Fetal Lymphangioma: Etiology and Pathogenesis
Fetal lymphangiomas (also called cystic hygromas) are congenital structural malformations caused by failure of the embryonic lymphatic system to properly connect with the venous drainage system, not proliferative tumors. 1, 2
Primary Embryologic Defect
The fundamental cause is a ductal plate malformation during fetal development where lymphatic channels fail to establish proper connections with the venous system, particularly in the neck region. 2 This represents a form of lymphatic dysplasia characterized by abnormal ductal plate maturation, resulting in disconnected lymphatic channels that progress into cystic structures filled with lymphatic fluid. 2, 3
Chromosomal and Genetic Causes
Turner syndrome (45,X) is the most common chromosomal cause, accounting for 50-80% of prenatally detected fetal cystic hygromas. 1, 2, 3 The chromosomal abnormality directly predisposes to lymphatic dysplasia and impaired venous return. 2
Additional chromosomal abnormalities associated with fetal lymphangiomas include: 1, 2
- Trisomy 21 (Down syndrome) - the second most common aneuploidy
- Trisomy 13 and trisomy 18
- Triploidy
In one prenatal series, 73% of fetuses with cystic hygromas had Turner syndrome karyotypes, and chromosomal abnormalities were present in the vast majority of cases. 3
Critical Clinical Distinction
Lymphatic malformations are structural anomalies and inborn errors of vascular morphogenesis—NOT vascular neoplasms. 1, 2 The historical terms "lymphangioma" and "cystic hygroma" are misleading because they incorrectly imply proliferative potential when these are actually static congenital malformations. 1, 2 This is a critical distinction because unlike infantile hemangiomas (which are true vascular tumors), lymphatic malformations do not involute spontaneously and do not respond to propranolol or other medical therapies used for vascular tumors. 4
Pathophysiologic Consequences
When lymphatic dysplasia is severe, the impaired venous return can lead to nonimmune hydrops fetalis (NIHF), which accounts for 5-6% of all NIHF cases. 1, 2 The accumulation of lymphatic fluid in tissue spaces and body cavities results from the fundamental failure of lymphatic drainage. 2 In prenatal series, the majority of fetuses with cystic hygromas were hydropic at diagnosis, and the prognosis was uniformly poor with high rates of fetal death. 3
Anatomic Distribution
The neck region is affected in 75% of cases, followed by the axilla (20%), retroperitoneum and intra-abdominal organs (2%), limbs and bones (2%), and mediastinum (1%). 5 Chest wall and other unusual locations are extremely rare. 6, 7, 8
Common Diagnostic Pitfall
Do not confuse deep lymphatic malformations with deep infantile hemangiomas or venous malformations—these are entirely different entities with different natural histories and treatment approaches. 1 Lymphatic malformations may be mistaken for infantile hemangiomas when there is bleeding into vesicles at the skin surface, but they lack the proliferative markers (such as GLUT1 expression) that characterize true hemangiomas. 1