Lecture 18 4/1/25 Flashcards
What is the biology of mast cells?
-contain characteristic granules containing histamine, heparin, TNF-alpha, and proteases
-normal mast cell differentiation, proliferation, and survival requires KIT receptor on cell surface binding to SCF ligand
What are the incidence and risk factors of mast cell tumors?
-most common cutaneous tumor in dogs
-typically seen in older dogs with no sex predilection
-brachycephalic dogs at increased risk
-breed predisposition in labs, goldens, sharpeis, and cocker spaniels
-no known causative chemical or infectious agents
What is the most common genetic change seen in mast cell tumors?
mutations in c-KIT that result in continual activation of KIT, allowing for uncontrolled proliferation and survival
What are the findings on physical exam and history for mast cell tumors?
-red, hairless masses in dermis/epidermis +/- ulceration
-waxing and waning masses
-edema in surrounding tissues
-subcutaneous version can palpate like a lipoma
-degranulation with palpation; erythema and wheals
-GI ulceration
-possible to collapse from histamine
-excessive bleeding from local or systemic heparin release
How are mast cell tumors diagnosed?
-FNA almost always diagnostic
-Diff-Quik staining generally diagnostic
-Wright Giemsa stains can improve staining quality
-biopsy with histopath. +/- KIT IHC can be performed for grading or diagnosis
-cytologic grading system developed to predict behavior
What are the characteristics of mast cell tumors on histopath?
-assessed with 2 main grading systems; 2 tier and 3 tier
-2 tiered system has high and low grades
-3 tiered system has grades 1, 2, and 3
-no grading system perfectly predicts mast cell tumor behavior
-pre-op biopsies match post-op grade in majority of cases
-low grade tumors are more common
What is the biologic behavior of mast cell tumors?
-notoriously unpredictable
-metastasis commonly to local lymph nodes, spleen, liver, and possibly bone marrow
-low grade tumors have 5% chance of metastasis, while high grade tumors have 50-95% chance
What is involved in staging of mast cell tumors?
-CBC
-chem
-local lymph node aspirates
-abdominal US with spleen and liver aspirates
-thoracic rads
-buffy coat smear
-bone marrow cytology
What are the characteristics of mast cell tumor staging?
-recommended for every high grade tumor due to high likelihood of metastasis
-can change best treatment option; surgery better with no metastasis, chemo better when metastasis is present
-staging is controversial for low grade tumors
What are the characteristics of surgery as a treatment for mast cell tumors?
-most consistent treatment option
-lateral surgical margin recommendations are debated; typically 1 to 3 cm
-deep margin is 1 uninvolved fascial layer
-removal local lymph node at time of surgery improves survival time, even if no metastasis is present
What is the prognosis for mast cell tumors treated with surgery?
-local recurrence after complete wide excision (greater than 5mm margins) is low
-local recurrence after narrow excision (1 to 5 mm) is low to moderate
-tumors that recur locally are often more aggressive
-complete excision is biggest predictor of survival in high grade MCTs
What are the anesthesia considerations when removing mast cell tumors?
-excessive surgical manipulation should be avoided if possible
-premedication with histamine-releasing drugs should be avoided when possible
What are the characteristics of radiation therapy for mast cell tumors?
-used to slow recurrence of high risk MCTs or incompletely excised MCTs
-local recurrence rates after radiation are low to moderate
What are the common early side effects of radiation?
-desquamation
-erythema
-ulceration
What are the common late side effects of radiation?
-leukotrichia
-hyperpigmentation
What are the rare late side effects of radiation?
-bone necrosis
-tumor formation
-vascular abnormalities
What are the characteristics of stelfonta?
-FDA approved drug for non-metastatic canine MCTs
-causes severe local inflammatory reaction and necrosis of tumor
-must give prednisone, H1 blockers, and H2 blockers prior to drug to prevent degranulation
-75% of masses have complete response with one injection
-low rate of recurrence within a year
-cannot get histologic grade or margins
What are the characteristics of steroids and histamine blockers as MCT treatment?
-can be given if other treatment options are not elected
-steroids directly cause apoptosis of mast cells via glucocorticoid receptor
-steroids can be used to pre-operatively shrink the tumor
What are the characteristics of chemo as a MCT treatment?
-used for high grade and/or metastatic tumors
-paladia is FDA approved for treatment and directly inhibits KIT protein
-can also use vinblastine, lomustine, and chlorambucil
-response rates are moderate to good
-works best after surgical reduction
-typically lifelong if used as primary treatment
What is the prognosis for MCTs?
-surgery provides good survival times for low grade tumors; poor survival for low grade tumors
-chemotherapy can have moderate to good survival
-grade is highly prognostic
What are the characteristics of subcutaneous MCTs?
-frequently misdiagnosed as lipomas via palpation
-metastasis is rarer than cutaneous form
-surgical removal with good margins frequently requires removal of muscle
-prognosis generally very good if surgical margins can be achieved
-stelfonta use is restricted based on location
What are some of the abnormal locations in which MCTs have been reported?
-spinal cord
-oral cavity
-nasal cavity
-pancreas
-lungs
-conjunctiva
-salivary gland
What are the three distinct entities of feline mast cell tumors?
-cutaneous
-visceral
-GI
What are the characteristics of feline MCTs?
-granules within cells contain vasoactive substances
-c-KIT is mutated in majority of cases
-anaphylactic reactions in cats can present as resp. distress
-2nd most common cutaneous tumor
-present as dermal red hairless nodule
-head and neck are most common locations
-multiple tumors common
What are the characteristics of feline MCT diagnosis?
-diagnosis via cytology in most cases
-histiocytic MCT requires biopsy
What are the characteristics of feline MCT treatment?
-surgery is treatment of choice if tumor is cutaneous with no splenic involvement
-most come back as benign; aggressive form is rare
-grading system proposed but not validated
-good survival rates
What are the characteristics of chemo for feline MCT?
-poorly studied
-lomustine or palladia + concurrent steroids
-can respond to steroids alone
What are the characteristics of splenic/visceral MCT?
-most common splenic dz in cats
-metastasis is extremely common at time of diagnosis
-40-100% of cases have detectable mast cells in circulation
-1/3 may have effusion with eosinophils and mast cells
-commonly present with vague clinical signs
-can have GI ulceration, hypotension, or labored breathing
What are the characteristics of splenic/visceral MCT treatment?
-treatment of choice is splenectomy even with widespread metastasis
-pretreatment with steroids and H1/H2 blockers may decrease anesthetic complications
-chemo has been used if mast cells return after surgery
What is the prognosis for splenic/visceral MCT?
-good survival with steroids +/- chemotherapy
-even better survival with splenectomy +/- chemotherapy
-splenectomy can cause regression of cutaneous lesions
