A mastocytoma or mast cell tumor is a type of round-cell tumor consisting of
mast cell
A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a pa ...
s. It is found in humans and many animal species; it also can refer to an accumulation or nodule of mast cells that resembles a tumor.
Mast cells originate from 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 hematopoieti ...
and are normally found throughout the
connective tissue
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops from the mesenchyme derived from the mesoderm the middle embryonic germ layer. Connective tissue ...
of the body as normal components 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 Tumor immunology, cancer cells and objects such ...
. As they release
histamine
Histamine is an organic nitrogenous compound involved in local immune responses, as well as regulating physiological functions in the gut and acting as a neurotransmitter for the brain, spinal cord, and uterus. Since histamine was discovered in ...
, they are associated with
allergic reaction
Allergies, also known as allergic diseases, refer a number of conditions caused by the hypersensitivity of the immune system to typically harmless substances in the environment. These diseases include hay fever, food allergies, atopic derm ...
s. Mast cells also respond to tissue trauma. Mast cell
granule
A granule is a large particle or grain. It can refer to:
* Granule (cell biology), any of several submicroscopic structures, some with explicable origins, others noted only as cell type-specific features of unknown function
** Azurophilic granul ...
s contain histamine,
heparin
Heparin, also known as unfractionated heparin (UFH), is a medication and naturally occurring glycosaminoglycan. Since heparins depend on the activity of antithrombin, they are considered anticoagulants. Specifically it is also used in the trea ...
, platelet-activating factor, and other substances. Disseminated mastocytosis is rarely seen in young dogs and cats, while mast cell tumors are usually skin tumors in older dogs and cats. Although not always malignant, they do have the potential to be. Up to 25 percent of skin tumors in dogs are mast cell tumors, with a similar number in cats.
Signs and symptoms
Humans
When mastocytomas affect humans, they are typically found in skin. They usually occur as a single lesion on the trunk or wrist. Although it is rare, mastocytomas are sometimes found in the lung. It can also affect children.
Other animals
Mast cell tumors are known among veterinary oncologists as 'the great pretenders' because their appearance can be varied, from a
wart
Warts are typically small, rough, hard growths that are similar in color to the rest of the skin. They typically do not result in other symptoms, except when on the bottom of the feet, where they may be painful. While they usually occur on the ...
-like nodule to a soft subcutaneous lump (similar on palpation to a benign
lipoma
A lipoma is a benign tumor made of fat tissue. They are generally soft to the touch, movable, and painless. They usually occur just under the skin, but occasionally may be deeper. Most are less than in size. Common locations include upper back, ...
) to an ulcerated skin mass. Most mast cell tumors are small, raised lumps on the skin. They may be hairless, ulcerated, or itchy. They are usually solitary, but in about six percent of cases, there are multiple mast cell tumors (especially in Boxers and Pugs).
Manipulation of the tumor may result in redness and swelling from release of mast cell granules, also known as Darier's sign, and prolonged local hemorrhage. In rare cases, a highly malignant tumor is present, and signs may include loss of appetite,
vomiting
Vomiting (also known as emesis and throwing up) is the involuntary, forceful expulsion of the contents of one's stomach through the mouth and sometimes the nose.
Vomiting can be the result of ailments like food poisoning, gastroenteri ...
,
diarrhea
Diarrhea, also spelled diarrhoea, is the condition of having at least three loose, liquid, or watery bowel movements each day. It often lasts for a few days and can result in dehydration due to fluid loss. Signs of dehydration often begin ...
, and
anemia
Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, ...
. The presence of these signs usually indicates mastocytosis, which is the spread of mast cells throughout the body. Release of a large amount of histamine at one time can result in ulceration of the
stomach
The stomach is a muscular, hollow organ in the gastrointestinal tract of humans and many other animals, including several invertebrates. The stomach has a dilated structure and functions as a vital organ in the digestive system. The stomach i ...
and
duodenum
The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms anterior intestine or proximal intestine ...
metastasis
Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...
does occur, it is usually to the
liver
The liver is a major organ only found in vertebrates which performs many essential biological functions such as detoxification of the organism, and the synthesis of proteins and biochemicals necessary for digestion and growth. In humans, it ...
,
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 .
,
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 inc ...
s and
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 hematopoieti ...
.
File:Mast cell tumor side.JPG, Mast cell tumor on the side of a dog
File:Mast cell tumor inner thigh.JPG, Mast cell tumor on the inner thigh of a dog
File:Mast cell tumor of the toe.JPG, Mast cell tumor of the paw
Diagnosis
A
needle aspiration biopsy
Fine-needle aspiration (FNA) is a diagnostic procedure used to investigate lumps or masses. In this technique, a thin (23–25 gauge (0.52 to 0.64 mm outer diameter)), hollow needle is inserted into the mass for sampling of cells that, aft ...
of the tumor will typically show a large number of mast cells. This is sufficient to make the diagnosis of a mast cell tumor, although poorly differentiated mast cells may have few granules and thus are difficult to identify. The granules of the mast cell stain blue to dark purple with a Romanowsky stain, and the cells are medium-sized. However, a surgical
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 d ...
is required to find the grade of the tumor. The grade depends on how well the mast cells are differentiated,
mitotic
In cell biology, mitosis () is a part of the cell cycle in which replicated chromosomes are separated into two new nuclei. Cell division by mitosis gives rise to genetically identical cells in which the total number of chromosomes is mainta ...
activity, location within the skin, invasiveness, and the presence of
inflammation
Inflammation (from la, wikt:en:inflammatio#Latin, inflammatio) is part of the complex biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or Irritation, irritants, and is a protective response involving im ...
or
necrosis
Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dig ...
.
*Grade I – well differentiated and mature cells with a low potential for metastasis
*Grade II – intermediately differentiated cells with potential for local invasion and moderate metastatic behavior
*Grade III – undifferentiated, immature cells with a high potential for metastasis
However, there is a significant amount of discordance between
veterinary pathologist
Veterinary pathologists are veterinarians who specialize in the diagnosis of diseases through the examination of animal tissue and body fluids. Like medical pathology, veterinary pathology is divided into two branches, anatomical patholog ...
s in assigning grades to mast cell tumors due to imprecise criteria.
The disease is also staged according to the WHO system:
*Stage I - a single skin tumor with no spread to
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 inc ...
s
*Stage II - a single skin tumor with spread to lymph nodes in the surrounding area
*Stage III - multiple skin tumors or a large tumor invading deep to the skin with or without lymph node involvement
*Stage IV – a tumor with metastasis to the spleen, liver, or bone marrow, or with the presence of mast cells in the blood
X-ray
X-rays (or rarely, ''X-radiation'') are a form of high-energy electromagnetic radiation. In many languages, it is referred to as Röntgen radiation, after the German scientist Wilhelm Conrad Röntgen, who discovered it in 1895 and named it ' ...
s,
ultrasound
Ultrasound is sound waves with frequencies higher than the upper audible limit of human hearing. Ultrasound is not different from "normal" (audible) sound in its physical properties, except that humans cannot hear it. This limit varies fr ...
, or lymph node, bone marrow, or organ biopsies may be necessary to stage the disease.
Treatment and prognosis
Removal of the mast cell tumor through surgery is the treatment of choice.
Antihistamine
Antihistamines are drugs which treat allergic rhinitis, common cold, influenza, and other allergies. Typically, people take antihistamines as an inexpensive, generic (not patented) drug that can be bought without a prescription and provide ...
s, such as diphenhydramine, are given prior to surgery to protect against the effects of histamine released from the tumor. Wide margins (two to three centimeters) are required because of the tendency for the tumor cells to be spread out around the tumor. If complete removal is not possible due to the size or location, additional treatment, such as
radiation therapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Rad ...
or
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. Chemothe ...
, may be necessary.
Prednisone
Prednisone is a glucocorticoid medication mostly used to 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 due to cancer and adren ...
is often used to shrink the remaining tumor portion. H2 blockers, such as cimetidine, protect against stomach damage from histamine. Vinblastine and lomustine are common chemotherapy agents used to treat mast cell tumors.Toceranib and masitinib, examples of receptor tyrosine kinase inhibitors, are used in the treatment of canine
mast cell
A mast cell (also known as a mastocyte or a labrocyte) is a resident cell of connective tissue that contains many granules rich in histamine and heparin. Specifically, it is a type of granulocyte derived from the myeloid stem cell that is a pa ...
cancer
Cancer is a group of diseases involving abnormal cell growth with the potential to invade or spread to other parts of the body. These contrast with benign tumors, which do not spread. Possible signs and symptoms include a lump, abnormal bl ...
drugs.
Grade I or II mast cell tumors that can be completely removed have a good
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 ...
. One study showed about 23 percent of incompletely removed grade II tumors recurred locally. Any mast cell tumor found in the
gastrointestinal tract
The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans a ...
, paw, or on the muzzle has a guarded prognosis. Previous beliefs that tumors in the groin or
perineum
The perineum in humans is the space between the anus and scrotum in the male, or between the anus and the vulva in the female. The perineum is the region of the body between the pubic symphysis (pubic arch) and the coccyx (tail bone), inclu ...
carried a worse prognosis have been discounted. Tumors that have spread to the lymph nodes or other parts of the body have a poor prognosis. Any dog showing symptoms of mastocytosis or with a grade III tumor has a poor prognosis. Dogs of the Boxer breed have a better than average prognosis because of the relatively benign behavior of their mast cell tumors. Multiple tumors that are treated similarly to solitary tumors do not seem to have a worse prognosis.
Mast cell tumors do not necessarily follow the histological prognosis. Further prognostic information can be provided by AgNOR stain of histological or cytological specimen. Even then, there is a risk of unpredictable behavior.
Other animals
Mast cell tumors are an uncommon occurrence in
horse
The horse (''Equus ferus caballus'') is a domesticated, one-toed, hoofed mammal. It belongs to the taxonomic family Equidae and is one of two extant subspecies of ''Equus ferus''. The horse has evolved over the past 45 to 55 million ...
s. They usually occur as benign, solitary masses on the skin of the head, neck, trunk, and legs. Mineralization of the tumor is common. In pigs and
cattle
Cattle (''Bos taurus'') are large, domesticated, cloven-hooved, herbivores. They are a prominent modern member of the subfamily Bovinae and the most widespread species of the genus '' Bos''. Adult females are referred to as cows and adult ...
, mast cell tumors are rare. They tend to be solitary and benign in pigs and multiple and malignant in cattle. Mast cell tumors are found in the skin of cattle most commonly, but these may be metastases from tumors of the
viscera
In biology, an organ is a collection of tissues joined in a structural unit to serve a common function. In the hierarchy of life, an organ lies between tissue and an organ system. Tissues are formed from same type cells to act together in a ...
. Other sites in cattle include the spleen, muscle, gastrointestinal tract,
omentum
Omentum (Latin for 'apron') is a medical term referring to layers of peritoneum that surround abdominal organs. The term may refer to:
* Greater omentum
* Lesser omentum
{{Disambig ...
, and uterus.
Dogs
Mast cell tumors mainly occur in older adult dogs, but have been known to occur on rare occasions in puppies. The following breeds are commonly affected by mast cell tumors:
* Boxer
* Staffordshire bull terrier
*
Bulldog
The Bulldog is a British breed of dog of mastiff type. It may also be known as the English Bulldog or British Bulldog. It is of medium size, a muscular, hefty dog with a wrinkled face and a distinctive pushed-in nose.Basset hound
*
Weimaraner
The Weimaraner ( ) is a large dog that was originally bred as a hunting dog in the early 19th century. Early Weimaraners were used by royalty for hunting large game such as boar, bear and deer. As the popularity of large game hunting began to ...
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 breed ...
Scottish terrier
The Scottish Terrier ( gd, Abhag Albannach; also known as the Aberdeen Terrier), popularly called the Scottie, is a breed of dog. Initially one of the highland breeds of terrier that were grouped under the name of ''Skye Terrier'', it is on ...
Rhodesian ridgeback
The Rhodesian Ridgeback is a large dog breed bred in the Southern Africa region. Its forebears can be traced to the semi-domesticated ridged hunting and guardian dogs of the Khoikhoi. These were interbred with European dogs by the early coloni ...
Cats
Two types of mast cell tumors have been identified in cats, a mast cell type similar to dogs and a histiocytic type that appears as subcutaneous nodules and may resolve spontaneously. Young
Siamese cat
The Siamese cat ( th, แมวไทย, Maeo Thai; แมวสยาม, Maeo Seeaam) is one of the first distinctly recognized breeds of Asian cat. Derived from the Wichianmat landrace, one of several varieties of cat native to Thailand ( ...
s are at an increased risk for the histiocytic type, although the mast cell type is the most common in all cats and is considered to be benign when confined to the skin.
Mast cell tumors of the skin are usually located on the head or trunk. Gastrointestinal and splenic involvement is more common in cats than in dogs; 50 percent of cases in dogs primarily involved the spleen or intestines. Gastrointestinal mast cell tumors are most commonly found in the muscularis layer of the
small intestine
The small intestine or small bowel is an organ in the gastrointestinal tract where most of the absorption of nutrients from food takes place. It lies between the stomach and large intestine, and receives bile and pancreatic juice through t ...
, but can also be found in the
large intestine
The large intestine, also known as the large bowel, is the last part of the gastrointestinal tract and of the digestive system in tetrapods. Water is absorbed here and the remaining waste material is stored in the rectum as feces before being r ...
. It is the third most common intestinal tumor in cats, after
lymphoma
Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enl ...
and
adenocarcinoma
Adenocarcinoma (; plural adenocarcinomas or adenocarcinomata ) (AC) is a type of cancerous tumor that can occur in several parts of the body. It is defined as neoplasia of epithelial tissue that has glandular origin, glandular characteristics, o ...
.
Diagnosis and treatment are similar to that of the dog. Cases involving difficult to remove or multiple tumors have responded well to strontium-90
radiotherapy
Radiation therapy or radiotherapy, often abbreviated RT, RTx, or XRT, is a therapy using ionizing radiation, generally provided as part of cancer treatment to control or kill malignant cells and normally delivered by a linear accelerator. Ra ...
as an alternative to surgery. The prognosis for solitary skin tumors is good, but guarded for tumors in other organs. Histological grading of tumors has little bearing on prognosis.