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 Downloaded from vet.sagepub.com at PENNSYLVANIA STATE UNIV on May 17, 2016 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- Downloaded from vet.sagepub.com at PENNSYLVANIA STATE UNIV on May 17, 2016 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. Downloaded from vet.sagepub.com at PENNSYLVANIA STATE UNIV on May 17, 2016 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. Downloaded from vet.sagepub.com at PENNSYLVANIA STATE UNIV on May 17, 2016 Feline Fibrodysplasia Ossificans 499 References 1 2 3 4 5 6 7 8 9 P.V.; VARNER, H.H.; WESTPHAL,M.C.: Studies on alkaline phosphatase activity in cultured cells from a patient BERATIS, N.G.; KAFFE,S.; ARON,A.M.; HIRSHORHORN, with fibrodysplasia ossificans progressiva. Lab Invest 37:254-259, 1977 K.: Alkaline phosphatase activity in cultured skin fibroUeber myositis ossificans progressiva. Z blasts from fibrodysplasia ossificans progressiva. 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Semin Arthritis Rheum 4:369-380, 1975 ultrastructural studies in fibrodysplasiaossificansprogressiva (myositis ossificans progressiva). Am J Pathol 18 THICKMAN, D.; BONAKDAR-POUR, A.; CLANCY, M.; VAN 87:483-492, 1977 ORDERN, J.; STEEL,H.: Fibrodysplasia ossificans progresMILLER,R.L.; MAXWELL, W.A.; SPICER,S.S.; HALUSKA, siva. AJR 139:935-941, 1982 Request reprints from Dr. Henry B. Warren, Department of Pathology, Brigham and Women’s Hospital, 75 Francis Street, Boston, MA 02 1 15 (USA). Downloaded from vet.sagepub.com at PENNSYLVANIA STATE UNIV on May 17, 2016
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