Prenatal Diagnosis of a Solitary Pulmonary Cyst in a Male Fetus

Robles BN, Hammas M, Saavedra C, Russell K and Faustin D

Published on: 2020-04-20


Solitary pulmonary nodules, most often an incidental finding during antenatal imaging, can have a wide range of etiologies. Due to the complex anatomy and the lack of direct access to the in-utero fetus, these pulmonary lesions were often diagnosed postnatally. However, with recent advancements in ultrasound technology and easier access, researchers in maternal-fetal medicine have released valuable literature that can aid in the diagnosis of pulmonary lesions in- utero.


Congenital pulmonary airway malformations; Broncho pulmonary dysplasia; Broncho pulmonary sequestration; Homeo Box B5 (HOXB5); Glial cell-derived neuro trophic factor (GDNF); Poly hydramnios hydrops; Mass to thorax ratio (MTR); Lung to head ratio (LHR); Color Doppler; Ultrasonography; Maternal steroids; Lung hypoplasia; Ex Utero intrapartum therapy (EXIT); Thoracentesis; Cyst aspiration; Thoracoamniotic shunts


Solitary pulmonary nodules, most often an incidental finding during antenatal imaging, can have a wide range of etiologies. Due to the complex anatomy and the lack of direct access to the in-utero fetus, these pulmonary lesions were often diagnosed postnatally. However, with recent advancements in ultrasound technology and easier access, researchers in maternal-fetal medicine have released valuable literature that can aid in the diagnosis of pulmonary lesions in- utero. This segment of the case report aims to provide a brief background on the most common differentials that are in contention when diagnosing a pulmonary lesion in a fetus.

Broncho pulmonary dysplasia/cyst

There is much debate on the exact definition of broncho pulmonary dysplasia (BPD). This condition is much better characterized by its pathogenesis than physiological parameters. Though a disease of prematurity, it may been seen in term infants as well. BPD is characterized by a disruption in the late canalicular or saccular phases of lung development [1]. As a result of this, there may be alveolar hypoplasia and a reduction in surface area available for gas exchange, dys regulation of pulmonary vascular and angiogenesis leading to pulmonary hypertension, and increased elastic tissue formation leading to disarrayed architecture and formation of anomalies such as cysts [1]. Careful consideration must be given on the management of these pulmonary disruptions as steroid and mechanical ventilation can further complicate the dysplasia leading to fibrosis, muscle hypertrophy and interstitial edema [2]. Broncho pulmonary dysplasia is a diagnosis made postnatally based on the clinical presentation. Whilst most are asymptomatic, some infants can be tachypnic, with scattered rales and intermittent expiratory wheezing when there is significant airway narrowing secondary to scar formation, mucus retention, collapse or edema [2]. Chest radiographs may show clear lung fields with diffuse haziness and coarsening of the interstitium [2]. Hyperinflation, streaky densities and cystic areas may be apparent in more severe cases. In rare occasions such as the one presented in this case report, hypo-echoic cysts with no enhancement and/or solid components may be picked up by skilled ultrasonography. BPD in some cases may look virtually indistinguishable from a congenital pulmonary airway malformation in utero and can present with similar mass effects.

Congenital pulmonary airway malformation (CPAM)

Congenital pulmonary airway malformations (CPAM) have now become a broad area of discussion in maternal-fetal and neonatal medicine. From a pathological standpoint CPAMs are hamartomatous lesions, meaning they are disorganized growths of normal tracheal, bronchial, bronchiolar and alveolar tissue. They are thought to originate during the morphogenesis of the tracheobronchial tree. While the exact molecular mechanism remains unclear, there is a consensus of an imbalance between cell proliferation and apoptosis with indications of faulty homeobox B5 (HOXB5) regulation [3]. A study in 1998 by Cass et al. found CPAMs resected from fetuses and newborns had a two-fold increase in cell proliferation and a five-fold increase in apoptotic bodies relative to normal neonatal and fetal lung tissue. More recent studies have documented the role of glial cell-derived neuro trophic factor (GDNF), a growth factor that mediates the interaction between epithelial and mesenchymal tissue in utero and persists into infancy [4]. This growth factor was documented to be reduced in CPAMs leading to decreased vascularity [4]. In evaluating a CPAM prenatally, ultrasonography remains the gold standard. Macro- and micro cysts surrounded by hyper-echogenic lung parenchyma is a finding initially picked up as early as 4 weeks of gestation. CPAMs demonstrate rapid growth between weeks 20-26 of gestation. Mass effect of these lesions can be seen in follow up imaging as: mediastinal shifts leading to compression of the vena cava and heart ultimately leading to hydrops fetalis. Additionally, the mass effect can compress the esophagus leading to polyhy dramnios as well as other esophageal complications such as fistulas and atresia.

Broncho pulmonary sequestration

Broncho pulmonary sequestrations (BPS) are congenital anomalies that consist of nonfunctioning lung mass/tissue that lack communication with the tracheobronchial tree and carry their own systemic blood supply [5]. It is further classified into intra lobar pulmonary sequestration and extra lobar pulmonary sequestrations (EBPS). Intra lobar pulmonary sequestrations are located within the normal lung and covered by the lung’s visceral pleura which accounts for 75% of BPS. Extra lobar pulmonary sequestrations are outside the normal lung and are covered with their own visceral pleura [5]. Extra lobar pulmonary sequestrations are often found in association with the diaphragm and has the propensity to extend into the abdomen in utero. Additionally, EBPS have been documented to be present with other foregut anomalies such as esophageal fistulas and atresia [5]. Furthermore, broncho pulmonary sequestrations can be solitary or they may occur as hybrid lesions with CPAMs, the latter differentiated due to the lack of its own systemic blood supply. BPS are often diagnosed prenatally via ultrasound displaying solid, triangular echogenic masses. Color doppler will show a characteristic and distinct systemic vascular supply that typically arises from the thoracic or abdominal aorta. The diagnostic workup and complications of BPS are similar to a CPAM and have been discussed above.

Other differentials

Several other differentials must be included when attempting to diagnose pulmonary lesions in a fetus. Pleural cysts are radio-opaque developmental anomalies composed of a collection of serous fluid encased by a thin fibrous membrane. These benign cysts often involve the parietal pleura and are commonly found on the diaphragmatic surface [6]. Although not many cases of congenital pleural cysts have been described in the literature, they should nonetheless be included within the differentials. Congenital neuro blastoma is the second most common type of tumor found during the neonatal period, accounting for nearly 20% of all congenital tumors. They are poorly differentiated embryonal nerve cell tumors which are commonly found within the adrenal glands. In some instances, however, these tumors can be found within the posterior mediastinum if they arise from the sympathetic chain. When suspected, ultrasonography is a valuable tool to determine the size and location of these hyper echogenic nodules. Complementary fetal MRI can subsequently be used for staging and evaluating metastasis if neuro blastoma is highly suspected [7]. Lastly, anatomical defects such as diaphragmatic hernias must also be excluded. Diaphragmatic hernias are congenital defects in the diaphragm which allow the herniation of visceral organs into the thoracic cavity. The defect results in pulmonary hypoplasia and pulmonary hypertension- conditions which contribute to increased morbidity and mortality of these patients [8]. Antenatal ultrasonography can be used to detect these anomalies which usually presents as a mediastinal mass with varying echogenicity in addition to mediastinal shifting. In most cases, diaphragmatic hernias occur on the left side, in which case the herniated fluid-filled stomach often appears cystic in nature during ultra sonography [9].

Case Report

This is a case report of a 34-year-old G3P1011, with a history of one normal spontaneous vaginal delivery, and one prior spontaneous abortion who was seen in our women’s health clinic due to delayed menses. Pregnancy was confirmed by urine test. A pap smear was performed and found to be negative for intraepithelial lesions or malignancy but positive for candida. She had no other complaints and expressed the desire to continue with the pregnancy. It was noted that her last menstrual period was April 19th, 2019 and she reported regular menses. Miscarriage precautions were discussed with the patient and she was given prenatal vitamins as well as clotrimazole cream. Follow-up was scheduled for three weeks. Upon return to the clinic, prenatal labs were drawn and were found to be unremarkable. On hemoglobin electrophoresis, she was noted to be a sickle cell disease carrier, the father of the baby was offered testing but refused. Dating ultrasound results were reviewed which confirmed a single intrauterine pregnancy with the fetal crown-rump length consistent with 6 weeks and 1 day which gave her a due date of 01/31/2020. The fetal heart rate was 116 beats per minute, her cervical length was within normal limits and she was told to follow up in two weeks. The patient had an early one hour glucose challenge test which resulted at 223. Her hemoglobin A1C was found to be 6.2. At 11 weeks gestational age, she was referred to a diabetes educator due to pregestational diabetes. She was given diet recommendations and started an insulin regimen prescribed by her physician. At her 19-week visit, her insulin dose was adjusted to 18U of NPH in the morning and 20U of NPH in the evening. During the level II sonogram, a left cystic structure measuring 1.5-2.0cm posterior to the descending aorta was noted. A sagittal view showed the cyst to be elongated with an encroachment at the level of the diaphragm. A small portion of the gastric bubble was able to be seen in the left upper abdomen adjacent to the cystic structure. Differential diagnoses included: congenital pulmonary airway malformation (CPAM), solitary cyst of the left posterior lobe, diaphragmatic hernia from partial herniation of the stomach, and aneuploid. At 20 weeks gestational age, a repeat FISH as well as repeat sonographic evaluation was performed. The FISH revealed a normal male fetus and the repeat sonogram confirmed the presence of a left posterior lobe cystic mass measuring 1.2cm x 0.6cm x 0.56cm, located above an apparently intact diaphragm (Figure 1).

Figure 1: Prenatal Ultrasound. Gestational Age: 20 weeks 0 days cyst Measurement: 0.99cm x 0.63cm transverse view.

For the remainder of the second trimester, she was seen in the antepartum testing unit every four weeks for ultrasonography. The left pulmonary cyst remained stable in size at approximately 1.7cm x 1.1cm x 0.77cm (Figures 2-3).

Figure 2: Prenatal Ultrasound.Gestational Age: 22 weeks 0 days Cyst Measurement: 1.8cm x1.0cm x 0.79cm Longitudinal view (left) Transverse view (right).

Figure 3: Prenatal Ultrasound.Gestational Age: 26 weeks 0 days Cyst Measurement: 1.6cm x 1.2cm x 0.75cm Longitudinal view (left) Transverse view (right).

Her blood glucose was noted to be elevated during the fasting and dinner time hours, so the insulin regimen was adjusted to 20U of NPH in the morning, 10U Regular insulin before dinner, and 25U of NPH in the evening. Throughout the third trimester, the patient continued to visit the antepartum testing unit for ultrasonography every 2-4 weeks. The left pulmonary cyst was noted to increase in size at the last visit at 38 weeks’ gestation to 2.3cm x 1.2cm x 1.0cm. The fetus was noted to be in the breech position and thus underwent a successful external cephalic version. The patient’s blood glucose was adequate with the new insulin regimen. The patient arrived to the labor and delivery unit at our institution at 39 weeks and 0 days for an induction of labor. Her cervical exam was 1cm dilated, 50% effaced, posterior, -3 station, medium consistency which gave a bishop score of 3. She was successfully induced with pitocin and had a normal spontaneous vaginal delivery of a liveborn infant with the pediatrics team at bedside. APGARS were 9 and 9 at 1 and 5 minutes, respectively. The physical exam performed by the pediatricians was unremarkable. Breath sounds were equal bilaterally. The neonate was admitted to the NICU for workup of the pulmonary cyst. Chest x-ray was performed which showed an indistinct, left retrocardiac opacity. CT of the chest without contrast was recommended and performed, which showed a 1.6cm x 1.2cm x 2.4cm, well-circumscribed, ovoid hypodense/cystic structure either in the left lower lobe posteromedially or left posterior mediastinum that may be a pulmonary cyst or neurenteric cyst (Figure 4).

Figure 4: Day of life 1 CT scan of the chest with contrast. Cyst Measurement: 1.6cm x 1.2cm x 2.4cm Coronal view.

No pleural effusion or pneumothorax was visualized. MRI of the chest was then performed without contrast, which revealed a 2.4cm pulmonary cyst in the left lower lobe posteromedially. Differential diagnoses that were considered were: neuroenteric duplication cyst and bronchogenic duplication cyst. However, based on the imaging, due to the small cleavage plane between the cyst and posterior mediastinum, a pulmonary cyst was favored. No solid components were seen to suggest congenital pulmonary airway malformation and there was no visible artery from the aorta to suggest pulmonary sequestration. Lastly, a CT angiogram of the chest was performed which showed a left paraspinal/posterior mediastinal cystic lesion without enhancement, vascular inflow or outflow, or spinal abnormality; consistent with benign pulmonary or pleural cyst. The lesion measured 2.7cm in length equating to 3-4 vertebral bodies, 1.5cm anterior-posterior and 1.3cm transverse; pulmonary parenchyma was otherwise normal. The neonate had an echocardiogram which showed good biventricular function with no evidence of pericardial effusion. The patient had an otherwise unremarkable course in the NICU, did not require any supplemental oxygen and was discharged home on day of life 3. The neonate is followed by pediatric surgery and is scheduled to have cyst removal between 3-4 months of life. The neonate has been followed in high-risk pediatric clinic and is growing well without complications. Oxygen saturation and respiratory rates have been within normal limits at all follow-up appointments. Physical exams at those times have been unremarkable.


Prenatal ultrasounds play a crucial role in the detection of congenital fetal malformations. In some occasions, such as the one described in this case report, hypo-echoic cysts with no enhancement or solid components can be incidentally picked up by skilled ultrasonography. Broncho pulmonary cysts, congenital pulmonary airway malformations (CPAM), pulmonary sequestration as well pleural cysts, neuro blastomas and diaphragmatic hernias can all be identified using the help of this imaging modality. The case discussed above was that of a broncho pulmonary cyst, which in many instances can look indistinguishable from congenital pulmonary airway malformations in utero and can present with similar mass effects. Nonetheless, the management of these broncho pulmonary malformations consist in non-invasive interventions to restore fetal hemodynamics, improve lung maturity and prevent lung hypoplasia. Numerous studies have demonstrated the benefit of maternal steroid administration for these broncho pulmonary malformations [10-12]. These studies have also highlighted the propensity of many broncho pulmonary malformations to spontaneously regress without intervention. Invasive interventions for in utero broncho pulmonary malformations are all currently considered investigational and are limited to case reports and small observational studies. Invasive procedures include thoracentesis, cyst aspiration, and thoracoamniotic shunts. Surgical resection and laser ablation have also been attempted with a higher incidence of intraoperative and post-surgical fetal demise [13]. Surgical procedures also put the pregnancy and subsequent pregnancies at risk for prematurity, premature rupture of membranes and uterine dehiscence or rupture [13]. Lastly, this pregnancy was complicated by gestational diabetes treated with insulin [14,15]. Future investigations of broncho pulmonary malformations should focus on determining if uncontrolled diabetes has an effect on surfactant development leading to broncho pulmonary malformationsy.


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