Tumor mesenquimático fosfatúrico de pelvis: abordaje multidisciplinario / Phosphaturic mesenchymal tumor of the pelvis: A multidisciplinary approach

El tumor mesenquimático fosfatúrico es una entidad clinicopatológica sumamente infrecuente. Además de provocar dolor óseo insidioso y polimialgias, se acompaña de alteraciones del metabolismo fosfocálcico de difícil manejo clínico. El abordaje multidisciplinario resulta la clave del éxito en esta enfermedad. Presentamos una paciente de 52 años de edad con antecedente de tumor mesenquimático fosfatúrico en la hemipelvis derecha con extensión a la cadera homolateral de 10 años de evolución. Clínicamente presentaba osteomalacia oncogénica (hipofosfatemia e hiperfosfaturia) que no se corregía, pese a un agente de última generación, el burosumab, un inhibidor del factor de crecimiento fibroblástico 23, que aumenta la reabsorción tubular renal de fosfatos. En un comité multidisciplinario, se decidió la resección con márgenes oncológicos y se logró una mejoría clínica franca. Comunicamos este caso, debido a que es un cuadro infrecuente. Nivel de Evidencia: IV

Phosphaturic mesenchymal tumor (PMT) is an infrequent clinicopathological entity. It presents insidious bone pain and polymyalgia, accompanied by alterations in calcium and phosphorus metabolism that are difficult to resolve clinically. A multidisciplinary approach is a key to success in this pathology. We present the case of a 52-year-old female patient with a 10-year history of PMT in the right hemipelvis with ipsilateral hip extension. From the clinical point of view, she presented oncogenic osteomalacia (hypophosphatemia and hyperphosphaturia) that did not correct despite being administered the latest generation medication, burosumab, an FGF-23 inhibitor that increases renal tubular phosphate reabsorption. Resection with oncological margins was decided by a multidisciplinary committee resolving her clinical condition. Due to the rarity of this pathology, we decided to report the case. Level of Evidence: IV

Osteomalacia oncogénica secundaria a tumor mesenquimal fosfatúrico del pie / Oncogenic osteomalacia secondary to phosphaturic mesenchymal tumour of the foot

RESUMEN La osteomalacia oncogénica es un síndrome metabólico paraneoplásico caracterizado por hipofosfatemia debida a la pérdida renal de fosfato, con nivel bajo de vitamina D. Este trastorno está asociado con la liberación de factores fosfatúricos por células tumorales, especialmente el factor de crecimiento fibrolástico 23 (FGF23). Las neoplasias relacionadas con la osteomalacia oncogénica suelen ser tumores pequeños de linaje mesenquimatoso y pueden ser difíciles de localizar en algunos casos debido a su tamaño y ubicación poco accesible al examen físico. Presentamos a un paciente que desarrolló fracturas vertebrales y de cadera debido a osteomalacia oncogénica asociada con un tumor mesenquimatoso fosfatúrico del tejido graso profundo de la planta del pie, que finalmente se diagnosticó después de 3 años del inicio de los síntomas, cuando el tumor pudo ser localizado por el rastreo gammagráfico óseo con pentatreótido marcado con indio-111 y por las imágenes de resonancia magnética nuclear.

ABSTRACT Oncogenic osteomalacia is a paraneoplastic metabolic syndrome characterised by a low phosphates in the blood due to renal phosphate losses with inadequately normal or low vitamin D levels. This disorder is associated with the release of tumour cell-secreted phosphaturic factor, most notably fibroblast growth factor 23 (FGF-23). The neoplasms related to oncogenic osteomalacia are usually small tumours of mesenchymal lineage, and they may be difficult to locate in the physical examination in some cases, due to their size and inaccessible location. The case is presented of a patient who developed vertebral and hip fractures due to oncogenic osteomalacia associated with a phosphaturic mesenchymal tumour of the deep fat tissue in the sole of the foot. This was finally diagnosed after 3 years of the onset of symptoms after being located by bone scintigraphy with Indium-111 labelled pentetreotide and magnetic resonance imaging.

Debilitating pain and fractures: A rare case of Hypophosphatemic Osteomalacia with Concomitant vitamin D Deficiency in Neurofibromatosis Type 1 / Journal of the ASEAN Federation of Endocrine Societies

@#Hypophosphatemic osteomalacia is a rare form of metabolic bone disorder in neurofibromatosis type 1 (NF1). The exact disease mechanism of this disorder in NF1 is yet to be established. We present a 44-year-old female known to have NF1, who presents with debilitating bone pain, weakness and multiple fractures. Laboratory investigations showed persistent hypophosphatemia with renal phosphate wasting suggestive of hypophosphatemic osteomalacia. She also had concomitant vitamin D deficiency which contributed to the disease severity. Medical therapy with oral phosphate and vitamin D improved her symptoms without significant changes in fracture healing or phosphate levels.

Osteomalacia. Diagnóstico y tratamiento / Osteomalacia. Diagnosis and treatment

Introducción: la osteomalacia se caracteriza por la falta de mineralización de la sustancia osteoide, que afecta al hueso cortical y al hueso esponjoso maduro. Es una enfermedad que se presenta en adultos y niños, aunque la causa es diferente en cada uno. Objetivo: exponer la generalidad de la osteomalacia por ser una enfermedad que produce serias afectaciones a la población que la padece, especialmente a los niños. Se enfatiza en el diagnóstico y su tratamiento. Desarrollo: a fin de resumir los elementos esenciales para establecer el diagnóstico de osteomalacia hay que plantear en primer lugar, la presencia de un trastorno de la mineralización ósea, de ahí que además de tener en cuenta las causas de la enfermedad, su curso clínico y la sintomatología. Conclusiones: una recomendación importante es no tener en cuenta la posibilidad de complicaciones en el curso de la enfermedad, como las fracturas, que, aunque sean parte del cuadro clínico, al producirse pueden ocasionar graves problemas, como el caso de las que aparecen en las costillas, que si se desplazan pueden interesar órganos vitales, de modo que en este tipo de pacientes no debe excluirse la posibilidad de emergencias o de urgencias reumatológicas tanto en los adultos como en los niños(AU)

Introduction: osteomalacia is characterized by the lack of mineralization of the osteoid substance, which affects cortical bone and mature cancellous bone. It is a disease that occurs in adults and children, although the cause is different in each. Objective: to expose the generality of osteomalacia for being a disease that causes serious affectations to the population that suffers it, especially to children. Emphasis is placed on the diagnosis and its treatment. Development: in order to summarize the essential elements to establish the diagnosis of osteomalacia, we must first consider the presence of a bone mineralization disorder, hence, in addition to taking into account the causes of the disease, its clinical course and the symptomatology. Conclusions: an important recommendation is not to take into account the possibility of complications in the course of the disease, such as fractures, which, although they are part of the clinical picture, can cause serious problems when they occur, as in the case of those that appear in the ribs, which if they move may involve vital organs, so that in this type of patients should not exclude the possibility of emergencies or rheumatological emergencies in both adults and children(AU)

Hypophosphatemic osteomalacia caused by urinary mesenchymal tumor: A case report / 北京大学学报(医学版)

This case report concerns a 34-year-old woman who had been diagnosed with ankylosing spondylitis (AS), fibromyalgia syndrome (FMS), osteoarthritis (OA), lumbar disc herniation and the like in different hospitals during the past 18 months. She had progressive osteoarthrosis, significant muscle weakness, gait abnormalities in weightbearing areas, however without typical inflammatory low back pain, while the treatment with non-steroidal anti-inflammatory drugs (NSAIDs) was invalid, with normal inflammation index, negative results for rheumatic factor (RF) and human leukocyte antigen (HLA)-B27, and normal erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). She had hyphosphatemia, normal serum calcium, 1,25-(OH)2-D3 reduction, elevated alkaline phosphatase (ALP) and normal parathyroid hormone (PTH), however with elevated urinary phosphorus. Finally, the medial thigh nodule was found in the subcutaneous of her inner leg by careful examination and imaging scans including B-ultrasound and PET/CT. The final pathology confirmed that the nodule was phosphate urinary mesenchymal tumors. After the tumor was removed, the patient was treated with anti-osteoporosis and phosphorus supplementation. The symptoms of bone pain and muscle weakness were alleviated, and hypophosphatemia was corrected. It was confirmed that the patient had low-phosphorus osteomalacia due to tumor. Tumor-induced hypophosphatemia osteomalacia (TIO) was a rare paraneoplastic syndrome which was caused by excessive phosphorus excretion induced by the tumor, and was thus categorized as an acquired hypophosphatemic osteomalacia. TIO had an occult onset and was associated with a high rate of misdiagnosis, although TIO has some typical clinical features. Early diagnosis, correctly positioning of the tumor, and surgical resection can achieve good outcomes.

Aluminum toxicity to bone: A multisystem effect?

Aluminum (Al) is the third most abundant element in the earth's crust and is omnipresent in our environment, including our food. However, with normal renal function, oral and enteral ingestion of substances contaminated with Al, such as antacids and infant formulae, do not cause problems. The intestine, skin, and respiratory tract are barriers to Al entry into the blood. However, contamination of fluids given parenterally, such as parenteral nutrition solutions, or hemodialysis, peritoneal dialysis or even oral Al-containing substances to patients with impaired renal function could result in accumulation in bone, parathyroids, liver, spleen, and kidney. The toxic effects of Al to the skeleton include fractures accompanying a painful osteomalacia, hypoparathyroidism, microcytic anemia, cholestatic hepatotoxicity, and suppression of the renal enzyme 25-hydroxyvitamin D-1 alpha hydroxylase. The sources of Al include contamination of calcium and phosphate salts, albumin and heparin. Contamination occurs either from inability to remove the naturally accumulating Al or from leeching from glass columns used in compound purification processes. Awareness of this long-standing problem should allow physicians to choose pharmaceutical products with lower quantities of Al listed on the label as long as this practice is mandated by specific national drug regulatory agencies.

Intramastoid Phosphaturic Mesenchymal Tumor Causing Hypophosphatemic Osteomalacia Detected on ⁶⁸Ga-DOTATATE PET/CT But Not on (99m)Tc-Sestamibi and ¹⁸F-FDG Scans / 대한핵의학회잡지

⁶⁸Ga-DOTATATE uptake in mesenchymal tumors causing hypophosphatemic osteomalacia has been recently described. Herein, we present a case of ⁶⁸Ga-DOTATATE uptake in an intramastoid phosphaturic mesenchymal tumor that had not been depicted in previous (99m)Tc-Sestamibi and ¹⁸F-FDG scans. The lesion was surgically removed and the phosphorus level increased to the normal range.

Uveítis anterior aguda asociada a raquitismo renal hipofosfatémico / Acute anterior uveítis associated to hypophosphatemic renal ricketts

Los raquitismos hipofosfatémicos hereditarios son un grupo de enfermedades caracterizadas por la pérdida renal de fosfatos. Cursan con hipocrecimiento disarmónico y deformidades óseas. La forma más común es el raquitismo hipofosfatémico ligado al cromosoma X, el cual es causado por mutaciones inactivantes en el gen PHEX. El objetivo de nuestro trabajo fue describir las alteraciones oculares encontradas y la evolución clínica en un paciente con raquitismo hipofosfatémico hereditario y uveítis anterior. Se presenta un niño de 9 años de edad con diagnóstico de raquitismo hipofosfatémico hereditario, valorado en el Servicio de Uveítis del Instituto Cubano de Oftalmología Ramón Pando Ferrer por presentar dolor ocular y molestias a la luz en el ojo derecho. En la exploración oftalmológica se constata una uveítis anterior con hipopión en el ojo derecho y depósitos de cristales en todo el espesor corneal y el iris en ambos ojos. Se indicaron esteroides tópicos con resolución del proceso inflamatorio. Los hallazgos en el segmento anterior del paciente son sugestivos de cistinosis, donde el acúmulo de cristales es la alteración corneal más típica de las manifestaciones oculares, con una incidencia del 90 por ciento en niños menores de un año, y los primeros órganos afectados son los riñones. Los raquitismos hipofosfatémicos hereditarios pueden cursar con depósitos de cristales corneales y procesos inflamatorios de la úvea anterior(AU)

Hereditary hypophosphatemic rickets are a group of diseases characterized by renal loss of phosphates. They appear with disharmonic hypogrowth and bone deformities. The most common form is the X-chromosome-linked hypophosphatemic rickets which is caused by inactivating mutations in PHEX gene. The objective of our work was to describe the ocular alterations and the clinical evolution in a patient with hereditary hypophosphatemic rickets and previous uveitis. Here is the case of a 9 years-old boy diagnosed with hereditary hypophosphatemic rickets, who was seen at the Uveitis Service of Ramon Pando Ferrer Cuban Institute of Ophthalmology. He presented with ocular pain and feeling of discomfort to light in his right eye. The ophthalmological exam yielded anterior uveitis with hypopyon in his right eye and crystal depots in the whole corneal thickness and the iris of both eyes. Topical steroids were prescribed to treat the inflammatory process. The findings in the anterior segment of the patients indicated the presence of cystinosis in which the accumulation of crystals is the most typical corneal alteration among the ocular manifestations. Its incidence reaches 90 percent in under one year-old children and the first affected organs are the kidneys. The hereditary hypophosphatemic rickets may appear with corneal crystal depots and inflammatory processes in the anterior uvea(AU)

Estudio Descriptivo: Niveles de 25 ­ Hidroxi Vitamina D en la Población que Acude al Servicio de Endocrinología del Instituto Ecuatoriano de Seguridad Social, Azogues ­ Ecuador, 2017 / Restrospective Research: Levels of 25 - Hydroxy Vitamin D in the population that goes to the Endocrinology Service of the Ecuadorian Institute of Social Security, Azogues - Ecuador, 2017

INTRODUCCIÓN: La Vitamina D es considerada una hormona, siendo químicamente liposoluble y se le relaciona con enfermedades inmunológicas, cardiometabólicas y cáncer. El objetivo es evaluar los niveles de 25 hidroxi vitamina D en los pacientes que acudieron al servicio de endocrinología. MÉTODOS: Se trata de un estudio retrospectivo, se tomaron 122 pacientes que acudieron al servicio de endocrinología del Instituto Ecuatoriano de Seguridad Social, durante el periodo durante el periodo de julio a septiembre del 2017. RESULTADOS: El promedio de vitamina D 23.99 ± 9.12 ng/ml, el 22 % presentaron vitamina D en rango normal (≥ 30 ng/ml) y el 78 % en insuficiencia/deficiencia (< 30 ng/ml). Los niveles de calcio y paratiroides no presentaron correlación con las disminuciones de vitamina D. CONCLUSIONES: Existe una importante disminución de la vitamina D en la población que acudió al servicio de Endocrinología durante el periodo estudiado, pese a la exposición solar directa que reciben los pobladores de la zona.

BACKGROUND: Vitamin D is considered a hormone, being chemically lipid soluble and is related to immunological, cardiometabolic and cancer diseases. This aim to evaluate the levels of 25 hydroxy vitamin D in the patients who attended the endocrinology service. METHODS: This was a retrospective study, taking 122 patients who attended the endocrinology service of the Ecuadorian Social Security Institute, during the period during the period from July to September 2017. RESULTS: The average of vitamin D was 23.99 ± 9.12 ng / ml, 22 % of vitamin D in normal range (≥ 30 ng / ml) and 78 % of insufficiency / deficiency (≥ 30 ng / ml). Calcium and parathyroid levels show no correlation with decreases in vitamin D. CONCLUSIONS: There is a significant decrease in the population in the population that went to the Endocrinology service during the period studied, to the direct solar incidence that the inhabitants of the area.

Successful Localization Using ⁶⁸Ga-DOTATOC PET/CT of a Phosphaturic Mesenchymal Tumor Causing Osteomalacia in a Patient with Concurrent Follicular Lymphoma / 대한핵의학회잡지

Diagnosing tumor-induced osteomalacia is often challenging because conventional imaging modalities may fail to locate the responsible tumor. This report describes the ability of ⁶⁸Ga-DOTATOC PET/CT to successfully distinguish between the responsible phosphaturic mesenchymal tumor and concurrent lymphoma lesions. A 52-year-old man with bone pain for several years was diagnosed with a vitamin D-resistant hypophosphatemic osteomalacia. Whole body ¹⁸F-FDG PET/CT revealed multiple enlarged hypermetabolic lymph nodes in his bilateral cervical, axillary, mediastinal, abdominal, pelvic, and inguinal regions. Core needle biopsy of the right cervical lymph node confirmed the diagnosis of follicular lymphoma. However, lymphoma was not considered the cause of osteomalacia. ⁶⁸Ga-DOTATOC PET/CT before chemotherapy showed a small nodule with intensely increased uptake in the right inguinal region, which was distinguished from the other enlarged lymph nodes. The nodule was surgically removed and histopathologically consistent with phosphaturic mesenchymal tumor. After surgery, the patient's serum phosphorus and alkaline phosphatase levels normalized without nutritional supplement.

Value of Ga-DOTA-TATE Positron Emission Tomography/Computed Tomography in the Localization of Culprit Tumors Causing Osteomalacia with Negative Tc-HYNIC-TOC Single Photo Emission Computed Tomography / 中国医学科学院学报

Objective To analyze Ga-DOTA-TATE positron emission tomography/computed tomography (PET/CT) imaging features of tumor-indud osteomalacia (TIO) patients with negative Tc-HYNIC-TOC single photo emission computed tomography (SPECT) findings and to investigate the value of Ga-DOTA-TATE PET/CT in accurate localization of culprit tumors.Methods We retrospectively analyzed Ga-DOTA-TATE PET/CT imaging features including location,size,density,the maximum and mean standardized uptake value in 37 TIO patients with negative Tc-HYNIC-TOC SPECT findings.Results Totally 37 solitary TIO tumors,including 35 phosphaturic mesenchymal tumors and 2 spindle cell tumors confirmed by pathological examinations,were detected via Ga-DOTA-TATE PET/CT scans in the included 37 cases. These 37 TIO tumors showed obviously increased activities,with an maximum standardized uptake value of 7.2±4.3 and mean standardized uptake value of 4.3±2.4. The average maximum diameter was (1.9±0.7) cm. The majority of the tumors occurred in the lower extremities (19/37),followed by the trunk (11/37),maxillary/mandibular bone (5/37),and upper extremities (2/37). In addition,24 bone lesions were located in long bones of lower extremities (13/24),most of which demonstrated eccentric growth (8/13). Osteolytic changes (14/24) were observed mainly in the lesions via the corresponding CT imaging;meanwhile,sclerotic changes presented in nine cases. Of the 13 soft-tissue lesions,the majority (10/13) showed well-circumscribed isodense or hypodense nodules on the CT images,with spot calcification in one lesion located in the pleura.Conclusions Ga-DOTA-TATE PET/CT scans can detect the TIO culprit tumors miss-diagnosed by Tc-HYNIC-TOC SPECT. Somatostatin-receptors highly expressed lesions with focal osteolytic or osteosclerotic change in bone and isodense or hypodense nodules in soft tissue will favor the diagnosis of TIO tumors.

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.

An Uncommon Case of Bilateral Pathologic Hip Fractures: Antiviral Drug-induced Osteomalacia in a Patient with Hepatitis B / 대한고관절학회지

The long-term use of adefovir and tenofovir–antiviral medications commonly used to treat chronic hepatitis B–can be associated with proximal renal tubular dysfunction resulting in significant hypophosphatemic osteomalacia. However, there have been few reports about pathological fractures requiring surgical stabilization in cases of antiviral drug-induced hypophosphatemic osteomalacia. We present the case of a 51-year-old man who sustained bilateral pathological hip fractures associated with antiviral drug-induced hypophosphatemic osteomalacia. To treat a lamivudine-resistant hepatitis-B viral infection, the patient received adefovir for 7 years followed by tenofovir for the subsequent 3 years. He had suffered from polyarthralgia and generalized weakness for 2 years prior to presentation at our clinic. Misdiagnosis and inadequate management of his condition accelerated weakness of the bone matrix and ultimately induced pathological fractures. The patient was managed via cementless total hip arthroplasty on the left hip and internal fixation on the right hip. This case highlights that orthopaedic surgeons should consider the possibility of hypophosphatemic osteomalacia if patients receiving antiviral drugs complain of polyarthralgia and generalized weakness.

Hypophosphatemic Osteomalacia with Multiple Bone Fractures: ADV-Induced Fanconi's Syndrome / 전남의대학술지

No abstract available.

Adefovir-induced Fanconi syndrome associated with osteomalacia

Fanconi syndrome is a dysfunction of the proximal renal tubules that results in impaired reabsorption and increased urinary loss of phosphate and other solutes. The pathophysiology of drug-induced Fanconi syndrome is unclear. Here we report the case of a 36-year-old woman who presented with pain in multiple bones and proteinuria. She had a 7-year history of taking adefovir at 10 mg/day for chronic hepatitis B. Three years previously she had received surgery for a nontraumatic right femur neck fracture, after which she continued to complain of pain in multiple bones, and proteinuria, glycosuria, and phosphaturia were noted. The findings of a light-microscope examination of a renal biopsy sample were normal, but mitochondrial damage of the proximal tubules was evident in electron microscopy. Western blot analysis revealed that the level of serum fibroblast growth factor 23 (FGF23) was lower than in normal controls. After 2 months of treatment, hypophosphatemia and proximal tubular dysfunction were reversed, and serum FGF23 had normalized. This case suggests that direct mitochondrial damage in proximal tubules can cause drug-induced Fanconi syndrome associated with osteomalacia.

Displasia fibrosa ósea / Fibrous dysplasia of bone

La displasia fibrosa ósea es un trastorno no hereditario del desarrollo esquelético caracterizado por una proliferación anormal de fibroblastos y diferenciación deficiente de osteoblastos que conduce a un reemplazo del tejido óseo esponjoso por tejido conectivo fibroso. Es producida por una mutación somática activadora del gen GNAS1 que induce una activación y proliferación de células mesenquimales indiferenciadas con formación de tejido fibroso y trabéculas óseas anómalas. Existen formas monostóticas, poliostóticas y craneofaciales con diversos grados de dolor, deformidades y fracturas óseas, aunque muchos casos son asintomáticos. En ocasiones se producen quistes óseos aneurismáticos, hemorragias, compromisos neurológicos y raramente osteosarcomas. Algunos casos se asocian a síndrome de McCune-Albright, síndrome de Mazabraud y a osteomalacia por hipofosfatemia por pérdida tubular renal inducida por el FGF23 producido por el tejido displásico. Los hallazgos en las radiografías convencionales son característicos, aunque variables y de carácter evolutivo. La gammagrafía ósea es la técnica de imagen con mayor sensibilidad para determinar la extensión de la enfermedad. El diagnóstico diferencial incluye múltiples lesiones óseas de características similares y en raras ocasiones se requiere biopsia ósea o estudio genético para confirmarlo. No existe un consenso unánime acerca del abordaje terapéutico de estos pacientes, razón por la cual es necesario un enfoque multidisciplinario. La conducta puede ser expectante o quirúrgica según el tipo de lesiones y es importante el manejo del dolor y de las endocrinopatías asociadas. La mayor experiencia publicada se refiere al uso de bifosfonatos y, más recientemente, denosumab. Los tratamientos actuales son insuficientes para modificar el curso de la enfermedad y es necesario el desarrollo de nuevas moléculas que actúen específicamente en el gen GNAS1 o sobre las células mesenquimales afectadas. (AU)

Fibrous dysplasia of bone is a noninherited developmental anomaly of bone characterized by abnormal proliferation of fibroblasts and differentiation of osteoblasts that cause a replacement of trabeculous bone by fibrous connective tissue. It is caused by a somatic mutation in the GNAS1 gene, which induces an undifferentiated mesenquimal cells activation and proliferation with formation of fibrous tissue and abnormal osseous trabeculae. There are monostotic, polyostotic and craniofacial variants with different grades of bone pain, deformities and fractures, although many cases remain asymptomatic. Aneurysmal bone cysts, bleeding, neurological compromise and infrequently osteosarcoma are possible complications. Some cases are associated to McCune-Albright syndrome, Mazabraud syndrome or hypophosphatemia and osteomalacia due to to renal tubular loss induced by FGF23 produced by dysplastic tissue. The findings on conventional radiography are characteristic although variable and evlolve with time. Bone scintigraphy is the most sensitive technique to evaluate the extent of disease. Differential diagnosis include several osseous lesions of similar appearance and, in some cases, bone biopsy or genetic testing may be necessary. Today, there is no consensus regarding the therapeutic approach for these patients and it is necessary a multidisciplinary medical team. Watchful waiting or surgical interventions can be indicated, depending on the type of bone lesions. Bone pain and associated endocrinopathies management are very important. Most published experience refers to the use of bisphosphonates and, more recently, denosumab. Current treatments are insufficient to modify the natural curse of the disease and therefore, new molecules with specific action on GNAS1 gene or affected mesenchymal cells are necessary. (AU)

Phosphaturic mesenchymal tumor (PMT): exceptionally rare disease, yet crucial not to miss

Phosphaturic mesenchymal tumors (PMTs) are very rare tumors which are frequently associated with Tumor Induced Osteomalacia (TIO), a paraneoplastic syndrome that manifests as renal phosphate wasting. The tumor cells produce a peptide hormone-like substance known as fibroblast growth factor 23 (FGF23), a physiologic regulator of phosphate levels. FGF23 decreases proximal tubule reabsorption of phosphates and inhibits 1-α-hydroxylase, which reduces levels of 1-α, 25-dihydroxyvitamine D3. Thus, overexpression of FGF23 by the tumor cells leads to increased excretion of phosphate in the urine, mobilization of calcium and phosphate from bones, and the reduction of osteoblastic activity, ultimately resulting in widespread osteomalacia. Patients typically present with gradual muscular weakness and diffuse bone pain from pathologic fractures. The diagnosis is often delayed due to the non-specific nature of the symptoms and lack of clinical suspicion. While serum phosphorus and FGF23 testing can assist in making a clinical diagnosis of PMT, the responsible tumor is often difficult to locate. The pathologic diagnosis is often missed due to the rarity of PMTs and histologic overlap with other mesenchymal neoplasms. While patients can experience severe disabilities without treatment, excision is typically curative and results in a dramatic reversal of symptoms. Histologically, PMT has a variable appearance and can resemble other low grade mesenchymal tumors. Even though very few cases of PMT have been reported in the world literature, it is very important to consider this diagnosis in all patients with hypophosphatemic osteomalacia. Here we present a patient who suffered for almost 5 years without a diagnosis. Ultimately, the PMT was located on a 68Ga-DOTA TATE PET/CT scan and subsequently confirmed by histologic and immunohistologic study. Interestingly, strong positivity for FGFR1 by IHC might be related to the recently described FN1-FGFR1 fusion. Upon surgical removal, the patient's phosphate and FGF23 levels returned to normal and the patient's symptoms resolved.

Renal Tubular Acidosis in Patients with Primary Sjögren's Syndrome

Primary Sjögren's syndrome (pSS) is characterized by lymphocytic infiltration of the exocrine glands resulting in decreased saliva and tear production. It uncommonly involves the kidneys in various forms, including tubulointerstitial nephritis, renal tubular acidosis, Fanconi syndrome, and rarely glomerulonephritis. Its clinical symptoms include muscle weakness, periodic paralysis, and bone pain due to metabolic acidosis and electrolyte imbalance. Herein, we describe the cases of two women with pSS whose presenting symptoms involve the kidneys. They had hypokalemia and normal anion gap metabolic acidosis due to distal renal tubular acidosis and positive anti-SS-A and anti-SS-B autoantibodies. Since one of them experienced femoral fracture due to osteomalacia secondary to renal tubular acidosis, an earlier diagnosis of pSS is important in preventing serious complications.