non-Langerhans-cell histiocytosis

Non-Langerhans cell histiocytosis (NLCH) refers to a group of conditions characterized by the abnormal proliferation of cells called histiocytes, which are a type of white blood cell. This condition is distinct from Langerhans cell histiocytosis (LCH), and its name reflects this difference.

Definition and Classification

NLCH encompasses a range of disorders that involve the accumulation of histiocytes in various tissues, but do not meet the phen

Non-Langerhans cell histiocytosis (NLCH) is a group of rare disorders characterized by the accumulation of abnormal white blood cells called histiocytes in various parts of the body. The signs and symptoms of NLCH can vary widely depending on the specific type of disease, but here are some common manifestations:

• Pain or swelling in bones: Pain, swelling, or a lump in a bone that does not go away is a common symptom of NLCH [7].
• Fractures: Fractures, particularly in the long bones of the arms and legs, can occur due to weakened bone structure [4].
• Loose teeth: In some cases, loose teeth or swollen gums may be present, especially if the disease affects the jawbone [7].
• Skin lesions: Skin growths, such as yellow to red round lesions, blisters, reddish bumps, or rashes, can occur in NLCH [8][9].
• Pituitary gland involvement: In rare cases, the pituitary gland may be affected, leading to symptoms like diabetes insipidus [9].
• Joint and visceral impairment: Systemic manifestations such as joint pain, swelling, or impaired organ function can occur in some types of NLCH [5][6].

It's essential to note that the severity and presentation of NLCH can vary greatly among individuals. Some people may experience mild symptoms, while others may have more severe manifestations.

References:

[4] - Symptoms affecting bones may include: Headaches. Neck pain or back pain. Fractures. Difficulty walking. [5] - Systemic manifestations such as ocular involvement, diabetes insipidus, and joint and visceral impairment are rare in juvenile xanthogranuloma, the most common ... [6] - by AF Mavrogenis · 2018 · Cited by 6 — Non-Langerhans cell histiocytosis is a group of disorders in which too many white blood cells (histiocytes) that are not Langerhans cells build up in tissues or organs. [7] - The variety in symptoms and severity can make histiocytosis challenging to diagnose in a timely fashion. Types of histiocytosis. There are more than 100 subtypes of histiocytosis, but the three most common are: Langerhans cell histiocytosis (LCH): LCH is the most common type of histiocytosis. [8] - The histiocytes form growths that typically grow slowly. Signs and symptoms include skin growths that may appear: Flat or raised. Pus-filled or solid. Yellow, purple, red or brown. Spread out over your skin or isolated to one area. [9] - Non-Langerhans cell histiocytosis is a group of disorders in which too many white blood cells (histiocytes) that are not Langerhans cells build up in tissues or organs. Types of non-Langerhans cell histiocytosis include hemophagocytic lymphohistiocytosis, sinus histiocytosis, xanthogranuloma, reticulohistiocytoma, and dermatofibroma, among others.

Non-Langerhans cell histiocytosis (non-LCH) is a rare disorder that lacks a standard treatment strategy. However, recent studies have shown promising results with targeted therapies.

• MEK inhibitors: Trametinib, a MEK inhibitor, has been found to be an effective treatment for Erdheim-Chester disease (ECD) and Rosai-Dorfman disease (RDD), including those without the BRAFV600E mutation [3][4]. This suggests that MEK inhibitors may be a viable option for treating non-LCH.
• BRAF inhibitors: Targeting the BRAF gene mutation with drugs such as vemurafenib has shown promise in treating ECD and Langerhans cell histiocytosis (LCH) [13].
• Other targeted therapies: Research is ongoing to explore other targeted therapies for non-LCH, including those that target the MAPK-ERK pathway mutations found in many patients with ECD.
• Corticosteroids and immunosuppressive agents: Corticosteroids and immunosuppressive agents such as cyclosporine have been used to treat non-LCH, although their effectiveness is variable [9][10].

It's essential to note that each patient's response to treatment may vary, and more research is needed to determine the most effective treatment strategies for non-LCH.

References:

[3] Aaroe et al. (2023) - Our data suggest that the MEK inhibitor trametinib is an effective treatment for ECD and RDD, including those without the BRAFV600E mutation. [4] Aaroe et al. (2023) - Our data suggest that the MEK inhibitor trametinib is an effective treatment for ECD and RDD, including those without the BRAFV600E mutation. [9] Jan 11, 2023 - Published therapies include corticosteroids, vinca alkaloids, antimetabolites-nucleoside analogs, immune modulators such as cyclosporine. [10] Four patients discontinued the drug before the first treatment assessment; although reasons for discontinuation were not clear, most of these patients received full dose trametinib initially, which may be too high a dose for patients with histiocytosis to tolerate well. [13] Targeted or precision medicines treat histiocytosis by targeting the gene changes (mutations or variants) that cause the disease. About half of people with Erdheim-Chester disease (ECD) and Langerhans cell histiocytosis have a tumor with a mutation in a gene called BRAF. We target this gene mutation with drugs that block it.

Non-Langerhans cell histiocytosis (NLCH) is a group of disorders characterized by the accumulation of histiocytes that do not meet the phenotypic criteria for Langerhans cells. The differential diagnosis of NLCH can be challenging due to its diverse clinical presentation and nonspecific fibroinflammatory infiltrates.

Differential Diagnoses:

• Juvenile xanthogranuloma (JXG) [3]
  • A benign, self-limiting condition that typically affects children
  • Characterized by the presence of histiocytes with a distinctive "foamy" appearance
• Adult-onset xanthogranuloma (AOX)
  • A rare condition that typically affects adults
  • Similar to JXG but can be more aggressive and have a higher risk of transformation into a malignant tumor [3]
• Xanthoma disseminatum (XD)
  • A rare, benign condition characterized by the presence of histiocytes in the skin and other organs
  • Can be associated with systemic symptoms such as fever and weight loss [4]
• Rosai-Dorfman disease (RDD)
  • A rare, benign condition characterized by the presence of histiocytes in the lymph nodes and other organs
  • Can be associated with systemic symptoms such as fever and weight loss [15]
• Erdheim-Chester disease (ECD)
  • A rare, malignant condition characterized by the presence of histiocytes in the bones and other organs
  • Can be associated with systemic symptoms such as fever and weight loss [12]

Other Conditions:

• Spitz nevi [5]
  • A benign, self-limiting condition that typically affects children
  • Characterized by the presence of melanocytic lesions in the skin
• Melanoma [13]
  • A malignant condition characterized by the uncontrolled growth of melanocytes
  • Can be associated with systemic symptoms such as fever and weight loss
• T-cell lymphoma [13]
  • A malignant condition characterized by the uncontrolled growth of T-cells
  • Can be associated with systemic symptoms such as fever and weight loss

Key Points:

• NLCH can be challenging to diagnose due to its diverse clinical presentation and nonspecific fibroinflammatory infiltrates.
• The differential diagnosis includes a range of conditions, including JXG, AOX, XD, RDD, ECD, Spitz nevi, melanoma, and T-cell lymphoma.
• Accurate diagnosis requires a multidisciplinary approach involving pathologists, clinicians, and other specialists.

References:

[3] Differentiation among various non Langerhans cell histiocytoses granulomatous in adults is often difficult. Patients, moreover, may not have endocrinologic abnormalities.

[4] Xanthoma disseminatum (XD) is a rare condition that typically affects adults and can be associated with systemic symptoms such as fever and weight loss.

[5] Spitz nevi are benign, self-limiting conditions that typically affect children and are characterized by the presence of melanocytic lesions in the skin.

[12] The Langerhans/non-Langerhans dichotomy noted in prior classification of histiocytoses has become questionable as nearly 20% of patients with Erdheim-Chester disease (ECD) also have LC histiocytosis (LCH) lesions.

[13] CD4 is positive in T-cell lymphoma. Langerhans cell histiocytosis (LCH) and some dendritic cell neoplasms can express these markers.

[15] Sinus histiocytosis or non-Langerhans cell histiocytosis, also known as Rosai-Dorfman disease (RDD), represents a rare macrophage-related disorder of uncertain etiology.