Veterinary Surgical Oncology. Группа авторов

Tumors

      PNSTs include a variety of neoplasms including (malignant) schwannoma, neurofibroma, and neurofibrosarcoma. Reported incidence is 0.5–2% of all skin tumors in dogs (Goldschmidt and Shofer 1992; Kaldrymidou et al. 2002; Pakhrin et al. 2007), although reported data vary considerably, depending on varying classification of these tumors. They are locally aggressive and metastasize rarely (<20% in dogs). These tumors arise from peripheral nerves, resulting in locally infiltrative neoplasia in skin and subcutaneous tissue.

      PNST can also arise in a nerve plexus and in nerve roots, which can result in compression of nerves resulting in unilateral lameness, muscle atrophy, pain, and paresis (Brehm et al. 1995; Harcourt‐Brown et al. 2009). One case report describes a concomitant malignant PNST and benign cutaneous PNST in a 10‐year‐old cocker spaniel causing respiratory impairment (Silva et al. 2017). In dogs, they arise in the subcutaneous tissues of the extremities most commonly.

      If they appear in the region of the spinal canal, they frequently cause painful nerve compression and neurologic deficits, but in more distant locations pain is often absent. Spinal nerves of the brachial plexus (C6–T2) and nerve roots are the most common sites for proximal PNSTs in dogs (Anderson et al. 1999; Essman et al. 2002; Kim et al. 2003; Patterson et al. 2008; Sugiyama et al. 2008).

      Electrophysiology may define the location of peripheral nerve involvement.

      A CT scan or MRI of the tumor region is strongly advised before surgery to evaluate the extension of tumor involvement and surgical possibilities.

      Malignant lesions are more often positive for S‐100 and present a proliferation index significantly higher compared to the benign lesions (Teixeira et al. 2016).

      In general, the prognosis for dogs with proximally (centrally) located PNSTs is poor, and the recurrence rate after surgery is high. Survival times up to 27 months after surgical intervention have been reported but usually are much shorter (Bagley et al. 1998; De Queiroz et al. 2008; LeCouteur 2001; Sawamoto et al. 1999). Distally located PNSTs have a much more favorable prognosis. Tumor recurrence after surgery (resection type not specified) was 20% in one retrospective study and occurred for both histologically benign and malignant tumors (Schulman et al. 2009). Distant metastasis was not seen.

      Treatment of MRI‐Diagnosed Trigeminal PNSTs by stereotactic radiotherapy (3 dose fractions of 8 Gy on consecutive days or every other day to a total of 24 Gy) in 6 dogs resulted in a disease‐specific survival of 745 days (99–1375 days) (Hansen et al. 2016).

      In cats, PNSTs are rare. They mostly arise in the dermis or subcutis of the head, neck, or limbs (Schulman et al. 2009). They are underestimated relative to the more common spindle cell tumors of soft tissue. A constant concurrent expression of vimentin, NSE, and laminin might confirm the diagnosis of PNST in the absence of clear S‐100 protein positivity, especially in the malignant forms (Mandara et al. 2013).

      Perivascular Wall Tumors

      Perivascular wall tumors (PWTs) are defined as neoplasms deriving from mural cells of blood vessels, excluding the endothelial lining. The spectrum of human cutaneous PWT includes glomus tumor, hemangiopericytoma (HEP), myopericytoma, angioleiomyoma/sarcoma, angiomyofibroblastoma, and angiofibroma (Avallone et al. 2007).

      PWTs commonly arise in soft tissue. Their histopathological features are quite similar to those of canine malignant PNSTs, making their differential diagnosis challenging. Suzuki et al. suggest that NGFR and Olig2 are useful to distinguish between PWTs and malignant PNSTs as PWT cells displayed significantly weaker immunoreactivity than MPNSTs to these markers (Suzuki et al. 2014).

In cases of undifferentiated canine PWTs further evaluation has been reported by transmission electron microscopy. By electron microscopy, ultrastructural findings support a perivascular wall origin for all cases with 4 categories of differentiation: myopericytic, myofibroblastic, fibroblastic, and still undifferentiated (Palmieri et al. 2013).

      Proteins of the VEGF‐, PDGFB‐, and bFGF‐mediated pathways have been reported to be highly expressed in 47.5–76.5 %, and in 10–35% of TGFβ1‐ and COX2‐mediated pathways of PWTs (Avallone et al. 2015). No association with the Ki67 labeling index was found in this study. Blockade of tyrosine kinase receptors after surgery could represent a promising therapy with the aim to reduce the PWT relapse rate and prolong the time to relapse (Avallone et al. 2015).

      PWT can locally recur after a long time after surgery. Recurrence was reported in 2, 8, 20, and 24% at six months, one, two, and three years, respectively. Size of the tumor was a significant prognostic factor. An early diagnosis of PWT associated with small tumor size (<5 cm) and clean surgical margins ensures a good prognosis independently of histological grade (Stefanello et al. 2011). Major prognostic factors for perivascular wall tumors reported by Avallone et al. (2014) are tumor size, depth of growth, and pathological profiles. Smoothelin, heavy caldesmon, desmin, myosin, calponin, and CMG‐3G5 were the most valuable markers to differentially diagnose canine PWT (Avallone 2007).

      Hemangiopericytomas (HEPs) are derived from pericytes, spindle cells surrounding blood vessels. Distinguishing these pericytes from endothelial cells, fibroblasts, and other spindle cells surrounding blood vessels is difficult based on morphologic and immunophenotypic assessment. Canine HEP has been proposed to be a diagnosis of immunohistochemical exclusion (Schulman et al. 2009; Mazzei et al. 2002; Williamson and Middleton 1998). The biological behavior of HEPs resembles that of PNSTs, and they stain similarly positive for the histochemical marker s100 (Chijiwa et al. 2004). Reported prevalence in dogs varies from 2 to 7% (Goldschmidt and Shofer 1992; Kaldrymidou et al. 2002; Mukaratirwa et al. 2005; Pakhrin et al. 2007), although they may have been formerly over diagnosed. The tumors are predominantly located on the extremities; however, other regions including the perineal area have been described. Only one case of HEP is reported in a cat (Baldi and Spugnini 2006). HEPs grow slowly and are locally aggressive because of infiltration into the surrounding tissues. Dogs with HEP showed higher serum VEGF levels compared to the patients with malignant PNSTs (De Quieroz et al. 2013). In a study by Stefanello et al. (2008), 35 dogs with marginal excision of low‐grade spindle cell sarcoma incurred a local recurrence rate of 10.8% and a metastatic rate of 0% (Avallone et al. 2007; Bostock and Dye 1980; Chijiwa et al. 2004; Fossum et al. 1988; Graves et al. 1988; Mayr et al. 1990; Stefanello et al. 2008).

      Myxosarcoma

      Myxosarcoma are tumors of fibroblast origin that characteristically produce myxoid matrix, resembling mucus, containing mucopolysaccharides. Myxosarcoma develops commonly as cyst‐like masses filled with mucoid fluid. They are rare and mainly occur on the chest or limbs. Myxosarcomas have also been reported in the heart, eye, spinal canal, temporomandibular joint, brain, and bone. Biologically, they behave like any STS, with aggressive first surgery after diagnosis being the treatment of choice (Dennis 2008; Foale et al. 2003; Kirby et al. 2014; Levy et al. 1997; Manfredi et al. 2015; Parslow 2016). Pulmonary metastasis of a myxosarcoma in a dog has been reported (Headley et al. 2011).

      Cutaneous Hemangiosarcoma

      Hemangiosarcoma (HSA) is a malignant neoplasm arising from vascular endothelial cells (Liptak 2007). HSAs may be associated with ultraviolet exposure (Hargis et al. 1992). Prevalence appears to be higher in tropical and subtropical areas (Mukaratirwa et al. 2005). Skin HSAs account for less than 1% of all (sub)cutaneous tumors in dogs and 2–3% in cats (Goldschmidt and Shofer 1992; Miller et al. 1991; Schultheiss 2004). In dogs, 17–35% of all HSAs (including both visceral and nonvisceral) are cutaneous (Schultheiss 2004; Brown et al. 1985), and 50–77% of all HSAs in cats are (sub)cutaneous (Johannes et al. 2007; Scavelli et al. 1985). Dermal HSA is commonly observed in shorthaired dogs on the poorly pigmented skin of the ventral abdomen, medial thigh, inguinal region, and scrotum (Trappler et al. 2014). This is typically seen in “sun bathers” dogs that lie on their back in the sun. Cutaneous HSA has been reported in a Golden retriever appearing from the left elbow to the digits (Tsuji et al. 2013).

      Subcutaneous HSAs are more commonly observed in dogs with variable hair coat and pigmentation. The most common primary sites for cutaneous