Pulmonary lymphangiomatosis as a cause of first trimester nuchal cysts in a euploid fetus

Introduction

In 1990 in the Lancet, Szabó and Gellén [7] described the accumulation of nuchal subcutaneous fluid in the first trimester of pregnancy in fetuses with trisomy 21. Fluid accumulation is related to either heart defects or malfunctioning of the lymphatic system [5]. Since Szabó and Gellén [7] report, an exhaustive list of syndromes and diseases associated with increased nuchal translucency (NT) or nuchal lateral cysts has been published by Nicolaides and Falcon [4] among others.

We report on a case of isolated pulmonary lymphangiomatosis in a fetus that was noted to have bilateral anterolateral neck cysts around 6.5 mm in size in the first trimester ultrasound scan. The fluid accumulation resolved spontaneously, and pregnancy was uneventful until hydrothorax developed at week 29.

Increased NT or nuchal bilateral cysts in euploid fetuses are an indication for a detailed anatomical survey and for karyotyping [4]. It has been demonstrated that the majority of fetuses that show no anomalies by ultrasound at 20 weeks of gestation and had a NT above the 99th percentile in the first trimester are healthy when followed until early childhood [6].

To the best of our knowledge, there have been no published reports of pulmonary lymphangiomatosis associated with perinuchal cysts in euploid fetuses.

The article is in compliance with the World Medical Association Declaration of Helsinki regarding ethical conduct of research involving human subjects.

Case report

The patient is a Caucasian 38-year-old primigravida with a non-contributing family history and no consanguinity. Due to primary sterility, pregnancy was achieved after in vitro fertilization. The patient presented for the first trimester Down’s syndrome screening where laterocervical non-septated fluid accumulation measured 6.5 mm (Figure 1). Amniocentesis revealed normal karyotype 46XX, and maternal serology result for parvovirus, syphilis, toxoplasmosis, rubella, cytomegalovirus infection and herpes simplex (TORCH) was negative. Thorough anatomical examination by ultrasound scan on the 20th week of gestation showed no anomalies. The parents decided against termination. Pregnancy was uneventful until week 29 when a bidimensional ultrasound scan showed right hydrothorax (Figure 2). Massive bilateral hydrothorax developed within a week, and intrauterine treatment was deemed necessary due to prematurity.

Figure 1

First trimester ultrasound scan showing nuchal translucency. (A) Oblique view of the fetus at 13 weeks. Note the left lateral nuchal cyst. (B) Posteroanterior view of the fetus at 13 weeks. Note the bilateral nuchal cysts.

Figure 2

Third trimester ultrasound scan showing the evolution of the fetal hydrothorax. (A) Twenty-nine weeks of pregnancy. Sagittal view of the thorax. Note the hydrothorax. (B) Twenty-nine weeks of pregnancy. Transverse view of the thorax. Note the right hydrothorax. (C) Thirty weeks of pregnancy. Transverse view of the thorax. Note the bilateral hydrothorax.

Drainage of the fetal hydrothorax was decided and a shunt was successfully placed, but fluid accumulation recurred within 24h (Figure 3). Biochemical analysis of the fluid ruled out chylothorax (1000 red blood cells/mm³, 350 polymorphonuclear leukocytes /mm³, segmented neutrophils 2%, lymphocytes 98%, glucose 71 mg/dL, protein 2.8 g/dL, lactate dehydrogenase 192 U/L, cholesterol 53 mg/dL, triglycerides 10 mg/dL, albumin 2.24 g/dL and lipase 4.9 U/L).

Figure 3

Third trimester ultrasound scan showing recurrent fetal hydrothorax after pleuro-amniotic shunting. Posteroanterior view of the fetus at 32 weeks. Note the bilateral massive hydrothorax and collapsed lungs.

Despite the drainage, hydrothorax persisted and cesarean section was performed at 32 weeks of gestation after fetal lung maturation. The baby weighed 1900 g and died in the early perinatal period due to severe hydrops. Pleural fluid drainage was started immediately after the cesarean section and 80 mL of fluid was removed from the left side and 30 mL from the right hemithorax. The newborn survived for 36 h in the neonatal intensive care unit where a tube thoracostomy was placed in each hemithorax and high frequency ventilation initiated.

At necropsy, lymphatic thoracic vessels had no anatomical anomalies. Histological study of the lung showed dilated lymphatic vessels in the pleura, interlobular septa and peribronchiolar areas. The cells lining the lymphatic vessels were spindle-shaped and had no atypias. Microscopically, the abnormal vascular lymphatic proliferation seen in lung biopsy specimens was present in all sections of both lungs. These thin-walled, endothelium-lined channels with empty lumina were most prominent in the subpleural regions and pulmonary septa, and particularly in the hila. These changes are consistent with pulmonary lymphangiomatosis (Figure 4A and B). Cardiac autopsy findings were negative.

Figure 4

View of the lungs at fetal necropsy. (A) Macroscopic picture of the fetal lungs. The arrow points to a dilated lymphatic duct. (B) Microscopic picture of the fetal lungs. The arrows point to the abnormal vascular lymphatic proliferation.

Discussion

To the best of our knowledge, this is the first report of a case of pulmonary lymphangiomatosis in a euploid fetus with nuchal fluid accumulation in the first trimester. Nuchal thickening consisted of a bilateral laterocervical non-septated collection of fluid.

The etiology of the nuchal cysts is heterogeneous. Elejalde et al. [1] in 1982 classified fetuses showing nuchal cysts and determined that only 16% of them had monosomy X and the rest were possibly due to recessive, sporadic or congenital syndromes. More recent research has demonstrated that nuchal fluid accumulation can be caused by congenital heart defects or it can appear as part of an abnormality of the lymphatic system [4], which was the case in this fetus.

In 1998, Fryns and Moerman [2] described a Down’s syndrome-affected male fetus with nuchal and thoracic lymphangiomatosis among other malformations in a second trimester ultrasound scan. Walker and Landas [8] published the case of a stillborn female fetus with a nuchal cystic hygroma associated with massive lymphangiomatosis of the upper extremity as well as of the myocardium.

Treatment of fetal hydrothorax has been described elsewhere and clinical guidelines published [3]. Experts agree that treatment outcomes are related to the etiology of the fluid accumulation and that indications and timing for the procedure must be individualized taking gestational age and other factors into account.

Pulmonary lymphangiomatosis in the first trimester probably impaired drainage of the fetal neck transiently causing the fluid accumulation seen in the ultrasound image. The cysts resolved spontaneously and obstruction reappeared in the second trimester. Parental counseling in a case of a euploid fetus with NT above the 99th percentile that does not progress to hydrops is made once the result of the ultrasound scan on the 20th week of gestation is normal. In all cases, follow-up should include high-resolution frequent ultrasound scans as structural abnormalities may become apparent later in gestation. Future studies should aim to investigate whether laterocervical cysts correlate with different fetal anomalies than posterior nuchal translucency.