Distribution Analysis of Iron and Copper by STEM-EDX Spectroscopy of Hemosiderin Particles in the Liver of Rats Overloaded With Iron.

BACKGROUND/AIM: Our recent studies have indicated that trace copper co-existed with iron in hemosiderin particles of human genetic iron overload. To understand this phenomenon, we analyzed hemosiderin particles in iron-overloaded rat liver by using scanning transmission electron microscopy - energy-dispersive X-ray (STEM-EDX) spectroscopy. MATERIALS AND METHODS: Samples for STEM-EDX spectroscopy were prepared from the liver of rats administered an intraperitoneal injection of dextran iron. RESULTS: The micro-domain analysis with STEM-EDX spectroscopy showed that dense bodies contained high levels of iron and trace copper. Quantitative analysis of copper levels in the liver specimen using atomic spectrophotometry showed that copper concentration in the liver was not increased by iron overload. These findings suggest that the overload of iron induced distribution of trace copper to hemosiderin particles without changing cellular copper levels. CONCLUSION: Co-existence of copper with iron was observed in hemosiderin particles of the liver of an experimental model of iron overload, suggesting that iron overload induced distribution of trace copper into hemosiderin particles.

Assessment of Imaging Findings of Renal Carcinoma Subtypes with 3.0T MRI.

BACKGROUND: The prevalence of renal masses has escalated as a result of the augmented utilization of cross-sectional imaging techniques. The approach to managing renal masses may exhibit variability contingent upon the subtype of renal cell carcinoma (RCC). AIM: This research aimed to distinguish between clear cell and papillary RCCs, utilizing dynamic contrast magnetic resonance imaging (MRI) and diffusion-weighted imaging (DWI). MATERIALS AND METHODS: The study assessed the MR images of 112 patients with RCC. Two radiologists independently analyzed tumor size, vascular involvement, signal characteristics in T1- and T2-weighted sequences, the presence of hemosiderin, both microscopic and macroscopic fat content, enhancement patterns, and apparent diffusion coefficient (ADC) values derived from b-values of 1000 s/mm². RESULTS: Seventy patients had clear cell RCC, and 42 had papillary. In the clear cell RCC, microscopic fat content was significantly higher than the papillary RCC (P < 0.001). However, in papillary RCC, hemosiderin content was substantially greater (P = 0.001). On T2-weighted MR images, clear cell RCCs were usually hyperintense, while papillary RCCs were hypointense (P < 0.001). Even though the rapid enhancement pattern was observed in clear cell RCCs, the progressive enhancement pattern was more prevalent in papillary RCCs (P < 0.001). CONCLUSION: Hyperintensity on T2-weighted images, microscopic fat content, and rapid enhancement pattern may be indicative of clear cell RCC, whereas hypointensity on T2-weighted images, hemosiderin content, and a progressive contrast pattern may be diagnostic for papillary RCC.

Comparison of four different displays for identification of select pathologic features extracted from whole slide images of surgical pathology cases.

BACKGROUND: The establishment of minimum standards for display selection for the whole slide image (WSI) interpretation has not been fully defined. Recently, pathologists have increasingly preferred using remote displays for clinical diagnostics. Our study aims to assess and compare the performance of three fixed work displays and one remote personal display in accurately identifying ten selected pathologic features integrated into WSIs. DESIGN: Hematoxylin and eosin-stained glass slides were digitized using Philips scanners. Seven practicing pathologists and three residents reviewed ninety WSIs to identify ten pathologic features using the LG, Dell, and Samsung and an optional consumer-grade display. Ten pathologic features included eosinophils, neutrophils, plasma cells, granulomas, necrosis, mucin, hemosiderin, crystals, nucleoli, and mitoses. RESULTS: The accuracy of the identification of ten features on different types of displays did not significantly differ among the three types of "fixed" workplace displays. The highest accuracy was observed for the identification of neutrophils, eosinophils, plasma cells, granuloma, and mucin. On the other hand, a lower accuracy was observed for the identification of crystals, mitoses, necrosis, hemosiderin, and nucleoli. Participant pathologists and residents preferred the use of larger displays (>30″) with a higher pixel count, resolution, and luminance. CONCLUSION: Most features can be identified using any display. However, certain features posed more challenges across the three fixed display types. Furthermore, the use of a remote personal consumer-grade display chosen according to the pathologists' preference showed similar feature identification accuracy. Several factors of display characteristics seemed to influence pathologists' display preferences such as the display size, color, contrast ratio, pixel count, and luminance calibration. This study supports the use of standard "unlocked" vendor-agnostic displays for clinical digital pathology workflow rather than purchasing "locked" and more expensive displays that are part of a digital pathology system.

Hemosiderin induced acute kidney injury requiring hemodialysis in patients with paroxysmal nocturnal hemoglobinuria: A case report.

RATIONALE: Paroxysmal nocturnal hemoglobinuria (PNH) is a rare hematopoietic stem cell disease with features of hemolytic anemia, thrombosis, and bone marrow failure. Due to intravascular hemolysis and hemoglobinuria, renal dysfunction is often accompanied in PNH patients. PATIENT CONCERNS: A 25-year old woman presenting gross hematuria after coronavirus disease 2019 infection was admitted to our medical center. She had mild nausea and headache. She was diagnosed with iron deficiency anemia few years ago and had no other underlying disease. Her laboratory findings showed acute kidney injury (AKI) and severe anemia, with evidences of hemolysis. DIAGNOSIS: Renal biopsy was done to determine the cause of renal failure and the result was acute tubular necrosis with deposition of golden pigments, hemosiderin. With pathologic result and laboratory finding of hemolysis, we did flow cytometry for PNH, and the patient was finally diagnosed with PNH. INTERVENTIONS: With AKI and oliguria, the patient started to take hemodialysis. OUTCOMES: After taking 5 sessions of hemodialysis, the patient's renal function was recovered from AKI. With diagnosis of PNH, the patient is now being treated with complement C5 inhibitor. LESSONS: This challenging case tells us that we should consider the first manifestation of PNH as a cause of severe AKI requiring hemodialysis in a patient with anemia and evidence of hemolysis.

Case report: a case of primary intracranial parasagittal meningeal angiosarcoma.

BACKGROUND: Angiosarcoma, also known as malignant hemangioendothelioma, is a rare vasogenic malignant tumor, commonly found on the skin of the head and neck, rarely occurring in the intracranial region. As for intracranial meningeal angiosarcoma, only 8 cases have been reported before and there is no clinical study with large sample size. We report here a case of parasagittal meningeal angiosarcoma. CASE DESCRIPTION: A 48-year-old Chinese male patient was admitted to our hospital due to headache accompanied by bilateral lower limb weakness. On admission, CT showed a high-density mass on both sides of the sagittal sinus at the top of the frontal lobe. We performed exploratory surgical resection of the tumor. During the operation, it was found that the tumor originated from the dura mater and extensively invaded the surrounding brain tissue and skull, and the surrounding hemosiderin deposition was observed. Postoperative pathology suggested angiosarcoma. CONCLUSIONS: Intracranial meningeal angiosarcoma is difficult to accurately diagnose before surgery, so radiologists and neurosurgeons need to strengthen their understanding of this disease. The presence of extensive superficial hemosiderin deposition during operation may contribute to the diagnosis, and immunohistochemistry is very important for the diagnosis of intracranial angiosarcoma.

Histotripsy Treatment of Murine Brain and Glioma: Temporal Profile of Magnetic Resonance Imaging and Histological Characteristics Post-treatment.

OBJECTIVE: Currently, there is a knowledge gap in our understanding of the magnetic resonance imaging (MRI) characteristics of brain tumors treated with histotripsy to evaluate treatment response as well as treatment-related injuries. Our aim was to bridge this gap by investigating and correlating MRI with histological analysis after histotripsy treatment of mouse brain with and without brain tumors and evaluating the evolution of the histotripsy ablation zone on MRI over time. METHODS: An eight-element, 1 MHz histotripsy transducer with a focal distance of 32.5 mm was used to treat orthotopic glioma-bearing mice and normal mice. The tumor burden at the time of treatment was ∼5 mm3. T2, T2*, T1 and T1-gadolinium (Gd) MR images and histology of the brain were acquired on days 0, 2 and 7 for tumor-bearing mice and days 0, 2, 7, 14, 21 and 28 post-histotripsy for normal mice. RESULTS: T2 and T2* sequences most accurately correlated with histotripsy treatment zone. The treatment-induced blood products, T1 along with T2, revealed blood product evolution from oxygenated, de-oxygenated blood and methemoglobin to hemosiderin. And T1-Gd revealed the state of the blood-brain barrier arising from the tumor or histotripsy ablation. Histotripsy leads to minor localized bleeding, which resolves within the first 7 d as evident on hematoxylin and eosin staining. By day 14, the ablation zone could be distinguished only by the macrophage-laden hemosiderin, which resides around the ablation zone, rendering the treated zone hypo-intense on all MR sequences. CONCLUSION: These results provide a library of radiological features on MRI sequences correlated to histology, thus allowing for non-invasive evaluation of histotripsy treatment effects in in vivo experiments.

Cytopathological findings of intranodal palisaded myofibroblastoma: Case report and review of the literature.

INTRODUCTION: Intranodal palisaded myofibroblastoma (IPM) is an exceedingly rare benign mesenchymal tumor of the lymph nodes. Magnetic resonance imaging (MRI) findings are unspecific, which may present diagnostic challenges to fine-needle aspiration cytology (FNAC). The histological and immunohistochemical features of IPM are unique. CASE REPORT: A previously healthy 40-year-old male patient presented a slow-growing solitary left inguinal mass. FNAC revealed clustered cells within a metachromatic stroma, single spindle cells without atypia, hemosiderin pigment, and siderophages. An MRI showed a central hyperintense septum in fat-suppressed, T2-weighted sequences. The excised lymph node contained central haphazard fascicles of spindle cells with focal nuclear palisading, hemosiderin pigment, extravasated erythrocytes, and hemorrhagic areas. Vimentin and smooth muscle actin were diffusely positive. Amianthoid collagen fibers were not clearly observed. CONCLUSION: IPM is an extremely rare mesenchymal benign intranodal tumor that should be included in the differential diagnosis of spindle cell lesions in the inguinal region.

Corneal Perforation as a Rare and Late Manifestation of Choroidal Melanoma.

PURPOSE: To report a case of corneal perforation as a rare and late manifestation of choroidal melanoma and to highlight the major histopathological findings of this unusual combined clinical presentation. METHODS: A 74-year-old male patient presented to our department due to corneal perforation of the right eye with the absence of light perception for 6 months. The intraocular pressure was hard on palpation. Because of the protracted finding and reduced visual prognosis, primary enucleation was performed. RESULTS: The histopathological examination revealed choroidal melanoma with epithelioid and spindle cell components at the posterior pole, which was positive for Melan-A, Human Melanoma Black 45 (HMB45), BAP1, and SOX10. The anterior segment showed complete anterior chamber hemorrhage and blood remnants in the trabecular meshwork. The cornea displayed diffuse blood staining with hemosiderin and hemosiderin-loaded macrophages and keratocytes. No inflammatory cells were present near the corneal perforation, which had a width of 3 mm. Intraocular heterotopic ossification was indicative of a long-standing condition. Postoperative cancer staging was normal. CONCLUSION: Corneal perforation should be considered as a very rare and late manifestation of advanced choroidal melanoma and may result from interaction between intraocular hemorrhage, elevated IOP, and its secondary signs such as corneal blood staining.

Technical note: Improved differentiation of calcification from hemosiderin using paramagnetic- and diamagnetic-specific magnetic resonance susceptibility weighted imaging (p-SWI, d-SWI).

INTRODUCTION: Differentiation of calcification and calcium-containing tissue from blood products remains challenging using magnetic resonance imaging (MRI). We developed a novel post-processing algorithm which creates both paramagnetic- and diamagnetic-specific SWI images generated from T2* weighted images using distinct "positive" and "negative" phase masks. METHODS: 10 patients who had undergone clinical MRI scanning of the brain with a rapid echo planar based T2*-weighted EPI-GRE pulse sequence with evidence for either hemosiderin and/or calcifications were retrospectively identified. Complex raw k-space data from individual imaging coils were then extracted, reconstructed, and appropriately combined to produce magnitude and phase images using a phase preserving method. The final reconstructed images included the T2* EPI-GRE magnitude images, p-SWI and d-SWI images. Filtered phase images were also available for review. Correlation with CT scans and MR imaging appearance over time corroborated the composition of the voxels. RESULTS: Differential "blooming" of diamagnetic and paramagnetic foci was readily identified on the corresponding p-SWI and d-SWI images and provided fast and reliable visual differentiation of diamagnetic from paramagnetic susceptibility effects by ascertaining which of the two images depicted the greatest "blooming" effect. Correlation with the available filtered phase maps was not necessary for differentiation of paramagnetic from diamagnetic image components. CONCLUSION: Clinical interpretation of SWI images can be further enhanced by creating specific p-SWI and d-SWI image pairs which contain greater visual information than the combination of standard p-SWI images and phase image.

Pediatric Cerebral Cavernous Malformation: A Single-Centered Experience of 23 Cases.

AIM: To describe, and to evaluate the clinical and radiological characteristics of pediatric cavernous malformations (CMs) and the surgical approaches and their outcomes in a single center. MATERIAL AND METHODS: We retrospectively reviewed pediatric patients with CMs that were treated in our center between 2010 and 2020. Radiological, clinical, and demographic features, as well as treatment details were evaluated. RESULTS: Of 23 patients, 12 were male, and 11 were female. Two patients with multiple CMs had a family history. The most common symptoms were headaches (9/23, 39.1%) and seizures (9/23, 39.1%). Twenty patients had single lesions and three patients had multiple lesions. According to Zabramski classification, eight (34.7%) patients had type 1, 11 (47.8%) had type 2 and four (17.3%) had type 3 lesions. Thirteen patients had recurrent preoperative hemorrhages and nine had increased lesion size. Seven patients (30.4%) had coexisting deep venous anomalies in the CM vicinity. Twenty-one patients underwent microsurgical resection (5/23 simple lesionectomy, 16/23 lesionectomy + resection of the surrounding hemosiderin ring). All lesions were completely resected. No surgical mortalities or major complications occurred. CONCLUSION: Since pediatric CMs are more aggressive than adult CMs, they should not be underestimated. Microsurgical total resection should be the first treatment choice where possible. We concluded that early surgical treatment and resection of perilesional hemosiderin-stained tissue, when feasible, yield the most favorable results at long-term follow-up including seizure outcomes.

Clinical characteristics and risk factors of cerebral cavernous malformation-related epilepsy.

PURPOSE: This study aimed to summarize the clinical characteristics and explore the risk factors for cerebral cavernous malformation (CCM)-related epilepsy (CRE). METHODS: We retrospectively analyzed the clinical data of patients with CCM in our cerebral vascular malformations database. Descriptive statistics were used to present the clinical characteristics of CRE patients. Patients were divided into a CRE and a non-CRE group according to clinical presentation. Binary logistic regression analysis was used to analyze the risk factors of CRE. RESULTS: A total of 199 patients with CCM confirmed by postoperative pathological examination were enrolled, 93 of whom were diagnosed with CRE, and 34 patients had drug-resistant epilepsy. The most common seizure type of CRE patients was focal to bilateral tonic-clonic seizure (FBTCS), followed by focal impaired awareness motor seizure. All CCM lesions were supratentorial, 97.8% of which involved the cerebral cortex, 86.0% of lesions had hemosiderin rim, and 50.5% of lesions were located in the temporal lobe. Binary logistic regression analysis indicated that CCM diagnosis age ≤ 44 years (odds ratio [OR] 2.79, p = 0.010), temporal lobe lesion location (OR = 9.07, p = 0.042), medial temporal lobe lesion (OR = 14.09, p = 0.002), cortical involvement of the lesion (OR = 32.77, p = 0.010), and hemosiderin rim around the lesion (OR = 16.48, p = 0.001) significantly increased the risk of CRE. CONCLUSIONS: The most common seizure type of CRE was FBTCS. Those whose CCM diagnosis age was ≤ 44 years, having a temporal lobe lesion location, especially the medial temporal lobe lesion, cortical involvement, and hemosiderin rim around the lesion had a higher risk of developing CRE.

Iron cycle disruption by heme oxygenase-1 activation leads to a reduced breast cancer cell survival.

Heme oxygenase-1 (HO-1), which catalyzes heme degradation releasing iron, regulates several processes related to breast cancer. Iron metabolism deregulation is also connected with several tumor processes. However the regulatory relationship between HO-1 and iron proteins in breast cancer remains unclear. Using human breast cancer biopsies, we found that high HO-1 levels significantly correlated with low DMT1 levels. Contrariwise, high HO-1 levels significantly correlated with high ZIP14 and prohepcidin expression, as well as hemosiderin storage. At mRNA level, we found that high HO-1 expression significantly correlated with low DMT1 expression but high ZIP14, L-ferritin and hepcidin expression. In in vivo experiments in mice with genetic overexpression or pharmacological activation of HO-1, we detected the same expression pattern observed in human biopsies. In in vitro experiments, HO-1 activation induced changes in iron proteins expression leading to an increase of hemosiderin, ROS levels, lipid peroxidation and a decrease of the growth rate. Such low growth rate induced by HO-1 activation was reversed when iron levels or ROS levels were reduced. Our findings demonstrate an important role of HO-1 on iron homeostasis in breast cancer. The changes in iron proteins expression when HO-1 is modulated led to the iron accumulation deregulating the iron cell cycle, and consequently, generating oxidative stress and low viability, all contributing to impair breast cancer progression.

Arteriolosclerosis differs from venular collagenosis in relation to cerebrovascular parenchymal damages: an autopsy-based study.

BACKGROUND AND PURPOSE: Cerebrovascular parenchymal damage is prevalent in ageing brains; however, its vascular aetiology has not been fully elucidated. In addition to the underlying role of sclerotic arterioles, the correlation between collagenised venules has not been clarified. Here, we aimed to investigate the associations between microvascular injuries, including arteriolosclerosis and venular collagenosis, and related parenchymal damages in ageing brains, to investigate the underlying correlations. METHODS: We evaluated arteriolosclerosis and venular collagenosis in 7 regions from 27 autopsy cases with no history of stroke or brain tumour. The correlations between the ratio of arteriolosclerosis, venular collagenosis and the severity of cerebrovascular parenchymal damage, including lacunes, microinfarcts, myelin loss, and parenchymal and perivascular haemosiderin deposits, were assessed. RESULTS: Arteriolosclerosis and venular collagenosis became more evident with age. Arteriolosclerosis was associated with lacunes (p=0.004) and brain parenchymal haemosiderin deposits in the superior frontal cortex (p=0.024) but not with leukoaraiosis severity. Venular collagenosis was not associated with the number of lacunes or haemosiderin, while white matter generally became paler with severe venular collagenosis in the periventricular (ß=-0.430, p=0.028) and deep white matter (ß=-0.437, p=0.025). CONCLUSION: Our findings imply an important role for venular lesions in relation to microvessel-related parenchymal damage which is different from that for arteriolosclerosis. Different underlying mechanisms of both cerebral arterioles and venules require further investigation.

The Acute Superficial Siderosis Syndrome - Clinical Entity, Imaging Findings, and Histopathology.

Superficial siderosis is a consequence of repetitive bleeding into the subarachnoid space, leading to toxic iron and hemosiderin deposits on the surface of the brain and spine. The clinical and radiological phenotypes of superficial siderosis are known to manifest over long time intervals. In contrast, this study defines the "acute superficial siderosis syndrome" and illustrates typical imaging and histopathological findings of this entity. We describe the case of a 61-year-old male patient who was diagnosed with a melanoma metastasis in the right frontal cortex in February 2019. Within a few weeks he developed a progressive syndrome characterized by cerebellar ataxia, gait disturbance, signs of myelopathy, and radiculopathy. MRI revealed ongoing hemorrhage from the metastasis into the lateral ventricle and the subarachnoid space. A semiquantitative assessment of three subsequent MRI within an 8-week period documented the rapid development of superficial siderosis along the surface of the cerebellum, the brain stem, and the lower parts of the supratentorial regions on T2*-weighted sequences. The diagnosis of a superficial siderosis was histopathologically confirmed by identifying iron and hemosiderin deposits on the cortex along with astrogliosis. The recognition of this "acute superficial siderosis syndrome" triggered surgical removal of the hemorrhagic metastasis. Based on a single case presentation, we define the "acute superficial siderosis syndrome" as a clinical entity and describe the radiological and histopathological characteristics of this entity. Early recognition of this syndrome may allow timely elimination of the bleeding source, in order to prevent further clinical deterioration.

Magnetic Resonance Imaging Features and Misdiagnosis of Spinal Epidural Cavernous Hemangioma.

OBJECTIVE: Spinal epidural cavernous hemangiomas (SECHs) are rare, and merely a few have previously been described in case reports. The present study aims to explore the magnetic resonance imaging (MRI) features of SECHs and analyze the causes of their preoperative misdiagnosis. METHODS: The present retrospective study included 11 patients (three male and eight female patients, mean age ± standard deviation: 47.55±17.39 years old) with histopathologically confirmed SECH between January 2015 and April 2021. The MRI features of SECH were analyzed by two radiologists. RESULTS: The cervical, thoracic and thoracolumbar segments were involved in 2, 7 and 2 patients, respectively. All lesions grew along the long axis of the spine. The tumors were shuttle-shaped in six patients, oval in two patients, pseudopodia-shaped in one patient, clamp-shaped in one patient, and growing outward along the intervertebral foramen in one patient. Nine SECHs had relatively uniform isointense or hypointense T1-weighted imaging (T1WI) and hyperintense T2-weighted imaging (T2WI) signals. On the T2WI, filamentary low-signal shadows (i.e., the hairline or grid sign) with significant contrast enhancement and asymptotic strengthening were observed. Two SECHs had mixed high and low signals on T1WI and T2WI, with significant heterogeneous enhancement, hemorrhage, and hemosiderin deposition. The SECH was misdiagnosed as meningioma, neurofibromatosis and schwannoma in 1, 1 and 4 patients, respectively, while this was not diagnosed in one patient. The preoperative diagnosis was correct in merely approximately 36% of patients. Among the four patients with a correct preoperative diagnosis, hemosiderin deposition was found in three patients and small tortuous vascular shadows were found in one patient. CONCLUSION: SECH presents as a long spindle-shaped mass, and the "'pen cap sign" is common at the lesion edges. SECH also exhibits a hairline or grid sign on T2WI. Furthermore, some lesions present with hemorrhage and hemosiderin deposition. Therefore, the hairline, grid sign and hemosiderin deposition are valuable diagnostic features of SECH.

Tenosynovial giant cell tumors of digits: MRI differentiation between localized types and diffuse types with pathology correlation.

OBJECTIVE: To compare the MRI findings between the localized- and diffuse-type tenosynovial giant cell tumors (TSGCTs) of digits with pathology correlation. METHODS: Twenty-eight patients with newly diagnosed TSGCTs of digits (22 localized and 6 diffuse types) who underwent preoperative MRI and surgical excision were included from Jan. 2015 to September 2021. MRI findings regarding nodularity, margins, morphology of hypointensity with pathology correlation, and disease extent (bone erosion, articular involvement, muscle involvement, tendon destruction, and neurovascular encasement) were assessed. RESULTS: Diffuse type was significantly larger (P = 0.006), more multinodular on both MRI and pathology (P = 0.038, both) with significant agreement, and infiltrative on both MRI and pathology (P < 0.001, both) with substantial agreement, and showed central granular on MRI and strong hemosiderin deposition on pathology (P = 0.022 and P = 0.021) with moderate agreement than localized type. Localized type showed significantly more frequent peripheral capsules on both MRI and pathology (P < 0.001, both) with moderate agreement than diffuse type. However, the septum on both MRI and pathology showed no statistically significant difference between the two groups (P = 0.529 and P = 0.372) without significant agreement. The disease extent was more severe in the diffuse type than the localized type regarding articular involvement (P < 0.001), muscle involvement (P < 0.001), and tendon destruction (P = 0.010). No statistically significant differences were found between the two groups regarding bone erosion (P = 0.196) or neurovascular bundle encasement (P = 0.165). CONCLUSIONS: Diffuse-type TSGCTs of digits presented as locally aggressive lesions with larger, multinodular, infiltrative masses exhibiting stronger hemosiderin deposition and more severe disease extents of articular, muscle, and tendon involvement than the localized type.

Pathologic characteristics of human venous in-stent stenosis and stent occlusion.

OBJECTIVE: The objective of this study was to determine the pathologic features of venous in-stent stenosis over time occurring in bare metal stents. METHODS: Endovascular biopsy samples were obtained prospectively from venous bare metal stents implanted in 2009 through 2018. All samples were formalin-fixed, paraffin-embedded and stained with hematoxylin and eosin. Samples were examined by a cardiovascular pathologist to estimate the amount of its constituent components, which included fresh thrombus, organizing thrombus, old thrombus, or diffuse intimal thickening (DIT), and pathologic features including calcification, neovascularization, and hemosiderin deposition. This pathologic characterization was correlated with time following stent implantation to discern time-dependence of pathologic evolution of in-stent stenosis using both descriptive statistics and binary logistic regression. RESULTS: A total of 254 post-stent venograms with biopsies of in-stent contents from 148 unique patients were studied. Fresh thrombus and organizing thrombus were both present across all studied time intervals. Old thrombus was seen beginning at approximately 2 weeks and DIT at approximately 4 weeks. Calcification was a rare finding encountered at later time intervals. The prevalence of each component varied with time: the probability of encountering fresh thrombus (P = .010) and organizing thrombus (P = .008) decreased over time. By contrast, the probability of finding DIT (P = .002) and calcifications (P < .001) increased over time. The presence of old thrombus, neovascularization, or hemosiderin did not demonstrate time dependence. Diffuse intimal thickening was frequently seen along with organizing thrombus as well as independently, and in many instances, these two features were directly merged. CONCLUSIONS: The evolution of human venous in-stent restenosis appears to follow a time-dependent course, suggesting a possible progressive evolution from fresh and organizing thrombus to DIT. Contrasted with the literature on arterial in-stent restenosis, vein in-stent restenosis may have an increased thrombus prevalence (both organizing and old thrombus). DIT is a primary feature of late in-stent stenosis and may explain in part why many of these lesions may not respond to thrombolytic or anticoagulant treatment alone.

Hemosiderin-Laden Macrophages in Bronchoalveolar Lavage Samples of Children with Bronchopulmonary Dysplasia.

OBJECTIVES: To evaluate the prevalence of hemosiderin-laden macrophages in children with bronchopulmonary dysplasia (BPD) and assess for an association between hemosiderin-laden macrophages and pulmonary arterial hypertension. STUDY DESIGN: Retrospective case-control study of infants and children with and without BPD who underwent bronchoscopy with bronchoalveolar lavage (BAL) the at Children's Hospital of Philadelphia between 2012 and 2021. RESULTS: BAL from 205 children with BPD and 106 controls without BPD matched for tracheostomy, infection, and age were reviewed for hemosiderin-laden macrophages. Seventy-one individuals (34.6%) with BPD had a BAL with 10% or more hemosiderin-laden macrophages compared with 3 (2.8%) controls (P < .0001; OR, 18.19; 95% CI, 5.57-59.41). Patients with pulmonary hypertension by echocardiogram (P = .04; OR, 3.69; 95% CI, 1.05-12.96) or an elevated mean pulmonary artery pressure during cardiac catheterization, rs (14) = 0.56, P = .04, were more likely to have elevated hemosiderin-laden macrophages on BAL samples less than 60 days from bronchoscopy. After adjusting for birth weight, gestational age, BPD grade, and age at the time of bronchoscopy using logistic regression, pulmonary hypertension was associated with a higher odds of hemosiderin-laden macrophages of 10% or more (P = .02; OR, 6.37; 95% CI, 1.28-31.87). No association was observed between hemosiderin-laden macrophages and sex, race, gestational age, birth weight, tracheostomy, or infectious studies. CONCLUSIONS: This retrospective study revealed increased hemosiderin-laden macrophages in BAL samples from patients with BPD and a significant association with pulmonary arterial hypertension. It is unclear whether elevated hemosiderin-laden macrophages within BPD contributes to the pathogenesis of lung and pulmonary vascular disease or is simply a biomarker of pulmonary arterial hypertension.

Iron-laden blasts in refractory acute myeloid leukemia.

We report a case of refractory acute myeloid leukemia with DEK-NUP214 rearrangement showing circulating monocytic blasts with abundant green cytoplasmic granules on the Wright-Giemsa stain. The granules were strongly positive for Perls' Prussian blue, consistent with hemosiderin deposits. This previously unreported finding is suggestive of siderophage activity by leukemic blasts, likely associated with monocytic differentiation.

Obsessive-compulsive symptoms in ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome.

Symptoms of obsessive-compulsive disorder (OCD) may rarely occur in the context of genetic syndromes. So far, an association between obsessive-compulsive symptoms (OCS) and ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome has not been described as yet. A thoroughly phenotyped patient with OCS and ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome is presented. The 25-year-old male patient was admitted to in-patient psychiatric care due to OCD. A whole-exome sequencing analysis was initiated as the patient also showed an autistic personality structure, below average intelligence measures, craniofacial dysmorphia signs, sensorineural hearing loss, and sinus cavernoma as well as subtle cardiac and ophthalmological alterations. The diagnosis of Baraitser-Winter cerebrofrontofacial syndrome type 2 was confirmed by the detection of a heterozygous likely pathogenic variant in the ACTG1 gene [c.1003C > T; p.(Arg335Cys), ACMG class 4]. The automated analysis of magnetic resonance imaging (MRI) revealed changes in the orbitofrontal, parietal, and occipital cortex of both sides and in the right mesiotemporal cortex. Electroencephalography (EEG) revealed intermittent rhythmic delta activity in the occipital and right temporal areas. Right mesiotemporal MRI and EEG alterations could be caused by a small brain parenchymal defect with hemosiderin deposits after a cavernomectomy. This paradigmatic case provides evidence of syndromic OCS in ACTG1-associated Baraitser-Winter cerebrofrontofacial syndrome. The MRI findings are compatible with a dysfunction of the cortico-striato-thalamo-cortical loops involved in OCD. If a common pathophysiology is confirmed in future studies, corresponding patients with Baraitser-Winter cerebrofrontofacial syndrome type 2 should be screened for OCS. The association may also contribute to a better understanding of OCD pathophysiology.