Pathology in Practice

Allison L. Gerras Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI

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Kimberly A. Thompson Binder Park Zoo, Battle Creek, MI

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Victoria E. Watson Department of Pathobiology and Diagnostic Investigation, College of Veterinary Medicine, Michigan State University, East Lansing, MI

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Abstract

In collaboration with the American College of Veterinary Pathologists

Abstract

In collaboration with the American College of Veterinary Pathologists

History

An adult female wallaby was euthanized after a 9-month history of progressive bilateral enlargement of the mandibles. Although housed at a zoo for 2.5 years, the exact age and previous history of the wallaby were unknown as this animal was acquired during a legal confiscation and removal from a private individual. The wallaby had been maintained outdoors in a group of 8 wallabies, and its diet was considered well balanced, consisting of natural grass for grazing, ad libitum grass hay, mineral block access, and ad libitum herbivore zoo pelleted diet (HMS Zoo Diets Inc; calcium 1% to 1.5% and phosphorous 0.7%).

When bilateral enlargement of the mandibles was first noted and several months later, there was no growth on aerobic and anaerobic bacterial cultures performed on tissue biopsy samples. Histopathology was suggestive of reactive bone without evidence of inflammation, neoplasia, necrosis, or lysis. Results of repeated CBCs and biochemical analyses had been unremarkable. The animal had clinically normal feed consumption for 7 months and maintained its body condition score between 4/9 and 5/9 and body weight between 11.6 and 12.9 kg. Initial and repeated radiographic examination revealed smooth osseous proliferation bilaterally along the mandibles, particularly the ventral surfaces. When the condition was first observed, the animal’s ionized calcium concentration was 1.22 mmol/L (no available reference range [RR] for this species), creatinine concentration was 0.9 mg/dL (RR,1 0.8 to 1.6 mg/dL), and BUN concentration was 20.3 mg/dL (RR,1 17.9 to 31.9 mg/dL). Empirical treatment with tulathromycin (2.5 mg/kg, SC, q 7 days for 7 weeks) was performed but not effective in reducing the size or halting the progression of the masses.

On the day of euthanasia, the wallaby had been anesthetized (ketamine [3.4 mg/kg], midazolam [0.2 mg/kg], and dexmedetomidine [21 µg/kg]) and then intubated and maintained with isoflurane delivered in oxygen. During physical examination, a wound was noted beneath the left mandible, and radiography revealed marked progression of the smooth osseous proliferation bilaterally. Due to poor prognosis and loss of body condition (then a score of 3/9), the wallaby was euthanized with pentobarbital sodium (5 mL IV).

Clinical and Gross Findings

At necropsy, the wallaby was in lean body condition and weighed 10.9 kg. The left and right mandibles were focally expanded by hard, smooth, rounded masses that measured 3 X 3 X 2 cm and 2 X 2 X 0.5 cm, respectively (Figure 1). On the ventral aspect of the left mandibular mass, there was a 3 X 2 cm area of alopecia, and the underlying skin was erythematous. Deep to the rostral aspect of this alopecic area, encompassing an area of 0.3 X 0.5 X 0.3 cm, the subcutis and fascia were mildly expanded by dark red, soft material that did not extend into the periosteum or underlying bone. Serial cross-sections from the rostral aspects of the mandibles and maxilla to the osseous bullae were examined. On cut section, both mandibular rami were expanded by round, tan, masses that contained approximately ten, 1-mm-diameter, light brown foci. The left mandibular lymph node was slightly enlarged and measured 1.5 X 0.6 X 0.2 cm, and the right mandibular lymph node measured 1 X 0.7 X 0.3 cm. All other organs were grossly unremarkable.

Figure 1
Figure 1

Necropsy images of the left side of the head (A), ventral view of mandibles and masses (B), and cross-section of the skull and mandibles at the level of the mandibular masses (C) of adult female wallaby euthanized after a 9-month history of progressive bilateral enlargement of the mandibles. The left and right mandibular bodies were focally expanded by hard, smooth, rounded, masses, with the left more severely affected with dense bony proliferation with smooth, rounded edges, and scattered miliary light brown foci.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.20.05.0272

Formulate differential diagnoses, then continue reading.

Histopathologic Findings

The sections of mandible contained proliferative periosteal bone composed of trabeculae of reactive woven bone intermixed with spaces filled with variable amounts of fibrous connective tissue. Within and deep to this area of proliferative periosteal bone were multifocal areas of lysis (1 to 2.5 mm in diameter) that were filled with nodular aggregates of neutrophils, macrophages, multinucleated giant cells, lymphocytes, and plasma cells (Figure 2). These inflammatory aggregates often surrounded filamentous, eosinophilic, globular material (Splendore-Hoeppli phenomenon). In one of the aggregates, there was a free fragment of hair. The skin overlying the mandibular mass contained multifocal, perivascular to diffusely scattered lymphocytes and plasma cells. The epidermis was mildly hyperplastic, and there was follicular atrophy. The cortices of the lymph nodes were expanded by follicular hyperplasia, and the medullary sinuses often contained aggregates of hemosiderin-laden macrophages. There were few aggregates of lymphocytes and plasma cells in the salivary gland attached to the lymph node. Aerobic bacterial culture of the mandible yielded Escherichia coli and Corynebacterium spp, and anaerobic bacterial culture grew Clostridium perfringens, Actinomyces hyovaginalis, Prevotella heparinolytica, Peptostreptococcus canis, Bacteroides pyogenes, Porphyromonas spp, and moderate growth of Clostridium septicum. A Gram stain, Grocott methenamine silver (GMS) stain, and periodic acid–Schiff staining were performed on the section of mandible and revealed dense staining along the leading edge of the Splendore-Hoeppli phenomenon. The GMS stain also revealed branching stained filamentous material.

Figure 2
Figure 2

Photomicrographs of tissue sections of the left mandibular bony mass from the wallaby described in Figure 1. A—Subgross view showing proliferative periosteal bone. H&E stain; bar = 5 mm. B—Focus of inflammation within proliferative periosteal bone. H&E stain; bar = 1 mm. C—Radiating material (Splendore-Hoeppli phenomenon) surrounded by neutrophils. H&E stain; bar = 50 µm. D—Abundant macrophages and a single multinucleated giant cell (arrowhead) are shown. H&E stain; bar = 20 µm.

Citation: Journal of the American Veterinary Medical Association 259, S2; 10.2460/javma.20.05.0272

Morphologic Diagnosis and Case Summary

Morphologic diagnosis: severe bilateral periosteal proliferation with intraperiosteal and subperiosteal multifocal pyogranulomatous osteomyelitis and Splendore-Hoeppli phenomenon of the mandibles with mild, chronic perivascular to interstitial dermatitis of the overlying skin; reactive submandibular lymph nodes.

Case summary: bilateral mandibular osteomyelitis in a wallaby.

Comments

Based on gross postmortem examination, the differential diagnoses included osteomyelitis or oral necrobacillosis either primary or secondary to trauma (lumpy jaw), craniomandibular osteopathy, osteoma, and less likely osteosarcoma. Findings on antemortem radiographic images were consistent with bilateral proliferative lesions due to the well-circumscribed nature and expansile presentation. Additionally, there was no evidence of retained molars. At necropsy, histopathologic examination revealed that the mass consisted of a reactive bony proliferation and chronic inflammation (osteomyelitis). Due to the presence of hair deep within the reactive periosteal bone, it was possible that a past trauma allowed for infection with microorganisms, which would have been most consistent with oral necrobacillosis or lumpy jaw, although the bilateral presentation was unusual. Actinomyces hyovaginalis may have been the pathogenic agent as this agent causes necrotizing pneumonia in pigs and the Actinomyces genus causes mandibular osteomyelitis in bovids.2,3

Actinomyces is one of the genera of bacteria that causes Splendore-Hoeppli phenomenon. Spendore-Hoeppli phenomenon is a unique tissue reaction that includes strongly eosinophilic and amorphous material that surrounds microorganisms, such as fungi, bacteria, parasitic agents, and biologically inert substances.4 This material is described as a mixture of a deposition of antigen-antibody complexes and inflammatory cell debris, but the mechanism is not clearly defined.46 In human medicine, Splendore-Hoeppli is commonly differentiated from Actinomycotic sulfur granules based on an absence of central branching filaments.4,6 This differentiation has not been clarified or deemed necessary in veterinary species. This wallaby was not receiving antimicrobial treatment at the time of euthanasia, and although the causative agent was presumed to have been Actinomyces, the authors were not convinced by the filamentous material identified in the GMS-stained section. In general, antimicrobial susceptibility testing is not performed for Actinomyces spp; however, macrolide antimicrobials, like tulathromycin, have treated Actinomyces infections successfully in humans.7

Macropods, especially wallabies, are prone to developing mandibular osteomyelitis. Fusobacterium necrophorum is the primary etiologic agent cultured, although coinfections with Actinomyces spp, Streptococcus spp, and Bacteroides spp are common.8 Although bacterial agents are often implicated in osteomyelitis, there are many other noninfectious causes to consider, and a more encompassing term for this disease in macropods is macropod progressive periodontal disease (MPPD), which includes infectious agents and compounding factors such as trauma, age, and the natural progression of molar development.9,10 Macropods undergo molar progression, wherein the most rostral molars become nonfunctional and are shed, but if these molars are retained, they may act as a nidus for infection.10

In the human literature, mandibular osteomyelitis is classified into 2 categories: bacterial osteomyelitis or synovitis, acne, pustulosis, hyperostosis, and osteitis (SAPHO) syndrome.11 Bacterial osteomyelitis is most commonly associated with Actinomyces israelii, Staphylococcus spp, Peptostreptococcus spp, and Pseudomonas aeruginosa.12,13 The lesions associated with bacterial osteomyelitis are neutrophilic infiltration with a fistulous tract and lamellated periosteal reaction.12 Additionally, bacterial osteomyelitis is effectively treated with antimicrobials. Osteomyelitis in SAPHO syndrome has an unclear etiology, is unresponsive to antimicrobial treatment, and is a progressive disease. It is thought to originate in the periosteum and is associated with a solid periosteal reaction, bone reabsorption, and bone enlargement,12,14 like the histopathologic lesions seen in this wallaby.

This wallaby had gross lesions and clinical signs that were unusual for mandibular osteomyelitis—the bilateral, smooth proliferation of periosteal bone and no signs of discomfort while eating during the 9-month history of the disease. We suspected that trauma near the mandibular symphysis was the initiating event, with secondary bacterial spread to the rami making it difficult for antimicrobials to penetrate the site of infection leading to the presence of chronic inflammation and bilateral presentation. Furthermore, similarities between the lesions of MPPD in wallabies and SAPHO in humans were demonstrated in this case.

References

  • 1.

    Vongelnest L. Marsupialia (marsupials). In: Miller RE, Fowler ME, eds. Fowler’s Zoo and Wild Animal Medicine. 8th ed. Philadephia, PA: WB Saunders Co; 2005:255274.

    • Search Google Scholar
    • Export Citation
  • 2.

    Aalbaek B, Christensen H, Bisgaard M, Liljegren CH, Nielsen OL, Jensen HE. Actinomyces hyovaginalis associated with disseminated necrotic lung lesions in slaughter pigs. J Comp Pathol. 2003;129(1):7077.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Liljegren CH, Aalbaek B, Nielsen OL, Jensen HE. Some new aspects of the pathology, pathogenesis, and aetiology of disseminated lung lesions in slaughter pigs. APMIS. 2003;111(5):531538.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Gopinath D. Splendore-Hoeppli phenomenon. J Oral Maxillofac Pathol. 2018;22(2):161162.

  • 5.

    Liber AF, Choi HS. Splendore-Hoeppli phenomenon about silk sutures in tissue. Arch Pathol. 1973;95(4):217220.

  • 6.

    Hussein MR. Mucocutaneous Splendore-Hoeppli phenomenon. J Cutan Pathol. 2008;35(11):979988.

  • 7.

    Valour F, Sénéchal A, Dupieux C, et al. Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect Drug Resist. 2014;7:183197.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Samuel JL. Jaw disease in macropod marsupials: bacterial flora isolated from lesions and from the mouths of affected animals. Vet Microbiol. 1983;8(4):373387.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9.

    Brookins MD, Rajeev S, Thornhill TD, Kreinheder K, Miller DL. Mandibular and maxillary osteomyelitis and myositis in a captive herd of red kangaroos (Macropus rufus). J Vet Diagn Invest. 2008;20(6):846849.

    • Search Google Scholar
    • Export Citation
  • 10.

    McLelland D. Macropod progressive periodontal disease (‘lumpy jaw’). In: Vogelnest L, Portas T, ed. Current Therapy in Medicine of Australian Mammals. Clayton, Australia: CSIRO; 2019:451462.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Suei Y, Taguchi A, Tanimoto K. Diagnosis and classification of mandibular osteomyelitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(2):207214.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12.

    Koorbusch GF, Fotos P, Goll KT. Retrospective assessment of osteomyelitis. Etiology, demographics, risk factors, and management in 35 cases. Oral Surg Oral Med Oral Pathol. 1992;74(2):149154.

    • Search Google Scholar
    • Export Citation
  • 13.

    Finley AM, Beeson MS. Actinomycosis osteomylelitis of the mandible. Am J Emerg Med. 2010;28(1):118.e1118.e4.

  • 14.

    Suei Y, Taguchi A, Tanimoto K. Diagnostic points and possible origin of osteomyelitis in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome: a radiographic study of 77 mandibular osteomyelitis cases. Rheumatology (Oxford). 2003;42(11):13981403.

    • Search Google Scholar
    • Export Citation
  • Figure 1

    Necropsy images of the left side of the head (A), ventral view of mandibles and masses (B), and cross-section of the skull and mandibles at the level of the mandibular masses (C) of adult female wallaby euthanized after a 9-month history of progressive bilateral enlargement of the mandibles. The left and right mandibular bodies were focally expanded by hard, smooth, rounded, masses, with the left more severely affected with dense bony proliferation with smooth, rounded edges, and scattered miliary light brown foci.

  • Figure 2

    Photomicrographs of tissue sections of the left mandibular bony mass from the wallaby described in Figure 1. A—Subgross view showing proliferative periosteal bone. H&E stain; bar = 5 mm. B—Focus of inflammation within proliferative periosteal bone. H&E stain; bar = 1 mm. C—Radiating material (Splendore-Hoeppli phenomenon) surrounded by neutrophils. H&E stain; bar = 50 µm. D—Abundant macrophages and a single multinucleated giant cell (arrowhead) are shown. H&E stain; bar = 20 µm.

  • 1.

    Vongelnest L. Marsupialia (marsupials). In: Miller RE, Fowler ME, eds. Fowler’s Zoo and Wild Animal Medicine. 8th ed. Philadephia, PA: WB Saunders Co; 2005:255274.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 2.

    Aalbaek B, Christensen H, Bisgaard M, Liljegren CH, Nielsen OL, Jensen HE. Actinomyces hyovaginalis associated with disseminated necrotic lung lesions in slaughter pigs. J Comp Pathol. 2003;129(1):7077.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 3.

    Liljegren CH, Aalbaek B, Nielsen OL, Jensen HE. Some new aspects of the pathology, pathogenesis, and aetiology of disseminated lung lesions in slaughter pigs. APMIS. 2003;111(5):531538.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4.

    Gopinath D. Splendore-Hoeppli phenomenon. J Oral Maxillofac Pathol. 2018;22(2):161162.

  • 5.

    Liber AF, Choi HS. Splendore-Hoeppli phenomenon about silk sutures in tissue. Arch Pathol. 1973;95(4):217220.

  • 6.

    Hussein MR. Mucocutaneous Splendore-Hoeppli phenomenon. J Cutan Pathol. 2008;35(11):979988.

  • 7.

    Valour F, Sénéchal A, Dupieux C, et al. Actinomycosis: etiology, clinical features, diagnosis, treatment, and management. Infect Drug Resist. 2014;7:183197.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 8.

    Samuel JL. Jaw disease in macropod marsupials: bacterial flora isolated from lesions and from the mouths of affected animals. Vet Microbiol. 1983;8(4):373387.

    • Search Google Scholar
    • Export Citation
  • 9.

    Brookins MD, Rajeev S, Thornhill TD, Kreinheder K, Miller DL. Mandibular and maxillary osteomyelitis and myositis in a captive herd of red kangaroos (Macropus rufus). J Vet Diagn Invest. 2008;20(6):846849.

    • PubMed
    • Search Google Scholar
    • Export Citation
  • 10.

    McLelland D. Macropod progressive periodontal disease (‘lumpy jaw’). In: Vogelnest L, Portas T, ed. Current Therapy in Medicine of Australian Mammals. Clayton, Australia: CSIRO; 2019:451462.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11.

    Suei Y, Taguchi A, Tanimoto K. Diagnosis and classification of mandibular osteomyelitis. Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 2005;100(2):207214.

    • Search Google Scholar
    • Export Citation
  • 12.

    Koorbusch GF, Fotos P, Goll KT. Retrospective assessment of osteomyelitis. Etiology, demographics, risk factors, and management in 35 cases. Oral Surg Oral Med Oral Pathol. 1992;74(2):149154.

    • Search Google Scholar
    • Export Citation
  • 13.

    Finley AM, Beeson MS. Actinomycosis osteomylelitis of the mandible. Am J Emerg Med. 2010;28(1):118.e1118.e4.

  • 14.

    Suei Y, Taguchi A, Tanimoto K. Diagnostic points and possible origin of osteomyelitis in synovitis, acne, pustulosis, hyperostosis and osteitis (SAPHO) syndrome: a radiographic study of 77 mandibular osteomyelitis cases. Rheumatology (Oxford). 2003;42(11):13981403.

    • Search Google Scholar
    • Export Citation

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