Mesenteric lymphatic malformation with chylothorax in a cat

Abstract

Case summary

An 8-year-old female spayed Russian Blue cat presented for acute progressive dyspnoea. The patient had pleural effusion and was diagnosed with chylothorax. A multiphase contrast-enhanced CT scan of thoracic and abdominal cavities was performed to facilitate diagnosis and surgical planning. Incidentally, a large lobulated, elongated, cystic and encapsulated peritoneal mass was found. Contrast pooled within the peritoneal mass during lymphography, suggesting lymphatic origin. The patient was eventually euthanased as a result of recurrence of chylothorax. Necropsy revealed multiple irregular, thin-walled pockets of chylous fluid pooling within the mesentery. Histopathology of the affected mesentery was compatible with a diagnosis of lymphatic malformation.

Relevance and novel information

To the authors’ knowledge, this is the first case describing a feline presentation of mesenteric lymphatic malformation. This is also the first case reporting the presentation of chylothorax for a veterinary patient with mesenteric lymphatic malformation.

Introduction

Lymphatic malformation (LM) is a rare congenital anomaly of lymphatic origin. LM was formerly known as ‘lymphangioma’, which is gradually being abandoned owing to the outdated association with neoplasia. According to recent publications, the umbrella term ‘LM’ was described as congenital low-flow vascular abnormalities in the lymphatic system characterised by excessive growth of lymphatic tissue, suggesting an embryological disorder instead.^1,2 LMs encompass a wide spectrum of subcategories and each has different clinical manifestations, including isolated cystic masses, osteolysis involving vascular fibrous connective tissue replacement and lymphatic vessel obstruction.^1,3 Treatment varies depending on the clinical signs, size and anatomic location of the lesion and associated complications. ⁴

In humans, the incidence rate of LM is approximately one in 2000–4000 patients. ¹ In veterinary medicine, the incidence is approximately one in 1,120,000 canine patients and one in 366,667 feline patients over a 30-year period (1964–1993) from a database shared by 23 veterinary colleges. ⁵ In that publication, the most commonly involved locations were the skin and lymphatics. Only five (7%) cases involved the abdominal viscera. ⁵ Since then, there have only been two case reports describing LMs in the mesentery in dogs.^6,7 To date, only one case report has documented a feline LM involving intraperitoneal organs, identified as a hepatic cavernous lymphangioma. ⁵ This study was published before the term ‘LM’ was established and the lymphangioma described was associated with a cancerous proliferation of lymphatic vessels.

This is the first case report describing a feline mesenteric LM with concurrent chylothorax.

Case description

An 8-year-old female spayed Russian Blue cat was presented to a veterinary emergency service for acute onset progressive dyspnoea. The patient was an indoor cat with no known trauma and no other significant medical history.

On presentation, the patient was tachypnoeic (respiratory rate 68 breaths/minute) with marked increased respiratory effort. Point-of-care ultrasound identified the presence of pleural effusion bilaterally. Immediate stabilisation included sedation with butorphanol (0.3 mg/kg IM, Butorgesic; Ilium) and oxygen supplementation. Additional sedation (0.1 mg/kg butorphanol, Butorgesic; Ilium, 0.2 mg/kg midazolam, Midazolam injection; Pfizer and 2 mg/kg alfaxalone IV, Alfaxan Multidose; Jurox) was administered to facilitate thoracocentesis. A total of 310 ml of milky white fluid was recovered from both hemithoraces. Tachypnoea subsequently improved. A full physical examination was performed and was otherwise unremarkable. Thoracic radiographs confirmed the presence of pleural effusion and secondary atelectasis.

Complete blood count, biochemistry and venous blood gas analysis were performed. There was eosinopenia (0.1 × 10⁹/l, reference interval [RI] 0.17–1.571), hyperglycaemia (12.56 mmol/l, RI 3.95–8.84) and low alanine aminotransferase (10 U/l, RI 12–130) and alkaline phosphatase (13 U/l, RI 14–111). There was a mixed respiratory and metabolic acidosis (pH 7.18, RI 7.35–7.46; pCO₂ 58.1 mmHg, RI 32–43; base excess −6.7 mmol/l, RI −2 to 2). Feline leukaemia virus antigen and feline immunodeficiency virus antibody tests (WITNESS) were negative.

Pleural effusion was analysed by a board-certified pathologist. There was a total nucleated cell count of 3920/µl with neutrophil (54%) and lymphocyte (39%) predominance. Most of the macrophages had fine cytoplasmic vesiculation, consistent with intracellular lipid. Based on these findings and the milky appearance, the fluid was classified as a chylous effusion.

The patient was hospitalised overnight. Oxygen supplementation was weaned within 12 h. Other therapies included maropitant (1 mg/kg IV q24h, Prevomax; Dechra) and intravenous fluids (0.45% NaCl + 2.5% glucose, 2.6 ml/kg/h).

The following morning, an echocardiogram was performed by a board-certified cardiologist, which identified a structurally normal heart, excluding a cardiogenic cause of chylothorax. A multiphase contrast-enhanced CT scan (Revolution EVO 128-slice CT; GE Healthcare) of the thoracic and abdominal cavities was performed. All images were interpreted by board-certified radiologists. Abnormalities included large-volume bilateral pleural effusion, small-volume right-sided pneumothorax (suspected to be iatrogenic secondary to thoracocentesis), thickened pleura and pulmonary hypoinflation or atelectasis. The caudodorsal mediastinum and cranial retroperitoneal space were widened with fluid. A large lobulated and elongated, fluid-attenuating (10 HU), cystic, encapsulated peritoneal mass measuring 12.62 cm (length) × 5.31 cm (width) × 3.24 cm (height) (Figure 1) was noted in the mid-abdomen. Indirect contrast lymphography was performed by administering 450 mg iohexol into the metatarsal pads. Multifocal contrast media pooling occurred within the caudal dorsal mediastinum and cranial retroperitoneal area, suggesting a markedly distended thoracic duct and cisterna chyli, respectively. Contrast also pooled within the peritoneal mass, supporting lymphatic involvement. The peritoneal mass was confluent with the distended cisterna chyli, and differential diagnoses included lymphatic pooling in intra-abdominal lymphatics, LM and lymphangiocele.

Figure 1.

Multiplanar CT images demonstrating the mesenteric lymphatic malformation. (a–c) Venous phase-post contrast images in the sagittal, dorsal and transverse planes, respectively. (d) Post-lymphography transverse plane image. The images illustrate a large, lobulated, thinly encapsulated, fluid-attenuating mass occupying the mid-abdomen (stars). After lymphography, contrast medium pooled in the dependent aspect of the cranial portion of the mass (arrow)

Ultrasound-guided fine-needle aspiration of the liver, spleen and the peritoneal mass was performed. Milky white fluid was aspirated from the peritoneal mass and was presumed to be chylous because of its resemblance with the pleural effusion. The sample was not submitted for analysis. Cytology of the spleen and liver returned with no evidence of neoplasia.

After recovery from the general anaesthesia, the patient developed recurrent pleural effusion and tachypnoea, necessitating repeat thoracocentesis. The owner elected euthanasia owing to financial constraints.

A full necropsy was performed by a board-certified anatomic pathologist. A distinct peritoneal mass was not grossly evident. Instead, multiple irregular, thin-walled pockets of chylous fluid pooling within the mesentery were present (Figure 2). This lesion spanned from the caudal border of the liver to the midpoint of the kidneys. On injection with air, the pockets were noted to be continuous. Mesenteric lymph nodes were not identifiable within this space but many anastomosing, tortuous white linear structures, presumptively lymphatic vessels, were coursing through the area. It was suspected that these pockets of fluid were more extensive when the cat was alive and accounted for the mass-like lesion noted on CT.

Figure 2.

Gross image of the mesenteric lymphatic malformation at necropsy after removal of the gastrointestinal tract. A distinct mass lesion is not appreciable, but there is pooling of opaque pink fluid (presumptive chyle) within the root of the mesentery (arrows). Mesenteric lymph nodes were not identified. Bar = 5 cm

Microscopically, the mesentery in the areas of chylous fluid pooling consisted of anastomosing irregular and variably sized channels (Figure 3). These spaces were divided by thick collagenous trabeculae lined by a single layer of thin, elongated endothelial cells. The endothelial cells were uniform with minimal cytoplasm and elongated hyperchromatic nuclei. There were no mitoses, minimal anisocytosis or anisokaryosis. Immunohistochemical staining of the cells was positive for factor VIII-related antigen (Figure 4). Collagenous septae contained small to moderate numbers of lymphocytes and plasma cells, which occasionally aggregated into lymphoid follicles. Incorporated into some septae were pockets of adipocytes. Many of the vascular spaces were devoid of cells and discernible material. Sections of the affected mesentery were histologically compatible with an LM. The cholesterol and triglycerides level of the pleural effusion were 1.92 mmol/l and 20.12 mmol/l, respectively, confirming the diagnosis of chylothorax. Other findings included fibrinous pleuritis secondary to chylothorax, pulmonary atelectasis with fibrinosuppurative bronchopneumonia and mild splenic congestion and hepatic necrosis.

Figure 3.

Post-mortem histopathology of the mesenteric lymphatic malformation. (a) Low-power view of the mesenteric tissue showing irregular anastomosing vascular channels divided by thick collagenous trabeculae that occasionally contain small lymphoid aggregates and pockets of adipocytes. H&E, bar = 500 µm. (b) Trabeculae are composed of mature collagen which stains blue. Masson’s Trichome, bar = 500 µm. (c) Some vascular spaces contain aggregates of amorphous proteinaceous material (presumptive lymph fluid, asterisk). H&E, bar = 200 µm. (d) High-power view showing empty vascular spaces lined by thin, elongate endothelial cells (arrow). H&E, bar = 50 µm. H&E = haematoxylin and eosin

Figure 4.

Immunohistochemistry for factor VIII. Note the strong dark brown cytoplasmic positivity of the endothelial cells lining the collagenous trabeculae (arrow) as well as the vessels within the trabecula (white asterisk). Bar = 50 µm

Discussion

This is the first case report describing a mesenteric LM in a cat. The described case presented for dyspnoea caused by a large volume chylothorax. It is unclear whether the mesenteric LM was an incidental finding or if it was associated with the pathology of chylothorax. Multiple human publications have described the association between spontaneous chylothorax and mediastinal lymphangioma, but not mesenteric lymphangioma.^8–10 Smeltzer et al ¹¹ reported a possible relationship between chylothorax and generalised lymphatic dysplasia. Lymphatic dysplasia is a congenital maldevelopment of the lymphatic system causing accumulation of chyle or lymph in the limbs, the pleural or peritoneal cavities. Common manifestations for lymphatic dysplasia include chylothorax, chylous ascites and lymphoedema. ¹¹ The cat in the current report only had chylothorax but was also euthanased, eliminating the chance to follow disease progression.

CT was the chosen imaging modality as it provided the opportunity to perform lymphography, helped rule out neoplasia and thromboembolism, and provided more tomographic information for surgical planning compared with thoracic radiography or ultrasonography. In humans, CT, ultrasound and MRI are all utilised in the investigation of LMs.^2,3,12,13 On ultrasonography, anechoic multilocular cystic masses are usually observed. A solid lesion is rare but possible. On MRI, lesions display marked T2-weighted hyperintensity with contrast uptake of the cyst walls.^2,14 In humans, MRI is the imaging modality of choice as it excels in differentiating cystic and septal structures.^12,14 In veterinary medicine, MRI is often not performed because of cost, limited availability and the length of anaesthesia required. In the described case, CT did not identify contrast enhancement of the lining of the peritoneal mass. Contrast-enhanced MRI or ultrasonography may have been more sensitive in identifying cystic walls, with ultrasonography potentially better at detecting a multilocular appearance.

Confirmation of lymphatic origin can still be challenging after advanced imaging, and a definitive diagnosis requires histopathology and immunostaining. Both the present case and the only other published case of feline lymphangioma relied on histopathology. In the present case, only factor VIII immunohistochemistry was performed because of the limited availability of appropriate lymphatic endothelial cell markers in Australia. In human medicine, the marker Podoplanin D2-40 is used to diagnose LM, whereas in veterinary medicine, the use of lymphatic vessel endothelial hyaluronan receptor 1 (LYVE-1), vascular endothelial growth factor receptor 3 (VEGFR-3) or prospero homeobox protein-1 (PROX-1) have been reported.^2,7,13 PROX-1 and VEGFR-3 are both transcription factors for developing lymphatic endothelium while LYVE-1 is a cell surface receptor for the extracellular matrix glycosaminoglycan hyaluronan, which is a feature unique to lymphatic vessels. ¹³ Wider availability in the future may improve understanding of these stains.

Both the present case and the other published feline LM case were euthanased without pursuing treatment. In both human and canine medicine, surgical removal is the recommended treatment for LM; however, complete resection is not always possible depending on the location.^12,13 Local recurrence occurs in approximately 20% of human cases. ¹⁵ When complete excision is not possible, treatment options include benign neglect, sclerotherapy with doxycyline, radiation therapy or bleomycin.^1,6,16 When surgery was declined in this case, glucocorticoids were considered a potential treatment option. Glucocorticoids reduce lymphangiogenesis by inhibiting VEGF expression, inhibiting matrix metalloprotease activity and reducing endothelial cell proliferation. ¹⁷ However, a potential drawback to glucocorticoid therapy includes fluid retention, which may worsen the chylothorax. ¹⁸ In humans, clinical trials have been undertaken for novel medical treatments to reduce lymphangiogenesis, such as sirolimus, but require further evaluation before being a viable option in veterinary medicine.^1,3

Conclusions

This is the first case report describing mesenteric LM in a cat, which should be considered a differential diagnosis if a cystic mass containing chylous fluid is noted in the mesentery. It is also the first description of concurrent mesenteric LM and chylothorax in veterinary medicine, although the relationship between the two is unclear. CT lymphography was used to identify and localise the lesion. MRI and ultrasound may also be helpful but were not pursued in the described case. Ultimately, histopathology and immunostaining are required for definitive diagnosis. Unfortunately, the owner elected euthanasia. Further studies are required to evaluate diagnosis, potential treatment options and prognosis in veterinary patients with mesenteric LM.