Analysis of MDM2 and TP53 genes in canine liposarcoma.

Canine liposarcoma is an uncommon tumor that shares morphological similarities with its human counterpart. In dogs, the genetic features of this tumor are unknown and, based on immunohistochemical studies, amplification of the gene MDM2 and the mutation of TP53 are suspected. In this study 51 cases of primary liposarcomas were immunohistochemically stained for MDM2 and p53 and subjected to fluorescent in situ hybridization and next-generation sequencing to detect MDM2 amplification and TP53 mutations, respectively. MDM2 and p53 were expressed in 21 and 6 cases, respectively. MDM2 amplification and TP53 mutations were identified in 10 and 15 cases, respectively. Statistical analysis revealed an association of the myxoid subtype and the mitotic count with p53 expression and TP53 mutation. No association was found between MDM2 amplification and MDM2 expression or tumor subtype. These results suggest that despite morphological similarities, canine liposarcoma differs from its human counterpart, for which MDM2 amplification is diagnostic for well differentiated and de-differentiated variants, and TP53 mutations are more common in pleomorphic liposarcoma rather than the myxoid one as occur in our cases. Furthermore, canine myxoid liposarcoma likely represents a distinct disease rather than a mere morphological variant.

Surgical management of urethral obstruction secondary to perineal liposarcoma in a dog: a case report.

BACKGROUND: Swelling of the perineal region in male dogs is most commonly caused by a perineal hernia. Clinical signs associated with perineal hernia are constipation, tenesmus or stranguria. This case report documents a rare cause of perineal swelling created by the growth of a malignant tumour leading to urethral obstruction and subsequent stranguria. CASE PRESENTATION: An 11-year-old neutered male German Shepherd was presented for swelling in the perineal region and stranguria for three days. Complete blood count and serum biochemistry were unremarkable. Ultrasound revealed a heterogeneous mass in the perineal region. Retrograde urethrography showed a severe narrowing of the urethra caudal to the pelvis. A fine-needle aspirate of the mass was highly suspicious for liposarcoma. Staging was performed by computed tomography (CT) of the thorax and abdomen. Total penile amputation in combination with pubic-ischial pelvic osteotomy, transposition of the remaining urethra through the inguinal canal, V-Y-plasty cranial to the prepuce and preputial urethrostomy were performed to remove the tumour. Histopathology confirmed a well-differentiated liposarcoma with complete histological margins. Six months after the surgery the dog was doing well and there were no signs indicating local tumour recurrence. CONCLUSIONS: Wide surgical excision is generally recommended for soft tissue sarcomas, however this is sometimes not feasible for large tumours. In the case reported here, tumour resection was achieved by a combination of several surgical techniques with a good clinical outcome.

Computed tomographic features of an axillary liposarcoma with hepatic metastasis.

A geriatric dog presented for lethargy, dyspnea, and urinary incontinence. Thoracic radiographs demonstrated a large, mixed fat, and soft tissue opaque axillary mass and a pulmonary mass. Computed tomography (CT) further characterized these masses and revealed innumerable fat-attenuating hepatic masses and cranial mediastinal lymphadenopathy. Histopathology of the axillary and hepatic masses confirmed grade two primary axillary liposarcoma with hepatic metastasis. Cytology of the pulmonary mass was consistent with a pulmonary carcinoma. This is the first published CT description of fat-attenuating metastatic hepatic liposarcoma in a dog.

Primary well differentiated hepatic liposarcoma in a meerkat (Suricata suricatta).

A 9-year-old female meerkat (Suricata suricatta) succumbed to progressive abdominal distension, anorexia, and depression. Necropsy revealed an extensively distended abdomen with ascites and markedly enlarged liver. The liver had multiple yellowish masses and displaced the thoracic cavity and abdominal organs. There was no evidence of metastatic lesions based on the gross and microscopic findings. Histologically, the liver mass was composed of locally invasive well-differentiated neoplastic adipocytes with Oil Red O-positive lipid vacuoles. Immunohistochemistry revealed positive immunoreactivity to vimentin, S-100 and negative to pancytokeratin, desmin, smooth muscle actin (SMA), ionized calcium-binding adapter molecule 1 (IBA-1). Thus, the primary well differentiated hepatic liposarcoma was diagnosed based on gross, histological and immunohistochemistry results.

Liposarcoma of Probable Medullary Bone Origin in a Lovebird (Agapornis roseicollis).

A 15-year-old female peach-faced lovebird (Agapornis roseicollis) was presented to the hospital for a possible left wing injury and an inability to fly after falling in its cage. On physical examination the left elbow was swollen and painful. Radiographic images revealed left wing soft tissue swelling surrounding the elbow and lysis of the distal humerus with extensive cortical thinning. Subsequent high-definition volumetric-imaging 3-dimensional computed tomography (HDVI 3D CT) revealed a pathological fracture, cortical lysis, periosteal reaction, and abnormal intraosseous soft tissue of the left humerus with associated soft tissue swelling, suggestive of neoplasia. No evidence of metastatic disease was identified. Surgical amputation of the left wing was elected. A liposarcoma and pathologic fracture of the humerus were diagnosed histologically and by oil red O staining for lipids in the neoplastic cells. The morphologic features of the tumor suggested that it developed within the adipocyte component of the medullary bone. The incision at the amputation site healed without complication. A follow-up HDVI 3D CT performed 4 months postsurgery showed no evidence of metastatic disease. To the authors' knowledge, this is the first report of a primary liposarcoma of medullary bone origin in an avian species.

p53 Expression in Canine Liposarcoma Correlates With Myxoid Variant and Higher Proliferative Activity.

Canine liposarcoma is classified as well differentiated (WDL), dedifferentiated (DDL), myxoid (ML), and pleomorphic (PL). Overexpression of the protooncogene MDM2 has been reported in WDL and DDL, but little is known regarding the role of p53 in their tumorigenesis. The aim of this study was to assess p53 expression in canine liposarcoma and compare it with subtype, grade, mitotic count (MC), Ki67 labeling index (LI), and MDM2 expression. Forty-seven cases were included (13 WDL, 3 DDL, 7 ML, and 24 PL); 17 were MDM2-positive (13 WDL, 3DDL, and 1ML). Five were p53-positive (4 ML and 1 WDL) but DDL and PL were consistently negative. p53 expression correlated with higher Ki67-LI, higher MC, and myxoid histotype. No correlation was found with grade and MDM2 expression. Based on these results canine liposarcoma seems to embody a group of neoplasms whose subtypes, especially ML, may represent distinct diseases rather than morphological variants of the same entity.

Spontaneous retroperitoneal liposarcoma in a free-ranging juvenile golden-headed lion tamarin (Leontopithecus chrysomelas).

Malignant adipocytic neoplasia is rare among nonhuman primates. We report the gross and microscopic features of a retroperitoneal liposarcoma with myxofibrosarcoma-like dedifferentiation in a free-ranging juvenile golden-headed lion tamarin (Leontopithecus chrysomelas). To our knowledge, this is the first report of such tumor subtype in New World primates.

Liposarcoma in a Backyard Silkie and Retrospective Summary of Neoplasms Diagnosed in Backyard Chickens Submitted to the California Animal Health and Food Safety Laboratory System, 2008-2017.

Liposarcomas are a malignant neoplasm of adipocytes, and are rarely diagnosed in avian species. This case report describes the evidence supporting a diagnosis of metastatic liposarcoma in a backyard silkie chicken. On September 28, 2017, a dead 3-yr-old backyard silkie chicken, with a history of unknown skin lesions involving the entire body and severe weight loss, was submitted to California Animal Health and Food Safety Laboratory System-Turlock branch for necropsy. At necropsy, raised necrotic lesions involving the majority of the skin and multiple nodules in the liver, spleen, and bone marrow were noticed. Microscopically, stellate, spindle, and myxoid cells containing large vacuoles, which were confirmed as lipid droplets by Oil Red O, were observed infiltrating the dermis and underlying a necrotic epidermis, with metastasis to liver, spleen, bone marrow, and ovary being the most significant findings. PAS, Oil Red O, Ziehl-Neelsen, Congo red, Gram, and Von Kossa stains, along with immunohistochemistry for pan cytokeratin, vimentin, S100, CD3, pp38, and Meq were used to classify the lesions. Intensely positive vimentin immunohistochemistry, along with large quantities of Oil Red O-positive lipid droplets within the neoplastic cells, were supportive of our diagnosis of liposarcoma. The incidence of neoplastic diseases diagnosed in backyard flock submissions to CAHFS system wide from 2008 to 2017 was also reviewed.

Use of endoscopic-guided electrocautery ablation for treatment of tracheal liposarcoma in a dog.

CASE DESCRIPTION A 7-year-old 44-kg (97-lb) neutered male Great Pyrenees was referred for evaluation because of episodic dyspnea with cyanosis of 1 to 2 weeks' duration. Three days prior to evaluation, the clinical signs had worsened, including 1 episode of collapse. CLINICAL FINDINGS Thoracic radiography and CT revealed a well-delineated soft tissue mass, located approximately 1.5 cm cranial to the carina and occupying almost 90% of the tracheal lumen. A CBC and serum biochemical analysis were performed, and all results were within reference limits. TREATMENT AND OUTCOME Tracheoscopy confirmed the presence of a broad-based bilobate mass that was protruding from the right dorsal aspect of the trachea and occupied almost the entire tracheal lumen. The mass was successfully resected by endoscopic-guided electrocautery ablation. Findings of histologic evaluation were consistent with a diagnosis of liposarcoma. Immediately following the ablation procedure, the previously noted clinical signs of respiratory tract disease resolved. On follow-up examination 12 months later, no regrowth of the mass was evident on thoracic helical CT and tracheoscopy. CLINICAL RELEVANCE Endoscopic-guided electrocautery ablation of tracheal liposarcoma was a safe and effective minimally invasive treatment for the dog of this report. The procedure was brief and appeared to be well tolerated, resulting in immediate improvement of clinical signs.

Liposarcoma of the spermatic cord in a Toy Poodle.

Liposarcoma of the spermatic cord is extremely rare in dogs and humans. This report describes the clinical signs, typical diagnostic imaging including ultrasound and computed tomography, and treatment of a liposarcoma of the spermatic cord of a Toy Poodle confirmed by histological examination after a surgical procedure. This case highlights the importance of preoperative diagnostic imaging and histopathological examination in dogs with an inguinal or scrotal mass.

Well-differentiated inflammatory liposarcoma with metastasis in a 6-y-old cat.

Liposarcomas are rare malignant tumors showing adipocytic differentiation. We report a well-differentiated liposarcoma in a 6-y-old, male neutered cat with a prominent inflammatory component and metastatic spread to the lungs. The patient was initially presented because of fever, lethargy, and a firm subcutaneous inguinal mass. A Tru-cut biopsy of the mass revealed a mixture of well-differentiated adipocytes and lymphoplasmacytic-histiocytic inflammation, interpreted as panniculitis. The mass was surgically excised but recurred 4 mo later. A second excisional biopsy yielded similar histologic findings. A third recurrence of the mass was associated with lung nodules. Histopathology of the recurring and metastatic masses confirmed the diagnosis of well-differentiated inflammatory liposarcoma with pulmonary metastases. The neoplasm had an intense inflammatory component, which obscured the underlying features of liposarcoma and made differentiation from steatitis difficult. This inflammatory variant of a well-differentiated liposarcoma should be considered as a differential in tumorous steatitis-like lesions.

Immunoreactivity of Canine Liposarcoma to Muscle and Brown Adipose Antigens.

Liposarcoma, rhabdomyosarcoma, and hibernoma share some overlapping histologic and immunohistochemical features. Although immunohistochemistry (IHC) is commonly used in the diagnosis of these neoplasms, expression of muscle markers has been reported in human liposarcoma and canine hibernoma in addition to rhabdomyosarcoma. Thus, these neoplasms are a diagnostic challenge but important to distinguish because of differences in prognosis and treatment. Rhabdomyosarcoma and liposarcoma are both malignant, but rhabdomyosarcoma has a higher potential for metastasis. In contrast, hibernomas are benign with low risk of recurrence. This study investigated expression of the muscle markers desmin, myogenin, and α-smooth muscle actin (α-SMA) and the brown fat marker uncoupling protein 1 (UCP1) in 25 cases of canine liposarcoma using IHC. Oil red O histochemistry was performed to confirm the presence of lipid and the diagnosis of liposarcoma in cases that were not well-differentiated. The 25 cases included 15 well-differentiated, 5 pleomorphic, 3 myxoid, and 2 dedifferentiated subtypes of liposarcoma. By IHC, 23 of 25 expressed UCP1, 7 of 25 expressed α-SMA, 7 of 25 expressed desmin, and 3 of 25 expressed myogenin with no clear relationship of antigen expression and tumor subtype. These findings clarify the immunohistochemical profile of canine liposarcoma and suggest overlap in the expression of several muscle antigens and UCP1 between liposarcoma, hibernoma, and rhabdomyosarcoma.

Well-differentiated liposarcoma with chondroid metaplasia in the auricle of a dog.

A 13-year-old spayed female dog had a mass in the left auricle. Grossly, connection between the mass and original auricular cartilage was not recognized. The mass was unencapsulated and contained multiple islands of mature hyaline cartilage and neoplastic adipocytes. The neoplastic cells comprised predominant mature adipocytes, scattered lipoblasts and irregular round to spindle cells with moderate atypia. The atypical cells occasionally had lipid droplets. A diagnosis of well-differentiated liposarcoma (WDL) with chondroid metaplasia was made. This is the first report for liposarcoma with chondroid metaplasia in the auricle of domestic animals.

Well-differentiated Liposarcoma in a Bonnet Macaque (Macaca radiata).

Here we describe the occurrence of a subcutaneous liposarcoma in a geriatric bonnet macaque (Macaca radiata). Clinical presentation was a rapidly growing, ulcerated, subcutaneous mass in the umbilical region of a 28-y-old intact female macaque. The mass was successfully removed through excisional biopsy, and histopathology provided a morphologic diagnosis of well-differentiated liposarcoma. The macaque recovered without complication and displayed no signs of recurrence for at least 18 mo after excision. To our knowledge, this case represents the first report of liposarcoma in a bonnet macaque.

Tyrosine Kinase Receptor Expression in Canine Liposarcoma.

The expression of tyrosine kinase receptors is attracting major interest in human and veterinary oncological pathology because of their role as targets for adjuvant therapies. Little is known about tyrosine kinase receptor (TKR) expression in canine liposarcoma (LP), a soft tissue sarcoma. The aim of this study was to evaluate the immunohistochemical expression of the TKRs fibroblast growth factor receptor 1 (FGFR1) and platelet-derived growth factor receptor-ß (PDGFRß); their ligands, fibroblast growth factor 2 (FGF2) and platelet-derived growth factor B (PDGFB); and c-kit in canine LP. Immunohistochemical labeling was categorized as high or low expression and compared with the mitotic count and MIB-1-based proliferation index. Fifty canine LPs were examined, classified, and graded. Fourteen cases were classified as well differentiated, 7 as myxoid, 25 as pleomorphic, and 4 as dedifferentiated. Seventeen cases were grade 1, 26 were grade 2, and 7 were grade 3. A high expression of FGF2, FGFR1, PDGFB, and PDGFRß was identified in 62% (31/50), 68% (34/50), 81.6% (40/49), and 70.8% (34/48) of the cases, respectively. c-kit was expressed in 12.5% (6/48) of the cases. Mitotic count negatively correlated with FGF2 ( R = -0.41; P < .01), being lower in cases with high FGF2 expression, and positively correlated with PDGFRß ( R = 0.33; P < .01), being higher in cases with high PDGFRß expression. No other statistically significant correlations were identified. These results suggest that the PDGFRß-mediated pathway may have a role in the progression of canine LP and may thus represent a promising target for adjuvant cancer therapies.

COMPUTED TOMOGRAPHIC FINDINGS IN 24 DOGS WITH LIPOSARCOMA.

Computed tomography (CT) continues to become more widely available for assessment of tumors in dogs, yet there are no studies describing the CT appearance of canine liposarcomas. In this retrospective, multicenter study, CT images of dogs with histologically confirmed liposarcomas were reviewed for size, location, attenuation, contrast enhancement, border definition, internal homogeneity, local infiltration, and mineralization. A total of 24 dogs with 26 liposarcomas were sampled. Mean attenuation was +15.2 (SD = 22.3) Hounsfield units (HU) with a range of -36 to +47.5 HU based on representative regions of interest. Twenty tumors (77%) contained focal areas of fat attenuation. All masses enhanced with contrast medium administration, which is distinct from what has been reported previously in infiltrative lipomas. Other CT features associated with canine liposarcomas included heterogeneous internal attenuation (81%) and lack of a clearly defined capsule (38%) suggesting infiltration of local structures. Six tumors (23%) had foci of mineralization. Findings from the current study indicated that liposarcoma should be considered as a differential diagnosis for mixed-attenuation, contrast-enhancing masses in dogs that contain at least one focus of fat attenuation on precontrast images; however, presence of foci of fat attenuation was not a necessary finding for the diagnosis of canine liposarcoma.

COMPARISONS AMONG COMPUTED TOMOGRAPHIC FEATURES OF ADIPOSE MASSES IN DOGS AND CATS.

A better understanding of the CT features of different forms of canine and feline adipose tumors would be valuable for improving patient management and treatment. The purpose of this retrospective, cross-sectional study was to describe and compare the CT features of pathologically confirmed lipomas, infiltrative lipomas, and liposarcomas in a sample of canine and feline patients. A total of 50 animals (46 dogs, four cats) and a total of 60 lesions (23 lipomas, 20 infiltrative lipomas, and 17 liposarcomas) were included in the study. Lipomas appeared as round to oval-shaped (n = 21), well-marginated (n = 20) fat-attenuating lesions. Infiltrative lipomas appeared as homogeneous, fat-attenuating masses but, unlike lipomas, they were most commonly characterized by an irregular shape (75%; P < 0.001), and linear components, hyperattenuating relative to the surrounding fat (100%; P < 0.05). Liposarcomas were represented exclusively by heterogeneous lesions with soft tissue attenuating components with a multinodular appearance (76.5%; P < 0.05). Regional lymphadenopathy (n = 10) and amorphous mineralization (n = 4) were also observed in association with liposarcomas. Computed tomography can provide useful information regarding disease location, extent, and involvement of the adjacent structures. Tumor definition and shape were the most useful parameters to differentiate between lipomas and infiltrative lipomas. The presence of a heterogeneous mass, with a multinodular soft tissue component and associated regional lymphadenopathy and mineralization, were features favoring a diagnosis of liposarcoma.

Co-occurrence of a metastatic mammary liposarcoma and an ovarian sex-cord stromal tumor in a dog.

Sarcoma arising in the mammary gland is a rare tumor in dogs, and primary liposarcoma with metastatic behavior has never been previously reported among canine mammary tumors. A 14-year old female poodle had a mammary mass diagnosed as pleomorphic liposarcoma. Two years following surgical removal, the tumor recurred in the mammary gland with lymph node metastases. In addition, a sex-cord stromal tumor was identified in the ovary. Immunohistochemistry was performed on both tumors that were positive for oestrogen and progesterone receptors. Moreover, the ovarian tumor was positive for calretinin. This is the first report to the authors' knowledge, of the co-occurrence of a pleomorphic liposarcoma of the mammary gland and an ovarian sex-cord stromal (gonadostromal) tumor in the dog.