Feline ventral abdominal wall angiosarcoma: haemangiosarcoma or lymphangiosarcoma? Clinical and pathological characteristics in nine cases.

OBJECTIVES: Angiosarcomas are rare malignant mesenchymal neoplasms of endothelial cell origin with a predilection to the ventral abdominal wall in cats. Larger case series describing this entity are lacking. METHODS: Two referral centre laboratory databases were searched for angiosarcoma of the ventral abdominal wall. Nine cases with a histological diagnosis were included. Immunohistochemistry (factor VIII and PROX-1 antibodies) was used to phenotype them as haemangiosarcoma or lymphangiosarcoma. RESULTS: All cats presented with a ventral abdominal mass, five of which were producing a serosanguinous discharge. Eight underwent tumour staging and pulmonary metastases were suspected in one cat (but not histologically confirmed). With histopathology alone, a diagnosis of angiosarcoma and lymphangiosarcoma was made in four and five cases, respectively. After immunohistochemistry, five cases had a haemangiosarcoma phenotype and four had a lymphangiosarcoma phenotype, including two cases of lymphangiosarcoma that were reclassified as hemangiosarcoma. Eight cats received treatment (either surgery with or without adjuvant therapies or medical management alone). Six cats were euthanased due to local disease progression. The median survival time for haemangiosarcoma was 166 days (range 137-381), and for lymphangiosarcoma it was 197 days (range 67-208). Two cats with haemangiosarcoma remained alive for a follow-up period of 329 and 580 days, respectively. CONCLUSIONS AND RELEVANCE: Feline ventral abdominal angiosarcomas are rare locally aggressive neoplasms. While histology often provides a diagnosis of angiosarcoma, immunohistochemistry is ultimately required to differentiate between haemangiosarcoma and lymphangiosarcoma phenotypes. Further studies are required to evaluate whether the different phenotypes have an impact on treatment response and outcome.

Primary small intestinal lymphangiosarcoma in a dog presenting with a segmental partial mesenteric volvulus.

A 3-year-old Great Dane presented with a history of chronic vomiting and diarrhoea. Abdominal computed tomography followed by exploratory laparotomy revealed a perforated, segmental partial mesenteric volvulus, affecting an abnormal section of distal jejunum, which was resected. Histopathology and immunohistochemistry results were consistent with jejunal lymphangiosarcoma. This case represents the first report of primary small intestinal lymphangiosarcoma in dogs and the importance of immunohistochemistry for definitive diagnosis.

Primary Lymphangiosarcoma of the Urinary Bladder in a Dog.

Abdominal ultrasonographical and computed tomography examinations of a 12-year-old neutered female toy poodle revealed a protruding mass, approximately 2 cm in diameter, at the apex of the bladder. The mass was firm and haemorrhagic with a homogeneously brownish-yellow cut surface. Microscopically, it was unencapsulated and located in the muscle layer with invasion of the extra-muscular layer. It was composed of spindloid to oval neoplastic cells that formed irregular clefts and diffuse sheets that dissected bundles of collagen. Immunohistochemically, the neoplastic cells were positive for vimentin and lymphatic vessel endothelial hyaluronan receptor 1 antigens, but negative for cytokeratin AE1/AE3, factor VIII-related antigen, CD31, CD34, Prox-1, S100, desmin, α-smooth muscle actin and MyoD1. Negative immunolabelling for laminin antigen supported the absence of evidence of a basal lamina on ultrastructural examination. Based on these findings, this tumour was identified as a lymphangiosarcoma. To the best of our knowledge, this case is the first report of lymphangiosarcoma arising from the bladder in a dog.

Pathologic and flow cytometric features of a case of canine ventral cervical lymphangiosarcoma.

An 11-y-old spayed female German Shepherd was presented for a second opinion of ventral cervical swelling of 3-mo duration. On examination, the dog had significant dependent ventral cervical swelling. Enlarged lymph nodes with cystic changes and severe edematous facial swelling were noted on computed tomography. Fine-needle aspiration of the ventral cervical swelling revealed yellow-tinged fluid, with a predominance of lymphoid cells noted on cytologic examination. On cervical exploratory surgery, the left mandibular lymph node was surrounded by a large fluid pocket; biopsies of the lymph node were obtained. Impression smear cytology, flow cytometry, PCR for antigen receptor gene rearrangements, and histopathology were performed on samples from the left mandibular lymph node. Impression smear cytology revealed a population of atypical discrete cells. Flow cytometry identified a population of CD34+/CD45- large cells. A tumor of endothelial origin within the medulla of the lymph node was identified by histopathology, and lymphangiosarcoma was confirmed based on prospero-related homeobox gene 1 (PROX1) immunoreactivity. Our study describes the challenges in the diagnosis of a rarely reported entity and highlights that neoplastic endothelial cells should be considered as a differential when high proportions of CD34+/CD45- cells are present in flow cytometry.

Successful management of lymphangiosarcoma in a puppy using a tyrosine kinase inhibitor.

A puppy was diagnosed with lymphangiosarcoma associated with lymphedema based on lymphography and histopathology. The lesions resolved after toceranib therapy, and the dog remains in remission 1 year later. This is the first report of a successful outcome following oral toceranib as first-line therapy for lymphangiosarcoma in a dog.

Gestion réussie d'un lymphangiosarcome chez un chiot à l'aide d'un inhibiteur de la tyrosinekinase. Un chiot a été diagnostiqué avec un lymphangiosarcome associé à un lymphoedème en se basant sur une lymphographie et l'histopathologie. Les lésions se sont résorbées après un traitement au tocéranib et le chien demeurait en rémission un an plus tard. Il s'agit du premier rapport d'un résultat favorable après le recours au tocéranib oral comme traitement de premier recours pour le lymphangiosarcome chez un chien.(Traduit par Isabelle Vallières).

Lymphangiosarcoma in 12 dogs: a case series (1998-2013).

Lymphangiosarcoma (LAS) is an uncommon malignant neoplasia arising from lymphatic endothelium; little information exists regarding therapy. Single institutional retrospective review for canine LAS histopathology diagnoses over a 15-year period yielded 12 dogs. Ten dogs were presented for a mass and/or swelling at cervical, trunk or limb regions. Prior to diagnosis, 10 dogs received empiric wound therapy. Cytology performed in 10 consisted of mild inflammation. Survival ranged from 60, 168 and 876 days for three dogs with palliation; 90 days with prednisone in one; 182 days with chemotherapy in one; 240, 267, 487, 630 and 941 days for five receiving surgery; and 574 days for one receiving surgery, radiation and chemotherapy. One dog is alive with recurrence at 243 days following surgery and carboplatin chemotherapy. Clinical improvement existed in LAS dogs receiving multimodal therapies. Early tissue biopsies are recommended for progressive oedematous lesions of unknown origin.

Lymphangiosarcoma with bone formation of the auricle in a dog.

A 12-year-old mixed-breed neutered female dog was referred with cutaneous tumors at the left auricle. Histologically, the cutaneous tumor located in the dermis comprised numerous clefts and cavernous channels lined by neoplastic endothelial cells with no erythrocytes. Bone tissue without direct contact with neoplastic cells was seen in the well-developed stromal connective tissue. The neoplastic endothelial cells exhibited mild to moderate atypia. Immunohistochemically, neoplastic cells were positive for vimentin and negative for cytokeratin and factor VIII-related antigen. Basement membrane around the neoplastic lumens was positive for laminin in a linear or granular pattern. Ultrastructural examination revealed discontinuous basement membrane beneath the tumor cells. Histopathological features of this case were consistent with lymphangiosarcoma, and stromal ossification was characteristic.

Presumed primary ocular lymphangiosarcoma with metastasis in a miniature horse.

A 7-year-old, 153.0-kg American Miniature mare presented for evaluation of keratoconjunctivitis of the right eye (OD). A superior palpebral conjunctival mass and stromal keratitis were diagnosed. The incisional biopsy diagnosis was a presumptive corneal hemangiosarcoma. Transpalpebral enucleation was performed, and histopathologic evaluation confirmed angiosarcoma of the conjunctiva, cornea, and extraocular muscles. The horse developed progressive epistaxis and orbital swelling following surgery. A systemic workup was performed 3 months after enucleation, revealing regrowth within the orbit and marked cranial cervical lymphomegaly, suggestive of metastasis. Humane euthanasia was performed, and necropsy confirmed a locally invasive periorbital tumor with metastasis to the submandibular tissue, submandibular lymph node, and thoracic inlet. Histopathologic evaluation of necropsy specimens revealed polygonal to spindle neoplastic cells lining neoplastic vascular channels lacking erythrocytes. Immunohistochemically, the neoplastic cells labeled strongly positive for PROX-1, vimentin, CD-31, VEGF, weakly positive for factor VIII-related antigen, and negative for collagen IV. Based on the clinical, histological, and immunohistochemical features of this tumor, a primary ocular lymphangiosarcoma with metastasis was diagnosed.

Lymphangiosarcoma with systemic metastases in a Japanese domestic cat.

A 4-year-2-month-old female Japanese domestic cat was diagnosed with lymphangiosarcoma through tissue biopsy of an amputated leg. Two months later, the cat was euthanized, and postmortem findings revealed edema, and bruising at the caudal region of the trunk, pulmonary hemorrhage, pulmonary nodules and mediastinal lymphadenopathy. Microscopically, neoplastic tissues were observed in the dermis and subcutis of the trunk, lung, mediastinal lymph nodes, diaphragm, omentum and mesentery. The tumor cells were spindle to polygonal-shaped with nuclear pleomorphism aligning along pre-existing collagen bundles and forming irregular vascular channels in which the erythrocytes were rarely observed. These cells were immunopositive for vimentin, von Willebrand factor and CD31. Based on the histopathological and immunohistochemical features, the neoplasia was diagnosed as lymphangiosarcoma with systemic metastases.

A novel approach to treatment of lymphangiosarcoma in a boxer dog.

A five-year-old female boxer presented with a swelling in the area of the caudal mammary gland. The mass was surgically excised and histopathological examination revealed a poorly demarcated lesion, extending into mammary tissue and infiltrating the sinuses of adjacent lymph nodes. The diagnosis was lymphangiosarcoma. Full blood work, thoracic radiographs, abdominal and scar ultrasound were unremarkable, apart from possible inflammatory reactions in the latter and reactive/metastatic changes in inguinal lymph nodes. Doxorubicin treatment resulted in a 6-month recurrence free interval. At relapse, the dog was treated with metronomic chemotherapy using chlorambucil and meloxicam, which failed to adequately control the disease. Toceranib phosphate was introduced and resulted in almost complete regression of the mass, leaving just a skin plaque. To the authors' knowledge this is the first report describing the use of two novel therapeutic approaches to treat canine lymphangiosarcoma that resulted in a higher than previously described survival time.

Use of surgery and mitoxantrone chemotherapy in a dog with disseminated lymphangiosarcoma.

CASE DESCRIPTION: A 5-year-old sexually intact male Giant Schnauzer was evaluated because of difficulty breathing and left pelvic limb swelling. Eighteen months previously, the patient had had intermittent left pelvic limb swelling, but the owner declined further testing at that time. CLINICAL FINDINGS: Physical examination revealed severe pitting edema of the left pelvic limb and prepuce and muffled heart sounds on thoracic auscultation. Results of thoracic radiography and thoracocentesis were consistent with chylothorax, and CT imaging of the thorax and abdomen revealed a mass involving the whole left sublumbar area. TREATMENT AND OUTCOME: In an attempt to treat the chylothorax, pleural omentalization and pericardectomy were performed. Histologic evaluation of several biopsy specimens harvested in the abdominal and thoracic cavities revealed disseminated lymphangiosarcoma. The patient recovered well from surgery, and mitoxantrone chemotherapy was administered. As of 10 months after surgery, the dog was clinically normal except for mild pelvic limb edema. CLINICAL RELEVANCE: The combination of clinical signs, multiple imaging features, surgical findings, and histologic examination findings enabled the final diagnosis of lymphangiosarcoma. Clinical management that included medical and surgical treatments and chemotherapy resulted in improved quality of life and extended survival time in a dog with metastatic lymphangiosarcoma.

Locally invasive lymphangiosarcoma in a young domestic shorthair.

A 2-year-old, female spayed, domestic shorthair cat presented to the University of Missouri-Veterinary Medical Teaching Hospital (UMC-VMTH) with an approximately 11-month history of fluid-draining pockets along her ventral thorax and axillae. The skin in these regions was erythematous, and multiple areas drained a serous to serosanguinous fluid. Fluid-filled, nodules formed along the ventrum, but these nodules disappeared as fluid drained spontaneously. Histologic assessment of skin biopsies revealed areas of vascular proliferation extending along the deep margin of the section and rare instances of invasion into the superficial dermis. These vascular channels were devoid of cells, lined by variably pleomorphic endothelial cells which had a low mitotic index. Based on the mild to moderate pleomorphism, positive staining with prospero-related homeobox gene-1 (PROX-1), and the locally aggressive nature of the tumor, a final diagnosis of lymphangiosarcoma was made.

Resection of a large intra-abdominal tumor in the Mexican axolotl: a case report.

OBJECTIVE: This case report describes the surgical removal of an intra-abdominal tumor from a Mexican axolotl (Ambystoma mexicanum). The animal was admitted with left abdominal swelling that had increased over 4 months. METHODS: Surgical removal was performed under general anesthesia with MS222 under an operating microscope. Exploratory laparotomy was performed through 2.5 dorsocranial skin incision in the left flank, followed by subcutaneous dissection. RESULTS: The tumor involved the spleen, was adjacent to the descending colon, and supplied by vessels from the spleen, stomach, and colon. The mass was removed by clamping and transecting the spleen and the peritoneum was closed with a continuous suture pattern, while abdominal muscles and skin were closed in layers. After a total duration time of anesthesia of 90 minutes the animal was kept in prophylactic antibiotic baths. Tissue sections revealed characteristics of both lymphangiosarcoma and lymphosarcoma with an appearance typical for a malignant tumor. CONCLUSIONS: Abdominal surgery was performed in an axolotl and the surgical wound healed without complication.

Paresis in an Asian small clawed otter (Aonyx cinereus) associated with vertebral and ischial osteolysis caused by a malignant lymphangiosarcoma.

A 10-yr-old male intact Asian small clawed otter (Aonyx cinerus) was presumptively diagnosed by histopathology and immunohistochemistry with lymphangiosarcoma after bony destruction of the ischium and spinal column from local tumor invasion had caused progressive signs of hind limb lameness and paresis/paralysis, which led to humane euthanasia. At necropsy, the primary tumor was identified as a flocculent mass present under the caudal lumbar vertebrae. Multiple nerves were seen to run from the spinal cord into the wall of the mass. This mass had locally invaded the surrounding muscle, vertebral column, and spinal cord, which led to the clinical signs noted at presentation. Bony destruction was severe with almost complete obliteration of the right ischium and osteolysis of L6, exposing the spinal cord beneath. The tumor had metastasized to at least two different sites within the spleen. The abdominal tumor was confirmed to be of endothelial origin by the use of immunohistochemical staining for factor VIII-related antigen and was confirmed as lymphatic origin versus vascular origin because of the lack of red blood cells within the vessels. The length of time from initial presentation with hind limb lameness to euthanasia because of hind limb paralysis was 4 mo. This is the first report of lymphangiosarcoma, an uncommon malignant neoplasm of lymphatic origin, in a mustelid and the first report of neoplastic disease in an Asian small clawed otter. In addition, the presentation of hind limb paresis associated with bony lysis because of local tumor invasion has not been previously reported with lymphangiosarcoma in humans, domestic animals, or nondomestic animals.

Lymphangiosarcoma in the nictitating membrane of a horse.

A 15-year-old Haflinger gelding presented with a mass in the left nictitating membrane. Two biopsies and the excised nictitating membrane were taken at different time points as a result of reoccurrence of the mass and submitted for histopathologic evaluation. The horse was euthanized as a result of poor prognosis following the reoccurrence of the mass after surgical removal. Histologically, the mass consisted of dilated, thin-walled vascular clefts and channels, lined by flattened to cuboidal endothelial cells with moderate cellular pleomorphism. There was up to 1 mitotic figure per high power field. The channels were empty or contained few erythrocytes. In the collagen-rich stroma, few lymphocytes, focal follicular lymphoid aggregations, and marked lymphangiectasia were observed. Immunohistochemically, the neoplastic cells stained positive for vimentin and partially positive for factor VIII-related antigen. Ultrastructural analysis revealed discontinuous endothelial lining vascular channels that partially lacked a basal membrane. Based on the histopathologic, immunohistochemical, and ultrastructural features lymphangiosarcoma was diagnosed.

Lymphangiosarcoma in a cat.

This report describes a 5-year-old female cat with lymphangiosarcoma arising within the dermis and subcutis of the caudal mammary region. The mass presented as a large, poorly demarcated and fluctuant swelling with bruising of the overlying skin. Histopathologically, the dermis and subcutis in the affected region were diffusely oedematous, haemorrhagic, and infiltrated by plump spindle cells that formed irregular vascular clefts and cavernous channels. Neoplastic cells were aligned in one or more layers along oedematous collagenous trabeculae. The vascular clefts and channels contained only a few or no erythrocytes. The neoplastic cells had moderate to marked nuclear pleomorphism and prominent nucleoli. Lymphocytes and plasma cells were scattered throughout the neoplasm and the adjacent soft tissues. Immunohistochemical labelling revealed the neoplastic cells to express vimentin, factor VIII-related antigen and the lymphatic endothelial cell marker PROX-1, but the cells did not express cytokeratin. The nuclei of many neoplastic cells expressed the proliferation marker Ki67. These histopathological and immunohistochemical findings confirmed the diagnosis of lymphangiosarcoma. This is the first report describing the usefulness of expression of PROX-1 for differentiating between angiosarcoma of lymphatic and vascular origin in cats.

Lymphangiosarcoma in two cats.

Lymphangiosarcoma is a malignant neoplasm of the lymphatic endothelium that is rare in cats. This report describes two cases of feline lymphangiosarcoma that originated in the distal limb, causing intractable lymphoedema and serosanguineous discharge with ecchymoses in local and distant sites. In association with the neoplasia, one cat had cortical bone lysis of multiple metacarpal bones of the affected limb and the other had severe immune-mediated haemolytic anaemia (IMHA). The disease in both cases affected young cats and progressed rapidly. Persistent distal limb lymphoedema with serosanguineous discharge is suggestive of lymphangiosarcoma especially when local or distal ecchymoses are evident.

Imaging findings in pancreatic neoplasia and nodular hyperplasia in 19 cats.

Pancreatic neoplasia in cats is rare and associated with a poor prognosis, but pancreatic nodular hyperplasia is a common incidental finding. The purpose of this study was to describe radiographic and ultrasonographic findings in cats with pancreatic neoplasia or nodular hyperplasia. Fourteen cats (age 3-18 years) were diagnosed with malignant pancreatic tumors: carcinoma/adenocarcinoma (n = 11), lymphoma (n = 1), squamous cell carcinoma (n = 1), and lymphangiosarcoma (n = 1). The most common radiographic findings were an abdominal mass or mass effect (6/6) and lack of serosal margin detail (4/6). On ultrasound, the most common finding was a focal pancreatic mass or nodule, with a size range from 0.4 cm to more than 7.0 cm (8/14). Lymphadenopathy (7/14) and abdominal effusion (7/14) were frequently seen. Five cats (age 10-16 years) with adenomatous/nodular hyperplasia had an abdominal mass or mass effect as the most common radiographic finding (3/3). On ultrasound, all cats had multiple hypoechoic nodules between 0.3 and 1.0 cm associated with the pancreas. Other common findings were pancreatic thickening (2/5), lymphadenopathy (2/5), and abdominal effusion (2/5). The only imaging finding unique to malignant pancreatic tumors was the presence of a single pancreatic nodule or mass exceeding 2cm in at least one dimension (4/14). Although there was a tendency for neoplastic lesions to manifest as single larger lesions and for nodular hyperplasia to manifest as multiple smaller lesions, there was overlap of the imaging findings in both entities. Radiographs and ultrasound can complement but not replace cytology and histopathology in the diagnosis of feline pancreatic neoplasia.

Fat necrosis simulating recurrent neoplasia following external beam radiotherapy in a dog.

A 4.5-year-old neutered male dog was diagnosed with incompletely excised well-differentiated lymphangiosarcoma in the right inguinal subcutaneous region. The mass had metastasized to the right hypogastric and medial iliac lymph nodes. Surgery followed by definitive radiation therapy was administered to the primary site and the sites of metastasis. The dog had a complete response to radiotherapy, and minimal acute side effects. Doxorubicin was administered after radiotherapy. Approximately 4 months following radiation therapy, the dog developed a mass, presumed recurrent tumor, in the original site. In a biopsy only steatitis and fibrosis were found. The mass continued to grow and conservative surgical excision was elected. Histopathologically the diagnosis was fat necrosis and steatitis, with a microscopic focus of lymphangiosarcoma. Fat necrosis is an uncommon sequelum to breast irradiation in people and also appears to be rare in animals. Fat necrosis should be considered as a differential diagnosis when recurrent tumor is suspected in a previously irradiated subcutaneous site in a dog.