Spontaneous Leiomyosarcoma Arising from the Ethmoid Turbinate of a Rat

Abstract

Spontaneous leiomyosarcoma arising from the left ethmoid turbinate was observed microscopically in an 83-week-old male F344 rat. The tumor cells showed smooth-muscle differentiation with prominent nuclear pleomorphism and a small number of mitotic figures. The tumor cells were also immunohistochemically positive for smooth-muscle actin. The tumor protruded slightly into the nasal cavity and invaded the surrounding tissues. The present article is the first case of spontaneous leiomyosarcoma in the rat nasal cavity.

Spontaneous tumors in the nasal cavity are rare in animals. In rats, however, several types of primary epithelial and nonepithelial tumors have been reported (Brown et al., 1991). The most common spontaneous tumor seen in the nasal cavity in F344 rats is squamous cell carcinomas. Nonepithelial tumors, such as fibrosarcomas, osteosarcomas, and chondromas, are occasionally seen, but there are no reports of occurrence of smooth-muscle–derived tumors. This article describes the histopathological nature of spontaneous leiomyosarcoma arising from the left ethmoid turbinate in an F344 rat.

In this case, a 5-week-old male F344 rat was received from Charles River Laboratories Japan, Inc. (Kanagawa, Japan) and kept without treatment for its entire life span. The animal was housed individually in a wire mesh cage under routine controlled conditions (temperature, 23 ± 3 °C; humidity, 50% ± 20%; lighting, 12 hours) and had free access to a CRF-1 diet (Japan Clea, Shizuoka, Japan) and tap water.

The animal was found dead at the age of 83 weeks without showing any symptoms before death. Macroscopically, there were no abnormal findings except for a cystic nodule in the cecum and atrophy of testes with several yellow foci. The nose was fixed in a solution of 5% formic acid and 5% formalin and cut into 2 pieces at the following level: just behind the upper incisor teeth and the first palatal ridge. The tissue specimens were embedded in paraffin and cut into 4-μm sections. The sections were stained with hematoxylin and eosin (HE). Some sections were processed for immunohistochemical staining using mouse monoclonal antibodies against smooth-muscle actin, S-100 protein (DAKO, Japan), and desmin (Biomeda, USA) at 4 °C overnight. The sections were processed for the labeled polymer method using an Envision kit (DAKO, Japan) according to the manufacturer’s instruction. Counterstaining was performed with hematoxylin.

The tumor, which was detected microscopically as a small protrusion on the left ethmoid turbinate, was characterized as poorly delineated and nonencapsulated with dense cellular mass and consisted of interwoven fascicles of long, spindle-shaped eosinophilic cells with blunt-ended oval nuclei with nuclear pleomorphism and a small number of mitotic figures. The tumor cells invaded the surrounding tissues with small necrotic foci, while the surface on the side of the nasal cavity was well preserved and was covered with normal mucosal epithelial cells. The tumor cells were immunohistochemically positive for smooth-muscle actin but negative for S-100 protein and desmin (Figure 1).

In F344 rats, the most frequently occurring nonepithelial tumor is mononuclear cell leukemia in both sexes and uterine stromal polyps in females. Other nonepithelial tumors, such as fibromas or fibrosarcomas, hemangiomas or hemangiosarcomas, lipomas or liposarcomas, and leiomyomas or leiomyosarcomas, are seen in various organs and tissues, but the incidences of these tumors are extremely low. Spontaneous leiomyomas or leiomyosarcomas are known to arise in the stomach, intestine, spleen, vagina, uterus, and urinary bladder but not in the nasal cavity (Joseph et al., 1998). The authors diagnosed this tumor as leiomyosarcoma and distinguished it from the fibrous type of malignant fibrous histiocytomas (MFH) according to the morphological differences that MFH show distinct storiform or cartwheel arrangement of the tumor cells and abundant collagen production. It has been reported that some cases of poorly differentiated leiomyosarcomas in humans were immunohistochemically negative for desmin (de Saint Aubain Somerhausen and Fletcher, 1999; Yamamoto et al., 2003; Hemmi et al., 1998), although the tumor cells showed good differentiation into smooth muscle in the present case. To our knowledge, several cases of leiomyosarcomas of the sinonasal tract have been reported in humans (Fu and Perzin, 1975; Lippert et al., 1996; Josephson et al., 1985) and dogs (Wilson and Dungworth, 2002). In rodents, chemically induced rhabdomyosarcoma (“NT Toxicology and Carcinogenesis Studies,” 1990), hemangioma, and hemangiosarcoma (“Carcinogenesis Bioassay,” 1982; Renne et al., 1986; Brown, 1990) have been reported in the nasal cavity, but no leiomyosarcoma has been reported.

The origin of the present tumor is unclear. In a human case, Lippert et al. (1996) suggested that leiomyosarcomas of the nasal cavity arise from the smooth muscles in the tunica media of the vessel walls because the blood vessels are the only structures in this anatomical region, while Josephson et al. (1985) speculated that possibly, the origin of the tumor is undifferentiated mesenchymal cells. To clarify the derivation of the tumor, more similar cases should be collected and further studied.

In conclusion, this report represents the first case of spontaneous leiomyosarcoma in the rat nasal cavity.