Canine mast cell tumors

Despite the fact that the mast cell tumor is a common neoplasm of the dog, we still have only a meager understanding of its etiology and biologic behavior. Many of the published recommendations for treatment are based on opinion rather than facts derived from careful studies and should be viewed with some skepticism. Because of the infrequent occurrence of this tumor in man, only a limited amount of help can be expected from human oncologists; therefore, burden of responsibility for progress in predicting behavior and developing treatment effective for canine mast cell tumors must fall on the shoulders of the veterinary profession.     

Canine oral mucosal mast cell tumours

Mast cell tumours (MCTs) are the most common cutaneous tumours of dogs, however rarely they can arise from the oral mucosa. This subset of MCT is reported to demonstrate a more aggressive clinical course than those tumours on the haired skin and the authors hypothesised that dogs with oral, mucosal MCT would have a high incidence of local lymph node metastasis at presentation and that this would be a negative prognostic factor. An additional hypothesis was that mitotic index (MI) would be prognostic. This retrospective study examines 33 dogs with MCTs arising from the oral mucosa. The results suggest that oral mucosal MCTs in the dog have a high incidence of lymph node metastasis at diagnosis (55%) which results in a poor prognosis. MI and nodal metastasis is highly prognostic. Loco‐regional progression is common in these patients and dogs with adequate local control of their tumour had an improved outcome. Despite a more aggressive clinical course, treatment can result in protracted survivals, even when metastasis is present.     

Canine mast cell tumors: correlation of apoptosis and proliferation markers with prognosis

The Patnaik histologic grading system is commonly used to predict the behavior of cutaneous mast cell tumors (MCTs) in dogs, but it is less useful for grade 2 MCTs because they exhibit considerable variation in biological behavior. In this retrospective study, immunohistochemical staining for Ki-67, proliferating cell nuclear antigen (PCNA), and survivin and a standardized argyrophilic staining of nucleolar organizer regions (AgNOR) protocol were performed on 121 archived paraffin-embedded specimens of canine cutaneous MCTs, for which clinical follow-up data were available. Cox regression models indicated that the Ki-67 score (hazard ratio, 1.92; P < .001) and mean AgNOR score (hazard ratio, 2.57; P < .001) were significantly associated with Patnaik grade and survival time. A binary Ki-67 variable (cutoff point Ki-67 score = 1.8) was a significant predictor of survival for dogs with grade 2 MCTs. The estimated 1-, 2-, and 3-year survival probabilities for dogs with grade 2 MCTs and Ki-67 scores less than 1.8 were 0.92, 0.86, and 0.77, respectively (SEs, 0.08, 0.14, and 0.23, respectively; median not estimable). The corresponding survival probabilities for dogs with grade 2 MCTs and Ki-67 scores higher than 1.8 were 0.43, 0.21, and 0.21, respectively (SEs, 0.19, 0.18, and 0.18, respectively; median survival time, 395 days). No significant association was identified between survival and survivin score or PCNA score. This study shows that both mean AgNOR score and Ki-67 score are prognostic markers for canine MCTs. The Ki-67 score can be used to divide Patnaik grade 2 MCTs into 2 groups with markedly different expected survival times.     

Canine and feline mast cell tumors: biologic behavior, diagnosis, and therapy

Our understanding of the etiology, behavior, and most effective form of mast cell tumor treatment is rudimentary. I have tried to indicate specific areas that need further study in order to resolve some of the present controversies. Clinicians should recognize that many of the published recommendations for treatment of mast cell tumors are based on opinion and should be viewed with skepticism. Because of the infrequence of this tumor in man, limited help can be expected from human oncologists, and thus the burden of responsibility for progress in predicting behavior and developing effective treatment for canine mast cell tumors falls on the shoulders of veterinarians.     

Canine subcutaneous mast cell tumors: cellular proliferation and KIT expression as prognostic indices

Molecular assays are widely used to prognosticate canine cutaneous mast cell tumors (MCT). There is limited information about these prognostic assays used on MCT that arise in the subcutis. The aims of this study were to evaluate the utility of KIT immunohistochemical labeling pattern, c-KIT mutational status (presence of internal tandem duplications in exon 11), and proliferation markers--including mitotic index, Ki67, and argyrophilic nucleolar organizing regions (AgNOR)--as independent prognostic markers for local recurrence and/or metastasis in canine subcutaneous MCT. A case-control design was used to analyze 60 subcutaneous MCT from 60 dogs, consisting of 24 dogs with subsequent local recurrence and 12 dogs with metastasis, as compared to dogs matched by breed, age, and sex with subcutaneous MCT that did not experience these events. Mitotic index, Ki67, the combination of Ki67 and AgNOR, and KIT cellular localization pattern were significantly associated with local recurrence and metastasis, thereby demonstrating their prognostic value for subcutaneous MCT. No internal tandem duplication mutations were detected in exon 11 of c-KIT in any tumors. Because c-KIT mutations have been demonstrated in only 20 to 30% of cutaneous MCT and primarily in tumors of higher grade, the number of subcutaneous MCT analyzed in this study may be insufficient to draw conclusions on the role c-KIT mutations in these tumors.     

Canine ovarian tumors of germ cell origin

Fourteen ovarian germ cell tumors were diagnosed in the dog--seven dysgerminomas and seven teratomas. Six of the teratomas had immature components and were judged malignant; three had metastasized. One dysgerminoma had metastasized. The dysgerminomas developed in dogs ten years of age and older, and the teratomas developed in dogs nine years old and younger.     

Canine subcutaneous mast cell tumor: characterization and prognostic indices

Histologic grading schemes for canine cutaneous mast cell tumors (MCTs) were not developed for subcutaneous MCTs. Despite this, subcutaneous MCTs are currently categorized by many as grade II or higher. The aim of this investigation was to assess the pathology and clinical outcome for subcutaneous MCTs to provide a more accurate prognosis. Information on clinical outcome for 306 dogs was obtained from veterinarians and correlated with histologic features. Mean and median follow-up was 842 and 891 days, respectively (range, 3-2,305 days). Only 27 (9%) were confirmed as mast cell-related deaths. Metastasis occurred in 13 (4%), and 24 (8%) had local reoccurrence, even though 171 (56%) cases had incomplete surgical margins. Median survival time was not reached, and the estimated 6-month, 1-, 2-, and 5-year survival probabilities were 95%, 93%, 92%, and 86%, respectively. Dogs were euthanized or died as a result of local tumor reoccurrence, additional MCT development distant to the surgical site, or metastasis. Decreased survival time was linked to mitotic index (number of mitotic figures per 10 high-power fields), infiltrative growth pattern, and presence of multinucleation. Both univariable and multivariable analysis showed mitotic index to be strongly predictive of survival, local reoccurrence, and metastasis. The results of the study indicate that the majority of subcutaneous MCTs have a favorable prognosis, with extended survival times and low rates of reoccurrence and metastasis.     

Principles of treatment for mast cell tumors

Mast cell tumors (MCT) are the most common malignant cutaneous tumors that occur in dogs. They are most commonly found on the trunk, accounting for approximately 50% to 60% of all sites. MCTs associated with the limbs account for approximately 25% of all sites. Cutaneous MCTs have a wide variety of clinical appearances. Histologic grade is the most consistent prognostic factor available for dogs. MCTs located at 'nail bed' (subungual), inguinal/preputial area, and any mucocutaneous area like perineum or oral cavity carry a guarded prognosis and tend to metastasize. MCTs usually exfoliate well and are cytologically distinct. The extent of staging procedures following fine-needle aspirate cytologic diagnosis is based on the presence or absence of negative prognostic indicators. Surgery is the treatment of choice for solitary MCTs with no evidence of metastasis. Reponses rates to chemotherapy, (partial response) as high as 78% have been reported, and preliminary evidence suggests that multiagent (prednisone and vinblastine) protocols may confer a higher response rate than single-agent therapy. MCTs are the second most common cutaneous tumor in the cat. There are two distinct forms of cutaneous MCTs in the cat. The more common form is the mastocytic form, and the less common is the histiocytic form. Unlike in the dog, the head and neck are the most common sites for MCTs in the cat followed by the trunk and limbs. Cats with disseminated forms of MCT often present with systemic signs of illness, which include depression, anorexia, weight loss, and vomiting. The diagnosis and staging of MCTs in cats is similar to that in the dog. As with dogs with cutaneous MCTs, surgery is the treatment of choice. Little is known about the effectiveness of adjunctive chemotherapy options for cutaneous MCTs. Adjunctive chemotherapy does not appear to increase survival times.     

Multicentric mast cell tumors in a horse

Abstract: A 6‐year‐old female Rocky Mountain horse was presented for evaluation of draining tracts and distal limb subcutaneous edema on the left front and left hind limbs that had been present for 2 weeks. Direct smears of fluid collected by fine‐needle aspiration of subcutaneous fluid from both limbs were highly cellular with a predominance of eosinophils accompanied by numerous, moderately atypical, variably granulated mast cells. The cytologic diagnosis was mast cell tumor (MCT) with prominent eosinophilic infiltration with a differential diagnosis of eosinophilic granuloma. Histologic evaluation of surgical biopsies of lesions from both limbs was performed on sections stained with H&E, toluidine blue, and Luna stains. The histologic diagnosis was MCT, and staining with toluidine blue and Luna stains confirmed the presence of mast cells and eosinophils, respectively. In addition, the mast cells strongly expressed CD117. This is the first reported case of cutaneous mast cell neoplasia in a horse in which primary presenting complaints were draining tracts and distal limb subcutaneous edema involving multiple limbs. This case illustrates the utility of staining for CD117 expression in combination with traditional stains, such as toluidine blue and Luna, in differentiating MCTs from other eosinophilic lesions in horses.     

Morphometry of canine cutaneous mast cell tumors

Twenty-four canine cutaneous nodules, diagnosed as mast cell tumors by fine-needle aspiration biopsy and confirmed by histopathologic analysis by staining with hematoxylin and eosin (HE) and toluidine blue, were analyzed by computerized nuclear morphometry on panoptic- and HE-stained cytopathology slides. Two hundred nuclei per lesion were examined. The morphometric parameters investigated were nuclear area, mean diameter, perimeter, regularity factor, and ellipticity factor. Lesions were graded as I (well differentiated), II (intermediate differentiation), or III (poorly differentiated) according to the following morphologic features: invasiveness, cellularity and cellular morphology, mitotic index, and stromal reaction. Nuclear morphometric results were then compared with histopathologic grades. Values of nuclear area, mean diameter, and perimeter increased with increase in histopathologic grade, but statistical analysis revealed significant differences only between grades II and III and between grades I and III when HE was used (P < 0.01) and between grades I and III with panoptic stain (P < 0.05). The ellipticity factor and regularity factor did not reveal significant differences between histopathologic grades. The results indicate that nuclear morphometric analysis, in combination with the rapid and inexpensive cytopathology technique, can help in mast cell tumor grading, thus contributing to the establishment of a more precise prognosis and treatment.