46 J. max.-fac. Surg. 14 (1986)

J. max.-fac. Surg. 14 (1986) 46-52 © Georg Thieme Verlag Stuttgart • New York

Myxoma of the Jaws An Analysis of 15 Cases

Pieter J. Slootweg, Albert R. M. Wittkampf

Department of Oral Pathology (Head: P. J. Slootweg, M. D., D. M. D.), State University Utrecht and Clinic for Maxillofacial Surgery (Head: Prof. P. Egyedi, M.D., D. M. D.), University Hospital Utrecht, The Netherlands

Submitted 20.12. 1984; accepted 4.3. 1985.

Introduction

Since first described by Tboma and Goldman (1947), myx- omas of the jaw have continually been the subject of much debate. The discussion has mainly been on therapy with recommendations varying from enucleation (Zimmerman and Dahlin, 1958) to extensive surgery followed by radiotherapy (Killey and Kay, 1964). Also the derivation from odontogenic tissues, originally proposed by Tboma and Goldman (1947) and generally accepted by the major- ity of other authors is based on circumstantial evidence as recently stressed by Adekeye et al. (1984). Moreover the discussion has been complicated by the possibility that other tumour entities have been included in some series of myxomas, mimicing these by myxomatous degeneration (Fu and Perzin, 1977; Adekeye et al., 1984). The purpose of the present paper is to present data from 15 patients with jaw myxoma with emphasis on biological behaviour and histological features that permit differentia- tion from other myxomatous jaw tumours.

Material and Methods

During I953-1984, 15 cases of myxoma were be obtained from the files of the Department of Oral Pathology of the

Summary

A retrospective study on 15 patients with myxomas of the jaws was carried out. The series consisted of 3 males and 12 females. The mean age was 26 years. The maxilla was involved in 4 cases whereas the tumour was situated in the mandible in 11 cases. Of the 9 patients who underwent conservative treatment, one exhibited recurrent tumour. Six patients were treated by resection including uninvolved adjacent tissue; none of them has so far exhibited recurrence. These results indicate that carefully performed conservative treat- ment for myxomas is justified in some instances. Histologically, myxomas of the jaw exhibit mitotic activity in the majority of cases which indicates a distinct proliferative activity. Myxomatous degenera- tion in neurofibromas may mimic myxoma. Therefore the present cases were compared with 2 cases of intramandibular neurofibroma. It is concluded that differences in nuclear morphology are sufficient to distinguish between both neoplasms.

Key-Words

Jaw tumours - Myxoma - Neurofibrolna - Follow up

TOTAL NUMBER

OF

CASES

15

• . . , . . . . , . . . . , . . . . ,

0 ]5 25 35 45

AGE IN YEARS

Fig. 1 Diagrammatic depiction of distribution of the present myxoma series according to age and sex.

Fig. 2 Multilocular radiolucency in the posterior mandible, This myxema shows the typical "soap-bubble" appearance which consists of a a scalloped radiolucency in which coarse bony trabecuiae sepa- rate individual cavities.

Fig. 3 External root resorption of a premolar tooth by a mandibular myxoma of the multilocular type,

Myxoma of the jaws J. max.-fac. Surg. 14 (1986) 47

Fig. 4 Maxillary myxpma with cortical bulging and tooth displace- ment. Atso in this case, tiny bone septa traverse the radiolucent lesion while crossing each other.

Fig, 5 Radiographed surgical specimen of a mandibular neurofi- broma. In the mandibular body, the picture is obscured by excessive reactive periosteal bone apposition, but in the ramus a multilocular "soap-bubble" appearance similar to myxoma is observed.

Table 1 Clinical data of reported patients.

Case no. Age in years Sex Time interval between Location at time of onset of symptoms diagnosis and diagnosis

Therapy Follow-up

1. 37 F 7 years*

2. 25 F 2 years

3. 25 F 6 months

4. 35 F 3 months

5. 31 F 4 years**

6. 30 M 2 years

7. 26 F 1½ year

8. 32 M 2 years

9. 40 F 1 year

10. 15 F 1 year

11. 29 M 3 months

12. 19 F ?

13. 14 F 6 months

14. 21 F 1 month

15. 14 F ?

mandibular premolar- molar area

maxillary canine premolar area

interradicular between mandibular molars

mandibular body and ascending ramus

mandibular premolar- molar area

maxillary molar area

mandibular molar area

mandibular body and ascending ramus

maxillary premolar- molar area

mandibular premolar- molar area

mandibular premolar- molar area

maxillary premolar- molar area

mandibular premolar- molar area

mandibular premolar- molar area

anterior mandible

enucleation, curettage

resection

excision, curettage

excision, c u rettag e

enucleation, curettage

resection

enucteation, curettage

enucleation, curettage

excision

enucleation, curettage

enucleation, curettage

resection

resection

resection

resection

no evidence of recurrence after 31 years

no evidence of recurrence after 30 years

no evidence of recurrence after 28 years

no evidence of recurrence after 27 years

no evidence of recurrence after 23 years

refused to attend for follow- up after 24 years

lost to follow-up after 1 year

died of other cause after 14 years

no evidence of recurrence after 15 years

no evidence of recurrence after 14 years

recurrence after 15 years

no evidence of recurrence after 9 years

no evidence of recurrence after 8 years

no evidence of recurrence after 6 months

no evidence of recurrence after 6 months

* Including initial treatment elsewhere 7 years previously * * Including initial treatment elsewhere 4 years previously

48 J. max.-fac. Surg. 14 (1986) Pieter J. Slootweg, Albert R. M. Wittkampf

Fig. 6 Transected surgical specimen of a mandibular myxoma. The white glistening tumour mass fills a bony cavity, without encapsula- tion. (Same case as shown in Fig. 4).

Fig. 7 Transected surgical specimen of a mandibular neurofibroma. In contrast to myxoma, the cut tumour surface is dun and fibrous whorls are macroscopicaily visible.

e + + + , + + - + : , + . } + +

Fig. 8 The myxoma infiltrates into the marrow spaces while leaving the bony structures initially uninvolved. Cortical (top) as well as cancellous bone are still present whereas the marrow spaces are completely replaced by tumour. HE, x 24.

University of Utrecht. These cases formed part of a total number of approximately 15.000 specimens that were received in our diagnostic service during the same period.

For comparison, 100 cases of ameloblastoma were dia- gnosed during this time span. Histological slides were reviewed. Additional sections (7 bt) were processed and stained with haematoxylin-eosin, Alcian Blue and van Gieson techniques. Slides were examined for the presence of cellular and nuclear pleomorphism, mitotic activity, binucleate cells, odon- togenic epithelium and invasion into surrounding tissues. Moreover, the presence of alcianophilic myxomatous mate- rial and fibrous tissue stained by the van G~eson method were scored. Clinical and radiographic data, including follow-up, were present in the files of the Clinic for Maxillofacial Surgery of the University Hospital. Clinical data of the patients reported are presented in Table 1. Two patients (cases 1, 5) had undergone initial limited treatment elsewhere without additional diagnostic procedures or pathological investiga- tion. They have been considered as if no initial therapy had been given. Two patients with neurofibroma of the mand- ible (M, 52 yrs.; F, 25 yrs.) were included for comparison of radiological and histological features.

Results

Clinical data Age and sex distribution are illustrated diagramatically in Fig. 1. There were 3 males and 12 females (20 % : 80 %). The mean age at time of diagnosis was 26 years. The age of all patients was between 10 and 40 years. In 4 cases, the turnour was situated in the maxilla whereas in 11 cases the mandible was the site of disease. In the maxilla the turnout involved the canine-premolar area in one case, the other 3 being located in the premolar-molar area. In the mandible, 8 cases were located in the premolar- molar area, 2 cases extended from the mandibular body into the ascending ramus and one case was located in the anterior mandible. All patients presented with a painless swelling. In one patient, loose teeth and paraesthesia of the mandibular nerve were additional tumour signs. The mean time interval from onset of symptoms until diagnosis was 1.6 year with a range from 1 month to 7 years.

Myxoma of the jaws J. max.-fac. Surg. 14 (1986) 49

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i

I "

.~ f . ~4 / " "

Fig. 9 Nests of odontogenic epithelium are only encountered spora- dically in myxoma. They should be considered to be a fortuitous feature and are by no means atypical diagnostic appearance. HE, x 60.

Fig. 10 Binucleate tumour cells are a constant feature in myxoma. HE, x 320.

Radiographic features Radiographs were not available in 2 cases. In the remaining 13 cases, radiographs showed a rather variable appearance. The following 2 patterns could be observed: (1) a "soap bubble" appearance in which the cystic radiolucent areas were separated by coarse bony trabeculae; and (2) an irregularly outlined radiolucency traversed by fine crossing bony trabeculae. External root resorption was seen in some cases. Representative radiographs are shown in Figures 2-4. With respect to both mandibular neurofibromas, one case showed a pronounced multilocular appearance (Fig. 5) whereas the other had a vaguely-outlined radiolucent appearance.

Gross pathology Four recent cases (12-15) were available for macroscopical examination. In all of these, a white glistening gelatinous turnout mass was present in a bony cavity (Fig. 6). Encapsu- lation of the turnout was absent. When a finger was placed on the cut surface, clear shiny threads were seen as it was withdrawn. In contrast the neurofibromas were firm-elastic with a dull cut surface and fibrous whorls being visible macroscopically (Fig. 7).

Microscopic aspects Histological examination revealed the bulk of the tumour to consist of alcianophilic ground substance. Intermingling fibrous tissue stained red with the van Gieson stain. Some- times the amount was rather extensive but in most cases there were only tiny fibres lying dispersed in the alcianophilic myxomatous background. In all cases the fibrous areas formed a minor fraction in comparison with the alcianophilic parts. Cellular density was varyable throughout the turnout. Cell-rich parts alternated with relatively acellular areas. The tumour cells exhibited a divergent morphology. The amounts of cytoplasm varied from almost invisible to extensive. The cellular contour was sometimes round to ellipsoid but was mostly stellate with multiple elongated tapering cellular processes. The cytoplasm exhibited intense eosinophilia and in one case cytoplasmic granules were present. Nuclear morphology was also diverse. There were cells with compact fusiform nuclei but also cells with large, irregularly outlined and vesicular nuclei were present. Binucleate tumour cells were present in all cases. In these binucleate cells, the nuclei were unvariably compact and round to fusiform. Nuclear pleomorphism was present in 8 out of 15 cases and mitotic figures, although scarce, were

5 0 J. max.-fac. Surg. 14 (1986) PieterJ. Slootweg, Albert R. M. Wittkampf

4

Q

4

r

, I

h

I

Fig. 11 Myxoma cells occasionally exhibit vesicular nuclei with pro- nounced nucleon as illustrated in this photomicrograph. A mitotic figure is also present. HE, x 240.

i

L~

Fig. 12 Sometimes the amount of cytoplasm in the myxoma cells is abundant as is shown in this photomicrograph. Arrow points to a ceil with abundant granular eosinophilic cytoplasm. HE, x 240.

observed in 10 out of 15 myxomas. Odontogenic epithelium was only encountered in 4 cases. In 12 cases the slides showed tumour as well as adjacent tissue. In all of them invasion by the myxoma into the surrounding bone or soft tissue was present. Histological examination of the neurofibromas revealed the following. The background tissue was, just as in the myx- omas, composed-of an alcianophilic matrix with interming- ling Van Gieson positive fibres. There was also infiltration of the turnout tissue into adjacent bone or soft tissue. In contrast to myxomas, however, cellular morphology was monotonous. Cigar-shaped nuclei were parallel with the long axis of the fusiform cells. Stellate cells were not present and the background tissue exhibited intertwining fibrous bands with parallel arrangement of cells and fibres within the fascicles. Nuclear pleomorphism, mitoses, and binucle- ate cells were not present in the neurofibromas. Representa- tive histopathological details are shown in Figures 8-14.

Treatment In 9 cases, the primary treatment was conservative consist- ing of careful enucleation or excision of all macroscopically visible tumour tissue followed by curettage of the bony turnout bed. When this procedure led to exposure of the inferior alveolar nerve, the nerve was sacrificed when sur- rounded by or adherent to the turnout. Only if technically

feasible was it peeled away from the tumour and left in situ. When the jaw was resected, the inferior alveolar nerve was unvariably sacrificed. Six patients underwent resection of the involved jaw segment. In general, conservative treat- ment was performed in earlier years whereas resection has been carried out in recent cases. One patient treated in a conservative way exhibited recurrent turnout after 15 years. None of the other patients treated conservatively nor those having undergone jaw resection have exhibited recurrent turnout so far. Mean follow-up time for the patients who were treated without sacrificing apparently uninvolved jaw bone is 18.7 years with a range from 1 to 31 years.

Discussion and Conclusion

Epidemiological data on jaw myxomas are scarce. Barros et al. (1969) found a relative incidence of 21 myxomas out of a total of 3,500 surgical specimens in an oral pathology service (0.6 %). Ghosh et al. (1973) reported 10 myxomas among 8,723 primary bone tumours (0.1%). Fu and Perzin (1977) found 6 maxillary myxomas among 256 non-epithe- lial turnouts of the nasal cavity, paranasal sinuses and nasopharynx (2.3 %). Finally, Regezi et al. (1978) encoun- tered 20 myxomas among 54,534 biopsies submitted to a department of oral pathology (0.04%). In the present series, 15 myxomas formed part of a total number of

Myxoma of the jaws J. max.-fac. Surg. 14 (1986) 51

Fig. 13 Low power view of another case of mandibular neurofi- broma which is more cellular than that shown in Fig. 19 and 20. It shows the same whorling arrangement of fibrous bundles, HE, x 40.

Fig. 14 High power view of the same case as shown in Fig. 21 shows spindle-shaped to thread-like nuclei that lie parallel with the surrounding stroma] fibres. HE, x 240.

15,000 specimens sent to our oral pathology service (0.1%). In comparison with other odontogenic tumours, the myx- oma of the jaw is a rare entity. Regezi et al. (1978) found a ratio of myxoma to ameloblastoma of 3:11. In our material this ratio was 3 : 20. Mean age at which the myxoma is diagnosed ranges from 34 years (Gundlach and Schulz, 1977) to 22 (Ghosh et al., 1973). In the present series, mean age at time of diagnosis was 26 years which agrees very well with other series. In our series there was a distinct predominance of females (80 %). The same excess of myxoma in females has been found by Barros et al. (1969); Gundlach and SchuIz (1977); Regezi et al. (1978); Harder (1978); and Adekeye et al. (1984). Other reports (Zimmerman and Dahlin 1958, Fu and Perzin 1977) failed to establish this predilection for females, reporting approximately equal numbers of male and female cases. With respect to location, most cases occur in the mandible, this becoming apparent from the literature (Barros et al., 1969; Adekeye et al., 1984) as well as from the present series although some authors report an equal number of maxillary and mandibular cases (Zimmerman and Dahlin, 1958; Regezi et al., 1978). Opinions concerning treatment of jaw myxoma are rather divergent. On one side one finds those who advocate radi-

cal surgery (Killey and Kay, 1964; Fu and Perzin, 1977; Schmidseder et al., 1978). On the other side there are those who prefer limited conservative treatment: excision or enucleation followed by curettage of the surrounding bony tissue (Kangur et al., 1975; Harder, 1978). Barros et al. (1969) reported in a review series that 75 % of all recurrent tumours had initially been treated conservatively. In the series of Ghosh et al. (1973) the only case that recurred had been treated by excision; the same applies to the recurrent case in the series of Gundlach and Schulz (1977). In Har- der's series (1978), 6 out of 10 conservatively treated patients exhibited recurrent tumours. From these figures it emanates that the myxoma is a lesion that requires careful surgical removal in order to prevent recurrence. Our treat- ment results, one recurrence out of 9 conservatively treated patients, indicate that permanent cure does not always require extensive surgery with removal of adjacent unin- vol!ved bone. In the mandible it should be possible to extirpate carefully all macroscopically visible turnout tissue by enucleation followed by curettage of the surrounding bone. This procedure was successful in achieving perma- nent cure in 8 out of 9 cases. In the maxilla conservative treatment seems not to be indicated. The vicinity of vital structures in this location precludes in our opinion any mode of therapy that leaves, although small, the chance of recurrence.

52 j . max.-fac. Surg. 14 (1986) PieterJ. Slootweg, Albert R. M. Wi t tkampf : M y x o m a o f the jaws

With respect to histology, our observations disagree with the general opinion that the myxoma cells are inconspicu- ous with compact nuclei and scarce cytoplasm. In the present cases, cellular morphology was rather variable and the presence of large vesicular tumour nuclei with promi- nent nucleoli, also the mitotic activity indicate the myxoma cell to be active in matrix production as well as prolifera- tion. It is often mentioned that the jaw myxoma has to be distinguished from other tumour entities that may mimic myxoma by an extensive myxomatous degeneration (Fu and Perzin, 1977; Adekeye et al., 1984); diagnostic confu- sion mostly arising with neurofibroma. In the present series, the tumour nuclei in myxoma exhibited distinctive features enabling us to discern them from the nuclei in 2 cases of neurofibroma. In the latter cases the nuclei were uniformly cigar-shaped to thread-like whereas in the former cases, they exhibited a divergent morphology as described before. Careful analysis of the appearance of the tumour nuclei should enable the pathologist to distinguish between genuine myxoma and myxomatously degenerated other turnout entities. Other jaw tumours that could give rise to differential dia- gnostic problems are desmoplastic fibroma and odon- togenic fibroma. The former lesion can be distinguished by its compact whorling fibrous fascicles and threadlike nuclei. Odontogenic fibroma on the other hand can be disting- uished by having a more fibrous character than myxoma and it also lacks the stellate-shaped cells typical of myxoma. Moreover, this lesion shows definite encapsulation (Sloot- weg and M~iller, 1983). Finally, the odontogenic derivation of the jaw rnyxoma, originally proposed by Thoma and Goldman (1947) largely rests on circumstantial evidence as recently pointed out (Farman et al., 1977; Adekeye et al., 1984). In a biochemi- cal study on the myxoma matrix (Slootweg et al., in press) the myxoma matrix was shown to be entirely different from the extracullular matrix of the normal dental soft tissues: gingiva, pulp, and periodontal ligament. This may be consi- dered evidence against an odontogenic derivation of the jaw myxoma but can also be interpreted as a result of metabolic changes accompanying neoplastic change of dental mesen- chyme. At present there are no reasons to reject an odon- togenic derivation of jaw myxomas nor to consider this origin to be proven beyond doubt.

Acknowledgements Financial support was obtained from the "Stichting tot Bevordering van de Kaakchirurgie" at Utrecht.

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P. J. Slootweg, M.D., D. M. D. Department of Oral Pathology Dental Institute Sorbonnelaan 16 3485 CA Utrecht The Netherlands