Kamis, 15 Juli 2010

REFERAT LYMPHANGIOMA

CHAPTER I

PREFACE

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. (Ramesh Venkatesh & HL Trivedi, 2008)

Most lymphangiomas are benign lesions that result only in a soft, slow-growing, "doughy" mass. Since they have no chance of becoming malignant, lymphangiomas are usually treated for cosmetic reasons only. Lymphangiomas can occur anywhere in the skin and the mucous membranes. The most common sites are the head and the neck, followed by the proximal extremities, the buttocks and the trunk. However, they sometimes can be found in the intestines, the pancreas, and the mesentery. Deeper cystic lesions usually occur in areas of loose and areolar tissue, typically the neck, the axilla, and the groin. Their skin involvement ranges from small, well-demarcated areas to large, diffuse regions with unclear borders. Lymphangioma are usually noted at birth; the remainder usually manifest before age 2 years. Lymphangioma can appear suddenly in childhood and occasionally in adolescence or adulthood (Glenn R. Jacobowitz, et al, 2005; Ramesh Venkatesh & HL Trivedi, 2008)

This paper has the goal of keeping the doctor is able to identify and understand the disease lyphangioma to be useful in the field during practice one day.


CHAPTER II

LITERATURE REVIEW

2.1 Definition

Lymphangiomas are malformations of the lymphatic system, which is the network of vessels responsible for returning to the venous system excess fluid from tissues. Lymphangioma is benign multilobular, multinodular cystic masses lined by endothelial cells. They result from maldevelopment and obstruction of the lymphatic system. Eventually, sequestrations of lymphatic tissue that do not communicate with the normal lymphatic system develop. (Craig T. Albanese & Karl G. Sylvester, 2006)

2.2 Epidemiology

Lymphangiomas are rare. They account for 4% of all vascular tumors and approximately 25% of all benign vascular tumors in children. Whereas Cystic hygroma (lymphangioma) occurs as a result of sequestration or obstruction of developing lymph vessels in approximately 1 in 12,000 births. (Robert A Schwartz & Geover Fernandez, 2009; Henri R. Ford et al, 2007)

2.3 Embriology

Failure of one of the initial jugular lymphatic sacs to develop proper connections and drainage with the lymphatic and, subsequently, venous system may produce focal lymph cysts (cavernous lymphangiomas) also known as cystic hygromas. Similarly, failure of embryologic remnants of lymphatic tissues to connect to efferent channels leads to the development of cystic lymphatic formations (simple capillary lymphangiomas) that, depending on their location, are classified as truncal, mesenteric, intestinal, and retroperitoneal lymphangiomas. (Iraklis I. Pipinos & B. Timothy Baxter, 2004)

At about the sixth week of gestation, a system of clefts develops in the cervical mesenchyme that subsequently form lymph channels. These channels give rise to jugular lymph sacs that become the cervical lymph nodes and lymphatics, ultimately draining into the internal jugular venous system (Fig 2.1).


Figure 2.1 Lymphatic system in an 8-week-old human embryo. Development of the major and minor lymphatic sacs is well under way. The jugular lymphatic sac in the neck is prominent. Sequestration of tissue from any of the developing lymphatic structures leads to formation of a lymphangioma or cystic hygroma. (John Aiken & Keith Oldham, 2006)

2.4 Classification

Lymphangiomas have traditionally been classified into three subtypes: capillary and cavernous lymphangiomas and cystic hygromas. This classification is based on their microscopic characteristics. A fourth subtype, the hemangiolymphangioma is also recognized. (Giguère CM et al, 2002)

a. Capillary lymphangiomas

Capillary lymphangiomas are composed of small, capillary-sized lymphatic vessels and are characteristically located in the epidermis.

b. Cavernous lymphangiomas

Composed of dilated lymphatic channels, cavernous lymphangiomas characteristically invade surrounding tissues.

c. Cystic hygromas

Cystic hygromas are large, macrocystic lymphangiomas filled with straw-colored, protein-rich fluid.

d. Hemangiolymphangioma

As suggested by their name, hemangiolymphangiomas are lymphangiomas with a vascular component. (Giguère CM et al, 2002)

The cavernous lymphangiomas almost invariably occur in the neck or the axilla and very rarely in the retroperitoneum. The simple capillary lymphangiomas also tend to occur subcutaneously in the head and neck region as well as the axilla. Rarely, however, they can be found in the trunk within the internal organs or the connective tissue in and about the abdominal or thoracic cavities. (Iraklis I. Pipinos & B. Timothy Baxter, 2004)

Lymphangiomas may also be classified into microcystic, macrocystic, and mixed subtypes, according to the size of their cysts.

a. Microcystic lymphangiomas

Microcystic lymphangiomas are composed of cysts, each of which measures less than 2 cm3 in volume. Microcysts are less than 1 cm in diameter. (Giguère CM et al, 2002; Baird M. Smith & Craig T.Albanese, 2006)

b. Macrocystic lymphangiomas

Macrocystic lymphangiomas contain cysts measuring more than 2 cm3 in volume.. Macrocysts are greater than 1 cm in diameter and tend to be less invasive, less numerous, and less difficult to remove. (Giguère CM et al, 2002; Baird M. Smith & Craig T.Albanese, 2006)

c. Mixed lymphangiomas

Lymphangiomas of the mixed type contain both microcystic and macrocystic components. (Giguère CM et al, 2002)

Both microcysts and macrocysts may contain blood and/or lymph, a consequence of similar lymphatic and vascular embryology. In general, microcysts are more likely to contain blood and macrocysts more likely to contain lymph.Macrocysts that contain lymph are also called cystic hygromas and they are subsumed in the general category of lymphatic malformations.(Baird M. Smith & Craig T.Albanese, 2006)

Finally, lymphangiomas may be described in stages, which vary by location and extent of disease. In particular, stage depends on whether lymphangiomas are present above or superior to the hyoid bone (suprahyoid), below or inferior to the hyoid bone (infrahyoid), and whether the lymphangiomas are on one side of the body (unilateral) or both (bilateral). (Giguère CM et al, 2002)

o Stage I à Unilateral infrahyoid.

o Stage IIàUnilateral suprahyoid.

o Stage IIIàUnilateral suprahyoid and infrahyoid.

o Stage IVàBilateral suprahyoid.

o Stage VàBilateral suprahyoid and infrahyoid.

2.5 Clinical Features

Lymphangioma occur in recognized locations with a variable combination of microcystic and macrocystic elements. The most common locations for lymphangioma are the axilla/chest, cervicofacial region, mediastinum, retroperitoneum, buttock, and anogenital areas (Fig. 2.2 and 2.3). Often the overlying skin is normal or a bluish hue. Dermal involvement manifests as puckering or deep cutaneous dimpling. Lymphangioma in the subcutis or submucosa presents as tiny vesicles, and often there is intravesicular bleeding. Lymphangioma in the forehead and orbit cause proptosis, strabismus, amblyopia, and recurrent intralesional bleeding. Facial lymphangioma is the most common basis for macrocheilia, macroglossia, macrotia, and macromala (overgrown check or malar bone). Cervicofacial lymphangioma is associated with the overgrowth of the mandibular body, which typically results in open bite and underbite. Lymphangioma in the floor of the mouth and tongue are characterized by mucosal vesicles, intermittent swelling, bleeding, and often oropharyngeal obstruction. Cervical Lymphangioma involving the supraglottic upper airway often necessitate early tracheostomy. (Glenn R. Jacobowitz et al, 2005)


Figure 2.2 Newborn Kenyan baby with a large cystic hygroma
(lymphangioma) extending from the axilla into the neck.


Figure 2.3 A, Macrocystic lymphatic malformation in the left chest. MRI showed involvement of brachial plexus and mediastinum. B, Appearance 8 years after subtotal resection. (Glenn R. Jacobowitz et al, 2005)

Mediastinal lymphangioma is an extension of cervical or axillary lymphangioma. Lymphatic anomalies of the thoracic duct or cisterna chyli present as recurrent pleural and pericardial chylous effusions or chylous ascites. Anomalous lymphatics in the gastrointestinal tract can cause hypoalbuminemia as the result of a chronic protein-losing enteropathy; often there is lymphangioma in other organ systems (generalized lymphangiomatosis). Lymphangioma in an extremity cause diffuse or localized swelling or gigantism with soft tissue and skeletal overgrowth. There is a rare type of spongiform lymphangioma in the lower extremity with a large proximal cystic lymphatic reservoir in the groin. Pelvic lymphangioma may cause bladder outlet obstruction, constipation, and recurrent infection. Progressive osteolysis, caused by diffuse soft tissue and skeletal lymphangioma, is called Gorham-Stout syndrome, also known as “disappearing bone disease” and “phantom bone disease. (Glenn R. Jacobowitz et al, 2005)

2.6 Physical Features

· Lymphangioma circumscriptum

o Lymphangioma circumscriptum involves small clusters of vesicles measuring about 2-4 mm. These clear vesicles can vary from pink to red to black secondary to hemorrhage.

o The lesions can have a warty appearance on their surface; as a result, these lesions are often confused with warts.

o Shah et al report a lymphangioma presenting on the penis. (Robert A Schwartz & Geover Fernandez, 2009)

· Cavernous lymphangioma

o Typically, cavernous lymphangiomas appear as subcutaneous nodules with a rubbery consistency. They may have large dimensions.

o The overlying skin has no lesions or changes.

o The area of involvement varies, ranging from lesions smaller than 1 cm in diameter to larger lesions that involve an entire limb. (Robert A Schwartz & Geover Fernandez, 2009)

· Cystic hygroma

o Cystic hygromas are usually larger than cavernous lymphangiomas, and they more commonly occur in the neck and parotid area.

o Often, deep cavernous lymphangiomas are not evident on superficial examination, but cystic hygromas are detected with ease because of their size and location. These large cystic lesions are soft and translucent. (Robert A Schwartz & Geover Fernandez, 2009)


Figure 2.4 Lymphangioma Circumscriptum. Multiple, 1- to-4-mm, clear, pink, red and black vesicles overlying hyperpigmented and erythematous indurated plaques were present on the right thigh. (Marissa Heller & Stephanie Mengden, 2008)

2.7 Diagnosis

The determination of a lymphangioma’s size and character is based on location, clinical examination and investigation. Some regions tend to have typical lesions: for example, reddish lesions in the base of the tongue are typically microcystic with a significant vascular component; soft boggy masses in the superficial neck or axilla – sometimes with a bluish hue – are often macrocysts with lymph. The best investigations to determine cyst contents is either a T2-weighted gadolinium-enhanced magnetic resonance imaging (MRI) or needle aspiration of the dominant cyst. Lymph is straw-coloured; thin bloody fluid may occur when a lymphatic cyst is enlarged by a ruptured blood vessel.Abundant dark or red blood indicates a significant vascular component. Viscid yellow- clear fluid from an intra-oral lesion may signal a ranula, deriving from salivary tissue. Depth of invasion and an estimate of the structures involved is best determined by MRI scanning. Rarely, a neck lesion may extend to the anterior mediastinum and compress the trachea. Spontaneous enlargement may occur following an upper respiratory tract infection; spontaneous regression is rare although sometimes follows local infection. (Baird M. Smith & Craig T.Albanese, 2006)

2.8 Histologic Findings

Microscopically, the vesicles in lymphangioma circumscriptum are greatly dilated lymph channels that cause the papillary dermis to expand. They may be associated with acanthosis and hyperkeratosis. These channels are numerous in the upper dermis and often extend to the subcutis. These deeper vessels seem to have a large caliber, and they often have a thick wall that contains smooth muscle. The lumen is filled with lymphatic fluid, but it often contains red blood cells, lymphocytes, macrophages, and neutrophils. These channels are lined by flat endothelial cells, which stain positive for Ulex europaeus agglutinin-I. The interstitium often has numerous lymphoid cells and shows evidence of fibroplasia. (Robert A Schwartz & Geover Fernandez, 2009)


Figure 2.5 Lymphangioma Circumscriptum. Within the papillary dermis in close approximation to the epidermis, there are multiple thin-walled, dilated lymphatic spaces that contain lymph with a few erythrocytes. The overlying epidermis is thin, and there are elongated rete ridges that appear to surround the lymphatic channels. (Marissa Heller & Stephanie Mengden, 2008)

Nodules in cavernous lymphangioma are characterized by large, irregular channels in the reticular dermis and subcutaneous tissue that are lined by a single layer of endothelial cells. An incomplete layer of smooth muscle often lines the walls of these malformed channels. The surrounding stroma consists of loose or fibrotic connective tissue with a number of inflammatory cells. These tumors often penetrate muscle. (Robert A Schwartz & Geover Fernandez, 2009)

Cystic hygroma is indistinguishable from cavernous lymphangiomas on histology. (Robert A Schwartz & Geover Fernandez, 2009)

2.9 Imaging

MRI is the best imaging study; ultrasonography confirms the presence of macrocystic lymphangioma. Because of a high water content, lymphangioma is hyperintense on T2-weighted sequences. Macrocystic lesions often have fluid levels because of contained protein or blood. Contrast administration usually gives rim enhancement around large cysts or within septae, although the contents of the microcysts also can enhance, especially in patients with intralesional bleeding. Large or anomalous venous channels are part of lymphangioma. Teratoma and infantile fibrosarcoma can appear cystic on radiologic imaging and be confused with cystic lymphangioma. Magnetic resonance lymphangiography shows the dilated or interrupted lymphatic channels, especially in the limbs. Although conventional contrast lymphangiography is rarely performed, it is still used to determine the precise location of lymphatic or chylous leakage in a patient with a thoracic lymphatic anomaly. (Glenn R. Jacobowitz et al, 2005)


Figure 2.6 Cavernous lymphangioma. Approximately 10% of lymphangiomas of the neck in children extend into the antero-superior mediastinum. This specimen is from a 4-yr old boy who presented with soft fluctuant mass in the anterior neck. The image shows lymphatic channels lined by attenuated endothelial cells. Lymphoid aggregates are present to the right. (Web Patologi, 2009)


A B

Figure 2.7 Lymphangioma in a 13-month-old boy. (A) Transverse US image shows a hypoechoic multiloculated mass (). (B) Fat-suppressed long-TR MR image helps confirm a multiloculated mass with fluid levels and variable signal intensity (arrows). The mass is seen infiltrating the parotid, parapharyngeal, and masticator (M) spaces.


Figure 2.8 Fetal ultrasound demonstrating an anechoic, cystic structure with septation in the posterior neck. (Daniel H. Hechtman & David S. Shapiro, 2007)

2.10 Treatment

The risks of expectant management include infection, progressive growth and disfigurement, extension into previously uninvolved areas, dysphagia, airway compromise, and erosion into vascular structures. Asymptomatic cysts in the premature or smallfor- dates child may await growth and development of the infant. For the majority of patients there is no need to defer excision. (Baird M. Smith & Craig T.Albanese, 2006)

The two major complications of lymphangioma are intralesional bleeding and infection. Bleeding is either spontaneous or secondary to trauma. The lymphangioma suddenly enlarges, turns bluish in color, and is exquisitely painful. Analgesic medication, rest, and time are all that are needed. If there is a large collection of intralesional blood, prophylactic antibiotics may be indicated. Lymphangioma often swells coincident with a viral or bacterial infection anywhere in the body. This is a harmless event, presumably the result of changes in flow or stimulation of the lymphocytic component in the walls of the anomalous channels. Bacterial cellulitis in lymphangioma is more dangerous. Infection in a cervicofacial lymphangioma can cause obstruction of the upper airway and difficulty in swallowing. The incidence of cellulitis in cervicofacial lymphangioma is reported to be 17%. There is rapid onset of localized swelling, tenseness, erythema, pain, and systemic signs of toxicity. Parents become alert to these signs and symptoms and learn to administer antibiotics immediately. Often these infections cannot be controlled by oral antibiotics, and the child must be hospitalized for prolonged intravenous therapy. Blood cultures rarely isolate the responsible organism. The choice of antibiotic is based on the presumption that oral pathogens are the source of infection in the head and neck, and enteric organisms are responsible for infection in the trunk, perineum, or lower extremities. Aspiration of fluid from a macrocystic lymphangioma gives only temporary decompression and rarely provides a positive culture, and needle aspiration of cysts is no longer recommended except to decompress a cyst emergently and relieve airway obstruction. (Glenn R. Jacobowitz et al, 2005; John Aiken & Keith Oldham, 2006)

The two strategies for interventional treatment of lymphatic anomalies are sclerotherapy and resection. The treatment of lymphangiomas should be surgical excision, taking care to preserve all normal surrounding infiltrated structures. Only two thirds of lymphatic malformations are amenable to complete excision. One third requires partial excision or, in the case of extensive or complex lesions, staged excision because of involvement of vital structures within the lesion. Resection offers the only potential cure of lymphangioma. Often staged excision is necessary, and total removal is rarely possible. For each resection, the surgeon should :

(1) concentrate on a defined anatomic region,

(2) try to limit the blood loss to less than the patient’s blood volume,

(3) perform as thorough a dissection as possible (given anatomic restrictions and preserving vital structures), and

(4) be prepared to operate for as long as necessary. Neural and vascular structures must be dissected painstakingly; otherwise, disappointing results are expected. (Glenn R. Jacobowitz et al, 2005; Iraklis I. Pipinos & B. Timothy Baxter, 2004; John Aiken & Keith Oldham, 2006)

Lymphangioma must be macrocystic to permit injection of sclerosant. The commonly used sclerosing agents are pure ethanol, sodium tetradecyl sulfate, and doxycycline. More recently, large cystic lesions in locations difficult to manage surgically have been treated by injection of OK-432, a monoclonal antibody produced by incubation and interaction of Streptococcus pyogenes with penicillin. OK-432 (a killed strain of group A Streptococcus pyogenes) is also used for macrocystic lymphangioma. At present this treatment remains experimental but has demonstrated success in some difficult cases. Injection of sclerosing agents, most commonly bleomycin, has been used but is associated with significant potential complications of infection, gastrointestinal problems, and pulmonary fibrosis. (Glenn R. Jacobowitz et al, 2005; John Aiken & Keith Oldham, 2006)

Other techniques (i.e., cryotherapy, diathermy, sclerotherapy) have marginal success, and may exacerbate infection. Sclerosing agents may have a role in the therapy of cystic hygromas in situations in which anatomy prevents complete surgical resection. Therapy in these special situations may include repeated aspiration of the macrocystic lesions and injection of OK-432 (picibanil), a sclerosing agent. A pronounced inflammatory response can occur with the treatment, necessitating observation for airway compromise. (Daniel H. Hechtman and David S. Shapiro, 2007)

Prolonged suction drainage is necessary after resection. Immediate postoperative complications include protracted serous drainage, hematoma, and cellulitis. Often a cystic area must be tapped repeatedly after the operation to remove serous fluid and to allow the cutaneous flaps to adhere. (Glenn R. Jacobowitz et al, 2005)

Lymphangioma in particular areas demands specialized surgical expertise. Cutaneous lymphangioma (lymphangioma circumscriptum) must be resected widely, and the defect often requires closure with a split-thickness skin graft. Management of orbital lymphangioma necessitates craniofacial surgical techniques. Cervical and axillary lesions require experience in the dissection of the brachial plexus. Cervicofacial lymphangioma with associated maxillary and mandibular overgrowth necessitates orthognathic correction. Mediastinal lymphatic anomalies must be teased from the cardiovascular structures and the vagus, phrenic, and recurrent laryngeal nerves. Intrapelvic and extrapelvic lymphangioma require a thorough knowledge of the anatomy of the ischiorectal fossa and sciatic nerve. (Glenn R. Jacobowitz et al, 2005)

Radiation treatment has not been of benefit in the treatment of lymphatic malformations and causes significant morbidity in the growing child. (John Aiken & Keith Oldham, 2006)

2.11 Complication and Recurrences

The two major complications of lymphangioma are intralesional bleeding and infection. Management of cystic hygromas universally includes surgical excision. With surgical excision, recurrence rates for cystic hygroma have been reported at 6% to 50%. Recurrence of cystic hygromas can be attributed to previously unidentified cystic tissue, or incompletely resected lesions. (Daniel H. Hechtman and David S. Shapiro, 2007)

The recurrence rate is 40% after incomplete excision and 17% after macroscopically complete excision. The surgeon should not be surprised if postoperative imaging shows that the resection was less than estimated in the operating room. Regrowth and re-expansion from microcystic channels are responsible for postoperative recurrence. Regeneration also produces the typical warty vesicles in the surgical scar. (Glenn R. Jacobowitz et al, 2005)

In cystic hygroma, large cysts can cause dysphagia, respiratory problems, and serious infection if they involve the neck. A cystic lymphangioma of the scrotum may present as an acute scrotum, owing to the rare complication of hemorrhage. (Robert A Schwartz & Geover Fernandez, 2009)

2.12 Differential Diagnosis

a. Lymphadenopathy

When the neck nodes are firm and fixed, and others also are present in the axillae or groin, or the history suggests the presence of a hematologic malignancy, excisional biopsy is indicated. In these cases, a chest radiograph must be obtained to evaluate whether a mediastinal mass also is present. The presence of a large mediastinal mass should be identified preoperatively, as this may cause airway compression when muscle relaxants are administered. Under these cirumstances, tissue should be obtained under local anesthesia. The tissue is sent to pathology fresh for evaluation. (Henri R. Ford, et al, 2007)

b. Thyroglossal Duct Remnants

The thyroid gland buds off the foregut diverticulum at the base of the tongue in the region of the future foramen cecum at 3 weeks of embryonic life. As the fetal neck develops, the thyroid tissue becomes more anterior and caudad until it rests in its normal position. The "descent" of the thyroid is intimately connected with the development of the hyoid bone. Residual thyroid tissue left behind in the migration may persist and subsequently present in the midline of the neck as a thyroglossal duct cyst. The mass is most commonly appreciated in the 2- to 4-year-old child when the baby fat disappears and irregularities in the neck become more readily apparent. Usually the cyst is encountered in the midline at or below the level of the hyoid bone, and moves up and down with swallowing or with protrusion of the tongue. Rarely, midline ectopic thyroid tissue masquerades as a thyroglossal duct cyst, and may represent the patient's only thyroid tissue. Therefore, if there is any question regarding the diagnosis or if the thyroid gland cannot be palpated in its normal anatomic position, it is advisable to obtain a nuclear scan to confirm the presence of a normal thyroid gland. The presence of malignancy in a thyroglossal cyst should be suspected when the cyst grows rapidly, or when the ultrasound demonstrates a complex anechoic pattern or the presence of calcification. (Henri R. Ford, et al, 2007)

c. Lymphoma

Lymphoma is a type of blood cancer that occurs when lymphocytes--white blood cells that help protect the body from infection and disease--begin behaving abnormally. Abnormal lymphocytes may divide faster than normal cells or they may live longer than they are supposed to. (Lymphoma Research Foundation, 2010)

Lymphoma may develop in many parts of the body, including the lymph nodes, spleen, bone marrow, blood or other organs. (Lymphoma Research Foundation, 2010)

There are two main types of lymphomas are Hodgkin lymphoma (HL) that involves the Reed-Sternberg cells, and Non-Hodgkin lymphoma (NHL) that does not involve Reed-Sternberg cells. (Lymphoma Research Foundation, 2010)

Common symptoms include swelling of lymph nodes, which may or may not be painless, fever, unexplained weight loss, sweating (often at night), chills, lack of energy, and itching. At the end of the day, the only true way to diagnose lymphoma is to do a biopsy of the suspect tumour/tissue. Examinations of blood is necessary to diagnose lymphoma, where large increases in the levels of lymphosit will lead to the disease, after that it is should performed a biopsy to make diagnostic of lymphoma. (Lymphoma Research Foundation, 2010)

2.13 Prognosis

Lymphangiomas are benign hamartomatous malformations instead of true neoplasms. The prognosis for lymphangiomas is excellent. (Robert A Schwartz & Geover Fernandez, 2009)

CHAPTER III

CONCLUSION

Lymphatic malformations are benign vascular lesions of the lymphatic system. They encompass a wide spectrum of abnormalities, including cystic lymphatic lesions (formerly referred to as lymphangioma), lymphangiectasias, and lymphedema. Lymphangioma result from maldevelopment and obstruction of the lymphatic system. Lymphangioma more common in children. Clinical features depends on site of the lymphangioma in the body. Two strategies for interventional treatment of lymphatic anomalies are sclerotherapy and resection. And lymphangioma have excellent prognosis.

REFERENCES

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11. Ramesh Venkatesh and HL Trivedi. 2008. Facial Lymphangioma with Orbital Involvement In: Bombay Hospital Journal, Vol. 50, No. 2, 2008. From: www.bhj.org/journal/2008_5002_april/download/page-305-309.pdf date 13 April 2010.

12. Robert A Schwartz and Geover Fernandez. 2009. Lymphangioma In: E Medicine. From: http://emedicine.medscape.com/article/1086806-overview date 13 April 2010.

13. Web Patologi. 2009. Cystic Lymphangioma : Mediastinum. From http://webpathology.com/image.asp?case=412&n=5 Date 14 April 2010.

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