Retroperitoneal Lymphangioma

Martin Cherk, Mehrdad Nikfarjam and Christopher Christophi, Department of Surgery, University of Melbourne,
Austin Hospital, Victoria, Australia.
Lymphangiomas are rare cystic tumours that may present as cystic masses in the retroperitoneum. Retroperitoneal lymphangiomas account for approximately 1% of all lymphangiomas. Confusion with other cystic tumours of the retroperitoneum including those arising from the liver, kidney and pancreas is common. A case of a retroperitoneal cystic lymphangioma occurring in a 41-year-old woman raising interesting diagnostic and
management issues is reported. The patient presented with vague abdominal pain and persistent nausea. Radiological imaging demonstrated a large multiloculated thin-walled cyst involving the upper retroperitoneum. Surgical resection was complete, revealing a benign cavernous lymphangioma. The patient made a complete recovery and was disease-free 30 months postoperatively. [Asian J Surg 2006;29(1):51–4]

Key Words: cystic tumour, lymphangioma, retroperitoneum

Address correspondence and reprint requests to Professor Christopher Christophi, Department of Surgery, University of Melbourne, Austin Hospital, Lance Townsend Building Level 8, Studley Road, Heidelberg, Victoria 3084, Australia.

E-mail: surgery-armc@unimelb.edu.au

• Date of acceptance: 18 August 2004

Introduction

An interesting and rare differential diagnosis for a retroperitoneal
cystic mass is cystic lymphangioma. A case of a patient
presenting with a multicystic mass in the retroperitoneum
that was identified as a lymphangioma is reported. These
tumours are commonly confused with other cystic masses in
the retroperitoneum. The particular diagnostic features and
treatment outcomes relating to retroperitoneal lymphangiomas
are discussed.

Case report

A 41-year-old woman presented with a 3-month history of
vague upper abdominal pain and persistent nausea. She had
no previous illness episodes. Colonoscopy and gastroscopy
were normal. Full blood count and liver function tests were
within normal limits. An ultrasound scan revealed a large
cystic mass (8 × 9 × 7 cm) in the region of the porta hepatis
(Figure 1A), which was thought to be extrahepatic. Computed
tomography (CT) showed a multiloculated cyst possibly arising
from outside the liver, compressing the adjacent liver and
extending medial to the second part of the duodenum towards
the pancreas (Figure 1B). Magnetic resonance imaging (MRI)
confirmed a cystic non-enhancing extrahepatic lesion (Figures
1C and D). Carcinoembryonic antigen and CA19-9 were not
elevated and hydatid serology was negative.

Preoperative diagnosis based on imaging investigations
could not be made with any certainty and a percutaneous
biopsy of the lesion was deemed too high-risk due to the
location and the possibility of malignant seeding if the lesion
was neoplastic.

A laparotomy was ultimately performed. A large retroperitoneal
multicystic tumour attached to the uncinate process
of the pancreas and coeliac axis and extending to the porta
hepatis between the inferior vena cava and portal vein was
identified. The cyst was excised intact, with a small portion of
attached pancreatic capsule and tissue.

The operation was made technically difficult by the retroperitoneal
location of the mass and its intricate relationship
with the pancreas and coeliac axis and its tributaries. The thinwalled
nature of the cyst rendered it liable to rupture and
required handling with extreme care.

Histology

Multiple cystic locules containing thin opaque fluid were
noted. The cyst lining comprised trabeculated white tissue
with a scattering of firm white and grey nodules within the
cyst wall. Histopathology revealed a mass with a central
cystic space and a multiloculated appearance, in part lined
by a flattened endothelium, with underlying small nodular
proliferations of smooth muscle. Large adjoining lymphoid
collections were identified (Figure 2). The cyst was adherent
in part to a small portion of pancreas tissue. Findings were
consistent with a retroperitoneal cavernous lymphangioma.

Follow-up

Recovery was uncomplicated. The patient was symptom-free
30 months postoperatively with no evidence of recurrence on
subsequent abdominal imaging.

Discussion


The differential diagnosis of cystic tumour in the retroperitoneum
raises several possibilities. These include both malignant
and benign tumours. Malignant causes include necrotic
neoplasms, germ cell tumours (teratoma), undifferentiated
sarcoma, cystic metastases (gastric/ovarian), malignant
mesenchymoma, biliary cystadenoma/carcinoma and cystic
mesothelioma.1 Benign cystic lesions of the retroperitoneum
include lymphangioma, microcystic pancreatic adenoma and
cysts of urothelial and foregut origin. Cysts of foregut origin
are subdivided into bronchogenic cysts, which contain cartilage
or seromucinous respiratory glands, oesophageal cysts,
that are composed of well-developed layers of smooth muscle
without cartilage, and simple foregut cysts, which have none
of these distinguishing features.2

In the case presented, the unusual location of the cyst and
its intimate relationship with the liver contributes a myriad
of other diagnostic possibilities including simple liver cyst,
choledochal cyst, biliary cystadenoma/carcinoma, cystic hepatic
metastases, hamartomas and parasitic infections such
as hydatid disease.3

Lymphangiomas are extremely rare benign neoplasms of
the lymphatic system with no reports of incidence due to their
rarity. They can occur in any location in which lymphatics are
normally found. Head and neck lymphangiomas (cystic
hygromas) account for 75% of reported cases.4 The remainder
occur in the axillary region (20%) or in other less common
locations (5%). Retroperitoneal lymphangiomas account
for approximately 1% of all lymphangiomas, with 185 cases
identified in a review of international literature.5

The aetiology of these benign neoplasms is uncertain, with
most authors postulating a combination of inflammatory
and fibrotic processes or genetic predisposition. Other factors
implicated include mechanical pressure and retention, traumatic
factors, degeneration of lymph nodes and disorders
of endothelial lymphatic vascular secretion or permeability.

The frequent development within areas where primitive lymph
sacs occur suggests that lymphangiomas are malformations
arising from sequestrations of lymphatic tissue that fail to
communicate normally with the lymphatic system.6 This results
in the formation of unicystic or multicystic tumours
whose cavity is covered with a layer of endothelium and filled
with chylous or serous material.

Intra-abdominal lymphangiomas may arise from the
mesentery, greater omentum or retroperitoneum and tend to
grow slowly within the abdomen. The majority are asymptomatic
and are discovered incidentally on abdominal imaging
for other conditions. Symptoms are usually related to tumour
size. Approximately 40% of cases present with symptoms of
obstruction.7 Other symptoms include ascites and intermittent
fever. Rarely, bleeding or rupture of the tumour will cause
an acute abdomen.5 Clotting disorders have also been described
in patients with lymphangiomas.8 Acute symptoms
are more common in children than adults. The average time
from occurrence of symptoms to operation is more than 7
months.9

In contrast to mesenteric cysts, lymphangiomas not
only have the typical characteristics of the lymphatic system,
but also have smooth-muscle cells in their walls. Histologically,
lymphangiomas are classified as capillary, cavernous or cystic,
with only the latter two reported to occur in the retroperitoneal
region.

Preoperative diagnosis of lymphangiomas is rare prior to
laparotomy or laparoscopy.5 Abdominal X-rays generally
show nonspecific expansion and, in some cases, foci of calcification
may be seen. Lymphangiography is seldom used but
is sometimes useful in preoperative diagnosis. CT and MRI
features of lymphangiomas have been described. The diagnosis
of lymphangioma based on these modalities is generally
one of many potential differentials for a multiloculated cystic
mass arising retroperitoneally. One of the main features of
retroperitoneal lymphangioma is that the mass is generally of
water density on CT or MRI.10 Guided biopsy of the lesion is
often difficult and rarely attempted due to the location of
tumours and concerns of potential dissemination of
malignancy. When fine-needle biopsy is performed, characteristic
abundant lymphocytes may be apparent.10 The likelihood
of preoperative diagnosis is greatest when imaging is
combined with biopsy.11

Outcomes following complete resection of retroperitoneal
lymphangiomas are generally good. Surgery is often required
for symptom control or diagnosis.12 Recurrence of
symptoms with incomplete excision is possible. Dissemination
in the retroperitoneum is very rare but potentially a
fatal complication.13 Injection of sclerosants such as alcohol
and bleomycin into lymphangiomas has been described
in the literature in nonsurgical candidates. However,
induration of the cyst and infection often complicate these
procedures.14,15

In conclusion, the differential diagnosis of a retroperitoneal
cystic lesion raises several possibilities. Cystic lymphangioma
should be considered. Despite being rare, these tumours
have an excellent prognosis, with symptom relief and cure
achieved with complete surgical excision.

References

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cystic lymphangioma. J Surg Oncol 1996;61:234–7.
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cyst: report of a case and literature review. Pathol Int 1999;49:
152–5.
3. Regev A, Reddy KR, Berho M, et al. Large cystic lesions of the liver in
adults: a 15-year experience in a tertiary center. J Am Coll Surg 2001;
193:36–45.
4. Sarno RC, Carter BL, Bankoff MS. Cystic lymphangiomas: CT
diagnosis and thin needle aspiration. Br J Radiol 1984;57:424–6.
5. Hauser H, Mischinger HJ, Beham A, et al. Cystic retroperitoneal
lymphangiomas in adults. Eur J Surg Oncol 1997;23:322–6.
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Mosby, 1995.
7. Henzel JH, Pories WJ, Burget DE, et al. Intra-abdominal lymphangiomata.
Arch Surg 1966;93:304–8.
8. Dietz WH Jr, Stuart MJ. Splenic consumptive coagulopathy in a
patient with disseminated lymphangiomatosis. J Pediatr 1977;90:
421–3.
9. Takiff H, Calabria R, Yin L, et al. Mesenteric cysts and intraabdominal
cystic lymphangiomas. Arch Surg 1985;120:1266–9.
10. Breidahl WH, Mendelson RM. Retroperitoneal lymphangioma.
Australas Radiol 1995;39:187–91.
11. Hayami S, Adachi Y, Ishigooka M, et al. Retroperitoneal cystic
lymphangioma diagnosed by computerized tomography, magnetic
resonance imaging and thin needle aspiration. Int Urol Nephrol 1996;
28:21–6.
12. Burkett JS, Pickleman J. The rationale for surgical treatment of
mesenteric and retroperitoneal cysts. Am Surg 1994;60:432–5.
13. Nishio I, Mandell GL, Ramanathan S, et al. Epidural labor analgesia
for a patient with disseminated lymphangiomatosis. Anesth Analg
2003;96:1805–8.
14. Chait D, Yonkers AJ, Beddoe GM, et al. Management of cystic
hygromas. Surg Gynecol Obstet 1974;139:55–8.
15. Tanigawa N, Shimomatsuya T, Takahashi K, et al. Treatment of
cystic hygroma and lymphangioma with the use of bleomycin fat
emulsion. Cancer 1987;60:741–9.

Asian Journal of Surgery

Thoracic Lymphangiomas, Lymphangiectasis, Lymphangiomatosis, and Lymphatic Dysplasia Syndrome

American Journal of Respiratory and Critical Care Medicine

JOHN L. FAUL, GERALD J. BERRY, THOMAS V. COLBY, STEPHEN J. RUOSS, MATTHEW B. WALTER, GLENN D. ROSEN, and THOMAS A. RAFFIN

Division of Pulmonary and Critical Care Medicine and the Department of Pathology, Stanford University School of Medicine, Stanford, California; and the Department of Pathology, Mayo Clinic, Scottsdale, Arizona

Contents:

Introduction
Classification
Lymphangiomas
Pulmonary Lymphangiectasis
Lymphangiomatosis
Lymphatic Dysplasia Syndrome
Other Thoracic Lymphatic Disorders
Lymphatic Embryogenesis
Lymphangiomas
Pulmonary Lymphangiectasis
Lymphangiomatosis
Lymphatic Dysplasia Syndrome
Pathology
Clinical Features
Lymphangiomas
Pulmonary Lymphangiectasis
Lymphangiomatosis
Lymphatic Dysplasia Syndrome
Diagnosis
Lymphangiomas
Pulmonary Lymphangiectasis
Lymphangiomatosis
Lymphatic Dysplasia Syndrome
Treatment
Lymphangiomas
Pulmonary Lymphangiectasis
Lymphangiomatosis
Lymphatic Dysplasia Syndrome
Conclusion

Introduction

The lymphatic system plays an important role in human circulation and organ perfusion homeostasis (1). Disorders of the pulmonary lymphatic system occur in a variety of clinical settings (ranging from trauma to cancer) and may lead to serious pulmonary disease (Figure 1A). In addition, congenital errors of lymphatic development can lead to primary pulmonary lymphatic disorders (lymphangiomas, lymphangiectasis, lymphangiomatosis, and lymphatic dysplasia syndrome) (2). Because of their scarcity, these latter conditions are often misdiagnosed (Figure 1B) and their management is difficult. Research on thoracic lymphatic disorders has been hampered by a confusing and inconsistent use of terminology. Their origins and pathogenesis are currently unknown. Future advances in our understanding of vasculogenesis may provide clues about the relation between abnormal embryogenesis and the development of lymphatic disease.

Classification

The classification of pulmonary lymphatic disorders is challenging (6). The literature uses inconsistent terminology and describes only case reports and a handful of small case series (6). Several investigators have proposed classification systems for lymphatic disorders based on pathology or presumed pathophysiologic mechanisms (2). We believe that the classification of thoracic lymphatic disorders should be based on clinical presentation and pathologic features, rather than on their assumed pathophysiology (Table 1). In this report, we employ a modification of Hilliard's classification (6). The identification of characteristic features should allow patients to be placed into one of the categories listed in Table 1.

Lymphangiomas

Lymphangiomas are focal proliferations of well differentiated lymphatic tissue that present as multicystic or spongelike accumulations (Figure 1C) (11, 12). They are subdivided into three pathologic categories (11, 12): lymphangioma simplex (capillary lymphangioma) describes thin-walled lymphatic channels that occur as small, well circumscribed cutaneous lesions; cavernous lymphangiomas are microscopic thin-walled lymphatic channels with associated stroma; and cystic lymphangiomas (cystic hygromas) are large, well-circumscribed, multiloculated cystic spaces lined by endothelium that contain a significant connective tissue component. Cavernous and cystic lymphangiomas can coexist within the same lesion (12).

Pulmonary Lymphangiectasis

Lymphangiectasis describes pathologic dilation of lymphatics (Figures 1E, 1F, 1G, and 1H) (13, 14). Primary (congenital) and secondary forms have been described. The primary form presents in neonates and is usually fatal. Secondary forms of lymphangiectasis result from a variety of processes that impair lymph drainage and increase lymph production. We propose that primary and secondary lymphangiectasis are distinguishable by their age of presentation and their clinical courses.

Lymphangiomatosis

Lymphangiomatosis describes the presence of multiple lymphangiomas (15). It is frequently associated with other lymphatic related abnormalities and usually (in 75% of cases) involves multiple organs. Diffuse pulmonary lymphangiomatosis (Figures 1A and 1B) (10) has been reported in the literature as pulmonary lymphangiectasis (2, 3, 13), generalized lymphangiectasis (14), intrathoracic lymphangiomatosis (15), thoracic lymphangiomatosis (16), and diffuse pulmonary angiomatosis (17).

Lymphatic Dysplasia Syndrome

The term "lymphatic dysplasia syndrome" includes primary (idiopathic) lymphedema syndromes, congenital chylothorax (18), idiopathic effusions (often chylous), and the yellow nail syndrome (19). The yellow nail syndrome describes a triad of idiopathic pleural effusions, lymphedema, and dystrophic nails. The lymphatic dysplasia syndrome encompasses effusions of the pericardium, pleura, peritoneum, and lymphedema (19), without an identifiable cause, such as cancer or injury (20), and in the absence of lymphangiomas, lymphangiectasis, or lymphangiomatosis. Primary lymphedema has been subdivided into categories based upon the age of presentation (19): lymphedema congenita (neonates), lymphedema precox (<> 35 yr) (19).

Other Thoracic Lymphatic Disorders

Lymphedema can arise due to disruption of the normal lymphatic circulation by trauma, infection, surgery, radiation, or cancer (e.g., lymphoma, lymphangitis carcinomatosis) (19). Acquired progressive lymphangiomas, sometimes referred to as angioendothelioma (lymphatic type), are localized cutaneous macular or papular lesions that appear brown or violaceous. They can occur on the chest after local trauma and have a benign natural history (33, 34).

Lymphangioleiomyomatosis (LAM) is a disease of premenopausal women characterized by proliferation of abnormal smooth muscle cells and cyst formation in lung parenchyma. LAM can involve mediastinal and retroperitoneal lymphatics and lymph nodes (35). Pneumothoraces and chylous effusions are common and patients typically develop end-stage restrictive ventilatory defects. Lymphangiosarcoma is a vascular malignancy that develops in areas of chronic lymphedema (12, 38). It most commonly presents as a large arm mass in a woman many years after a radical mastectomy (Stewart-Treves syndrome) (12, 38). The histology is indistinguishable from angiosarcoma and poorly differentiated lesions that share the features of both lymphatics and blood vessels have been termed hemangiolymphangiomas or hamartomatous heme-lymphangiomatosis (42).

Lymphatic Embryogensis

Lymphangiomas, lymphangiectasis, lymphangiomatosis, and lymphatic dysplasia syndrome are thought to result from congenital errors of lymphatic development (4, 18). The lymphatic vascular system develops during the sixth week of life as an outgrowth of the venous system or as a de novo differentiation within mesenchymal tissues (1, 49). Primordial lymphatic tissues join one another to form lymphatic channels and six lymph sacs. Paired juguloaxillary lymph sacs, paired inguinal lymph sacs, a retroperitoneal lymph sac, and a single cisterna chyli sprout endothelial buds that grow with the venous system to form the peripheral lymphatic plexus. Before the twentieth week of fetal development, the pulmonary lymphatic channels and surrounding mesenchymal tissues are prominent and individual pulmonary lobules can be delineated. After the twentieth week, the alveolar tissues grow and the lymphatic and connective tissue elements start to regress (50, 51).

Lymphangiomas

Lymphangiomas probably represent embryologic remnants of lymphatic tissues that either failed to connect to efferent channels or arose from portions of lymph sacs that were sequestered during development (50, 51). Most lymphangiomas are discovered in fetuses, neonates, or young children, at the sites of the primordial lymph sacs. Acquired or secondary lymphangiomas develop in areas of chronic lymphatic obstruction related to surgery, chronic infection, or radiation (52). There is a propensity for lymphangiomas to recur at sites of surgical resection, because of their autonomous growth (55, 56) and also by their reaccumulation of lymph fluid (12).

Lymphangiectasis

Congenital lymphangiectasis probably results from a failure of pulmonary interstitial connective tissues to regress (this normally occurs in the fifth month of fetal life) leading to dilation of pulmonary lymphatic capillaries (Figures 1F, 1G, and 1H) (51). Secondary lymphangiectasis can occur if surgery, radiation, infection, tumor, or trauma disturbs effective lymphatic drainage. Children with congenital heart diseases (for example, total anomalous pulmonary venous return or hypoplastic left heart syndromes) and adults with severe mitral valve disease have increased lymphatic circulation that contributes to the lymphatic dilatation (2, 3, 57) and the severity of lymphangiectasis.

Lymphangiomatosis

Lymphangiomatosis also appears to be due to a lymphatic developmental abnormality (4), but presents at a later age than solitary lymphangiomas either because of an influence of hormonal factors or because a more subtle, albeit more widespread, defect requires a longer period for growth.

Lymphatic Dysplasia Syndrome

The lymphatic dysplasia syndrome includes a diverse group of disorders with variable prognosis (58). In primary lymphedema, for example, at least four separate distinct patterns are found on lymphangiography. The majority of patients have hypoplastic or aplastic peripheral lymphatics; one-third have obstructed proximal lymphatics; a few have hyperplastic peripheral lymphatics; and some have incompetent lymphatic valves that develop into megalolymphatics (19, 58, 59).

Abnormalities of lymphatic development are associated with a variety of inheritance patterns (18), including congenital anomaly syndromes (achondrogenesis Type 1), and aneuploidy syndromes (Turner syndrome). Familial Milroy lymphedema is inherited in an autosomal dominant pattern, with variable penetrance, whereas congenital chylothorax appears to be inherited in an autosomal recessive pattern (18). Therefore, several factors, some of them genetic, probably lead to the development of a broad range of diseases of the lymphatic system (9).

In neonates, most chylous effusions are congenital. In older children and adults they result from malignancy, infection, or trauma (8). Primary chylous effusion formation is attributable to reflux of chyle from the thoracic duct, or cisterna chyli, through incompetent lymphatic channels (7, 8, 23, 60). The yellow nail syndrome is thought to be due to impaired lymphatic drainage, based on abnormal lymphangiography studies and delayed albumin turnover in the pleural space (63). Moreover, the nail changes, lymphedema, and pleural effusions can be reversible (69).

Pathology

Lymphangiomas

The first detailed description of a lymphangioma is attributed to Redenbacker in 1828 (70). Wernher first used the term cystic hygroma in 1843 (71). Capillary lymphangiomas appear as wartlike or vesicular lesions that are unrelated to internal lymphangiomas (53, 54). Cavernous lymphangiomas have indiscrete margins and insinuate themselves into the surrounding structures. Cystic lymphangiomas, in contrast, are multiloculated fluctuant growths often enveloped in a fibrous capsule (72, 73). Individual cysts contain serous fluid and vary in size from 2-3 millimeters to several centimeters.

Histologically, (Figure 1D) lymphangiomas are composed of an increased number of dilated lymphatic channels, lined by endothelium (12, 74). The cystic spaces are filled with proteinaceous lymph fluid (without erythrocytes). Surgical trauma or damage caused by tissue handling during processing can result in hemorrhage that can make the diagnosis of lymphangioma difficult to differentiate from hemangioma or Kaposi's sarcoma. Cavernous lymphangiomas have inconspicuous amounts of loose connective tissue compared with cystic lesions, which can have thick adventitial coats. The connective tissue stroma consists of varying amounts of spindle-shaped smooth muscle cells, collagen bundles, fibroblasts, and lymphocytes (12, 75, 76). The presence of benign lymphoid aggregates is helpful in the identification of lymphangiomas. The cellular components are generally well-differentiated and lack cytologic atypia.

Lymphangiectasis

Virchow first reported the primary (congenital) form of lymphangiectasis (a rare disease of neonates) in 1856 (77). In pulmonary lymphangiectasis, the lungs appear heavy and noncompliant (Figure 1F). The visceral pleura has a network of dilated lymphatics that weep lymph fluid when sectioned. In some cases, simple cystic spaces can be macroscopically identified along the anatomic lymphatic routes. The interlobular septa are widened and prominent. The lymphatic spaces are dilated and, in some instances, cystic. A small amount of collagen and smooth muscle may be found in the walls of the vessels, particularly in the secondary form of pulmonary lymphangiectasis (10). Lymphangiectasis should be morphologically distinguished from interstitial emphysema (78, 79).

Lymphangiomatosis

The histology of lymphangiomatosis can pathologically resemble a lymphangioma (12, 74, 80). Lymphangiomatosis can appear to infiltrate tissues, raising concern for a more aggressive lesion, but histopathology demonstrates that they are always comprised of mature cells (Figure 1D) (80).

Diffuse pulmonary lymphangiomatosis involves both lungs and, by definition, is without extrathoracic lymphatic abnormalities. Pathologic features (10) include a proliferation of complex anastamosing lymphatic channels that markedly expand the typical lymphatic routes within the lungs and mediastinum. Compared with primary pulmonary lymphangiectasis, there is a prominence of collagen and spindle-shaped cells surrounding the endothelial-lined channels. The adjacent lung parenchyma may contain collections of hemosiderin-laden macrophages but in contrast to lymphangioleiomyomatosis, the lung parenchyma is preserved (35, 36). Pleural effusions are common. The containment of diffuse pulmonary lymphangiomatosis to normal lymphatic pathways within the lung, and the small proportion and more mature appearance and alignment of smooth muscle cells, help to distinguish this from lymphangioleiomyomatosis (10).

Lymphatic Dysplasia Syndrome

In primary lymphedema, prominent fibrous septations may develop in subcutaneous adipose tissue. Histology reveals epidermal atrophy, dermal fibrosis, perivascular inflammation, and dilated lymphatics. Enlarged regional lymph nodes and sinusoidal fibrosis are found in some cases of primary lymphedema (76). In 1964 Samman and White coined the term "yellow nail syndrome" to describe 13 patients with idiopathic lymphedema and yellow, dystrophic, fingernails (63). Later, Emerson added the presence of idiopathic pleural effusions to complete the triad of clinical features by which the syndrome is recognized today (81, 82). In the yellow nail syndrome, nail matrix biopsies may reveal dense stromal fibrosis with numerous ectatic endothelial-lined vessels (83). Pleural biopsies have demonstrated features of lymphocytic pleuritis associated with moderate fibrosis and dilated lymphatics (84, 85).

Clinical Features

Lymphangiomas

Although the majority of lymphangiomas present in the first 2 yr of life (4), there has recently been an increased recognition of lymphangiomas in adults (86, 87). Over 40% of 151 lymphangiomas seen in consultation by the Armed Forces Institute of Pathology between 1980 and 1989 were from patients older than 16 yr of age (mean 19 yr) (86). The manifestations of thoracic lymphangiomas are believed to present after a period of latency because of their slow growth. Most appear as a swelling in the head, neck, or axilla and approximately 10% extend into the mediastinum (12, 73, 88, 89). Approximately 1% of all lymphangiomas are confined to the chest (73). Mediastinal lymphangiomas are equally distributed between the anterior, middle, and posterior compartments (73). Intrapulmonary lymphangiomas are rare: approximately a dozen cases, with patient ages ranging from 6 mo to 54 yr, are described in the literature (88, 90).

Thoracic lymphangiomas may remain asymptomatic for many years and only become apparent when patients develop problems related to compression of vital structures. Alternatively, they present as incidental findings on roentgenograms (73, 89, 92, 93, 98, 99). A thoracic lymphangioma can appear as a multicystic mass, or as a more amorphous configuration that insinuates itself into mediastinal structures. Patients can complain of cough and dyspnea (from extrinsic compression of airways), stridor, hemoptysis, Horner's syndrome, dysphagia, superior vena cava syndrome, constrictive pericarditis, phrenic nerve palsy, or of symptoms related to a secondarily infected lymphangioma (91, 100).

Lymphangiectasis

Primary pulmonary lymphangiectasis is often fatal in early life, and cases are frequently stillborn (103). Secondary pulmonary lymphangiectasis can present with respiratory distress at any age (57, 90, 104, 105). Cases associated with pulmonary venous obstruction or other congenital heart defects, usually present in early childhood. In addition, a number of congenital and genetic diseases have been associated with pulmonary lymphangiectasis, including Noonan, Ullrich-Turner, Ehlers-Danlos, and Down syndromes (2, 57, 106).

Lymphangiomatosis

Lymphangiomatosis has been described in patients ranging from birth up to 80 yr (86, 109). It most frequently presents in late childhood. There is no clear sex predilection (72, 86). The lesions of lymphangiomatosis can occur in any tissue in which lymphatics are normally found, but there appears to be a predilection for thoracic and neck involvement (76). Up to 75% of patients with lymphangiomatosis have bony involvement (17, 55, 74, 80, 110). Single or multiple lymphangiomas may be found within the mediastinum, adherent to the pleura, or within the chest wall (10, 17, 72, 74, 80, 113, 125). Mediastinal fat may be diffusely infiltrated with anastamosing, dilated lymphatics (14, 128). Chylous effusions are common. Associated chyloptysis (108), hemoptysis (18, 126, 129), chylopericardium (8, 10, 13, 17, 112, 130), chylous ascites (8, 132), protein wasting enteropathy (134, 136), peripheral lymphedema (9, 129, 134), hemihypertrophy (105), lymphopenia (140), and disseminated intravascular coagulopathy (141) have been described. Interestingly, many patients with lymphangiomatosis experience wheeze and may be misdiagnosed with asthma prior to the recognition of the lymphatic disorder (10, 57).

Lymphatic Dysplasia Syndrome

The incidence of primary lymphedema is estimated at 0.1 per 100,000 persons under the age of 20 yr (females more than males). When the cause is related to agenesis or hypoplasia of distal lymphatics, the extremity swelling is usually bilateral. The swelling is unilateral and more severe if proximal lymphatics or nodes are obstructed (19, 58). Early in lymphedema, soft "pitting" edema is indistinguishable from vascular forms of edema. Later, chronic lymphedema can cause the skin to become thickened and brawny, with accentuated pitting of hair follicles ("peau d'orange"). Primary lymphedema has been associated with several congenital disorders including Noonan's and Turner's syndromes.

Primary chylothorax constitutes approximately one-sixth of all chylothoraces (23). Among newborns, chylothorax is the most common type of pleural effusion and in this age group males outnumber females (8). Patients with chylothorax usually present with a history of the insidious onset of dyspnea (a result of the space occupying effect of the pleural fluid). Fever, pleuritic chest pain, and chyloptysis are rare (142). Congenital chylothorax has a variable prognosis, dependent on gestational age at birth, the presence of other congenital abnormalities, and the severity of pulmonary hypoplasia.

Primary pericardial lymphedema has been reported in approximately 80 patients (ranging in age from 1 d to 77 yr) (60, 61, 143). Many cases are asymptomatic and present with an abnormal chest roentgenogram. One-third have dyspnea, approximately 10% have cough, and, rarely, cases may present with palpitations and chest pain (60). Of all the primary lymphatic disorders discussed in this review, the yellow nail syndrome is the most likely to present in adulthood. The male to female ratio is 1:1.5, the median age at presentation is 40 to 50 yr [range, birth to 80 yr (64, 69, 84)]. The complete triad of yellow nails (89%), lymphedema (80%), and idiopathic pleural effusions (36%) is seen in a minority of patients (20%) (64, 150). Any case with two of the three findings (yellow nails, pleural effusion, lymphedema) is accepted as having clinical evidence of yellow nail syndrome (64, 84, 151, 152). The nail abnormalities include shades of yellow-green-brown discoloration, longitudinal ridges, onycholysis, slow growth.

Diagnosis

Lymphangiomas

Thoracic lymphangiomas are usually detected as nodules or cystic masses on chest radiographs. Mediastinal lymphangiomas commonly envelop great vessels and displace mediastinal organs (89, 93). Plain radiographs, barium meal, ultrasound, computer tomographic (CT) scanning, and magnetic resonance imaging (MRI) have proven useful in determining the number and extent of lesions (155). Accurate anatomic localization plays an important role in the management of lymphangioma, because the diagnosis is ultimately made postoperatively (after the histopathologic examination of resected tissue). Three-dimensional ultrasonography may reveal cystic masses with thin septations, consistent with lymphangioma (158). MRI is probably the diagnostic modality of choice for lymphangiomas, because it accurately predicts subsequent intraoperative findings, and it helps to demonstrate lymphatic architecture at different tissue levels (159).

Lymphangiectasis

Primary pulmonary lymphangiectasis presents soon after birth and is commonly fatal in early life (Figure 1E). The dilated lymphatics, in association with chylothoraces, lead to life-threatening pulmonary hypoplasia and respiratory failure. Secondary lymphangiectasis presents as localized or diffuse pulmonary interstitial infiltrates, or cystic lesions, on chest radiography and MRI (see Figure 1E) (162). Lymphangiography demonstrates abnormally dilated lymphatics with obstructive changes and collateral channels in the retroperitoneal, mediastinal, and cervical lymphatic systems (156). The presence of pulmonary lymphangiectasis may be confirmed by lung biopsy (10).

Lymphangiomatosis

Congenital lymphangiomatosis is a rare disorder that is often fatal. In lymphangiomatosis, multiple lymphangiomas occur most commonly in lung and bone. The coexistence of lytic bone lesions and chylothorax serves as an important diagnostic clue. The diagnosis is sometimes made by bone biopsy that shows that these lytic lesions are lymphangiomas containing lymph fluid (10, 165). Lymphangiography reveals multiple lesions of the thoracic duct, dilated lymphatic channels, and lymphangiomas throughout the bones and lungs (156).
Bilateral interstitial infiltrates and pericardial or pleural effusions are evident on chest radiograph (14, 18). Pulmonary function testing may reveal a mixed obstructive and restrictive pattern (10). CT scans of the thorax reveal diffuse smooth thickening of interlobular septa and bronchovascular bundles with extensive involvement of mediastinal fat and perihilar regions. Lymphangiography is useful to exclude the presence of a mediastinal tumor, but is rarely required for the diagnosis of chylothorax or lymphangioma in infants and children. Obstruction of the thoracic duct is a rare cause of chylothorax in children (23). The radiologic findings and the clinical course of lymphangiomatosis may mimic that of lymphangioleiomyomatosis (35, 36, 166). Histopathology demonstrates anastomosing endothelial lined spaces along pulmonary lymphatic routes accompanied by asymmetrically spaced bundles of spindle cells. Factor VIII related antigen and CD31 are endothelial markers that are useful in immunohistochemical staining of these channels (167).

Lymphatic Dysplasia Syndrome

The clinical diagnosis of the yellow nail syndrome is based on the presence of two of the following features: yellow or dystrophic nails, chylous effusions, and lymphedema (66, 82). Chylous effusions have a protein content greater than 30 g/L; fat content greater than 10 g/L (with elevated concentrations of chylomicrons and triglycerides), and a specific gravity greater than 1.012, in the absence of microorganisms (23). Lymphangiography and lymphoscintigraphy allow an anatomic and functional assessment of lymphatic transport, and a depiction of regional lymph nodes (67, 161, 162, 168

Treatment

Lymphangiomas

In contrast to hemangiomas, which usually resolve spontaneously, congenital lymphangiomas typically require excision (165). Hemangiomas and lymphangiomas may coexist in the same patient. Important differential diagnoses of lymphangioma include acute suppurative lymphadenitis, which is common and easily diagnosed; and chronic lymphadenitis, which should be biopsied to exclude malignancy (163). Surgical resection, or sclerotherapy, of lymphangiomas are the therapies of choice (161, 165). Surgery is frequently mandated both to confirm the diagnosis, and to prevent complications that arise from compressive effects on vital structures (101, 102). Complete surgical resection may prove technically difficult, because lymphangiomas may surround large blood vessels, airways, and mediastinal organs (73, 89, 93). Incomplete resection, or sclerosis, can result in recurrence of the lymphangioma and a return of symptoms. Before surgical exploration and excision, it is prudent to investigate for other lymphangiomatous lesions and associated congenital anomalies (50, 105).

Lymphangiectasis

Thoracic lymphangiectasis usually leads to respiratory failure (106, 107, 109). Conservative treatment includes a low-fat, high-protein diet, with medium chain triglyceride (MCTG) and vitamin supplementation, in addition to repeated aspirations of the lymph accumulations (108). A low fat intake is thought to reduce the flow of lymph and the size of the lymphatic channels. Heart and lung transplantation has been attempted with poor results (169) (J. Theodore, personal communication).

Lymphangiomatosis

The natural history of pulmonary lymphangiomatosis is characterized by progressive growth and compression of adjacent structures (10, 161). Therapy should aim to decrease the symptoms that arise from compressive effects, to control chylous fluid accumulations, and to maintain optimal cosmesis (161). The success of surgical resection is impaired by an inability to separate lymph collections from normal structures, leading to high rates of recurrence (118, 124). Anatomically complicated lesions may be impossible to completely excise without damage to adjacent structures. In patients with widespread disease, therefore, therapeutic options are palliative. Percutaneous sclerotherapy with doxycycline has been employed with good results (161). CT and magnetic resonance (MR) not only help to define the size and location of lesions, but may also serve to guide sclerosis and monitor follow-up. Lymphoscintigraphy helps to guide therapy, by helping to delineate the direction of lymphatic flow and the relation between normal and abnormal lymphatics (168).

Lymphatic Dysplasia Syndrome

The treatment of chylothorax in infancy and childhood has become standardized (23). After the initial thoracentesis, one or two more therapeutic taps should be performed to eliminate the effusion. In addition, a high-protein, MCTG diet with fat-soluble vitamin supplements should lessen the flow of chyle from the intestinal tract (133). If the chylothorax remains after 2 wk, a chest drain with slight negative pressure should be inserted, and total parenteral nutrition instituted. Antenatal drainage of large congenital chylothoraces helps neonatal survival and perinatal resuscitation.

In addition to the management of chylothorax (as discussed previously), some patients with lymphatic dysplasia syndrome are treated with antibiotics for recurring pulmonary infections (150). Impaired lymphatic drainage is associated with immunoglobulin deficiencies. Patients with lymphatic dysplasia syndrome suffer recurrent infections, in part because of an IgG2 deficiency, but also because of the associated bronchiectasis and rhinosinusitis. Intravenous immunoglobulin and albumin therapies have been used in selected patients with marked IgG deficiency (151). Conservative management of lymphatic dysplasia syndrome includes high-protein, MCTG diet and vitamin supplementation, reduced oral nutrition, and repeated aspirations of fluid collections or pleurodesis (167).

Most patients with primary lymphedema are managed conservatively, by means of various forms of compression therapy, including massage, physical therapy, intermittent pneumatic compression pumps, and compressive garments (25, 26, 29, 170). Volume-reducing surgery and lymphatic microsurgery have been reported to provide favorable outcomes. The mainstay of treatment, however, is the reduction of edema by regular elevation, massage, and external compression with elastic stockings (25, 30, 170). Gross edema may be reduced surgically by simple excision (Homans' operation) or complete excision and skin grafting (Charles' operation) (170). Combined medical, surgical, and physiotherapeutic approaches benefit patients with marked lymphedema (25, 170).

Conclusion

Diseases of the thoracic lymphatic circulation should be differentiated on the basis of their pathologic and clinical features (6, 9, 10). The characteristic features of lymphangiomas, pulmonary lymphangiectasis, lymphangiomatosis, and lymphatic dysplasia syndrome are summarized in Table 2. Characteristic clinical features and radiographic appearances, the analysis of chylothorax fluid, and the presence of features of extrathoracic lymphatic dysfunction should prompt a differential diagnosis of disordered thoracic lymphatic function (6). Many of these disorders are diagnosed in childhood. In adulthood they are probably under-recognized (14, 86, 87). Their pathogenesis is unknown, but appears to be related, in part, to congenital malformations of the thoracic lymphatic system (10, 17, 50). Surgical excision of localized lesions (100, 165) and CT-guided sclerotherapy of large and numerous lymphangiomas are useful management strategies (161). Sclerotherapy provides relief of lymphedema, lymphorrhea, and a decrease in size of lymph accumulations. Sclerotherapy is acutely painful, and requires careful analgesic management with intravenous narcotics, benzodiazepines, and/or intracavitary lidocaine (161). Dietary modifications reduce the flow of lymph in subjects with widespread lymphatic dysfunction (133). Standardized therapy for chylothorax and lymphedema can lead to improved patient functionality (23, 25, 170). There is a need for a greater awareness of disorders of the thoracic lymphatic circulation, because accurate and early diagnosis may prompt more effective management strategies.

Article with Tables, Footnotes and References