Areas Of Calcification Research Articles

CALCIFICATION OF ARTERIES IN PATIENTS WITH ATHEROSCLEROSIS: CAUSES AND MECHANISMS OF DEVELOPMENT

The paper shows analogies between the mechanisms of calcification of arteries, various tissues and bone mineralization. In calcification the same mechanisms are involved, as at ossification of an organic matrix of a bone, including participation of stem cells. In the arteries and capillaries of various organs found polypotent precursors – mesenchymal stem cells, presumably responsible for the pathological mineralization of the arterial wall. Circulating in the blood and present in the intima of the human atheromatous aorta colony-forming stem cells of the stromal line of differentiation. Adventitia cells or pericytes are considered as a pluripotent mesenchymal reserve for replenishment of some cellular forms of connective tissue. Bone marrow stem cells of the stromal line of differentiation with the presence of pluripotent stromal cells in the blood and granulomas (plaques) and their transformation into bone tissue cells are involved in atherogenesis. Smooth muscle cells (SMCs) and myofibroblasts of the arterial wall adventitia have an osteoblast-like phenotype. Collagen and elastic fibers are involved in the calcification of blood vessels and soft tissues. Calcification of granulomas (plaques) accompanies their inflammatory morphogenesis, accompanied by the development of scar tissue. It often accompanies and completes the inflammation in them. This process is observed with the gradual replacement of the parenchyma of some organs with connective tissue. The mineral phase in bones and soft tissues, represented by calcium (Ca) and phosphate (P), contacts with nucleators - specific areas of collagen fibers. Non-collagen proteins are also involved in arterial calcification. With the progression of atherosclerosis and calcification of granulomas/plaques by cells present in the arterial wall, osteonectin is expressed. Osteopontin content is associated with Ca deposits in them; in particular, it correlates with the Ca level in the coronary arteries. In the processes of ossification and calcification, phosphatases play a certain role. In areas of calcification of granulomas/plaques, osteoprotegerin is found, which inhibits the activity of alkaline phosphatase in the aorta and prevents calcification of the media. Arterial wall calcification and inflammation are inhibited by fetuin-A and matrix γ-carboxyglutaric protein (MGP). The rate of bone formation and tissue calcification depends on the concentration of Ca and P in plasma and extracellular fluid. With their high concentration in the extracellular fluid, the mineral phase appears where it normally does not exist. Lipids are among the initiators of granuloma / plaque calcification in the arteries. The role of inflammation and necrosis in the calcification of the arteries is confirmed by experiments on animals with repeated intravenous injections of adrenaline, which causes focal necrosis of the middle membrane, which then undergoes calcification. In arterial walls, heart muscle, bone and cartilage tissue, osteonectin, osteocalcin, osteopontin, bone sialoprotein are often formed. In general, the mechanisms of arterial and soft tissue calcification are poorly understood. There are no effective remedies for calcification.

Radiogenomic Analysis of Papillary Thyroid Carcinoma for Prediction of Cervical Lymph Node Metastasis: A Preliminary Study.

BackgroundPapillary thyroid carcinoma (PTC) is characterized by frequent metastases to cervical lymph nodes (CLNs), and the presence of lymph node metastasis at diagnosis has a significant impact on the surgical approach. Therefore, we established a radiomic signature to predict the CLN status of PTC patients using preoperative thyroid ultrasound, and investigated the association between the radiomic features and underlying molecular characteristics of PTC tumors.MethodsIn total, 270 patients were enrolled in this prospective study, and radiomic features were extracted according to multiple guidelines. A radiomic signature was built with selected features in the training cohort and validated in the validation cohort. The total protein extracted from tumor samples was analyzed with LC/MS and iTRAQ technology. Gene modules acquired by clustering were chosen for their diagnostic significance. A radiogenomic map linking radiomic features to gene modules was constructed with the Spearman correlation matrix. Genes in modules related to metastasis were extracted for Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses, and a protein-protein interaction (PPI) network was built to identify the hub genes in the modules. Finally, the screened hub genes were validated by immunohistochemistry analysis.ResultsThe radiomic signature showed good performance for predicting CLN status in training and validation cohorts, with area under curve of 0.873 and 0.831 respectively. A radiogenomic map was created with nine significant correlations between radiomic features and gene modules, and two of them had higher correlation coefficient. Among these, MEmeganta representing the upregulation of telomere maintenance via telomerase and cell-cell adhesion was correlated with ‘Rectlike’ and ‘deviation ratio of tumor tissue and normal thyroid gland’ which reflect the margin and the internal echogenicity of the tumor, respectively. MEblue capturing cell-cell adhesion and glycolysis was associated with feature ‘minimum calcification area’ which measures the punctate calcification. The hub genes of the two modules were identified by protein-protein interaction network. Immunohistochemistry validated that LAMC1 and THBS1 were differently expressed in metastatic and non-metastatic tissues (p=0.003; p=0.002). And LAMC1 was associated with feature ‘Rectlike’ and ‘deviation ratio of tumor and normal thyroid gland’ (p<0.001; p<0.001); THBS1 was correlated with ‘minimum calcification area’ (p<0.001).ConclusionsThe radiomic signature proposed here has the potential to noninvasively predict the CLN status in PTC patients. Merging imaging phenotypes with genomic data could allow noninvasive identification of the molecular properties of PTC tumors, which might support clinical decision making and personalized management.

A Rare Case of Primary Breast Osteosarcoma Evaluated with Multiple Modalities

Primary breast osteosarcoma (PBO) is very rare. This report presents a case of POB that was evaluated by multiple modalities. A woman in her 70s presented with a mass of increasing size in her right breast. A mammogram and an ultrasound visualized a lobulated mass containing coarse calcification in the right breast. Magnetic resonance imaging showed a strong enhancement effect and high signal on diffusion-weighted imaging. Further imaging on 18F-fluorodeoxyglucose positron-emission tomography and computed tomography exhibited a high uptake. A right total mastectomy was performed. Histologic examination revealed abundant periosteal formation, areas of calcification and moderately pleomorphic oval to spindle-shaped stromal cells, leading to the diagnosis of PBO. The presence of calcified breast tumors exhibiting aggressive growth indicates that PBO should be added to the differential diagnosis.

Ectopic mineralisation of the mandibular symphysis in ENT1 knockout mice: A model of dystrophic calcification

Equilibrative nucleoside transporter 1 (ENT1) transfers nucleosides, such as adenosine, across plasma membranes. We reported previously that mice lacking ENT1 (ENT1−/−) exhibit progressive ectopic calcification of spinal tissues—a phenotype resembling diffuse idiopathic skeletal hyperostosis (DISH) in humans. Our objective was to investigate potential calcification of orofacial tissues in ENT1−/− mice. Heads of wild-type mice and ENT1−/− mice from 3 to 17 months were evaluated using microcomputed tomography (μCT). Some heads were decalcified and processed for histological assessment. Other heads were examined using energy dispersive X-ray spectroscopy and micro X-ray diffraction. Using μCT, ENT1−/− mice showed extensive radiopaque lesions within the mandibular symphysis, the severity of which increased with advancing age. Histologically, at 6 months these ectopic radiopacities were found to correspond to acellular, amorphous, eosinophilic material, with no evidence of inflammatory cells. Because lesions were localised to the symphysis, we identified early pathological changes at 3 months and observed that lesions initiated specifically within the fibrocartilage pad. Energy-dispersive X-ray spectroscopy of ectopic lesions revealed large amounts of calcium and phosphorous in a molar ratio of ~1.59, and X-ray diffraction profiles matched that of calcium-deficient hydroxyapatite. This is the first characterisation of ectopic calcifications within the mandibular symphysis of ENT1−/− mice, indicating a role for ENT1 and adenosine metabolism in regulating calcification of fibrocartilaginous tissues. Moreover, these murine lesions resemble areas of dystrophic calcification in the spinal tissues of humans with DISH. Importantly, ectopic calcifications develop in a reproducible temporal pattern within a well-defined anatomical region and, thus, provide a model for determining the cellular and molecular pathways underlying ectopic calcification in DISH and related disorders.

Comparing the Efficacy of a Microperforated Titanium Membrane for Guided Bone Regeneration with an Existing Mesh Retainer in Dog Mandibles.

Acute-type lateral ridge defects (25 mm × 6 mm × 5 mm) were bilaterally created in the mandibles of four dogs (two defects per animal). The defects were reconstructed with particulate autologous bone and covered with a microperforated titanium membrane (Ti-honeycomb membrane, TiHM) or an existing conventional titanium mesh as control. The samples were dissected after 16 weeks postoperatively and processed for radiographic, histologic, and histomorphometric analyses. Regenerated tissue and bone volume were significantly larger in the TiHM group than in the control group (p = 0.05; p = 0.049). In contrast, bone mineral density was similar between the two groups. Histomorphometric analysis revealed that the regenerated bone area and calcific osseous area were larger in the TiHM group than in the control group; however, the differences were not significant. The efficacy of TiHM was generally satisfactory with the potential to become a standard tool for the GBR procedure; however, early membrane exposure will be a major problem to overcome.

MiR-93 inhibits the vascular calcification of chronic renal failure by suppression of Wnt/β-catenin pathway.

To explore the effect of miR-93-mediated Wnt/β-catenin pathway on the vascular calcification (VC) of chronic renal failure (CRF). SD rats were utilized to construct CRF models and divided into Control, CRF, CRF + LV (lentiviral vector)-miR-93 and CRF + LV-Con groups. Renal tissues collected from rats were performed hematoxylin and eosin (HE) staining and Masson staining, while the abdominal aorta was dissected for alizarin red staining and Von Kossa staining. VC-related genes were determined by qRT-PCR while Wnt/β-catenin pathway-related proteins were examined by Western blotting. As compared to Control group, the serum levels of blood urea nitrogen (BUN), serum creatinine (Scr), phosphorus (P), cystatin C (Cys-C) and 24-h urea protein (24h Upro), and the scores of renal interstitial lesion and fibrotic area in rats from CRF group were elevated, with the increased calcified area of aorta as well as the enhanced calcium content and ALP. Meanwhile, rats in the CRF group had up-regulated expression of OPN, OCN, RUNX2 and BMP-2 and down-regulated expression of miR-93. As for the expression of Wnt/β-catenin pathway, rats in the CRF group had sharp increases in the protein expression of TCF4 and β-catenin, while α-SMA was down-regulated. However, changes of the above were reversed in rats from CRF + LV-miR-93 group, and TCF4 was confirmed to be a target gene of miR-93. MiR-93, via inhibiting the activity of Wnt/β-catenin pathway by targeting TCF4, can improve the renal function of CRF rats, thereby mitigating the vascular calcification of CRF.

Procyanidin B2 Reduces Vascular Calcification through Inactivation of ERK1/2-RUNX2 Pathway.

Vascular calcification is strongly associated with atherosclerotic plaque burden and plaque instability. The activation of extracellular signal-regulated kinase 1/2 (ERK1/2) increases runt related transcription factor 2 (RUNX2) expression to promote vascular calcification. Procyanidin B2 (PB2), a potent antioxidant, can inhibit ERK1/2 activation in human aortic smooth muscle cells (HASMCs). However, the effects and involved mechanisms of PB2 on atherosclerotic calcification remain unknown. In current study, we fed apoE-deficient (apoE−/−) mice a high-fat diet (HFD) while treating the animals with PB2 for 18 weeks. At the end of the study, we collected blood and aorta samples to determine atherosclerosis and vascular calcification. We found PB2 treatment decreased lesions in en face aorta, thoracic, and abdominal aortas by 21.4, 24.6, and 33.5%, respectively, and reduced sinus lesions in the aortic root by 17.1%. PB2 also increased α-smooth muscle actin expression and collagen content in lesion areas. In the aortic root, PB2 reduced atherosclerotic calcification areas by 75.8%. In vitro, PB2 inhibited inorganic phosphate-induced osteogenesis in HASMCs and aortic rings. Mechanistically, the expression of bone morphogenetic protein 2 and RUNX2 were markedly downregulated by PB2 treatment. Additionally, PB2 inhibited ERK1/2 phosphorylation in the aortic root plaques of apoE−/− mice and calcified HASMCs. Reciprocally, the activation of ERK1/2 phosphorylation by C2-MEK1-mut or epidermal growth factor can partially restore the PB2-inhibited RUNX2 expression or HASMC calcification. In conclusion, our study demonstrates that PB2 inhibits vascular calcification through the inactivation of the ERK1/2-RUNX2 pathway. Our study also suggests that PB2 can be a potential option for vascular calcification treatment.

Childhood-onset Craniopharyngioma.

Craniopharyngiomas are rare embryonic malformational tumors of the sellar/parasellar region, classified by the World Health Organization (WHO) as tumors with low-grade malignancy (WHO I). The childhood adamantinomatous subtype of craniopharyngioma is usually cystic with calcified areas. At the time of diagnosis, hypothalamic/pituitary deficits, visual disturbances, and increased intracranial pressure are major symptoms. The treatment of choice in case of favorable tumor location (without hypothalamic involvement) is complete resection. It is important to ensure that optical and hypothalamic functionality are preserved. In case of unfavorable tumor location, that is with hypothalamic involvement, a hypothalamus-sparing surgical strategy with subsequent local irradiation of residual tumor is recommended. In the further course of the disease, recurrences and progression often occur. Nevertheless, overall survival rates are high at 92%. Severe impairment of quality of life and comorbidities such as metabolic syndrome, hypothalamic obesity, and neurological consequences can be observed in patients with disease- and/or treatment-related lesions of hypothalamic structures. Childhood-onset craniopharyngioma frequently manifests as a chronic disease so that patients require lifelong, continuous care by experienced multidisciplinary teams to manage clinical and quality of life consequences. For this review, a search for original articles and reviews published between 1986 and 2020 was performed in Pubmed, Science Citation Index Expanded, EMBASE, and Scopus. The search terms used were "craniopharyngioma, hypothalamus, pituitary obesity, irradiation, neurosurgery.

Massive Retinal Gliosis in Microphthalmic Globe With Cyst Masquerading as a Neoplasm

We report a rare case of a bilaterally blind, 33-year-old male, who presented with rapidly progressive, painless swelling in the right orbit for two months, in the absence of ocular trauma. Suspecting an intraocular neoplasm, a contrast-enhanced MRI (CE-MRI) orbit was performed, which was suggestive of a right-sided superomedial eccentric soft-tissue lesion with bilateral rudimentary globes associated with cyst, hypoplastic optic nerves, and focal areas of calcification. Diffusion-weighted MRI demonstrated diffusion restriction and yielded an indeterminate value of apparent diffusion coefficient (ADC). A right enucleation with excision of the cyst was performed. Histopathological examination confirmed the diagnosis of a right-sided massive retinal gliosis (MRG) with bilateral microphthalmia with cyst. This case demonstrates the role of a detailed histopathological analysis along with immunohistochemistry (IHC) in differentiating MRG from a neoplasm.

EPEN-12. MULTIPLE RECURRENCES OF ANAPLASTIC EPENDYMOMA WITH EXTRA AXIAL AND EXTRA NEURAL METASTASIS IN A PEDIATRIC PATIENT

BackgroundEpendymomas are the third most common CNS tumor in the pediatric population, accounting for 10% of all CNS tumors. Co-occurring extraneural and extracranial metastasis of ependymomas are extremely rare, with only 1 reported adult case in current literature. Case DescriptionWe describe the case of a patient with multiple reoccurrences of anaplastic ependymoma. Initial imaging showed a 5 x 8 x 8 cm complex cystic mass with nodular enhancing components within the left occipital lobe. The 4th ventricle was intact and imaging was negative for metastasis. Pathology following resection demonstrated perivascular pseudorosettes, areas of calcification, and increased mitotic activity. Biopsy revealed GFAP, EMA, neurofilament, INI-1, and was negative for CAM5.2, confirming anaplastic ependymoma. Methylation studies for PFA or PFB subgroup differentiation were not available. The patient had recurrences at 4-, 5-, and 6-years after his initial diagnosis. Seven years from his initial diagnosis, the patient underwent resection of four nodular lesions from the occipital lobe and surrounding soft tissue. Pathology of these lesions and the lymph nodes/soft tissue confirmed anaplastic ependymoma. A PET scan showed increase uptake in the supraclavicular lymph nodes and had multiple bilateral pulmonary nodules. Scans at 3 months post-surgery were negative for leptomeningeal metastases but showed further lymph node involvement with progression of pulmonary disease. ConclusionCo-occurring extraneural and extracranial metastasis of ependymoma is a rare occurrence across all populations. To our knowledge, this would be the first published pediatric case of anaplastic ependymoma with lymph node, soft tissue, and pulmonary involvement. Treatment of ependymoma itypically local and the utility of chemotherapy remains unclear. Treatment options for extraneural mets is very limited, illustrating the need for new therapies and further studies directed at understanding the biology of these tumors and the factors that could influence their ability to metastasize to extraneural and extracranial sites.

Carotid Atherosclerotic Calcification Characteristics Relate to Post-stroke Cognitive Impairment

Background: Together with cerebral small vessel disease (CSVD), large vessel atherosclerosis is considered to be an equally important risk factor in the progression of vascular cognitive impairment. This article aims to investigate whether carotid atherosclerotic calcification is associated with the increased risk of post-stroke cognitive impairment (PSCI).Methods: A total of 128 patients (mean age: 62.1 ± 12.2 years, 37 women) suffering from ischemic stroke underwent brain/neck computer tomography angiography examination. The presence and characteristic of carotid calcification (size, number and location) were analyzed on computer tomography angiography. White matter hyperintensity (WMH) was assessed using Fazekas scales. PSCI was diagnosed based on a battery of neuropsychological assessments implemented 6−12 months after stroke.Results: Among 128 patients, 26 developed post-stroke dementia and 96 had carotid calcification. Logistic regression found carotid calcification (odds ratio [OR] = 7.15, 95% confidence interval [CI]: 1.07–47.69) and carotid artery stenosis (OR = 6.42, 95% CI: 1.03–40.15) both significantly increased the risk for post-stroke dementia. Moreover, multiple, thick/mixed, and surface calcifications exhibited an increasing trend in PSCI (Ptrend = 0.004, 0.016, 0.045, respectively). The prediction model for post-stroke dementia including carotid calcification (area under curve = 0.67), WMH (area under curve = 0.67) and other covariates yielded an area under curve (AUC) of 0.90 (95% CI: 0.82–0.99).Conclusion: Our findings demonstrated that the quantity and location of carotid calcifications were independent indicators for PSCI. The significant role of large vessel atherosclerosis in PSCI should be concerned in future study.

Acute Calcific Tendinitis of the Forefoot in Young Women- A Presentation of Two Cases

Introduction: Calcific tendinitis is an uncommon presentation in the forefoot with relatively few cases reported in the medical literature. It is commonly overlooked and should form part of a differential diagnosis when assessing patients presenting with acute pain of the forefoot localised to a single joint or tendon. We present two cases of young women involved in amateur running and martial arts respectively who presented with acute pain of their forefoot. Case Description: These 2 cases describe a 44 year old amateur female runner and 23 year old female martial arts athlete who presented with acute onset of pain affecting the dorsal aspect of their great toe interphalangeal joint and base of 1st metatarsal respectively. Both patients had tender erythematous swellings at the site of pain and difficulty weightbearing. Plain radiography revealed areas of calcification at the respective sites which was confirmed with ultrasound. Both patients underwent US guided corticosteroid injections with significant symptom improvement within 48 hours of injections and rapid return to sport. Discussion: These two cases demonstrate an atypical presentation of acute calcific tendinitis affecting the forefoot and add two more cases to the reported literature. Combining the characteristic clinical presentation of acute pain affecting a tendon or joint with a tender erythematous swelling on examination with the typical radiographic features of calcification can promptly diagnose this often misdiagnosed condition and avoid unnecessary investigations. Conservative treatment and intralesional injection with corticosteroids can lead to rapid resolution and favourable patient outcomes.

Plaque Longitudinal Heterogeneity in Morphology, Property, and Mechanobiology

Background and Purpose: The hemodynamic environment of an atherosclerotic plaque varies along the longitudinal direction. Investigating the changes in plaque morphology and its biomechanical environment along the longitudinal direction and their correlations will enhance our understanding of plaque progression and arterial remodeling. Methods: Six male patients with carotid stenosis >70% were recruited. Multisequence high-resolution MRI was performed at the carotid bifurcation. Carotid endarterectomy was performed following MRI, and the plaque tissue was collected for histological and mechanical testing. Patient-specific biomechanical modeling and simulations were conducted to calculate the mechanical stresses (wall shear stress [WSS] and von Mises stress [VMS]). Changes in plaque cross-sectional morphology, WSS, and VMS as well as their correlations were evaluated. Results: Positive correlations were found between % stenosis and % inflammation (MA) (p = 0.019), % lipid area and % MA (p = 0.026), and % calcification area and VMS (p = 0.007). Negative correlations were found between VMS and % stenosis (p = 0.028) and VMS and average WSS (p = 0.034). Moreover, the peak stresses and neovessels were found to be in the shoulder regions. High-stress concentrations were found in the interface regions of the calcification and surrounding tissue, thereby increasing plaque vulnerability. Conclusions: Correlations between the morphology and stresses suggest that arterial remodeling is a dynamic interaction between mechanical environment and plaque progression resulting in plaque heterogeneity. Our finding indicates that plaque heterogeneity is associated with plaque progression and can be combined with mechanical stresses for identifying high-risk plaques.

The Role of Glucagon-Like Peptide 1 Receptor PET/CT With Ga-68-NODAGA-exendin in Localising an Insulinoma: Lessons From a Clinical Case

We present a clinical case highlighting the diagnostic challenges in a patient with an insulinoma. A 57-year-old lady initially presented with sweating on waking. Investigation documented a fasting blood glucose of 2 mmol/L (3.9-5.4) and the presence of anti-endomysial antibodies. On the basis of a diagnosis of Coeliac disease, the patient was commenced on a gluten free diet with apparent resolution of symptoms for 9 years. Subsequently, she re-presented with recurrent episodes of confusion which resolved with a ‘sugary’ drink. Consequently, she underwent a prolonged supervised fast: glucose 1.9 mmol/L (neuroglycopaenic symptoms), insulin 76 pmol/L (<20), c-peptide 763 nmol/L (<200) and β-hydroxybutyrate (BHB) 131 μmol/L (<2700). A diagnosis of endogenous hyperinsulinaemic hypoglycaemia resulted in radiological investigation (CT thorax/ abdomen/pelvis, MRI pancreas and endoscopic ultrasound [EUS] of pancreas) with no tumor identified. Due to persisting symptoms, in addition to dietary changes, diazoxide and octreotide were commenced. She was referred for a second opinion where a repeat 72-hour fast (at the time of hypoglycaemia symptoms) showed: glucose 2.3 mmol/L, Insulin 51 pmol/L, C-Peptide 513 pmol/L, BHB 1580 μmol/L and proinsulin 31 pmol/L (<10). Insulin antibody and sulphonylurea screens were negative. Her symptoms resolved after carbohydrate ingestion. Further imaging including a Ga-68-DOTATATE PET/CT, selective arterial calcium stimulation and hepatic venous sampling failed to localise an insulinoma. Despite pharmacological treatment hypoglycaemia continued to impede the patient’s quality of life and both octreotide and diazoxide were stopped due to side effects and minimal benefit. A glucagon-like peptide 1 receptor (GLP-1R) PET/CT scan with Ga-68-NODAGA-exendin-4 was performed and revealed uptake in a lesion in the ventral pancreatic body, suggestive of an insulinoma. A further EUS showed a corresponding 10 mm calcified area in the pancreatic body. The surgeon was unable to identify the tumor intra-operatively (macroscopically and ultrasound guided) and therefore performed a distal pancreatectomy which encompassed a 13 mm tumor. Histopathology demonstrated a 13 mm well differentiated, Grade 1 pancreatic neuroendocrine tumor (Ki67 1%) staining positively for AE1/AE3, synaptophysin, chromogranin and insulin (GLP-1R and pro-insulin staining awaited). Post-operatively, there was complete resolution of hypoglycaemia. In summary the learning points are the 9-year interval between initial presentation and confirmation of the diagnosis and the challenge of tumor localisation. There is no published evidence about gluten free diets reducing hypoglycaemia in insulinomas, but our patient described symptomatic improvement. GLP-1R are expressed in >90% of insulinomas and this case underlines the utility of GLP-1R PET/CT in insulinoma localisation.

Catecholamine-Producing Adrenal Schwannoma: A Rare Pheochromocytoma Imposter

Abstract Background:Adrenal schwannoma is a tumor of the adrenal medulla that poses a pre-operative diagnostic challenge due to its non-specific imaging findings and rarity. Even more uncommon are functional catecholamine-producing adrenal schwannomas (CPAS) that can lead to the clinical presentation of catecholamine excess. Here, we present a case of biochemically and histopathologically confirmed CPAS and provide a review of the existing cases in the literature. Clinical Case: A 43-year old woman with a history of hypertension was incidentally found to have a 4 cm left adrenal lesion. Computed tomography of the mass demonstrated indeterminate enhancement and washout characteristics. Upon evaluation, she had episodes of palpitations and fatigue without headache or flushing. Her medications were notable for metoprolol, vortioxetine, and lisdexamfetamine. Laboratory results were notable for elevated 24-hour urine metanephrine and normetanephrine of 551 mcg/24hr (normal: 58–203 mcg/24hr) and 927 mcg/24hr (normal: 88–649 mcg/24hr) respectively. Due to the possibility of pheochromocytoma, the patient elected for surgery and underwent laparoscopic left adrenalectomy after pre-treatment with an alpha-1-antagonist. Pathology demonstrated a 4.8 cm well-circumscribed tumor arising from the adrenal medulla that showed mostly hypercellular areas of spindled cells with wavy nuclei and focal nuclear palisading along with hypocellular areas with loose edematous stroma with focal areas of calcification and microcyst formation. IHC of the tumor cells was diffusely positive for S-100 and SOX-10, consistent with adrenal schwannoma. Laboratory results approximately 2 months post-operative on the same medications demonstrated normalization of 24-hour urine metanephrine and normetanephrine, confirming CPAS. A search of PubMed was performed using the search terms “adrenal schwannoma,” which returned 41 reports, of which 2 confirmed CPAS. Of the 3 cases, including ours, patients had a mean age of 44 years old and M:F ratio of 1:2. Each of the 3 tumors were left-sided with sizes ranging from 4.8 cm to 7.7 cm, which were all surgically removed. In the two previously published reports, the reported pre-operative laboratory markers were serum catecholamines and urine catecholamines, respectively, but neither compared levels to a reference range. In all cases, catecholamine levels normalized following surgical removal. Conclusion: Adrenal schwannoma is a rare entity in the differential diagnosis of non-functioning adrenal incidentaloma, but it should be considered for catecholamine-producing adrenal tumors as well. A summary of published cases suggests that these are typically large tumors with possible female predominance. This case is the first to document levels of catecholamine metabolite concentrations in CPAS.

Papillary Thyroid Carcinoma Within Thyroglossal Duct Cyst

A 55-year-old female with medical history of hypothyroidism and fibrocystic disease of the breast presented with complains of a painful anterior neck mass, difficulty swallowing and hoarseness of the voice. Symptoms had progressed over a period of 5 months. CT neck with contrast indicated the presence of an ectopic thyroid tissue anterior to the thyroid cartilage measuring approximately 1.7 x 1.2 x 3.1 cm, with indistinct inferior margins and internal calcifications. The hyoid bone or thyroid cartilage had no irregularities. The thyroid gland itself was unremarkable except for small complex thyroid nodules in both lobes. No masses within the pharynx or larynx were noted.Family history was significant for lymphoma in her father.On physical exam, a hard, mobile right anterior neck mass was appreciated. Labs showed normal TSH of 1.05 uIU/mL and normal free T4 of 1.2 ng/dL.Further evaluation with a dedicated neck US showed a right submandibular mass, superior to the thyroid, lobulated and heterogeneous measuring 2.0 x 1.0 x 2.3 cm with multiple areas of calcifications and internal Doppler flow. The thyroid gland had normal size and texture with bilateral sub centimeter non-concerning nodules.After ENT evaluation and an unremarkable flexible fiberoptic nasolaryngoscope, patient underwent surgical excisional biopsy of the neck mass. Pathology was consistent with thyroglossal duct cyst with the presence of thyroid follicles. An incidental finding of a 0.9 cm papillary microcarcinoma was noted, which was encapsulated with focal extracapsular follicular structures showing papillary nuclear features with no perineural or lymphovascular invasion. The tumor cells were immunoreactive for TTF-1 and PAX8.Development of papillary thyroid cancer within the thyroglossal duct cyst is a rare event, reportedly occurring in 1% of thyroglossal duct cysts. There are no well-established management guidelines.Current management strategies consist of monitoring with serial neck ultrasound versus total thyroidectomy with consideration of postsurgical I-131 treatment, based on pathology results. Our patient opted for undergoing total thyroidectomy.

Multi-Material Decomposition for Single Energy CT Using Material Sparsity Constraint.

Multi-material decomposition (MMD) decomposes CT images into basis material images, and is a promising technique in clinical diagnostic CT to identify material compositions within the human body. MMD could be implemented on measurements obtained from spectral CT protocol, although spectral CT data acquisition is not readily available in most clinical environments. MMD methods using single energy CT (SECT), broadly applied in radiological departments of most hospitals, have been proposed in the literature while challenged by the inferior decomposition accuracy and the limited number of material bases due to the constrained material information in the SECT measurement. In this paper, we propose an image-domain SECT MMD method using material sparsity as an assistance under the condition that each voxel of the CT image contains at most two different elemental materials. L0 norm represents the material sparsity constraint (MSC) and is integrated into the decomposition objective function with a least-square data fidelity term, total variation term, and a sum-to-one constraint of material volume fractions. An accelerated primal-dual (APD) algorithm with line-search scheme is applied to solve the problem. The pixelwise direct inversion method with the two-material assumption (TMA) is applied to estimate the initials. We validate the proposed method on phantom and patient data. Compared with the TMA method, the proposed MSC method increases the volume fraction accuracy (VFA) from 92.0% to 98.5% in the phantom study. In the patient study, the calcification area can be clearly visualized in the virtual non-contrast image generated by the proposed method, and has a similar shape to that in the ground-truth contrast-free CT image. The high decomposition image quality from the proposed method substantially facilitates the SECT-based MMD clinical applications.

Complex fibroadenoma with focal ossification- an enigmatic finding in a less common tumor

Breast lumps have diverse causes including benign as well as malignant lesions. Fibroadenoma (FA) is a common cause of breast lump. Complex fibroadenomas, a particular subtype, pose diagnostic dilemmas due to confusing the radiological findings and hold higher incidence of transformation to malignancy. A 49 year old female presented with a painless lump in right breast for 2 years which appeared calcified on radiology. Excision biopsy was performed which grossly revealed an encapsulated grey-white firm to hard with cystic areas. Microscopically the sections showed a well encapsulated fibroepithelial tumor showing areas of sclerosing adenosis, hyalinization, cysts lined by cuboidal cells with eosinophilic secretions, areas of calcification and ossification. No evidence of lobular hyperplasia or in-situ carcinoma was seen. Patient was advised follow up. This case represents the unusual occurrence of complex fibroadenoma in a middle-aged female showing with ossification.

Colocalization of Erythrocytes and Vascular Calcification in Human Atherosclerosis: A Systematic Histomorphometric Analysis.

Background Intimal calcification typically develops in advanced atherosclerosis, and microcalcification may promote plaque progression and instability. Conversely, intraplaque hemorrhage and erythrocyte extravasation may stimulate osteoblastic differentiation and intralesional calcium phosphate deposition. The presence of erythrocytes and their main cellular components (membranes, hemoglobin, and iron) and colocalization with calcification has never been systematically studied. Methods and Results We examined three types of diseased vascular tissue specimens, namely, degenerative aortic valve stenosis ( n = 46), atherosclerotic carotid artery plaques ( n = 9), and abdominal aortic aneurysms ( n = 14). Biomaterial was obtained from symptomatic patients undergoing elective aortic valve replacement, carotid artery endatherectomy, or aortic aneurysm repair, respectively. Serial sections were stained using Masson–Goldner trichrome, Alizarin red S, and Perl's iron stain to visualize erythrocytes, extracelluar matrix and osteoid, calcium phosphate deposition, or the presence of iron and hemosiderin, respectively. Immunohistochemistry was employed to detect erythrocyte membranes (CD235a), hemoglobin or the hemoglobin scavenger receptor (CD163), endothelial cells (CD31), myofibroblasts (SMA), mesenchymal cells (osteopontin), or osteoblasts (periostin). Our analyses revealed a varying degree of intraplaque hemorrhage and that the majority of extravasated erythrocytes were lysed. Osteoid and calcifications also were frequently present, and erythrocyte membranes were significantly more prevalent in areas with calcification. Areas with extravasated erythrocytes frequently contained CD163-positive cells, although calcification also occurred in areas without CD163 immunosignals. Conclusion Our findings underline the presence of extravasated erythrocytes and their membranes in different types of vascular lesions, and their association with areas of calcification suggests an active role of erythrocytes in vascular disease processes.

Relationship between calcification, atherosclerosis and matrix proteins in the human aorta

Extracellular matrix (ECM) proteins have been associated with atherosclerotic complications, such as plaque rupture, calcification and aneurysm. It is not clear what role different types of collagen play in the pathomechanism of atherosclerosis. The aim of the study was to analyze the content of elastin and major types of collagen in the aortic wall and how they associated are with course of atherosclerosis. . In this work we present six biochemical parameters related to ECM proteins (collagen type I, III, and IV, elastin, proline and hydroxyproline) analyzed in 106 patients' aortic wall specimens characterized by different degree of atherosclerosis. Liquid Chromatography Electrospray Ionization Tandem Mass Spectrometry (LC/ESI-MS/MS), ELISA and immunohistochemical methods were used. The severity of atherosclerosis was assessed on the six-point scale of the American Heart Association, taking into account the number and location of foam cells, the presence of a fatty core, calcium deposits and other characteristic atherosclerotic features. The results show that there is a relationship between the content of collagen-specific amino acids and development of atherosclerosis. The degree of atherosclerotic lesions was negatively correlated with the content of proline, hydroxyproline and the ratio of these two amino acids. Calcium deposits and surrounding tissue were compared and it was demonstrated that the ratio of type I collagen to type III collagen was higher in the aortic tissue than in aortic calcification areas, while the ratio of collagen type III to elastin was smaller in the artery than in the calcium deposits. We suggest that increase in collagen type III presence in the calcification matrix may stem from disorders in the structure of the type I and III collagen fibers. These anomalous fibers are likely to favor accumulation of the calcium salts, an important feature of the atheromatotic process.