Gastrointestinal stromal tumor of the posterior mediastinum

Abstract

Gastrointestinal stromal tumor (GIST) is a rare, but potentially aggressive tumor. We present an asymptomatic 64-year-old man with an incidental 9-cm GIST that arose in the posterior mediastinum. Wide surgical excision was performed with rotation of an intercostal muscle flap to buttress a surgically created esophageal wall defect. The patient is now free of disease 26 months postoperative. This tumor is defined by the carcinogenic over-expression of KIT-protein, a tyrosine kinase receptor. Accurate diagnosis of gastrointestinal stromal tumor is imperative, as specific medical therapy is now available for potential control of recurrent or metastatic disease.

1 Introduction

Over the past two decades, a new category of gastrointestinal mesenchymal tumors has emerged. These tumors demonstrate a pathobiology and clinical behavior different from those of smooth muscle [1] and Schwann cell tumors, and are known as gastrointestinal stromal tumors (GISTs). GISTs have been reported to arise in all areas of the alimentary tract, and from the omentum, mesentery, peritoneum and retroperitoneum [2]. Although the majority of GISTs occur in the subdiaphragmatic gastrointestinal tract, a small number of cases have been reported in the posterior mediastinum, exclusively arising in the esophagus.

Herein we present a patient with a posterior mediastinal GIST treated with wide surgical excision. To date, there have been 19 cases of thoracic esophageal GIST, two with a gastrointestinal autonomic nerve (GANT) phenotype [3–5]. Most of these patients presented with large tumors and associated dysphagia. The clinical outcome was generally poor. Recently, however, it has been discovered that GISTs harbor carcinogenic gain-of-function mutations of the c-kit gene with over-expression of the KIT-protein (tyrosine kinase receptor) [6], and this finding has lead to important therapeutic strategies [7].

2 Case report

A 64-year-old man was referred for treatment of a large posterior mediastinal mass found on routine chest X-ray during an evaluation for trauma. He had no dysphagia or chest symptoms. Barium swallow was not performed. Chest computerized tomography (CT) revealed that this mass was adjacent to the distal esophagus (Fig. 1a) . Endoscopy was normal, and endoscopic ultrasound did not clearly demonstrate esophageal wall invasion. Operative findings at the time of thoracotomy revealed a 9 cm well-circumscribed mass that was adherent to the right inferior pulmonary vein, right hemidiaphragm, and to a small portion of the distal esophagus. A wide excision was performed including the resection of a 2-cm area of the outer esophageal wall. An intercostal muscle flap was used to buttress the esophagus at the surgical defect, and the chest was closed. The patient did well postop.

Grossly, the 8×9 cm tumor demonstrated a thin pseudocapsule. It was white, bosselated with central necrosis (Figs. 1b,c). Microscopically the tumor had uniform spindled cells with evenly distributed chromatin with absent nucleoli. Many areas demonstrated nuclear palisading reminiscent of schwannoma (Fig. 2) . A thin rim of uninvolved esophageal smooth muscle was seen at the edge of the tumor. Positive immunostaining for CD117 (KIT), however, confirmed the diagnosis of GIST. Electron microscopy demonstrated a GANT phenotype of GIST.

The patient was counseled regarding treatment options for this rare neoplasm and offered esophagectomy. He refused further surgery and only agreed to follow-up for clinical evidence of recurrent or metastatic disease. Twenty-six months postoperative, the patient is free of disease.

3 Discussion

In 1983, Mazur and Clark challenged the longstanding concept that most mesenchymal tumors of the stomach were of smooth muscle origin, and introduced the concept of stromal tumor [1]. Soon thereafter, an enteric neural tumor of the small bowel was described [8] that is now known as a gastrointestinal autonomic nerve (GAN) tumor [9]. Recently, a report in the literature concluded that GANT was indeed a phenotypic variant of GIST [10]. Over the years, the term introduced by Mazur and Clark has expanded into all regions of the alimentary tract and now encompasses mesenchymal tumors that do not demonstrate smooth muscle or Schwannian differentiation. KIT (CD117) immunostaining is found in all GISTs [2], and as a result it is postulated that they arise from the interstitial cells of Cajal (ICC) or from a mesenchymal progenitor cell with the potential to differentiate into smooth muscle cells or into ICC [10].

GISTs occur in an older patient population (50–60 years) and demonstrate a spectrum of clinical behavior. The majority of GISTs are benign (60–80%). The most consistent prognostic factors are site of presentation and tumor size [2,10]. A high percentage of tumors arising in the stomach are benign, whereas tumors that arise in the small intestine, colon and esophagus are more aggressive [2,10]. Tumor size of less than 5 cm, especially in the face of a low mitotic count, appears to predict a benign behavior. Although the mitotic rate is not a consistent predictor of outcome, high mitotic counts are indicative of malignancy [2].

The tumor described in this report could represent a pedunculated esophageal GIST, but without clear-cut involvement of the gut wall, it is possible that it originated from tissues outside the alimentary tract. To our knowledge this site of origin has not been reported. Of the other 19 reported cases of posterior mediastinal GIST (all arising in the esophagus), the age of onset ranged from 49 to 75 years (mean 61.8 years). Most patients presented with dysphagia, however three tumors were incidental findings. The tumor size at presentation ranged from 2.6 to 25 cm with a mean of 8.9 cm. Nine of the 13 patients with tumors over 5 cm died of disease (mean follow-up of 42 months (6–140 months)) [3–5].

Management of mediastinal mesenchymal tumors is challenging. ‘Stacked’ endoscopic biopsies through epithelium may afford diagnostic material if the tumor is superficial. Fine needle biopsies may not be definitive unless a core of tissue is obtained for immunohistochemistry. If preoperative diagnosis is elusive, then thoracotomy should be entertained. Frozen section analysis at the time of resection should be interpreted with caution, as most mesenchymal tumors will harbor areas of spindle cells, and differential diagnosis may be difficult. The diagnosis of GIST should be entertained in larger tumors, with or without a high mitotic rate. Aggressive en bloc surgical extirpation is the treatment of choice for these tumors. Conservative surgical management may expose the patient to incurable tumor recurrences. Definitive surgery may be delayed pending immunohistochemical evaluation.

Recognition of KIT positivity in GISTs has lead to clinical trials using the drug STI571 (Gleevec/Glivec, Novartis, Basel, Switzerland), a small molecule tyrosine kinase inhibitor. Some patients with advanced KIT positive tumors have demonstrated clinical improvement with treatment [7]. Further, patients may qualify for a phase II trial to study the efficacy of adjuvant STI571 in high-risk GIST (American College of Surgeons Oncology Group; protocol #Z9000).

References

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