A congenital periocular leiomyosarcoma in a dairy calf

Abstract

A mass was removed surgically from the right orbit of a 1-d-old Holstein calf. Grossly, the mass filled the rostral part of an enlarged orbit and compressed the globe toward the caudal pole of the orbit. The brown, 6-cm tumor had central yellow and brown areas, and a smooth, glistening cut surface. Microscopically, the neoplasm was highly cellular and composed of spindle cells arranged in irregular, broad, interlacing streams and bundles, forming a herringbone pattern and supported by a sparse collagenous matrix. Neoplastic cells infiltrated surrounding soft tissues and compressed the globe. The neoplastic cells had positive immunolabeling for α–smooth muscle actin, desmin, and vimentin, and negative immunolabeling for factor VIII, myoglobin, cytokeratin, and skeletal muscle actin. Histopathology and immunohistochemistry results confirmed a diagnosis of leiomyosarcoma. To our knowledge, congenital periocular leiomyosarcoma has not been reported in cattle previously. This rare tumor could be included as a differential diagnosis in newborn calves with periocular masses.

Ocular tumors are relatively rare in domestic animals. ⁶ Several tumors, including fibrosarcoma, malignant schwannoma, myxosarcoma, meningioma, fibroma, lymphoma, and leiomyosarcoma can affect the eye and periocular tissues. ¹⁷ In cattle, ocular squamous cell carcinoma (SCC) is the most common and economically important tumor, as well as the primary cause of enucleation.^6,15

Leiomyosarcomas, which originate from smooth muscle cells, have been reported in various species of domestic animals and in humans.^{8,9,17,19,21,32} Leiomyosarcomas are locally infiltrative and rarely metastasize.^4,9 These tumors are uncommon in species other than small domestic animals, in which they are seen as primary hepatic and splenic tumors. ⁵ Angioleiomyosarcoma has been described in the hearts of cattle 1–3-y-old. ⁵ Clinical signs of leiomyosarcomas are associated with the location of the tumor; gastrointestinal leiomyosarcomas have been associated with vomiting, diarrhea, colic, anorexia, weight loss, weakness, recumbency, and fever.^5,19,31 Uterine leiomyosarcomas cause recurrent hemorrhage from the vulva and spontaneous lactation.^5,31 In addition, leiomyosarcomas have been described affecting the eye, urinary bladder, and rumen in several ruminant species.^2,5,9,21 However, few cases of leiomyosarcoma have been reported affecting the periocular tissues of the eyes of calves. ⁸ Our thorough review of PubMed, Google Scholar, and CABI Direct did not yield any reference describing a congenital periocular leiomyosarcoma in a newborn calf.

Here we describe a congenital periocular leiomyosarcoma in a 1-d-old male Holstein calf. The calf, born on a dairy farm located in the southeast of Buenos Aires province, Argentina, was admitted to the Large Animal Teaching Hospital of the Faculty of Veterinary Medicine, National University of Central Buenos Aires Province, for diagnostic work-up of globe deformation and its treatment. The history indicated that the calf had been born with a mass in the right orbit. Initial examination revealed a tumor affecting the rostral region of the right orbit and covering the globe. Three days after admission, the tumor and globe were removed surgically under general anesthesia and fixed by immersion in 10% neutral-buffered formalin, pH 7.2, for 48 h.

The enucleated globe was deformed and atrophic due to compression by an 8-cm, partially encapsulated tumor located in the rostral pole of the orbital cavity, which was also bulging out of the orbit, delimited ventrally by the zygomatic and maxilla orbital bone and dorsally by the frontal bone, infiltrating the eyelids, and impeding eyelid closure (Fig. 1). The external surface of the tumor was dry and covered by sloughing tissue. On cut surface, the tumor had central, yellow irregular areas and cystic cavities surrounded by pale and moderately firm tissue with irregular brown areas (Fig. 2).

Figures 1–6.

Periocular leiomyosarcoma in a 1-d-old calf. Figure 1. A large tumor affected the right orbit with protrusion of the mass and the globe. Figure 2. The globe (asterisk) is surrounded and severely compressed by a tumor with central coagulative necrosis (arrows). C = caudal; R = rostral. Figure 3. Histologically, interlacing streams and bundles form a “herringbone” pattern (arrows) supported by sparse collagenous matrix. H&E. Bar = 100 µm. Figure 4. Most of the fusiform neoplastic cells have intense cytoplasmic α–smooth muscle actin immunostaining. Immunohistochemistry (IHC). Bar = 50 µm. Figure 5. Most of the fusiform neoplastic cells have intense desmin-positive immunostaining. IHC. Bar = 30 µm. Figure 6. Most of the fusiform neoplastic cells have intense diffuse cytoplasmic vimentin immunostaining. IHC. Bar = 50 µm.

Although the calf recovered uneventfully from anesthesia, 4 d after surgery he developed omphalophlebitis and septicemia, and despite aggressive treatment, he died 2 d later. An autopsy was performed 3–5 h after death. Apart from the surgical wound associated with the enucleation, the navel was enlarged and there were petechiae in the lungs and liver. Samples of liver, heart, lungs, spleen, kidneys, and brain were collected and fixed in 10% neutral-buffered formalin for 48 h. These tissues, plus all of the tissues collected during the enucleation surgery, were processed routinely for the production of 4-μm sections and stained with H&E. Selected sections of the ocular mass were also processed for immunohistochemistry (IHC) for α–smooth muscle actin (α-SMA), vimentin, desmin, factor VIII, myoglobin, cytokeratin, and skeletal myosin according to the standard operating procedures of the Veterinary Teaching Hospital, UC Davis (Davis, CA, USA). Negative controls were sections of the tumor for which the primary antibody had been replaced by normal serum from the species in which the primary antibody had been produced. Positive controls were sections containing the tissues against which each primary antibody had been produced.

Microscopically, the distorted globe was compressed by a well-demarcated, expansive, moderately cellular, and partially capsulated tumor composed of spindle cells arranged in irregular, broad, interlacing streams and bundles forming a herringbone pattern and supported by a low-density collagenous matrix (Fig. 3). Occasionally, polygonal cells with sparse cytoplasm and multinucleate giant cells were observed. Most of the neoplastic cells had indistinct cell borders, moderate amounts of eosinophilic cytoplasm, and occasionally hypereosinophilic cytoplasm with pyknotic nuclei. The nuclei were elongated and had finely stippled chromatin and a single nucleolus. Anisokaryosis was moderate to severe. The mitotic count was <1 per 10 hpf. Irregular areas of coagulative necrosis, hemorrhage, fibrin deposition, and proteinaceous edema were also observed. Large numbers of viable and degenerate macrophages and lymphocytes admixed with cellular debris were present in the walls of blood vessels within the neoplasm. Subpleural and subcapsular hemorrhages were observed in the lungs and liver, respectively. No significant microscopic lesions were evident in any of the other organs examined histologically. The cytoplasm of most neoplastic cells had positive staining for α-SMA (Fig. 4), desmin (Fig. 5), and vimentin (Fig. 6). No positive staining was seen for pancytokeratin, factor VIII, myoglobin, or skeletal myosin. ²⁵

Based on cell and tissue morphology, and positivity for desmin, vimentin, and α-SMA, a diagnosis of leiomyosarcoma was established. Other tumors, including fibrosarcoma, rhabdomyosarcoma, hemangiosarcoma, and histiocytic sarcoma, were ruled out based on morphology and IHC results.

This neoplasm was present at birth, indicating that it had developed in utero, and hence was considered congenital. Because no other neoplasm was observed in the carcass of this animal, the mass in the orbit was considered a primary periocular leiomyosarcoma. We speculate that the tumor developed in utero from mesenchymal cells located near the globe. However, the origin of the neoplastic mesenchymal cells was not elucidated definitively.

Although the mass was growing from the periocular tissue but not from the globe itself, enucleation and removal of the periocular mass was the only treatment instituted to improve the quality of life of the animal. Eye tumors in this area may produce significant deleterious effects, including visual impairment and severe discomfort. ⁶ Surgical removal of a compressed globe is indicated as the best treatment given the close anatomic interrelationships between the globe and the periocular tissues. ⁶

On reviewing the literature available in PubMed, Google Scholar, Web of Science, and CABI Direct, we did not find any report of congenital intra- or periocular leiomyosarcomas in calves. Various publications indicate that congenital tumors in calves are rare.^14,20 Malignant melanoma, dermoid cysts, congenital mast cell tumors, and undifferentiated sarcoma were the only congenital growth disorders described in the eyes of calves.^13,14,20 An intraocular leiomyosarcoma developed over a 6-wk period, it was secondary to a traumatic event, and produced shrinkage of the eye with infiltration into the cranium. ¹⁵ As is characteristic of leiomyosarcomas, our case had mild invasion of adjacent tissues and no metastases, which differs from other sarcomas that have local metastasis and increased aggressiveness.^7,13

Smooth muscle tumors of domestic and wild animals have been described affecting the gastrointestinal and urogenital tracts, with rare presentations in other locations, such as tongue, mesentery, and subcutaneous and other non-visceral locations.^{1,3,11,12,17,23,24,26,27} Ocular leiomyosarcoma is uncommon, with reports in humans, dogs, cats, horses, and cattle, occurring as intra- or periocular tumors.^{10,15,16,22,28} Specific information on congenital leiomyosarcomas in cattle is scant in the literature. ³⁰

Reports of non-congenital uterine leiomyoma and leiomyosarcoma in cattle have been published.^18,27,29 However, detailed descriptions of the microscopic pathology and immunohistochemical confirmation are lacking. A vaginal leiomyosarcoma was clinically, histologically, and immunohistochemically described in a 4-y-old Holstein cow. ⁷ An intestinal myxoid leiomyosarcoma in a sambar deer (Rusa unicolor) was described and confirmed immunohistochemically. ¹⁹

Leiomyosarcoma should be included among the differential diagnoses in cases of periocular tumors affecting newborn calves and be defined by immunohistochemical staining.