Search Results (59)

Background and Objectives: Extramedullary plasmacytoma (EMP) is a rare monoclonal B-cell neoplasm that typically affects the head and neck region, with a predilection for the sinonasal tract. Clinical presentation is often nonspecific, leading to delayed diagnosis. This study aims to improve our understanding of sinonasal EMP by reviewing the recent literature and presenting a case series from our clinical experience. Materials and Methods: A systematic review of published cases of sinonasal EMP from 2000 to 2023 was conducted using the PubMed database, yielding 28 eligible cases. Additionally, we retrospectively analyzed three patients diagnosed and treated at our institutions. Inclusion criteria included histologically and immunohistochemically confirmed EMP without evidence of systemic multiple myeloma. Data on demographics, tumor location, symptoms, treatment, and outcomes were collected and analyzed descriptively. Results: Sinonasal EMP most commonly presented with unilateral nasal obstruction and epistaxis. Tumors were primarily located in the nasal cavity and paranasal sinuses, often extending beyond a single anatomical site. In the literature cohort, the most frequent treatment was combined surgery and radiotherapy (35.71%), followed by radiotherapy alone (17.86%). Recurrence was reported in 10.71% of cases, and 7.14% of patients died due to disease progression. All three patients in our case series underwent surgical excision; two received postoperative radiotherapy. No recurrences or progression to multiple myeloma were observed during follow-up (12–24 months). Conclusions: Sinonasal EMP is a rare but radiosensitive tumor with a favorable prognosis when treated with surgery and/or radiotherapy. Early diagnosis, histopathological confirmation, and exclusion of systemic disease are essential. Multidisciplinary management and long-term follow-up are critical due to the risk of recurrence and transformation into multiple myeloma. Full article

Solitary plasmacytoma refers to a neoplastic, clonal proliferation of plasma cells forming a single mass. They are divided based on their origin site; solitary bone plasmacytomas originate from the bones, and extramedullary plasmacytomas represent extraosseous tumors. These are rare tumors but carry a risk of transforming to multiple myeloma; thus, optimal management and meticulous follow-up are needed. Their rarity poses a major challenge in conducting large-scale clinical trials, leaving important gaps in evidence regarding best practices. Newer imaging techniques have improved the quality of staging, management decisions, and outcomes. Radiation still has a significant role in treatment algorithms, and adjuvant chemotherapy is gaining more importance; trials are underway in this area. Follow-up should contain biochemical tests as the proposed response definition criteria. We aimed to review the key studies and guidelines in this paper. Full article

Introduction: Intradural extramedullary and intramedullary spinal tumors are rare, complex to treat, and require advanced surgical techniques. Ultrasonic aspirators, commonly used for tumor removal, can cause sensory and motor deficits, including loss of motor evoked potentials (MEPs). This study aims to evaluate the safety and efficacy of ultrasonic aspirators in intramedullary tumor surgery using a swine model, comparing different systems and techniques. Methods: Ten pigs underwent D1-D3 laminectomy and myelotomy, with adipose tissue simulating a tumor. The ultrasonic aspirators were tested under varying conditions (fragmentation power, suction, application time, and vibration mode). The primary endpoint is to evaluate the impact of the chosen variables on motor function damage. The secondary endpoints are histological evaluation of the type of damage caused by ultrasound aspirators and the effect of steroid drugs on MEPs’ impairment recovery. Results: Ultrasound aspirators can cause a significant MEP signal reduction when used in continuous mode, with fragmentation power >30 for more than 2 min (p < 0.001). Suction does not affect MEPs. When used in alternating/pulsatile mode, fragmentation power and application time do not affect MEPs. The two-way ANOVA analysis on the interaction between fragmentation power and application time in continuous mode did not demonstrate a significant interaction (p = 0.155). Time alone does not affect motor damage (p = 0.873). Betamethasone can restore MEPs’ signal after damage if administered immediately. Conclusions: Using ultrasonic aspirators in an animal model of intramedullary tumor surgery is safe. The main factor that resulted in the responsibility of motor function impairment is the fragmentation power. Full article

In children without Down syndrome who have acute megakaryoblastic leukemia (AMKL), inv(16)(p13q24)/CBFA2T3::GLIS2 is the most frequent genetic aberration. Pediatric CBFA2T3::GLIS2-positive AMKL is strongly associated with a poor prognosis and a high cumulative incidence of relapse. One of the key laboratory signs of CBFA2T3::GLIS2-positive AMKL is the RAM immunophenotype, which looks very similar to that of solid-tumor bone marrow (BM) infiltration. For this reason, in cases of isolated extramedullary involvement of CBFA2T3::GLIS2-positive AMKL, excluding solid tumors may be challenging. We report a case of a girl with isolated extramedullary CBFA2T3::GLIS2-positive AMKL relapse, which was misdiagnosed as secondary Ewing sarcoma. The morphological differential diagnosis between Ewing sarcoma and AMKL presented significant challenges owing to their overlapping histological features (small, round blue-cell morphology and similar growth patterns). The tumor cells’ immunophenotype completely mirrored that at the initial diagnosis of AMKL. Additional cytogenetic and molecular studies confirmed the presence of the CBFA2T3::GLIS2 fusion, but no Ewing sarcoma-specific EWSR1, FUS and CIC fusion transcripts were found. Thus, extramedullary CBFA2T3::GLIS2-positive AMKL relapse was confirmed. The presented case demonstrates the difficulties in differential diagnosis between AMKL relapse and the development of a secondary tumor. Full article

Background/Objectives: In recent years, efforts by the scientific community to elucidate the underlying mechanisms of clonal expansion and selection within tumors have led to the theory of “tumor ecosystems”, implicating, among other factors, the role of the microenvironment in therapy resistance and tumor progression. In this context, the contribution of the microenvironment in the development of multiple myeloma (MM) is being investigated, imparting great emphasis on continuous clonal evolution. This process gives rise to aggressive clones with the potential to spread to extramedullary sites, rendering any treatment strategy practically ineffective. This systematic review aimed to gather knowledge about the immune microenvironment (IME) of extramedullary plasma cell myeloma and the differences in immune synthesis between medullary and extramedullary disease (EMD). Methods: A search strategy according to PRISMA guidelines was conducted in seven databases, and six articles meeting the inclusion criteria were encompassed in the study. Results: Results obtained from molecular analysis as well as flow cytometry and immunofluorescence indicated profound genetic instability at EMD sites along with spatial and temporal heterogeneity of the IME, implying a possible correlation between them. Both genetic and microenvironment variability were notably greater in EMD compared to medullary disease. The establishment of an immunosuppressive microenvironment was the rule, with exhausted CD8+ and natural killer (NK) cells, M2 macrophages, and inactivated dendritic cells found co-localized with neoplastic plasma cells, whereas cytotoxic CD8+ cells, M1 macrophages, and active dendritic cells congregated in tumor-free areas. Post-therapy alterations in the immune milieu were also noted and were concerned mostly the percentages of Tregs and MDSCs. Conclusions: The recognition of the microenvironment-myeloma cell interplay is essential for designing specific therapeutic strategies and ameliorating disease prognosis. Full article

Osteosarcoma is medically defined as a bone-forming tumor with associated bone-degrading activity. There is a lack of knowledge about the network that generates the overproduction of bone. We studied the early stage of osteosarcoma development with mice enduring a periosteum injection of osteosarcoma cells at the proximal third of the tibia. On day 7 (D7), tumor cells activate the over-synthesis of bone-like material inside the medulla. This overproduction of bone is quickly (D13) followed by degradation. Samples were characterized by microfocus small-angle X-ray scattering (SAXS), wide-angle X-ray scattering (WAXS), optical and electron microscopies, and micro-indentation. This intramedullary apatite–collagen composite synthesis highlights an unknown network of bone synthesis stimulation by extramedullary osteosarcoma cells. This synthesis activation mechanism, coupled with the well-known bone induced osteosarcoma growth activation, produces a rare synergy that may enlighten the final osteosarcoma morphology. With this aim, a 3D cellular automaton was developed that only included two rules. Simulations can accurately reproduce the bi-continuous sponge macroscopic structure that was analyzed from mice tumor micro-tomography. This unknown tumor activation pathway of bone synthesis, combined with the known bone activation of tumor growth, generates a positive feedback synergy explaining the unusual sponge-like morphology of this bone cancer. From a biomaterials point of view, how nature controls self-assembly processes remains an open question. Here, we show how the synergy between two biological growth processes is responsible for the complex morphology of a bone tumor. This highlights how hierarchical morphologies, accurately defined from the nanometer to the centimeter scale, can be controlled by positive feedback between the self-assembly of a scaffold and the deposition of solid material. Full article

Multiple myeloma is biologically and clinically a complex and heterogeneous disease which develops late in life, with the median age at the time of initial diagnosis being 66 years. In 1975, Durie and Salmon developed the first broadly adopted staging system in multiple myeloma, and in the ensuing decades, the risk stratification tools have improved and now incorporate different parameters to better predict the prognosis and to guide the treatment decisions. The International Staging System (ISS) was initially developed in 2005, revised in 2015 (R-ISS), and again in 2022 (R2-ISS). Tremendous progress has been achieved in multiple myeloma therapy over the past 25 years with the approval of immunomodulatory drugs, proteasome inhibitors, and anti-CD38 monoclonal antibodies, resulting in a major paradigm shift. The dysfunction of the innate and adaptive immune system, especially in the T cell repertoire, represents a hallmark of multiple myeloma evolution over time, supporting the need for additional therapeutic approaches to activate the host’s immune system and to overcome the immunosuppressive tumor microenvironment. Novel T cell-directed therapies include chimeric antigen receptor (CAR) T cell therapies and bispecific antibodies that leverage the immune system’s T cells to recognize and attack the tumor cells. Second-generation anti-BCMA CAR T cell therapies and bispecific antibodies that bind the tumor antigen BCMA or GPRC5D onto myeloma cells and CD3 on the T cell’s surface are currently available for the treatment of relapsed/refractory multiple myeloma. Despite impressive results obtained with currently approved treatments, multiple myeloma remains incurable, and almost all patients eventually relapse. Moreover, patients with extramedullary disease and plasma cell leukemia represent an unmet medical need that require additional strategies to improve the outcome. In this review, we provide an overview of the evolution of risk stratification and the treatment of multiple myeloma. Full article

Background: Multiple myeloma (MM) is a hematologic malignancy characterized by the clonal proliferation of plasma cells, with extramedullary myeloma (EMM) being an aggressive form involving malignant infiltration beyond the bone marrow. Copper metabolism is essential for tumor proliferation and metastasis, with copper metabolism MURR1 domain (COMMD) proteins regulating these processes and maintaining copper homeostasis. Dysregulated copper homeostasis contributes to cancer progression, including MM, with elevated copper levels linked to disease aggressiveness and poor prognosis. This study investigates the role of the COMMD3 in mediating MM cell progression, particularly its influence on copper metabolism. Methods: Comprehensive bioinformatics analyses were conducted on bone marrow and extramedullary samples to determine the expression of COMMD3, which was validated through in vitro and in vivo functional assays. The MM cell lines RPMI8226 and MM1S underwent lentiviral transfection for COMMD3 overexpression and knockdown. RNA sequencing was conducted on COMMD3 knockdown cells to identify differentially expressed genes. Functional assays measured cell proliferation, migration, apoptosis, and copper metabolism, with a non-obese diabetic severe combined immune-deficiency gamma (NSG) mouse xenograft model providing in vivo validation. Results: Elevated COMMD3 expression was correlated with extramedullary myeloma and poor prognosis in MM patients. COMMD3 promoted MM cell proliferation and migration, modulating intracellular copper levels, likely through the ATOX1-ATP7A-LOX copper-metabolism-related pathway. High ATOX1 expression was correlated with worse outcomes, and ATOX1 inhibition abolished COMMD3’s effects. Conclusions: This study highlights the pivotal role of COMMD3 in MM progression, particularly via the ATOX1-ATP7A-LOX axis. These findings provide insights into EMM mechanisms and position COMMD3 as a potential therapeutic target. Future research is needed to validate these findings in larger clinical cohorts and to unravel the precise molecular interactions between COMMD3 and copper metabolism proteins. Full article

Pleural thickening can be the result of inflammation or infection but can also have a neoplastic origin. Depending on the clinical context, a pleural lesion or mass is often initially suspected of malignancy. Benign pleural tumors are rare, and their appearance on ultrasound (US) is also described less frequently than pleural metastases or malignancies. There are few descriptions of contrast-enhanced Ultrasound (CEUS) in particular. This review introduces the basics of transthoracic ultrasound (TUS) of the pleura and CEUS of the pleura and lung. CEUS is recommended for pulmonary applications in the EFSUMB guidelines in non-hepatic applications. This article provides an overview of the characteristics of benign pleural thickening, tumor-like lesions, and benign pleural tumors on transthoracic B-mode US with color Doppler imaging (CDI) and CEUS. In detail, characteristics in TUS and CEUS are described for infectious/inflammatory pleural thickening (empyema, tuberculous pleuritis, hemothorax, fibrothorax), pleural thickening in various systemic diseases, in tumor-like conditions (plaques, splenosis, endometriosis, mesothelial cysts, lymphangiomatosis) and benign tumors (lipoma, benign SFT, schwannoma, solitary extramedullary/extraosseous plasmacytoma). The descriptions are illustrated by corresponding US and CEUS images. Full article

Background/Objectives: While most studies on the postoperative condition of patients with spinal cord tumors describe long-term outcomes, data are needed on immediate surgical outcomes demanding rehabilitation to make informed assessments for postoperative planning. The aim of this study was to identify factors predicting function and rehabilitative needs after intradural spinal tumor surgery. Methods: Eighty-five prospectively recruited patients underwent surgery for intradural intramedullary (ID-IM; n = 23) and extramedullary (ID-EM; n = 62) tumors. Neurological and functional status were assessed before surgery, after surgery, and at discharge using the modified McCormick scale (MMS), Karnofsky performance status (KPS) scale, Barthel index (BI), and the gait index (GI). Results: There were no significant predictors of early postoperative rehabilitation in the ID-IM group. In the ID-EM group, age, thoracic level, subtotal resection (STR), repeat surgery, and functional scale scores predicted the need for rehabilitation. In multivariable analysis, MMS (odds ratio (OR) 8.7; 95% confidence interval (CI): 2.37–32.44) and STR (OR 13.00; 95%CI: 1.56–107.87) remained independent predictors of rehabilitation need (area under curve, 92%). Despite their younger age, most patients with ID-IM tumors, especially ependymomas, required rehabilitation but improved quickly (KPS, BI, p < 0.001). Among ID-EM tumors, meningiomas were characterized by poorer preoperative function and low gross total resection (GTR) rates, but did not deteriorate neurologically after surgery. Patients with schwannoma and ID-EM ependymomas achieved the highest GTR rate and had the best function both before and after surgery. Conclusions: These results may be useful for estimating early rehabilitation needs after intradural tumor surgery and counseling patients before surgery about the expected postoperative course. Full article

Background: Although its validity has recently been questioned since its introduction, the Simpson grade has remained one of the most relevant factors in estimating the recurrence risk of intracranial meningiomas. This study aims to assess its role in spinal meningiomas through a retrospective analysis of a mono-institutional surgical series and literature meta-analysis. Methods: We conducted a systematic review and meta-analysis of the literature from 1980 to 2023, complemented by a mono-institutional series of 74 patients treated at “Santa Maria delle Grazie” hospital. Demographic, clinical, neuroradiological, pathological, surgical, and outcome data of case series were analyzed. For the meta-analysis, studies were selected based on predefined inclusion criteria, and a fixed-effects model was used to synthesize data due to assumed homogeneity among included studies. Statistical analyses included odds ratios (OR) for recurrence risk and assessment of publication bias using Peter’s test. Results: Mono-institutional sample included 74 patients, most of whom were women (85%) with a median age of 61.9 years. The thoracic spine was the most common tumor location (81%). Recurrences occurred in patients with Simpson grade II and III resections. The meta-analysis involved 2142 patients from 25 studies and revealed a significantly higher recurrence rate for Simpson grades III–V compared to grades I–II (OR 0.10; CI95 0.06–0.16). Additionally, Simpson grade II had a higher recurrence risk than grade I (OR 0.42; CI95 0.20–0.90). Conclusions: The Simpson grading remains a valid predictor of recurrence also for spinal meningiomas. Our findings revealed a significant increase in recurrence rate with higher Simpson grades. These results support the need to strive for Simpson grade I resection when feasible. Full article

Background/Objectives: Developing high-performance artificial intelligence (AI) models for rare diseases is challenging owing to limited data availability. This study aimed to evaluate whether a novel three-class annotation method for preparing training data could enhance AI model performance in detecting osteosarcoma on plain radiographs compared to conventional single-class annotation. Methods: We developed two annotation methods for the same dataset of 468 osteosarcoma X-rays and 378 normal radiographs: a conventional single-class annotation (1C model) and a novel three-class annotation method (3C model) that separately labeled intramedullary, cortical, and extramedullary tumor components. Both models used identical U-Net-based architectures, differing only in their annotation approaches. Performance was evaluated using an independent validation dataset. Results: Although both models achieved high diagnostic accuracy (AUC: 0.99 vs. 0.98), the 3C model demonstrated superior operational characteristics. At a standardized cutoff value of 0.2, the 3C model maintained balanced performance (sensitivity: 93.28%, specificity: 92.21%), whereas the 1C model showed compromised specificity (83.58%) despite high sensitivity (98.88%). Notably, at the 25th percentile threshold, both models showed identical false-negative rates despite significantly different cutoff values (3C: 0.661 vs. 1C: 0.985), indicating the ability of the 3C model to maintain diagnostic accuracy at substantially lower thresholds. Conclusions: This study demonstrated that anatomically informed three-class annotation can enhance AI model performance for rare disease detection without requiring additional training data. The improved stability at lower thresholds suggests that thoughtful annotation strategies can optimize the AI model training, particularly in contexts where training data are limited. Full article

Background: Schwannomas, predominantly benign nerve sheath tumors, are typically found within the intradural extramedullary space of the spinal cord with potential extradural expansion. Other typical localizations are the upper limbs and neck area. Pure epaxial paraspinal schwannomas are very rare, often asymptomatic, and predominantly occur in the thoracic region, with only a handful of cases reported globally. The range of differential diagnoses for paraspinal lesions is extensive, emphasizing the importance of accurate diagnosis to ensure optimal therapy and avoid unnecessary treatments. Method: We conducted a systematic literature review searching for published recommendations for paraspinal lesion management in addition to examining the case of a 49-year-old male patient who presented with a history of persistent back pain. A thorough medical history and physical examination were followed by ultrasound and MRI, revealing a well-defined paravertebral mass spanning from T7 to T9. A secure ultrasound-guided biopsy was performed, leading to a preliminary diagnosis of paraspinal schwannoma. Subsequently, complete surgical resection was performed. Results: pathological reports confirmed the initial diagnosis of paraspinal schwannoma. Further investigation using FMI and RNA sequencing did not detect any specific genetic anomalies aside from an NF2 gene mutation. A follow-up MRI conducted six months later showed no signs of recurrence. Conclusions: The broad spectrum of differential diagnoses for paraspinal lesions necessitates a multidisciplinary approach to ensure accurate diagnosis and tailored treatment. This approach involves meticulous imaging interpretation followed by a secure biopsy procedure to obtain preliminary pathology results, ultimately leading to the implementation of the most suitable surgical treatment. Full article

Myeloid sarcoma (MS), an extramedullary form of acute myeloid leukemia (AML) is a rare tumor mass of myeloid blasts. It can disseminate to any one or multiple anatomical sites, with (synchronous MS) or without (isolated MS) bone marrow (BM) involvement. The aim of this review is to describe the most recent advances in MS regarding diagnosis, molecular background, various clinical manifestations from several organs, and treatment approaches. Due to the lack of prospective, randomized clinical trials, therapeutic decisions are a challenge for the clinician. In the era of novel targeted AML treatments, a critical analysis of how to decide the best option for individual patients, also covering the possible central nervous system (CNS) prophylaxis is provided. For the majority of the patients, AML induction chemotherapy, followed by hematopoietic stem cell transplantation (HSCT) is generally recommended. This paper discusses the role of radiotherapy, the treatment of refractory and relapsed disease, along with the therapeutic approach of difficult-to-treat patients, due to specific problems related to different anatomical sites of MS. Full article

Background/Objectives: The craniovertebral junction (CVJ) poses unique challenges in the surgical management of intradural extramedullary (IDEM) tumors due to its complex anatomy and proximity to critical neurovascular structures. This study presents a comprehensive review of a single center’s experience over three years in managing IDEM tumors at the CVJ, emphasizing a novel approach to dural opening aimed at improving surgical access and patient outcomes. Materials and Methods: A retrospective analysis was conducted on patients with confirmed IDEM tumors involving the CVJ who underwent surgical intervention between January 2019 and December 2021 at the “ARNAS Garibaldi” Neurosurgical Department. The surgical technique involved a posterior midline approach with a modified dural opening technique, facilitating lateral dural incisions based on tumor location and size. Clinical, radiological, and surgical data were collected and analyzed, including patient demographics, tumor characteristics, surgical details, complications, and postoperative outcomes. Results: Eight patients (mean age: 53.87 ± 8.9 years) with diverse IDEM tumors (meningiomas, schwannomas, neurofibromas) at various locations, from the foramen magnum to the C2 vertebra, were included. Common symptoms included paresthesia (62.5%) and neck/head pain (62.5%). The modified dural opening technique enabled complete tumor resection in all cases, demonstrating favorable postoperative outcomes with no significant postoperative complications except for one case with CSF leak. Conclusions: This study highlights the complexity of managing IDEM tumors at the CVJ and introduces a novel modified dural opening technique aimed at optimizing surgical access while minimizing spinal cord retraction. Early outcomes suggest improved postoperative neurological status and reduced surgical complications. However, careful patient selection and meticulous technique are crucial. Further studies are warranted to validate the safety and efficacy of this approach, fostering advancements in the surgical management of IDEM tumors at the CVJ. Full article