Introduction

Acinar cell carcinoma (ACC) of the pancreas is a rare cancer that originates from acinar cells in the pancreatic parenchyma and accounts for approximately 1 % of pancreatic exocrine malignancies [1, 2]. Reports of ACC in children are very rare, with only 25 cases in the literature. Since adult ACC is also rare, the prognosis has been unclear due to lack of data. Large-scale studies have been published recently, and the results have suggested that ACC has a better prognosis than pancreatic ductal carcinoma. However, the prognosis of pediatric ACC remains unclear due to the scarcity of reports. Here, we report a 12-year-old Japanese girl who underwent radical resection of pancreatic ACC, and we also review the relevant literature.

Case report

A 12-year-old girl developed upper abdominal pain on exercise that was improved by rest. However, mild upper abdominal pain persisted and the patient consulted a local physician after 3 days. Imaging studies revealed a very large mass in the abdomen, and the patient was referred to our department. There was no relevant past history or family history. On examination, a poorly mobile periumbilical mass was palpated and abdominal tenderness was noted. Blood chemistry tests did not show any abnormalities. Regarding tumor markers, AFP was increased to 173.1 ng/ml and elastase 1 was elevated to 36,440 ng/dl, but CEA, CA19-9, and DUPAN-2 were normal at 0.8 ng/l, <0.2 and <25 U/ml, respectively (Table 1). CT scans showed a 17 × 17 × 12 cm mass lesion with a clear and regular margin that occupied the right abdominal cavity, being centered around the right anterior pararenal space posterior to the head of the pancreas and below the liver. The mass was heterogeneous, containing cystic areas and solid areas with uneven contrast enhancement. No dilation of the bile ducts or pancreatic duct was noted. The duodenum was displaced laterally, but there was no evidence of ileus. The large and small intestines were markedly displaced to the left by the mass, but the right ureter was not dilated. The border between the mass and the liver parenchyma was clear. No metastasis to other organs was identified (Fig. 1a–d). MRI revealed that mass contained a small amount of fat. On T2-weighted images, the solid areas showed a high signal intensity, as well as slow and uneven contrast enhancement (Fig. 1e). On PET scanning, the solid areas of the mass were seen as hot spots (SUVmax = 2.7), but there were no hot spots suggestive of metastasis. From these findings, a retroperitoneal tumor (e.g., immature teratoma) or a pancreatic tumor (e.g., solid pseudopapillary tumor) was suspected, and surgery was performed. At operation, the tumor was continuous with the head of the pancreas, but there was no invasion of other organs. Accordingly, we performed pylorus-preserving pancreatoduodenectomy with D1 (+12, 8a) lymphadenectomy and reconstruction by the modified Child procedure, and pancreatojejunostomy with complete drainage (Fig. 2a). The resected specimen contained a tumor measuring 19 × 18 cm that arose from the head of the pancreas, and the cut surface showed both yellowish-white solid areas and cystic areas (Fig. 2b–d). The cysts were filled with brown liquid that was considered to represent old blood. Histopathological examination demonstrated tumor cells with an acinar pattern of proliferation that had small round nuclei, mild atypia, and eosinophilic cytoplasm (Fig. 3a, b). The tumor had a fibrotic capsule and featured internal hemorrhage and necrosis. It invaded the adjacent pancreatic tissue and duodenal muscle layer through the capsule, but no vascular invasion was noted. All of the resection margins were negative. The results of immunostaining were as follows: α1 trypsin (+) (Fig. 3c), α1 chymotrypsin (+) (Fig. 3d), S-100 (−), NSE (−), chromogranin A (−), synaptiphysin (−), amylase (−), vimentin (−), β-catenin (cell membrane (+), nucleus (−)), CD10 (+), CD56 (−), ER (−), and PgR (−). In addition, AFP was slightly positive in some areas (Fig. 3e). These findings were consistent with a diagnosis of ACC of the pancreas (T3N0M0, stage IIA). No complications occurred after surgery, and the patient was discharged on the 32nd postoperative day. Since the tumor was of low malignancy and radical surgery was performed, postoperative adjuvant chemotherapy was not given. AFP and elastase-1 levels were elevated preoperatively, but were normalized after surgery and did not increase again during the follow-up period. At present (52 months after surgery), the patient is alive without recurrence. She has no postoperative growth disorder, and no symptoms such as abdominal pain or diarrhea. Her height and body weight were low before surgery, being 132.5 cm (−2.2 SD) and 29.4 kg (−1.3 SD), respectively, but showed improvement to 154.7 cm (−0.6 SD) and 53.9 kg (−0.1 SD) at the latest review.

Table 1 Laboratory data for the patient (normal range)
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Fig. 1
figure 1

Enhanced CT (a–d) and MR (e) images of the pancreatic acinar cell carcinoma. A 17 × 17 × 12-cm, heterogeneous mass occupied the right abdominal cavity. The tumor had solid and cystic lesions, and the solid lesion showed enhanced heterogeneity

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Fig. 2
figure 2

Scene of the operation (a). A pylorus-preserving pancreatoduodenectomy was performed, because the tumor invaded the pancreatic head. Macroscopic findings (b–d). The tumor was an encapsulated 19 × 18-cm mass derived from the pancreatic head, and the cut surface (d) had yellowish white solid parts and cystic parts

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Fig. 3
figure 3

Histological examination. The tumor cells had small, round nuclei with mild atypia, and showed an acinar arrangement. a hematoxylin and eosin (H&E) stain, ×. b H&E stain, ×. Immunohistochemically, tumor cells showed positive staining for α1 trypsin, α1 chymotrypsin, and AFP. c Immunohistochemical staining of α1 trypsin (×). d Immunohistochemical staining of α1 chymotrypsin (×). e Immunohistochemical staining of AFP (×)

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Discussion

Because ACC is rare, only a few patients have been reported from each institution and there is no consensus concerning the treatment or prognosis. The first large-scale study was published in 2007, which was a report by Kitagami et al. on 115 patients with pancreatic ACC in the Cancer Registry of the Japan Pancreas Society [3]. Resection was performed in 76.5 % of these patients, and their 5-year survival rate was 43.9 % (median survival time: 41 months). In 2008, Nicolas et al. published an analysis of 672 patients with pancreatic ACC registered in the Surveillance, Epidemiology, and End Results (SEER) database, reporting a resection rate of 38.7 % and a 5-year survival rate after resection of 71.6 % (median 123 months) [4]. However, the 5-year survival rate of unresectable patients was 0 % according to Kitagami et al. and 22 % according to Nicolas et al., indicating that unresectable ACC has a very poor prognosis. Despite differences between the two reports, which are considered to be due to differences of the surgical indications, the data at least suggest that the prognosis of resectable ACC is more favorable than that of pancreatic ductal carcinoma and that resectable tumors should be treated surgically. Chemotherapy and radiotherapy could also be considered, but there are insufficient data on the efficacy of these modalities for ACC and large-scale studies are needed.

There have been fewer reports of pancreatic ACC in children, and no large-scale analyses. Among 55 cases of pancreatic exocrine tumors in patients aged 16 years or younger accumulated in Germany by Ellerkamp et al. [5] between 1980 and 2007, 5 patients had ACC and this is the largest series. In addition, Dall’igna et al. [6] reviewed 21 patients aged 18 years or younger with pancreatic tumors reported in Italy between 2000 and 2009, including 2 cases of ACC. Table 2 summarizes the 26 reported pediatric cases, including the patients from the above reports and our case [5–21]. Although the details are often unclear, the following characteristics of pediatric ACC can be suggested: (1) the tumors tend to be very large at diagnosis, (2) distant metastasis is rare and in most cases lesions are resectable, (3) patients who undergo resection show long survival and a high long-term survival rate, and (4) many patients have a high AFP level. Similarly to adult ACC, long-term survival can be expected after radical surgical resection.

Table 2 Case of acinar cell carcinoma in childhood in the literature
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One characteristic of ACC in children is that all of the tumors were very large masses ranging from 6 to 20 cm in diameter, probably because asymptomatic children are rarely examined for tumors. Despite the large size of their tumors, few of the patients had distant metastasis. There was no mention of lymph node metastasis in the other reports. Since the tumors were very large and preoperative diagnosis was difficult, it is likely that few patients underwent lymphadenectomy. With respect to adult patients, Kitagami et al. [3] reported that the disease was N0 in 57.6 % of 115 patients with ACC, suggesting that lymph node metastasis is less frequent than in pancreatic ductal carcinoma. In our patient, the tumor was also very large (19 cm in diameter), but there was no distant metastasis or lymph node involvement. On the basis of these results, surgery should be the first option even in children and even if the tumor is very large. However, considering the possibility of long-term survival and subsequent growth of juvenile patients, it is important to avoid lymphadenectomy around the pancreatic head plexus. The AFP level was high in most patients in whom it was measured, although AFP was not mentioned in many reports. In adult patients, Shimizu et al. [22] reported that ACC accounted for 27 % of AFP-producing pancreatic tumors and that AFP is frequently elevated in patients with this disease. AFP was also elevated in our patient. Therefore, an increase of AFP may be frequent in ACC patients and it seems to be a useful tumor marker, particularly in children.

In conclusion, we encountered a 12-year-old girl with pancreatic ACC who underwent surgical resection. At present, she is alive without recurrence at 52 months after surgery, and we hope for long-term survival, as reported in many cases. Many points about ACC remain unclear because of the small number of cases, including the usefulness of postoperative adjuvant chemotherapy, but information regarding effective treatment is expected to increase with accumulation of further reports.