Malignant histiocytosis is a rare

hereditary disease A genetic disorder is a health problem caused by one or more abnormalities in the genome. It can be caused by a mutation in a single gene (monogenic) or multiple genes (polygenic) or by a chromosomal abnormality. Although polygenic disorders ...

found in the

Bernese Mountain Dog The Bernese Mountain Dog (german: Berner Sennenhund) is a large dog breed, one of the four breeds of Sennenhund- type dogs from Bern, Switzerland and the Swiss Alps. These dogs have roots in the Roman mastiffs. The name ''Sennenhund'' is derived ...

and humans, characterized by

histiocytic A histiocyte is a vertebrate cell that is part of the mononuclear phagocyte system (also known as the reticuloendothelial system or lymphoreticular system). The mononuclear phagocytic system is part of the organism's immune system. The histiocyt ...

infiltration of the lungs and

lymph node A lymph node, or lymph gland, is a kidney-shaped organ of the lymphatic system and the adaptive immune system. A large number of lymph nodes are linked throughout the body by the lymphatic vessels. They are major sites of lymphocytes that inclu ...

s. The

liver The liver is a major Organ (anatomy), organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the Protein biosynthesis, synthesis of proteins and biochemicals necessary for ...

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

, and

central nervous system The central nervous system (CNS) is the part of the nervous system consisting primarily of the brain and spinal cord. The CNS is so named because the brain integrates the received information and coordinates and influences the activity of all par ...

can also be affected. Histiocytes are a component of the

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

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 is a semi-solid tissue found within the spongy (also known as cancellous) portions of bones. In birds and mammals, bone marrow is the primary site of new blood cell production (or haematopoiesis). It is composed of hematopoietic ce ...

. The source for histiocytes is the

monocyte Monocytes are a type of leukocyte or white blood cell. They are the largest type of leukocyte in blood and can differentiate into macrophages and conventional dendritic cells. As a part of the vertebrate innate immune system monocytes also inf ...

macrophage Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer cel ...

line. Monocytes (found in the blood) and macrophages (found in tissue) are responsible for

phagocytosis Phagocytosis () is the process by which a cell uses its plasma membrane to engulf a large particle (≥ 0.5 μm), giving rise to an internal compartment called the phagosome. It is one type of endocytosis. A cell that performs phagocytosis is ...

(ingestion) of foreign material in the body.

Langerhans cell A Langerhans cell (LC) is a tissue-resident macrophage of the skin. These cells contain organelles called Birbeck granules. They are present in all layers of the epidermis and are most prominent in the stratum spinosum. They also occur in the ...

s are

dendritic cell Dendritic cells (DCs) are antigen-presenting cells (also known as ''accessory cells'') of the mammalian immune system. Their main function is to process antigen material and present it on the cell surface to the T cells of the immune system. ...

s found in the skin and function by internalizing

antigen In immunology, an antigen (Ag) is a molecule or molecular structure or any foreign particulate matter or a pollen grain that can bind to a specific antibody or T-cell receptor. The presence of antigens in the body may trigger an immune response. ...

s (foreign particles) and presenting them to

T cell A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

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 A histiocytoma is a tumour consisting of histiocytes. Histiocytes are cells that are a part of the mononuclear phagocytic system, a part of the body's immune system that consists of phagocytic cells, which are responsible for engulfing solid parti ...

s * Reactive histiocytosis (immunohistochemical features show that interstitial/dermal DCs are involved) ** Cutaneous

histiocytosis In medicine, histiocytosis is an excessive number of histiocytes (tissue macrophages), and the term is also often used to refer to a group of rare diseases which share this sign as a characteristic. Occasionally and confusingly, the term "histioc ...

(CH) ** Systemic histiocytosis (SH) * Reactive diseases of macrophages **

Hemophagocytic syndrome Hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a ...

– a condition where macrophages phagocytose myeloid and

erythroid Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "hol ...

precursors (similar to

hemophagocytic lymphohistiocytosis Hemophagocytic lymphohistiocytosis (HLH), also known as haemophagocytic lymphohistiocytosis (British spelling), and hemophagocytic or haemophagocytic syndrome, is an uncommon hematologic disorder seen more often in children than in adults. It is a ...

in humans) * Histiocytic sarcoma complex (immunohistochemical features of dendritic cells, possibly interdigitating or perivascular DCs) ** Malignant histiocytosis ** Diffuse

histiocytic sarcoma Histiocytic sarcoma is a tumor derived from histiocytes. The tumor is often positive for CD163 and can appear in the thyroid. However, in some cases it can also appear in the brain A brain is an organ (biology), organ that serves as the cen ...

** 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 The Rottweiler (, ) is a breed of domestic dog, regarded as medium-to-large or large. The dogs were known in German as , meaning Rottweil butchers' dogs, because their main use was to herd livestock and pull carts laden with butchered mea ...

Flat-Coated Retriever The Flat-coated Retriever is a gundog breed originating from England. It was developed as a retriever both on land and in the water. Description Appearance The Flat-Coated Retriever breed standard calls for males to be tall at the withers, w ...

s, and

Golden Retriever The Golden Retriever is a Scottish breed of retriever dog of medium size. It is characterised by a gentle and affectionate nature and a striking golden coat. It is commonly kept as a pet and is among the most frequently registered breeds ...

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 A pleural effusion is accumulation of excessive fluid in the pleural space, the potential space that surrounds each lung. Under normal conditions, pleural fluid is secreted by the parietal pleural capillaries at a rate of 0.6 millilitre per kilog ...

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

Seizure An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with los ...

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

pancytopenia Pancytopenia is a medical condition in which there is significant reduction in the number of almost all blood cells (red blood cells, white blood cells, platelets, monocytes, lymphocytes, etc.). If only two parameters from the complete blood coun ...

. Diagnosis requires a

biopsy A biopsy is a medical test commonly performed by a surgeon, interventional radiologist, or an interventional cardiologist. The process involves extraction of sample cells or tissues for examination to determine the presence or extent of a diseas ...

Treatment

Treatment with

chemotherapy Chemotherapy (often abbreviated to chemo and sometimes CTX or CTx) is a type of cancer treatment that uses one or more anti-cancer drugs (chemotherapeutic agents or alkylating agents) as part of a standardized chemotherapy regimen. Chemotherap ...

has been used with some success, particularly using

lomustine Lomustine (INN); abbreviated as CCNU; original brand name CeeNU, now marketed as Gleostine) is an alkylating nitrosourea compound used in chemotherapy. It is closely related to semustine and is in the same family as streptozotocin. It is a high ...

prednisone Prednisone is a glucocorticoid medication mostly used to immunosuppressive drug, suppress the immune system and decrease inflammation in conditions such as asthma, COPD, and rheumatologic diseases. It is also used to treat high blood calcium ...

doxorubicin Doxorubicin, sold under the brand name Adriamycin among others, is a chemotherapy medication used to treat cancer. This includes breast cancer, bladder cancer, Kaposi's sarcoma, lymphoma, and acute lymphocytic leukemia. It is often used toge ...

, and

cyclophosphamide Cyclophosphamide (CP), also known as cytophosphane among other names, is a medication used as chemotherapy and to suppress the immune system. As chemotherapy it is used to treat lymphoma, multiple myeloma, leukemia, ovarian cancer, breast cancer ...

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

prognosis Prognosis (Greek: πρόγνωσις "fore-knowing, foreseeing") is a medical term for predicting the likely or expected development of a disease, including whether the signs and symptoms will improve or worsen (and how quickly) or remain stabl ...

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. Other signs and symptoms include weight loss and loss of appetite.

References

External links

{{Histiocytosis Dog diseases Lymphoid-related cutaneous conditions Histiocytosis