Ⅰ. INTRODUCTION

Osteochondral injuries are frequent in temporomandibular joint (TMJ) due to masticatory and facial musculoskeletal trauma, and can lead to disabling arthritis if not recognized and treated appropriately in the early stages. The anatomic configuration and biomechanical functions of TMJ are important for understanding its particular pattern of osteochondral injury in radiological imaging appearance.¹⁾ The term of osteochondritis dissecans was used when the lesion showed dominant inflammatory signs of osteoarthritis, while osteochondrosis dissecans (OCD) was involved with only mild inflammatory reaction. But clinically the inflammatory signs are sometime indistinguishable, therefore, both of osteochondritis dissecans and osteochondrosis dissecans (OCD) were tend to be used indifferently. However, the present case was found only mild inflammatory reaction localized at the epiphyseal area of condyle through pathological examination of removed specimen, and it did not show diffuse inflammatory cell infiltration frequent in osteoarthritis. So that it was diagnosed as osteochondrosis dissecans (OCD), and further investigation was done with literature review `in the term of OCD.

Osteochondrosis dissecans (OCD) is a common and clinically important joint disorder that occurs in human beings and in multiple animal species, most commonly pigs, horses, and dogs.²⁾ This disorder is defined as a focal disturbance of endochondral ossification and is regarded as having a multifactorial etiology, with no single factor accounting for all aspects of the disease. The most commonly cited etiologic factors are heredity, rapid growth, anatomic conformation, trauma, and dietary imbalances; however, only heredity and anatomic conformation are well supported by the scientific literature.^{3, 4)}

The way in which the disease is initiated has been debated. Although formation of a fragile cartilage, failure of chondrocyte differentiation, subchondral bone necrosis, and failure of blood supply to the growth cartilage all have been proposed as the initial step in the pathogenesis, the recent literature strongly supports failure of blood supply to growth cartilage as being the most likely.^5-7) The term OCD has been used to describe a wide range of different lesions among different species, including epiphyseal cartilage lesions accompanied by delay in endochondral ossification, and cleft formation through articular cartilage (dissecans).

OCD is a common condition in children, adolescents, and young adults. Describing OCD together with osteochondral fractures and epiphyseal ossification disturbances, OCD represents an osseous lesion with secondary involvement of the overlying cartilage. OCD is a form of osteochondrosis limited to the articular epiphysis. The most commonly affected areas include, in decreasing order of frequency, the femoral condyles, talar dome and capitellum of the humerus. OCD rarely occurs in the shoulder joint, where it involves either the humeral head or the glenoid.So far only one case of OCD occurred in human TMJ was diagnosed with the radiological findings of loose bodies in the joint space,and another case of human mandibular OCD was found as palaeopathological and variant conditions of the Homo heidelbergensis type specimen.¹²⁾

The clinical courses of osteochondral lesions are sometimes variable and showed quite different prognosis, but their disease patterns has been not clearly defined. The longitudinal analyses in literatures usually discussed about the natural history of the disease, conservative treatment, surgical options like debridement and anterograde drilling, retrograde drilling, osteochondral transplantation and autologous chondrocyte transplantation.^13-15)

A staged treatment regime was advised depending on the radiological and histological changes of condyle. Beginning as avascular osteonecrosis, OCD forms a transitional zone that harbors the potential of restoration with complete healing or progression to an osseous defect.¹⁶⁾ Mechanical and traumatic factors are etiologically dominant in OCD, but a predisposition seems to be a contributing factor in some patients.³⁾ OCD is generally diagnosed by conventional radiology. Its therapy is determined by the stage of the lesion and MRI will become the method of choice for staging. Intact cartilage, contrast enhancement of the lesion, and absent "cystic" defects are findings of MRI stage I and justify conservative therapy, obviating arthroscopy.^1718,) Cartilage defect with or without incomplete separation of the fragment, fluid around an undetached fragment, and a dislodged fragment are MRI findings observed in stage II and require arthroscopy with possible intervention.^1920,) The present study demonstrated a case of stage II OCD at TMJ, which had been partly resected a portion of over-grown condyle to treat severe TMJ pain and occlusal deviation. The removed condyle specimen was precisely examined histomorphometrically to define the final diagnosis and its pathogenetic progresses.

Ⅱ. CASE REPORT

A 57 years old female complained of severe pain on the right temporomandibular joint (TMJ) area. Her right condyle head had been partly resected under surgical operation 13 years ago due to condyle hypertrophy, thereafter she felt dull pain on TMJ area and recently the lesion became severely swelled and painful leading to cancer phobia. At that time, the resected specimen was simply diagnosed as condyle hyperplasia with thick cartilaginous cap. The present radiological views showed slightly enlarged and sclerosed condyle with the increased radiopacity (Fig. 1A), but its articular sliding function was almost disabled by condyle head locking in glenoid fossa during mouth opening (Fig. 1B and C). The TMJ lesion was carefully managed with conservative physiotherapy and pain treatment.

In this study the microsection of condyle head examined previously was re-evaluated to define the ongoing pathology histomorphometrically, and finally diagnosed as osteochondrosis dissecans (OCD). The pathogenetic mechanisms of OCD were further explored for the changes of endochondral ossification. Cross section of condyle head showed both the main pathological lesion (anterior 4/5 area) and normal condylar tissue (posterior 1/5 area) (Fig. 2A). On the top of condyle head several huge clefts were found in the cartilage tissue, which were deeply extended to the marrow trabecular bones (Fig. 2B1). In the cleft area the cartilage tissue contained the reduced number of chondrocytes and showed diffuse hyaline degeneration (Fig. 2B2). However, in the histological observation, there clearly showed the border area (line α in Fig. 2A) between pathological lesion and normal condylar tissue (Fig. 2C1).

The pathological lesion was composed of irregular hypertrophic chondrocytes with immature endochondral ossification in the marrow tissue (Fig. 2C3), while the normal condylar tissue showed the well-aligned hypertrophic proliferation of chondrocytes approximating the endochondral ossification (Fig. 2C2). The hypertrophic zone was much thickened, and some hypertrophic chondrocytes were surrounded by eosinophilic cartilaginous matrix and abruptly underwent cellular apoptosis (Fig. 2C3).

In the histomorphometric analysis several areas of condyle microsection were analyzed in high magnification under light microscope, and disclosed the frequent vertical and horizontal cleft formation in the superficial layer of condylar cartilage, resulted in diffuse hyaline degeneration (Fig. 2D).

On the other hand, chronic inflammatory reaction was found in the epiphyseal marrow tissue of condyle head, which resulted compensatory deposition of osteophytes (Fig. 2E). The inflammatory reaction was mild and localized at the epiphyseal area condyle head, infiltrated with small round cells and macrophages (Fig. 2E2 and 2E3). There appeared no abscess formation causing osteomyelitis, but some capillary channels in sub-epiphyseal marrow tissue were much dilated (Fig. 2E4).

Ⅲ. DISCUSSION

Osteochondrosis is a term used to describe a group of disorders that affect the growing skeleton. These disorders result from abnormal growth, injury, or overuse of the developing growth plate and surrounding ossification centers. The exact etiology of these disorders is unknown, but genetic causes, repetitive trauma, vascular abnormalities, mechanical factors, and hormonal imbalances may all play a role.21, 22)

During the early stages of articular osteochondrosis, genes encoding vacuolar H(+)-ATPase V0 subunit d2 (ATP6V0D2), cathepsin K, integrin-binding sialoprotein, integrin αV, low density lipoprotein receptor-related protein 4, lumican, osteopontin, and thymosin β4 (TMSβ⁴⁾ were expressed at higher levels in lesions than in control cartilage. Some genes identified as associated with early lesions are known chondrocyte hypertrophy-associated genes, and in transmission electron microscopy studies normal hypertrophic chondrocytes were observed in lesions. Differential expressions of ATP6V0D2 and TMSβ4 in the cartilage of early naturally occurring osteochondrosis lesions was found by immunohistochemistry.^{23, 24,)} The present case of OCD showed a cartilaginous cap composed of normal and young chondrocytes undergoing hypertrophic chondrocytes, which abruptly died of apoptosis at epiphyseal area. But the cartilaginous tissue contained no dysplastic chondrocytes forming tumorous growth.

Failure of the cartilage canal blood supply to epiphyseal growth cartilage has been implicated in the pathogenesis of articular osteochondrosis in horses and other animal species.²⁵⁾ The lesions were located in regions where cartilage canal vessels traversed the chondro-osseous junction, and showed ischemic chondronecrosis that preceded and predisposed to the development of osteochondrosis dissecans (OCD) and subchondral bone cysts.²⁶⁾ The present cases showed severe dilatation of capillary channels in epiphyseal zone of condyle. These findings may suggest the abnormal blood supply and also caused the persistent dull pain in this bony lesion.

Besides OCD, synovial chondromatosis (SC) is another disease with loose bodies in joint space. It is assumed that OCD is a reaction of some type of joint trauma, while gene mutations similar to what is known in chondrosarcomas can be found in metaplastic SC. However, both diseases have very similar symptoms. Patients suffer from pre-auricular swelling, facial or temporomandibular joint pain, and occasional joint locking.¹¹⁾ OCD is a retrogressive disease of the articular-epiphyseal cartilage and subchondral bone layers, leading to pain and decreased mobility. In OCD samples, there was significantly increased gene expressions of caspase-10, Fas, cytochrome C, and thymosin-β10 in chondrocytes along the osteochondral junction and increased Fas gene expression in chondrocytes adjacent to cartilage canals, compared to controls. Higher matrix Fas and cytochrome C protein expressions, lower mitochondrial cytochrome C protein expression, and a trend for higher cytoplasmic caspase-10 protein expression were also found. Collectively, these results suggest that both extrinsic and intrinsic apoptotic pathways were activated in OCD cartilage.²⁷⁾

Increased apoptosis of osteochondral junction chondrocytes may be one of characteristic features in OCD, and then the present case of OCD also showed many apoptotic chondrocytes which were gradually surrounded by basophilic cartilaginous matrix produced by themselves and abruptly underwent cellular apoptosis. Although the present study did not perform immunohistochemical staining using pro-apoptotic markers, the microsection of OCD clearly showed hyperplastic chondrocytes, which were normal looking but progressed to pre-mature apoptosis in the histological observation based on the routine hematoxylin and eosin stain.

In the present study, a complicated TMJ lesion, which had been performed for partial condylectomy under the clinical and radiological diagnosis of condyle hypertrophy 13 years ago, was re-evaluated due to the persistent pain and swelling at right pre-auricular area. The microsections of condyle specimen showed thick cartilaginous cap which was normal looking, but the histomorphometric analysis of the hypertrophic cartilaginous tissue disclosed numerous hyperplastic chondrocytes in its inner area and degenerative hyalinous tissue in its outer area. The proliferating zone in the outer surface area of cartilaginous cap disappeared, while the hyperplastic chondrocytes in the inner area were proliferative and became swelled to be hypertrophic chondrocyte zone. This growth discrepancies between the outer degenerative hyalinous cartilage tissue and the inner hyperplastic cartilaginous tissue may produce the vertical and horizontal clefts and cartilage peeling off in the outer surface of cartilage cap spontaneously, that is, the formation of dissecans and resulted in the loose body in joint space. Therefore, the present case of mandibular condyle was diagnosed as OCD differentially from condyle hypertrophy, osteochondroma, and osteoarthritis.