Gastrointestinal Mesenchymal Neoplasms other than Gastrointestinal Stromal Tumors: Focusing on Their Molecular Aspects

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.

Figure 1

Photomicrograph of H&E-stained section from a desmoid tumor. Note the moderately cellular sweeping fascicles of bland spindle cells. The lower left inset contains a high-power photomicrograph of the same tumor to demonstrate the characteristic pinpoint nucleoli and collagenous stroma of desmoids.

Figure 2

Schematic of Wnt signaling pathway. In demoid tumors, mutations are usually found in the APC gene or CTNNB1 gene, which encodes β-catenin. Regardless of the primary defect, the end result is nuclear accumulation of β-catenin, which fails to undergo cytoplasmic degradation.

Figure 3

Photomicrograph of H&E-stained section from an inflammatory myofibroblastic tumor. The tumor is relatively cellular and composed of a mixture of plump spindle cells and inflammatory cells, particularly lymphocytes and plasma cells.

Figure 4

Photomicrograph of FISH break apart probe that targets the ALK gene. The normal chromosome (lower middle) shows a green signal and red signal in close proximity, whereas the green and red signals are far apart in the left aspect of the photomicrograph, confirming 1 copy of the ALK translocation.

Figure 5

Photomicrograph of H&E-stained section from an inflammatory fibroid polyp. The lesion is moderately cellular with concentric whorls of spindle cells around blood vessels and numerous interspersed eosinophils.

Figure 6

Schematic of platelet-derived growth factor receptor- (PDGFR-)related signaling pathways. Mutations can lead to activation of PDGFR independent of ligand binding. Numerous downstream pathways may lead to neoplastic advantages such as cell proliferation, growth, and survival.

Figure 7

Photomicrograph of H&E-stained section from a conventional clear cell sarcoma. The cells are relatively bland with variably prominent nucleoli, low mitotic activity, and pale to clear cytoplasm. Fibrous bands illicit a compartmentalized appearance.

Figure 8

Photomicrograph of FISH break apart probe that targets the EWSR1 gene. The normal chromosome (upper middle) shows a green signal and red signal in close proximity, whereas the green and red signals are far apart in the lower aspect of the photomicrograph, confirming EWSR1 translocation.

Figure 9

Photomicrograph of H&E-stained section from a leiomyomatous polyp. The leiomyoma is composed of bland smooth muscle cells with eosinophilic cytoplasm. The tumor is directly apposed to the colonic mucosa, suggesting derivation from the muscularis mucosae.

Figure 10

Photomicrograph of H&E-stained section from a gastric schwannoma. These tumors are often more easily recognized by their prominent lymphoid reaction at the periphery and lack of encapsulation rather than classic soft tissue schwannoma features such as Verocay bodies or thick, hyalinized vessels.

Figure 11

Photomicrograph of H&E-stained section from a submucosal lipoma in the colon. The tumor is composed of mature fibroadipose tissue with sharp demarcation from the overlying mucosa.