Chronic multifocal Langerhans cell histiocytosis

History

Evidence of the disease has been found in a mummy dating to 900–790 B.C. The condition was described by Alfred Hand Jr. in 1893, Arthur Schüller in 1915, and Henry Asbury Christian in 1919. In 1924 and 1933, Letterer and Siwe described a fatal childhood form with hepatosplenomegaly and bone damage.

In 1940, Lichtenstein and Jaffe identified a self-limiting form with isolated bone lesions. Recognizing histiocytes in biopsies, Lichtenstein grouped these as Histiocytosis X. In 1973, Nezelof identified the abnormal cell as Langerhans-like, and by the 1980s the term Langerhans cell histiocytosis was accepted. The Histiocyte Society published classification and diagnostic criteria in 1987.

Signs and symptoms

The classic triad of bulging eyes, lytic bone lesions (often in the skull with a punched-out pattern), and diabetes insipidus occurs in about 25% of cases. Skin may show rashes, bumps, or ulcers, and bones can be painful. Enlarged lymph nodes, fever, weight loss, and signs of lung or liver disease may appear. Facial asymmetry, ear infections, and oral findings such as mouth ulcers, swollen gums, loose teeth, and jaw destruction resembling advanced gum disease are reported.

Cause

The condition results from a genetic mutation in the MAPKinase pathway occurring during early development. It originates from a dendritic cell, not a histiocyte as previously thought.

The mutation attracts lymphocytes, macrophages, and eosinophils to dendritic cells, causing damage in any organ except the heart and kidneys. Although lesions contain high cholesterol, blood cholesterol is usually normal. Some sources classify it as a cancer; others explicitly state it is not.

Diagnosis

MRI may reveal bone destruction, thickening of the pituitary stalk, prominent perivascular spaces, cystic pituitary changes, white matter signs, a hypothalamic mass, or meningeal enhancement. X-rays often show sharp punched-out skull lesions and generalized alveolar bone destruction with displaced teeth. Blood tests may indicate anemia and, less commonly, low white blood cell or platelet counts. PET scans can be useful, but tissue biopsy confirms the diagnosis.

Did You Know?

• The disease was once thought to be a lipid storage disorder because lesions have high cholesterol content.
• A good response to chemotherapy within the first six weeks of treatment indicates a better prognosis.
• The prognosis is poor if the liver, spleen, lung, or bone marrow is affected.