Neurofibromatosis type-1 with retroperitoneal stromal tumour: one case report

Introduction

Extragastrointestinal stromal tumours (EGISTs) have been reported recently.^1–3 They also originate from or differentiate toward interstitial cells of Cajal, and show strong immunohistochemical staining for c-kit, which is the single best marker of gastrointestinal stromal tumours (GISTs). Neurofibromatosis type 1 (NF-1) is an autosomic dominant condition affecting the central nervous system and presenting a disposition towards development of stromal tumours. ⁴ Cases which include NF-1 with retroperitoneal stromal tumour are extremely rare.

Case report

The patient is a 44-year-old man who presented to the Department of General Surgery of the 81st hospital of P.L.A. with complaints of severe constipation and left leg pain. He described a long history of neurofibromatosis. When he was 16 years old, he found a mass on his left shoulder and underwent resection of it, after the operation, the pathological examination confirmed it was neurofibroma. Since then, more and more mass had been found in his body, especially in his abdomen. In the last 1 year, he experienced more and more serious constipation, and chronic left leg pain, which had significantly worsened in the 20 days before admission. Pain limited his ability to ambulate and was never as severe as on admission. He had to have Celecoxib a kind of COX-2 inhibitors to mitigate pain.

On physical examination, the patient’s examination showed prominent peripheral cutaneous neurofibromas mainly in the belly and limbs, especially a huge mass in his abdomen (Figure 1), no less than ten café-au-lait spots, four Lisch nodules of the iris. There were no axillary or inguinal freckling, optic gliomas, distinctive osseous lesions. There was also no previous history of neurofibromatosis in his family. The patient fulfilled the diagnostic criteria for NF1 according to Gutmann et al. ⁵ OPEN IN VIEWER

Computed tomography (CT) and magnetic resonance imaging (MRI) revealed a round and lobular mass in the retroperitoneum. As a well-circumscribed, hypervascular mass with cystic necrosis, it showed low and moderate heterogeneous density on plain CT scans, and on contrast-enhanced scan, moderate or remarkable enhancement was seen in the parenchyma of the tumour, while no enhancement was revealed in the necrosis and cystic areas of the tumours. On plain MRI scans, it had a hypointense signal on T1-weighted images and hyperintense signal on T2-weighted images (Figure 2). OPEN IN VIEWER

The patient underwent resection of the abdominal tumour on 29 September 2011. Upon opening the peritoneum and retroperitoneum, a well-circumscribed, thick and medium texture tumour was found. The tumour was firm and not easily suctionable. Lot of nerves were found to be travelling through the superficial and substance of the tumour, but the tumour themselves appeared to be not related with the nervers, and it was rich in blood supply. The entire tumour was carefully dissected free and removed. Postoperatively, the patient experienced significant relief of his left leg pain and constipation, but remained neurologically intact.

Microscopic examination of the abdominal mass specimen revealed features consistent with a typical stromal tumour characterised by interlacing fasciculi of spindle cells (Figure 3). On immunohistochemical evaluation, the tumour cells expressed strong and diffuse staining for c-kit (CD117) and CD34 (Figure 4); but the tumour cells showed no staining with a-smooth muscle actin (a-SMA), S-100 protein and desmin. The c-kit gene (exon 9,11,13,17) and platelet-derived growth factor receptor-α (PDGFR) gene (exon12,18) mutations were not observed in the specimen. OPEN IN VIEWER

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Figure 4.

Immunohistochemical finding of the tumour cells: (a) tumour cells showing strongly positive for immunoreactive c-kit (original magnification × 200); (b) tumour cells showing positive for immunoreactive CD34 (original magnification × 200).

Based on these findings, a diagnosis of neurofibromatosis type-1 with retroperitoneal stromal tumour was made.

Discussion

EGISTs comprises about 5–7% of all GISTs. ⁶ They are based on characteristics, which are outside the gastrointestinal tract, and the histopathological expression closely resembles GISTs. ⁷ NF-1 with GIST have been reported several times,^8–10 but with retroperitoneal stromal tumour, which is a kind of EGIST, just is rare case in the world as we have known.

Neurofibromatosis-related stromal tumours may be misdiagnosed as neurofibroma or other tumours. ¹¹ Radiological examination such as MRI may distinguish them. MRI of stromal tumour characteristically reveals a discrete mass, that is iso- to hypointense on T1-weighted images, hyperintense on T2-weighted images, and enhances with contrast. Microscopic examination of stromal tumours revealed features consistent with spindle cells mainly, but epithelioid cell is not frequent in NF-1 with stromal tumour. ¹⁰ Utilising the immunohistochemical method, we can distinguish stromal tumour by CD117 (c-kit), CD34 and S-100 protein.

As we have known that c-kit gene mutations with exon 9,11,13,17 and PDGFRA gene mutations including exon 12,18 are very frequent events in sporadic GIST,^12–14 many research works have shown that the mutations are very rare events in EGISTs especially in NF-1 with stromal tumour,^8,10,15,16 our case showed similar results. So some other occurrence mechanism may play an important role, such as the activation of the Ras-MAPK pathway associated with the inactivation of the NF1 gene may play an important role in the cell proliferation of NF-1 with stromal tumour. Additionally, LOH at 14q and 22q may contribute to the relatively early phase of tumour development of NF-1 GIST. ¹⁷ The activation of RAS pathway may cause neurofibroma, at the same time it may cause the Cajal cell hyperplasia, resulting in stromal tumour.

According to the research, GISTs are responsive to the c-kit inhibitor imatinib or sunitinib. ¹⁸ But EGISTs will have high resistance to imatinib, so complete surgical resection may be the initial means of cure for EGIST. In the current case, tumour was grossly removed. Symptomatic signs such as left leg pain and constipation had been relieved.

In conclusion, the present case report has shown that NF-1 with EGIST is very rare, and radiological, pathological and immunohistochemical examination may identify it. Surgical resection may be the unique method of cure for it.