Oral fibrosarcoma

Oral fibrosarcoma Peter C. Reade, Y.D.S., Ph.D., F.D.S.R.C.S. (Eng.), and B. G. Radden, B.D.Sc., Ph.D., P.D.S.R.C.S. (Ihg.), Adelaide, South Australia DENTAL

SCHOOL,

UNIVERSITY

OF ADELAIDE

T

he recognition of fibrosarcoma constitutes one of the most baffling problems of oncology. Because of this, Stout,l in his extensive review on the subject, suggests that a number of different conditions have been confused with fibrosarcomas. Willis’ considers that between the cellular anaplastic, highly malignant form of fibrosarcoma and the slowly growing, densely fibrous benign growths that structurally resemble normal fibrous tissue there is a complete series of neoplasms of intermediate structure and behavior. He states that neoplasms which primarily produce fibrous tissue cannot bc sharply demarcated from other mesenchymal growths which can have a.rca.s of met.apl&ic change simulating other tissues. Oral fibrosarcomas are rare lesions and, as in other regions of the body, their identity is difficult to establish. Some authors attempt t.o subdivide these lesions in the jaws into those arising from odontogenic tissues and those arising from osteogenic t.issues, but BcrnieP claims that no clear-cut example of an odontogenic fibrosarcoma has been reported. It would appear extremely difficult to establish such a diagnosis. However, Bernier3 considers that fibrosarcomas of the jaws may be of peripheral (periosteal) or central (endosteal) origin. Van Wyk and Jonck4 have rerently reported two cases of tibrosarcoma of the jawsone of peripheral origin and the other considered to be of central origin. They have described the difficulty experienced in making the diagnosis of a. cent.rally arising fibrosarcoma. Stout? and Geschichter 5*o doubt the existence of such an entity as the endosteal fibrosarcoma and suggest that this lesion is probably a poorly differentiated osteogenic sarcoma or chondrosarcoma. Both of these authors claim t.hat fibrosarcomas can arise in either the periosteum or the periosteal tissues, and they agree that t,he latter is frequently the more malignant and has a greater tendency to invade bone. It seems, however, that such fine 217

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distinctions can rarely be made cxccpt in the very earliest of lesions. For example, as soon as the periosteum is involved by a fibrosarcoma extending from the surrounding tissues, it. becomes difficult to detcrminc the origin of the lesion. Further difficulty is encountered in det.ermining which of t.hese lesions has the greater capacit.y to inva.de bone. Diffcrcntiation between a fibroma and a fibrosarcoma may be extremely difficult, and Stout’ suggests that in some cases the histologic picture may be the same. He says that in these cases diagnosis is dependent on such clinical criteria as size and behavior of the lesion. In a number of recorded eases of fibrous tissue tumor of the jaws, no fina. decision was made as to whether the tumor was benign or malignant. In view of the experimental work of Bhaskar and Lilly,’ which demonstrated that chronic trauma can produce lesions resembling sarcomas, it seems reasonable to doubt the neoplastic nature of some of the reported cases. It is clear, therefore, that there are considerable difficulties to be found in establishing a diagnosis of fibrosarcoma and, consequently, in making a realistic prognosis and performing adequate therapy. For this reason, we have undertaken a review, with particular reference to oral fibrosarcomas, in an attempt to clarify as far as possible the confusion surrounding this subject. We arc presenting two cases which illustrate the criteria used for diagnosis and the extremes in presentation and behavior of this neoplasm. CASE

1

man presented for investigation and treatment of a painful slvelling which for 2 weeks in the upper left buceal sulcus. Although the patient had an extensive medical history, none of it was relevant to the present complaint. Examination of the head and neck disclosed a diffuse soft enlargement of the face, detectable in the upper left maxillary region. Intraoral examination revealed many carious teeth, including carious remnants of the upper left first and second incisors and the upper left canine. No upper left posterior teeth were present. There was a diffuse soft swelling, extending from the apical region of the canine area to the molar region, in the upper left vestibule. Radiographic examination of this region showed a diffuse radiolucent area extending posteriorly from the apex of the upper left second incisor and involving the apex of the upper left canine. Surgical removal of the root fragments of the upper left central and lateral incisors and the upper left canine was not followed by a reduction in the size of the swelling. Although them appeared to be some fluctuation in the swelling, no fluid contents could be obtained by aspiration. Further investigations mere considered necessary, and the patient was admitted to the hospital for exploration of the upper left maxillary region under general anesthesia At operation, reflection of the buceal mueosa over the upper left maxillary region disclosed a grayish, rubbery mass extending from a perforation in the lateral wall of the left maxilla into the muscle of the cheek. The bony perforation measured 1.5 by 1.0 cm. Exploration of the left maxillary sinus showed that the entire sinus cavity was occupied by the msss and that, following its piecemeal removal, all the bony walls of the sinus were involved. The flaps were replaced and sutured. Histologic examination showed the mass to be a pleomorphic fibrosareoma (Fig. 1). Sections taken from numerous pieces of tissue had essentially the same histologic appearance markedly pleomorphic, the of very cellular fibrous tissue with areas of necrosis. Although cells were predominantly of a fibroblastic type. There were some multinucleated cells with appearances of a syncytial arrangement. Mitotic figures were present in moderate numbers. Immature blood vessels with thin walls were also obvious, and there was evidence of thrombosis A 73-year-old had been present

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pleomorphic cell1 Case “i. Ai -~h&omikgrsph of-biopsy speeinien showin B, High-power photomicrograph showing examples o5 bizarre mitotic

tumor

I. (Hematoxylin

2 19

and eosin stain.)

occurr ing in snme of the vessels. It was suggested that, because of the rolative pleomo of the! cells, this tumor may have been more sensitive to radiotherapy t.han many fibrosa trcomas. examination of the patient disclosed the presence of a diffuse svveiling, PCjstoperativc posterior and i nferior appeal ring as a soft fleshy mass, in the cervical region immediately to the angle of t.he mandible and extending into the deep cervical region. The swelling vPa8 not margins; and it measured approximately 1.5 cm. in diameter. It was toncler ‘; it had indistinct

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not possible to determine whether this lymph node was involved by neoplastie infiltration, but on subsequent clinical examinations it was no longer palpable. Radiotherapy, chosen in preference to radical surgical removal of the left maxilla, was commenced and continued for 2 months. Three weeks after completion of this treatment there was persistent pain in the region, and the radiotherapist reported that there was evidence of the continuation of active disease. Intraarterial infusion of 5-fluoro-uraeil was instituted, and this was followed by a significant improvement in the patient’s condition. Twelve months later the patient returned, complaining of pain in the area of the left maxillary sinus. No facial swelling was apparent. It was decided that surgical exploration of the involved sinus was indicated, and, under general anesthesia, the sinus was opened through a Caldwell-Luc approach. No evidence of tumor was found, and, except for one small nodule, the epithelial lining was smooth and intact. Home mucopus was present in the sinus, and it was thought that an infection was the cause of the patient’s pain. Histologic examination of the nodule showed no tumor to be present. CASE 2 A 14-year-old boy was referred by his general dental practitioner for investigation and treatment of an ulcerative lesion between the lower left canine and the lower left premolar. The patient complained of a dull ache which had been present in this region for 6 months. The patient had been aware of a small lump for about 3 months. Aside from routine dental treatment, the only significant fact in the dental history was that an impacted lower left premolar had been removed surgically for orthodontic purposes 5 years previously. There was no relevant medical history. Examination revealed an apparently healthy boy. Bilateral enlargement of lymph nodes in the upper deep cervical region was assumed to be due to a common cold from which the patient was suffering when examined. All teeth except the third molars and the lower left second premolar were present. Between the lower left canine and first premolar there was an ulcerated area, about 0.5 cm. square, associated with considerable loss of normal interdental structure. The surface of the ulcer was granular and grayish red; its margin was indistinct. The ulcer was not painful to palpation; there was no discharge and only slight hemorrhage on palpation. The contiguous mucous membrane appeared unaffected. Deep periodontal pockets, up to 10 mm. in depth, were present on the distal aspect of the lower left canine and the mesial aspect of the lower left first premolar. Both of these teeth exhibited slight mobility, but neither of them was periostotic. The teeth mere at tho

Fig. 8. Case 2. Lateral lower left canine and flrst

jaw radiograph showing premolar giv&ng evidence

well-de6ned radiolucent lesion between of resorption of bone and tooth roots.

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normal occlusal level, although the first premolar was tipped mesially and contacted the distal aspect of the canine. Radiographs disclosed the presence of a radiolucent area between these teeth and showed extensive resorption of their roots (Fig. 2). This resorption was irregular and appeared to involve the root canals of both teeth. The boric surrounding the lesion exhibited no gross changes. No further defects were disclosed by radiographic examination of the remainder of the skclcton, by serum chemistry, or by hematologic examination. Microscopic examination of a fragment of soft tissue removed from the buccal aspect of the lesion disclosed an ulcerat.ed oral mucosa with a chronic inflammatory infiltration. Beneath

A

B

reb&ively uniform cellular Fig. 3. Case 2. A, Photomicrograph of biopsy sphmeh &o&g nature of tumor. B, High-power photomicrograph showing area of muWnucleated pleomorphic cells close to epithelial Rnrface. (Hematoxylin and eoain stain.)

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of fibrous tissue, the cpithclium there was a very cellular neoplasm, composed predominantly although thero was lit.tle or no mature collagen. The cells were mostly spindle shaped, and in some places they exhibited palisading. Mitoses were not frequent, but multinucleated cells were present in one area. Pleomorphism and, to a lesser extent, polychromatism were evident. Some hemorrhage was present, hut there was no evidence of encapsulation. The histologic appearance was that of a fibrosarcoma of a low grade of malignancy (Fig. 3). Consultation with two general pathologists led to confirmation of this diagnosis, and adequate local excision was recommended as the best treatment available. This recommendation was reaffirmed by a radiotherapy consultation board. Under general anesthesia the lower left canine and first premolar in a block of surrounding tissue were removed. The operation site was then closely inspected t.o determine whether the lesion had extended beyond tho limits of the excision. No evidence of neoplaatic infiltration could be seen. The wound was cleaned, rough bony edges were smoothed, and the lingual mucosal flap was sewed across the mandibular defect with interrupted sutures. Healing was rapid and uneventful. Histologic examination of serial sections of the excised specimen cut in a mesiodistal plane showed evidence of considerable resorption of the roots of both teeth, and in the case of the lower left canine the pulp was involved. This resorption appeared to be inactive at the time of removal, but there was little indication of deposition of calcifie repair tissue on the tooth roots. The area between the two roots showed absence of bone and was occupied almost entirely by young granulation tissue with only a small area of the original fibrous tumor tissue remaining. The patient has now been followed for 4 years and there is no evidence of recurrence of the lesion.

DISCUSSION

Considerable difficulty is often experienced in making a diagnosis of fibrosarcoma. Difficulties occur not only in distinguishing fibrosarcomas from other sarcomas but also in determining whether a fibrous tissue growth is benign or malignant, or even whether it is a tumor or a connective tissue hyperplasia. Although the difference between a fibrosarcoma and other sarcomas may be considered essentially academic, it is important to note that in many cases of fibrosarcoma there is a significantly better prognosis than in cases involving other sarcomas. Strenuous efforts should be made, therefore, to determine the exact nature of a suspected sarcoma. By the use of connective tissue stains, such as Van Gieson’s for collagen and silver stains for reticulin fibers, it is often possiblc to determine whether a sarcoma is, in fact, producing fibers. In that way a fibrosarcoma can be distinguished from sarcomas arising from muscle, fat, or bone. It is perhaps of even greater importance, however, to distinguish between benign fibromas and their malignant counterparts. The reliability of employing the usual histologic criteria for determining the degree of malignancy of a fibrous tissue tumor has been questioned by Stout,l because in some instances the histologic appearances of fibroma and fibrosarcoma have been very similar. Stout suggests that in these circumstances clinical evidence must be used to determine the degree of malignancy. A similar opinion has been expressed by O’Day, Soule, and Gores,8 who add that the successful treatment of a fibrosarcoma may depend more on the size and location of the lesion than on the grade of malignancy as determined by histologic evidence. Alt,hhm~rrh it

icl tme

thnt.

classic signs of being either

fihrnn~~~m~n,

benign

like

or frankly

nt.hw

tl1mnpFI:

malignant,

pxi&,

with

t,he

such lesions seldom

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give rise to difficulties in diagnosis. It is the borderline lesions which pose the problems. Many of the classic histological signs of malignancy a.ppear inadequate to distinguish bctwecn such neoplasms. The presence or absence of a detectable capsule is not reliable, for many clinically benign lesions appear to have no recognizable capsule and, in fact, may cvcn appear locally invasive. Nuclear activity is also misleading, for in malignant lesions there may be only small numbers of mit.ot.ic figures, and bizarre mitoses may bc absent. Pleomorphism of cells, hyperchromatism of nuclei, and imma.turity of cells arc other features that may be misleading. Howcrcr, immature blood vessels in the tumor and areas of necrosis are more likely to occur in the malignant forms than in the benign lesions. The difficu1t.y in distinguishing between a fibroma and a low-grade fibrosarcoma in the oral region is similar to that encountered in any other region of the body. Ward and Hendrick9 describe a case of a centrally occurring fibroma which, 6 years later, became frankly fibrosarcomatous. It is possible, however, that this lesion was malignant initially but inactive in its behavior. Burch and Woodward10 reported the case of a lCyear-old girl with a fibrous tissue tumor in the mandible which was similar in many respects to our Case 2. Their patient showed signs of bone destruction and tooth root resorption, and there was histologic evidence of muscle invasion. Although histologic examination of the lesion showed marked cellularity, there was little plcomorphism and no mitotic figures were seen. Eventually, after consultation with several tumor boards, it was decided that this lesion was probably benign although there were signs of local invasion. Conservative surgical removal was followed by no recurrence of the lesion over a 3 year period. This lesion obviously had both benign and malignant properties, yet, from its over-all clinical behavior, it must be considered a benign lesion. The report of this case serves as additional evidence to illustrate the difficulties experienced in the diagnosis of this t.ype of lesion. Many fibrous tissue prolifera.tions, usually resulting from chronic inflammatory processes, may rcscmble fibrosarcomas both clinically and histologically. Stout? states that a number of fibrous tissue proliferations probably have been misdiagnosed as malignant tumors. This nmy account for some of the fibrosarcomas reported and may, in turn, lead to an incorrect estimation of the prognosis of t.ruc fibrosarcomas. Trauma may be followed by unusual fibrous tissue proliferations. Bhaskar and Lilly7 have observed patients with persistent ulcera.tive lesions of the oral mncosa. which harp hecn misdiagnosed, on the basis of their hist,ologic appeara.nces, as sarcomas but which, on clinical grounds, have been caused by healing traumatic injuries. Those authors? by subjecting animals to chronic f.rauma, have produced lesions which superficially resembled maligna.nt mcsenchymal tumors and yet were bizarre connective tissue reactions. Although the role of chronic trauma in the production of tumors is uncertain, this work by Bhaskar and Lilly showed that lesions resembling tumors may result from trauma. It is therefore of interest to postulate whether the surgical removal of a lower premolar in Case 2 initiated the lesions which subsequently developed in that area. Several cases have been reported in which a fibrosarcoma has arisen at the

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site of a previous dernal cxt,raction. For cxamplc, MarkI’ has reported the cast of an l&year-old girl who developed what was considcrctd to bc a central fibroma in a region where a tooth had been extracted some yea.rs previously, and Stuteville12 has described a fibrosarcoma arising in the mandible of a &year-old man in the region of a previous dental extraction. Although the cause of fibrosarcoma is not known, these lesions have been produced experimentally in rat submaxillary salivary glands by the injection of 3 :4 benzpyrene in corn oil .I3 It may now be possible to study the early stages of fibrosarcoma formation with a view to determining the exact nature of the distinction between fibroma and fibrosarcoma, particularly from the histologic standpoint. Hoggins and Brady14 claim that these tumors are invariably found in patients below the age of 50 years, and usually between the ages of 20 and 40 years. It is our experience that this claim is incorrect, for the age incidence appears to be extremely wide and cases have been reported in patients between 6 and 72 years of age. In cases of fibrosarcoma radiotherapy is usually avoided, for it is generally believed that these tumors are relatively insensitive to radiation. Surgical removal is often followed by good results, and a number of published reports support the use of this method.12-14 If there is doubt that a fibrous tissue tumor is malignant, adequate surgical excision is the treatment of choice. Fibrosa.rcomas occur in the oral region, however, where surgical removal is frequently too mutilating, as in Case 1. In these cases, the administration of cytotoxic drugs by local arterial infusion might be preferable to radiotherapy. In Case 1 radiotherapy was tried and found unsatisfactory, but the use of cytotoxic drug infusion techniques appears to have been of considerable value; although this patient has been followed for only 12 months, no recurrence has been found. The incorrect diagnosis of simple fibrous tissue hyperplasias as fibrosarcomas has possibly confused our understanding of the metastatic capacity of this tumor. It seems that metastases arc infrequent, and when they occur it is likely to be late in the disease.‘* I2 We have had an opportunity to review the records of a patient in whom a pathologic fracture in the femur was caused by a fibrosarcoma of the thigh. The patient was a 60-year-old woman who died 21/ years after the initial pathologic fracture. At autopsy there was evidence of only one metastatic lesion, and that was in a rib. It had the typical appearance of a uniformly cellular fibrosarcoma, and it had destroyed bone. The only case we could find of a metastatic lesion in the jaws was recorded by Breslin. l6 In that case a 32-yea.r-old man had a metastatic fibrosarcoma, the primary site in the thigh having been diagnosed 3 years previously. The prognosis for fibrosarcomas may, therefore, be described as significantly better than for other sarcomas. They metastasize late, if at all, and they are amenable to both surgical and cytotoxic drug infusion treatments. Their diagnosis remains a problem which can be solved to some extent by careful attention to the numerous variables which inevitably accompany these lesions.

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SUMMARY In this report we have presented the problems surrounding the diagnosis of fibrosarcomatous lesions, particularly those of t.hc mouth. The variable clinical and histologic features of this neoplasm have been described, and the simi1arit.y t.o fibrous tissue hyperplasias and healing wounds has been discussed. Criteria for distinguishing fihrosarcomas from other true neoplasms and pseudoneoplaams haye been reviewed. Two cases which illustrate the variability of presentation and the problem of diagnosis have been reported. The authors wish to thank Professor J. S. R.obertson for his permission to review material in the Department of Pathology and Mrs. I. &&ski of the Phot.ographic Section of the Dental School for her assistance with the illustrations. REFERENCES

1. Stout, A. P.: Fibrosarcoma, Cancer 1: 30-63, 1948. 2. Willis, R. A.: Pathology of Tnmonrs, ed. 2, London, 1953, Butterworth & Co., Ltd., pp. 647-648. 3. Bernier, J. L.: The Management of Oral Disease, ed. 2, St. Louis, 1959, The C. V. Yosby Company, pp. 601, 821. Fibrosarcoma of the Upper Jaw and 4. Van Wyk, C. W., and Jonck, L. M.: A Peripheral a Central Fibrosarcomatons Tnmonr of the Lower Jaw, J. D. A. South Africa 19: 18-22, 1964. of bone; Bone Involvement by Sarcoma of 5. Geschichtcr, C. F.: So-called Fibrosarcoma Neighboring Soft Parts. Arch. Burg. 24: 231-291, 1932. 6. Geschichter, C. F.: Boric Tumors, Am. J. Roentgenol. 34: l-29, 1935. Injuries on Rat Tongue, I.A.D.R. 7. Bhaakar, 8. N., and Lilly, G. E.: Effect of Traumatic 40: 64, 1962 (abstract). Soft Tissue Sarcomas of the Oral 8. O’Day, R. A., Sonle, E. H., and Gores, R. J.: Primary Cavity, I.A.D.R. 41: 93, 1963 (abstract). of Tumors of the Head 9. Ward, Cr. E., and Hendrick, .J. W.: The Diagnosis and Treatment and Neck, Baltimore, 1950, Williams & Wilkins Company, p. 364. 10. Bnrch, R. a., and Woodward, H. W.: Central Fibroma of the Mandible, J. Oral Burg. Am&h. & Hosp. D. Serv. 18: 432-435, 3960. 11. Mark, II. I. : Central Fibroma of t.he Mandible, ORAL SURG., ORAL MED. & ORAL PATH. 8: 366-371, 1955. 12. Stnteville, 0. H.: Fibrosarcoma of the Mandible, Quart. 13~11. Northwestern Univ. M. School 29: 400402, 1955. 13. Channcey, H. H., Shklar, Cf.? and @int.arelli, G. : Histochemist,ry of Experimentally Induced Fibrosarcoma in Rat Submaxillary Gland, ORAJ, SIIRG., ORAL MED. & ORAL PATH. 18: 389-398, 1964. of the Maxilla, ORAL SURG.. ORAL MED. & 14. Hoetins, G. S.. and Bradv. C. L.: Fibrosarrcoma 15. Fletcher, ,J. P., and Ckabb, H. A. M.: Fibrosareomat,ons Epnlis, ORAJ. SURG., ORAJ, MED. & ORAL PATH. 14: 1091-1098, 1961. of the Mandible, J. Canad. I). A. 22: 351-153, 1956. Lti. Breslin, W. W.: Fihrosarcoma