Address correspondence to Alfredo Cacciari, MD . Department of Paediatric Surgery, University of Bologna. Via Massarenti 11, 40138 Bologna - ITALY Ph: 39-51-636-3651; Fax: 39-51-636-3657 ¶Department of Obstetrics and Gynecology, Section of Prenatal Pathophysiology, University of Bologna.

Synonyms: Infantile pancreatic adenocarcinoma.

Definition: Rare pancreatic neoplasm.

Prevalence: Unknown.

Etiology: Unknown.

Pathogenesis: Hamartomatous or dysembryogenic development of ductal cells of ventral portion of primordial pancreas.

Associated anomalies: None known.

Differential diagnosis: Ovarian cysts, mesenteric/enteric cysts, urachal cysts, multicystic kidneys, hydrocolpos.

Prognosis: Mostly favorable for lesion of the body and tail of the pancreas. The prognosis for lesion of the head is more severe due to the extent of the surgery.

Recurrence risk: Unknown.

Management: Standard obstetrical care and neonatal surgery.

MESH Pancreas, tumor ICD9 751.7 CDC 751.780

Introduction

Pancreatic neoplasms rarely affect children, and, among these, pancreatoblastoma is extraordinary rare. If they present, it is usually during infancy, exceptionally in younger children, and the antenatal diagnosis is almost never available. To our knowledge, the case described is the first suspected prenatal diagnosis, confirmed after birth.

Case report

A 31-year-old primigravida was referred in the third trimester of pregnancy for level II real-time ultrasonography due to a suspected fetal abdominal mass. Ultrasound examination revealed a single fetus, with biometry corroborating the gestational age of 35 weeks calculated from the patient"s last menstrual period. The fetus had a 80x50mm multiloculated heterogeneous subhepatic mass in the left hemiabdomen. The stomach, kidneys and bladder appeared normal. A pancreatic origin was suspected because of the location. The amniotic fluid volume was within normal limits. The mass remained unchanged at follow-up examinations at 37 and 38 weeks. At 38 weeks, a 4080gm male neonate with an Apgar score of 8 and 10 at 1 and 5 minutes, respectively, was delivered by cesarean section. At birth the abdomen was tense, air-filled, and tender. A hard, firm mass was palpated in the left hemi-abdomen. A postnatal ultrasound revealed a heterogeneous retroperitoneal mass, anterior to the aorta and medial to the left adrenal and kidney. An X-ray of the abdomen did not reveal calcifications. Laboratory examinations were all normal except for an alfa-fetoprotein which was far above normal range (>>100,000 ng/ml). On the second day, the abdomen enlarged drammatically and bile-stained vomiting started. The scheduled MRI was cancelled, and the newborn was taken to surgery. At surgical exploration, an irregular, capsulated mass originating from the body and tail of the pan- creas was observed. Isolation and complete resection of the mass were performed, without damaging the pancreatic tissue. The histology of the excised specimen was pancreatoblastoma. The post-operative course was uneventful. Repeat a-fetoprotein values were within normal range (<<30 ng/ml). No chemotherapy or radiotherapy was performed. The infant is doing well at 12 months postoperative follow-up, and several repeated ultrasound examinations did not reveal any disease relapse.

Discussion

Incidence

The occurrence of pancreatic tumors in children is a rarity (<<0.5:10,000 surgical operations).

Pathology

Pancreatoblastoma or infantile adenocarcinoma is an unusual non-functional tumor of the pancreas; it is generally encapsulated, presents organoid pattern containing globular structures with elongate cells (squamoid corpuscles) and acinar or ductal cells or both⁴. It contains both epithelial and mesenchymal elements²⁰. Horie has subclassified them into two groups: ventral type, occurring in the head, and dorsal type occurring in body and tail with relatively immature histology and poor prognosis⁷.

Ultrasound findings

This case demonstrates that it is possible to suspect pancreatic origins of a heterogeneous mass, predominantly located under the left lobe of the liver, detected by ultrasound in the 3rd trimester of pregnancy. Our case demonstrated some cystic and solid components.

Differential diagnosis

The differential diagnosis of fetal pancreatic tumor includes hamartoma, hemangioendothelioma, benign teratomas (mainly dermoid cysts), and lymphosarcomas²⁰. There is as yet no information on how to differentiate these tumors.

The differential diagnosis of fetal cystic intra-abdominal includes ovarian cysts^8-10, mesenteric and enteric cysts, urachal cysts, multicystic kidneys^11-13 and hydrocolpos. Ovarian cysts appear predominantly fluid and are present only in female fetuses. Renal dysplasias appear in the renal fossa on both sides of the spine. Meconium peritonitis is characterized by multiple calcifications. The prenatal diagnosis of intrabdominal neoplasm is only presumptive and is limited to a few cases which have been described in the literature referring to nephroblastoma^14,15 (more solid appearing and more lateral) or sacrococcygeal teratoma of the intra-abdominal type^16-19 (lower in the abdomen). The significance of the high a-fetoprotein values is uncertain.

Associated anomalies

Pancreatoblastomas have been found in neonates with Beckwith-Wiedemann syndrome²⁰ and associated findings of this syndrome should be sought (macroglossia, visceromegaly, omphalocele, polyhydramnios,..).

Prognosis

The overall prognosis of pancreatoblastoma depends on the site of origin, since excision of the mass in the body and tail is more complete and less aggressive than excision in the head.

These tumors tend to have a good prognosis, accounting only for 0.2% of deaths for malignancies in this age¹ , although poor results and occasional distant metastases (lung, liver or lymph nodes^5,6) have been reported. Some series have also reported a high surgical mortality²¹, that some tumors may not be amenable to surgical resection²² and that the tumor may require chemotherapy and even recur²³. Considering the favorable prognosis after excision, this tumor should be differentiated from the usual adenocarcinoma of the pancreas that afflicts adults.

Management

Prenatal management: Since prenatal diagnosis of pancreatoblastoma has not been previously reported, we believe that no alteration of the prenatal care is suggested at this time. Polyhydramnios may occur if the neoplasm resides in the head of the pancreas and may contribute to the onset of premature labor; tocolytic agents are indicated in these patients, and amniotic fluid drainage may also be considered. Delivery is recommended in a tertiary care center, where neonates can receive adequate surgical care.

Postnatal management: Surgery offers the best treatment. The success of the operation largely depends on the site of the tumor. Excision of the mass in the tail or body is easier and less disruptive than removal in the head which requires major procedures such as pancreatoduodenostomy. Once surgery has been radical, chemo- and radiotherapy have proved to be unnecessary^{2, 3}.

Postnatal presentation

The most common presentations of pancreatoblastoma are abdominal distension and a palpable mass. If the tumor arises from the head of the pancreas, vomiting and jaundice are often present.

Postnatal diagnosis

When suspected, diagnosis is confirmed by CT scan or MRI which shows the pancreatic origin of the mass.

References

1. Tsukimoto I, Watanabe K, Lin J, et al: Pancreatic carcinoma in children in Japan. Cancer 31:1203-1207, 1973.

2. Hampton Rich R, Weber JL, Shandling B: Adenocarcinoma of the pancreas in a neonate managed by pancreatoduodenectomy. J Ped Surg 21:806-808, 1986.

3. Maeda H, Matsumoto K, Ohmiya A, et al: A case of pancreatoblastoma. Pediatr Oncol 27:144-146, 1990.

4. Horie A, Yano Y, Miwa A: Morphogenesis of pancreoblastoma. Infantile carcinoma of the pancreas. Report of 2 cases. Cancer 39:247- 254, 1977.

5. Buchino JJ, Castello FM, Nagaraj HS: Pancreatoblastoma. A histochemical and ultrastructural analysis. Cancer 53: 963-969, 1984.

6. Immamura M, Yokoama S, Nishino C, et al: A case of AFP producing pancreatoblastoma. Pediatr Oncol 20:212-213, 1984.

7. Horie A: Pancreatoblastoma. Histologic criteria based upon a review of six cases. In Humphrey GB, Grindey GB, Dehner LP et al (eds): Pancreatic Tumors in Children. The Hague, The Netherlands, Martinus Nijhof pp.159-166, 1982.

8. Tabsh KM: Antenatal sonographic appearence of a fetal ovarian cyst. JCU 1:329, 1982.

9. Rizzo N, Gabrielli S, Perolo A, et al: Prenatal diagnosis and management of fetal ovarian cyst. Prenat Diagn 9:97, 1989.

10. Lindeque BG, Du Toit JP, Muller LMM, et al: Ultrasonographic criteria for the conservative management of antenatally diagnosed fetal ovarian cyst. J Reprod Med 33:196, 1988.

11. Friedberg JE, Mitnick JS, David DA: Antepartum ultrasonic detection of multicystic kidney. Radiology 131:198, 1979.

12. Greene LF, Feinzaig W, Dahlin DC: Multycistic dysplasia of the kidney with special reference to the controlateral kidney. J Urol 103:482. 1971.

13. Henderson SC, Van Kolken RJ, Rahatzad M: Multicystic kidney with hydramnios. JCU 8:249, 1980.

14. Warkany J: Wilms"tumor. In: Congenital Malformation. Chicago, Year Book, 1981, p.1061.

15. Wexler HA, Poole CA, Fojaco RM: Metastatic neonatal Wilms" tumor: a case report with review of the literature. Pediatr Radiol 3:179, 1975.

16. Gergely RZ, Edn R, Schriffin BS, et al: Antenatal diagnosis of congenital sacral teratoma. J Reprod Med 24:229, 1980.

17. Flake AW, Harrison MR, Adzick NS, et al: Fetal sacrococcygeal teratoma. J Pediatr Med 21:563, 1986.

18. Holzgreve W, Mahoney BS, Glick P, et al: Sonographic demonstration of fetal sacrococcygeal teratoma. Prenat Diagn 5:245, 1985.

19. Pringel KC, Weiner CP, Sopper RT, et al: Sacrococcygeal teratoma. Fetal Therapy 2:80, 1987.

20. Jaffe R: The Pancreas. In Wigglesworth JS, Singer DB (Eds): Textbook of Fetal and Perinatal pathology. Blackwell Scientic Publications, Cambridge, MA, 1991.

21. Jaksic T., Yaman M. Thorner P. et al. A 20-Year Review of Pediatric Tumors. J Pediatric Surg 27:1315-7, 1992.

22. Inomata Y., Nishizawa T., Takasan H. et al. Pancreatoblastoma Resected by Delayed Primary Operation After Effective Chemotherapy. J Pediatric Surg 27:1570-2, 1992.

23.Vannier JP, Flamant F., Hemet J. et al. Pancreatoblastoma: Response to Chemotherapy. Med Pediatr Oncol 19:187-91, 1991.