A 40‐Year‐Old Female with Dural‐Based Lesions

Clinical History

A 40‐year‐old female presented to the neurosurgery department with a history of new onset, severe, pressure‐like headaches. MRI (Figure 1A) revealed multiple mass lesions in the spinal cord, at C4–6 and T3 with infiltration of the neuroforamina. An epidural component was associated with spinal cord compression. In addition, there were lesions in the hip and shoulder, liver and small intestine, as well as right parietal and frontal, dural‐based lesions, 3 × 3 × 4 and 1.5 × 1 × 1 cm. Subsequent surgical removal of the dural tumors was complete. The postoperative course was uneventful and the patient described relief from the headaches. The intracranial tumors recurred at 1 and 2 years after the initial surgery.

Figure 1.

Microscopic Pathology

Histologic examination of the biopsy revealed a pleomorphic, spindle cell neoplasm with a fascicular growth pattern (Figure 1B). Occasional whorl‐like structures were seen. The closely packed, eosinophilic tumor cells harbored dark, elongated nuclei with few nuclear pseudoinclusions (Figure 1B insert). In 10 high power fields (hpf)/40×, up to 13 mitotic figures were observed (Figure 1C, arrowheads). The tumor cells were focally positive for the immunostain CD34 (Figure 1D) but negative for EMA (Figure 1E) and STAT6 (not shown). In addition, there was strong, diffuse immunolabeling with CD117 (Figure 1F) and Dog1 (Figure 1G). The proliferation marker Mib1 labeled about 25% of the tumor cells (Figure 1H). What is your diagnosis?

Diagnosis

Metastatic gastrointestinal stromal tumor (GIST)

Discussion

GIST is a tumor entity that belongs to the group of soft tissue sarcomas. It primarily affects patients between the ages of 60 and 65; however, familial cases may present at an earlier age. GIST, which occurs most frequently in the stomach and small intestine, is thought to arise from mesenchymal cells, the interstitial cells of Cajal, part of the autonomic nervous system of the gastrointestinal tract 3. The tumor cells typically harbor a driver mutation in CD117 (tyrosine protein kinase KIT receptor) or in approximately 10% cases, mutations in the platelet derived growth factor receptor A (PDGFRA receptors. Of note, cKIT and PDGFRA mutations are mutually exclusive. Although historically considered benign, metastatic potential varies according to location and size of the tumor (>5 cm) and mitotic count (>5/50 hpf) 2. GIST commonly metastasizes to the liver (65%) and peritoneum (21%) 4.

There is a lower propensity for bone metastases, ranging from 3% to 6% in larger studies 1.

GIST that develops outside the gastrointestinal tract is termed extra gastrointestinal stromal tumor (EGIS). A rare variant is thought to originate from neuronal cells of the intestine the gastrointestinal autonomic nerve tumor (GANT).

The differential diagnosis of dural‐based neoplasms is extensive and can be diagnostically challenging. Primary considerations for tumors with similar morphologic features encompass atypical or even anaplastic meningioma (>20 mitoses/10 hpf), followed by a solitary fibrous tumor (SFT), malignant peripheral nerve sheath tumor (MPNST) and other sarcomas. In fact, evidence of CD34 positivity may mislead toward the diagnosis of SFT/hemangiopericytoma. In contrast, the lack of STAT6 immunolabeling militates against SFT/hemangiopericytoma and favors meningioma or MPNST. However, the history of multiple lesions in the intestines and liver should alert the pathologist to consider the possibility of a GIST metastasis. In fact, the combined strong expression of CD117 and the marker “discovered on GIST 1” (Dog1) confirms the diagnosis. The other biopsies from the patient showed similar histomorphological and immunohistochemical profiles.

Even though the likelihood for GIST metastases is very rare, the present case illustrates that in unresolved cases of dural‐based tumor masses, the differential diagnosis of tumors mimicking meningioma should also include GIST.