Treatment of giant cervico-mediastinal lymphatic malformations: a case series
Lymphatic malformations are histologically benign vascular structures that vary in anatomic lesion and size. Extensive head and neck lymphatic malformations may be life-threatening. In the present study, we described three difficult-to-treat infants with giant cervico-mediastinal lymphatic malformations accompanied by severe respiratory distress.
Case 1. A Korean girl born at a gestational age of 37 weeks and weighing 2920 g had a large cervical mass compressing the trachea. Despite initial OK-432 sclerotherapy, the mass extended over the contralateral retropharyngeal space and mediastinum. Although the cervical mass was completely excised, our patient was not weaned off the ventilator. The mediastinal lymphatic malformation was excised, and our patient underwent continued intensive respiratory care with nasal continuous positive airway pressure for 6 months. She is now 5 years old and doing well without any sequelae. Case 2. A 5-month-old Korean boy showed respiratory difficulty with feeding intolerance after partial excision of a neck lymphatic malformation. We found that the remnant cervical mass had grown into the retropharyngeal space and mediastinum. After a second operation for the cervico-mediastinal mass, he experienced severe respiratory difficulty requiring ventilator care for 6 months. However, he died from central-line fungal sepsis. Case 3. A 30-day-old Korean girl was referred for remnant lymphatic malformation after partial excision. The cervical mass extended to the mediastinum and occupied half of the thoracic cavity, encasing all of the major vessels. After surgical excision, she underwent ventilator care and pleurodesis three times with doxycycline for recurrent pleural effusion. At the age of 26 months, she was weaned off supplementary oxygen and she showed normal development without any sequelae.
Despite difficulties in the treatment process, combinations of delicate surgical treatment, appropriate adjuvant sclerotherapy, and intensive respiratory supportive care could result in a good outcome. However, complications due to long-term intensive care could still be considered.
KeywordsLymphatic malformations Neck Mediastinum
Lymphatic malformations (LMs) are benign vascular lesions that arise from disturbances during embryologic development of the lymphatic system. It can form variable-sized cystic lesions within lymphatic channels [1, 2, 3, 4, 5]. Most of these lesions are in the head and neck area (80–90%), but they can appear anywhere in the body, including in the extremities, trunk, abdomen, retroperitoneum, and thorax [1, 3, 4, 5]. Although histologically benign, these lesions are regarded as clinically intractable because disease progression would not be expectable and treatment could be supportive rather than curative. Small-sized LMs may be asymptomatic even if identified during radiologic examination. Symptoms can be serious if the malformations are large, compress surrounding structures, or invade vital organs. In particular, head and neck LMs involving the oral cavity, pharynx, larynx, esophagus, and/or trachea may be life-threatening. The treatment of choice, such as observation, excision, or sclerotherapy, depends on many factors, including associated symptoms and complications, disfigurement, and the surgeon’s experience [1, 2, 3, 4, 5]. Surgery is the definitive treatment, but complete excision is often not feasible because of the anatomic location of these lesions and their tendency to infiltrate surrounding tissue [3, 6]. In addition, LMs may widely displace or entirely envelop nerves and blood vessels; they may also cross fascial boundaries and distort normal anatomy [6, 7, 8]. This report describes three patients with giant cervico-mediastinal LMs accompanied by severe respiratory distress. We discuss the difficulties and the lessons learned during the treatment process.
We described three cases of cervico-mediastinal lymphatic malformations requiring extensive surgery with long-time respiratory supportive treatment. Previous reports in the literature were sporadic and varied in age. This report only includes neonates with respiratory compromise caused from cervico-mediastinal LM. We wanted to share a difficult treatment course.
Two types of treatment are available for LMs: sclerotherapy and surgery. Surgical intervention is the best method for complete resection, but it is often difficult and insufficient. Surgery can damage the surrounding structures, particularly the nerves and blood vessels, and can cause scarring; sometimes, there is recurrence due to incomplete excision [2, 9, 10, 11]. Complete excision of LM with vital organs, such as the tongue, pharynx, and orbit, should not be performed. Thus, intralesional sclerotherapy using bleomycin, tetracycline, alcohol, and OK-432 should be the treatment of choice [2, 12]. Sclerotherapy can induce endothelial inflammation in vascular structures, resulting in thrombosis, occlusion, and fibrosis [1, 2, 13]. OK-432, which is derived from a strain of Streptococcus pyogenes, is usually the first choice for a sclerosing agent . Although effective for single cystic lesions and macrocystic lesions, OK-432 has been found to be less effective for microcystic and cavernous lesions . OK-432, however, may be useful as neoadjuvant treatment before surgical excision and as postoperative adjuvant treatment following incomplete excision. In addition, it reduces lymphatic fluid retention after surgery . We thought that sclerotherapy and surgical treatment could complement each other.
None of these patients could be treated by sclerotherapy alone because all the masses were large and deep with areas that were inaccessible to intralesional injection of sclerosing agents. The first line of treatment, comprising partial excision or OK-432 sclerotherapy, was ineffective and exacerbated respiratory symptoms. We made a decision that extensive excision for cervical lesions was necessary for airway management. It was successful, but we confronted persistent pulmonary dysfunction. Unlike the previous reports of asymptomatic mediastinal LMs connected to cervical lesions, these lesions caused severe respiratory distress with a mass effect in the thoracic cavity. We found that the mediastinal LMs in this series were mostly composed of microcystic lesions. The clear and tiny vesicles made it denser and harder than macrocystic lesions . Moreover, these malformations infiltrate more and are difficult to resect surgically [8, 14, 15]. While the LMs in the neck were relatively soft and cystic, the LMs in the mediastinum were very hard, without the cystic portion. It definitely seemed to interfere with respiratory function. We learned that mediastinal LMs extending from cervical LMs can affect respiratory function, and they required surgical intervention.
Partial resection of a large LM was not beneficial to our patients. It resulted in severe fibrosis and adhesion of the overlying skin and subcutaneous tissue. The remaining LM did not grow outward but grew into the head and neck cavity, severely compressing the airway and esophagus. The overall recurrence rate after surgical treatment ranges from 35 to 64%, with at least 17% of LMs recurring even after complete removal [16, 17]. Postoperatively, remnant lymphatic channels dilate with marked regenerative ability [3, 18]. Lesion regeneration has been associated with increased activity of vascular endothelial growth factor and decreased activity of pigment epithelium-derived factor . Thus, partial resection was not ideal for our cases.
Of note, it took considerable time for patients to recover pulmonary function after mediastinal mass removal. The reasons for this delay are unclear, although surgical removal of a mediastinal LM relieves compression on the lung parenchyma. One possible reason is the presence of reactive fluid from the cut surface of the lymphatics and postoperative swelling, which could generate another space-occupying lesion in the thoracic cavity. Another possibility is that the mediastinal mass in the thoracic cavity interferes with the development of normal lung parenchyma during the fetal period, which could affect overall pulmonary function. Fortunately, we found that positive pressure support sufficiently improves gas exchange. Although patients were on assisted ventilation for a long time, they could be weaned off supplementary oxygen.
This series describes three difficult-to-treat patients with extensive cervico-mediastinal LMs. The two surviving patients will require careful long-term follow-up for recurrence and pulmonary function. Despite difficulties during the treatment process, combinations of delicate surgical treatment, appropriate adjuvant sclerotherapy, and intensive respiratory supportive care resulted in a good outcome. However, complications due to long-term intensive care could still be considered.
Giant cervico-mediastinal lymphatic malformations in infants could be treated with surgical removal and adjuvant sclerotherapy. Overall, pulmonary dysfunction caused from mediastinal lymphatic malformations could be overcome with long-time respiratory supportive care.
SHN was the treating physician involved in the initial clinical assessment and operation. She organized all of the patient’s records and obtained consent from the parents. K-AK reviewed all treatment processes and wrote part of the discussion. Both authors read and approved the final manuscript.
Ethics approval and consent to participate
The authors declare that ethics approval was not required for this case report as we did not use any new procedures or any treatment that was not approved for clinical use in our institution.
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Written informed consent was obtained from the patient’s legal guardian(s) for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.
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