Splenopancreatic Field Abnormality Is Not Unique to Trisomy 13
Department of Pathology, Ribeira˜o Preto Medical School, University of Sa˜o Paulo, Av. Bandeirantes, 3900, Ribeira˜oPreto,SP14049-900,Brazil 2Department of Genetics, Ribeira˜o Preto Medical School, University of Sa˜o Paulo, Ribeira˜o Preto, SP 14049-900, Brazil
Received June 16, 2003; accepted October 1, 2003; published online March 17, 2004.
ABSTRACT Splenopancreatic fusion is an uncommon finding, usu- ally only seen as part of the splenopancreatic field ab- normality associated with trisomy 13. It may present itself either as ectopic splenic tissue in the cauda pan- creatis, as ectopic pancreatic tissue in the spleen or accessory spleen, or as fusion of the cauda pancreatis and splenic hilum. In this study, we report four unre- lated congenital anomaly cases presenting trisomy 21, osteocraniostenosis syndrome, isolated congenital heart defect, and oligohydramnios sequence due to prune belly syndrome, in which fusion was observed. This demonstrates that, although it may be more common in trisomy 13, this phenomenon should not be interpreted as pathognomonic to that syndrome. congenital heart defect, oligohydramnios sequence, os- teocraniostenosis syndrome, splenopancreatic field dys- plasia, splenopancreatic fusion, trisomy 21
INTRODUCTION Splenopancreatic field abnormality is an uncom- mon finding usually reported in cases of trisomy 13. It is characterized by splenomegaly, presence of intrasplenic pancreatic tissue, intrapancreatic splenic tissue, pancreatic dysplasia, and by the fre-quent presence of accessory spleens[1].Here in, we describe four congenital anomaly cases that were unrelated to trisomy 13. Splenopancreatic fusion was found in all these cases, therefore demonstrating that the condition is not pathognomonic to trisomy 13.
CASE REPORTS Case 1 Term baby from a consanguineous couple (third cousin). A female infant presented dysmorphic fea- tures such as flat face, upslanting palpebral fissure, epicanthal folds, short neck, brachydactyly, bilat- eral fifth finger clinodactyly, single palmar crease, hypotonia,andacongenitalheartdefectcharacter- ized by atrioventricular canal associated with patent ductus arteriosus and pulmonary hyperten- sion. Her karyotype was 47, XX 21. Death oc- curred at 18 months, 2 days after cardiovascular corrective surgery. The only other feature noted at autopsy was a reddish area in the cauda pancreatis that proved, under microscopy, to be ectopic splenic tissue with no capsule separating spleen and pancreas (Fig. 1B,C).*Corresponding author, e-mail: [email protected]
Case 2 A female baby born at 32 wk of gestation to a G4P4A0 mother. She was the fourth child of this consanguineous couple (uncle–niece). She was hydropic, macrocephalous with a cloverleaf skull, confirmed by radiography, bulging fore- head, low hairline, small face, and very small nose. She also presented microstomia and mi- crognathia, and short limbs with redundant skin. Whole body x-ray showed thin brittle bones and undermineralized calvaria. These features char- acterize osteocraniostenosis syndrome [2,3]. Her karyotype was 46, XX. Death occurred due to respiratory failure secondary to lung hypoplasia 26 min after birth. Autopsy disclosed an acces- sory spleen in which an area of white-tan tissue could be seen. Microscopy of this accessory spleen revealed intermingling of ectopic pancreatic and splenic tissue with no capsule separat- ing the two (Fig. 2B,D).
Case 3 A female baby from a nonconsanguineous couple born at 36 wk of gestation. The mother was a smoker and was hypertensive. The baby pre- sented no dysmorphic features. The only anom- aly was a congenital heart defect characterized by pulmonary valve stenosis, right-ventricular hypertrophy, atrial septal defect of the ostium secundum type, and patent ductus arteriosus. She was submitted to surgical correction when she was 6 months old and death occurred on the 1st postoperative day. Her karyotype was 46, XX. Autopsy revealed fusion of the cauda pancreatis and splenic hilum. Histological analysis con- firmed that the pancreatic and splenic tissues
Figure 1. Case 1: Photomicrographs (A, C) of splenic tissue in the cauda pancreatis. Note that there is no capsule separating the tissues.
Case 2: Photomicrographs (B, D) of the accessory spleen and interdigitating pancreatic tissue showing no separating capsule. (Original magnifi- cation: B,  20; C, 100.)
were intermingled with no capsule separating them (Fig. 2A,C). No other anomalies were noted.
Case 4 Fresh stillborn male delivered at 30 wk of gestation to a 22-year-old, G2P2A0 mother. Prenatal ultra- sound revealed the absence of amniotic fluid and a fetus with ascites, a short thorax, and a voluminous abdomen due to a large cystic mass. Autopsy showed dilatation and hypertrophy of the bladder, ascites, pulmonary hypoplasia, andaoligo hydramnios sequence secondary to a massive cystic dilatation of the right kidney. The cauda pancreatis was near the splenic hilum, but had not fused. Two small accessory spleens were seen in this area, one of which had fused with the pancreas both macroscopically and microscopically (Fig. 2B,D).
DISCUSSION It is quite common to see ectopic splenic tissue and, less often, ectopic pancreatic tissue. Acces- sory spleens, a presentation of ectopic spleen, are found in approximately 14% of all autopsies [4] and 16% of those found [5] are located in the cauda pancreatis. Ectopic pancreatic tissue is usually found in the wall of the stomach or in Meckel’s diverticulum. Although its presence in the spleen is uncommon, some authors speculate that it may provoke the epithelial cysts occasionally found in the spleen [6] or accessory spleen [7]. Splenopancreatic field abnormality is frequently seen in trisomy 13 and is characterized by splenomegaly, frequent accessory spleens, presence of intrasplenic pancreatic tissue, intrapancreatic splenic tissue, and pancreatic dysplasia [1,8]. Fusion of splenicandpancreatic tissue is seen in three different presentations. Ectopic splenic
Figure 2. Case 3: Photomicrographs (A, C) of the area of fusion of the cauda pancreatis and splenic hilum showing the interdigitating tissues. Note the absence of a separating capsule. Case 4: Macroscopic view of the
Cauda pancreatic with an intrapancreatic spleen(B).Photomicrograph of this fused accessory spleen and pancreatic tissue (D) with underdevelopment of the separating capsule. (Original magnification: A,  20; C, D, 100.)
tissue may be found in the cauda pancreatis [1,8, 9], as it was in our cases 1 and 4. Alternately, as found in our case 2, ectopic pancreatic tissue may appear in the spleen or accessory spleen [10,11]. At times, as in our case 3, fusion of the cauda pancreatis and splenic hilum is also seen [1]. This curious association of tissues may result from disturbances in the embryogenesis of both organs as they arise from the dorsal mesogastrium in close proximity to each other. The spleen develops from hillocks of tissues that usually coalesce to form a single mass that migrates to its anterior left. At the same time, the body and cauda pancreatis are derived from a mass of cells caudal to the splenic hillocks in the dorsal mesogastrium. The growth and rotation of all abdominal organ tissue cause the pancreas and spleen to be positioned to the left. During this process, one or more splenic hillocks may fail to fuse with the main mass. This results in the cre- ation of accessory spleens, some of which may be entrapped by the cauda pancreatis and become intrapancreatic accessory spleens, as in our cases 1 and 4. The close juxtaposition of the cauda pancre- atis and splenic hilum may result in a fusion that is characterized by the lack of a splenic capsule and inter digitation of both splenic and pancreatic tis- sues, as seen in our case 3. If a portion of the pancreatic primordium is proximal to the splenic hillocks, two different presentations may arise: intrasplenic pancreatic tissue, as in our cases 1 and 4; or, as in our case 2, splenopancreatic fusion involving an accessory spleen. The cases presented here show that spleno- pancreatic fusion is not restricted to trisomy 13 and so should not be considered a pathognomonic condition. It has probably been interpreted as such due to the fact that accessory spleens appear 30 to 60% more frequently in trisomy 13 than they do in other disorders [8]. The effects of disturbances during embryogenesis or during visceral rotation on the dorsal mesogastrium constitute a potential cause of splenopancreatic fusion. Among these effects, chromosomal abnormalities, of which trisomy 13 is one, are much more likely to give rise to such fusion (as seen in our case 1). However, fusion may also be associated with other conditions, including: congenital anomalies of monogenic origin, such as osteocraniostenosis syndrome (see case 2); multifactorial conditions, such as isolated congenital heart defect (see case 1) or prune belly syndrome (see case 4); or even in cases with no identified malformation, represented by the occasional discovery of intrasplenic epithelial cysts [6, 7, 12].
ACKNOWLEDGMENTS The authors thank Deise Lucia Chesca Simo˜es for her technical assistance. We are also grateful to FAEPA (Fundac¸a˜o de Apoio ao Ensino, Pesquisa e Assisteˆncia)fortheirfinancialsupport.
1. Yang YX, Heller D, Baergen RN. Splenopancreatic field dysplasia in trisomy 13. Pediatr Dev Pathol 2002;5:414– 415.
2. Verloes A, Narcy F, Grattagliano B, et al. Osteocraniosteno- sis. J Med Genet 1994;31:772–778.
3. Costa T, Azouz EM, Fitzpatrick J, Kamel-Reid S, Smith CR, Silver MM. Skeletal dysplasia with gracile bones: three new cases, including two offspring of a mother with a dwarfing condition. Am J Med Genet 1998;76:125–132.
4. Halpert B, Gyo¨rkey F. Lesions observed in accessory spleens of 311 patients. Am J Clin Pathol 1959;32:165–168.
5. Halpert B, Gyo¨rkey F. Accessory spleen in the tail of the pancreas. Arch Pathol 1957;64:266–269.
6. Sasou S, Nakamura S, Inomata M. Epithelial splenic cysts in an intrapancreatic accessory spleen and spleen. Pathol Int 1999;49:1078–1083.
7. Davidson ED, Campbell WG, Hersh T. Epidermoid splenic cyst occurring in an intrapancreatic accessory spleen. Dig Dis Sci 1980;25:964–967.
8. Hashida Y, Jaffe R, Yunis EJ. Pancreatic pathology in tri- somy 13: specificity of the morphologic lesion. Pediatr Pathol 1983;1:169–178.
9. Lauffer JM, Baer HU, Maurer CA, Wagner M, Zimmermann A, Buchler MW. Intrapancreatic accessory spleen. A rare cause of a pancreatic mass. Int J Pancreatol 1999;25:65–68.
10. Mottet NK, Jensen H. The anomalous embryonic develop- ment associated with trisomy 13–15. Am J Clin Pathol 1965; 46:334–337.
11. Clein GP, Mitchinson MJ. Abnormalities of spleen and pan- creas in trisomy D syndrome. Postgrad Med J 1967;43:495– 497.
12. Horibe Y, Murakami M, Yamao K, Imaeda Y, Tashiro K, Kasahara M. Epithelial inclusion cyst (epidermoid cyst) formation with epithelioid cell granuloma in an intrapan- creatic accessory spleen. Pathol Int 2001;51:50–54.