Multilobular Tumor of Bone: Case Report and Literature Review

Norman L. Wilt, III, DVM; Kenneth S. Latimer, DVM, PhD; Bruce E. LeRoy, DVM, PhD; Heather L. Tarpley, DVM; Elizabeth W. Howerth, DVM, PhD; Marc Kent, DVM

Class of 2005 (Wilt), Department of Pathology (Latimer, LeRoy, Tarpley, Howerth), and Department of Small Animal Medicine and Surgery (Kent), College of Veterinary Medicine, University of Georgia, Athens, GA 30602

Case History

An 11-year-old, spayed female, Staffordshire terrier was presented to the University of Georgia Veterinary Teaching Hospital for examination of a mass on the cranium (Fig. 1 A and B). The owners first noticed atrophy of the musculature of this dog’s head in October, 2003 and a noticeable incline of the head had developed by April, 2004. The owners also related that the dog had experienced several episodes of disorientation over the past few months.

Figure 1. Frontal and lateral views of a multilobular tumor of bone on the cranium of a dog (the haircoat has been shaved prior to surgery).

Physical examination revealed a large mass on the head. On palpation, the cranial mass was very firm, immobile, and non-painful. It measured 25 cm across the dorsum of the head from ear to ear, 15 cm from the base of the ear forward to the frontal bone, and 8.5 cm from the base of the ears to the dorsum of the head. The remainder of the physical examination was within normal limits.

Clinical laboratory abnormalities included mild leukocytosis (WBC = 15,600 x 10³/µl; reference interval = 5.1 to 13 x 10³/µl), increased alkaline phosphatase activity (ALP = 240 U/L; reference interval = 13 to 122 U/L), and a urine specific gravity of 1.005.

Thoracic radiographs were unremarkable. There was no evidence of pulmonary metastases. Computed tomography (CT) of the head was performed to evaluate the extent of the mass (Fig. 2). Transverse images were made from the level of the third maxillary premolar caudally to the second cervical vertebra. The mass was visualized at the level of the frontal sinuses and extended caudally to the external occipital protuberance. A stippled mineral opacity mass was identified dorsal to and including the calvaria, frontal, parietal, and occipital bones. The mass also involved the right and left frontal sinuses. Proliferation of new bone was observed involving the frontal, parietal, and dorsal occipital bones. The mass extended into the cranial vault, compressing the cerebral hemispheres and thalamus bilaterally. There was a slight deviation of the falx cerebri to the left. The mass measured approximately 12.4 cm in width, 7.5 cm in depth, and 9 cm in length. Enhancement was not appreciated with intravenous administration of 60 ml of sodium lothalamate (Conray 400).

Figure 2. Multilobular tumor of bone involving the skull and extending into the cranial vault, slightly displacing the underlying brain.

An incisional biopsy was taken for histopathology and touch imprints were prepared for cytologic examination. Wright-stained tissue imprints contained scattered, large- to medium-sized mesenchymal cells (Fig. 3A). Moderate anisocytosis and anisokaryosis were present. Individual cells appeared round to spindle-shaped to stellate and often had wispy trails of cytoplasm. Nuclei were often eccentrically located, giving the cells a plasmacytoid appearance (Fig 3B). Individual nuclei were round to oval and had a fine to coarse chromatin pattern that often contained 1 to 3 prominent nucleoli. The cytoplasm of these cells was deeply basophilic and often contained a prominent Golgi zone. Rare cells had dust-like, reddish, cytoplasmic granules. A few multinucleated neoplastic cells, resembling osteoclasts, also were observed (Fig. 3C). Cytological interpretation was a mesenchymal neoplasm, probably an osteosarcoma or chondrosarcoma.

Figure 3. Cytologic appearance of a Wright-stained biopsy imprint of a multilobular tumor of bone. A. Two mesenchymal cells with a stellate to spindle appearance. B. Neoplastic cells with a plasmacytoid (upper left) and spindle (lower right) appearance. C. A multinucleated cell resembling an osteoclast.

Histologic sections were composed of multilobulated neoplastic tissues consisting of irregular islands of well defined bone and cartilage (Fig. 4). The neoplastic islands consisted of osteoblasts and osteoclasts surrounded by spindle cells. Chondrocytes were present within irregular lacunae and were occasionally binucleated. Mitotic figures were rare (< 1 mitosis per 45x field of view). The histologic diagnosis was a low-grade multilobular tumor of bone.

Figure 4. Histologic section of a multilobular tumor of bone containing lobules of cartilage and mineralized bone surrounded by mesenchymal cells (hematoxylin and eosin stain).

Discussion

Although multilobular tumor of bone (MLTB) is reported to be the most common tumor involving the flat bones of the calvaria dogs, it is relatively uncommon.¹ A detailed literature review of this neoplasm is difficult because of the diverse nomenclature applied to this tumor. Other synonyms include chondroma rodens, multilobular osteochondrosarcoma (MLO), calcifying aponeurotic fibroma, multilobular osteoma, multilobular chondroma, juvenile aponeurotic fibroma, cartilage analogue of fibromatosis, and multilobular osteoma and chrondroma (MLO/C).²

Multilobular tumor of bone is a slow growing neoplasm, but it may be locally invasive.² These tumors are likely to recur locally following incomplete surgical resection and have been reported to metastasize to the lungs.^2,3,4 A breed predisposition has not been reported; however, the neoplasm occurs most frequently in older, medium-to large-breed dogs.⁵ Furthermore, MLTB also has been reported in young⁶ and small breed dogs.^7,8 While dogs are the species primarily affected by this tumor, additional cases of MLTB have been reported in human beings,⁹ a horse,¹⁰ and cats.¹¹ The human and animal neoplasms differ distinctly. MLTB in animals often arises on the head (including the mandible, maxilla, zygomatic arch, and tympanic bulla^5,12), while human neoplasms involve the palms and soles.¹³ Age of onset of MLTB also differs between humans and animals. Typically, animals are affected later in life whereas humans are affected at a young age (children and young adults).^9,13

Grossly, MLTB consists of multiple, small, compact, osteocartilagenous lobules.¹³ The consistency of this neoplasm is described as firm and gritty with grayish-white to yellow color.⁵ Radiographically, MLTB appears diffusely nodular or stippled. Computed tomography (CT) is preferred over routine survey radiographs to determine the extent of the neoplasm and involvement of adjacent tissues. CT or magnetic resonance imaging allows three dimensional visualization of the nasal cavity and paranasal sinuses, orbits, calvaria, cranial vault, and various other bone and soft-tissue structures of the head.¹² This information is very important when considering surgical resection.

Microscopically, MLTB consists of small islands of chondroid, osseous, or osteocartilagenous tissue surrounded by spindle-shaped mesenchymal cells.¹⁴ MLTB must be histologically differentiated from other neoplasms such as parosteal sarcoma, ossifying fibroma, benign osteoma, chondroma, chondrosarcoma, and osteosarcoma, as well as dystrophic calcification of soft-tissue. All of these diagnostic possibilities may appear similar radiographically.³ Histologically, MLTB are classified into one of three grades (I, II, or III). The higher the histological grade, the shorter the time until local recurrence following surgical resection, metastasis, and expected survival.⁵ Table 1 presents the criteria for the histologic grading of MLTB.

Table 1. Histological grading criteria for multilobular osteochondroma⁵
(from Dernell et al, 1998).

*HPF= 45x fields of view.

Recently, Dernell et al. (1998) performed a retrospective study (1979-1993) of 39 cases of multilobular osteochondrosarcoma (MLO) in older, large-breed dogs (Table 2).⁵ These neoplasms primarily involved the flat bones of the skull. Cases were selected for study based on a histological diagnosis of MLO and availability of adequate information on each individual. Eighteen different breeds were represented and tumors involved the maxilla, mandible, calvaria, orbit, tympanic bulla, both the orbit and maxilla, and both the zygomatic arch and the maxilla. Of the 39 cases investigated, 13 cases were classified as grade I, 17 were grade II, and nine were grade III. Treatment was attempted in 34 of 39 individuals. Twenty-five dogs were treated with surgery alone while combined surgical and adjuvant therapy was performed in nine dogs. Adjuvant therapy was used in dogs where complete surgical resection was not possible or in patients with histologic evidence of incomplete surgical resection. Adjuvant therapy consisted of surgical implantation of cisplatin-containing polymer, intravenous cisplatin administration, and radiation therapy (none of the dogs were treated with all three methods concurrently). Of the five untreated dogs, three died from neoplasia (two from local neoplasia only and one from local disease and metastatic neoplasia). The median survival time was 24 days (range 2 to 530 days). One dog died from concurrent chondrosarcoma of the pelvis with pulmonary metastasis and one dog was lost to follow-up. Of the 34 dogs subjected to treatment, 19 dogs died from their neoplasia (five with local recurrence, five with metastasis, and nine with both local and metastatic disease). Eleven dogs died from causes unrelated to their neoplastic disease. One dog was alive at 2,340 days post treatment with no evidence of neoplasia and three dogs were lost to follow-up. The median survival time in the 34 treated dogs was 797 days (range 28 to 1,670 days). Local recurrence of the neoplasm occurred in 47% of treated animals. The median time to recurrence was 797 days. Metastasis developed in 56% of treated dogs with a median time to metastasis of 542 days.⁵

Table 2. Survival outcome for multilobular osteochondroma based on tumor grade
(from Dernell et al, 1998).

Treatment

The current treatment protocol for MLTB is early surgical intervention involving complete resection of the neoplasm with attainment of histologically clean borders. Complete excision of large neoplasms involving the flat bones of the skull may involve wide resection of the calvaria below the horizon of the brain and/or removal of the dorsal orbital rims.¹⁵ Wide resection of the calvaria will predispose the brain and eyes to potential trauma and/or infection. Protection of these structures can be provided by molded polymethylmethacrylate implants that cover and protect the brain and orbital structures.¹⁵ Other polymers that have been used to serve as protective implants following removal of skull tissue include polytetrafluoroethylene, high-density polyethylene, polyester and polyamide mesh, and silicate implants.¹⁵ In humans, autogenous bone grafting techniques have been described.¹⁵ Reported complications from surgical implants include pressure necrosis, infection (especially if the implant covers a portion of the nasal sinuses or prolonged pressure necrosis), subcutaneous emphysema, and lagopthalamos.¹⁵ Currently, the effectiveness of adjuvant therapy has not been demonstrated.^4,5 Protocols are currently unavailable for radiation treatment and chemotherapy of MLTB in dogs.

References

1. Slatter D. Textbook of Small Animal Surgery, 3rd ed. W. B. Saunders, Philadelphia, PA, 2003.

2. Straw RC, LeCouteur RA, Powers BE, Withdrow SJ. Multilobular osteochondrosarcoma of the canine skull: 16 cases (1978-1988). J Am Vet Med Assoc 195:1764-1769, 1998.

3. McLain DL, Hill JR, Pulley LT. Multilobular osteoma and chondroma (chondroma rodens) with pulmonary metastasis in a dog. J Am Anim Hosp Assoc 19:359-362, 1983.

4. Withdrow SJ, MacEwen EG. Small Animal Clinical Oncology, 3rd ed. W. B. Saunders, Philadelphia, PA, 2001.

5. Dernell WS, Straw RC, Cooper MF, Powers BE, Larue SM, Withdrow SJ. Multilobular osteochondrosarcoma in 39 dogs: 1979-1993. J Am Anim Hosp Assoc 34:11-18, 1998.

6. Jacobson SA, Chondroma rodens. In Jacobson SA (ed). The Comparative Pathology of Tumors of Bones, part III: Chondroblastic Tumors. Charles C. Thomas, Springfield, IL, 1971, pp. 102-109.

7. Diamond SS, Raflo CP, Anderson MP. Multilobular osteosarcoma in the dog. Vet Pathol 17:759-780, 1980.

8. Fukui K, Takamori Y. Multilobular osteoma (chondroma rodens) in a pekingnese. Vet Rec 118:483, 1986.

9. Allen PW, Enzinger FM. Juvenile aponeurotic fibroma. Cancer 26:857-867, 1970.

10. Richardson DW, Acland HM. Multilobular osteoma (chondroma rodens) in a horse. J Am Vet Med Assoc 182:289-291, 1983.

11. Yildiz F, Gurel A, Yesildere T, Ozer K. Frontal chondrosarcoma in a cat. J Vet Sci 4:193-194, 2003.

12. Hathcock JT, Newton JC. Computed tomographic characteristics of multilobular tumor of bone involving the cranium in 7 dogs and zygomatic arch in 2 dogs. Vet Radiol Ultrasound 41:214-217, 2000.

13. Selcer BA, McCracken MD. Chondroma rodens in dogs: A report of two case histories and a review of the veterinary literature. J Vet Orthopedics 2:7-11, 1981.

14. Jones TC, Hunt RD, King NW. Veterinary Pathology, 6th ed. Williams & Wilkins, Baltimore, MD, 1997.

15. Bryant KJ, Steinberg H, McAnulty JF. Cranioplasty by means of molded polymethylmethacrylate prosthetic reconstruction after radical excision of the skull in two dogs. J Am Vet Med Assoc 223:67-72, 2003.

Acknowledgement

The image American Staffordshire Pit Bull Terrier Art Print, Dog Lithograph by Stephen Kline is from the website galleryNOW.

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