Xanthogranuloma

Juvenile xanthogranuloma, also known as JXG, is a rare, non-Langerhans cell histiocytosis that is usually benign and self-limiting.

It occurs most often in the skin of the head, neck, and trunk but can also occur in the arms, legs, feet, and buttocks. JXG can affect the eye, most commonly in young children with multiple skin lesions. Less commonly JXG may involve locations such as the lung, liver, adrenal gland, appendix, bones, bone marrow, pituitary gland, central nervous system, kidney, heart, small and large intestines, and spleen.

JXG involves the over-production of a kind of histiocyte called a dendritic cell (not a macrophage). These cells then accumulate and lead to various symptoms, depending on location. The cause of this disease is not known.

This disease may have been first reported by Rudolf Virchow in 1871 and again in 1905 by H.G. Adamson. In 1954, it was named juvenile xanthogranuloma to reflect the appearance of the cells under a microscope.

JXG mainly affects infants and small children with an average age of 2 years, although it can also occur in adults of all ages. Most of the time, it presents as a single skin lesion which varies in size, but children less than 6 months of age are more likely to have multiple lesions. It occurs at birth in about 10% of patients, and more males are affected than females. When JXG occurs in adults, it tends to be more complicated and is not known to spontaneously improve. The total number of patients with JXG is not known, but it may be higher than reported since this disease is sometimes misdiagnosed or may spontaneously improve in children.

Skin lesions are self-limited and rarely require treatment in most patients. Those with large abdominal masses, liver, bone marrow, or central nervous system involvement may do well with treatment such as chemotherapy similar to that used for Langerhans cell histiocytosis. Because this disease is so rare, no large studies have been performed, and there is no established, proven treatment for the more complicated cases. However, the Histiocytosis Association continues to work closely with an international group of physicians, known as the Histiocyte Society, who are dedicated to studying all of the histiocytic disorders. Through their combined efforts, awareness about JXG has increased, and progress has been made in the understanding of this disease.

Symptoms

Juvenile xanthogranuloma (JXG) can affect the skin only, the eye, and/or other locations in the body such as the lung, liver, adrenal gland, appendix, bones, bone marrow, pituitary gland, central nervous system, kidney, heart, small and large intestines, and spleen. The skin is the most common location of involvement and often does not require treatment. Eye lesions may or may not occur in the presence of skin involvement. Eye involvement with JXG needs to be treated to prevent visual problems. Systemic JXG, where lesions are present in more than one organ or body system, has been reported only in single- or small-case studies and usually requires treatment.

In one study of 129 patients (Kiel Pediatric Tumor Registry), 71% of the cases were diagnosed within the first year of life, and 81% were single skin lesions. There is an overall rate of 7% to 10% of patients (including adults) with multi-system JXG. Children younger than 6 months are more likely to have multiple lesions.

Skin lesions usually do not have symptoms such as pain or itching. They present as reddened, yellowish or brownish, slightly raised, and rubbery bumps on the skin. They may also appear in the fat layer beneath the skin.

JXG involving the eye, which is the second most common location, usually affects the iris, which is the colored, ring-shaped part of the eye. Lesions can, however, occur in other parts of the eye including the eyelid or inside of the eye, usually on one side only. Approximately one-half of patients with eye involvement also have skin lesions. Eye lesions are less likely to improve without treatment than skin involvement and can progress without treatment.

Because many patients with JXG of the eye are without symptoms, the diagnosis may be delayed and/or difficult. Eye lesions may be discovered by accident, often noted by watchful parents or the primary care physician. It is generally recommended that young children with multiple skin lesions be seen by an ophthalmologist every 3 months until 3 years of age.

Other symptoms related to JXG depend on the location of the disease. For example, if the bone marrow is involved, patients may have abnormalities in blood counts. Liver involvement can cause abnormalities in blood liver tests, as well as an elevated inflammation level (sedimentation rate) in the blood. Pituitary gland involvement can lead to diabetes insipidus.

It is important to remember that the diagnosis of JXG cannot be made on symptoms alone as it may present very similarly to LCH. It is therefore necessary to consult a knowledgeable physician to receive a thorough work-up and accurate diagnosis.

Diagnosis and Treatment

Juvenile xanthogranuloma is the disease most commonly confused with LCH. Presenting symptoms may be similar, so a biopsy is necessary to tell the difference between the two diseases.

When a biopsy is performed, a small piece of the tissue is obtained so that it can be viewed under a microscope by a pathologist. If the cells in the tissue have certain characteristics, the diagnosis of JXG can be made. JXG cells are negative for the presence of proteins called S-100 and CD1a, while LCH cells are positive. Instead JXG cells are positive for proteins called CD68 and factor XIIIa. A type of cell called a Touton giant cell is present in 85% of JXG cases. This is a histiocyte filled with fat that has a specific way of clustering that helps make the diagnosis.

An ultrasound may be performed to see if the JXG is also in the abdominal organs such as liver or spleen. In this procedure, high-energy sound waves are bounced off organs and tissue and make echoes, which form a picture of the internal body. In addition depending on the symptoms other tests such as CAT scans or MRI scans or bone X-rays may be done.

Treatment varies according to the extent and severity of disease involvement. Observation only is often a reasonable approach. Patients with a single lesion or just a few lesions usually need no therapy. Surgical removal may be undertaken for several reasons: to obtain a biopsy for diagnosis, when there is an organ-function problem because of disease, for cosmetic reasons or to remove scar tissue. Apart from these reasons, skin-only JXG in children should be observed without therapy. For the small percentage of patients who have symptomatic or rapidly growing disease, treatment with chemotherapy or low-dose radiation has been reported, although there is no standard treatment that is agreed upon. With eye involvement, steroids may be applied to the surface of a lesion, injected within the lesion, or taken in pill form. Rarely low dose radiation treatment may be given to the eye to prevent visual loss.

JXG in adults tends to be more complicated and is not known to improve spontaneously without treatment. However, most cases of childhood JXG are self-limited and resolve without treatment. Adult JXG does not tend to resolve spontaneously and usually requires some form of therapy. This may involve surgical removal alone or additional therapy depending on the clinical situation.

FAQ

What Do I Do Now?

A new diagnosis of a histiocytic disorder can bring feelings of being overwhelmed, bewildered, scared, angry, sad, disappointed, helpless, and sometimes even feelings of guilt.  It is a time filled with unknowns, change, and new people and situations.  Most parents feel ill-equipped to understand what is happening to their child and how to navigate through the illness to recovery.  There are, however, strategies and resources that can help you, your child, and other family members get through the uncertain times that lie ahead. One step at a time, you can gather information, create a support system, learn how to cope with stress, and become a strong advocate for your Histio Warrior as part of the medical team. The following tips and suggestions are provided to help guide you through this journey toward your Histio Warrior's good health.

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