Langerhans Cell Sarcoma
Langerhans cell sarcoma is a rare and aggressive cancer that develops from specialized immune cells called Langerhans cells, which normally help protect the body from infection. Unlike the related but less serious condition called Langerhans cell histiocytosis, this disease shows clearly malignant features and often affects multiple parts of the body.
Table of contents
- Classification and identification
- How common is this disease
- What happens in the body
- Signs and symptoms
- How the disease is diagnosed
- Treatment approaches
- Outlook and survival
Classification and identification
Langerhans cell sarcoma belongs to a group of diseases affecting special immune cells. The World Health Organization classifies it as a type of dendritic cell neoplasm, which means it is an abnormal growth of cells that normally help the immune system recognize threats.[1]
Dendritic cell neoplasms include several related conditions. Langerhans cell sarcoma is listed alongside Langerhans cell histiocytosis, interdigitating dendritic cell sarcoma, follicular dendritic cell sarcoma, and other dendritic cell tumors. While Langerhans cell histiocytosis is considered benign in its cellular appearance, Langerhans cell sarcoma shows overtly malignant features that make it far more dangerous.[1][2]
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How common is this disease
Langerhans cell sarcoma is extremely rare. The exact number of cases is unknown because the condition occurs so infrequently. For comparison, the related condition Langerhans cell histiocytosis affects about 5 people per 1 million each year.[1] Langerhans cell sarcoma appears to be far less common than this.
Information about who develops this disease varies between studies. One review of Japanese patients found that the middle age at diagnosis was 41 years, and women were twice as likely to develop the disease as men.[1] However, another larger review found a middle age of 50 years with a slight preference for males.[1][7] When the disease affects the head and neck area specifically, the middle age of diagnosis is about 56.5 years.[3]
What happens in the body
To understand Langerhans cell sarcoma, it helps to know about the cells involved. Throughout the body, especially in areas like the skin, mucous membranes, lymph nodes, thymus, and spleen, there are cells called antigen-presenting cells. These cells act as surveillance guards, finding foreign substances that might harm the body and presenting them to other immune cells called T-cells for action.[1][3]
Langerhans cells are a specific type of these antigen-presenting cells, and they are most commonly found in the skin and mucous membranes. In Langerhans cell sarcoma, these cells multiply in an uncontrolled way, creating cancerous growths.[1]
The disease can develop in two ways. It may appear on its own without any previous illness, which doctors call developing “de novo.” Alternatively, it can occur when a person who already has Langerhans cell histiocytosis experiences a transformation of that disease into the more aggressive sarcoma form.[1][2][3]
Because Langerhans cells are concentrated in the skin and mucous membranes, doctors believe the disease usually starts in these locations and then spreads to other parts of the body through the lymphatic system, which is the network of vessels that carries immune cells throughout the body.[1]
Research has identified changes in certain genes, including mutations in the BRAF gene and others in the RAS-MAPK and MTOR signaling pathways, in many cases of related histiocytic diseases.[3]
- Skin
- Lymph nodes
- Lung
- Liver
- Spleen
- Bone marrow
- Mucous membranes
- Thymus
Signs and symptoms
The symptoms of Langerhans cell sarcoma depend on which parts of the body are affected. The disease most commonly appears in the skin and lymphatic tissue, but can also involve the lung, liver, spleen, and bone marrow.[1][4]
Many patients experience general symptoms that affect the whole body. These often include fever and unintended weight loss. Blood tests frequently show pancytopenia, which means an overall reduction in all types of blood cells.[1]
Patients may also develop swollen lymph nodes, called lymphadenopathy, and enlargement of the liver and spleen, known as hepatosplenomegaly. The disease can create lesions in the bones, lungs, and skin.[1]
When Langerhans cell sarcoma affects the skin, it appears as patches of redness, often with raised bumps called nodules and areas where the skin surface has broken down, called ulceration. These skin changes most commonly develop on the trunk of the body, scalp, and legs.[1] In one reported case, a patient presented with widespread skin bumps without itching or pain.[9]
The tumors vary in size, typically ranging from 1 to 6 centimeters, though they can grow larger. They usually have clear borders and may appear pink, white, or tan in color. The surface often has small bumps or protrusions. In more aggressive cases, the tumors can grow much larger and cause bleeding and death of surrounding tissue.[1]
One unusual case involved a young girl who had extreme difficulty walking, numbness in both legs, and chest pains at night. Medical imaging revealed a lesion on her spine that was pressing on the spinal cord, which would have caused paralysis without treatment.[15]
How the disease is diagnosed
Diagnosing Langerhans cell sarcoma relies primarily on examining tissue samples under a microscope, a process called pathologic diagnosis. Cells from tumor samples show features characteristic of Langerhans cells but with additional signs of cancer.[1]
When examined under a microscope, the tumor contains large cells with unusual shapes and clearly abnormal nuclei (the control centers of cells). These cells have abundant pale pinkish fluid inside them and are mixed with other immune cells called eosinophils.[2][3] The cancer cells show greater variation in appearance and more cell division than would be seen in the benign condition Langerhans cell histiocytosis. Generally, doctors can identify more than 50 dividing cells per 10 high-powered microscope fields, though this is not a strict requirement for diagnosis.[3]
Special staining techniques called immunohistochemistry help confirm the diagnosis. The tumor cells test positive for certain markers including S-100 protein, CD1a, and sometimes langerin, which are characteristic of Langerhans cells.[1][2][3] However, the degree to which these markers appear can vary in Langerhans cell sarcoma.[3] The cells may also show positivity for CD68 and other markers.[9]
Doctors must distinguish Langerhans cell sarcoma from several similar conditions, including the benign Langerhans cell histiocytosis, other types of histiocytic and dendritic cell tumors, and even certain cancers like melanoma.[3]
Imaging tests help determine how far the disease has spread. These may include CT scans, MRI scans, PET-CT scans, and ultrasound examinations. Blood tests and bone marrow biopsies may also be performed to assess the extent of disease.[2][9]
Treatment approaches
Treatment for Langerhans cell sarcoma typically involves surgery, chemotherapy, radiation therapy, or combinations of these approaches. The specific treatment depends on whether the disease is limited to one area or has spread to multiple sites.[1][3]
For patients with disease in a single location, surgical removal with wide margins is often the most effective treatment. This may be combined with radiation therapy or chemotherapy, especially when the disease involves distant organs or tissues.[12]
Various chemotherapy regimens have been tried, often adapted from treatments used for aggressive lymphomas. One successful approach reported in an elderly patient used a combination called EPOCH chemotherapy, which includes the drugs etoposide, prednisone, vincristine, cyclophosphamide, and doxorubicin.[9][14]
Bone marrow transplant may be considered in cases of widespread disease, and appears to be particularly effective when the disease has spread throughout the body.[3][12]
Newer treatment approaches are being explored based on the genetic changes found in the disease. Some patients have been treated with targeted drugs that block specific mutations, such as BRAF V600E inhibitors, though results have been mixed.[3] Immunotherapy drugs called checkpoint inhibitors, which help the immune system attack cancer cells, have shown promise. One patient with widespread disease achieved prolonged remission with the immunotherapy drug pembrolizumab combined with radiation therapy.[10]
In one documented case, a young girl with Langerhans cell sarcoma affecting her spine underwent emergency surgery to relieve pressure on her spinal cord, followed by a second extensive operation to remove the tumor completely and stabilize her spine. After surgery, she received chemotherapy and made a complete recovery.[15]
Outlook and survival
Langerhans cell sarcoma is generally considered a serious disease with poor prognosis, particularly when it has spread to multiple organs. The disease is described as aggressive and high-grade, meaning it grows and spreads quickly.[4][12]
Survival rates depend heavily on the extent of disease at diagnosis. For patients with disease limited to one area, the five-year disease-specific survival rate is 61%. For those with disease that has spread to nearby regions, the rate drops to 24%. Patients with widespread disease at diagnosis have a five-year survival rate of 0%, meaning none survive beyond five years.[3]
One systematic review found that the median overall survival was 19 months, with a one-year overall survival rate of 62%.[12] The disease is frequently lethal, especially when detected after it has already spread throughout the body.[3]
However, there have been successful cases with appropriate treatment. The documented case of the young girl with spinal involvement made a complete neurological recovery after surgery and chemotherapy, becoming cancer-free after two years of treatment.[15] Another case involving a patient who developed Langerhans cell sarcoma from pre-existing Langerhans cell histiocytosis in the lung showed that careful monitoring and prompt treatment when the disease transforms can be important.[2]
The outcome does not appear to differ significantly based on where in the body the disease occurs. Disease-specific and disease-free survival rates are similar for patients with head and neck Langerhans cell sarcoma compared to those with disease in other locations.[3]
