CASE REPORT
published: 04 July 2022
doi: 10.3389/fvets.2022.886495
Case Report: Unable to Jump Like a
Kangaroo Due to Myositis Ossificans
Circumscripta
Enrice I. Huenerfauth 1*, Viktor Molnár 2 , Marco Rosati 3 , Malgorzata Ciurkiewicz 4 ,
Franz J. Söbbeler 1 , Oliver Harms 1 , Robert Hildebrandt 1 , Wolfgang Baumgärtner 4 ,
Andrea Tipold 1 , Holger A. Volk 1 and Jasmin Nessler 1
1
Department of Small Animal Internal Medicine and Surgery, University of Veterinary Medicine Foundation, Hannover,
Germany, 2 Hannover Adventure Zoo, Hannover, Germany, 3 Section of Clinical and Comparative Neuropathology, Centre for
Clinical Veterinary Medicine, Ludwig-Maximilians-Universität, Munich, Germany, 4 Department for Pathology, University of
Veterinary Medicine Foundation, Hannover, Germany
Edited by:
William B. Thomas,
The University of Tennessee, Knoxville,
United States
Reviewed by:
Regina Zavodovskaya,
University of California, Davis,
United States
James Carmalt,
University of Saskatchewan, Canada
*Correspondence:
Enrice I. Huenerfauth
[email protected]
Specialty section:
This article was submitted to
Veterinary Neurology and
Neurosurgery,
a section of the journal
Frontiers in Veterinary Science
Received: 28 February 2022
Accepted: 31 May 2022
Published: 04 July 2022
Citation:
Huenerfauth EI, Molnár V, Rosati M,
Ciurkiewicz M, Söbbeler FJ, Harms O,
Hildebrandt R, Baumgärtner W,
Tipold A, Volk HA and Nessler J
(2022) Case Report: Unable to Jump
Like a Kangaroo Due to Myositis
Ossificans Circumscripta.
Front. Vet. Sci. 9:886495.
doi: 10.3389/fvets.2022.886495
A male 10-year-old captive red kangaroo (Macropus rufus) was presented with a chronic
progressive pelvic limb lameness and reluctance to jump. The general examination
revealed a palpable induration of the lumbar epaxial muscles. Magnetic resonance
imaging performed under general anesthesia revealed bilateral almost symmetric,
well-circumscribed mass lesions in superficial erector spinae muscles. The lesions had
irregular to multilobulated appearance with hyper-, hypo-, and isointense areas in T2- and
T1-weighted (w) sequences without contrast enhancement. On computed tomography,
a peripheral rim of mineralization was apparent. Histopathological analysis of a muscle
biopsy showed osseous trabeculae with rare clusters of chondrocytes indicating
metaplasia of muscle tissue to bone. No indications of inflammation or malignancy
were visible. The clinical, histopathological, and imaging workup of this case was
consistent with myositis ossificans circumscripta. This disorder is particularly well-known
among human professional athletes such as basketball players, where excessive,
chronic-repetitive force or blunt trauma causes microtrauma to the musculature.
Metaplasia of muscle tissue due to abnormal regeneration processes causes heterotopic
ossification. The kangaroo’s clinical signs improved with cyto-reductive surgery, cage
rest, weight reduction, and meloxicam without further relapse.
Keywords: macropod, lameness, traumatic, calcification, myopathy
INTRODUCTION
In macropods, pelvic limb lameness manifests as unwillingness to move, asymmetrical jumping,
stiffness, kyphosis, increased flexion in the stifle or tarsus, deterioration when starting to jump, and
in the worst case complete failure of weight-bearing (1).
The most commonly reported etiology for lameness in macropods are orthopedic diseases
including lesions of bones, joints, and ligaments such as fractures (1), metastatic osteolytic
angioleiomyosarcoma (2), or osteophytes and osteoporosis due to osteofluorotic bone changes
(3). Lameness because of myopathy is reported rarely in kangaroos; the most common myopathy
is exertional rhabdomyolysis secondary to stress (capture myopathy) causing acute, severe,
generalized weakness, and hyperthermia (4, 5).
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Kangaroo With Myositis Ossificans Circumscripta
ml, Boehringer Ingelheim Vetmedica GmbH, Germany) followed
by oral application for 14 days, resulted in amelioration of
clinical signs.
After 9 months, the asymmetric pelvic limb lameness
recurred. The general examination revealed subjectively
increased body condition score. Neurological and orthopedic
examination were limited to observation only, as it was
not possible to restrain the kangaroo properly. During slow
jumping, lameness of the left pelvis limb was visible resulting
in asymmetrical and short steps with weight shifting to the
right pelvic limb. In addition, the tone of the cranial and lateral
tibial muscles seemed to be decreased. There was subjectively
decreased muscle volume of the hamstring and gastrocnemius
muscles on both sides, worse on the left side. Tail movement and
strength seemed to be normal. A suspected L4–S1 myelopathy
vs. orthopedic etiology was discussed.
Further diagnostics were obtained under general anesthesia.
The kangaroo was immobilized at the zoo with medetomidine
60 µg/kg (Zalopine R 10 mg/ml, Orion Corporation, Finland),
ketamine 5 mg/kg (Ketamin 10%, Selectavet, Germany), and
midazolam 0.07 mg/kg (Midazolam B. Braun 5 mg/ml, B.
Braun, Germany) via intramuscular blowpipe injection. A
second injection with medetomidine 40 µg/kg, ketamine 3
mg/kg, and midazolam 0.04 mg/kg was administered due to
insufficient sedation 20 min after the first injection. The kangaroo
was transported deeply sedated to the clinic. Upon arrival, a
venous catheter was placed in the left lateral saphenous vein.
After induction of general anesthesia with sevoflurane (Sevoflo,
Zoetis, Germany) via mask, the kangaroo was intubated and
anesthesia was maintained with isoflurane end-tidal 0.9–1.1
volume % (Isofluran CP, CP pharma, Germany) throughout
the procedures.
Magnetic resonance imaging (MRI; 3.0 Tesla MRI scanner
Achieva, Philips Medical Systems, Best, The Netherlands) of the
thoracolumbar spine and paraspinal musculature was performed
in a sagittal, transversal, and dorsal plane in T2-weighted (w)
sequence, T2w Spectral Attenuated Inversion Recovery, T1w preand postcontrast (Gadolinium, 0.2 ml/kg intravenously).
Magnetic resonance imaging of the lumbar vertebral column
showed bilateral well-demarcated lesions (11 × 5 × 4 cm),
more severe on the left side, within the superficial erector
spinae muscles (Figure 1). The lesions were of heterogenic
signal intensity: In T2w and T1w some areas were markedly
hyperintense to normal musculature, some were isointense and
some areas showed complete signal void. The lesions lacked the
typical structure of muscle fibers. There was no pathological
contrast enhancement. All the muscles in the field-of-view
showed mild-to-moderate fat deposition.
Computed tomography (CT; Phillips Brilliance 64, Philips
GmbH, Hamburg, Germany) of the vertebral column with
epaxial musculature from T1 to S2 vertebra was performed. The
lesions were mostly iso- to mildly hypodense to surrounding
musculature and revealed a hyperattenuating rim surrounding a
hypoattenuating center (Figure 1). In addition, there was mild
arthrosis of the facet joints in the lumbar vertebrae.
Differential diagnoses included myositis ossificans
circumscripta, fibrodysplasia ossificans progressiva (FOP),
In human patients, focal pain because of myopathy may
be caused by myositis ossificans circumscripta (MO), a benign
ossification of muscle and other soft tissue (6, 7). The previous
nomenclature using the term myositis is misleading as it suggests
primary inflammation (7, 8). Currently, the pathogenesis is not
completely understood, but it is assumed that an inflammatory
cascade follows injury (6, 9). Subsequently, pathological repair
processes may lead to formation of metaplastic osseous,
cartilaginous, and osteochondral tissue (6, 10). Diagnosis is made
via computed tomography (CT) or magnetic resonance imaging
(MRI) displaying early changes of soft tissue edema in the initial 4
weeks (11, 12), and in the later course of the disease, calcification
(9, 11). Primary inflammatory processes or neoplasia are ruled
out via muscle biopsy (6).
Trauma is thought to initiate the formation of excessive
bone tissue (6, 13). It may be blunt trauma or minor muscle
damage due to excessive stress (6, 13). However, intramuscular
injections are also thought to contribute due to the iatrogenically
induced trauma (13).
In the veterinary medicine, MO is described in horses and
dogs and usually occurs in the muscles of pelvic limbs (13–
18). Especially in the Doberman Pinscher lesions in the area
of the hip joint are well described (16, 19). Here, due to von
Willebrand disease presumed chronic microvascular hemorrhage
(atraumatic) or increased bleeding after acute direct penetrating
or non-penetrating trauma is suggested to cause fibrosis and
mineralization (12, 16, 19). Myopathy with histological signs
of MO in the sartorius, gracilis, hamstring, or triceps muscles
has been described in several dog breeds (13, 14, 17). The
exact trigger is mostly unknown, previously witnessed direct or
indirect trauma is only described in the minority of dogs (19, 20).
In horses, fibrotic myopathy of the gracilis muscles after an
antecedent injury has been described (15).
This case report describes the clinical, diagnostic imaging,
and histopathological findings of a kangaroo with myositis
ossificans circumscripta.
CASE DESCRIPTION
The animal, a 10-year-old, 75 kilograms (kg) male red giant
kangaroo (Macropus rufus) was presented with an 11-months
history of chronic progressive recurrent lameness of both pelvic
limbs, worse on the left side, and difficulties in rising (21).
All the examinations were performed with informed
consensus of the animal’s owner.
At initial examination performed by the local veterinarian,
radiographs of the skull/teeth, cervical-, thoracic vertebral
columns, hip, tarsi, and tail, a complete blood count, and serum
chemistry did not reveal any abnormalities (22–24). Further
evaluation revealed an elevated antibody titer against Toxoplasma
gondii (indirect Hemagglutination test 1: 2,560). Treatment
with trimethoprim and sulfadiazine for a potential Toxoplasma
gondii infection could only be continued for 5 days, since the
patient refused to take tablets. Paired serology for Toxoplasma
gondii was not performed during the course of clinical signs.
Meloxicam 0.2 mg per kg subcutaneous (Metacam 20 mg per
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FIGURE 1 | (A) Magnetic Resonance Imaging (MRI) T2-weighted (w) transversal MRI sequence; (B,C) computed tomography (CT), CT transversal (B) and dorsal (C)
region of the lumbar epaxial muscles arrows: bilateral mildly asymmetric, multilobulated, well-circumscribed mass lesions in the superficial erector spinae muscles that
present hyper-, hypo-, and isointense areas in T2w in MRI without contrast enhancement. On CT scan, the preceding lesion presents a hypodense center surrounded
by a hyperattenuating rim giving an “eggshell appearance”.
chronic inflammatory process, and low-grade extra-skeletal
osteo-/chondrosarcoma and other neoplasia.
Subsequently to the imaging, biopsies for histopathological
examination were taken in the course of the same general
anesthesia under aseptic conditions in the area of the
muscle indurations of the left dorsal longissimus muscle.
Cefazoline 22 mg/kg and butorphanol 0.1 mg/kg (Butorgesic,
CP pharma, Germany) were administered intravenously before
surgery and biopsy of the muscle. Following a focal biopsy,
removal of all macroscopically abnormal muscle tissue via
curettage was carried out aiming at a cyto-reduction. The
skin was covered in layers with a continuous intracutaneous
Frontiers in Veterinary Science | www.frontiersin.org
suture. For postoperative analgesia, the kangaroo received
meloxicam 0.2 mg/kg (Metacam 5 mg/ml, Boehringer Ingelheim
Vetmedica GmbH, Germany) subcutaneously, and orally for
the subsequent 2 weeks. By antagonization with atipamezole
(Revertor, CP-Pharma, Germany) and flumazenile (Anexate,
CHEPLAPHARM Arzneimittel GmbH, Germany) a quick
and uneventful recovery was facilitated. Postoperatively, the
kangaroo received amoxicillin/clavulanic acid for 8 days orally
(15 mg/kg twice daily).
After sampling, parts of muscle biopsy were immediately
immersed in neutral buffered 10 % formalin while the other
was covered in a humidified gauze with saline solution (NaCl
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Kangaroo With Myositis Ossificans Circumscripta
cells to form cartilage tissue and bone (6, 27). Fibroblasts
are part of the mesenchymal cells that can differentiate into
various connective tissue cells such as inter alia, osteoblasts,
chondrocytes, or smooth muscle cells (28). In addition
to fibroblasts, other pluripotent mesenchymal cells may be
found in muscle tissue such as endothelial cells, cells for
neovascularization, or adipogenesis, which may act as potential
precursors for the ectopic tissue (29, 30). The assumption of
a failure in the regeneration process is based on a misdirected
differentiation of fibroblasts into chondrocytes and then into
osteogenic cells (6, 10).
In human medicine, the majority of cases of MO occur in
young to middle-aged, mostly male athletes (9, 26, 31). Here,
MO often occurs in regularly overused muscle groups, such
as thigh muscles in football, soccer, or basketball players (11,
12, 32), or triceps muscles in swimmers (33). As a result of
intensive exercise, chronic and repeated muscular microtrauma
lead to heterotopic ossification caused by pathological repair
mechanisms (6, 11). In contrast to the described kangaroo
with lumbar MO, MO has rarely been described in the lumbar
musculature in humans (31). Due to their vertically oriented
vertebral column, kangaroos are often used as an animal model
for human vertebral column diseases to describe biomechanical
properties and treatment options (34–36). Nevertheless, there
are major differences in the anatomy of humans and kangaroos
(34, 35). Especially, the lumbar spinal processes are much bigger
in kangaroos than in humans (22). It is suspected that this
increases the surface area for muscle insertion so that more force
can be applied (34). The movement of jumping needs more
muscle power than upright walking (34). This could explain why
the present case showed the expression of MO in the lumbar
musculature compared with the typical occurrence in humans in
the thigh musculature (6, 9, 37).
Clinical signs in humans are mostly related to pain,
and sometimes an induration of muscles can be palpated
(7, 37). First diagnostic signs are easily missed in early
radiographs although a calcification might become evident
after 4 weeks (6, 11, 38). In the described kangaroo, the
induration could be palpated in the region of the epaxial
lumbar muscles. The initial radiographs unfortunately did
not include the lumbar vertebral area, radiographs of other
localizations were unremarkable. CT scans can reveal soft
tissue edema in the first 4 weeks and hyperintensity in T2w
MRI can also be present (11, 12). Further general workup
including electrolytes, serum alkaline phosphate (SAP), Creactive protein (CRP), and creatinine phosphokinase (CK)
can be informative for the different stages that can also be
detected in early phases and lead to a presumptive diagnosis
(11). Thus, an increased CRP and CK value with a decreased
calcium level can be detected in the first 4 weeks whereas SAP
increases first after 4 weeks (11). A diagnosis is made based
on history, clinical and neurologic examination, and imaging
diagnostics, and also a biopsy to exclude inflammatory or
neoplastic diseases (6).
Preferred treatment in human medicine is mostly conservative
treatment with exercise restriction and pain medication (26).
Surgical removal of the mass is only indicated after unsuccessful
0.9 %) and shipped cooled overnight to the neuromuscular lab
and frozen in isopentane, cooled in liquid nitrogen (−130 ◦ C).
Formalin fixation was followed by decalcification for a few days
in a mild decalcifier-solution (OSTEOSOFT R , Merck KGaA,
Darmstadt, Germany) for histology. Once processed for paraffin
embedding, muscle sections were obtained in longitudinal and
transverse planes and stained with hematoxylin–eosin (H&E)
and Giemsa using standard protocols (15–17). Transverse
cryosections (10 micrometers thick) were stained with H&E,
Engel’s modified Gomori trichrome, periodic acid Schiff, oilred O, cytochrome oxidase, nicotinamide adenine dinucleotide
dehydrogenase-tetrazolium reductase histochemistry, and fiber
typing through immunolabeling of myosin heavy chains
as described (25).
The macroscopic evaluation identified skeletal muscle with
normal fascicular architecture and multifocal white spots
of dystrophic tissue mineralization. Microscopic examination
revealed a non-encapsulated, solid, highly cellular proliferation
of fibroblasts lined by well-differentiated and organized bony
trabeculae (osseous metaplasia) recreating bone marrow spaces
filled with adipose tissue (Figure 2). In addition, some islets
of cartilage with a low density of chondrocytes were detected.
Dystrophic mineralization was identified together with some
degenerated myofibers. Myofiber necrosis was observed in a
subset of fascicles. No signs of malignant or inflammatory
processes were found. The described findings led to the diagnosis
of myositis ossificans circumscripta.
One day after anesthesia the kangaroo’s gait remained
unchanged. Subsequent therapy included cage rest for 3
weeks and weight reduction. Four weeks after the cytoreductive biopsy, he jumped slowly and the lameness was
much less severe but there was still a mild shift of weight
to the right limb. One year after biopsy and cyto-reduction,
a neurological check-up showed that the animal’s gait had
improved significantly. No lameness was visible when he was
jumping fast, but when standing a very mild weight shift to the
right was visible. Muscle volume of the hamstring muscles has
increased and muscle of the pelvic limbs were symmetrical. The
remaining mild residual lameness did not require permanent
analgesic therapy.
DISCUSSION
This is the first case report of myositis ossificans circumscripta
in a red giant kangaroo to the best of the authors’ knowledge.
Myositis ossificans is a benign self-limiting, metaplastic osseous,
and osteochondral tissue disorder typically occurring within the
skeletal muscles (6, 10).
Currently, the pathogenesis is not completely understood
(11, 26). Most likely, muscle injury incites a focal inflammatory
cascade with a release of cytokines (6, 11). This results
in myositis with inappropriate production of fibroblasts (6,
11). Due to the influence of cytokines on the vascular
endothelial cells of the musculature, an endothelial mesenchymal
transition is initiated (6, 27). Dysregulation of local stem
cells provides the basis for pluripotent mesenchymal stem
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Kangaroo With Myositis Ossificans Circumscripta
FIGURE 2 | Histopathology-biopsy of affected lumbar muscles, hematoxylin and eosin (HE) stain, magnification 100 x. Extensive proliferation of fibroblasts (black
arrows) encasing multiple myofibers (asterisks) accompanied by marked myofiber diameter variations and boarding well-differentiated bony trabeculae (between
dotted lines). Cell atypia and inflammation are missing.
conservative therapy and persistent pain (6, 26, 31). Recurrence
has been reported after resection (10).
Differential diagnoses include chronic inflammatory or
degenerative processes such as focal myositis, muscle abscess,
or rhabdomyolysis (25, 26). Neoplasia such as extra skeletal
osteosarcoma, soft tissue sarcoma, epithelioid sarcoma (6, 31), or
chondrosarcoma should be considered as a malignant differential
diagnosis for MO in the chronic stage (9, 39). Muscle biopsy
and histopathologic examination are very helpful to rule out any
neoplastic disease (6, 9).
The initial blood sample of the kangaroo revealed an
elevated Toxoplasma gondii titer. The clinical presentation of
toxoplasmosis in macropodids varies, clinical signs may include
pneumonia, diarrhea, neurological deficits, or myositis and
also an asymptomatic course (40). The tachyzoite stage of
toxoplasma gondii is a known trigger of inflammatory reactions
(40). However, it is described that a reliable diagnosis of
toxoplasmosis in macropodids can sometimes only be made by
postmortem examination (40). Muscle biopsy in our case did
not reveal tachyzoites or any evidence of an active underlying
inflammation, and clinical signs resolved without antiprotozoal
therapy. Therefore, clinically relevant toxoplasmosis infection
was considered unlikely in the patient.
Disorders of calcium metabolism, for example, due to
metabolic or nutritional vitamins D, A, and K imbalances
Frontiers in Veterinary Science | www.frontiersin.org
might cause soft tissue calcification (41, 42). Here, serum levels
of phosphate, calcium, vitamins D and K, and parathormone
are essential to rule out metabolic reasons for pathologic
calcification and to examine feed composition and adjust it if
necessary (41, 42). As hypervitaminosis D and other calcium
disorders are systemic diseases, very often other organ systems
are additionally affected by metastatic mineralization: cardiac
muscle and vascular wall calcification leads to the cardiovascular
failure, renal tubular calcification leads to kidney failure (43, 44).
None of the mentioned clinical signs was seen in this kangaroo,
therefore, no further examinations were performed to rule out a
metabolic cause.
Fibrodysplasia ossificans progressive (FOP) shares excessive
ossification of soft tissue as a key sign with MO (12, 45,
46). FOP is an autosomal dominant inherited disease in
humans involving the activin receptor-like kinase 2 receptors
and favors a dysregulation of the bone morphogenic protein
(47). Like in MO, mild soft tissue trauma followed by an
inflammatory response, muscle injury, necrosis, and ultimately
fibroproliferation provokes bone formation (47). Based on the
mouse models with the described mutation, it is hypothesized
that the high concentrations of Activin A induced by trauma
or tissue injury promote ossification and thus FOP (48).
This contrasts with the presentation by Hildebrand et al.
(49) who showed that there is no impairment of activin A
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Kangaroo With Myositis Ossificans Circumscripta
DATA AVAILABILITY STATEMENT
and cytokines in human patients with FOP (49). Classical
FOP signs in humans are deformations of the hallux as well
as the typical extra skeletal upper back and neck lesions
(50, 51). Episodic progression in patients with FOP is wellknown because of secondary irritation and inflammation of
the surrounding tissue in response to the changed calcified
soft tissue (50). Ossification of different stages and chronicity
can be observed in patients with FOP (29, 47). In veterinary
medicine, only a few cases have been described to date in
cats (47, 52, 53), one whale (54), dogs, and pigs (46, 55). The
majority of cases have been reported before the discovery of
the human gene mutation of FOP. Therefore, it is unknown
if the described animals really suffered from a genetic defect
(46, 55–58). In one of the described cats, a mutation in
ACVR1 was detected at post mortem examination similar to
human FOP (47).
Guzu et al. (47) summarize that nearly all eleven cats
diagnosed with FOP-like conditions were euthanized due to
disease progression a few months after presentation. The
average life expectancy for people with FOP is 40 years, with
cardiorespiratory failure and falls being the most common cause
of death (59). In the last decade of their lives, people are mostly
bound to a wheelchair (59). In contrary, the prognosis for
MO is favorable; almost 90 % of athletes reach their previous
sports performance following 6 months of sports abstinence (26).
Given the benign course of the disease in this kangaroo and its
association with a good quality-of-life, the most likely diagnosis
is MO. Based on remission of the clinical signs, FOP also
appears less likely and this term should be used in cases where
genetic abnormalities have been proven (47). In the patient, no
further genetic test was performed, as none of his parents have
been reported to be affected by FOP and there was no further
progression of the clinical signs.
The presented case report shows that in a kangaroo, lameness
associated with the lumbar muscle indentation can be caused by
myositis ossificans circumscripta, suspected secondary to chronic
myopathic microtrauma probably after jumps, comparable to
human professional athletes. The prognosis with symptomatic
treatment and elective cyto-reduction can be favorable.
The original contributions presented in the study are included
in the article/supplementary material, further inquiries can be
directed to the corresponding author/s.
ETHICS STATEMENT
Ethical review and approval was not required for the animal study
because the case report describes normal routine clinical workup.
Written informed consent was obtained from the owners for the
participation of their animals in this study.
AUTHOR CONTRIBUTIONS
VM, AT, JN, and HV performed initial neurological assessment.
EH wrote the draft of the manuscript and reexamined the red
kangaroo. FS managed the kangaroo’s anesthesia. OH performed
the surgery. MR, WB, and MC performed histopathological
examinations. JN supervised and finalized the manuscript. All
authors contributed to manuscript revision, read, and approved
the submitted version.
FUNDING
This open access publication was funded by the Deutsche
Forschungsgemeinschaft (DFG, German Research Foundation)
within the programme LE 824/10-1 Open Access
Publication Costs and University of Veterinary Medicine
Hannover, Foundation.
ACKNOWLEDGMENTS
We would like to thank the neurology team for their support.
Our greatest thanks go to the Adventure Zoo Hannover for their
trust in us and for the excellent collaboration to help the diseased
animals. Preliminary results were presented as a poster at the
33rd European College of Veterinary Neurology (ECVN) Annual
Symposium Online, 16–18.09.2021.
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Kangaroo With Myositis Ossificans Circumscripta
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