Malignant histiocytosis (also known as "Histiocytic medullary reticulosis") is a rare hereditary disease found in the Bernese Mountain Dog

Bernese Mountain Dog

The Bernese Mountain Dog, called in German the Berner Sennenhund, is a large breed of dog, one of the four breeds of Sennenhund-type dogs from the Swiss Alps. The name Sennenhund is derived from the German "Senne" and "hund" , as they accompanied the alpine herders and dairymen called Senn...

 and humans, characterized by histiocytic

Histiocyte

A histiocyte is a cell that is part of the mononuclear phagocyte system . The mononuclear phagocytic system is part of the organism's immune system...

 infiltration of the lungs and lymph node

Lymph node

A lymph node is a small ball or an oval-shaped organ of the immune system, distributed widely throughout the body including the armpit and stomach/gut and linked by lymphatic vessels. Lymph nodes are garrisons of B, T, and other immune cells. Lymph nodes are found all through the body, and act as...

s. The liver

Liver

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

, spleen

Spleen

The spleen is an organ found in virtually all vertebrate animals with important roles in regard to red blood cells and the immune system. In humans, it is located in the left upper quadrant of the abdomen. It removes old red blood cells and holds a reserve of blood in case of hemorrhagic shock...

, and central nervous system

Central nervous system

The central nervous system is the part of the nervous system that integrates the information that it receives from, and coordinates the activity of, all parts of the bodies of bilaterian animals—that is, all multicellular animals except sponges and radially symmetric animals such as jellyfish...

 can also be affected. Histiocytes are a component of the immune system

Immune system

An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...

 that proliferate abnormally in this disease. In addition to its importance in veterinary medicine, the condition is also important in human pathology.

Histiocytic disorders

A histiocyte is a differentiated tissue cell that has its origin in the bone marrow

Bone marrow

Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...

. The source for histiocytes is the monocyte

Monocyte

Monocytes are a type of white blood cell and are part of the innate immune system of vertebrates including all mammals , birds, reptiles, and fish. Monocytes play multiple roles in immune function...

/macrophage

Macrophage

Macrophages are cells produced by the differentiation of monocytes in tissues. Human macrophages are about in diameter. Monocytes and macrophages are phagocytes. Macrophages function in both non-specific defense as well as help initiate specific defense mechanisms of vertebrate animals...

 line. Monocytes (found in the blood) and macrophages (found in tissue) are responsible for phagocytosis (ingestion) of foreign material in the body. Langerhans cell

Langerhans cell

Langerhans cells are dendritic cells of the skin and mucosa, and contain large granules called Birbeck granules. They are present in all layers of the epidermis, but are most prominant in the stratum spinosum. They also occur in the papillary dermis, particularly around blood vessels, as well as...

s are dendritic cell

Dendritic cell

Dendritic cells are immune cells forming part of the mammalian immune system. Their main function is to process antigen material and present it on the surface to other cells of the immune system. That is, dendritic cells function as antigen-presenting cells...

s found in the skin and function by internalizing antigen

Antigen

An antigen is a foreign molecule that, when introduced into the body, triggers the production of an antibody by the immune system. The immune system will then kill or neutralize the antigen that is recognized as a foreign and potentially harmful invader. These invaders can be molecules such as...

s (foreign particles) and presenting them to T cell

T cell

T cells or T lymphocytes belong to a group of white blood cells known as lymphocytes, and play a central role in cell-mediated immunity. They can be distinguished from other lymphocytes, such as B cells and natural killer cells , by the presence of a T cell receptor on the cell surface. They are...

s. They arise from monocytes. Histiocytic disorders refer to diseases that are caused by abnormal behavior of these cells. They include the following:

• Reactive diseases of Langerhans cells (most important feature in immune histochemistry is expression of E-cadherin)
  • Histiocytoma
    Histiocytoma (dog)
    A histiocytoma in the dog is a benign tumor. It is an abnormal growth in the skin of histiocytes , a cell that is part of the immune system. A similar disease in humans, Hashimoto-Pritzker disease, is also a Langerhans cell histiocytosis. Dog breeds that may be more at risk for this tumor...
    
    s
• Reactive histiocytosis (immunohistochemical features show that interstitial/dermal DCs are involved)
  • Cutaneous histiocytosis
    Histiocytosis
    In medicine, histiocytosis refers to an excessive number of histiocytes, , and is typically used to refer to a group of rare diseases which share this as a characteristic...
    
     (CH)
  • Systemic histiocytosis (SH)
• Reactive diseases of macrophages
  • Hemophagocytic syndrome - a condition where macrophages phagocytose myeloid
    Myeloid
    The term myeloid suggests an origin in the bone marrow or spinal cord, or a resemblance to the marrow or spinal cord.In hematopoiesis, the term "myeloid cell" is used to describe any leukocyte that is not a lymphocyte...
    
     and erythroid precursors (similar to hemophagocytic lymphohistiocytosis in humans)
• Histiocytic sarcoma complex (immunohistochemical features of dendritic cells, possibly interdigitating or perivascular DCs)
  • Malignant histiocytosis
  • Diffuse histiocytic sarcoma
    Histiocytic sarcoma
    Histiocytic sarcoma is a tumor derived from histiocytes. The tumor is often positive for CD163 and can appear in the thyroid....
    
    
  • Localized histiocytic sarcoma
• Malignant diseases of macrophages
  • Histiocytic lymphoma

Breed disposition

Up to 25 percent of Bernese Mountain Dogs may develop malignant histiocytosis in their lifetime. Other breeds with a possible genetic tendency toward malignant histiocytosis include Rottweiler

Rottweiler

The Rottweiler is a medium to large size breed of domestic dog that originated in Rottweil, Germany. The dogs were known as "Rottweil butchers' dogs" because they were used to herd livestock and pull carts laden with butchered meat and other products to market...

s, Flat-Coated Retriever

Flat-Coated Retriever

The Flat-Coated Retriever is a gundog breed originating from the United Kingdom. It was developed as a retriever both on land and in the water.-Appearance:...

s, and Golden Retriever

Golden Retriever

The Golden Retriever is a medium-sized breed of dog. They were historically developed as gundogs to retrieve shot waterfowl such as ducks and upland game birds during hunting and shooting parties. As such, they were bred to have a soft mouth to retrieve game undamaged and have an instinctive love...

s.

Signs and symptoms

The disease in the lungs is characterized by enlargement of the tracheobronchial lymph nodes and infiltration of the lungs, sometimes leading to lung lobe consolidation and pleural effusion

Pleural effusion

Pleural effusion is excess fluid that accumulates between the two pleural layers, the fluid-filled space that surrounds the lungs. Excessive amounts of such fluid can impair breathing by limiting the expansion of the lungs during ventilation.-Pathophysiology:...

. Signs and symptoms include cough, loss of appetite, weight loss, anemia, and difficulty breathing. Seizure

Seizure

An epileptic seizure, occasionally referred to as a fit, is defined as a transient symptom of "abnormal excessive or synchronous neuronal activity in the brain". The outward effect can be as dramatic as a wild thrashing movement or as mild as a brief loss of awareness...

s and rear limb weakness can be seen. Invasion of the bone marrow can cause pancytopenia

Pancytopenia

Pancytopenia is a medical condition in which there is a reduction in the number of red and white blood cells, as well as platelets.If only two parameters from the full blood count are low, the term bicytopenia can be used...

. Diagnosis requires a biopsy

Biopsy

A biopsy is a medical test involving sampling of cells or tissues for examination. It is the medical removal of tissue from a living subject to determine the presence or extent of a disease. The tissue is generally examined under a microscope by a pathologist, and can also be analyzed chemically...

.

Treatment

Treatment with chemotherapy

Chemotherapy

Chemotherapy is the treatment of cancer with an antineoplastic drug or with a combination of such drugs into a standardized treatment regimen....

 has been used with some success, particularly using lomustine

Lomustine

Lomustine is an alkylating nitrosourea compound used in chemotherapy. It is in the same family as streptozotocin. This is a highly lipid soluble drug, and thus crosses the blood brain barrier. This property makes it ideal for treating brain tumors, and is its primary use...

, prednisone

Prednisone

Prednisone is a synthetic corticosteroid drug that is particularly effective as an immunosuppressant drug. It is used to treat certain inflammatory diseases and some types of cancer, but has significant adverse effects...

, doxorubicin

Doxorubicin

Doxorubicin INN is a drug used in cancer chemotherapy. It is an anthracycline antibiotic, closely related to the natural product daunomycin, and like all anthracyclines, it works by intercalating DNA....

, and cyclophosphamide

Cyclophosphamide

Cyclophosphamide , also known as cytophosphane, is a nitrogen mustard alkylating agent, from the oxazophorines group....

. Because of the rapid progression of this aggressive disease, the prognosis

Prognosis

Prognosis is a medical term to describe the likely outcome of an illness.When applied to large statistical populations, prognostic estimates can be very accurate: for example the statement "45% of patients with severe septic shock will die within 28 days" can be made with some confidence, because...

 is very poor.

Other histiocytic diseases in Bernese Mountain Dogs

A similar disease is diffuse histiocytic sarcoma, a term used to designate a localized histiocytic sarcoma that has spread throughout the body.

Another disease of histiocytic origin that affects Bernese Mountain Dogs is systemic histiocytosis. This condition generally begins as lesions on the eyelid

Eyelid

An eyelid is a thin fold of skin that covers and protects an eye. With the exception of the prepuce and the labia minora, it has the thinnest skin of the whole body. The levator palpebrae superioris muscle retracts the eyelid to "open" the eye. This can be either voluntarily or involuntarily...

s, nasal mucosa

Mucous membrane

The mucous membranes are linings of mostly endodermal origin, covered in epithelium, which are involved in absorption and secretion. They line cavities that are exposed to the external environment and internal organs...

, and skin, especially the scrotum

Scrotum

In some male mammals the scrotum is a dual-chambered protuberance of skin and muscle containing the testicles and divided by a septum. It is an extension of the perineum, and is located between the penis and anus. In humans and some other mammals, the base of the scrotum becomes covered with curly...

. It progresses to a more generalized disease affecting the lymph nodes, bone marrow and spleen. Other signs and symptoms include weight loss and loss of appetite. It also has a very poor prognosis.

External links

• Berner-Garde Foundation
• School of Veterinary Medicine Canine Histiocytosis Site at University of California, Davis
  University of California, Davis
  The University of California, Davis is a public teaching and research university established in 1905 and located in Davis, California, USA. Spanning over , the campus is the largest within the University of California system and third largest by enrollment...
  
  
• Berner-Garde Foundation Articles on Malignant Histiocytosis
• Histiocytoma and Histiocytic Sarcoma in Cats and Dogs from Pet Cancer Center
• Stories of Malignant Histiocytosis victims