NOTE Surgery

Primary Hemangiosarcoma of the Humerus in a Maltese

Yuichi HIDAKA1), Mitsuyoshi HAGIO1)*, Kazuyuki UCHIDA2) and Yae HARA2)

Departments of 1)Veterinary Surgery and 2)Veterinary Pathology, Faculty of Agriculture, University of Miyazaki, 1–1 Gakuen Kibanadai Nishi, Miyazaki City, Miyazaki 889–2192, Japan

(Received 15 February 2006/Accepted 19 April 2006)

ABSTRACT. A 14-year-old intact male was presented with a history of pain and swelling of the left upper forelimb and lame- ness for 3 weeks. Hematological and radiographical examinations showed regenerative anemia and osteolysis of the humerus. Fine nee- dle aspiration biopsy detected epithelioid- and fibroblast-like anaplastic cells with blood components. A hemorrhagic and osteolytic malignant tumor was suspected, and the affected forelimb was amputated. Histopathologically, the dog was diagnosed with primary hemangiosarcoma of the humerus. Thereafter, metastatic lesions appeared in the skin, and the dog was euthanized 1 month after the operation. KEY WORDS: hemangiosarcoma, humerus, Maltese. J. Vet. Med. Sci. 68(8): 895–898, 2006

Hemangiosarcoma (HS) arises in any tissue with blood Lytic change was predominant in the proximal humerus, vessels, and the most common sites in are the spleen, especially in the region of the greater tubercle (Fig. 1). heart, skin, and liver [7, 15, 17]. Primary HS of bones is There were no abnormal findings found in other long and rare, and the incidence is less than 5% of all primary canine axial bones or in the thoracic and abdominal cavities by sur- bone tumors [1, 7, 10, 15, 17]. This tumor is predisposed to vey radiographs. Routine blood work revealed regenerative medium-sized and large breed dogs, including German anemia (erythrocytes, 2,790,000/µl; hemoglobin, 7.2 g/dl; Shepherds, Great Danes, and Boxers, with a median age of hematocrit, 24%), thrombocytopenia (42,000/µl), and leu- 6 years [1, 3, 7, 16]. The proximal humerus, rib, femur, and kocytosis (31,100/µl). Blood smear showed anisocytosis vertebra are the bones most commonly involved [1, 3, 10, with mild poikilocytosis and neutrophilia. Plasma alkaline 17]. Recently, we encountered primary HS of the humerus in a Maltese dog. There are eight clinical articles available on primary HS of canine bones in America and England [2–6, 9, 12, 13]. Although there is one report of a dog with HS attributed to an aneurysmal bone cyst [14], osseous HS seems to be extremely rare in Japan. Furthermore, occur- rence is uncommon in toy breed dogs, although a case has been reported of a West Highland White Terrier with pri- mary HS of the radius [13]. In this paper, we describe the clinical and pathological findings of this case and review the clinical literature con- cerning primary HS of canine bones. A 14-year-old intact male Maltese dog weighing 2.9 kg was presented with a history of lameness and pain in the left upper forelimb for 3 weeks. Rheumatoid disease was sus- pected by a private practitioner because of no significant radiographical changes in the bone. At presentation, physi- cal examination revealed marked swelling and hardening of the upper forelimb. Regional and other superficial lymph nodes were not enlarged. A cardiac systolic murmur (Levine IV/VI) was auscultated. Echocardiography demon- strated that the murmur was caused by mitral valve regurgi- tation, and there were no other changes in the heart. Radiographs showed a diffuse, mottled, “moth-eaten” appearance of the humerus without periosteal osteogenesis. Fig. 1. Radiophotograph of the humerus in the present case at first presentation. A “moth-eaten” appearance indicating *CORRESPONDENCE TO: HAGIO, M., Department of Veterinary Sur- osteolysis was observed in the whole humerus. Lysis was gery, University of Miyazaki, 1–1 Gakuen Kibanadai Nishi, more prominent in the region of the greater tubercle. Peri- Miyazaki City, Miyazaki 889–2192, Japan. osteal osteogenesis was not observed. 896 Y. HIDAKA, M. HAGIO, K. UCHIDA AND Y. HARA

Fig. 2. Photomicrograph of the smear obtained by fine needle aspiration biopsy in the fractured proximal humerus showing a clump of epithelioid-like cells with blood components. The cells had abundant cytoplasm with round to ovoid nuclei. Fig. 3. Histopathological findings of the amputated humerus. Some cells contained distinct vacuoles in their cytoplasm. Neoplastic tissue (N) originated in the subperiosteal region and protruded to the adjacent muscle through the periosteum (Po). B: Bone (Hematoxylin and eosin stain × 52). phosphatase (ALP) activity was 208 U/l. Since the clinical findings suggested a malignant tumor or infection of the forelimb, a biopsy was recommended; however, the owner did not give consent. An antibiotic (Viccillin, Meiji Seika Kaisha Ltd., Tokyo, Japan) was prescribed, but the dog’s condition did not improve. A week later, the affected forelimb became reddish in color and hotness and fluctuation were palpated. The dog’s anemia progressed (erythrocytes, 1,630,000/µl; hemoglo- bin, 4.6 g/dl; hematocrit, 17%), and plasma ALP activity increased slightly (304 U/l). Radiographs suggested a pathologic fracture at the proximal region of the humerus. Fine needle aspiration (FNA) biopsy was performed at the site, and its smear was chiefly composed of blood compo- nents with a small aggregation of epithelioid- and solitary fibroblast-like anaplastic cells (Fig. 2). These were large cells that had ovoid to round nuclei and abundant cytoplasm that frequently had vacuoles. Since an osteolytic and hem- orrhagic malignant tumor, likely HS, was suspected on the Fig. 4. Gross appearance of the present case at 20 days post oper- basis of these findings, amputation was recommended. The ation. Dark red, rice-sized, hematoma-like nodules (arrows) owner agreed to the surgery, but the dog’s condition did not with purpura were scattered in the skin. improve in spite of treatment, including fluid therapy, blood transfusion, and tranexamic acid (Transamin, Daiichi Phar- with isoflurane in oxygen. Surgery and recovery were maceutical Co., Ltd., Tokyo, Japan). ALP activity was uneventful. Histopathological examination revealed HS of strikingly elevated (1342 U/l), and the left axillary lymph the humerus. The sarcoma tissue was derived from the sub- node was mildly swelled during hospitalization. On the periosteal region and protruded to the adjacent muscle 14th day in hospital, forequater amputation was performed through the periosteum (Fig. 3). with elimination of the left axillary lymph node. The dog The dog recovered day by day and was discharged 1 week was premedicated with atropine sulfate (Fuso Phamaceuti- post operation (PO). At 20 days PO, however, dark red, cal Industries, Ltd., Osaka, Japan) and flunitrazepam rice-sized, hematoma-like nodules with purpura appeared in (Silece, Eisai Co., Ltd., Tokyo, Japan). Anesthesia was the skin (Fig. 4). FNA biopsy was performed in the nodules, induced by intravenous injection of ketamine hydrochloride and anaplastic cells were detected as previously seen in the (Ketalar, Sankyo Co., Ltd., Tokyo, Japan) and maintained humerus. Although metastatic lesions were not detectable PRIMARY HEMANGIOSARCOMA OF CANINE BONE 897 in thoracic radiographs, the dog deteriorated again. The surmise that regional ischemia as a result of severe hemor- owner did not wish any further laboratory tests or treatment rhage from the sarcoma may prevent the reaction leading to including chemotherapy. Upon request from the owner, the osteogenesis. Differentiation of the osseous HS from com- dog received euthanasia at 1 month PO. monly occurring osteosarcoma seems to be difficult in Necropsy demonstrated hematomatous lesions in the radiographs. However, Ling et al. [11] pointed out that the heart, lung, greater omentum, small intestine, kidney, and pattern of spread of HS and the osteoblastic pattern aid in adrenal gland. Histopathologically, they were regarded to differentiation because the clinical signs appear later and be metastasis from the primary affected humerus. early radiographic changes are rarely observed. In the present case, the disease originated in the left upper Definitive diagnosis of HS is subject to histopathological forelimb, and radiography indicated severe osteolysis only examination. Cytology by FNA biopsy has not been avail- in the humerus. Physical examination, radiography, and able for HS because samples mostly consist of blood with echocardiography showed no findings associated with only a few to moderate numbers of spindle shaped cells with splenic, hepatic, and cardiac HSs. We also speculated that the features of malignant mesenchymal cells [16]. In our subcutaneous HS secondarily infiltrated the humerus. How- case, fortunately, clumps of epithelioid- and solitary fibro- ever, histopathological observation of the amputated fore- blast-like cells were found in the smear. Erdem and Pead [6] limb suggested that the sarcoma tissue was derived from the also observed epithelial cells in smears obtained from pri- subperiosteal region of the humerus. These findings indi- mary HS of the scapula in a dog by FNA biopsy. FNA cated that the humerus was the primary site, and not second- biopsy may allow diagnostic of HS in bones by detecting ary metastasis from other organs or tissues with HS. these cells and large amounts of blood, simultaneously. Furthermore, it is necessary to distinguish osseous HS from To date, treatment of osseous HS in dogs has been unre- telangiectatic osteosarcoma, which is characterized by warding (Table 1) [2–6, 9, 12, 13]. Amputation is a pallia- osteolysis, many blood filled spaces, and osteoid formation tive measure, and the median survival time after surgery is [8, 16]. These findings are very similar to those of HS in less than 5 months [7, 17]. Amputation was also conducted bones, but without osteoid formation [8, 16]. In our case, for our dog, and the dog was euthanized at 1 month PO. osteoid formation was not found in the sarcoma tissue, and Chemotherapy was not performed in this case. Although therefore telangiectatic osteosarcoma was also excluded. Crow [4] described that a mixed breed dog treated with dox- In primary HS of canine bones, radiographs reveal mas- orubicin and cyclophosphamide survived for 13 months PO, sive destruction, with often a pathologic fracture [10, 16, the effect of chemotherapy in prolonging survival time is 17]. The tumor expands proximally and distally along the also uncertain in primary HS of bones [7]. medullar cavity and is expressed as a soap-bubble-like We conclude that primary HS of bones should be sus- expansile growth in radiographs [10]. It is believed that the pected in dogs with hemorrhagic and osteolytic disease. manner of expansion is less painful and that symptoms may However, even if HS could be diagnosed, clinicians and not develop until a pathologic fracture occurs [11, 16]. owners would be troubled by the therapy and prognosis. However, our dog suffered from pain and swelling of the forelimb before pathologic fracture. 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Table 1. Review of clinical reports concerning primary hemangiosarcoma of canine bones Dogs Authors Sites Treatments Prognosis (survival time) Agea) Sex Breed Barber et al. [2] 3 F Basset Femur Antibiotics, prednisone Euthanasia (53 days*) Bingel et al. [3] 2.5 SF Irish Setter Humerus Exploratory surgery Euthanasia (11 days PO) Crow [4] 3 F Mixed Femur Amputation, chemotherapy Euthanasia (13 months PO) Dueland et al. [5] 8 M Boxer Tibia Nothing Euthanasia (—) Erdem and Pead [6] 13 F Collie cross Scapula Nothing Euthanasia (—) 1.5 NM Lurcher Scapula Blood transfusion Euthanasia (—) 3 SF Doberman-Boxer cross Scapula Partial scapulectomy Euthanasia (6 months PO) Jennings et al. [9] 2•2/3 — Belgian Malinois Rib Drainage, antibiotics, Euthanasia (18 days*) Exploratory surgery Parchman et al. [12] 11•1/3 SF Cocker Spaniel Vertebra Cage rest, glucocorticoid, Euthanasia (3 months*) Methylprednisolone Quigley et al. [13] 6 F Terrier cross Radius, ulna Amputation Euthanasia (3 months PO) 8 F WHWTb) Radius Amputation Euthanasia (10 months PO) a) Years. b) West Highland White Terrier. F: Female. SF: Spayed female. M: Male. NM: Neutered male. — : Unknown. PO: Post operation. *After development of clinical symptoms associated with hemangiosarcoma of the bone. 898 Y. HIDAKA, M. HAGIO, K. UCHIDA AND Y. HARA

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