Chest Mass in a Newborn Infant.

Abstract

A term, large-for-gestational age boy is transferred from an outside hospital with a right anterior chest wall mass noted since birth. His mother is a healthy 33-year-old gravida 4, para 4 woman with good prenatal care and normal prenatal laboratory values who had an uncomplicated pregnancy and elective cesarean delivery. None of the patient’s siblings or family members have had similar masses.On physical examination the patient is well-appearing and moving all 4 extremities spontaneously without obvious limitations. Vital signs on admission to the hospital are normal. There is a nontender, boggy, fluctuant, flesh-colored, grapelike mass from his right nipple to the midaxillary line that extends to the right upper arm, with dimpling of the skin throughout the right upper extremity (Fig 1). No bruit is heard over the lesion. There is no palpable bony abnormality. Radial pulses are 2+. Capillary refill is less than 2 seconds. His lungs are clear to auscultation. The cardiovascular examination reveals a normal heart rate, rhythm, S1, and S2 and no murmurs. The abdomen is soft, nontender, and nondistended, with no palpable masses or hepatosplenomegaly.Chest radiography is normal. Complete blood cell count with differential count is normal. Ultrasonography of the right superolateral chest shows a multiloculated fluid collection with undulating borders measuring 6 × 1.7 cm. Magnetic resonance imaging (MRI) with contrast of the chest and right upper extremity reveals a multiloculated macrocystic mass in the superficial right chest wall, additional cysts in the right arm, and a partially cystic right mediastinal mass (Figs 2 and 3). MRI also shows multiple cysts in both kidneys (Fig 4). Review of the findings from MRI and genetic testing reveal the diagnoses.The differential diagnosis includes lymphatic malformation, venous malformation, vascular tumor, arteriovenous malformation, arteriovenous fistula, and capillary malformation. The patient was diagnosed as having lymphatic malformation. In addition, rapid genome sequencing revealed de novo pathogenic variant of PKD1 mutation, supporting an incidental second diagnosis of autosomal dominant polycystic kidney disease (ADPKD).Lymphatic malformations are a type of vascular anomaly. The International Society for the Study of Vascular Anomalies stratifies vascular anomalies into vascular tumors (benign, locally aggressive or borderline, and malignant) and vascular malformations (simple, combined, anomalies of major named vessels, and vascular malformations associated with other anomalies). (1)(2) Lymphatic malformations are low-flow, nonmalignant vascular malformations of the lymphatic system with dilated lymphatic channels or cysts thought to occur during lymphatic development.Lymphatic malformations can affect 1 location or can be loculated and/or multifocal (eg, lymphangiomatosis). (3) Lymphatic malformation is an umbrella term that includes all subtypes of lymphatic malformations, including cystic lymphatic malformations (macrocystic, microcystic, or mixed), generalized lymphatic anomalies such as kaposiform lymphangiomatosis, channel-type lymphatic malformation, acquired progressive lymphatic anomaly (acquired progressive lymphangioma), and primary lymphedema. Lymphatic malformations can affect any area of the body but most commonly occur in the head and neck regions, followed by the extremities. (4) They are classified as macrocystic, microcystic, or mixed. Most are noted at birth or within the first 2 years after birth.Superficial lymphatic malformations or deep vascular lesions may have no skin discoloration. In contrast, superficial arterial, capillary, or venous vascular anomalies can appear red, pink, violaceous, or blue, depending on the mix of oxygenated (arterial) or deoxygenated (venous) blood. Superficial lymphatic malformations can have clear vesicles or pitting of the skin or appear bruised if bleeding occurs within the malformation. Venous malformations are often bluish, soft, and compressible papules. Capillary malformations are often pink, red, or purple flat macules or patches. High-flow malformations, such as arteriovenous malformations and arteriovenous fistulas, can have a palpable bruit or thrill. Vascular anomalies can cause overgrowth and swelling in the affected area, which could cause pain.Lymphatic malformations can be associated with other anomalies. Gorham-Stout syndrome, also known as vanishing bone disease, is a rare condition characterized by proliferation of lymphatic vessels adjacent to single or multiple bones, leading to osteolysis and resorption of bone, oftentimes the ribs, spine, pelvis, skull, clavicle, or jaw. (5) Several PIK3CA-related overgrowth spectrum conditions also have lymphatic malformations, such as Klippel-Trenaunay syndrome, a rare congenital syndrome characterized by cutaneous capillary malformations (port-wine stain), vascular or lymphatic malformations, and limb overgrowth. (1)(6) Many patients with lymphatic malformations have an activating somatic PIK3CA gene mutation. (7) This was not the case for our patient.Diagnosis of vascular malformation or neoplasm is often made clinically and confirmed by imaging. For initial imaging, the 2019 American College of Radiology Appropriateness Criteria for Clinically Suspected Vascular Malformation of the Extremities deems magnetic resonance angiography with and without contrast, MRI with and without contrast, computed tomographic (CT) angiography with contrast, and duplex Doppler ultrasonography as appropriate for suspected vascular malformation of the extremity presenting with physical deformity. (8) However, because our patient also had a suspected abnormality in the chest wall, MRI or magnetic resonance angiography with and without contrast would be the best initial study to better evaluate deeper lesions than ultrasonography and better evaluate soft tissue contrast than CT angiography.The presence of renal cysts initially raised concern for underlying lymphangiomatosis. Lymphangiomatosis is the term used to describe lymphatic malformations in multiple organs. (3) It can affect any region of the body, although it is most common in the neck, axilla, retroperitoneum, and mediastinum. Renal lymphangiomatosis in pediatric patients is rare but should be included in the differential diagnosis for conditions such as ADPKD, nephroblastomatosis, lymphoma, and hydronephrosis with perinephric urinoma. (9) Several case reports describe initial misdiagnosis of renal lymphangiomatosis as ADPKD. Imaging and genetic testing can help differentiate between renal lymphangiomatosis and ADPKD. In renal lymphangiomatosis, renal cysts are central in the renal sinus, whereas in ADPKD, renal cysts are peripheral and parenchymal, as was seen with this patient. (9) In addition, the patient’s rapid genome sequencing reveals de novo pathogenic variant of PKD1 mutation, which supports a diagnosis of ADPKD being a separate etiology for renal cysts from that underlying the lymphatic malformations in the chest and right upper extremity. Differentiation between renal lymphangiomatosis and ADPKD can affect the treatment regimen and prognosis. A case report describing an infant with biopsy-proven bilateral renal lymphangiomatosis with 1-year follow-up suggests a self-limiting course in some patients, although it can expand before regression. (10) Successful treatment for renal lymphangiomatosis with sclerotherapy has been described. (3)(9)A case report describing an adult with comorbid lymphangiomatosis and ADPKD hypothesized a link between ADPKD and lymphangiomas as cystic pathologies sharing common genetic and congenital processes; however, no genetic mechanism has been identified. (11)ADPKD is the most common hereditary kidney disease, with a prevalence of 1:1,000 to 1:2,500. Patients with ADPKD develop cysts in the kidney parenchyma, which often leads to end-stage kidney disease by age 50 to 60 years. Our patient’s incidental diagnosis of ADPKD is atypical for several reasons. There was no family history, he developed cysts in the neonatal period, and his presenting complaint was lymphatic malformations. Our patient had a de novo PKD1 mutation, the most common mutation seen in ADPKD. Patients with PKD1 mutations have a less favorable kidney prognosis than patients with PKD2 mutations, who have end-stage kidney disease in their 70s and 80s. The Predicting Renal Outcomes in Polycystic Kidney Disease score combines predictive genetic factors with clinical information to predict risk of progression to end-stage kidney disease for patients with ADPKD in patients older than 35 years. (12) ADPKD is typically diagnosed using renal ultrasonography in patients with an affected first-degree relative. Genetic analysis can be useful in very young patients without a family history of ADPKD, as in our patient, who was found to have a de novo PKD1 mutation.Symptoms from lymphatic malformations vary depending on location of involvement and extent of invasion. Management varies depending on location, size and symptoms (including compression or obstruction of adjacent structures), infection, and interference with quality of life, including cosmetic concerns. Generally, microcystic lymphatic malformations are more challenging to treat than are macrocystic lymphatic malformations because they are less accessible for aspiration or sclerosing. (1)Observation for potential spontaneous regression can be appropriate for small lymphatic malformations without compromise of other systems. (13) Compression dressing is a conservative, first-line option for symptomatic treatment of lymphatic malformations limited to the extremities to prevent pain or growth of the malformation. (4) Treatment options for large or symptomatic lymphatic malformations include sclerotherapy, endovenous laser ablation, radiofrequency ablation, and surgical resection. Drug therapy with sirolimus, sildenafil, or propranolol has been described in case reports. Antibiotics should be used to treat infected lymphatic malformations.Clinical trials in adults with ADPKD show that angiotensin-converting enzyme inhibitors and possibly vasopressin antagonists decrease renal cyst growth. (14) A randomized controlled trial with tolvaptan, a selective vasopressin antagonist, for pediatric ADPKD is underway for children aged 12 to 17 years; results are not yet available. (15) Schaefer et al suggest angiotensin-converting enzyme inhibitors and angiotensin receptor blockers for management of hypertension and proteinuria in the setting of pediatric ADPKD. (15) In addition, there is limited evidence that statin therapy slows the progression of structural kidney disease in children and young adults with ADPKD. (16)The patient was evaluated by a multidisciplinary team including surgery, hematology/oncology, nephrology, genetics, and interventional radiology; he was referred for sclerotherapy but was lost to follow-up.Five months later he presented with cough and was diagnosed as having a parainfluenza infection. Chest radiography revealed airway compromise; CT showed that the intrathoracic extent had dramatically increased, resulting in mediastinal shift and tracheal narrowing (Fig 5). Dark, sanguineous fluid was drained from the lesion, and sclerotherapy was performed using bleomycin. The postsclerotherapy radiograph showed mass reduction and improved lung expansion.Persistent hypertension was treated with enalapril. Repeated renal ultrasonography, compared with postnatal imaging, showed an enlarging right cyst and a new left cyst. Intrathoracic sclerotherapy was repeated 40 days later. Further treatment will be required.