a: No systemic signs of disease; Substage b: Signs of systemic disease.
FNA cytologic examination of the regional lymph node should be performed in all cases of cytologically confirmed cutaneous MCT, regardless of whether the lymph node is enlarged or not, to detect early metastasis (Langenbach et al. 2001). Dogs with metastasis to the regional lymph node are classified as clinical stage II tumors and have a poorer prognosis (Krick et al. 2009). Lymph node aspirates from normal dogs can contain mast cells (Bookbinder et al. 1992), so diagnosis of lymph node involvement based on FNA cytology should be if greater than 3% of the cell population are mast cells (Dobson et al. 2004). Cytology is a useful method for staging purposes, especially for lymph nodes that are not easily amenable to surgical removal. No standardized cytologic criteria exist for differentiating reactive and metastatic MCT in lymph nodes. The use of methanolic Romanowsky stains rather than rapid aqueous Romanowsky stains should be used for cytology of suspected nodal metastases to increase the identification of isolated mast cells (Sabattini et al. 2018). Cytologic criteria for metastatic mast cell disease in lymph nodes have been described and dogs with stage II disease have a significantly shorter survival time than dogs with stage I disease independent of grade and dogs with grade III primary MCTs were more likely to have stage II disease (Krick et al. 2009).
Lymph node histology is more accurate than cytology for diagnosis of metastatic MCT disease (Ku et al. 2017; Fournier et al. 2018; Lapsley et al. 2021). Therefore, if cytology is negative for MCT metastasis, extirpation of the regional draining lymph node, regardless of size of the lymph node, should still be performed for staging purposes before or during local MCT treatment as nearly 50% of LNs can show histologically detectable metastatic disease (Ferrari et al. 2018). Furthermore, histology of the lymph node provides a classification of the metastasis (HN0‐HN3), which is prognostic for outcome (Weishaar 2014). Sampling of lymph nodes in dogs with MCTs that, anatomically, would be expected to be the SLN does not accurately reflect which lymph node is actually the SLN. SLN mapping is recommended to identify the true SLN so that it can be extirpated at the time of surgery to provide the most accurate staging. Identification of the sentinel lymph node for canine MCTs has been shown to be reliable with regional lymphoscintigraphy combined with intraoperative lymphoscintigraphy and blue dye (Worley 2014). CT lymphangiography using peritumoral injections of an aqueous contrast solution has also been described to successfully identify sentinel lymph nodes of MCTs and other tumors (Grimes et al. 2017; Lapsley et al. 2021). However, CT lymphangiography was not accurate to assess presence or absence of mast cell tumor metastasis to the sentinel lymph node according to contrast enhancement pattern or attenuation values (Grimes et al. 2020).
Abdominal ultrasonography is recommended as part of complete staging to assess the liver, spleen, and abdominal lymph nodes for metastasis (Stefanello et al. 2009; Book et al. 2011; Warland et al. 2014). Dogs with mast cell infiltration of either or both the spleen or liver, have decreased survival times compared to those without infiltration. The routine aspiration cytology of a normal liver and spleen is controversial. One study frequently identified mast cells in normal livers and spleens and concluded that routine aspiration cytology could not be recommended (Finora et al. 2006). Later studies found that dogs with cutaneous MCTs that had cytologic evidence of splenic mast cell metastases, using criteria of clustering of mast cells and atypical mast cell morphology, had a decreased survival time compared to dogs without cytologic evidence of distant disease (Stefanello et al. 2009; Book et al. 2011). All dogs that had cytologic evidence of mast cell metastasis in the liver or spleen had abnormal ultrasonographic findings. The authors concluded that cytology of the liver and spleen regardless of the ultrasonographic appearance of the liver or spleen was indicated as part of clinical staging for dogs with cutaneous MCTs, especially MCT with high biologic behavior (Stefanello et al. 2009).
The utility of computed tomography (CT) of the abdomen has been reported for staging of the liver and spleen for MCT disease and was found to be equivocal (Hughes et al. 2019). No consistent imaging pattern was associated with mast cell metastasis for the liver and mast cell metastasis of the spleen coincided with multifocal splenic hypoattenuating lesions.
Thoracic radiography is reported to not be useful in the staging of canine cutaneous MCTs as MCTs have not been reported to metastasize to the lungs (Warland et al. 2014; Pizzoni et al. 2018; Cartagena‐Albertus et al. 2019). The only rationale for doing thoracic radiographs as part of the staging process is to assess for thoracic lymph node enlargement or evidence of concurrent intrathoracic disease.
The routine use of buffy coat smears and bone marrow evaluation are not advocated for routine staging of cutaneous MCTs due to the rarity of bone marrow involvement and the common finding of mastocytemia in dogs with disease other than cutaneous MCTs (McManus 1999; LaDue et al. 1998; Endicott et al. 2007; Warland et al. 2014). The presence of neoplastic mast cell infiltration in the bone marrow seems rare and is generally more common in dogs with grade III primary cutaneous tumors (O’Keefe et al. 1987). Reported indications for bone marrow sampling as part of the clinical staging process of dogs with cutaneous MCTs include abnormal hemogram findings or presentation for tumor regrowth, progression, or new occurrence (Endicott et al. 2007).
Treatment of Canine Cutaneous MCTs
The optimal treatment for an individual patient with MCT disease depends on the tumor grade, anatomical site, clinical stage, and surgical and radiation therapy facilities available. Available treatment options for cutaneous MCTs include surgical excision, radiation therapy, and chemotherapy.
Surgery
Perioperative Management
Perioperative surgical complications may be encountered related to the release of vasoactive substances from mast cell granules secondary to tumor manipulation. MCTs should not be manipulated extensively during the (pre)operative period to avoid the risk of a degranulation reaction.
Preoperative treatment with H1 blocker (diphenhydramine) and H2 blockers (cimetidine, ranitidine, or famotidine) and corticosteroids has historically been recommended in dogs with cutaneous MCTs that will be surgically manipulated, including biopsy, and those that show evidence of degranulation, melena, or hemoptysis associated with gastrointestinal ulcerations secondary to histamine release. It has been suggested that hypotension during surgery may be caused by mast cell degranulation and histamine release. A recent study, however, showed that administration of diphenhydramine did not provide any clear benefit in preventing hypotension in dogs undergoing MCT removal (Sanchez et al. 2017).
The use of neoadjuvant corticosteroid (prednisone) treatment may facilitate resection of MCT when adequate surgical margins cannot be confidently expected because of location, size, or both (Stanclift and Gilson 2008; Dobson et al. 2004). Mean reduction in MCT volume was 80.6% in 70% of cases treated with neoadjuvant prednisolone. Reduction in tumor size may be related to the anti‐inflammatory effect of prednisolone, reducing tumor‐related inflammation and edema secondary to tumor cytokine release. There was no difference in response rate between a high dose (2.2 mg/kg) and a low dose (1.0 mg/kg) prednisone protocol. Using neoadjuvant prednisone did not increase the risk of incomplete margins or local recurrence in one study (Saunders 2020).
Margins
Surgical Margins
Wide surgical excision with adequate lateral and deep margins has historically been the primary treatment of choice for most MCTs. The deep surgical margin is a qualitative margin rather than a quantitative margin. Fascia and collagen‐dense tissues are good barriers to tumor infiltration. The deep margin should include at least one fascial plane deep to the tumor that has not been invaded by the tumor. This margin should be removed en bloc with the tumor so that tumor contamination is not encountered during the surgery. The appropriate lateral surgical margin is grade and tumor size dependent. Historically,
