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 group, M group, R 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 (or cancerous) 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:
- Simple excision (removal of the tumour and surrounding tissue).
- Curettage ( a procedure that involves scraping lesions off of bones).
- Organ transplant.
- Radiation therapy.
- Cryotherapy.
- Photodynamic therapy.
- Immunotherapies.
- Targeted therapies.
- Corticosteroids.
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia treatment options page.
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.
Early 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/diagnosing
If your doctor suspects you have an L group histiocytic disorder, they will order a variety of tests to confirm the diagnosis and refer you to a specialist for treatment.
Physical examination
Your doctor will collect your overall medical history, as well as your current symptoms. Following this, they may examine your body to check for any abnormalities.
Neurological exam
A neurological examination assesses sensory and motor functions, and can generally be done in your GPs office. The doctor may check your vision, hearing, balance, coordination, strength and reflexes, depending on the signs and symptoms you have described. Any problem that is detected in this exam can help determine which portion of the CNS needs further investigation.
Urine & blood tests
Urine and blood tests are used to assess overall health and detect any abnormalities. Some of these tests may include:
- General blood test to assess overall health.
- Full blood count, which measure the levels of red blood cells, white blood cells and platelets.
- Liver function test.
- Blood chemistry and/or blood hormone studies, which analyse the levels of certain hormones and other substances in the blood.
- Genetic testing to check for any abnormalities, specifically with the BRAF, MAP2K1, RAS and ARAF genes.
- Water deprivation test, which analyses urine output on little water.
- Urinalysis, which analyses the colour of your urine and its contents (e.g., sugar, protein, red and/or white blood cells etc.).
Imaging tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), ultrasound, bone scan and/or positron emission tomography (PET scan), depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and look for signs of metastasis.
Pulmonary function test (PLT)
A pulmonary function test, or lung function test, determines how well your lungs are working. This test measures the amount of air the lungs can hold, as well as airflow in and out of the lungs, how much oxygen is used and how much carbon dioxide is exhaled.
Exploratory procedures
You may require an exploratory procedure may be required if the imaging scans were inconclusive, or if there were any abnormalities detected in your blood/urine tests.
Bone marrow aspiration
This process involves inserting the needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow. These samples will then be analysed for abnormalities.
Endoscopy
An endoscopy is a day procedure that is often performed to examine the tracts of the digestive system. To look for LCH, the doctor will place a long, thin tube with a light and a camera attached (endoscope) into your mouth or nose to check for any abnormalities.
Bronchoscopy
A bronchoscopy is a day procedure that examines the trachea and lungs. A long, thin tube with a light and camera attached (bronchoscope) is inserted through the mouth or nose and into trachea and lungs to check for any abnormalities.
Biopsy
Once the location(s) of the cancer has been identified, the doctor will perform a biopsy to remove a section of tissue using a needle. The tissue sample will then be analysed for cancer cells. This can be done by a fine needle aspiration (FNA) or a core needle biopsy (CNB).
Prognosis (Certain factors affect the prognosis and treatment options)
While it is not possible to predict the exact course of the disease, your doctor may be able to give you a general idea based on the rate and depth of tumour growth, susceptibility to treatment, age, overall fitness, and medical history. Generally, early-stage L group histiocytic disorders have a better prognosis and survival rates. However, if the tumour has become malignant and spread, the prognosis may not be as good and there may be a higher risk of recurrence. It is very important to discuss your individual circumstances with your doctor to better understand your prognosis.
References
Some references are to overseas websites. There may be references to drugs and clinical trials that are not available here in Australia.