Gastroblastoma in a 28-Year-Old Man With Nodal Metastasis: Proof of the Malignant Potential

The patient was a previously healthy 28-year-old man who had a motor vehicle accident in September 2010. He was treated for a concussion at the emergency department and was discharged. Subsequently, he returned to the emergency department with complaints of constipation. A computed tomography scan revealed a tumor in the distal stomach (Figure 1). The patient underwent a percutaneous needle biopsy, and the lesion was diagnosed as an adenocarcinoma. The patient received 6 weeks of chemotherapy. A follow-up positron emission tomography scan showed no response of the tumor to therapy. In February 2011, a partial gastrectomy was performed. Intraoperatively, it was noted that the patient had peritoneal studding, liver metastases, and drop metastases to the pelvis with tumor adherent to the bladder. These separate lesions were not biopsied or resected.

On gross inspection, the partial gastrectomy specimen consisted of a 5.5-cm portion of distal stomach in which there was a transmural, partly circumscribed mass, measuring 3.8 × 3.3 × 2.5 cm. The mass was tan, mostly solid, with a cystic hemorrhagic focus (Figure 2). In addition, there were a few enlarged, firm lymph nodes in the perigastric adipose tissue.

Microscopically, the tumor involved the lamina propria, coursed transmurally, and dissected through the muscularis propria into the subserosa. It consisted of epithelial structures mixed with spindled stroma (Figure 3). The more prominent epithelial component was composed of highly cellular, large nests and sheets of cells that formed tubular structures and rosettes. Many of the rosettes contained mucin and more frequently, dense eosinophilic globules (Figure 4). The cells had scant to moderate amounts of cytoplasm and ovoid nuclei with stippled chromatin. Most of the nuclei were folded or grooved. Nucleoli were small to absent. There were scattered foci of epithelial cells with clearing of the cytoplasm and convoluted, condensed nuclei (Figure 5). The epithelial component was well demarcated from the spindled stroma. The spindled areas were less cellular and varied from loose, reticular arrangements to short fascicular, whorled patterns. The nuclei were similar to those seen in the epithelial areas with the exception of being slightly smaller and more elongated. There were rare mitotic figures (up to 2 mitoses per 10 high-power fields). In addition, there was metastatic tumor in 1 of the 4 perigastric lymph nodes (Figure 6).

Differential expression of immunohistochemical markers was noted between the 2 morphologic patterns (Table). The epithelial component stained strongly and diffusely for pancytokeratin (AE1/AE3/CAM 5.2) and low-molecular-weight cytokeratin (CK8). CK7 stained the epithelial cells focally, particularly in cells around the eosinophilic globules. In contrast, the spindled areas were negative for pancytokeratin but positive for vimentin. CD56 patchily stained the epithelial elements with a strong membranous pattern, while the spindled areas had focal weak to moderate staining. CD10 staining was diffusely positive in the spindled cells, with patchy membranous staining in the epithelial elements and strong staining of the eosinophilic globules. Curiously, the eosinophilic globules stained with inhibin, although the tumor cells did not. The Table lists the immunohistochemical findings of the current case as well as those of the previously reported cases of gastroblastoma.

Approximately 3 months post operatively, the patient returned for clinical follow-up. He is clinically stable, and his positron emission tomography scan showed no significant changes in the metastatic lesions.

For the 4 previously reported cases, 3 of the patients were male and the ages ranged from 9 years to 30 years. None of the patients had evidence of tumor outside the stomach. The tumors ranged in size from 5 to 15 cm and had variable involvement of the gastric wall (either transmural or limited to muscularis propria or serosa). Grossly, the tumors were multinodular, partly cystic, with pink-tan to hemorrhagic, yellow-gray cut surfaces. Microscopically, the tumors contained variable proportions of epithelial and mesenchymal elements with an infiltrative growth pattern. The epithelial component ranged from primitive-appearing structures intimately associated with the stroma to well-developed luminal structures, well demarcated from the stroma. Some cases had lumina containing eosinophilic, inspissated secretions, a striking finding in our case. The mesenchymal component consisted of mildly atypical spindled cells with blunt-ended nuclei. Mitoses were variable, ranging from 0 to 30 mitoses per 50 high-power fields. Neither component had sufficient atypia to be considered carcinoma or sarcoma.

Between the 2 growth patterns in the prior cases, there was a somewhat dichotomous immunostaining pattern. The epithelial component was positive for low-molecular-weight keratin, while the mesenchymal element was cytokeratin negative and vimentin positive. The 2 growth patterns did share some staining characteristics, although variably, with CD56 and CD10. A complete listing of immunohistochemical staining patterns is displayed in the Table. Other ancillary studies performed included fluorescence in situ hybridization for SS18 gene rearrangement1 and c-KIT mutation analysis,2 and the findings were negative. In ultrastructural studies, the epithelial cells had desmosomes and microvilli.2 

The case we present shares with the previously reported cases a similar immunomorphology, invasive architecture, yet overall bland cytology, and young patient age. This case is different because of the histologically proven nodal metastasis and the clinical findings of peritoneal spread. The previous cases had disease limited to the stomach, and on follow-up, the patients had no recurrent or metastatic disease. In addition, the patient reported here had clinically apparent metastatic disease to the liver and pelvis and peritoneal studding. These findings suggest that at least some gastroblastomas are malignant.

Gastroblastoma has been compared to other blastomas, such as pleuropulmonary blastoma, hepatoblastoma, and nephroblastoma.1 These dysembryonic tumors tend to have immature elements and clear malignant potential, whereas gastroblastoma seems to have a more developed architecture, low-grade cytologic features, and an indolent clinical behavior, at least in the previously reported cases. It has been proposed that gastroblastoma may relate better to the spindle epithelial tumor with thymuslike differentiation and the desmoplastic nested spindle cell tumor of liver rather than blastomas.2 These other tumors have demonstrated indolent behavior and excellent prognoses comparable to the previously reported cases of gastroblastoma.4–6 In any event, gastroblastoma is a rare tumor, and optimal therapeutic strategies are unknown. Interestingly, the patient in the case we present was treated with chemotherapy before resection, with no response.

The major problem pathologists will have in diagnosing this tumor relates to the fact that it is so rare that hardly anyone has ever seen one. Diagnosing gastroblastoma on a biopsy specimen is probably impossible, because of its different histologic features. The spindle cell areas might be called some type of sarcoma. The solid nest might be thought of as an endocrine tumor. The tubules with the central material might be diagnosed as some type of epithelial neoplasm. In fact, the pathologist who saw the original biopsy specimen, which we did not review, called it an adenocarcinoma.

In summary, gastroblastoma is a recently described, biphasic neoplasm of the stomach. The 4 previous reports suggest an indolent clinical behavior. Our reported case of gastroblastoma with regional nodal metastasis and distant clinical metastases is proof that some of these tumors are malignant.