RESUMEN
A female in her 50s developed a headache, collapsed and was noted to have an acute atraumatic subdural haemorrhage (SDH) requiring surgical evacuation and intracranial pressure-directed therapy. Her background included recurrent epistaxis, severe generalised bone pain and multiple insufficiency fractures and an undifferentiated autoimmune connective tissue disease. Chronic hypophosphataemia, elevated alkaline phosphatase and raised fibroblast growth factor 23 (FGF23) were also noted. An MRI head and subsequent 68Ga CT/positron emission tomography scan demonstrated an intensely avid tumour in the right ethmoid sinus, extending intracranially. Phosphate was aggressively replaced, and alfacalcidol was initiated to circumvent the effects of FGF23 on her kidneys and bone minerals. The tumour was biopsied and then definitively resected via combined endonasal and craniotomy approaches, resulting in good clinical improvement. FGF23 titre and serum phosphate both normalised leaving the diagnosis of a phosphaturic mesenchymal tumour-secreting FGF23, leading to tumour-induced osteomalacia.
Asunto(s)
Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos , Hematoma Subdural Agudo , Osteomalacia , Humanos , Osteomalacia/etiología , Femenino , Factores de Crecimiento de Fibroblastos/sangre , Factores de Crecimiento de Fibroblastos/metabolismo , Persona de Mediana Edad , Hematoma Subdural Agudo/etiología , Hematoma Subdural Agudo/cirugía , Hematoma Subdural Agudo/diagnóstico por imagen , Neoplasias de los Senos Paranasales/complicaciones , Neoplasias de los Senos Paranasales/cirugía , Síndromes Paraneoplásicos , Neoplasias de Tejido Conjuntivo/cirugía , Neoplasias de Tejido Conjuntivo/diagnóstico , Senos Etmoidales/cirugía , Imagen por Resonancia MagnéticaRESUMEN
Sjogren's syndrome is a known cause of renal tubular acidosis (RTA). However, osteomalacia associated with Sjogren's syndrome is rare and seldom reported in literature. We report a case of pseudofractures of both femora due to osteomalacia as a result of RTA secondary to Sjogren's syndrome, which was initially misdiagnosed as a stress fracture. A man in his 30s presented with hip pain and was initially misdiagnosed to have stress fractures because of the 'through and through' extension of the 'fracture' lines at the neck of both femora. The patient had a normal serum biochemistry profile except for elevated alkaline phosphatase levels. On further evaluation, he was found to have distal RTA secondary to Sjogren's syndrome. The patient responded to sodium bicarbonate therapy with clinical, biochemical and radiological improvement. A high index of suspicion for RTA should be kept in a patient with osteomalacia with a normal calcium profile and vitamin D level.
Asunto(s)
Osteomalacia , Síndrome de Sjögren , Humanos , Síndrome de Sjögren/complicaciones , Síndrome de Sjögren/diagnóstico , Masculino , Osteomalacia/etiología , Osteomalacia/diagnóstico , Adulto , Acidosis Tubular Renal/diagnóstico , Acidosis Tubular Renal/etiología , Acidosis Tubular Renal/complicaciones , Diagnóstico Diferencial , Fracturas por Estrés/etiología , Fracturas por Estrés/diagnóstico por imagen , Fracturas por Estrés/diagnóstico , Bicarbonato de Sodio/uso terapéuticoRESUMEN
Introduction: This study explores tumor-induced osteomalacia (TIO) through a case series and literature review, assessing the diagnostic potential of 18F-AlF-NOTA-octreotide (18F-OC) positron emission tomography/computed tomography (PET/CT). Methods: We analyzed TIO patients who underwent 18F-OC PET/CT. Parameters such as tumor dimension, the maximum standardized uptake value (SUVmax), the mean standardized uptake value (SUVmean) and metabolic tumor volume (MTV) were meticulously assessed. Clinical features and imaging characteristics pertinent to TIO were reviewed. Results: 6 patients with clinical suspicion of TIO exhibited hypophosphatemia (0.25 to 0.64 mmol/L), elevated alkaline phosphatase (ALP) levels (142 to 506 U/L), and increased parathyroid hormone (PTH) levels (92.9 to 281.7 pg/mL). Of these patients, two underwent FGF-23 testing, with results of 3185.00 pg/ml and 17.56 pg/ml, respectively. Conventional imaging modalities depicted widespread osteoporosis, with several cases demonstrating fractures indicative of osteomalacic and associated pathological fractures. Subsequent 18F-OC PET/CT facilitated the accurate localization of causative tumors, with histopathological examination confirming the diagnosis of phosphaturic mesenchymal tumor (PMT). The interval from initial clinical presentation to definitive TIO diagnosis spanned approximately 2.5 years (range: 1 - 4 years), with tumors varying in size (maximum diameter: 7.8 to 40.0 mm), SUVmax (5.47 to 25.69), SUVmean (3.43 to 7.26), and MTV (1.27 to 18.59 cm3). Conclusion: The implementation of whole-body 18F-OC PET/CT imaging emerges as a critical tool in the identification of occult tumors causing TIO. Future investigations incorporating a broader cohort are imperative to further delineate the diagnostic and therapeutic implications of 18F-OC PET/CT in managing TIO.
Asunto(s)
Osteomalacia , Tomografía Computarizada por Tomografía de Emisión de Positrones , Humanos , Factor-23 de Crecimiento de Fibroblastos , Radioisótopos de Flúor , Compuestos Heterocíclicos , Compuestos Heterocíclicos con 1 Anillo , Neoplasias de Tejido Conjuntivo/diagnóstico por imagen , Octreótido/análogos & derivados , Osteomalacia/diagnóstico por imagen , Osteomalacia/etiología , Síndromes Paraneoplásicos/diagnóstico por imagen , Tomografía Computarizada por Tomografía de Emisión de Positrones/métodos , RadiofármacosRESUMEN
OBJECTIVE: The orthopedic surgical treatment strategies for patients with tumor-induced osteomalacia (TIO) require improvement, especially for patients where the causative tumors are located in surgically challenging areas, requiring a greater degree of in-depth investigation. This work aims to summarize and investigate clinical features and orthopedic surgical treatment effects of patients with tumor-induced osteomalacia (TIO), whose causative tumors are located in the hip bones. METHODS: A retrospective analysis was conducted on the clinical data of all patients diagnosed with culprit tumors located in the hip bones who underwent surgical treatment at the orthopedic bone and soft tissue tumor sub-professional group of Peking Union Medical College Hospital from January 2013 to January 2023. This retrospective study summarized the clinical data, preoperative laboratory test results, imaging findings, surgery-related data, perioperative changes in blood phosphorus levels, and postoperative follow-up data of all patients who met the inclusion criteria. Normally distributed data are presented as mean and standard deviation, while non-normally distributed data are shown as the means and 25th and 75th interquartile ranges. RESULTS: The clinical diagnostic criteria for TIO were met by all 16 patients, as confirmed by pathology after surgery. Among the 16 patients, we obtained varying degrees of bone pain and limited mobility (16/16), often accompanied by difficulties in sitting up, walking, and fatigue. An estimated 62.5% (10/16) of patients had significantly shorter heights during the disease stages. All 16 patients underwent surgical treatment for tumors in the hip bones, totaling 21 surgeries. In the pathogenic tumor, there were 16 cases of skeletal involvement and none of pure soft tissue involvement. Out of the 16 patients, 13 cases had a gradual increase in blood phosphorus levels following the latest orthopedic surgery, which was followed up for 12 months to 10 years. Due to unresolved conditions after the original surgery, four patients received reoperation intervention. Two cases of refractory TIO did not improve in their disease course. CONCLUSION: In summary, the location of the causative tumor in the hip bone is hidden and diverse, and there is no defined orthopedic surgical intervention method for this case in clinical practice. For patients with TIO where the tumors are located in the hip bones, surgical treatment is difficult and the risk of postoperative recurrence is high. Careful identification of the tumor edge using precise preoperative positioning and qualitative diagnosis is crucial to ensure adequate boundaries for surgical resection to reduce the likelihood of disease recurrence and improve prognosis.
Asunto(s)
Neoplasias Óseas , Osteomalacia , Síndromes Paraneoplásicos , Humanos , Estudios Retrospectivos , Osteomalacia/cirugía , Osteomalacia/etiología , Masculino , Femenino , Persona de Mediana Edad , Adulto , Síndromes Paraneoplásicos/cirugía , Síndromes Paraneoplásicos/etiología , Neoplasias Óseas/cirugía , Neoplasias Óseas/complicaciones , Neoplasias de Tejido Conjuntivo/cirugía , Adulto Joven , Huesos Pélvicos/cirugía , Procedimientos Ortopédicos/métodos , Anciano , AdolescenteRESUMEN
Tumour-induced osteomalacia is caused by tumorous production of fibroblast growth factor 23 (FGF23) leading to urinary phosphate wasting, hypophosphataemia and decreased vitamin D activation. The resulting osteomalacia presents with muscle weakness and bone pain but progresses to multiple pathological fractures. Patients often remain undiagnosed for years with severe physical, psychological and economic ramifications. A young woman presented with multiple spontaneous fractures including bilateral femoral fractures. Laboratory tests revealed severe hypophosphataemia, elevated bone turnover markers and low to normal calcium and 25-hydroxy-vitamin D levels. Treatment with phosphate, alfalcalcidol, calcium and magnesium was initiated. 68Gallium-DOTATOC positron emission tomography imaging revealed a mass in the right foot and venous sampling of FGF23 from all extremities confirmed this tumour as the culprit. Biopsy and histology were consistent with a phosphaturic mesenchymal tumour, which was surgically resected. Phosphate levels quickly normalised postoperatively but a long convalescence with hungry bone syndrome, fracture healing and physical therapy followed.
Asunto(s)
Factor-23 de Crecimiento de Fibroblastos , Neoplasias de Tejido Conjuntivo , Osteomalacia , Humanos , Osteomalacia/etiología , Femenino , Neoplasias de Tejido Conjuntivo/diagnóstico , Neoplasias de Tejido Conjuntivo/cirugía , Adulto , Síndromes Paraneoplásicos/diagnóstico , Hipofosfatemia/etiología , Factores de Crecimiento de Fibroblastos/sangre , Fracturas del Fémur/cirugía , Fracturas del Fémur/diagnóstico por imagen , Fracturas Espontáneas/etiología , Fracturas Espontáneas/cirugía , Fracturas Espontáneas/diagnóstico por imagen , Fosfatos/sangreRESUMEN
Phosphaturic mesenchymal tumors (PMT) are rare and distinctive tumors that typically result in paraneoplastic syndrome known as tumor-induced osteomalacia (TIO). We report a case of bilateral osteoporotic femoral neck fracture caused by PMT. PMT was surgically resected, followed by sequential treatment of bilateral femoral neck fractures with total hip arthroplasty (THA). A 49-year-old perimenopausal woman experienced consistent bone pain with limb weakness persisting for over 2 years. Initially, she was diagnosed with early osteonecrosis of the femoral head and received nonsurgical treatment. However, from 2020 to 2022, her pain extended to the bilateral shoulders and knees with increased intensity. She had no positive family history or any other genetic diseases, and her menstrual cycles were regular. Physical examination revealed tenderness at the midpoints of the bilateral groin and restricted bilateral hip range of motion, with grade 3/5 muscle strength in both lower extremities. Laboratory findings revealed moderate anemia (hemoglobin 66 g/L), leukopenia (2.70 × 109/L), neutropenia (1.28 × 109/L), hypophosphatemia (0.36 mmol/L), high alkaline phosphatase activity (308.00 U/L), and normal serum calcium (2.22 mmol/L). After surgery, additional examinations were performed to explore the cause of hypophosphatemic osteomalacia. After definitive diagnosis, the patient underwent tumor resection via T11 laminectomy on August 6, 2022. Six months after the second THA, the patient regained normal gait with satisfactory hip movement function without recurrence of PMT-associated osteomalacia or prosthesis loosening. By providing detailed clinical data and a diagnostic and treatment approach, we aimed to improve the clinical understanding of femoral neck fractures caused by TIO.
Asunto(s)
Fracturas del Cuello Femoral , Neoplasias de Tejido Conjuntivo , Osteomalacia , Síndromes Paraneoplásicos , Humanos , Femenino , Osteomalacia/etiología , Persona de Mediana Edad , Fracturas del Cuello Femoral/cirugía , Fracturas del Cuello Femoral/etiología , Fracturas del Cuello Femoral/complicaciones , Síndromes Paraneoplásicos/etiología , Neoplasias de Tejido Conjuntivo/etiología , Neoplasias de Tejido Conjuntivo/diagnóstico , Neoplasias de Tejido Conjuntivo/cirugía , Hipofosfatemia/etiología , Artroplastia de Reemplazo de CaderaRESUMEN
BACKGROUND Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome caused by aberrant fibroblast growth factor-23 (FGF-23)-producing tumors. Early surgical resection is the optimal strategy for preventing TIO progression. Thus, tumor localization is a priority for successful treatment. A simple and safe examination method to identify functional endocrine tumors is essential to achieve better outcomes in patients with TIO. CASE REPORT A 64-year-old Japanese man with recurrent fractures, hypophosphatemia, and elevated alkaline phosphatase and FGF-23 levels (109 pg/mL) was admitted to our university hospital and was diagnosed with FGF23-related hypophosphatemic osteomalacia. Notably, the superficial dorsal vein in the patient's left foot exhibited a high FGF-23 level (7510 pg/mL). Octreotide and ¹8F-fluorodeoxyglucose (FDG) scintigraphy and systemic venous sampling revealed that the tumor in the third basal phalanx of the left foot was responsible for FGF-23 overproduction. Tumor resection resulted in a rapid decrease in serum FGF-23 levels and an increase in serum phosphorus levels. CONCLUSIONS Octreotide scintigraphy, FDG-positron emission tomography, and systemic venous sampling are the standard methods for localizing functional endocrine tumors. However, the limited availability and invasive nature of these examinations hinder effective treatment. Here, we highlight the importance of peripheral superficial blood sampling as an alternative to conventional systemic methods for confirming the presence of FGF-23-producing tumors. Clinicians should consider TIO as a potential cause of acquired hypophosphatemic osteomalacia. Furthermore, peripheral superficial vein blood sampling may be useful for confirming the localization of FGF-23-producing tumors.
Asunto(s)
Neoplasias , Osteomalacia , Síndromes Paraneoplásicos , Masculino , Humanos , Persona de Mediana Edad , Osteomalacia/etiología , Factor-23 de Crecimiento de Fibroblastos , Fluorodesoxiglucosa F18 , OctreótidoRESUMEN
BACKGROUND: Phosphaturic Mesenchymal Tumors (PMTs) are rare mesenchymal neoplasms known for producing Tumor-induced Osteomalacia (TIO). TIO is an uncommon paraneoplastic syndrome characterized by radiographic evidence of inadequate bone mineralization and analytical abnormalites. METHODS: We sought to present a case of TIO caused by skull base PMT with intracranial extension, manifesting with pain, progressive weakness, and multiple bone fractures. Furthermore, a systematic review was performed, following the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. A search was conducted in PubMed database with title/abstract keywords "Phosphaturic mesenchymal tumor" and "Osteomalacia." Search results were reviewed looking for intracranial or skull base tumors. RESULTS: Our systematic review included 29 reported cases of intracranial PMT. In the reviewed cases there was a significative female predominance with 22 cases (75,86%). Osteomalacia was presented in 25 cases (86,20%). Bone fractures were present in 10 cases (34,48%). The most common site of involvement was the anterior cranial fossa in 14 cases (48,27%). Surgery was performed in 27 cases (93,10%) with previous tumor embolization in 4 cases (13,79%). Total recovery of the presenting symptoms in the first year was achieved in 21 cases (72,41%). Recurrence of the disease was described in 6 cases (25%). CONCLUSIONS: Skull base PMTs with intracranial extension are extremely rare tumors. Most patients are middle-aged adults with a PMT predominantly located in anterior cranial fossa. Surgery is the current treatment of choice with optimal outcome at 1-year follow-up, although recurrence could be present in almost 25% of the cases.
Asunto(s)
Osteomalacia , Síndromes Paraneoplásicos , Femenino , Humanos , Masculino , Neoplasias Encefálicas/complicaciones , Neoplasias Encefálicas/cirugía , Neoplasias Encefálicas/diagnóstico por imagen , Mesenquimoma/cirugía , Mesenquimoma/complicaciones , Mesenquimoma/patología , Mesenquimoma/diagnóstico por imagen , Neoplasias de Tejido Conjuntivo/diagnóstico por imagen , Neoplasias de Tejido Conjuntivo/cirugía , Osteomalacia/etiología , Neoplasias de la Base del Cráneo/cirugía , Neoplasias de la Base del Cráneo/diagnóstico por imagen , Neoplasias de la Base del Cráneo/complicacionesRESUMEN
PURPOSE OF REVIEW: Fibroblast growth factor 23 (FGF23) is a hormone to reduce blood phosphate concentration. Excessive actions of FGF23 induce FGF23-related hypophosphatemic disorders, such as X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia (TIO). We will summarize recent advances in the diagnosis and treatment of FGF23-related hypophosphatemic disorders. RECENT FINDINGS: The measurement of blood FGF23 is useful to make a diagnosis of FGF23-related hypophosphatemic disorders. It was reported that many patients with FGF23-related hypophosphatemic disorders, especially TIO, were misdiagnosed, therefore, it is necessary to enhance the awareness of these diseases. A novel method to inhibit excessive actions of FGF23 by a human monoclonal antibody for FGF23, burosumab, has been approved in several countries. In more long-term observation than clinical trials, burosumab has also been shown to improve biochemical abnormalities and symptoms of rickets/osteomalacia. Following these advances, several registries and consensus recommendations on FGF23-related hypophosphatemic disorders, especially XLH, have been established in each country or region. SUMMARY: Further long-term effects of burosumab and the precise mechanism of FGF23 overproduction in patients with FGF23-related hypophosphatemic disorders need to be clarified in the future studies.
Asunto(s)
Anticuerpos Monoclonales Humanizados , Raquitismo Hipofosfatémico Familiar , Factor-23 de Crecimiento de Fibroblastos , Factores de Crecimiento de Fibroblastos , Osteomalacia , Humanos , Factores de Crecimiento de Fibroblastos/sangre , Osteomalacia/etiología , Raquitismo Hipofosfatémico Familiar/tratamiento farmacológico , Raquitismo Hipofosfatémico Familiar/diagnóstico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Hipofosfatemia/etiología , Síndromes Paraneoplásicos , Neoplasias de Tejido Conjuntivo/etiología , Anticuerpos Monoclonales/uso terapéutico , Fosfatos/metabolismo , Fosfatos/sangreRESUMEN
Vitamin D is mainly produced in the skin (cholecalciferol) by sun exposure while a fraction of it is obtained from dietary sources (ergocalciferol). Vitamin D is further processed to 25-hydroxyvitamin D and 1,25-dihydroxy vitamin D (calcitriol) in the liver and kidneys, respectively. Calcitriol is the active form which mediates the actions of vitamin D via vitamin D receptor (VDR) which is present ubiquitously. Defect at any level in this pathway leads to vitamin D deficient or resistant rickets. Nutritional vitamin D deficiency is the leading cause of rickets and osteomalacia worldwide and responds well to vitamin D supplementation. Inherited disorders of vitamin D metabolism (vitamin D-dependent rickets, VDDR) account for a small proportion of calcipenic rickets/osteomalacia. Defective 1α hydroxylation of vitamin D, 25 hydroxylation of vitamin D, and vitamin D receptor result in VDDR1A, VDDR1B and VDDR2A, respectively whereas defective binding of vitamin D to vitamin D response element due to overexpression of heterogeneous nuclear ribonucleoprotein and accelerated vitamin D metabolism cause VDDR2B and VDDR3, respectively. Impaired dietary calcium absorption and consequent calcium deficiency increases parathyroid hormone in these disorders resulting in phosphaturia and hypophosphatemia. Hypophosphatemia is a common feature of all these disorders, though not a sine-qua-non and leads to hypomineralisation of the bone and myopathy. Improvement in hypophosphatemia is one of the earliest markers of response to vitamin D supplementation in nutritional rickets/osteomalacia and the lack of such a response should prompt evaluation for inherited forms of rickets/osteomalacia.
Asunto(s)
Raquitismo Hipofosfatémico Familiar , Osteomalacia , Raquitismo , Deficiencia de Vitamina D , Humanos , Calcitriol , Receptores de Calcitriol , Osteomalacia/tratamiento farmacológico , Osteomalacia/etiología , Osteomalacia/metabolismo , Deficiencia de Vitamina D/complicaciones , Deficiencia de Vitamina D/tratamiento farmacológico , Raquitismo/tratamiento farmacológico , Raquitismo/etiología , Vitamina D/uso terapéutico , Vitamina D/metabolismo , VitaminasRESUMEN
BACKGROUND: extended curettage is generally used to treat infiltrative bone tumours. However, the extent of the curettage performed in previous studies remains unclear. This study aimed to investigate the efficacy of extended curettage for bone tumour-induced osteomalacia. METHODS: we included 12 patients with tumour-induced osteomalacia who underwent extended curettage at our hospital between 2000 and 2022. Extended curettage was applied in cases where tumour resection could cause functional impairment or necessitate complex reconstruction. We investigated patients' clinical and oncological outcomes. RESULTS: patients had a mean age of 55 (24-81) years, and the median follow-up duration after surgery was 3.9 (1.0-14.0) years. The causative tumours were located in the pelvis and lumbar spine. Imaging revealed the tumours to be of the sclerotic, intertrabecular, lytic and mixed types. Intraoperative 3D fluoroscopy was used in 10 patients. Extended curettage with high-speed burring and adjuvant therapy with cauterization using an electric scalpel and ethanol resulted in a remission rate of 83%; no recurrence or metastasis was observed in cases of early postoperative biochemical remission. In cases where the causative tumour was at the lumbar spine and ischium close to the acetabulum, no postoperative biochemical remission was observed, and conservative treatment was continued. Except for one patient with a tumour in the lumbar spine, all patients could walk without a cane. CONCLUSIONS: extended curettage for bone tumour-induced osteomalacia is oncologically and functionally favourable, especially in cases where resection of the causative tumour could cause functional impairment or necessitate complex reconstruction.
Asunto(s)
Neoplasias Óseas , Osteomalacia , Síndromes Paraneoplásicos , Humanos , Persona de Mediana Edad , Neoplasias Óseas/complicaciones , Neoplasias Óseas/cirugía , Neoplasias Óseas/patología , Síndromes Paraneoplásicos/cirugía , Osteomalacia/etiología , Osteomalacia/cirugía , Legrado/métodos , Estudios RetrospectivosRESUMEN
BACKGROUND: Spinal phosphaturic mesenchymal tumor (PMT) is a rare disorder but can be cured once the diagnosis is clear and a complete removal by surgery is performed. To the best of our knowledge, only 22 cases in the spine have been described, and we report a case with the largest number of spinal segments (T12-L5) affected among spine PMT cases. METHODS: A comprehensive literature search was performed until May 23, 2023, following the Preferred Reporting Items for Systematic Reviews guidelines. Studies were chosen through relevant PubMed, Web of Science, and EMBASE searches to prioritize obtaining the largest studies. The Medical Subject Headings and Boolean operators employed for this search were ("PMT" or "TIO" or "Tumor-induced osteomalacia" or "phosphaturic mesenchymal tumor") and ("spine" or "spinal"). Two researchers (L.S.Z. and D.B.C) independently reviewed and evaluated the included articles. Any differing opinions were discussed until a consensus was reached. A total of 18 studies were included. A case report is also presented. RESULTS: We report a case of spinal PMT. The full text of the relevant articles was construed. A total of 18 studies were reviewed and consolidated. These articles are roughly divided into the following 5 subcategories: 1) clinical features and baseline distribution, 2) laboratory and imaging findings, 3) pathological manifestations, and 4) surgical methods and treatment options. CONCLUSIONS: Spinal PMT is very rare with a high rate of misdiagnosis and debilitating complications, so it is of significance to increase awareness of the disease among spine surgeons consulted by patients with spinal PMT. 68Ga-DOTATOC-PET/CT shows very high sensitivity to the spinal PMT but there is no way to exactly determine the location of the tumor. PMT has unique immunohistochemical characteristics and malignant PMT is rare. Once diagnosed, complete surgical excision is the recommended treatment. Burosumab is one of the available options, especially in cases that are recurrent and difficult to surgically resect.
Asunto(s)
Osteomalacia , Neoplasias de la Columna Vertebral , Humanos , Neoplasias de la Columna Vertebral/cirugía , Neoplasias de la Columna Vertebral/diagnóstico por imagen , Neoplasias de la Columna Vertebral/complicaciones , Osteomalacia/etiología , Síndromes Paraneoplásicos , Neoplasias de Tejido Conjuntivo/cirugía , Neoplasias de Tejido Conjuntivo/diagnóstico por imagen , Femenino , Mesenquimoma/cirugía , Mesenquimoma/complicaciones , Mesenquimoma/diagnóstico , Mesenquimoma/diagnóstico por imagen , Mesenquimoma/patología , MasculinoRESUMEN
Phosphaturic mesenchymal tumor (PMT) is a rare neoplasm causing tumor-induced osteomalacia (TIO) and is characterized by secretion of FGF23, renal phosphate wasting and hypophosphataemia. It can be completely cured by resection and therefore its diagnosis is of utmost importance. Although the histology is well described, there is sparse literature on cytology of PMT and only three cases have been described so far. A 45-year-old lady presented with a non-tender mass in hard palate for 2 years from which fine-needle aspiration was done. The smears were paucicellular and showed bland spindle cells embedded in osteoid-like stromal matrix in a hemorrhagic background. Here we take the opportunity to describe the cytological findings of PMT along with its cytological differentials and a summary of prior published cases.
Asunto(s)
Mesenquimoma , Osteomalacia , Síndromes Paraneoplásicos , Neoplasias de los Tejidos Blandos , Femenino , Humanos , Persona de Mediana Edad , Neoplasias de los Tejidos Blandos/patología , Mesenquimoma/patología , Biopsia con Aguja Fina/efectos adversos , Síndromes Paraneoplásicos/complicaciones , Síndromes Paraneoplásicos/diagnóstico , Osteomalacia/etiologíaRESUMEN
Tumor-induced osteomalacia (TIO) is rare paraneoplastic syndrome of hypophosphatemic osteomalacia, caused by phosphaturic factors secreted by small mesenchymal origin tumors with distinct pathological features, called 'phosphaturic mesenchymal tumors'. FGF23 is the most well-characterized of the phosphaturic factors. Tumors are often small and located anywhere in the body from head to toe, which makes the localisation challenging. Functional imaging by somatostatin receptor-based PET imaging is the first line investigation, which should be followed with CT or MRI based anatomical imaging. Once localised, complete surgical excision is the treatment of choice, which brings dramatic resolution of symptoms. Medical management in the form of phosphate and active vitamin D supplements is given as a bridge to surgical management or in inoperable/non-localised patients. This review provides an overview of the epidemiology, pathophysiology, pathology, clinical features, diagnosis, and treatment of TIO, including the recent advances and directions for future research in this field.
Asunto(s)
Mesenquimoma , Neoplasias de Tejido Conjuntivo , Osteomalacia , Síndromes Paraneoplásicos , Humanos , Neoplasias de Tejido Conjuntivo/diagnóstico , Neoplasias de Tejido Conjuntivo/etiología , Neoplasias de Tejido Conjuntivo/terapia , Osteomalacia/etiología , Osteomalacia/diagnóstico , Osteomalacia/patología , Mesenquimoma/complicaciones , Mesenquimoma/diagnóstico , Mesenquimoma/patología , Síndromes Paraneoplásicos/diagnóstico , Síndromes Paraneoplásicos/etiología , Síndromes Paraneoplásicos/patologíaRESUMEN
A sporadic occurrence of Fanconi syndrome associated with adefovir dipivoxil (ADV) has been reported, particularly when confirmed by renal biopsy. This study presents the case of a 53-year-old man who had been taking ADV 10 mg daily for 10 years to treat chronic hepatitis B (CHB) and subsequently developed Fanconi syndrome. The clinical manifestations included hypophosphatemic osteomalacia, glucosuria, renal tubular acidosis, low-molecular-weight proteinuria, and renal insufficiency. Renal biopsy revealed significant injury to proximal tubular epithelial cells, including vacuolar degeneration and regeneration of tubular epithelial cells. The ultrastructural pathology indicated severe morphological abnormalities of mitochondria, such as densely packed and enlarged mitochondria, with loss, blunting, and disordered arrangement of cristae. Following discontinuation of ADV and supplementation with oral phosphate, hypophosphatemia, glucosuria, and proteinuria were resolved. These findings support the previous hypothesis that ADV-induced nephrotoxicity may involve mitochondrial injury.
Asunto(s)
Adenina/análogos & derivados , Síndrome de Fanconi , Glucosuria , Hepatitis B Crónica , Hipofosfatemia , Organofosfonatos , Osteomalacia , Insuficiencia Renal , Masculino , Humanos , Persona de Mediana Edad , Síndrome de Fanconi/inducido químicamente , Síndrome de Fanconi/diagnóstico , Síndrome de Fanconi/complicaciones , Hepatitis B Crónica/tratamiento farmacológico , Riñón , Hipofosfatemia/inducido químicamente , Glucosuria/inducido químicamente , Proteinuria/tratamiento farmacológico , Osteomalacia/etiología , Antivirales/efectos adversosRESUMEN
CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome usually caused by oversecretion of fibroblast growth factor 23 (FGF23) from a phosphaturic mesenchymal tumor (PMT). PMTs are usually benign neoplasms but some of them show malignant characteristics. OBJECTIVE: The aim of this study was to compare the clinical characteristics of benign and malignant PMTs inducing TIO. METHODS: On March 31, 2023, we performed a systematic review of individual patient data analysis in Medline, Google Scholar, Google book, and Cochrane Library using the terms "tumor induced osteomalacia," "oncogenic osteomalacia," "hypophosphatemia," with no language restrictions and according to Preferred Reporting Items for Systematic reviews and Meta-Analyses criteria. RESULTS: Overall, we collected data from 837 patients with TIO in which the diagnosis of benign and malignant PMT was specified. Of them, 89 were affected by malignant PMT and 748 by benign PMT. Patients with malignant PMTs were younger and presented bone pain, functional impairment, and bone deformities more frequently. Malignant PMTs showed higher values of intact FGF23 and a higher mortality rate. CONCLUSION: The study results identify the clinical characteristics of patients with malignant TIO, permitting the early identification of patients with PMT at increased risk of malignancy. This may significantly improve the diagnostic approach to disease. Further experimental studies are mandatory to clarify the role of FGF23 in the pathogenesis of malignancy in PMTs.