| Background:Phosphaturic mesenchymal tumor(PMT)is associated with tumor-induced osteomalacia(TIO).PMT are mesenchymal-originated and can involve any bone or soft tissue location.They lack prominent clinicopathological features,and are typically slow-growing,difficult to locate,and thus easy to be misdiagnosed.At present,with only a few cases or case series reported,the histological features and immunohistochemical profiles of PMT needs further elucidated.Purposes:1.To summarize clinical,biochemical and imaging features of PMT.2.To observe the change of preoperative and postoperative serum phosphate level.3.To analyze histological features and immunohistochemical profile of PMT.Methods:Two hundred and nine cases pathologically diagnosed PMT cases from Janurary,2004 to September,2017 in Peking Union Medical College Hospital(PUMCH)were collected.Informations including gender,age,past and family history,clinical signs and symptoms,duration of osteomalacia,tumor size,tumor location,biochemical and bone metabolic indices,imaging features,operation and treatment plan were gathered.Their histological and immunohistochemical features were analyzed.Results:Two hundred and nine PMT cases showed a male to female ratio of 1.13 to 1,and an average age of 42 years old.Patients generally presented with bone pain(93.8%,196/209),followed by fatigue,limitation of activity,lose in height,thoracic deformation and pathological fracture.The average duration of osteomalacia was 5.7 years(ranged from 20 days to 40 years)in 197 cases with available documentation.Preoperative and postoperative serum phosphate level could be tracked in 165 cases.Average preoperative serum phosphate concentration was 0.49mmol/L,with 2.27%in normal range,comparing with a postoperative concentration of 0.92mmol/L and 82.39%in normal range(p<0.001).The postoperative accumulated recovery rate of serum phosphate was 79.78%in average.It was 87%in patients with en bloc excision comparing to 24%in patients with residual tumor(p<0.001).PMT was most frequently located in lower limbs(54.5%,114/209),followed by head and neck(29.7%,62/209).Octreotide Scanning(87.8%,129/147)and 68Ga-DOTA-TATE PET/CT(96.5%,82/85)could detect occult focus,with higher sensitivity and specificity in 68Ga-DOTA-TATE PET/CT.Immunohistochemical staining revealed a variety ratio of positive staining by vimentin(166/166,100%),NSE(143/148,96.6%),CD56(162/175,92.6%),FGF23(88.4%,114/129).CF68(88.0%,95/108),D2-40(65.4%,87/133),bcl-2(62.4%,108/173),SMA(55.5%,81/146),CD99(48.1%,78/162)and CD34(23.1%,40/173).Ki-67 index was less than 5%in 70.1%cases,and was more than 10%in 7%cases.Conclusions:1.PMT displayed distinct clinical and serum biochemical features,most often located in lower limbs,followed by head and neck.2.Precise location and complete excision were effective treatment.3.Serum phosphate level could essentiallyrecovered in PMT patients underwent complete excision and negative margin.4.PMT displayed a variety of histological morphology and expression of many immunohistochemical markers,indicating a multipotential differentiation potential,5.Clinical features and symptoms,serum biochemical indexes,imaging and immunohistochemical profile contributed to the correct diagnose and treatment of PMT.Background:Phosphatruic mesenchymal tumor(PMT)is associated with tumor-induced osteomalacia(TIO).Studies concerning the heterogeneity of PMT were limited.We retrospectively analyzed 209 PMT cases(largest sample size as far as we know)of PUMCH,and revealed 22 cases displayed histological characteristics different from conventional PMT(phosphatruic mesenchymal tumor/conventional mixed connective tissue type,PMT/PMTMCT).These tumors had both epithelial and mesenchymal components.Epithelial cells were widely distributed in the tumor,forming small irregular nests,similar with odontogenic epithelium.Mesenchymal part was composed of spindle fibroblast-like or myofibroblast-like cells,arranged in storiform or fascicular pattern.Tumors harbored less vessels and cell types than conventional PMT/PMTMCT.We named this tumor type as(PMT,mixed epithelial and connective tissue type;PMTMECT).The clinicopathological features and immunohistochemical profiles with PMT/PMTMCT of the same location remained to be elucidated.Purposes:1.To observe the histological features of PMTMECT.2.To Compare the differences of clinicopathological features and histological characteristics between PMTMECT and PMTMCT.Methods:1.Cases diagnosed as PMT in PUMCH from January 2004 to September 2017 were reviewed by two experienced pathologists independently.Twenty-two cases of PMTMECT were selected.2.Select twenty-two cases of PMTMCT in head and neck for comparison.3.Collect informations including gender,age,past and family history,clinical signs and symptoms,duration of osteomalacia,tumor size,tumor location,biochemical and bone metabolic indices,imaging features,operation and treatment plan.4.Perform immunohistochemical staining of FGF23,SSTR2A,FGFR1,AE1/AE3,Vimentin,NSE,CD56,CD68,SMA,CD34,Bcl-2,D2-40 and CD99.5.Analyze the differences of histological features and immunohistochemical profiles between PMTMECT and conventional PMTMCT.Results:1.PMTMECT had preponderance of male(M:F=2.67:1),while PMTMCT had preponderance of female(M:F=0.57:1)(p<0.01).PMTMECT had earlier onset than PMTMCT(mean age:36.8 ±14.7v.s.47.6 ± 9.4 years old,p<0.01).2.PMTMECT more often involved maxilla(45.5%,10/22)and mandible(54.5%,12/22),while PMTMCT more often involved nasal cavity and paranasal sinus(72.7%,16/22)(p<0.01).3.PMTMECT and PMTMCT displayed no significant differences in clinical features and biochemical profiles.Patients generally presented with bone pain,fatigue,hypophophate,hyper-ALP,and normal to lower level of 1,25-Vitamin D.Patients of PMTMECT all had swollen ingival or alveolar bone,and loosening of teeth.4.PMTMECT had both epithelial and mesenchymal components.Epithelial cells were widely a scattered distributed in the tumor,forming small patches or irregular nests,similar with odontogenic epithelium.Mesenchymal part was composed of spindle fibroblast-like or myofibroblast-like cells,arranged in storiform or fascicular pattern,with the presence of mature bone tissue and myofibroblast cells.PMTMCT were purely mesenchymal,mainly composed of round,oval and short spindle cells.PMTMCT had rich blood vessels,including malformed thick wall vessels,and often displayed perivessel mucinous degeneration.5.Immunohistochemistry:PMTMECT showed strong AE1/AE3 staining in epithelial components and strong Vimentin staining in mesenchymal component,while FGF23,SSTR2A and NSE were positive in both components.In most cases,CD99(21/22,95.5%),CD56(16/22,72.7%),Bcl-2(21/22,95.5%),D2-40(19/22,86.4%)and FGFR1(8/22,36.4%)were positive in one or both components.One case was positive for S-100(1/7,14.3%).Mesenchymal components has scatteredstaining of CD68,mainly in histiocytes(22/22,100%),and focus staining of SMA(15/22,68.2%)and CD34(9/19,47.4%).No case was positive for Desimin(0/22)and Syn(0/6).Among primary tumors,Ki-67 index was less than 1%in 68.2%(15/22)cases,2-5%in 27.3%(2/22)cases and more than 5%in 4.5%cases(1/22).PMTMCT had strong Vimentin,SSTR2A and NSE staining in mesenchymal components,and variable staining of FGF23(18/22,81.8%),Bcl-2(19/22,86.3%),CD68(21/22,95.5%),CD56(19/22,86.3%),CD34(17/22,77.2%),D2-40(13/20,65%),SMA(11/21,52.3%),CD99(10/20,50.0%),S-100(5/11,45.4%)and FGFR1(7/22,31.8%).AE1/AE3(0/22),Desmin(0/20)and Syn(0/12)were negative in all cases.Ki-67 index was less than 1%in 45.4%(10/22)cases,2-5%in 45.4%(10/22)cases and more than 5%in 9%cases(2/22).Conclusion:1.PMTMECT had preponderance for male,mainly located in alveolar bone and invaded surrounding soft tissue and oral mucosa.Tumor could be discovered in preoperational oral examination.Average age of diagnosis was less than 40 years old.2.PMTMECT was histologically distinguishable from PMTMCT,they were composed of both epithelial(similar to odontogenic epithelium)and mesenchymal(spindle cells in fascicular or storiform pattern)components,with less blood vessels and less variety of cell types.Mature bone tissue and myofibroblast cells often presented.3.PMTMECT had unique AE1/AE3 staining for epithelial components,but relatively concordant expression of other markers,including FGF23.SSTR2A.FGFR1?Vimentin?NSE?CD99?CD56?Bcl-2?D2-40?CD68?SMA?CD34 and S100.4.PMTMECT was a distinct subtype of PMT.When TIO was suspected,periodontal examination should be included as clinical routine,especially for young male patients. |
PDF Full Text Request