JPC SYSTEMIC PATHOLOGY
Musculoskeletal System
April 2019
M-N04

Signalment (JPC #1901223):  A male Doberman Pinscher

HISTORY:  This dog had a slowly developing swelling around the orbit and over the frontal bone. 

HISTOPATHOLOGIC DESCRIPTION:  Skull, orbit, and frontal bone (per contributor):  Extending to all borders is a multilobulated neoplasm composed of numerous variably sized, circular to oval to irregular islands of woven bone and well-differentiated cartilage, surrounded by spindle cells that form short irregular streams separated by narrow anastomosing and/or thick fibrovascular septa. Islands of cartilage contain chondrocytes within irregularly spaced lacunae surrounded by a basophilic cartilaginous matrix that occasionally mineralizes at the center. Trabeculae of immature woven bone have scalloped margins and are lined by osteoblasts and fewer osteoclasts within Howship’s lacunae, with numerous resting and reversal lines (remodeling) and haphazardly arranged osteocytes within lacunae. Immediately surrounding these islands of cartilage and bone are plump spindle cells (fibroblasts), with moderate amounts of pale eosinophilic cytoplasm and an oval nucleus, admixed with moderately dense fibrous connective tissue. In all cell populations there is mild anisocytosis and anisokaryosis and the mitotic count averages 0-1 per ten 400x HPF. There is scattered hemorrhage and mild edema.

MORPHOLOGIC DIAGNOSIS:  Skull, orbit, and frontal bone (per contributor):  Multilobular tumor of bone, Doberman Pinscher, canine.

CONDITION:  Multilobular tumor of bone (MTB)

SYNONYMS:  Chondroma rodens, multilobular osteosarcoma (MLO), multilobular osteochondrosarcoma, cartilage analogue of fibromatosis, calcifying aponeurotic fibroma, juvenile aponeurotic fibroma, multilobular osteoma, multilobular chondroma

GENERAL DISCUSSION:

• Locally aggressive, slow-growing nodular tumor of the membranous flat bones of the canine skull and the hard palate; potentially malignant
• Affects primarily middle-aged, medium and large breed dogs> young and small dogs
• Rarely seen in cats and horses
• Malignant transformation with metastasis (primarily to lungs) is most common in long-standing tumors or those that recur

PATHOGENESIS:

• Unknown

TYPICAL CLINICAL FINDINGS:

• Firm, immovable mass involving skull bones
  • Common: Zygomatic arch, occipital and parietal bones, maxilla, mandible, and tympanic bulla
  • Rare: Extracranial sites
• Clinical signs are related to compression and disturbance of function in adjacent structures: Neurologic signs, exophthalmia, sinus obstruction, jaw pain, or interference with mastication

TYPICAL GROSS FINDINGS:

• Very hard, smoothly contoured, nodular mass with a discrete border
• On cut surface: multiple, gritty foci on a background of fibrous tissue

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Multiple nodules of cartilaginous, osseous, or osteocartilaginous tissue separated by narrow fibrous septa
• Ill-defined areas of mesenchymal tissue may merge with nodules
• Cartilaginous nodules – usually surrounded by spindle-shaped cells w/ neoplastic chondrocytes in the center
• Resorption of mineralized cartilage and endochondral bone formation can occur
• Osseous and cartilaginous tissue may be present in the same nodule
• Mineralization progresses from the center outwards (centrifugally)
• Bone produced by osteoblasts or oval cells of indeterminate origin
• Grading system exists based on indicators of malignancy listed below
• Overgrowth of one mesenchymal element
• Loss of lobular architecture
• Necrosis and hemorrhage
• Increased mitotic activity

ADDITIONAL DIAGNOSTIC TESTS:

• Radiography: Ranged from: well-demarcated, multinodular or granular lesions with a “popcorn ball” appearance to poorly demarcated, largely radiolucent lesions with variably mineralized foci, cortical disruption, and radiating spicules
• Immunohistochemistry:
  • Mesenchymal origin
    • Cytokeratin: Negative
    • Vimentin: Positive
  • Osteoblastic origin:
    • Osteocalcin and osteonectin: Positive

DIFFERENTIAL DIAGNOSIS:

• Benign bone forming tumors:
  • Osteoma: Usually found on the head; dense coalescing spicules and trabeculae of bone lined by the usual compliment of osteoblasts and osteoclasts; intertrabecular connective tissue is composed of decreasing amounts of normal spindle cells and collagen, as the tumor becomes more compact and sclerotic
  • Fibrous dysplasia: Non-neoplastic condition with whirling loose fibrous connective tissue and thin, curved trabeculae of woven bone that lack osteoblasts; expands and replaces normal bone structure, thin outer shell of bone formed by the periosteum
  • Ossifying fibroma: Mandible, composed of spindle cells that transform to osteoblasts as they line spicules of bone; central-woven bone, peripheral- lamellar bone; replaces underlying tissue
  • Osteochondromatosis: Feline- involves flat bones, and produce bony masses that arise as multifocal areas of osteocartilaginous hyperplasia in the periosteum that undergo progressive enlargement with unknown pathogenesis but virus particles that resemble feline leukemia virus and transmissible feline sarcoma have been found in the cartilage of lesions

• Malignant bone forming tumors:
  • Osteosarcoma: Often pleomorphic cells, varying patterns, producing varying amounts of osteoid; lacks cartilage and multilobular appearance
  • Maxillary fibrosarcoma: Less cellular, lacks interweaving pattern
• Cartilage forming tumors:
  • Chondrosarcoma: Irregular, disorderly masses of immature cartilage that invade tissue and metastasize via lymphatics and blood
  • Chondroma: Lacks local invasiveness, cartilage cells orderly arranged, resemblance normal-mature cartilage
  • Osteochondroma: Cartilage-capped, exophytic lesions usually in metaphysis of young animals, thought to arise from ectopic growth-plate cartilage

COMPARATIVE PATHOLOGY:

• Cats: Rare, reported in four cases from 9 months to 12 years of age
• Horse: Rare, single report arising from zygomatic process

REFERENCES:

1. Olson EJ, Carlson CS. Bones, joints, tendons, and ligaments. In: Zachary JF, ed. Pathologic Basis of Veterinary Disease. 6th ed. St. Louis, MO: Elsevier; 2017:995.
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. 6th ed., St. Louis, MO: Elsevier; 2016:117-118.
3. Rissi DR. A retrospective study of skull base neoplasia in 42 dogs. J Vet Diagn Invest. 2015;27(6):743-748.

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