In 2009,Miettinen et al. first described a novel bidirectional differentiated gastric tumor in young adults,called“gastruloblastoma” (Gastroblastoma,GB)[1].The pathogenesis of this tumor is still unclear,but some scholars believe that it was developed from a totipotent stem cell[2].To date, a total of 17 cases were reported in the domestic and foreign literature[1,3-16],Among which,13 cases were reported in the English literature[1,2-12],4 cases were reported in the Chinese literature[13-16],The clinicopathological characteristics of the 17 gastric oblastomas are shown in Table 1. The WHO (2019) 5th edition of the digestive system tumor classification first included gastric blastoma,and placed under the malignant epithelial tumor category of the stomach, ICD-O code is 1,suggesting that it has low malignant potential[2]。
Gastroblastoma occurs in young patients,occasionally in the elderly,the onset age is 9~79 years old,the average age is 35 years old,the proportion of male and female onset is close to 1:1. Gastrlastoma occurs in the antrum,followed by the greater curvature of the gastric body,with a maximum diameter of 1.3-15 cm and an average of 5.7 cm. In most of the reported cases,patients often have no obvious and specific clinical manifestations,and most of them are abdominal pain,abdominal space occupying,hematochezia, anemia and fatigue,or no obvious symptoms.This 19-year-old young female patient,with no obvious clinical symptoms,was initially diagnosed as “gastrointestinal stromal tumor” by physical examination and was admitted for CT and MRI,which showed a solid mass in the pancreatic head with clear boundary,necrosis and cystic changes, and “solid pancreatic pseudoppapilloma” was considered.“pancreaticoduodenal radical duodenectomy” was proposed. During the operation,the tumor was swollen from the posterior wall of the antrum,with exogenous type,the root was located in the dorsal side of the antrum and pylorus,and compressed to the pancreatic head, and no mass in the pancreas,so it was changed to “partial gastrectomy”.
Gastroblastomas are generally exophytic growth,relatively large multinodular or lobulated,often solid,can also be cystic or ulcerated,the boundary is clear,the maximum diameter of the tumor is about 1.3~15.0 cm.Tumor section changes diversified,can be colorful,flower spot or mottled bleeding.Microscopically, the tumor showed infiltrative growth and could involve the whole layer of the gastric wall or be confined to the serosal layer. The tumor mainly consists of two components with different proportions of epithelioid cells and spindle cells. Epithelioid cells can be arranged in nest clumps, cables, tufts or ducts,in the lumen with or without eosrotropic secretion, with mild cell morphology and partial fine nucleoli. The dle cell area is bundle,sheet,can also be loose network,vortex,cell morphology is more consistent, oval or short spindle, less cytoplasm, cell nucleus has no obvious atypia. Stroma can be accompanied by sclerosis or myxoid degeneration, and some cases show pulmonary edema-like structure,multinucleated giant cells,erythrocyte extravasation,occasional necrosis and calcification[8-9]. Although the epithelial and mesoee components often exist,the boundary between the two components is still clear. Nuclear otic images are rare,mostly 0-5 / 50 HPF,only one case up to 30/50 HPF. In this case,the main body of the tumor was located in the submucosa,muscle layer and serosa layer,locally invaded the mucosal lamina propria, and partially separated by smooth muscle bundles,with nodular,mild cell shape, mostly spindle, epithelioid, fine nucleoli,rare nucleotic images,and interstitial myxoid degeneration in some areas.
Immunohistochemical staining showed that epithelial regional tumor cells CK (AE1/AE3),CK7,CAM 5.2,and EMA were all positive, expressing CD56 and CD10 to varying degrees,some cases expressed CK8 and CK18,but CK20 was usually negative,mesenchymal regional tumor cells were positive for Vimentin,CD56,and CD10,expressing CD99 to varying degrees. In some cases,desmin was patchy positive in stromal area or CD117 positive in epithelial area, and Ki-67 proliferative index was low (<5%). Tumor cells in the epithelial and mesenchymal regions were negative for DOG-1, CD34, S-100, SOX-10, STAT6, SMA, C-Kit, Calretinin, Syn, CgA, TTF-1, ER,and PR. The immunohistochemical results of this case are consistent with the reported gastruloblastoma. In terms of cellular and molecular genetics,six of the reported cases of confirmed MALAT1-GLI 1 fusion gene[5,15,17],Graham class[17]For the first time in four cases of gastroblastoma by reverse transcription-polymerase chain reaction (RT-PCR) and fluorescence in situ hybridization (FISH) at the transcriptional and genomic level, respectively, the immunohistochemistry of gastroblastoma showed GLI1 overexpression, diffuse strong positive expression of the nucleus and cytoplasm of epithelial and mesoplastic components,thus further provide reliable support for the diagnosis of gastroblastoma. Meanwhile,the fusion of the MALAT1-GLI 1 gene,which indicates the activation of the Sonic hedgehog pathway in gastroblastoma,is thus expected to provide precise targeted therapy for patients with locally advanced or metastatic tumors. However, it should not be ignored that for another recently reported rare gastric tumor, plexiform fibromyxoma,MALAT1-GLI1 fusion gene and GLI1 protein were also detected in some cases of this tumor,and the structure of the fusion gene was consistent with that of gastroblastoma[18]. However,the histological features of plexiform fibromyxoma lack biphasic differentiation,which can facilitate the differentiation. In addition,the KOO et al[12]In 2021,a gastric submucosal tumor developed in a 17-year-old young man with Wiskott-Aldrich syndrome and a history of multiple allogeneic bone marrow transplantation and radiotherapy was reported. The histological morphology of tumor components and immunohistochemical results supported the diagnosis of gastrroblastoma. However,genetic tests showed that no MALAT1-GLI 1 fusion gene was found in the tumor of this patient,instead,comprehensive molecular analysis revealed a new EWSR1-CTBP1 fusion gene,with no specific changes in other genes. In this case,a 19-year-old young woman supported the diagnosis of gastroblastoma based on the histological morphology,IHC results and the opinions of several consultation units. However,FISH results showed that the broken rearrangement of GLI1 gene and EWSR1 gene were not found in the tumor of this patient. Therefore, in view of the limited number of cases reported in gastroblastoma at home and abroad, there is still a lack of sufficient understanding of the nature of the disease and the exact gene mutation,that is,the mechanism of the development of the disease still needs more cases and data accumulation.
Because its histological morphology is bidirectional differentiation of epithelium and interstitial lobe,gastric blastoma should be differentiated from the following diseases at diagnosis: (1) carcinosarcoma: highly malignant and high-grade,and the epithelial components are squamous,adenoid and other arrangement ways.(2) Synovial sarcoma: rare in the stomach,mostly nodular or lobulated,cytogenetically specific t (X,18) (p11,q11),and produce SS18 (SYT) -SSX fusion gene, (3) Teratoma: relatively diverse tumor components, tissues with three germ layers, such as body cavity epithelium,neuroepithelium and cartilage components.(4) Gastrointestinal stromal tumor (GIST): mainly spindle or epithelioid cells without epithelial cell differentiation, were positive for DOG1, CD34 and CD117,and SDHB expression was positive in this case, so SDHB-deficient GIST was excluded. In addition, PDGFR and c-kit gene mutations are often present in GIST.(5) Neuroendocrine tumors: often with organoid structures,positive for Syn and CgA.(6) Angiotumor: tumor cells grew sheets or sheets around the vessels, both positive for SMA and vimentin, special PAS staining showed positive luminal eosin secretion.(7)Pleexiform fibromyxoma: tumors has MALAT1-GLI1 fusion gene,but histological features lack biphasic differentiation.
Gastroblastoma is a low-grade malignancy, and its biological behavior is not clear. Among the 17 cases reported so far,most of their biological behavior are indolent,and they usually avoid recurrence and metastasis after complete surgical resection,with a good prognosis. However, three cases of regional lymph nodes and distant liver and retroperitoneal metastasis have been reported,one of which died after 7 months of follow-up[6,10,17]. In this case,the gastric space was found by physical examination, and the tumor was followed for 19 months after complete resection, with no tumor recurrence or metastasis.
In conclusion,gastroblastoma is a recently discovered gastric tumor with epithelial and interlobe bipolar differentiation. Due to the small number of cases reported in the domestic and foreign literature,the lack of sufficient understanding of the nature of this disease,and its biological behavior is unclear. At present, most of the cases in follow-up are relatively indolent clinical procedures,and complete surgical resection often presents with disease-free survival and a relatively good prognosis,but there is also a risk of lymph nodes and distant metastasis. Therefore,it is hoped that more cases can be found,which is expected to help medical workers deepen their understanding of the disease and avoid missed diagnosis and misdiagnosis.