Veterinary Surgical Oncology. Группа авторов

skin tumor resection. Wound healing time is prolonged compared to reconstructive procedures (Prpich et al. 2014).

      Adjunctive Therapies for Skin Tumors

      Radiation therapy and/or chemotherapy are the main treatment modalities used as adjunctive therapies to surgical excision of cutaneous tumors. These therapies may be used for palliative or curative‐intent treatment. The indication for adjunctive therapy is based on the specific tumor type, biology, histologic grade, clinical stage, and completeness of surgical excision of the primary tumor. Other less‐commonly used adjunctive therapies include immunotherapy, photodynamic therapy, cryotherapy, and electrochemotherapy.

Mast Cell Tumors

      Mast Cell Tumors (MCTs) are the most common malignant cutaneous tumor in dogs and the second most common cutaneous tumor in cats (Miller et al. 1991; Villamil et al. 2011; Shoop et al. 2015; Graf et al. 2018). Cutaneous MCTs arise from the dermis and subcutaneous tissues. MCTs are round cell tumors that have characteristic cytoplasmic granules that contain bioactive substances, including histamine, heparin, proteases, chemotactic factors, and cytokines. There is a large degree of variation in the histologic appearance and biological behavior of MCTs in dogs.

      Clinical Presentation

Dogs with MCTs are generally middle aged (>5 years) and no sex predisposition is observed (Murphy et al. 2004). Breeds reported to have a high incidence of cutaneous MCTs include Boxers, Boston terriers, Weimaraners, shar‐peis, Golden retrievers, Labrador retrievers, Beagles, and Schnauzers (Murphy et al. 2004; Gieger et al. 2003; Hahn et al. 2008, 2004; Kok et al. 2019; Reynolds et al. 2019). Shar‐peis have been reported to be the breed most likely to have high‐grade MCTs, whereas the Pug and the Golden Retriever are the least likely breeds to develop high‐grade MCTs (Reynolds et al. 2019).

Figure 4.3 Surgical en bloc resection of cutaneous tumor with planned reconstructive skin fold transposition flap. (a) Preoperative skin marking of proposed en bloc tumor excision and axial skin fold transposition flap. (b) En bloc tumor excision. (c) En bloc tumor excision completed with deep margins. (d) Flank fold transposition flap raised to close tumor resection site. (e) Completed tumor resection and reconstructive procedure closure.

      Source: Images courtesy of Dr. Julius Liptak.

The majority (65–80%) of cutaneous MCTs is solitary. Approximately, 50–60% of canine cutaneous MCTs occur on the trunk, with 25% occurring on the limbs and the remainder on the head and neck areas. All MCTs are locally aggressive but low‐ and intermediate‐grade MCTs have a lower metastatic potential than high‐grade MCTs. The gross appearance of cutaneous MCTs is very variable, ranging from raised hairless masses to aggressive, invasive ulcerated lesions (Figure 4.4).

      Owners may report that MCT masses fluctuate in size over a short period of time. Local and paraneoplastic effects can result from release of inflammatory mediators contained within the MCT cytoplasmic granules.

MCT palpation or manipulation may cause release of histamine, leading to local redness, swelling, and pruritis. This can progress to degranulation of mast cells, producing erythema, edema, and wheal formation (Darier’s sign) (Figure 4.5).

      Histamine release can cause gastrointestinal ulceration by stimulating H2 receptors on parietal cells of the stomach and increased secretion of hydrochloric acid.

      Diagnosis of MCTs

FNA cytology is an inexpensive diagnostic test that can be done in‐house to confirm the diagnosis of cutaneous MCTs in approximately 90% of cases. Cytologically, MCTs consist of large round cells with central nuclei and abundant cytoplasm. The cytoplasm contains intracytoplasmic granules that stain purple with methanolic Romanowsky stains (e.g. May‐Grunwald‐Giemsa, Wrights) (Figure 4.6).

Figure 4.4 Range of cutaneous mast cell tumor appearances. (a) Ulcerated grade III MCT. (b) Grade II MCT over the mandible area.

Figure 4.5 Darier’s sign secondary to vasoactive substance release of an MCT.

      In clinical practice, rapid aqueous Romanowsky stains (e.g. Diff Quik) are commonly used, but these stains may not adequately stain mast cell granules.

      Other inflammatory cells such as eosinophils and neutrophils are frequently observed mixed with the MCT cells on cytologic examination.

      Historically, cytology was not able to predict histological grade. Cytological grading systems have now been developed and evaluated to determine if FNA cytology can provide accurate information regarding MCT grade prior to definitive excision (Camus et al. 2016; Hergt et al. 2016; Scarpa et al. 2016). The cytograding system correctly predicted the histological grade with an accuracy of 94%, sensitivity of 84.6–88%, and specificity of 94–97.3%.

      Incisional or excisional biopsy is required to provide enough tissue to determine the histologic grade of cutaneous MCTs. An incisional biopsy, obtained via wedge, skin punch, or needle core techniques can be done to establish MCT grade if negative prognostic factors are present or the surgical site is not amenable to wide surgical resection (e.g. distal extremity) to determine if a more conservative marginal excision is appropriate (e.g. for a low‐grade tumor) or if or more radical surgery or other adjunctive therapies (e.g. radiation and/or chemotherapy) are indicated for higher grade MCTs. Incisional biopsy grade has been shown to have a high concordance (92–96%) to definitive excisional grade. and are sufficiently accurate for differentiating low‐grade from high‐grade MCTs (Shaw et al. 2018).

      Clinical Staging

A modified version of the WHO TNM clinical staging scheme is used to stage canine cutaneous MCTs into one of four stages (Table 4.2) (Turrel et al. 1988).

      Preoperative staging is important to determine prognosis and appropriate treatment options, including surgical dose, radiation, and chemotherapy. A minimum database of a complete blood count, serum biochemistry, and urinalysis is indicated as part of a presurgical workup for any patient with cancer, including MCTs.

      Preoperative imaging of the cutaneous MCT mass with ultrasonography, computer tomography, or MRI can facilitate definition of anatomical margins, especially deep margins, prior to surgery and assist with surgical planning if reconstructive procedures are planned. Assessment of size and shape of intracavitary lymph nodes can also be obtained from CT or MRI imaging.

      The metastatic pathway for cutaneous MCTs is first to the sentinel and regional lymph nodes and then to distant sites of spleen, liver, or bone marrow (Pizzoni et al. 2018). Complete staging for cutaneous MCT should include FNA cytology of the sentinel or other regional lymph nodes, abdominal ultrasound