Embryonal Rhabdomyosarcoma in a Young Maine Coon Cat

Introduction

Although rhabdomyosarcomas are the most common soft-tissue tumors in children younger than the age of 15, they are relatively rare in veterinary medicine.^1,2 Most veterinary case reports involve dogs; however, sporadic reports have documented rhabdomyosarcomas in other domestic species including cats, cows, sheep, and horses, as well as several laboratory animal species (notably rats and ferrets).^2–6 Certain forms of rhabdomyosarcoma in people have been associated with hereditary familial disease syndromes, such as Li-Fraumeni syndrome, in which tumor development is associated with mutated p53.¹ In veterinary medicine, the histological appearance of rhabdomyosarcomas is often distinctive and has been divided into three categories: embryonal (with botryoid variant), alveolar, or pleomorphic. In human medicine, the conventional treatment for these tumors is a combination of surgery, radiation, and chemotherapy.⁷ In veterinary medicine, surgical excision remains the primary treatment because of a lack of information about the biological behavior of this tumor and its response to various chemotherapeutic agents. This report describes a young Maine coon with progressive growth of a ventral abdominal mass since the age of 4 months.

Case Report

A14-month-old, 6.7-kg, castrated male Maine coon cat was examined for a history of progressive prepubic abdominal swelling since the age of 4 months. At the time of examination, the cat was healthy. Feline immunodeficiency virus and feline leukemia virus tests were negative, and the only previous illness was esophoria (i.e., inward deviation of the eyes) that had been diagnosed at 1 year of age. At the time of initial examination by the referring veterinarian, a female littermate of this cat had developed a large (4 × 4 × 4 cm), solid, white to tan tumor on the hip at 3 months of age; an excisional biopsy confirmed embryonal rhabdomyosarcoma (myotubular subtype). At the time of this biopsy, although the neoplastic cells were within 0.1 cm of the surgical margins, the cat was deemed clear of tumor; however, subsequent regrowth was considered possible. The female littermate was not treated with any adjuvant chemotherapy or radiation therapy, and no tumor progression was seen at her most recent follow-up examination, which was 20 months after surgery.

Physical examination of the male Maine coon revealed a large, immovable, prepubic mass that was intimately associated with the ventral abdominal musculature but free of the abdominal viscera. Results of thoracic radiography and serum biochemical and complete blood count analyses were within normal limits except for a mild lymphocytosis (13.8 × 10³/μL; reference range 1.2 to 6.9 × 10³/μL). Abdominal ultrasonography revealed a large, homogenous, hypoechoic mass in the caudal abdomen that was closely associated with the right rectus abdominus muscle. The mass was well circumscribed and did not invade adjacent tissues. Computed tomography (CT) of the abdomen revealed that the mass had a homogenous, soft-tissue density that was isodense to muscle and originated from within the belly of the right rectus abdominus muscle [Figure 1].

Although neoplasia was initially suspected, true-cut surgical biopsies were obtained before complete surgical removal at the request of the owner. The cat recovered uneventfully from the biopsy procedure, and postoperative treatment included hydromorphone^a (0.05 mg/kg subcutaneously [SC] q 6 to 8 hours as needed) and cefazolin^b (22 mg/kg intravenously [IV] q 8 hours). On histopathology, the mass was composed of variably cellular accumulations of interlacing neoplastic mesenchymal cells and a small number of degenerate muscle fibers embedded in a variably myxoid stroma. The neoplastic mesenchymal cells had indistinct margins; moderate amounts of foamy, amphophilic cytoplasm; and moderately pleomorphic nuclei [Figure 2]. Three mitotic figures were seen in 10 high-power fields. Rare neoplastic cells had more abundant, deeply eosinophilic cytoplasm and often peripheralized, hyperchromatic nuclei (myotubes). Intracytoplasmic cross-striations were also seen occasionally within the neoplastic cells.

Although a myogenic origin was suspected based on the hematoxylin and eosin staining, a battery of immunohistochemical stains was used to definitively determine the histogenesis of the neoplasm. Most of the neoplastic cells were positive for desmin, muscle actin, and myoglobin. Lesser numbers of neoplastic cells were positive for sarcomeric actin, and occasional cells were positive for smooth-muscle actin. The desmin and muscle actin stains clearly delineated the cytoplasmic striations [Figure 3] and therefore confirmed the diagnosis of an embryonal rhabdomyosarcoma (myotubular subtype).

Surgical resection first involved making a wide elliptical incision through the abdominal skin and subcutaneous tissue circumferentially around the tumor. The abdomen was entered cranial to the mass, and the expansile body wall mass was observed from the peritoneal surface. The zone of transition from grossly normal abdominal wall to tumor was short. En bloc resection was performed, including full-thickness resection of grossly normal abdominal wall approximately 2 cm from observable tumor. After the mass was successfully removed, the body wall was reconstructed with 3-0 polydioxanone suture in a simple interrupted pattern using an advancement flap of body wall. The subcutaneous tissue was closed with 3-0 poliglecaprone 25 suture (Monocryl)^c in both simple interrupted and simple continuous patterns. Finally, the skin was closed with 3-0 Ethilon^d in a cruciate pattern. Postoperative treatment involved hydromorphone^a (0.05 mg/kg SC q 6 to 8 hours as needed) and cefazolin^b (22 mg/kg IV q 8 hours). Histological examination of the entire excised mass was consistent with the diagnosis of embryonal rhabdomyosarcoma. Additionally, histological evidence showed that the mass was completely surrounded by a pseudocapsule composed of condensed stroma and attenuated myocytes; no infiltration of this pseudocapsule was noted.

Follow-up evaluations at 3-month intervals were recommended, but the owner declined. The cat remained clinically healthy as described via intermittent telephone communication with the owner until 7 months after the second surgery. At this time, the cat had a recheck appointment for evaluation of progressive tachypnea and dyspnea that had begun to develop 3 to 4 weeks previously. The owner reported weight loss and occasional nonproductive cough over that time period. Thoracic radiographs taken at this time revealed multiple, large soft-tissue nodules (2 to 4 cm in diameter) indicative of metastasis scattered throughout the lung fields [Figure 4]. No evidence of local mass recurrence was seen at the prior surgical site. Because of the severity of disease progression and the associated poor prognosis, the owner elected to take the cat home, where it died several weeks later. The owner declined a necropsy.

Discussion

Embryonal rhabdomyosarcomas are uncommon tumors in domestic animals.² They are typically derived from progenitor cells that are capable of differentiation into striated muscle cells; however, they can arise from areas in the body where skeletal muscle is not present.² In animals, these tumors are typically classified into three major categories based on the predominant histological feature: pleomorphic, alveolar, or embryonal (with botryoid subtype). The botryoid subtype classification, although considered a variant of embryonal rhabdomyosarcoma, is reserved for those tumors that arise as polypoid projections into a mucosal-lined surface, most commonly the urinary bladder or uterus.²

Embryonal rhabdomyosarcomas are typically divided into two histological variants. The first and most common is composed of round to polygonal neoplastic cells with deeply eosinophilic cytoplasm (rhabdomyoblasts).² These tumors often have high levels of pleomorphism and multinucleate neoplastic cells, and cytoplasmic cross-striations are uncommon. The second and less common form is composed of spindle cells that resemble primitive myogenic precursors (myotubes).² The spindle cells are often admixed with an abundant myxoid matrix, and the myotubular cells often have cytoplasmic cross-striations that can be accentuated with immunohistochemistry.² Analysis of the histological subtypes of rhabdomyosarcoma in people is purported to have some prognostic significance; however, the subtyping used in human medicine is different than that used in veterinary medicine.⁸ No prognostic studies have been done in domestic animals; however, reports have anecdotally noted that the myotubular subtype seems to be highly invasive and has a greater potential for metastasis.²

The neoplasm reported here was classified as a myotubular subtype of an embryonal rhabdomyosarcoma based on histological and immunohistochemical findings and on the time interval between the cat’s first presentation for the mass and the cat’s death (16 months). A female littermate of this cat also had a myotubular-predominant embryonal rhabdomyosarcoma and was free of further tumor development at her most recent examination (20 months after surgery). Early surgical removal of the tumor in this latter cat likely contributed to a longer disease-free interval.

Immunohistochemical analysis for intermediate filaments and other cytoarchitectural proteins is considered important in determining the diagnosis of tumors originating in muscle.⁹ Typical advancement from poorly differentiated to more differentiated neoplasms includes a step-wise progression of the expression of vimentin, desmin, sarcomeric actin to fast myosin, and finally myoglobin.¹⁰ Vimentin is typically expressed in tumors of mesenchymal origin and is generally lost as myogenic tumors mature.¹⁰ Recently, transcriptional proteins (i.e., myogenin and MyoD) expressed during muscle development have been used to further classify those tumors that express only broad markers such as vimentin and desmin. Myogenin and MyoD play an important role in the subsequent evolution of the myoblast to the multinucleated myotube and are directly related to the degree of differentiation in neoplastic striated muscle cell tumors.¹¹

In human medicine, surgery is important in effecting a cure for this disease.⁷ To date, no long-term studies in veterinary medicine have been performed to assess the outcomes for animals that have had a rhabdomyosarcoma removed surgically. In the case reported here, surgical resection was complete, with no evidence of metastasis at the time of surgery. Nevertheless, the cat succumbed to presumptive pulmonary metastatic disease 7 months after surgery. In human medicine, surgery has been incorporated into a multimodality approach that includes chemo- and radiation therapy. ⁷ Typical chemotherapeutic agents used in human medicine include combinations of vincristine, actinomycin-D, and cyclophosphamide.¹² Unfortunately, reports are few regarding the efficacy of chemotherapeutic drugs in the treatment of rhabdomyosarcomas in animals, and most reports indicate that animals do not respond well to chemotherapy. However, one dog had complete remission with adjuvant chemotherapy after incomplete surgical excision of a urinary bladder rhabdomyosarcoma.^13–15

Large percentages of rhabdomyosarcomas in people are linked to genetic defects, with embryonal rhabdomyosarcomas typically having a loss of heterozygosity on the short arm of chromosome 11.¹ In people, this genetic sequence is the site of the insulin-like growth factor (IGF) II gene.¹ Surprisingly, even though IGF II function is lost in these human patients, embryonal rhabdomyosarcomas have been shown to overproduce this factor, which may relate to the sustained growth pattern of these tumors.¹ Impaired expression of p53 has also been noted in the development of tumors in children <3 years of age.¹⁶ Although a heritable trait is often implicated in the pathogenesis of these tumors in animals, the underlying genetic defect is rarely discovered. However, a report documented a large grouping of rhabdomyosarcomas in 25 piglets that was proven to have a genetic cause.¹⁷ The fact that a littermate of the cat in this report developed the same tumor at a young age, with identical histological appearances, suggests an inborn genetic error and warrants further investigation. When the cat of this report was presented, the tumor was already quite large, so it is unknown whether surgery alone would have been curative had treatment been pursued earlier. Based on the aggressive metastatic behavior of the tumor described here, early surgical resection appears to be important, and the use of adjuvant chemotherapy should be considered to prevent recurrence or disease progression.

Conclusion

Rhabdomyosarcomas are uncommon to rare tumors in all domestic animals, especially cats. These tumors are most commonly sporadic events; however, in this case, a littermate of the subject cat also developed a histologically similar tumor. Inherited and genetic factors in the formation of rhabdomyosarcomas are well recognized in people, but they are not as commonly recorded in veterinary medicine. Further investigation into this line of cats is warranted to determine a possible genetic variation. The development of pulmonary metastasis in this case, even after apparent complete excision, highlights the aggressive and malignant nature of these neoplasms as well as the potential importance of early surgical removal relative to the clinical progression of the neoplasm.