Intracranial Phosphaturic Mesenchymal Tumors: A Systematic Literature Review of a Rare Entity.

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.

Treatment and Diagnose of Spinal Phosphaturic Mesenchymal Tumor: A Case Report and a Systematic Literature Review.

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.

Phosphaturic mesenchymal tumor: two cases highlighting differences in clinical and radiologic presentation.

Phosphaturic mesenchymal tumors are rare, usually benign neoplasms that occur in the soft tissue or bone and are the cause of nearly all cases of tumor-induced osteomalacia. Tumor-induced osteomalacia due to phosphaturic mesenchymal tumor is a challenging diagnosis to make-patients present with variable clinical and radiologic findings and the culprit neoplasm is often small and can occur anywhere head to toe. We present two cases of phosphaturic mesenchymal tumor in the scapular body and plantar foot. In both cases, the patient endured years of debilitating symptoms before a tissue diagnosis was eventually reached. Descriptions of clinical presentation, laboratory workup, surgical resection, and imaging characteristics, with a focus on CT, MRI, and functional imaging, are provided to assist with the diagnosis and management of this rare entity. A brief review of current literature and discussion of the differential diagnoses of phosphaturic mesenchymal tumor is also provided.

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.

Sinonasal phosphaturic mesenchymal tumour: radiation oncologist's perspective.

Tumour-induced osteomalacia is a rare cause of osteomalacia, the majority of which is of mesenchymal origin. Oncogenic osteomalacia is a potentially curable condition caused by phosphaturic mesenchymal tumours. We present the case of a woman in her 30s with a sinonasal phosphaturic mesenchymal tumour, treated with surgical excision followed by adjuvant intensity-modulated radiotherapy and subsequent adjuvant chemotherapy. The patient experienced minimal adverse effects during radiation. There was good local control and cosmetic outcomes with no radiation-related toxicity at a follow-up period of 32 months.

A Phosphaturic Mesenchymal Tumor Presenting as Reversible Metabolic Myopathy.

Tumor-induced osteomalacia (TIO) is a disorder in which the clinical signs and symptoms of osteomalacia and the biochemical abnormalities of hypophosphatemia, phosphaturia, and low serum levels of 1,25(OH)2 Vitamin D3 are secondary to a neoplasm. A 33-year-old woman presented with musculoskeletal pain and proximal myopathy with a duration of 2.5 years which was treated with Vitamin D supplements. On the basis of the biochemical tests and histopathology, she was reevaluated and found to have TIO secondary to a phosphaturic mesenchymal tumor. The tumor was resected (limb salvage with endoprosthesis), and she had no pain or weakness at followup. The case reminds the readers to consider the possibility of TIO when evaluating patients with isolated hypophosphatemia, which may lead to long-term disability and prolonged morbidity if untreated. Early recognition and diagnosis of TIO is crucial since resection of the tumor usually reverses its manifestations.

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.

Oncogenic osteomalacia due to phosphaturic mesenchymal tumour in the upper thoracic spine.

Oncogenic osteomalacia (OO) is an uncommon paraneoplastic syndrome occurring due to the presence of a tumour that oversecretes fibroblast growth factor-23, which impairs renal phosphate handling. In most cases, the tumour is a morphologically distinct entity called 'phosphaturic mesenchymal tumour' (PMT). Spinal tumours causing OO are exceedingly rare. A 55-year-old man presented with multiple bone pain and proximal muscle weakness in the lower limbs. The constellation of biochemical findings (hypophosphataemia, normocalcaemia, increased alkaline phosphatase, low-normal serum vitamin D and hyperphosphaturia) with radiographical rarefaction of the skeleton and pseudofractures led us to consider OO as a possibility. Functional imaging (68Ga DOTA-NOC positron emission tomography/CT scan) localised the tumour to the D2 vertebra. Complete surgical resection led to resolution of symptoms, improved ambulatory status, normalisation of biochemical parameters and healing of pseudofractures. PMT should be considered in the differential diagnosis of hypophosphataemic osteomalacia with hyperphosphaturia. Tumour localisation with functional imaging and complete surgical resection produces satisfactory outcome.

Tumor-Induced Osteomalacia Caused by a Phosphaturic Mesenchymal Tumor of the Sole Presenting as a Crippling Illness in a Postmenopausal Woman.

Tumor-induced osteomalacia, a rare and intriguing paraneoplastic syndrome that is usually caused by a phosphaturic mesenchymal tumor, leads to severe pain and hypophosphatemia. However, during clinical practice, most patients suffer from significant delay of diagnosis and treatment because the symptoms are similar to those of some very common diseases, such as osteoporosis and osteoarthritis. Moreover, physical complaints from postmenopausal women usually exacerbate the possibility of such delays. We describe a case of a postmenopausal woman with crippling bone pain and weakness, who had been diagnosed with a case of simple osteoporosis and osteoarthritis for 3 years, even with fine-needle aspiration biopsy of the offending phosphaturic mesenchymal tumor. After surgical removal of the 2 × 3-cm2 tumor in her sole, we observed immediate relief of her systemic symptoms, with visual analogue scale improvement from 5 of 10 preoperatively to 2 of 10 5 days after surgery. There were no signs of recurrence during 2-year follow-up. This case highlights the significance of thorough history-taking as a fundamental tool for diagnosis even in the era of advanced technology, and that the awareness of tumor-induced osteomalacia should be raised. Otherwise, such a small localized soft tissue mass would seldom be associated with the severe systemic symptoms.

Tumor-induced Osteomalacia due to a Phosphaturic Mesenchymal Tumor in the Cervical Spine: A Case Report and Literature Review.

Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome of certain mesenchymal tumors which secrete fibroblast growth factor-23 (FGF-23) responsible for causing features of hypophosphatemia and osteomalacia in these patients. Most of them involve the appendicular skeleton and occasionally the craniofacial regions. Involvement of spine is exceedingly rare. Through this paper, the authors present a rare case of a 71-year-old male with TIO due to a lesion in the cervical spine (right C2 lamina) which was proven to be a phosphaturic mesenchymal tumor-mixed connective tissue type on histopathology. This is the fifth reported case of TIO localized to the cervical spine. The patient underwent a hemilaminectomy and gross total resection of the tumor following which he made a gradual but steady recovery and does not have any recurrence 24 months after surgery. The authors not only provide a comprehensive literature review of all 18 spinal cases reported till date but also discuss the management of these patients in light of the published literature.

Successful treatment of tumor-induced osteomalacia causing by phosphaturic mesenchymal tumor of the foot.

Tumor-induced osteomalacia causing by phosphaturic mesenchymal tumor of the foot is exceedingly rare, thus may bring great challenges to the timely and proper diagnosis and treatment of clinicians. The only definitive management is removal of the phosphaturic mesenchymal tumor completely. The objective of this article is to report 2 unusual cases with tumor-induced osteomalacia causing by phosphaturic mesenchymal tumor of the foot.We describe 2 patients with phosphaturic mesenchymal tumor involving the foot who were successfully treated with tumor resection. On presentation to our institution, the patients both had signs of severe osteomalacia, and the patients' most outstanding complaints were diffuse bone pain, general weakness, and disabled walking. A 53-year-old female underwent surgical excision of pathogenic tumor on the sole of left foot. A 62-year-old female underwent complete excision of pathogenic tumor of right plantar. The patients showed appropriate destruction of the tumor, adequate pain relief, and the elevated blood phosphorus levels compared with the previous status.Surgical resection is the most effective treatment option for patients with tumor-induced osteomalacia who can undergo appropriate surgical treatment. This represents a safe and reasonable approach to sustainably relieve pain and other symptoms with tumor-induced osteomalacia in the foot.

Tumour-induced Osteomalacia Secondary to Intracranial Tumours - Report of 2 Cases.

Tumor induced osteomalacia (TIO) is a paraneoplastic syndrome which is mostly caused by a phosphaturic mesenchymal tumour mixed connective tissue variant (PMTMCT). These tumours do not have any specific site predilection but their presence in cranial compartment is very rare. Two cases of TIO secondary to phosphaturic mesenchymal tumour at the skull base are described ahead, one of which was in the posterior fossa and the other in middle cranial fossa. Early diagnosis and complete excision of PMT is essential in preventing morbidity secondary to osteomalacia. This case report stands distinct in highlighting a rare site of a phosphaturic mesenchymal tumour and the need to keep a high index of suspicion in cases of TIO especially wherein localization of the tumour is unsuccessful.

Phosphaturic mesenchymal tumors: A review and update.

Perhaps the rarest cause of osteomalacia is that caused by a neoplasm, so-called "tumor-induced osteomalacia" (TIO). Although very rare cases of TIO have been associated with carcinomas and syndromes such as neurofibromatosis type-1 and McCune-Albright syndrome, the overwhelming majority of TIO is caused by tumors of mesenchymal origin. Although it was historically felt that almost any mesenchymal tumor type could occasionally result in TIO, it has become increasingly clear over the past several decades that almost all cases of mesenchymal tumor-associated TIO are caused by a single entity, known as "phosphaturic mesenchymal tumor" (PMT). This article will review historical aspects of this tumor, as well as its clinical, morphological, immunohistochemical and molecular genetic features. The distinction of PMT from its many potential morphological mimics is discussed in detail.

Spinal phosphaturic mesenchymal tumors: Case report and literature review.

Tumor-induced osteomalacia (TIO) is regarded as a rare paraneoplastic syndrome generally caused by phosphaturic mesenchymal tumors (PMTs). As far as we know, only 18 spinal PMTs have been described in the world's English literature. The purpose of this study is to increase familiarity with its clinical features, diagnosis, and treatment of spinal PMTs. A 34-year-old woman presented with bone pain for more than 3 years and was found to have decreased serum phosphorus, elevated serum alkaline phosphatase. A full body 68Ga-DOTA-TATE PET/CT revealed increased uptake at the left posterior L5 neural arch. Then the tumor was totally resection and the histopathology revealed a PMT. Postoperatively, the patient's symptoms were relieved and experienced no recurrence during the 3-year follow-up. Generally, the preoperative diagnosis and location of spinal PMT still remains challenging. We also retrospectively analyzed 18 cases of patients with spinal PMTs published in English. Clinical symptoms, laboratory findings, treatment and outcome were retrospectively analyzed. Spinal PMTs are extraordinary and it is challengeable in locating tumors. Besides surgical resection, the treatment also included radiation, monoclonal antibodies or medical therapy. However, the optimal treatment remains controversial. Therefore, we should exert all our energies on the exploration of etiology and adjuvant therapy for this disease.