1Sultan Alamri,1Mohammed Badran

1King Faisal Specialist Hospital and Research Center

Introduction:

Cystic lymphatic malformations (LMs) are benign abnormal embryologic development of slow-flow vascular lesions composed of dilated lymphatic channels or cysts lined by endothelial cells, occurring anywhere in the fetal body. (1) The overall incidence of LMs range from 1 out of 2000 to 20,000 live births. (2) They occur most commonly in the nuchal region (75%) and least common in the limbs and bones (2%) and lastly mediastinum (1%). They could be microcystic (diameter of <1 cm), macocystic (diameter of >1 cm)  or mixed. (1) Presenting symptoms primarily depends on the location and severity of the lesion with LMs being more prone to infections, as compared with other vascular malformations.  Doppler ultrasonography (US) is traditionally used as the primary screening method, especially prenatally, which classically demonstartes absence of blood flow, in contrast to hemangioma. Magnetic resonance imaging (MRI) is essential in evaluating anatomy and the extent of the vascular malformation. (2) Conventionally, most lymphatic anomalies were observed, and if clinically indicative, treated with either aspiration or complete or partial surgical resection. Given the difficulty of treating LMs and in cases where surgery is not feasible, conservative standard treatments have been used, such as percutaneous sclerotherapy (i.e., doxycycline, bleomycin, ethanol, and others) or ablation and laser therapy. (3,4) Evolving treatments have also been experimented, including medications. Owing to the rarity of case reports demonstrating such endovascular management, the authors herein describe this novel treatment technique via direct-puncture lymphangiogram followed by duct glue embolisation of a thigh congenital lymphatic malformation in an adult patient showing promising results.

Material(s) and Method(s):

Case Report:
A 25-year-old male patient who was referred to our hospital in 2011 as a case of congenital microcystic LM of the right lower thigh (Elephantiasis nostra verrucosa). The patient also had a history of road traffic accident (RTA), for which he was surgically treated with intramedullary nails of the femur and tibia at the age of 12 years old, where the presence of malformation complicated his management further. A plethora of diagnostic modalities were used to reach the diagnosis. Doppler US was initially done, which was inconclusive. Subsequently, femur MRI was done but aborted midway, for the patient could not tolerate the exam; however, conclusion was consistent with lymphatic malformation. Additionally, multiple nuclear medicine lymphangiograms to rule out lymphatic obstruction took place, all of which showed no overt obstruction. On follow-ups, the patient’s known LM showed gradual increase in size until it affected his quality of life, preventing him from easily moving due to its heavy weight. Therefore in 2016, the decision was made by his orthopedic surgeon to go on with surgical excision and primary closure. The patient was then followed up by dermatology. Upon follow-up after excision, there was recurrence of the known LM with history of recurrent infections. Hence, another excision with primary closure took place in 2017. Consequently, gradual regrowing of the lesion was noticed in his subsequent follow-ups; therefore, it was decided that conservative management was favorable. Then, interventional radiology (IR) was consulted. The patient had a long course of sclerotherapy sessions starting from 2018 until 2021. Sclerotherapy agents including bleomycin and doxycycline were used with persistent recurrence. Additionally, the patient has been on oral Sirolimus since 2017, with dose modifications. In one of the patient’s IR follow-ups and under general anesthesia, the patient was in supine position and under US and fluoroscopic guidance, it was decided to proceed with intranodal lymphangiogram; the right groin lymph node was accessed under US guidance using 25G needle. Lipidol was injected, which showed a large lymphatic duct parallel to the superficial femoral vein refluxing inferiorly toward the known LM. Then, the posterior tibial vein was accessed using a micropuncture set and sheath, afterwards, venogram was done showing a patent femoral vein running parallel to the femoral lymphatic duct with no clear communication. Consequently, under fluoroscopic guidance and in multiple projections, the femoral lymphatic duct was accessed directly at the mid-thigh using 22G spinal needle, lymphangiogram was done to confirm the needle’s location within the duct, followed by duct embolization using 0.5 ml glue (25%). The medial aspect of the lower thigh, popliteal fossa and upper medial calf were targeted. A total of 1000mg doxycycline was injected through multiple punctures distributed along the malformation using gravity technique. The patient was then discharged home in good health without immediate complications. On short-term follow-up, the patient continued on oral Sirolimus and was satisfied with the result. MRI follow-up was recommended.

Result(s): Discussion

This report describes a case of right thigh congenital LM in an adult patient who received combined sclerotherapy and surgical treatment to no avail. Eventually, the decision was made to do a direct-puncture lymphangiogram with evidence of refluxing lymphatic duct, which embolised utilizing glue, showing significant regression in size. The management of LMs have recently been dealt with in a conservative approach which includes observation, sclerotherapy, and surgery. Additionally, new medications such as Sirolimus, an mTOR inhibitor, which our patient has been on, have been reported recent literature as efficacious, though prospective randomized trials are still lacking. (5) In regard to interventional radiology-related treatments, a study done by Gilony et al. which included 45 patients showed that 95% of patients had excellent to fair response to conventional sclerotherapy (i.e., Picibanil (OK-432)) alone. (6) It is essential to note that despite the plethora of sclerosing agents, there is no consensus on which one is optimal as of yet. (5) On the other hand, the efficacy of sclerotherapy in treating microcytic LMs has been established in an array of published reports. (7)  Our novel technique which targeted the patient’s lymphatic duct using direct-puncture lymphangiogram and then embolisation with 0.5 ml glue has only been described in the literature by Dionisio et al. A case of leaking central conducting lymphatic malformation in a neonate, in which the author attempted, twice, percutaneous n-Butyl cyanoacrylate (n-BCA) glue for embolisation of the disrupted lymphatic channels. The patient, however, experienced a protracted course, unlike our case, complicated by pleural effusion, adrenal hemorrhage, acute kidney injury, and multimicrobial infections, that warranted multiple subsequent surgeries. (2) Other reports described using a similar treatment technique in a case of orbital lymphatic-venous malformation with concomitant fistula, in which glue embolization was utilized. (8)  In terms of complications, our patient had no immediate complications, though long-term follow-up is needed in order to establish a strong evidence. In terms of complications, glue embolization could generally lead to glue migration leading to pulmonary embolism, lower extremity swelling or diarrhea. (2) Here is a single case of cystic LM of the thigh, with a history of numerous failed attempts of surgical and sclerotherapy treatments.

Conclusion(s):

To the authors’ knowledge, this progressive approach of managing thigh intractable LM demonstrated by direct-puncture lymphangiogram and duct glue embolisation is effective and considered a potential treatment of choice for extremity LM.