Lymphangiomatosis (limf-an-jee-oh-mah-TOE-sis). In medical terminology lymphangiomatosis means: lymphatic system (lymph) vessel (angi) tumor or cyst (oma) condition (tosis). There is no standard definition describing this disease that has been agreed to by the medical/scientific community.

The lymphatic system, like the blood circulatory system, is composed of an extensive network of vessels that connect with lymph nodes throughout the body. All parts of the body are touched by lymphatics, except the central nervous system, which is lacking any lymphatics. This complex system handles the body's internal fluids, separate from blood, and contributes enormously to the immune function. An abnormality or lymphatic malfunction (LM) may take the form of a lymphangioma or lymphatic lesion.

Lymphangiomas are considered to be either congenital malformations of the lymphatic system, or true neoplasms (new growth tumors); the cause is unclear. Lymphangioma is solitary and localized; lymphangiomatosis is a diffuse (scattered) condition. Lymphangiomatosis has been characterized as a rare pathological condition in which multiple lymphangiomas appear in various body constituents and can involve the skeletal system, connective tissue, and visceral organs which can obstruct, compress, or destroy vital structures. Occasionally, they are diffuse within one organ, or they can become generalized to involve multiple organs. Although considered benign and not metastatic, lymphangiomatosis can be persistently invasive, making treatment challenging and problematic.

A wide and varied number of terms have been used in the medical literature to describe, classify, and reference lymphangiomas and lymphangiomatosis (see synonyms below). This reflects the fact that the biological nature of this condition is not understood and is controversial. There is no standard definition, nor are there any standard diagnoses or treatments. Lymphangiomatosis presents in a number of ways, has been described in a variety of terms, and for these reasons is often misdiagnosed. It has been recommended by medical professionals who have seen the disease, that a multidisciplinary approach be chosen in forming the patient's medical team.

What causes lymphangiomatosis?

The cause, or etiology of lymphangiomatosis is not yet known. It has been presumed to be caused by a multi-focal malformation of the lymphatic system - alone, or combined with malformation of the vascular system. Other pathogeneses have been suggested and reviewed - none studied extensively, so the cause is poorly understood. The lymphatic system begins to appear in the early embryonic stage and a congenital malformation is suggested. Inflammation, neoplasm, and lymphatic obstruction have been suggested as well.

Who has lymphangiomatosis?

Lymphangiomatosis can occur at any age, but the incidence is highest in infants and young children. It typically presents in the first two decades of life. The disease does not appear to be inherited, and seems to have no sex predilection or familial tendency. It has been found to affect people of every race, age and gender. Because it is so rare and commonly misdiagnosed, it is not known exactly how many people are affected by this disease.

What are the symptoms of lymphangiomatosis?

Lymphangiomatosis is a multi-system disorder. Symptoms depend on where in the body it presents. Cases have been reported differing in severity, presentation, course, response to treatment, and outcome. Although the onset of symptoms may be very early in infancy, patients are often misdiagnosed, and a definite diagnosis is usually delayed because of the rarity and slow course of the disease.

Early in the course of the disease, patients are usually asymptomatic, but as these abnormally proliferating lymphatic channels (also referred to as benign neoplasms, tumors, or cysts) grow, they are capable of massive expansion and infiltration into surrounding tissues, bone, and viscera, irrespective of anatomical barriers. Soft tissue and viscera symptoms depend on the organ system involved and the extent of the disease. Although many patients may be asymptomatic, pleural involvement and osteolytic (bony) lesions can bring on respiratory difficulty and pathological fracture respectively. Chronic bone pain often accompanies the manifestation of skeletal lesions - commonly a result of an impending fracture. Dyspnea (breathlessness) may result from compression caused by mediastinal/pulmonary masses or from interstitial (organ/tissue space) fluid infiltration.

Cardiacthoracic ( mediastinum, lung, pleura, heart) - In the cardiothoracic region, the mediastinum, lungs, pleura, heart or pericardium, may be involved independently or at the same time. Symptoms that arise from respiratory involvement include a chronic cough, wheezing, dyspnea (shortness of breath), fever, chest pain, rapid heart beat, and coughing up blood. These symptoms are usually present due to a pneumothorax that has been caused by pleural effusions and the collection of fluid in the pleural cavity called a chylothorax.

Gastrointestinal - Patients that present with problems in the area of the stomach, intestines, and/or peritoneal cavity may experience abdominal pain & distension, nausea, vomiting, diarrhea, and protein losing enteropathy. This is largely due to the presence of loculated pockets or multiple large cyst-like cavities filled with fluid in the peritoneal cavity or as lesions or nodules within the small intestine or colon. These cysts can cause significant pressure on adjacent structures. Intra-abdominal lymphangiomatosis is generally considered to be a developmental anomaly of the lymphatics, usually involving limited portions of the small intestine, spleen and liver, and may involve protein-losing enteropathy and intestinal bleeding.

Kidneys - Renal lymphangiomatosis may be unilateral or bilateral and can present with pain, a palpable mass or elevated blood pressure. It can easily be confused with other cystic diseases of the kidney. In the literature the few available case reports almost all emphasize their image findings as subcapsular and peripelvic accumulations of fluid.

Liver - Reports of lymphangiomatosis of the liver are extremely rare. When it does occur, it is usually associated with an enlarged liver (hepatomegaly) which may cause abdominal pain and displacement of surrounding organs.

Skeleton - Skeletal involvement can be an incidental finding. Bone involvement is usually asymptomatic unless significant loss of structural support results in pathological fracture, bone pain, or nerve compression by deforming vertebra. Occurrence is most commonly in the skull, ribs, pelvis, femur, humerus and vertebra. The cervicothorax involvement has included replacement of bone with lymph tissue, resulting in direct neural compression or bony instability.

Lesions have been reported in almost every bone and usually there is a gradual increase in the size of bone lesions over time. Lesion growth however can spontaneously start and stop at any time and without warning. Bony lesions can be associated with local pain, and present with pathological fractures; involvement in the spine may cause neurological deficit. It has been observed as well that lymphangiomatosis may involve the bone without affecting the overlying soft tissues. Replacement of a single or several contiguous bones by lymphangiomatous tissue is known as Gorham's disease, (described below). Gorham's disease is very rarely multi-centric; widespread bony involvement associated with diffuse soft tissue disease is characterized as generalized lymphangiomatosis.

The exact incidence of pure lymphangiomatosis involving the skeleton is not well documented - perhaps because of its clinical, radiologic, and histologic similarity to hemangiomas, and because of the common overlapping elements in both entities. Thus, multiple terms have been used, including: skeletal hemangiomatosis, cystic lymphangiomatosis of the bone, etc.

Spleen - Many patients with lymphangiomatosis of the spleen are asymptomatic and it is discovered incidentally though at times it can be accompanied by pain or discomfort in the upper left quadrant, anemia, or thrombocytopenia.

How is lymphangiomatosis diagnosed?

Medical diagnostic protocols recommend that a diagnosis should be made in association with clinical, radiologic, and histologic analysis. A clinical diagnosis may frequently be delayed because multi-system involvement often results in a variety of manifestations. Radiologically a number of conditions have to be considered in the differential diagnosis. Radiographic findings are non-specific and historically, imaging evaluation was performed using lymphangiography. CT scan and MRI are the current techniques used to evaluate lymphangiomas. Imaging is often helpful in distinguishing lymphangiomatosis from other vascular disorders and is commonly used for pre-operative planning. They are of particular importance because when revealed, multi-organ involvement suggests the diagnosis of lymphangiomatosis. Co-existence of bone lesions and chylothorax serve as an important diagnostic clue. Biopsy is stressed for accurate diagnosis. The histological diagnosis may be difficult to establish and several biopsies may be necessary. A high index of clinical suspicion is needed to arrive at an early, accurate diagnosis.

In differentiating, there are a number of disorders which have been cited in the differential considerations. These include: Langerhans cell, histiocytosis X, fibrous dysplasia, fibromatosis, lymphangioleimyomatosis (LAM), hemangiomatosis, Gorham's disease, and eosinophilic granulomatosis. There are many more listed in the medical literature. It has been observed that the histologic, radiologic, and clinical characteristics of lymphangiomatosis overlap those of Gorham's disease, massive osteolysis and those of hemangiomatosis so that these entities are grouped together as angiomatous bone lesions.

What are the treatments for lymphangiomatosis?

The treatment of lymphangiomatosis varies a great deal from patient to patient. It is for the most part palliative and is usually started due to a new symptom in an affected area. There is no standard approach and different treatments have been reported as working for some and not others. Sometimes several methods are exhausted before finding one that is effective and in some cases, no treatment has been reported as needed at all. For many cases reported though, intense intervention has been indicated, especially if the disease was reported as diffuse, or if the cardiothoracic region spine, or skull were reported as involved. To summarize, no single treatment modality has been reported to be proven effective for arresting this disease and there are no known treatments that prevent or control the disease itself.

 

Treatment modalities reported
Cardiothoracic		Pleurodesis, ligation of thoracic duct, pleurperitoneal shunt, radiation therapy, pleurectomy, surgical resection, thalidomide, Interferon Alpha2b, TPN nutrition, thoracentesis, medium chain triglyceride and high protein diet, chemotherapy, sclerotherapy, transplantion
Gastrointestinal		Interferon Alpha2b, sclerotherapy, resection, percutaneous drainage
Kidneys		Percutaneous drainage
Liver		Resection, transplantation
Skeleton		Interferon Alpha2b, bisphosphonates (i.e. pamidronate), surgical resection, radiation therapy, sclerotherapy, percutaneous bone cement, bone grafts, prosthesis, surgical stabilization
Spleen		Interferon Alpha2b, splenectomy

Synonyms, homonyms and miscellaneous names used in the literature to describe lymphangiomatosis

Lymphangiomatosis: generalized, diffuse, disseminated, multi-organ, pulmonary, thoracic, cystic, skeletal/extraskeletal, cranial, of the bone, of the spine, cervicothorax, abdominal, splenic, renal, etc.

Vascular Malformation: vascular anomaly, lymphatic malformation (microcystic or macrocystic). Lymphatic malformation (LM) is a classification from Mulliken-Glowacki (1982) which was adopted by the ISSVA in 1996.

Lymphangioma: cystic, mesenteric, retroperitoneal, abdominal, vertebral, etc.

Angioma: angiomatosis, hemangioma, hemangiomatosis

Gorham's disease, Gorham-Stout syndrome, disappearing, vanishing or phantom bone disease, massive osteolysis

*There is a great deal of debate and confusion surrounding the terminology used when a patient is given the diagnosis of lymphangiomatosis (or variation of the name). It is apparent that there's a need for a universal name for this disease that can be agreed upon and then communicated to the medical community so we're all on the same page. This will help physicians and we as a community to get a better grasp on how many people actually have this disease. We are making it a goal for the LGD Alliance to work with the medical community to try to find a consensus.

It is our hope that through the work of the LGD Alliance, progress will be made to help better understand the symptoms, diagnosing techniques and treatments for lymphangiomatosis. With increased research, discovering the cause, improving treatment and finding a cure may be well within our reach.

References:

The foregoing has been extracted from information provided from among the several hundred case reports in the medical literature. Abstracts are available from PubMed, the NIH medical database; full text is available generally from the publishing journal at a reprint fee. In addition the following references have been consulted:

Winegard, Bruce. Unlocking Medical Terminology. Prentice Hall 2006.

Taber, Clarence W. Taber's Cyclopedic Medical Dictionary. 20th edition. Philadelphia: F.A. Davis, 2005.

Last updated: 09/06/07