INTRODUCTION
Partial anomalous pulmonary venous return (PAPVR) is a cardiovascular congenital anomaly characterised by a partial alteration in the venous connection of the oxygenated blood of the pulmonary vein to the left atrium resulting in a left to right shunt. The venous drainage point of return of the partial anomalous pulmonary vein can vary in its site; occurring most frequently supracardial (63%), followed by the cardial (20%), mixed (11%) and infracardial (6%) variants [14]. In contrast to the total anomalous pulmonary venous return (TAPVR), which is a deadly anomaly, PAPVR does not necessarily demonstrate clinical symptoms. The actual prevalence could therefore be even higher than the reported 0.4–0.7% of adults shown in autopsy cases [12]. Although the literature shows that right sided PAPVR is more frequent [1, 7, 21], a study with computed tomography images from 29 adults showed a connection of the superior left pulmonary vein into the left persistent vertical vein in 79% of their studied cases [11].
Partial anomalous pulmonary venous return often exists in combination with other multiple congenital anomalies [21]. An interesting clinical case report about PAPVR with persistent left superior vena cava, ‘bovine arch’ aortic branching, tracheal diverticulum, aberrant lung fissure and an annular pancreas (AP) has been published [17]. We introduce a similar constellation; however, in a cadaveric gross anatomy, where we could find PAPVR combined with other multiple congenital anomalies (MCA) such as AP and patent umbilical vein (PUV) with connection to the left portal vein of the liver.
Annular pancreas is a congenital anomaly in which the pancreas either completely or partially encircles the descending portion of duodenum. This phenomenon can obstruct the gastrointestinal lumen, occasionally leading to duodenal stenosis [10].
This constellation will be discussed in detail with the available literature of comparable cases for specific genetic mutations being associated with the individual variations observed in the described case and an effort will be made to find a common ground to explain the coexistence of the MCA.
CASE REPORT
The formalin-fixed cadaver of an 88-year-old female body donor came from the body donor system of the LMU, Munich, Germany. Photos were taken using a Canon Camera (G9 X, Tokyo, Japan) and measurements were taken using a digital calliper (Ovibell GmbH, Mühlheim, Germany). Haematoxylin and eosin staining was performed in the Institute of Pathology, General Hospital Nuremberg to verify the observation. The histological image was taken using a DM1000 LED light microscope (Leica, Wetzlar, Germany). Literature research related to the anomalies was undertaken using Medline and Google Scholar by searching mesh terms for genetic mutations such as: partial anomalous, persistent right umbilical vein, annular pancreas and persistent umbilical vein.
Aberrant pulmonary vein
The aberrant/displaced superior left pulmonary vein measuring 63 mm in length and 6.2 mm in diameter drained from the left superior lobe through the pulmonary hilum into the left brachiocephalic vein (Fig. 1A, B). The 37.3 mm long and 12.4 mm thick left brachiocephalic vein joined together with the right brachiocephalic vein to form the superior vena cava, finally draining into the right atrium. However, an additional venal tributary from the lowest portion (segment V) of the left superior lobe drained into the left inferior pulmonary vein from the inferior lobe of the left lung (Fig. 2A, B) entering together as a single left entrance into the left atrium. On the other side there were three separate entries, instead of two, into the left atrium from the three lobes of the right lung (Fig. 2B). The left and right lungs were of normal size and both possessed a regular oblique fissure.
Neither any irregularity in size of the heart chambers nor in any septation of the heart could be observed. The coronary sinus had no connection to the variant vein and was not enlarged.
Annular pancreas
The pancreas formed a complete circular ring surrounding the descending part of the duodenum (Fig. 3). The narrowest part of the pancreatic ring measured 8 mm and was located lateral on the right. The anterior part measured 17 mm and the posterior part was 13 mm. The duct system of the pancreas was regular. The common bile duct ended at the descending part of the duodenum just above the AP. It showed no sign of compression, neither of the duodenum nor the common bile duct.
Persistent umbilical vein and connection to the portal vein
The persistent umbilical vein had a lumen, which was < 1 mm with a very thick wall of 4 mm (Fig. 4A). Haematoxylin and eosin staining of this vein could verify this observation (Fig. 4B). Interestingly, a connection between this lumen structure and the inferior branch of the extra hepatic left portal vein running in the round ligament fissure of the liver was seen (Fig. 5). Histologically, the thick wall of the persistent umbilical vein consisted of several layers of smooth muscle cells. The inner and outermost layer contained more longitudinally aligned muscle cell bundles and the layer between them had a more oblique orientation. The lumen was lined by flattened cells like an endothelium (Fig. 4B).
DISCUSSION
Systematic analyses concerning the frequencies of aberrant pulmonary veins are rare. Among 140 lung resection surgery patients, 23 variations were found [22], but no case was comparable with the variation presented here. According to the different types of PAPVR mentioned in the introduction section, our case report represents supracardial type where oxygenated blood from the left lung is directly released into the left brachiocephalic vein building a left to right shunt and subsequently collecting the mixed blood into the superior cava vein. Many of the affected patients do not present evident clinical impairments under normal conditions. However, in circumstances such as thorax surgery this large diameter vein anomaly can present a high risk. Studies have reported that superior pulmonary vein [18] or even the left inferior pulmonary vein [2] joining the left brachiocephalic vein have been detected during clinical examination. Additional clinical relevance of this variation was observed during insertion of central venous catheter [5, 15]. The aforementioned anomalies have been associated with genetic mutations. However, only few candidate genes are known so far. A missense gene mutation of bone morphogenetic protein receptor II could be detected in a case of anomalous unilateral single pulmonary vein [16]. In addition, a phenylalanine-to-leucine substitution that adversely affects Semaphorin 3d has been identified as a putative crucial pulmonary venous patterning cue [6]. A more severe version of this anomaly is the TAPVR, which can be lethal if not corrected at an early stage. A genetic mutation in the centromeric region of chromosome 4, 4p13-q12 has been defined as a candidate for both familial and sporadic cases of TAPVR [4]. A family case of TAPVR has been reported, where a father who underwent surgical correction had 2 children with TAPVR. This supports the hypothesis of a genetic transfer pattern on the development of this anomaly [20].
Interestingly, rare variations including those of pulmonary veins are often combined with other MCA. A combination of AP with malformations of the lung [17] has already been described in a clinical setting. Even though half of the cases are asymptomatic until the third to fifth decade [10], AP presents the risk of duodenal stenosis [23]. The sonic hedgehog signalling pathway has been implicated in the development of AP [8]. Specific involvement of sonic hedgehog in mouse embryonic lung development, growth and morphogenesis has already been proven [3, 9], but no association with the development of PAPVR has been confirmed yet. Also, chromosome 1p36 deletion syndrome has been implicated in the development of AP [19].
Additionally, a persistent umbilical vein was observed in our case report. The connection of the left umbilical vein into the left portal vein during the embryological development is common. A recent study observed that 56 out of 58 embryos of gestational age 5–7 weeks showed the left sided umbilical vein draining into the left portal vein, which usually closes postnatally [13]. The closing of the umbilical vein can either be due to obliteration or simply due to collapse of the vein. This patent umbilical vein can provide access to the liver for a hepatoportography as a superior approach to diagnosis in liver disease [24]. However, recanalization of the umbilical vein is also associated with cirrhotic or non-cirrhotic portal hypertension. In our case, no macroscopic alteration of the liver could be detected.
CONCLUSIONS
Even though we could not prove a common genetic mutation for the constellation of the mentioned anomalies, we propose that genomic sequencing in clinical settings with this constellation of anomalies could possibly help to find the genetic common ground and provide an approach in understanding the aetiology. A regular collection of tissue sample before the fixation of the cadavers could make it possible to perform genome sequencing in case of such diagnosis. However, this review should also help to highlight the cadaveric approach to define the anomaly constellation and help surgeons, radiologists and other clinicians to consider the possibility of such a combination of anatomical variations in their setting.
Acknowledgements
We are very thankful to the body donors for their contribution to the academic teaching and research field of anatomy. We would also like to thank the Institute of Pathology, General Hospital Nuremberg for performing the haematoxylin and eosin staining required for the study. Finally, special thanks to Ms. Laura Seidel for proofreading this article.
