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 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 nodessmall bean-shaped structures that filters harmful substances from lymph fluid. 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 benignnot cancerous, can grow but will not spread to other body parts (non-cancerous), and often have an excellent prognosisto predict how a disease/condition may progress and what the outcome might be.
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 testinga procedure that analyses DNA to identify changes in genes, chromosomes and proteins, which can be used to analyse tumour DNA to help determine which treatment has the greatest chance of success, 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 waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen (may be an option for some asymptomatic patients).
- Surgery, potentially including:
- Excision of the tumour.
- Curettagea procedure where the cancer is scraped out with a small, sharp instrument (curette).
- Organ transplant.
- Radiation therapya treatment that uses controlled doses of radiation to damage or kill cancer cells.
- Cryotherapythe process of freezing off cancerous tumours and/or lesions using liquid nitrogen.
- Photodynamic therapya procedure that involves inserting a light-sensitive drug (photosensitiser) to shrink and damage cancer cells when exposed to a light source.
- Immunotherapya treatment that uses a person's immune system to fight cancer.
- Targeted therapymedication that targets specific molecular features of cancer cells.
- Corticosteroidsa type of anti-inflammatory medication that is used to treat inflammation.
- Clinical trialsresearch studies performed to test new treatments, tests or procedures and evaluate their effectiveness on various diseases.
- Palliative carea variety of practices and exercises used to provide pain relief and improve quality of life without curing the disease.
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 marrowsoft, spongy tissue found in bones that makes blood cells.
- 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 examinationan examination of your current symptoms, affected area(s) and overall medical history.
- Neurological examinationan assessment of sensory and motor functions, such as vision, balance and coordination.
- Blood teststesting done to measure the levels of certain substances in the blood.
- Urine tests.
- Imaging tests, potentially including:
- MRI (magnetic resonance imaging)a type of medical imaging that uses radiowaves, a strong magnet and computer technology to create detailed images of the body.
- CT (computed tomography) scana type of medical imaging that uses x-rays and computer technology to create detailed images of the body.
- X-raya type of medical imaging that uses x-ray beams to create detailed images of the body .
- Bone scana type of medical imaging that uses a radioactive tracer to detect bone conditions or abnormalities.
- Pulmonary function testa test that examines how well your lungs are working.
- Exploratory surgerya surgical procedure used for conditions that cannot be confirmed by scans and tests alone, potentially including:
- Endoscopya procedure that involves inserting a long, flexible tube with a light and small camera (endoscope) into the body to view internal organs.
- Bronchoscopyan examination of the trachea and lungs with a small, flexible instrument known as a bronchoscope.
- Bone marrow aspirationa procedure that involves inserting a needle into the hipbone (or the breastbone in some cases) to remove samples of solid and liquid bone marrow.
- Biopsyremoval of a section of tissue to analyse for cancer cells.
