Extended curettage for tumour-induced osteomalacia in the bone.

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.

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.

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.

Pancreatic follicular dendritic cell sarcoma: one case report and literature review.

Pancreatic follicular dendritic cell sarcoma (FDCS) is a rare neoplasm with unclear pathological characteristics. In this study, we report one case of pancreatic FDCS and review published cases to summarize the characteristics and treatment of pancreatic FDCS. A man in his early 30 s was admitted for jaundice, abdominal fullness, and weight loss for 15 days. Computed tomography revealed a large capsule solid mass in the pancreatic head together with a dilated bile duct and enlarged retroperitoneal lymph nodes. Serum biochemistry revealed high total bilirubin levels (313.9 µmol/L) and normal tumor marker levels. Pancreatoduodenectomy was performed, but no chemotherapy was administrated at the patient's behest. The pathologic diagnosis was pancreatic FDCS infiltrating the duodenal seromuscular layer and common bile duct. The patient presented with liver metastasis 3 months after surgery and died 8 months after surgery from multiorgan failure. Pancreatic FDCS is a rare disease with high invasiveness. Our previous case exhibited paraneoplastic syndrome together with this disease, and further investigation is needed to confirm whether paraneoplastic syndrome is a typical syndrome of pancreatic FDCS.

Complete resolution of paraneoplastic syndrome of inappropriate antidiuretic hormone secretion following thymic small-cell carcinoma thoracoscopic resection.

Thymic neuroendocrine tumours are rare anterior mediastinal neoplasms often associated with paraneoplastic syndromes. A patient presented with intractable hyponatraemia and a DOTATATE-avid mediastinal mass. Following medical optimization, she underwent thoracoscopic thymectomy with en bloc thymic small-cell carcinoma resection. Her symptoms resolved and her sodium levels normalized. In localized disease, curative-intent, minimally invasive thymic neuroendocrine tumour resection is safe and effective following preoperative staging and paraneoplastic syndrome management.

Prolonged Hypophosphatemia and Intensive Care After Curative Surgery of Tumor Induced Osteomalacia: A Case Report.

Introduction: Rare FGF23-producing mesenchymal tumors lead to paraneoplastic tumor-induced osteomalacia (TIO) presenting with phosphate wasting, hypophosphatemia, chronic hypomineralization of the bone, fragility fractures and muscle weakness. Diagnosis of TIO requires exclusion of other etiologies and careful search for a mesenchymal tumor that often is very small and can appear anywhere in the body. Surgical removal of the tumor is the only definitive treatment of TIO. Surgical complications due to chronic hypophosphatemia are not well recognized. Case Description: The current case describes severe fragility fractures in a 58-year-old woman, who lost her ability to walk and was bedridden for two years. First, the initial diagnostic laboratory work-up did not include serum phosphorus measurements, second, the suspicion of adverse effects of pioglitazone as an underlying cause delayed correct diagnosis for at least two years. After biochemical discovery of hyperphosphaturic hypophosphatemia at a tertiary referral centre, a FGF23-producing tumor of the mandible was discovered on physical examination, and then surgically removed. Postoperatively, severe hypophosphatemia and muscle weakness prolonged the need for ventilation support, intensive care and phosphate supplementation. After two years of rehabilitation, the patient was able to walk short distances. The tumor has not recurred, and serum phosphate concentration has remained within normal limits during 3.5 years of follow-up. Conclusions: The case report illustrates knowledge gaps in the diagnostic work-up of rare causes of low bone mass and fragility fractures. Compared to other low phosphate conditions, surgical recovery from TIO-induced hypophosphatemia warrants special attention. Increased alkaline phosphatase concentration may indicate impaired postsurgical recovery due to prolonged hypophosphatemia, underlining the need for proactive perioperative correction of hypophosphatemia.

Nasal hemangiopericytoma presenting with oncogenic osteomalasia: A case report and literature review.

Sinonasal type hemangiopericytoma is a rare soft tissue tumor. Oncogenic osteomalacia (tumor-induced osteomalacia) is a rare syndrome that develops especially due to benign mesenchymal tumors. Nonspecific general bone pain and weakness delay the diagnosis and treatment of oncogenic osteomalacia, and it is difficult to determine the localization of the primary tumor causing oncogenic osteomalacia. A 43-year-old male patient with nasal hemangiopericytoma with symptoms of oncogenic osteomalacia is presented. The patient had musculoskeletal complaints at first and was diagnosed with lumbar disc herniation and surgery was performed. When his complaints recurred 1 year later, he was re-evaluated and diagnosed with hypophosphatemic osteomalacia. Despite the various treatments he received, his complaints did not decrease but increased, so a detailed examination was decided. When the positive PHEX mutation and very high fibroblast growth factor 23 level were detected, PET-CT imaging was performed with a pre-diagnosis of possible oncogenic osteomalacia, but no finding was found. Then he was evaluated with Ga-68 DOTATATE, and the soft tissue mass filling the right ethmoidal sinus was detected. Due to the relation of the mass with surrounding structures, it was considered unsuitable for total excision and incomplete surgical excision was performed. Pathologic evaluation revealed sinonasal type hemangiopericytoma (glomangiopericytoma). A significant remission in the patient's complaints was observed after the operation. Young patients with osteomalacia with unknown causes should be evaluated for malignancy, and screening and further examinations should be performed.

Clinical Characteristics and Surgical Outcomes of Sinonasal Lesions Associated With Tumor-Induced Osteomalacia.

OBJECTIVE: To investigate the clinical characteristics and surgical outcomes of sinonasal tumors associated with tumor-induced osteomalacia (TIO). STUDY DESIGN: Retrospective case series. SETTING: Single tertiary center. METHODS: We studied the clinical characteristics and surgical outcomes of 43 patients (22 male, 21 female) who had lesions in the nasal cavity and paranasal sinus associated with TIO and underwent surgery between August 2006 and November 2019. RESULTS: The mean ± SD duration between the onset of symptoms and surgery was 3.9 ± 2.6 years. The most common tumor site was the ethmoid sinus (76.7%), and the skull base was involved in 12 cases. Phosphaturic mesenchymal tumors were diagnosed in 41 patients, among whom there was 1 multifocal case. Another 2 cases involved odontogenic fibroma and hemangiofibroma, respectively. Serum phosphorus normalized in 39 cases within 4.4 ± 2.3 days, and serum fibroblastic growth factor 23 normalized within 1 day; clinical symptoms, however, gradually improved within several months after the first operation. There was no significant difference in the recovery rate between endoscopic and open surgery (P = 0.639). Two patients with recurrent cases and 2 with nonremission cases recovered after a sinonasal reoperation. The patient with a multifocal case recovered after the resection of the tumors in the ethmoid sinus and mandible. The overall recovery rate was 97.7%. CONCLUSION: Most sinonasal tumors associated with TIO are located in the ethmoid sinus, and the skull base is involved in some cases. Complete excision of the tumor leads to recovery, and endoscopic surgery could achieve recovery rates similar to those of open surgery.

Atypical and incomplete pulmonary hypertrophic osteoarthropathy in the left distal femur: a case report.

BACKGROUND: Pulmonary hypertrophic osteoarthropathy (PHO) is a rare paraneoplastic syndrome that mainly occurs in patients with lung cancer. Most symptoms occur symmetrically, and unilateral symptoms without clubbing are infrequent. This report presents the case of a rare atypical symptom that was highly suspected of being PHO. CASE PRESENTATION: A 77-year-old woman with swelling and severe pain in the left femur for 2 months was referred to our hospital. Radiography revealed a remarkably osteogenic thickening and sclerotic lesion in her distal femur. Preliminary diagnoses of malignant bone tumor and hematological tumor were made based on laboratory test results, radiological examination, and clinical manifestation. A needle biopsy was performed, which ruled out the diagnosis of malignant bone tumors. A low-grade bone tumor was still suspected. After that, en bloc resection was performed, followed by replacement of the femur with a mega-prosthesis. Pathological analysis revealed no malignant tumor cells, and immunohistochemical staining for CDK4 and MDM2 yielded negative results. Meanwhile, pulmonary large cell carcinoma was identified on biopsy. Based on published studies, a diagnosis of atypical PHO was made according to clinical and imaging manifestations. CONCLUSIONS: This is an infrequent case of PHO with unilateral symptoms in the left femur. When clinical manifestations and radiological findings are inconsistent with the pathological results, the possibility of benign lesions with malignant clinical manifestations or imaging features should be carefully considered.

Surgical Treatment and Outcomes for Sinonasal and Skull Base Phosphaturic Mesenchymal Tumors.

OBJECTIVE: To describe our clinical experience with surgical treatments for sinonasal phosphaturic mesenchymal tumors diagnosed at our institution. STUDY DESIGN: Retrospective case series. SETTING: Affiliated Sixth People's Hospital, Shanghai Jiao Tong University. SUBJECTS AND METHODS: We retrospectively reviewed the medical records of 10 patients diagnosed with phosphaturic mesenchymal tumors associated with tumor-induced osteomalacia between December 2014 and October 2019. RESULTS: There were 4 men and 6 women with a disease course of 1 to 19 years. All patients exhibited hypophosphatemia and tumor-induced osteomalacia. The tumor was located in the sinonasal region, frontal bone, and temporal bone in 8 patients, 1 patient, and 1 patient, respectively. Technetium-99m octreotide scintigraphy was used for tumor localization in 4 cases. Six patients underwent endoscopic resection; the remaining 4 underwent unilateral transorbital anterior and posterior ethmoid artery ligation + endoscopic resection, endoscopic resection + skull base repair, internal carotid artery stenting + transcatheter arterial embolization + temporal bone tumor excision + adipose tissue plugging, and endoscopic resection + transfrontal craniotomy (n = 1 each). Two patients had a history of incomplete endoscopic resection. All patients achieved clinical remission and normalized biochemical indices after surgery. Only 1 patient developed recurrence and died of a brain hernia. CONCLUSIONS: A diagnosis of sinonasal phosphaturic mesenchymal tumors should be based on a combination of clinical, imaging, and pathological findings. Technetium-99m octreotide scintigraphy helps in locating the tumor. Complete surgical excision guarantees clinical remission, and preoperative transcatheter arterial embolization or feeding artery ligation may reduce intraoperative bleeding in cases of highly vascularized tumors.

Paraneoplatic Obstruction of Descending Thoracic Aorta: A New Indication for Endovascular Surgery?

We describe the rare case of a 61-year-old man admitted to our emergency department with visceral-organ and lower-limb malperfusion because of an unknown retroperitoneal high-grade undifferentiated pleomorphic sarcoma and a severe paraneoplastic obstruction of the descending thoracic aorta, treated with thoracic endovascular aortic repair. The postoperative period was uneventful, and the patient was discharged within 4 days. At 6-month follow-up, computed tomography showed complete patency of the descending thoracic aorta. This single case experience shows that thoracic endovascular aortic repair can be a less invasive and effective off-label alternative to exclude infiltrated or obstructed descending thoracic aorta, thus avoiding conventional surgery.

The Role of Insulin-like Growth Factor (IGF) Axis in Early Diagnosis of Pancreatic Adenocarcinoma (PDAC).

New-onset diabetes mellitus (DM) is one of the first symptoms of pancreatic adenocarcinoma (PDAC). The frequency of endocrine disorders is estimated between 40% and 80% in patients with pancreatic cancer. DM is a risk factor for cancer development but it may also be a consequence of the tumor growth. Data confirming the existence of a relationship between long standing type 2 DM and an increased risk of PDAC comes from numerous clinical studies. Insulin resistance phenomenon and hyperinsulinemia may result in the increased proliferation of pancreatic islets which in turn may cause a predisposition to cancer development. In contrast, it is proved that new-onset DM among patients over 50 years old significantly increases the risk of PDAC recognition. Insulin-like growth factor 1 (IGF-1) and their complex proteins, IGF binding proteins, which comprise the IGF axis play a crucial role in carbohydrate metabolism disorders and, studies have shown that they may contribute to PDAC growth. Some studies confirm that IGF-1 is connected with early carcinogenesis in animals and humans. Assessing the levels of these proteins may thus be helpful in early recognition of PDAC in patients with recently detected endocrine disorders, especially pancreatic DM.

Treatment and outcomes of tumor-induced osteomalacia associated with phosphaturic mesenchymal tumors: retrospective review of 12 patients.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by severe hypophosphatemia and osteomalacia. Nonspecific symptoms make the diagnosis elusive. In addition, locating the responsible tumor(s) is challenging. The aim of this study was to investigate the clinical management and outcomes of TIO. METHODS: The clinical features, diagnostic procedures, treatment, and outcomes of 12 patients were reviewed retrospectively. RESULTS: The cohort comprised six men and six women (mean age 45.5 ± 9.9 years, range 23-61 years). The mean duration of disease was 3.7 ± 2.6 years. All patients manifested progressive bone pain, muscle weakness, and/or difficulty walking. Serum phosphorus concentrations were low in all patients (mean 0.42 ± 0.12 mmol/L). Technetium-99m octreotide scintigraphy was performed in 11 patients and showed lesions in the right distal femur, left femoral head, and right tibial plateau, respectively, in three patients. Magnetic resonance imaging (MRI) was negative for lesions in one patient. Two patients underwent biopsies that showed negative histopathology. Two patients, at 2 years and 8 months, respectively, after having negative technetium-99m octreotide studies, underwent 18F-fluorodeoxyglucose positron emission tomography/computed tomography (CT), which revealed lesions in the sacrum and soft tissue of the left palm, respectively. One tumor was detected by CT and MRI. Overall, lesion sites were the head (two patients, 16.7%), thoracic and lumbar region (two, 16.7%), pelvis (three, 25%), lower limbs (four, 33.3%), and upper limbs (one, 8.3%). All patients underwent surgery, and histopathology showed phosphaturic mesenchymal tumors in each. Postoperatively, serum phosphorus concentrations normalized within 2-7 days in 11 patients. With follow-ups of 1-41 months, surgery was effective in 10 patients. One patient developed local recurrence and another had metastases. CONCLUSIONS: Locating tumors responsible for tumor-induced osteomalacia is often challenging. Although complete tumor resection confers a good prognosis in most patients, surveillance for recurrence and metastasis is necessary. Before surgery or when surgery is not indicated, oral phosphate can alleviate symptoms and metabolic imbalance.

Doege-Potter syndrome: A review of the literature including a new case report.

RATIONALE: We reviewed 76 published cases of Doege-Potter syndrome, and non-islet cell tumor hypoglycemia (NICTH) secondary to a solitary fibrous tumor (SFT) between 1989 and 2016, to study disease pathogenesis, diagnosis, and treatment of this rare paraneoplastic disease. Further, we report 1 new case of a patient presenting with Doege-Potter syndrome. PATIENTS CONCERNS: The tumors originated from the pleural cavity, lung, pelvis, liver, retroperitoneum, kidney, mediastinal, the sella, uterus, bladder, intestine, mandibular, and the thigh. The most common location was the pleural cavity (left 12 cases and right 28 cases). Moreover, 28/71 (39.4%) were benign and 43/71 (60.6%) were malignant. SFTs with NICTH were more likely to be malignant and present at a higher rate than previously published (5%-10.4%). The malignancy rate of extrathoracic SFTs was higher than that of thoracic SFTs, 20 (66.7%) as compared with 23 (56.1%). Age of onset varied from 24 to 85 years (mean 59 years), with 47 males and 28 females, and gender unavailable for 1 case. When comparing clinical characteristics of patients with benign as compared malignant tumors, no significant differences in the age of onset, gender, or size of tumor were seen. Among 15/19 cases, the insulin-like growth factor II (IGF-II)/IGF-I ration was >10.0. Complete tumor resection remained the only definitive treatment. OUTCOMES AND LESSENS: Glucocorticoids dose-dependently reduce the frequency and severity of hypoglycemic episodes. Low doses of prednisone were ineffective at relieving hypoglycemia. The effect of neoadjuvant treatment, consisting of chemoradiation, and consecutive selective embolization of vessels feeding the tumor were not identified.

Tumor-induced osteomalacia: experience from a South American academic center.

The majority of tumor-induced osteomalacia cases have been reported in the Northern Hemisphere and Asia. In this first series of South American patients, we show that the clinical presentation and sensitivity of plasmatic fibroblast growth factor 23 and somatostatin analog-based imaging are similar to those described in other populations. INTRODUCTION: Describe the experience of clinical presentation, diagnostic study, and treatment of patients with tumor-induced osteomalacia (TIO) in a South American academic center in comparison to literature. METHODS: Analysis of the records of patients diagnosed with TIO. The clinical presentation, diagnostic studies, and treatment were analyzed. Fibroblast growth factor 23 (FGF23) was measured by ELISA. RESULTS: Six patients were diagnosed with TIO during the studied period. The patients' median age was 53 years (range 22-64). All patients presented with weakness and pain in the extremities. Four experienced fractures during their evolution. The median time to diagnosis was 4.5 years (1-20). Biochemical studies showed hypophosphatemia, median of 1.4 mg/dL (1.2-1.6), with low maximum rates of tubular reabsorption of phosphate adjusted for glomerular filtration rate. FGF23 was elevated in 4/6 patients and inappropriately normal in the other two. In three patients, the location of the tumor was clinically evident and confirmed with anatomical imaging. In the remaining patients, two tumors were located with 68Ga DOTATATE-PET/CT and one with OctreoScan. The causal tumors were located in the lower extremities in five patients and invading the frontal sinus in one patient. In all patients, tumors were successfully removed. Within 14 days, there was normalization of phosphate and FGF23 levels and resolution of clinical symptoms in all patients. In all cases, the histopathology was compatible with a phosphaturic mesenchymal tumor. CONCLUSIONS: The clinical presentation, delay time to diagnosis, FGF23 diagnostic sensitivity and histopathology in this first series of South American patients is similar to those described in other populations. The success of localization by somatostatin analog-based imaging, suggests this may the optimal imaging modality.

A rare case of multiple phosphaturic mesenchymal tumors along a tendon sheath inducing osteomalacia.

BACKGROUND: Tumor-induced osteomalacia (TIO) is a rare paraneoplastic syndrome characterized by renal phosphate wasting, hypophosphatemia, reduction of 1,25-dihydroxyl vitamin D, and bone calcification disorders. Tumors associated with TIO are typically phosphaturic mesenchymal tumors that are bone and soft tissue origin and often present as a solitary tumor. The high production of fibroblast growth factor 23 (FGF23) by the tumor is believed to be the causative factor responsible for the impaired renal tubular phosphate reabsorption, hypophosphatemia and osteomalacia. Complete removal of the tumors by surgery is the most effective procedure for treatment. Identification of the tumors by advanced imaging techniques is difficult because TIO is small and exist within bone and soft tissue. However, systemic venous sampling has been frequently reported to be useful for diagnosing TIO patients. CASE PRESENTATION: We experienced a case of 39-year-old male with diffuse bone pain and multiple fragility fractures caused by multiple FGF23-secreting tumors found in the hallux. Laboratory testing showed hypophosphatemia due to renal phosphate wasting and high levels of serum FGF23. Contrast-enhanced MRI showed three soft tissue tumors and an intraosseous tumor located in the right hallux. Systemic venous sampling of FGF23 revealed an elevation in the right common iliac vein and external iliac vein, which suggested that the tumors in the right hallux were responsible for overproduction of FGF23. Thereafter, these tumors were surgically removed and subjected to histopathological examinations. The three soft tissue tumors were diagnosed as phosphaturic mesenchymal tumors, which are known to be responsible for TIO. The fourth tumor had no tumor structure and was consisting of hyaline cartilage and bone tissue. Immediately after surgery, we noted a sharply decrease in serum level of FGF23, associated with an improved hypophosphatemia and a gradual relief of systematic pain that disappeared within two months of surgery. CONCLUSION: The authors reported an unusual case of osteomalacia induced by multiple phosphaturic mesenchymal tumors located in the hallux. Definition of tumors localization by systemic venous sampling led to successful treatment and cure this patient. The presence of osteochondral tissues in the intraosseous tumor might be developed from undifferentiated mesenchymal cells due to high level of FGF23 produced by phosphaturic mesenchymal tumors.