The tumor invading the splenic vein and transverse colon was removed totally (Figure 2). On gross examination, the perforated capsule surrounding the tumor was seen. The tumor measured 12.5x12x6 cm. On cut section there was hemorrhage and also necrosis. We observed a hypercellular tumor in the histopathological examination. The tumor had cell clusters separated by stromal bands and composed of squamoid morules (corpuscles) and epithelial acinar cells. An increase in the nucleus/cytoplasm ratio and nucleomegaly were seen in the epithelial cells that had a pancreatic acini-like pattern. Although the nuclear membranes of the neoplastic cells were regular, coarse chromatin and multiple conspicuous nucleoli were observed and the cells had a pale eosinophilic cytoplasm. Squamoid corpuscles were seen in many clusters of tumor cells. In the squamoid corpuscles, the epithelioid cells were plump and contained dense eosinophilic cytoplasm (Figure 3). Immunohistochemically, the neoplastic cells were positive with alpha-1-antitrypsin but showed no staining with WT-1, monoclonal carcinoembryogenic antigen or Tag72. CD10 and fascin were positive in squamoid corpuscle cells. Nuclear and strong cytoplasmic staining for ß-catenin (Figure 4) was seen in squamoid corpuscle cells but non-neoplastic pancreatic acini showed the expected membranous and faint cytoplasmic staining. In addition, chromogranin A and synaptophysin showed positivity in a few endocrine cells. Typical histological features and immunohistochemistry were suggestive of the diagnosis of PB. After surgery, AFP levels decreased to 72.6 IU/ ml gradually. Adjuvant chemotherapy was used as of the 14th day after surgery. The chemotherapy regimen was as follows: every fifteen days; cisplatin 80 mg/m2, 24 hours constant infusion; carboplatin 500 mg/m2, 1-hour infusion and doxorubicin 60 mg/m2, 48 hours constant infusion. On the postoperative 43rd day, metastatic lesions in the liver were stable and there was a recurrent mass in the pancreas region. With these findings, we concluded that the disease had progressed. The chemotherapy regimen was changed to carboplatin 400 mg/m2/day, intravenous, 1-day infusion for 2 days; ifosfamide 1800 mg/m2/day, intravenous, 1-day infusion for 5 days; etoposide 100 mg/m2/day, intravenous, 1-day infusion for 5 days. The radiological evaluation after 6th chemotherapy regimen revealed that the recurrent mass in the pancreatic region had disappeared and metastatic lesions in the liver had regressed. However, an operation was not considered in the case of this patient as the metastatic lesions in the liver were multiple and unresectable. The chemotherapy was therefore continued. Severe neutropenia and progression in the metastatic lesions in the liver were detected during the evaluation following the 9th chemotherapy regimen, The treatment was discontinued upon the request of the parents. The patient died on the 14th month following the operation.
As already known, both the pancreas and the liver stem from the same primitive cells [12]. Therefore, the fact that serum AFP levels are increased in PB cases is not surprising, as in hepatoblastoma [7]. Some authors reported a loss of heterozygosity (LOH) on chromosome 11 in PBs [13,14]. According to Kerr et al. [14], although extensive LOH of the chromosome 11 encompassed the WT-1 gene, mutations were not detected in WT1 gene exons. Abraham et al. [13] observed somatic mutations in the APC/ß-catenin pathway but they did not detect any changes in the p53 and K-ras genes. Also, they postulated that a significant correlation was detected between immunohistochemical ß-catenin positivity and the APC/ß-catenin gene alterations [13]. The molecular and immunohistochemical studies suggest that most PBs exhibit typical genetic alterations and they are similar to other embryonal tumors such as acinar cell carcinoma and hepatoblastoma [12-15]. In our case, immunohistochemically, ßcatenin positivity and WT-1 negativity resemble the data in the literature. Molecular studies in large series may help elucidate the pathogenesis of PB.
The radiological differential diagnosis includes pancreatic cystic neoplasm, ductal adenocarcinoma, acinar cell carcinoma, nonfunctioning endocrine pancreatic tumors, solid pseudo papillary tumors, peripancreatic and pancreatic lesions, especially tuberculosis and autoimmune pancreatitis [4,16]. In early childhood, the spectrum of differential diagnosis is wide when it cannot be clearly seen that the tumor arises from the pancreas [11]. The tumors that must be considered first are Wilms tumor, neuroblastoma, hepatoblastoma, and other primary liver tumors [12,13]. Acinar cell carcinoma and PB have similar histopathological and radiologic appearances [1,11]. However, PB usually occurs in the first decade of childhood, whereas acinar carcinoma is encountered in older patients. Moreover, squamoid corpuscles are typical in PB but they do not exist in acinar cell carcinoma [1,12].
Clinicopathologic features, treatment and prognosis of PB were evaluated in the paper by Dhebri et al. [17]. They reported that 78% of the 153 patients were under 10 years. The symptoms and signs were like those described in other articles [10,18]. Moreover, 17% of their patients had metastatic disease at the time of diagnosis. The study of Dhebri et al. [17] showed that the 5-year survival rate of patients after total resection was 65% whereas median survival of their patients with non resectable disease at the time of diagnosis was 36 months. Furthermore, all of these patients died before 40 months. According to their study, the best choice of treatment is complete resection. If the tumor is unresectable, PB is treated with chemotherapy [17,19]. Although vincristine, doxorubicin, etoposide, cyclophosphamide, cisplatin and adriamycin have turned out to be effective chemotherapeutic agents, there are no established or proven chemotherapy regimens [19]. The efficiency of neoadjuvant chemotherapy was not clearly proven in any studies [17]. New studies with larger series are still needed. Our patient underwent chemotherapy that contained two different groups of medicine for 12 cycles. The first group contained carboplatin, doxorubicin and cisplatin and early relapse and progression were detected during this treatment. The second group contained ifosfamide, carboplatin and etoposide. Regression was found during the 6 courses of chemotherapy but the disease then progressed. Data on the basis of similar cases are needed in order to determine the alternative treatment options and the efficiency of the chemotherapy treatments.
According to SEER data (1973-2004), median survival in PB is 193 months and the 15-year survival rate is 75% but the initial tumor stage was not reported in this study [2]. Our patient had metastatic disease at the time of diagnosis. Although the primary tumor was completely resected in our patient, metastatic lesions in the liver could not be resected. While the first chemotherapy regime was inefficient, response to the second chemotherapy regimen was limited. When these findings were assessed together with literature, early diagnosis and complete resection of the tumors seem to be important in order to decrease the tumor load and to increase the response to treatment. All data about PB have to be collected in order to choose the treatment to elucidate the molecular pathogenesis of the tumor, to enable early diagnosis, and to develop targetspecific treatments.
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