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Chondromyxoid fibroma
Int. J. Oral Maxillofac. Surg, 1986: 15: 553-564 (Key words: fibroma. chondromyxoid; rumor. benign; surgery. oral and maxillofacial)
Chondromyxoid fibroma ELSE PIN HOLT, MOHAMED ELDEEB AND DANIEL WAITE
Department of Oral and Maxillofacial Surgery, University of Minnesota, USA
A brief review of the literature concerning chondromyxoid fibroma is presented. 7 previous cases and the present case of the tumor in the jaws are described. Parallels to the extra oral lesions are drawn and in the light of previously published data, distinctive diagnostic features are discussed. The importance of close cooperation between the surgeon, the radiologist and the pathologist is stressed to avoid a misdiagnosis and radical treatment of the malignant counterpart of a rare benign tumor.
ABSTRACf -
(Accepted for publication 10 August 1985)
Chondromyxoid fibroma (CMF) is a slow growing benign tumor derived from cartilage-forming connective tissue>. The tumor is rare, the incidence being less than I % of all bone tumors". The tumor most commonly occurs in the proximal metaphyseal end of long bones; only a few cases have been reported in the maxillofacial area. In long bones CMF originates from the epiphyseal cartilage and, in the mandible, may have its origin from remnants of Meckel's cartilage. According to CHAUDRY et al), areas of chondroid bone, which may contribute to its origin, are found as nests of cartilage in rapidly growing areas such as the alveolar ridge and angle of the mandible. Chondromyxoid fibroma was first described by JAFFE & LICHTENSTEIN l 8 as a distinctive benign tumor likely to be mistaken for chondrosarcoma. They mentioned that the tumor probably had been previously
diagnosed as enchondroma, myxoma, chondrosarcoma or osteogenic sarcoma. However, LICHTENSTEIN23 included CMF in the group of benign tumors of cartilaginous derivation and JAFFE17 estimated the total number of cases to be somewhat more than 30. Among the larger collections of long bone cases reported in the literature are 117 cases by SALZER & SALZER - KUNTSCHICK32, 41 cases by the Collection of the Bone Tumor Committee of the Japanese Orthopedic Association National Cancer Center', 91 cases by FRANK & ROCKWOClD 13, 207 cases by FELDMANN et a/. II , 32 cases reported by SCHAJOWICZ & GALLAROOJ.l and 76 cases by RAHIMI et al."; Before 1971, all CMF reported were unrelated to the jaw and the summary of 315 cases from the reports of FELDMAN et a/. II , SCHAJOWICZ & GALLAROOJ.l and RAHIMI et a/.30 is shown in Tables Ia, b. CMF involving the craniofacial area
554
PINHOLT, ELDEEB AND WAITE
Table la. Summary of 315 extra oral cases of chondromyxoidfibroma Reference II
No. of cases 207
Sex M:F 101 :68 (39 unknown)
32
17: 15
21 <25 68%
76
43:33
51 <30 71%
315
161: 116 58%:42%
190<30 60%
30
totals
Age 118<30 57%
Location tibia - 58 cases femur - 37 cases fibula - 17 cases other - 77 cases unknown - 18 sites tibia - 10 cases fibula - 6 cases other - 16 cases tibia - 28 cases femur - 10 cases fibula - 3 cases other - 35 cases tibia - 96 cases femur - 47 cases fibula - 26 cases other - 128 cases unknown - 18 cases
Table lb. Summary of 315 cases of chondrornyxoidfibroma Clinical features Reference X-ray pain, lobulated, circumscribed, excentenderness, trically metaphyseal radioluand swelling cency; sclerotic scalloped margin; pseudotrabeculation; and outer cortex expanded and thinned
(parietal bone) was first reported by JAFFE17• EVERKE'o reported a case which affected the base of the skull. RAHIMI et al.30 described CMF in the occipital bone. TOREMALM et al.43 reported a case in which the pterygopalatine space was involved, and THURNER & LISANTI 42 and MIYAMOTO et al" reported frontal bone involvement. The purpose of this article is to review literature concerning CMF, and to report a case which occurred in the mandible.
Treatment resection or curettage
(28%) (18%) (8%) (37%) (9%) (31%) (19%) (50%) (37%) (13%) (4%) (46%) (30%) (15%) (8%) (41%) (6%)
Recurrence 10-25%
noted in a minority of cases. The radiologic features of CMF in long tubular bones as reported by JAFFE & LICHTENSTEIN'S and RAHIMI et al:", were a well-demarcated, eccentrically located metaphyseal radiolucency not encroaching on the epiphyseal end-proper. The lesion is usually of appreciable size and round or oval with the long axis paralleling that of the bone. A sclerosed, scalloped peripheral margin is typical, and within the lesion pseudotrabeculation is common.
Clinical features Pain and slowly increased swelling were the predominant findings. The duration of pain ranged from months to years. According to RAHI?vlI et al.", a history of trauma was
Histopathology Grossly, the specimen is whitish, glistening, firm, and compressible". The tumor destroys bone in proportion to the rate of
CHONDROMYXOID FIBROMA
growth. Residual spongy trabeculae are not usually found within it. As the tumor grows it erodes and thins the cortex and at times, newly reactive bone is formed . Where the cortical shell is absent, the tumor will still be contained by the periosteum and the overlying connective tissue. Myxoid foci, small cysts, hemorrhagic zones and calcification may be seen", Light microscopic features include a tumor tissue in lobules surrounded by loose, richly vascularized non-neoplastic connective tissue. The connective tissue continues between the lobules and may contain large, thin-walled vessels. According to JAFFE & LiCHTENSTEiN 18, depending on maturation in the least mature fields, the tissue consists of tumor cells lying loosely within a myxoid intercellular matrix, demarcated peripherally into pseudolobules by narrow tracts of more closely compacted tumor cells. The tendency toward lobular arrangement is maintained in the more mature lesion. The central portion depends upon myxoid or chondroid preponderance of the tissue elements of the tumor. The myxoid portion shows vague lobulation. The cellular arrangement in the central portion of the lobules consists of stellate cells with ovoid or multipolar prominent nuclei separated by a mucin-like material. Ncar the periphery of the lobule, the cells have indistinct cytoplasmic borders and contain prominent nuclei. In this area, multinucleated giant cells, blood extravasation, macrophages, smallnucleated cells and polymorphic neutrophiles are also present. Small blood vessels are closely interwoven with these cellular components and within the connective tissue sheet. The chondroid portion of the tumor tends to show less lobulation and its intercellular material is less vacuolated and more homogeneous in character. Increased maturity is associated with progressive collagenization of the intercellular matrix (LiCHTENSTEiN 22) . There is often a loose network
555
of crossing collagen fibers interwoven into a dense mat, and smaller or larger hyaline patches may appear. The matrix may appear chondroid, and since many of the tumor cells come to lie in lacunae, the tissue as a whole may simulate cartilage. At the periphery of the lobules, where the tumor cells are more closely compacted, it is common to find tumor cells with particularly prominent nuclei. These cells may have large plump nuclei, hyperchromatism and atypically large double or multiple nuclei. Because of the bizarre nuclei in the peripheral tumor cells, JAFFE & LiCHENSTEiN I8 indicated that the tumor is likely to be mistaken for chondrosarcoma. When the intracellular matrix is less chondroid and predominantly myxoid a misdiagnosis of myxosarcoma is possible. It has been shown that the diagnosis of myxoma can be excluded because of the lack of mucin reaction of the tumor - a reaction to be expected of myxomatous tissue. The peripheral condensation of tumor cells further speaks again st myxoma. Electron microscopic features include focal calcification and ossification in the periphery are found in occasional small foci. The tumor cells vary in shape from stellate to elong ated and varied cells40•47• Two types of cells are present; fibroblast and chondrocyte-like cells", Various projections of the cytoplasm are seen. Prominent rough surfaced endoplasmatic reticulum, small mitochondria, well-developed Golgi areas, numerous pinocytotic vesicles and dense bodies suggesting lysosomal structures were also present. Glycogen particles are seen, occasionally in large numbers, while lipid droplets are very rare . The nuclei have a very irregular contour, often associated with nuclei bridges. A fibrous lamina is located along the inner nuclear membrane. This fibrous lamina presents as an electron dense zone 700 A wide located between the inner and outer membranes and, according
556
PINHOLT, ELDEEB AND WAITE
to TORNBERG et al.4-I should represent a useful ultrastructural diagnostic feature. In the intercellular spaces of the loose matrix, periodicity of fine immature filaments and collagen fibers with evidence of banding is present as well as electron dense granules of proteoglycans. Differential diagnosis concerning the radiologic features (MURPllY & PRICE28) include giant cell granuloma, bone cyst, enchondroma, benign chondroblastoma, benign fibrous lesion, aneurysmal bone cyst, monostotic fibrous dysplasia, hyperparathyroidism, myxoma, and neurofibromatosis .
Treatment The common treatment of CMF has been simple curettage, curettage and cauterization, local resection and amputation", JAFFE & LICHTENSTEIN 18 stated that curettage which docs not completely remove the tumor is not followed by recurrence. This was later proved not to be the case. Recurrence rates between 12.5%31 and 25%6 have been observed where treatment was simple curettage. Because the recurrence rate after simple curettage is so high, the treatment of choice is conservative resection followed by immediate bone grafting when indicated and, where this has been performed, the recurrence rate has been minimal. According to DAHLIN 6 and SCHAJOWICZ & GALLARD0 34, recurrence is mainly due to residual lobular extensions, which arc separated from the main tumor and therefore impossible to remove by curettage. RALPH 31, MIKULOWSKI & OSTBERG 26 , and RAHIMI et al.30 have reported a few cases in which there was recurrence by soft tissue involvement without simultaneous recurrence within the adjacent bone. In the review of Mayo Clinic cases , RAHIMI et al.30 mentioned a case in which a subcutaneous nodule of recurrent tumor was re-
moved prior to discovery of a later recurrence in the underlying bone. According to KYRIAKOS21, extensive surgical manipulation can cause recurrence because of adjacent vascular plugging by the tumor tissue. GALLIA et al:" indicated that the recurrent tumor orginates in the periosteum rather than in the osseous tissue . Radiation is not advisable because the main part of the tumor is not radiosensitive and malignant degeneration has been reported (Uematsu et al. 46). Malignant transformation has been mentioned by many authors I2,16.36.49. SCllAJWICZ & GALLAROO 34 found none in their review of 32 cases. RAHI~H et al.30 commented on this in further detail and found no case in which malignant change has been convincingly documented. In their study, the only malignant change was observed in a patient who developed an anaplastic fibrosarcoma following radiation therapy for CMF. They concluded that the risk of malignant transformation is so minimal that radical treatment is unnecessary. Tumors reported as producing metastases have been viewed as ' low-grade chondrosarcomas, which have been histologically misinterpreted as CMF.
Case report A 24-year-old white male was referred to the Department of Oral and Maxillofacial Surgery, School of Dentistry at the University of Minnesota, Minneapolis, in July, 1980 for routine removal of impacted third molars. The mandibular radio graph demonstrated an extensive radiolucency associated with the left lower molar area (Fig. I). The rad iolucency extended to the angle of the mandible. Thinning of the cortex and expansion of the inferior border of the mandible were noted . Pseudotrabeculation as well as some opacities were present within the lesion. The second molar showed resorption of apices. Bone scan revealed an area of increased activity along the left mandibular alveolar ridge near the angle. Two separate discrete foci appeared and these likely represented a dental process . No oth er bony
CHONDROMYXOID FIBROMA
557
Fig. 2. Specimens include the second and first molars. Note size and resorption of apices. Fig. I. Orthopantomograph X-ray shows an extensive radiolucency associated with the left lower third molar area. Notice the extension and expansion of the lesion. Also notice the resorption of the second molar's roots.
abnormalities were noted. The pat ient was asymptomatic and had not experienced any paresthesia, anesthesia or swelling of the mandible. His previous medical history included two right hip surgeries 10 years earlier for chronic synovitis and osteomyelitis. The family history was without history of neoplasia. Physical examination was normal. There seemed to be slight expansion of the left angle of the mand ible. No bruit or thrill was present. The area was firm and painl ess, and the dentition was intact as was the mucosa. The neurological exam was within normal limits . Chest radiograph was also within normal limits. Laboratory exams which included CBC with diff., platelets, electrolytes, PT, PIT and VA were within normal limits. A tentative diagnosis of fibro-osseous lesion in connection with an impacted left third mandibular molar was established. The patient underwent removal of his third molars and biopsy was performed. An initial histological diagnosis of osteogenic sarcoma was made independently by two different pathologists. Because it did not fit the clinical signs, history or examination, the lesion was re-biopsied a nd additional consultation with a number of pathologists was obtained. The diagnosis of chondromyxoid fibroma was then established. The patient was hospitalized and under general a nesthesia the tumor was totally removed along with the adjacent first and second molars (Fig. 2). During surgery, the inferior border, the cortical plates, both buccal and lingual, were noted to be
intact and the tumor was removed easily from the bone cavity. Immediate bone grafting using iliac crest cancellous bone was done, and the jaws immobilized by intermaxillary fixation. The hospital course was uneventful, good healing was obtained, and a V) paresthesia was noted. The patient was followed closely the first year, and no recurrence has been observed clinically or radiographically (Fig . 3). The patient mo ved out of town which made bi-annual follow up impossible. However, a 5year clinical exam and post-op rad iograph revealed satisfactory healing without signs of recurrence. On th e radiograph an upper distal radiolucency is present, probably due to fibrous healing of the central part of the bone graft.
Histology of the tumor Gross: (A) Partially calcified, irregular fragments were received measuring less than 1.0 em. in greatest dimension. The material was divided into routinely processed and that to be decalcified prior to histologic evaluation. (B) An additional soft tissue portion was received that proved to be normal peripheral nerve on histologic examination. Light microscopy The tumor is composed of smaIl uniform spindle cells which are set in a background which varies from chondroid to a more myxoid type. The tumors comprise irregular eosinophilic fragments that were necrotic in part and featured neoplastic calcification. Additional, a small, connective tissue appearing, cellular component was observed that featured additional, small and globular calcification and irregular zones of homogenization resembling osteoid (Fig. 4a) . Component cells were characterized by vesicular, small and irregu-
558
PINHOLT, ELDEEB AND WAITE
•. . - p
Fig. 3. Pre- and post-operative orthopantomographs, and a five year post-op, orthopantomogram show the healing process. No recurrence was observed. Note the healing, the bone level of the healed surgical defect and the upper distal radiolucency which might represent fibrous tissue completing the healing.
lar nuclei. Occasional larger nuclei and multipolar cells were identified but mitotic figures were not present (Fig. 4b). Electron microscopy Most of the tumor consists of a cellular lesion having ultrastructural features reminiscent of hemangiopericytoma. Although vascular spaces are not prominent, the cells have large numbers of thin filaments showing focal condensations, plasmalemmal vesicles, and poorly developed basal lamina along the cytoplasmic margin. A moderate amount of depolymerized fibrin is seen in the interstitium between these cells which ultrastructurally has features of smooth muscle differentiation. The other major pattern seen ultrastructurally corresponds to the loose myxoid areas seen by light microscopy. The myxoid stroma surrounds isolated cells which have irregular cell borders, fewjunctions, and prominent Iysosomes, lipid, and dilated rough endoplasmic reticulum. Although these cells have many features of histi-
ocytes, they somewhat resemble cartilaginous cells (Fig. 5). The presence of even a fewjunctions proves that they are not histiocytes. Also seen in the myxoid areas are undifferentiated elongated cells.
Discussion Within the maxillofacial area, this tumor is extremely rare. In a review of the literature, we found only 7 earlier cases documented as CMF. The first well-documented case was by SCHUTT & FRosT3s, who reported a mandibular CMF. The patient was a 10year-old female with a history of trauma, presenting with the lesion in the mandibular symphysis (see Table 2). Four cases were reported prior to that of SCHUTT & FROST3s• One of these, PAUL29,
CHONDROMYXOID FIBROMA
559
was diagnosed as chondromyxosarcoma; consequently it is not included in our table, SLEEPER37 reported a chondromyxoma of the mandible; it is excluded from our table since it is not a true example of CMF. DAVIS & TIDEMAN 8 reported a case of CMF ina 16-year-old male. The tumor was located within the symphysis menti. Here too a history of trauma was reported. After removal of the tumor, there was recurrence two years later. A second report was made , by GALLIA et af.14 stating that the CMF " ... . ' .. was misdiagnosed and that the original and , -, ... recurrent tumor was chondrosarcoma and :-.4.. • for that reason was excluded also. SRIVASTAVA39 reported a case of CMF in a 25'0 . : year old female in whom the lesion was • located within the symphysis menti. SPJUT et 0/.38 mentioned a case of CMF located in " , the mandible but with incomplete accompanying data. We included this case beFig. 4. (A) Small and lobular calcification and cause of its mandibular location. A sumirregular zones of homogenization resembling osteoid. (HE, 312 X). (B) Larger nuclei and multi- mary of the eight cases of CMF involving polar cells were identified. Also, some joint cells the mandible is shown in Tables 2a, b. were observed. (HE, 3l2x). Our review reveals that CMF is predomi-
.. .'
..
..
.'
..
..
.
a
.. . ...
-.
b
Fig. 5. (A) Transmission electron micrograph (T.E.M.) magnified x 11232, shows large numbers of
thin filaments showing focal condensations, plasmalemmal vesicles, and poorly developed basal lamina along the cytoplasmic margin. (B) Transmission electron micrograph magnified x 11232, shows the myxoid stroma surrounds isolated cells which have irregular cell borders, fewjunctions, and prominent lysosomes, lipid and dilated rough endoplasmic reticulum.
560
PINHOLT, ELDEEB AND WAITE
Table 2a. Summary of 8 intra-oral cases of chondromyxoidfibroma Age (years) Case # Reference Sex 39 25 I female 38 unknown unknown 2 3l female 10 3 Il 16 4 female male 13 5 41 female 42 6 19 12 female 7 24 this study male 8 total M:F 20 8 cases 2:5 37%:63% Table 2b. Summary of 8 intra-oral cases of chondromyxoidfibroma Reference Clinical features X-ray 38 unknown unknown 39 hard swelling radiolucency around roots of anterior teeth; cortex expanded Il swelling; well-defined radiolucency; ground glass; outer cortex expanded; dispain placed 3rd molar 3l swelling; radiolucency; displaced dentition history of trauma radiolucency; sclerotic scalloped history of trauma, margin; cortex thinned, impacswelling ted & displaced 3rd molar 41 radiolucency; sclerotic scalloped pain, swelling margin; intralesional trabeculation 19 swelling, diffuse radiolucency, displaced displaced teeth teeth with lost lamina dura radiolucency and small opacities asymptomatic this study around 3rd molar; sclerotic scalloped border, expansile inferior mandibular rim; resorption of apices of 2nd molar
nantly an extraoral lesion. As previously indicated, the lower limb is predominantly involved, the upper end of the tibia being the preferred site (30%) (Table I). Among the 8 cases involving the jaws, the mandible was found to be the exclusive area of involvement. The extraoral tumors occurred most frequently in the second and third decades of life. This correlated with the average age for involvement of the mandible,
Location mandible mandible symphysis mandible left molar mandible right molar mandible left molar mandible symphysis mandible left molar mandible mandible
Treatment unknown enucleation
Recurrence unknown unknown
curettage
no
enucleation
no
curettage
yes (2 years)
curettage
no
resection no and rib graft no enucleation & immediate bone grafting
which was twenty years. In the extraoral review, 116 (42%) cases occurred in females while 161 (58%) were found in males. In the mandible, 5 cases (71 %) occurred in females and 2 (29%) in males. A history of trauma was present in 2 (25%) of the oral cases. In the extraoral cases, as mentioned by RAHIMI et a/. 3D, a history of trauma was infrequent. The clinical features of the intraoral cases include history of pain and
CHONDROMYXOID FIBROMA
swelling. The radiologic characteristic was a multilocular radiolucency with a scalloped sclerotic margin. Expansion and thinning of the cortex was usual and pseudotrabeculation was common. The treatment in the oral cases was simple curettage, enucleation or resection, followed by bone grafting. Recurrence was seen in I case', 20% of cases of chondrogenic origin reported in the literature have been underdiagnosed at the first microscopic interpretation because the difference between benign/malignant in these tumors does not always predict the conduct of the tumor CHAUDRY et al.'. The diagnosis of CMF has been difficult to make. LICHTENSTEIN & JAFFE24 mentioned three cases which they had great difficulty in classifying. They mentioned certain criteria by which underdiagnosis of chondrosarcoma in the early stage of malignancy could be avoided. Among the criteria were: (1) many cells with plump nuclei; (2) more than an occasional cell with two such nuclei; (3) any giant cells with large single or multiple nuclei or with clumps of chromatin. They also mentioned that in the histologic diagnosis of chondrosarcoma, not too much importance should be attached to the scarcity or even absence of mitotic figures, since cell division in chondrosarcomas tends to be amitotic. The characteristics indicated above are found especially in the peripheral compacted cell layer in CMF and often confuse the pathologist who subsequently may diagnose CMF as chondrosarcoma. This was further confirmed by JAFFE & LICHTENSTEIN I8• They described CMF as a distinctive benign tumor likely to be mistaken especially for chondrosarcoma. They indicate that the tumor may have been diagnosed as enchondroma or myxoma, or their cancerous counterparts. DAHLIN & IRVING? stressed the importance of the morphological relationship to benign chondroblastoma, and that it is of the utmost importance to recognize the various features that make
561
possible the correct classification of CMF, thereby avoiding the misdiagnosis of CMF as a malignant tumor. 4 of II reported tumors originally were considered to possess a low degree of malignancy such as chondrosarcoma, chondromyosarcoma and osteogenic sarcoma. TuRCOTTE et 0/.45, and WILLIS48 believed that there was a histogenic link between CMF and osteoclastoma. AEGERTER & KIRKPATRICK) mentioned the possibility of CMF as a slowly progressive malignant tumor showing aggresive behavior and even metastasizing features. They believed that all CMF should be considered at least partially malignant and treated as such. RAHIMI et 0/. 30 added criteria to the histologic differences between chondrosarcoma and CMF. They stated that even though chondrosarcoma may have prominently myxoid areas, the tumor has a more distinctly hyaline cartilage quality; furthermore, it lacks the characteristic admixture of fibromatous elements. Chondrosarcoma lacks the abrupt boundary of CMF, and this aggressive quality is reflected in the radiograph Which contrasts with the benign appearance found in CMF. Electronmicroscopy may help to distinguish between CMF and chondrosarcoma, but the final diagnosis rests at the light microscope level. Electronmicroscopically, in the CMF, in contrast to chondrosarcoma the tumor cells are more pleomorphic and have irregular and elongated cell projections which often extend away from the cells and contact adjacent cells. The chondrosarcoma tends to have numerous lipid droplets and often dilated rough endoplasmic reticulum more than do CMF cells", TORNBERG et a/.44 mentioned some consistent differences electronmicroscopically between CMF and chondrosarcoma.. The cell population observed in chondrosarcoma is predominantly chondroid. The nucleus of these cells is characteristically lobulated and frequently contains a large prominent nucleolus having
562
PINHOLT, ELDEEB AND WAITE
a complex substructure. Large lipid vacuoles are present in both the cytoplasm and matrix of chondrosarcoma. These findings, notably absent in CMF, could serve to differentiate the two at the ultrastructural level. A distinctive feature of both cell types of CMF is the presence of a 700 A electron dense band between the inner and outer nuclear membranes. Typically, the nucleus of a cell is enclosed by two parallel membranes 70-80 A thick that are separated by a less dense perinuclear space of 120-140 A. Throughout, the matrix of CMF fiber aggregations having an average major banding periodicity of 973 A are present, which is a rare biological occurrence representing fibrous long spaced collagen (FLS). ERLANDSON & Huvos? and BATSAKIS et al? emphasized that it is ultramiscroscopically hard to point out differences between "normal" chondrocytes and neoplastic cartilage cells present in low-grade chondrosarcoma because the features of the cells in low grade chondrosarcoma are also found in cells comprising a variety of benign and nonneoplastic lesions of hyaline cartilage. SCHAJOWICZ et al.J3 add to the characteristics of chondrosarcoma an inverse relationship between :the glycogen amount and the grade of malignancy. Preliminary studies of the chemical composition of CMF reveal the presence of high levels of glutamic acid in the tumor matrix. This was not observed in chondrosarcoma according to MASHBURN 25• A study by KUHLMAN & McNAMEE20 evaluating enzymes mediating carbohydrate metabolism as well as specialized phosphatase revealed that CMF reflected more enzyme activity than did active areas of the epiphyseal line. In the same way that it has been difficult to differentiate benign versus malignant in the extraoral cases, it has been equally difficult to differentiate benign vs. malignant in intraoral cases. As noted earlier, GALLIA et al:" reported a misdiagnosed chondrosarcoma of
the mandible in a 16-year-old male. It was previously diagnosed as CMP. Recurrence occurred 3 years later and an incisional biopsy was reported as consistent with lowgrade chondrosarcoma, mainly because of the increased number of mitotic figures and occurrence of bi- and multi-nucleated cells. Review of the original resected tumor demonstrated a similar histological pattern in minor fragments. In our case, the initial biopsy was read as probable osteogenic sarcoma. However, because oflack ofclinical confirmation, further histologic sampling was examined, and because of the lack of reasonable diagnostic alternatives, osteogenic sarcoma was necessarily excluded. Consultations, additional sections, and interpretation of frozen sections at the time of conservative surgical removal confirmed the impression of chondromyxoid fibroma of the mandible. The operative specimen was carefully and completely evaluated to exclude osteosarcoma. The initial treatment which was planned to be hemimandibulectomy, based on the limited histopathologic diagnosis, was therefore changed to radical blockresection of the mandible, leaving the inferior border, followed by grafting with cancellous bonechips. Finally, we would like to stress the importance of correlating the relation between clinical features, radiographic appearance and histologic diagnosis, of CMF. Complete cooperation and communication between the surgeon, radiologist and pathologist is needed to establish a definitive diagnosis and treatment plan for unusual and rare tumors of the jaws.
Conclusions On the basis of the case reported and the review of the literature, the following should be stressed:
CHONDROMYXOID FIBROMA
1. Chondromyxoid fibroma of the jaws are more common in females (63%) than males (37%). 2. The mandible was the site of invasion when CMF affected the jaws. 3. CMF is a rare benign tumor likely to be mistaken for chondrosarcoma because of the bizarre nuclei in the peripheral tumor cells. 4. The treatment of choice of CMF is conservative resection followed by immediate bone grafting. 5. Radiotherapy is contraindicated because the main part of the tumor is not radiosensitive and malignant degeneration has been reported. 6. The recurrence rate of CMF is very low. The risk of malignant transformation is so minimal that radical treatment is unnecessary. 7. Clinical, radiographic and histological data are all essential to confirm the diagnosis of CMF. 8. Complete cooperation and communication between the surgeon, radiologist and pathologist is needed to establish a definitive diagnosis and treatment plan for unusual and rare tumors of the jaws.
Acknowledgement - The authors would like to acknowledge Dr. Robert Vickers for the review of the histopathological evaluation and photomicrography for the pathological specimens.
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tativc microchemical studies of chondroblastoma, giant-cell tumor, chondromyxoid fibroma and desmoplastic fibroma. Clin . Orthop, 1976: 69; March-April. KYRIAKOS, M.: Soft tissue implantation of chondromyxoid fibroma . Am. J. Surg, Pathol . 1979: 3: 363-372. LICHTENSTEIN, L.: BOlle tumors, 5th edition. St. Louis, C. V. Mosby Co. 1977, pp. 63-77. LICIITENSTEIN, L.: Classification of primary tumors of bone. Cancer 1951: 4: 335-341. LICHTENSTEIN, L. & JAFfE, H. L.: Chondrosarcoma of bone. Alii. J. Path. 1943: 19: 553-574. MASHBURN, A.: Personal communication, 1980. MIKULOWSKI, P. & OSTBERG, G.: Recurrent chondromyxoid fibroma. Acta Orthop Scand. 1971: 42 : 385-390. MIYAMOTO, E., KURIYAMA, T., IWAMOTO, M., TSUGI, N . & SIIIZUKI, K .: Cranial chondromyxoid fibroma. J. Neurosurg, 1981: 55: 1001-1003. MURPHY, N. B. & PRICE, C. H. G.: The radiological aspects of chondromyxoid fibroma of bone. Clin. Radio11971: 22: 261-269. PAUL, J. K.: Chondromyxosarcoma of the mandible. J. Oral Surg, 1951: 9: 319-328. RAIIIMI, A., BEABOUT, J. w., IVINS, J. C. & DAHLIN, D. C.: Chondromyxoid fibroma: a clinicopathologic study of 76 cases. Cancer 1972: 30: 726--736. RALPH, L. L.: Chondromyxoid fibroma of bone. J. BOlle Joint Surg, (AM). 1962: 443: 7-24. SALZER, M. & SALZER-KUNTSCIIICK, M.: Langenbrecks. Arch. Klin . cu« 1965: 312: 216. SClIAJO\VICZ, E, CABRINI, R. L., SIMES, R. J. & KLEIN-SZANTO, J. P.: Ultrastructure of chondrosarcoma. Clin. Orthop, 1974: 100: 378-386. SCHAJo\VICZ, E & GALLARDO, H.: Chondromyxoid fibroma (fibromyxoid chondroma) of bone. Bone Joint Surg (AM) 1971: 538: 198-216. SCHUTT, P. G. & FROST, H. M.: Chondromyxoid fibroma. Clin. Orthop. 1971: 78: 323-329. SElIAYlK, S. & ROS~IAN, M. A.: Malignant degeneration of a chondromyxoid fibroma in a child. Can . J. Surg, 1975: 18: 354-360. SLEEPER, E. L.: Chondromyxorna of the mandible. Oral Surg , 1952: 5: 816--822.
38. SPJUT, H. J., DORFMAN, M . D., FECHNER, R. E. & ACKERMAN, L. U.: Tumors of bone and cartilage. In: Atlas of tumor pathology, Washington, D.C. Armed Forces Institute of Pathology 1971, pp. 50-59. 39. SRIVASTAVA, S. P.: Tumors of the jaw. The Indian Surg, 1955: 17: 1-5. 40. STEll'o'ER, G. C.: Ultrastructure of benign cartilaginous tumors of intraosseous origin. HIlIII. Pathol. 1979: 10: 71-86. 41. THOMPSON, S. H., WEATHERS, D. R. & VATRAL, J. J.: Chondromyxoid fibroma of the jaws. Head Neck Surg , 1982: 4: 330-334. 42. THURl'o'ER, V. J. & LISANTI, M.: Ein Chondromyxoidfibroma dcr Stimbeinschuppe. Zbl. Patho!. Pathol. Anat, 1981: 125: 473-480. 43. TOREMALM, N. G., LINSTROM, C. & MAUl, L.: Chondromyxoid fibroma of the pterygopalatine space. Laryngol Otol. 1976: 90: 971-979. 44. TORNBERG, D. N ., RICE, R. W. & JOHNSTON, A. D.: The ultrastructure of chondromyxoid fibroma. Clin. Orthop, 1973: 95: 295-299. 45. TuRCOTTE, B., PUGH, D. G. & DAHLIN, D. The roentgenologic aspects of chondromyxoid fibroma of bone. Alii. Rod. Ther. Nllc/ . Med. 1962: 87: 1085-1095. 46. UEMATSU, A., COY, III, J. T., HODGES, S. D., GOODMAN, R. P. & BROWER, T. D.: Malignant chondromyxoid fibroma of the scapula. S. Med. J. 1977: 70: 1469-1471. 47. USlIlGmIE, S., TAKAKUWA, T., SIIIWAGAWA, T., KISlIlDA, H. & YAMAZAKI, M .: Chondromyxoid fibroma of bone: an electron microscopic observation. Acta Pathol. Jpn. 1982: 32: 113-122. 48. WtLLlS, R. A.: Pathology of tumors, 4th edition. Butterworth & Co., London 1967, p . 700 . 49. WlnVIcKI, T. & DZIAK, A.: Fibroma Chondromyxoides Malignum et Benignurn. Wiad. Lek. 1967: 20: 2211-2213.
c.
Address:
Mohamed £1 Deeb Department of Oral and Maxillofacial Surgery School of Dentistry University of Minnesota 7-174 Malcolm Moos Health Sciences Tower 515 Delaware Street S .E. Minneapolis, MN 55455 USA
Chondromyxoid fibroma ELSE PIN HOLT, MOHAMED ELDEEB AND DANIEL WAITE
Department of Oral and Maxillofacial Surgery, University of Minnesota, USA
A brief review of the literature concerning chondromyxoid fibroma is presented. 7 previous cases and the present case of the tumor in the jaws are described. Parallels to the extra oral lesions are drawn and in the light of previously published data, distinctive diagnostic features are discussed. The importance of close cooperation between the surgeon, the radiologist and the pathologist is stressed to avoid a misdiagnosis and radical treatment of the malignant counterpart of a rare benign tumor.
ABSTRACf -
(Accepted for publication 10 August 1985)
Chondromyxoid fibroma (CMF) is a slow growing benign tumor derived from cartilage-forming connective tissue>. The tumor is rare, the incidence being less than I % of all bone tumors". The tumor most commonly occurs in the proximal metaphyseal end of long bones; only a few cases have been reported in the maxillofacial area. In long bones CMF originates from the epiphyseal cartilage and, in the mandible, may have its origin from remnants of Meckel's cartilage. According to CHAUDRY et al), areas of chondroid bone, which may contribute to its origin, are found as nests of cartilage in rapidly growing areas such as the alveolar ridge and angle of the mandible. Chondromyxoid fibroma was first described by JAFFE & LICHTENSTEIN l 8 as a distinctive benign tumor likely to be mistaken for chondrosarcoma. They mentioned that the tumor probably had been previously
diagnosed as enchondroma, myxoma, chondrosarcoma or osteogenic sarcoma. However, LICHTENSTEIN23 included CMF in the group of benign tumors of cartilaginous derivation and JAFFE17 estimated the total number of cases to be somewhat more than 30. Among the larger collections of long bone cases reported in the literature are 117 cases by SALZER & SALZER - KUNTSCHICK32, 41 cases by the Collection of the Bone Tumor Committee of the Japanese Orthopedic Association National Cancer Center', 91 cases by FRANK & ROCKWOClD 13, 207 cases by FELDMANN et a/. II , 32 cases reported by SCHAJOWICZ & GALLAROOJ.l and 76 cases by RAHIMI et al."; Before 1971, all CMF reported were unrelated to the jaw and the summary of 315 cases from the reports of FELDMAN et a/. II , SCHAJOWICZ & GALLAROOJ.l and RAHIMI et a/.30 is shown in Tables Ia, b. CMF involving the craniofacial area
554
PINHOLT, ELDEEB AND WAITE
Table la. Summary of 315 extra oral cases of chondromyxoidfibroma Reference II
No. of cases 207
Sex M:F 101 :68 (39 unknown)
32
17: 15
21 <25 68%
76
43:33
51 <30 71%
315
161: 116 58%:42%
190<30 60%
30
totals
Age 118<30 57%
Location tibia - 58 cases femur - 37 cases fibula - 17 cases other - 77 cases unknown - 18 sites tibia - 10 cases fibula - 6 cases other - 16 cases tibia - 28 cases femur - 10 cases fibula - 3 cases other - 35 cases tibia - 96 cases femur - 47 cases fibula - 26 cases other - 128 cases unknown - 18 cases
Table lb. Summary of 315 cases of chondrornyxoidfibroma Clinical features Reference X-ray pain, lobulated, circumscribed, excentenderness, trically metaphyseal radioluand swelling cency; sclerotic scalloped margin; pseudotrabeculation; and outer cortex expanded and thinned
(parietal bone) was first reported by JAFFE17• EVERKE'o reported a case which affected the base of the skull. RAHIMI et al.30 described CMF in the occipital bone. TOREMALM et al.43 reported a case in which the pterygopalatine space was involved, and THURNER & LISANTI 42 and MIYAMOTO et al" reported frontal bone involvement. The purpose of this article is to review literature concerning CMF, and to report a case which occurred in the mandible.
Treatment resection or curettage
(28%) (18%) (8%) (37%) (9%) (31%) (19%) (50%) (37%) (13%) (4%) (46%) (30%) (15%) (8%) (41%) (6%)
Recurrence 10-25%
noted in a minority of cases. The radiologic features of CMF in long tubular bones as reported by JAFFE & LICHTENSTEIN'S and RAHIMI et al:", were a well-demarcated, eccentrically located metaphyseal radiolucency not encroaching on the epiphyseal end-proper. The lesion is usually of appreciable size and round or oval with the long axis paralleling that of the bone. A sclerosed, scalloped peripheral margin is typical, and within the lesion pseudotrabeculation is common.
Clinical features Pain and slowly increased swelling were the predominant findings. The duration of pain ranged from months to years. According to RAHI?vlI et al.", a history of trauma was
Histopathology Grossly, the specimen is whitish, glistening, firm, and compressible". The tumor destroys bone in proportion to the rate of
CHONDROMYXOID FIBROMA
growth. Residual spongy trabeculae are not usually found within it. As the tumor grows it erodes and thins the cortex and at times, newly reactive bone is formed . Where the cortical shell is absent, the tumor will still be contained by the periosteum and the overlying connective tissue. Myxoid foci, small cysts, hemorrhagic zones and calcification may be seen", Light microscopic features include a tumor tissue in lobules surrounded by loose, richly vascularized non-neoplastic connective tissue. The connective tissue continues between the lobules and may contain large, thin-walled vessels. According to JAFFE & LiCHTENSTEiN 18, depending on maturation in the least mature fields, the tissue consists of tumor cells lying loosely within a myxoid intercellular matrix, demarcated peripherally into pseudolobules by narrow tracts of more closely compacted tumor cells. The tendency toward lobular arrangement is maintained in the more mature lesion. The central portion depends upon myxoid or chondroid preponderance of the tissue elements of the tumor. The myxoid portion shows vague lobulation. The cellular arrangement in the central portion of the lobules consists of stellate cells with ovoid or multipolar prominent nuclei separated by a mucin-like material. Ncar the periphery of the lobule, the cells have indistinct cytoplasmic borders and contain prominent nuclei. In this area, multinucleated giant cells, blood extravasation, macrophages, smallnucleated cells and polymorphic neutrophiles are also present. Small blood vessels are closely interwoven with these cellular components and within the connective tissue sheet. The chondroid portion of the tumor tends to show less lobulation and its intercellular material is less vacuolated and more homogeneous in character. Increased maturity is associated with progressive collagenization of the intercellular matrix (LiCHTENSTEiN 22) . There is often a loose network
555
of crossing collagen fibers interwoven into a dense mat, and smaller or larger hyaline patches may appear. The matrix may appear chondroid, and since many of the tumor cells come to lie in lacunae, the tissue as a whole may simulate cartilage. At the periphery of the lobules, where the tumor cells are more closely compacted, it is common to find tumor cells with particularly prominent nuclei. These cells may have large plump nuclei, hyperchromatism and atypically large double or multiple nuclei. Because of the bizarre nuclei in the peripheral tumor cells, JAFFE & LiCHENSTEiN I8 indicated that the tumor is likely to be mistaken for chondrosarcoma. When the intracellular matrix is less chondroid and predominantly myxoid a misdiagnosis of myxosarcoma is possible. It has been shown that the diagnosis of myxoma can be excluded because of the lack of mucin reaction of the tumor - a reaction to be expected of myxomatous tissue. The peripheral condensation of tumor cells further speaks again st myxoma. Electron microscopic features include focal calcification and ossification in the periphery are found in occasional small foci. The tumor cells vary in shape from stellate to elong ated and varied cells40•47• Two types of cells are present; fibroblast and chondrocyte-like cells", Various projections of the cytoplasm are seen. Prominent rough surfaced endoplasmatic reticulum, small mitochondria, well-developed Golgi areas, numerous pinocytotic vesicles and dense bodies suggesting lysosomal structures were also present. Glycogen particles are seen, occasionally in large numbers, while lipid droplets are very rare . The nuclei have a very irregular contour, often associated with nuclei bridges. A fibrous lamina is located along the inner nuclear membrane. This fibrous lamina presents as an electron dense zone 700 A wide located between the inner and outer membranes and, according
556
PINHOLT, ELDEEB AND WAITE
to TORNBERG et al.4-I should represent a useful ultrastructural diagnostic feature. In the intercellular spaces of the loose matrix, periodicity of fine immature filaments and collagen fibers with evidence of banding is present as well as electron dense granules of proteoglycans. Differential diagnosis concerning the radiologic features (MURPllY & PRICE28) include giant cell granuloma, bone cyst, enchondroma, benign chondroblastoma, benign fibrous lesion, aneurysmal bone cyst, monostotic fibrous dysplasia, hyperparathyroidism, myxoma, and neurofibromatosis .
Treatment The common treatment of CMF has been simple curettage, curettage and cauterization, local resection and amputation", JAFFE & LICHTENSTEIN 18 stated that curettage which docs not completely remove the tumor is not followed by recurrence. This was later proved not to be the case. Recurrence rates between 12.5%31 and 25%6 have been observed where treatment was simple curettage. Because the recurrence rate after simple curettage is so high, the treatment of choice is conservative resection followed by immediate bone grafting when indicated and, where this has been performed, the recurrence rate has been minimal. According to DAHLIN 6 and SCHAJOWICZ & GALLARD0 34, recurrence is mainly due to residual lobular extensions, which arc separated from the main tumor and therefore impossible to remove by curettage. RALPH 31, MIKULOWSKI & OSTBERG 26 , and RAHIMI et al.30 have reported a few cases in which there was recurrence by soft tissue involvement without simultaneous recurrence within the adjacent bone. In the review of Mayo Clinic cases , RAHIMI et al.30 mentioned a case in which a subcutaneous nodule of recurrent tumor was re-
moved prior to discovery of a later recurrence in the underlying bone. According to KYRIAKOS21, extensive surgical manipulation can cause recurrence because of adjacent vascular plugging by the tumor tissue. GALLIA et al:" indicated that the recurrent tumor orginates in the periosteum rather than in the osseous tissue . Radiation is not advisable because the main part of the tumor is not radiosensitive and malignant degeneration has been reported (Uematsu et al. 46). Malignant transformation has been mentioned by many authors I2,16.36.49. SCllAJWICZ & GALLAROO 34 found none in their review of 32 cases. RAHI~H et al.30 commented on this in further detail and found no case in which malignant change has been convincingly documented. In their study, the only malignant change was observed in a patient who developed an anaplastic fibrosarcoma following radiation therapy for CMF. They concluded that the risk of malignant transformation is so minimal that radical treatment is unnecessary. Tumors reported as producing metastases have been viewed as ' low-grade chondrosarcomas, which have been histologically misinterpreted as CMF.
Case report A 24-year-old white male was referred to the Department of Oral and Maxillofacial Surgery, School of Dentistry at the University of Minnesota, Minneapolis, in July, 1980 for routine removal of impacted third molars. The mandibular radio graph demonstrated an extensive radiolucency associated with the left lower molar area (Fig. I). The rad iolucency extended to the angle of the mandible. Thinning of the cortex and expansion of the inferior border of the mandible were noted . Pseudotrabeculation as well as some opacities were present within the lesion. The second molar showed resorption of apices. Bone scan revealed an area of increased activity along the left mandibular alveolar ridge near the angle. Two separate discrete foci appeared and these likely represented a dental process . No oth er bony
CHONDROMYXOID FIBROMA
557
Fig. 2. Specimens include the second and first molars. Note size and resorption of apices. Fig. I. Orthopantomograph X-ray shows an extensive radiolucency associated with the left lower third molar area. Notice the extension and expansion of the lesion. Also notice the resorption of the second molar's roots.
abnormalities were noted. The pat ient was asymptomatic and had not experienced any paresthesia, anesthesia or swelling of the mandible. His previous medical history included two right hip surgeries 10 years earlier for chronic synovitis and osteomyelitis. The family history was without history of neoplasia. Physical examination was normal. There seemed to be slight expansion of the left angle of the mand ible. No bruit or thrill was present. The area was firm and painl ess, and the dentition was intact as was the mucosa. The neurological exam was within normal limits . Chest radiograph was also within normal limits. Laboratory exams which included CBC with diff., platelets, electrolytes, PT, PIT and VA were within normal limits. A tentative diagnosis of fibro-osseous lesion in connection with an impacted left third mandibular molar was established. The patient underwent removal of his third molars and biopsy was performed. An initial histological diagnosis of osteogenic sarcoma was made independently by two different pathologists. Because it did not fit the clinical signs, history or examination, the lesion was re-biopsied a nd additional consultation with a number of pathologists was obtained. The diagnosis of chondromyxoid fibroma was then established. The patient was hospitalized and under general a nesthesia the tumor was totally removed along with the adjacent first and second molars (Fig. 2). During surgery, the inferior border, the cortical plates, both buccal and lingual, were noted to be
intact and the tumor was removed easily from the bone cavity. Immediate bone grafting using iliac crest cancellous bone was done, and the jaws immobilized by intermaxillary fixation. The hospital course was uneventful, good healing was obtained, and a V) paresthesia was noted. The patient was followed closely the first year, and no recurrence has been observed clinically or radiographically (Fig . 3). The patient mo ved out of town which made bi-annual follow up impossible. However, a 5year clinical exam and post-op rad iograph revealed satisfactory healing without signs of recurrence. On th e radiograph an upper distal radiolucency is present, probably due to fibrous healing of the central part of the bone graft.
Histology of the tumor Gross: (A) Partially calcified, irregular fragments were received measuring less than 1.0 em. in greatest dimension. The material was divided into routinely processed and that to be decalcified prior to histologic evaluation. (B) An additional soft tissue portion was received that proved to be normal peripheral nerve on histologic examination. Light microscopy The tumor is composed of smaIl uniform spindle cells which are set in a background which varies from chondroid to a more myxoid type. The tumors comprise irregular eosinophilic fragments that were necrotic in part and featured neoplastic calcification. Additional, a small, connective tissue appearing, cellular component was observed that featured additional, small and globular calcification and irregular zones of homogenization resembling osteoid (Fig. 4a) . Component cells were characterized by vesicular, small and irregu-
558
PINHOLT, ELDEEB AND WAITE
•. . - p
Fig. 3. Pre- and post-operative orthopantomographs, and a five year post-op, orthopantomogram show the healing process. No recurrence was observed. Note the healing, the bone level of the healed surgical defect and the upper distal radiolucency which might represent fibrous tissue completing the healing.
lar nuclei. Occasional larger nuclei and multipolar cells were identified but mitotic figures were not present (Fig. 4b). Electron microscopy Most of the tumor consists of a cellular lesion having ultrastructural features reminiscent of hemangiopericytoma. Although vascular spaces are not prominent, the cells have large numbers of thin filaments showing focal condensations, plasmalemmal vesicles, and poorly developed basal lamina along the cytoplasmic margin. A moderate amount of depolymerized fibrin is seen in the interstitium between these cells which ultrastructurally has features of smooth muscle differentiation. The other major pattern seen ultrastructurally corresponds to the loose myxoid areas seen by light microscopy. The myxoid stroma surrounds isolated cells which have irregular cell borders, fewjunctions, and prominent Iysosomes, lipid, and dilated rough endoplasmic reticulum. Although these cells have many features of histi-
ocytes, they somewhat resemble cartilaginous cells (Fig. 5). The presence of even a fewjunctions proves that they are not histiocytes. Also seen in the myxoid areas are undifferentiated elongated cells.
Discussion Within the maxillofacial area, this tumor is extremely rare. In a review of the literature, we found only 7 earlier cases documented as CMF. The first well-documented case was by SCHUTT & FRosT3s, who reported a mandibular CMF. The patient was a 10year-old female with a history of trauma, presenting with the lesion in the mandibular symphysis (see Table 2). Four cases were reported prior to that of SCHUTT & FROST3s• One of these, PAUL29,
CHONDROMYXOID FIBROMA
559
was diagnosed as chondromyxosarcoma; consequently it is not included in our table, SLEEPER37 reported a chondromyxoma of the mandible; it is excluded from our table since it is not a true example of CMF. DAVIS & TIDEMAN 8 reported a case of CMF ina 16-year-old male. The tumor was located within the symphysis menti. Here too a history of trauma was reported. After removal of the tumor, there was recurrence two years later. A second report was made , by GALLIA et af.14 stating that the CMF " ... . ' .. was misdiagnosed and that the original and , -, ... recurrent tumor was chondrosarcoma and :-.4.. • for that reason was excluded also. SRIVASTAVA39 reported a case of CMF in a 25'0 . : year old female in whom the lesion was • located within the symphysis menti. SPJUT et 0/.38 mentioned a case of CMF located in " , the mandible but with incomplete accompanying data. We included this case beFig. 4. (A) Small and lobular calcification and cause of its mandibular location. A sumirregular zones of homogenization resembling osteoid. (HE, 312 X). (B) Larger nuclei and multi- mary of the eight cases of CMF involving polar cells were identified. Also, some joint cells the mandible is shown in Tables 2a, b. were observed. (HE, 3l2x). Our review reveals that CMF is predomi-
.. .'
..
..
.'
..
..
.
a
.. . ...
-.
b
Fig. 5. (A) Transmission electron micrograph (T.E.M.) magnified x 11232, shows large numbers of
thin filaments showing focal condensations, plasmalemmal vesicles, and poorly developed basal lamina along the cytoplasmic margin. (B) Transmission electron micrograph magnified x 11232, shows the myxoid stroma surrounds isolated cells which have irregular cell borders, fewjunctions, and prominent lysosomes, lipid and dilated rough endoplasmic reticulum.
560
PINHOLT, ELDEEB AND WAITE
Table 2a. Summary of 8 intra-oral cases of chondromyxoidfibroma Age (years) Case # Reference Sex 39 25 I female 38 unknown unknown 2 3l female 10 3 Il 16 4 female male 13 5 41 female 42 6 19 12 female 7 24 this study male 8 total M:F 20 8 cases 2:5 37%:63% Table 2b. Summary of 8 intra-oral cases of chondromyxoidfibroma Reference Clinical features X-ray 38 unknown unknown 39 hard swelling radiolucency around roots of anterior teeth; cortex expanded Il swelling; well-defined radiolucency; ground glass; outer cortex expanded; dispain placed 3rd molar 3l swelling; radiolucency; displaced dentition history of trauma radiolucency; sclerotic scalloped history of trauma, margin; cortex thinned, impacswelling ted & displaced 3rd molar 41 radiolucency; sclerotic scalloped pain, swelling margin; intralesional trabeculation 19 swelling, diffuse radiolucency, displaced displaced teeth teeth with lost lamina dura radiolucency and small opacities asymptomatic this study around 3rd molar; sclerotic scalloped border, expansile inferior mandibular rim; resorption of apices of 2nd molar
nantly an extraoral lesion. As previously indicated, the lower limb is predominantly involved, the upper end of the tibia being the preferred site (30%) (Table I). Among the 8 cases involving the jaws, the mandible was found to be the exclusive area of involvement. The extraoral tumors occurred most frequently in the second and third decades of life. This correlated with the average age for involvement of the mandible,
Location mandible mandible symphysis mandible left molar mandible right molar mandible left molar mandible symphysis mandible left molar mandible mandible
Treatment unknown enucleation
Recurrence unknown unknown
curettage
no
enucleation
no
curettage
yes (2 years)
curettage
no
resection no and rib graft no enucleation & immediate bone grafting
which was twenty years. In the extraoral review, 116 (42%) cases occurred in females while 161 (58%) were found in males. In the mandible, 5 cases (71 %) occurred in females and 2 (29%) in males. A history of trauma was present in 2 (25%) of the oral cases. In the extraoral cases, as mentioned by RAHIMI et a/. 3D, a history of trauma was infrequent. The clinical features of the intraoral cases include history of pain and
CHONDROMYXOID FIBROMA
swelling. The radiologic characteristic was a multilocular radiolucency with a scalloped sclerotic margin. Expansion and thinning of the cortex was usual and pseudotrabeculation was common. The treatment in the oral cases was simple curettage, enucleation or resection, followed by bone grafting. Recurrence was seen in I case', 20% of cases of chondrogenic origin reported in the literature have been underdiagnosed at the first microscopic interpretation because the difference between benign/malignant in these tumors does not always predict the conduct of the tumor CHAUDRY et al.'. The diagnosis of CMF has been difficult to make. LICHTENSTEIN & JAFFE24 mentioned three cases which they had great difficulty in classifying. They mentioned certain criteria by which underdiagnosis of chondrosarcoma in the early stage of malignancy could be avoided. Among the criteria were: (1) many cells with plump nuclei; (2) more than an occasional cell with two such nuclei; (3) any giant cells with large single or multiple nuclei or with clumps of chromatin. They also mentioned that in the histologic diagnosis of chondrosarcoma, not too much importance should be attached to the scarcity or even absence of mitotic figures, since cell division in chondrosarcomas tends to be amitotic. The characteristics indicated above are found especially in the peripheral compacted cell layer in CMF and often confuse the pathologist who subsequently may diagnose CMF as chondrosarcoma. This was further confirmed by JAFFE & LICHTENSTEIN I8• They described CMF as a distinctive benign tumor likely to be mistaken especially for chondrosarcoma. They indicate that the tumor may have been diagnosed as enchondroma or myxoma, or their cancerous counterparts. DAHLIN & IRVING? stressed the importance of the morphological relationship to benign chondroblastoma, and that it is of the utmost importance to recognize the various features that make
561
possible the correct classification of CMF, thereby avoiding the misdiagnosis of CMF as a malignant tumor. 4 of II reported tumors originally were considered to possess a low degree of malignancy such as chondrosarcoma, chondromyosarcoma and osteogenic sarcoma. TuRCOTTE et 0/.45, and WILLIS48 believed that there was a histogenic link between CMF and osteoclastoma. AEGERTER & KIRKPATRICK) mentioned the possibility of CMF as a slowly progressive malignant tumor showing aggresive behavior and even metastasizing features. They believed that all CMF should be considered at least partially malignant and treated as such. RAHIMI et 0/. 30 added criteria to the histologic differences between chondrosarcoma and CMF. They stated that even though chondrosarcoma may have prominently myxoid areas, the tumor has a more distinctly hyaline cartilage quality; furthermore, it lacks the characteristic admixture of fibromatous elements. Chondrosarcoma lacks the abrupt boundary of CMF, and this aggressive quality is reflected in the radiograph Which contrasts with the benign appearance found in CMF. Electronmicroscopy may help to distinguish between CMF and chondrosarcoma, but the final diagnosis rests at the light microscope level. Electronmicroscopically, in the CMF, in contrast to chondrosarcoma the tumor cells are more pleomorphic and have irregular and elongated cell projections which often extend away from the cells and contact adjacent cells. The chondrosarcoma tends to have numerous lipid droplets and often dilated rough endoplasmic reticulum more than do CMF cells", TORNBERG et a/.44 mentioned some consistent differences electronmicroscopically between CMF and chondrosarcoma.. The cell population observed in chondrosarcoma is predominantly chondroid. The nucleus of these cells is characteristically lobulated and frequently contains a large prominent nucleolus having
562
PINHOLT, ELDEEB AND WAITE
a complex substructure. Large lipid vacuoles are present in both the cytoplasm and matrix of chondrosarcoma. These findings, notably absent in CMF, could serve to differentiate the two at the ultrastructural level. A distinctive feature of both cell types of CMF is the presence of a 700 A electron dense band between the inner and outer nuclear membranes. Typically, the nucleus of a cell is enclosed by two parallel membranes 70-80 A thick that are separated by a less dense perinuclear space of 120-140 A. Throughout, the matrix of CMF fiber aggregations having an average major banding periodicity of 973 A are present, which is a rare biological occurrence representing fibrous long spaced collagen (FLS). ERLANDSON & Huvos? and BATSAKIS et al? emphasized that it is ultramiscroscopically hard to point out differences between "normal" chondrocytes and neoplastic cartilage cells present in low-grade chondrosarcoma because the features of the cells in low grade chondrosarcoma are also found in cells comprising a variety of benign and nonneoplastic lesions of hyaline cartilage. SCHAJOWICZ et al.J3 add to the characteristics of chondrosarcoma an inverse relationship between :the glycogen amount and the grade of malignancy. Preliminary studies of the chemical composition of CMF reveal the presence of high levels of glutamic acid in the tumor matrix. This was not observed in chondrosarcoma according to MASHBURN 25• A study by KUHLMAN & McNAMEE20 evaluating enzymes mediating carbohydrate metabolism as well as specialized phosphatase revealed that CMF reflected more enzyme activity than did active areas of the epiphyseal line. In the same way that it has been difficult to differentiate benign versus malignant in the extraoral cases, it has been equally difficult to differentiate benign vs. malignant in intraoral cases. As noted earlier, GALLIA et al:" reported a misdiagnosed chondrosarcoma of
the mandible in a 16-year-old male. It was previously diagnosed as CMP. Recurrence occurred 3 years later and an incisional biopsy was reported as consistent with lowgrade chondrosarcoma, mainly because of the increased number of mitotic figures and occurrence of bi- and multi-nucleated cells. Review of the original resected tumor demonstrated a similar histological pattern in minor fragments. In our case, the initial biopsy was read as probable osteogenic sarcoma. However, because oflack ofclinical confirmation, further histologic sampling was examined, and because of the lack of reasonable diagnostic alternatives, osteogenic sarcoma was necessarily excluded. Consultations, additional sections, and interpretation of frozen sections at the time of conservative surgical removal confirmed the impression of chondromyxoid fibroma of the mandible. The operative specimen was carefully and completely evaluated to exclude osteosarcoma. The initial treatment which was planned to be hemimandibulectomy, based on the limited histopathologic diagnosis, was therefore changed to radical blockresection of the mandible, leaving the inferior border, followed by grafting with cancellous bonechips. Finally, we would like to stress the importance of correlating the relation between clinical features, radiographic appearance and histologic diagnosis, of CMF. Complete cooperation and communication between the surgeon, radiologist and pathologist is needed to establish a definitive diagnosis and treatment plan for unusual and rare tumors of the jaws.
Conclusions On the basis of the case reported and the review of the literature, the following should be stressed:
CHONDROMYXOID FIBROMA
1. Chondromyxoid fibroma of the jaws are more common in females (63%) than males (37%). 2. The mandible was the site of invasion when CMF affected the jaws. 3. CMF is a rare benign tumor likely to be mistaken for chondrosarcoma because of the bizarre nuclei in the peripheral tumor cells. 4. The treatment of choice of CMF is conservative resection followed by immediate bone grafting. 5. Radiotherapy is contraindicated because the main part of the tumor is not radiosensitive and malignant degeneration has been reported. 6. The recurrence rate of CMF is very low. The risk of malignant transformation is so minimal that radical treatment is unnecessary. 7. Clinical, radiographic and histological data are all essential to confirm the diagnosis of CMF. 8. Complete cooperation and communication between the surgeon, radiologist and pathologist is needed to establish a definitive diagnosis and treatment plan for unusual and rare tumors of the jaws.
Acknowledgement - The authors would like to acknowledge Dr. Robert Vickers for the review of the histopathological evaluation and photomicrography for the pathological specimens.
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Address:
Mohamed £1 Deeb Department of Oral and Maxillofacial Surgery School of Dentistry University of Minnesota 7-174 Malcolm Moos Health Sciences Tower 515 Delaware Street S .E. Minneapolis, MN 55455 USA