Long-term postsurgical outcomes of mast cell tumors resected with a margin proportional to the tumor diameter in 23 dogs.

We evaluated the postsurgical outcomes of cutaneous or subcutaneous mast cell tumors (MCTs, n=25) in 23 dogs, resected with lateral surgical margins proportional to the widest tumor diameter, including at least one facial plane. The tumor diameter range was 0.3-2.6 cm (median: 0.9 cm), and all were histologically diagnosed as Kiupel's low-grade MCT. Resection was histologically complete in 20, close (deep margin) in three, and incomplete (deep margin) in two. No dogs developed local recurrence at the site of initial surgery during follow-up of 161-2,219 days (median: 976 days). These results suggest that resection of low-grade, relatively small MCTs with surgical margins proportional to the tumor diameter is a practical procedure with high success rates.

Periocular cutaneous mast cell tumors in cats: evaluation of surgical excision (33 cases).

OBJECTIVE: To describe feline periocular cutaneous mast cell tumor (CMCT) clinical features, rates of local tumor recurrence and metastases, and cat survival time following surgical excision. ANIMALS STUDIED: Thirty-three cats with periocular CMCTs. PROCEDURES: Medical records of cats diagnosed with periocular CMCTs were reviewed; cats were included if CMCTs were surgically excised and the diagnosis confirmed by histopathology. The appearance, size, location and histopathology findings of CMCTs were recorded. Rates of local recurrence, metastasis, and survival time following surgical excision were collected when available. RESULTS: All periocular CMCTs were restricted to the eyelids. In addition to surgical excision, three cats were treated with adjunctive therapy (strontium-90 irradiation or cryotherapy) intraoperatively. Local tumor control was achieved in 22/23 cats with a minimum follow-up of 30 days (median follow-up time of 711 days); one cat developed disseminated CMCTs but no local recurrence. Cats with periocular CMCTs had a median survival time of 945 days. Metastatic disease involving peripheral lymph nodes or abdominal viscera was not detected in any cat at any time during the study. All periocular CMCTs were classified as low-grade based on histopathology, and complete excision was achieved in approximately 50% of cases. CONCLUSIONS: Surgical excision of periocular CMCTs in cats is an effective treatment option with rare local recurrence and metastases, even following incomplete surgical excision.

Mutation and methylation status of KIT and TP53 in canine cutaneous and subcutaneous mast cell tumours.

Cutaneous and subcutaneous mast cell tumours (MCTs) are counted among the most frequent cancers in dogs. However, the genetic aetiology of their development is still mostly unknown, with the exception of KIT and tumor protein p53 (TP53 ) mutations reported in less than a half of cutaneous MCTs. In subcutaneous MCTs, no gene alterations were previously detected. We analysed KIT and TP53 mutations in cutaneous and subcutaneous MCTs, and identified methylated CpG sites in KIT and TP53 promoters and adjacent exon 1 regions. The mutation analysis focused on KIT exons 8, 9 and 11, and TP53 exons 5-8, and revealed mutations in 26% and 7% cutaneous MCT cases, respectively. Moreover, we report a first case of KIT mutation ever detected in subcutaneous MCTs. KIT exon 11 mutations and high Kiupel and Patnaik grades were associated with reduced survival in this study. Both KIT and TP53 gene were generally unmethylated in canine cutaneous MCTs. A sporadic methylation of the CpG positions in KIT promoter and adjacent exon 1 was detected in 70.4% of cutaneous and 82% of subcutaneous MCTs. A sporadic methylation of the CpG positions in the TP53 promoter and exon 1 was observed in 36.8% of the analysed cutaneous MCT samples. Only in two subcutaneous MCTs, we observed more than 30% of clones showing KIT methylation at the CpG positions 13 or 14. The CpG position 14 is involved in a predicted binding site for Sp1 transcription factor. However, the significance of KIT promoter methylation at this specific position needs further evaluation.

Retrospective outcome evaluation for dogs with surgically excised, solitary Kiupel high-grade, cutaneous mast cell tumours.

Published outcomes for dogs with specifically high-grade mast cell tumours (MCTs), controlled for clinical stage, are few. Clinical outcomes for 49 dogs with Kiupel high-grade, clinical stage I, cutaneous MCTs were evaluated. Median survival time (MST) was 1046 days; 1 and 2-year survival rates were 79.3% and 72.9%, respectively. At study end 24 dogs had died, 23 dogs were alive (median follow-up 980 days) and 2 dogs were lost to follow-up. Death was considered MCT-related in 14 of 20 dogs with a known cause of death. Local tumour recurrence developed in nine dogs (18.4%); regional lymph node metastasis occurred in six dogs (12.2%); and a new MCT developed in 15 dogs (30.1%). Tumour location, histologic margin size and use of chemotherapy did not affect MST; increasing mitotic count (P = .001) and increasing tumour diameter (P = .024) were independently negatively prognostic. Six dogs that developed lymph node metastasis after surgery had worse MST (451 days) than 42 dogs that did not develop metastasis (1645 days); (P < .001). Our study suggests that dogs with local surgical control of clinical stage I histologically high Kiupel grade cutaneous MCT may have a long survival time; especially those with smaller tumours and a lower mitotic count. Our results suggest that evaluation of staging information and mitotic count may be equally helpful as histologic grading when making a prognosis; and highlight the importance of not relying on histologic grade alone when predicting survival for dogs with MCT.

Therapeutic impact of regional lymphadenectomy in canine stage II cutaneous mast cell tumours.

Lymph node (LN) metastasis in canine cutaneous mast cell tumours (cMCTs) is a well-known negative prognostic factor. The role of lymphadenectomy in the treatment of stage II disease remains controversial because of its uncertain therapeutic benefit. Aim of this retrospective study was to investigate the impact of lymphadenectomy on tumour control and survival for dogs with stage II cMCTs. Dogs with firstly occurring, histologically confirmed cMCT with LN metastasis undergoing resection of the primary tumour and medical treatment thereafter were retrospectively enrolled. Dogs were classified into two groups: LN sampling (LNS; diagnosis of metastasis obtained by cytology) and regional LN dissection (LND; diagnosis obtained by histopathology). To determine the therapeutic value of lymphadenectomy, the characteristics of recurrence (local, nodal and distant) and survival were compared between groups. Evaluated outcome variables included signalment, anatomic location, diameter, ulceration, substage, surgical margins, Patnaik grading, Kiupel grading and medical treatment. Overall, 152 dogs were included: 81 underwent LND as part of primary surgery and 71 LNS. The median follow-up time was 409 days for LND group and 620 days for LNS group. On univariable analysis, the risk of developing local, nodal or distant relapse was significantly higher in the LNS group compared with LND (P < 0.001). On multivariable analysis, the risk of tumour progression and tumour-related death were 5.47 and 3.61 times higher in the LNS group, respectively (P < 0.001). Regional lymphadenectomy may have therapeutic value and improve prognosis in dogs with stage II cMCTs undergoing surgical removal of the primary tumour and medical treatment.

Comparison of histologic margin status in low-grade cutaneous and subcutaneous canine mast cell tumours examined by radial and tangential sections.

BACKGROUND: Radial sections are widely used to estimate adequacy of excision in canine cutaneous mast cell tumours (MCTs); however, this sectioning technique estimates only a small fraction of total margin circumference. This study aimed to compare histologic margin status in grade II/low grade MCTs sectioned using both radial and tangential sectioning techniques. MATERIALS AND METHODS: A total of 43 circumferential margins were evaluated from 21 different tumours. Margins were first sectioned radially, followed by tangential sections. Tissues were examined by routine histopathology. RESULTS: Tangential margin status differed in 10 of 43 (23.3%) margins compared with their initial status on radial section. Of 39 margins, 9 (23.1%) categorized as histologic tumour-free margin (HTFM) >0 mm were positive on tangential sectioning. Tangential sections detected a significantly higher proportion of positive margins relative to radial sections (exact 2-tailed P-value = .0215). The HTFM was significantly longer in negative tangential margins than positive tangential margins (mean 10.1 vs 3.2 mm; P = .0008). A receiver operating characteristic curve comparing HTFM and tangentially negative margins found an area under the curve of 0.83 (95% confidence interval: 0.71-0.96). Although correct classification peaked at the sixth cut-point of HTFM ≥1 mm, radial sections still incorrectly classified 50% of margins as lacking tumour cells. Radial sections had 100% specificity for predicting negative tangential margins at a cut-point of 10.9 mm. CONCLUSION: These data indicate that for low grade MCTs, HTFMs >0 mm should not be considered completely excised, particularly when HTFM is <10.9 mm. This will inform future studies that use HTFM and overall excisional status as dependent variables in multivariable prognostic models.

The impact of extirpation of non-palpable/normal-sized regional lymph nodes on staging of canine cutaneous mast cell tumours: A multicentric retrospective study.

Metastasis to regional lymph nodes (RLNs) in dogs with cutaneous mast cell tumour (cMCT) has been correlated with shortened survival time and higher risk of spread to distant sites. In the present study, extirpation of non-palpable or normal-sized RLNs was included in the surgical management of cMCT in dogs. Correlations between histological nodal status (HN0-3) and tumour variables were analysed. Ninety-three dogs with single cMCT without distant metastasis that underwent wide surgical excision of the primary tumour and extirpation of non-palpable or normal-sized RLN were included. The association between HN (HN0 vs HN > 0; HN0-1 vs HN2-3) and tumour variables (site, longest diameter, ulceration, 3-tier and 2-tier histological grades) was analysed by a generalized linear model with multinomial error. Then, 33 (35.5%) RLNs were HN0, 14 (15%) were HN1, 26 (28%) were HN2 and 20 (21.5%) were HN3. The presence of positive (HN > 0) RLN was significantly associated with cMCT larger than 3 cm. No other association was statistically significant. Non-palpable/normal-sized RLN in dogs with cMCT can harbour histologically detectable metastatic disease in nearly half of the cases. Extirpation of the RLN should always perfomed to obtain a correct staging of the disease, even in the absence of clinical suspicion of metastasis. Further studies should evaluate the possible therapeutical effect of the tumour burden reduction obtained by exrtipartion of a positive RLN.

Recurrence rates and clinical outcome for dogs with grade II mast cell tumours with a low AgNOR count and Ki67 index treated with surgery alone.

Grade II mast cell tumours (MCT) are tumours with variable biologic behaviour. Multiple factors have been associated with outcome, including proliferation markers. The purpose of this study was to determine if extent of surgical excision affects recurrence rate in dogs with grade II MCT with low proliferation activity, determined by Ki67 and argyrophilic nucleolar organising regions (AgNOR). Eighty-six dogs with cutaneous MCT were evaluated. All dogs had surgical excision of their MCT with a low Ki67 index and combined AgNORxKi67 (Ag67) values. Twenty-three (27%) dogs developed local or distant recurrence during the median follow-up time. Of these dogs, six (7%) had local recurrence, one had complete and five had incomplete histologic margins. This difference in recurrence rates between dogs with complete and incomplete histologic margins was not significant. On the basis of this study, ancillary therapy may not be necessary for patients with incompletely excised grade II MCT with low proliferation activity.

Manejo anestésico de paciente con mastocitosis cutánea / Anaesthetic managemet of cutaneous mastocytosis

Mastocytosis consists of a heterogeneous group of disorders characterized by an abnormal increase of mast cell in one or more organs or tissues. The degranulation of mast cells with subsequent clinical symptoms can be triggered by psychological, chemical or traumatic agents. The main challenge of these patients is to avoid these triggers in order to prevent an anaphylactic shock. We report a case of a patient diagnosed with cutaneous mastocytoses who underwent urgent appendicectomy. Their perioperative management involves a multidisciniplinary approach. We report the anaesthetic management in this disease.

Las mastocitosis son un grupo heterogéneo de enfermedades que se caracterizan por la proliferación de mastocitos y su posterior acumulación. La degranulación de los mastocitos puede desencadenarse por diferentes agentes como la cirugía, el estrés o los fármacos histaminoliberadores. El principal reto que plantea a un anestesiólogo un paciente con mastocitosis es la posibilidad de que se desencadene una reacción anafiláctica. Se describe el manejo anestésico de un paciente con mastocitosis cutánea. El desconocimiento de esta entidad puede suponer un aumento de la morbimortalidad de estos pacientes.

Surgically planned versus histologically measured lateral tumor margins for resection of cutaneous and subcutaneous mast cell tumors in dogs: 46 cases (2010-2013).

OBJECTIVE: To compare preplanned lateral surgical margins and measured lateral histologic margins for cutaneous and subcutaneous mast cell tumor (MCT) resections in dogs. DESIGN: Retrospective case series. SAMPLE: 51 biopsy specimens from dogs (n = 46) with MCTs. PROCEDURES: All canine patients that underwent curative-intent surgical resection of cutaneous or subcutaneous MCTs from January 1, 2010, through June 30, 2013, with complete medical records including signalment, body condition score (BCS), surgery report (with measured surgical margins), and histopathology report were included. The surgically measured tumor margins in each quadrant were grouped and compared with the corresponding histologic margins. Specimens from dogs with truncal MCTs and a BCS of 7 to 9 on a scale from 1 to 9 (ie, high) were compared with those of dogs with a BCS of 4 to 6 to evaluate effect of BCS on tissue margins. RESULTS: 51 specimens were included. Surgically mapped lateral margins differed significantly from histologically reported margins in all 4 quadrants. The mean histologic margins were 35% to 42% smaller than the surgical margins for the combined 51 specimens. A higher BCS did not significantly influence the magnitude of the decrease in lateral margins measured histologically. No significant difference was found for the magnitude of the differences between any of the 4 lateral margins. CONCLUSIONS AND CLINICAL RELEVANCE: Results of this study suggested that surgical and histologic margins may differ significantly for canine cutaneous and subcutaneous MCTs. This may be a result of tissue shrinkage following excision and fixation, extension of the MCT beyond palpable margins, or both. Histologic measurements may significantly underestimate the tumor-free margins in dogs with cutaneous and subcutaneous MCTs.

Feline cutaneous mast cell tumours: a UK-based study comparing signalment and histological features with long-term outcomes.

Feline cutaneous mast cell tumours (MCTs) are the second most common skin tumour in cats; but, unlike in dogs, there is currently no histological grading system for this type of tumour. This study recorded the signalment and anatomical location from a total of 287 records from MCTs submitted to a UK commercial diagnostic laboratory. Questionnaires to submitting practices were used to obtain follow-up data, and the histological features of 86 tumours were evaluated from 69 cats with a known outcome. Twelve of the 69 cats (17.4%) died of MCTs, with significantly lower survival times. The median age of cats presenting with MCTs was 11 years (range 5 months-19 years), with no sex or neutered status predilection. Some pedigree breeds were more susceptible to MCTs, particularly the Siamese, Burmese, Russian Blue and Ragdoll. The head was the most common site in younger cats, compared with the trunk in older cats. The number of tumours had no effect on survival. A new subcategory of well-differentiated MCTs with prominent multinucleated cells is described, and three of the five cats with this novel form died from MCT-related disease. There was an association between mitotic index and survival time. However, there was no significant association between histological type and survival.

Evaluation of a modified proportional margins approach for surgical resection of mast cell tumors in dogs: 40 cases (2008-2012).

OBJECTIVE: To evaluate a modified proportional margins approach to resection of mast cell tumors (MCTs) in dogs. DESIGN: Retrospective case series. ANIMALS: 40 dogs with subcutaneous and cutaneous MCTs undergoing curative intent surgery. PROCEDURES: Medical records were searched to identify dogs with a cytologically or histologically confirmed diagnosis of MCT that had not previously been treated surgically and that had undergone full oncological staging. In those dogs, tumors were resected with lateral margins equivalent to the widest measured diameter of the tumor and a minimum depth of 1 well-defined fascial plane deep to the tumor. Surgical margins were evaluated histologically. Cutaneous tumors were graded by use of the Patnaik system and the 2-tier system described by Kiupel et al. The prognosis for subcutaneous tumors was assessed in accordance with published recommendations. Follow-up information on dog health status was obtained through clinical examination, the dog owners, and the referring veterinarians. RESULTS: The 40 dogs had 47 tumors. Forty-one (87%) tumors were cutaneous, and 6 (13%) were subcutaneous. On the basis of the Patnaik system, 21 (51%) cutaneous tumors were considered grade I, 18 (44%) were considered grade II, and 2 (5%) were considered grade III. On the basis of the Kiupel system, 37 (90%) cutaneous tumors were considered low grade, and 4 (10%) were considered high grade. The prognosis for the 6 subcutaneous tumors was classified as likely resulting in a shorter (2) or longer (4) survival time. Forty tumors were deemed to have been excised with clear margins and 7 with incomplete margins. Local recurrence was not recorded for any dog but was suspected for 1 (2%) tumor, although not confirmed. Interval from tumor excision to follow-up ranged from 30 to 1,140 days (median, 420 days). CONCLUSIONS AND CLINICAL RELEVANCE: The modified proportional margins system resulted in satisfactory local disease control in dogs with MCTs.

c-KIT messenger RNA and protein expression and mutations in canine cutaneous mast cell tumors: correlations with post-surgical prognosis.

Cutaneous mast cell tumors (MCTs) are among the most common neoplasms in dogs and show a highly variable biologic behavior. Histological grading, cell proliferation markers, and KIT immunohistochemistry are typically used to predict post-surgical prognosis. In the present study, c-KIT messenger RNA (mRNA) expression was measured in canine MCTs and its relationship with tumor grade, immunohistochemical staining pattern, post-surgical prognosis, and mutations was investigated. A significant increase of c-KIT mRNA was observed in MCTs versus healthy skin and surgical margins. Mutations were observed in 8.3% of cases. The KIT staining pattern was investigated for both grading systems. In particular, staining pattern III was associated with grade II (G2) and G3 MCTs, while staining patterns I and II were associated with G1 and G2 MCTs. Considering the 2-tier histological grading, the high grade was mainly associated with pattern III (71%) while the low grade was associated with patterns II (70%) and I (28%). A weak association between the KIT staining pattern and outcome was also observed. The results obtained suggest that c-KIT mRNA is overexpressed in canine MCT, although the fold variations were not associated with the protein localization or complementary DNA mutations. These observations suggested that the 3 events were independent. The histological grading and the KIT staining pattern have prognostic value as previously published. Staining pattern I could be especially helpful in predicting a good prognosis of G2 MCTs. Sequence mutations were not necessarily suggestive of a worse prognosis, but might be useful in choosing a chemotherapy protocol.