JPC SYSTEMIC PATHOLOGY
Signalment (JPC #3026261): 11-month-old male Rocky Mountain elk (Cervus elaphus nelsoni)
HISTORY: This elk presented for anorexia, lameness and thickening of all four distal limbs. Pulmonary nodules were diagnosed radiographically. Tuberculosis was suspected and the animal was euthanized.
HIST0PATHOLOGIC DESCRIPTION: Bone, metatarsus (per contributor): Diffusely extending from the cortical surface and markedly elevating the periosteum are numerous perpendicular trabeculae of bone up to 12mm in length, delineated from the peripheral edge of the normal cortex by a basophilic line (resting cement line). The deep third of new bone extending from the pre-existing cortex is dense and composed of mature lamellar bone, forming well-organized osteons with lower numbers of osteocytes and minimal intertrabecular fibrovascular tissue. Peripheral trabeculae are composed of irregular woven bone with scalloped margins and numerous haphazardly arranged osteocytes within lacunae. Between trabeculae of woven bone there is absence of normal marrow elements and trabeculae are separated by a moderate amount of loose intertrabecular fibrovascular tissue. Woven trabecular bone immediately beneath the periosteum is lined by osteoid seams with 1-2 cells layers of plump reactive osteoblasts. The periosteum is expanded up to 1.5mm by abundant fibrous connective tissue.
Lung: Multifocally disrupting and replacing over 70% of the normal lung are multiple coalescing pyogranulomas up to 8 mm in diameter that compress surrounding tissue. Pyogranulomas are characterized by a large central region of abundant eosinophilic cellular and karyorrhectic debris (lytic necrosis) and numerous variably discernible fungal hyphae. Necrotic centers are surrounded by a basophilic rim of degenerate neutrophils and necrotic debris, and further surrounded by epithelioid macrophages, reactive fibroblasts and mature collagen (fibrosis) and few multinucleated giant cells. Multifocally surrounding pyogranulomas are few lymphocytes, plasma cells, eosinophils and small caliber blood vessels often regularly spaced and interspersed with active fibroblasts (granulation tissue), and lined by plump endothelium (reactive). Fungal hyphae are 3-6um wide and regularly septate with dichotomous acute angle branching and parallel walls. Multifocally, remaining alveoli contain an eosinophilic fibrillar material (fibrin and edema) admixed with occasional neutrophils, macrophages and rare multinucleated giant cells. Focally few bronchioles contain abundant fibrin, neutrophils, macrophages and necrotic debris which replace bronchiolar epithelium. Diffusely, interlobular septa are expanded up to 3mm by fibrous connective tissue.
- Bone, metatarsus: Periosteal new bone formation (hyperostosis), diffuse, severe, Rocky Mountain elk (Cervus elaphus nelsoni), cervid.
- Lung: Pyogranulomas, multiple, marked, with numerous fungal hyphae.
CONDITION: Hypertrophic osteopathy
SYNONYMS: Hypertrophic pulmonary osteoarthropathy; “Marie’s disease” or Marie-Bamberger’s disease
- Characterized by diffuse, periosteal new bone formation along the diaphysis and metaphysis of certain limb bones, without involving the joint (arthritis is not a component), frequently associated with neoplastic or chronic inflammatory lesions
- Occurs secondary to space occupying masses (i.e. neoplasms) or granulomatous lesions, most often in the thorax or, less commonly, the abdomen; often referred to as pulmonary hypertrophic osteopathy even though not always related to the pulmonary or thoracic area
- Reported in humans and domestic and wild animals, with the dog being the most commonly affected
Can occur with:
- Primary or secondary pulmonary neoplasms (most frequent in the dog); neoplasms of the thoracic wall
- Granulomatous pleuritis (most often granulomatous thoracic lesions in horse)
- Mycotic pneumonia
- Granulomatous lymphadenitis of bronchial and mediastinal lymph nodes
- Patent ductus arteriosus (dogs)
- Chronic bronchitis
- Dirofilaria immitis
- Esophageal granulomas and neoplasia induced by Spirocerca lupi
- Botryoid rhabdomyosarcoma of the urinary bladder (young dogs)
- Ovarian tumors (mares)
- Renal adenoma (cats)
- Pulmonary tuberculosis
- Pulmonary Eikenella corrodens infection
- Lesions likely reflect the limited range of periosteal reaction to diverse stimuli
- Increased blood flow to the distal limbs is a consistent early change
- Theories (none consistently fits clinical and experimental observations):
- Neurogenic theory: Impulses originating in the thoracic lesion travel via the vagus nerve (simulation of afferent visceral nerves) to the brainstem and initiate reflex vasodilation in the limbs, either by humoral or neural means
- Humoral theory: Either the primary lesion produces a hormone or hormone-like substance or arteriovenous anastomoses in the primary lesion prevent catabolism of such a substance in the lung à the hormone then produces the secondary skeletal lesions
- Vascular endothelial growth factor and platelet derived growth factor are released secondary to platelets within abnormal limb circulation and may contribute to bone lesions
- Hypoxic theory: Reduced oxygenation of peripheral blood resulting from congenital or acquired arteriovenous shunts stimulates periosteal osteophyte production
- Extra-renal volume receptor system: In primary thoracic lesion, blood flow in anomalous blood vessels activate the cerebral salt center through the vagus and glossopharyngeal nerves – leading to retention of extracellular sodium, fluid retention and increased blood supply to limbs
- Bone lesions can regress if the primary lesion is resolved
TYPICAL CLINICAL FINDINGS:
- Pain on movement and palpation
- Bony proliferations of the distal limb bones, which then extend proximally
- Earliest radiographic lesions tend to affect the second and fifth metacarpal/tarsal bones
- Progressive, but may regress if the primary lesion is removed
TYPICAL GROSS FINDINGS:
- Marked thickening and deformity of the long bones, with a rough surface
- In the dog, the radius, ulna, tibia, metacarpals, and metatarsals are most frequently involved
TYPICAL LIGHT MICROSCOPIC FINDINGS:
- Earliest changes are hyperemia and edema, with proliferation of highly vascular connective tissue in the periosteum; severe hemorrhage possible
- Osteoid is deposited on the existing cortical bone
- New trabecular bone forms perpendicular to the original cortex; with chronicity, original cortex is converted to trabecular bone by endosteal surface resorption
- Remodeling and formation of pseudocortices
ADDITIONAL DIAGNOSTIC TESTS:
- Thoracic radiographs may be useful in identifying an inciting lesion
Gross (periosteal proliferative lesion)
- Hepatozoon americanum (M-P01): Very similar to hypertrophic pulmonary osteopathy histologically and grossly; generally affects the proximal long bones before affecting the distal long bones and rarely affects the metacarpals; pulmonary osteopathy generally affects the metacarpals and distal long bones before the more proximal bones and has a slower onset
- Craniomandibular osteopathy (M-M18): Skull/mandibular lesions, rarely long bones; bilateral, generally symmetrical proliferation of non-neoplastic periosteal new bone; typically young animals with open growth plates; West Highland white, Scottish and Cairn terriers most commonly affected
- Neoplasia: Generally unilateral; may occur with renal carcinoma with pulmonary metastasis
- Periosteal osteosarcoma (M-N02): Generally unilateral
- Callus: Generally unilateral
- Reported in a variety of animals; dog most commonly affected
- Hypertrophic osteopathy reported in a roe deer associated with mycotic pneumonia caused by Aspergillus fumigatus
- In humans, this disease is referred to as hypertrophic osteoarthropathy and associated in 1-10% of patients with bronchogenic carcinoma; affects the same bones as in dogs, but causes arthritis in adjacent joints and clubbing of the digits
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