Fibrodysplasia Ossificans in Three Cats

Vet. Pathol. 21:495-499 (1984)
Fibrodysplasia Ossificans in Three Cats
H. B. WARRENAND J. L. CARPENTER
The Department of Pathology, Angel1 Memorial Animal Hospital, Boston, Massachusetts
Abstract. A disseminated disorder of epimysial connective tissue characterized by hyperplasia and ossification causing
atrophy and displacement of skeletal muscles, entrapment of vessels and nerves, and progressive immobility is described in
three domestic cats. The condition has some features in common with fibrodysplasia ossificans progressiva in man.
Fibrodysplasia ossificans is rare in domestic animals. healthy except for progressively altered gaits over periods of
In 1918, case reports of a condition in dogs probably six weeks to several months.
Stiff and awkward limb movements and a painful response
referred to hypertrophic osteoarthropathy associated
to handling were common findings during physical examiwith pulmonary masses.14 More recently, a report of a nation. Manual flexion and extension of most limbs was not
hereditary condition in swine similar to fibrodysplasia possible. The deep subcutaneous tissue over much of the
ossificans was termed generalized myositis ossifican~.~’ body, especially the upper portions of the limbs and over and
A review of primary and secondary tumors of the feline between the shoulders, was firm and irregular. The six-yearskeleton included a single case of myositis ossificans old female and one young male had dificulty in rising to
and often required help.
which was limited to both elbows and did not recur stand
Radiographic examination revealed increased soft tissue
after excision.’ In 1980, a single case of generalized and bony densities in the subcutis and muscles of the foremyositis ossificans was reported in a cat” with features arms, arms, shoulders, withers, thighs, and calves in all three
apparently similar to the connective tissue disorder in cats (figs. 1, 2). Lesions observed radiographically at other
sites varied among the three cats. Bony densities varied in size
our three unrelated domestic cats.
and
shape from small needle-like structuresto larger irregular
Fibrodysplasia ossificans of cats differs from localized
masses up to 3.0 x 4.0 cm.
myositis ossificans. The former does not involve muscle
Values for serum blood urea nitrogen, creatinine, calcium,
and is multicentric, often symmetrical, and unrelated phosphorus, alkaline phosphatase, and total protein were
to trauma. It also differs microscopically from myositis normal for all three cats. Aldolase and creatine kinase serum
ossificans in which a pathognomonic feature of the levels were also normal in the two cats tested. The cats ate
lesion is a peripheral zone of orderly maturation from well and had normal temperatures while in the hospital, but
fibrous to osseous tissue. This condition should not be their conditions did not improve and euthanasia was requested by the owners.
called generalized myositis ossificans since it neither
Tissues for histologic examination were obtained both by
begins in muscle nor is it inflammatory.
surgical biopsy and at necropsy, fixed in 10% buffered forIn cats, fibrodysplasia ossificans has soft tissue malin, decalcified when appropriate in 5 % nitric acid, embedchanges similar to those found in man, but to date, ded in parafin, sectioned at 6 pm, and stained with hematoxthere is no evidence that it is inherited or strongly ylin and eosin (HE). Selected tissues were stained with Masson’s trichrome and luxol fast blue.
associated with skeletal abnormalities like the human
disease.
Results
Case Report
Gross lesions were largely confined to the subcutis
Fibrodysplasia ossificans was diagnosed by histologic eval- and epimysium (figs. 3,4) of the neck, dorsum, groin,
uation in three domestic tabby cats; two were one-year-old
male longhairsand the other was a six-year-old spayed female and extremities (table I). Lesions were usually symmetshorthair. One cat had a normal sister, but no further genea- rical (fig. 3) but often varied in size. The proliferative
logical information was available. All three cats appeared tissue was of variable thickness, white to gray, glisten495
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496
Warren and Carpenter
Fig. 1: Forelimb, cat 3. Increased volume of soft tissues and mineralized densities within fascia1 planes of extensor and
flexor muscles.
Fig. 2: Ventro-dorsalview, cat 2. Symmetricalintermuscularmineralized densitiesof bone in thighs and calves. Subluxation
of right hip; tail short and kinked.
Fig. 3: Ventral view of chest and elbows, cat 3; white thickened fibrous tissue covering elbows and proximal forearms.
ing, and firm, and contained many hard, gritty, or bony
foci 0.1 to 4.0 cm. in diameter.
Microscopically, abundant collagen and well-differentiated fibroblasts with rare mitotic figures characterized most of the lesions. Masses of dense collagenous
connective tissue contained foci of mineralized bone
formed from both cartilaginous and osseous metaplasia
(figs. 5-7). The hyperplastic connective tissue displaced
adjacent skeletal muscles, which had lesions of atrophy
and regeneration (amphophilic sarcoplasm, proliferation and internalization of nuclei). Perivascular lymphocytic aggregates occasionally were seen at the junctions of the abnormal connective tissue and normal
muscles. The demarcation between normal and abnormal connective tissues was strikingly abrupt (fig. 8).
Perimysium and endomysium of affected muscles ap-
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Feline Fibrodysplasia Ossificans
497
Table I. Fibrodysplasia ossificans in three cats
Cat
Age
hears)
1
1
M
2
1
M
3
6
F/S
Fig. 4: Transverse section of upper left tibia (arrow),cat 1;
excess white intermuscular fibrous tissue around gastrocnemius and flexor muscles.
peared normal. The proliferation of collagen and bone
surrounded and encased sciatic and other major nerves
to the limbs, but usually did not directly involve either
the perineurium or epineurium (fig. 6). Occasionally
the bony foci consisted of marrow and cartilage as well
as woven and lamellar bone (fig. 7).
In one of the year-old cats, a web-like, irregular net
of firm tissue extended over the visceral pleura of all
lung lobes. Microscopically, in most areas the pleura
was normal; at areas of thickening, however, fibroblasts
accumulated outside the elastic membrane. The immediate subjacent pulmonary parenchyma was atelectatic and without inflammation. In the oldest cat, other
apparently unrelated lesions were multifocal fibrosing
and edematous myocarditis, hepatic congestion, and
mild multifocal encephalitis due to Toxoplasmagondii.
Sex
number
Sites of involvement
Forearms, arms, shoulders,
withers, thighs, calves,
groin
Forearms, arms, shoulders,
withers, thighs, calves, lateral thorax
Forearms, arms, shoulders,
withers, thighs, calves,
neck, midback, groin, visceral pleura
starts early in childhood and progresses with intermittent remissions and rare regression. When biopsied,
swellings in the muscles of the back, shoulder, hip, and
jaw are sites of fibroplasia, and often ossification. Eventually the victim is incapable of moving affected parts
because of bony bridges and displacement and atrophy
of muscle.3.7. 10.14.17
In man, skeletal abnormalities are prominent. Of
these, microdactyly of the great toe is the most common, frequently caused by a missing phalanx. Short
thumbs, short, broad femoral necks, abnormal cervical
vertebrae, hallux valgus, and temporomandibular ab12, 14* 17*
normalities also are seen radi~graphically.~.~.
These skeletal aberrations are consistent with a generalized mesenchymal cell disorder. No similar skeletal
oddities were found in the cats in this study; however,
one young cat (cat 2) had bilateral coxofemoral osteoarthritis, an easily luxating and reducible left hip, and a
short, kinked tail with only seven vertebrae. A metabolic study of human patients has shown calcium and
phosphorus balance and parathyroid function to be
normal.l6
In cats, fibrodysplasia ossificans appears to be an
acquired, progressive, non-malignant, multifocal, and
usually symmetrical proliferation of epimysial fibrous,
cartilaginous, and osseous connective tissue. Visceral
involvement, as seen in cat 3, also may be a feature of
this condition. At present, there is no evidence that the
condition in cats is inherited. Breeding studies and
biochemical a n a l y s e ~ ' . ~of* ~tissues
* ~ should be done
with cases diagnosed in the future.
Discussion
Fibrodysplasia ossificans has been described previously in one cat, but it was reported as generalized
myositis ossificans.I ' A similar condition may have
been observed in pigs." There have been attempts to
relate increased ossification of the appendicular skeleton of dogs having pulmonary masses with fibrodysplasia progressiva of man.I4 Multifocal calcifications
throughout the skeletal muscles in a horse unaccompanied by fibrous tissue proliferation also was compared to this condition.6
In man, the condition is inherited as an autosomal
dominant with complete penetrance and variable expressivity. Each of 44 cases in one study represented
Acknowledgements
new mutations: The disorder has been known to be
This work was supported in part by National Institute of
associated with advanced paternal age.4*l 3 Acquired
Health, National Research Service Award 2 T32 RR 07000hyperplasia of aponeurotic, tendinous, and epimysial 09.
connective tissue were followed by ossification within
The authors also wish to acknowledge a photomicrograph
the sites of fibroplasia. Characteristically, the disease (fig. 7) kindly donated by Dr. M. J. van Zwieten.
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Warren and Carpenter
498
Fig. 5: Histological section of thickened epimysium; abundant dense collagenous tissue of low cellularity adjacent to area
of osseous metaplasia. HE.
Fig. 6: Branches of sciatic nerve surrounded by dense collagenous tissue; foci of osseous metaplasia (arrows). HE.
Fig. 7: Endochondral ossification and trabecular lamellar bone with marrow in lesion of fibrodysplasia ossificans. HE.
Fig. 8: Abrupt transition between myocytes (arrow) with normal endomysium and hypertrophied epimysium with promi-
nent collagen bundles and low cellulanty.
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