Lymphangiomatosis: a case report.

Abstract: Lymphangiomatosis is a rare congenital malformation that can involve visceral organs, soft tissue, and bone. This report describes a 5-year-old female with this disorder who presented with respiratory distress and subsequently died. Clinical, diagnostic, and treatment aspects of this entity are discussed.

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Lymphangiomatosis is a condition of lymphatic tissue maldevelopment with diffuse involvement of soft tissues, lungs, abdominal organs, and bones. The clinical presentation is varied and can be confusing, with diagnosis made at autopsy. We report a case of this rare disease, emphasizing its clinical presentation, diagnosis, radiographic findings, and potential treatment options.

Case Report

A 5-year-old female presented with an 8-month history of shortness of breath, occasional wheezing, poor appetite, and weight loss. The dypsnea and wheezing were worse with mild physical exertion and on warm and humid days. Before her symptoms began, she had no history of trauma, illness, or surgery. She had met all developmental milestones and had no history of pulmonary disease. The symptoms were initially attributed to asthma, but the child's fatigue progressed to the point of being unable to climb stairs.

On physical examination, she weighed 15.8 kg (10th percentile), with a temperature of 37.5 [degrees]C; heart rate, 105 bpm; blood pressure, 112/61 mg Hg; and respiratory rate, 36 breaths per minute. She appeared emaciated and had decreased breath sounds over the right chest. The remainder of her physical examination was unremarkable.

Chest radiographs demonstrated complete opacification of the right hemithorax with a mediastinal shift to the left. There was compressive atelectasis of the lower lobe with intersitial infiltrate. Lytic lesions were noted on right ribs 7, 8, and 9, and in the right humerus (Fig. 1) and pelvis. Computed tomography scan of the chest demonstrated complete opacification of the right hemithorax with no obvious abnormality of lung parenchyma.

The child underwent video-assisted thoracoscopy with removal of 1,500 mL of unclotted serosanguinous fluid. The collapsed lung reexpanded well, and the only gross abnormality seen was the presence of tiny bullous lesions on the diaphragm surface. These lesions and the pleural fluid were sent for pathologic examination, and a chest tube was placed.

After extubation in the recovery room, the child became cyanotic, unresponsive, and hypotensive. She was reintubated, central access was obtained, and Pediatric Advanced Life Support protocol was begun. During this time, the chest tube output was minimal, and chest radiography was normal, with bilaterally expanded lungs. A bedside echocardiogram failed to show an obvious cardiac abnormality. She became hypotensive and asystolic and was pronounced dead.

Cytologic examination of the thoracentesis fluid revealed a mixture of numerous mature lymphocytes and blood consistent with a chylothorax with hemorrhage. Gross findings at autopsy included markedly thickened mediastinal soft tissues and cystic spaces in the ribs (Fig. 2), spleen (Fig. 3), and lungs. Microscopic examination revealed these cystic spaces to be lymphangiomatous malformations (Fig. 4). Additional lymphangiomatous malformations involved the mediastinal soft tissues, liver, and kidneys.

Discussion

Lymphangiomatosis is a rare, benign disease resulting from abnormal development of the lymphatic system. Unlike lymphangiomas, in which there is a focal proliferation of lymphatic tissue, lymphangiomatosis is a disease of diffuse infiltration by lymphatic channels involving one or more soft tissue organs, commonly the lungs or spleen. (1) Bony infiltrates are often seen, causing massive osteolysis, commonly at the diaphysis or metaphysis of the tibia and humerus, as well as ilium, skull, mandible, and vertebrae.

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The disease can occur at any age, but commonly is found in patients 20 years of age or younger, and has no sex predilection. Radiographic findings may include massive chylothorax, bilateral pulmonary infiltrates, splenomegaly, and translucent bone lesions. These bone lesions, which are characterized by progressive dissolution of part or all of one or several adjacent bones, can mimic neoplasms or dysplasia. Patients often present with dypsnea and wheezing, which may be misdiagnosed as asthma. Lymphangiomatosis of bone (eponymously termed Gorham-Stout disease) may be asymptomatic or present with local pain from pathologic fracture through a lytic lesion. (2) Other physical findings include failure to thrive and wasting caused by protein loss or left upper quadrant abdominal pain caused by splenic involvement.

The diagnosis of lymphangiomatosis is made through clinical suspicion combined with radiographic findings. A common diagnostic clue is the coexistence of lytic bone lesions and chylothorax. Chest radiographs often show bilateral interstitial infiltrates with pericardial or pleural effusions. On radiography, bone lesions have a well-defined rim of sclerosis that varies in size. Medullary involvement usually predominates. Cortical invasion, osseous expansion, and periosteal reaction can occur, giving rise to a radiographic appearance that is often described as soap bubble, sucked candy, or honeycomb. (3) Technetium-99 scan may show increased uptake in patients with bone lesions. Bone biopsy will show benign lymphangiomas. Magnetic resonance imaging is the most reliable diagnostic modality for detecting both soft tissue and bony lesions.

Treatment is mainly palliative. Surgical treatment may be indicated for resection of solitary mediastinal or lung lesions in rare cases. Lymphangiomatosis of the spleen can result in splenomegaly with left upper quadrant pain and a risk of bleeding from splenic rupture or consumptive coagulopathy. In these cases, total splenectomy is warranted. Accessory spleens should be removed because they may be a source of disease recurrence. (4) Bader-Meunier et al (5) reported a beneficial effect of partial splenic embolization to treat disseminated intravascular coagulopathy associated with lymphangiomatosis.

Recurrent chylothorax can be treated with percutaneous drainage and pleurodesis with talc or bleomycin. (6) Interferon-[alpha] therapy has been used with limited success. Leverdiere reported significant clinical and radiologic improvement of a 3-year-old patient with disseminated lymphangiomatosis after 1 month of treatment using recombinant interferon-[alpha]-2b. (7) Kandil et al (8) reported successful treatment with irradiation of three patients with extensive thoracic lymphangiomatosis. Patients with recurrent chylothorax may benefit from a medium-chain triglyceride and high protein diet. Cases of recurrent thoracic lymphorrhagia and disseminated lymphangiomatosis have been successfully treated with somatostatin. (9)

The prognosis for lymphangiomatosis is usually poor, particularly among patients with pulmonary involvement and chylothorax. The natural history tends to be that of slow progression with recurrent chylous accumulations and associated mediastinal compression. The principle cause of death in most patients is respiratory failure secondary to infections and rapid chylous accumulation. Aviv et al (2) also reported one death caused by catastrophic skull base collapse and spinal cord impingement as the result of massive osteolysis of the vertebra and skull base.

Conclusion

Lymphangiomatosis is a rare, benign disease caused by maldevelopment of the lymphatic system. It usually presents in young patients with progressive dypsnea, massive chylothorax, and lytic bone lesions. The disease is progressive, and pulmonary involvement with chylothorax carries a poor prognosis. Diagnosis requires clinical suspicion and can be best aided by chest radiography, T2-weighted magnetic resonance imaging, and bone biopsy. Treatment is mainly palliative, although limited success has been reported with a variety of therapies.

"Without freedom, no art; art lives only on the restraints it imposes on
itself and dies of all others."
--Albert Camus, Resistance, Rebellion, and Death

Accepted June 21, 2004.

References

1. Faul JL, Berry GJ, Colby TV, et al. Thoracic lymphangiomas, lymphangiectasis, lymphangiomatosis, and lymphatic dysplasia syndrome. Am J Respir Crit Care Med 2000;161:1037-1046.

2. Aviv RI, Mchugh K, Hunt J. Angiomatosis of bone and soft tissue: a spectrum of disease from diffuse lymphangiomatosis to vanishing bone disease in young patients. Clin Radiol 2001;56:184-190.

3. Dahlin DC, Unni KK. Bone tumors. 4th ed. Springfield, IL, Thomas Books, 1986, pp 307-316.

4. Barrier A, Lacaine F, Callard P, et al. Lymphangiomatosis of the spleen and two accessory spleens. Surgery 2002;131:114-116.

5. Bader-Meunier B, Husseini K, Nouyrigat V, et al. Partial splenic embolization in lymphangiomatosis. J Pediatr 2001;138:613-614.

6. Aoki M, Kato F, Saito H, et al. Successful treatment of chylothorax by bleomycin for Gorham's disease. Clin Orthop Relat Res 1996;330:193-197.

7. Laverdiere C, David M, Dubois J, et al. Improvement of disseminated lymphangiomatosis with recombinant interferon therapy. Pediatr Pulmonol 2000;29:321-324.

8. Kandil A, Rostom AY, Mourad WA, et al. Successful control of thoracic lymphangiomatosis by irradiation. Clin Oncol 1997;9:407-411.

9. Collard JM, Laterre PF, Boemer F, et al. Conservative treatment of post-surgical lymphatic leaks with somatostatin-14. Chest 2000;117:902-905.

RELATED ARTICLE: Key Points

* Lymphangiomatosis is a rare congenital malformation that can involve visceral organs, soft tissue, and bone.

* Lymphangiomatosis typically occurs in the first and second decades of life.

* Treatment is palliative, and prognosis is poor, often resulting in death caused by respiratory failure.

Dan Tran, MD, Mary E. Fallat, MD, and John J. Buchino, MD

From the Division of Pediatric Surgery, Department of Surgery, and Departments of Pediatrics and Pathology, University of Louisville and Kosair Children's Hospital, Louisville, KY.

Reprint requests to Dr. John J. Buchino, Kosair Children's Hospital, PO Box 35070, Louisville, KY 40232. E-mail: [e-mail]