Pancreatoblastoma masquerading as hepatoblastoma: A diagnostic dilemma.

Clinicoradiological and histopathological differentiation of pancreatoblastoma from hepatoblastoma can often be a challenge in clinical practice owing to their peculiar resemblance. We report a case of a 4-year-old boy with a right hypochondriac region mass, which was diagnosed as hepatoblastoma on the basis of imaging, raised tumor marker, and biopsy; however, pancreatic origin of the mass was ascertained on exploration and pancreatoblastoma was confirmed on histopathology.

INTRODUCTION

Pancreatoblastoma, though a rare childhood tumor, is the most common malignant pancreatic tumor in children. Clinicoradiological and histopathological resemblance to hepatoblastoma can make its diagnosis and management challenging. To the best of our knowledge, there have been no reports of a pancreatoblastoma diagnosed and initially treated as hepatoblastoma. We hereby report a 4-year-old boy with pancreatoblastoma masquerading as hepatoblastoma and the treatment outcome.

CASE REPORT

A 4-year-old boy presented with complaints of abdominal fullness and low-grade fever for the duration of 1 month. On examination a 12 cm × 10 cm, firm, nontender mass was present in the right hypochondrium in continuation with the liver. Ultrasonography suggested a necrotic mass in the inferior surface of the right lobe of the liver. Computed tomography (CT) scan of the abdomen revealed an 8.5 cm× 8.3 cm × 7.2 cm nonenhancing necrotic mass in segment V of the liver, closely abutting the inferior vena cava, portal vein, and superior mesenteric vein [Figure 1: CT scan showing a well-defined mass with necrotic, nonenhancing areas within arising exophytically from segment V of the liver. The lesion displaces the portal and superior mesenteric veins]. Laboratory investigations revealed hypochromic microcytic anemia, normal liver function test, lactate dehydrogenase (LDH) of 330 U/L, and serum alpha-fetoprotein (AFP) was 3,971 ng/mL. Image-guided core biopsy of the mass suggested fetal epithelial type hepatoblastoma. CT scan of the thorax did not show any pulmonary metastasis. A diagnosis of nonmetastatic pretreatment tumor extension (PRETEXT) I hepatoblastoma was made and the patient was stratified to standard risk (SR) as per the International Childhood Liver Tumours Strategy Group (SIOPEL) system.

Figure 1

Computed tomography scan showing a well-defined mass with necrotic, nonenhancing areas within arising exophytically from segment V of the liver. The lesion displaces the portal and superior mesenteric vein (arrows)

The patient received two cycles of single agent cisplatin as per the SIOPEL 3 SR protocol. Although after the first cycle of chemotherapy the serum AFP level dropped to 3217 ng/mL, it increased to 4,260 ng/mL after the second cycle. In view of poor biochemical response, the chemotherapy was changed to cisplatin and doxorubicin (PLADO). At the end of two cycles of PLADO, the serum AFP level was 2,170 ng/mL; however, there was negligible change in the mass on CT scan. At this point, surgery was contemplated. On exploration, a lobulated mass was found arising from the head of the pancreas with flimsy adhesions with the liver and ascending colon [Figure 2a: Intraoperative image showing the mass arising from the head of pancreas. Duodenum is seen draping the mass]. No other metastatic deposit in the abdomen or retroperitoneum was found. Intraoperatively a decision for pancreaticoduodenectomy (Whipple's procedure) was taken and a complete resection was accomplished. The postoperative course was uneventful and the patient was discharged on the sixth postoperative day.

Figure 2

(a) Intraoperative image showing the mass arising from the head of the pancreas. Duodenum is seen draping the mass (b) Cut-open specimen showing the cystic and lobulated solid areas (arrow: Gallbladder, arrowhead: Proximal jejunum (c) Pancreatoblastoma composed of sheets and nests of small, round, uniform cells. Tubular differentiation is seen in small parts of the tumor. Haematoxylin and eosin staining, 20×

On gross examination, a solid globular tumor measuring 10 cm × 8.2 cm × 6 cm was present in the head of the pancreas with submucosal extension into the duodenum. The cut surface was cystic with lobulated gray white areas [Figure 2b: The cut-open specimen showing the cystic and lobulated solid areas (arrow: Gallbladder, arrowhead: Proximal jejunum]. Microscopically, the tumor was predominantly composed of nests of uniform round cells separated by fibrovascular stroma. [Figure 2c: Pancreatoblastoma composed of sheets and nests of small, round, uniform cells. Tubular differentiation is seen in small parts of the tumor. Hematoxylin and eosin staining, 20×]. Interspersed within the cellular nests were conspicuous acinar and focal glandular structures; however, typical squamous morules were absent. Based on the morphology a diagnosis of pancreatoblastoma was made. The focal parts of the tumor showed “hepatoid” morphology, which seemed a variation of the cell type within the tumor. On immunohistochemistry, the tumor showed positivity for CK7 and CK19 highlighted interspersed ductal elements. Chromogranin was focally positive while synaptophysin, AFP, and beta-catenin were negative. All nodes and cut margins were negative. No further adjuvant treatment was offered to the patient. The patient has been on regular follow-up and remains disease-free 4 years after completion of therapy.

DISCUSSION

Pancreatoblastoma is a rare childhood tumor but the most common malignant pancreatic tumor in young children with the median age of diagnosis being 5 years.[12] It originates from the epithelial exocrine cells of the pancreas and can develop in any part of the pancreas but commonly affects the head.

Pancreatoblastoma may be diagnosed incidentally with the child being asymptomatic. However, being a slow-growing tumor, pancreatoblastomas are often clinically occult until quite large, when symptoms due to the mass effect in the upper abdomen occur.[1] In the present case, the child was investigated for abdominal fullness, which revealed a necrotic mass probably arising from the inferior surface of the right lobe of the liver on imaging. The large size of the tumor posed a diagnostic difficulty in determining the organ of origin on CT scan, which mimicked an exophytic growth from segment V of the liver.

Pancreatoblastomas show resemblance with hepatoblastoma in many characteristics; they arise from the same primitive cells and can therefore, have increased serum AFP levels. Both have been associated with Beckwith-Wiedemann syndrome and share similar molecular pathogenesis.[3] Histologically pancreatoblastoma consists of small round cells, which together with an elevated AFP and the close spatial relation with the liver may pose a challenge in differentiating with hepatoblastoma. The presence of hepatoid variant could have also been a confounding influence.

Surgical resection is the mainstay of treatment, which may entail a Whipple's procedure or a distal pancreatectomy with or without splenectomy, depending on the location of tumor. Long-term survival is possible with complete resection of the tumor though pancreatoblastoma has a high recurrence rate.[2] The role of chemotherapy is not precise; however, it has been used for unresectable or metastatic disease and cisplatin, carboplatin, cyclophosphamide, doxorubicin, and etoposide-based chemotherapy regimens have been found to be effective. The Italian Tumori Rari in Eta’ Pediatrica (the Italian TREP project) has provided guidelines for pancreatoblastoma. The recommended chemotherapy regimen is cisplatin at 80 mg/m2 as a continuous 24-h intravenous infusion followed by doxorubicin 60 mg/m2 over 48 h (PLADO) for four cycles for completely resected patients and six cycles for resection with microscopic residual or nodal involvement.[4] For cases with initial biopsy only or metastatic disease, four cycles of preoperative, cisplatin, and doxorubicin are recommended followed by surgery and two further cycles of chemotherapy.[5] The effectiveness of radiation therapy for local control in pediatric patients is questionable. However, it has been often utilized after incomplete resection, positive surgical margins, or tumor spillage.[6]

CONCLUSION

In conclusion, the difficulty in detecting the organ of origin, coupled with raised serum AFP levels in pancreatoblastoma may make diagnosis challenging; therefore, it is pertinent for the clinician to be aware of the differentials so that effective therapy can be delivered.

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Conflicts of interest

There are no conflicts of interest.