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World J Gastrointest Surg. Apr 27, 2024; 16(4): 1030-1042
Published online Apr 27, 2024. doi: 10.4240/wjgs.v16.i4.1030
Blastomas of the digestive system in adults: A review
Yu Liu, Jonathan Somma, Zhi-Yan Fu, Department of Pathology, LSU Health Sciences Center School of Medicine, New Orleans, LA 70112, United States
Tony El Jabbour, Saverio Ligato, Department of Pathology, Hartford HealthCare, Hartford, CT 06102, United States
Yukihiro Nakanishi, Department of Pathology, Moffitt Cancer Center, Tampa, FL 33612, United States
Hwajeong Lee, Department of Pathology and Laboratory Medicine, Albany Medical Center, Albany, NY 12208, United States
ORCID number: Yu Liu (0009-0005-3537-9465); Tony El Jabbour (0000-0002-6823-1919); Jonathan Somma (0000-0002-5617-833X); Yukihiro Nakanishi (0000-0001-7345-9005); Saverio Ligato (0000-0002-4152-8157); Hwajeong Lee (0000-0001-7005-6278); Zhi-Yan Fu (0000-0002-9541-9968).
Author contributions: Liu Y and Fu ZY are acknowledged for their substantial contributions to drafting the work, conducting a comprehensive literature review for all discussed sections, revising critically important intellectual content, and giving final approval to the published version; Jabbour T and Lee H are credited for providing guidance on the topic; Jabbour T, Nakanishi Y, and Ligato S are acknowledged for their contributions to pathology imaging; Somma J is credited with aiding in the final polishing of content language; All authors have actively participated in the creation of the manuscript and agree with the final version of the manuscript.
Conflict-of-interest statement: All the authors report no relevant conflicts of interest for this article.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: Https://creativecommons.org/Licenses/by-nc/4.0/
Corresponding author: Zhi-Yan Fu, MD, Attending Doctor, Department of Pathology, LSU Health Sciences Center School of Medicine, 1901 Perdido St, New Orleans, LA 70112, United States. zfu@lsuhsc.edu
Received: January 1, 2024
Peer-review started: January 1, 2024
First decision: January 25, 2024
Revised: February 3, 2024
Accepted: March 25, 2024
Article in press: March 25, 2024
Published online: April 27, 2024
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Abstract

Blastomas, characterized by a mixture of mesenchymal, epithelial, and undifferentiated blastematous components, are rare malignant neoplasms originating from precursor blast cells. This review focuses on digestive system blastomas in adult patients, including gastroblastoma, hepatoblastoma, and pancreatoblastoma. Gastroblastoma is a biphasic, epitheliomesenchymal tumor, with only sixteen cases reported to date. In addition to the characteristic histology, metastasis-associated lung adenocarcinoma transcript 1 - glioma-associated oncogene homolog 1 gene fusion is typical, although recently novel ewing sarcoma breakpoint region 1 - c-terminal binding protein 1 and patched 1 - glioma-associated oncogene homolog 2 fusions have been described. Hepatoblastoma is exceptionally rare in adults and can show a variety of histologic patterns which may cause diagnostic difficulty. Pancreatoblastoma, primarily a pediatric tumor, displays acinar differentiation and squamoid nests with other lines of differentiation also present, especially neuroendocrine. Diagnostic approaches for these blastomas include a combination of imaging modalities, histopathological examination, and molecular profiling. The treatment generally involves surgical resection, which may be supplemented by chemotherapy or radiotherapy in some cases. Prognoses vary with gastroblastoma generally showing favorable outcomes post-surgery whereas hepatoblastoma and pancreatoblastoma often have poorer outcomes, particularly in the setting of metastases. This review highlights the complexity of diagnosing and managing these rare adult blastomas as well as the need for ongoing research to better understand their pathogenesis and improve treatment strategies.

Key Words: Adult blastomas, Gastroblastoma, Hepatoblastoma, Pancreatoblastoma, Digestive system

Core tip: Adult digestive system blastomas, including gastroblastoma, hepatoblastoma, and pancreatoblastoma, are rare neoplasms with less than a hundred cases reported for each type. They have nonspecific clinical presentations and imaging findings. Gastroblastoma diagnosis hinges on biphasic histology and the metastasis-associated lung adenocarcinoma transcript 1 - glioma-associated oncogene homolog 1 gene fusion. Hepatoblastoma recapitulates the different embryological stages of liver development and can be epithelial or mixed epitheliomesenchymal. Pancreatoblastoma demonstrates multidirectional differentiation and contains squamoid nests. Surgical resection is the primary treatment for these tumors with adjuvant chemotherapy or radiotherapy in some cases. Prognoses vary, with gastroblastoma typically having better post-surgical outcomes. In contrast, hepatoblastoma and pancreatoblastoma frequently recur and metastasize.



INTRODUCTION

A blastoma is a malignant neoplasm consisting of a combination of mesenchymal, epithelial, and undifferentiated blastematous components. It originates from precursor cells called blasts. Blastomas arise at a variety of sites, and typical examples include medulloblastoma and neuroblastoma. However, the primary digestive system blastomas, hepatoblastoma, pancreatoblastoma, and gastroblastoma, are uncommon, and the literature on these tumors is limited, particularly for cases arising in adults. In fact, no comprehensive resource is presently available. Thus, we aim to present a thorough review of digestive system blastomas in adults which, among other things, will highlight up to date information regarding the complexity of diagnosis, molecular pathogenesis, and management.

Gastroblastoma is a rare tumor, first described by Miettinen et al[1] in 2009. It was added to the World Health Organization (WHO) Classification of Tumors of the Digestive System in 2019. Only sixteen cases have been reported to date, most occurring in young adults. However, six have been reported in patients over 30, and the oldest reported case was in a 74-year-old[2]. Gastroblastoma is an epitheliomesenchymal neoplasm primarily developing in the gastric body and antrum[3] . Diagnosis typically relies on the presence of the metastasis-associated lung adenocarcinoma transcript 1 - glioma-associated oncogene homolog 1 (MALAT1-GLI1) gene fusion and its biphasic (epitheliomesenchymal) histology[3]. However, recent discoveries, such as the ewing sarcoma breakpoint region 1 - c-terminal binding protein 1 (EWSR1-CTBP1) gene fusion in a patient with Wiskott-Aldrich syndrome[4] and the patched 1 - glioma-associated oncogene homolog 2 (PTCH1-GLI2) gene fusion[5,6], suggest more genetic diversity than was originally thought.

Hepatoblastoma accounts for 79% of all pediatric malignant liver tumors. Almost 90% of tumors appear before the age of 5, and only 3% occur in patients older than 15 years[7]. Adult hepatoblastoma was first reported by Marx[8] in 1904, and, to date, only about 75 cases of adult hepatoblastoma have been reported[9,10]. Compared to childhood hepatoblastoma, where the 5-year overall survival rates exceed 70%[11,12], adults have a high rate of mortality and poor prognosis, with a 1-year survival rate of 24%[13]. Frequently, patients present with an elevated serum alpha-fetoprotein (AFP) level, which can be used to monitor response to therapy[14]. Although the etiology and pathogenesis of hepatoblastoma are poorly understood, mutations in the β-catenin gene, which plays a critical role in the WNT signaling pathway, are commonly observed in both pediatric and adult cases[15]. Due to its rarity in adults, treatment is not as standardized as it is in children, but surgical management is the mainstay of therapy in both populations[12].

Pancreatoblastoma is a rare malignancy, accounting for less than 1% of all exocrine neoplasms of the pancreas[16]. It is characterized by a multilineage cellular proliferation predominantly showing acinar differentiation with distinctive squamoid nests often present. Additionally, neuroendocrine differentiation is common whereas ductal and mesenchymal components are less pronounced[17]. It is most prevalent in pediatric patients, comprising 25% of pancreatic neoplasms in children in the first decade of life[18]. In adults, however, pancreatoblastoma is uncommon, with an incidence rate of just 0.004 per 100000 individuals aged 19 and older, and less than 80 such cases have been reported in the literature to date[19-22]. The genetic landscape of pancreatoblastoma often involves somatic alterations, including the loss of chromosome 11p, which is also implicated in Beckwith-Wiedemann Syndrome, and mutations in the Wnt/β-catenin signaling pathway[16,23,24]. Notably, the clinical course of pancreatoblastoma in adults is more aggressive than in children. Metastasis and/or invasion of adjacent structures contribute to 58% of adult pancreatoblastoma cases, leading to three-year survival rates of less than 40%. This sharply contrasts with the 94.4% 5-year overall survival observed in children[25-27].

CLINICAL MANIFESTATIONS

In most cases of gastroblastoma, adult patients present with non-specific symptoms and, in some, the diagnosis is incidental. Reported symptoms include fatigue, abdominal mass, abdominal and/or epigastric pain, and hematemesis[28]. Similarly, hepatoblastoma has non-specific initial clinical manifestations. Pain is the most common symptom including epigastric, abdominal, and low back pain. Fever, vomiting, nausea, anorexia/weight loss, and hepatomegaly/ abdominal mass are also reported. Rarely described manifestations are gastrointestinal bleeding, dyspnea, and lower extremity edema[29]. Pancreatoblastoma is frequently asymptomatic early on; late manifestations include abdominal pain/mass, splenomegaly, obstructive jaundice, fever, diarrhea, melena, weight loss, and occult blood in urine[26].

LABORATORY/IMAGING FINDINGS

The imaging findings of blastomas are similar to those of more common tumors of the digestive system. Gastroblastomas appear heterogeneous on abdominal computed tomography (CT)[30], and magnetic resonance imaging (MRI) offers superior soft tissue contrast to clarify the tumor's extent and relationship to adjacent structures. Gastroendoscopy typically reveals an ulcerated, submucosal based mass[4,31]. Although not specific for gastroblastoma, serum markers like Carcinoembryonic Antigen and Carbohydrate Antigen 19-9 (CA19-9) can be elevated in some cases and can be helpful in monitoring for disease recurrence.

Hepatoblastoma may be detected as unifocal or multifocal lesions by imaging. On ultrasound, the tumor is reported as a hyperechoic and solid mass[32]. CT scans and MRIs provide superior delineation of tumor characteristics, extent, and vascular involvement. The use of contrast agents, particularly during the arterial phase, can highlight tumor vascularity. Serum AFP level is usually increased but nonspecific[10,33].

Pancreatoblastomas are single, large, well-delineated, circular or lobulated masses with scattered or aggregate calcifications visible on both CT and MRI. Heterogeneous character may reflect a cystic component of some tumors[34]. Contrast imaging shows enhancement in the arterial phase that can mimic a hypervascular neuroendocrine tumor[34-36]. Common bile duct involvement (i.e., dilatation) is apparent in some pancreatic head tumors[34,35,37,38]. Serum AFP has been noted to be increased in 68% cases[18,39] and may be used to monitor the effectiveness of therapy[40]. In the case reported by Li et al[35], the patient showed elevated CA19-9 and Cancer Antigen 125 levels[35,38]. Rarely adrenocorticotropic hormone can be secreted from the tumor[40-42].

CASE REPORTS

Table 1 summarizes adult gastroblastoma case reports from 2009 to present[43-48]. Patients were on average 37-years-old (range 19-74 years old) at the time of diagnosis. Surgical management was the primary treatment modality, and the gastric antrum was the most common tumor site. Molecular testing was not conducted in the majority of cases, but among those cases tested, all had the MALAT1-GLI1 gene fusion except for one case with a PTCH1-GLI2 gene fusion. Although reported follow-up times varied substantially, ranging from 3 months to 14 years, the clinical course was favorable in the majority of patients.

Table 1 Summary of reported cases of adult gastroblastoma.
Ref.
Age/sex
Location
Molecular alteration (s)
Treatment
Follow-up
Recurrence or metastasis
Castri et al[43], 201974/MGastric antrumMALAT1::GLI1Partial gastrectomy5 yearsRecurrence after 5 years
Centonze et al[28], 201943/FGastric antrumNot performedPartial gastrectomy100 monthsNo
Fernandes et al[44], 201419/FGastric antrumNot performedPartial distal gastrectomy20 monthsNo
Graham et al[3], 201727/MStomachMALAT1::GLI1Partial gastrectomy12 monthsNo
Graham et al[3], 201756/FStomachMALAT1::GLI1N/AN/AMetastasis to liver
McCammon et al[2], 202326/MGastric pylorus extending through the first and second portions of the duodenumMALAT1::GLI1Tumor resection from the mucosa of pylorus and duodenum2 monthsNo
Miettinen et al[1], 200930/MGastric antrumNot performedAntrectomy, postoperative radiation14 yearsNo
Miettinen et al[1], 200927/FGastric bodyNot performedPartial gastrectomy5 yearsNo
Miettinen et al[1], 200919/MGastric bodyNot performedSubtotal gastrectomy3.5 yearsNo
Pinto et al[31], 201953/FGastric antrumNot performedPartial gastrectomy18 monthsNo
Poizat et al[45], 201222/FDuodenumNot performedPartial resection of the distal duodenum16 monthsNo
Toumi et al[46], 201729/FGastric bodyNot performedPartial gastrectomy + splenectomy6 monthsLocal recurrence after 6 months
Wey et al[30], 201228/MDistal stomachMALAT1::GLI1Preoperative chemotherapy + partial gastrectomy3 monthsMetastasis to lymph nodes, liver, pelvis; clinically stable at 3 months
Gong et al[47], 202319/MGastric antrumNo gene break rearrangement detected by FISHPartial gastrectomy19 monthsNo
Zhu et al[48], 201865/FGastric bodyNot performedFull-thickness resection of the gastric wall4 yearsNo
Chen et al[5], 2022 and Liu et al[6], 202258/MGastric bodyPTCH1::GLI2Endoscopic submucosal dissection1 yearNo

A total of 12 adult hepatoblastoma cases have been reported in the English literature from 2013 to 2023 (Table 2)[49-56]. The average age was 44 years old with a wide range from 22 to 84 years old, and tumors were more frequently right sided. Twelve cases demonstrated elevated serum AFP, and hepatitis B infection and liver cirrhosis were present in 40%. Metastasis at the time of disease presentation was infrequent. Histologically, 75% of cases exhibited mixed epithelial and mesenchymal patterns, and the remainder were purely epithelial. Surgical resection constituted the primary treatment modality, often followed by adjuvant chemotherapy. Follow-up periods were generally short. However, this may be due to the aggressive course of most patients; short term recurrence or metastasis and death were frequent outcomes.

Table 2 Summary of reported cases of adult hepatoblastoma from recent 10 years (2013-2023).
Ref.
Age/sex
Location
Hepatitis B
Liver cirrhosis
AFP
Metastasis at diagnosis
Histology
Treatment
Follow-up
Recurrence or metastasis
Pagarigan et al[49], 202349/FRight hepatic lobeHBsAg (+); anti-HBc (+)Yes> 50000 ng/mLNoMixedSurgical resection + postoperative chemotherapy4 monthsRecurrence
Ihssan et al[10], 202226/FRight Hepatic lobeNoNo2275 ng/mLNoEpithelial (the mixed fetal and embryonic pattern)Surgical resectionN/AN/A
Ihssan et al[10], 202250/MEntire liverNoNo6386 ng/mLNoMixedN/AN/AN/A
Park et al[50], 201536/FRight hepatic lobeHBsAg (+); anti-HBc (+)Yes676.5 ng/mLNoMixedSurgical resection + postoperative chemotherapy5 monthsIntraperitoneal metastasis, died
Caso-Maestro et al[51], 201327/MRight hepatic lobeHBsAg +, HBcAb +, HBeAb +No1166000 ng/mLMixedSurgical resection27 monthsLeft adrenal recurrence followed by total adrenalectomy; alive
Al-Jiffry et al[33], 201322/MLeft hepatic lobeNoNoNormalDiaphragm, pericardial, and IVC infiltrationMixedSurgical resection16 dDied
Cienfuegos et al[52], 201337/FSegment 5 and 6 of the liverHBsAg +, HBcAb +, HBeAb +Yes1556.3 ng/mLNoMixedSurgical resection10 monthsRecurrence and died
Zhang et al[53], 201332/FLeft hepatic lobeNoNoNormalNoEpithelial, neuroendocrine differentiationN/AN/AN/A
Park et al[50], 201536/FRight hepatic lobeHBsAg +, HBcAb +, HBeAb +676.5 ng/mLNoMixedSurgical resection + postoperative chemotherapy12 monthsLeft subphrenic area metastasis; died
Celotti et al[54], 201668/MLeft hepatic lobeNoNo1231 ng/mLPericardial metastasisMixedLeft lobectomy +; diaphragm resection + extended pericardiectomy21 monthsNo recurrence
Urdiain et al[55], 201965/MRight hepatic lobeNoNoN/ANoEpithelialSurgical resection10 monthsRecurrence, died
Dave et al[56], 201984/MLeft hepatic lobeN/AN/A708 IU/mLMetastatic to left lower bronchus, left descending pulmonary artery and left descending pulmonary veinMixedN/AN/AN/A

A total of 47 adult pancreatoblastoma cases have been reported since 2018 (Table 3)[57-68]. The average age of affected individuals was 45 years old (range 19 to 75 years old). Half of the patients were diagnosed with metastasis at the time of initial diagnosis, typically to the liver. Tumors arose throughout the pancreas with no discernable pattern. Primary treatment modalities included surgical resection and chemotherapy. Follow-up ranged from several months to a few years, and, although many patients experienced disease recurrence or metastasis, there were several instances of better outcomes during the follow-up period.

Table 3 Summary of reported cases of adult pancreatoblastoma from recent 5 years (2018-2023).
Ref.
Age/sex
Location
Metastasis before treatment
Treatment
Follow-up (months/years)
Recurrence/metastasis
Outcome
Rojas et al[22], 2023 45/FPancreatic tailNoPancreatectomy and splenectomy; Chemotherapy; stem cell transplant3 monthsLiver metastasisN/A
Machado et al[57], 20233 patients (2F, 1M); avg age: 51Tail and body of pancreasLiver and lung metastasisSurgical resection6 years 2 monthsRegional or distant metastasis2 died; 1 alive after 6 years 2 months following surgery
Hussain and Farrukh[58], 2023 75/MPancreatic headLiver metastasisChemotherapy; stent insertion5 monthsNoStable
Wu et al[34], 20227 patients (2M, 5F); avg age: 56.71Pancreatic head (n = 3), tail (n = 2), gastric antrum (n = 1), neck (n = 1)Liver (n = 2), Lymph node (n = 2), kidney adrenal (n = 1)N/ANot reported in 3 cases, 24, 26, 4, 4 months in othersN/A4 patients died during follow-up
Suemitsu et al[59], 2021 74/MTail of pancreasNoOpen distal pancreatectomy and splenectomy36 monthsNoRecurrence-free
Li et al[35], 2021 60/FTail of the pancreasRight liver metastasisResection and chemotherapy16 monthsN/ADeath
Morales et al[20], 202176/MPancreatic headLymphovascular and perineural invasionChemotherapy32 monthsNoStable
Raoul et al[60], 2021 33/FPancreasInvading gastric wallPancreatectomy, Chemotherapy14 monthsLiver metastasisStable
Raoul et al[60], 2021 33/FPancreatic tailLiver metastasisChemotherapy20 monthsNoStable
Elghawy et al[61], 202123/FPancreatic tailLiver metastasisChemotherapy; autologous hematopoietic cell transplant57 monthsN/AStable
Zhang et al[36], 2020 7 patients (7M); Avg age: 44.71Pancreatic head (n = 3), neck (n = 1), body (n = 1), tail (n = 2)Only 1 patient liver metastasisSurgical resection1.5 months, 6 months, 8 months, 8.5 months, 10 months, 2 years, 4 years3 patients developing liver metastasisAlive = 2, lost to follow-up = 5
Snyder et al[62], 2020 28/FN/ALiver metastasisChemotherapy; left suboccipital craniotomyMore than 51 monthsBrain metastasisAlive
Morrissey et al[63], 202069/MPancreatic headNoAdjuvant chemotherapy; Surgical resection10 weeksNoAlive (tumor-free)
Berger et al[64], 2020 32/FPancreatic headLiver metastasisPancreaticoduodenectomy and Lymphonodectomy; Right hemihepatectomy for liver metastasis; Chemotherapy14 monthsLung metastasisDied
Berger et al[64], 2020 19/MPancreasNoChemotherapy, pylorus-preserving pancreaticoduodenectomy; autologous stem cell transplantation24 monthsLiver and abdominal lymph node metastasisDied
Berger et al[64], 2020 30/MPancreatic headNoComplete pancreatectomy; adjuvant chemotherapy: Immunotherapy17 monthsLiver metastasisDied
Berger et al[64], 2020 20/FPancreatic tailDiffuse liver metastasisChemotherapy14 monthsN/ADied
Liu et al[65], 2020 49/MPancreatic tailLiver metastasisComplete resection of the primary and metastatic lesions.2 yearsN/AStable
Yin et al[66], 2019 27/FPancreatic headNoPancreatoduodenectomy1 year and 10 monthsLiver metastasisAlive
Reid et al[67], 2019 11 adults (6M, 5F); median age: 45Pancreatic head (n = 7), tail (n = 4)3 patients, location N/ANot mentioned in detail; suggestive of surgical resectionAverage 39.8 months4 cases developing metastasisAlive = 6, died = 5
Chen et al[19], 2018 26/MHead of pancreasLiver metastasisTACE4 yearsNoDied
Yamaguchi et al[24], 2018 37/FPancreas headNoPancreaticoduodenectomy and chemotherapy13 monthsLiver metastasisDied
Nunes et al[68], 2018 31/MPancreatic tailLiver metastasisHemodialysis3 monthsN/ADied
HISTOPATHOLOGY

Histopathological assessment plays a pivotal role in the diagnosis of blastomas of the digestive system. Gastroblastomas arise within the gastric muscularis propria, and neither component of its biphasic histology displays much cytologic atypia (Figure 1). The epithelial component consists of cells with round uniform nuclei, slightly eosinophilic cytoplasm, and inconspicuous nucleoli. These cells are arranged in sheets, nests, cords, and tubules. Notably, the epithelial component in some cases forms gland- or rosette-like structures that may contain mucin or dense eosinophilic globules. In contrast, the mesenchymal component consists of homogeneous and slender spindle cells often embedded within a myxoid matrix[28,30]. Immunohistochemistry can be helpful in highlighting these components and confirming the diagnosis. The epithelial component expresses various cytokeratins including AE1/AE3, Cytokeratin 7 (CK7), Cytokeratin 19 (CK19), CAM5.2, and epithelial membrane antigen (EMA). The spindle cells are negative for cytokeratin and express CD56 and CD10. Of diagnostic significance, gastroblastoma does not express CD117 antigen (KIT), Discovered on GIST-1 (DOG1), CD34, Smooth Muscle Actin (SMA), Desmin, synaptophysin, chromogranin, and S100, which separate it from other gastric neoplasms that may be considered in the histologic differential diagnosis[26,29]. Besides its biphasic differentiation, detection of MALAT1-GLI1 gene fusion was traditionally regarded as confirmatory, although EWSR1-CTBP1 ( in a pediatric case[4]) and PTCH1-GLI2 fusions have been described more recently[5,6].

Figure 1
Figure 1 Gastroblastoma in a 19-year-old patient. A and B: The tumor involves the muscularis propria of the antrum (20 ×); C: The tumor shows a biphasic histology with spindle stromal component more prominent in left lower of the image (40 ×); D: The high-magnification image shows the epithelial cells with glandular formation (400 ×); E: Cytoketatin staining (AE1/3) labels the epithelial cells but not the mesenchymal component (200 ×).

The histology of hepatoblastoma may reflect any stage of hepatic development and, thus, can be quite varied. Some tumors are purely epithelial while others show mixed epithelial and mesenchymal differentiation. The epithelial elements can range in appearance from that of early immature embryonal hepatocytes to a well differentiated hepatocellular phenotype. When present, fetal-type cells are characterized by eosinophilic cytoplasm and distinct cell borders, often arranged in cords or nests reminiscent of, but disorganized as compared to normal liver architecture. In contrast, embryonal components appear more basophilic and densely packed, with a tendency to form pseudoacinar structures. Adding to the potential for diagnostic confusion, ductular (cholangioblastic) differentiation may also be found, and some cases show small cell undifferentiated (SCUD) histology. Mesenchymal components are also varied and can range from fibroblastic to heterologous elements such as bone or cartilage (Figure 2), and some tumors are divided into lobules by non-neoplastic fibrous bands[9,28,29,32,69,70]. There is no definitive immunomarker to distinguish hepatoblastoma from hepatocellular carcinoma, although the latter is positive only for hepatocellular markers, usually occurs in a cirrhotic liver background, and will not contain immature or mesenchymal components. That said, immunohistochemical markers still play a role in the diagnostic and prognostic evaluation of hepatoblastoma[10,28,70,71] with at least some tumor cells, depending on their histologic appearance, expressing AFP, HepPar1, glypican 3, and/or β-catenin (nuclear and cytoplasmic). Pancytokeratins are variably positive in epithelial components, and CK7 and CK19 will highlight cholangioblastic elements when present. Importantly, SWI/SNF-related matrix-associated actin-dependent regulator of chromatin subfamily B member 1 (SMARCB1/INI1) is expressed in almost all cases of hepatoblastoma, throughout its varied components. SMARCB1 negative tumors are rare, limited to a subset of those with SCUD histology, and have a poor prognosis.

Figure 2
Figure 2 Mixed epithelial mesenchymal hepatoblastoma in an adult patient, showing a heterogeneous mix of epithelial and mesenchymal components. Well differentiated fetal-type epithelial component is characterized by their eosinophilic cytoplasm and cords or nests-like growth reminiscent of normal liver architecture. The mesenchymal part shows heterologous osteoid elements (100 ×).

Histology of adult pancreatoblastoma is characterized by a multilineage cellular proliferation predominantly showing acinar differentiation with distinctive squamoid nests always present. Additionally, neuroendocrine differentiation is common whereas ductal, mesenchymal, or more primitive components are less pronounced. Its acinar component can mimic acinar cell carcinoma as well as the related typical histologic differential diagnosis of pancreatic endocrine tumors and solid pseudopapillary neoplasms too. However, none of these display the prototypical squamoid nests of pancreatoblastoma[22]. While the neuroendocrine component of pancreatoblastoma may be detectable as increased serum levels of hormones, this is uncommon in the adult population[21]. Immunohistochemistry plays a critical role in diagnosing pancreatoblastoma. Acinar differentiation is highlighted with immunolabeling for trypsin, chymotrypsin, and B-cell Lymphoma/Leukemia 10. Neuroendocrine differentiation is evidenced by the expression of Synaptophysin, Chromogranin, and Insulinoma-Associated Protein 1, but should not be diffuse as in the case of pancreatic endocrine tumors. The squamoid component is positive for EMA and beta-catenin (nuclear staining) whereas the latter would be diffusely evident in a solid pseudopapillary neoplasm. Although these tumors may be histologically complex, the synchronous presence of acinar differentiation with immunochemical confirmation plus squamoid nests typically allows for straightforward diagnosis in well sampled tumors[22] (Figure 3).

Figure 3
Figure 3 Pancreatoblastoma in the pancreatic head of a 42-year-old male patient. A: The tumor is composed of acinar and ribbonlike morphology composed of relatively monotonous cells with basophilic nuclei, mimicking a pancreatic endocrine tumor (100 ×); B: In a few foci, squamoid nests, consisting of circumscribed whorled nests of polygonal cells with abundant eosinophilic cytoplasm and a squamous appearance, are present (200 ×).
MOLECULAR PATHOLOGY

A molecular hallmark of adult gastroblastoma is the MALAT1-GLI1 fusion, which is considered essential for diagnosis according to the 2019 WHO classification of digestive system tumors[3]. However, recent literature calls this into question. A pediatric patient with Wiskott-Aldrich syndrome, reported by Koo et al[4] in 2021, presented with a gastric submucosal tumor. Despite showing typical histological and immunohistochemical features of gastroblastoma, molecular analysis revealed an EWSR1-CTBP1 fusion gene. Chen et al[5] recently identified a PTCH1::GLI2 gene fusion in another adult patient with otherwise prototypical gastroblastoma[5,6]. Both cases showed no evidence of the MALAT1-GLI1 fusion. These genes, PTCH1 and GLI2, are integral to the Hedgehog (Hh) signaling pathway, which plays a vital role in embryonic development[5,6]. These reports suggest a broader spectrum of genetic aberrations in gastroblastoma than was previously thought.

Genomic sequencing studies have established that mutations in the Wnt-β-catenin signaling pathway are prevalent in hepatoblastoma, with alterations in the Catenin Beta 1 (CTNNB1) gene detected in about 90% of cases[15,72]. These mutations are central to disease pathogenesis and are often accompanied by changes in other Wnt signaling genes. Additionally, a subpopulation of high-risk hepatoblastomas exhibits alterations in the Nuclear Factor, Erythroid 2 Like 2 (NFE2L2) gene, indicating oxidative stress as a contributing factor to cellular transformation and disease progression. The Yap signaling pathway collaborates with β-catenin in tumor development. Nevertheless, the activation mechanism of Yap in hepatoblastoma cases is still unclear, necessitating further studies[72]. Such molecular profiling highlights the complex genetic landscape of hepatoblastoma, may impact patient management presently, and potentially has implications for targeted therapy in the future.

Adult pancreatoblastomas exhibit loss of heterozygosity on chromosome 11p in 86% of cases and alterations in the APC/β-catenin signaling pathway in 67% of cases, including biallelic inactivation of APC and activating CTNNB1 mutations[23]. Interestingly, there is an overlap here with the molecular pathology of hepatoblastoma. Most recently, studies have identified alterations in the Fibroblast Growth Factor Receptor (FGFR) signaling pathway, including FGFR1 mutations and FGFR2 rearrangements, in pancreatoblastomas[64]. Additionally, high-level amplification of Myeloid Cell Leukemia Sequence 1 (MCL1) has been identified in a small percentage of pancreatoblastoma patients. The patients with MCL1-amplified pancreatoblastoma could potentially benefit from targeted MCL1 inhibition[73].

TREATMENT AND PROGNOSIS

Surgical resection is the primary treatment approach in all blastomas of the digestive system with chemotherapy or radiotherapy considered for some patients. Generally, post-surgical outcomes are favorable in adult gastroblastoma patients. However, in some cases, local recurrence, metastasis, and death have been reported[30,43]. The case report by Liu et al[6] demonstrating successful treatment with endoscopic submucosal dissection offers an insight into less invasive treatment for localized disease[6].

Outcomes are markedly different in adult hepatoblastoma. For unresectable tumors, the one-year survival rate is 0% whereas it is 41% for resectable tumors[69]. Prognosis is dependent on various factors including patient age, extent of resection, and stage of disease. Outcomes are much better in patients who had complete surgical resection before the age of 45 years compared to those who were treated after that[69]. Adjunctive chemotherapy including vincristine, 5-fluorouracil, and cisplatin have improved the 5-year survival rate[69].

Adult pancreatobastoma, even with aggressive therapy, has poor outcomes and its optimal treatment strategy is not known. While controversial, adjuvant chemotherapy, including 5-flurororacil/doxorubicin/mitoycin and dororubicin/carboplatin, and radiotherapy may be used as palliative treatment in advanced disease[41]. The average survival in adults is only 15-18 months[37,41]. Nearly half of patients have either local invasion and/or metastasis at diagnosis[41]. The most common site for metastasis is the liver, followed by regional lymph nodes and lung[41]. BRAF and MEK inhibitors such as Dabrafenib and Trametinib showed transient response at advanced stage, given the novel IQ Motif and Sec7 Domain 1 - Rapidly Accelerated Fibrosarcoma 1 (IQSEC1-RAF1) fusion in pancreatoblastoma[74].

COMPARISON OF DIGESTIVE SYSTEM BLASTOMA IN PEDIATRIC AND ADULT POPULATIONS

To date, only 16 cases of gastroblastoma in adults have been reported. Acknowledging the limited number of cases available for comparison, pediatric patients tend to present with more pronounced clinical symptoms, such as intermittent blood in stools and significant abdominal pain[75-77]. Moreover, a distinctive demographic difference is apparent, with all reported pediatric cases occurring in males[4,75-77], as opposed to adult gastroblastoma, which affects both males and females. The remaining disease features are consistent between the two populations, and, regardless of age, patients generally show a favorable prognosis following surgical resection.

Hepatoblastoma exhibits distinct characteristics in adults. Pediatric patients typically show symptoms like abdominal swelling and pain, whereas adult symptoms are subtler[69]. Notably, about 40% of adult cases from 2013 to 2023 have underlying liver conditions like viral hepatitis or cirrhosis (Table 2), unlike the pediatric cases, which generally occur in patients without pre-existing liver disease. Histologically, adult cases also often show a more aggressive, undifferentiated histology whereas pediatric hepatoblastoma tends to show more typical epithelial and mesenchymal components including heterologous elements that indicate a favorable prognosis[69,78,79]. In adult hepatoblastoma, the presence of embryonal or undifferentiated cells often indicates a poorer prognosis[69]. Most significantly, adults are more prone to recurrence or metastasis than children despite similar treatment approaches.

Pancreatoblastoma certainly shows significant differences between adults and children. Because only 17% of pediatric cases demonstrate extrapancreatic disease at the time of diagnosis[80], presenting symptoms, like abdominal pain, palpable abdominal masses, jaundice, and vomiting, are all attributable to local tumor effect. In contrast, adults have a poorer prognosis and often present with symptoms and signs related to the more aggressive disease course, which includes frequent invasion of adjacent organs and structures as well as frequent metastases. Histology is similar in the age groups, but adult pancreatoblastomas typically contain less stroma[81]. Surgical resection is the primary treatment for both groups, often supplemented with chemotherapy and radiation therapy. However, adults generally have a poorer prognosis, frequently due to the invasion of adjacent organs or metastasis at the time of diagnosis.

CONCLUSION

In this review, we focus on adult digestive system blastomas, covering aspects like histopathology, molecular pathology, and treatment outcomes, along with comparisons between pediatric and adult cases. Gastroblastoma is characterized by biphasic morphology and distinctive genetic features, notably the MALAT1-GLI1 fusion. Hepatoblastoma shows diverse morphology and commonly exhibits mutations in the Wnt-β-catenin signaling pathway. Pancreatoblastoma is marked by acinar differentiation and squamoid nests, sharing molecular pathology similarities with hepatoblastoma. Treatment mainly involves surgery, possibly with adjunct chemotherapy or radiotherapy. This review underscores the importance of ongoing research for a deeper understanding and improved management of these rare blastomas.

Footnotes

Provenance and peer review: Invited article; Externally peer reviewed.

Peer-review model: Single blind

Specialty type: Gastroenterology and hepatology

Country/Territory of origin: United States

Peer-review report’s scientific quality classification

Grade A (Excellent): 0

Grade B (Very good): B

Grade C (Good): 0

Grade D (Fair): 0

Grade E (Poor): 0

P-Reviewer: Yang JS, China S-Editor: Li L L-Editor: A P-Editor: Yu HG

References
1.  Miettinen M, Dow N, Lasota J, Sobin LH. A distinctive novel epitheliomesenchymal biphasic tumor of the stomach in young adults ("gastroblastoma"): a series of 3 cases. Am J Surg Pathol. 2009;33:1370-1377.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 32]  [Cited by in F6Publishing: 37]  [Article Influence: 2.5]  [Reference Citation Analysis (0)]
2.  McCammon N, Dunn A, Graham R, McHugh J, Lamps L, Bresler SC, Cole T, Rottmann D. Gastroblastoma of the Pylorus: A Case Report and Review of the Literature. Int J Surg Pathol. 2023;31:1516-1521.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
3.  Graham RP, Nair AA, Davila JI, Jin L, Jen J, Sukov WR, Wu TT, Appelman HD, Torres-Mora J, Perry KD, Zhang L, Kloft-Nelson SM, Knudson RA, Greipp PT, Folpe AL. Gastroblastoma harbors a recurrent somatic MALAT1-GLI1 fusion gene. Mod Pathol. 2017;30:1443-1452.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 63]  [Cited by in F6Publishing: 83]  [Article Influence: 11.9]  [Reference Citation Analysis (0)]
4.  Koo SC, LaHaye S, Kovari BP, Schieffer KM, Ranalli MA, Aldrink JH, Michalsky MP, Colace S, Miller KE, Bedrosian TA, Leraas KM, Voytovich K, Wheeler G, Brennan P, Fitch J, Kelly BJ, McGrath SD, Miller AR, White P, Magrini V, Wilson RK, Mardis ER, Lauwers GY, Baker PB, Cottrell CE. Gastroblastoma with a novel EWSR1-CTBP1 fusion presenting in adolescence. Genes Chromosomes Cancer. 2021;60:640-646.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 13]  [Article Influence: 4.3]  [Reference Citation Analysis (0)]
5.  Chen C, Lu J, Wu H. Case Report: Submucosal gastroblastoma with a novel PTCH1::GLI2 gene fusion in a 58-year-old man. Front Oncol. 2022;12:935914.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 4]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
6.  Liu Y, Wu H, Wu X, Feng Y, Jiang Q, Wang Q, Yang A. Gastroblastoma Treated by Endoscopic Submucosal Excavation with a Novel PTCH1::GLI2 Fusion: A Rare Case Report and Literature Review. Curr Oncol. 2022;29:8862-8873.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 1]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
7.  Papry A, Kamal M, Khalid MS. Hepatoblastoma in a child with dextrocardia and possible histopathological alteration reminiscent of hepatocellular carcinoma after neoadjuvant chemotherapy. Clin Case Rep. 2018;6:1070-1073.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 0.3]  [Reference Citation Analysis (0)]
8.  Marx H. Ueber einen eigenartigen primaren Tumor der Leber. Nebst Bemerkungen zur Chorion epitheliomfrage. Beit Path Anat. 1904;36:585-605.  [PubMed]  [DOI]  [Cited in This Article: ]
9.  Celotti A, D'Amico G, Ceresoli M, Tomasoni M, Raimondo S, Baggi P, Baiocchi GL. Hepatoblastoma of the adult: A systematic review of the literature. Surg Oncol. 2016;25:339-347.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 8]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
10.  Ihssan E, Hajar E, Salma B, Soumaya EC, Youssef M, Mouna K, Basma EK. Two Cases of Hepatoblastoma in Adults. Clin Pathol. 2022;15:2632010X221129592.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
11.  Roebuck DJ, Perilongo G. Hepatoblastoma: an oncological review. Pediatr Radiol. 2006;36:183-186.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 45]  [Cited by in F6Publishing: 46]  [Article Influence: 2.6]  [Reference Citation Analysis (0)]
12.  Allan BJ, Parikh PP, Diaz S, Perez EA, Neville HL, Sola JE. Predictors of survival and incidence of hepatoblastoma in the paediatric population. HPB (Oxford). 2013;15:741-746.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 69]  [Cited by in F6Publishing: 71]  [Article Influence: 6.5]  [Reference Citation Analysis (0)]
13.  Pila-Pérez R, Saurith-Monterrosa JL, Rosales-Torres P, Pila-Peláez R, Artola-González JA. A case of adult hepatoblastoma. Rev Colomb Gastroenterol. 2020;35:220-225.  [PubMed]  [DOI]  [Cited in This Article: ]
14.  Agarwal M, Kanodia S, Singh J, Giri V. Hepatoblastoma in adults with clinical symptoms and histopathological evaluation. Pharm Anal Acta. 2023;128-131.  [PubMed]  [DOI]  [Cited in This Article: ]
15.  Tsvetkova V, Magro G, Broggi G, Luchini C, Cappello F, Caporalini C, Buccoliero AM, Santoro L. New insights in gastrointestinal "pediatric" neoplasms in adult patients: pancreatoblastoma, hepatoblastoma and embryonal sarcoma of the liver. A practical approach by GIPPI-GIPAD Groups. Pathologica. 2022;114:64-78.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 3]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
16.  Omiyale AO. Adult pancreatoblastoma: Current concepts in pathology. World J Gastroenterol. 2021;27:4172-4181.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in CrossRef: 7]  [Cited by in F6Publishing: 10]  [Article Influence: 3.3]  [Reference Citation Analysis (0)]
17.  Luchini C, Grillo F, Fassan M, Vanoli A, Capelli P, Paolino G, Ingravallo G, Renzulli G, Doglioni C, D'Amuri A, Mattiolo P, Pecori S, Parente P, Florena AM, Zamboni G, Scarpa A. Malignant epithelial/exocrine tumors of the pancreas. Pathologica. 2020;112:210-226.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 11]  [Cited by in F6Publishing: 4]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
18.  Kohda E, Iseki M, Ikawa H, Endoh M, Yokoyama J, Mukai M, Hata J, Yamazaki H, Miyauchi J, Saeki M. Pancreatoblastoma. Three original cases and review of the literature. Acta Radiol. 2000;41:334-337.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 27]  [Article Influence: 1.1]  [Reference Citation Analysis (0)]
19.  Chen M, Zhang H, Hu Y, Liu K, Deng Y, Yu Y, Wu Y, Qi A, Li Y, Wen G. Adult pancreatoblastoma: A case report and clinicopathological review of the literature. Clin Imaging. 2018;50:324-329.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 9]  [Cited by in F6Publishing: 9]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
20.  Morales GES, Payan HL, Valladares RAM, Rosado ID, Chan C. Adult pancreatoblastoma: A rare malignant tumor of the pancreas. Ann Hepatobiliary Pancreat Surg. 2021;25:436-439.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
21.  Kulak O, Osipov A, Hendifar AE, Nissen NN, Cox BK, Hruban RH, Hutchings DA. Pancreatoblastoma in Elderly Adults: Report of Two Patients. Int J Surg Pathol. 2023;31:772-777.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
22.  Rojas A, Wodskow J, Hogg ME. Adult Pancreatoblastoma: a Rare Pancreatic Tumor. J Gastrointest Surg. 2023;27:3102-3104.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
23.  Abraham SC, Wu TT, Klimstra DS, Finn LS, Lee JH, Yeo CJ, Cameron JL, Hruban RH. Distinctive molecular genetic alterations in sporadic and familial adenomatous polyposis-associated pancreatoblastomas : frequent alterations in the APC/beta-catenin pathway and chromosome 11p. Am J Pathol. 2001;159:1619-1627.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 209]  [Cited by in F6Publishing: 160]  [Article Influence: 7.0]  [Reference Citation Analysis (0)]
24.  Yamaguchi S, Fujii T, Izumi Y, Fukumura Y, Han M, Yamaguchi H, Akita T, Yamashita C, Kato S, Sekiya T. Identification and characterization of a novel adenomatous polyposis coli mutation in adult pancreatoblastoma. Oncotarget. 2018;9:10818-10827.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 11]  [Article Influence: 1.8]  [Reference Citation Analysis (0)]
25.  Omiyale AO. Clinicopathological review of pancreatoblastoma in adults. Gland Surg. 2015;4:322-328.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 13]  [Reference Citation Analysis (0)]
26.  Zouros E, Manatakis DK, Delis SG, Agalianos C, Triantopoulou C, Dervenis C. Adult pancreatoblastoma: A case report and review of the literature. Oncol Lett. 2015;9:2293-2298.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 17]  [Cited by in F6Publishing: 17]  [Article Influence: 1.9]  [Reference Citation Analysis (0)]
27.  Huang Y, Yang W, Hu J, Zhu Z, Qin H, Han W, Wang H. Diagnosis and treatment of pancreatoblastoma in children: a retrospective study in a single pediatric center. Pediatr Surg Int. 2019;35:1231-1238.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 19]  [Cited by in F6Publishing: 19]  [Article Influence: 3.8]  [Reference Citation Analysis (0)]
28.  Centonze G, Mangogna A, Salviato T, Belmonte B, Cattaneo L, Monica MAT, Garzone G, Brambilla C, Pellegrinelli A, Melotti F, Testi A, Monti V, Kankava K, Gasparini P, Dagrada G, Mazzaferro V, Cotsoglou C, Collini P, Pruneri G, Milione M. Gastroblastoma in Adulthood-A Rarity among Rare Cancers-A Case Report and Review of the Literature. Case Rep Pathol. 2019;2019:4084196.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 6]  [Article Influence: 1.2]  [Reference Citation Analysis (0)]
29.  Wang YX, Liu H. Adult hepatoblastoma: systemic review of the English literature. Dig Surg. 2012;29:323-330.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 30]  [Cited by in F6Publishing: 27]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
30.  Wey EA, Britton AJ, Sferra JJ, Kasunic T, Pepe LR, Appelman HD. Gastroblastoma in a 28-year-old man with nodal metastasis: proof of the malignant potential. Arch Pathol Lab Med. 2012;136:961-964.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 17]  [Cited by in F6Publishing: 24]  [Article Influence: 2.0]  [Reference Citation Analysis (0)]
31.  Pinto DN VJ, Gomes D, Brito T, Leite M, Monteiro C, Matos C, Fazeres F, Lopes L, Midões A. Gastroblastoma described in adult patient. Int J Case Rep Images. 2019;10:100995.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 0.4]  [Reference Citation Analysis (0)]
32.  Yamazaki M, Ryu M, Okazumi S, Kondo F, Cho A, Okada T, Takayama W, Kawashima T, Furuki A, Hirata T. Hepatoblastoma in an adult A case report and clinical review of literatures. Hepatol Res. 2004;30:182-188.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 25]  [Cited by in F6Publishing: 25]  [Article Influence: 1.3]  [Reference Citation Analysis (0)]
33.  Al-Jiffry BO. Adult hepatoblastoma: A case report and literature review. Int J Surg Case Rep. 2013;4:204-207.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 9]  [Cited by in F6Publishing: 8]  [Article Influence: 0.7]  [Reference Citation Analysis (0)]
34.  Wu M, Lin J, Liu Z, Huang Z, Wang R. CT, MRI, and (18)F-FDG PET/CT imaging features of seven cases of adult pancreatoblastoma. BMC Med Imaging. 2022;22:228.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Reference Citation Analysis (0)]
35.  Li J, Peng C, Fan X, Wang L, Wang J. Adult pancreatoblastoma: a case report. J Int Med Res. 2021;49:3000605211039565.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 1]  [Reference Citation Analysis (0)]
36.  Zhang X, Ni SJ, Wang XH, Huang D, Tang W. Adult pancreatoblastoma: clinical features and Imaging findings. Sci Rep. 2020;10:11285.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 3]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
37.  Cavallini A, Falconi M, Bortesi L, Crippa S, Barugola G, Butturini G. Pancreatoblastoma in adults: a review of the literature. Pancreatology. 2009;9:73-80.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 41]  [Cited by in F6Publishing: 35]  [Article Influence: 2.2]  [Reference Citation Analysis (0)]
38.  Du E, Katz M, Weidner N, Yoder S, Moossa AR, Shabaik A. Ampullary pancreatoblastoma in an elderly patient: a case report and review of the literature. Arch Pathol Lab Med. 2003;127:1501-1505.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 17]  [Cited by in F6Publishing: 20]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
39.  Yang X, Wang X. Imaging findings of pancreatoblastoma in 4 children including a case of ectopic pancreatoblastoma. Pediatr Radiol. 2010;40:1609-1614.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 18]  [Cited by in F6Publishing: 16]  [Article Influence: 1.1]  [Reference Citation Analysis (0)]
40.  Qureshi SS, Bhagat M, Kurkure PA, Kembhavi SA. Ectopic Cushing syndrome secondary to recurrent pancreatoblastoma in a child: Lessons learnt. J Cancer Res Ther. 2015;11:1027.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4]  [Cited by in F6Publishing: 4]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
41.  Salman B, Brat G, Yoon YS, Hruban RH, Singhi AD, Fishman EK, Herman JM, Wolfgang CL. The diagnosis and surgical treatment of pancreatoblastoma in adults: a case series and review of the literature. J Gastrointest Surg. 2013;17:2153-2161.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 40]  [Cited by in F6Publishing: 34]  [Article Influence: 3.1]  [Reference Citation Analysis (0)]
42.  Kletter GB, Sweetser DA, Wallace SF, Sawin RS, Rutledge JC, Geyer JR. Adrenocorticotropin-secreting pancreatoblastoma. J Pediatr Endocrinol Metab. 2007;20:639-642.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 13]  [Cited by in F6Publishing: 11]  [Article Influence: 0.6]  [Reference Citation Analysis (0)]
43.  Castri F, Ravegnini G, Lodoli C, Fiorentino V, Abatini C, Giustiniani MC, Angelini S, Ricci R. Gastroblastoma in old age. Histopathology. 2019;75:778-782.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 5]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
44.  Fernandes T, Silva R, Devesa V, Lopes JM, Carneiro F, Viamonte B. AIRP best cases in radiologic-pathologic correlation: gastroblastoma: a rare biphasic gastric tumor. Radiographics. 2014;34:1929-1933.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 5]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
45.  Poizat F, de Chaisemartin C, Bories E, Delpero JR, Xerri L, Flejou JF, Monges G. A distinctive epitheliomesenchymal biphasic tumor in the duodenum: the first case of duodenoblastoma? Virchows Arch. 2012;461:379-383.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 10]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
46.  Toumi O, Ammar H, Korbi I, Ayed M, Gupta R, Nasr M, Salem R, Hadhri R, Zayed S, Noomen F, Zakhama A, Zouari K. Gastroblastoma, a biphasic neoplasm of stomach: A case report. Int J Surg Case Rep. 2017;39:72-76.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 16]  [Article Influence: 2.3]  [Reference Citation Analysis (0)]
47.  Gong C, Xu J, Qiao S, Zhang X, Yi M. Gastroblastoma without GLI1 and EWSR1 gene breaks. World J Surg Oncol. 2023;21:274.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
48.  Zhu N, Hou YY, Ge XW, Yao JM. A small volume gastroblastoma occurred in a 65-year-old woman. Zhenduan Binglixue Zazhi. 2018;25:2.  [PubMed]  [DOI]  [Cited in This Article: ]
49.  Pagarigan AKL, Mendoza PGL. Adult hepatoblastoma: making the challenging distinction from hepatocellular carcinoma. J Liver Cancer. 2023;23:219-224.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
50.  Park KW, Seo CJ, Yun DY, Kim MK, Kim BS, Han YS, Oh HK, Lee CH. A case of hepatoblastoma misdiagnosed as combined hepatocellular carcinoma and cholangiocarcinoma in an adult. Clin Mol Hepatol. 2015;21:300-308.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 8]  [Cited by in F6Publishing: 7]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
51.  Caso-Maestro Ó, Justo-Alonso I, Cambra-Molero F, Manrique-Municio A, Calvo-Pulido J, Jiménez-Romero C. Adult hepatoblastoma: case report with adrenal recurrence. Rev Esp Enferm Dig. 2013;105:638-639.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 4]  [Cited by in F6Publishing: 4]  [Article Influence: 0.4]  [Reference Citation Analysis (0)]
52.  Cienfuegos JA, Labiano T, Pedano N, Zozaya GN, Martí-Cruchaga P, Panizo Á, Rotellar F. Adult hepatoblastoma. Rev Esp Enferm Dig. 2013;105:229-231.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 10]  [Article Influence: 0.9]  [Reference Citation Analysis (0)]
53.  Zhang Q, Ming J, Zhang S, Guo D, Qiu X. A rare case of adult hepatoblastoma with neuroendocrine differentiation misdiagnosed as neuroendocrine tumor. Int J Clin Exp Pathol. 2013;6:308-313.  [PubMed]  [DOI]  [Cited in This Article: ]
54.  Celotti A, Baiocchi GL, Ceresoli M, Bartoli M, Ulinici S, Portolani N. Hepatoblastoma of the adult with pericardial metastasis: A case report. Int J Surg Case Rep. 2016;20:80-83.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 5]  [Cited by in F6Publishing: 5]  [Article Influence: 0.6]  [Reference Citation Analysis (0)]
55.  Goikoetxea Urdiain A, Sánchez Acedo P, Mateo Retuerta J, Tarifa Castilla A, Zazpe Ripa C, Herrera Cabezón J. [Adult hepatoblastoma. A case report]. An Sist Sanit Navar. 2016;39:301-304.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 0.3]  [Reference Citation Analysis (0)]
56.  Dave M, Vignesh K, Bordi S, Saini H, Sukhwal D, Sareen M. Hepatoblastoma: A rare presentation in elderly. BJKines-NJBAS. 2019;11:63-67.  [PubMed]  [DOI]  [Cited in This Article: ]
57.  Machado I, López-Guerrero JA, Fernandez A, López R, García Casado Z, Ferrandez A, Llombart-Bosch A, Charville GW. Adult Pancreatoblastoma: Report of 3 new Cases With Genetic Diversity and Autopsy Findings. Int J Surg Pathol. 2023;31:896-906.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
58.  Hussain A, Farrukh J. Adult Pancreatoblastoma: An Uncommon Pancreatic Malignancy. Cureus. 2023;15:e48063.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
59.  Suemitsu Y, Ono Y, Mizukami Y, Ye J, Yamakawa K, Takamoto T, Nakano-Narusawa Y, Mukai Y, Takamatsu M, Nakazawa A, Mino-Kenudson M, Kumasaka T, Matsuda Y. A Case of Adult Pancreatoblastoma With Novel APC Mutation and Genetic Heterogeneity. Front Oncol. 2021;11:725290.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 2]  [Article Influence: 0.7]  [Reference Citation Analysis (0)]
60.  Raoul JL, Oziel-Taieb S, Lecomte T, Adelaide J, Guille A, Chaffanet M, Poizat F, Heymann MF, Barbier L, Bertucci F. Case Report: Two Cases of Metastatic Pancreatoblastoma in Adults: Efficacy of Folfirinox and Implication of the Wnt/β-Catenin Pathway in Genomic Analysis. Front Oncol. 2021;11:564506.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 3]  [Article Influence: 1.0]  [Reference Citation Analysis (0)]
61.  Elghawy O, Wang JS, Whitehair RM, Grosh W, Kindwall-Keller TL. Successful treatment of metastatic pancreatoblastoma in an adult with autologous hematopoietic cell transplant. Pancreatology. 2021;21:188-191.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 0.7]  [Reference Citation Analysis (0)]
62.  Snyder MH, Ampie L, Mandell JW, Helm GA, Syed HR. A Rare Case of Pancreatoblastoma with Intracranial Seeding. World Neurosurg. 2020;142:334-338.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 2]  [Cited by in F6Publishing: 2]  [Article Influence: 0.5]  [Reference Citation Analysis (0)]
63.  Morrissey G, Cohen P, Julve M. Rare case of adult pancreatoblastoma. BMJ Case Rep. 2020;13.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 1]  [Cited by in F6Publishing: 3]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
64.  Berger AK, Mughal SS, Allgäuer M, Springfeld C, Hackert T, Weber TF, Naumann P, Hutter B, Horak P, Jahn A, Schröck E, Haag GM, Apostolidis L, Jäger D, Stenzinger A, Fröhling S, Glimm H, Heining C. Metastatic adult pancreatoblastoma: Multimodal treatment and molecular characterization of a very rare disease. Pancreatology. 2020;20:425-432.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 6]  [Cited by in F6Publishing: 6]  [Article Influence: 1.5]  [Reference Citation Analysis (0)]
65.  Liu ET, Liu C, Wang HL, Sun TT, Wang SX. Adult Pancreatoblastoma With Liver Metastasis Diagnosed by 18F-FDG PET/CT and 2 Years' Postoperative Follow-up. Clin Nucl Med. 2020;45:e24-e28.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 3]  [Cited by in F6Publishing: 3]  [Article Influence: 0.8]  [Reference Citation Analysis (0)]
66.  Yin SM, Liu YW, Chou FF, Kuo FY, Tsang LC. Complete Surgical Resection and Aggressive Treatment for Liver Metastasis May Be Beneficial to Adult Patients With Pancreatoblastoma: A Case Report and Review of Literature. Int Surg. 2019;104:149-154.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
67.  Reid MD, Bhattarai S, Graham RP, Pehlivanoglu B, Sigel CS, Shi J, Saqi A, Shirazi M, Xue Y, Basturk O, Adsay V. Pancreatoblastoma: Cytologic and histologic analysis of 12 adult cases reveals helpful criteria in their diagnosis and distinction from common mimics. Cancer Cytopathol. 2019;127:708-719.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 10]  [Cited by in F6Publishing: 18]  [Article Influence: 3.6]  [Reference Citation Analysis (0)]
68.  Nunes G, Coelho H, Patita M, Barosa R, Pinto Marques P, Roque Ramos L, Brito MJ, Tomaz A, Fonseca J. Pancreatoblastoma: an unusual diagnosis in an adult patient. Clin J Gastroenterol. 2018;11:161-166.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 7]  [Cited by in F6Publishing: 4]  [Article Influence: 0.6]  [Reference Citation Analysis (0)]
69.  Rougemont AL, McLin VA, Toso C, Wildhaber BE. Adult hepatoblastoma: learning from children. J Hepatol. 2012;56:1392-1403.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 31]  [Cited by in F6Publishing: 34]  [Article Influence: 2.8]  [Reference Citation Analysis (0)]
70.  Musick SR, Smith M, Rouster AS, Babiker HM.   Hepatoblastoma. 2023 Jul 17. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-.  [PubMed]  [DOI]  [Cited in This Article: ]
71.  Hager J, Sergi CM.   Hepatoblastoma. In: Liver Cancer [Internet]. Brisbane (AU): Exon Publications; 2021-Apr-6.  [PubMed]  [DOI]  [Cited in This Article: ]
72.  Bell D, Ranganathan S, Tao J, Monga SP. Novel Advances in Understanding of Molecular Pathogenesis of Hepatoblastoma: A Wnt/β-Catenin Perspective. Gene Expr. 2017;17:141-154.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 71]  [Cited by in F6Publishing: 66]  [Article Influence: 9.4]  [Reference Citation Analysis (0)]
73.  Reissig TM, Uhrig S, Jost PJ, Luchini C, Vicentini C, Liffers ST, Allgäuer M, Adsay V, Scarpa A, Lawlor RT, Fröhling S, Stenzinger A, Klöppel G, Schildhaus HU, Siveke JT. MCL1 as putative target in pancreatoblastoma. Virchows Arch. 2022;481:265-272.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 2]  [Reference Citation Analysis (0)]
74.  Goto H, Koga Y, Kohashi K, Ono H, Takemoto J, Matsuura T, Tajiri T, Ihara K, Oda Y, Ohga S. Pancreatoblastoma with a novel fusion gene of IQSEC1-RAF1. Pediatr Blood Cancer. 2023;70:e30155.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in F6Publishing: 3]  [Reference Citation Analysis (0)]
75.  Shin DH, Lee JH, Kang HJ, Choi KU, Kim JY, Park DY, Lee CH, Sol MY, Park JH, Kim HY, Montgomery E. Novel epitheliomesenchymal biphasic stomach tumour (gastroblastoma) in a 9-year-old: morphological, ultrastructural and immunohistochemical findings. J Clin Pathol. 2010;63:270-274.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 28]  [Cited by in F6Publishing: 29]  [Article Influence: 2.1]  [Reference Citation Analysis (0)]
76.  Ma Y, Zheng J, Zhu H, Dong K, Zheng S, Xiao X, Chen L. Gastroblastoma in a 12-year-old Chinese boy. Int J Clin Exp Pathol. 2014;7:3380-3384.  [PubMed]  [DOI]  [Cited in This Article: ]
77.  Feng J, Ling C, Xue Y, Li J. Gastroblastoma in a 5-year-old child: a case report and literature review. Front Oncol. 2023;13:1198762.  [PubMed]  [DOI]  [Cited in This Article: ]  [Reference Citation Analysis (0)]
78.  Kasai M, Watanabe I. Histologic classification of liver-cell carcinoma in infancy and childhood and its clinical evaluation. A study of 70 cases collected in Japan. Cancer. 1970;25:551-563.  [PubMed]  [DOI]  [Cited in This Article: ]
79.  González-Crussi F, Upton MP, Maurer HS. Hepatoblastoma. Attempt at characterization of histologic subtypes. Am J Surg Pathol. 1982;6:599-612.  [PubMed]  [DOI]  [Cited in This Article: ]
80.  Dhebri AR, Connor S, Campbell F, Ghaneh P, Sutton R, Neoptolemos JP. Diagnosis, treatment and outcome of pancreatoblastoma. Pancreatology. 2004;4:441-51; discussion 452.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 82]  [Cited by in F6Publishing: 87]  [Article Influence: 4.4]  [Reference Citation Analysis (0)]
81.  Klimstra DS, Wenig BM, Adair CF, Heffess CS. Pancreatoblastoma. A clinicopathologic study and review of the literature. Am J Surg Pathol. 1995;19:1371-1389.  [PubMed]  [DOI]  [Cited in This Article: ]  [Cited by in Crossref: 192]  [Cited by in F6Publishing: 125]  [Article Influence: 4.3]  [Reference Citation Analysis (0)]