JPC SYSTEMIC PATHOLOGY

MUSCULOSKELETAL SYSTEM

April 2025

M-V03 (NP)

 

Signalment (JPC #1692713): Chicken  

HISTORY: This chicken had enlarged long bones of the wings and legs.

HISTOPATHOLOGIC DESCRIPTION: Long bone, diaphysis, cross section: Diffusely and circumferentially, the cortex is markedly thickened and the medullary cavity markedly reduced by an increase in both subperiosteal and endosteal woven bone (hyperostosis) that surrounds and separates a variably distinct layer of preexisting cortex composed of mature lamellar bone. Hyperostotic areas are composed of irregular, often basophilic, variably thick, irregularly interlacing trabeculae of immature woven bone containing numerous closely arranged, disorganized lacunae containing osteocytes. There are few osteoclasts within Howship’s lacunae. These trabeculae of new woven bone occasionally lack normal bone marrow elements and are separated by loose fibromyxomatous connective tissue; however, there are large, irregular spaces within the outer third of the hyperostotic bone that contain moderate amounts of hematopoietic marrow elements admixed with few loosely arranged spindle cells. Multifocally the periosteum is moderately thickened by disorganized spindle cells that extend into and occasional are surrounded by underlying bone (fibrosis).

MORPHOLOGIC DIAGNOSIS: Long bone, diaphysis: Hyperostosis, subperiosteal and endosteal, circumferential, diffuse, severe (osteopetrosis), with multifocal periosteal thickening, chicken, avian.

ETIOLOGIC DIAGNOSIS: Avian alpharetroviral osteopetrosis

CAUSE: Avian leukosis virus (alpharetrovirus)

SYNONYMS: Thick leg disease, marble bone disease

GENERAL DISCUSSION:

• Osteopetrosis: Avian osteopetrosis is induced by avian leukosis virus (ALV) and causes uniform or irregular diaphyseal or metaphyseal thickening, usually in the long bones of the leg
• Avian Leukosis Virus: The avian leukosis/sarcoma viruses are strains of a single-stranded, RNA, oncogenic alpharetrovirus; strains are classified by lesions they cause, with 10 subgroups A – J
  • The most common lesion is lymphoid leukosis (gradual onset in a flock, persistent low mortality predominantly in older chickens 16+ weeks old, bursal neoplasia with metastasis to other organs); in the United States, subgroup A viruses are the most common and most frequently associated with lymphoid leukosis
  • Subgroup A includes fowl glioma-inducing virus prototype which induces cardiomyocyte abnormalities and gliomas in chickens (Nishiura et al., J Vet Diagn Invest, 2023)
  • Subgroup B is occasionally identified
  • Subgroups C and D are rare
  • Subgroup E is considered endogenous because it is integrated into the host DNA
  • Subgroups F-I primarily cause leukosis in non-chicken species

PATHOGENESIS:

• Avian Leukosis Virus:
  • Egg transmission (vertical) of virus is an important mechanism of spread of avian leukosis virus, and infected chicks are immune tolerant and persistently infected, with increased risk of death from lymphoid leukosis and prolific viral shedding
  • Horizontal transmission also occurs, especially with ALV-J
  • Provirus integrates into the host DNA close to the c-myc gene; activation of this oncogene is considered the primary event in starting the neoplastic process
• Osteopetrosis: Avian leukosis virus alters the growth and differentiation of osteoblasts (rather than a defect in osteoclastic function, as in mammalian osteopetrosis [M-M02])

TYPICAL CLINICAL FINDINGS:

• Avian leukosis virus: Commonly nonspecific or no clinical signs, poor thrift, pallor, emaciation, decreased egg production, anemia, neoplasia in chickens 16+ weeks old
• Osteopetrosis: Limping, elevated alkaline phosphatase

TYPICAL GROSS FINDINGS:

• Avian leukosis virus, variable presentations:
  • Lymphoma may cause abdominal enlargement due to massive hepatomegaly, and commonly also affects kidney, ovary, and bursa of Fabricious; lesions can be diffuse or focal
    • The bursa is nearly always involved, but may not be detected without incision and examination of the epithelial surface
  • Myelocytomatosis causes multiple masses on the shanks, head, and thorax
  • Osteopetrosis: affects the long bones resulting in “boot” shanks appearance, due to thickening of the diaphysis and metaphysis of long bones

TYPICAL LIGHT MICROSCOPIC FINDINGS:

• Lymphoid leukosis: Lymphomatous cells are lymphoblastic and originate from the bursa (B-lymphocytes with surface IgM expression)
• Osteopetrosis: Initially, focal hypertrophy and hyperplasia of periosteum with increased numbers of large, basophilic osteoblasts; spongy bone converges centripetally towards center of the shaft; large, irregular Haversian canals; an increase in number and size of lacunae with numerous large eosinophilic osteocytes; increased basophilic and fibrous new bone

ADDITIONAL DIAGNOSTICS:

• PCR, IHC
• All avian leukosis viruses produce a group-specific antigen that can be detected in egg albumen and body tissues and fluids
• Transmission electron microscopy: 85-105nm diameter icosahedral virions with central cores

DIFFERENTIAL DIAGNOSIS:

Other osteopathies in birds:

• Rickets: Abnormal endochondral ossification characterized by failure of cartilage and osteoid matrix mineralization in young animals (see M-M08)
• Osteoporosis: Reduction in bone mass with increased porosity (see M-M16)
• Tibial dyschondroplasia: Defect in endochondral ossification due to inability of chondrocytes to hypertrophy, with retention of nonvascularized, unmineralized cartilage in the proximal metaphysis of the tibiotarsus and tarsometatarsus of rapidly growing birds (see M-T06)

COMPARATIVE PATHOLOGY:

Non-viral osteopetrosis in avian species

• Tracheal stenosis has been reported in a yellow-crowned parrot as a result of osteopetrosis of tracheal rings; the atypical pattern of the lesions, affected sites, age, and absence of other avian leukosis lesions make it unlikely that case was due to viral infection. (Santana et al., J Comp Pathol, 2023)

Osteopetrosis in other species:

• Virus-associated hyperostosis (osteopetrosis-like lesions):
  • Bovine viral diarrhea virus can induce multifocal retention of primary spongiosa à osteopetrosis-like lesions
  • Feline leukemia virus is associated with medullary osteosclerosis
• Mammalian osteopetrosis (see M-M02): Defect in osteoclastic bone resorption à accumulation of primary spongiosa; described in the ox, sheep, deer, rat, rabbit, mouse, dog, cat, pig, and horse; probably autosomal recessive condition
• Congenital cortical hyperostosis in pigs (see M-M05): Excessive periosteal new bone formation on long bones (radius and ulna most severely affected), extensive edema, muscle atrophy of affected limb; presumed autosomal recessive

Other Alpharetroviruses:

• Rous sarcoma virus

REFERENCES:

1. 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. Philadelphia, PA: Elsevier; 2016:50-52, 91-94.
2. Nishiura H, Nakajima T, Saito S, Kato A, Hatai H, Ochiai K. Assessing avian leukosis virus proviral load and lesion correlates in fowl glioma-inducing virus-infected Japanese bantam chickens. J Vet Diagn Invest. 2023;35(5):484-491.
3. Ojkic D, Sellers H, et al. Viral diseases. In: Boulianne M., ed. Avian Disease Manual. 8^th Jacksonville, FL: American Association of Avian Pathologists; 2019: 37-39.
4. Olson EJ, Carlson CS. Bones, joints, tendons, and ligaments. In: McGavin MD, Zachary JF, eds. Pathologic Basis of Veterinary Disease. 7th ed. St. Louis, MO: Elsevier; 2022: 1057-1059.
5. Santana CH, Oliveira AR, Carvalho TP, Pereira FMAM, Santos DOD, Soares-Neto LL, Ramos MK, Novais TM, Paixão TAD, Santos RL, Serakides R. Tracheal stenosis in a yellow-crowned parrot (Amazona ochrocephala) due to diffuse ossification and osteopetrosis of tracheal rings. J Comp Pathol. 2023;204:7-10.
6. Schmidt R, Reavill DR, Phalen DN. Pathology of Pet and Aviary Birds. 2nd ed. Ames, IA: John Wiley & Sons, Inc.; 2015, p. 213.

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