The Clinical Features, Imaging Localization And SSTR2&5 Immunohistochemical Analysis Of Neoplastic Osteomalacia

Part Ⅰ The clinical study of tumor induced osteomalacia and localization of tumorBackgroundTumor-induced osteomalacia(TIO)is a metabolic bone disease caused by tumors.It is characterized by abnormal phosphorus and bone turnover caused by increased phosphorus in the kidneys.Its common clinical manifestations are bone pain,muscle pain,fatigue,and limited mobility.Typical biochemical features are normal levels of calcium and PTH in the blood,normal or reduced levels of 1,25-(OH)2D3,and elevated alkaline phosphatase levels.Most of the pathological types of tumors were phosphaturic mesenchymal tumors.In addition to common imaging methods,such as ultrasound,CT,MRI,etc.,somatostatin receptor imaging is widely used in the localization of TIO lesions.PurposeTo summarize the clinical features of tumor osteomalacia patients and the choice of imaging methods.MethodA total of 250 patients with tumor-induced hypophosphatemia osteomalacia diagnosed at Peking Union Medical College Hospital from January 1998 to December 2017 were studied.The patient’s medical history,physical examination,bone metabolism-related biochemical examination,bone mineral density,bone X-ray were collected,and the patient with suspected tumor-associated low-phosphorus osteomalacia was further examined with technetium-99m labeled octreotide(99mTc-OCT).The octreotide-positive patients were further subjected to ultrasound,CT,MRI,and other specific tumor sites.Patients with octreotide-negative but highly suspicion of TIO underwent whole-body PET examination and actively sought tumor sites.Surgical treatment was performed on well-defined patients,and pathological diagnosis was made clear.Results1.Of the 250 patients with TIO,137(54.8%)were male and 113(45.2%)were female.The average age of visit was 42.7113.5 years,the median duration was 4 years,and the average age of onset was 38.1 ± 12.2 years.Clinical manifestations,249 cases(99.6%)with bone pain,173 cases(69.2%)with fatigue,239 cases(95.6%)with difficulty in movement,175 cases(70.0%)with shorter height,shorter 7.4±5.0 cm,77 cases(30.8%)with skeletal deformity,46 cases(18.4%)with teeth loose/shed2.X-ray plain film showed 241 cases of trabecular bone texture blurred(96.4%),64 cases of pelvic deformation(25.6%),203 cases of fracture(81.2%),137 cases of vertebral body deformation(54.8%),false fracture line Of the 71 patients(28.4%),21(8.4%)had femoral head deformities and 3(1.2%)had femoral head necrosis.3.250 patients with TIO had an average blood phosphorus of 0.45±0.13mmol/l,an average total calcium of 2.23±0.15mmol/l,a blood iCa of 1.10±0.08mmol/l,a blood ALP of 291±143U/L,and blood PTH.66.8±32.9pg/ml,24-hour urinary calcium 2.32±1.26mmol,24-hour urinary phosphorus 16.90±10.55mmol,serum 1,25(OH)2D3 was 18.9±10.8pg/ml,serum 25(OH)D was 19.8 ±21.3 ng/ml,β-CTX was 0.79±0.73 ng/ml,and the phosphorus clearance index TmP/GFR was 0.46±0.17 mmol/l.4.Of the 248 TIO patients,179 had a positive finding of 99mTc-OCT(72.2%),indicating that 99mTc-OCT is an effective method for detecting TIO tumors.99mTc-OCT examination combined with ultrasound,CT,MRI contributes to tumor localization.5.67 of the 99mTc-OCT negative or false positive patients underwent 68Ga-DOTATATE PETCT,all positive(100%).It shows that 68Ga-DOTA PET is more sensitive to TIO tumors and is a more effective localization method.6.TIO tumors can be located throughout the body,most commonly in the lower extremities(112 cases,44.8%),followed by the head(71 cases,28.4%).Most of the tumors were located in soft tissue(162/250,64.8%)and the rest were located in bone tissue(88/250,35.2%).7.The tumor of tumorous osteomalacia is a mesenchymal tumor,and the pathological type is a phosphate-urinary mesenchymal tissue tumor(PMT).There are also some rare tumors that can cause neoplastic osteomalacia,such as renal clear cell carcinoma and thymic carcinoid.8.Although most tumors are benign,they may be malignant or even metastasized.Part Ⅱ Immunohistochemical analysis of SSTR2&5 in tumors of tumor induced osteomalaciaBackgroundThere are six different subtypes of somatostatin receptors(SSTRs)(SSTR1,SSTR2A,SSTR2B,SSTR3,SSTR4,and SSTR5).Most neuroendocrine neoplasms(NETs)express high levels of SSTRs,as do PMTs that cause neoplastic osteomalacia.Somatostatin receptor imaging agents are used to localize TIO pathogenic tumors.68Ga-DOTATATE,a 68Ga-labeled somatostatin receptor imaging agent,showed better localization in TIO tumors that were not mapped by octreotide.Octreotide imaging has a good affinity for SSTR2 and SSTR5,and 68Ga-DOTATATE has a higher affinity for SSTR2 than SSTR5.PurposeTo investigate whether the difference in TIO pathogenic tumors between octreotide imaging and 68Ga-DOTATATE PETCT is related to the difference in tumor expression between SSTR2 and SSTR5.MethodIn this study,29 cases of paraffin-embedded specimens of patients with osteomalacia diagnosed in Beijing Union Medical College Hospital from 2015 to 2017 were collected as experimental group.Among them,group 1,10 cases with positive octreotide imaging but no 68Ga-DOTATATE PETCT,group 2,There were 14 cases with negative octreotide imaging and 68Ga-DOTATATE PETCT positive,and group 3 and 5 cases with both positive.SSTR2/5 immunohistochemical staining was performed on it and then read by a pathology specialist.Grouped summary data for chi-square analysis.Results1.According to the current results,the expression level of SSTR2 in group 2 is higher than that in group 1,and it is more prone to tumor localization by 68Ga-DOTATATE PETCT.2.Expected results:SSTR5 staining results in group 2 were weaker than group 1,and tumor SSTR expression in group 2 was mainly concentrated on SSTR2 subtype,octreotide imaging could not effectively locate it,and 68Ga-DOTATATE PETCT was more valuable for its localization.