Histiocytic Disorders (L Group)

Histiocytic disorders are a group of rare disorders characterised by the abnormal accumulation of histiocytes, a type of immune cell often found in tissues that regulates immune functions. There are three primary types of histiocytes, including monocytes (plays a role in inflammatory and anti-inflammatory responses during an immune response), macrophages (responsible for ingesting and eliminating foreign substances during an immune reaction), and dendritic cells (initiate and regulate the adaptive immune response).

Histiocytic disorders are broadly classified into five different groups: L group, C groupM groupR group, and H group. The L group, or Langerhans group, are classified as diseases involving Langerhans cells (an immune cell responsible for initiating an immune response when coming into contact with a foreign material), such as Langerhans cell histiocytosis (LCH). The C group, also known as cutaneous and mucocutaneous non-Langerhans cell histiocytosis, are classified as non-Langerhans cell histiocytic disorders that are localised to the skin or mucosal surfaces, such as the mouth, nose, and gastrointestinal system. The M group, also known as malignant histiocytic disorders, are classified by the presence of malignant cells within the tumour(s). The R group, also known as Rosai-Dorfman disease and miscellaneous non-cutaneous non-Langerhans cell histiocytosis or sinus histiocytosis, are classified as non-Langerhans histiocytic disorders that often involve lymph nodes. The H group, also known as hemophagocytic lymphocytosis and macrophage activation syndrome, is composed entirely of hemophagocytic lymphohistiocytosis, a rare and aggressive disease caused by the overactivation of the immune system.

This page will focus specifically on L group histiocytic disorders, which includes Langerhans cell histiocytosis (LCH)Erdheim-Chester disease (ECD), indeterminate cell histiocytosis, and mixed LCH and ECD.

L group histiocytic disorders are slightly more common in males, with the average age of diagnosis varying between subtypes. However, anyone can develop this disease.

Types of L Group Histiocytic Disorders

There are four primary types of L Group histiocytic disorders, which are classified by the types of cells affected.

Langerhans Cell Histiocytosis (LCH)

Langerhans cell histiocytosis (LCH) is a rare cancer-like disease that causes excess production of a certain type of dendritic immune cell. More specifically, they form from Langerhans cells, which initiate an immune response when the body has come into contact with foreign material, such as bacteria. These cells are most commonly found in the skin, but can also be found in the bone/bone marrow, lymph nodes and thymus, eyes, endocrine organs, central nervous system, liver and spleen, and/or lungs.

For more information on LCH, please refer to the Rare Cancers Australia Langerhans Cell Histiocytosis page.

Erdheim-Chester Disease (ECD)

Erdheim-Chester disease (ECD) is a rare cancer-like disorder that causes an abnormal increase in a type of white blood cell (WBC) called histiocytes, which play a significant role in many vital immune functions. It is most commonly found as lesions on the long bones of the legs, however it can also develop in the cardiovascular system, central nervous system (CNS), and other organs within the body. ECD often affects many systems within the body.

Although ECD does not typically present with Langerhans cells, it was recently reclassified as an L group histiocytic disorder as both LCH and ECD share the MAPK pathway mutation(s).

For more information on ECD, please refer to the Rare Cancers Australia Erdheim-Chester Disease page.

Indeterminate Cell Histiocytosis (ICH)

Indeterminate cell histiocytosis is a rare subtype of L group histiocytic disorders that occurs when the disease presents with features of LCH and non-LCH. It is most commonly found on the skin, but can also occur in the lymph nodes and spleen. ICH is generally benign (non-cancerous), and often have an excellent prognosis.

Mixed LCH/ECD

Mixed LCH/ECD is a rare subtype of L group histiocytosis that occurs when the disease presents with features of both LCH and ECD. In most cases, ECD will present before or at the same time as LCH, however in rare instances LCH can present before ECD. Mixed LCH/ECD is often aggressive, and may not have as good of a prognosis as other histiocytic disorders.

Treatment

Each patient with an L group histiocytic disorder will present with a unique disease behaviour, with varying locations, and symptoms. As such, there is no one treatment method that will work for everyone, and there is no standard staging system for this disease.  Instead of staging and grading, your doctor will recommend a treatment plan based on the following factors:

  • Cancer location.
  • Whether or not the tumour(s) have spread.
  • Your age.
  • General health.
  • Treatment preferences.

Your doctor may recommend genetic testing, which analyses your tumour DNA and can help determine which treatment has the greatest chance of success. Your doctor will discuss the most appropriate course of treatment for you.

Treatment options for an L group histiocytic disorder may include:

  • Watch and wait (may be an option for some asymptomatic patients).
  • Surgery, potentially including:
    • Excision of the tumour.
    • Curettage.
    • Organ transplant.
  • Radiation therapy.
  • Cryotherapy.
  • Photodynamic therapy.
  • Immunotherapy.
  • Targeted therapy.
  • Corticosteroids.
  • Clinical trials.
  • Palliative care.

Risk factors

While the cause of L group histiocytic disorders remains unknown, the following factors may increase the likelihood of developing the disease:

  • Having a parent who was exposed to:
    • Certain solvents.
    • Metal, granite and/or wood dust in the workplace.
  • Having a family history of cancer or LCH.
  • Having previously been diagnosed with a thyroid disease.
  • Having a family history of thyroid disease.
  • Having had infections as a newborn.
  • Smoking.
  • Being unvaccinated as a child.
  • Being Hispanic.
  • Having mutations of BRAF, MAP2K1, RAS and/or ARAF genes.
  • Being diagnosed with Epstein-Barr virus.

Not everyone with these risk factors will develop the disease, and some people who have the disease may have none of these risk factors. See your general practitioner (GP) if you are concerned.

Symptoms

The symptoms of an L group histiocytic disorder often vary by subtype.

Symptoms of LCH

General symptoms of LCH may include:

  • Fever.
  • Unexplained sweating.
  • Unexplained weight loss.
  • Small pink or reddish-brown lesions.

LCH can also affect a variety of bodily structures and systems, including:

  • Bone and/or bone marrow.
  • Skin and/or nails.
  • Mouth.
  • Lymph nodes and/or thymus.
  • Endocrine system.
  • Eyes.
  • Central nervous system (CNS).
  • Liver, spleen and/or abdomen.
  • Lungs.

For more information on specific symptoms of LCH, please refer to the Rare Cancers Australia Langerhans Cell Histiocytosis page.

Symptoms of ECD

General symptoms of ECD may include:

  • Unexplained weight loss/loss of appetite.
  • Fever.
  • Fatigue.
  • Muscle and/or joint aches.
  • General feeling if discomfort.
  • Weakness.

ECD can also affect a variety of bodily structures and systems, including:

  • Bones.
  • Cardiovascular system.
  • Central nervous system (CNS).
  • Retro-orbital tissues.
  • Skin.
  • Lungs.
  • Retroperitoneum.

For more information on specific symptoms of ECD, please refer to the Rare Cancers Australia Erdheim-Chester Disease page.

Symptoms of ICH

General symptoms of ICH may include:

  • Pink to reddish nodules on the skin.
  • Non-itchy nodules on the skin.
  • Painless nodules on the skin.

These nodules often occur on the trunk or limbs, however can develop in other areas of the body.

Symptoms of Mixed LCH/ECD

The symptoms of mixed LCH/ECD are often a combination of both LCH and ECD symptoms.

Not everyone with the symptoms above will have cancer, but see your general practitioner (GP) if you are concerned.

Diagnosis

If your doctor suspects you have an L group histiocytic disorder, they may order the following tests to confirm the diagnosis and refer you to a specialist for treatment:

  • Physical examination.
  • Neurological examination.
  • Blood tests.
  • Urine tests.
  • Imaging tests, potentially including:
    • MRI (magnetic resonance imaging).
    • CT (computed tomography) scan.
    • X-ray.
    • Bone scan.
  • Pulmonary function test.
  • Exploratory surgery, potentially including:
    • Endoscopy.
    • Bronchoscopy.
  • Bone marrow aspiration.
  • Biopsy.

References

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