Gastrointestinal stromal tumors and leiomyomas in the dog: a histopathologic,immunohistochemical, and molecular genetic study of 50 cases

Fifty canine gastrointestinal (GI) mesenchymal tumors were examined to determine the occurrence of leiomyomas (LM) and GI stromal tumors and to compare their clinicopathologic features. Twenty-one tumors (42%) were histologically reclassified as gastrointestinal stromal tumors (GISTs) and 29 tumors (58%) as LMs on the basis of their histologic similarity with homologous human tumors. The GISTs occurred equally in males and females, with a mean age of 11 years (range 5-14 years). Five GISTs (24%) were associated with clinical signs and six (29%) had metastasis in liver or abdominal cavity. The GISTs occurred in large intestine (10, 48%), small bowel (six, 29%), stomach (four, 19%), and mesentery of small intestine (one, 5%). Histologically, they were highly cellular spindle, or less commonly epithelioid tumors with mitotic rates ranging from 0 to 19 per 10 HPF. Eleven tumors (52%) were positive for CD117 (KIT); seven (33%) were positive for smooth muscle actin but none for desmin and S-100 protein. Sequences of KIT exon 11, often mutated in human GISTs, were evaluated from four GISTs. Deletion of Try556-Lys557 coexisting with duplication of Gln555 in one case of GIST and T to C transition resulting in substitution of Pro for Leu575 in another were identified. The LMs occurred predominantly in males (82%) with a mean age of 11 years (range 8-17 years). Nine tumors (31%) had associated clinical signs. They occurred in the stomach (22, 76%), esophagus (four, 14%), and intestines (three, 10%); all were paucicellular, had no mitoses, and were composed of mature smooth muscle cells. Twenty-eight (97%) were positive for smooth muscle actin and 18 (62%) for desmin but none for CD117 and S-100. Both GISTs and true LMs occur in the GI tract of dogs. Both tumors have distinctive pathologic features.     

Immunohistochemical Differentiation and Clinicopathological Features of Canine Gastrointestinal Stromal Tumors and Leiomyosarcomas

Introduction:  Gastrointestinal stromal tumors (GIST) and leiomyosarcomas (LMS) have recently been differentiated by immunohistochemical staining techniques and have been shown to have different biological behaviors in humans. Expression of the c‐kit protein, a transmembrane tyrosine kinase receptor, occurs in nearly all GISTs. The aim of this study was to differentiate canine GIST from LMS, and to compare their clinicopathological features.
Methods:  Archived blocks of previously diagnosed LMS were analyzed. Immunohistochemical staining using antibodies against c‐kit, smooth muscle actin (SMA), desmin, vimentin and S100 was performed. GISTs were diagnosed based on positive c‐kit staining. LMS were diagnosed based on absence of c‐kit staining and positive SMA staining. Follow‐up information was obtained from medical records and telephone interviews with owners.
Results:  Forty‐two dogs were included in the study. Mean age was 10.9 yrs (range 5–15 yrs). There were 18 females and 24 males. Twenty‐eight tumors were GISTs, 10 were LMS and 4 stained negatively for c‐kit, SMA and S100 (sarcomas). GISTs were more likely to occur in the large intestine and LMS were more common in the small intestine (p = 0.01). All were surgically excised and only two were treated with adjunctive chemotherapy. Only two GISTs and one sarcoma had metastasized at the time of surgery. Survival time in dogs discharged after surgery for GIST, LMS and sarcomas was 1123, 233 and 88 days respectively (p = 0.08).
Conclusions:  Many previously diagnosed LMS should be reclassified as GIST based on the results of immunohistochemical staining. The biological behavior of these tumors appears to be different.     

KIT-positive gastrointestinal stromal tumor in a 22-year-old male chimpanzee (Pan troglodites)

Gastrointestinal stromal tumors (GIST), KIT-positive and KIT signaling driven or platelet-derived growth factor receptor alpha (PDGFRA) signaling driven mesenchymal tumors, are poorly known in nonhuman primates. Availability of KIT- and PDGFRA-inhibitor drug imatinib mesylate has greatly raised the interest for these tumors. At necropsy of a 22-year-old male chimpanzee, a round, firm 2-cm intramural tumor was incidentally found in the midbody of the stomach and diagnosed as a GIST. Histologically, the mass was composed of spindle to polygonal epithelioid cells arranged in short to intermediate-length, interlacing streams, bundles, and nodular whorls often separated by hyalinized eosinophilic matrix. The mitotic rate was a maximum 1/50 high-power field. Immunohistochemically, the tumor cells were diffusely positive for KIT and CD34, focally positive for alpha-smooth muscle actin, and negative for muscle specific actin, desmin, S-100 protein, synaptophysin, and glial fibrillary acidic protein. Because the majority of human GISTs have gain-of-function KIT or PDGFRA mutations, genomic sequences of KIT exons 9, 11, 13, and 17 and PDGFRA exons 12 and 18 from this chimpanzee GIST were polymerase chain reaction amplified and sequenced. However, no mutation was identified in the analyzed "mutational hot spots." This study is the first extensive histomorphologic, immunohistochemical, and molecular genetic analysis of a chimpanzee GIST. More cases of nonhuman primate GISTs should be analyzed to discover the clinicopathologic spectrum of GISTs in these species.     

Imatinib mesylate treatment in a dog with gastrointestinal stromal tumors with a c-kit mutation

A 13-year-old spayed mixed-breed dog was diagnosed with a gastrointestinal stromal tumor (GIST) after histopathological examination of an abdominal mass. Five months after surgical resection of the tumor, we detected the recurrence of GIST with multiple disseminated abdominal lesions. A sequence analysis of cDNA obtained from a biopsy of the recurrent tumors revealed a mutation within exon 9 of the c-kit gene (1523A>T, Asn⁵⁰⁸Ile), which has been shown to cause ligand-independent phosphorylation of the KIT protein in GISTs and canine mast cell tumors (MCTs). Upon detection of the recurrent tumors, we initiated treatment with imatinib mesylate (10 mg/kg, q 24 hr). After 2 months, the dog achieved complete remission. Our findings indicate that canine GIST, and possibly MCT, may be responsive to molecular-targeted therapy.     

Cutaneous leiomyosarcoma with visceral metastases in a White Carneau pigeon and literature review

Cutaneous leiomyosarcomas are malignant mesenchymal tumors of smooth muscle origin and are reported occasionally in avian species. A 14-y-old male laboratory White Carneau pigeon (Columba livia) was presented for surgical excision of a cervical soft tissue mass. Ultrasonography with color flow Doppler imaging revealed multiple cavitations of mixed echogenicity within the mass and vascularization. Histologically, the dermis and subcutis were expanded by a densely cellular multinodular mass comprised of fusiform cells forming haphazardly arranged broad streams and short interwoven bundles, often surrounding blood vessels and variably sized cavitations. Neoplastic cells were strongly immunopositive for desmin and α–smooth muscle actin, and negative for pancytokeratin, S100, and von Willebrand factor. Based on histopathology and IHC findings, the cutaneous mass was diagnosed as leiomyosarcoma (LMS). The pigeon died 312 d post-operatively. Postmortem examination revealed masses infiltrating the left and right pulmonary airways and one hepatic nodule, but no regrowth at the surgical site. Histologic and IHC evaluation of the pulmonary and hepatic masses were consistent with LMS, representing metastatic foci from the primary cutaneous LMS. Our case highlights the malignant behavior and histomorphologic features of cutaneous LMS in an avian species.     

Prognostic factors for dogs with surgically resected gastrointestinal stromal tumors

Few reports have investigated prognosis of canine gastrointestinal stromal tumor (GIST) cases treated by surgical resection alone. In the present study, we investigated the overall survival (OS) and prognostic factors for dogs with GIST treated by surgical complete resection alone. Fifty-three dogs were included, and the median OS was 18 months. Multivariate analysis showed that primary tumors in small intestine (P=0.04) is significantly associated with shorter OS, and median OS of the cases with cecum lesion and those with small intestine lesion was 22 and 6 months, respectively. The present study suggested primary tumor site was a novel prognostic factor for dogs with GIST treated by surgical complete resection alone.     

Mammary tumor recurrence in bitches after regional mastectomy

Objectives— To investigate the histologic diagnosis and incidence of new mammary tumor growth in the remaining mammary chain tissue after regional mastectomy.
Study Design— Prospective clinical study.
Animals— Female dogs (n=99) that had excision of a single mammary tumor.
Methods— Female dogs that had regional mastectomy to remove a single tumor were followed for ≥1 year postoperatively. Data regarding tumor type, tumor recurrence, and development of metastasis were recorded.
Results— Fifty-seven (58%) dogs developed a new tumor in the ipsilateral mammary chain after the 1st surgery; 77% had repeat surgery. There was no significant correlation between the time to new tumor development and the histologic diagnosis for the 1st and 2nd tumor types. In 31 dogs, the histologic diagnosis for initial and subsequent tumors was identical and there was a significant correlation such that dogs with an initial malignant tumor are likely to develop another malignant tumor ( P =.0089). The histologic classification of the new tumor was likely to be malignant if it was located close to the side where the initial tumor had been removed ( P =.026).
Conclusions— Our results show that 58% of dogs developed a new tumor in the remaining mammary glands of the ipsilateral chain after regional mastectomy for removal of a single tumor.
Clinical Relevance— This should be taken into account when deciding on the surgical management (radical or regional mastectomy) in dogs with single mammary tumors.     

Histologic prognosticators in feline osteosarcoma: a comparison with phenotypically similar canine osteosarcoma

Objective— To investigate the histologic characteristics of feline osteosarcoma (OS) and compare the histologic data with phenotypically comparable canine OS. The effects of histologic and clinical variables on survival statistics were evaluated.
Study Design— Retrospective study.
Animals— Cats (n=62) and dogs (22).
Methods— Medical records of 62 cats with OS were reviewed for clinically relevant data. Clinical outcome was obtained by telephone interview. Histologic characteristics of OS were classified using a standardized grading system. Histologic characteristics in 22 feline skeletal OS were compared with 22 canine skeletal OS of identical location and subtype. Prognostic variables for clinical outcome were determined using multivariate analysis.
Results— Feline OS was characterized by moderate to abundant cellular pleomorphism, low mitotic index, small to moderate amounts of matrix, high cellularity, and a moderate amount of necrosis. There was no significant difference between histologic variables in feline and canine OS. Histologic grade, surgery, and mitotic index significantly influenced clinical outcome as determined by multivariate analysis. Tumor invasion into vessels was not identified as a significant prognosticator.
Conclusion— Feline and canine skeletal OS have similar histologic but different prognostic characteristics.
Clinical Relevance— Prognosis for cats with OS is related to histologic grade and mitotic index of the tumor.     

Gastrointestinal stromal tumors in equids.

Eleven gastrointestinal neoplasms from 10 aged horses and 1 pony were examined grossly, his tologically, immunohistochemically, and (in two cases) ultrastructurally. Clinical signs were associated with two neoplasms, and the other nine tumors were incidental findings at laparotomy or necropsy. The neoplasms were solitary (9/11) or multifocal (2/11), well demarcated, serosal or mural masses of stomach (1), jejunum (1), ileum (3), cecum (5), and/or colon (2). Microscopic examination revealed discrete spindle cells arranged in compact patterns with fascicles and whorls or cribriform pattern with fascicles and rare palisades, often with a myxoid interstitial matrix. Three tumors infiltrated between the muscularis interna and the muscularis externa at the myenteric plexi. All neoplasms were vimentin positive, 3/11 were S-100 positive, 2/11 were muscle actin positive, and no neoplasm was positive for glial fibrillary acid protein, desmin, factor VIII, chromogranin, or neuron-specific enolase. Of the two tumors studied ultrastructurally, one contained an admixture of smooth muscle cells and cells resembling Schwann cells, and the second was populated by homogeneous fusiform mesenchymal cells separated by homogeneous matrix. Gastrointestinal stromal tumors (GIST) have been recognized in humans, more recently in dogs and nonhuman primates, and now in equids. Most of these tumors are comprised of a loosely arranged network of spindled cells separated by myxoid matrix. GIST may be composed of myogenic, neurogenic, combined myogenic and neurogenic, and undifferentiated mesenchymal cells.     

Gastrointestinal stromal tumors of the equine cecum

Ten cecal tumors were identified during the postmortem examination of seven horse carcasses at slaughter (one horse had three tumors). The multinodular and hemorrhagic tumors ranged from 1 to 10 cm in diameter and consisted of spindle cells arranged in thin, interconnected trabeculae that were often separated by sinuses filled with mucinous fluid, erythrocytes, and siderophages. Spindle cells of all tumors were immunopositive for vimentin, neuron-specific enolase, and c-kit protein but lacked reactivity with antibodies to glial fibrillary acidic protein, S100 protein, and desmin. In one tumor, spindle cells diffusely bound antibodies to synaptophysin. Most tumors contained focal reactivity to smooth muscle actin antibodies; one tumor reacted diffusely. Ultrastructurally, tumor cells were connected by desmosome-like structures and exhibited extended cell processes; some contained dense core neurosecretory granules. These equine stromal tumors appeared to share some characteristics with human gastrointestinal stromal tumors.     

Expression of the KIT protein (CD117) in primary cutaneous mast cell tumors of the dog.

Thirty-one canine cutaneous masses, diagnosed as mast cell tumors (MCT) by histopathologic analysis, were used to evaluate the immunohistochemical pattern of expression of KIT protein (CD117), a type III tyrosine kinase protein involved in mast cell growth and differentiation. 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. Immunohistochemical KIT expression was compared with histologic grade and some histomorphologic features (cell differentiation and nuclear grade) evaluated separately. A possible predictive role of biologic behavior in MCTs for KIT expression was also investigated. Immunohistochemical analysis revealed three different patterns of KIT expression: a cytoplasmic diffuse pattern, a membranous pattern with immunostaining located on the cell surface, and a cytoplasmic perinuclear pattern, where KIT expression was detected in the cytoplasm of the neoplastic mast cells, close to the nucleus. Statistical analysis showed a close relationship between different KIT immunohistochemical patterns and histologic grade (P < 0.00000), cell differentiation (P < 0.00000), and nuclear grade (P < 0.0024). According to Kaplan-Meier-estimated survival curves compared by survival analysis, KIT expression was significantly associated with survival time (P = 0.037) but not cancer-free interval (P = 0.50). Similar to other well-known histomorphological features, KIT expression is a useful parameter of malignancy in cutaneous MCTs. KIT expression also predicted the biological behavior of the tumors in this study.     

Marginal excision of low-grade spindle cell sarcoma of canine extremities: 35 dogs (1996-2006)

Objective— To evaluate recurrence rate and disease-free interval (DFI) of dogs with low-grade soft tissue spindle cell sarcoma of the extremities treated by marginal excision.
Study Design— Retrospective study.
Animals— Dogs (n=35) with soft tissue low-grade spindle cell sarcoma.
Methods— Medical records were reviewed and dogs that had marginal surgical resection of low-grade soft tissue spindle cell sarcoma at or distal to elbow and stifle were included.
Results— Histopathologic margins were dirty (12 dogs), clean but close (12), and clean (11). Follow-up after surgery occurred from 210 to 2202 days (minimum, 180 days). Local recurrence and metastatic rates were 10.8% and 0%, respectively. Median DFI and survival time were not reached, because <50% of dogs died of disease-related events. Mean DFI and mean survival time were 697.8 days (95% CI: 559.7–836 days) and 703.5 days (95% CI: 566.6–840.5 days), respectively. There were no significant differences among survival functions stratified by histologic margins.
Conclusion— Marginal surgical excision without adjuvant treatment of low-grade soft tissue spindle cell sarcoma of the extremities results in a low local recurrence rate.
Clinical Relevance— Low-grade spindle cell sarcomas located at or distal to the elbow and stifle joints can be excised without need for wide or radical surgery.     

Analysis of Sodium Carboxymethylcellulose Administration and Related Factors Associated with Postoperative Colic and Survival in Horses with Small Intestinal Disease

Objective— To analyze the effect of the intraoperative use of sodium carboxymethylcellulose (CBMC) and related perioperative factors on postoperative colic and survival in horses that had abdominal surgery for colic.
Study Design— Retrospective study.
Animals— Horses (n=203) that had surgery for small intestinal disease; 33 horses had intraoperative administration of CBMC.
Methods— Information was obtained from medical records for 170 horses that had surgery for colic before use of CBMC and 33 horses that had intraoperative CBMC. Kaplan–Meier survival curves were used to estimate median survival time and a Cox proportional hazards model was used to estimate the hazard ratio for the effect of CBMC and other perioperative variables on survival.
Results— Seventy-five percent of horses administered CBMC survived to 180 days, whereas 75% of untreated horses survived 8 days (median survival time=18 days). Horses not administered CBMC were twice as likely to die compared with horses administered CBMC. Horses that had postoperative ileus (POI) were 1.4 times more likely to die than horses without ileus. Similarly, horses with signs of colic after surgery were 1.3 times more likely to die than horses without postoperative signs of colic.
Conclusions— CBMC administration is seemingly protective against death and prolongs survival when used intraoperatively in horses with small intestine disease, particularly horses with postoperative colic or POI. Both POI and colic increased risk of death after surgery.
Clinical Relevance— Intraoperative administration of CBMC in horses that have surgery for small intestinal disease may improve survival, possibly by reducing early adhesion formation.     

Hypotonic water as adjuvant therapy for incompletely resected canine mast cell tumors: a randomized, double-blind, placebo-controlled study

Objective— To evaluate efficacy of hypotonic water as adjuvant therapy after marginal resection of canine mast cell tumors (MCT).
Study Design— Double-blinded, placebo-controlled, prospective, randomized study.
Animals— Dogs (n=30) with spontaneous, cutaneous, solitary MCT.
Methods— The wound bed of MCT, resected with margins <0.5 cm, was injected with either hypotonic or isotonic water according to a standardized protocol. Follow-up was obtained by clinical examination at 1, 2, 3, 6, and 12 months and annual telephone contact with the owner.
Results— Eighteen dogs were treated with isotonic lactated Ringer's solution and 12 dogs with hypotonic distilled water. All MCT were stage 0 tumors and most grade II. Six tumors (4 isotonic, 2 hypotonic) recurred locally, 3 of these dogs died from disease-related reasons within 4 months. The surviving 3 dogs were alive with a median survival time (ST) of 1092 days. The calculated 2-year recurrence-free rate was 92.7%; the 2-year disease-free rate 79.1%; and the 2-year survival rate 89.5%. No significant differences in local recurrence and ST were observed between treatment groups. Histologic grading was the only significant prognosticator for ST and recurrence-free periods.
Conclusion— No significant differences in local recurrence and ST were observed between adjunctive hypotonic water and placebo treatment after marginal resection of solitary MCT.
Clinical Relevance— Hypotonic water does not decrease the rate of local recurrence in dogs with solitary MCT after marginal surgical excision.     

Prognosis Factors for Survival in Cats After Removal of a Primary Lung Tumor: 21 Cases (1979–1994)

Objective —To identify possible prognostic factors for survival time in cats with a primary lung tumor after surgical excision.
Study Design —Retrospective clinical study.
Animal Population —21 cats with histologically confirmed primary lung tumors removed surgically.
Methods —Medical records for cats treated between 1979 and 1994 at 14 participating veterinary referral hospitals were reviewed.
Results —After surgical resection and recovery, 18 cats died from metastatic disease with a median survival time of 115 days (range, 13 to 1,526 days). Three cats were lost to follow-up at 119 days, 251 days, and 410 days after the surgical procedure. Contingency table analysis to determine if an association existed between clinical findings (breed, age, gender, body weight, clinical signs, duration of clinical signs, and radiographic findings) or histological features and survival time was performed. Only histological morphology of the primary lung tumor showed a significant association with survival time. Twelve cats with moderately differentiated tumors had a significantly longer survival time (median, 698 days; range, 19 to 1,526 days) than the nine cats with poorly differentiated tumors (median, 75 days; range, 13 to 634 days).
Conclusions —Surgical resection of a solitary primary lung tumor in cats is indicated.
Clinical Relevance —A poor prognosis for long-term survival is warranted for those cats having a poorly differentiated primary lung tumor.     

Effect of Tissue Processing on Assessment of Endoscopic Intestinal Biopsies in Dogs and Cats

Background: Prior studies failed to detect significant association between hypoalbuminemia and small intestinal lesions.
Hypothesis: Use of pictorial templates will enhance consistency of interpathologist interpretation and identification of intestinal lesions associated with hypoalbuminemia.
Animals: Tissues from 62 dogs and 25 cats examined as clinical cases at 7 referral veterinary practices in 4 countries.
Methods: Retrospective, observational study. Histopathology slides from sequential cases undergoing endoscopic biopsy were examined by 4 pathologists by pictorial templates. Changes for 9 microscopic features were recorded as normal, mild, moderate or severe, and 2- and 4-point scales were tested for consistency of interpretation. Logistic regression models determined odds ratios (OR) of histologic lesions being associated with hypoalbuminemia while κ statistics determined agreement between pathologists on histologic lesions.
Results: There was poor agreement (κ=−0.013 to 0.3) between pathologists, and institution of origin of slides had effect (κ= 1.0 for 3 of 4 lesions on slides from Institution 5) on agreement between pathologists on selected histologic features. Using 2 point as opposed to 4-point grading scale increased agreement between pathologists (maximum κ= 0.69 using 4-point scale versus maximum κ= 1.0 using 2-point scale). Significant association ( P = .019– .04; 95% OR = 3.14–10.84) between lacteal dilation and hypoalbuminemia was found by 3 pathologists.
Conclusions and Clinical Importance: Substantial inconsistency between pathologists remains despite use of pictorial template because of differences in slide processing. Distinguishing between mild and moderate lesions might be important source of the disagreement among pathologists.     

Risk Factors for Equine Postoperative Ileus and Effectiveness of Prophylactic Lidocaine

Background: Postoperative ileus (POI) is a frequent and often fatal complication of colic surgery. Reliably effective treatments are not available.
Objectives: To determine risk factors and protective factors associated with POI, and to assess the effect of lidocaine IV on short-term survival.
Animals: One hundred and twenty-six horses that underwent small intestinal colic surgery and that survived for at least 24 hours postoperatively.
Methods: Retrospective cross-sectional study. The association of 31 pre-, intra-, and postoperative variables with POI and the association of lidocaine treatment with short-term survival were investigated. Associations were evaluated with univariable logistic regression models, followed by multivariable analysis.
Results: Significant associations of high heart rate (odds ratio [OR] = 1.05, 95% confidence interval [CI] 1.03–1.08), the presence of more than 8 L of reflux at admission (OR = 3.02, 95% CI 1.13–8.02) and the performance of a small intestinal resection (OR = 2.46, 95% CI 1.15–5.27) with an increased probability of POI were demonstrated. Prophylactic lidocaine treatment was significantly associated with a reduced incidence of POI (OR = 0.25, 95% CI 0.11–0.56). Lidocaine treatment was also significantly associated with enhanced short-term survival (OR = 0.30, 95% CI 0.09–0.98).
Conclusions and Clinical Importance: The variables associated with an increased risk of POI can be useful in identifying horses at risk of POI and in providing a more accurate prognosis. The results are supportive for lidocaine IV as an effective prokinetic treatment after small intestinal colic surgery.     

Probable paraneoplastic leukocytosis in a dog with a gastrointestinal stromal tumor

A 9-year-old female spayed Boston Terrier presented for diagnostic investigation of lethargy, poor appetite, weight loss, and a marked leukocytosis. Significant muscle wasting and a palpable abdominal mass were present on physical examination. Abdominal imaging revealed the mass to be of small intestinal origin; consequently, an intestinal resection and anastomosis were performed without complication. The histopathologic diagnosis was a gastrointestinal stromal tumor, verified by immunohistochemical positivity to CD117 (KIT). Two weeks after discharge, the leukocytosis had resolved. Though the exact molecular mediator of the severe leukocytosis was undetermined, resolution following tumor removal suggests a paraneoplastic cause. To the authors' knowledge, this is the first reported case of probable paraneoplastic leukocytosis secondary to a gastrointestinal stromal tumor in the dog. Gastrointestinal tract imaging should be performed when this uncommon hematologic abnormality is present.     

Prognostic value of histologic stage and proliferative activity in canine malignant mammary tumors.

The aim of this study was to investigate the correlation between the histologic invasiveness (histologic stage) and various cell proliferation activity assays (quantity of argyrophil proteins associated with nucleolar organizer regions [AgNORs], mitotic activity, MIB1 [Ki67] immunohistochemical detection) for predicting the biologic behavior of malignant canine mammary tumors. Sixty specimens from malignant canine mammary tumors with no distant metastases (M0) at surgery were selected, and follow-up data were collected over a 2-year period. The histologic invasiveness was graded by histologic stage (stage 0 = tumors without stromal invasion; stage I = tumors with stromal invasion; stage II = tumors with neoplastic emboli in vessels), and the proliferative indices were expressed as MIB1 index (the percentage of nuclear area immunohistochemically stained by MIB1 antibody), mitotic index (the number of mitoses per 1,000 neoplastic cells), and AgNOR index (the ratio between mean AgNOR area of tumor cells and the mean AgNOR area of fibroblasts/lymphocytes). The measures of proliferative activity were compared among groups with different histologic stages, and the influence of different prognostic variables (histologic stage, AgNOR index, mitotic index, MIB1 index) on survival time was evaluated. A significant difference in the proliferation patterns was recorded between the different histologic stages for the mitotic index (P = 0.0006) and MIB1 index (0.0013). Among the different parameters considered, histologic stage (P < 0.05), AgNOR index (P = 0.0291), and MIB1 index (P = 0.014) revealed a significant association with prognosis in univariate analysis. AgNOR index for 1-year survival and histologic stage for 2-year survival were the most significant parameters influencing survival, as determined by multiple nonlinear logistic regression.     

Clinical study of cryosurgery efficacy in the treatment of skin and subcutaneous tumors in dogs and cats

Objective— To evaluate the efficacy of cryosurgery for treatment of skin and subcutaneous tumors in dogs and cats.
Study Design— Prospective study.
Animals— Dogs (n=20), cats (10).
Methods— Cutaneous or subcutaneous tumors were treated by liquid nitrogen cryosurgical spray (1 cm from target tissue at 90° until a 5-mm halo of frozen tissue was achieved) for 15–60 seconds. Malignant lesions had 3 freeze–thaw cycles benign tumors, 2 cycles. The second or third freeze cycle was performed after complete thaw of the preceding freeze. Wounds healed by second intention. Follow-up was weekly for 1 month and then twice monthly until wounds healed, and final outcome was determined by telephone interview of owners.
Results— Tumor size ranged from 0.3 to 11 cm diameter with 28 (60%) being 0.3–1 cm; 8 (17%) 1.1–3 cm, and 11 (23%) >3.4 cm. Complications included edema, erythema and for extremity lesions, pain and lameness. Treated lesions (n=47) had an overall remission of 98% (mean follow-up, 345±172.02 days [range, 150–750 days]). One malignant peripheral nerve sheath tumor recurred 7 months after cryosurgical treatment.
Conclusion— Cryosurgery is an efficient method for treatment of skin and subcutaneous tumors in dogs and cats.
Clinical Relevance— Cryosurgical ablation is an effective means of treating small cutaneous or subcutaneous tumors in dogs and cats, especially in older animals where wound closure or cosmetic outcome might limit surgical excision alone.