Adult pancreatoblastoma: A case report and review of the literature

  • Authors:
    • Efstratios Zouros
    • Dimitrios K. Manatakis
    • Spiros G. Delis
    • Christos Agalianos
    • Charina Triantopoulou
    • Christos Dervenis
  • View Affiliations

  • Published online on: March 2, 2015     https://doi.org/10.3892/ol.2015.3001
  • Pages: 2293-2298
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Abstract

The present study describes the case of a 24‑year‑old patient who presented with obstructive jaundice and weight loss, and was diagnosed with pancreatoblastoma (PB). Abdominal imaging studies revealed a heterogenous lesion of the pancreatic head with dilatation of the common bile duct. The patient underwent pancreaticoduodenectomy, however, three months after surgery multiple liver and bone metastases were identified on follow-up computed tomography scans. Despite treatment with four cycles of systemic chemotherapy and five courses of radiofrequency ablation, the patient succumbed due to tumour dissemination 13 months after initial diagnosis. PB is a malignant tumour of the pancreas that typically occurs in the pediatric population. The aim of the present study was to highlight the aggressive behavior of this rare clinical entity, focusing on the pitfalls of pre‑operative diagnosis and the lack of management strategy guidelines in adults. Preoperative diagnosis of PB based on radiographic features may be difficult, as the imaging characteristics are non-specific. Furthermore, cytology may also be misleading, as the neoplasm consists of multiple cell lines (acinar, ductal and neuroendocrine cells) and diagnosis depends largely on the identification of the distinctive histological characteristic of squamoid corpuscles, which present as nests of flattened cells with a squamous appearance. Despite the use of surgical resection and adjuvant chemoradiotherapy for the treatment of this malignancy, its aggressive nature means that PB is associated with a poor prognosis in adult patients.

Introduction

Pancreatoblastoma (PB) is a rare epithelial neoplasm of the pancreas, typically occurring in the pediatric population. Since the first report of PB in 1957, >200 cases have been described in children, yet only 39 cases have been described in adult patients (1,2).

PB is an aggressive and malignant tumour, exhibiting high rates of local invasion, recurrence and distant metastatic potential. Furthermore, adult patients with PB have a poor prognosis compared with pediatric patients (3). Symptoms are usually vague and radiological features are non-specific. Thus, diagnosis depends largely on the identification of characteristic squamoid corpuscles on histopathological examination, which would appear as whorled nests of flattened cells with a squamous appearance.

Due to its rarity, no guidelines currently exist on the management protocols for PB. Surgery is considered to be the chief treatment strategy, while the role of chemoradiotherapy remains unclear and the significant benefits of the currently employed regimens are limited (3).

The current study presents the case of a 24-year-old patient who was diagnosed with a rare pathology of PB, but succumbed one year later due to disseminated metastatic disease. In addition, a brief review of the relevant literature is discussed. Written informed consent was obtained from the patient's family.

Case report

In March 2013, a 24-year-old Caucasian, male patient was admitted to the Department of Surgery, Konstantopouleio General Hospital (Athens, Greece) with a three-week history of vague upper abdominal discomfort, anorexia and weight loss. A physical examination revealed obstructive jaundice and mild tenderness over the epigastrium.

Laboratory tests identified elevated serum levels of aspartate aminotransferase (247 IU/l; normal range, 10–37 IU/l), alanine aminotransferase (289 IU/l; normal range, 12–78 IU/l), alkaline phosphatase (563 IU/l; normal range, 46–116 IU/l), γ-glutamyl transpeptidase (703 IU/l; normal range, 15–85 IU/l), direct bilirubin (15.9 mg/dl; normal range, <0.3 mg/dl) and total bilirubin (17 mg/dl; normal range, <1 mg/dl). However, carcinoembryonic antigen (CEA), α-fetoprotein (AFP) and cancer antigen (CA)19-9 levels were within the normal ranges.

An abdominal ultrasound demonstrated the presence of an encapsulated and well-defined mass in the head of the pancreas. Contrast-enhanced computed tomography (CT) scans confirmed a heterogeneous, hypodense mass in the pancreatic head, with no dilatation of the main pancreatic duct and no vascular involvement (Fig. 1). Furthermore, contrast-enhanced magnetic resonance imaging indicated the presence of a hypoenhancing, low-intensity mass in the posterior aspect of the pancreatic head abutting the distal section of the common bile duct on T1-weighted images (Fig. 2). A high signal intensity was observed on T2-weighted images (Fig. 3). In addition, magnetic resonance cholangiopancreatography revealed obliteration of the distal common bile duct, with marked proximal dilatation (Fig. 4).

The patient underwent an exploratory laparotomy, during which a palpable mass measuring ~8×7×8 cm was identified in the pancreatic head. No vascular invasion or distant metastases were observed, therefore, a pylorus-preserving pancreaticoduodenectomy was performed. The post-operative course was uneventful and the patient was discharged on the seventh post-operative day.

Histopathological analysis of the resected lesion demonstrated typical features of PB. The tumour was composed of a combination of undifferentiated small cells, and epithelial and stromal components with partial encapsulation. The epithelial component was dominant and demonstrated an acinar architecture, solid sheets and squamoid corpuscles.

Follow-up abdominal CT scans were performed three months post-operatively, and revealed multiple liver and bone metastases. The patient underwent five courses of radiofrequency ablation (15-minute courses of 60 W thermoablation with Elektrotom 106 HiTT needle, Berchtold GmbH and Co. KG, Tuttlingen, Germany) combined with four cycles of systemic chemotherapy, consisting of cisplatin (80 mg/m2 over 24 h) and doxorubicin (60 mg/m2 over 48 h), each course lasted three weeks; however, no response was observed and the patient succumbed 13 months after initial diagnosis due to tumour dissemination.

Discussion

Adult PB is a rare neoplasm of epithelial origin, accounting for <0.5% of exocrine pancreatic tumours (3). PB was initially described by Becker (1) in 1957 as infantile pancreatic carcinoma, however, Horie et al (4) coined the term pancreatoblastoma in 1977. To date, since Palosaari et al (5) reported the first case of PB in a 37-year-old patient in 1986, only 39 cases have been published in the literature (Table I) (3,533). A literature search of PubMed was conducted with no language restrictions; studies published between 1986 and 2014 were searched using the key words ‘pancreatoblastoma’, ‘pancreas’, ‘pancreatic tumour’ and ‘pancreatic neoplasm’. Additional studies were identified from the references of the retrieved papers. Cases of PB affecting patients ≥18 years of age were included in the analysis.

Table I.

Adult pancreatoblastoma cases in the literature (1986–2014).

Table I.

Adult pancreatoblastoma cases in the literature (1986–2014).

First author/s (ref.)YearAgea/genderSymptomsTumour detailsTreatment strategyFollow-up
Palosaari et al (5)198637/MAbdominal pain, weight loss, diarrhea8 cm, head, LN and vascular involvementIncomplete resection, chemoradiotherapyWith liver metastases at 15 months
Hoorens et al (6)199439/FAbdominal mass13 cm, tailResectionNED at 30 months
Dunn and Longnecker (7)199561/MSplenomegaly9 cm, tailResection, chemotherapySuccumbed after 11 months
Klimstra et al (8)199519/MAbdominal mass15 cm, head; LN involvement, multiple metastasesResectionSuccumbed after 10 months
36/MObstructive jaundice‘Large’, head, LN involvement, liver metastasisNoneSuccumbed after 5 months
37/MAbdominal mass, weight loss12 cm, head, liver metastasis ChemoradiotherapySuccumbed after 38 months
54/FAbdominal pain20 cm, tailResectionNED at 15 months
56/MAbdominal mass20 cm, tailResectionNED at 5 months
Levey and Banner (9)199668/FDiarrhea, weight loss9 cm, headResectionSuccumbed after 4 months
Robin et al (10)199720/MAbdominal mass9 cm headResection, chemotherapySuccumbed after 7 months
Hayasaki et al (11)199948/FUrinary occult blood5 cm, tailResectionNED at 15 months
Montemarano et al (12)200020/FObstructive jaundiceHeadResectionNo data
Mumme et al (13)200122/FAbdominal pain, mass, weight loss9 cm, tailResection, intraoperative radiotherapy, chemotherapySuccumbed after 9 months
Benoist et al (14)200148/FAbdominal pain, melaena10 cm, body, liver metastasisResection, metastasectomy, chemotherapyNED at 36 months
Abraham et al (15)200145/FNo dataNo dataNo dataNo data
200151/FNo dataNo dataNo dataNo data
Gruppioni et al (16)200230/MAbdominal pain8 cm, headResectionNED at 10 months
Du et al (17)200378/FObstructive jaundice2.7 cm, ampulla of VaterResectionNED at 6 months, alive at 4 years
Pitman and Faquin (18)200418/MAbdominal pain, weight loss, diarrhea9 cm, head, vascular involvementNeoadjuvant chemoradiotherapy, resection, multiple metastasectomiesWith lung metastases at 7 years
Rosebrook et al (19)200529/FAbdominal pain2 cm, bodyResectionNo data
Sheng et al (20)200518/MAbdominal pain, obstructive jaundice10 cm, bodyResection, adjuvant chemoradiotherapy, liver TAESuccumbed after 26 months
Zhu et al (21)200524/FObstructive jaundice4 cm, body, liver metastasesChemotherapy, unresectableWith liver metastases at 9 months
Kuxhaus et al (22)200569/MFever, weight loss‘Large’, tail, peritoneal carcinomatosisUnresectableNo data
Rajpal et al (23)200650/MAbdominal pain, weight loss13 cm, tail, colon invasion, liverResection, chemotherapySuccumbed after 17 months metastasis
Charlton-Ouw et al (26)200833/MAbdominal pain, mass, weight loss5 cm, head, liver metastasisMetastectomy, resection, chemoradiotherapyNED at 60 months
Ohike et al (27)200874/FAsymptomatic4.5 cm, headExcisionNED at 108 months
Cavallini et al (24)200969/MAsymptomatic6 cm, bodyResectionNED at 15 months
26/MAbdominal pain5 cm, headResectionNED at 51 months
Comper et al (25)200927/MNo data5.5 cm, headResectionNo data
69/MNo data5.5 cm, bodyResectionNo data
Savastano et al (28)200936/FObstructive jaundice4.3 cm, head, LN involvementResection, adjuvant chemoradiotherapyNo data
Boix et al (29)201033/FAbdominal pain3.5 cm, bodyResectionSuccumbed after 3 months
Balasundaram et al (30)201227/FWeight loss3.6 cm, body, liver and lung metastasesChemotherapySuccumbed after 1 month
Gringeri et al (31)201238/FNo dataHeadResection, chemotherapy, CyberKnife®, liver metastasectomiesNED at 44 months
Hammer and Owens (32)201337/MAbdominal pain, obstructive jaundice7 cm, headResectionNo data
Redelman et al (33)201326/FNo data7.5 cm, headResectionNo data
Salman et al (3)201360/MAbdominal pain1.8 cm, head, liver metastasisResection, chemotherapyNED at 41 months
51/MObstructive jaundice, weight loss4 cm, head, duodenum invasion, LN involvementChemotherapy, resectionSuccumbed after 51 months
58/FAbdominal pain4.5 cm, tail, LN involvementResectionNED at 30 months
Present case201524/MAbdominal pain, weight loss, obstructive jaundice8 cm, headResection, chemotherapySuccumbed after 13 months

{ label (or @symbol) needed for fn[@id='tfn1-ol-0-0-3001'] } Table adapted from reference (26).

a Age in years. M, male; F, female; LN, lymph nodes; NED, no evidence of disease; TAE, transarterial embolisation.

PB displays a bimodal age distribution (modal ages, 2.5 and 40 years), while both genders are equally affected (male:female ratio, 1:1) (3,31). The majority of cases are sporadic, however, specific cases are associated with hereditary syndromes, such as Beckwith-Wiedeman and familial adenomatous polyposis syndromes (32).

Symptoms are typically vague and non-specific (3,17,24,30). For example, the majority of adult patients present with abdominal pain or a palpable mass. Additionally, weight loss, anorexia and a change in bowel habits are common symptoms on initial presentation. PBs arising in the pancreatic head may cause biliary obstruction and jaundice, as in the present case. Furthermore, patients may manifest symptoms of endocrine abnormalities (15).

In the present literature review, the pancreatic head, observed in 20/38 patients (53%) was the most common site of tumour origin, followed by the tail, the body and the ampulla of Vater (no tumour site data for two patients). The liver has been found to be the most common site of distant metastasis and 25% of cases are diagnosed with secondary liver disease upon initial staging (19,24,30). However, bone, pulmonary, peritoneal, brain and mediastinal metastases have also been described (19,26).

In paediatric PB patients, elevated AFP and CEA levels are the most common abnormal serological markers, and elevated AFP expression has been reported in ≤68% of cases (12,24,25,32), By contrast, these PB tumour markers are typically within the normal range in adult patients (1,3). Serum AFP levels may be used to monitor clinical response to therapy or recurrence in those patients whose tumors produce it (32).

Forming an accurate pre-operative diagnosis may be difficult when based solely on radiographic features, as these are non-specific and thus, PB cases may be mistaken for more common entities, such as adenocarcinoma or neuroendocrine tumours. The majority of PB tumours are well-defined, large and heterogeneous on cross-sectional imaging, with mixed solid-cystic appearance (3,19,24,26,30). On magnetic resonance, the tumours are most commonly described as heterogeneous with low-intermediate T1 signal intensity and high T2 intensity. Furthermore, PB tumours exhibit enhancement on contrast-enhanced CT scans, with calcifications and internal fibrous septa observed (3,24,30).

The differential diagnosis for PB includes benign and malignant processes of the pancreas, including autoimmune pancreatitis, adenocarcinoma, neuroendocrine tumours, solid pseudopapillary tumours, mucinous cystic neoplasms and serous microcystic adenoma (3,32).

Macroscopically, PB lesions are typically large (≤20 cm in diameter), partially-encapsulated, greyish or tan in colour, with a soft consistency and areas of focal necrosis (3). Microscopic diagnosis may be difficult due to histological heterogeneity. PB tumours often contain multiple cell types, and demonstrate variable combinations of ductal, acinar and neuroendocrine components. This variety of elements is one of the distinctive pathological features of PB, the other being the presence of squamoid corpuscles (i.e., circumscribed, whorled nests of flattened cells with a squamous appearance, separated by dense stromal bands) (3,32).

Ductal adenocarcinoma, acinar cell carcinoma, neuroendocrine neoplasms and solid pseudopapillary tumours all lack the characteristic squamoid corpuscles observed in PB. Therefore, pre-operative cytology is rarely useful, as accurate pre-operative identification of squamoid corpuscles cannot be performed due to sampling errors (3,18,21,33,34). However, PB does not demonstrate the desmoplastic reaction that occurs in adenocarcinoma, allowing differentiation from PB (32).

Immunohistochemistry may facilitate the characterisation of various components of the tumour. For example, acinar cell lines stain positive for trypsin, chymotrypsin and lipase, whereas neuroendocrine cells stain positive for synaptophysin, chromogranin and neuron-specific enolase (3,32). In addition, immunohistochemical analysis of AFP expression may be positive within solid regions of the epithelial component.

Unlike pancreatic ductal adenocarcinoma, PB does not appear to express the K-ras oncogene or p53 tumour suppressor mutations (15,26). However, mutations of the adenomatous polyposis coli/β-catenin pathway have been described, and allelic loss on chromosome 11p (Wnt signaling pathway) is the most common type of genetic alteration that has been identified in PB (12,15,26,35,36). Furthermore, numerous paediatric cases of PB have occurred in patients with Beckwith-Wiedemann syndrome and familial adenomatous polyposis (12,15,19,26,32).

Due to the rarity of PB, an optimal treatment strategy has yet to be standardised, however, in the adult population, surgical resection remains the primary treatment strategy (3,24). The roles of adjuvant chemotherapy and radiotherapy remain under debate due to the small number of patients treated thus far. Typically, chemotherapy with or without radiotherapy has a role in the treatment of recurrent, residual, unresectable and metastatic disease, although with variable outcomes (3,24). However, the development of optimal chemotherapeutic regimens remain under discussion due to the small number of patients reported in the literature (26). In patients with incompletely resected disease, post-operative radiotherapy may be administered as a palliative treatment (3).

PBs exhibit malignant behaviour, with local invasion, recurrence and distant metastasis, and adult PB patients have a poorer prognosis compared with children, exhibiting three-year survival rates of <40% (3,12,19,24). Patients with unresected tumours have a median overall survival time of five months, whereas surgery alone is associated with an overall survival time of 15 months. Furthermore, treatment with chemoradiotherapy following surgery appears to increase the overall survival time to 20.5 months (3). The limited number of reported cases does not allow for valid conclusions to be drawn, however, positive lymph node involvement has been associated with a poorer outcome (overall survival of 12 vs. 36 months with negative node involvement) (3). In addition, there is insufficient data available to evaluate survival with or without vascular or perineural invasion (3).

Although the benefits of neoadjuvant chemotherapy have yet to be studied in randomised trials, it has demonstrated a survival benefit in a small pediatric series (37). Of six pediatric patients treated with neoadjuvant chemotherapy, five exhibited >50% tumour remission, allowing for complete surgical resection in four of the five patients, the fifth patient underwent a laparotomy, however the tumour remained unresectable due to regional extension, and one patient achieved complete tumour regression (37). Therefore, neoadjuvant chemotherapy may have a role in the treatment of adult PB, predominantly in identifying patients with responsive disease, who may be candidates for surgical resection.

In conclusion, PB is an extremely rare neoplasm in adults and the present study showcases its aggressive biological and clinical behaviour. The patient presented with a three-week history of obstructive jaundice and weight loss, and was diagnosed with a pancreatic head mass. Following pancreaticoduodenectomy, the patient developed multiple liver and bone metastases three months later, and despite systemic chemotherapy and radiofrequency ablation, succumbed to tumour dissemination. Pitfalls in the pre-surgical diagnosis of PB, based currently on radiological and cytological findings, and lack of management guidelines, due to the paucity of the tumour, result in a generally unfavourable patient prognosis.

Glossary

Abbreviations

Abbreviations:

PB

pancreatoblastoma

AFP

α-fetoprotein

CEA

carcinoembryonic antigen

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Zouros E, Manatakis DK, Delis SG, Agalianos C, Triantopoulou C and Dervenis C: Adult pancreatoblastoma: A case report and review of the literature. Oncol Lett 9: 2293-2298, 2015.
APA
Zouros, E., Manatakis, D.K., Delis, S.G., Agalianos, C., Triantopoulou, C., & Dervenis, C. (2015). Adult pancreatoblastoma: A case report and review of the literature. Oncology Letters, 9, 2293-2298. https://doi.org/10.3892/ol.2015.3001
MLA
Zouros, E., Manatakis, D. K., Delis, S. G., Agalianos, C., Triantopoulou, C., Dervenis, C."Adult pancreatoblastoma: A case report and review of the literature". Oncology Letters 9.5 (2015): 2293-2298.
Chicago
Zouros, E., Manatakis, D. K., Delis, S. G., Agalianos, C., Triantopoulou, C., Dervenis, C."Adult pancreatoblastoma: A case report and review of the literature". Oncology Letters 9, no. 5 (2015): 2293-2298. https://doi.org/10.3892/ol.2015.3001