JPC SYSTEMIC PATHOLOGY
MUSCULOSKELETAL SYSTEM
MARCH 2022
M-N04

Signalment (JPC #4116933): 14 year old female spayed German Shepherd dog

 

HISTORY: Presented anorexic for 5 days with polydipsia and intermittent vomiting over the previous week. The animal had lost 3.5 kg in the past 3 months. The dog had previously been diagnosed with degenerative joint disease that was being treated with robenacoxib, amantadine, gabapentin, pentosan, and fish oil supplementation. On clinical examination, the dog was tachycardiac and tachypneic with harsh lungs sounds. A marked azotemia was noted on a biochemistry profile with moderate elevation in ALT/ALKP. The dog was euthanized at the owner’s request and submitted for post-mortem examination.

 

HISTOPATHOLOGIC DESCRIPTION: Flat bone (parietal bone per contributor): Infiltrating and extending peripherally from the cortex and elevating the periosteum is an exophytic, poorly demarcated, multilobulated, moderately cellular neoplasm composed of numerous, variably sized, circular to ovoid neoplastic islands composed of a variable amount of central cartilage containing chondrocytes within irregularly spaced lacunae surrounded by a pale basophilic cartilaginous matrix.  This central cartilage blends into surrounding irregular woven bone with scalloped margins, a wide osteoid seam, resting and reversal lines, and haphazardly arranged osteocytes within lacunae in both the mineralized and non-mineralized osteoid.  The woven bone is further surrounded by a layer of plump spindle to stellate cells with a moderate amount of pale eosinophilic cytoplasm and an oval nucleus embedded in dense eosinophilic matrix, and these islands are separated by thin, dense, fibrous septa. In all neoplastic cell populations there is mild anisocytosis and anisokaryosis and the mitotic count averages 1 per 2.37 mm². The adjacent flat bone cortex is focally infiltrated predominantly by neoplastic spindle cells without cartilage or bone components; this infiltration results in scalloped bone margins with small numbers of osteoclasts within Howship’s lacunae.

 

MORPHOLOGIC DIAGNOSIS: Flat bone: Multilobular tumor of bone, German Shepherd dog, 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
• 3-tier grading system exists based on indicators of malignancy including
• Borders of the tumor (pushing, pushing and invasive, invasive)
• Size of lobules (small and medium, large)
• Architectural organization (well organized, moderately well organized, poorly organized)
• Mitotic count per 2.37 mm² (0-5, 6-10, >10)
• Cellular pleomorphism (monomorphic, mild, moderate, marked)
• Necrosis (none, present)

 

ADDITIONAL DIAGNOSTIC TESTS:

• Radiography: Ranges 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 complement 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; may have disorganized cartilage components; lacks an organized 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:

Multilobular tumor of bone in other species:

• Cats: Rare, reported in four cases from 9 months to 12 years of age
• Horse: Rare, single report arising from zygomatic process
• Nondomestic canids: Described in the calvarium of an African wild dog and a black-backed jackal
• Rodents: Single case reported on the head of a guinea pig

REFERENCES:

1. Avallone G, Rasotto R, Chambers JK, et al. Review of histological grading systems in veterinary medicine. Vet Pathol. 2021;58(5):809-828.
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. Hatai H, Kido N, Ochiai K. Multilobular tumor of bone on the forehead of a guinea pig. J Vet Diag Invest. 2020;32(5):747-749.
4. Keel MK, Terio KA, McAloose D. Canidae, Ursidae, and Ailuridae. In: Terio KA, McAloose D, St. Leger J, eds. Pathology of Wildlife and Zoo Animals. San Diego, CA:Elsevier. 2018:238.
5. 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.
6. Rissi DR. A retrospective study of skull base neoplasia in 42 dogs. J Vet Diagn Invest. 2015;27(6):743-748.
7. Thompson KG, Dittmer KE. Tumors of Bone. In: Meuten DJ, ed. Tumors in Domestic Animals, 5th Ed. Ames, IA:John Wiley & Sons, Inc. 2017:409.

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