Gastroblastoma in a 12-year-old Chinese boy

Abstract

Gastrablastoma is a rare epitheliomesenchymal biphasic tumor of stomach in children and young adults first reported by Miettinen et al in 2009. Five cases have been reported up to date including only one case with the nodal metastasis and distant metastases. With little atypism gastroblastoma is suggested to be a low-grade malignancy. Here we report one case of gastroblastoma in a 12-year-old boy with review of the literature. This is the first case of gastroblastoma in Chinese to our knowledge.

Introduction

Gastroblastoma is a rare epitheliomesenchymal biphasic tumor in stomach first reported by Miettinen et al in 2009 [1]. Only five cases have been reported since then [2,3]. All these tumors had mesenchymal component and epithelial elements morphologically. Vimentin, CD10, CD56, and cytokeratins were differently expressed in the two components of the tumors on immunohistochemistry. Little atypism, rare mitosis, low ki-67 indexes, local invasive growth pattern, and indolent clinical course suggest that gastroblastoma may be a low-grade malignant tumor. Poizat et al reported an epitheliomesenchymal tumor in duodenum in 2012 [4]. Though some morphological similarities can be found between that case and gastroblastoma, the immunohistochemical expression was distinct. Here we report the first case of gastroblastoma in Chinese people and review the literature.

Case report

In July 2013, a 12-year-old boy presented to our hospital with an abdominal mass and intermittent blood in stool for more than three months. CT scan and MRI scan revealed a mass measuring 62.3 x 41.0 x 37.5 mm in the gastric antrum (Figure 1). The same mass along with an ulcer about 2 x 1 cm was also detected by gastroscope. The tumor was completely resected. Subtotal gastrectomy and gastroduodenostomy were performed. The mass was found located in the antrum near the lesser curvature and protruded towards the liver during the operation. The child is still alive without evidence of recurrence and metastasis 8 months after surgery. Written informed consent was got from the child’s parents.

Figure 1.

Enhanced computed tomography scan showed a mass in the gastric antrum (arrow).

Pathological findings

Grossly, the partial gastrectomy specimen consisted of a 7 x 5 x 3.5 cm portion of distal stomach in which there was a transmural, red-gray, and well-circumscribed mass measuring 4.5 x 2.5 x 2.5 cm (Figure 2). The tumor grew in an infiltrative pattern and involved the gastric wall structures. The cut surface was tan and jelly-like. There was an ulcer about 1 x 1 x 0.8 cm in the overlaying mucosa.

Figure 2.

Gross photo of gastroblastoma. The mass was transmural, red-gray, well-circumscribed and protruded towards the serosal surface.

Microscopically, the tumor was composed of uniformly short spindle-shaped to oval cells (Figure 3A) which infiltrated in the smooth muscle (Figure 3B). These cells had small round nucleoli, little cytoplasm and ill-defined cell borders (Figure 3C). The tumor was biphasic in composition. Most cells were arranged in the fascicles, sheets and cords comprising the majority of the tumor (so-called mesenchymal component) (Figure 3A). Obvious extravasation of red blood cells was observed in some mesenchymal area. Focally the epithelial elements had nests or glands containing inspissated eosinophilic secretions in the lumina (Figure 3D). And the epithelial component blended into the mesenchymal component. Unbalanced cell density appeared in the tumor. In the loose reticular area the tumor cells were less and aligned like the hemangioma partly (Figure 3E). Focal dense tumor cells displayed spirally in that area (Figure 3F). There was slight nuclear atypia and rare mitotic figures (up to 2 mitoses per 10 high-power fields). Necrosis and calcification could be found in the perpherial area of the tumor.

Figure 3.

Microscopic findings of gastroblastoma. A: The tumor consisted of spindle to oval cells and the tumor cells were mainly arranged in the fascicles, sheets and cords (x 100). B: The tumor exhibited invasive property in the smooth muscle layers of the stomach (x 50). C: The tumor cells had small round nucleoli and the boundaries were not clear (x 400). D: The epithelial elements had luminal differentiation with intraluminal inspissated eosinophilic secretions and blended into the mesenchymal component (x 200). E: The tumor cells were aligned like the hemangioma partly in the loose area (x 200). F: In the loose reticular area some tumor cells arranged in a spiral pattern (x 100).

Immunohistochemically, the mesenchymal component were positive for vimentin (Figure 4A), CD10 (Figure 4B) and CD56 (Figure 4C). The epithelial component was positive for pancytokeratin (AE1/AE3) (Figure 4D) and CAM5.2 (Figure 4E). All the components were negative for CK5/6, S-100, SMA, DES, CD34, c-KIT, PLAP, ALK and DOG1. In the major area the proliferation index Ki-67 of the tumor cells was estimated at 1%, but focally it was about 40% (Figure 4F). The tumor cells were negative for PAS stain and had absent reticular fibers for reticulin stain. SS18 gene rearrangement was not detected in the tumor.

Figure 4.

Immunohistochemical features of gastroblastoma. A: Vimentin was strongly positive in the mesenchymal components (x 100). B: The mesenchymal cells were diffusely positive for CD10 (x 100). C: CD56 was diffusely positive for the mesenchymal elements (x 100). D: The epithelial component was positive for pancytokeratin (x 200). E: CAM5.2 was found positive in the epithelial elements (x 200). F: Ki-67 index was about 40% in focal areas (x 200).

Discussion

Miettinen et al. first reported a series of 3 cases of epitheliomesenchymal biphasic tumor in stomach and designated the tumor as gastroblastoma in 2009 [1]. Two more cases were detected in 2010 and 2012 [2,3]. Six cases were reported up to date including our case. Clinicopathologic features of all the cases were summarized in Table 1. For all the six cases, 5 were male and 1 was female. The patients ranged in ages from 9 to 30 years old. The most common presentations were abdominal pain and masses. The tumors were 3.8-15 cm in maximum diameter. Of the six tumors, 2 were located in the gastric body, 3 in the antrum, and 1 in the distal stomach. The tumors infiltrated variably in the gastric wall. 3 was transmural, 2 spanned from the muscularis propria to the subserosa, and 1 was centered in the muscularis propria. Grossly, the tumors were multinodular or mostly solid with a cystic hemorrhagic portion. The cut surfaces were yellow-gray to pink-tan, grey flesh-like or tan. Microscopically, the tumors were composed of mesenchymal and epithelial elements in different proportions with an invasive growth pattern. The tumor cells were uniformly short spindle-shaped or oval, scant to moderate amounts of weakly eosinophilic cytoplasm, and small or absent nucleoli without obvious nuclear atypia. Mitotic figures were sparse in all the cases. The tumor cells usually displayed in the fascicles, sheets, cords, and nests. Specially, the mesenchymal elements also displayed in loose reticular or whorled patterns and the epithelial elements grew in glands or rosette-like structures containing luminal eosinophilic secretions.

Table 1.

Clinicopathologic features of gastroblastomas

Case	Age (yr)	Sex	presentation	Tumor size (cm)	Location	Treatment	Outcome
1 Miettinen et al [1]	19	M	Abdominal pain and mass	5 x 4 x 2.5	Greater curvature, gastric body	Subtotal gastrectomy	AWRM for 3.5 y
2 Miettinen et al [1]	27	F	Abdominal pain and mass	6 x 4 x 3.5	Greater curvature, gastric body	Partial gastrectomy	AWRM for 5 y
3 Miettinen et al [1]	30	M	Anemia, fatigue, and abdominal mass	15 x 12	Gastric antrum	Antrectomy, radiation therapy after operation	AWRM for 14 y
4 Shin et al [2]	9	M	Abdominal pain and mass	9 x 6.5	Gastric antrum	Tumor resection and a segmental resection of gastric antrum and pylorus	AWRM for 9 m
5 Wey et al [3]	28	M	Constipation and abdominal mass	3.8 x 3.3 x 2.5	Distal stomach	No response to chemotherapy before operation, Partial gastrectomy	Clinically stable for 3 m
6 our case	12	M	Intermittent blood in stool and abdominal mass	4.5 x 2.5 x 2.5	Gastric antrum	Subtotal gastrectomy and gastroduodenostomy	AWRM for 8 m

Yr, years old; cm, centimeter; M, male; F, female; AWRM, alive without recurrences and metastases; y, years; m, months.

Of the previous cases, the predominant components were the mesenchymal elements in 3 cases and the epithelial elements in the other 2 cases respectively. Evident luminal differentiation with luminal eosinophilic secretory material could be found in 3 cases. The tumors had distinctive immunohistochemical features. The mesenchymal elements were positive for vimentin and CD10, and the epithelial elements were positive for pancytokeratin. The immunohistochemical markers were listed in Table 2. The result of SS18 gene rearrangement examination by fluorescence in situ hybridization and c-KIT mutation analysis was negative. Ultrastructually, the epithelial components had desmosomes and microvilli supporting the epithelial differentiation.

Table 2.

Immunohistochemical features of gastroblastoma

	Miettinen et al [1]		Shin et al [2]		Wey et al [3]		Our case
	Epithelial element	Mesenchymal element	Epithelial element	Mesenchymal element	Epithelial element	Mesenchymal element	Epithelial element	Mesenchymal element
Vimentin		+	-	+		+	-	+
CD10		+	-	+ (focal)	+	+	-	+
Pancytokeratin	+		+	-	+	-	+	-
LMWCK	+		+	-	+		+	-
CK7	+ (focal)				+ (focal)		-	-
CK5/6							-	-
CK19							-	-
CK20	-						-	-
HMWCK			-	-			-	-
EMA	-	-	-	+	-		-	-
SMA	-	-	-	-	-		-	-
Desmin	-	-	-	-	-		-	-
Caldesmon							-	-
C-kit (CD117)	-	-	+	-	+		-	-
DOG-1	-	-					-	-
CD56			+	+	+	+ (focal)		+
S-100	-	-			-		-	-
SYN	-	-	-	-			-	-
CgA	-	-	-	-			-	-
NSE	-	-	-	-			-	-
HMB45							-	-
A103							-	-
Calretinin	-	-	-	-	-		-	-
P63	-	-	-	-	-		-	-
ALK							-	-
CD34	-	-	-	-			-	-
CD99	-	-					-	-
Inhibin			-	-	-	-	-	-
CDX2	-	-			-		-	-

+, positive; -, negative. Abbreviations: LMWCK, low-molecular-weight cytokeratin; HMWCK, high-molecular-weight cytokeratin; EMA, epithelial membrane antigen; SMA, smooth muscle actin; SYN, Synaptophysin; CgA, chromogranin A; NSE, neuron-specific enolase; ALK, anaplastic lymphoma kinase. Blank: the result unclear or not performed.

Our case shares with the reported five cases the similar clinicopathological features: young patient age, typical location, relatively large tumor size, invasive growth pattern, biphasic components, bland cytology, similar microscopic morphology and immunohistochemical phenotype.

However, some differences could be found between our case and the other reported cases. Morphologically, angiomatoid area, prominent extravasated red blood cells, necrosis and calcification could be found in our case. Immunohistochemically, c-KIT was negative in our case. Ki-67 index showed an uneven distribution in the tumor cells with 1% in the most area and 40% in focal areas, suggesting some tumor cells had relatively strong proliferative activity.

The differential diagnosis of gastroblastoma includes inflammatory myofibroblastic tumor (IMT), teratoma, gastrointestinal stromal tumor (GIST), synovial sarcoma, carcinosarcoma. IMT usually has an obvious inflammatory infiltrate and rearrangements of the anaplastic lymphoma kinase (ALK) locus on chromosome 2p23, but does not have epithelial component. Teratoma is based on the differentiation of multiple germ layers. GIST would have immunoreactivity for c-KIT and DOG1 and would not display prominent epithelial differentiation. Synovial sarcoma is very rare in stomach and SYT-SSX gene rearrangements could be detected in the tumor. Carcinosarcoma is an advanced malignant tumor and is unlikely in children.

The biological behavior of gastroblastoma is unclear. 4 of 5 previous reported cases and our case suggest it indolent though only 1 case reported developed regional nodal metastasis and distant metastases. No standard therapy has been established for this tumor. Surgical resection may be the best strategy. One reported case had received the chemotherapy before resection but with no response. Another had got postoperative radiation but the detailed effect was not described. The prognosis remains uncertain. The follow-up periods were 3 months to 14 years. All the patients were event-free in the reported follow-up time. All the clinicopathological features indicate the tumor may be a low-grade malignancy.

In summary, we report a case of gastroblastoma which is a low-grade malignant biphasic tumor. This is the first case in Chinese. More data are needed to understand the biology and clinical behavior of this tumor.

Disclosure of conflict of interest

None.