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.

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.

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.

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.