Abstract

Background: Here, we report a sigmoid mucosal Schwann cell hamartoma as an uncommon entity. Though unexpected, the pathologist should consider this among differential diagnoses and be able to distinguish the microscopic features when examining colorectal biopsies. Finally, we have reviewed the literature for similar cases reported over the past two decades. Case presentation: A 55-year-old woman was found to have a 5 mm sessile polyp during her screening colonoscopy. The microscopic study revealed colonic mucosa with ill-defined proliferation of uniform spindle-shaped cells arranged in a haphazard pattern within the lamina propria. All cells had elongated bland nuclei with eosinophilic cytoplasm and unclear cell borders. Edema and mild lymphoplasmacytic infiltration were noticed in the lamina propria. No nuclear atypia, necrosis, or mitosis was identified. On immunohistochemistry, Schwann cells showed diffuse and strong nuclear and cytoplasmic positivity for S-100 protein. CD117 (C-kit) and desmin were negative. Conclusion: Colorectal MSCH has a benign nature, and the lack of axons and strong immunoreactivity for S-100 protein can help distinguish MSCH from most similar entities.

1. Introduction

Originating from the perineural Schwann cells, colorectal mucosal Schwann cell hamartomas (MSCHs) are classified as nonepithelial tumors and are relatively rare benign tumors. However, over the past years, centers have increasingly been reporting these benign tumors, possibly due to widely used colorectal cancer screening colonoscopies. Here, we are reporting a case of sigmoid MSCH located during a screening colonoscopy. We also review the literature for cases reported over the past two decades.

2. Case Presentation

Clinical Findings: A 55-year-old female with a remote history of HIV infection, status post-HARRT, now with undetectable virus load, was referred for CRC screening.

Gross Features: Colonoscopy showed medium-sized internal hemorrhoids and also a sessile polyp of about 5 mm in the sigmoid colon. (Figure 1-A) The biopsy removed the entire lesion. Computed tomography with intravenous contrast was negative for metastasis or colonic wall thickening.

Histologic Findings: Hematoxylin and eosin stains revealed colonic mucosa with ill-defined proliferation of uniform spindle-shaped cells arranged in a haphazard pattern within the lamina propria. (Figure 1-B) All cells had elongated bland nuclei with eosinophilic cytoplasm and unclear cell borders. Edema and mild lymphoplasmacytic infiltration were noticed in the lamina propria. No nuclear atypia, necrosis, or mitosis was identified. (Figure 1-C).

Immunohistochemical Findings: Schwann cells showed diffuse and strong nuclear and cytoplasmic positivity for S-100 protein. (Figure 1-D) Desmin and CD117 (C-kit) were negative.

Diagnosis: The patient denied any personal or family history suggesting MEN 2B or NF1, including neurofibromatosis, café au lait spots, or adrenal or thyroid diseases. Dermatological examination, laboratory tests, and imaging also found no relevant findings to MEN 2B or NF1. Considering the history and microscopic findings, the diagnosis of the sigmoid colon MSCH was made.

3. Review

Here, we reported a case of an MSCH in a patient with a history of HIV. We also searched PubMed for Mesh and non-Mesh terms related to colorectal mucosal Schwann cell hamartoma. This search found twenty case reports ^{1, 2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20} (Table 1) and two series. ^{21, 22} (Table 2) We did not include studies that solely reported tactile corpuscle-like bodies or neurofibromal polyps in the gastrointestinal mucosa unless an ultimate diagnosis of Schwann cell hamartoma was made.

In 2009, Gibson et al. ²² reported 26 cases of MSCH with 1– 6 mm colorectal sessile polyps, while most were asymptomatic. After their series, several others presented similar entities as single case reports until Li et al. ²¹ published the second series, including 48 MSCH patients.

Histologically, MSCHs comprise uniform spindle cells spreading between the glands or crypts in the lamina propria. Cell borders are unclear, and cells appear bland and have eosinophilic cytoplasm with elongated, tapering, or wavy nuclei. MSCH might occasionally show degenerative atypia (ancient change), but nuclear atypia is uncommon, and mitosis is always absent. Immunohistochemically, cells are positive for S100 protein and negative for GFAP, CD34, EMA, CD117, SMA, CD68, and DOG1. ²³ The differential diagnoses are GIST and colorectal neural lesions, including neurofibromas, schwannomas, neuromas, perineuriomas, granular cell tumors, ganglioneuromas, and benign mucosal epithelioid nerve sheath tumors.

Distinguishing Schwannoma from Schwann cell hamartoma is often challenging, but colonic schwannomas can occur throughout the colon as an intraluminal polypoid mass with or without mural involvement. ²⁴ Histologically, GI schwannomas are relatively well-circumscribed but unencapsulated lesions showing peripheral lymphoid cuff with germinal centers. Conversely, the microscopic study of the present report found a lack of circumscription and crypt entrapment, which is typical of the MSCH polyps. Given their marked propensity for the rectosigmoid colon, much higher prevalence, and discussed histologic differences, MSCH polyps can be differentiated from Schwannomas. Also, MSCHs are generally smaller in size.

Visceral neurofibromas are known to be highly associated with NF1. Considering the rarity of colorectal sporadic neurofibromas, finding any neurofibroma in the colon should raise the suspicion for NF1. Neurofibromas have a heterogeneous cellular composition, including Schwann cells, perineurial-like cells, fibroblasts, and axons. In contrast, the MSCHs depict uniform cytology, comprised of a pure population of Schwann cells with diffuse immunoreactivity for S-100 protein. Also, while all colorectal neurofibromas contain scattered axons, only a small subset of the MSCHs contain these cellular microstructures. ²²

A more recent body of evidence indicates that GISTs are more common than neurofibromas as GI presentations of NF1. ²⁴ Thus, many noted “leiomyomas” in the past literature might have been GISTs. GISTs are positive not only often for S-100 but also characteristically for c-Kit (CD117), distinguishing them from mucosal Schwann cell hamartomas. ¹⁵

The mucosal neuroma is another differential diagnosis, an infrequent entity highly associated with MEN 2B. ²⁵ Histologically, mucosal neuromas consist of hyperplastic bundles of nerve fibers associated with abundant axons. In contrast, in MSCHs, axons are not frequent, and hyperplastic nerves are absent. ²²

The MSCHs can also be mistaken for ganglioneuromas. Ganglioneuromas are benign lesions of ganglion cells, nerve fibers, and Schwann cells. Colorectal ganglioneuromas can be seen as solitary polypoid ganglioneuromas, diffuse ganglioneuromatosis, and ganglioneuromatous polyposis. Ganglioneuromatous polyposis is associated with Cowden syndrome ²⁶, and ganglioneuromatosis is associated with MEN 2B or NF1. ²⁷ History and the presence of multiple neural polyps can distinguish these two inherited syndromes from MSCH. Also, in contrast to solitary polypoid ganglioneuromas, in terms of IHC study, MSCH is negative for ganglion cells, and axons are usually absent. ²²

Another diagnosis to exclude is intramucosal perineuriomas, most commonly seen in the distal colon as small, sessile polyps. ²⁸ Intramucosal perineuriomas are poorly circumscribed and, like MSCHs, show entrapment of colonic crypts. Still, the stroma is looser and less eosinophilic, and the cells are usually slender or ovoid in a lamellar or whorled pattern. Perineuriomas are negative for S-100 protein, immunoreactive for EMA, and sometimes positive for claudin-1. Finally, not seen in MSCHs, two-thirds of intramucosal perineuriomas are associated with hyperplastic polyps. ²⁸

Incidentally detected during endoscopy, granular cell tumors are seen as small mucosal nodules, while extracolonic tumors might also be present. Histologically, lesions comprise large cells with small nuclei and ample granular cytoplasm. MSCHs are positive only for S-100, but granular cell tumors are positive for CD68 and S-100. ⁵

Finally, similar to the MSCHs, mucosal benign epithelioid nerve sheath lesions can surround crypts, show strong positivity for S-100, and cells lack axons. ²⁵ While the MSCHs are solely restricted to the lamina propria, the mucosal epithelioid nerve sheath tumors often expand into the superficial submucosa. Further studies might answer if these two entities are distinct lesions or parts of the same benign intramucosal Schwann cell proliferation spectrum. ²²

4. Conclusions

In conclusion, we described an incidentally noted sigmoid mucosal Schwann cell hamartoma found during a screening colonoscopy. To our knowledge, this is the first report of this mucosal anomaly in a patient with a history of treated HIV. Clinically, this lesion is benign and is not associated with inherited polyposis syndromes, and follow-up colonoscopy is not different from the recommended schedule in the healthy population. Strong immunoreactivity for S-100 protein and lack of axons can help distinguish MSCHs from similar entities.

ACKNOWLEDGEMENTS

Not applicable.

Statement of Competing Interests

Not applicable.

List of Abbreviations

MSCH, mucosal schwann-cell hamartoma; CRC, colorectal cancer; GIST, gastrointestinal stromal tumor; IHC, immunohistochemistry; LGIB, lower gastrointestinal bleeding; NFP, neurofilament protein; GFAP, glial fibrillary acidic protein; EMA, epithelial membrane antigen; SMA, smooth muscle actin; NF1, neurofibromatosis 1; MEN, multiple endocrine neoplasia.

References