5 Mattie J. Hendrick Marshfield Labs, Pennsylvania, USA Mesenchymal tumors include those tumors arising from the supporting mesenchymal tissues of the dermis and subcutis (fibrous connective tissue, blood vessels, lymphatics, nerves, adipose tissue, and smooth muscle) and those round cell tumors of mesenchymal origin that present as cutaneous masses. The tumors described below comprise a wide range of entities, some of which are of uncertain classification. Various spindle cell and round cell neoplasms are included, but the term tumor is used broadly, and includes non‐neoplastic lesions of clinical importance or interest. These tumors have been classified using the revised International Histological Classification of Skin Tumors and Tumor‐like Lesions of Domestic Animals.1,2 This classification system is similar to that found in several old and new texts that deal with skin tumors.3–6 These references will not be further cited in the text, but they provide extensive information on the clinical aspects and histopathology of skin tumors. Spindle cell tumors of the skin and subcutis comprise a large diverse group but tend to have some features that encompass the group. They are locally expansile or infiltrative, but have low metastatic potential. Many have peripheral compression of their cells, creating a pseudocapsule that can lead to misinterpretation of margins and incomplete excisions. Although various treatment modalities have been employed, wide surgical excision remains the treatment of choice. Recurrence is usually dependent on adequacy of excision, mitotic count, and grade. Spindle cell tumors with excision margins that are free of tumor cells recur in less than 5% of cases. Even when tumor cells are present at the excision margin recurrence is expected in only 25% of the cases (see Appendix). Many grading systems have been used over the years in an attempt to predict the behavior and outcome of skin and soft tissue spindle cell tumors in dogs. Most are flawed, in the opinion of this author, due to low numbers, lack of controls, lack of consistency in treatment modalities given to the canine patients, and lack of documentation of metastasis. Even in those grading systems that have good quality control, successful prognostication is often hampered by interpathologist discordance and subjectivity. These problems are also seen in grading schemes in human pathology. In an elegant discussion on this subject in the American Journal of Clinical Pathologists,7 the authors state: The main purpose of an effective grading system is to segregate tumors into those with a favorable prognosis and those with a poor prognosis, leaving as few cases as possible in the uninformative intermediate grade 2 category. Ideally, the good prognosis group should encompass all tumors that, while having a propensity for local recurrence, have very low metastatic potential and are amenable to surgical treatment alone. The tumors in the poor prognosis group should include sarcomas likely to metastasize and for which adjuvant therapy might prove beneficial. Apart from this main function, histologic grading also constitutes a vital aspect of the comparison of patient outcomes in clinical trials. … Pathologists must take responsibility for informing and educating clinicians about the problems and present subjectivity of grading. Otherwise, the increasing obsession with selecting treatment based on histologic grade (type often being regarded clinically as irrelevant) can lead only to less sophisticated and less scientific treatment of patients with a soft tissue sarcoma. Because of the inherent problems and frustration with grading, some veterinary pathologists and training programs are starting to diagnose spindle cell tumors as “Spindle cell tumor, Grade __.” A better approach, exemplified by some recent publications,8 is to try to improve the grading systems. In the Appendix are algorithms and/or grading schemes modified from these references for your review that are used at North Carolina State University. The future should aim at consistency between pathologists using the same grading system. This author believes that although a good grading system can be valuable, the best predictor of outcome of these tumors is the histologic examination and accurate diagnosis of the specific tumor type by an experienced, knowledgeable pathologist. Therein lies the purpose of this chapter. Fibromas are benign neoplasms of fibrocytes with abundant collagenous stroma. Fibromas are uncommon, and are most often seen in the dog. They have been reported in cats, but some investigators believe that feline tumors with the histological appearance of fibromas are actually well‐differentiated fibrosarcomas. Canine breeds that are predisposed to the formation of these tumors include Rhodesian ridgebacks, doberman pinschers, and boxers. Fibromas in the skin and subcutis are rare in horses and food production animals.1 Fibromas occur most commonly on the limbs and heads of dogs. The majority of tumors are small, round to oval intradermal or subcutaneous masses. They are firm, rubbery, and gray/white on cut surface. Fibroma is a benign, well‐circumscribed but unencapsulated neoplasm. It is composed of mature fibrocytes producing abundant collagen (Figure 5.1). The collagenous fibers are repetitive and are usually arranged in interwoven fascicles, more rarely in whorls. The neoplastic fibrocytes are uniform and low in number compared to the abundant dense collagen. They have oval normochromatic nuclei and an indistinct cytoplasm that blends into the extracellular collagenous stroma. Mitotic figures are rarely observed in fibromas. Figure 5.1 Fibroma, skin, canine. Note the dense pattern of repetitive collagen. Collagenous hamartomas (see below) can be distinguished from fibromas by the haphazard arrangement of the collagen fibers in hamartomas, which is similar to normal collagen, and by their superficial dermal location, which often raises the epidermis. Fibromas are slow‐growing, and complete excision is curative. This rare variant of fibroma is unique in that much of the collagen is brightly eosinophilic and hyaline, resembling keloids in humans. These rare tumors are mostly seen in the dog, and can be seen in any breed and at any age. There is a male predominance. Keloidal change in a feline vaccine‐site sarcoma has been reported.2 Most tumors arise on the flank, thorax, or shoulder. Occasionally, multiple tumors arise simultaneously or sequentially. This author has seen multiple sequential tumors in vaccination sites in one dog, suggesting local trauma/wound healing as part of the pathogenesis. Grossly, they can be found in the dermis and/or subcutis, and resemble other fibromas. Keloidal fibromas are well circumscribed but unencapsulated. They are composed of mature fibrocytes producing abundant collagen. However, some of the collagen fibers are wide, bright pink, and shiny (Figure 5.2A,B). There are variable numbers of thin, more normal‐appearing collagen fibers intermingled with the hyalinized ones. Nuclei are more prevalent than in fibromas. Mitotic figures are rarely observed. Malignant variants have been reported,3 based on local infiltration, increased cellular density, nuclear pleomorphism, and mitotic activity, however, metastasis has not been reported. Figure 5.2 (A) Keloidal fibroma, skin, canine. (B) Higher magnification of (A) showing smudgy pink “keloid”‐like collagen. Complete excision for keloidal fibromas and keloid fibrosarcomas is typically curative. This malignant neoplasm has variable presentations depending on species, age, site, and etiopathogenesis. Many other neoplasms (e.g., myopericytoma, malignant melanoma, and leiomyosarcoma) can have regions that are consistent with fibrosarcoma, but careful examination of several sections will usually identify areas characteristic of these other tumors. Although fibrosarcomas occur in all domestic species, they are most commonly seen in adult and aged cats and dogs (mean age of 9 years). Fibrosarcoma is the most common tumor of the cat and has increased in incidence over the last two decades, most likely because of its association with vaccination (see below). No breed or sex predisposition has been reported in the cat, but in canines golden retrievers and doberman pinschers are at increased risk. Most tumors are focal and can develop anywhere on the body, although head and limbs are most often involved. One exception is the fibrosarcoma of cats that is induced by feline sarcomavirus (FeSV). FeSV is a defective mutant of feline leukemia virus (FeLV); in the presence of FeLV, it can replicate, resulting in oncogenesis. FeSV‐associated tumors can occur in individuals as young as a few months of age, with a mean age of 3 years. They are often multicentric and can metastasize.4 FeSV‐associated neoplasms are rarely encountered (or the viral etiology documented) outside of the laboratory. Only 2% of fibrosarcomas in cats are virally induced. The rapid and unique clinical course is pathognomonic. Fibrosarcomas can be circumscribed or infiltrative, small or extremely large and disfiguring. Capsules are usually not seen. The cut surface is gray/white and glistening, often with an obvious interwoven fascicular pattern. Tumors can be well differentiated, with spindle‐shaped tumor cells arranged in interwoven or herringbone patterns (Figure 5.3). Cytoplasm in well‐differentiated tumors is scant, and nuclei are fairly uniform, elongated to oval with inconspicuous nucleoli. Mitotic figures are infrequent. More anaplastic tumors have marked cellular and nuclear pleomorphism. Ovoid, polygonal, and multinucleated giant cells are seen, often with large round to oval nuclei and prominent nucleoli. Multinucleation is a more prominent feature of fibrosarcomas in cats than dogs. The number of mitotic figures varies and increased numbers are associated with more aggressive tumors. Peripheral aggregates of lymphocytes are occasionally seen; some may contain eosinophils and a hypereosinophilic syndrome is seen rarely. Figure 5.3 Fibrosarcoma, subcutis, canine. High nuclear density and paucity of collagen differentiate this from fibroma. The diagnosis of fibrosarcoma is usually not difficult; however, in rare instances differentiation from peripheral nerve sheath tumors (PNSTs) and leiomyosarcomas can be problematic. PNSTs usually have finer, more delicate cells arranged in shorter interwoven fascicles, palisades, or whorls. The collagenous stroma can be more pronounced in fibrosarcomas than in PNSTs or leiomyosarcomas, and a Masson’s trichrome stain will distinguish between collagen and smooth muscle. There has been much ado about the more rounded shape of nuclei in leiomyosarcomas as opposed to fibrosarcomas, but this feature is not reliable. The cytoplasm of leiomyosarcoma cells tends to be more eosinophilic and abundant and can have a bubbly or vacuolar appearance. Immunohistochemistry is not particularly useful as all these tumors are vimentin positive, and S100 positivity is notoriously nonspecific; however, if needed, smooth muscle actin will stain the cytoplasm of smooth muscle tumors. Fibrosarcoma is one variant of injection‐site sarcoma (see below). The unique clinical, gross, and histologic changes are discussed in that section. Tumors are infiltrative and recurrent, but metastasis is uncommon. Surgical excision remains the treatment of choice. Radiation can be a successful adjunct therapy, especially when complete excision is difficult. Surgery with follow‐up radiotherapy can result in increased tumor‐free intervals and overall improved long‐term control.5 Grading schemes for spindle cell tumors of dogs can be found in the Appendix of this book. Pathologists have recognized foreign body and wound‐associated sarcomas in animals and humans since an initial report by Virchow in 1863.6 Rodents are especially predisposed to the development of these types of tumors.7 Most of our domestic species are not, and have an extremely low incidence, so low as to be clinically insignificant. The few reports of sarcomas arising in sites other than vaccination sites in cats and dogs (those associated with long‐acting antibiotics, steroids, the benzoylurea pesticide lufenuron, nonabsorbable suture material, and microchip implants)8,9 are consistent with this extremely low incidence. It was only after the development of new killed adjuvanted vaccines in the mid to late 1980s that the incidence of injection‐site sarcomas in cats rose to noticeable and alarming levels. Vaccine‐associated sarcomas in cats continue to be a significant disease and will be the focus of this discussion. This entity was first described in 1991.10 Since then it has been shown to be an especially aggressive, recurrent variant of fibrosarcoma with high mortality.11,12 Vaccine‐associated sarcomas occur in the cat (malignant fibrous histiocytomas, osteosarcomas, chondrosarcomas, and rhabdomyosarcomas), but these are seen at decreased incidence.11,12 The histological features of these other sarcomas are described below and in other chapters, but the information listed here concerning signalment, incidence, site, gross morphology, growth, metastasis, and treatment pertain to all vaccine‐associated sarcomas. The tumor is seen in cats as young as 3 years of age, but the mean age is 8.1 years, which is slightly younger than that seen in cats with fibrosarcomas that are not vaccine associated (mean 9.2 years).13 There is no sex predilection. True incidence is difficult to determine, but estimates range from 1:1000 to 1:10,000 tumors per vaccinated cat.13–15 Vaccine‐associated sarcomas arise at vaccination sites on the neck, thorax, lumbar region, flank, and limbs. Since protocols proposed in 1996 recommending the right distal limb for feline rabies vaccination, there has been a decrease in interscapular tumors (Figure 5.4A) and a significant increase in tumors on the right limbs.16 Figure 5.4 (A) Vaccine‐associated fibrosarcoma in the interscapular region, feline. (B) Vaccine‐associated sarcoma with giant cells. Note band of macrophages at top. Inset: Cytological preparation with a few macrophages and a giant cell with numerous nuclei. (C) Vaccine product in macrophages. This material is not birefringent. The most typical presentation is a well‐circumscribed, firm white mass in the subcutis or skeletal muscle, with a cystic center containing thin watery or mucinous fluid. Size of the tumor varies widely and is probably dependent on how long owners wait before seeing veterinary care. The tumors tend to be very infiltrative and imaging studies may reveal foci or extension of the tumors into deep fascial planes. At low magnification, the tumor is circular. When in the subcutis, it is usually associated with and extends downward from the panniculus carnosus muscle. There is often a partial fibrous capsule. Despite the circumscribed gross appearance of the tumor, histological “tongues” of tumor are often seen extending away from the mass along fascial planes. Vaccine‐associated fibrosarcomas may be well differentiated, with plump spindle cells arranged in interwoven bundles; however, they tend to be more anaplastic, with cells of variable size and shape, pleomorphic nuclei, and increased numbers of multinucleated cells (Figure 5.4B). Multinucleation is marked in some tumors, with more than 20 nuclei seen in histologic and cytologic preparations (Figure 5.4B inset). Peripheral inflammation, consisting predominantly of lymphocytes and macrophages, is common. The presence of peripheral aggregates of macrophages containing globular gray/brown intracytoplasmic material (shown to be aluminum, a common vaccine adjuvant) supports the diagnosis of vaccine‐associated sarcoma (Figure 5.4C).11 However, this material is found in a minority of cases. The cytological distinction between vaccine‐associated fibrosarcoma and postvaccinal inflammation is extremely difficult because fibroblasts arising in granulation tissue are often pleomorphic and anaplastic, mimicking neoplastic cells. Excisional biopsy is more reliable and is the method of choice for a definitive diagnosis; however, since there appears to be a continuum from inflammation and fibroplasia to neoplasia, even some histological preparations can be problematic. Large lesions that have fully transformed into a sarcoma are more easily diagnosed – by cytology or biopsy, especially for lesions located in vaccine sites. These tumors are highly recurrent, requiring surgical excision one, two, or three times within a 1‐ or 2‐year period.10 The majority of cats end up being euthanized after repeated surgeries, with or without adjuvant therapy. The metastatic potential of these neoplasms is low initially, but appears to increase with prolonged survival.17 Metastasis has been reported to occur in regional lymph nodes, mediastinum, and lungs.13,18,19 Wide surgical margins in all directions should be obtained, which in some cases may include either partial scapulectomy or excision of epaxial muscles and dorsal cervical vertebral processes. Amputation of an involved limb should also be considered. Tail vaccinations are increasing in some parts of the country and have been shown to have no untoward effect. Aggressive surgical excision with wide margins appears to contribute to extended tumor‐free interval and survival times in cats.20,21 Various combinations of immunostimulatory agents and radiotherapy have been used to treat vaccine‐associated sarcomas in cats.17,22,23 Reports suggest that they can extend tumor‐free interval and survival times. Targeted therapy using the tyrosine kinase inhibitor imatinib mesylate (Gleevac) – aimed at breaking the autocrine stimulation of platelet‐derived growth factor and its receptor – has resulted in stabilization of tumors for 2 months,17,24 but these were preliminary studies with low numbers of cats. This is an uncommon but distinctive variant of fibrosarcoma seen in the muzzle region of adult golden retrievers and other large breed dogs.25 This tumor usually manifests itself as a lumpy enlargement of the maxillary or, less commonly, the mandibular region (Figure 5.5A,B) On cut surface, there is a poorly defined firm gray/white mass involving the dermal and subcutaneous tissues. Figure 5.5 (A,B) Well‐differentiated fibrosarcoma, maxilla, canine. (C) Note the bland fibrocytes of the neoplasm. Other examples will be more cellular. The neoplasm is composed of well‐differentiated fibrocytes and fibroblasts in an extensive connective tissue stroma (Figure 5.5C). Nuclear pleomorphism and mitotic figures are rare. The collagen bundles are often haphazard as in the surrounding normal connective tissue, but often there is a repetitive fascicular pattern that sets the tumor apart. Rarely, there is an obvious border with compression, but more often the edge infiltrates the surrounding tissue, making complete excision difficult. There can be a superimposed inflammatory infiltrate, further obscuring the true nature of the neoplastic proliferation. Because of the bland histological appearance of this neoplasm, it could be misdiagnosed as a fibroma or not recognized as abnormal tissue. However, the constellation of breed, site, and histology should lead one to the correct diagnosis. Despite the bland appearance of the cells, the neoplasm is progressively infiltrative, with eventual disfigurement and loss of function. As mentioned above, complete surgical excision is difficult, necessitating partial mandidulectomy or removal of large portions of the maxilla. There are anecdotal reports that radiation with localized hyperthermia can result in longer survival times. This unique equine lesion is the result of a nonproductive infection with bovine papillomavirus types 1 and 2.1,2 It is worldwide in distribution and is not related to human sarcoidosis. This most common equine skin tumor can be seen in any age horse, but the majority of cases are seen in individuals younger than 4 years of age. Sarcoids can occur anywhere on the body, but especially the head, lips, legs, and ventral trunk (Figure 5.6A,B). About 40% of affected horses have multiple sarcoids.3 There are six gross morphological types: verrucous, fibroblastic, nodular, mixed, malevolent/malignant, and flat, the latter are also called “occult.” Figure 5.6 Equine sarcoid. (A) Nodular sarcoid on the eyelid/canthus. (B) Verrucous sarcoid on ear. (Image courtesy of Perry Habecker.) (C) Proliferation of interwoven fibroblasts. Most lesions are composed of a thickened epidermis with prominent epithelial pegs that extend into a dermal proliferation of spindle cells that are arranged in whorls, tangles, or herringbone patterns with a small amount of collagenous stroma (Figure 5.6C). Nuclear pleomorphism and mitoses vary, but can be pronounced in rapidly growing or recurrent tumors. There can be difficulty differentiating some sarcoids from fibrosarcomas or nerve sheath tumors, especially if the distinctive epidermal component has been lost by ulceration or is not present in the submitted section. In addition, a recent paper described an unusual variant of sarcoid without the epidermal component. These tumors were originally diagnosed as schwannomas, but were later found to have bovine papillomavirus (BPV) via polymerase chain reaction (PCR).4 Identification of bovine papillomavirus DNA in the nuclei of proliferating fibroblasts by in situ hybridization or PCR is diagnostic of equine sarcoid, but is seldom performed or considered necessary when the characteristic epidermal and fibroblastic proliferations are present. However, as just described these tools may have value on other spindle cell tumors of horses that lack concurrent epidermal proliferation. This distinction has clinical implications because sarcoids may require chemotherapy or immunotherapy (see below). Rare tumors spontaneously regress, but complete excision – often via cryosurgery – can be curative.5 Recurrence of inadequately excised masses is common. Other modalities, including radiation therapy, topical creams, and intralesional injections of BCG and cisplatin have been tried with variable success. Sarcoids do not metastasize. This disease of cats resembles equine sarcoid in many ways. Papillomavirus DNA with high analogy to BPV type 1 can be found in the feline tumors6,7 and the histologic changes in the epidermis and dermis are similar in the two diseases. This neoplasm occurs mostly in rural or barn cats that have exposure to cattle, hence the incidence is likely underreported. It is most common in young cats, and usually affects the nose or muzzle region. Tumors on the limbs, ventrum, and digits are less common. Tumors can be focal or multifocal, firm, and slightly raised – growing up to 2 cm in diameter. They can be ulcerated and are usually mildly infiltrative. As in equine sarcoids, these tumors are covered by a thickened epidermis with prominent epithelial pegs that extend into a dermal proliferation of spindle and stellate cells (Figure 5.7). The proliferation is unencapsulated and cells are arranged in haphazard streams and bundles, with occasional whorls. There is a variable amount of collageneous stroma often containing numerous mast cells. Spindle cell nuclei are mildly pleomorphic and the mitotic count is typically low – less than 3 per 10 HPFs. Figure 5.7 Feline sarcoid. Distinctive epidermal hyperplasia merging with a proliferating fibroblasts component is characteristic of feline and equine sarcoids. Both are associated with bovine papillomavirus DNA. PCR testing of affected tissues will reveal papillomavirus DNA in most cases. However, this is rarely necessary, as the clinical and histologic features of this disease are quite distinctive. Tumors are slow‐growing and self‐limiting. Like equine sarcoids they can be cured by complete excision, but recurrence is common. Metastasis has not been reported. Previously called malignant fibrous histiocytoma, this entity is still controversial in human and veterinary medicine. Initially thought to be one neoplasm with different variants, it has been shown to be a histologically and immunohistochemically diverse group of neoplasms, leading many to prefer the more generic diagnosis of “undifferentiated pleomorphic sarcoma” or “anaplastic sarcoma with giant cells.”1,2 This author believes there is within this group a tumor of primitive myofibroblast origin in dogs and cats that is analogous to the classical human entity called malignant fibrous histiocytoma (MFH). That tumor is briefly described below. However, the morphology of cells in this tumor merge easily into anaplastic versions of many other mesenchymal and histiocytic tumors in animals and humans, confounding definitive diagnosis and making prognostication difficult. Examination of large samples and further immunohistochemical testing can sometimes more specifically identify the histogenesis of the tumors. Without those aids, one can choose to “lump” these tumors into the grab bag diagnosis of “anaplastic sarcoma with giant cells,” or undifferentiated pleomorphic sarcoma, recognizing that one may be compromising one’s ability to prognosticate. Classic human MFH has been divided into subtypes based on the pattern and predominance of the cell types: storiform‐pleomorphic, giant cell, inflammatory, and myxoid.3 Only the first two types been found with any consistency in the skin/subcutis of domestic animals.4–7 These are described below. Classical MFH occurs in most domestic animal species, but is most frequently seen in the dog. It arises in the skin as a single, expansive tumor, or it may appear as part of a multi‐organ disease that often involves lungs, lymph nodes, spleen, liver, bones, and kidneys.5 Golden retrievers and rottweilers are overrepresented for MFH.5 The relative incidence of focal versus multi‐organ MFH in dogs is difficult to determine because most diagnoses are made on biopsy specimens with incomplete follow‐up. However, autopsy files at the University of Pennsylvania contain at least 40 cases of multi‐organ MFH in dogs. Two of these animals had skin masses. In the cat, MFH is one of the histological variants of vaccine‐associated sarcomas,8 and can also occasionally be seen in the dermis or subcutis in nonvaccine sites. There is no sex predilection. Middle‐aged or older individuals are usually affected. The tumor is usually gray/white but can also have red mottling, depending on the amount of hemorrhage and necrosis. Margins are often distinct, but without encapsulation. This is the most common variant in the skin and organs of dogs. In this variant, fibroblast‐like cells are arranged in cartwheel (storiform) patterns, mixed with histiocytoid cells and an infiltrate of lymphocytes, plasma cells, neutrophils, and occasional eosinophils (Figure 5.8A). Histiocytoid cells are frequently karyomegalic or multinucleated, often with marked nuclear atypia. Some tumors have patchy zones of sclerotic collagenous stroma. Figure 5.8 Malignant fibrous histiocytoma (pleomorphic sarcoma). (A) Storiform‐pleomorphic variant, subcutis, canine. (B) Giant cell variant, skin, canine. These tumors have numerous multinucleated giant cells mixed with spindle cells and mononuclear histiocytoid cells (Figure 5.8B). Although occasionally present, inflammatory cells are not a consistent feature of this variant. This is the most common subtype in cats. Cytology of MFH will show variable numbers of poorly cohesive spindle cells and rounder mononuclear or multinucleated histiocytoid cells along with some inflammatory cells. Immunohistochemical analysis is compatible with a fibroblastic/myofibroblastic phenotype, with consistent positivity for vimentin, and variable positivity for actin and desmin.8–10 The giant cells in MFH should have the same positivity as the fibroblastic cells. As histiocytic sarcoma is a primary differential for the giant cell variant of MFH, CD18 immunostaining should be performed to rule out that diagnosis. Complicating the diagnosis is the fact that reactive CD18‐positive multinucleated giant cells can be found in this neoplasm and other undifferentiated pleomorphic sarcomas. Diffuse CD18 positivity throughout the majority of fibroblastic and giant cells would support a diagnosis of histiocytic sarcoma. Ultrastructural studies reveal the tumor cells in MFH to be characteristic of fibroblasts with or without cytoplasmic filaments consistent with actin.3,11 Dermal or subcutaneous MFH tends to be locally expansile. Reports vary as to the metastatic potential of this neoplasm – again due to the lack of distinction between this and other pleomorphic sarcomas. Any individual with MFH should be given a guarded prognosis. Complete excision can be curative for solitary dermal or subcutaneous masses. There is no recognized successful treatment for multicentric MFH. These are tumors of fibroblast origin distinguished by their abundant myxoid matrix rich in mucopolysaccharides. Myxomas/myxosarcomas are rare, occurring in middle‐aged or older dogs and cats. The majority arise in the subcutis of the trunk or limbs. The gross appearance varies little between myxomas and myxosarcomas. They are soft, gray/white, poorly defined masses that exude a stringy clear mucoid fluid. Both tumors are composed of an unencapsulated proliferation of stellate to spindle‐shaped fibroblasts loosely arranged in an abundant myxoid matrix (Figure 5.9). This matrix, rich in acid mucopolysaccharides, stains light blue with routine hematoxylin and eosin (H&E) stains. Cellularity is low, mitoses are rare, and there is little or no cytological atypia in myxomas. Nuclei tend to be small and hyperchromatic. Increases in cellular density, nuclear pleomorphism, and mitoses warrant the diagnosis of myxosarcoma, but the distinction is often subtle. Figure 5.9 Myxosarcoma, subcutis, canine. Nuclear density warrants the diagnosis of sarcoma, but the histologic distinction between myxoma and myxosarcoma can be subtle, and not clinically relevant as the behavior is the same for both. Histologic features of myxosarcoma are similar to those seen in myxoid variants of PNSTs and myxoid liposarcomas (see below in this chapter), and when present as the primary pattern in the neoplasm, definitive diagnosis can be difficult. In those cases, this author prefers the term “myxoid sarcoma.” Surgical excision is the treatment of choice. Myxomas and myxosarcomas are infiltrative, with poorly defined margins. Recurrence is likely in either case; metastasis is rare, however. Cytological smears of these tumors are often difficult to prepare because of the slimy consistency of the tumor and the paucity of cells that adhere to slides. Differentiation from myxoid liposarcoma and PNST can sometimes be made based on special staining (Oil red O and S100, respectively) but the behavior and prognoses of these three entities are virtually identical, and the distinction is not clinically important. This common non‐neoplastic lesion of dogs is a nodular, poorly circumscribed focus of redundant collagen in the superficial dermis. Although this lesion is also called collagenous nevus, the term hamartoma, which precludes confusion of this lesion with pigmented (melanocytic) tumors or tumors present at birth, is preferred. The pathogenesis of collagenous hamartomas is unknown. It is one of the many common dermal proliferations in aged dogs, and there is no recognized breed or sex predilection. Hamartomas can occur anywhere, but there appears to be a predilection for the head and limbs. These masses are usually small nodular elevations of the epidermis. There can be mild alopecia but no evidence of erosion, ulceration, or other signs of self‐trauma. These lesions have abundant collagen devoid of adnexa, but in contrast to fibromas, the collagen fiber pattern is not repetitive and is similar to that seen in adjacent normal collagen (Figure 5.10). The proliferation is limited to the superficial dermis and usually results in slight elevation of the epidermis and loss, separation, or distortion of adjacent adnexal structures. Figure 5.10 Collagenous hamartoma, skin, canine. Note the haphazard arrangement of collagen that is similar to the adjacent normal collagen. The differentiation between skin tags and collagenous hamartomas is subtle in some instances and not clinically important. Unlike collagenous hamartomas, which usually show some loss or distortion of adnexa, skin tags are usually pedunculated pieces of excess skin that contain all of the skin’s normal constituents. Because of their nipple‐like growth, skin tags are subject to external trauma with secondary ulceration and inflammation. These masses are slow‐growing and usually are excised to rule out other more clinically significant lesions. Excision is curative.
Mesenchymal Tumors of the Skin and Soft Tissues
References
Fibroma
Incidence, age, breed, and sex
Site and gross morphology
Histological features
Additional diagnostic criteria
Growth, metastasis, and treatment
Keloidal fibroma/fibrosarcoma
Incidence, age, breed, and sex
Site and gross morphology
Histological features
Growth, metastasis, and treatment
Fibrosarcoma
Incidence, age, breed, sex, and site
Gross morphology
Histological features
Additional diagnostic criteria
Growth, metastasis, and treatment
Injection‐site sarcomas
General considerations
Feline vaccine‐associated fibrosarcoma
General considerations
Incidence, age, breed, and sex
Site and gross morphology
Histological features
Additional diagnostic criteria
Growth and metastasis
Treatment
Canine maxillary well‐differentiated fibrosarcoma
General considerations, age, sex, incidence, and site
Gross morphology
Histological features
Additional diagnostic criteria
Growth, metastasis, and treatment
References
Equine sarcoid
Incidence, age, breed, and sex
Site and gross morphology
Histological features
Additional diagnostic criteria
Growth, metastasis, and treatment
Feline sarcoid (feline fibropapilloma)
Incidence, age, breed, sex, and site
Gross morphology
Histological features
Additional diagnostic criteria
Growth, metastasis, and treatment
References
Pleomorphic sarcoma (anaplastic sarcoma with giant cells, malignant fibrous histiocytoma)
Gross morphology
Histology
Storiform‐pleomorphic
Giant cell
Additional diagnostic criteria
Growth, metastasis, and treatment
References
Myxoma and myxosarcoma
Gross morphology
Histological features
Growth, metastasis, and treatment
Additional diagnostic criteria
Tumor‐like lesions
Collagenous hamartoma
Site and gross morphology
Histological features
Additional diagnostic criteria
Growth and treatment
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