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mucosal Schwann cell hamartoma

Monday 31 December 2012

Mucosal Schwann cell "hamartoma"

Colorectal polyps containing S-100-positive neural proliferations in the lamina propria that lack ganglion cells have been variously referred to as "neuromas" or "neurofibromas."

However, these lesions have not been systematically examined, and whether they are associated with type 1 neurofibromatosis (NF1) or other inherited syndromes is unknown.

Solitary colorectal polyps containing pure Schwann cell proliferations in the lamina propria are not associated with NF1.

Distinguishing these lesions from NF1-associated neurofibromas is difficult based on histologic features; the presence of an underlying submucosal nodule or mass should be excluded endoscopically, and immunohistochemistry should be performed.

Although their nature is uncertain, we propose the interim designation "mucosal Schwann cell ’hamartoma’" to avoid confusion with the neural lesions that have significant associations with inherited syndromes.

Microscopy

- diffuse proliferation of spindle cells in the colonic mucosa, located in the lamina propria that separates and distorts the colonic crypt architecture.
- This lesion is poorly circumscribed and the muscularis mucosa is not involved.
- The surface epithelium is intact without ulceration or erosion.
- The lesion had a homogeneous and benign cytological appearance.
- All cells were spindle shaped with elongated, tapering nuclei, abundant dense eosinophilic cytoplasm with indistinct cell borders, and with no nuclear atypia, pleomorphism or mitoses.

Immunohistochemistry

- At immunohistochemistry all cells display strong positivity for S-100 protein.
- No immunoreactivity for CD34 (QB END/10), CD117 (KIT), or smooth muscle actin.
- Pure Schwann cell immunophenotype (S100+, CD34-, CD117-, smooth muscle actin and desmin-).

Differential diagnosis

The histological differential diagnosis of spindle cell proliferation that may present as colon polyp is broad and includes:
- GISTs,
- fibrous lesions,
- neoplasms of smooth muscle.

- GISTs

  • GISTs are more commonly found in the stomach and small intestine but a small percentage occurs in the colon.
  • Their recognition is important due to the variable malignant clinical course and the response to targeted therapy.
  • GIST may display neural features with S100 protein expression but they are characterized by peculiar immunoreactivity to C-KIT/CD117 antibodies.

- fibrous lesions

  • Inflammatory fibroid polyps (Vanek’s tumor) and benign fibroblastic polyps are benign fibrous lesions in which proliferating spindle cells typically display perivascular arrangement, diffuse immunoreactivity for vimentin, and characteristic inflammatory infiltrates.

- fibroblastic polyp/colonic perineuroma

  • The entities of fibroblastic polyp/colonic perineuroma have been recognized as the same lesion.
  • They display bland, spindle-shaped cells separating the mucosal crypt, and show serrated crypt architecture on top of or adjacent to the lesion.
  • The predilection site is the rectosigmoid colon.
  • The lesion is more frequently encountered in women.
  • The hypothesis has been confirmed by the immunohistochemical evaluation of fibroblastic polyps/perineuromas with markers of perineural differentiation, that, is claudin-1, GLUT-1, collagen type IV and epithelial membrane antigen (EMA), and partially confirmed by electron microscopy [18].
  • In a significant number of cases (63%), a V600E-BRAF mutation is present, and less frequently, a KRAS mutation.
  • The proposed pathogenesis of serrated fibroblastic polyps/intramucosal perineuromas is the perineural stromal component that arises from epithelial-stromal interaction with proliferation of pericryptic fibroblasts.
  • Different from perineuroma, our case showed a strong immunoreactivity for protein S-100 and lacked the serrated glands.
  • Also intramucosal perineuroma can display morphological features very similar to this entity, but lack of S100 expression and immunoreactivity to EMA aids the proper differentiation of these lesions.

- colorectal leiomyoma

  • Leiomyoma can also arise in association with muscularis mucosae and present as a polypoid lesion but display a smooth muscle cell immunophenotype that is strongly and diffusely positive for desmin and actin.

- neurofibroma, ganglioneuroma or mucosal neuroma

  • The lack of axons and ganglion cells argues against lesions such as neurofibroma, ganglioneuroma or mucosal neuroma.
  • Moreover, these tumors display significant association with inherited syndromes.
  • Colorectal neurofibroma is nearly pathognomonic of NF1.
  • Mucosal neuroma is highly associated with MEN 2B, and ganglioneuroma occurs frequently in association with Cowden syndrome, MEN 2B or NF1.

- intramucosal schwannoma

  • The diagnosis of intramucosal schwannoma has to be considered.
  • Schwannomas represent a small percentage of GI mesenchymal tumors and rarely occur in the colon.
  • In contrast to their soft tissue counterpart, nuclear palisading, typical Verocay bodies, vascular hyalinization and xanthoma cells are not seen.
  • Colon schwannoma could present as polypoid intraluminal mass but intramural extension, more circumscribed margins, and characteristic peripheral lymphoid cuffs differentiate it from the lesion described.

Open references

- Schwann cell hamartoma: case report. Rocco EG, Iannuzzi F, Dell’Era A, Falleni M, Moneghini L, Di Nuovo F, Braidotti P, Bulfamante G, Romagnoli S. BMC Gastroenterol. 2011 Jun 10;11:68. doi : 10.1186/1471-230X-11-68 PMID: 21663626 [Free]

- Mucosal Schwann cell "Hamartoma": a new entity? Pasquini P, Baiocchini A, Falasca L, Annibali D, Gimbo G, Pace F, Del Nonno F. World J Gastroenterol. 2009 May 14;15(18):2287-9. PMID: 19437573 [Free]

References

- Mucosal Schwann cell "hamartoma": clinicopathologic study of 26 neural colorectal polyps distinct from neurofibromas and mucosal neuromas. Gibson JA, Hornick JL. Am J Surg Pathol. 2009 May;33(5):781-7. doi : 10.1097/PAS.0b013e31818dd6ca PMID: 19065103