History and Clinical Findings
A 9-year-old 3.9-kg neutered male domestic shorthair cat was referred for investigation of a rapidly growing subcutaneous mass in the region of the left scapula. According to the referring veterinarian, the mass had been first noted 1 month earlier. At the referral examination, the cat was bright, alert, and responsive with a body condition score of 4/9. The cat's heart rate, respiratory rate, and rectal temperature were within reference limits. The subcutaneous mass was located over the craniodorsal aspect of the left scapula, was freely mobile, and did not appear to be attached to the underlying tissues. On palpation, the mass was firm and lobulated in texture but apparently nonpainful; it measured 3.6 × 1.2 × 2 cm. The cat was kept indoors at all times and had no other relevant health problems in the past. The cat had been regularly vaccinated with a core vaccine (live attenuated vaccine) against feline panleukopenia virus, feline herpesvirus, and feline calicivirus as well as with a vaccine against FeLV (live attenuated vaccine) and rabies (inactivated, killed vaccine) because of frequent travel outside of the United Kingdom.
Cytologic Findings
A fine-needle aspirate specimen of the mass was obtained for cytologic examination. Smears had high nucleated cellularity, moderate numbers of erythrocytes, and occasional lysed nucleated cells on a background with a high amount of viscous-appearing, pale-pink extracellular matrix (Figure 1). There were different populations of cells present, mostly mixed together, that often appeared in windrowing formation. High numbers of oval to occasionally plump spindle-shaped cells were present individually or in loose aggregates. The spindle-shaped cells each had a round to oval nucleus, prominent nucleolus, coarse chromatin, and a low amount of variably basophilic cytoplasm that was occasionally vacuolated and rarely contained small, pink granules. Purple extracellular matrix material was evident, woven between the cells. Criteria of atypia included marked anisocytosis and anisokaryosis (maximum dimension of nuclei ranging from 15 to 50 μm), frequent macrokaryosis, occasional binucleation, and rare multinucleation (≤ 7 nuclei/cell) with intracellular anisokaryosis, nuclear molding, and prominent multiple nucleoli that varied in number (≤ to 4) and shape (oval to angular), even within the same cell. Mitotic figures were frequently noted, including aberrant figures. Additionally, there were low numbers of scattered macrophages, multinucleated giant cells, siderophages, small lymphocytes, plasma cells, nondegenerated neutrophils (in hemic proportions), and rare eosinophils admixed with the aforementioned pleomorphic spindle-shaped cells.
Photomicrographs of preparations of fine-needle aspirate specimens obtained from a subcutaneous mass over the craniodorsal aspect of the left scapula of a cat. A—Mixed inflammatory cells have a windrowing formation. Modified Wright stain; bar = 20 μm. B—High numbers of oval to occasionally plump spindle-shaped cells are present individually or in loose aggregates. C—Plump spindle-shaped cells have prominent multiple nucleoli. Modified Wright stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.853
Photomicrographs of preparations of fine-needle aspirate specimens obtained from a subcutaneous mass over the craniodorsal aspect of the left scapula of a cat. A—Mixed inflammatory cells have a windrowing formation. Modified Wright stain; bar = 20 μm. B—High numbers of oval to occasionally plump spindle-shaped cells are present individually or in loose aggregates. C—Plump spindle-shaped cells have prominent multiple nucleoli. Modified Wright stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.853
Photomicrographs of preparations of fine-needle aspirate specimens obtained from a subcutaneous mass over the craniodorsal aspect of the left scapula of a cat. A—Mixed inflammatory cells have a windrowing formation. Modified Wright stain; bar = 20 μm. B—High numbers of oval to occasionally plump spindle-shaped cells are present individually or in loose aggregates. C—Plump spindle-shaped cells have prominent multiple nucleoli. Modified Wright stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.853
Clinicopathologic and Histopathologic Findings
The cytologic interpretation of this case was challenging because of the multiple cell populations in the mass as well as windrowing formation of the cells and the presence of extracellular matrix. The spindle-shaped cells with prominent criteria of atypia and extracellular matrix were supportive of a sarcoma with differential diagnoses including myxosarcoma, fibromyxosarcoma, and fibrosarcoma. However, evidence of prior hemorrhage with macrophagic and mild lymphoplasmacytic inflammation supported inclusion of reactive fibroplasia secondary to inflammation as a possible differential diagnosis. On the basis of the cytologic findings, anatomic location, and clinical features of the mass, surgical removal of the mass was elected.
Wide surgical excision of the mass (with 4-cm-wide lateral margins) and left partial scapulectomy was performed. The mass was then submitted for histologic examination. Sections were routinely processed and stained with H&E, Alcian blue, or periodic acid–Schiff stain. The latter stain was also performed on some cytologic specimens. Histologic examination revealed a relatively well-demarcated, unencapsulated, lobulated, expansile, loosely cellular neoplasm within the subcutis. Neoplastic cells formed vague streams and were small and polygonal to spindle-shaped with distinct cell borders separated by a sparse fibrovascular stroma and wide clear spaces. Each neoplastic cell contained a moderate amount of eosinophilic cytoplasm and at least 1 small, ovoid, and hyperchromatic nucleus with a variably prominent single nucleolus. There was moderate anisocytosis and anisokaryosis, and there were 7 mitoses/10 hpf (×400).
The histologic characteristics of the subcutaneous mass confirmed a sarcoma (Figure 2). The presence of associated macrophages in multiple sections, which often appeared to contain granular pink to gray-blue adjuvant-type material, was a feature that is evident in vaccine-associated sarcomas (Figure 3). Staining with Alcian blue or periodic acid–Schiff stain revealed an abundant, diffusely blue (positive), mucopolysaccharide matrix (Figure 4). This finding was most consistent with a myxosarcoma.
Photomicrographs of a section of the excised subcutaneous mass. Spindle-shaped and stellate cells are present in an abundant myxoid stroma. H&E stain; bar = 200 μm. Inset—Notice the cellular hyperchromasia and pleomorphism. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.853
Photomicrographs of a section of the excised subcutaneous mass. Spindle-shaped and stellate cells are present in an abundant myxoid stroma. H&E stain; bar = 200 μm. Inset—Notice the cellular hyperchromasia and pleomorphism. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.853
Photomicrographs of a section of the excised subcutaneous mass. Spindle-shaped and stellate cells are present in an abundant myxoid stroma. H&E stain; bar = 200 μm. Inset—Notice the cellular hyperchromasia and pleomorphism. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.853
Photomicrograph of a section of the excised subcutaneous mass. Notice the macrophages containing vaccine-associated adjuvant. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.853
Photomicrograph of a section of the excised subcutaneous mass. Notice the macrophages containing vaccine-associated adjuvant. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.853
Photomicrograph of a section of the excised subcutaneous mass. Notice the macrophages containing vaccine-associated adjuvant. H&E stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.853
Photomicrographs of a section and cytologic preparation of a fine-needle aspirate specimen of the excised subcutaneous mass following special staining. The myxomatous stroma is Alcian blue positive. Alcian blue stain; bar = 20 μm. Inset—Periodic acid–Schiff stain highlights the extracellular matrix. Periodic acid–Schiff stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.853
Photomicrographs of a section and cytologic preparation of a fine-needle aspirate specimen of the excised subcutaneous mass following special staining. The myxomatous stroma is Alcian blue positive. Alcian blue stain; bar = 20 μm. Inset—Periodic acid–Schiff stain highlights the extracellular matrix. Periodic acid–Schiff stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.853
Photomicrographs of a section and cytologic preparation of a fine-needle aspirate specimen of the excised subcutaneous mass following special staining. The myxomatous stroma is Alcian blue positive. Alcian blue stain; bar = 20 μm. Inset—Periodic acid–Schiff stain highlights the extracellular matrix. Periodic acid–Schiff stain; bar = 20 μm.
Citation: Journal of the American Veterinary Medical Association 259, 8; 10.2460/javma.259.8.853
Morphologic Diagnosis and Case Summary
Morphologic diagnosis and case summary: subcutaneous myxosarcoma with adjuvant-containing macrophages in a cat.
Comments
For the cat of the present report, the anatomic location of the mass and the mass's malignant mesenchymal population with mixed inflammation and macrophages containing presumptive adjuvant-type material established a diagnosis of feline injection-site sarcoma (FISS).1 Even though the mass was not tested for feline sarcoma virus (FeSV) or FeLV, this cat was regularly vaccinated against FeLV; moreover, the age of the cat and location of the mass were highly compatible with development of an FISS.2 In young cats, FeSV can induce fibrosarcomas that are multicentric and locally invasive and tend to metastasize to the lungs or other sites.3 Vaccination of cats against FeLV makes FeSV-induced fibrosarcoma less likely because FeLV subgroup A acts as a protein supplier for the development of FeSV-induced fibrosarcoma.3 Thus, given the clinical features of the sarcoma and the cat's prior history of vaccination against FeLV, it was extremely unlikely that the neoplasm was FeSV induced, regardless of the fact that a vaccine does not always provide 100% effective protection. The cat was also vaccinated against rabies virus before the mass developed. It has been previously reported4 that there is a correlation between rabies vaccination and the development of FISS. Furthermore, the risk of developing FISS is increased as the number of vaccines administered per site increases, as reflected in the case described in the present report.
Feline injection-site sarcoma is characterized by an aggressive biological behavior, which is mainly a consequence of the neoplasm's highly infiltrative growth and results in high rates of recurrence.1,3 Commonly, FISSs are fibrosarcomas, but other injection-site sarcomas have been described, including osteosarcomas, chondrosarcomas, rhabdomyosarcomas, malignant fibrous histiocytomas, and myofibroblastic sarcomas.1 Histologic examination of tissue biopsy specimens is usually required to determine a final diagnosis. In the case described in the present report, additional special staining of cytologic and histologic preparations was performed to confirm the presence of myxosarcoma and reveal the myxoid differentiation in all areas of the neoplasm. Myxosarcomas and fibromyxosarcomas are sporadically reported as FISSs5,6 and are considered to be rare neoplasms in cats.7 Other differential diagnoses for masses with the same histomorphological appearance include the myxoid variant of peripheral nerve sheath tumor and liposarcoma.
For the cat of the present report, the cytologic interpretation was challenging because different cell populations, including mesenchymal and inflammatory cells, were present. An initial diagnosis of sarcoma with macrophagic and lymphocytic inflammation was made. However, a reactive process could not be ruled out entirely, although it appeared less likely. Lymphocytic inflammation, typically involving T lymphocytes, is frequently reported as a histopathologic finding of FISSs, in addition to the macrophagic inflammation associated with the presence of foreign material (supposed adjuvant) within the macrophages.1 In the fine-needle aspirate specimens obtained from the cat, a striking finding was the windrowing of the cells attributed to the proteinaceous background that was further identified as mucopolysaccharide matrix by means of additional staining methods. The frequent erythrophagia noted most likely reflected previous collection of samples of the mass by the referring veterinarian.
Myxosarcoma is recognized as a mesenchymal tumor of fibroblast or myofibroblast origin that produces an abundant myxomatous matrix of mucopolysaccharides. Histologically, myxomatous tumors have a resemblance to primitive mesenchymal tissue. They are mainly composed of a mixed population of spindle-shaped and stellate cells; the cells are supported by a loose matrix of reticulum and collagen fibers and separated by a mucoid material, which consists mainly of polysaccharides. The presence of abundant extracellular matrix was a most interesting feature of the case described in the present report. On the basis of cytologic examination findings alone, it was challenging to determine the exact nature of the extracellular eosinophilic material; amyloid, mucins, or extracellular matrices, such as chondroid, collagen, or osteoid, were possible considerations.8 Hyaluronic acid within the polysaccharide matrix was the cause of the characteristic blue color generated by Alcian blue staining.9
Although myxosarcomas and fibrosarcomas have common histologic features, there are distinct differences between the 2 types of neoplasm. Fibrosarcomas can produce mucin but typically in small amounts; thus, myxosarcoma was the more likely diagnosis in the case of the present report because of the abundant myxoid extracellular material in the mass. Soft tissue sarcomas may have a mixture of various proteoglycans and glycosaminoglycans.10
The treatment of choice for FISSs is surgical excision with a wide clean margin (defined as a 3- to 5-cm-wide border of grossly normal tissue in all directions around the tumor and 1 or 2 fascial planes deep to it). Adjuvant radiotherapy and chemotherapy are generally considered for cats in which mass excision is incomplete or in which the soft tissue sarcoma is high grade and likely to metastasize.11,12 For the cat of the present report, complete mass excision with clean margins was achieved and at 4 months after surgery, no tumor recurrence was apparent. The cat was reexamined at 21 months after surgery, at which time there was no recurrence of the tumor and no additional concerns were reported by the owner.
To our knowledge, this is the first reported case of vaccine-associated myxosarcoma in a cat. Most studies have grouped together all FISSs despite fibrosarcomas being overrepresented; therefore, there is no specific information regarding the outcome or metastasis and recurrence rates for vaccine-associated myxosarcomas in cats.
References
- 1. ↑
Couto SS, Griffey SM, Duarte PC. Feline vaccine-associated fibrosarcoma: morphologic distinctions. Vet Pathol 2002;39:33–41.
- 3. ↑
Hartmann K, Day MJ, Thiry E, et al. Feline injection-site sarcoma: ABCD guidelines on prevention and management. J Feline Med Surg 2015;17:606–613.
- 4. ↑
Vaccine-Associated Feline Sarcoma Task Force. The current understanding and management of vaccine-associated sarcomas in cats. J Am Vet Med Assoc 2005;226:1821–1842.
- 5. ↑
Doddy FD, Glickman LT, Glickman NW, et al. Feline fibrosarcomas at vaccination sites and non-vaccination sites. J Comp Pathol 1996;114:165–174.
- 6. ↑
Holtermann N, Kiupel M, Hirschberger J. The tyrosine kinase inhibitor toceranib in feline injection site sarcoma: efficacy and side effects. Vet Comp Oncol 2017;15:632–640.
- 7. ↑
Manfredi S, Volta A, Fabbi M, et al. What Is Your Diagnosis? Myxosarcoma in a cat. J Am Vet Med Assoc 2015;247:597–599.
- 8. ↑
Attipa C, Beck S, Lipscomb V, et al. Aldosterone-producing adrenocortical carcinoma with myxoid differentiation in a cat. Vet Clin Pathol 2018;47:660–664.
- 9. ↑
Headley SA, Faria Dos Reis AC, Bracarense AP. Cutaneous myxosarcoma with pulmonary metastases in a dog. J Comp Pathol 2011;145:31–34.
- 10. ↑
Willems SM, Wiweger M, van Roggen JFG, et al. Running GAGs: myxoid matrix in tumor pathology revisited: what’s in it for the pathologist? Virchows Arch 2010;456:181–192.
- 12. ↑
Saba CF. Vaccine-associated feline sarcoma: current perspectives. Vet Med (Auckl) 2017;8:13–20.
