The Clinico-Pathological And Pathogenic Study On Diffuse Tenosynovial Giant Cell Tumor Of Temporomandibular Joint

Objectives:Firstly,to provide evidences for the differential diagnosis and treatment of temporomandibular joint(TMJ)diffuse tenosynovial giant cell tumor(D-TSGCT)by retrospectively analyzing the clinical and imaging features,treatment methods,histopathological features and immunophenotypes.Then,to explore the mechanism of the bone destruction in D-TSGCT by analyzing the expression of related proteins and the characteristics of CD 14-negative(CD14-)and CD 14-positive(CD 14+)cells.Lastly,to further analyze the histopathological and imaging findings of D-TSGCT with chondroid components,explore the origin of the chondroid components and the differential potiential of CD14-cells in D-TSGCT.Methods:1.Thirty-three cases of TMJ D-TSGCT or pigmented villonodular synovitis were enrolled in this study.The demographics,clinical manifestations,imaging features,treatment selections,complications and the recurrence rate were summarized and analyzed.Immunohistochemical staining was used to detect the expression of Ki67,CD68,and CD31.2.The expression of RANKL,RANK,M-CSF and MMP9 in tissues of D-TSGCT were detected by RT-PCR,western blot and immunofluorescence.Magnetic absorting cell sorting were used to isolate the CD14+cells and CD14-cells.The expression of related proteins in two types of cells were detected respectively.The roles of two types of cells on the formation of osteoclasts were verified through the induction of osteoclasts,cell migration and invasion assays.3.The histopathological and immunohistochemical charateristics of chondroid components in D-TSGCT were further analyzed.The expression of surface markers of stem cells,CD90,CD 105 and CD73,in CD 14-cells were analyzed by flow cytometry.The differential potential of osteogenesis,chondrogenesis and adipogenesis were detected.Results:1.The mean age of 33 cases of TMJ D-TSGCT was 47 years old(range,24-62 years old).The ratio of female to male was 1.2:1.All cases were unilateral onset.Swelling and mandibular dysfunction are dominant symptoms.15.2%of cases showed hearing loss.CT showed 93.9%with bone destruction and 48.5%with the skull-base destruction.Contrast-enhanced CT showed 88%with enhancement.Magnetic resonance imaging(MRI)revealed heterogeneous low signals in most cases on both T1WI and T2WI.The specimens were brownish and friable.Microscopic appearance revealed expansive sheets of mononuclear cells,scattered osteoclast-like multinucleated giant cells,inflammatory cells and foam cells.All cases underwent surgery.Ten patients received postoperative radiotherapy.The follow-up duration ranged from 2 months to 13 years.Five cases showed recurrence on imaging examination.The Ki67 index of the recurrent cases was higher than that of the non-recurrent ones.2.RANKL,M-CSF,RANK and MMP9,which were contributed to the formation and function of osteoclasts,were overexpressed in D-TSGCT.CD 14-cells had proliferation ability.CD 14-cells overexpressed M-CSF,and could promote the formation of osteoclasts.In addition,CD14-cells promoted the invasion and migration of CD14+cells.CD14+cells could fuse into osteoclasts and overexpress MMP9.3.Fifteen cases of D-TSGCT contained different proportion of chondroid components microscopically.The microscopic appearance of chondroid components revealed hyaline cartilage,chondro-osseous or lace-like intercellular calcification.A large amount of cartilage nodules and free bodies could be seen in three cases of simultaneous D-TSGCT and synovial chondromatosis.A subpopulation of CD14-cells express CD90,CD105 and CD73.These cells had chondrogenic,osteogenic and adipogenic potential.Conclusions:1.The common clinical manifestations of TMJ D-TSGCT are swelling and dysfunction of temporomandibular joint.The nonspecific clinical manifestations make TMJ D-TSGCT easily misdiagnosed as parotid tumors,temporomandibular disorders and tumors.D-TSGCT has aggressive and recurrent nature.Open surgery is the common treatment option.Adjunct postoperative treatment should be taken for the lesion with intracranial invasion and extensive margins.2.D-TSGCT has aggressive nature.The rate of skull-base destruction was 48.5%.The mechanism of bone destruction in D-TSGCT may be related to the overexpression of M-CSF,RANKL,RANK and MMP9.CD14-cells,with proliferation ability,overexpressed M-CSF which could promote the formation of osteoclasts.CD 14+cells which were progenitor cells of osteoclasts could fuse into multinucleated giant cells.CD 14+cells overexpressed MMP9,and had the invasion ability.Two sorts of cells interacted with each other to promote bone destruction in D-TSGCT.3.D-TSGCT with chondroid component is a rare subset of D-TSGCT whose predilection is TMJ.D-TSGCT with chondroid component is needed to be differentiated with chondroblastoma and synovial chondromatosis histologically.The chondroid components may be derived from the differential potential of CD 14-cells.