Equine Juvenile Mandibular Ossifying Fibroma

Transcription

1 Vet. Pathol (1988) Equine Juvenile Mandibular Ossifying Fibroma C. C. MORSE, J. E. SAIK, D. W. RICHARDSON, AND A. W. FETTER Laboratory of Large Animal Pathology and Section of Surgery, School of Veterinary Medicine, University of Pennsylvania, New Bolton Center, Kennett Square, PA, and Rorer Group Inc., Fort Washington, PA Abstract. Benign proliferative fibro-osseous lesions of the rostral in six young horses are classified as equine juvenile mandibular ossifying fibroma. Histologically there is a characteristic abrupt transition from subgingival fibroblastic stroma to a zone of proliferating osteoblasts that form irregular spicules of osteoid. The layer of proliferating osteoblasts blends with a deeper zone of bony trabeculae rimmed by osteoblasts and separated by intertrabecular spaces of moderate cellular density. Incomplete surgical excision resulted in local recurrence, while rostral mandibulectomies resulted in no recurrence. The predilection for the rostral of young horses coupled with the similar clinical, radiographic, and histological characteristics supports the classification of this lesion as a distinct entity. Benign proliferative fibro-osseous lesions of animals are uncommon. Osteoma, ossifying fibroma, and fibrous dysplasia, all of which are predominantly found in the intramembranous bone of the skull and, are most freq~ent.~j'j~ Exuberant, disfiguring, productive bony lesions of the rostral in young horses from 2 months to 1 year of age have been described as ossifying fibroma-osteoma,6 ~steoma,~ and osteo~arcoma.~j~ After review of the clinical, radiographic, surgical, and pathological data of six cases, we believe the bony proliferative lesion of these young horses represents a benign tumor that will recur locally if not totally excised. We suggest that this clinicopathologically distinct syndrome should be classified as equine juvenile mandibular ossifying fibroma (EJMOF). Materials and Methods From to 1987, equine juvenile mandibular ossifying fibroma (EJMOF) was diagnosed by clinical, radiographical, and pathological evaluation in six young horses ranging in age from 3 to 12 months (Table 1). All six horses appeared healthy except for a progressively enlarging mass involving the rostral. Routine clinical pathology data were within normal limits. Tissues for histologic examination were obtained by surgical biopsy, fixed in 10% neutral buffered formalin, decalcified, embedded in paraffin, sectioned at 6 fim, and stained with hematoxylin and eosin (HE). Selected sections were stained with Masson's trichrome. Results Horse 1 was a 4-month-old thoroughbred colt with a 3- x 3-cm protruding subgingival mass involving the left caudoventral to the second and third incisor (Fig. 1). The mass was first noticed 7 days prior 415 to admission. Radiographs showed a smooth bony proliferation involving the most rostral aspect of the left. The mass was surgically debulked. After recurrence, the colt reportedly received radiation therapy and went into remission. The colt was sold as a yearling and reported to have died of unrelated causes the following year. Horse 2 was a 3-month-old Arabian colt with a large (10- x 6- x 6-cm) proliferative, ulcerated mass involving the right just caudoventral to the third incisor. The mass was reported to have become progressively larger following a gingival laceration at 1 month of age. Radiographs revealed a soft tissue dense mass with bony proliferation along the rostral right. The mass was surgically debulked. Three months later the colt was readmitted because the mass had recurred. A 6- x 6-cm mass projected from the gingival surface, ventral to the right second and third incisors. The entire mass was removed by a right rostral hemimandibulectomy. recurrence of the tumor has been detected in the 48 months since surgery. Horse 3 was a 5-month-old thoroughbred colt with a 4-week history of a progressively enlarging, bilaterally symmetrical swelling of the rostral with extensive gingival ulceration. Radiographs revealed extensive proliferating bone and osteolytic changes involving the roots of the incisors. The poorly demarcated mass was surgically debulked, with removal of approximately 8 cm of proliferative tissue. The right third incisor was also removed. The mass recurred 4 weeks later, and radiographs revealed marked bilateral osteolysis of the rostral. A bilateral rostral mandibulectomy was done. There has been no detectable recurrence for 26 months.

2 416 Morse et al. Table 1. Horses with mandibular ossifying fibromas. Horse Num- (months) *ge Sex Breed Duration Radiology Site of Lesions ber Male Thoroughbred 7 days Male Arabian 2 months Male Throroughbred 4 weeks Female Throroughbred 3 weeks Male Throroughbred 3 weeks Male Standardbred 2 months Smooth bony proliferation Soft tissue mass with bony proliferation Large bony proliferation with underlying osteolysis of roots of incisors Large, partially calcified mass with lysis of tooth roots and cortical disruption Small flocculent calcified matrix with irregular margins Osteolytic changes of root of incisors with loss of normal contours of Left rostral Right rostral Rostral Rostral Left rostral Rostral Surgical Procedure Debulked Debulked Right rostral hemimandibulectomy Debulked Rostral mandibulectomy Rostral mandibulectom y En bloc Rostral mandibulectomy Recurrence Yes Yes Yes Horse 4 was a 7-month-old thoroughbred filly with a 3-week history of a rapidly enlarging, bilaterally symmetrical, approximately 4- x 3-cm ulcerated mass involving the rostral. Radiographic examination revealed a fairly well-circumscribed, approximately 6-cm soft-tissue dense mass with mottled bony density involving the ventral aspect of the rostral (Fig. 2). There were osteolytic changes extending to the roots of all incisors and evidence of cortical disruption of the. The mass was surgically removed by bilateral rostral mandibulectomy. There has been no recurrence of the tumor in the 22 months since surgery. Horse 5 was a 5-month-old thoroughbred colt with a 3-week history of a slowly enlarging mass of the left. The mass projected 2 x 3 cm from the gingival surface, was round, firm, nonulcerated, and located slightly caudolateral to the left lower third incisor. Radiographic examination of the mass revealed a flocculent, calcified matrix with irregular margins. The mass was removed en bloc, and the base of the lesion was frozen with liquid nitrogen. There has been no detectable recurrence for 28 months. Horse 6 was a 12-month-old standardbred colt with a 2-month history of an enlarging mass involving the rostral that was markedly displacing all the right incisors and the left central incisor. Radiographs showed osteolytic changes of the roots of the incisors and loss of the normal contours of the rostral. A complete rostral mandibulectomy was done. recurrence has been detected after 17 months. Gross examination of the excised rostral s from horses 3, 4, and 6 revealed each horse had a smooth, bilaterally symmetrical bony enlargement which was covered with extensive chronic gingival ulceration (Fig. 3). Horse 6 also had abnormally positioned incisors with hyperplastic gingiva. On cut surface, the proliferative tissue was firm, white to gray, and contained radiating bony islands (Fig. 4). Fragments of bony tissue were received from horses 1 and 2. The specimen from horse 5 consisted of a 2- x 3-

3 Equine Ossifi fing Fibroma 417 Fig. 1. Proliferative bony mass protruding from the left rostral. horse 1. x 2-cm mass of firm, gritty tissue covered by intact gingiva. Microscopic features of all six primary tumors and the two recurrences were similar and consisted of extensive proliferation of both fibrous and osseous elements. The proliferative mass was covered by a markedly hyperplastic or ulcerated gingiva (Fig. 5). The submucosa s normally thick collagenous stroma was replaced by a highly cellular fibroblastic stroma with interlacing fasicles of spindle to stellate-shaped cells which extended to the intact mucosa or blended with the immature granulation tissue below the areas of ulceration. The fibroblastic stroma blended with a zone of osteoblastic cells which were within highly cellular aggregates or were condensing around brightly eosinophilic osteoid (Fig. 6). identifiable periosteum was present, and there was an abrupt transition from the fibroblastic stroma to the formation of bony trabeculae (Fig. 7). The proliferating trabeculae formed perpendicularly to the fibroblastic stroma, in contrast to normal mandibular cortical intramembranous bone formation in which trabeculae form parallel to the periosteum. The fibroblastic stroma consisted of proliferating spindle cells which had oval nuclei with finely stippled chromatin (isochromic) and fusiform, slightly basophilic cytoplasm (isomorphic). Mitotic figures were rarely encountered. The fibroblast-like cells were within an eosinophilic, finely fibrillar collagenous stroma which also contained moderate numbers of blood vessels with pronounced perivascular hyalinization. Within the zone of transition to bony trabeculae, the osteoblastic cells were stellate to cuboidal and had abundant deeply basophilic cytoplasms. Nuclei were oval to round with finely stippled chromatin and one Fig. 2. Radiograph of ossifying fibroma, rostral, horse 4. te flocculent, calcified matrix. to two inconspicuous nucleoli. One to two mitotic figures per ten high power fields were seen (Fig. 8). Toward the central and deeper portions of the mass, the numerous thin radiating bony trabeculae which were rimmed by osteoblasts gradually increased in thickness. Osteocytes were numerous within the trabeculae. Polarization microscopy revealed a meshwork of thick collagen fibers exhibiting a crosshatched pattern indicative of woven bone. Within the deeper and peripheral portions, the bony trabeculae merged perpendicularly with the preexisting mandibular cortical bone. With polarized light, the trabeculae displayed parallel orientation of thick collagen fibers typical of lamellar bone. The intertrabecular spaces contained numerous spindle to stellate-shaped cells in a loose, finely fibrillar collagenous matrix with numerous blood vessels and occasional osteoclasts (Fig. 9). Toward the deeper portions, the intertrabecular cellularity decreased and blood vessels became more prominent. Sections from horse 4 also contained multifocal intertrabecular lymphoplasmacytic aggregates. Discussion In young horses, ossifying fibromas are a benign progressive proliferation of fibro-osseous tissue with predilection for the rostral. Local recurrence is probable if the mass is not totally excised. Ossifying fibromas are characterized histologically by dense fibroblastic stroma somewhat resembling disordered granulation tissue with isomorphic fibroblasts transforming into osteoblasts. The osteoblasts rim relatively

4 418 Morse et al. Fig. 5. Mandibular ossifying fibroma, subgross photomicrograph, horse 4. The bar marks the normal cortical bone contour; note marked proliferation of radiating bony trabeculae. Left second incisor also present within section. Area indicated by square is illustrated in Fig. 7. HE. Fig. 3. Resected biopsy specimen, frontal view, horse 3. Gingival hyperplasia and ulceration overlying the mass. Fig. 4. Sectioned surface of biopsy specimen, ventral view, horse 3. Firm, white to gray mass of proliferative fibrous tissue with radiating bony islands. regular spicules of woven bone within a moderately vascularized fibro-osseous stroma.lljs Ossifying fibroma can be distinguished histologically from fibrous dysplasia, osteoma, and osteosarcoma. Fibrous dysplasia consists of proliferating bony trabeculae within a benign, dense fibrous stroma. However, the bony trabeculae in fibrous dysplasia lack the characteristic rimming by osteoblasts present in ossifying fibroma. Osteoma contains predominantly lamellar bone with intertrabecular fatty or hematopoietic marrow. The connective tissue cells of ossifying fibroma lack the pleomorphism and high mitotic index of osteosarcoma. Ossifying fibromas appear to represent a morphologic continuum involving a spectrum varying from predominantly proliferating dense fibroblastic stroma with or without cords of osteoblasts, to predominantly proliferating bony trabeculae lined by osteoblasts, to thick bony trabeculae lined by inactive osteoblasts and intertrabecular hypocellular ma~~ow.~j~j~~~~ The condition in humans is occasionally subdivided into young, intermediate, and mature types.i4 Difficulty in the diagnosis of fibro-osseous lesions is reflected in the veterinary literature. A recent case report involving a 6-month-old quarterhorse colt with a mandibular mass apparently similar to those presented here was diagnosed as an osteosarcoma, resulting in destruction of the Another extremely large rostra1 mandibular mass reported in a 10-month-old colt, breed not specified, was diagnosed as an osteosarcoma.16 The mass was first noticed at 6 months of age as a small gingival enlargement located below the incisors. At the time of necropsy the mass had enlarged Fig. 6. Rostra1 border, ossifying fibroma in a juvenile horse (horse 3). Wide peripheral zone of proliferative fibroblastic stroma (top) merges with an intermediate zone of proliferative osteoblasts (bottom) which condense to form spicules of osteoid. HE.

5 Equine Ossifying Fibroma 419 Fig. 7. Abrupt transition from the fibroblastic stroma to the trabeculae of woven bone; enlargement of square from Fig. 5. HE. Fig. 8. Intermediate zone of proliferative stellate to cuboidal osteoblasts present condensing around osteoid in an ossifying fibroma, horse 4. HE. Fig. 9. Radiating spicules of woven bone in the deep zone or center of an ossifying fibroma in a young horse (horse 4). Regular pattern of the cancellous bone. Bony trabeculae formed of woven bone tissue and rimmed by osteoblasts. Fibrous stroma of moderate cellular density fills the intertrabecular spaces. HE.

6 420 Morse et al. to 24 x 13 x 28 cm and weighed 9 kg. metastases were reported. The photomicrograph from the mass was remarkably similar to the histologic appearance of the cases reported herein. Therefore, these proliferative fibro-osseous lesions apparently have the propensity for continuous growth, resulting in severe mandibular disfigurement if not surgically 'excised. A comparative survey reported 13 cases of ossifying fibroma-osteoma of the equine skull, stressing the difficulty in separating the two entities. In this series, the age range was 2 months to 6 years, and 92% were located in the jaws.6 Other masses remarkably similar radiographically to ours have been described as osteomas.3 Fibro-osseous lesions have been reported in a variety of other species. Proliferative fibro-osseous lesions of the rostra1 quite similar to our cases have been described in seven greater kudus (Strepsiceros strepsiceros) with an age range of 2 to 18 year^.',^,'^ However, the lesions were classified as fibrous dysplasials or ossifying fibroma.' Suggested pathogeneses include metabolic disorder,i8 neoplastic dis- ease,' or renal hyperparathyr~idism.~ Ossifying fibromas of the and maxilla have been reported in an Anglo-Nubian goat,12 a cat,i7 and four dogs8 In man, ossifying fibromas occur in younger age groups than osteomas (average 21 years versus 34 years), predominantly within the, and local recurrence following incomplete surgical excision has been rep~rted.~~~j~ A subset of ossifying fibromas in man has been reported to behave in an aggressive manner, reaching massive proportions with extensive cortical expansion. Most of these aggressive lesions occur in children and have been designated juvenile aggressive or active ossifying fibroma~.~j~ Some dental and oral pathologists suggest that benign fibro-osseous mandibular lesions in humans are of periodontal membrane origin, since the majority are associated with tooth-bearing ~egions.~.~ In our case series the subgingival fibrocellular stroma and delicate collagen fibers were morphologically similar to periodontal ligament stroma. Also, the fibro-osseous proliferations were intimately associated with the roots of the incisors, and there was radiographic evidence of osteolytic changes involving the roots of the incisors. Also, the young age observed in both man (4 years and horses suggests a strong developmental connection or some unknown interference with the normal intramembranous ossification process of the. The fibro-osseous proliferation observed is remarkably similar to the normal process of intramembranous ossification. Other possible pathogenic mechanisms include trau- ma in hurnan~,'~ and ossifying fibroma ofthe jaws have been reported to be a type of radiation-induced tumor occurring in mice after the incorporation of Ra-224 (Thorium X).'O We conclude that mandibular ossifying fibroma is a clinically, radiographically, and pathologically distinct syndrome of horses less than 1 year of age. Complete surgical excision resulted in no detectable recurrence in five of the six cases presented. We propose that this syndrome be classified and referred to as equine juvenile mandibular ossifying fibroma until sufficient numbers of cases have been recorded to further characterize the pathogenesis and biological behavior of this proliferative fibro-osseous lesion. Acknowledgements The authors thank Drs. L. C. Johnson, R. R. Pool, D. M. Gillette, and H. M. Acland for consultation and assistance. References 1 Boever WJ, Kennedy S, Kane KK: Ossifying fibroma in a greater kudu. Vet Med Small Anim Clin 72: , Eversole LR, Leider AS, Nelson K Ossifying fibroma: a clinicopathologic study of sixty-four cases. Oral Surg Oral Med Oral Pathol 60: , Gallina AM: Bone and joint pathology. In: Equine Medicine and Surgery, ed. Mansmann RA, McAllister ES, and Pratt PW, 3rd ed., pp American Veterinary Publications, Santa Barbara, Halliwell WH, Hahn FF Fibro-osseous lesions in the and maxilla of greater kudus. In: The Comparative Pathology of Zoo Animals, ed. Montali FU and Migaky G, pp Smithsonian Institute Press, Washington, DC, Hamner JE, Scofield HH, Cornyn J: Benign fibro-osseous jaw lesions of periodontal membrane origin: an analysis of 249 cases. Cancer , Jacobson SA: Ossifying fibroma and osteorna. In: The Comparative Pathology of the Tumors of Bone, pp Charles C Thomas, Springfield, IL, Jubb KVF, Kennedy PC, Palmer N: Pathology of Domestic Animals, 3rd ed., vol. 1. Academic Press, Orlando, FL, Liu SK, Dorfman HD, Hurvitz AI, Patnaik AK: Primary and secondary bone tumors in the dog. J Small Anim Pract 18: , Livesey MA, Wilkie IW: Focal and multifocal osteosarcoma in two foals. Equine Vet J 18: , Luz A, Hindringer B: Ossifying fibroma of the jaws in mice after incorporation of Ra-224 (Thorium X). Verh Dtsch Ges Pathol 54: , Pool RR: Tumors of bone and cartilage. In: Tumors in Domestic Animals, ed. Moulton JE, 2nd ed., pp University of California Press, Berkeley, Pritchard GC: Ossifying fibroma in an Anglo-Nubian goat. Goat Vet SOC J 5:31, Reaume CE, Schmid RW, Wesley RK: Aggressive ossifying fibroma of the. J Oral Maxillofac Surg 43: , 1985

7 14 Smith AG, Zavaleta A: Osteoma, ossifying fibroma, and fibrous dysplasia of facial and cranial bones. Am Med Assoc Arch Pathol 54: , Spjut HJ, Dorfman HD, Fechner RE, Ackerman LV: Tumors of bone and cartilage. In: Atlas of Tumor Pa- Equine Ossifying Fibroma 42 1 thology, 2nd series, fasc. 5, pp Armed Forces 147~ , 1965 Institute of Pathology, Washington, DC, Thorp F Jr, Graham R: A large osteosarcoma of the. J Am Vet Med Assoc 84: , Turrel JM, Pool RR: Primary bone tumors in the cat: a retrospective study of 15 cats and a literature review. Vet Radio1 23: , Williamson WM, Lombard LS, Firfer HS: Fibrous dysplasia in a monkey and a kudu. J Am Vet Med Assoc Request reprints from Dr. C. C. Morse, Parke-Davis Pharmaceutical Research Division, Warner-Lambert Company, 2800 Plymouth Road, Ann Arbor, MI (USA).