Priscilla, an 11 year old female neutered Labrador Retriever.

Clinical history:

Priscilla presented with a two-month history of left thoracic limb lameness and a palpable mass over the left scapula. CT scan showed an osteodestructive lesion, which was suspected to be a primary bone tumour. No metastasis was detected on staging. The entire left thoracic limb was amputated and sent to VPG for histopathological examination.

Histology:

Decalcified histological sections taken through the mass and entire thickness of the scapula revealed a poorly-demarcated mass that was associated with resorption of the bone medulla and cortex, and surrounded by a rim of reactive periosteal bone. The mass itself was formed of numerous large cavernous blood-filled spaces that were separated by a network of internal stromal septa. These septa comprised low numbers of spindle cells within collagenous matrix, with haemosiderophages and small spicules of reactive woven bone surrounded by plump reactive osteoblasts and osteoclasts. The spindle cells did not show atypia or mitotic activity.

Figure 1. This low power image shows the large central cavernous blood-filled spaces surrounding by a rim of reactive bone (blue arrows).

Figure 2. The peripheral rim of reactive bone is highlighted by the blue arrow. The black arrows indicate islands of reactive bone within the mass.

Figure 3. This high power image shows the spindle cells (red arrows) within collagenous stroma that form the internal septa of the aneurysmal bone cyst. These spindle cells do not show any evidence of atypia. The yellow arrows indicate osteoclasts that are lining and resorbing a spicule of reactive bone.

Histological diagnosis:

Aneurysmal bone cyst

More information on aneurysmal bone cysts:

Although rare, aneurysmal bone cysts (ABCs) are an important entity to be aware of, since they may have a clinical presentation and imaging findings that are similar to a malignant primary bone neoplasm, including osteosarcoma.

The exact pathogenesis of ABCs is uncertain. An aberration of local blood flow is suspected with arteriovenous shunting. An increase in venous pressure may drive the formation and subsequent dilation of the vascular cavities within the bone, resulting in bone lysis and driving proliferation of reactive bone surrounding the lesion. In humans, ABCs are designated as either primary or secondary. Secondary cases are associated with previous trauma or underlying bone tumours. Approximately 70% of human ABCs are associated with a chromosomal abnormality, and these are considered to be primary (1). In dogs, there are rare reported cases of ABCs arising following a history of trauma (2)

ABCs may arise in both the appendicular and axial skeleton of animals, but too few cases have been reported to determine predilection sites. With radiography, ABCs are described as expansile, osteolytic, and are surrounded by a thin layer of reactive bone. The lesion is often arranged eccentrically in the bone. There may be pathological fracture. In contrast to benign unicameral bone cysts, ABCs have multiple cavities separated by internal septa, which leads to a “soap-bubble” type appearance on X-ray. Clinical differentials include osteosarcoma (particularly telangiectatic subtype) and haemangiosarcoma. Fine needle aspirates will likely yield only blood. Histopathology is required to rule out malignancy.

Histologically, ABCs are characterised by multiple, cavernous, blood-filled spaces separated by thin septa that are formed of collagenous stroma and spindle cells. There may be scattered haemosiderophages, osteoclast-like giant cells and islands of reactive woven bone or osteoid. Histologically ABCs need to be differentiated from telangiectatic osteosarcoma and haemangiosarcoma. Telangiectatic osteosarcomas typically have atypical neoplastic osteoblasts lining the cavities whilst in haemangiosarcoma, the cavities are lined by atypical neoplastic endothelial cells. In contrast, in ABCs the blood-filled cavities are lined by the stromal septa or occasionally by an attenuated endothelium that does not exhibit atypia. Importantly, this distinction can be difficult to make on small incisional biopsies. In Priscilla’s case, a confident diagnosis of ABC was made on an excisional specimen (amputation) and following examination of multiple additional histological sections to be confident that a neoplasm was not present.

Malignant transformation of ABCs has been documented several times in the human literature following curettage (3, 4), but there is only a single report in a dog. In that case report, a 5 year old Labrador with an ABC in the distal right ulna treated with surgical curettage developed a chondrosarcoma at the surgical site 33 months later (5). However, recurrence following complete surgical excision has not been reported in animals.

How we process limb amputation specimens at VPG:

As with all complex tissue specimens at VPG, amputated limbs are examined grossly by an onsite anatomic pathologist. All parts of the limb are palpated and examined visually. Submitting CT or X-ray images is encouraged since it helps us to focus the gross examination and identify subtle lesions. We will accept a whole limb, but just an area of interest can also be submitted. Any lymph nodes included with the limb (e.g. popliteal, axillary) are sampled. In the case of a bone mass, the adjacent soft tissues and shaved muscle and skin margins are sampled if appropriate. Remaining soft tissues are stripped from the bone. If the bone margin is <1 joint or <5cm from the mass (for example, distal femoral mass amputated mid-shaft), a shaved bone margin is taken. Representative sections, including a full transverse section through the entirety of the bone in the region of the lesion, are taken. Bone sections usually require additional fixation in formalin followed by decalcification in the laboratory, before they can be processed. This adds approximately 7 days onto the standard turnaround time.

References:

1. Ye Y, Pringle LM, Lau AW, Riquelme DN, Wang H, Jiang T, Lev D, Welman A, Blobel GA, Oliveira AM, Chou MM. TRE17/USP6 oncogene translocated in aneurysmal bone cyst induces matrix metalloproteinase production via activation of NF-kappaB. Oncogene. 2010 Jun 24;29(25):3619-29.
2. Craig LE, Dittmer KE, Thompson KG. “Bones and Joints”, in Maxie, MG (ed.) Jubb, Kennedy, and Palmer’s Pathology of Domestic Animals. Vol 1, 6^th edn. Elsevier, 2016, 17-163.
3. Kyriakos M, Hardy D. Malignant transformation of aneurysmal bone cyst, with an analysis of the literature. Cancer. 1991 Oct 15;68(8):1770-80.
4. Brindley GW, Greene JF Jr, Frankel LS. Case reports: malignant transformation of aneurysmal bone cysts. Clin Orthop Relat Res. 2005 Sep;438:282-7.
5. Barnhart MD. Malignant transformation of an aneurysmal bone cyst in a dog. Vet Surg. 2002 Nov-Dec;31(6):519-24.