Imaging Characteristics of 68Ga-DOTATATE PET/CT in Tumor-Induced Osteomalacia / 罕见病研究

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by tumors secreting fibroblast growth factor 23 (FGF23) that promotes urinary phosphorus excretion. Thus, TIO is typically characterized by phosphoruria, hypophosphatemia, and osteomalacia. Diagnosis and localization of the tumor is often difficult due to its small size, slow growth and concealed location. Due to the high expression of somatostatin receptors in pathogenic tumors, nuclear medicine functional imaging, particularly somatostatin receptor imaging, is used for diagnosis and localization of culprit tumors with high sensitivity and specificity. Here we retrospectively analyze 25 cases in which 68Ga-DOTATATE PET/CT successfully localized and diagnosed TIO culprit tumors. The clinical features, pathological results and image characteristics of 68Ga-DOTATATE PET/CT imaging were analyzed and compared with other imaging diagnostic techniques. It was confirmed that 68Ga-DOTATATE PET/CT imaging was the preferred imaging technique for successful diagnosis and localization of TIO pathogenic tumors.

Phosphaturic mesenchymal tumor: An underdiagnosed rare entity

Tumor-induced osteomalacia is a paraneoplastic syndrome resulting in renal phosphate wasting and decreased bone mineralization. Phosphaturic mesenchymal tumors represent a rare etiology of tumor-induced osteomalacia. They are exceptionally rare, probably accounting for < 0.01% of all soft tissue tumors. Most PMTs present as small inapparent lesions that require very careful clinical examination and radionucleotide scan for localization. Here we describe a case in a 65 years old woman with recurrent multiple bone fractures and subsequent detection of a tumor involving right femur and adjacent soft tissue, low phosphate level and elevated serum Fibroblast growth factor-23 (FGF-23).

Tumor-induced osteomalacia

Tumor-induced osteomalacia (TIO), also known as oncogenic osteomalacia, is a rare paraneoplastic syndrome characterized by hypophosphatemia resulting from decreased tubular phosphate reabsorption, with a low or inappropriately normal level of active vitamin D. The culprit tumors of TIO could produce fibroblast growth factor 23 which plays a role in regulating renal Pi handling and 25-hydroxyvitamin D 1α-hydroxylase activity. Chronic hypophosphatemia could eventually lead to inadequate bone mineralization, presenting as osteomalacia. The diagnosis should be considered when patients manifest as hypophosphatemia and osteomalacia, or rickets and needs to be differentiated from other disorders of phosphate metabolism, such as the inhereditary diseases like X-linked hypophosphataemic rickets, autosomal dominant hypophosphataemic rickets, autosomal recessive hypophosphataemic rickets and acquired diseases like vitamin D deficiency. Localization of responsible tumors could be rather difficult since the vast majority are very small and could be everywhere in the body. A combination of thorough physical examination, laboratory tests and imaging techniques should be applied and sometimes a venous sampling may come into handy. The technology of somatostatin-receptor functional scintigraphy markedly facilitates the localization of TIO tumor. Patients undergoing complete removal of the causative neoplasm generally have favorable prognoses while a few have been reported to suffer from recurrence and metastasis. For those undetectable or unresectable cases, phosphate supplements and active vitamin D should be administrated and curative intended radiotherapy or ablation is optional.

Localization of Oncogenic Osteomalacia by Systemic Venous Sampling of Fibroblast Growth Factor 23

PURPOSE: Tumor-induced osteomalacia (TIO) is characterized by hypophosphatemia caused by a phosphaturic mesenchymal tumor. While surgical resection of the tumor leads to a cure, identification of the responsible tumor is challenging. Recently, several studies showed that systemic sampling of fibroblast growth factor 23 (FGF23) is helpful for localization of tumors. The present study aimed to evaluate the clinical utility of this method in Korean patients. MATERIALS AND METHODS: Six patients compatible with TIO who were admitted to our hospital between 2006 and 2015 were analyzed. Systemic venous sampling of FGF23 was performed to detect blind lesions or to confirm a suspicious lesion identified in previous imaging studies. RESULTS: Venous sampling helped confirming the tumor in five of the six patients. Three patients underwent surgery after sampling, and in two patients, the lesions were detected after 3 years by means of 68Ga-DOTATOC positron emission tomography with computed tomography. In one patient, there was a local elevation of serum FGF23 without any related lesion on additional imaging. CONCLUSION: Our data strengthened the value of venous sampling of FGF23 in predicting the location of tumors and suggested that it can be more effective in the presence of the relevant lesion in subsequent imaging analyses.

Phosphaturic mesenchymal tumor:clinicopathological analysis of 12 cases / 临床与实验病理学杂志

Purpose To study the clinicopathological features of the phosphaturic mesenchymal tumors. Methods The clinicopatho-logical data, histology and immunohistochemical findings of 12 cases of phosphaturic mesenchymal tumors were retrospectively analyzed with review of the relevant literature. Results Among the 12 patients studied, 8 were males and 4 were females. Their age at the time of operation ranged from 23 to 63 years (mean=40. 5 years). The duration of symptoms ranged from 1 to 14 years (mean =5. 6 years) . A history of long-standing bone pain, arthralgia, limitation in movement, accompanied with hypophosphatemia and hyperphos-phaturia were present in all cases. The tumors size ranged from 1 to 7. 5 cm ( mean size=2. 7 cm) . The tumors were primarily com-posed of spindle cells, and were accompanied with osteoclast-like giant cells partly. Their background were rich in blood vessels. In addition, there were scattered tufed thick vascular anomaly, thin vascular, islands of mature adipocytes and chondroid cells. In 7 of the 12 cases, there were dystrophic calcification in an unusual flocculent. Spindle epithelium were noted in 2 cases. Mitotic figures were rare in 10 cases. In 2 of the 12 cases however, mitotic figures were commonly encountered, and in 1 of the 2 cases, heterotypic cells were notablely observed as well. On immunohistochemical study, the tumor cells were all positive for vimentin and CD56. The positivi-ty for NSE, CD99, BCL-2 in 11, 8 and 7 cases were expressed in 12 cases. In 4 and 6 of the 12 cases, CD34 and SMA were positive in various degree. Ki-67 proliferation index were less than 5% in 10 cases, and 10% and 25% in 2 cases. The duration of follow-up ranged from 2 to 108 months ( mean=22 months) . 2 cases were recurred at 72 and 84 months after the operation, respectively. So far, the remaining 10 cases had no recurrence and metastasis. Conclusioin The phosphaturic mesenchymal tumors are either benign or low-grade malignant. Their histomorphology are multivariable and short of specificity. It is important to make the correct diagnosis in combination with their common features and clinical datas.

Tumor mesenquimatoso fosfatúrico de fosa nasal con compromiso intracraneano: reporte de un caso y revisión de la literatura / Nasal fossa phosphaturic mesenchymal tumor with intracraneal compromise: case report and review of the literature

El tumor mesenquimatoso fosfatúrico (TMF) es una enfermedad extremadamente rara. Según evidencia reciente es causado por la sobreexpresión del factor de crecimiento fibroblástico 23 (FGF23), el cual genera hipofosfemia y osteomalacia. A continuación presentamos el caso de un paciente de 42 años con un tumor mesenquimatoso fosfatúrico de fosa nasal izquierda con extenso compromiso intracraneano. Cabe destacar que hasta la fecha hay 142 casos reportados de TMF en la literatura de los cuales solo 11 se ubican en fosa nasaly cavidades sinusales, y sólo dos de ellos ubicados en fosa nasal¹. El paciente tuvo una exitosa resolución quirúrgica con la consecuente normalización de parámetros analíticos (incluido el FGF23), mejoría sintomática y ausenia de recidiva hasta la fecha.

The phosphaturic mesenchymal tumor (PMT) is an extremely rare disease. According to recent evidence is caused by overexpression of fibroblast growth factor 23 (FGF23) which generates hypophosphatemia and osteomalacia. We report the case of a 42 year old patient with a left nasal fossa phosphaturic mesenchymal tumor with intracranial involvement. Should be noted that to date there are 142 reported cases of PMT in the literature of which only 11 are located in nasal fossa and sinus cavities, two of them located in nasal fossa¹. The patient had a successful surgical resolution with consequent normalization of analytical parameters (including FGF23), absence of symptoms and no recurrence to date.

Osteomalacia inducida por tumor: hemangiopericitoma rinosinusal / Tumor-induced osteomalacia: rhinosinusal hemangiopericytoma

La osteomalacia inducida por tumor es una rara enfermedad del metabolismo óseo caracterizada por el aumento en la excreción de fosfato a nivel renal seguido de hipofosfatemia. Es causada por agentes fosfatúricos producidos por determinados tumores. La resección total del tumor resulta en la completa reversión de las anormalidades bioquímicas, la desaparición de las manifestaciones clínicas y los hallazgos en los estudios por imágenes. Presentamos el caso de un varón de 61 años con cuadro clínico y laboratorio compatibles con osteomalacia oncogénica inducida por tumor mesenquimático de localización rinosinusal. En nuestro caso el diagnóstico histológico correspondió a una neoplasia de tipo vascular: hemangiopericitoma.

Tumor-induced osteomalacia is a rare disease of bone metabolism. The characteristic of this disease is an increase in phosphate excretion followed by hypophosphatemia, due to phosphaturic agents produced by different types of tumors. Tumor resection results in complete resolution of clinical, biochemical and radiological abnormalities. We present the case of a 61 year old man with signs, symptoms and laboratory findings consistent with oncogenic osteomalacia due to a rhino-sinusal mesenchymal tumor. The histological diagnosis showed a vascular neoplasm: hemangiopericytoma.

Osteomalacia por tumor secretor de FGF-23 / Ostemalacia due to a tumor secreting FGF-23

Se presenta un caso de osteomalacia oncogénica en un varón de 50 años, con fuertes dolores óseos y gran debilidad muscular durante 4 años. Tenía varias deformidades vertebrales dorsales en cuña, fracturas en ambas ramas iliopubianas y en una rama isquiopubiana, y una zona de Looser en la meseta tibial derecha. Se localizó un tumor de 2 cm de diámetro en el hueco poplíteo derecho mediante centellograma con octreótido marcado con tecnecio. El tumor fue extirpado quirúrgicamente. La microscopía mostró un tumor mesenquimático fosfatúrico, de tejido conectivo mixto. La inmunotinción demostró FGF-23. Hubo rápida mejoría, con consolidación de las fracturas pelvianas y de la pseudofractura tibial y normalización de las alteraciones bioquímicas.

A case of oncogenic osteomalacia in a 50-year-old male is here presented. He suffered severe bone pain and marked muscular weakness of 4 years' duration. There were several vertebral deformities in the thoracic spine, bilateral fractures of the iliopubic branches, another fracture in the left ischiopubic branch, and a Looser's zone in the right proximal tibia. An octreotide-Tc scan allowed to identify a small tumor in the posterior aspect of the right knee. It was surgically removed. Microscopically, it was a phosphaturic mesenchymal tumor-mixed connective tissue (PMT-MCT). Expression of FGF-23 was documented by immune-peroxidase staining. There was rapid improvement, with consolidation of the pelvic fractures and the tibial pseudo-fracture. The laboratory values returned to normal.

Clinical management and postoperative follow up of 12 patients with tumor-induced osteomalacia / 中华内分泌代谢杂志

Objective To better understand the clinical management of tumor-induced osteomalacia (TIO) by analyzing the clinical features, diagnosis, treatment, postoperative biochemical changes, and clinical status in 12 cases of TIO. Methods Twelve cases of TIO hospitalized from 2004 to April 2010 were reviewed retrospectively. All cases were diagnosed based on their clinical manifestation, hypophosphatemia, and image study including technetium-99m octreotide scintigraphy (99mTc-Oct). Resuits There were 7 males and 5 females with mean age of (41.8±9.6) years (20 to 56 years). The course of disease was from 2 to 14 years ( median course 4.0 years). They all presented with bone pain, gait disturbance, muscle pain, and muscle weakness. Serum phosphate( Pi)levels were low in 12 cases with a range from 0.30 to 0.56 mmol/L. 99mTc-Oct was performed in 9 cases and it showed that the lesions were located in head of femur, fibula, retrocalcaneal area, foot, humerus,metacarpal, posterior chest wall or near nasal bone (apex partis petrosae ossis temporalis). Subcutaneous soft tissue mass was found in another 3 cases at loin, thigh, and foot by physical examination. The tumors were confirmed by CT, MRI or ultrasonography. Twelve patients underwent operation to remove the tumors and histopathology showed hemangioendothelioma or fibrous angioma (6 cases), giant cell tumor or fibroma of tendon sheath(4 cases), liposarcoma(1case), and phosphaturic mesenchymal tumor(1case). Serum Pi levels returned to normal in 10 patients after resection of tumor. During 2 to 64 months follow up, symptoms of bone pain and muscle weakness were improved obviously. Conclusions Patients with hypophosphatemic osteomalacia should be thoroughly investigated for TIO. 99mTc-Oct and other imaging examinations can effectively locate the tumors. Once the hidden tumor is found and excised, the patient will recover and enjoy normal life with normalized Pi concentrations and marked improvement of symptoms.

Osteomalacia hipofosfatémica secundaria a sarcoma de muslo: caso clínico / Hypophosphatemic osteomalacia secondary to a sarcoma: report of one case

Tumor induced osteomalacia is uncommon and is characterized by an isolated and not PTH dependent reduction in tubular phosphate reabsorption. This alteration is produced by phosphaturic factors, such as fibroblast growth factor-23 (FGF-23) that are secreted by tumors. We report a 41 years old female presenting with joint pain and progressive loss of muscle strength in the lower limbs. Initial laboratory assessment showed hypophosphatemia, elevated alkaline phosphatases, normal intact parathormone levels, low levels of 25 hydroxy vitamin D and an elevated 24 h phosphaturia. Bone mineral density showed spine and femoral neck osteopenia. A positron emission tomography (PET) revealed a right thigh tumor with lung metastases. Its biopsy disclosed a fibrosarcoma. FGF-23 levels, measured by ELISA were markedly elevated. The patient was discharged with palliative measures.