Approaching virtual osteoid volume estimation and in-depth tissue characterization in patients with tumor-induced osteomalacia.

Tumor-induced osteomalacia (TIO) poses a significant diagnostic challenge, leading to increased disease duration and patient burden also by missing clinical suspicion. Today, diagnosis of osteomalacia relies on invasive iliac crest biopsy, if needed. Therefore, a noninvasive method would be beneficial for patients with severe osteomalacia, such as TIO, to inform their clinical management and address specific needs, like estimating the regeneration capacity at high osteoid volumes (OVs) or the potential of a hungry bone syndrome after tumor removal. Furthermore, given the lack of comprehensive histological characterization of TIO, there is a need for additional tissue characterization. Therefore, our assessment encompassed iliac crest biopsies that were examined using quantitative electron backscattered microscopy, Raman spectroscopy, micro-computed tomography, and histology to analyze the biopsy tissue. Our clinical assessment encompassed DXA and high-resolution peripheral quantitative computed tomography (HR-pQCT) alongside with biochemical analyses and clinical evaluations. Combining imaging and clinical data, we established a model to predict the OV. We compared 9 TIO patients with 10 osteoporosis (OPO) patients and 10 healthy controls. Histological analyses confirmed a pronounced OV in TIO patients (OPO: 1.20% ± 1.23% vs TIO: 23.55% ± 12.23%, P < .0005), and spectroscopy revealed lower phosphate levels in TIO biopsies. By combining HR-pQCT and laboratory diagnostics, we developed a linear regression model to noninvasively predict the OV revealing significantly higher modeled OV/BVmodel values of 24.46% ± 14.22% for TIO compared to the control group (5.952% ± 3.44%, P ≤ .001). By combining laboratory diagnostics, namely, ALP and Tt.BMDRadius measured by HR-pQCT, we achieved the calculation of the virtual osteoid volume to bone volume ratio (OV/BVmodel) with a significant correlation to histology as well as reliable identification of TIO patients compared to OPO and control. This novel approach is potentially helpful for predicting OV by noninvasive techniques in diagnostic procedures and improving the clinical management of TIO.

Osteomalacia, a bone mineralization disease, results in soft bones due to a lack of calcium or phosphate. Tumor-induced osteomalacia (TIO) is an acquired and challenging form of osteomalacia due to low serum phosphate levels that often lead to prolonged patient suffering. Current diagnosis of osteomalacia involves surgical bone biopsies, but a noninvasive approach would be beneficial, improving clinical management and addressing specific needs like estimating the bone's quality and ability to recover. We used advanced techniques like electron microscopy, spectroscopy, and high-resolution CT to study bone samples from 9 TIO patients. Additionally, we assessed their bone health through sophisticated imaging and blood analyses. Microscopy confirmed huge amounts of soft bone tissue due to a severe mineralization defect. By combining imaging and blood analysis, we developed a noninvasive method to predict the amount of soft tissue (osteoid) to understand soft bones without the need for surgical interventions. In conclusion, our innovative approach, combining blood diagnostics (alkaline phosphatase) with total BMD from high-resolution 3D clinical imaging of the lower arm, allows us to predict the osteoid amount virtually. This method can also compare TIO patients with controls or those with osteoporosis and might be helpful in the future.

Histomorphometric analysis of patients with femoral neck fracture and 25-hydroxyvitamin D deficiency: a cross-sectional study.

INTRODUCTION: Vitamin D deficiency causes osteoporosis, bone mineralization disorders, and osteomalacia. Osteomalacia is diagnosed using blood biochemical tests, clinical symptoms, and imaging; however, accurate detection of mineralization disorders requires tissue observation. We investigated the prevalence of bone mineralization disorders and their relationship with serum 25-hydroxyvitamin D (25OHD) levels in patients with untreated osteoporosis with femoral neck fractures. MATERIALS AND METHODS: A non-demineralized specimen was prepared from the femoral head removed during surgery in 65 patients. Bone histomorphometry of cancerous bone in the femoral head center was conducted. Osteoid volume per bone volume (OV/BV) and osteoid thickness (O.Th) were measured as indicators of mineralization disorder. RESULTS: The mean serum 25OHD level (11.9 ± 5.7 ng/mL) was in the deficiency range (< 12 ng/mL). There were no clinically diagnosed cases of osteomalacia (OV/BV > 10% and O.Th > 12.5 µm); however, one case of mineralization disorder, considered histologically pre-osteomalacia (OV/BV > 5% and O.Th < 12.5 µm), was observed (OB/BV, 17.6%; O.Th, 12.3 µm). Excluding this case, those with severe (25OHD < 12 ng/mL, at risk of osteomalacia; n = 39) and non-severe deficiency (25OHD ≥ 12 ng/mL; n = 25) did not significantly differ in OV/BV (%; 0.77 ± 0.54 vs. 0.69 ± 0.38, p = 0.484) or O.Th (µm; 5.32 ± 1.04 vs. 5.13 ± 0.78, p = 0.410). Further, 25OHD and OV/BV were not significantly correlated (R = - 0.124, p = 0.327). CONCLUSION: This is the first study in the twenty-first century to examine serum 25OHD concentrations and bone mineralization disorders in Japanese patients with osteoporosis. The results indicate that vitamin D deficiency does not necessarily cause bone mineralization disorders and rarely leads to osteomalacia.

Tumor-induced osteomalacia: An overview.

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.

Combination of osteogenesis imperfecta and hypophosphatasia in three children with multiple fractures, low bone mass and severe osteomalacia, a challenge for therapeutic management.

Osteogenesis imperfecta (OI) and hypophosphatasia (HPP) are rare skeletal disorders caused by mutations in the genes encoding collagen type I (COL1A, COL1A2) and tissue-non-specific isoenzyme of alkaline phosphatase (ALPL), respectively. Both conditions result in skeletal deformities and bone fragility although bone tissue abnormalities differ considerably. Children with OI have low bone mass and hypermineralized matrix, whereas HPP children develop rickets and osteomalacia. We report a family, father and three children, affected with growth retardation, low bone mass and recurrent fractures. None of them had rickets, blue sclera or dentinogenesis imperfecta. ALP serum levels were low and genetics revealed in the four probands heterozygous pathogenic mutations in COL1A2 c.838G > A (p.Gly280Ser) and in ALPL c.1333T > C (p.Ser445Pro). After multidisciplinary meeting, a diagnostic transiliac bone biopsy was indicated for each sibling for therapeutic decision. Bone histology and histomorphometry, as compared to reference values of children with OI type I as well as, to a control pediatric patient harboring the same COL1A2 mutation, revealed similarly decreased trabecular bone volume, increased osteocyte lacunae, but additionally severe osteomalacia. Quantitative backscattered electron imaging demonstrated that bone matrix mineralization was not as decreased as expected for osteomalacia. In summary, we observed within each biopsy samples classical features of OI and classical features of HPP. The apparent nearly normal bone mineralization density distribution results presumably from divergent effects of OI and HPP on matrix mineralization. A combination therapy was initiated with ALP enzyme-replacement and one month later with bisphosphonates. The ongoing treatment led to improved skeletal growth, increased BMD and markedly reduced fracture incidence.

Occipital bone and tumor-induced osteomalacia: a rare tumor site for an uncommon paraneoplastic syndrome.

INTRODUCTION: Tumor-induced osteomalacia (TIO) is an uncommon paraneoplastic syndrome due to the overproduction of fibroblast growth factor 23 (FGF23). It is predominantly caused by mesenchymal tumors and cured upon their complete removal. Non-surgical treatment is an alternative option but limited to specific clinical conditions. METHODS: We report a challenging case of TIO caused by a tumor involving the occipital bone. We also performed a literature review of TIO caused by tumors localized at this site, focusing on clinical findings, treatment, and outcomes. RESULTS: The patient, a 62-year-old male, presented with a long-lasting history of progressive weakness. Biochemical evaluation revealed severe hypophosphatemia due to low renal tubular reabsorption of phosphate with raised intact FGF23 values. A 68 Ga-DOTATATE PET/TC imaging showed a suspicious lesion located in the left occipital bone that MRI and selective venous catheterization confirmed to be the cause of TIO. Stereotactic gamma knife radiosurgery was carried out, but unfortunately, the patient died of acute respiratory failure. To date, only seven additional cases of TIO have been associated to tumors located in the occipital bone. Furthermore, the tumor involved the left side of the occipital bone in all these patients. CONCLUSION: The occipital region is a difficult area to access so a multidisciplinary approach for their treatment is required. If anatomical differences could be the basis for the predilection of the left side of the occipital bone, it remains to be clarified.

Osteomalacia Prevalence, Biochemical Profile, and Histology in Patients with Low-Energy Hip Fractures Over the Age of 45.

Our objective was to determine the prevalence of osteomalacia in low-energy hip fracture patients over the age of 45, based on biochemical and histological measures. This cross-sectional study included 72 patients over 45 with low-energy mechanism hip fractures. Samples of fasting venous blood were taken for hemograms and serum biochemistry analyses. Bicortical biopsies of the iliac crest were obtained, processed, and evaluated by an expert pathologist for osteomalacia. Biochemical osteomalacia (b-OM) is defined according to a distinct criterion. A low level of serum calcium, phosphorus, albumin, and 25OHD was found in 43.1, 16.7, 73.6, and 59.7% of patients, respectively. 50.0% of patients had high serum alkaline phosphatase (ALP) levels. b-OM was found in 30 (41.7%), and no significant association was found with PTH, Cr, Alb, age, sex, fracture type, side of the trauma, and season were not associated with osteomalacia. Osteomalacia was diagnosed on histopathological analysis in 19/72 (26.7%), and 54/72 (75.0%) of all cases fulfilled b-OM criteria. In the histologic evaluation, osteoid seam width, osteoid surface, and osteoid volume were 28.5 µm, 25.6, and 12.1%, respectively. The sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of the biochemical test for detecting osteomalacia were 73.6, 64.2, 42.4, 87.2, and 66.7%, respectively. Up to 30% of elderly patients with low-energy hip fractures are affected by osteomalacia. A biochemical screening along with a bone biopsy and histopathologic evaluation may be logical in a high-risk population for osteomalacia diagnosis.

Tumor induced osteomalacia from a peripheral mesenchymal tumour of the foot.

Tumour induced osteomalacia (TIO) is a rare condition caused by peripheral mesenchymal tumours (PMT) which produce fibroblast-growth factor 23 (FGF23). FGF23 inhibits renal phosphate reabsorption leading to vitamin D resistant osteomalacia. The rarity of the condition and difficulty with isolating the PMT make diagnosis difficult, with delayed treatment leading to significant patient morbidity. We present a case of PMT of the foot with TIO, with a discussion on diagnosis and treatment.

Tumor-induced Osteomalacia in a Boy with Maxillary Ossifying Fibroma

Tumor-induced osteomalacia (TIO) is a rare, paraneoplastic disorder of hypophosphatemia associated with elevated tumor-produced fibroblast growth factor 23 (FGF23). Maxillofacial tumors are rarely involved in TIO, especially maxillary TIO in children. We present a 14-year-old boy with osteomalacia and high serum levels of FGF23, a hormone associated with decreased phosphate resorption, due to a maxillary tumor. The patient was treated with oral phosphorus and calcitriol, and surgical removal of the tumor was performed. After 21 months follow-up, he was pain free and had returned to full activity. We review the reported pediatric cases of TIO in the maxillofacial and oral region and discuss the management of these patients considering the published evidence.

[FGF23 tumor induced osteomalacia].

Tumor induced osteomalacia is a rare acquired disease. The cause is a mesenchymal tumor secreting fibroblast growth factor 23 (FGF23). An excessive amount of FGF 23 disrupts the metabolism of phosphorus and vitamin D, which leads to severe paraneoplastic syndrome, manifested in the form of multiple fractures, severe pain in the bones and generalized myopathy. With oncogenic osteomalacia, a complete cure is possible with radical resection of the tumor. Unfortunately, localization, small size of formations and rare frequency of occurrence lead to the fact that the disease remains unrecognized for a long time and leads to severe, disabling consequences. A step-by-step approach to diagnosis improves treatment outcomes. First, a thorough anamnesis is collected, then functional visualization is performed and the diagnosis is confirmed by anatomical visualization of the tumor. After that, the method of choice is a surgical treatment. If resection is not possible, then conservative therapy with active metabolites of vitamin D and phosphorus salts is indicated. New therapeutic approaches, such as the antibody to FGF23 or the pan-inhibitor of receptors to FGF, are actively developing. This article provides an overview of modern approaches to the diagnosis and treatment of this disease.

Tumor-Induced Osteomalacia: A Systematic Clinical Review of 895 Cases.

Tumor-induced osteomalacia (TIO) is a rare and largely underdiagnosed paraneoplastic condition. Previous reviews often reported incomplete data on clinical aspects, diagnosis or prognosis. The aim of this study was to present a systematic clinical review of all published cases of TIO. A search was conducted in Pubmed, Embase, Web of Science from inception until April 23rd, 2020. We selected case reports and case series of patients diagnosed with TIO, with information on tumor localization and serum phosphate concentration. Two reviewers independently extracted data on biochemical and clinical characteristics including bone involvement, tumor localization and treatment. 468 articles with 895 unique TIO cases were included. Median age was 46 years (range 9 months-90 years) and 58.3% were males. Hypophosphatemia and inappropriately low or normal 1,25-dihydroxyvitamin D levels, characteristic for TIO, were present in 98% of cases. Median tumor size was 2.7 cm (range 0.5 to 25.0 cm). Serum fibroblast growth factor 23 was related to tumor size (r = 0.344, P < 0.001). In 32% of the cases the tumor was detected by physical examination. Data on bone phenotype confirmed skeletal involvement: 62% of cases with BMD data had a T-score of the lumbar spine ≤ - 2.5 (n = 61/99) and a fracture was reported in at least 39% of all cases (n = 346/895). Diagnostic delay was longer than 2 years in more than 80% of cases. 10% were reported to be malignant at histology. In conclusion, TIO is a debilitating disease characterized by a long diagnostic delay leading to metabolic disturbances and skeletal impairment. Increasing awareness of TIO should decrease its diagnostic delay and the clinical consequences.

Intracranial phosphaturic mesenchymal tumors. A case report and review of literature.

Most osteomalacia-inducing tumors (OITs) are phosphaturic mesenchymal tumors (PMTs) that secrete fibroblast growth factor 23 (FGF23). These tumors usually occur in the bone and soft tissues, and intracranial OITs are rare. Therefore, intracranial OIT is difficult to diagnose and treat. This paper presents a case of intracranial OIT and shows a review of previous cases. A 45-year-old man underwent nasal cavity biopsy and treatment with active vitamin D3 and neutral phosphate for hypophosphatemia. Amplification of FGF23 mRNA level within the tumor was detected. Subsequently, the surgical specimen was diagnosed with a PMT and was considered the cause of the patient's osteomalacia. The patient was referred to a neurosurgery department for the excision of the intracranial tumor extending to the nasal cavity. After tumor removal, the serum levels of FGF23 and phosphorus were normalized as compared to preoperative those. The patient remains disease-free, without additional treatment, approximately 10 years after surgery, with no tumor recurrence. As per the literature, intracranial OITs usually occur in patients aged 8-69 years. Bone and muscle pain are major complaints. Approximately 60% of the patients reported previously had symptoms because of intracranial tumors. In some cases, it took several years to diagnose OIT after the onset of the osteomalacia symptoms. Laboratory data in such cases show hypophosphatemia and elevated FGF23 levels. Because FGF23 levels are associated with the severity of osteomalacia symptoms, total tumor resection is recommended. PMT and hemangiopericytoma (HPC) are histologically similar, but on immunochemistry, PMT is negative for signal transducer and activator of transcription 6 (STAT6), whereas HPC is positive. FGF23 amplification is seen in PMTs but not in HPCs. Therefore, the analysis of FGF23 and STAT6 was helpful in distinguishing PMTs from HPCs. In cases of hypophosphatemia and osteomalacia without a history of metabolic, renal, or malabsorptive diseases, the possibility of oncogenic osteomalacia should be considered.

Hypophosphatemia related to a neuro-endocrine tumor of the pancreas: A case report.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a paraneoplastic syndrome characterized by hypophosphatemia associated with elevated fibroblast growth factor 23 (FGF23). TIO is primarily caused by benign mesenchymal tumors of the soft tissue and skeleton. Rarely, it is associated with a solid tumor or hematological malignancy. To date, no case of osteomalacia related to pancreatic cancer has been reported in the literature. CASE REPORT: A 77-year-old woman was admitted to the rheumatology department (RD) of the Clermont-Ferrand University Hospital (France) for further evaluation of her hypophosphatemia. The patient reported bone pain, myalgia, and asthenia. Further laboratory tests revealed hyperphosphaturia, normocalcemia, low serum calcitriol, elevated serum alkaline phosphatase (ALP), and elevated plasma parathyroid hormone (PTH). A renal phosphate depletion disorder was suspected as an etiology for this hypophosphatemia. Finally, FGF23 levels were found to be significantly elevated, leading to a definitive diagnosis of pancreatic neuroendocrine tumor. CONCLUSION: This is the first report of hypophosphatemic osteomalacia related to pancreatic cancer. Therefore, in the setting of hypophosphatemia associated with renal phosphate wasting and low calcitriol level, plasma FGF23 measurement should be considered.

Diagnostic Utility of Somatostatin Receptor 2A Immunohistochemistry for Tumor-induced Osteomalacia.

CONTEXT: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic disorder caused by excessive fibroblast growth factor 23 (FGF23) secretion. FGF23 immunohistochemistry (IHC) is proposed as a useful adjunctive marker to confirm TIO diagnosis. However, it often stains focally, limiting its diagnostic utility. OBJECTIVE: This work aimed to compare the diagnostic performance between somatostatin receptor 2A (SSTR2A) and FGF23 IHC for TIO. METHODS: We retrospectively reviewed TIO-diagnosed patients in Severance Hospital between July 2006 and May 2020. Histologic evaluation was performed using histoscore (H score) (expression area proportion score [0-2] × intensity score [1-3], [total, 0-6]). FGF23 and SSTR2A IHC were performed using unstained slides from 18 localized TIO patients and 9 and 15 non-TIO controls with bone and soft-tissue tumors, respectively. SSTR2A positivity was defined as cytoplasmic, membranous, or Golgi staining in more than 1% of tumor cells, and negativity as nonspecific nuclear staining. FGF23 positivity was defined as cytoplasmic expression in more than 1% of the tumor area and negativity as nonspecific nuclear staining. RESULTS: Suspicious lesions were successfully detected in 14 of 15 patients who underwent 68Ga-DOTATOC scans. Diffuse cytoplasmic SSTR2A expression was identified in all TIO patients and focal weak nuclear staining in 12 of 15 controls. FGF23 cytoplasmic expression was identified in 11 of 18 TIO patients and diffuse nuclear staining in 9 of 9 controls. The H score was higher in SSTR2A than in FGF23 IHC (median [interquartile range]: 6 [6-6] vs 1 [0-2], P < .001). CONCLUSION: SSTR2A IHC with H-score quantification might be a more sensitive, adjunctive diagnostic tool than FGF23 IHC for TIO diagnosis.

Bone Impairment in a Large Cohort of Chinese Patients With Tumor-Induced Osteomalacia Assessed by HR-pQCT and TBS.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome caused by excessive production of fibroblast growth factor 23 (FGF23) by a tumor. Previous studies have revealed generalized mineralization defects and low areal bone mineral density (aBMD) in TIO. However, data on the bone microarchitecture in TIO are limited. In this study, we evaluated the microarchitecture in the peripheral (distal radius and tibia) and axial (lumbar spine) skeleton using high-resolution peripheral quantitative computed tomography (HR-pQCT) and trabecular bone score (TBS) and investigated related factors in a large cohort of Chinese patients with TIO. A total of 186 patients with TIO who had undergone dual-energy X-ray absorptiometry (DXA) or HR-pQCT scans were enrolled. Compared with age-, sex-, and body mass index (BMI)-matched healthy controls, TIO patients (n = 113) had lower volumetric BMD, damaged microstructure, and reduced bone strength in the peripheral skeleton, especially at the tibia. The average TBS obtained from 173 patients was 1.15 ± 0.16. The proportion of patients with abnormal TBS (<1.35) was higher than that with low L1 to L4 aBMD Z-score (Z ≤ -2) (43.9% versus 89.6%, p < 0.001). Higher intact fibroblast growth factor 23 (iFGF23), intact parathyroid hormone (iPTH), alkaline phosphatase, and ß-isomerized C-terminal telopeptide of type I collagen (ß-CTx) levels, more severe mobility impairment, and a history of fracture were associated with poorer HR-pQCT parameters but not with lower TBS. However, greater height loss and longer disease duration were correlated with worse HR-pQCT parameters and TBS. Moreover, TBS was correlated with both trabecular and cortical HR-pQCT parameters in TIO. In conclusion, we revealed impaired bone microarchitecture in the axial and peripheral skeleton in a large cohort of Chinese TIO patients. HR-pQCT parameters and TBS showed promising advantages over aBMD for assessing bone impairment in patients with TIO. A longer follow-up period is needed to observe changes in bone microarchitecture after tumor resection. © 2021 American Society for Bone and Mineral Research (ASBMR).

Phosphate Metabolism and Pathophysiology in Parathyroid Disorders and Endocrine Tumors.

The advent of new insights into phosphate metabolism must urge the endocrinologist to rethink the pathophysiology of widespread disorders, such as primary hyperparathyroidism, and also of rarer endocrine metabolic bone diseases, such as hypoparathyroidism and tumor-induced hypophosphatemia. These rare diseases of mineral metabolism have been and will be a precious source of new information about phosphate and other minerals in the coming years. The parathyroid glands, the kidneys, and the intestine are the main organs affecting phosphate levels in the blood and urine. Parathyroid disorders, renal tubule defects, or phosphatonin-producing tumors might be unveiled from alterations of such a simple and inexpensive mineral as serum phosphate. This review will present all these disorders from a 'phosphate perspective'.

Nutritional Secondary Hyperparathyroidism and Fibrous Osteodystrophy in a Captive African Penguin (Spheniscus demersus) Similar to Osteomalacia in Poultry.

A 9-yr-old female black-footed African penguin (Spheniscus demersus) was presented for necropsy after a history of reproductive abnormalities, paresis of limbs, weakness, and sudden death. Postmortem examination revealed soft keel, collapsed rib cage with beading of the ribs, and bilateral parathyroid enlargement. Classic histologic lesions of fibrous osteodystrophy with osteomalacia were observed in the ribs, vertebrae, and to a lesser extent in the femur and tibiotarsus associated with hyperplasia of parathyroid glands. This represents the first report of nutritional secondary hyperparathyroidism in birds of the order Spheniciformes, most likely caused by low levels of calcium supplementation during egg laying. The reproductive abnormalities observed in this penguin and others from the same group (asynchronous egg-laying cycles, abnormal breeding behavior) were most likely exacerbated by the lack of an adequate photoperiod mimicking the natural daylight pattern.

Reporte de caso­Hiperparatiroidismo secundario nutricional y osteodistrofia fibrosa en un pingüino africano (Spheniscus demersus) en cautiverio similar a la osteomalacia observada en de aves de corral. Una hembra de pingüino africano de patas negras (Spheniscus demersus) de nueve años fue sometida a necropsia después de un historial de anomalías reproductivas, paresia de extremidades, debilidad y muerte súbita. El examen post mortem reveló que la quilla del esternón estaba blanda, la caja torácica colapsada, se observaron "perlas raquíticas" en las costillas y agrandamiento bilateral de las paratiroides. Se observaron lesiones histológicas clásicas de osteodistrofia fibrosa con osteomalacia en las costillas, vértebras y en menor medida, en el fémur y tibiotarsus asociadas con hiperplasia de glándulas paratiroides. Esto representa el primer informe de hiperparatiroidismo secundario nutricional en un ave del orden Spheniciformes, muy probablemente causado por un bajo nivel de suplementos de calcio durante la producción de huevos. Las anomalías reproductivas observadas en este pingüino y otros del mismo grupo (ciclos de puesta de huevos asincrónicos, comportamiento de reproducción anormal) probablemente se vieron exacerbadas por la falta de un fotoperíodo adecuado que imitara el patrón de luz natural.

Phosphaturic mesenchymal tumors: radiological aspects and suggested imaging pathway.

Phosphaturic mesenchymal tumors (PMTs) are rare mesenchymal neoplasms of soft tissue or bone origin that can give rise to a challenge in diagnostic imaging. These tumors are frequently associated with tumor-induced osteomalacia, also called oncogenic osteomalacia, which is a rare paraneoplastic syndrome characterized by ectopic secretion of fibroblast growth factor 23, a hormone that regulates serum phosphate level. PMTs show polymorphic features on both radiological findings and histological examination, causing problems in diagnosis owing to their similarity with other mesenchymal tumors. Thus, this paper aims to describe radiological aspects of PMTs and suggest an imaging pathway for accurate diagnosis throughout the evidence from the literature review.

Clinical, morphological and immunohistochemical analysis of 13 cases of phosphaturic mesenchymal tumor - A holistic diagnostic approach.

BACKGROUND: Phosphaturic mesenchymal tumor-mixed connective tissue (PMT-MCT) is a rare tumor characterized clinically by presence of tumor-induced osteomalacia (TIO), subsequent to elevated fibroblastic growth factor 23 (FGF23) levels. This study aims to analyse the morphological spectrum of PMT along with clinico-pathological correlation and immunophenotype profile of this rare tumor. MATERIALS AND METHODS: Detailed histological analysis of all tumors presenting with TIO over past 7 years was done retrospectively. Immunohistochemistry was performed in all cases for SATB2, STAT6, CD34, FGF23, ERG, S100 and smooth muscle actin (SMA). RESULTS: A total of 13 cases were analysed (8 female and 5 male) with mean age of 39.8 years. Five cases were arising from bone while 4 each from soft tissue and nasal cavity/paranasal sinus. All presented with hypophosphatemia, hyperphosphaturia, elevated serum FGF23 and features suggestive of osteomalacia. Histological examination revealed basophilic 'grungy' calcification seen in 7 (53.8%), osteoid formation in 8 (61.5%), chondroid matrix in 4 (30.8%), adipose tissue in 6 (46.2%), osteoclast-like giant cells in 9 (69.2%) and hemangiopericytomatous (HPC like) blood vessels in 7 cases (53.8%). HPC like vessels and adipose tissue were more common in nasal tumors while calcification was more common in tumors arising from bone. All cases showed immunoreactivity for SATB2 and clinical improvement following resection except one case with residual tumor. CONCLUSION: PMT shows varied histological pattern with various matrix components depending on the site of the tumor. Serum FGF-23 is a useful adjunctive marker for diagnosis.