Colorectal fibroblastic polyp and intramucosal perineurioma are 2 synonyms for a recently described benign mucosal lesion with a predilection for the rectosigmoid colon. These lesions are characterized by aggregates of bland spindled cells separating and distorting mucosal crypts. The latter frequently showed a serrated architecture. The pathogenesis of fibroblastic polyp/intramucosal perineurioma and the nature of serrated crypts observed in them are poorly understood. We analyzed the clinicopathological features of 29 fibroblastic polyps and investigated them for the first time for mutations known to be involved in serrated colorectal epithelial polyps (BRAF, KRAS, and PIK3CA). Patients were 23 women and 6 men with a mean age of 64 years (range: 47 to 84 y). All lesions represented asymptomatic solitary polyps (mean size 3.5 mm) localized predominantly in the rectosigmoid colon (81%). Hyperplastic polyps, classical adenoma, and sessile serrated adenoma/lesion coexisted in 12 (44%), 12 (44%), and 5 (17%) patients, respectively. All lesions showed irregular aggregates of bland spindled cells separating and distorting mucosal crypts. Serrated (hyperplastic) crypts were observed on the top or contiguous with the lesion in all cases. Immunohistochemistry revealed expression of at least one perineurial cell marker (epithelial membrane antigen, claudin-1, and glucose transporter-1) in 26 out of 27 lesions (96%), but expression of CD34 was less common (8 of 27; 30%). Immunostaining for hMLH1 showed a normal nuclear expression. Molecular analysis in 22 cases showed V600E BRAF mutation in 14 cases (63%) and KRAS mutation in 1 (4%). The remainder were wild-type for all 3 genes. Our results indicate that serrated fibroblastic polyps/intramucosal perineuriomas represent a unique type of mixed epithelial-stromal polyps (hybrid hyperplastic polyp/mucosal perineurioma). The perineurial stromal component might be derived from modified pericryptic fibroblasts as a consequence of a yet poorly understood epithelial-stromal interaction.
"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 . 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. "
[Show abstract][Hide abstract] ABSTRACT: Colorectal polyps of mesenchymal origin represent a small percentage of gastrointestinal (GI) lesions. Nevertheless, they are encountered with increasing frequency since the widespread adoption of colonoscopy screening.
We report a case of a small colonic polyp that presented as intramucosal diffuse spindle cell proliferation with a benign cytological appearance, strong and diffuse immunoreactivity for S-100 protein, and pure Schwann cell phenotype. Careful morphological, immunohistochemical and clinical evaluation emphasize the differences from other stromal colonic lesions and distinguish it from schwannoma, a circumscribed benign nerve sheath tumor that rarely arises in the GI tract.
As recently proposed, this lesion was finally described as mucosal Schwann cell hamartoma.
"A recent study reported BRAF mutations in 63% of the epithelial component of these polyps. The authors concluded that the polyps are true mixed epithelial-mesenchymal neoplasms, but there remains no conclusive evidence that the spindle cell proliferation is truly neoplastic . Ganglioneuromas are benign lesions composed of ganglion cells, nerve fibers, and Schwann cells  that often arise in the setting of inherited tumor syndromes, including Cowden syndrome (PTEN mutations), MEN 2B, and NF1 , among others. "
[Show abstract][Hide abstract] ABSTRACT: Gastrointestinal (GI) mesenchymal tumors other than gastrointestinal stromal tumor (GIST) are rare neoplasms, but they often enter the differential diagnosis of more common GI lesions. Some of these mesenchymal tumors in the GI tract have well understood molecular pathologic aspects, including desmoid tumors, inflammatory myofibroblastic tumor (IMT), clear cell sarcoma (CCS), inflammatory fibroid polyp (IFP), and synovial sarcoma (SS). Molecular pathology is fast becoming a mainstream focus in laboratories because it aids in the precise classification of tumors, may be prognostic, and may help predict response to therapy. The following review is not intended as an exhaustive summary of all mesenchymal tumors that have been reported to involve the GI tract, but instead will highlight the current knowledge of the most important non-GIST GI mesenchymal neoplasms, focusing on those tumors with well-characterized molecular pathology and how the molecular pathologic features impact current diagnostic, therapeutic, and prognostic standards.
Pathology Research International 02/2011; 2011:952569. DOI:10.4061/2011/952569
[Show abstract][Hide abstract] ABSTRACT: Colonic perineuriomas are recently described benign mucosal polyps that are composed of a bland spindle cell proliferation surrounding crypts that often demonstrate hyperplastic/serrated epithelial changes. However, the origin of this unique stromal proliferation is still unclear, and the association with serrated polyps, including sessile serrated adenomas, has not been fully described. We evaluated the pathologic and molecular features of colonic polyps associated with perineurial-like proliferations in 2 retrospective cohorts: (1) a series of 198 consecutive sessile serrated adenomas and (2) 20 colonic polyps diagnosed as a perineurioma irrespective of the presence of serrated colonic crypts. Thirteen of 198 (6.5%) sessile serrated adenomas demonstrated a perineurial-like stromal proliferation, with most (12 of 13, 92%) involving the right (9 cases) and transverse colon (3 cases). In all 13 cases, the perineurial-like proliferation surrounded serrated colonic crypts and typically involved only a small area of the sessile serrated adenoma (average 9% of polyp size; range, 2% to 19%). All 11 polyps evaluated for epithelial membrane antigen (EMA) expression demonstrated stromal EMA staining limited to the perineurial-like proliferation. Twelve of 13 (92%) sessile serrated adenomas with perineurial-like proliferations demonstrated a pV600E BRAF mutation. Of the 20 colonic polyps diagnosed as a perineurioma, 18 (90%) demonstrated serrated crypts intimately associated with the perineurial-like proliferation. In 13 of 18 polyps with associated serrated crypts, all serrated crypts were invested with the perineurial proliferation. In 5 cases, serrated crypts were seen away from the perineurial proliferation. Of these 18 polyps, the majority (16 of 18, 89%) were microvesicular hyperplastic polyps involving the left colon. However, 2 (11%) polyps in the right colon demonstrated histologic features diagnostic of sessile serrated adenoma. All 18 polyps with serrated crypts demonstrated a pV600E BRAF mutation. In contrast, the 2 polyps not associated with serrated crypts were negative for a BRAF mutation. Our results show for the first time that perineurial-like stromal proliferations frequently occur in sessile serrated adenomas. The presence of focal perineurial-like stromal proliferations in sessile serrated adenomas and the common finding of serrated crypts in colonic perineuriomas are likely indicative of an epithelial-stromal interaction, possibly related to some factor elaborated by the serrated epithelium.
The American journal of surgical pathology 09/2011; 35(9):1373-80. DOI:10.1097/PAS.0b013e318224d9df · 5.15 Impact Factor
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