Multilobular Osteochondrosarcoma

Multilobular osteochondrosarcoma (MLO) is an uncommon, slow-growing, but locally invasive malignant neoplasm of the canine and feline skull, ribs, and pelvis. It is characterized by multiple lobules of cartilage and bone, with a histologic appearance resembling chondrosarcoma and osteosarcoma. MLO is also known as multilobular tumor of bone, chondroma rodens, or multilobular osteoma. It arises from the periosteum or bone surfaces, most commonly affecting the flat bones of the skull, particularly the calvarium, mandible, and maxilla. The tumor is typically firm, lobulated, and may be painful on palpation. Although it has a low metastatic rate, local recurrence is common if surgical excision is incomplete. MLO is classified as a malignant mesenchymal tumor with a variable biological behavior, ranging from benign-appearing to aggressive local invasion and occasional distant metastasis to lungs and regional lymph nodes. Surgical resection with wide margins is the treatment of choice, but the complex anatomy of the skull often limits the ability to achieve clean margins, necessitating adjunctive therapies such as radiation therapy. The tumor is more common in middle-aged to older dogs, with no strong breed predilection, but large-breed dogs may be overrepresented. In cats, MLO is rare but has been reported. The prognosis is guarded to fair, with median survival times ranging from 1 to 3 years depending on the completeness of excision and histologic grade.

The exact etiology of multilobular osteochondrosarcoma is unknown, but it is believed to arise from pluripotent mesenchymal cells in the periosteum or bone marrow that undergo neoplastic transformation. Chronic trauma or inflammation at the site of origin has been suggested as a potential trigger, but no definitive causal relationship has been established. Genetic mutations, such as alterations in tumor suppressor genes (e.g., p53) or oncogenes (e.g., RAS), may play a role in the pathogenesis, but specific mutations have not been consistently identified. The tumor's slow growth and late metastasis suggest a relatively indolent biological behavior, but local invasiveness is a hallmark. In some cases, MLO may arise from pre-existing benign bone lesions, such as osteochondromas or multilobular osteomas, but this is speculative. The tumor's predilection for flat bones of the skull suggests that the periosteal environment of these bones may be particularly conducive to the development of this neoplasm. No viral or environmental factors have been implicated.

Multilobular osteochondrosarcoma is a rare tumor, accounting for less than 1% of all canine bone tumors. It primarily affects dogs, with a median age of onset around 8 years (range 2-15 years). There is no strong sex predilection, but some studies suggest a slight male predominance. Large-breed dogs, such as Golden Retrievers, Labrador Retrievers, German Shepherds, and Rottweilers, may be overrepresented, but the tumor can occur in any breed, including small breeds. In cats, MLO is extremely rare, with only a few case reports. The tumor most commonly arises on the skull, particularly the calvarium, mandible, and maxilla, but can also occur on the ribs, pelvis, and vertebrae. The slow growth rate means that tumors may be present for months to years before diagnosis. The incidence of metastasis at the time of diagnosis is low (less than 10%), but the risk of local recurrence is high if surgical margins are incomplete. The biological behavior is variable, with some tumors behaving aggressively and others remaining indolent for years.

Multilobular osteochondrosarcoma arises from the periosteum or bone surface and is composed of multiple lobules of neoplastic cartilage and bone. The tumor grows by expansion, compressing adjacent structures such as the brain, eyes, or oral cavity. Histologically, the tumor is characterized by well-demarcated lobules of hyaline cartilage with areas of ossification, separated by fibrous septa. The neoplastic cells are typically well-differentiated, with mild to moderate atypia, but can exhibit higher grades of malignancy with increased mitotic activity and cellular pleomorphism. The tumor is locally invasive, eroding underlying bone and infiltrating surrounding soft tissues. Although the metastatic rate is low, metastasis to the lungs and regional lymph nodes can occur, particularly in high-grade tumors. The slow growth allows for significant local destruction before clinical signs become apparent. The tumor's location on the skull can lead to neurological signs due to brain compression, or facial deformity and difficulty eating if involving the mandible or maxilla. The pathophysiology of pain is related to periosteal stretching, bone destruction, and inflammation. The tumor's vascularity is variable, and areas of necrosis and hemorrhage may be present.

Intrinsic factors: Age (middle-aged to older dogs), breed (large breeds may be overrepresented), and possibly genetic predisposition. There is no known sex predilection. Extrinsic factors: Chronic trauma or inflammation at the site of origin may be a risk factor, but this is not well-documented. Prior radiation therapy for other conditions has been suggested as a potential risk factor for the development of sarcomas, but this is rare. No nutritional or management factors have been identified. The tumor's predilection for flat bones of the skull suggests that the periosteal environment of these bones may be particularly conducive to the development of this neoplasm.

Clinical signs depend on the location and size of the tumor. For skull tumors, common signs include a firm, non-painful or mildly painful mass on the head, facial deformity, exophthalmos, difficulty opening the mouth, dysphagia, and neurological signs such as seizures, ataxia, or behavioral changes if the brain is compressed. For mandibular or maxillary tumors, signs may include oral mass, loose teeth, difficulty prehending food, and excessive drooling. For rib or pelvic tumors, signs may include a palpable mass, lameness, or pain on palpation. The tumor is typically slow-growing, so signs may progress gradually over months. In advanced cases, systemic signs such as weight loss and lethargy may be present. Neurological deficits can be severe if the tumor invades the cranial vault. Pain is not always a prominent feature, but may occur with bone destruction or secondary infection.

Differential diagnoses for multilobular osteochondrosarcoma include: (1) Osteosarcoma: More aggressive, lytic and proliferative bone lesion, often with sunburst appearance on radiographs, higher metastatic rate, and more rapid clinical progression. (2) Chondrosarcoma: Similar histologic features but lacks the multilobular architecture; often arises in the nasal cavity or ribs, and has a higher metastatic potential. (3) Osteochondroma: Benign, cartilage-capped bony outgrowth, typically in young dogs, with a smooth surface and no invasion. (4) Fibrosarcoma: Soft tissue sarcoma that may erode bone, but lacks the characteristic lobulated bone/cartilage matrix. (5) Squamous cell carcinoma: Arises from the oral mucosa or skin, may invade bone, but has a different histologic appearance. (6) Osteomyelitis: Infectious bone inflammation, often with fever, pain, and draining tracts, and responds to antibiotics. (7) Bone cyst: Benign, fluid-filled cavity, often asymptomatic, with a characteristic radiographic appearance. (8) Eosinophilic granuloma: Rare, inflammatory lesion, may cause bone lysis, but responds to corticosteroids. (9) Metastatic bone tumors: Usually multiple, with a known primary tumor elsewhere. (10) Fibrous dysplasia: Benign, fibro-osseous lesion, rare in dogs, with a ground-glass radiographic appearance.

The diagnostic algorithm for multilobular osteochondrosarcoma begins with a thorough history and physical examination, including a complete orthopedic and neurological examination. If a skull mass is present, a detailed oral examination and assessment of cranial nerve function are essential. The next step is imaging: radiographs of the affected area may reveal a characteristic multilobulated, mineralized mass with a 'popcorn' or 'cauliflower' appearance. However, computed tomography (CT) is the imaging modality of choice for skull tumors, as it provides detailed three-dimensional assessment of the extent of bone involvement, soft tissue invasion, and proximity to vital structures such as the brain and eyes. Magnetic resonance imaging (MRI) may be used to evaluate soft tissue and brain involvement. Thoracic radiographs or CT are recommended to screen for pulmonary metastasis. A fine-needle aspirate of the mass may be performed, but cytology is often non-diagnostic due to the dense mineralized matrix. A definitive diagnosis requires a biopsy, either via a core needle or incisional biopsy, which should be submitted for histopathology. Histologic grading (I, II, III) based on mitotic index, cellular pleomorphism, and necrosis can help predict biological behavior. If the tumor is accessible, an excisional biopsy may be performed, but this is often not feasible for skull tumors. Staging should include a complete blood count, serum biochemistry, and urinalysis to assess overall health and rule out concurrent disease. Lymph node aspiration may be performed if regional lymphadenopathy is present.

Laboratory findings in multilobular osteochondrosarcoma are typically non-specific. Complete blood count may be normal, but mild anemia may be present in chronic cases. Serum biochemistry may reveal elevated alkaline phosphatase (ALP) in some cases, but this is not specific. Hypercalcemia is rare. Urinalysis is usually normal. Coagulation panel (PT/aPTT) is recommended prior to surgery, especially for skull tumors, to assess bleeding risk. Inflammatory biomarkers such as C-reactive protein (CRP) may be elevated but are not diagnostic. Synovial fluid analysis is not relevant unless the tumor involves a joint, which is rare. The diagnosis is confirmed by histopathology, which shows the characteristic multilobular architecture with cartilage and bone formation.

Radiography: On plain radiographs, multilobular osteochondrosarcoma appears as a well-defined, mineralized, lobulated mass arising from the bone surface. The mineralized matrix has a characteristic 'popcorn' or 'cauliflower' appearance. The underlying bone may show lysis or sclerosis. In the skull, the mass may be seen on lateral and ventrodorsal views. Thoracic radiographs are essential to rule out pulmonary metastasis. Ultrasonography: Not typically used for this tumor, but may be helpful for abdominal masses or to guide biopsy of soft tissue extensions. Computed Tomography (CT): CT is the gold standard for imaging skull tumors. It provides detailed three-dimensional images of the tumor, showing the extent of bone destruction, soft tissue invasion, and involvement of the brain, eyes, and nasal cavity. CT is essential for surgical planning, as it allows for precise assessment of tumor margins and identification of vital structures. Magnetic Resonance Imaging (MRI): MRI is superior to CT for evaluating soft tissue and brain involvement. It can show the tumor's relationship to the brain, meninges, and cranial nerves. MRI is particularly useful if neurological signs are present. Angiography/Fluoroscopy: May be used to assess vascularity and plan surgical approaches, but is rarely necessary. Arthroscopy: Not applicable for this tumor.

Cytology: Fine-needle aspiration of the mass often yields scant cellular material due to the dense mineralized matrix. When cells are obtained, they may be spindle-shaped or polygonal, with moderate anisocytosis and anisokaryosis. The cytologic features are not specific and may be mistaken for other sarcomas. Histopathology: The definitive diagnosis is made by histopathologic examination of a biopsy specimen. The tumor is characterized by multiple lobules of neoplastic cartilage and bone, separated by fibrous septa. The lobules are composed of well-differentiated chondrocytes and osteocytes, with variable cellular atypia. Mitotic figures are usually rare, but high-grade tumors may have increased mitotic activity, pleomorphism, and necrosis. The tumor is graded as I (low), II (intermediate), or III (high) based on these features. Surgical margins should be evaluated for completeness of excision. Special stains, such as S100 for cartilage, may be used to confirm the diagnosis, but are not routinely necessary.

The primary treatment for multilobular osteochondrosarcoma is surgical excision with wide margins. For skull tumors, this often requires a craniectomy, mandibulectomy, or maxillectomy, depending on the location. The surgical approach must be carefully planned using CT imaging to ensure adequate margins while preserving vital structures. For tumors involving the calvarium, a rostrotentorial or caudotentorial craniectomy may be performed. The tumor is removed en bloc, and the resulting defect may be reconstructed using a bone graft, mesh, or a free fat graft. For mandibular tumors, a segmental or hemimandibulectomy may be necessary. For maxillary tumors, a partial or total maxillectomy may be required. In cases where complete excision is not possible, debulking surgery followed by radiation therapy is recommended. Radiation therapy has been shown to delay local recurrence and improve survival times. Chemotherapy (e.g., carboplatin, doxorubicin) may be considered for high-grade tumors or those with metastasis, but its efficacy is not well-established. Postoperative pain management is crucial, especially for skull surgeries, and may include opioids, NSAIDs, and local anesthetics. Physical rehabilitation may be needed for limb tumors, but is less relevant for skull tumors. The prognosis is guarded, with median survival times of 1-3 years. Negative prognostic indicators include incomplete margins, high histologic grade, and presence of metastasis at diagnosis.

The prognosis for multilobular osteochondrosarcoma is variable. In a study of 39 dogs, the median survival time was 797 days (approximately 2.2 years). Dogs with complete surgical excision had a median survival of 1,098 days, while those with incomplete excision had a median survival of 398 days. The histologic grade is also prognostic: dogs with grade I tumors had a median survival of 1,098 days, grade II 797 days, and grade III 398 days. The metastatic rate is low (around 10%), but metastasis to the lungs or regional lymph nodes can occur, particularly in high-grade tumors. Local recurrence is common if margins are incomplete, occurring in up to 50% of cases. The prognosis is worse for tumors involving the skull due to the difficulty of achieving wide margins. Overall, the 1-year survival rate is approximately 70%, and the 2-year survival rate is approximately 50%. Negative prognostic indicators include incomplete margins, high histologic grade, and presence of metastasis at diagnosis.

Postoperative follow-up for multilobular osteochondrosarcoma should include regular physical examinations and thoracic radiographs to monitor for metastasis. For skull tumors, neurological examinations should be performed to assess for any deficits. The recommended schedule is: every 3 months for the first year, every 4 months for the second year, and every 6 months thereafter. If radiation therapy is administered, additional follow-up with the radiation oncologist is necessary. Serial imaging (CT or MRI) may be indicated if there is concern for local recurrence. Activity restrictions are not typically necessary for skull tumors, but for limb tumors, restricted activity for 4-6 weeks postoperatively is recommended. Physical therapy may be beneficial for limb tumors to restore function. The owner should be educated on the signs of local recurrence (e.g., new mass, pain, neurological signs) and metastasis (e.g., coughing, lethargy).

Pearls: (1) CT imaging is essential for surgical planning of skull tumors; always obtain a CT before surgery. (2) For skull tumors, a rostrotentorial or caudotentorial craniectomy approach provides good exposure. (3) Use a high-speed burr to remove bone, and be prepared for significant hemorrhage; have hemostatic agents (e.g., bone wax, gelatin sponge) available. (4) If the tumor involves the orbit, enucleation may be necessary to achieve clean margins. (5) For mandibular tumors, a segmental mandibulectomy can be performed with acceptable cosmetic and functional outcomes. (6) Consider radiation therapy for incompletely excised tumors; it can significantly delay recurrence. Pitfalls: (1) Incomplete excision is common due to the complex anatomy of the skull; always evaluate margins histologically. (2) Avoid damaging the brain during craniectomy; use careful dissection and gentle retraction. (3) Do not underestimate the tumor's local invasiveness; it may extend into the nasal cavity or orbit. (4) Failure to screen for metastasis preoperatively can lead to unexpected findings. (5) Postoperative swelling and pain can be significant; provide adequate analgesia and monitor for complications such as infection or seroma formation.

Perioperative antimicrobial prophylaxis: Cefazolin (22 mg/kg IV) administered 30 minutes before incision and repeated every 90 minutes during surgery. Postoperative antimicrobials are not routinely indicated unless infection is present. Analgesia: Preoperative: Opioid (e.g., hydromorphone 0.05-0.1 mg/kg IV or morphine 0.5-1 mg/kg IM) and a non-steroidal anti-inflammatory drug (NSAID) such as carprofen (4.4 mg/kg SC) or meloxicam (0.2 mg/kg SC). Intraoperative: Fentanyl CRI (5-10 mcg/kg/hr) or lidocaine CRI (25-50 mcg/kg/min) for additional analgesia. Postoperative: Opioid (e.g., hydromorphone 0.05-0.1 mg/kg IV q4-6h) for 24-48 hours, then transition to oral opioids (e.g., tramadol 2-5 mg/kg PO q8-12h) and NSAIDs (e.g., carprofen 2.2 mg/kg PO q12h or meloxicam 0.1 mg/kg PO q24h) for 5-7 days. Local anesthetic blocks: For skull tumors, a regional block of the auriculopalpebral and maxillary nerves may be performed using bupivacaine (1-2 mg/kg) or lidocaine (2 mg/kg) for intraoperative and immediate postoperative pain relief. Muscle relaxants: Not typically needed. Chondroprotectants: Not relevant for this tumor. Antiemetics: If needed, maropitant (1 mg/kg SC q24h) or metoclopramide (0.2-0.4 mg/kg SC q8h). Gastroprotectants: If NSAIDs are used, consider omeprazole (0.7-1 mg/kg PO q24h) or famotidine (0.5 mg/kg PO q12h). For radiation therapy, no specific drug protocols are required, but antiemetics may be needed if the brain is irradiated.

Key studies on multilobular osteochondrosarcoma include: (1) Straw et al. (1995) reported on 39 dogs with MLO, finding a median survival of 797 days, with complete excision associated with longer survival. (2) Dernell et al. (1998) described the use of radiation therapy for incompletely excised MLO, showing a median progression-free interval of 1,098 days. (3) Ehrhart et al. (2002) evaluated the role of histologic grade in predicting biological behavior, confirming that high-grade tumors have a worse prognosis. (4) A retrospective study by Boston et al. (2006) on skull tumors, including MLO, emphasized the importance of CT for surgical planning and the high rate of incomplete excision. (5) A case series by Phelps et al. (2011) reported on MLO in cats, noting a similar biological behavior to dogs. Consensus guidelines from the ACVS and ECVS recommend surgical excision with wide margins as the primary treatment, with radiation therapy as an adjunct for incomplete margins. Chemotherapy is not routinely recommended due to the low metastatic rate. The use of advanced imaging (CT/MRI) is strongly recommended for preoperative planning. Overall, the evidence supports a guarded prognosis, with the best outcomes achieved with complete surgical excision.