Pulmonary Cystic Lymphangiectasis
Alternative titles; symbols
Frank and Piper (1959) described 2 affected infants who were not related. One was stillborn and the other lived only about 2 hours. In 1 case there were similar lesions in the heart, pancreas, kidneys, and mesentery. Scott-Emuakpor et al. (1981) described the disorder in 2 sisters who showed acute respiratory distress soon after birth and died in the neonatal period. Changes at autopsy were limited to the lungs.
Moerman et al. (1993) reported on 7 perinatal autopsy cases of primary congenital pulmonary lymphangiectasis (CPL) with bilateral chylothorax. They demonstrated that primary CPL is often complicated by chylous pleural effusions with ensuing pulmonary hypoplasia. Conversely, CPL appears to be a constant pathologic finding in spontaneous congenital chylothorax. These observations indicated a common pathogenesis for the 2 disorders. The basic defect is not an intrinsic lung abnormality, but a developmental error of the lymphatic system resulting in a pulmonary lymphatic obstruction sequence.
Moerman et al. (1993) concluded that the cause of CPL is heterogeneous. Most cases are apparently sporadic occurrences. They reported the second instance of CPL in sibs. Thus, some cases are genetically determined with autosomal recessive inheritance. CPL may also be part of a multiple congenital anomalies (MCA) syndrome, such as Noonan syndrome (163950), Turner syndrome, and Down syndrome.
1. Frank, J.; Piper, P. G. :
Congenital pulmonary cystic lymphangiectasis. J.A.M.A. 171: 1094-1098, 1959.PubMed ID : 13824507
2. Moerman, P.; Vandenberghe, K.; Devlieger, H.; Van Hole, C.; Fryns, J.-P.; Lauweryns, J. M. :
Congenital pulmonary lymphangiectasis with chylothorax: a heterogeneous lymphatic vessel abnormality. Am. J. Med. Genet. 47: 54-58, 1993.PubMed ID : 8368253
3. Njolstad, P. R.; Reigstad, H.; Westby, J.; Espeland, A. :
Familial non-immune hydrops fetalis and congenital pulmonary lymphangiectasia. Europ. J. Pediat. 157: 498-501, 1998.PubMed ID : 9667408
4. Scott-Emuakpor, A. B.; Warren, S. T.; Kapur, S.; Quiachon, E. B.; Higgins, J. V. :
Familial occurrence of congenital pulmonary lymphangiectasis: genetic implications. Am. J. Dis. Child. 135: 532-534, 1981.PubMed ID : 7234788
Victor A. McKusick - updated : 2/20/1999Victor A. McKusick - updated : 8/21/1998
Victor A. McKusick : 6/4/1986
carol : 2/23/1999terry : 2/20/1999terry : 8/21/1998mimadm : 3/12/1994supermim : 3/17/1992supermim : 3/20/1990ddp : 10/27/1989marie : 3/25/1988reenie : 6/4/1986
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Pulmonary cystic lymphangiectasis
abnormal pleura/hydrothorax (Very frequent sign) autosomal recessive inheritance (Very frequent sign) respiratory distress (Very frequent sign) stillbirth/neonatal death (Very frequent sign) liver enlargement (excl. storage dis.) (Occasional sign) lymphoedema/oedema (Occasional sign) splenomegaly (Occasional sign)
Any outpatient pneumology clinic
Congenital pulmonary lymphangiectasis.
Report of four cases (author's transl)
Fidalgo I, Ortega F, Alustiza J, Pastor E, Cabrera A.
Four cases of congenital pulmonary lymphangiectasis were observed during a five year period. This represents an incidence of 1.11 per 10,000 cases among alive newborns and of 53 per 10,000 cases among pediatric necropsias performed during the same period. One case was observed in the clinical context of a generalized hemangiolymphangiomatosis, another was associated to tetralogy of Fallot and the remaining two cases were associated to obstruction of pulmonary venous return. Although one of the pathogenic theories generally accepted in the formation of pulmonary lymphangiectasis points to the presence of either hypertension or obstruction of pulmonary venous drainage, it is possible that such situation is only circumstantial. Among 40 personal cases of obstruction of pulmonary venous return proved anatomically, only in the two cases presented were pulmonary lymphangiectasis demonstrated.
The presence of dysplastic elements in pulmonary tissue in cases of lymphangiectasis suggests that a more possible mechanism is a primary defect in the development of pulmonary lymphatics.
Congenital pulmonary lymphangiectasis
Wockel W, Dietrich M.3 cases of congenital pulmonary lymphangiectasis are described. A girl, now 3 years old, underwent at the age of 4 weeks a resection of the left superior lobe of the lung which was singularly involved. A male newborn died 4 h after birth and showed the typical affection of both lungs. A second male infant died 19 d after birth and had an isolated involvement of the left lung. Post-mortem examination additionally revealed in both boys a cardiovascular malformation. Histologically, we especially observed a papillar endothelial hyperplasia in a dilated lymph vessel in case 1 and multinuclear giant cells of the foreign-body type in case 3. In the literature, there are reported 99 cases of congenital pulmonary lymphangiectasis. Including our case, a unilobar or unilateral involvement is described in only 8 cases.
The congenital pulmonary lymphangiectasis occurs more often in males than in females (1.8 : 1). 90 out of 93 life-born children suffering from this malformation died, 57 of them during the perinatal period. However, cardiovascular malformations, which were observed in 53 cases, are playing an important role as the cause of death. The aetiology of the congenital pulmonary lymphangiectasis remains unknown. There are 4 different theories concerning the pathogenesis, namely, a persistence of early-fetal lymphatic vessels, a missing connection between primitive lymphatic vessels, a hyperplasia of lymphatic ducts and, last but not least, a passive dilatation of the lymph vessels because of venous or lymphatic congestion.
Unusual diffuse pulmonary lymphatic proliferation in a young boy
Several rare disorders may affect the pulmonary lymphatic vessels of children,including lymphangioma, lymphatic dysplasia, and congenital pulmonary lymphangiectasis. An additional disorder of pulmonary lymphatics, lymphangiomyomatosis, has been reported only in women of childbearing age. We report the case of a 4-year-old boy who died of a pulmonary lymphatic disorder, the clinical and pathologic characteristics of which seem to share features with several of these disorders.
A 3-year-old boy with an uncomplicated perinatal course was reported by his mother to have had a "rattle in the chest" since birth. Pneumonia was diagnosed at age 8 months and treated with antibiotics given orally. At age 18 months, frequent coughing and wheezing episodes developed and asthma was diagnosed. He was treated with bronchodilators and occasionally with prednisone, which produced significant improvement. A second case of penumonia was diagnosed at age 36 months and again treated with antibiotics given orally. Three months later, the patient had increasing cough, and a chest roentgenogram revealed an enlarged cardiac shadow, bilateral pleural effusions, and interstitial densities (Fig 1). An echocardiogram demonstrated pericardial effusion but normal cardiac anatomy.
He underwent pericardiocentesis; however, the pericardial effusion reaccumulated and thoracotomy was performed. A large mediastinal mass was identified and resected and pericardiectomy was performed. The tissue from the pericardium and mediastinum aggregated to 6.5x5.5x1.3 cm. This tissue was characterizied histologically by adipose and fibrous tissue of varying density, containing multiple poorly delimited spindle cell aggregates arranged asymmetrically around ectatic lymphatic channels and blood vessels. The nuclei were cytologically bland, and mitoses were rare. Occasional lymphoid follicles and a moderate number of hemosiderin-laden macrophages were scattered throughout the tissues. A biopsy specimen from the pulmonary trunk demonstrated an identical lesion of spindle cells and ectatic lymphatic channels. A normal 6-g thymus was removed.
Postoperatively, he continued to have bilateral pleural effusions and pulmonary infiltrates, and a second thoractomy was performed for lung biopsy and pleurodesis. Histologic study of the lung biopsy specimen demonstrated poorly demarcated spindle cell aggregates subpleurally, along interlobular septa, focally within alveolar walls, adjacent to pulmonary blood vessels, and adjacent to bronchioles distally to the level of respiratory bronchioles. The lesions were associated with ectatic lymphatic channels at all sites. A small amount of hemosiderin deposition was present in the pulmonary interstitium and in intra-alveolar histiocytes, although the interventing pulmonary parenchyma was normal (Fig 2). He was treated with a low-fat diet and diuretics with a subsequent decrease in pleural effusion but persistence of pulmonary infiltrates. He continued to have significant respiratory distress and wheezing. His airway obstruction was partially reversible, and he was treated with bronchodilators and diuretics.
At age 3 years 5 months, hemoptysis developed. Treatment with prednisone decreased the frequency and severity of the hemoptysis. Several attempts to taper the prednisone dose resulted in increased hemoptysis. At age 4 years 6 months, he continued to have daily hemoptysis and required daily prednisone. Therefore, he was treated with interferon alfa in an attempt to control the lymphatic proliferation in the lungs. He subsequently had a marked decrease in hemoptysis. However, this treatment was discontinued after 3 1/2 weeks because his platelet count had decreased to 53x[10.sup.9]/L. One month later, his platelet count had recovered to 94x[10.sup.9]/L.
At age 4 years 9 months, massive hemoptysis developed that was uncontrollable and he died. At autopsy, blood was found in the nasopharynx, trachea, and bronchi from terminal pulmonary hemorrhage. The pleural sacs and mediastinum were extensively encased by dense fibrious adhesions. Histologically, poorly demarcated spindle cell aggregates were arranged asymmetrically around ectatic lymphatic spaces in the lung adjacent to bronchioles and blood vessels, within interlobular septa, covered the surface of the lungs, permeated the mediastinum, and were confined to the thoracic cavity (Fig 3).
The spindle cells resembled vascular smooth muscle, exhibiting elongated, blunt-ended nuclei and a pattern of staining with Masson's trichrome stain consistent with smooth muscle. Immunohistochemical studies with anti-desmin and anti-actin on formadehyde solution-fixed, paraffin-embedded tissue obtained at autopsy were noncontributory, however, because both appropirate internal controls and the spindle cells failed to stain. The thoracic duct could not be identified. Thus, the pulmonary distribution and histologic features had remained unchanged, although the lesions had increased in size since the pericardiectomy and lung biopsy. The amount of hemosiderin deposited in the pulmonary intersititium and number of intra-alveolar histiocytes had increased, and acute intrapulmonary hemorrhage was also present. The heart and all extrathoracic viscera were grossly and histologically normal.
This case emphasizes the complex nature of disorders of lymphatics that may manifest as lymphangiomas (tumors of lymphatic vessels), lymphangiectasis (dilation of lymphatic vessels), or lymphangiomyomatosis (proliferation of lymphatic smooth muscle). When these manifestations occur together, the distinction between them is often arbitrary. Distinction between lymphangioma and hemangioma may also be difficult. Lymphatic disorders may occur secondary to congenital maldevelopment of, or an acquired blockage in, the lymphatic system.
These conditions often lead to abnormal collections of chyle outside the lymphatic system, such as chylothorax.
Review of the literature [1-12] reveals several categories of rare lymphatic disorders that can affect the lungs and that can present in childhood. The first category is lymphangioma. This tumor may occur in the neck (cystic hygroma), axilla, subcutaneous tissue, liver, spleen, bone, lung, pleura, or mediastinum. These lesions may be isolated or may occur in association with other lymphatic dysplasia and freqeuntly result in the leakage of chyle. A recent review  of intrathoracic lymphangiomas did not describe pulmonary parenchymal involvement. However, there are rare reports [2-4] of pulmonary lymphangiomas confined to one or two lobes. When multiple lymphangiomas are present, the condition is termed lymphangiomatosis. Such multiple lesions almost always involve bone in which they may cause pathologic fractures or "disappearing bones." Lymphangiomatosis often causes chylothorax, frequently from a mediastinal lymphangioma, but to our knowledge, pulmonary parenchymal involvement has been described in only one such case. 
The second category of lymphatic disorders is lymphatic dysplasia. Dysplastic or ectatic lymphatics may cause leakage of chyle where these lesions occur. Lymphedema describes a swollen extremity or body region secondary to such a lymph accumulation. A congenital form occurs in patients younger than 3 months of age; if familial, it is called Milroy's disease.
Lymphedema praecox presents in patients older than 3 months of age; if familia, it is called Meige's disease. Intestinal lymphangiectasis describes dilation of intestinal lymphatics with leakage of chyle into the bowel lumen. Chyloperitoneum, chylothorax, and chylopericardium represent leakage of lymphatics in those cavities. In generalized lymphatic dysplasia or lymphangiectasis, the process occurs in several sites and may cause chyle accumulations in multiple locations. Generalized lymphatic dysplasia can involve the lung. [6-8] Lymphangiectasis may also be secondary to operation, trauma, infection, or neoplasm.
The third category is congenital pulmonary lymphangiectasis. This condition is most commonly associated with cardiac anomalies that cause pulmonary venous obstruction and dilated lung lymphatics. It also may occur as an isolated lesion. With or without cardiac anomalies, the disorder usually presents with severe respiratory distress at the time of birth. Congenital pulmonary lymphangiectasis is usually fatal in the newborn period whether or not it is secondary to heart lesions; however, prolonged survival has been reported. [9-11]