1Ministry of Health of the Republic of Moldova [600615]

1Ministry of Health of the Republic of Moldova
Public Institution “Nicolae Testemi țanu” State University of Medicine and
Pharmacy of the Republic of Moldova
FACULTY OF MEDICINE NR.2
Department PEDIATRIC SURGERY
DIPLOMA THESIS
LYMPHAGIOMAS IN CHILDREN
Conductor
Head of Departament of Surgery, Dr.hab. in med., Professor,
Orthopedics, Traumatology, Academician of ASM
Pediatric anesteziology: Eva GUDUMAC
Autor: Rabia BADARNI
Chisinau, 2015

2CONTENT 2
Abbreviations 3
Introduction 4
1. Literature Review 7
1.1.Definition 7
1.2.Classification 8
1.3.Lymphatic embryogenesis 14
1.4.Pathology 17
2. Materials and methods 21
2.1.Clinical features 21
3. Results and discussions 27
3.1.Diagnosis 27
3.2.Treatment 32
Conclusions 35
References 37
Declaration 47

3ABBREVIATIONS
LAM – Lymphangioleiomyomatosis
MCTG – medium chain triglyceride
MRI – magnetic resonance imaging
CT – computer tomographic

4INTRODUCTION
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 1 A). In addition, congenital errors of lymphatic
development can lead to primary pulmonary lymphatic disorders (lymphangiomas,
lymphangiectasis, lymphangiomatosis, and lymphatic dysplasia syndrome) [2-8].
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.

5Fig. 1. ( A)CT scan of the thorax of a patient with diffuse pulmonary lymphangiomatosis,
demonstrating bilateral chylous effusions ( arrow ) and diffuse lymphatic proliferations in the left
lung ( arrowheads ).
(B)Pulmonary lymphangiomatosis in a 34-yr-old woman with a long history of suspected
bronchiectasis. Multifocal lymphatic proliferations along the lymphatic routes of the interlobular
septa were found (hematoxylin–eosin; original magnification: ×60). Similar changes were also noted
along the bronchovascular bundles (not shown). The right panel shows bland endothelial cells lining
the lymphatic spaces.
(C )Pulmonary lymphangioma in a 25-yr-old woman with a solitary peripheral lung lesion in the
subpleural and interlobular septal tissues (hematoxylin– eosin; original magnification: ×40).
(D)High-power magnification demonstrating the anastomosing lymphatic channels. Occasional
clusters of small lymphocytes are found (hematoxylin–eosin; original magnification: ×400).

6(E )MRI of the thorax of an infant boy who underwent combined heart and lung transplantation at 7
wk for congenital Pulmonary lymphangiectasis, demonstrating widespread cyst formation and
abnormal lymphatic vessel (coronal section, T2-weighted image).
(F)Pulmonary lymphangiectasis: numerous cystic spaces, ranging from 5 to 20 mm are seen
throughout the lung fields. The right panel shows the smooth walled spaces distorting the
parenchyma.
(G)Pulmonary lymphangiectasis, demonstrating the characteristic massive dilatation without
proliferation of lymphatics (hematoxylin–eosin; original magnification: ×50).
(H )High- power magnification of panel G , demonstrating simple fluid-filled lymphatic spaces
(hematoxylin–eosin; original magnification: ×400).

74. Literature Review
4.1.Definition
Lymphangiomas are malformations of the lymphatic system characterized by
lesions that are thin-walled cysts; these cysts can be macroscopic, as in a cystic
hygroma, or microscopic.[1]The lymphatic system is the network of vessels
responsible for returning to the venous system excess fluid from tissues as well as the
lymph nodes that filter this fluid for signs of pathogens. These malformations can
occur at any age and may involve any part of the body, but 90% occur in children less
than 2 years of age and involve the head and neck. These malformations are either
congenital or acquired. Congenital lymphangiomas are often associated with
chromosomal abnormalities such as Turner syndrome, although they can also exist in
isolation. Lymphangiomas are commonly diagnosed before birth using fetal
ultrasonography. Acquired lymphangiomas may result from trauma, inflammation, or
lymphatic obstruction.
Lymphangiomas are uncommon, hamartomatous, congenital malformations of
the lymphatic system that involve the skin and subcutaneous tissues. The
classification of lymphangiomas lacks a standard clear definition and universal
application, in part because of the nature of lymphangiomas, which represent a
clinicopathologic continuum. The classification most frequently used divides these
lesions into 2 major groups based on the depth and the size of these abnormal lymph
vessels. The superficial vesicles are called lymphangioma circumscriptum. The more
deep-seated group includes cavernous lymphangioma and cystic hygroma. Many
categorize cystic hygroma as a variant of cavernous lymphangioma. Note the image
below.

8Fig. 1.1. 16-year-old obese boy with large unilateral verrucous lymphangioma.
4.2. 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 [6-8]. Several investigators have proposed classification systems
for lymphatic disorders based on pathology or presumed pathophysiologic
mechanisms [2-10]. 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 1.1.
Table 1. 1.DISORDERS OF THE LYMPHATIC SYSTEM
LymphangiomaCapillary
Cavernous

9Cystic
LymphangiectasisPrimary (congenital)
Secondary
LymphangiomatosisSingle organ system involvement (e.g.,
diffuse pulmonary lymphangiomatosis)
Multiple organ system involvement
Lymphatic dysplasia syndromePrimary lymphedema
Lymphedema congenita
Lymphedema precox
Lymphedema tarda
Idiopathic effusion(s)Pleural
Pericardial
Peritoneal
Yellow nail syndrome
Congenital chylothorax
Lymphatic injury (secondary chylous effusions and lymphedema) [19, 23-29]
Lymphangioma, acquired progressive [33, 34]
Lymphangiosarcoma [12, 38-41]
Lymphatic abnormalities combined with other tissue disorders
Lymphangioleiomyomatosis [35, 36]
Hemangiolymphangiomas [42, 43, 45-48]
Lymphangiolipoma [153, 154]

10Lymphangiomas
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].
Fig. 1.2. Patient suffering from macrocystic lymphangioma before treatment.
Pulmonary Lymphangiectasis
Lymphangiectasis describes pathologic dilation of lymphatics (Figures 1E, 1F,
1G, and 1H) [13, 14]. Primary (congenital) and secondary forms have been described.

11The primary form presents in neonates and is usually fatal (Fig.1.3.). 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.
Fig. 1.3. Primary pulmonary lymphangiectasia in infancy and childhood.
Lymphangiomatosis
Lymphangiomatosis describes the presence of multiple lymphangiomas [15-
17]. 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, Fig.1.4.) [10] has been reported in the literature as pulmonary
lymphangiectasis [2, 3, 13], generalized lymphangiectasis [14], intrathoracic

12lymphangiomatosis [15], thoracic lymphangiomatosis [16], and diffuse pulmonary
angiomatosis [17].
Fig. 1.4. Lymphangiomatosis.
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 [20-22], 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) (Fig. 1.5.), and lymphedema tarda (> 35 yr) [19].

13Fig. 1.5. Lymphedema of the feet in an infant is shown. The toes have the
characteristic sausagelike appearance. Hyperconvex nails in Turner syndrome.
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) [19-32]. Acquired progressive lymphangiomas, sometimes referred to
as angioendothelioma (lymphatic type), are localized cutaneous macular or papular
lesions that appear brown or violaceous (Fig.1.6). 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 [35-37].
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, 38-41]. 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 [42-48].

14Fig.1.6. This figure shows the lymphatic trunks and the duct system in the human
body.
4.3.LYMPHATIC EMBRYOGENESIS
Lymphangiomas, lymphangiectasis, lymphangiomatosis, and lymphatic
dysplasia syndrome are thought to result from congenital errors of lymphatic
development [4-7, 18]. The lymphatic vascular system (Fig. 1.7.) 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].

15Fig.1.7. Variations of the lymphatic junctions at the right venous angle. A)
Entry of the tributaries into the right lymphatic duct. B) Partial entry into the right
lymphatic duct.
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].

16Lymphangiomas
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 [52-54]. 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 [4-7], 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.

17Lymphatic Dysplasia Syndrome
The lymphatic dysplasia syndrome includes a diverse group of disorders with
variable prognosis [58-61]. 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, 60-62]. 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 [63-68].
Moreover, the nail changes, lymphedema, and pleural effusions can be reversible
[69].
1.4. 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

18lymphangiomas 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

19found 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

20with idiopathic lymphedema and yellow, dystrophic, fingernails [63-65]. 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].

215.MATERIALS AND METHODS
2.1. CLINICAL FEATURES
Lymphangiomas
Although the majority of lymphangiomas present in the first 2 yr of life
(Fig.1.8., 1.9.) [4], there has recently been an increased recognition of lymphangiomas
in adults [86, 87].
Fig.1.8. Clinically, lymphangioma of the oral cavity are rather characteristic.
Usually, the lesions present superficially as a pebbly.
Fig.1.9. On oral examination, we noted a slightly reddened, enlarged tongue
with multifocal, pebbly, vesicle-like lesions on the tip, dorsal and lateral surfaces.

22Over 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 (Fig.1.10).
Fig.1.10. Intraoperative image showing the intrathoracic large cyst.
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
(Fig.1.11.) 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,
90-97].

23Fig.1.11. Perioperative picture showing mediastinal cystic lymphangioma.
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, 100-102].
Lymphangiectasis
Primary pulmonary lymphangiectasis is often fatal in early life, and cases are
frequently stillborn (Fig.1.12.) [103].

24Fig. 1.12. One with primary intestinal lymphangiectasia.
Secondary pulmonary lymphangiectasis can present with respiratory distress at
any age (Fig. 1.13) [57, 90, 104, 105].
Fig.1.13. Lymphangiectasia Secondary.
Cases associated with pulmonary venous obstruction or other congenital heart
defects, usually present in early childhood. In addition, a number of congenital and

25genetic diseases have been associated with pulmonary lymphangiectasis, including
Noonan, Ullrich-Turner, Ehlers-Danlos, and Down syndromes [2, 57, 106-108].
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, 110-124]. 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, 125-127]. 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, 130-132], chylous ascites [8, 132-135], protein wasting enteropathy [134,
136-139], 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

26become 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, 143-149]. 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 (< 0.25 mm/wk), and
clubbing. The sino-respiratory tract is frequently involved (63%). Pleural effusions
(bilateral and exudative), bronchiectasis, and rhinosinusitis lead to shortness of breath
and a productive cough. Symptoms often predate the diagnosis of yellow nail
syndrome by more than 10 yr.

276. RESULTS AND DISCUSSIONS
6.1.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 (Fig.1.14), and magnetic resonance imaging
(MRI) have proven useful in determining the number and extent of lesions (Fig.1.15)
[155-157].
Fig.1.14. CT Subsequently, the lung resection of the mediastinal tumor was
performed by video-assisted thoracoscopy.

28Fig.1.15. Lymphangioma in a 1-year-old girl with a cervical mass. Coronal (a) and
parasagittal (b) and (c) T2-weighted images show a heterogeneous cervico-
mediastinal mass. Because of the simultaneous presence of fluid and hemorrhage the
mass appears heterogeneous on both T1- (not shown) and T2-weighted images.
References: – Matosinhos/PT.
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 [159-161].
Lymphangiectasis
Primary pulmonary lymphangiectasis presents soon after birth and is commonly
fatal in early life (Figure 1E). The dilated lymphatics, in association with

29chylothoraces, 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 ( seeFigure 1E) [162-164].
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
(Fig.1.16).

30Fig.1.16. MRI Lymphangiomatosis.
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

31course 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 (Fig.1.12) [66, 82-84]. 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].
Fig.1.17. Characteristic's of Noonan Syndrome in the infant.
Lymphangiography and lymphoscintigraphy allow an anatomic and functional
assessment of lymphatic transport, and a depiction of regional lymph nodes [67-69,
161, 162, 168].

323.2. 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, 93-95]. 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).

33Lymphangiomatosis
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 [150-152]. Impaired lymphatic drainage is associated with
immunoglobulin deficiencies. Patients with lymphatic dysplasia syndrome suffer

34recurrent 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].

35CONCLUSION
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 1.2. 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 [100-102, 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.
Table 1.2.DISEASES OF THE THORACIC LYMPHATIC SYSTEM: CLINICAL AND
PATHOLOGIC FEATURES
Lymphangioma Lymphangiectasis LymphangiomatosisLymphatic
Dysplasia
Syndrome
Age at
presentationChildhood (90%
of cases present
at < 2 yr of age)Primary: Neonate.
Secondary:
Majority in
childhood.Rare in neonate.
Majority of cases
occur by 20 yr of age.Adult (most
present at > 20 yr)

36Table 1.2.DISEASES OF THE THORACIC LYMPHATIC SYSTEM: CLINICAL AND
PATHOLOGIC FEATURES
Lymphangioma Lymphangiectasis LymphangiomatosisLymphatic
Dysplasia
Syndrome
Sex
predilectionNone Males > females None Females > males
Natural
historyNo spontaneous
resolution.
Changes in the
size of
lymphangiomas
are often
related to
secondary
infections.Primary: Leads to
severe
respiratory failure
that is commonly
fatal.Secondary:
Disease severity is
dependent on
inciting factors.Poor prognosis with
pulmonary or intra-
abdominal disease.
Good prognosis for
bony or soft tissue
involvement.Recurrent chest
infections,
pleural effusions,
and
bronchiectasis.
Prognosis is
related to the
severity of
bronchiectasis.
Thoracic
manifestationsMediastinal
mass,
intrapulmonary
mass, chylous
pleural effusion,
chylous
pericardial
effusion.Primary: Diffuse
dilation of
pulmonary lymph
vessels. Secondary:
Dilation of
pulmonary
lymph vessels due
to chronic
lymphatic
obstruction.Mediastinal,
pulmonary and chest
wall lymphangiomas.
Chylous pericardial
and/or pleural
effusions are
commonly seen.Chylothorax,
chylopericardium,
bronchiectasis.
Pathologic
featuresBenign
proliferations of
endothelial
lined channels
and cysts with
varying amounts
of intermixed
connective
tissue.Dilated pulmonary
lymphatics (not
increased in
number).Proliferation of
lymphatics
arranged as complex
anastomosing spaces
along anatomic
lymphatic routes.Chronic pleuritis,
fibrosis, and
dilated
lymphatics.
Treatment Excision or
sclerosis.MCTG, high-
protein diet.MCTG, high-protein
diet. Drainage of
large fluid
collections;
sclerotherapy.MCTG, high-
protein diet.
Drainage of
chylothorax.
Pleurodesis,
intravenous
immunoglobulin.
Definition of abbreviation : MCTG = medium chain triglyceride diet.

37REFERENCES
1. Miller W. S.The lymphatics and lymph flow in the human lung. Am. Rev. Tuberc.
1919;3:193–209.
2. Felman A. H., Rhatigan R. M., Pierson K. K.Pulmonary lymphangiectasia:
observation in 17 patients and proposed classification. Am. J. Roentgenol. Radium.
Ther. Nucl. Med. 1972;116:548–558.
3. Lloyd E. S., Press H. C.Congenital pulmonary lymphangiectasis. South. Med. J.
1979;72:1205–1206.
4. Bill A. H., Sumner D. S.A unified concept of lymphangioma and cystic hygroma.
Surg. Gynecol. Obstet. 1965;120:79–86.
5. Zadvinskis D. P., Benson M. T., Kerr H. H., Mancuso A. A., Cacciarelli A. A.,
Madrazo B. L., Mafee M. F., Dalen K.Congenital malformations of the
cervicothoracic lymphatic system: embryology and pathogenesis. Radiographics
1992;12:1175–1189.
6. Hilliard R. I., McKendry J. B., Phillips M. J.Congenital abnormalities of the
lymphatic system: a new clinical classification. Pediatrics 1990;86:988–994.
7. Levine C.Primary disorders of the lymphatic vessels—a unified concept. J. Pediatr.
Surg. 1989;24:233–240.
8. Smeltzer D. M., Stickler G. B., Fleming R. E.Primary lymphatic dysplasia in
children: chylothorax, chylous ascites, and generalized lymphatic dysplasia. Eur. J.
Pediatr 1986;145:286–292.
9. Witte M. H., Witte C. L.Lymphangiogenesis and lymphologic syndromes.
Lymphology 1986;19:21–28.
10. Tazelaar H. D., Kerr D., Yousem S. A., Saldana M. J., Langston C., Colby T.
V.Diffuse pulmonary lymphangiomatosis. Hum. Pathol. 1993;24:1313–1322.
11. Wegner G.Ueber Lymphangiome. Arch. Klin. Chir. 1877;20:641.
12. Enzinger, F. M., and S. W. Weiss. 1995. Tumors of lymph vessels. InS. M. Gay,
editor. Soft Tissue Tumors. Mosby, St. Louis. 679–700.
13. Kirchner, J., V. Jacobi, M. Schneider, and R. Wagner. 1997. Primary congenital
pulmonary lymphangiectasia—a case report. Wien. Klin. Wochenschr. 12:109:922–
924.
14. White J. E., Veale D., Fishwick D., Mitchell L., Corris P. A.Generalised
lymphangiectasia: pulmonary presentation in an adult. Thorax 1996;51:767–768.
15. Swank D. W., Hepper N. G., Folkert K. E., Colby T. V.Intrathoracic
lymphangiomatosis mimicking lymphangioleiomyomatosis in a young woman. Mayo
Clin. Proc. 1989;64:1264–1268.
16. Margraf L. R.Thoracic lymphangiomatosis. Pediatr. Pathol. Lab. Med. 1996;16:155–
160.

3817. Canny G. J., Cutz E., MacLusky I. B., Levison H.Diffuse pulmonary angiomatosis.
Thorax 1991;46:851–853.
18. Fox G. F., Challis D., O'Brien K. K., Kelly E. N., Ryan G.. Acta Pediatr.
1998;87:1010–1012.
19. Cooke, J. P., and T. W. Rooke. 1996. Lymphedema. InJ. Loscalzo, M. A. Creager,
and V. J. Dzau, editors. Vascular Medicine: A Textbook of Vascular Biology and
Diseases. Little, Brown and Co., Boston. 1133–1146.
20. Promisloff R. A., Hogue D. J.Chylothorax: the result of previous radiation therapy? J.
Am. Osteopath. Assoc. 1997;97:164–166.
21. Van Renterghem D. M., Pauwels R. A.Chylothorax and pleural effusion as late
complications of thoracic irradiation [Letter; Comment]. Chest 1995;108:886–887.
22. Berkman N., Breuer R., Kramer M. R., Polliack A.Pulmonary involvement in
lymphoma. Leuk. Lymphoma 1996;20:229–237.
23. Valentine V. G., Raffin T. A.The management of chylothorax. Chest 1992;102:586–
591.
24. Chan B. B., Murphy M. C., Rodgers B. M.Management of chylopericardium. J.
Pediatr. Surg. 1990;25:1185–1189.
25. Consensus document of the International Society of Lymphology Executive
Committee. The diagnosis and treatment of peripheral lymphedema. Lymphology
1995;28:113–117.
26. Harwood C. A., Mortimer P. S.Causes and clinical manifestations of lymphatic
failure. Clin. Dermatol. 1995;13:459–471.
27. Tanabe N., Muya M., Isonokami M., Kozuka T., Honda T., Ohtani H.Lymphedema
due to chronic penile strangulation: a case report. J. Dermatol. 1996;23:648–651.
28. Marcks P.Lymphedema: pathogenesis, prevention, and treatment. Cancer Pract.
1997;5:32–38. 29.
29. Witte C. L., Witte M. H.Disorders of lymph flow. Acad. Radiol. 1995;2:324–334.
30. Szuba A., Rockson S. G.Lymphedema: anatomy, physiology and pathogenesis [In
Process Citation]. Vasc. Med. 1997;2:321–326.
31. Kostman J. R., DiNubile M. J.Nodular lymphangitis: a distinctive but often
unrecognized syndrome. Ann. Intern. Med. 1993;118:883–888.
32. Ikezoe J., Godwin J. D., Hunt K. J., Marglin S. I.Pulmonary lymphangitic
carcinomatosis: chronicity of radiographic findings in long-term survivors. Am. J.
Roentgenol. 1995;165:49–52.
33. Watanabe M., Kishiyama K., Ohkawara A.Acquired progressive lymphangioma. J.
Am. Acad. Dermatol. 1983;8:663–667.
34. Soohoo L., Mercurio M. G., Brody R., Zaim M. T.An acquired vascular lesion in a
child: acquired progressive lymphangioma. Arch. Dermatol. 1995;131:341–345.

3935. Kalassian K. G., Doyle R., Kao P., Ruoss S., Raffin T.
A.Lymphangioleiomyomatosis: new insights. Am. J. Respir. Crit. Care Med.
1997;55:1183–1186.
36. Taylor J. R., Ryu J., Colby T. V., Raffin T. A.Lymphangioleiomyomatosis: clinical
course in 32 patients. N. Engl. J. Med. 1990;323:1254–1260.
37. Kitaichi M., Izumi T.Lymphangioleiomyomatosis. Curr. Opin. Pulm. Med.
1995;5:417–424.
38. Stewart N. J., Pritchard D. J., Nascimento A. G., Kang Y. K.Lymphangiosarcoma
following mastectomy. Clin. Orthop. 1995;320:135–141.
39. Gebhart M., Chasse E., Petein M.Lymphangiosarcoma: reports of 3 cases and review
of the literature. Eur. J. Surg. Oncol. 1995;21:211–214.
40. Andersson H. C., Parry D. M., Mulvihill J. J.Lymphangiosarcoma in late-onset
hereditary lymphedema: case report and nosological implications. Am. J. Med. Genet.
1995;56:72–75.
41. Tomita K., Yokogawa A., Oda Y., Terahata S.Lymphangiosarcoma in
postmastectomy lymphedema (Stewart-Treves syndrome): ultrastructural and
immunohistologic characteristics. J. Surg. Oncol. 1988;38:275–282.
42. Sammis A. F., Weitzman S., Arcomano J. P.Hemangiolymphangioma of spleen and
bone. N.Y. State J. Med. 1971;71:1762–1764.
43. Koblenzer P. J., Bukowski M. J.Angiomatosis (hamartomatous hem-
lymphangiomatosis): report of a case with diffuse involvement. Pediatrics
1961;28:65–76.
44. Gaillard de Collogny L., Delage J.[Cervical hemolymphangioma in a young patient].
J. Fr. Otorhinolaryngol. Audiophonol. Chir. Maxillofac. 1981;30:469–473.
45. Giacalone P. L., Boulot P., Marty M., Deschamps F., Laffargue F., Viala J. L.Fetal
hemangiolymphangioma: a case report. Fetal Diagn. Ther. 1993;8:338–340.
46. Chandna S., Bhatnagar V., Mitra D. K., Upadhyaya P.Hemangiolymphangioma of the
urinary bladder in a child. J. Pediatr. Surg. 1987;22:1051–1052.
47. Shah K. D., Chervenak F. A., Marchevsky A. M., Rosenberg J. C., Berkowitz R.
L.Fetal giant hemangiolymphangioma: report of a case. Am. J. Perinatol.
1987;4:212–214.
48. Vilalta J., Mascaro J. M.Hemangiolymphangioma of the tongue treated by transfixion
technique. J. Dermatol. Surg. Oncol. 1985;11:168–170.
49. Moore, K. L. 1988. The cardiovascular system. InM. Wonsiewicz, editor. The
Developing Human. W. B. Saunders, Philadelphia. 325–333.
50. Spencer, H. 1977. Congenital abnormalities of the lung. InH. Spencer, editor.
Pathology of the Lung. Pergamon Press, New York.
51. Laurence K. M.Congenital pulmonary cystic lymphangiectasis. J. Path. Bact.
1955;70:325–333.

4052. Fisher I., Orkin M.Acquired lymphangioma (lymphangiectasis): report of a case. Arch.
Dermatol. 1970;101:230–234.
53. Flanagan B. P., Helwig E. B.Cutaneous lymphangioma. Arch. Dermatol. 1977;113:24–
30.
54. Peachey R., Whimster I.Lymphangioma of skin: a review of 65 cases. Br. J. Dermatol.
1970;83:519–527.
55. Bowman C. A., Witte M. H., Witte C. L., Way D. L., Nagle R. B., Copeland J. G.,
Daschbach C. C.Cystic hygroma reconsidered: hamartoma or neoplasm? Primary culture of
an endothelial cell line from a massive cervicomediastinal hygroma with bony
lymphangiomatosis. Lymphology 1984;17:15–22.
56. Goetsch E.Hygroma colli cysticum and hygroma axillare: pathologic and clinical study
and report of 12 cases. Arch. Surg. 1938;36:394.
57. Noonan J. A., Walters L. R., Reeves J. T.Congenital pulmonary lymphangiectasis. Am. J.
Dis. Child. 1970;120:314–319.
58. Wolfe J. H. N.The prognosis and possible cause of severe primary lymphoedema. Ann.
R. Coll. Surg. Eng. 1984;66:251.
59. Kinmonth J. B., Young A. E., Edwards J. M., O'Donnell T. F., Thomas M. L.Mixed
vascular deformities of the lower limbs, with particular reference to lymphography and
surgical treatment. Br. J. Surg. 1976;63:899–906.
60. Akamatsu H., Amano J., Sakamoto T., Suzuki A.Primary chylopericardium. Ann.
Thorac. Surg. 1994;58:262–266.
61. Scholten C., Staudacher M., Girsch W., Wolf G., Grimm M., Binder T., Lang I.,
Stefenelli T.A novel therapeutic strategy for the management of idiopathic chylopericardium
and chylothorax. Surgery 1998;123:369–370.
62. Craven C. E., Goldman A. S., Larson D. L., Patterson M., Hendrick C. K.Congenital
chylous ascites: lymphangiography demonstration of obstruction of the cisterna chyli and
chylous reflux into the peritoneal space and small intestine. J. Pediatr. 1967;70:340–345.
63. Samman P. D., White W. F.The “yellow nail” syndrome. Br. J. Dermatol. 1964;76:153–
157.
64. Nordkild P., Kromann-Andersen H., Struve-Christensen E.Yellow nail syndrome: the
triad of yellow nails, lymphedema and pleural effusions. Acta Med. Scand. 1986;219:221–
227.
65. d'Souza M. F.Generalized lymphoedema and yellow nails, pleural effusions and
macroglobulinaemia. Proc. R. Soc. Med. 1970;63:24.
66. Muller R. P., Peters P. E., Echternacht-Happle K., Happle R.Roentgenographic and
clinical signs in yellow nail syndrome. Lymphology 1979;12:257–261.
67. Runyon B. A., Forker E. L., Sopko J. A.Pleural-fluid kinetics in a patient with primary
lymphedema, pleural effusions, and yellow nails. Am. Rev. Respir. Dis. 1979;119:821–825.

4168. Mambretti-Zumwalt J., Seidman J. M., Higano N.Yellow nail syndrome: complete triad
with pleural protein turnover studies. South. Med. J. 1980;73:995–997.
69. Bull R. H., Fenton D. A., Mortimer P. S.Lymphatic function in the yellow nail
syndrome. Br. J. Dermatol. 1996;134:307–312.
70. Redenbacker, E. A. H. 1828. De ranula sublingua, speciali, cum casa congenita.
Monachii, Lindhauer.
71. Wernher, A. 1843. Die angeborenen Kysten-Hygrome und die ihnen verwandten
Geschwültste in anatomischer, diagnostischer und therapeutischer Beziehung. Geissen: G. F.
Heyer, Vater.
72. Kransdorf, M. J. 1997. Vascular and lymphatic tumors. InM. J. Kransdorf and M. D.
Murphey, editors. Imaging of Soft Tissue Tumors. W.B. Saunders, Philadelphia. 118–123.
73. Brown L. R., Reiman H. M., Rosenow E. C., Gloviczki P. M., Divertie M.
B.Intrathoracic lymphangioma. Mayo Clin. Proc. 1986;61:882–892.
74. Ramani P., Shah A.Lymphangiomatosis: histologic and immunohistochemical analysis
of four cases. Am. J. Surg. Pathol. 1993;17:329–335.
75. Landing, B. H., and S. Farber. 1956. Tumors of the lymphatic vessels. InAtlas of Tumor
Pathology: Section III, Fascicle 7: Tumors of the Cardiovascular System. Armed Forces
Institute of Pathology, Washington, DC. F7.124–F7.138.
76. Rosai, J. 1995. Lymph vessels. InJ. Rosai, editor. Ackerman's Surgical Pathology.
Mosby, St. Louis. 2221–2226.
77. Virchow, R. 1856. Gesammelte Abhandlungen zur Wissenschaftlichen Medicin.
Meidinger Sohn, Frankfurt. 982.
78. Stocker J. T., Madewell J. E.Persistent interstitial pulmonary emphysema: another
complication of the respiratory distress syndrome. Pediatrics 1977;59:847.
79. Leonidas J. C., Bhan I., McCauley R. G.Persistent localized pulmonary interstitial
emphysema and lymphangiectasia: a causal relationship? Pediatrics 1979;64:165–171.
80. Carlson K. C., Parnassus W. N., Klatt E. C.Thoracic lymphangiomatosis. Arch. Pathol.
Lab. Med. 1987;111:475–477.
81. Emerson P.Clinical manifestations of disorders of the pulmonary and pleural lymphatics.
Thorax 1970;25:256.
82. Marks R., Ellis J. P.Yellow nails: a report of six cases. Arch. Derm. 1990;102:619–623.
83. DeCoste S. D., Imber M. J., Baden H. P.Yellow nail syndrome. J. Am. Acad. Dermatol.
1990;22:608–611.
84. Hiller E., Rosenow E. C., Olsen A. M.Pulmonary manifestations of the yellow nail
syndrome. Chest 1972;61:452–458.
85. Solal-Celigny P., Cormier Y., Fournier M.The yellow nail syndrome: light and electron
microscopic aspects of the pleura. Arch. Pathol. Lab. Med. 1983;107:183–185.
86. Kransdorf M. J.Benign soft tissue tumors in a large referral population: distribution of
specific diagnoses by age, sex, and location. A.J.R. 1994;164:395–402.

4287. Chou Y. H., Tiu C. M., Chiou H. J., Lai C. R., Hsu C. C., Yu C.Echo-enhancing
sonography of a large-vessel hemangioma of the neck. J. Clin. Ultrasound 1999;27:465–
468.
88. Drut R., Mosca H. H.Intrapulmonary cystic lymphangioma. Pediatr. Pulmonol.
1996;22:204–206.
89. Miyake H., Shiga M., Takaki H., Hata H., Onishi R., Mori H.Mediastinal
lymphangiomas in adults: CT findings. J. Thorac. Imaging 1996;11:83–85.
90. Wagenaar S. S., Swierenga J., Wagenvoort C. A.Late presentation of primary pulmonary
lymphangiectasis. Thorax 1978;33:791–795.
91. Holden W. E., Morris J. F., Antonovic R., Gill T. H., Kessler S.Adult intrapulmonary
and mediastinal lymphangioma causing haemoptysis. Thorax 1987;42:635–636.
92. Wright C. C., Cohen D. M., Vegunta R. K., Davis J. T., King D. R.Intrathoracic cystic
hygroma: a report of three cases. J. Pediatr. Surg. 1996;31:1430–1432.
93. Hamada K., Ishii Y., Nakaya M., Sawabata N., Fukuda K., Suzuki H.Solitary
lymphangioma of the lung. Histopathology 1995;27:482–483.
94. Karmazin N., Panitch H. B., Balsara R. K., Faerber E. N., de Chadarevian J. P.De novo
circumscribed pulmonary lobar cystic lymphatic anomaly in a young boy: a possible sequela
of bronchopulmonary dysplasia. Chest 1989;95:1162–1163.
95. Kim W. S., Lee K. S., Kim I., Yeon K. M., Kim C. J., Chi J. G., Han M. C.Cystic
intrapulmonary lymphangioma: HRCT findings. Pediatr. Radiol. 1995;25:206–207.
96. Milovic I., Oluic D.Lymphangioma of the lung associated with respiratory distress in a
neonate. Pediatr. Radiol. 1992;22:156.
97. Wada A., Tateishi R., Terazawa T., Matsuda M., Hattori S.Case report: lymphangioma
of the lung. Arch. Pathol. 1974;98:211–213.
98. Nakazato Y., Ohno Y., Nakata Y., Yamaguchi H., Hazato N., Nagasawa S., Yokoyama
M., Yamada T.Cystic lymphangioma of the mediastinum. Am. Heart J. 1995;129:406–409.
99. Swischuk L. E., Hoeffel J. C., John S. D.Primary intrathoracic lymphangioma
masquerading as teratoma. Pediatr. Radiol. 1996;26:827–829.
100. Grosfeld J. L., Weber T. R., Vane D. W.One-stage resection for massive
cervicomediastinal hygroma. Surgery 1982;92:693–699.
101. Papsin B. C., Evans J. N.Isolated laryngeal lymphangioma: a rare cause of airway
obstruction in infants. J. Laryngol. Otol. 1996;110:969–972.
102. Williams W. T., Cole R. R.Lymphangioma presenting as congenital stridor. Int. J.
Pediatr. Otorhinolaryngol. 1993;26:185–191.
103. Stocker, J. T. 1988. Congenital and developmental diseases. InD. H. Dail and S. P.
Hammar, editors. Pulmonary Pathology. Springer-Verlag, New York. 41–57.
104. Javett S. N., Webster I., Braudo J. L.Congenital dilatation of the pulmonary lymphatics.
Pediatrics 1963;31:416–425.

43105. Mann T. P.Hemihypertrophy left side of body: congenital lymphatic edema of left arm:
radiological enlargement of heart shadow. Proc. Royal Soc. Med. 1955;48:330.
106. 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. 1993;47:54–58.
107. Gilewski M. K., Statler C. C., Kohut G., Toriello H. V.Congenital pulmonary
lymphangiectasia and other anomalies in a child: provisionally unique syndrome? Am. J.
Med. Genet. 1996;66:438–440.
108. Sanders J. S., Rosenow E. C., Piehler J. M., Gloviczki P., Brown L. R.Chyloptysis
(chylous sputum) due to thoracic lymphangiectasis with successful surgical correction. Arch.
Intern. Med. 1988;148:1465–1466.
109. Moerman P., Van Geet C., Devlieger H.Lymphangiomatosis of the body wall: a report
of two cases associated with chylothorax and fatal outcome. Pediatr. Pathol. Lab. Med.
1997;17:617–624.
110. Asch M. J., Cohen A. H., Moore T. C.Hepatic and splenic lymphangiomatosis with
skeletal involvement: report of a case and review of the literature. Surgery 1974;76:334–
339.
111. Bell K. A., Simon B. K.Chylothorax and lymphangiomas of bone: unusual
manifestations of lymphatic disease. South. Med. J. 1978;71:459–460.
112. Goldstein M. R., Benchimol A., Cornell W., Long D. R.Chylopericardium with
multiple lymphangioma of bone. N. Engl. J. Med. 1969;280:1034–1037.
113. Case records of the Massachusetts General Hospital. Weekly clinicopathological
exercises. Case 30-. N. Engl. J. Med. 1980;303:270–276.
114. Ogita S., Deguchi E., Tokiwa K., Iwata J., Kubota Y., Iwai N.Ongoing osteolysis in
patients with lymphangioma. J. Pediatr. Surg. 1998;33:45–48.
115. Canil K., Fitzgerald P., Lau G.Massive chylothorax associated with lymphangiomatosis
of the bone. J. Pediatr. Surg. 1994;29:1186–1188.
116. Peh W. C., Ngan H.Lymphography: still useful in the diagnosis of lymphangiomatosis.
Br. J. Radiol. 1993;66:28–31.
117. Shah A. R., Dinwiddie R., Woolf D., Ramani R., Higgins J. N., Matthew D.
J.Generalized lymphangiomatosis and chylothorax in the pediatric age group. Pediatr.
Pulmonol. 1992;14:126–130.
118. Dunkelman H., Sharief N., Berman L., Ninan T.Generalised lymphangiomatosis with
chylothorax. Arch. Dis. Child. 1989;64:1058–1060.
119. Bhatti M. A., Ferrante J. W., Gielchinsky I., Norman J. C.Pleuropulmonary and skeletal
lymphangiomatosis with chylothorax and chylopericardium. Ann. Thorac. Surg.
1985;40:398–401.

44120. Young J. W., Galbraith M., Cunningham J., Roof B. S., Vujic I., Gobien R. P.,
Liebscher L., Butler W. M., Fudenberg H. H.Progressive vertebral collapse in diffuse
angiomatosis. Metab. Bone Dis. Relat. Res. 1983;5:53–60.
121. Reilly B. J., Davidson J. W., Bain H.Lymphangiectasis of the skeleton: a case report.
Radiology 1972;103:385–386.
122. Morphis L. G., Arcinue E. L., Krause J. R.Generalized lymphangioma in infancy with
chylothorax. Pediatrics 1970;46:566–575.
123. Gutierrez R. M., Spjut H. J.Skeletal angiomatosis: report of three cases and a review of
the literature. Clin. Orthop. 1972;85:82–97.
124. Gilsanz V., Yer H. C., Baron M. G.Multiple lymphangiomas of the neck, axillae,
mediastinum and bones in an adult. Radiology 1976;120:161–162.
125. White M. A.Lymphangioma of the tongue: report of case. A.S.D.C. J. Dent. Child.
1987;54:280–282.
126. Nair L. G., Kurtz C. P.Lymphangiomatosis presenting with bronchial cast formation.
Thorax 1996;51:765–766.
127. Takahashi K., Takahashi H., Maeda K., Homma S., Uekusa T., Dambara T., Kira S.An
adult case of lymphangiomatosis of the mediastinum, pulmonary interstitium and
retroperitoneum complicated by chronic disseminated intravascular coagulation. Eur. Respir.
J. 1995;8:1799–1802. 128. Swensen S. J., Hartman T. E., Mayo J. R., Colby T. V., Tazelaar
H. D., Muller N. L.Diffuse pulmonary lymphangiomatosis: CT findings. J. Comput. Assist.
Tomogr. 1995;19:348–352.
129. Bresser P., Kromhout J. G., Reekers J. A., Verhage T. L.Chylous pleural effusion
associated with primary lymphedema and lymphangioma-like malformations. Chest
1993;103:1916–1918.
130. de Haan H. P., Kolff J., Buis B.Isolated chylopericardium due to lymphangiomatous
dysplasia of the thymus. Eur. Heart. J. 1984;5:846–849.
131. Joshi M., Cole S., Knibbs D., Diana D.Pulmonary abnormalities in Klippel-Trenaunay
syndrome: a histologic, ultrastructural, and immunocytochemical study. Chest
1992;102:1274–1277.
132. Malek N. P., Ocran K., Tietge U. J., Maschek H., Gratz K. F., Trautwein C., Wagner S.,
Manns M. P.A case of the yellow nail syndrome associated with massive chylous ascites,
pleural and pericardial effusions. Z. Gastroenterol. 1996;34:763–766.
133. Calabrese P. R., Frank H., Taubin H. L.Lymphangiomyomatosis with chylous ascites:
treatment with dietary fat restriction and medium chain triglycerides. Cancer 1977;40:895–
897.
134. Duhra P. M., Quigley E. M., Marsh M. N.Chylous ascites, intestinal lymphangiectasia
and the “yellow-nail” syndrome. Gut 1985;26:1266–1269.
135. Joliat G., Stalder H., Kapanci Y.Lymphangiomyomatosis: a clinico-anatomical entity.
Cancer 1973;31:455–461.

45136. Case records of the Massachusetts General Hospital. Weekly clinicopathological
exercises. Case 8-: an elderly woman with protein-losing enteropathy and pleural effusions.
N. Engl. J. Med. 1984;310:512–520.
137. Ishida O., Tamura K., Uchida H., Kuroda C.Lymphographic studies on protein-losing
enteropathy. Lymphology 1979;12:26–28.
138. Nazer H. M., Abutalib H., Hugosson C., al-Mahr M., Ali M. A.Intestinal
lymphangiectasia masquerading as coeliac disease. Ann. Trop. Paediatr. 1991;11:349–355.
139. Sorensen R. U., Halpin T. C., Abramowsky C. R., Hornick D. L., Miller K. M., Naylor
P., Incefy G. S.Intestinal lymphangiectasia and thymic hypoplasia. Clin. Exp. Immunol.
1985;59:217–226.
140. Vardy P. A., Lebenthal E., Shwachman H.Intestinal lymphangiectasia: a reappraisal.
Pediatrics 1975;55:842–851.
141. Dietz W. H., Stuart M. J.Splenic consumptive coagulopathy in a patient with
disseminated lymphangiomatosis. J. Pediatr. 1977;90:421–423.
142. Buttiker V., Fanconi S., Burger R.Chylothorax in children: guidelines for diagnosis and
management. Chest 1999;116:682–687.
143. Groves L. K., Effler D. B.Primary chylopericardium. N. Engl. J. Med. 1954;250:520–
523.
144. Furrer M., Hopf M., Ris H. B.Isolated primary chylopericardium: treatment by
thoracoscopic thoracic duct ligation and pericardial fenestration [see comments]. J. Thorac.
Cardiovasc. Surg. 1996;112:1120–1121.
145. Yuksel M., Yildizeli B., Zonuzi F., Batirel H. F.Isolated primary chylopericardium. J.
Thorac. Cardiovasc. Surg. 1997;114:299–300.
146. Mewis C., Kuhlkamp V., Sokiranski R., Karsch K. R.Primary chylopericardium due to
partial aplasia of the thoracic duct. Eur. Heart J. 1997;18:880–881.
147. Svedjeholm R., Jansson K., Olin C.Primary idiopathic chylopericardium—a case report
and review of the literature. Eur. J. Cardiothorac. Surg. 1997;11:387–390.
148. Yuksel M., Yildizeli B., Zonuzi F., Batirel H. F.Isolated primary chylopericardium.
Eur. J. Cardiothorac. Surg. 1997;12:319–321.
149. Kentsch M., Doring V., Rodemerk U., Schumacher M., Stabenow I., Flor B., Muller-
Esch G.[Primary chylopericardium: stepwise diagnosis and therapy of a differential
diagnostically important illness]. Z. Kardiol. 1997;86:417–422.
150. Cordasco E. M., Beder S., Coltro A., Bavbek S., Gurses H., Mehta A. C.Clinical
features of the yellow nail syndrome. Cleve. Clin. J. Med. 1990;57:472–476.
151. Hershko A., Hirshberg B., Nahir M., Friedman G.Yellow nail syndrome. Postgrad.
Med. J. 1997;73:466–468.
152. Fields C. L., Roy T. M., Ossorio M. A., Mercer P. J.Yellow nail syndrome: a
perspective. J. Ky. Med. Assoc. 1991;89:563–565.

46153. Radivoyevitch M. A., Mirmiran-Yazdy S. A.Lymphangiolipoma of the mesentery. Am.
Surg. 1989;55:435–437.
154. Whitley J. M., Flannery A. M.Lymphangiolipoma of the thoracic spine in a pediatric
patient with Proteus syndrome. Childs. Nerv. Syst. 1996;12:224–227.
155. Ardenghy M., Miura Y., Kovach R., Hochberg J.Cystic hygroma of the chest wall: a
rare condition. Ann. Plast. Surg. 1996;37:211–213.
156. Jang H. J., Lee K. S., Han J.Intravascular lymphomatosis of the lung: radiologic
findings. J. Comput. Assist. Tomogr. 1998;22:427–429.
157. Pui M. H., Li Z. P., Chen W., Chen J. H.Lymphangioma: imaging diagnosis. Australas.
Radiol. 1997;41:324–328.
158. Mentzel H. J., Schramm D., Vogt S., Reuter A., Mentzel T., Kaiser W. A.Intra-
abdominal lymphangioma in a newborn. J. Clin. Ultrasound 1998;26:320–322.
159. Liu N. F., Wang C. G.The role of magnetic resonance imaging in diagnosis of
peripheral lymphatic disorders. Lymphology 1998;31:119–127.
160. Fung K., Poenaru D., Soboleski D. A., Kamal I. M.Impact of magnetic resonance
imaging on the surgical management of cystic hygromas. J. Pediatr. Surg. 1998;33:839–
841.
161. Molitch H. I., Unger E. C., Witte C. L., vanSonnenberg E.Percutaneous sclerotherapy
of lymphangiomas. Radiology 1995;194:343–347.
162. Bloomfield, F. H., W. Hadden, and T. R. Gunn. Lymphatic dysplasia in a neonate with
Noonan's syndrome. Pediatr. Radiol. 27:321–323.
163. Brown R. L., Azizkhan R. G.Pediatric head and neck lesions. Pediatr. Clin. North Am.
1998;45:889–905.
164. Gardner T. W., Domm A. C., Brock C. E., Pruitt A. W.Congenital pulmonary
lymphangiectasis: a case complicated by chylothorax. Clin. Pediatr. (Phila) 1983;22:75–78.
165. Vogt-Moykopf I., Rau B., Branscheid D.Surgery for congenital malformations of the
lung. Ann. Radiol. (Paris) 1993;36:145–160.
166. Adamson D., Heinrichs W. L., Raybin D. M., Raffin T. A.Successful treatment of
pulmonary lymphangiomyomatosis with oophorectomy and progesterone. Am. Rev. Respir.
Dis. 1985;132:916–921.
167. Hillerdal G.Chylothorax and pseudochylothorax. Eur. Respir. J. 1997;10:1157–1162.
168. Pui M. H., Yueh T. C.Lymphoscintigraphy in chyluria, chyloperitoneum and
chylothorax. J. Nucl. Med. 1998;39:1292–1296.
169. Collins M. H., Darragh R. K., Caldwell R. L., Turrentine M. W., Brown J. W.Short-
term survivors of pediatric heart transplantation: an autopsy study of their pulmonary
vascular disease. J. Heart Lung Transplant. 1995;14:1116–1125.

47Declaration
I hereby declare that the diploma thesis entitled " The Full Title of the Thesis"
is written by me and has not been presented before at another college or institution of
higher education in the country or abroad. Also, I declare that all sources used,
including the Internet sources, are indicated in the paper, considering the rules for
avoiding plagiarism:
-all text fragments are reproduced exactly, even the proper translations from
other languages are written in quotes and have detailed reference source;
-paraphrasing in own words of text written by other authors has detailed
reference;
-summary of the ideas of other authors has a detailed reference to the original
text.
Date Rabia BADARNI

_______________
Original signature