Understanding multicentric haemangioendothelioma: diagnostic dilemmas and treatment strategies.

Epithelioid haemangioendothelioma (EH) is a rare malignant vascular tumour occurring mainly in the liver and lungs, with bones being a rare site and primarily seen in the adult population. This case presents a male patient in his 40s who presented to the outpatient department with a chief issue of a painless swelling over the inguinal region for 4 months, gradually increasing in size, along with a history of a gradually enlarging, painless mass on his left knee over the past 5 years. Despite occasional discomfort during physical activities, the mass exhibited no associated trauma, fever, weight loss or systemic symptoms. Physical examination revealed a firm mass on the left knee and a matted lymph nodal swelling in the left inguinal region. Subsequent imaging studies identified multiple soft tissue lesions, osseous involvement and pulmonary metastases, suggestive of multicentric haemangioendothelioma. The patient underwent surgical excision of the inguinal mass and fixation of a pathological fracture in the left femur. He is currently undergoing chemotherapy and is scheduled for regular follow-up appointments. This case underscores the importance of thorough diagnostic evaluation and multidisciplinary management in complex oncological conditions like multicentric haemangioendothelioma.

Tumour-induced osteomalacia: the long road to diagnosis and recovery.

Tumour-induced osteomalacia is caused by tumorous production of fibroblast growth factor 23 (FGF23) leading to urinary phosphate wasting, hypophosphataemia and decreased vitamin D activation. The resulting osteomalacia presents with muscle weakness and bone pain but progresses to multiple pathological fractures. Patients often remain undiagnosed for years with severe physical, psychological and economic ramifications. A young woman presented with multiple spontaneous fractures including bilateral femoral fractures. Laboratory tests revealed severe hypophosphataemia, elevated bone turnover markers and low to normal calcium and 25-hydroxy-vitamin D levels. Treatment with phosphate, alfalcalcidol, calcium and magnesium was initiated. 68Gallium-DOTATOC positron emission tomography imaging revealed a mass in the right foot and venous sampling of FGF23 from all extremities confirmed this tumour as the culprit. Biopsy and histology were consistent with a phosphaturic mesenchymal tumour, which was surgically resected. Phosphate levels quickly normalised postoperatively but a long convalescence with hungry bone syndrome, fracture healing and physical therapy followed.

Reconstruction of the extensor mechanism using polypropylene mesh in a displaced pathological fracture of the patella affected by giant cell tumour.

A man in his 30s came to our clinic with a year-long history of progressive pain and swelling in his knee. Diagnostic imaging revealed a displaced patellar fracture with an osteolytic, septated lesion and thinned expanded cortex in both fracture fragments. A core needle biopsy confirmed the diagnosis of giant cell tumour. Treatment involved wide excision of the tumour and the use of polypropylene mesh and a peroneal longus tendon autograft to reconstruct the extensor mechanism of the knee joint. One year postoperatively, the patient experienced no pain, demonstrated full range of motion and showed no signs of functional impairment or local tumour recurrence. This case highlights that reconstruction of the extensor mechanism of the knee after tumour excision with synthetic mesh is an affordable, user-friendly and widely accessible method. It can address large defects effectively while minimising the risks of disease transmission and graft lengthening, resulting in satisfactory outcomes.

The Role of Surveillance in Predicting Fracture in Pediatric Patients With Incidentally Discovered Nonossifying Fibromas and Fibrous Cortical Defects: Is It Worth It?

BACKGROUND: Nonossifying fibroma (NOF) and fibrous cortical defect (FCDs), the most common benign pediatric bone lesions, are usually incidental x-ray findings. Surveillance of characteristic lesions has been recommended to monitor for enlargement and assess fracture risk. However, no accepted fracture risk prediction guidelines exist, so indications for prophylactic surgery are unclear. The study's purposes were to (1) characterize the timing of NOF/FCD-associated fractures, (2) quantify the resources devoted to surveillance, and (3) evaluate the potential for surveillance to prevent pathologic fracture. METHODS: A single institution retrospective review was conducted to identify pediatric patients (below 18 y old) with clinical-radiographic documentation of an NOF or FCD diagnosis from 2012 to 2020. Patients who presented with fracture were tallied but excluded from the surveillance analysis. Patients without at least one follow-up visit were also excluded. Lesional radiographic features were characterized on initial imaging. The number of visits and imaging studies devoted to surveillance were tabulated. The number of fractures and prophylactic surgeries were recorded to quantify the potential of surveillance to prevent pathologic fractures. RESULTS: The study population presenting without fracture consisted of 301 patients with 364 lesions with a mean follow-up of 20 months. By contrast, over the same period, 38 patients presented with NOF/FCD associated pathologic fractures. Surveillance included 1037 additional imaging tests over 1311 follow-up visits, or on average, 3.4 imaging studies and 4.4 visits per patient. During surveillance, only 2 (0.55%) lesions fractured. Another 10/364 (2.8%) patients underwent curettage and grafting, suggesting that-at best-the potential for preventing pathologic fracture by surveillance, assuming all 10 patients who underwent surgery would have subsequently fractured along with the 2 documented fractures, is 3.3% of lesions (12/364). CONCLUSIONS: The small number of fractures and surgeries during the follow-up period probably does not justify additional resources for surveillance beyond the initial visit, except in symptomatic patients with large lesions. However, subsequent visits may play a role in educating patients and their families regarding the natural history of these lesions. LEVEL OF EVIDENCE: Prognostic Level II-retrospective study.

Rare vertebral pathological fracture in primary amyloidosis.

Spinal involvement in primary amyloidosis is an exceedingly rare condition, presenting with typical pathological fracture symptoms that are often indistinguishable from other pathologies such as bone metastasis, metabolic disorders and infections. Histopathological studies for tissue diagnosis are the cornerstone of a definitive diagnosis, leading to successful treatment. Early diagnosis and intervention play a pivotal role in the care of patients with amyloidosis. Here, we present a unique case of a pathological fracture in the L4 vertebra following minor trauma. This fracture manifested with pain, instability and limitations in daily activities in a patient who had already been diagnosed with systemic amyloidosis and was undergoing chemotherapy. This case represents a distinct instance of vertebral involvement in amyloidosis and was managed with both chemotherapy and surgical intervention to address the spinal pathology, resulting in favourable outcomes.

Rare presentation of a primary intraosseous glomus tumor in the humerus of a teenager.

A glomus tumor is a benign mesenchymal tumor comprised of cells that resemble the perivascular modified smooth muscle cells of the glomus body. Glomus tumors typically appear in the superficial lesions of the soft tissue in the extremities, such as the subungual region. However, their occurrence in the bone is rare, with only about 30 cases reported to date. Half of these cases involved the distal phalanges of the fingers or toes, with only three reported cases involving the long bones. Here, we present the first case, a primary glomus tumor in the humerus of a 14-year-old female. An osteolytic and cystic lesion was detected after a pathological fracture occurred during exercise. Despite the tumor's large size, no pathological findings indicated malignancy. The fracture healed through conservative treatment, while the tumor was effectively managed with curettage. Appropriate medical care can be provided to patients by focusing on pathological findings.

Comparison of Hounsfield units and vertebral bone quality score for the prediction of time to pathologic fracture in mobile spine metastases treated with radiotherapy.

OBJECTIVE: Spine metastases are commonly treated with radiotherapy for local tumor control; pathologic fracture is a potential complication of spinal radiotherapy. Both Hounsfield units (HUs) on CT and vertebral bone quality (VBQ) on MRI have been argued to predict stability as measured by odds of pathologic fracture, although it is unclear if there is a difference in the predictive power between the two methodologies. The objective of the present study was to examine whether one methodology is a better predictor of pathologic fracture following radiotherapy for mobile spine metastases. METHODS: Patients who underwent radiotherapy (conventional external-beam radiation therapy, stereotactic body radiation therapy, or intensity-modulated radiation therapy) for mobile spine (C1-L5) metastases at a tertiary care center were retrospectively identified. Details regarding underlying pathology, patient demographics, and tumor morphology were collected. Vertebral involvement was assessed using the Weinstein-Boriani-Biagini (WBB) system. Bone quality of the non-tumor-involved bone was assessed on both pretreatment CT and MRI. Univariable analyses were conducted to identify independent predictors of fracture, and Kaplan-Meier analyses were used to identify significant predictors of time to pathologic fracture. Stepwise Cox regression analysis was used to determine independent predictors of time to fracture. RESULTS: One hundred patients were included (mean age 62.7 ± 11.9 years; 61% male), of whom 35 experienced postradiotherapy pathologic fractures. The most common histologies were lung (22%), prostate (21%), breast (14%), and renal cell (13%). On univariable analysis, the mean HUs of the vertebrae adjacent to the fractured vertebra were significantly lower among those experiencing fracture; VBQ was not significantly associated with fracture odds. Survival analysis showed that average HUs ≤ 132, nonprostate pathology, involvement of ≥ 3 vertebral body segments on the WBB system, Spine Instability Neoplastic Score (SINS) ≥ 7, and the presence of axial pain all predicted increased odds of fracture (all p < 0.001). Cox regression found that HUs ≤ 132 (OR 2.533, 95% CI 1.257-5.103; p = 0.009), ≥ 3 WBB vertebral body segments involved (OR 2.376, 95% CI 1.132-4.987; p = 0.022), and axial pain (OR 2.036, 95% CI 0.916-4.526; p = 0.081) predicted increased fracture odds, while prostate pathology predicted decreased odds (OR 0.076, 95% CI 0.009-0.613; p = 0.016). Sensitivity analysis suggested that an HU threshold of ≤ 132 and a SINS of ≥ 7 identified patients at increased risk of fracture. CONCLUSIONS: The present results suggest that bone density surrogates as measured on CT, but not MRI, can be used to predict the risk of pathologic fracture following radiotherapy for mobile spine metastases. More extensive vertebral body involvement and the presence of mechanical axial pain additionally predict increased fracture odds.

Two Pathological Fractures in a Patient with Chronic Abnormalities in Serum Markers Following Two Liver Transplantations: A Case Report and Literature Review.

Bone disease is a common complication following liver transplantation, often overlooked in clinical practice. Clinical diagnosis of post-liver transplantation bone disease is challenging, and there have been few case report in the literature. This case report presents a patient who underwent two liver transplant surgeries, exhibited good daily activity, and did not display typical clinical symptoms such as fatigue, bone pain, or spinal deformities associated with prolonged sitting or standing. However, within the fifth year after the second liver transplant, the patient experienced two consecutive fractures. In March 2023, the patient underwent the first bone density test, which revealed osteoporosis. This case highlights the fact that severe fractures after liver transplantation may not necessarily be accompanied by typical symptoms of bone disease. Without timely examination and early prevention, serious consequences may arise. Therefore, this condition requires attention, proactive prevention, early detection, and timely treatment. Additionally, a retrospective analysis of the patient's previous laboratory data revealed persistent abnormalities in serum markers such as hypocalcemia and elevated alkaline phosphatase levels after liver transplantation, emphasizing the importance of monitoring these serum markers.

A Case Report of Oral Bisphosphonate Treatment for Osteoporosis Leading to Atypical Femoral Fracture and Pathologic Mandibular Fracture.

BACKGROUND Bisphosphonates inhibit bone resorption in patients with postmenopausal osteoporosis and reduce osteoporotic fracture incidence. Medication-related osteonecrosis of the jaws (MRONJ) and atypical femoral fractures (AFF) are both rare but serious adverse effects of anti-resorptive drugs (ARD) such as bisphosphonates. The most advanced form of MRONJ is termed stage 3 and can lead to severe local sequelae like pathologic mandibular fractures (PMF). This study reports a case of MRONJ-related PMF and AFF with osteomyelitis secondary to bisphosphonate treatment for osteoporosis. CASE REPORT A 63-year-old white woman was diagnosed with PMF related to MRONJ stage 3 during treatment of an AFF with osteomyelitis. She had been treated for postmenopausal osteoporosis with 70 mg of alendronate weekly for 2 years. The PMF was treated by stable internal fixation combined with debridement and sequestrectomy, but further debridement was required and 2 mandibular implants were then removed. Postoperative recovery was uneventful and the mandibular infection was controlled after the second surgery. Three weeks later, she was discharged from the hospital, instructed to discontinue the use of alendronate, and referred for 30 sessions of hyperbaric oxygen therapy. At the 3-year follow-up, the PMF was completely healed without signs of mandibular infection or bone exposure. CONCLUSIONS This report raises awareness of both MRONJ and AFF as possible adverse effects of short-term bisphosphonate therapy for postmenopausal osteoporosis, and highlights the importance of dental and orthopedic follow-ups. It is crucial to emphasize the need for early diagnosis and treatment to prevent MRONJ progression to PMF.

Development and Validation of a Convolutional Neural Network Model to Predict a Pathologic Fracture in the Proximal Femur Using Abdomen and Pelvis CT Images of Patients With Advanced Cancer.

BACKGROUND: Improvement in survival in patients with advanced cancer is accompanied by an increased probability of bone metastasis and related pathologic fractures (especially in the proximal femur). The few systems proposed and used to diagnose impending fractures owing to metastasis and to ultimately prevent future fractures have practical limitations; thus, novel screening tools are essential. A CT scan of the abdomen and pelvis is a standard modality for staging and follow-up in patients with cancer, and radiologic assessments of the proximal femur are possible with CT-based digitally reconstructed radiographs. Deep-learning models, such as convolutional neural networks (CNNs), may be able to predict pathologic fractures from digitally reconstructed radiographs, but to our knowledge, they have not been tested for this application. QUESTIONS/PURPOSES: (1) How accurate is a CNN model for predicting a pathologic fracture in a proximal femur with metastasis using digitally reconstructed radiographs of the abdomen and pelvis CT images in patients with advanced cancer? (2) Do CNN models perform better than clinicians with varying backgrounds and experience levels in predicting a pathologic fracture on abdomen and pelvis CT images without any knowledge of the patients' histories, except for metastasis in the proximal femur? METHODS: A total of 392 patients received radiation treatment of the proximal femur at three hospitals from January 2011 to December 2021. The patients had 2945 CT scans of the abdomen and pelvis for systemic evaluation and follow-up in relation to their primary cancer. In 33% of the CT scans (974), it was impossible to identify whether a pathologic fracture developed within 3 months after each CT image was acquired, and these were excluded. Finally, 1971 cases with a mean age of 59 ± 12 years were included in this study. Pathologic fractures developed within 3 months after CT in 3% (60 of 1971) of cases. A total of 47% (936 of 1971) were women. Sixty cases had an established pathologic fracture within 3 months after each CT scan, and another group of 1911 cases had no established pathologic fracture within 3 months after CT scan. The mean age of the cases in the former and latter groups was 64 ± 11 years and 59 ± 12 years, respectively, and 32% (19 of 60) and 53% (1016 of 1911) of cases, respectively, were female. Digitally reconstructed radiographs were generated with perspective projections of three-dimensional CT volumes onto two-dimensional planes. Then, 1557 images from one hospital were used for a training set. To verify that the deep-learning models could consistently operate even in hospitals with a different medical environment, 414 images from other hospitals were used for external validation. The number of images in the groups with and without a pathologic fracture within 3 months after each CT scan increased from 1911 to 22,932 and from 60 to 720, respectively, using data augmentation methods that are known to be an effective way to boost the performance of deep-learning models. Three CNNs (VGG16, ResNet50, and DenseNet121) were fine-tuned using digitally reconstructed radiographs. For performance measures, the area under the receiver operating characteristic curve, accuracy, sensitivity, specificity, precision, and F1 score were determined. The area under the receiver operating characteristic curve was used to evaluate three CNN models mainly, and the optimal accuracy, sensitivity, and specificity were calculated using the Youden J statistic. Accuracy refers to the proportion of fractures in the groups with and without a pathologic fracture within 3 months after each CT scan that were accurately predicted by the CNN model. Sensitivity and specificity represent the proportion of accurately predicted fractures among those with and without a pathologic fracture within 3 months after each CT scan, respectively. Precision is a measure of how few false-positives the model produces. The F1 score is a harmonic mean of sensitivity and precision, which have a tradeoff relationship. Gradient-weighted class activation mapping images were created to check whether the CNN model correctly focused on potential pathologic fracture regions. The CNN model with the best performance was compared with the performance of clinicians. RESULTS: DenseNet121 showed the best performance in identifying pathologic fractures; the area under the receiver operating characteristic curve for DenseNet121 was larger than those for VGG16 (0.77 ± 0.07 [95% CI 0.75 to 0.79] versus 0.71 ± 0.08 [95% CI 0.69 to 0.73]; p = 0.001) and ResNet50 (0.77 ± 0.07 [95% CI 0.75 to 0.79] versus 0.72 ± 0.09 [95% CI 0.69 to 0.74]; p = 0.001). Specifically, DenseNet121 scored the highest in sensitivity (0.22 ± 0.07 [95% CI 0.20 to 0.24]), precision (0.72 ± 0.19 [95% CI 0.67 to 0.77]), and F1 score (0.34 ± 0.10 [95% CI 0.31 to 0.37]), and it focused accurately on the region with the expected pathologic fracture. Further, DenseNet121 was less likely than clinicians to mispredict cases in which there was no pathologic fracture than cases in which there was a fracture; the performance of DenseNet121 was better than clinician performance in terms of specificity (0.98 ± 0.01 [95% CI 0.98 to 0.99] versus 0.86 ± 0.09 [95% CI 0.81 to 0.91]; p = 0.01), precision (0.72 ± 0.19 [95% CI 0.67 to 0.77] versus 0.11 ± 0.10 [95% CI 0.05 to 0.17]; p = 0.0001), and F1 score (0.34 ± 0.10 [95% CI 0.31 to 0.37] versus 0.17 ± 0.15 [95% CI 0.08 to 0.26]; p = 0.0001). CONCLUSION: CNN models may be able to accurately predict impending pathologic fractures from digitally reconstructed radiographs of the abdomen and pelvis CT images that clinicians may not anticipate; this can assist medical, radiation, and orthopaedic oncologists clinically. To achieve better performance, ensemble-learning models using knowledge of the patients' histories should be developed and validated. The code for our model is publicly available online at https://github.com/taehoonko/CNN_path_fx_prediction . LEVEL OF EVIDENCE: Level III, diagnostic study.

Solitary intraosseous myofibroma: a rare case diagnosed from mandibular fracture.

Intraosseous myofibroma is a rare tumor of benign nature, slow growth, and low morbidity. The aim of this article is to report a case of pathologic fracture associated with the incidental diagnosis of myofibroma in the mandible of an adolescent. A 15-year-old girl reported that she experienced a physical assault resulting in facial injuries 1 month previously and had since experienced severe pain, malocclusion, and chewing difficulty. The cone beam computed tomographic examination revealed multiple features suggestive of pathologic fracture associated with a hypodense lesion with lobulated limits, as well as expansion and thinning of the cortical bone in the left mandible. The histopathologic diagnosis of the lesion indicated myofibroma. Treatment consisted of enucleation and curettage of the lesion with reduction and internal fixation of the fracture. After 18 months, the osteosynthesis plates and an impacted mandibular third molar were removed. Curettage of the lesion in association with treatment of the mandibular fracture proved to be effective for both bone consolidation and absence of recurrence while restoring mandibular functionality.

Multiple Myeloma (Part 1) - Update on Epidemiology, Diagnostic Criteria, Systemic Treatment and Prognosis / Mieloma múltiplo (Parte 1) - Atualização sobre epidemiología, critérios diagnósticos, tratamento sistêmico e prognóstico

Abstract Multiple myeloma (MM) is a hematological malignancy characterized by unregulated and clonal proliferation of plasma cells in the bone marrow; these cells produce and secrete an anomalous monoclonal immunoglobulin, or a fragment of this, called M protein. The clinical manifestations of MM result from the proliferation of these plasmocytes, the excessive production of monoclonal immunoglobulin and the suppression of normal humoral immunity, leading to hypercalcemia, bone destruction, renal failure, suppression of hematopoiesis and humoral immunity, increasing the risk for the development of infections. The increase in life expectancy of the world population led to a concomitant increase in the prevalence of MM, a pathology that usually affects the elderly population. The aim of this review is to update the reader on epidemiology, diagnostic criteria, differential diagnosis with other monoclonal gam-mopathies, systemic treatment and prognosis of MM.

Resumo O mieloma múltiplo (MM) constitui neoplasia maligna de origem hematológica caracterizada pela proliferação desregulada e clonal de plasmócitos na medula óssea; estas células produzem e secretam imunoglobulina monoclonal anômala, ou um fragmento desta, denominado proteína M. As manifestações clínicas do MM decorrem da proliferação destes plasmócitos, da produção excessiva de imunoglobulina monoclonal e da supressão da imunidade humoral normal, levando à hipercalcemia, destruição óssea, insuficiência renal, supressão da hematopoiese e da imunidade humoral,aumentandooriscoparaodesenvolvimento de infecções. O aumento na expectativa de vida da população mundial levou a concomitante incremento na prevalência do MM, patologia que habitualmente acomete a população idosa. O objetivo desta revisão é atualizar o leitor sobre a epidemiologia, critérios diagnósticos, diagnóstico diferencial com outras gamopatias monoclonais, tratamento sistêmico e prognóstico do MM.