Osteolytic Lesions Research Articles

Clinical decision-making in bone cancer care management and forecast of ICU needs based on computed tomography

ObjectiveThis study aimed to evaluate the role of computed tomography (CT) imaging in the diagnosis and management of bone cancer during periods of limited access to histopathological testing. We aimed to determine the correlation between CT severity levels and subsequent patient management and care decisions, adhering to established oncological CT reporting guidelines. MethodologyA retrospective analysis was conducted on 60 symptomatic patients from January 2021 to January 2024. The cohort included patients aged between 50 and 86 years, with a mean age of 68 years, and 75 % were male. All patients had their bone cancer diagnosis confirmed through histopathological examination, and CT imaging was used as the reference method. The analysis involved assessing the correlation between CT severity scores and patient management, including ICU admissions. ResultsThe study found that CT imaging demonstrated a sensitivity of 92.6% in diagnosing bone cancer, with accuracy increasing to 97.6% in cases with high-probability CT characteristics. CT specificity also showed a consistent rise. Osteolytic lesions were the predominant finding, detected in 85.9% of cases. Among these, 88% exhibited engagement across multiple skeletal regions, 92.8% showed bilateral distribution, and 92.8% presented with peripheral involvement. In ICU patients, bone consolidation was observed in 81.5% of cases and was predominant in 66.7% of the ICU cohort. Additionally, ICU patients had significantly higher CT severity scores, with scores exceeding 14 being notably prevalent. ConclusionsDuring the management period of bone cancer at our hospital, characteristic features on CT imaging facilitated swift and sensitive investigation. Two distinct CT phenotypes, associated with the primary osteolytic phenotype and severity score, emerged as valuable indicators for assessing the severity of the disease, particularly during ICU care. These findings highlight the diverse manifestations and severity levels encountered in bone cancer patients and underscore the importance of CT imaging in their diagnosis and management.

Abstract A010: Development and characterization of novel models of lobular breast cancer metastases

Abstract Invasive lobular carcinoma (ILC) is the most common special histological subtype of breast cancer, after No Special Type (NST, ductal carcinoma/IDC), and affects 10-15% of all breast cancer patients. ILC is characterized by E-cadherin loss, Estrogen Receptor (ER) positivity, and a distinct single file invasive growth pattern associated with a unique pattern of metastasis. ILC metastasizes to common breast cancer sites like bone and lung, but ILC also spreads to gynecologic tissues, the peritoneum, gastrointestinal tract and central nervous system - with enrichment for orbital and leptomeningeal metastases. In vitro and in vivo models of ILC metastasis have not been extensively developed. Models of spontaneous metastasis from ER+ breast cancer overall are critically limited; ER+ ILC metastases models present only micro-metastatic disease with extremely long latency (>9 months). Together these issues limit research on the unique nature of metastatic ILC. We leveraged mammary intraductal (MIND) xenografting with two ER+ ILC cell lines (MM134 and 44PE) and confirmed prior reports that these lines spontaneously metastasize to bone, brain, ovary, uterus, lung, and adrenal glands with up to 100% incidence. Importantly, we find that supplementation with low dose estradiol (E2) in drinking water rapidly advances metastatic progression, but not primary tumor growth. Using ex vivo bioluminescence imaging (BLI), we find BLI+ lesions are detectable as early as 90 days. At 150 days post-challenge, 100% of mice have BLI+ metastases at multiple sites. Beyond 22 weeks, 100% of mice present with symptomatic and ultimately lethal CNS metastases. BLI+ macro-metastatic lesions were isolated and expanded ex vivo as organotrophic cell line variants. Analysis of RNA-seq data is ongoing to evaluate 1) common factors enriched in metastatic ILC, and 2) organotrophic factors and pathways enriched in specific metastatic sites. In patients with ILC, bone metastases are typically the first site of metastatic development, occur at a higher incidence versus NST, and are associated with increased morbidity. Bone metastases from ILC patients are more osteogenic compared to the characteristically osteolytic lesions of NST. To examine how ILC cells may promote osteoblastic responses, we prepared ILC and NST conditioned media (CM) and applied it to differentiating osteoblasts (OB). We observed increased OB differentiation and increased mineral deposition with ILC CM compared to NST CM, supporting that ILC cell lines have a distinct impact on the bone microenvironment which may manifest in vivo yet be defined in vitro. Collectively, our observations support that ER+ ILC cell lines can recapitulate key features of clinical disease progression, including spontaneous metastasis mimicking clinical phenotypes. We are leveraging these models to better understand the ILC metastatic cascade and adaptation to unique metastatic niches, and to identify shared and unique attributes of ILC metastases that can be exploited for advancing therapeutics. Citation Format: Joseph L. Sottnik, Matthew J. Sikora. Development and characterization of novel models of lobular breast cancer metastases [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Tumor-body Interactions: The Roles of Micro- and Macroenvironment in Cancer; 2024 Nov 17-20; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(22_Suppl):Abstract nr A010.

Multifocal osteolytic lesions of the skull: a primary cavernous hemangioma mimicking a neoplastic invasive lesion

Multifocal osteolytic lesions of the skull: a primary cavernous hemangioma mimicking a neoplastic invasive lesion

NCMP-12. AN ATYPICAL CASE OF POEMS WITH MACROFOCAL MYELOMA

Abstract Polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes (POEMS) syndrome is a rare paraneoplastic syndrome secondary to an underlying plasma cell dyscrasia. Symptoms of peripheral neuropathy dominate the clinical picture and is postulated to be related to serum vascular endothelial growth factor (VEGF) mediated altered permeability of the blood nerve barrier. The classic presentation includes a solitary osteosclerotic plasmacytoma and an elevation of VEGF. In this case, we present a patient with neither of these features who met diagnostic criteria for POEMS though had predominantly osteolytic lesions and was diagnosed with macrofocal myeloma, a unique subset of multiple myeloma. Our patient is a young male who presented with progressive leg numbness/weakness and was found to have marked ankle weakness, diffuse areflexia and unilateral gynecomastia on examination. EMG showed a motor predominant demyelinating polyneuropathy. Labs showed a serum IgG lambda M protein, low estradiol and low testosterone. He had a normal serum VEGF level though the lab was drawn after treatment initiation. Bone biopsy of a dominant osteolytic lesion was consistent with a plasma cell neoplasm (light chain restricted). Of note, he had mild cauda equina nerve root and ventral conus enhancement initially concerning for leptomeningeal involvement however, two lumbar punctures were negative for malignant cells. Spinal enhancement has been reported in POEMS. The patient underwent chemotherapy, radiation therapy and autologous stem cell transplantation. We present a patient diagnosed with MFMM, a rare subset of multiple myeloma, comprising only 3% of all cases, along with POEMS, a rare paraneoplastic syndrome. Interestingly, as osteolytic lesions can be seen in POEMS alone though not predominantly so, it is possible the patient could have atypical POEMS without underlying multiple myeloma. POEMS may remain under-recognized when presentations or setting are atypical.

Chondroblastoma of the occipital bone with aneurysmal bone cyst: A rare case report.

Chondroblastoma is a rare, benign bone tumor originating from immature chondrocytes, typically found in the epiphyseal plates of long bones. Its occurrence in the skull, particularly the occipital bone, is extremely rare. We report a 10-year-old girl presenting with paroxysmal dizziness, occipital pain, and a palpable mass. Imaging studies revealed an osteolytic lesion in the occipital bone with a multiloculated appearance, indicating a concomitant aneurysmal bone cyst. The patient underwent craniotomy with complete tumor excision. Postoperative follow-up showed no neurological deficits or complications and MRI confirmed no recurrence. This case highlights the rare presentation of occipital bone chondroblastoma and emphasizes the importance of early surgical intervention for positive outcomes in pediatric patients.

AI-Assisted Detection and Localization of Spinal Metastatic Lesions.

The integration of machine learning and radiomics in medical imaging has significantly advanced diagnostic and prognostic capabilities in healthcare. This study focuses on developing and validating an artificial intelligence (AI) model using U-Net architectures for the accurate detection and segmentation of spinal metastases from computed tomography (CT) images, addressing both osteolytic and osteoblastic lesions. Our methodology employs multiple variations of the U-Net architecture and utilizes two distinct datasets: one consisting of 115 polytrauma patients for vertebra segmentation and another comprising 38 patients with documented spinal metastases for lesion detection. The model demonstrated strong performance in vertebra segmentation, achieving Dice Similarity Coefficient (DSC) values between 0.87 and 0.96. For metastasis segmentation, the model achieved a DSC of 0.71 and an F-beta score of 0.68 for lytic lesions but struggled with sclerotic lesions, obtaining a DSC of 0.61 and an F-beta score of 0.57, reflecting challenges in detecting dense, subtle bone alterations. Despite these limitations, the model successfully identified isolated metastatic lesions beyond the spine, such as in the sternum, indicating potential for broader skeletal metastasis detection. The study concludes that AI-based models can augment radiologists' capabilities by providing reliable second-opinion tools, though further refinements and diverse training data are needed for optimal performance, particularly for sclerotic lesion segmentation. The annotated CT dataset produced and shared in this research serves as a valuable resource for future advancements.

Children with Osteolytic Lesions – Enigmatic Presentation of a Life-Threatening Condition: Case Report and Literature Review

Children with Osteolytic Lesions – Enigmatic Presentation of a Life-Threatening Condition: Case Report and Literature Review

Dynamic transcriptome analysis of osteal macrophages identifies distinct subset with senescence features in experimental osteoporosis.

Given the potential fundamental function of osteal macrophages in bone pathophysiology, we study here their precise function in experimental osteoporosis. Gene profiling of osteal macrophages from ovariectomized mice demonstrated the upregulation of genes that were involved in oxidative stress, cell senescence and apoptotic process. A scRNA-seq analysis revealed that osteal macrophages were heterogenously clustered into 6 subsets that expressed proliferative, inflammatory, anti-inflammatory and efferocytosis gene signatures. Importantly, postmenopausal mice exhibited a 20-fold increase in subset-3 that showed a typical gene signature of cell senescence and inflammation. These findings suggest that the decreased production of estrogen due to postmenopause altered the osteal macrophages subsets, resulting in a shift toward cell senescence and inflammatory conditions in the bone microenvironment. Furthermore, adoptive macrophage transfer onto calvarial bone was performed and mice that received oxidative-stressed macrophages exhibited greater osteolytic lesions than control macrophages, suggesting the role of these cells in development of inflammaging in bone microenvironment. Consistently, depletion of senescent cells and oxidative-stressed macrophages subset alleviated the excessive bone loss in postmenopausal mice. Our data provided a new insight into the pathogenesis of osteoporosis and sheds light on a new therapeutic approach for the treatment/prevention of postmenopausal osteoporosis.

Multiple Myeloma Presenting with Severe Back Pain: A Case Report

This study aims to highlight the diagnostic challenges and management strategies in a case of Multiple Myeloma (MM), a hematologic malignancy characterized by malignant plasma cells in the bone marrow. The case involves a 40-year-old male who presented with persistent back pain for two months, impacting his mobility. Initial physical and neurological assessments were largely unremarkable, but laboratory and radiological investigations revealed multiple osteolytic lesions suggestive of MM. Typical MM symptoms include hypercalcemia, renal dysfunction, anemia, and bone pain, though this patient did not present all the classical signs, which underscores the diagnostic complexity. A bone marrow puncture was planned for definitive diagnosis. The study emphasizes the importance of radiological evaluation in MM diagnosis and the need for prompt treatment addressing acute symptoms, such as hypercalcemia and renal insufficiency, followed by a comprehensive long-term management plan. Early oncology consultation and a multidisciplinary approach are critical for improving patient outcomes. The case demonstrates the importance of a holistic, symptom-based approach in MM management, incorporating regular monitoring and coordinated care to address the multifaceted nature of the disease.

Rare presentation of primary synovial chondrosarcoma arising in the shoulder: a case report.

Synovial chondrosarcoma (CHS) is a rare malignant tumor arising from the synovial tissue and is often associated with synovial chondromatosis. Herein, we present a unique case of primary synovial CHS in the shoulder joint without evidence of synovial chondromatosis. A 60-year-old man presented to our hospital with a complain of left shoulder pain that persisted for 6years, which was initially misdiagnosed as synovitis. Radiography revealed an osteolytic lesion involving the humerus and the scapula. Histologically, the tumor exhibited features of grade 2 synovial CHS, infiltrating the trabecular bones and intra-articular space. Wide resection led to a 9-year recurrence-free survival. This case underscores the challenges in diagnosing and managing synovial CHS, particularly in cases with atypical presentations lacking synovial chondromatosis, necessitating careful follow-up and adequate surgical intervention.

8557 Osteitis Fibrosa Cystica as the Initial Manifestation of Severe Primary Hyperparathyroidism: A Case Report

Abstract Disclosure: L.A. Robles Gomez: None. G. Gill: None. A. Vincent, DO: None. A. Mahmoud, MD: None. Introduction: Osteitis fibrosa cystica (OFC) is a pathognomonic yet uncommon finding of hyperparathyroidism seen in less than 2% of patients with primary hyperparathyroidism in Western countries. We present a case of infrequent finding of late-stage severe hyperthyroidism with asymptomatic hypercalcemia and incidental findings of osteolytic bone lesions. Clinical Case: A 28-year-old female with a history of PCOS, fatigue, and chronic abdominal pain presents to the clinic after recent work-up during an ED visit demonstrated incidental findings of osteolytic bone lesions in the setting of mild hypercalcemia. Physical examination was relatively unremarkable except for mild tenderness to palpation on the right lower quadrant. Laboratory significant calcium 10.7 mg/dl (8.6-10.2 mg/dL), albumin 3.6 g/dL, Creatinine 0.56 mg/dL, GFR 127 mL/min, Alkaline phosphatase 187 IU/L (37-127 IU/L), AST 24 IU/L, ALT 45 IU/L, Intact PTH and calcium: PTH 413 pg/mL (15-65 pg/mL), Calcium 11.5 (8.7-10.4 mg/dL), Bone Specific Alkaline Phosphatase: 54.5 mcg/L (4.7-17.8 mcg/L), Phosphorus 2.1 mg/dL (2.4-4.8 mg/dL), Magnesium 1.7 mg/dL (1.5-2.5 mg/dL), Vitamin D 25 10 mg/mL (20-100 ng/mL), TSH 2.12 uIU/mL (0.46-5.05 uIU/mL). CT abdomen pelvis w/o contrast with multiple predominantly lytic expansile bone lesions, mainly in the pelvis, with the most extensive 6.2 cm lesion in the superior, posterior right ilium, the anterior acetabulum, and the posterior right ischium. A prior CT done in 2018 showed a similar distribution of lytic lesions. The patient denied any previous personal or family history of hypercalcemia or parathyroid abnormalities despite a review of prior outside records revealed abnormal labs dating back to 2018 with intact PTH 406 pg/mL, calcium 10.3 mg/dL, Ionized calcium 10.7 mg/dl (3.30-6.0 mg/dL), albumin 3.3g/dL, alkaline phosphatase 288 IU/L. The patient denied prior symptomatology of hypercalcemia, including renal stones, or prior treatment for hypercalcemia. Further work-up was ordered, and the patient was referred to endocrine surgery for management. Conclusion: Osteitis fibrosa cystica (OFC) has become a rare manifestation of primary hyperparathyroidism (PHPT) due to early diagnosis of hypercalcemia by routine lab monitoring. Skeletal findings typically seen on PHPT can vary from bone reabsorption-acroosteolysis, subchondral bone resorption, brown tumors, salt-and-pepper skull, and osteopenia. Subchondral reabsorption around specific joints commonly affects pubic symphysis and sacroiliac joints, as seen in our patient. The mechanism is due to PTH-mediated osteoclastic absorption of bone and surrounding cartilage. Due to the rare presentation of PHPT with associated osteitis fibrosa cystica, diagnosis requires a high degree of clinical suspicion, as delayed diagnosis can lead to avoided manifestation, as described by our report. Presentation: 6/3/2024

12214 Metastatic Functional Thyroid Carcinoma As An Unusual Cause Of Hyperthyroidism

Abstract Disclosure: S. Jimenez Salazar: None. N. Aristizabal Henao: None. C. Aguilar Londoño: None. N. Buitrago Gómez: None. S. Saldarriaga Betancur: None. D.L. Beltran: None. J.L. Torres: None. Background: Differentiated thyroid carcinoma (DTC) represents the most prevalent endocrine neoplasm. Less than 10% present distant metastases, with the lung (50%), and skeleton (25%) being the most frequently affected sites. The location of bone metastases predominates in the spine and pelvis; usually as osteolytic lesions, being more frequent in follicular thyroid cancer (FTC) (7-28%) than in patients with papillary thyroid cancer (PTC) (1.4-7%). In rare cases this metastasis can be functional and trigger a thyrotoxicosis syndrome with or without recombinant human TSH injections prior to therapy with 131-I. Clinical case: 59-year-old woman with a history of bone metastatic follicular thyroid cancer (FTC) presented with 1 month of palpitations, 4 kg weight loss, non-dysenteric diarrhea and progressive dyspnea. Her FTC had been diagnosed 8 years prior her consultation. In that time iodine refractoriness was considered due to the progression of bone lesions, and Sorafenib 800 mg per day was initiated, which was not tolerated due to severe dermatological manifestations, and the patient decided not to continue with TKI therapy. Since then, she has been treated with zoledronic acid and local radiotherapy as part of palliative care. On physical examination, she was tachycardic (150 bpm), and hypertensive (BP 160/100 mmHg). A suppressed TSH (<0.01 uUI/mL, n: 0.4-4 uUI/mL) with elevation of thyroid hormones (free T4 3.99 ng/dL, n: 0.8-2 ng/dL and total T3 480 ng/dL, n: 45-140 ng/dL) was documented, associated with a patient who had required a dose adjustment of levothyroxine from 700 mcg to 350 mcg weekly 2 months prior to admission. Additionally, she had a significantly elevated thyroglobulin (>5000 ng/mL, n: 0.1-64.1 ng/mL) with undetectable antithyroglobulin antibodies (1.09 UI/mL, n: 0-4.11 UI/mL). Considering the history of total thyroidectomy and the high tumor burden, secondary thyrotoxicosis due to functioning bone metastases of DTC was considered. Levothyroxine was discontinued, and propranolol was initiated for the control of adrenergic symptoms, along with methimazole, cholestyramine, and systemic steroids to control thyroid hormone production. 3 days after therapy adjustment dyspnea, palpitations, and thyroid function tests improved significantly (free T4 1.43 ng/dL, n: 0.8-2 ng/dL and total T3 178 ng/dL, n: 45-140 ng/dL). A new administration of therapy with 131-I 200 mCi was indicated. Antithyroid therapy and beta-blockers were continued with sustained biochemical control. Conclusion: Functional bone metastases of FTC can lead to high morbidity and mortality. Treatment consists of surgical cytoreduction of any large accessible metastatic lesion, therapy with 131-I, and high-dose antithyroid drugs to control hyperthyroidism. It is important to avoid the use of recombinant human TSH due to the risk of secondary thyrotoxicosis following its administration. Presentation: 6/2/2024

8031 Pelvic Fracture Related to Brown Tumor in Severe Secondary Hyperparathyroidism

Abstract Disclosure: M. Bodenstab: None. M. Lieberman-Ulm: None. V.S. Lagari-Libhaber: None. Background: Severe hyperparathyroidism can result in end-organ damage to the skeleton, known as osteitis fibrosa cystica (OFC). Histologically, OFC manifests as “Brown tumors”, which are so named due to the hemosiderin deposition that occurs from recurring microtraumas with subsequent hemorrhage. Typical sites of presentation include the mandible, clavicle, ribs, or pelvis, but can occur anywhere in the body. Patients can present with diffuse bone pain, pathological fracture, or bone deformities, though some may be asymptomatic and diagnosed incidentally. While these tumors do not have malignant potential, they can become debilitating in their burden and mimic malignant disease. Treatment focuses on treating the underlying cause of the hyperparathyroidism. Clinical Case: A 52-year-old female with ESRD on thrice weekly hemodialysis secondary to T2DM and HTN presented with right thigh pain and difficulty bearing weight, which began one week after a mechanical fall from standing. X-ray on admission revealed acute nondisplaced pathologic fracture of the right superior pubic ramus related to an underlying 4.7 x 2.2 cm expansile osteolytic lesion. Calcium level corrected for albumin on admission was 9.3 mg/dL, phosphorous 5.6 mg/dL, and PTH 563 pg/mL. Review of our institution’s electronic medical record revealed a maximum PTH level of 1,808 pg/mL three months prior. On CT pelvis, the patient was found to have multiple osteolytic lesions also involving the sacrum, multiple vertebral bodies, and the left pubic ramus, concerning for metastatic disease. Patient underwent pelvic rami bone biopsy resulting as osteoclast type giant cells, hemosiderin deposition and fibrosis in keeping with "brown tumor" of hyperparathyroidism. The patient was started on Cinacalcet 30 mg daily, with plans to titrate as outpatient to target PTH levels. She was also instructed to continue calcium, vitamin D and calcitriol to treat the underlying condition of metabolic bone disease from CKD. Referrals were given for both orthopedic spine and orthopedic oncology for surgical evaluation of her lesions. Discussion: Osteitis fibrosa cystica has become exceedingly rare in the United States and occurs in about 2% of patients with hyperparathyroidism. Due to their low prevalence and radiologic similarity to neoplasm, “Brown tumors” may be mistaken for metastatic disease and can lead to delay in diagnosis. Histology reveals collections of osteoclasts due to excess activity intermixed with fibrous tissue and poorly mineralized woven bone, which will differentiate brown tumor from malignancy. However, further correlation with hypercalcemia and hyperparathyroidism is imperative as brown tumors and other giant cell-containing lesions may be difficult to differentiate histologically. We present this case due to its rarity in clinical practice. Presentation: 6/2/2024

8802 A Rare Case Of Symptomatic Hypercalcemia In A Patient With Untreated Chronic Tophaceous Gout

Abstract Disclosure: S. Avula: None. A. Kumar: None. Z.J. Anderson: None. A. Chauhan: None. L.T. LaFave: None. Background: Hypercalcemia is a medical condition with abnormally high serum calcium levels. There are numerous mechanisms for the development of hypercalcemia, but gout is not well documented.Hypercalcemia attributed to Tophaceous gout is a rare phenomenon that is not well studied. Here we report a case of symptomatic hypercalcemia in a patient with a history of untreated tophaceous gout, leading to hypercalcemia and osteolytic lesions. Clinical Case: The patient is a 52-year-old male with a medical history of hypertension, rheumatoid arthritis, and tophaceous gout who immigrated from Tanzania. He presented with two weeks of abdominal pain that acutely worsened the morning of his presentation. He reported a 16-year history of tophaceous gout, for which he had been treated with allopurinol without success. On physical examination polyarticular subcutaneous nodules were present in the bilateral upper and lower extremities, primarily over the joints. There were similar lesions on the buttocks. Initial laboratory evaluation included a complete blood count which was notable for a hemoglobin of 10.3 g/dL (13.1 - 17.5 g/dL). His albumin was normal at 4 g/dl. (3.8 - 5.1 g/dl). Serum calcium was elevated at 12.9 mg/dL (8.8-10.0 mg/dL), with a serum ionized calcium level of 6.52 mg/dL(4.40-5.20 mg/dL). PTH was low at 15.8 pg/mL (16.0 - 65.0 pg/mL), and PTHrP was 2.9 pg/ml (<4.5 pg/ml). Uric acid level on admission was elevated to 11.4 mg/dL (3.4 - 7.0 mg/dL). 1-25 dihydroxy vitamin D elevated at 93.2 pg/mL (19.9 - 79.3 pg/mL). Computed tomography (CT) with intravenous contrast of the chest, abdomen, and pelvis was notable for axillary, pelvic, and inguinal lymphadenopathy concerning for lymphoproliferative or neoplastic processes. Biopsy of right inguinal node biopsy showed benign-appearing lymphoid tissue. Additional findings included multiple lobulated calcified hyperdense foci throughout the subcutaneous and muscular tissues of the buttocks with resorptive changes of the axial skeleton. Spectral CT reconstruction determined these to be uric acid deposits. Radiographs of his extremities were consistent with advanced gouty arthropathy. Infectious work-up was negative. Patient was given 3 liters of 0.9% sodium chloride. He received four doses of Calcitonin (4 units/kg) followed by one dose of Zoledronic acid 5 mg I.V. He was treated with Febuxostat, solumedrol and Azathioprine for his tophaceous gouty arthritis. Conclusion: Hypercalcemia is a commonly encountered yet a very important clinical condition. Parathyroid and malignant etiologies of hypercalcemia account for approximately 90% of cases of hypercalcemia. Gout as the inciting factor for developing hypercalcemia is a rarely documented phenomenon. This case highlights hypercalcemia as an unusual yet severe manifestation of untreated chronic gout and demonstrates the need for additional studies and reviews. Presentation: 6/2/2024

Xanthogranulomatous osteomyelitis of pubic bone mimicking neoplasm: a case report and literature review

BackgroundXanthogranulomatous osteomyelitis (XO) is a rare disease characterized radiologically by an osteolytic lesion with cortical expansion or disruption. Differentiating this condition from other osteolytic diseases such as primary or metastatic bone neoplasms is imperative. Several case reports have been published on XO, with previous reports predominantly identifying bacteria such as Pseudomonas or Staphylococcus as causative organisms. However, fungal infection-induced XO has not yet been reported.Case presentationWe present the case of a 23-year-old woman with a tumor-like osteolytic lesion in the pubic bone. The patient had experienced pelvic pain and intermittent febrile episodes for 2 months. Plain radiography revealed an osteolytic lesion in the right pubic tubercle. Magnetic resonance imaging suggested a cystic bone tumor or tubercular infection. Surgical intervention included curettage of the lesion and irrigation with normal saline. Histopathological examination of the specimen revealed abundant foamy histiocytes with inflammatory infiltrates consistent with XO. Culture of the osteolytic lesion confirmed an Aspergillus species infection and antifungal treatment was initiated. At 1-year follow-up, no evidence of local recurrence was observed.ConclusionsAlthough rare, XO requires differentiation from similar conditions and is treated with surgical intervention and targeted medical therapy based on the identified organisms. Clinicians should be mindful that XO can also be induced by fungal infections and that combination antifungal treatments may be beneficial in such cases.

MRI-based Zero Echo Time and Black Bone Pseudo-CT Compared with Whole-Body CT to Detect Osteolytic Lesions in Multiple Myeloma.

Background MRI is highly sensitive for assessing bone marrow involvement in multiple myeloma (MM) but does not enable detection of osteolysis. Purpose To assess the diagnostic accuracy, repeatability, and reproducibility of pseudo-CT MRI sequences (zero echo time [ZTE], gradient-echo black bone [BB]) in detecting osteolytic lesions in MM using whole-body CT as the reference standard. Materials and Methods In this prospective study, consecutive patients were enrolled in our academic hospital between June 2021 and December 2022. Inclusion criteria were newly diagnosed MM, monoclonal gammopathy of undetermined significance at high risk for MM, or suspicion of progressive MM. Participants underwent ZTE and BB sequences covering the lumbar spine, pelvis, and proximal femurs as part of 3-T whole-body MRI examinations, as well as clinically indicated fluorine 18 fluorodeoxyglucose PET/CT examination within 1 month that included optimized whole-body CT. Ten bone regions and two scores (categorical score = presence/absence of osteolytic lesion; semiquantitative score = osteolytic lesion count) were assessed by three radiologists (two experienced and one unfamiliar with pseudo-CT reading) on the ZTE, BB, and whole-body CT images. The accuracy, repeatability, and reproducibility of categorical scores (according to Gwet agreement coefficients AC1 and AC2) and differences in semiquantitative scores were assessed at the per-sequence, per-region, and per-patient levels. Results A total of 47 participants (mean age, 67 years ± 11 [SD]; 27 male) were included. In experienced readers, BB and ZTE had the same high accuracy (98%) in the per-patient analysis, while BB accuracy ranged 83%-100% and ZTE accuracy ranged 74%-94% in the per-region analysis. An increase of false-negative (FN) findings in the spine ranging from +17% up to +23%, according to the lumbar vertebra, was observed using ZTE (P < .013). Regardless of the region (except coxal bones), differences in the BB score minus the ZTE score were positively skewed (P < .021). Regardless of the sequence or region, repeatability was very good (AC1 ≥0.87 for all), while reproducibility was at least good (AC2 ≥0.63 for all). Conclusion Both MRI-based ZTE and BB pseudo-CT sequences of the lumbar spine, pelvis, and femurs demonstrated high diagnostic accuracy in detecting osteolytic lesions in MM. Compared with BB, the ZTE sequence yielded more FN findings in the spine. ClinicalTrials.gov Identifier: NCT05381077 Published under a CC BY 4.0 license. Supplemental material is available for this article.

Report of six cases with mast cell leukemia and a literature review

From October 2021 to February 2023, we retrospectively analyzed the clinical and laboratory data of six patients (three male and three female, median age: 54 years, age range: 29-73 years) with mast cell leukemia (MCL) diagnosed in the First Affiliated Hospital of Soochow University (The Mastocytosis Collaborative Network of China). All patients had acute MCL, with at least one C-finding present. The main clinical presentations were hypoalbuminemia (n=4), fatigue (n=3), fever (n=2), abdominal discomfort (n=2), osteolytic lesions (n=2), dizziness (n=1), skin flushing (n=1), and weight loss (n=1). Splenomegaly and lymphadenopathy were noted in six and three patients, respectively. Six patients were strongly positive for CD117, five were positive for CD30 and CD25, and four were positive for CD2. Four patients had a normal karyotype and two patients had an abnormal karyotype. Gene mutations were detected in 4/6 cases. The median serum tryptase level was 24.9 (range: 20.1-171.9) μg/L. Two patients were treated with venetoclax and azacitidine for induction (one patient achieved partial remission by combination with afatinib, while there was no remission after combination with dasatinib in the other patient). Two patients did not achieve complete remission despite treatment with cladribine and imatinib, respectively. One patient treated with interferon combined with glucocorticoids was lost to follow-up, and one patient abandoned treatment. The follow-up time ranged from 1.1 to 21.7 months. Three patients died and two survived. Overall, MCL is a rare subtype of systemic mastocytosis with heterogeneous clinical course, and these patients have poor outcome. A better understanding of the clinical characteristics, treatment, and prognosis of MCL is urgently needed.

HTLV-1 infected T cells cause bone loss via small extracellular vesicles.

Adult T cell leukaemia (ATL), caused by infection with human T- lymphotropic virus type 1 (HTLV-1), is often complicated by hypercalcemia and osteolytic lesions. Therefore, we studied the communication between patient-derived ATL cells (ATL-PDX) and HTLV-1 immortalized CD4+ T cell lines (HTLV/T) with osteoclasts and their effects on bone mass in mice. Intratibial inoculation of some HTLV/T leads to a profound local decrease in bone mass similar to marrow-replacing ATL-PDX, despite the fact that few HTLV/T cells persisted in the bone. To study the direct effect of HTLV/T and ATL-PDX on osteoclasts, supernatants were added to murine and human osteoclast precursors. ATL-PDX supernatants from hypercalcemic patients promoted the formation of mature osteoclasts, while those from HTLV/T were variably stimulatory, but had largely consistent effects between human and murine cultures. Interestingly, this osteoclastic activity did not correlate with expression of osteoclastogenic cytokine receptor activator of nuclear factor kappa-B ligand (RANKL), suggesting an alternative mechanism. HTLV/T and ATL-PDX produce small extracellular vesicles (sEV), known to facilitate HTLV-1 infection. We hypothesized that these sEV also mediate bone loss by targeting osteoclasts. We isolated sEV from both HTLV/T and ATL-PDX, and found they carried most of the activity found in supernatants. In contrast, sEV from uninfected activated T cells had little effect. Analysis of sEV (both active and inactive) by mass spectrometry and electron microscopy confirmed absence of RANKL and intact virus. Viral proteins Tax and Env were only present in sEV from the active, osteoclast-stimulatory group, along with increased representation of proteins involved in osteoclastogenesis and bone resorption. sEV from osteoclast-active HTLV/T injected over mouse calvaria in the presence of low-dose RANKL caused more osteolysis than osteoclast-inactive sEV or RANKL alone. Thus, HTLV-1 infection of T cells can cause release of sEV with strong osteolytic potential, providing a mechanism beyond RANKL production that modifies the bone microenvironment, even in the absence of overt leukaemia.

Langerhans cell histiocytosis of the orbit: pediatric case series

ObjectiveTo describe the clinical, imaging characteristics, and treatment of pediatric orbital Langerhans cell histiocytosis (LCH). DesignRetrospective case series. ParticipantsChildren with orbital LCH. MethodsChildren with orbital LCH who presented to 4 different centres over the past 10 years. Demographic details, presenting features, imaging, histopathology, immunohistochemistry, and management outcomes were analyzed. ResultsSixteen patients were reviewed. The mean age of presentation was 6.56 ± 4.38 years (range, 1−18 years). Eyelid swelling was the most common presenting feature (13, 81%), followed by proptosis (1, 5%), eyebrow swelling (1,5%), and temple swelling (1, 5%). Imaging revealed superior orbital lesions with osteolytic defects of the orbital roof in 13 (72.2%) patients. Frontal and zygomatic bones were the most commonly affected. All the orbital lesions were extraconal. All patients in the study were diagnosed with LCH from orbital tissue biopsy. Three patients also demonstrated extra-orbital involvement. Two patients (12.5%) had intraoperative steroid injection with curettage, and 1 patient (6.25%) underwent curettage only. The remainder of the patients (n = 13, 81.25%) received systemic steroids and chemotherapy after undergoing biopsy. All patients had complete remission of disease without any signs of recurrence, except for 1 case of refractory LCH. ConclusionsLCH is a rare disorder of the orbit and should be considered in the differential diagnosis for osteolytic lesions involving the superior orbit among the pediatric age group. Histopathologic confirmation is mandatory. Although optimal treatment remains controversial, complete removal of unifocal orbital LCH is recommended and may be achieved through excision and curettage.

A Rare Case of Primary Bone Follicular Lymphoma with Multiple Osteolytic Lesions: A Case Report and Review of the Literature

Introduction: Primary bone lymphoma (PBL) is a rare clinical entity, accounting for less than 5% of all extranodal non-Hodgkin lymphomas and approximately 5% of primary bone tumors. Diffuse large B-cell lymphoma (DLBCL) is the most common histotype, accounting for about 80% of all PBL cases. Conversely, the incidence of indolent primary bone lymphomas (iPBL) represents less than 1% of all reported PBL cases, and data on these rarer lymphomas are scarce. Drawing on diagnostic criteria developed by the World Health Organization (WHO) and the International Extranodal Lymphoma Study Group (IELSG), we report a rare case of primary bone follicular lymphoma, focusing specifically on the clinical presentation and treatment. Discussion: Additionally, we provide a systematic review of the literature data on this very rare lymphoproliferative entity.