Is melanoma an associated cutaneous disorder in Erdheim-Chester disease (ECD)?

From the Guidelines

No, melanoma is not typically associated with Erdheim-Chester disease (ECD). Erdheim-Chester disease is a rare non-Langerhans cell histiocytosis characterized by the abnormal accumulation of histiocytes in various tissues and organs. The cutaneous manifestations of ECD most commonly include xanthelasma-like lesions around the eyelids and xanthomas on the trunk or extremities, which appear as yellow-orange papules or nodules, as described in the study by Goyal et al 1. These skin findings are due to the infiltration of foamy histiocytes rather than melanocytic proliferation.

Some key points to consider in ECD include:

• Cutaneous manifestations occur in up to 30% of patients, with half of these patients having cutaneous involvement at diagnosis 1
• The most common cutaneous manifestations are xanthelasma-like lesions around the eyes, but the face, neck, and inframammary, axillary, and inguinal folds can also be affected 1
• While patients with ECD may develop various complications including bone pain, diabetes insipidus, exophthalmos, and cardiovascular or central nervous system involvement, melanoma is not considered a characteristic or associated cutaneous disorder in this disease
• The pathophysiology of ECD involves BRAF V600E mutations in approximately 50-70% of cases, which is distinct from the genetic alterations typically seen in melanoma, despite some overlap in BRAF mutation status 1

Patients with ECD require monitoring for their specific disease manifestations rather than melanoma surveillance beyond routine skin checks recommended for the general population. The study by the Mayo Clinic Histiocytosis Working Group 1 provides a comprehensive overview of the diagnosis and evaluation of adult patients with histiocytic neoplasms, including ECD, and highlights the importance of distinguishing ECD from other histiocytic disorders.

From the Research

Erdheim-Chester Disease and Cutaneous Manifestations

• Erdheim-Chester disease (ECD) is a rare form of non-Langerhans cell histiocytosis that can present with various cutaneous manifestations, including xanthelasma-like lesions, nonfacial cutaneous xanthomas, panniculitis-like lesions, and granuloma annulare-like lesions 2, 3.
• The most common cutaneous manifestation of ECD is the presence of periorbital xanthelasma-like lesions, which can be distinguished from classic xanthelasma palpebrarum by their involvement of the reticular dermis and presence of multinucleated or Touton cells 3.
• Cutaneous involvement is found in approximately 25% of patients with ECD, and associated symptoms at presentation can include bone/extremity pain, weight loss, and other constitutional symptoms 2, 3.

Association with Melanoma

• There is no direct evidence in the provided studies to suggest that melanoma is a commonly associated cutaneous disorder in Erdheim-Chester disease 2, 3, 4, 5, 6.
• The studies primarily focus on the cutaneous manifestations of ECD, such as xanthelasma-like lesions and other non-malignant skin lesions, without mentioning melanoma as a associated condition.

Diagnosis and Treatment

• Diagnosis of ECD requires a combination of clinical, radiographic, and pathological features, including biopsy demonstrating characteristic histopathologic features and detection of somatic MAPK pathway mutations 6.
• Treatment of ECD typically involves therapy with interferon-α (IFN-α) and/or MAPK inhibition, and is recommended at diagnosis in all patients, except for those with minimally symptomatic disease 4, 6.