Angioma/Lymphangioma

Lymphangiomas are benign malformations of the lymphatic system, composed of thin-walled, cystically dilated vascular channels lined by inconspicuous endothelial cells and filled with proteinaceous lymph fluid¹. 

The estimated incidence ranges from 0.008% to 0.18%. They are relatively rare, the most common area is the neck (75%), followed by the axillary region (20%), retroperitoneum and abdominal viscera (2%), limbs and bones (2%), and cervico-mediastinum (1%)^2-4.

Lymphangioma is one of the developmental abnormalities of the lymphoid system which occurs at the site of the lymphatic–venous connections. It is a failure of the lymphatic system to connect or separate from the venous system or due to abnormal budding of lymphatic tissue from the cardinal vein. There are some theories about the pathogenesis of lymphangiomas, however, the consensus has been maintained that it is the result of obstruction of lymph vessels. Lymphangiomas are divided morphologically into macrocystic, microcystic, or mixed subtypes according to the size of the locules^1,2. 

Ultrasonographic characteristics for prenatal diagnosis include a multicystic and sonolucent mass, with a thick or subdivided septum, with blurred boundaries. Approximately 17% may present without septa presented with a clear border. Colour Doppler ultrasound reveals no venous or arterial blood flow within the mass^5,6.

Lymphangiomas often grow proportional to the patients’ body growth, so correct diagnosis and accurate assessment of its size and location is necessary to avoid perinatal complications. However, in a cohort of 79 patients, the rate of resolution of lymphangioma was 8.9% during the gestational period and 17.7% in the post-natal period, before the age of 2 years⁶.

Two morphological changes in these masses have been described on prenatal ultrasound: firstly, a uniloculated mass can change to exhibit multiloculated features. Secondly, the size of the largest macrocyst can decrease and the sizes of the smaller microcysts can increase over time⁷.

Three-dimensional ultrasound has been used to diagnose tumors with a complex 2D appearance. This technology provides additional information about the exact location and extent to which the tumor extends into surrounding structures, particularly the face and can complement the information acquired with 2D images⁸.

The differential diagnosis includes lymphangiomas, teratomas, hemangiomas, cervical meningoceles, thyroglossal duct cysts, esophageal diverticula, dermoid cysts, brachial cleft cysts, epignathus, and congenital goiters⁸.

Complications that may occur during prenatal evaluations are related to the penetration or invasion of neighboring tissues with extensive involvement of the respiratory tract or other vital structures. For example, pulmonary hypoplasia and heart failure can result, due to compression of the vein and displacement of the mediastinum and heart, causing hydrops fetalis^9,10.

The risk of chromosomal abnormalities is very low in pregnancies with isolated lymphangioma, associated with 2% ^6,11,12.

Serial prenatal ultrasound evaluation is suggested at 2-week intervals, to inform pregnancy-related decisions, including expectant management or expediting delivery planning, including the preferred method of and venue for delivery. Early diagnosis of fetal lymphangioma is critical for clear advice to parents and planned delivery^3,13.
In patients with evidence of compression of the trachea and esophagus, initial management has consisted of the EXIT procedure, which allows the fetal airway to be secured before completion of delivery and umbilical cord clamping maintaining the uteroplacental circulation¹⁴. 
However, currently in fetal surgery, it is recommended to perform a fetoscopic endoscopic tracheal intubation procedure (FETI) to ensure extrauterine tracheal permeability before delivery, avoiding possible limitations of the procedure and the maternal and neonatal morbidity that can be associated with EXIT¹⁵.

Sclerotherapy is the preferred treatment for a lymphangioma in which cysts are >1 cm in diameter, as well as for lesions that penetrate into adjacent tissues^5,7.
In intrauterine treatment with sclerotherapy, successful cases have been reported with OK-432 (inactivated streptococcal organisms)¹⁶.
In the case of neonatal treatment, surgery has historically been considered the treatment of choice, but today less invasive therapeutic options are preferred; cases of success have been reported with bleomycin and sirolimus.  Further research is needed to establish the best treatment.^5,17,18.

Upper airway obstruction is life-threatening with subsequent perinatal mortality and morbidity, often associated with a delay or inability to obtain an airway at birth¹⁵. 
The resolution rate of lymphangioma has been reported as 8.9% during the gestational period and 17.7% in the postnatal period, before 2 years of age.
Patients requiring sclerosing therapy have presented a rate of good to excellent results in 91.5%, however, the most common complications are recurrence, inflammation, persistent pain and infection^18,19.

1.    Wiegand, S., Eivazi, B., Barth, P. J., von Rautenfeld, D. B., Folz, B. J., Mandic, R., & Werner, J. A. (2008). Pathogenesis of lymphangiomas. Virchows Archiv: An International Journal of Pathology, 453(1), 1–8. https://doi.org/10.1007/s00428-008-0611-z
2.    Ho M, Lee CC, Lin TY. Prenatal diagnosis of abdominal lymphangioma. Ultrasound Obstet Gynecol. 2002 Aug;20(2):205-6. doi: 10.1046/j.1469-0705.2002.00750_2.x. PMID: 12153677.
3.    Francavilla, M. L., White, C. L., Oliveri, B., Lee, E. Y., & Restrepo, R. (2017). Intraabdominal lymphatic malformations: Pearls and pitfalls of diagnosis and differential diagnoses in pediatric patients. AJR. American Journal of Roentgenology, 208(3), 637–649. https://doi.org/10.2214/AJR.16.17008
4.    Al-Salem AH. Lymphangiomas in infancy and childhood. Saudi Med J. 2004 Apr;25(4):466-9. PMID: 15083217.
5.    Ersoy, A. O., Oztas, E., Saridogan, E., Ozler, S., & Danisman, N. (2016). An unusual origin of fetal lymphangioma filling right axilla. Journal of Clinical and Diagnostic Research: JCDR, 10(3), QD09-11. https://doi.org/10.7860/JCDR/2016/18516.7513
6.    Li, J.-L., Hai-Ying, W., Liu, J.-R., He, Q.-M., Chen, K.-S., Yang, J., & Qian, F. (2018). Fetal Lymphangioma: Prenatal diagnosis on ultrasound, treatment, and prognosis. European Journal of Obstetrics, Gynecology, and Reproductive Biology, 231, 268–273. https://doi.org/10.1016/j.ejogrb.2018.10.018
7.    Inde, Y., Yamagishi, E., Kawabata, I., Sekiguchi, A., Nakai, A., & Takeshita, T. (2013). Morphological changes observed via fetal ultrasound in prenatally diagnosed and isolated congenital lymphangiomas: three case reports. Journal of Medical Ultrasonics (2001), 40(3), 265–269. https://doi.org/10.1007/s10396-012-0421-4
8.    Machado LE, Osborne NG, Bonilla-Musoles F. Three-dimensional sonographic diagnosis of a large cystic neck lymphangioma. J Ultrasound Med. 2004 Jun;23(6):877-81. doi: 10.7863/jum.2004.23.6.877. PMID: 15244316.
9.    Ono, K., Kikuchi, A., Miyashita, S., Iwasawa, Y., Miyachi, K., Sunagawa, S., Takagi, K., Nakamura, T., & Sago, H. (2007). Fetus with prenatally diagnosed posterior mediastinal lymphangioma: characteristic ultrasound and magnetic resonance imaging findings. Congenital Anomalies, 47(4), 158–160. https://doi.org/10.1111/j.1741-4520.2007.00164.x
10.    Suzuki, N., Tsuchida, Y., Takahashi, A., Kuroiwa, M., Ikeda, H., Mohara, J., Hatakeyama, S., & Koizumi, T. (1998). Prenatally diagnosed cystic lymphangioma in infants. Journal of Pediatric Surgery, 33(11), 1599–1604. https://doi.org/10.1016/s0022-3468(98)90589-9
11.    Arisoy, R., Erdogdu, E., Kumru, P., Demirci, O., Yuksel, M. A., Pekin, O., Tugrul, S., & Aydin, H. (2016). Prenatal diagnosis and outcome of lymphangiomas and its relationship with fetal chromosomal abnormalities. The Journal of Maternal-Fetal & Neonatal Medicine: The Official Journal of the European Association of Perinatal Medicine, the Federation of Asia and Oceania Perinatal Societies, the International Society of Perinatal Obstetricians, 29(3), 466–472. https://doi.org/10.3109/14767058.2015.1004536
12.    Goldstein, I., Leibovitz, Z., & Noi-Nizri, M. (2006). Prenatal diagnosis of fetal chest lymphangioma. Journal of Ultrasound in Medicine: Official Journal of the American Institute of Ultrasound in Medicine, 25(11), 1437–1440. https://doi.org/10.7863/jum.2006.25.11.1437
13.    Farnaghi, S., & Kothari, A. (2013). The value of early recognition of fetal lymphangioma. Australasian Journal of Ultrasound in Medicine, 16(3), 147–152. https://doi.org/10.1002/j.2205-0140.2013.tb00103.x
14.    García-Díaz, L., Chimenea, A., de Agustín, J. C., Pavón, A., & Antiñolo, G. (2020). Ex-Utero Intrapartum Treatment (EXIT): indications and outcome in fetal cervical and oropharyngeal masses. BMC Pregnancy and Childbirth, 20(1), 598. https://doi.org/10.1186/s12884-020-03304-0
15.    Cruz-Martinez, R., Moreno-Alvarez, O., Garcia, M., Méndez, A., Pineda, H., Cruz-Martinez, M. A., & Martinez-Morales, C. (2015). Fetal endoscopic tracheal intubation: A new fetoscopic procedure to ensure extrauterine tracheal permeability in a case with congenital cervical teratoma. Fetal Diagnosis and Therapy, 38(2), 154–158. https://doi.org/10.1159/000362387
16.    Sasaki, Y., & Chiba, Y. (2003). Successful intrauterine treatment of cystic hygroma colli using OK-432. A case report. Fetal Diagnosis and Therapy, 18(6), 391–396. https://doi.org/10.1159/000073129
17.    Amodeo, I., Colnaghi, M., Raffaeli, G., Cavallaro, G., Ciralli, F., Gangi, S., Leva, E., Pignataro, L., Borzani, I., Pugni, L., & Mosca, F. (2017). The use of sirolimus in the treatment of giant cystic lymphangioma: Four case reports and update of medical therapy. Medicine, 96(51), e8871. https://doi.org/10.1097/MD.0000000000008871
18.    Bawazir OA, Bawazir R, Bawazir A, Kausar N, Said H. Efficacy and Clinical Outcomes of Bleomycin in the Treatment of Lymphangiomas: A Multicenter Experience. Dermatol Surg. 2021 Jul 1;47(7):948-952. doi: 10.1097/DSS.0000000000002976. PMID: 33625132.
19.    Jiao-Ling L, Hai-Ying W, Wei Z, Jin-Rong L, Kun-Shan C, Qian F. Tratamiento y pronóstico del linfangioma fetal. Eur J Obstet Gynecol Reprod Biol. 2018 Dec;231:274-279. doi: 10.1016/j.ejogrb.2018.10.031. Epub 2018 15 de octubre. PMID: 30482553

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