A helpful tool in treating pets with cancer is to identify factors that help establish which group of pets with a particular type of cancer are likely to do better or worse with treatment. Prognostic factors are features of a tumor that have been shown to predict outcome of animals with that specific tumor type. Prognostic factors play an important role in the management of a dog with mast cell tumor disease. The approach to managing a dog with mast cell tumor varies much on the presence or absence of these prognostic factors. The most useful tool in predicting outcome of dogs with mast cell tumor disease is the histological grade. Interpretation of the histological grade of a mast cell tumor is aided by an assessment of the mitotic index (number of dividing cells) of the tumor.
Histological grade of mast cell tumors in dogs as a prognostic indicator
Histological grade is the most important and consistent factor that is predictive of outcome in dogs with mast cell tumors. Most dogs with grade I (one) mast cell tumors (>90%) and grade II (two) mast cell tumors (approximately 75%) have long survival times after complete surgical removal of their mast cell tumors. Dogs with grade III (three) mast cell tumors typically have survival times of less than 1 year due to local recurrence of their tumor or its spread to other locations such as the regional lymph nodes, liver or spleen. The histological grade can only be determined by evaluation of tissue samples histologically by a board-certified veterinary pathologist.
Mitotic index of mast cell tumors in dogs as a prognostic indicator
One of the key features of a mast cell tumor that a pathologist should evaluate is the number of dividing cells (mitotic activity) present in the tumor. The pathologist should define the mitotic activity of the tumor in terms of the mitotic index of the tumor. The mitotic index of a mast cell tumor is determined by looking at the tumor with the microscope under 40x magnification, called high-powered field. The numbers of dividing (mitotic) cells observed in ten different areas of the tumor under 40x magnification are added up to give a total number of dividing cells in 10 high-powered field, which is the mitotic index of that tumor. The common cut off between high and low mitotic activities of a mast cell tumor is 5 mitoses per 10 high-powered field. Most grade I mast cell tumors have a low mitotic index (< 5), where as grade III mast cell tumors tend to have a high mitotic index (>5). The mitotic index is particularly helpful in determining if a grade II mast cell tumor is trending more toward a grade I or a grade III mast cell tumor based on the parameters previously noted. One study found that dogs with grade II mast cell tumors with a mitotic index < 5 had long survival times of more than 5 years, compared to less than 4 months if the mitotic index was >5.
Prognostic factors are features of a tumor that have been shown to predict outcome of animals with that specific tumor type. The approach a veterinarian or owner might pursue to manage a dog with mast cell tumor often varies much on the presence or absence of these negative prognostic factors. Grade of a mast cell tumor has been found to be the strongest predictor of outcome in dogs with mast cell tumors. However, many other factors have also been found useful for predicting behavior and survival time for dogs with mast cell tumors.
Stage of mast cell tumors in dogs as a prognostic indicator
Stage of mast cell tumors is a description of where the disease is in the patient. Mast cell tumors of the skin or subcutaneous tissues that are localized to one area of the body and that have not spread to the regional lymph node carry a better prognosis than tumors that have spread to the regional lymph node or other internal organs. Many of these dogs can be cured with surgery, particularly if the tumor is a grade 1 or grade 2 tumor. Tumors that have spread to the lymph node or other organs are systemic in nature and control of the disease will require some form of chemotherapy to try and control the cancer. Large tumors tend to be of higher grade and are more difficult to remove completely with surgery, which makes treatment more involved to control the disease.
Mast cell tumors that occur in internal organs such as the liver, spleen or intestinal tract of dogs are called visceral mast cell tumors. They are less common, but if present carry a very poor prognosis with very short survival times typically of less than 3 months, even with treatment.
Common sense would suggest that a dog with multiple mast cell tumors in the skin would do very poorly, however this is not always the case. In particular, certain breeds of dogs such as pugs and boxers are prone to developing multiple grade I mast cell tumors. These dogs can have long survival times in spite of inability to remove all of the mast cell tumors.
Other prognostic indicators of mast cell tumors in dogs
There are a number of other factors that are thought to have predictive value in determining survival time in dogs with mast cell tumors. It has been suggested that tumors located in the preputial (skin covering the penis), scrotal, nail bed region, oral cavity or mucocutaneous sites (areas where mucous membrane and skin meet) tend to be of higher grade and behave more aggressively than other locations.
Any mast cell tumor that has recurred will tend to have shorter survival times. Typically, by the time a mast cell tumor has recurred, it has already spread to the regional lymph node. For this reason, appropriate aggressive treatment to remove a mast cell tumor when first diagnosed is advised to avoid recurrence of the disease.
Tumors that have been present for 6 months or longer with little change in character tend to carry a more favorable prognosis as those tumors tend to be low grade mast cell tumors. Tumors that grow rapidly tend to carry a worse prognosis as more often than not, those mast cell tumors are high grade tumors. Ulceration is a negative prognostic sign of mast cell tumor disease and is commonly seen in higher grade tumors that grow rapidly. Large size is also considered a negative prognostic indicator.
It discusses the use of stage of mast cell tumor disease in evaluation of survival time in dogs. It describes a number of other features of mast cell tumor disease that can be predictive of outcome including: location, recurrence of disease, rate of growth, presence of ulceration and size of the tumor.
Prognostic factors are helpful in guiding treatment of animals with cancer. They help identify which pets with a particular type of cancer are likely to do better or worse with treatment. They play an important role in the management of a dog with mast cell tumor disease. Some prognostic factors are more commonly used to predict outcome in dogs with mast cell tumor such as grade of tumor and mitotic index, and have been discussed elsewhere. Mitotic index is a reflection the degree to which the tumor cells are actively dividing (proliferating). There are additional tests that can be performed on mast cell tumors to determine the rate at which the cells of a mast cell tumor are actively dividing. These tests have some ability to predict the behavior of mast cell tumors in dogs, but involve special testing of the tissues, at an additional cost and are less commonly performed.
Other proliferation markers of mast cell tumors in dogs as a prognostic indicator
A number of other tests exist to evaluate the mitotic activity of cells. These additional tests include evaluation of Argyrophilic nucleolar organizer regions (AgNORs), proliferating cell nuclear antigen (PCNA), and Ki67 expression in the tumor. These tests are not commonly performed, but in some cases may offer additional information of benefit in planning treatment for a dog with a mast cell tumor. They are all indirect measures of cell division and have some predictive value of behavior of mast cell tumors. The greater the degree of expression of these factors in cells, the more active the cells in the tumors are proliferating or dividing. These tests involve staining procedures that use special stains that look for these markers that are expressed when cells are actively dividing.
AgNORs are a set of nuclear proteins present in dividing cells that have an affinity to staining with silver stains. PCNA is an protein that is expressed in the nuclei of cells during the DNA synthesis phase of the cell cycle. Ki67 is a nuclear protein that is associated with and appears to be necessary for cellular proliferation. Special stains for AgNORs, PCNA or Ki-67 can be used to aid the grading of mast cell tumors. These proliferation tests are performed at certain institutions including Colorado State University, Michigan State University and the Animal Medical Center, NYC.
Title Tag: mast cell tumor | Mitotic activity as a prognostic indicator in dogs with mast cell tumor disease
It describes tests of mitotic activity that exist for evaluation of mast cell tumors that are not commonly performed. It describes evaluation of argyrophilic nucleolar organizer regions, proliferating cell nuclear antigen and Ki67 in canine mast cell tumors.