Langerhans Cell Histiocytosis (LCH)

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 on Langerhans cell histiocytosis (LCH), a common subtype of L group histiocytic disorders. It is defined as a rare cancer-like disease that causes excess production of a certain type of dendritic immune cell, known as Langerhans cells. 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.

LCH is more common in boys, and is generally diagnosed in children (especially children under the age of 5). However, anyone can develop this disease.

Types of Langerhans Cell Histiocytosis

There are various types of LCH, which can be classified by the number of bodily systems affected.

Single-System LCH

Single-system LCH is the most common form of LCH, and occurs when the disease is only present in one organ or system of the body. It is most commonly found in children between the ages of five and ten, and is generally discovered as a bone lesion. Single-system LCH can be aggressive, however it can have an excellent prognosis.

Multi-System LCH

Multi-system LCH is a less common form of LCH, and occurs when the disease is present in two or more organs or bodily systems. It is most commonly found in children under three years old or in adults. Multi-system LCH can be aggressive, and may not have as good of a prognosis as single-system LCH.

Eosinophillic Granuloma

Eosinophilic granuloma is the most common form LCH that generally appears as a benign bone lesion. It is most commonly found in the skull, but can also be found in the mandible (jaw), spine, ribs, long bones and less commonly the skin. In most cases, eosinophilic granuloma is found as a single lesion, will require little to no treatment and generally has a good prognosis. In rare instances, multiple bones or organ systems may be involved requiring more extensive treatment.

Hand-Schüller-Christian Disease

Hand-Schüller-Christian disease is an intermediate form of LCH that generally affects multiple areas of one organ system (often including the bone). It is often associated with a triad of diabetes insipidus (a rare disorder where the body produces too much urine), exophthalmos (medical term for bulging eyes) and bone lesions (most commonly in the skull). Hand-Schüller-Christian has a varying level of aggressiveness and prognosis depending on how many organs and lesions are involved.

Letterer-Siwe Disease

Letterer-Siwe disease is a rare form of LCH that generally affects many organ systems of the body. It is most commonly diagnosed before the age of three, and most commonly affects the lungs, bones, liver and lymph nodes. Letterer-Siwe disease is often very aggressive, and may not have as good of a prognosis as other types of LCH.

Treatment

Each patient with LCH 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. Generally, the treatment of LCH is based upon whether it is single or multi-system LCH, and which organs/systems are, or could potentially be, affected.

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 patients with LCH may include:

Surgery, potentially including:
- Simple excision (removal of tumour and surrounding tissue).
- Curettage (a procedure that involves scraping the lesions off of bones).
- Organ transplant.
Radiation therapy.
Cryotherapy.
Photodynamic therapy.
Immunotherapies.
Targeted therapies.
Watch and wait.
Clinical trials.
Palliative care.

For more information on the treatment options, please refer to the Rare Cancers Australia Treatment Options page.

Some of the information regarding treatment was obtained from the Langerhans Cell Histiocytosis Treatment (PDQ) page published by the National Cancer Institute.

Risk factors

While the exact cause of LCH remains unknown, the following factors may increase the likelihood of developing this 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.

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.

Some of the information regarding risk factors was obtained from the Langerhans Cell Histiocytosis Treatment (PDQ) page published by the National Cancer Institute.

Early symptoms

The symptoms of LCH will vary depending on the location(s) of the disease.

General LCH symptoms

General symptoms of LCH that may occur in patients with the disease in any location include:

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

LCH affecting the bone and/or bone marrow

Some patients with LCH may appear asymptomatic. Symptoms of LCH affecting the bone include:

Localised bone pain.
Swelling or a lump over a bone.

If the patient has LCH in the bone marrow, some of these symptoms may also appear:

Easy bruising and/or bleeding.
Fever.
Frequent and/or recurrent infections.

LCH affecting the skin and nails

The symptoms of LCH in the skin and/or nails will vary between infants and children/adults.

Infants

In infants, LCH usually appears on the skin, but not the nails. Some of these symptoms include:

Flaking of the scalp. This may resemble the condition ‘cradle cap’.
Flaking in creases of the skin, such as the armpit, inner elbow or perineum (area between the genitals and anus).
Skin rash that may appear anywhere on the body:
- Raised.
- Brown or purple in colour.

Children and adults

The symptoms of LCH of the nails and skin in adults may include:

Flaking of the scalp. This may resemble dandruff.
Skin rash that may appear:
- Raised.
- Brown or purple in colour.
- Crusty.
- Itchy and/or painful.
- Occurring on the abdomen, pelvic region back and/or chest.
Ulcers and/or bumps on the scalp, behind the ears, under the breasts or in the pelvic region.
Fingernails that have fallen off or appear discoloured.

LCH affecting the mouth

Symptoms of LCH in patients with the disease in their mouth may present with some of the following symptoms:

Swollen gums.
Sores that may appear on the roof of the mouth, inside of the cheeks, on the tongue or on the lips.
Dental issues, such as teeth falling out or becoming uneven.

LCH affecting the lymph nodes and/or the thymus

Patients with LCH in the lymph nodes or thymus may present with some of the following symptoms:

Swollen lymph nodes.
Persistent cough.
Changes in breathing, such as accelerated breathing or difficulties breathing.
Superior vena cava syndrome, which has its own set of symptoms:
- Coughing.
- Difficulty breathing (dyspnea).
- Swelling of the face, neck and/or upper arms.

LCH affecting the endocrine system.

The endocrine system is the network of organs and glands in the body that is responsible for the production of hormones. Symptoms of LCH in the pituitary gland of the endocrine system may include:

Diabetes insipidus, which causes extreme thirst (polydipsia) and excess urine production (polyuria).
Growth/developmental delay.
Early or late puberty.
Obesity.

Symptoms of LCH in the thyroid gland of the endocrine system may include:

Swollen thyroid gland.
Hypothyroidism (underactive thyroid), which has varying symptoms between infants, children/adolescents and adults.
Difficulty breathing.

LCH affecting the eye

The most common symptom of LCH affecting the eye is vision changes, such as difficulties seeing, blurriness and/or blindness.

LCH affecting the central nervous system (CNS).

The central nervous system (CNS) is responsible for all sensory and motor functions in the body, and is composed of the brain and spinal cord. Symptoms of LCH in the CNS may include:

Changes in balance and coordination.
Difficulty walking.
Difficulties with speaking and/or seeing.
Diplopia (double vision).
Headaches.
Changes in behaviour and/or personality.
Memory difficulties.
Altered mental status.

LCH affecting the liver, spleen and/or abdomen

Symptoms of LCH affecting the liver, spleen and/or abdomen may include:

Abdominal pain and/or swelling.
Diarrhoea.
Unexplained weight loss.
Jaundice (yellowing of skin and/or whites of the eyes).
General itchiness.
Easy bruising and/or bleeding.
Fatigue

LCH affecting the lungs

Symptoms of LCH affecting the lungs may include:

Collapsed lung, which carries its own set of symptoms:
- Chest pains and/or tightness.
- Breathing difficulties.
- Fatigue.
- Skin turning a bluish colour due to a lack of oxygen.
Difficulties breathing (dyspnea).
Persistent dry cough.
Chest pain

Not everyone with the symptoms above will have cancer, but see GP if you are concerned.

Some of the information regarding symptoms was obtained from the Langerhans Cell Histiocytosis Treatment (PDQ) page published by the National Cancer Institute.

Diagnosis/diagnosing

If your doctor suspects you have LCH, 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 & biopsy

You may require an exploratory procedure 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.

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 LCH has a better prognosis and survival rates. However, if the cancer is advanced and has spread, the prognosis may not be as good and there may be a higher risk of cancer 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.}