Gastric Leiomyosarcoma Unmasked by Bleeding From a Percutaneous Endoscopic Gastrostomy Tube

ABSTRACT

Gastrointestinal bleeding from percutaneous endoscopic gastrostomy tubes and malignancy are uncommon. Gastric leiomyosarcomas are rare and differentiated from other gastric tumors with histology and immunohistochemical staining. We present a case of upper gastrointestinal bleeding from a percutaneous endoscopic gastrostomy tube manifesting as a gastric leiomyosarcoma in a 50-year-old man with a medical history of Wilms tumor. We reviewed the epidemiology, diagnosis, and management of gastric leiomyosarcomas. We also explored the risk factors and potential mechanisms in the pathogenesis of gastric leiomyosarcoma in our patient.

INTRODUCTION

Gastrointestinal (GI) leiomyosarcomas are rare, occurring at 1.4 cases per 100,000 patients.¹ They arise from the smooth muscle cells in the muscularis propria or mucosa, unlike gastrointestinal stromal tumors, which share immunophenotypic similarities with interstitial cells of Cajal.² Leiomyosarcomas are characterized by spindle cells with high proliferation rates and positivity for desmin, α–muscle-specific actin, and vimentin. Differentiating between leiomyosarcomas and gastrointestinal stromal tumor is important as the latter is responsive to tyrosine kinase inhibitors.³ GI leiomyosarcomas may present as bleeding, abdominal pain, weight loss, and gastroesophageal reflux.⁴ Although the etiology of leiomyosarcomas is unclear, immunosuppression, Epstein-Barr virus (EBV), and exposure to chemicals and radiation may play a role in its pathogenesis.^5,6

CASE REPORT

A 50-year-old man with a medical history of Wilms tumor and previous nephrectomy complicated by end-stage renal disease resulting in dual kidney transplant took tacrolimus and prednisone. He also had severe neuroinvasive West Nile virus complicated by flaccid quadriparesis and chronic respiratory failure with tracheostomy and percutaneous endoscopic gastrostomy (PEG) and was admitted with dyspnea and fevers and was found to have ventilator-associated pneumonia. Gastroenterology was consulted for bleeding from the PEG tube. One year earlier, the patient had an esophagogastroduodenoscopy (EGD) for dysphagia, which revealed Los Angeles grade D esophagitis, but no evidence of a gastric mass, and was treated with a proton-pump inhibitor.

On evaluation, the patient was hemodynamically stable. He had abdominal pain but denied any hematemesis, melena, or hematochezia. Hemoglobin was 7.8 g/dL on admission, which dropped to 6.5 g/dL over 2 days. The patient was transfused with 1 unit packed red blood cells with improvement in his hemoglobin to 8.5 g/dL. Gastric lavage via the PEG was notable for blood-tinged output. An EGD was performed, which demonstrated a large, ulcerated, and noncircumferential mass on the anterior wall of the gastric body (Figure 1). The gastrostomy tract had no bleeding or ulceration. Clean based ulcers (Forrest class III) with friable mucosa were found on the mass (Figure 2). Biopsies were taken for histology. Staging cranial, thoracic, abdominal, and pelvic computed tomography was most notable for an ill-defined amorphous 3.5 cm hyperdensity in the stomach with no evidence of metastatic disease (Figure 3).

Figure 1.

Esophagogastroduodenoscopy revealing a large fungating, infiltrative and ulcerated, noncircumferential mass on the anterior wall of the gastric body concerning for malignancy.

Figure 2.

Esophagogastroduodenoscopy revealing clean based ulcers (Forrest class III) on the contralateral wall of the gastric mass with friable mucosa with mild bleeding after biopsies.

Figure 3.

Abdominal and pelvic computed tomography revealing an ill-defined amorphous 3.5 cm hyperdensity in the stomach (white arrow) consistent with the mass seen on esophagogastroduodenoscopy.

Pathology demonstrated gastric mucosa with a spindle cell neoplasm involving the submucosa and extending into the lamina propria (Figure 4). The cells appeared epithelioid to spindled and had frequent mitotic figures with atypical forms (mitoses enumerated at 12 per 10 high power field). Helicobacter pylori stains were negative. Immunohistochemical stains were positive for cytokeratin, calponin, actin, and focal staining for desmin (Figure 5). Cytokeratin AE1/AE3 showed dot-like cytoplasmic staining in a subset of tumor cells. The tumor cells were negative for CD117, S100, CK5/6, Cam5.2, ALK-1, CD34, CD31, and myogenin. The overall findings were compatible with a leiomyosarcoma. After the diagnosis was confirmed, the patient and his family did not want surgery or chemotherapy because of his poor prognosis and comorbidities; thus, endoscopic ultrasound and positron emission tomography were not pursued. The patient was discharged home with hospice care.

Figure 4.

Biopsy results of the gastric mass demonstrating gastric mucosa with a spindle cell neoplasm involving the submucosa and extending into the lamina propria, epithelioid to spindled-appearing cells with elongate eosinophilic cytoplasm, and frequent mitotic figures.

Figure 5.

Immunohistochemical stains showing positivity for cytokeratin, calponin, actin, and desmin.

DISCUSSION

Our case highlights the importance of assessing for bleeding from PEG tubes and maintaining a broad differential diagnosis. Given the patient's previous EGD and late presentation of GI bleeding, our leading differential diagnoses included esophagitis, peptic ulcer, and gastrostomy tract erosion or ulceration. Imaging did not reveal any abdominal wall, rectus sheath, or retroperitoneal hematomas. We pursued an EGD, given blood from lavage of the PEG tube and significant hemoglobin drop and were surprised by the presence of a gastric mass.

A surveillance epidemiology and end results analysis with leiomyosarcomas demonstrated that gastric leiomyosarcomas were more common in younger female patients, were more likely to occur in the gastric fundus or the greater curvature, and were less likely to present with advanced disease.⁷ The median overall survival for gastric leiomyosarcoma patients was 36 months. Prognostic factors associated with poor survival include metastasis, tumor size, histologic grade, deoxyribonucleic acid ploidy, and ulceration of the overlying gastric mucosa.⁸ Common sites of metastases include the peritoneum, liver, retroperitoneal soft tissues, and regional lymph nodes.⁹

Clinical experience has led to laparoscopic wedge resection surgery as a first-line therapy.¹⁰ Chemotherapy and radiation are used in patients with advanced disease with response rates below 40%.⁸ One case report demonstrated the use of endoscopic submucosal dissection in a patient with a 15-mm submucosal gastric leiomyosarcoma in the posterior wall of the body.¹¹ However, long-term safety and efficacy of endoscopic submucosal dissection for GI leiomyosarcomas for risk of perforation and dissemination of malignant cells to the peritoneum warrants further investigation.

Several factors may have predisposed our patient to develop a gastric leiomyosarcoma. First, a history of Wilms tumor may have increased his genetic susceptibility. Interestingly, previous cytogenetic analyses of leiomyosarcomas have demonstrated an association with abnormalities in the chromosomal region 11p, which have also been reported in Wilms tumor.^12,13 One case reported colon leiomyosarcoma developing in a patient with a medical history of Wilms tumor years after intra-abdominal radiation.¹⁴ Second, the patient's post-transplant immunosuppression likely increased his risk of malignancy by impairing cancer surveillance and facilitating the action of oncogenic viruses.¹⁵ Historically, gastric leiomyosarcoma was the first malignant tumor observed in renal transplant patients who received immunosuppressive therapy.¹⁶ Our patient's gastric leiomyosarcoma developed 1 year after initiation of immunosuppression. Finally, our patient had a past EBV infection (positive EBV IgG) and immunosuppression may have reactivated EBV and driven the development of leiomyosarcoma. EBV-associated leiomyosarcomas have been well described among organ transplant recipients on immunosuppression and in patients with human immunodeficiency virus.^6,17,18

In conclusion, we present a gastric leiomyosarcoma as an unexpected and rare cause of bleeding from a PEG tube. Our case illustrates the importance of keeping a broad differential diagnosis and how a recent EGD cannot exclude a fast-growing malignancy. Gastric leiomyosarcomas are diagnosed histologically with spindle cells with frequent mitoses and smooth muscle immunohistochemical stains. A history of Wilms tumor, immunosuppression, or EBV may be predisposing factors to GI leiomyosarcomas.

DISCLOSURES

Author contributions: J. Gubatan reviewed the literature, wrote the manuscript, and is the article guarantor. N. Shah provided the pathology images and revised the manuscript for intellectual content.

Financial disclosure: None to report.

Informed consent was obtained for this case report.