Korean Journal of
Veterinary Service

Leiomyosarcomas are commonly encountered mesenchymal neoplasms in animals (Firat et al., 2007; Cooper and Valentine, 2017; Munday et al., 2017). Leiomyosarcomas are slow growing and locally invasive malignant tumor that originated from the smooth muscle and common in the canine gastrointestinal tract (LaRock and Ginn, 1997; Park et al., 2007). A retrospective study for 5 years at the animal medical center in USA found that 23 of 44 leiomyosarcomas in dogs occurred within the gastrointestinal tract (Kapatkin et al., 1992). Gastrointestinal leiomyosarcomas are much less common in other animal species. According to previous literatures, several cases of feline leiomyosarcoma were reported in skin, female genital tract, stomach, small and large intestine, and eye (Barrand and Scudamore, 1999; Jacobsen and Valentine, 2000; Firat et al., 2007; Labelle and Holmberg, 2010; Hart et al., 2018).

Primary non-lymphoid gastric tumors are rare in cats (Morini et al., 2011; Cooper and Valentine, 2017; Munday et al., 2017). Feline gastrointestinal adenocarcinomas are the most common nonhematopoietic gastrointestinal tumors in cats (Cribb, 1988). Single case including mast cell tumor, extramedullary plasmacytoma, and carcinoid has been reported in feline stomach (Rossmeisl et al., 2002; Morini et al., 2011). Mesenchymal spindle cell tumors are extremely uncommon in cats. One feline gastric leiomyoma was reported in a series of 5,000 feline necropsy examinations (Turk et al., 1981; Cooper and Valentine, 2017; Munday et al., 2017). Recently a case of gastrointestinal stromal tumor (GIST), a subset of gastrointestinal mesenchymal tumor derived from the interstitial cells of Cajal, was described in the stomach of 10-year-old cat (Morini et al., 2011).

A case of gastric leiomyosarcoma in a 10-year-old male neutered domestic shorthair cat was recently reported in clinical aspect (Hart et al., 2018). In this study, we describe the histopathologic and immunohistochemical findings of a gastric leiomyosarcoma in a very young cat. To the author’s best knowledge, this is the second case of feline gastric leiomyosarcoma.

A 2-year-old intact male Himalayan cat was presented with two-month history of anorexia, vomiting and loss of body weight. Physical examination, complete blood count (CBC), serum chemistry profile, and ultrasonography were performed. All parameters in CBC revealed within normal ranges. Serum chemistry profile was normal range except for mild decrease in creatine phosphokinase, total protein, alanine aminotransferase, albumin and packed cell volume (PCV) (Table 1). Abdominal ultrasonography revealed abnormal mass in stomach. Surgical removal of gastric pyloric mass at greater curvature was performed in local animal hospital. Excised gastric mass was fixed in 10% buffered formalin and was submitted to the pathology laboratory at the College of Veterinary Medicine in Jeju National University. Submitted gastric mass was trimmed, embedded in paraffin, sectioned at 3 µm, and stained with hematoxylin and eosin (H&E), Masson’s trichrome, and van Gieson stain for light microscopic examination. Additional paraffin-embedded sections were used for immunohistochemistry (IHC). After mounting on silane coated glass slides, each section was stained by a labeled streptavidin-biotin peroxidase method. To clarify the origin of neoplastic spindle cells, several antibodies including mouse anti-vimentin (Clone V9, 1:100, Dako, Denmark), mouse anti-desmin (Clone D33, 1:100, Dako, Denmark), mouse anti-smooth muscle actin (Clone 1A4, 1:100, SMA, Dako, Denmark), mouse anti-neuron specific enolase (1:200, NSE, Dako, Denmark) and rabbit anti-CD117 protein (1:400, c-kit, Dako, Denmark) were used.

Table 1 . Serum biochemical profiles of Himalayan cat.

Parameters	Results	Reference range	Unit
Glucose	113	63∼140	mg/dL
BUN	26	17∼35	mg/dL
AST	13	13∼46	U/L
Creatinine	1.1	0.7∼2.1	mg/dL
CPK	50	71∼502	U/L
Total protein	6.0	6.7∼8.5	g/dL
Cholesterol	124	73∼265	mg/dL
Total bilirubin	0.2	0∼0.4	mg/dL
ALT	19	29∼186	U/L
Albumin	2.3	2.9∼4.3	g/dL
PCV	32	37∼55	%

BUN, blood urea nitrogen; AST, aspartate aminotransferase; CPK, creatine phosphokinase; ALT, alanine aminotransferase; PCV, packed cell volume..

Grossly, round gastric pyloric mass was 3×3×1.5 cm in size (Fig. 1). Focal ulcerative lesion was observed in the mucosa of gastric mass. The cut surface of the mass was lobulated and greyish-white in color.

Figure 1. Large round mass about 3 cm in diameter was located in the pyloric region of feline stomach.

Histopathologically, focal ulceration and beneath inflammation were observed in the mucosa of stomach mass. Large neoplastic foci were neither circumscribed nor encapsulated with connective tissues, and were occupied from submucosa to serosa in the stomach (Fig. 2A). Multifocal small pieces of pancreatic tissues also included in the peripheral area of requested mass (Fig. 2B). Most of neoplastic foci were composed of densely or loosely packed spindle or ovoid tumor cells (Fig. 2C). Sometimes spindle cells formed interlacing fascicles, however round, ovoid or spindle cells exhibited marked cellular pleomorphism characterized by anisokaryosis and anisocytosis. Most of tumor cells had frequently vacuolated eosinophilic cytoplasm, and central or eccentric nuclei with oval or elongate pattern and prominent nucleoli. Bi-nucleated tumor cells were also presented in the mass. Lots of mitotic figures (1∼2/high power field, Fig. 2D) and bizarre mitosis were observed throughout the neoplastic foci. Most tumor cells showed strong invasive tendency to adjacent tissues such as muscularis mucosa, serosa, and embedded pancreatic tissues in the tissue section. Severe diffuse erosion with hemorrhage and beneath inflammation was also presented in the serosal surface of stomach mass. Most tumor cells stained red with Masson’s trichrome (Fig. 3A) and yellow with van Gieson staining methods. According to IHC, the tumor cells in stomach mass demonstrated strong positive signals for vimentin and SMA (Fig. 3B, 3C). Only small number of solitary tumor cells showed positive reactions for desmin (Fig. 3D). However, there were no positive reactions for NSE, and CD117.

Figure 2. (A) Large neoplastic foci were existed from gastric submucosa to serosa. H&E, bar=200 µm. (B) Pancreatic tissues (P) were occupied at the peripheral area of gastric mass. H&E, bar=200 µm. (C) Neoplastic foci were composed of densely or loosely packed spindle or ovoid cells. H&E, bar=50 µm. (D) Note marked cellular pleomorphism and high mitotic figures (arrows) of tumor cells in gastric mass. H&E, bar=20 µm.

Figure 3. (A) Tumor cells stained red with Masson’s trichrome, bar=50 µm. Tumor cells showed diffuse positive reactions for vimentin (B), smooth muscle actin (C), but focal positive for desmin (D). IHC, bar=50 µm.

Based on the gross findings, histopathologic and immunohistochemical features, this case was diagnosed as feline gastric leiomyosarcoma.

Gastrointestinal tumors are uncommon in dogs and cats, representing about 2% of all tumors detected (Hart et al., 2018). Based on the previous retrospective study of pathology records, incidences of gastrointestinal adenocarcinoma were ranged from 0.7 to 1.2% of feline necropsies and 0.4 to 8.3% of all feline neoplasias (Cribb, 1988). Alimentary tumors most commonly detected in the small intestine of cats (Hart et al., 2018). Only 1% of gastrointestinal adenocarcinomas were found in feline stomach (Cribb, 1988). And adenocarcinomas accounted for the majority of nonhematopoietic intestinal tumors in cats (Turk et al., 1981). Gastric neoplasia commonly affected middle-aged to geriatric cats, and Siamese cats appear to be predisposed to the development of gastrointestinal adenocarcinomas (Rossmeisl et al., 2002).

Leiomyosarcoma is the second most common malignant tumor in the canine gastrointestinal tract (Cooper and Valentine, 2017; Munday et al., 2017). According to reviews of the Cornell files, 61% (100/158 cases) of canine leiomyosarcomas were reported in the gastrointestinal tract, and approximately 50% of these were in small intestine. However canine gastric leiomyosarcomas have been reported in 9.7% (2/23 cases) and 11.0% (11/100 cases) of all examined gastrointestinal leiomyosarcomas (Kapatkin et al., 1992; Cooper and Valentine, 2017; Munday et al., 2017). There were eight published cases of feline intestinal leiomyosarcoma; seven cases in the small intestine and one in the rectum (Barrand and Scudamore, 1999). The Cornell files also demonstrated that the small intestine was the most common site of gastrointestinal leiomyosarcoma (6 of 14) (Cooper and Valentine, 2017; Munday et al., 2017). Only single case of feline gastric leiomyosarcomas of 10-year-old cat was demonstrated in the previous literature (Hart et al., 2018). In dog, most of gastrointestinal leiomyosarcoma cases occurred in dogs 10 years of age or older (Cooper and Valentine, 2017; Munday et al., 2017). Although several gastrointestinal leiomyosarcoma cases occurred in domestic cats as young as 2 years of age, but they were most common in middle-aged to aged cat (Cooper and Valentine, 2017; Munday et al., 2017). In the current case, gastric leiomyosarcoma was diagnosed in a 2-year-old Himalayan breed cat. And the site of leiomyosarcoma was the pyloric region of the stomach, as previously reported (Hart et al., 2018).

The tumor in this case should be differentiated from many spindle cell tumors such as fibrosarcoma, GIST, Schwannoma, malignant peripheral nerve sheath tumor, hemangiosarcoma, and rhabdomyosarcoma. These spindle cell tumors share many common microscopic features. Therefore, various diagnostic methods are being applied for the accurate diagnosis for these tumors. Special staining including Masson’s trichrome and van Gieson stain could make a differential diagnosis for this case of muscle origin from collagenous elements. In the present case, the tumor cells were strongly positive for vimentin, confirming its mesenchymal origin, and positive for SMA, supporting the final diagnosis of leiomyosarcoma. Schwannoma and malignant peripheral nerve sheath tumor could be successfully ruled out as the negative results for NSE in this case. Immuno-positive reactions for desmin were observed in small number of solitary tumor cells in this case but not in whole mass. The lack of desmin immunoreactivity was considered to be consistent with previous literatures for feline leiomyosarcomas in intestine, vulva, and skin (Barrand and Scudamore, 1999; Jacobsen and Valentine, 2000; Firat et al., 2007). Desmin was also known to be variably expressed in 50 to 80% of leiomyosarcomas in dogs and humans (LaRock and Ginn, 1997; Barrand and Scudamore, 1999). Therefore, desmin might be a less reliable marker than SMA in the diagnosis of smooth muscle origin tumors, especially in feline leiomyosarcomas. Recent literature demonstrated the correlation between morphologic features of tumor cells in leiomyosarcoma and desmin immunoreactivity. In that paper, authors suggested that strong vimentin and weak desmin expression many predict malignant behavior in leiomyosarcomas (Hayes et al., 2013). Although the diagnostic hallmark of GIST is the immunohistochemical expression of CD117 antigen (Park et al., 2007; Morini et al., 2011), the tumor cells in this case were negative for CD117 antigen. Hence, GIST could be successfully ruled out in the present stomach mass of Himalayan breed cat. The distinction between GISTs and smooth muscle tumors relies primarily on IHC for CD117 and SMA (LaRock and Ginn, 1997; Cooper and Valentine, 2017; Munday et al., 2017).

Criteria for malignancy of canine gastrointestinal leiomyosarcomas have historically included invasiveness, mitotic rate, cellularity, and atypical nuclear morphology (LaRock and Ginn, 1997; Cooper and Valentine, 2017; Munday et al., 2017). In this case, neoplastic foci were consisted of interlacing fascicles of spindle cells with marked cellular pleomorphism including anisokaryosis, anisocytosis, and bi-nucleation. High mitotic figures and bizarre mitoses were observed in this case. Similarly to this case, an average mitotic index of 1.65 (1∼2 mitoses/400X field) has been reported in canine leiomyosarcoma (Johnson et al., 1995). In addition, very strong invasiveness of tumor cells to adjacent tissues including pancreas also observed in this feline gastric mass. Overall histopathologic findings supported the diagnosis of a gastric leiomyosarcoma.

Leiomyosarcomas are usually large, solitary, and present expansional growth, which may lead to ruminal narrowing and obstruction in alimentary system and consequently to recurrent vomiting, as observed in this case (Cooper and Valentine, 2017; Munday et al., 2017; Henker et al., 2022). Clinical signs in the cat with intestinal leiomyosarcoma were mostly non-specific, such as lethargy, chronic vomiting, weight loss and inappetence (Barrand and Scudamore, 1999; Cooper and Valentine, 2017; Munday et al., 2017), as seen in this case. The cat with gastric leiomyosarcoma also showed non-specific signs including nausea and weight loss over a 6-month period (Hart et al., 2018). Because of the absence of previous literature, the prognosis in the cat with gastrointestinal leiomyosarcoma is unclear. One study for feline case of jejunal leiomyosarcoma demonstrated that there was tumor metastasis without available information for metastatic site and post-diagnosis survival time (Turk et al., 1981). Some intestinal leiomyosarcomas in dogs showed local invasion to the adjacent omentum (Henker et al., 2022), as observed in the present case. Previous literature has suggested the need for radical surgical excision to prevent local recurrence of feline intestinal leiomyosarcoma (Barrand and Scudamore, 1999).

In this case, we describe differences between leiomyosarcomas of the gastric wall and other malignant non-epithelial tumors such as gastrointestinal stromal tumors and schwannoma based on histopathology, IHC, and special staining. To the author’s best knowledge, this is the second case of feline gastric leiomyosarcoma in a very young cat. Although very rare, leiomyosarcoma should be include the differential diagnosis for the cat with gastric mass.

This work was supported by the 2024 education, research and student guidance grant funded by Jeju National University.

No potential conflict of interest relevant to this article was reported.