Clinical Outcome for MCTs of Canine Pinnae Treated with Surgical Excision (2004–2008)
Canine mast cell tumors (MCTs) are the most common cutaneous neoplasm in the dog. It has been suggested that MCT in certain locations may behave in a more biologically aggressive fashion than MCTs located in others; however, no published data are available for MCTs of canine pinnae treated with surgical excision. A retrospective study of 28 animals with surgical excision of MCTs of pinnae was completed with a medical record review and follow-up questionnaire to the operating veterinarian. The effect of tumor grade, clean or dirty excision, cartilage penetration, and mitotic index (MI) on local recurrence and survival time (ST) was evaluated. There was local recurrence in one dog with a grade 2 MCT and in seven of eight dogs with grade 3 MCTs. The median ST of animals with grade 1 and 2 MCTs was not reached, whereas the median ST of animals with grade 3 MCTs was 10 mo. There was no statistical association between histologically clean and dirty margins and either local recurrence or ST. A prolonged disease free interval without local recurrence may be achieved with local excision of grade 1 and 2 MCTs. Animals with grade 3 MCTs had a uniformly poor outcome with short times to local recurrence and death.
Introduction
Mast cell tumors (MCTs), the most commonly encountered cutaneous neoplasm in the dog, represent 7–27% of all skin tumors.1–4 Tumor grade is highly correlated with the biologic behavior of the neoplasm and long-term prognosis.5 Dogs with grade 1 tumors typically have a good long-term prognosis and survival, whereas dogs with grade 3 tumors have a median survival time (ST) of 6 mo.1,5–7 Grade 2 tumors have a variable biologic behavior, with some behaving in a more benign fashion and others are more aggressive, metastasizing to locoregional lymph nodes.7 The mitotic index (MI) of MCTs is predictive of ST and helps to differentiate between more benign and aggressive tumor behavior.8
MCTs are usually identified as solitary skin tumors, usually on the trunk (48–58%) or limbs (25–47%), but may occur anywhere.1,4,6,9,10 Visceral, gastrointestinal, and digital MCTs are proposed to have a more aggressive behavior with an increased incidence of systemic involvement, metastasis, and decreased ST.11–16 Additionally, MCTs located on the muzzle, oral mucosa, oral mucocutaneous junction, or perioral regions may have a more malignant behavior than other haired-skin regions, with an increased risk of local lymph node metastasis.17,18 Prolonged STs are typically achieved with multimodal treatment of affected animals.18 The purpose of this retrospective study was to analyze the clinical outcome of dogs with MCTs of pinnae that were treated with surgical excision.
Materials and Methods
Case Selection
All cases of canine MCTs on pinnae that were submitted for histopathologic evaluation to the Laboratory of Pathology and Toxicology at the University of Pennsylvania, School of Veterinary Medicine between 2004 and 2008 were included in this study. Animals were excluded from the study if there were either incomplete medical/surgical records or if only an incisional biopsy was performed.
Data Collection
A survey questionnaire and medical records request was submitted to the primary veterinarian who performed the surgical resection of the MCT, which included general veterinarians and veterinary surgical specialists. Follow-up information regarding recurrence, outcome, and ST was derived from the medical records and by telephone conversations with either the owner or veterinarian. Time to local recurrence, ST from surgical excision, and cause of death were also recorded. Data from the surgical record included size of surgical and histologic margins, adherence to underlying cartilage, and type of surgery performed (local excision versus pinnectomy). One pathologist (M.G.) reviewed all of the biopsy samples to confirm the diagnosis, grade, tumor-free margin, and MI of the tumor. The tumors were graded based on the criteria established by Patniak et al. (1984) from grades 1 to 3.19 The following data were also retrieved from the medical records: sex, breed, previous MCTs, growth rate and appearance of the tumor, tumor size, staging, presence of multicentric disease, chemotherapy protocol, recurrence rate (RR), and ST.
Outcomes
RR was defined as the time between surgical excision and evidence of local recurrence. ST was defined as the time between surgical excision of the MCT and death attributed to local recurrence, metastatic disease, euthanasia, or unrelated causes. Dogs were censored from the survival data at the date of last contact.
Statistical Analysis
The effect of tumor grade, MI, clean surgical margins, and cartilage penetration on RR and ST was analyzed using a Kaplan-Meier log-rank survival analysis and the Holm-Sidak correction between groups. A MI of either ≤ 5 or > 5, and a tumor size of either < 2 cm or ≥ 2 cm was used to compare local recurrence and survival, as those values were suggested to indicate more aggressive biologic behavior.4–6,8 Statistical significance was set at P < .05 for all variables analyzed, and all statistical testing was performed using commercially available softwarea.
Results
Twenty-eight dogs with MCTs of pinnae were included in the study. Boxers (n = 9), mixed-breed dogs (n = 6), and Labrador retrievers (n = 4) were the most common breeds with pinnal MCTs. Eight other breeds were also represented. There were 6 castrated males, 3 females, and 19 spayed females. Median age at the time of diagnosis was 8 yr (range, 2–15 yr). Tumors were located on the left pinnae in 10 dogs (35.7%) and on the right in 18 dogs (64.3%). Fourteen of the tumors were < 2 cm in diameter and 14 were ≥ 2 cm in diameter. Two animals had mandibular lymph node aspirates that were negative for evidence of metastasis.
All 28 dogs were treated with surgical excision of the mass, with surgical procedures ranging from local lumpectomy to complete pinnectomy. Local lumpectomy was performed in 24 dogs, partial pinnectomy in 1 dog, and complete pinnectomy in 3 dogs (Table 1). Grade, microscopic tumor margins, and MI were evaluated in all tumors. The majority of tumors were histologically classified as grade 2 MCTs (n = 16; 57.1%). Eight of the remaining tumors were grade 3 MCTs (28.6%) and four were grade 1 MCTs (14.3%). Histologically clean margins were achieved in 78.6% of animals (n = 22). Histologic clean margins ranged from a mean of 0.1 cm to 2 cm (standard deviation, 0.48 cm ± 0.5 cm). Clean margins were achieved in all grade 1 MCTs, 11 of 16 grade 2 MCTs, and 7 of 8 grade 3 MCTs. Clean margins were achieved in all of the three dogs that had a complete pinnectomy performed. There were histologically dirty margins in the one dog that had a partial pinnectomy. Six dogs with grade 3 MCTs and one dog with a grade 2 MCT had a MI > 5, and the remaining 21 dogs had a MI < 5.
One dog received a partial pinnectomy.
MCT, mast cell tumor; n, number of dogs; NA, not achieved; ST survival time.
Adjuvant chemotherapy was used in six animals: two dogs with grade 2 MCTs and four dogs with grade 3 MCTs. Drugs used included prednisone, lomustine, chlorambucil, and vinblastine (manufacturer information unknown). Of the six animals receiving chemotherapy, there was local recurrence in one dog with a grade 2 MCT and in all four dogs with grade 3 MCTs.
Twenty-one dogs (75%) had no evidence of recurrence at the time of last contact (median follow-up time 18 mo (range, 6–59 mo). None of the animals with grade 1 MCT had local recurrence. One dog with a grade 2 MCT that had a complete surgical excision experienced local recurrence 2 mo postoperatively. There was no local recurrence within the study period (median ± standard deviation, 19.8 mo ± 16 mo) of any of the grade 2 MCTs that were excised with dirty surgical margins. Seven of 8 dogs (87.5%) with grade 3 MCTs had local recurrence within a median time of 5 mo (P < .001). Dogs with grade 3 MCTs that were excised with clean margins and subsequently recurred had a mean histologically clean margin of 0.33 cm ± 0.34 cm. There was no association between clean versus dirty margins and either time to local recurrence or survival (P = .987 and P = .987, respectively). Animals with MCTs with a MI > 5 or MCT ≥ 2 cm were associated with a significantly shorter median recurrence time of 5.5 mo and 5.7 mo, respectively (P < .001 and P < .017, respectively) compared with dogs with MCTs with a MI < 5 or with an MCT measuring < 2 cm in which the median recurrence time was not achieved.
There was no significant association with cartilage involvement and either time to local recurrence or ST (P = .112 and P = .209, respectively). Two grade 2 tumors and three grade 3 tumors either involved or penetrated through the auricular pinnal cartilage. Local recurrence occurred in a median of 13 mo (range, 5–13 mo) for three grade 3 tumors with cartilage penetration. There was no recurrence of either grade 2 tumors with cartilage involvement. The median ST of animals with cartilage involvement was 13 mo (range, 5–36 mo).
Median ST was not reached for dogs with grade 1 and 2 MCTs. Median ST of dogs with grade 3 MCTs was 10 mo. Local tumor regrowth was present in seven of the eight dogs with grade 3 MCTs at the time of death and was cited as the cause of death in five of those dogs. Two dogs with grade 3 MCTs were euthanized for concurrent neoplasia (lymphosarcoma and transitional cell carcinoma), and both dogs had local recurrence of MCTs at the time of death. There was no information on the presence of metastatic disease in those dogs. A MI > 5 or tumor size ≥ 2 cm had a decreased ST of a median of 10 mo each (P < .001 and P < .033, respectively) compared with dogs with MCTs with a MI < 5 or tumor size < 2 cm in which the median ST was not met.
Discussion
This study suggests that dogs with MCTs of pinnae without evidence of gross metastatic disease have a similar prognosis compared with dogs with MCTs in other haired areas of the body that are treated with surgical excision. In this study, dogs with grade 1 and 2 MCTs had median STs that were not reached within the study period. As expected, animals with a more aggressive MCT grade were more likely to have a poor long-term prognosis. Previous studies reported median STs of 6 mo (range, 1.3–13 mo) for animals with grade 3 MCTs.1,4–7 In this study, animals with grade 3 MCTs had a median ST of 10 mo. Dogs with tumors measuring ≥ 2 cm or with a MI > 5, had faster local RRs and decreased STs.
Dogs with grade 1 or 2 MCTs had very low local RRs within this study. Of the 20 dogs with either a grade 1 or 2 MCT, only 1 dog with a grade 2 MCT had evidence of recurrence within the study period. That finding was in accordance with a previous study that suggested resection of grade 1 and 2 MCTs with smaller surgical margins than current recommendations resulted in low local recurrence.20 In agreement with the findings of Michels et al. (2002), no significant correlation was found between the presence of dirty surgical margins and local recurrence in animals with grade 2 MCTs.21 It has been suggested that cells seen microscopically at the surgical margins may represent a normal population of mast cells that have been recruited to the tumor as part of the inflammatory cycle. Those mast cells may not represent neoplastic cells, the remaining tumor could become dormant, or there could be immune destruction of the residual tumor. There was local recurrence in 87.5% of dogs with grade 3 MCTs during the study period, with the majority of those tumors having been excised with clean but close surgical margins. That finding may indicate that the tumors were not completely excised initially. Dogs in this study may still have developed local recurrence after the study period but had no evidence of disease at the time of last contact.
Ideally, an initial biopsy of the mass to determine if the lesion represents a high-grade MCT followed by a more aggressive surgical excision is recommended. An additional surgical excision with larger surgical margins and potential pinnectomy should be considered in all animals with high-grade MCTs of pinnae. Hahn et al. (2004) showed a median ST of approximately 28 mo for animals with grade 3 MCTs in aggressive areas, including pinnae, with incomplete surgical margins that received radiation therapy.22 However, radiation therapy helps with local control only and does not address metastatic spread. Chemotherapy has also been shown to improve quality of life, STs, and decrease metastasis in the treatment of animals with MCTs.22–26 Therefore, adjuvant chemotherapy and/or radiation therapy should play a significant role in treating animals with high-grade MCTs to prolong STs and local control.
There are certain limitations inherent with a retrospective study and a small sample size. Information was derived from the medical records, communication with the veterinarian performing the surgery, and with the owners. The majority of the dogs had surgery performed by their primary veterinarian without preoperative cytology to aid in tumor type classification and surgical planning, resulting in a less aggressive initial surgical excision. None of the dogs in this study had evidence of metastatic disease at the time of surgery; however, routine preoperative staging was not performed. It is, therefore, possible that dogs with metastatic disease were included in this study. Given the prolonged ST of dogs with grade 1 and 2 MCTs, it is unlikely that there was significantly advanced metastatic disease at the time of surgery in this population of dogs. Also, dogs with evidence of metastatic disease may not have received surgical excision of the mass and were thereby excluded from the study population biasing the results for improved long-term outcomes. This study, therefore, cannot address the long-term prognosis and outcomes of dogs with MCTs of pinnae treated with surgical excision with concurrent metastatic disease or that are treated without surgical excision. There was no control group making it impossible to address the biologic behavior of pinnal MCTs in general.
In many instances, the medical records were incomplete in regards to gross surgical margins at the time of surgery; however, margins were evaluated histologically by a pathologist. Dogs may have been treated with wide surgical excision around the mass leading to more animals with clean surgical margins. Previous studies have suggested that surgical excision with clean margins is curative in the majority of animals with grade 1 and 2 MCTs with a low percentage of local recurrence.9,20,21,27–30 A prolonged disease-free interval without local recurrence may be achieved with local excision of low-grade MCT. Future prospective studies evaluating the size of surgical margins required to achieve complete surgical excision is indicated.
Conclusion
The median ST of grade 1 and 2 MCTs was not reached, whereas the median ST of animals with grade 3 MCTs was 10 mo within this study. There was no statistical association between histologically clean and dirty margins and either local recurrence or ST. A prolonged disease-free interval without local recurrence may be achieved with local excision of grade 1 and 2 MCTs. Animals with grade 3 MCTs had a uniformly poor outcome with short times to local recurrence and death, consistent with previous studies.
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