Nodular Fasciitis (Fibromatosis, Pseudosarcomatous Fibromatosis)

Nodular fasciitis is a benign nonneoplastic lesion arising from the subcutaneous fascia or superficial portions of the deep fascia in dogs. These lesions are usually nodular, poorly circumscribed, and very invasive.²⁴ Histologically, nodular fasciitis is characterized by large plump or spindle-shaped fibroblasts in a stromal network of variable amounts of collagen and reticular fibers with scattered lymphocytes, plasma cells, and macrophages.²⁴ The morphologic and pathologic characteristics of nodular fasciitis can result in these lesions being misdiagnosed as fibrosarcoma. Infantile desmoid-type fibromatosis is a variant of nodular fasciitis and is characterized by fibroblast proliferation with a dense reticular fiber network and mucoid material.²⁵ Wide excision of both nodular fasciitis and infantile desmoid-type fibromatosis lesions is usually curative.²⁶ Local recurrence is possible with incomplete resection. These tumors do not metastasize.²⁴

Fibrosarcoma

Most fibrosarcomas arise from the skin, subcutaneous tissue, or oral cavity and represent malignant fibroblasts. Tumors can be well differentiated, exhibiting spindle-shaped tumor cells with scant cytoplasm. The more anaplastic tumor is very cellular with closely packed spindle-shaped fibroblasts showing many mitotic figures and marked cellular pleomorphism.²⁷ Tumors tend to occur in older dogs and cats with no breed or sex predilection; however, one reference states a higher predilection in golden retrievers and Doberman Pinschers.²⁸ A unique form, histologically low-grade, yet biologically high-grade fibrosarcoma, is seen in the oral cavity and has a tendency to grow quite large and invade deeper structures, including bone. Metastasis can be seen in up to 20% of the cases.¹⁹ Metastasis is rare, but these tumors are infiltrative, with microscopic tumor cells invading along fascial planes, and often recur after surgical excision.

Peripheral Nerve Sheath Tumor (Neurofibrosarcoma, Malignant Schwannoma, Hemangiopericytoma)

The PNSTs are malignant tumors of nerve sheath origin and have been referred to as neurofibrosarcoma, malignant schwannoma, and hemangiopericytoma. The confusion regarding hemangiopericytoma is the fact that blood vessel pericyte origin has yet to be proven in dogs. Most hemangiopericytomas will have features of nerve sheath tumors histologically.²⁷ Malignant PNSTs will stain positive with S-100 and vimentin, indicating peripheral nerve origin.²⁹

Regardless of the nomenclature, these tumors can occur anywhere in the body. A PNST may involve nerves away from the brain or spinal cord (peripheral group), or they may involve nerves immediately adjacent to the brain or spinal cord (root group) or the brachial or lumbosacral plexus (plexus group).³⁰ The true peripheral form is much more treatable than the plexus or root form. Despite appearing encapsulated at surgery, these tumors are similar to fibrosarcomas and occur as poorly defined tumors without histologic encapsulation. Most of the tumors are adherent to deeper tissues and may infiltrate underlying fascia, muscle, and skin. Although these tumors are considered malignant, they have a modest metastatic rate. As with fibrosarcomas, local recurrence for PNSTs is common following conservative surgery. They tend to grow slowly and can range in size from 0.5 cm to over 10 to 12 cm in diameter. In some cases, they can easily be confused with lipomas on initial clinical examination.²⁷

PNSTs located in the proximal axial region may result in the compression of nerves. The vast majority of cases will show signs of unilateral lameness, muscle atrophy, paralysis, and pain.³⁰ They can invade the spinal cord, and about 50% will invade the cord if a grade III tumor is diagnosed.³⁰ However, local disease usually limits survival before metastasis occurs.

Lipoma

Lipomas are benign tumors of adipose tissue. Variants of lipomas have been reported and include angiolipoma and angiofibrolipoma.³¹ Lipomas are relatively common in older dogs, especially in subcutaneous locations, and are rarely symptomatic. Lipomas can also occur in the thoracic cavity, abdominal cavity, spinal canal, and vulva and vagina of dogs and can cause clinical abnormalities secondary to either compression or strangulation.^32–40 Parosteal and infiltrative lipomas have been rarely reported and these tumors can have a more aggressive behavior despite their benign histologic appearance.^41–46 Marginal resection is recommended for lipomas that interfere with normal function; however, the majority are asymptomatic and do not require surgical intervention. Lipomas can be differentiated from liposarcomas based on morphologic and histologic appearance. Histologically, lipomas have indistinct nuclei and cytoplasm resembling normal fat, whereas liposarcomas are characterized by increased cellularity, distinct nuclei, and abundant cytoplasm with one or more droplets of fat.³⁸ Surgical resection is usually curative, but local recurrence has been reported.³⁹

Intermuscular Lipoma

Intermuscular lipomas are a variant of the subcutaneous lipoma and are located in the intermuscular region of the caudal thigh of dogs, particularly between the semitendinosus and semimembranosus muscles (Figure 21-1).⁴⁷ Clinically, intermuscular lipomas appear as a slow-growing, firm, and fixed mass in the caudal thigh region and may occasionally cause lameness.⁴⁷ Cytologic analysis of fine-needle aspirates is usually diagnostic. The recommended treatment is surgical resection, involving blunt dissection and digital extrusion, and placement of either a Penrose or negative-suction drain. Seromas are a common complication in dogs in which a drain is not used. The prognosis is excellent with no recurrence reported in 11 dogs following surgical removal.⁴⁷

Infiltrative Lipoma

Infiltrative lipomas are uncommon tumors composed of well-differentiated adipose cells without evidence of anaplasia. These tumors cannot be readily distinguished from the more common simple lipoma by cytology or small biopsy specimens. They are considered “benign” and do not metastasize. However, infiltrative lipomas are locally aggressive and commonly invade adjacent muscle, fascia, nerve, myocardium, joint capsule, and even bone.42,48,49 Computed tomography (CT) is used to better delineate these tumors; however, they do not contrast enhance and differentiating infiltrative lipomas from normal fat is problematic.⁴⁷ One retrospective analysis of 16 cases reported a 4 : 1 female-to-male ratio.⁴⁴ Aggressive treatment, including amputation, may be necessary for local control. RT can be considered either alone or in combination with surgical excision.⁴⁶

Liposarcoma

Liposarcomas are uncommon malignant tumors originating from lipoblasts in older dogs.⁵⁰ Liposarcomas apparently do not arise from malignant transformation of lipomas. Specific causes are not known, but foreign body–associated liposarcoma has been reported in one dog.⁵ There is no breed or sex predilection.⁵⁰ They are commonly reported in subcutaneous locations, especially along the ventrum and extremities, but can also occur in other primary sites such as bone and the abdominal cavity. Liposarcomas are differentiated from lipomas based on morphologic appearance and cytologic characteristics. Liposarcomas are usually firm and poorly circumscribed. They are locally invasive with a low metastatic potential. Metastatic sites include the lungs, liver, spleen, and bone.^27,50

The prognosis for liposarcoma is good with appropriate surgical management. The median survival time (MST) following wide surgical excision is 1188 days; this is significantly better than either marginal excision or incisional biopsy, which have MSTs of 649 days and 183 days, respectively (Figure 21-2).⁵⁰ Liposarcoma is histologically classified as well-differentiated, myxoid, round cell (or poorly differentiated), pleomorphic, or dedifferentiated. This classification scheme has clinical and prognostic importance in humans because pleomorphic liposarcomas have a high metastatic rate, myxoid liposarcomas are more likely to metastasize to extrapulmonary soft tissue structures, and well-differentiated liposarcomas are unlikely to metastasize.^51–53 In a retrospective study in dogs, histologic subtype was not prognostic, but metastatic disease was more common in dogs with pleomorphic liposarcomas.⁵⁰

Leiomyoma and Leiomyosarcoma

Leiomyomas and leiomyosarcomas are tumors arising from smooth muscle cells. The gastrointestinal (GI) tract is most commonly affected, but other primary sites include the spleen, liver, genitourinary tract, retroperitoneal space, vessel wall, and subcutaneous tissue.54–57 Paraneoplastic syndromes associated with smooth muscle tumors, particularly GI leiomyomas and leiomyosarcomas, include hypoglycemia, nephrogenic diabetes insipidus, and secondary erythrocytosis.^55,58–61

Leiomyomas are benign and usually small, localized, and well encapsulated. Leiomyomas of the vagina and vulva are often pedunculated, protrude from the vulva, and are hormonally dependent. Ovariohysterectomy is recommended in the management of dogs with vulval or vaginal leiomyomas.

Leiomyosarcomas are malignant tumors with a moderate metastatic potential, depending on the primary site.55,62 The metastatic rate for dogs with hepatic leiomyosarcoma is apparently 100% but is approximately 50% for other primary intraabdominal sites and 0% for dermal smooth muscle tumors.^55,61,63,64 Regional lymph nodes, mesentery, and liver are the most common metastatic sites for GI leiomyosarcoma, although other sites include the spleen, kidneys, and peritoneum.^55,61–64

Leiomyosarcoma is the second most common GI tumor in dogs and has a predilection for the jejunum and cecum, but any region of the GI tract can be affected from the esophagus to the rectum.55,61–63,65 An immunohistochemical review of previously diagnosed GI leiomyomas and leiomyosarcomas has resulted in the vast majority of these tumors being reclassified as GI stromal tumors (GISTs) or GI stromal-like tumors.^66,67 Leiomyosarcomas have strong immunoreactivity to actin and desmin and rarely stain positively with c-kit, CD34, or S-100 protein. In contrast, true GISTs are consistently associated with mutations of the tyrosine kinase receptor gene c-kit and will have strong immunoreactivity to c-kit and CD34 proteins with variable reactivity to actin, desmin, and S-100 protein.^62,65–67 The GI stromal-like tumors have an identical immunohistochemical profile to GISTs, except they do not express c-kit.⁶⁶

Older dogs are more commonly affected and there is no sex or breed predisposition.55,61–63 In contrast, there is a male predisposition for GI leiomyomas and these tumors have a predilection for the stomach rather than the jejunum and cecum.^62,68 Presenting signs can include inappetence, weight loss, vomiting, diarrhea, polyuria, polydipsia, anemia, and hypoglycemia.^55,61–63

Surgical resection is the recommended treatment for dogs with leiomyosarcomas. Intestinal perforation with localized to diffuse peritonitis is relatively common in dogs with GI leiomyosarcoma and is reported in up to 50% of cases.⁶¹ Local tumor control is good following complete resection, but recurrence has been reported following incomplete resection of a gastric leiomyoma and cutaneous leiomyosarcomas.^64,66,68

Prolonged survival and possibly cure has been reported following surgery in dogs with gastrointestinal leiomyosarcoma and GIST tumors.54,55,59,67 Prognostic factors in humans with GIST include tumor size, metastasis, and histologic criteria such as tumor necrosis, number of mitotic figures, and proliferating cell nuclear antigen (PCNA) index⁶⁹; however, prognostic factors have not been investigated in dogs with leiomyosarcoma. The MST for dogs with GI leiomyosarcoma and GIST surviving the immediate postoperative period is up to 37.4 months, with 1-, 2-, and 3-year survival rates of 75% to 83%, 62% to 67%, and 60%, respectively.^{55,61,63,66,67} In addition, metastasis did not have a negative impact on survival time in one report with a 21.7 month MST for dogs with documented metastasis at the time of surgery.⁶¹ However, other investigators have found metastasis significantly decreases survival time.⁶³ The MST is 8 months for dogs with splenic leiomyosarcoma, and all dogs with hepatic leiomyosarcoma in one series had evidence of metastasis at initial surgery and were euthanized.⁵⁵

Rhabdomyosarcoma

Rhabdomyosarcomas are rare malignant tumors originating from myoblasts or primitive mesenchymal cells capable of differentiating into striated muscle cells.⁷⁰ In dogs, rhabdomyosarcomas are most frequently reported to arise from skeletal muscle of the tongue, larynx, myocardium, and urinary bladder. They are locally invasive with a low-to-moderate metastatic potential. Metastatic sites include the lungs, liver, spleen, kidneys, and adrenal glands.⁷⁰

Rhabdomyosarcomas are histologically classified as embryonal, botryoid, alveolar, and pleomorphic. The histologic diagnosis of rhabdomyosarcoma is difficult and immunohistochemical staining for vimentin, skeletal muscle actin, myoglobin, myogenin, and myogenic differentiation (MyoD) may be required for definitive diagnosis.⁷¹ Embryonal rhabdomyosarcomas have a predilection for the head and neck region of older dogs, such as the tongue, oral cavity, and larynx. In contrast, botryoid rhabdomyosarcoma commonly arises in the urinary bladder of young, female large breed dogs with Saint Bernard dogs possibly being overrepresented in one data set.⁷⁰ Botryoid tumors are characterized by their grapelike appearance. The histologic classification scheme for rhabdomyosarcoma has prognostic significance in humans, but this has not been investigated in dogs. In humans, botryoid rhabdomyosarcoma has a good prognosis, embryonal rhabdomyosarcoma has an intermediate prognosis, and alveolar rhabdomyosarcoma has a poor prognosis.^70,72

Rhabdomyosarcomas, particularly those involving the extremities, have a high rate of metastasis in humans; major metastatic sites include the lungs, lymph nodes, and bone marrow. The metastatic potential and prognosis in dogs with rhabdomyosarcoma have not been determined because it is rarely diagnosed and even more rarely treated with curative intent. However, disease-free and overall survival times have been encouraging in the few dogs treated with surgical resection with or without RT and chemotherapy.73–77 In humans, in contrast to many other types of soft tissue sarcomas, multimodality treatment with surgery, RT, and chemotherapy has significantly improved survival rates, particularly in children with embryonal and botryoid rhabdomyosarcoma.^51,53,72

Lymphangiosarcoma

Lymphangiosarcomas are rare tumors seen in young dogs and cats that arise from lymphatic endothelial cells.27,78,79 They are usually soft, cystic-like, and edematous, usually occurring in the subcutis (Figure 21-3).²⁷ In most cases, clinical signs are associated with extensive edema and drainage of lymph through the skin or a cystic mass. Aspiration may reveal a fluid-filled mass. Histopathologically, these tumors resemble normal endothelial cells and may be confused with hemangiosarcomas because of the vascular channels; however, red blood cells are not seen.²⁷ Lymphangiosarcomas tend to have a moderate-to-high metastatic potential.⁸⁰ In a single case report, a dog treated with surgery that had local recurrence had a complete response following doxorubicin chemotherapy with no evidence of recurrence or metastasis 9 months after remission.⁸¹

Hemangioma

Hemangiomas and hemangiosarcomas (HSAs) are tumors of vascular endothelial origin. Hemangioma is a benign tumor that can occur in a variety of sites, including skin, liver, spleen, kidneys, bone, tongue, and heart.82–84 Dermal hemangiomas may be induced by ultraviolet (UV) light in short-haired dogs with poorly pigmented skin.²⁷ Despite their benign biologic behavior, hemangiomas can cause severe anemia secondary to tumor-associated blood loss.^82,84 In humans, hemangiomas can spontaneously regress or be responsive to intralesional corticosteroids, but this has not been observed in dogs.²⁷ Complete surgical resection is usually curative.

Hemangiosarcoma

HSAs are highly malignant tumors. The most common primary sites in cats and dogs involve visceral organs, especially the spleen, right atrial appendage, and liver.²⁴ Other primary sites include the skin, pericardium, lung, kidneys, oral cavity, muscle, bone, genitourinary tract, and peritoneum and retroperitoneum.^24,85 A thorough review of HSAs is presented in Chapter 33, Section A. The discussion here is limited to dermal and subcutaneous HSAs. Primary dermal HSAs have a predilection for light-haired or poorly pigmented skin on the ventral abdomen and preputial region of dogs, particularly those confined to the dermis, and solar radiation has been proposed as a cause of dermal HSAs in dogs.⁸⁶

Canine cutaneous HSAs are clinically staged according to depth of involvement with stage I tumors confined to the dermis, stage II tumors extending into subcutaneous tissue, and stage III HSAs involving the underlying muscle (Figure 21-4).⁸⁶ Stage II and III dermal HSAs are typically large and poorly circumscribed and have a bruised appearance that can be mistaken for a traumatic hematoma. The recommended treatment is wide surgical resection and adjuvant doxorubicin.⁸⁷ Doxorubicin-based chemotherapy protocols have been investigated in dogs with nonresectable stage II and III cutaneous HSAs, with approximately 40% of dogs showing a measurable response with a median response duration of 53 days.⁸⁸ Treatment with doxorubicin-based chemotherapy protocols may downstage dogs with large subcutaneous and intramuscular HSAs and thus decrease the size of the tumor, allowing for complete surgical excision.⁸⁸

Clinical staging provides prognostic information on the success of local treatment, metastatic potential, and survival time. Dogs with stage I dermal HSAs have a complete surgical resection rate of 78%, 30% metastatic rate with all metastases occurring in distant dermal sites, and a MST of 780 days.⁸⁶ In contrast, dogs with stage II and III hypodermal HSAs have a complete surgical resection rate of only 23%, principally because these tumors are larger and less well circumscribed; are 60% metastatic to lungs, regional lymph nodes, and distant dermal sites; and have a significantly lower MST of 172 to 307 days (Figure 21-5).⁸⁶ For dogs with aggressive local control (using adequate surgery with or without RT) of subcutaneous or intramuscular HSA, the use of adjuvant doxorubicin results in encouraging survival times. The median disease-free interval (DFI) and survival time for dogs with subcutaneous and intramuscular HSAs treated with surgery and doxorubicin are 1553 and 1189 days and 266 and 273 days, respectively.⁸⁷

Feline cutaneous HSAs are usually solitary tumors in older cats, with a mean age of 11.5 to 12.5 years and males possibly being overrepresented.89,90 Unlike cutaneous hemangiomas, which have no site predilection, cutaneous HSAs occur primarily in poorly pigmented skin, particularly the skin of the pinna, head, and ventral abdomen and subcutaneous tissue of the inguinal region.^89–91 Local tumor control is poor following surgical resection, with local recurrence reported in 50% to 80% of cases at a median of 420 days postoperatively.^89–91 Metastasis has been reported but occurs less frequently than in dogs with dermal and hypodermal HSAs.^89–91 The MST of greater than 1460 days for cats treated with wide surgical resection is significantly better than the MST of 60 days reported for untreated cats with cutaneous HSAs.⁹⁰

Synovial Cell Sarcoma

Synovial cell sarcomas are malignant tumors arising from synoviocytes of the joint capsule and tendon sheath. The two types of synoviocytes are type A synoviocytes, which are phagocytic and resemble macrophages, and type B synoviocytes, which are fibroblastic.⁹² Synovial cell sarcomas have been classified as monophasic or biphasic, depending on the proportion of malignant epithelial (synovioblastic) and mesenchymal (fibroblastic) cells within the tumor. However, this classification scheme was adopted from human medicine and is probably not applicable in small animals because of the rarity of epithelial cells in canine synovial cell sarcomas.⁹² To add further confusion to the nomenclature, synovial cell sarcomas and histiocytic sarcomas are often considered to be different types of joint tumors, but both may originate from synovial cells, with synovial cell sarcomas arising from type B synoviocytes and histiocytic sarcomas arising from type A synoviocytes. Expression of CD18 does not differentiate between the macrophages (or type A synoviocytes) and dendritic antigen-presenting cell (APC) lineage of histiocytic cells (P.F. Moore, personal communication). Recent immunohistochemical evidence, however, indicates that periarticular histiocytic sarcomas do arise from subsynovial dendritic APCs and not type A synoviocytes (P.F. Moore, unpublished data). Rare canine synovial myxomas have been reported. They were most common in large breed middle-aged dogs⁹³ and were reported most often at the stifle or a digit and may be confused with the more common synovial cell sarcoma.

The diagnosis of synovial cell sarcoma is controversial and immunohistochemistry (IHC) is recommended to differentiate synovial cell sarcomas from other types of joint tumors.12,94,95 The immunohistochemical panel should include vimentin and cytokeratin for synovial cell sarcoma, CD18 for histiocytic sarcoma, and actin for malignant fibrous histiocytoma.⁹⁴ However, other investigators have questioned the value of IHC in the diagnosis of synovial cell sarcoma.⁹⁵ Synovial cell sarcomas are histologically graded from I to III based on criteria such as nuclear pleomorphism, mitotic figures, and necrosis, and this grading scheme provides prognostic information.¹²

Synovial cell sarcomas are locally aggressive with a moderate-to-high metastatic potential, depending on histologic grade.¹² Up to 32% of dogs with synovial cell sarcomas have evidence of metastatic disease at diagnosis and 54% by the time of euthanasia.^10,12 Regional lymph nodes and lungs are the most common metastatic sites.¹² Synovial cell sarcomas have a greater metastatic potential and a higher incidence of lymph node metastasis compared to typical soft tissue sarcomas. Synovial cell sarcomas are rare in cats, but feline and canine synovial cell sarcomas are similar in terms of histologic appearance, biologic behavior, and distribution of metastatic lesions.⁹⁶

In dogs, synovial cell sarcomas usually occur in large breeds, with a predisposition for flat-coated and golden retrievers. Middle-aged dogs are most commonly affected, and there is no sex predilection. Synovial cell sarcomas usually involve the larger joints, particularly the stifle, elbow, and shoulder, but any joint can be affected. Lameness is the most common presenting complaint and can be confused with other orthopedic conditions.¹² Radiographic features of synovial cell sarcomas in dogs include periarticular soft tissue swelling and bone invasion, ranging from an ill-defined periosteal reaction to multifocal punctate osteolytic lesions, involving bones on either side of the joint.^12,92 Bone involvement is rare in cats.⁹⁶ Limb amputation is recommended for treatment of the local tumor because local tumor recurrence is significantly lower compared to marginal or wide resection.^12,95 Local tumor recurrence following limb amputation, known as stump recurrence, occurs at a relatively higher rate than other types of tumors for which limb amputation is commonly performed.¹² Thus the level of amputation should be as proximal as possible to minimize the risk of local tumor recurrence, such as forequarter amputation for synovial cell sarcomas of the thoracic limb and coxofemoral disarticulation or hemipelvectomy for synovial cell sarcomas of the pelvic limb. The role of adjuvant therapy is unknown, but synovial cell sarcomas in humans are more responsive to chemotherapy agents such as anthracyclines and ifosfamide than many other types of soft tissue sarcomas.⁵¹ Doxorubicin-based chemotherapy protocols may be warranted in dogs with nonmetastatic grade III synovial cell sarcomas.^12,97

Prognostic factors in dogs with synovial cell sarcoma include clinical stage, histologic grade, and extent of surgical treatment. Dogs with evidence of lymph node or lung metastasis at diagnosis have a MST of less than 6 months compared to 36 months or greater if there is no evidence of metastasis.¹² The MST for dogs treated with limb amputation is 850 days, which is significantly better than the 455 days reported following marginal resection.⁹⁵ Finally, the MST for dogs with grade III synovial cell sarcomas is 7 months and significantly worse than either grade I or II synovial cell sarcomas, with MSTs greater than 48 months and 36 months, respectively.¹² In one study comparing canine joint tumors, the metastatic rate and MST for dogs with synovial cell sarcoma was 25% and 31.8 months, 0% and 30.7 months for dogs with synovial myxoma, 91% and 5.3 months for dogs with histiocytic sarcoma, and 100% and 3.5 months for dogs with other types of periarticular sarcomas.⁹⁴

Myxosarcoma

Myxosarcomas are neoplasms of fibroblast origin with an abundant myxoid matrix composed of mucopolysaccharides. These rare tumors occur in middle-aged or older dogs and cats. The majority are subcutaneous tumors of the trunk or limbs,²⁷ but there are reports of myxosarcomas arising from the heart, eye, and brain.^98–100 These tumors tend to be infiltrative growths with ill-defined margins.²⁷

Malignant Mesenchymoma

Malignant mesenchymomas are rare soft tissue sarcomas comprising a fibrous component with two or more different varieties of other types of sarcoma.²⁴ Malignant mesenchymomas have been reported in the lungs, thoracic wall, liver, spleen, kidney, digits, and soft tissue.^101–106 They have a slow rate of growth and can grow very large. Metastasis has been reported.^105,106 The outcome for dogs with splenic mesenchymomas is better than other types of splenic sarcomas, with a MST of 12 months and a 1-year survival rate of 50%.¹⁰¹