-mm polyp was found in the sigmoid colon and was resected endoscopically. Microscopic examination of the lesion revealed a proliferation of bland spindle cells in the lamina propria mucosae, which were immunohistochemically positive for epithelial membrane antigen, claudin 1, and glucose transporter-1. A colonic perineurioma was diagnosed.

Perineurioma is occasionally encountered in the large intestine, especially distal colon. Many are small intramucosal lesions barely detectable with endoscopy, but some are more conspicuous. Here, we report an example with polypoid growth protruding into the intestinal lumen.

A woman in her 60s underwent follow-up colonoscopy after a prior endoscopic resection of a benign polypoid lesion. A 6-mm sessile polypoid lesion was seen in the sigmoid colon, which was not detected previously (Figure 1A). The lesion was endoscopically resected.

Figure 1.

A colonic perineurioma. (A) Endoscopic image. A colonoscopic examination found a 6-mm sessile polypoid lesion with a smooth surface in the sigmoid colon, suggestive of a submucosal tumor. (B, C) Histological examination. Short spindle cells with bland nuclei are proliferating in the lamina propria mucosae, intimately associated with intestinal crypts with microvesicular cytoplasm and architectural serration and dilation (reminiscent of sessile serrated adenoma/polyp) (hematoxylin and eosin, original magnification ×10 [B], and ×400 [C]). (D) Immunohistochemistry for GLUT1. Spindle cells are positive for GLUT1 (original magnification ×400). GLUT1 indicates glucose transporter-1.

Histological examination revealed a proliferation of short spindle cells with pale cytoplasm and indistinct cell borders, whose nuclei were bland and not wavy. Between spindle cells were intervening delicate collagen fibers, which were positive for Type 4 collagen on immunohistochemistry. The lesion was well-circumscribed and situated in the lamina propria mucosae (Figure 1B and C). Necrosis was absent and mitotic figures not identified. Some intestinal crypts were entrapped in the lesion and had microvesicular cytoplasm and architectural serration and dilation, which were reminiscent of colonic serrated lesions. On immunohistochemistry, spindle cells were negative for smooth muscle actin (SMA), S100, c-kit, or CD34; focally positive for epithelial membrane antigen (EMA); and diffusely strongly positive for claudin 1 and glucose transporter-1 (GLUT1) (Figure 1D). A perineurioma was diagnosed.

Perineuriomas are better known in soft tissue and peripheral nerves, but some examples arise in the large intestine. Their perineural nature can be difficult to appreciate histologically, and Eslami-Varzaneh et al ¹ first reported them as “benign fibroblastic polyps” of the colon. Groisman et al ² revealed their perineural differentiation and now the 2 terms are used interchangeably by many gastrointestinal pathologists.

In gastrointestinal tract, other spindle cell tumors such as gastrointestinal stromal tumor (GIST), Schwannoma, and leiomyoma are more widely known. But, when considering a colonic intramucosal spindle cell lesion, GISTs and Schwannomas are rare diagnoses. Much more realistic are possibilities of ganglioneuroma, perineurioma, and leiomyoma. ³ These entities have more or less characteristic histology and immunohistochemical profile. In short, perineurioma entraps intestinal crypts and immunohistochemically positive for EMA, claudin 1, and GLUT1; ganglioneuroma can entrap crypts but contain S100-positive ganglion cells; leiomyoma does not entrap intestinal crypts and SMA- and desmin-positive. Antibodies against claudin 1 and GLUT1 might not be available in some institutions. While EMA staining could be a key study in this situation, EMA positivity of perineurioma can be weak or absent, thus rendering the diagnosis of perineurioma somewhat moot. It is reported that, with modifications in the antigen-retrieval protocol and use of a kit for signal amplification, most examples of perineurioma would prove EMA-positive. ²

Colonic perineuriomas are known to be associated with serrated crypts,^1,4 though its interpretation has been controversial. It has been suggested^3,4 that the perineurioma might induce epithelial changes or that serrated polyps promote perineural proliferation in the stroma. Two components could be merely coincidental. More recently, it is proposed that they are true mixed epithelial–stromal polyps, involving epithelial–mesenchymal transition. ⁵ BRAF V600E mutation, which is well known in conventional hyperplastic polyps and sessile serrated adenoma/polyps (SSA/P), has been detected in these seemingly composite lesions, both cytogenetically and immunohistochemically,^5-7 supporting the notion that the epithelial components are true serrated lesions. But the exact nature, neoplastic or reactive, of mesenchymal component is still controversial. Also it is not understood whether serrated lesions associated with perineural proliferations have the same precancerous status as conventional serrated lesions. The perineurioma from our case had entrapped crypts with morphological resemblance to those of SSA/P, though falling short of being diagnostic of SSA/P. Our case failed to show immunoreactivity with BRAF V600E mutation–specific antibodies.

Perineurioma, although rare, is a well-established entity in gastrointestinal pathology and, along with its association with serrated lesions, should be widely recognized.