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 cellsthe basic structural and functional unit of all living things (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 localisedaffecting only one area of body to the skin or mucosal surfaces, such as the mouth, nose, and gastrointestinal system. The M group, also known as malignantcancerous, may grow and spread to other areas of the body 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 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 prognosisto predict how a disease/condition may progress and what the outcome might be.
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 benignnot cancerous, can grow but will not spread to other body parts 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), proptosisbulging or protrusion of one or both of the eyes out of the eye sockets, also known as exophthalmos, 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 stagingthe process of determining how big the cancer is, where it started and if it has spread to other areas 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 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 tumoura tissue mass that forms from groups of unhealthy cells 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:
- Surgerytreatment involving removal of cancerous tissue and/or tumours and a margin of healthy tissue around it to reduce recurrence, potentially including:
- Tumour excisionto surgically remove/cut out.
- Curettagea procedure where the cancer is scraped out with a small, sharp instrument (curette).
- Organ transplanta surgical procedure that involves removing a failing or damaged organ and replacing it with a healthy one from a donor.
- 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.
- Watch and waitthe close monitoring of a cancer without giving treatment until symptoms appear or worsen.
- 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.
Some of the information regarding treatment was obtained from the Langerhans Cell Histiocytosis Treatment (PDQ) page published by the National Cancera disease where abnormal cells split without control and spread to other nearby body tissue and/or organs 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 riskthe possibility that something bad will happen 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.
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 marrowsoft, spongy tissue found in bones that makes blood cells, 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 perineumthe space between the scrotum and anus in males, and vaginal opening and anus in females (area between the genitals and anusthe opening where solid waste (faeces or stool) exits the body).
- 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 abdomenstomach, stomach area, belly, 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:
- Lymphadenopathyswollen lymph nodes/glands, also known as adenopathy.
- Persistent cough.
- Changes in breathing, such as accelerated breathing or dyspneadifficulty breathing, shortness of breath.
- Superior vena cava syndrome, which has its own set of symptoms:
- Coughing.
- 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 polydipsiaabnormal or escessive thirst and polyuriafrequent urination.
- Growth/developmental delay.
- Early or late puberty.
- Obesity.
Symptoms of LCH in the thyroid gland of the endocrine system may include:
- Swollen thyroid gland.
- Hypothyroidisma condition that occurs when the thyroid doesn't produce enough thyroid hormones, also known as underactive thyroid, which has varying symptoms between infants, children/adolescents and adults.
- Dyspnea.
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.
- Diplopiaseeing two images of a single object, also known as 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.
- Diarrhoeafrequent discharge of watery or loose stools from the body.
- Unexplained weight loss.
- Jaundiceyellowing of the skin and the whites of the eyes.
- General itchiness.
- Easy bruising and/or bleeding.
- Fatiguea state of extreme tiredness or exhaustion, can be physical or mental
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.
- Dyspnea.
- Fatigue.
- Skin turning a bluish colour due to a lack of oxygen.
- 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
If your doctor suspects you have LCH, they may order the following tests to confirm the diagnosisthe process of identifying a disease based on signs and symptoms, patient history and medical test results 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 teststesting done to measure the levels of certain substances in the urine.
- Imagingtests that create detailed images of areas inside the body 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.
- PET (positron emission tomography) scana type of medical imaging that uses radioactive tracers to create detailed images of the body.
- Ultrasounda type of medical imaging that uses soundwaves 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 surgeryan exploratory 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.
