Diagnosis
Differential Diagnosis
Included in the broad differential diagnosis of GIST are true smooth muscle tumors (leiomyosarcomas, leiomyomas), schwannomas, desmoid fibromatosis, and inflammatory fibroid polyps (Figure 1).1-3 Although GISTs are the most common primary mesenchymal tumors of the GI tract, differential diagnosis may be complicated by the fact that certain histogenetically and pathogenetically unrelated tumors may simulate GISTs (Table 1).1 These tumors are usually more collagenous and less cellular than GISTs, and are negative for KIT and, in most cases, for CD34, but they may be variably positive for desmin and actins.
Figure 1
Differential diagnosis of gastrointestinal stromal tumor (GIST). Immunohistochemistry of tumors included in the differential diagnosis of GIST is shown. (A) Intestinal leiomyosarcoma showing fascicles of well-differentiated smooth muscle cells. (B) Gastric schwannoma with a peritumoral lymphoid cuff and relatively low cellularity. (C) Inflammatory fibroid polyp with a mixture of oval lesional cells and eosinophils. (D) Inflammatory myofibroblastic tumor composed of large tumor cells with amphophilic cytoplasm and prominent nucleoli. Significant lymphoplasmacytic infiltration is typical. (E) Desmoid tumor with fascicles of fibroblasts in a collagenous background, with prominent mildly dilated vessels. (F) Undifferentiated sarcoma with a spindle-cell pattern. This diagnosis is made by exclusion and is based on immunohistochemistry. (G) Metastatic melanoma can have epithelioid or spindle-cell pattern and can simulate GIST. (H) Intestinal true histiocytic lymphoma contains large, epithelioid tumor cells. Reprinted with permission from Miettinen M et al. Pol J Pathol. 2003;54:3-24.3
| Tumor Type | Similarities to and Differences From GISTs |
|---|---|
| Esophageal leiomyoma | Paucicellular (comprising few cells), composed of well differentiated smooth muscle cells Positive for desmin and SMA |
| Uterine-type leiomyoma | Usually pelvic, in young to middle-aged women Positive for desmin, SMA, and estrogen and progesterone receptors |
| True leiomyosarcoma | Composed of well-differentiated smooth muscle cells, positive for desmin and SMA Often presents as a polyploid intraluminal tumor |
| Inflammatory fibroid polyp | Spindle-cell lesion, often CD34 positive Slender spindle cells, admixed lymphoid cells, and eosinophils |
| Inflammatory myofibroblastic | Often in children May form a transmural tumor gastric or intestinal mass, but more often an omental or mesenteric mass |
| Mesenteric desmoid | May have GIST-like gastric or intestinal involvement Grossly very firm Fibroblasts and myofibroblasts in collagenous background, CD34 negative |
| Dedifferentiated liposarcoma | Mesenteric, retroperitoneal, and may involve intestinal walls May have a lipomatous component or have myxoid or pleomorphic MFH-like or fibrosarcoma-like features |
| Schwannoma | Usually small, yellow, circumscribed submucosal tumors Slender, often bundled S100 protein–positive cells in S100 protein–negative fibrous background |
MFG, malignant fibrous histiocytoma; SMA, smooth muscle actin. Adapted with permission from Miettinen M, Lasota J. Virchows Arch. 2001;438:1-12.1
Other non-GIST, KIT-positive tumors of the GI tract include angiosarcoma and malignant melanoma. Approximately half of these tumors are reported to express KIT, but other specific immunohistochemical and histologic features distinguish them from GISTs.1,4
Because GISTs are fragile and bleed easily, biopsy before surgery is not recommended for a suspected resectable GIST because of the high risk of tumor spillage and cellular dissemination.5,6 Fine-needle aspirates and small biopsies performed endoscopically, however, are increasingly used in the diagnosis of GIST.1,4 Although fine-needle aspirates allow diagnosis of GIST with a high level of certainty, immunohistochemical analysis remains important for differential diagnosis.
References:
1. Miettinen M, Lasota J. Gastrointestinal stromal tumors—definition, clinical, histological, immunohistochemical, and molecular genetic features and differential diagnosis. Virchows Arch. 2001;438:1-12.
2. Rubin BP. Gastrointestinal stromal tumours: an update. Histopathology. 2006;48:83-96.
3. Miettinen M, Lasota J. Gastrointestinal stromal tumors (GISTs): definition, occurrence, pathology, differential diagnosis and molecular genetics. Pol J Pathol. 2003;54:3-24.
4. Miettinen M, Sobin LH, Sarlomo-Rikala M. Immunohistochemical spectrum of GISTs at different sites and their differential diagnosis with a reference to CD117 (KIT). Mod Pathol. 2000;13:1134-1142.
5. Blay JY, Bonvalot S, Casali P, et al. Consensus meeting for the management of gastrointestinal stromal tumors. Report of the GIST. Consensus Conference of 20-21 March 2004, under the auspices of European Society for Medical Oncology. Ann Oncol. 2005;16:566-578.
6. Demetri G, Benjamin R, Blanke CD, et al. NCCN Task Force report: optimal management of patients with gastrointestinal stromal tumor (GIST)—expansion and update of NCCN Clinical Practice Guidelines. J Natl Compr Canc Netw. 2004;2(suppl 1):S1-S26.