Lymphatic malformations in humans tend to occur in infants and are believed to arise from a congenital failure of primitive lymphatic sacs to develop communications with the venous system . Mutations have been suggested as an underlying cause for lymphatic malformations in humans .
Only few case-reports about lymphatic malformations have been published in veterinary literature and classification of vascular malformations in veterinary medicine has not been well established due to their infrequency [16,17,18,19,20,21]. Gross et al.  classified lymphatic anomalies in dogs and cats and refers to lymphangiomatosis when the anomaly is caused by malformation, while lymphangioma has been suggested for a neoplastic origin. Whereas, in human medicine, lymphangiomatosis referrers to diffuse lymphatic malformations involving multiple organs . As this scatters confusion, the authors suggest the use of the human nomenclature from the International Society for the Study of Vascular Anomalies, where non-neoplastic lymphatic lesions with a presumed congenital origin are referred to as lymphatic malformations [3, 27, 29].
Lymphatic malformations in the retroperitoneum and abdominal viscera are a rare entity and account for 2% of all lymphatic malformations in humans . Although lymphatic malformations can be subclassified as microcystic (diameter ≤ 5 mm), macrocystic (> 5 mm) or combined; retroperitoneal malformations are mostly macrocystic [2, 30,31,32], as seen in our patient. The most common presenting signs in humans with retroperitoneal cystic lymphatic malformations are abdominal pain and abdominal distension, but patients can also be presented with a palpable mass, back pain, anorexia, fever, nausea and diarrhoea [33,34,35,36,37,38,39]. Haemorrhage within the cystic space is common, indicating recent trauma or spontaneous intralesional bleeding [27, 32]; therefore symptoms can occur when patients become older due to increased size of the cystic space. Our patient was presented with a painful abdomen, as described in humans, but also with pollakiuria and dysuria. The latter symptoms are most likely the results of compression of the bladder and/or urethra. Our patient had no history of recent trauma. Bleeding into the cyst could be due to a minor traumatic event, unnoticed by the owner, but spontaneous intra-cystic bleeding seemed more likely.
Initial evaluation of cystic structures by ultrasonography, CT scanning or magnetic resonance imaging is advised, however definitive diagnosis can only be made through histopathology [27, 31]. CT-scan provided the best pre-operative information in our patient, as it gave a better understanding of the origin of the lesion and its association to surrounding organs, compared to abdominal ultrasound. Histopathology shows that vascular malformations are composed of a single layer of flattened-to-slightly hobnailed endothelial cells, rimmed by rare pericytes, with macrocystic lesions having thicker, irregular coats of smooth muscle and/or fibrous tissue and possibly valves . As differentiation between blood vessel or lymphatic origin can be challenging on histopathology, immunoreactions for antigens as podoplanin (D2-40 antibody), PROX-1, LYVE-1 and vascular endothelial growth factor receptor-3 (VEGFR-3) help to make a final diagnosis [23,24,25,26,27,28]. Positive staining for CD31 and vWF, and absence of staining for cytokeratin in our patient indicate a vascular origin of the cyst and effectively rules out a mesothelial origin. CD31 and vWF have been used by others to make a diagnosis of vascular malformations in canine patients; however definitive diagnosis of lymphatic origin was based on presumptions or appearance on histopathology [16, 18,19,20,21]. Although PROX-1 is not a lymphatic specific marker, it helps in the differentiation between blood vessel and lymphatic origin as lymphatic endothelium use PROX-1 as transcription factor during development, whereas blood vessel endothelium does not. LYVE-1 is a cell surface receptor for the extracellular matrix glycosaminoglycan hyaluronan (HA) and the HA receptor is almost exclusively expressed on moderately to well-differentiated lymphatic vessel and absent in blood vessels . Hence positive staining for LYVE-1 and PROX-1 confirmed the suspicion of a lymphatic malformation.
Invasive or infiltrative growth is commonly associated with malignant behaviour. However, vascular malformations have been reported to have a progressive behaviour and a tendency to expand into surrounding tissues [2, 25, 26]. Progressive angiomatosis is well known for its invasive behaviour, which is also described in previous cases of canine vascular- and lymphatic malformations [8, 9, 25]. Thus, differentiation between a tumor and a vascular malformation can be challenging.
In humans, the ideal treatment for symptomatic or large retroperitoneal cystic lymphatic malformations is surgical resection to achieve complete excision [33,34,35,36,37,38,39], although this is not always possible, leading to frequent recurrence [23,24,25,26,27,28,29]. Recurrence after apparently complete surgical excision (up to 30% in some reports) is not uncommon [1, 17, 18, 32]. Surgery involves the risk of damage to surrounding tissues, persistent chylous ascites and re-enlargement of residual lesions . Dissection of the cyst in our patient had to be performed with precision, due to close proximity and enveloping vital structures as the ureter and terminal branches of the aorta and the caudal vena cava. Omentalisation has not been opted as therapy before in lymphatic vascular malformations in veterinary or human patients. However, the omentum has been proven to actively participate in the immune response and has the ability of absorbing fluid, therefore its use in abdominal and thoracic surgery is widely accepted . Once recurrence occurred in our patient, a PleuralPort was placed to pursue occasional drainage of the cyst via the subcutaneous access port. In humans, closed suction drains are occasionally placed in large macrocystic lymphatic malformations, and can be combined with sclerosing therapy . Unfortunately, our patient deteriorated acutely due to active spontaneous bleeding into the lesion, with fluid extravasation into the abdominal- and thoracic cavities. Due to the connection between the peritoneum and the thoracic cavity in between the diaphragm and the psoas muscles, the fluid most likely leaked from the peritoneum into the thoracic cavity, as described before . As the patient quickly deteriorated, the owner opted for euthanasia, which was also the outcome in other veterinary cases due to infiltrative behaviour of the malformations, inability of surgical resection or risk of recurrence [16, 21].
Despite documentation of recurrence of the cystic structures in some cases, long term prognosis of lymphatic malformations in dogs is not well-established [16,17,18,19,20,21]. No human data is available for long term prognosis in retroperitoneal cystic lymphatic malformations [33,34,35,36,37,38,39].
Vascular malformations should be taken into consideration in a patient presented with a retroperitoneal cyst containing haemorrhagic fluid. Additional imaging, histopathology and LYVE-1 and PROX-1 immunohistochemistry can be used to diagnose lymphatic malformations.