What Is Langerhans Cell Histiocytosis?

Is it potentially linked to lymphoma?

Dendritic cell as visualized using scanning electron microscopy, artistic rendering. Paul Langerhans identified this immune cell in the skin
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Paul Langerhans was born in Berlin, Germany, on July 25,1847, the son of a German physician. Off to study medicine like his father, the young he made an important discovery while still an undergraduate. His discovery is what has become known as the epidermal Langerhans cells, which are a key player in a condition known as Langerhans cell histiocytosis.

Discovering Langerhans Dendritic Cells

Langerhans took part in an open competition organized by Berlin University.

A scientist named Julius Cohnheim had already developed a method for visualizing nerves using special gold staining and light microscopy.

Using Cohnheim’s gold chloride techniques in 1868, Langerhans visualized and described something in the skin that wasn’t like the other skin cells—he described it as dendritic because it had branches resembling a tree; but he also said it was non-pigmentary. In other words, it did not contain the pigment melanin that is present in other cells called melanocytes, which are also branched, and are the cells from which melanoma develops.

At the time, he theorized this non-pigmented branching cell was some kind of receptor for signaling through the skin to the nervous system. More than a century later, scientists would learn that Langerhans cells of the skin have important functions in the immune system. In 1973, Dr. Inga Silberberg discovered that the epidermal Langerhans cells represent “the most peripheral outpost of the immune system.” Today, Langerhans cells are considered a subset of a family of dendritic cells, and they are the best-studied subset.

The Langerhans cells discovered in the skin are thought to act as antigen presenting cells. Antigens are essentially cellular 'tags' that the immune system can recognize. Antigen presenting cells (APCs) are cells that specialize in capturing antigens, processing them, and displaying them in a special way so that other immune cells can be alerted to the presence of foreign antigen.

With the help of APCs, the lymphocyte white blood cells are able to recognize and respond to specific microbes and other invaders.

Characteristics of Langerhans Cell Histiocytosis (LCH)

Langerhans cell histiocytosis, or LCH, is preferred to an older term, “histiocytosis X,” but both names appear in medical literature. LCH is actually a group of diseases that have in common uncontrolled growth of Langerhans-type cells. It can occur at any age, though it’s rarely seen in adults. Although LCH has been known for about a century, scientists still don’t understand all the details about what causes it.

LCH is most commonly associated with single or multiple “punched out” appearing areas of missing bone on imaging scans—areas that, when biopsied, show that bone has been replaced by histiocytes with bean-shaped nuclei.

Histiocytes, like macrophages or dendritic cells, are immune cells that destroy foreign substances in an effort to protect the body from infection. These histiocytes, along with lymphocytes, macrophages, and eosinophils, may invade nearly every organ but especially the skin, lymph nodes, lungs, thymus, liver, spleen, bone marrow, or central nervous system.

What Does LCH Have to Do With Lymphoma?

Some experts theorize that LCH may be a reactive growth of Langerhans cells following chemotherapy or radiotherapy for Hodgkin's disease. This is just one of several theories.

A number of cases of Langerhans' cell histiocytosis associated with malignant lymphoma have been reported in the past. Reported cases, however, have occurred with the malignant lymphoma, as well as following the lymphoma.

LCH is most common in children from one to three years old, which might sound frightening, but remember that LCH is rare.

Symptoms depend on the sites of involvement and the disease is limited to one organ system—just bone, for instance, in about half of cases. Sometimes invasion of the bone produces no symptoms, but other times there may be pain in a localized area of bone. Skin involvement is seen in about 40 percent of cases, and the most common skin symptom is an eczema-like rash similar to a yeast infection.

LCH can be difficult to diagnose, but remember that regular visits to your physician and an open dialogue greatly increases chances of detection if something is out of the ordinary.

Sources:

Langerhans P. Uber die nerven der menschlichenhaut. Archives of Pathological Anatomy 1868;44:325–37.

Diapedia. The Living Textbook of Diabetes. Paul Langerhans. Accessed July, 2016.

Satter EK, High WA. Langerhans cell histiocytosis: a review of the current recommendations of the Histiocyte Society. Pediatr Dermatol. 2008 May-Jun. 25(3):291-5.

Li X, Deng Q, Li Y-M. A case of Langerhans’ cell histiocytosis following Hodgkin’s disease. Molecular and Clinical Oncology. 2016;5(1):27-30.

Jaitley S, Saraswathi T. Pathophysiology of Langerhans cells. Journal of Oral and Maxillofacial Pathology : JOMFP. 2012;16(2):239-244.

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