Focal Accumulation Research Articles

Bone marrow breakout lesions act as key sites for tumor-immune cell diversification in multiple myeloma.

The bone marrow microenvironment plays a crucial role in the development of multiple myeloma. As the disease progresses, malignant myeloma cells can evolve to survive outside the bone marrow. However, the processes underlying bone marrow independence and their consequences for immune control remain poorly understood. Here, we conducted single-cell and spatial multiomics analyses of bone marrow-confined intramedullary disease and paired breakout lesions that disrupt the cortical bone. These analyses revealed a distinct cellular microenvironment and architectural features of breakout lesions, characterized by extensive areas of malignant plasma cells interspersed with lesion-specific solitary natural killer and macrophage populations, as well as focal accumulations of immune cell agglomerates. Within these agglomerates, spatially confined T cell clones expanded alongside various immune cells, coinciding with the local genomic evolution of tumor cells. These analyses identify breakout lesions as a hotspot for tumor-immune cell interactions and diversification, representing a key event in myeloma pathogenesis.

SLC9A6-Linked Parkinson Syndrome in Female Heterozygotes Is Associated With PET-Detectable Tau Pathology.

A previous postmortem study of men with Christianson syndrome, a disorder caused by loss-of-function mutations in the gene SLC9A6, reported a mechanistic link between pathologic tau accumulation and progressive symptoms such as cerebellar atrophy and cognitive decline. This study aimed to characterize the relationships between neuropathologic manifestations and tau accumulation in heterozygous women with SLC9A6 mutation. We conducted a multimodal neuroimaging and plasma biomarker study on 3 middle-aged heterozygous women with SLC9A6 mutations (proband 1: mid-50s; proband 2: early 50s; proband 3: mid-40s) presenting with progressive extrapyramidal symptoms. Examinations included 11C-PiB PET; 18F-florzolotau PET; structural MRI; and plasma measures of neurofilament light chain (NfL) polypeptide, glial fibrillary acidic protein, phosphorylated (p)Tau181, Aβ40, and Aβ42. Neuroimaging results of all 3 patients were compared with those of 12 healthy age-matched women (49.8 ± 4.7 years) while plasma biomarker levels of probands 1 and 2 were compared with those of 14 age-matched healthy women (54.1 ± 9.0 years). Proband 1 was diagnosed with Parkinson disease while probands 2 and 3 were diagnosed with atypical parkinsonism. 11C-PiB PET results were negative in all patients. 18F-florzolotau PET revealed focal tau accumulations in all 3 patients, predominantly in the striatum contralateral to motor symptoms. Moreover, greater extrapyramidal symptom severity was associated with higher standardized uptake value ratios (SUVRs) for 18F-florzolotau in the striatum. Multiple comparisons showed significantly higher 18F-florzolotau SUVR values in both the caudate and putamen of proband 1, who exhibited the most severe extrapyramidal signs, while no significant increases in 18F-florzolotau SUVR values were detected in any brain region of probands 2 and 3. Structural MRI revealed slightly lower regional subcortical and gray matter volumes in all patients but not significant after multiple comparisons. Finally, plasma NfL concentration was significantly higher in probands 1 and 2 compared with healthy controls. Our 18F-florzolotau PET analysis revealed greater tau accumulation in the striatum of heterozygous women with SLC9A6 mutation associated with worsening extrapyramidal symptom severity. The heterozygosity of loss-of-function SLC9A6 mutations further suggests that tauopathy may be a primary contributor to extrapyramidal signs.

Matched three-dimensional organoids and two-dimensional cell lines of melanoma brain metastases mirror response to targeted molecular therapy

Despite advances in the treatment paradigm for patients with metastatic melanoma, melanoma brain metastasis (MBM) continues to represent a significant treatment challenge. The study of MBM is limited, in part, by shortcomings in existing preclinical models. Surgically eXplanted Organoids (SXOs) are ex vivo, three-dimensional cultures prepared from primary tissue samples with minimal processing that recapitulate genotypic and phenotypic features of parent tumors without an artificial extracellular scaffold. MBM SXOs were created by a novel protocol incorporating techniques for establishing glioma and cutaneous melanoma organoids. A BRAFV600K-mutant and BRAF-wildtype MBM sample were collected directly from the operating room. Organoids were cultured in an optimized culture medium without an artificial extracellular scaffold. Concurrently, matched patient-derived cell lines were created. Organoid growth was observed within 3–4 weeks, and MBM SXOs retained histological features of the parent tissue, including pleomorphic epithelioid cells with abundant cytoplasm, large nuclei, focal melanin accumulation, and strong SOX10 positivity. After sufficient growth, organoids could be manually parcellated to increase the number of replicates. Matched SXOs and cell lines demonstrated sensitivity to BRAF and MEK inhibitors. Further study using SXOs may improve the translational relevance of preclinical studies and enable the study of the metastatic melanoma tumor microenvironment.

Intravascular Nodular Fasciitis Mimicking Thrombotic Complications in a 16-year-old male with May-Thurner Syndrome

Abstract Introduction/Objective Nodular fasciitis is a rare benign myofibroblastic proliferation commonly mistaken for malignant tumors due to its rapid growth and clinical presentation. May-Thurner Syndrome (MTS), characterized by compression of the left common iliac vein by the right common iliac artery, predisposes individuals to deep vein thrombosis (DVT). However, here we present a unique case of intravascular nodular fasciitis presenting as thrombotic complications in the context of MTS in a 16-year-old male. Methods/Case Report A 16-year-old male presented with progressive left hip and leg pain accompanied by recent swelling. Ultrasound revealed occlusive thrombi within the left side external iliac, common superficial femoral, and great saphenous veins, along with nonocclusive thrombi in left deep femoral vein. Magnetic resonance venography confirmed MTS and extensive thrombosis. Thrombectomy was done with fragments sent to pathology. Microscopic examination showed cellular areas with loose myxoid composition, proliferating spindle, myofibroblastic/fibroblastic, and stellate cells arranged in irregular bundles. Additional microscopic findings included mild cellular atypia, mitoses, focal macrophage aggregates, occasional multinucleate forms, foci of hemorrhage, fibrin exudate, ingrowing fibroblasts, and increased vascularization. Immunohistochemical stains demonstrated positivity for SMA, CD31, ERG, and CD34, highlighting prominent vascularization, while desmin, myogenin, myoglobin, STAT6, beta-catenin, S100, and AE1/AE3 were negative. Differential diagnosis included intravascular fasciitis, and possibly organizing thrombus with myxoid stroma. USP6 gene rearrangement (FISH) study was positive, confirming the diagnosis of nodular fasciitis. Results (if a Case Study enter NA) N/A Conclusion This case emphasizes the significance of maintaining a broad differential diagnosis when assessing specimens sent as thrombectomies. Recognizing intravascular nodular fasciitis as a potential presentation mimicking thrombosis is essential for accurate diagnosis and management.

Use of Laxative-Augmented Contrast Medium Increases the Accuracy in the Detection of Colorectal Neoplasms.

Colonic adenomas are considered a precursor of colorectal cancer. A 75-year-old woman had a history of post-operation left breast cancer. She received an excision when the left chest wall recurred. A later FDG PET/CT scan revealed a focal intense FDG accumulation in the sigmoid, a focal mild FDG uptake in the pericolic lymph node, and a focal increased FDG accumulation in the transverse colon. A delayed FDG PET/CT scan after the per-rectal administration of the laxative-augmented contrast medium revealed a filling defect with persistent FDG uptake in the sigmoid and transverse colon and mild FDG uptake in the pericolic lymph node. In addition, more lesions were observed in the rectum and descending colon. The pathology reports showed sigmoid adenocarcinoma with lymph node metastasis, and adenomas in the transverse colon, descending colon, and rectum.

Neurološki simptom kao prvi znak kolorektalnog karcinoma

Aim: To present a rare case of a patient with an isolated brain metastasis from colorectal carcinoma in whom an extensive diagnostic workup failed to identify the primary tumour. Case report: A 73-year-old female patient was admitted to the Neurology Department due to weakness in the right side of her body. Imaging with multislice computed tomography (MSCT) and brain magnetic resonance (MR) confirmed an expansive lesion in the left frontal region with surrounding oedema. Radiological findings suggested either a metastasis or a high-grade primary glioma. As the diagnostic workup did not reveal the primary tumour, the patient was transferred to Clinical Hospital Dubrava for surgical treatment. An intracranial tumour resection was performed with a histopathological confirmation of colon carcinoma metastasis. Postoperative brain irradiation was administered. A positron emission tomography scan (PET) showed focal accumulation of radioisotopes without clear pathological substrate in the appendix and cecoascedent junction area. Repeated colonoscopy did not find any pathological mucosal changes. The patient declined systemic treatment. Overall survival was 11 months, in line with literature data. Conclusion: The diagnosis of brain metastases from colorectal carcinoma is very rare, and even rarer is the diagnosis of isolated brain metastases without extracranial progression, counting for <0.5%. Therapeutic options for brain metastases from colorectal carcinoma include surgery, radio-neurosurgery, stereotactic radiotherapy, and brain irradiation. In our opinion, diagnostic evaluation of the central nervous system in patients with colorectal carcinoma should be considered if the patient has neurological symptoms or if there is an increase in carcinoembryonic antigen (CEA) levels without signs of extracranial disease progression.

Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS

RNA binding proteins have emerged as central players in the mechanisms of many neurodegenerative diseases. In particular, a proteinopathy of fused in sarcoma (FUS) is present in some instances of familial Amyotrophic lateral sclerosis (ALS) and about 10% of sporadic Frontotemporal lobar degeneration (FTLD). Here we establish that focal injection of sonicated human FUS fibrils into brains of mice in which ALS-linked mutant or wild-type human FUS replaces endogenous mouse FUS is sufficient to induce focal cytoplasmic mislocalization and aggregation of mutant and wild-type FUS which with time spreads to distal regions of the brain. Human FUS fibril-induced FUS aggregation in the mouse brain of humanized FUS mice is accelerated by an ALS-causing FUS mutant relative to wild-type human FUS. Injection of sonicated human FUS fibrils does not induce FUS aggregation and subsequent spreading after injection into naïve mouse brains containing only mouse FUS, indicating a species barrier to human FUS aggregation and its prion-like spread. Fibril-induced human FUS aggregates recapitulate pathological features of FTLD including increased detergent insolubility of FUS and TAF15 and amyloid-like, cytoplasmic deposits of FUS that accumulate ubiquitin and p62, but not TDP-43. Finally, injection of sonicated FUS fibrils is shown to exacerbate age-dependent cognitive and behavioral deficits from mutant human FUS expression. Thus, focal seeded aggregation of FUS and further propagation through prion-like spread elicits FUS-proteinopathy and FTLD-like disease progression.

Frontotemporal dementia-like disease progression elicited by seeded aggregation and spread of FUS.

RNA binding proteins have emerged as central players in the mechanisms of many neurodegenerative diseases. In particular, a proteinopathy of fu sed in s arcoma (FUS) is present in some instances of familial Amyotrophic lateral sclerosis (ALS) and about 10% of sporadic FTLD. Here we establish that focal injection of sonicated human FUS fibrils into brains of mice in which ALS-linked mutant or wild-type human FUS replaces endogenous mouse FUS is sufficient to induce focal cytoplasmic mislocalization and aggregation of mutant and wild-type FUS which with time spreads to distal regions of the brain. Human FUS fibril-induced FUS aggregation in the mouse brain of humanized FUS mice is accelerated by an ALS-causing FUS mutant relative to wild-type human FUS. Injection of sonicated human FUS fibrils does not induce FUS aggregation and subsequent spreading after injection into naïve mouse brains containing only mouse FUS, indicating a species barrier to human FUS aggregation and its prion-like spread. Fibril-induced human FUS aggregates recapitulate pathological features of FTLD including increased detergent insolubility of FUS and TAF15 and amyloid-like, cytoplasmic deposits of FUS that accumulate ubiquitin and p62, but not TDP-43. Finally, injection of sonicated FUS fibrils is shown to exacerbate age-dependent cognitive and behavioral deficits from mutant human FUS expression. Thus, focal seeded aggregation of FUS and further propagation through prion-like spread elicits FUS-proteinopathy and FTLD-like disease progression.

Protective effect of arginine glutamate (glutargin) in chronic pancreatitis induced by nitric oxide synthase blocker

Introduction. Nitric oxide (NO) is a gaseous molecule that is a biological mediator that carries out important regulation of physiological processes necessary for the functioning of tissues. We hypothesized that nonspecific inhibition of all isoforms of NOs would cause pancreatic damage and created a model of experimental pancreatitis based on NOs inhibition. Along with the study of the mechanisms of development of chronic pancreatitis, the search for medicines to treat and inhibit the progression of this disease continues. Purpose of the research. To study the protective effect of glutargin on the pancreas of rats with chronic pancreatitis induced by a blocker of NOs. Material and methods. The work was carried out on 21 laboratory white male Wistar rats weighing 180-230 g. Chronic pancreatitis was induced by intraperitoneal administration of the NOs blocker - N-nitro-L-arginine (L-NNA) (Sigma-Aldrich, USA) at a dose of 40 mg/kg of body weight. Rats in group I (n = 7) were injected with L-NNA for 12 days, rats in group II (n = 7) were injected intraperitoneally with glutargin 20 mg/kg, after 20 minutes they were injected with L-NNA - within 12 days. Rats of the control group (n = 7) were injected intraperitoneally with 0.9% NaCl solution. The rats were euthanized on the 45th day and biochemical and morphological studies were carried out. Results. After the introduction of the NOs blocker, deterioration of the general condition of the animals was determined, a sharp increase in the level of nitrites/nitrates to 80.22±19.91 μmol/l, control 32.61±4.55 μmol/l (р < 0.05); protein-bound hydroxyproline (PBH) to 215.21±22.01μmol/l, control 178.67±26.39 μmol/l, (p < 0.05); free hydroxyproline (FH) to 14.74±1.84 μmol/l, control 9.96±0.71 μmol/l, (p < 0.05); malondialdehyde (MDA) to 5.67±0.88 nmol/ml, control 3.62±0.13, (р < 0.05). Pronounced structural changes with stasis of formed blood elements in the vessels, focal accumulation of leukocytes in the parenchyma, dystrophy of acinar cells and fibrosis in the atrophy zone were determined in the pancreas of rats. Administration of glutargin contributed to the restoration of general behavioral reactions of rats, normalization of MDA – 4.81±0.15 nmol/ml, control 4.50±0.23, (p > 0.05); ceruloplasmin (CP) – 591.71±68.07 mg/ml, control – 663.25±34.05 mg/ml, (p > 0.05); PBH 183.62±5.98 μmol/l, control – 179.28±9.19 μmol/l, (p > 0.05); FH – 9.44±1.13 μmol/l, control – 9.96±0.71 μmol/l, (p > 0.05) and prevented the development of pronounced structural changes in the pancreas. Conclusions. In chronic pancreatitis induced by a NOs blocker, glutargin can prevent chronic pancreatitis by normalizing collagen metabolism, inhibiting oxidative stress, and severity of pancreatic parenchymal damage.

Matched Three-Dimensional Organoids and Two-Dimensional Cell Lines of Metastatic Melanoma to the Brain Mirrors Response to Targeted Molecular Therapy

INTRODUCTION: Metastatic melanoma to the brain (MMB) represents a significant treatment challenge. Limitations in preclinical models, namely the lack of heterogeneity in cell lines and low throughput of xenograft models, have thwarted novel therapeutic development. Surgically eXplanted Organoids (SXOs) are ex vivo, three-dimensional models that recapitulate genotypic and phenotypic features of parent tumors with minimal extracranial processing. We aim to develop the first known matched patient-derived SXO and cell line of BRAF-mutant MMB to investigate responses to targeted therapy. METHODS: MMB SXOs were created by a novel protocol incorporating techniques for creating glioma and cutaneous melanoma organoids. A BRAFV600K-mutant MMB sample was collected and processed within 30 minutes of resection. SXOs were created using a 1.0 mm biopsy punch. Organoids were cultured in low-adherence plates in an optimized culture medium under continuous orbital rotation without an artificial extracellular scaffold. Organoid media was changed every 48 hours. Concurrently, matched patient-derived cell lines were created and passaged weekly. Drug screens were conducted with the CellTiter-Glo Luminescence Viability Assay (cell line) and ReadyProbe Cell Viability Imaging Kit (SXOs). RESULTS: After an initial shedding period, organoid growth was observed within 3-4 weeks. MMB SXOs retained histological phenotypes of the parent tissue, including pleomorphic epithelioid cells with abundant cytoplasm, large nuclei, focal melanin accumulation, strong Sox10 positivity, and HMB45 positivity. After sufficient growth, organoids could be manually parcellated to increase the number of replicates. Matched SXOs and cell lines demonstrated sensitivity to BRAF-V600 and MEK inhibitors. CONCLUSIONS: Here, we outline the creation of the first known scaffold-free organoid model of MMB. Further study using SXOs will improve the translational relevance of preclinical studies and enable the study of the melanoma tumor microenvironment.

MCRP-Induced Focal Adhesion Kinase-Dependent Monocyte Aggregation and M1 Polarization, Which Was Partially Blocked by the C10M Inhibitor.

Monomeric C-reactive protein (mCRP) has recently been implicated in the abnormal vascular activation associated with development of atherosclerosis, but it may act more specifically through mechanisms perpetuating damaged vessel inflammation and subsequent aggregation and internalization of resident macrophages. Whilst the direct effects of mCRP on endothelial cells have been characterized, the interaction with blood monocytes has, to our knowledge, not been fully defined. Here we showed that mCRP caused a strong aggregation of both U937 cell line and primary peripheral blood monocytes (PBMs) obtained from healthy donors. Moreover, this increase in clustering was dependent on focal adhesion kinase (FAK) activation (blocked by a specific inhibitor), as was the concomitant adhesive attachment to the plate, which was suggestive of macrophage differentiation. Confocal microscopy confirmed the increased expression and nuclear localization of p-FAK, and cell surface marker expression associated with M1 macrophage polarization (CD11b, CD14, and CD80, as well as iNOS) in the presence of mCRP. Inclusion of a specific CRP dissociation/mCRP inhibitor (C10M) effectively inhibited PBMs clustering, as well as abrogating p-FAK expression, and partially reduced the expression of markers associated with M1 macrophage differentiation. mCRP also increased the secretion of pro-inflammatory cytokines Interleukin-8 (IL-8) and Interleukin-1β (IL-1β), without notably affecting MAP kinase signaling pathways; inclusion of C10M did not perturb or modify these effects. In conclusion, mCRP modulates PBMs through a mechanism that involves FAK and results in cell clustering and adhesion concomitant with changes consistent with M1 phenotypical polarization. C10M has potential therapeutic utility in blocking the primary interaction of mCRP with the cells-for example, by protecting against monocyte accumulation and residence at damaged vessels that may be predisposed to plaque development and atherosclerosis.

False-Positive Iodine-131 Uptake Due to Wasp Sting.

A 38-year-old woman with papillary carcinoma of the thyroid who underwent total thyroidectomy followed by high-dose radioiodine ablation was called for Iodine-131 (I-131) whole-body follow-up scan. Her follow-up scan revealed focal tracer accumulation in the lower aspect of the right posterior neck region. Her stimulated serum thyroglobulin and anti-thyroglobulin antibodies were 0.27 ng/ml and undetectable, respectively. Further clinical examination of the patient revealed a black scab in the same region. The patient revealed a history of wasp bite 2 days before iodine administration.

Evaluation of the Effectiveness of Dantrolene Sodium against Digoxininduced Cardiotoxicity in Adult Rats.

Digoxin poisoning commonly occurs in people treated with digoxin. It has been suggested that treatment with dantrolene may be a suitable strategy for digoxin-induced cardiotoxicity. The aim of this study was to evaluate the protective effect of dantrolene on digoxininduced cardiotoxicity in male rats. This study was approved by the ethics committee of Birjand University of Medical Sciences (Ethical number: IR.BUMS.REC.1400.067). Forty-two Wistar rats weighing between 300- 350 gr were randomly allocated to 7 groups (n = 6) as follows: Normal Saline (NS) group, Normal Saline + Ethanol (NS + ETOH) group, Normal Saline + dantrolene 10 mg/kg (NS + Dan 10) group, Digoxin (Dig) group), Digoxin + dantrolene 5 mg/kg (Dig + Dan 5) group, Digoxin + dantrolene 10 mg/kg (Dig + Dan 10) group, Digoxin + dantrolene 20 mg/kg (Dig + Dan 20) group, Dig was injected intravenously at 12 mL / h (0.25 mg / mL). Dan (5, 10 and 20 mg/kg) was injected intravenously at 5-8 min/mL. After 1 hour, blood samples were obtained from the animals' cavernous sinus and each animal's heartremoved. The blood sample was rapidly centrifuged at 2,500 rpm for 10 minutes and the serum was separated for measurement of creatine phosphokinase (CPK), potassium (K), sodium (Na), calcium (Ca), and magnesium (Mg). The samples were stored at -20°C. The heart samples were fixed in formalin 10% for histopathological evaluation. K levels slightly increased in the dig group versus the NS group. A significant increase in the K levels was observed in the Dig + Dan 20 group versus the NS group (p < 0.001). Dig slightly decreased Ca levels in the treated group versus the NS group. The levels of Ca significantly increased in the Dig + Dan 10 group versus the Dig group (p < 0.05). Histological examination of the heart tissue in the dig group showed cardiomyocyte degeneration, increased edematous intramuscular space associated with hemorrhage, and congestion. Focal inflammatory cell accumulation in the heart tissue was also seen. Cardiomyocytes were clear and arranged in good order in the Dig + Dan 10 group. dantrolene (10 mg/kg) was cardioprotective in a model of digoxin-induced cardiotoxicity, secondary to cardiac remodeling and hyperkalemia. However, further research is necessary to determine dantrolene's cardioprotective and cardiotoxic doses in animal models.

A Structured Approach for Treating Calcium Hydroxylapatite Focal Accumulations.

Radiesse, a widely utilized calcium hydroxylapatite (CaHA) dermal filler, has shown effectiveness in soft tissue augmentation and regeneration. As with all dermal fillers, the potential for nodules may arise. Understanding the pathogenesis of these nodules and exploring effective treatment methodologies are crucial for optimizing patient outcomes. A literature search was carried out to identify published literature documenting reversal of CaHA nodules. After identification, a consensus panel developed a structured approach, denoted by levels, for applying such reversal methods. This concise review presents an algorithmic approach to addressing CaHA focal accumulations (noninflammatory nodules) based on invasiveness, cost, and potential risks based on published literature. Level 0 involves no intervention, relying on natural degradation for asymptomatic nodules. Level 1 interventions utilize mechanical dispersion techniques, including massage and in situ dispersion, which have demonstrated high success rates, cost effectiveness, and minimal invasiveness. Level 2 introduces alternative modalities such as pharmacological treatments with 5-fluorouracil and corticosteroids, lasers, and experimental approaches. Level 3 represents last-resort options, including calcium-chelating agents, manual removal, and surgical excision. The article offers a structured approach to managing CaHA focal accumulations.

Unnatural Amino Acid-Based Ionic Liquid Enables Oral Treatment of Nonsense Mutation Disease in Mice.

This investigation addresses the challenge of suboptimal unnatural amino acid (UAA) utilization in the site-specific suppression of nonsense mutations through genetic code expansion, which is crucial for protein restoration and precise property tailoring. A facile and economical oral liquid formulation is developed by converting UAAs into ionic liquids, significantly enhancing their bioavailability and tissue accumulation. Empirical data reveal a 10-fold increase in bioavailability and up to a 13-fold rise in focal tissue accumulation, alongside marked improvements in UAA incorporation efficiency. A 4-week oral administration in mdx mice, a model for Duchenne muscular dystrophy (DMD), demonstrates the formulation's unprecedented therapeutic potential, with up to 40% dystrophin expression restoration and 75% recovery of normal fiber functions, surpassing existing treatments and exhibiting substantial long-term safety. This study presents a potent oral dosage form that dramatically improves UAA incorporation into target proteins in vivo, offering a significant advance in the treatment of nonsense mutation-mediated disorders and holding considerable promise for clinical translation.

Ocrelizumab reduces cortical and deep grey matter loss compared to the S1P-receptor modulator in multiple sclerosis.

Ocrelizumab (OCR) and Fingolimod (FGL) are two high-efficacy treatments in multiple sclerosis which, besides their strong anti-inflammatory activity, may limit neurodegeneration. To compare the effect of OCR and FGL on clinical and MRI endpoints. 95 relapsing-remitting patients (57 OCR, 38 FGL) clinically followed for 36months underwent a 3-Tesla MRI at baseline and after 24months. The annualized relapse rate, EDSS, new cortical/white matter lesions and regional cortical and deep grey matter volume loss were evaluated. OCR reduced the relapse rate from 0.48 to 0.04, FGL from 0.32 to 0.05 (both p < 0.001). Compared to FGL, OCR-group experienced fewer new white matter lesions (12% vs 32%, p = 0.005), no differences in new cortical lesions, lower deep grey matter volume loss (- 0.12% vs - 0.66%; p = 0.002, Cohen's d = 0.54), lower global cortical thickness change (- 0.45% vs - 0.70%; p = 0.036; d = 0.42) and reduced cortical thinning/volume loss in several regions of interests, including those of parietal gyrus (d-range = 0.65-0.71), frontal gyrus (d-range = 0.47-0.60), cingulate (d-range = 0.41-0.72), insula (d = 0.36), cerebellum (cortex d = 0.72, white matter d = 0.44), putamen (d = 0.35) and thalamus (d = 0.31). The effect on some regional thickness changes was confirmed in patients without focal lesions. When compared with FGL, patients receiving OCR showed greater suppression of focal MRI lesions accumulation and lower cortical and deep grey matter volume loss.

Calyceal Diverticulum Found Incidentally on 18 F-FDG PET/CT Imaging.

A 69-year-old man with pancreatic cancer underwent 18 F-FDG PET/CT examination for tumor staging. The PET images showed a focal mass-like FDG accumulation in the left kidney mimicking malignancy, whereas simultaneous CT and fused PET/CT images suggested a cystic lesion. On subsequent MR examination, the lesion appeared cystic on T2-weighted, contrast-enhanced arterial phase, and contrast-enhanced venous phase images. In addition, excretory phase images showed filling contrast medium to the cystic cavity, leading to a diagnosis of calyceal diverticulum. This report suggests that the possibility of a calyceal diverticulum should be considered in cases with focal FDG accumulation in renal cystic lesions.

Noninfectious Granulomatous Lung Disease: Radiological Findings and Differential Diagnosis.

Granulomatous lung diseases (GLDs) are a heterogeneous group of pathological entities that can have different clinical presentations and outcomes. Granulomas are histologically defined as focal aggregations of activated macrophages, Langerhans cells, and lymphocytes, and may form in the lungs when the immune system cannot eliminate a foreign antigen and attempts to barricade it. The diagnosis includes clinical evaluation, laboratory testing, and radiological imaging, which especially consists of high-resolution computed tomography. bronchoalveolar lavage, transbronchial needle aspiration or cryobiopsy, positron emission tomography, while genetic evaluation can improve the diagnostic accuracy. Differential diagnosis is challenging due to the numerous different imaging appearances with which GLDs may manifest. Indeed, GLDs include both infectious and noninfectious, and necrotizing and non-necrotizing granulomatous diseases and the imaging appearance of some GLDs may mimic malignancy, leading to confirmatory biopsy. The purposes of our review are to report the different noninfectious granulomatous entities and to show their various imaging features to help radiologists recognize them properly and make an accurate differential diagnosis.

Tumour deposits are independently associated with recurrence in colon cancer.

Tumour deposits are focal aggregates of cancer cells in pericolic fat and mesentery, distinct from vessels, nerves and lymphatics. Their presence upstages lymph node negative patients but is ignored in lymph node positive patients. We investigated the clinicopathological factors associated with tumour deposits and their impact on recurrence in lymph node positive and negative patients. Clinicopathological variables were collected from the medical records of patients with Stage I-III colon cancer who underwent resection in 2017-2019. Pathology was reviewed by a gastrointestinal pathologist. Patients with rectal cancer, metastasis, and concurrent malignancy were excluded. Tumour deposits were noted in 69 (9%) of 770 patients. They were associated with the presence of lymph node metastasis, advanced T category, poorly differentiated tumours, microsatellite stable subtype and lymphovascular and perineural invasion (p < 0.05). The presence of tumour deposits (hazard ratio 2.48, 95% CI 1.49-4.10) and of lymph node metastasis (hazard ratio 3.04, 95% CI 1.72-5.37) were independently associated with decreased time to recurrence. There was a weak correlation (0.27) between the number of tumour deposits and the number of positive lymph nodes. Tumour deposits are associated with more advanced disease and high-risk pathological features. The presence of tumour deposits and lymph node metastasis were found to be independent risk factors for decreased time to recurrence. A patient with both lymph node metastasis and tumour deposits is more than twice as likely to have recurrence compared with a patient with only lymph node metastasis. Tumour deposits independently predict recurrence and should not be ignored in lymph node positive patients.

Evaluating the Patterns of FAPI Uptake in the Shoulder Joint: a Preliminary Study Comparing with FDG Uptake in Oncological Studies

BackgroundFibroblast activation protein inhibitor (FAPI) targeting PET has been introduced as a novel molecular imaging modality for visualizing cancer-associated fibroblasts. There have also been reports suggesting incidental findings of localized accumulation in the shoulder joints. However, further characterization in a larger patient cohort is still lacking.Methods77 consecutive patients (28 females; mean age, 63.1 ± 11.6) who underwent Ga-68 FAPI-04 PET/CT for diagnosis of solid tumors were included. The incidence and localization of tracer uptake in shoulder joints were investigated and compared with available F-18 FDG scans serving as reference.ResultsGa-68 FAPI-04 uptake was evaluated in 77 patients (154 shoulder joints), of whom 54 subjects (108 shoulder joints) also had available F-18 FDG scans for head-to-head comparison. On FAPI-targeted imaging, 67/154 shoulders (43.5%) demonstrated increased radiotracer accumulation in target lesions, which were distributed as follows: acromioclavicular (AC) joints in 25/67 (37.3%), followed by glenohumeral and subacromial (GH + SA) joints in 23/67 (34.3%), or both (AC and GH + SA joints) in the remaining 19/67 (28.4%). Ga-68 FAPI-04 correlated with quantified F-18 FDG uptake (r = 0.69, p < 0.0001). Relative to the latter radiotracer, however, in-vivo FAP expression in the shoulders was significantly increased (Ga-68 FAPI-04, 4.7 ± 3.2 vs F-18 FDG, 3.6 ± 1.3, p < 0.001).ConclusionOur study revealed focal accumulation of Ga-68 FAPI-04 in the shoulders, particularly in the AC joints, with higher uptake compared to the inflammatory-directed PET radiotracer F-18 FDG in oncological studies. As a result, further trials are warranted to investigate the potential of FAPI-directed molecular imaging in identifying chronic remodeling in shoulder joints. This could have implications for initiating anti-FAP targeted photodynamic therapy based on PET signal strength.