患皮肤淋巴管肉瘤犬的头部和颈部CT淋巴管造影。 机翻

Abbreviations

contrast enhanced computed tomography

CT lymphangiography

Hounsfield units

sentinel lymph node

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Signalment, History, and Clinical Findings

A 9‐year‐old neutered male Australian Cattle dog presented to the veterinary emergency department of the University of Montréal for a chronic, severe, and progressive swelling of the neck and face.

Twenty‐two months before presentation, the owner first noticed the neck swelling after a heavy object fell on the dog's back. Twelve months before presentation, the swelling persisted and was continuously increasing over 3 months, extending up to the lips. Cervical radiographs performed by the referring veterinarian were unremarkable, and fine needle aspirations of the cervical swelling revealed only small lymphocytes in a cystic liquid. Two months before presentation at the emergency department, the swelling acutely worsened, and a sero‐hemorrhagic discharge was noted at the corner of the lower lip. Treatment with amoxicillin–clavulanic acid and deracoxib was initiated by the referring veterinarian but was unsuccessful. The owners reported that the dog was in good general condition despite the persistent swelling.

Physical examination revealed severe, fluctuant, non‐painful subcutaneous swelling of the face and neck clinically consistent with edema, which abruptly stopped in the mid‐cervical region. Biochemistry and complete blood count revealed mild neutrophilic leukocytosis and mild hypoalbuminemia, suggestive of mild inflammation. C‐reactive protein level was normal (3.7 mg/L, reference range: 0–7 mg/L). Fine‐needle aspirations of the swelling revealed a mild mononuclear inflammation with macrophages and lymphocytes and evidence of acute and chronic hemorrhage. Prior to advanced imaging, the medial retropharyngeal lymph nodes appeared enlarged on ultrasound, and ultrasound‐guided fine needle aspirates of the medial retropharyngeal lymph nodes revealed atypical cells, suggestive of a mesenchymal neoplasm or a reactive process such as fibroplasia.

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Imaging, Diagnosis, and Outcome

A contrast‐enhanced CT (CECT) study of the head, cervical region, and thorax was performed with pre‐contrast and post‐contrast acquisitions, early arterial phase, and delayed phases at 30 and at 60 s after IV manual injection in the right cephalic vein (2 mL/kg of iopamidol at 300 mg I/mL—Isovue 300, Bracco Imaging Canada, Montreal, QC, Canada). The CT was performed under general anesthesia with a Canon Aquilion One Prism Edition (320 slices) and the following technical parameters: 120 kVp, 300 mA, acquisition slice thickness: 0.5 mm, spiral pitch factor: 0.638. The patient was in sternal recumbency. Axial images were reconstructed with a slice thickness of 0.5 mm in soft tissue, bone, and lung algorithms and then interpreted using multiplanar reconstruction. From the rostral part of the mandible to the caudal margin of C3, there was a severe, ventral, subcutaneous, and intramuscular, bilateral and symmetrical accumulation of fluid‐attenuating non‐enhancing material (15–20 HU) with a large amount of peripheral fat stranding. Bilaterally, the sternocephalic muscles were severely thickened and partially fluid‐attenuating. Mandibular lymph nodes were normal in size. Medial retropharyngeal and parotid lymph nodes were moderately enlarged bilaterally (11.4 mm × 18.2 mm × 65.2 mm on the right, 10.5 mm × 18.0 mm × 59.6 mm on the left, and 8.5 mm × 16 mm × 9.9 mm on the right and 8.7 mm × 18.4 mm × 8.6 mm on the left, respectively—mediolateral × dorsoventral × rostrocaudal) as were the superficial cervical lymph nodes (25.1 mm × 19.2 mm × 14.7 mm on the left and 28.5 mm × 15.7 mm × 19.7 mm on the right—mediolateral × dorsoventral × rostrocaudal). These lymph nodes were heterogeneously contrast‐enhancing with internal non‐enhancing nodular regions. Regional veins and arteries were unremarkable except for incidental congenital absence of the left external carotid artery. The cranial mediastinum and the heart were unremarkable. The lungs were normal with no evidence of metastasis.

Immediately after the CECT, CT lymphangiography (CTL) of the head and neck was performed, under the same general anesthesia, using a modified version of a previously described protocol (Table 1) [1]. After disinfection, 5 mL of iopamidol (300 mg I/mL—Isovue 300, Bracco Imaging Canada, Montreal, QC, Canada) was injected submucosally in the upper rostral lips bilaterally using a 22 Ga needle and 5 mL syringe manually, over 2 min. No local anesthesia was performed. The same CT machine and acquisition parameters as for the CECT were used. No endotracheal tube tie was used to prevent potential obstruction of the lymphatic vessels. The injection sites were then massaged for 2 min, and acquisitions were performed at 3, 5, 15, and 30 min post‐injection. In order to limit the radiation dose, the number of acquisitions was reduced from 7 to 4 compared to the original protocol [1]. Starting at 3 min post‐injection, a moderate amount of contrast traveled in a caudal direction, bilaterally and symmetrically, in moderately dilated lymphatic vessels of the lips and head (Figure 1). At the level of the ventral subcutaneous hypoattenuating non‐enhancing fluid accumulation, a large area of poorly defined contrast accumulation appeared gradually over time. The successive acquisitions at 5, 15, and 30 min after injection demonstrated a gradual symmetrical diffusion of the contrast medium in the ventral neck fluid accumulation (46 HU at 3 min, 51 HU at 5 min, 55 HU at 15 min, 78 HU at 30 min) (Figure 2). There was no contrast enhancement of the lymphatic vessels caudal to the site of leakage, nor of the mandibular, medial retropharyngeal, or superficial cervical lymph nodes at any time point of the CTL study, suggesting mid‐cervical lymphatic path obstruction. Differentials included a regional neoplastic infiltration of the lymphatic system or of peri‐lymphatic tissues (e.g., lymphangioma, lymphangiosarcoma, lymphoma, and mastocytoma), severe cicatricial changes of the lymphatic system secondary to chronic lymphangitis (e.g., distortion/obstruction and/or loss of function of the valves). Post‐traumatic lymphatic disruption with secondary scarring due to the old trauma reported was considered less likely given the symmetry.

[图：Computed tomographic lymphangiography study of the head at the level of the fourth maxillary premolar demonstrating a cl]

[图：Computed tomographic lymphangiography study of the head at the level of the pterygoid bones demonstrating contrast leaka]

Three skin punch biopsies of the swollen neck region revealed dissecting channels lined by neoplastic mesenchymal cells with abundant collagen. Peripheral areas showed variably sized, tortuous, and often empty vascular spaces lined by one or more layers of atypical spindle‐shaped cells with moderate pleomorphism and occasional hyperchromatic nuclei. There were 26 mitoses per 2.37 mm2 and moderate anisocytosis and anisokaryosis. A mild‐to‐moderate lymphoplasmacytic infiltrate was also noted near obliterated appendages. Findings were consistent with cutaneous lymphangiosarcoma (Figure 3). A 16S ribosomal RNA PCR was performed on an additional sample and returned negative.

[图：Photomicrograph of a skin biopsy (face and neck), showing dissecting channels lined by a single layer of plump neoplasti]

Treatment with oral prednisolone 1 mg/kg SID and pentoxifylline at 16 mg/kg BID was initiated. Fifteen days later, prednisolone was diminished to 0.7 mg/kg SID, and palliative chemotherapy with mitoxantrone intravenously at 4.8 mg/m2 was initiated, as previously reported [2]. The dog was euthanized 1 week later due to sudden worsening of the general condition. No necropsy was performed.

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Discussion

Lymphangiosarcoma is a rare malignant neoplasm arising from the lymphatic endothelium [2, 3, 4, 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, 15, 16]. In humans, lymphangiosarcoma tends to induce chronic lymphedema, often developing after radical mastectomy and regional lymphadenectomy [4, 5]. In veterinary medicine, most reported cases are large breed dogs, as in this case, with no apparent sex predilection and a vast age range (8 weeks to 13 years old) [3, 4]. Survival is highly variable, ranging from 60 days to 876 days without treatment. In our case, the duration of clinical signs before presentation was approximately 648 days; the dog was euthanized approximately 3 weeks after diagnosis. The survival time from the appearance of the clinical sign to death was 669 days, and from diagnosis to death was about 3 weeks. The most common clinical signs are a subcutaneous mass or a focal swelling, with frequent sero‐hemorrhagic discharge. Most cases of canine lymphangiosarcoma are located in ventral subcutaneous tissues (cervical, thorax, abdomen, and limbs), with only six cases reported in the cervical region similar to our patient [3, 6, 7, 8].

Lymphangiosarcoma can occur in various locations due to the widespread distribution of lymphatic vessels. Obstruction of lymphatic drainage associated with lymphangiosarcoma has been reported to result in fluid stasis and leakage, leading to lymphedema [6, 9, 10]. In the present case, the exact mechanism of obstruction could not be definitively determined, as CTL did not directly identify the obstructing lesion. We postulate the cause of the obstruction was most likely due to either lymphatic vessel infiltration/dysfunction, tumor‐associated lymphadenopathy causing increased upstream pressure, or a combination of both. This is supported by the absence of contrast progression into regional lymph nodes and the presence of contrast leakage rostral to their level, suggesting impaired lymphatic flow cranial to these structures. Normally, lymph fluid flows unidirectionally from capillaries to larger vessels, then to the thoracic and right cervical ducts, and finally returns to circulation via the cranial vena cava [17]. Congenital lymphatic anomalies are a primary cause of lymphedema, whereas secondary causes reported in humans include surgery, radiation, trauma, infection, chronic venous insufficiency, immobility, or tourniquet effects [1, 17, 18].

A previous case report of lymphedema in a 1‐year‐old German pointer dog described the use of a head CTL as an aid in diagnosis [1]. In this case report, a dog with isolated head/neck lymphedema had a suspected congenital unilateral hypoplasia of the right medial retropharyngeal and mandibular lymph nodes, and an absence/malformation of the right lymphatic vessels of the face, causing unilateral muzzle swelling [1]. In our case, primary edema was considered unlikely given the senior age and bilaterally symmetrical changes. In our case, the CTL was easy to perform and provided a functional assessment of lymphatic drainage that could not be obtained with conventional CECT alone, allowing visualization of contrast leakage and lack of progression to regional lymph nodes, thereby supporting the presence and approximate localization of lymphatic obstruction. The etiology of the lymphatic obstruction was unclear; causes considered included regional lymphadenopathy causing functional obstruction with retrograde lymphatic congestion or primary lymphatic vessel infiltration by neoplasia (or both). In the present case, CTL was a key diagnostic step to approach the underlying pathophysiological process responsible for the neck edema and to determine the best location to perform biopsies. Histopathology was necessary for definitive diagnosis. The histomorphological features of the tumor were consistent with a lymphatic origin; therefore, immunohistochemistry was not deemed essential for the final diagnosis.

Diagnosis of lymphatic vessel obstruction was rapid (noted at 3 min post‐injection and confirmed on following acquisitions). This is in accordance with a previous study. Although obstruction detection was not specifically evaluated, the median time to identify the sentinel lymph node (SLN) by lymphangiography was 0 min (range 0–3 min), supporting that lymphatic contrast progression can be visualized within minutes following injection [19].

In our case, no adverse effect was noted immediately post‐lymphangiography procedure nor reported by the owner following discharge. This is in accordance with previous publications where no adverse events were reported with peritumoral/peri‐scar contrast administration in or adjacent to the lips. Although the present case used submucosal lip injection rather than true peritumoral injection, these findings similarly support that lip injection is a safe method for head CTL [1, 19]. One CTL study to detect SLN noted the importance of ensuring the endotracheal tube tie is not around the nose, as this can occlude the lymphatic vessels of the lips and restrict lymphatic flow [19].

In a previous study [19], CTL was performed prior to injection of intravenous contrast to avoid enhancement of the lymph nodes, potentially obscuring early localization of peritumoral injected contrast uptake in the lymph nodes and thus SLN detection [19]. In our case, the CTL was performed approximately 10 min after the standard CECT scan, by which time most of the contrast had washed out; the amount of residual contrast in the blood vessels and enhanced tissues was minimal, and it did not interfere with the visualization of the highly enhanced patent lymphatic structures.

This case report has some limitations. First, no necropsy was performed. Moreover, although the tumor's histomorphological features were indicative of a lymphatic origin, additional immunohistochemical characterization may have provided further insight; however, this was not undertaken due to financial constraints.

In conclusion, this case report emphasizes the usefulness of head and neck CTL for the diagnosis of lymphangiosarcoma; in this case, it allowed for the identification of the site of lymphatic obstruction, demonstrated symmetry of the lesions, aiding in narrowing the differential diagnoses, and guided the selection of biopsy sites. Head and neck CTL proved to be safe, cost‐effective, and easy to perform following a standard post‐contrast CT scan, with no interference between vascular and lymphatic enhancement. This report also presents a protocol with a reduced number of CTL acquisitions post‐contrast compared to the previously reported protocol, which reduces the radiation dose to the patient as well as the time under anesthesia. Future studies are needed to determine the optimal injection volumes and post‐contrast acquisition times for head and neck CTL.

Author Contributions

Conception and design: Megan Murphy, Jeanne Bleuet, and Vincent Auffret. Acquisition of data: Jeanne Bleuet, Vincent Auffret, Marilène Paquet, and Megan Murphy. Analysis and interpretation of data: Jeanne Bleuet, Vincent Auffret, Edouard Martin, Marilène Paquet, and Megan Murphy. Drafting the article: Jeanne Bleuet and Vincent Auffret. Reviewing the article for intellectual content: Jeanne Bleuet, Vincent Auffret, Edouard Martin, Marilène Paquet, and Megan Murphy. Final approval of the completed article: Jeanne Bleuet, Vincent Auffret, Edouard Martin, Marilène Paquet, and Megan Murphy. Agreement to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved: Jeanne Bleuet, Vincent Auffret, Edouard Martin, Marilène Paquet, and Megan Murphy.

Conflicts of Interest

The authors declare no conflicts of interest.

Disclosure

The authors have nothing to report.

Acknowledgments

The authors acknowledge the veterinary staff at the Veterinary Teaching Hospital of the Faculté de Médecine Vétérinaire of Université de Montréal who were involved in the case.

Data Availability Statement

The data used in this study are available from the corresponding author upon reasonable request.

References

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Associated Data

Data Availability Statement

The data used in this study are available from the corresponding author upon reasonable request.