Perineurioma of Esophagus: A First Case Report

Abstract

Benign peripheral nerve sheath tumors occur uncommonly in the gastrointestinal (GI) tract. Perineurioma located in the GI tract is an extremely rare entity, and only 14 cases have been reported in colon, 1 in jejunum, and 1 in stomach. However, perineurioma of the esophagus presenting with dysphagia has not been reported before, and we describe, to our knowledge, the first case in the literature. We suggest that localization of such submucosal tumors can be challenging, and injection of the lesion with dye preoperatively can increase the chances of localization and successful resection of such tumors. Perineuriomas should be included in the complete differential diagnosis of GI tumors.

Benign peripheral nerve sheath tumors, including perineuriomas, located in the gastrointestinal (GI) tract are an extremely rare entity, and 16 cases have been reported in colon, in jejunum, and in stomach. However, perineurioma of the esophagus has not been described before, and we describe, to our knowledge, the first case in the literature.

CASE REPORT

A 28-year-old healthy man presented with dysphagia to solid foods and significant odynophagia when swallowing solid foods for 2 months, associated with 10 pound weight loss. The findings of physical examination were unremarkable, and a magnetic resonance imaging of the head and neck demonstrated a submucosal esophageal mass at the level of C7–T1 (Figure 1). The patient then underwent a right-sided open neck exploration, including intraoperative esophagoscopy, but because of the submucosal nature of the lesion, it could not be localized. The neck was reexplored on postoperative day 2 immediately after injection of methylene blue dye to the lesion under sonographic guidance. At that time, the mass was found at the upper one third of the esophagus and was excised. The patient did well postoperatively and reported no further symptoms of dysphagia. The histopathologic findings and pattern of immunoreactivity of the tumor were found to be consistent with benign peripheral nerve sheath tumor, and more specifically perineurioma (Figures 2 and 3). More specifically, specimens of the tumor were composed of spindle-shaped cells with variably storiform whorled and reticular appearance, with striking elongated bipolar cytoplasmic processes and tapered nuclei. Tumor necrosis, nuclear atypia, or pleomorphisms were absent (Figure 2). Immunohistochemically, the tumor cells stained strongly positive for vimentin and weakly positive for smooth muscle actin. The tumor cells showed negative immunoreactivity for muscle-specific actin, desmin, S-100 protein, glial fibrillary acid protein, and c-kit protein. Additional stains show positivity for claudin-1, glucose transporter protein 1, and epithelial membrane antigen, which support perineurial origin of the tumor. Of note, the patient did not have any family history of neurofibromatosis.

FIGURE 1.

Magnetic resonance imaging of the neck (T1 sagittal view) where a fusiform-shaped submucosal mass is identified at the level of C7–T1.

FIGURE 2.

Tumor composed of benign-appearing spindle cells in a loose myxoid stroma with architectural features of perineurial differentiation. Hematoxylin eosin stain (magnification, 400×).

FIGURE 3.

Immunostaining of tumor cells for claudin-1 (magnification, 400×). Additional stains show positivity for claudin-1 and epithelial membrane antigens, which support perineurial origin of the tumor.

DISCUSSION

Benign peripheral nerve sheath tumors occur uncommonly in the GI tract and include ganglioneuromas,¹ neurofibromas, schwannomas,² and perineuriomas. Perineuriomas are uncommon benign peripheral nerve sheath tumors.

The perineurium is composed of concentric layers of perineurial cells, which envelop myelinated and unmyelinated nerve fascicles, and are uncommonly implicated in neoplastic processes. According to the World Health Organization classification of nervous system tumors, perineurioma is a benign tumor of neoplastic perineurial cells.³ Histologically, perineurioma is subclassified as “intraneural” or “extraneural (soft tissue)” if the perineurial cell proliferation is confined within or unassociated with a nerve, respectively, while a sclerosing variant has also been described.⁴ Perineuriomas differ from other peripheral nerve sheath tumors, such as neurofibromas and schwannomas, in their immunohistochemical and/or ultrastructural analysis. The majority of soft tissue perineuriomas arise in the subcutis, whereas a subset occur in deep soft tissue or skin.^3,5 Perineuriomas arising in the GI tract have been described recently,^5–7 and, more specifically, 14 cases have been reported in colon,^5,6 1 in jejunum,⁵ and 1 in stomach⁷ (Table 1). However, perineurioma of the esophagus presenting with dysphagia has not been reported before, and we describe, to our knowledge, the first case in the literature.

TABLE 1.

Perineuriomas of the gastrointestinal tract reported in the literature

Author (No. cases)	Age (yr)	Sex	Site (n)	Indication for resection (n)	Depth (n)	Size (cm)	Staining	Comments
Homick and Fletcher5; case series (10)	35–72	8 F, 2 M	Colon (9), jejunum (1)	Abdominal pain (1); abdominal pain, nausea, and vomiting (1); GI bleeding (1); polyp on screening colonoscopy (6); and NA (1)	Mucosa (8), submucosa (2)	Mucosal lesions: 0.2–0.6. Submucosal lesions: 3 (colon), and 4.5 (jejunum)	EMA (+) (9/10); claudin-1 (+) (4/10); and CD34 (2/10)	The 1 tumor lacking EMA staining showed characteristic ultrastructural features of perineurioma
Zamecnick and Chlumska6; case series (5)	52–77 (average 64.6)	3 F, 2 M	Colon (5)	Polyp on screening colonoscopy (5); and suspected colitis (1)	Mucosa (5)	Mucosal lesions (polyps): 0.2–0.4	EMA (+) (3/5); claudin-1 (+) (4/5); and Glut-1(5/5)	The 2 tumors lacking EMA staining showed characteristic ultrastructural features of perineurioma
Agaimy and Wuensch7; case report	30	1 F	Stomach	Upper GI bleeding	Submucosa	1.5	EMA (+), CD56 (+)	Combined morphologic and immunohistochemical features confirmed a diagnosis of primary perineurioma of the stomach

GI, gastrointestinal; NA, not available; EMA, epithelial membrane antigen; Glut-1, glucose transporter protein 1.

Based on the literature, it seems that GI perineuriomas are most common in middle-aged women (12 of 16, 75%) and usually present as asymptomatic intramucosal lesions, detected during screening colonoscopy as small polyps (11 of 16, 69%). In 2 cases, perineuriomas presented with GI bleeding.^5,7 Only 3 cases (1 in colon, 1 in jejunum, and 1 in stomach) had submucosal location and tended to have larger size (1.5–4.5 cm) and be more symptomatic (Table 1). The diagnosis of perineurioma in our case was based on previously published criteria, including cytoarchitectural features of perineurial differentiation (Figure 2), and immunohistochemical profile of perineurioma, including absence of S-100 staining, weak positive staining for epithelial membrane antigen, and strikingly positive immunoreactivity for claudin-1 (Figure 3), in parallel to other previously reported GI perineuriomas.^5–7 These features distinguish perineurioma from other nerve sheath tumors, such as neurofibromas and schwannomas.³ More specifically, claudin-1 is a relatively new immunohistochemical marker, is an integral membrane protein, and is a component of tight junction strands, which are important for cell-to-cell adhesion in perineurial cells.^3,8 Similar to the 3 previously described submucosal GI perineuriomas, the tumor in our case was relatively large (2 cm) and was symptomatic.^5–7 The lesion had negative margins and was completely excised. Although the chance of recurrence is very small, close follow-up is recommended because of insufficient clinical experience with these tumors.

The presented case is of great interest, because of the extremely low grade of incidence of GI perineuriomas and the fact that this is the first reported case of esophageal submucosal perineurioma. The perineurioma presented with dysphagia and odynophagia and such clinical presentation of GI perineurioma has not been described previously. We also indicate that localization of such submucosal tumors can be challenging and injection of the lesion with methylene blue dye preoperatively can increase the chances of localization and successful resection of such tumors. Perineuriomas should be included in the complete differential diagnosis of GI tumors. Although no recurrence has been described to date with these tumors, close follow-up is recommended in all cases because of lack of experience with these tumors.