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 M group histiocytic disorders, which includes histiocytic sarcoma, Langerhans cell sarcoma, interdigitating cell sarcomas, indeterminate cell sarcoma, and malignant histiocytosis not otherwise specified.
M 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 M Group Histiocytic Disorders
There are many types of malignant histiocytic disorders, which are classified by the types of cells they develop from.
Histiocytic Sarcoma
Histiocytic sarcoma is a very rare non-Langerhans histiocytic disorder that most commonly presents in the lymph nodes, skin, and/or gastrointestinal tract of the body. This subtype can occur randomly, however it has also been reported in patients with haematological (relating to the blood) cancers, most notably follicular lymphoma, myelodysplasia, and acute lymphoblastic leukaemia. Histiocytic sarcomas are often very aggressive, and may not have as good of a prognosis as other histiocytic disorders.
Interdigitating Dendritic Cell Sarcoma (IDCS)
Interdigitating dendritic cell sarcoma (IDCS), also known as reticulum cell sarcoma, is a very rare histiocytic disorder that most commonly presents in the lymph nodes, but may also present in the bladder, bowel, intestines, nasopharynx, salivary glands, skin, spleen, testicles and/or tonsils. This subtype can occur randomly, however it has also been reported in patients with haematological (relating to the blood) cancers, most notably follicular lymphoma, hairy cell leukaemia, chronic lymphoblastic leukaemia, acute lymphoblastic leukaemia, and chronic myelomonocytic leukaemia. IDCS is often very aggressive, and may not have as good of a prognosis as other histiocytic disorders.
Langerhans Cell Sarcoma
Langerhans cell sarcoma (LCS) is a very rare histiocytic disorder characterised by the overproduction of Langerhans cells within a malignant tumour. In some cases, LCS is thought to develop from untreated Langerhans cell histiocytosis (LCH) (a benign and less aggressive histiocytic disorder that also originates from Langerhans cells), however it is possible for the disease to develop sporadically. LCS is most commonly found in the skin, lungs, liver, and bone, however, may develop in other areas as well. LCS is often very aggressive, and may not have as good of a prognosis as other histiocytic disorders.
Indeterminate Cell Histiocytosis (Malignant)
Indeterminate cell histiocytosis is a rare subtype of 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. While ICH is generally considered benign, in rare cases it may be malignant. Malignant ICH is often more aggressive than benign ICH, and may not have as good of a prognosis.
Treatment
Each patient with an M 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 M group histiocytic disorder may include:
- Surgery to remove as much of the tumour(s) as possible.
- Radiation therapy.
- Chemotherapy.
- Clinical trials.
- Palliative care.
For more information on the treatment options, please refer to the Rare Cancers Australia treatment options page.
Risk factors
Because of how rare M group histiocytic disorders are, there has been limited research done into the risk factors of this disease.
Early symptoms
The symptoms of an M group histiocytic disorder often vary depending on the location of the tumour (s).
Many patients with the disease may appear asymptomatic during the early stages. As the cancer(s) progress, some of the following symptoms may appear:
- A palpable mass on the affected area.
- Symptoms of compression of surrounding organs, such as an intestinal obstruction.
- Persistent fevers.
- Unexplained weight loss/loss of appetite.
- Unusual rash on the skin.
- Unusual growths on the skin.
- Fatigue.
- Cytopenia (a condition where one or more types of blood cells have abnormally low levels).
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 a M group histiocytic disorder, they will order a range of diagnostic 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. More specifically, they will examine the suspicious lesion, papule and/or nodule.
Imaging & blood tests
The doctor will take images of your body using magnetic resonance imaging (MRI), a computed tomography scan (CT scan), positron emission tomography scan (PET scan) and/or ultrasound, depending on where it is suspected the cancer is. The doctor may also look at other parts of the body and looks for signs of metastasis. Additionally, a blood test may be taken to assess your overall health and help guide treatment decisions.
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.
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 M group histiocytic disorders have a better prognosis and survival rates. However, if the tumour has become advanced 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.