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We aim (a) to introduce an easy-to-perform multi-echo gradient-echo sequence (mGRE) for the detection of hemosiderin deposition in the ankle joints of boys with haemophilia (b) to explore the associations between the presence and severity of hemosiderin deposition and the other components of haemophilic arthropathy, the clinical score, and the number and chronicity of joint bleeds. An MRI of 41 ankle joints of 21 haemophilic boys was performed on a 3 T MRI system using an mGRE sequence in addition to the conventional protocol. Conventional MRI and mGRE were separately and independently assessed by three readers, namely, two musculoskeletal radiologists and a general radiologist for joint hemosiderin. We set as a reference the consensus reading of the two musculoskeletal radiologists, who also evaluated the presence of synovial thickening, effusion, and osteochondral changes. Excellent inter-reader agreement was obtained using the mGRE sequence compared to the conventional protocol (ICC: 0.95–0.97 versus 0.48–0.89), with superior sensitivity (90–95% versus 50–85%), specificity (95.2–100% versus 76.2–95.2%), and positive (95–100% versus 71–94.4%) and negative predictive value (91.3–95.5% versus 87–63%). Hemosiderin deposition was associated with osteochondral changes, synovial thickening, clinical score, and the total number of ankle bleeds, while it was inversely related with the time elapsed between the last joint bleed and MRI. (p < 0.05). The application of an mGRE sequence significantly improved hemosiderin detection, even when performed by the less experienced reader. Joint hemosiderin deposition was associated with the other components of haemophilic arthropathy and was mostly apparent in recent joint bleeds. [ABSTRACT FROM AUTHOR]

No studies have reported breast cancer cases developed in the chronic expanding hematoma (CEH). Case presentation: A 47-year-old woman was referred to our hospital for the treatment of a large breast mass. Ultrasound showed that the tumor had an intra-cystic tumor pattern. Magnetic resonance imaging (MRI) of the mass component showed a hypo intense pattern on T1-weighted images, a mosaic pattern on T2 weighted images, and a faint enhancement on time-signal intensity images. Core needle biopsy pathologically showed connective tissue, hematoma, and hemosiderin laden macrophages neither with any mammary gland components nor with malignant cells. These image findings and the presence of hemosiderin laden macrophages led us to the diagnosis of CEH despite the lack of prior breast surgery. The large tumor size of the presumed CEH and its tendency for rapid growth made us attempt to treat the breast lesion with lumpectomy. Frozen section, however, revealed malignant cells in the hard part of the capsule, leading to the conversion of breast surgery from lumpectomy to nipple-preserving mastectomy. Postoperative pathological study showed that the tumor was composed of atypical cells growing in cribriform, tubular, and papillary fashions. In addition to the malignant cells, cyst wall of the CEH had abundant fibrosis and hemosiderin deposits. This is the first CEH case after no prior breast surgery, which had breast cancer within it. When a breast CEH is suspected, careful follow-up is imperative to avoid underestimating a possible concomitant breast cancer.

Sickle cell disease patients have routinely been excluded from liver transplant donation due to patients historically manifesting liver disease themselves. Marginal donors have become increasingly more welcome given organ shortage. Our institution performed a liver transplant in a recipient with cholangiocarcinoma using a sickle cell disease donor liver. Postoperatively, patient progressed well and is now cancer free. Pathology indicated sickle cells, and hemosiderin present at time of transplant had largely resolved by repeat biopsy on postoperative day 5. We conclude that sickle cell disease patients should be considered as donors for liver transplant in the appropriate setting. [ABSTRACT FROM AUTHOR]

Superficial siderosis (SS) of the central nervous system is a rare disease characterized by deposition of hemosiderin along the leptomeninges due to chronic or recurrent bleeding into the subarachnoid space. The association of unruptured intracranial aneurysm (IA) and cortical SS is quite rare. A systematic literature review to assess possible commonalities and/or differences of previous reported cases was undertaken. We report an additional case from our institution. A 40-year-old woman presented with a history of generalized seizures over the past year. There was no clinical history suggestive of aneurysm rupture. Magnetic resonance imaging revealed 2 aneurysms of the right middle cerebral artery (MCA) bifurcation associated with hemosiderin deposition along the right sylvian fissure and a third aneurysm of the left MCA bifurcation. Magnetic resonance imaging showed wall enhancing thickening of the larger right MCA aneurysm. The patient underwent surgical clipping of all 3 MCA aneurysms in a staged procedure. Histological examination revealed hemosiderin deposits within the aneurysm wall and surrounding gliosis. Our literature review found 24 reported cases of unruptured IA associated with cortical SS. The possible source for leakages could be neovessels visible in IA walls. The case reported illustrates an uncommon presentation of recurrent bleeding from an IA as a source of SS. The presence of an apparently unruptured IA surrounded by cortical SS on imaging studies is of high relevance as this should be considered a sign of aneurysm wall instability and should indicate prompt treatment. [ABSTRACT FROM AUTHOR]

Cerebral microbleeds (CMBs) detected on magnetic resonance imaging are common in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). The neuropathologic correlates of CMBs are unclear. In this study, we characterized findings relevant to CMBs in autopsy brain tissue of 8 patients with genetically confirmed CADASIL and 10 controls within the age range of the CADASIL patients by assessing the distribution and extent of hemosiderin/iron deposits including perivascular hemosiderin leakage (PVH), capillary hemosiderin deposits, and parenchymal iron deposits (PID) in the frontal cortex and white matter, basal ganglia and cerebellum. We also characterized infarcts, vessel wall thickening, and severity of vascular smooth muscle cell degeneration. CADASIL subjects had a significant increase in hemosiderin/iron deposits compared with controls. This increase was principally seen with PID. Hemosiderin/iron deposits were seen in the majority of CADASIL subjects in all brain areas. PVH was most pronounced in the frontal white matter and basal ganglia around small to medium sized arterioles, with no predilection for the vicinity of vessels with severe vascular changes or infarcts. CADASIL subjects have increased brain hemosiderin/iron deposits but these do not occur in a periarteriolar distribution. Pathogenesis of these lesions remains uncertain.

Angiosarcoma is an uncommon cause of soft tissue malignancy, accounting for approximately 2% of all soft tissue sarcomas. Of these, epithelioid angiosarcoma represents a morphologic subtype, where the malignant endothelial cells demonstrate a predominantly or exclusively epithelioid appearance. Overall, epithelioid angiosarcoma shares similar imaging characteristics to conventional angiosarcoma including a T1 hypointense to isointense and T2 hyperintense mass, which demonstrates avid enhancement, serpentine feeding vessels, and overlying skin thickening on MRI. The case herein describes a case of epithelioid angiosarcoma in a 65-year-old female presenting with an enlarging calf mass and lower extremity pain. Initial imaging features, particularly on MRI, were highly unusual for angiosarcoma which was thus not strongly considered in the initial differential diagnosis. However, once diagnosis of epithelioid angiosarcoma was confirmed following resection, pathologic correlates were utilized to account for the unusual imaging findings retrospectively. The goal of this study is to not only describe an atypical presentation of an uncommon diagnosis but also attempt to rationalize the unexpected imaging findings with gross and microscopic correlates. Further, the utility of radiology-pathology correlation demonstrated in this case may be useful to others when evaluating similar lesions with unexpected MRI characteristics. [ABSTRACT FROM AUTHOR]

Objectives Aneurysmal dermatofibroma (ADF) and hemosiderotic dermatofibroma (HDF) are rare variants of dermatofibroma (DF) characterized by distinct histologic features. While HDF is traditionally considered a precursor to ADF, supporting evidence is limited, and the etiology remains unclear. A retrospective analysis of 2128 DF cases (2016-2019) was conducted to investigate the clinicopathologic characteristics of ADF, HDF, and other DFs. Methods Histopathologically diagnosed DF cases were examined for ADF and HDF. Univariate analyses were performed to compare clinicopathologic features. Results Among the cases, 168 (7.9%) were ADF and 29 (1.4%) were HDF. Aneurysmal dermatofibroma and HDF shared several common characteristics, including lower occurrence in females, larger size, and increased cellularity (all P <.0001). Notably, 29% of ADFs lacked hemosiderin deposition. Aneurysmal dermatofibroma primarily manifested on exposed areas (face and forearm, both P <.001). In contrast, 41% of HDFs occurred on the lower leg (P =.018), and all lower leg HDFs exhibited signs of venous stasis, distinguishing them from other HDFs (P <.0001). Conclusions Our findings indicate a potential close relationship between ADF and HDF. Contrary to conventional beliefs, we also presented the possibility of ADF progressing into HDFs. Physical trauma may induce ADF, and HDFs may emerge from ADFs in conjunction with venous stasis in the lower extremities. [ABSTRACT FROM AUTHOR]

Exercise-induced pulmonary hemorrhage (EIPH) is a common condition of Thoroughbred racehorses that is usually responsible for reduced performance, while exercise-associated fatal pulmonary hemorrhage (EAFPH) is characterized by severe pulmonary bleeding of unknown pathogenesis resulting in sudden death during strenuous exercise. The aim of the study was to characterize and compare anamnestic data together with pulmonary gross, histologic, and ultrastructural findings in racehorses with EIPH (n = 10), EAFPH (n = 10), and control horses (n = 5). No differences in anamnesis were identified between the 3 groups. Grossly cranial lobe reddening and edema scores were significantly more prevalent and severe in the EAFPH group compared with the EIPH and control groups. Histologically, hemorrhage scores were higher in the EAFPH group, while hemosiderophages, iron encrustations of collagen and elastin fibers, and vascular remodeling scores were significantly higher in EIPH group compared with the EAFPH and control groups. In all groups, caudal lung locations exhibited a significantly higher score for vascular remodeling, hemosiderophage accumulation, iron encrustation, and type II pneumocyte hyperplasia when compared with cranial, dorsal, and ventral locations. Ultrastructural analysis of perivascular collagen showed fibrils with significantly larger diameters in the EAFPH group compared with the EIPH group but not compared with the control group. This study demonstrates that lungs of horses that experienced EAFPH show significantly less vascular remodeling and other long-term pulmonary abnormalities that characterize horses with EIPH.

Hemorrhage inside the mammillary bodies (MMBs) is known to be one of the findings of Wernicke encephalopathy. Brain MRI of two patients with Wernicke-Korsakoff syndrome (WKS) demonstrated high susceptibility values representing hemosiderin deposition in MMBs by using quantitative susceptibility mapping (QSM). QSM provided additional information of susceptibility values to susceptibility-weighted imaging in diagnosis of WKS. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Introduction: In chronic venous insufficiency (CVI), an increase in venous pressure causes the passage of intravascular blood cells and molecules into the surrounding tissues and induces histopathological changes in the lower extremities, leading to increased pigmentation in the legs, ulceration, and tissue loss to various degrees. This study aimed to investigate whether an increase in venous pressure in the coronary veins can lead to the aforementioned histopathological changes. Material and methods: Twenty-four New Zealand rabbits were divided into the following three groups: experimental model of coronary venous hypertension (CVH) (n = 8), sham group (n = 8), and control group (n = 8). After 21 days postoperatively, tissue samples from each group were compared for perivascular inflammation, erythrocyte extravasation, macrophage infiltration, and hemosiderin deposits by histopathological scoring under a light microscope. Matrix metalloproteinase-2 (MMP-2) activation was evaluated using immunohistochemical staining. Results: In the CVH group, hemosiderin accumulation was significantly higher than in the sham and control groups (1.0 (1.0-3.0), 0.0 (0.0-1.0), 0.0 (0.0-0.0); p < 0.001). Immunohistochemically, in the CVH group, MMP-2 levels were significantly higher than in the sham and control groups (2.0 (1.0-3.0), 0.0 (0.0-1.0), 0.0 (0.0-0.0); p < 0.001). Conclusions: This experimental study showed for the first time the histopathological and immunohistochemical changes in myocardial tissue, similar to those observed in CVI, as a result of increased coronary venous pressure due to coronary vein ligation. Further studies are needed to understand the clinical implications of these results. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Amide proton transfer (APT) and semi-solid magnetization transfer (ssMT) imaging can predict clinical outcomes in patients with glioma. However, the treatment of brain tumors is accompanied by the deposition of blood products within the tumor area in most cases. For this reason, the objective was to assess whether the diagnostic interpretation of the APT and ssMT is affected by methemoglobin (mHb) and hemosiderin (Hs) depositions at the first follow-up MRI 4 to 6 weeks after the completion of radiotherapy. A total of 34 participants underwent APT and ssMT imaging by applying reconstruction methods described by Zhou et al. (APTwasym), Goerke et al. (MTRRexAPT and MTRRexMT) and Mehrabian et al. (MTconst). Contrast-enhancing tumor (CE), whole tumor (WT), mHb and Hs were segmented on contrast-enhanced T1wCE, T2w-FLAIR, T1w and T2*w images. ROC-analysis, Kaplan–Meier analysis and the log rank test were used to test for the association of mean contrast values with therapy response and overall survival (OS) before (WT and CE) and after correcting tumor volumes for mHb and Hs (CEC and WTC). CEC showed higher associations of the MTRRexMT with therapy response (CE: AUC = 0.677, p = 0.081; CEC: AUC = 0.705, p = 0.044) and of the APTwasym with OS (CE: HR = 2.634, p = 0.040; CEC: HR = 2.240, p = 0.095). In contrast, WTC showed a lower association of the APTwasym with survival (WT: HR = 2.304, p = 0.0849; WTC: HR = 2.990, p = 0.020). Overall, a sophisticated correction for blood products did not substantially influence the clinical performance of APT and ssMT imaging in patients with glioma early after radiotherapy. [ABSTRACT FROM AUTHOR]

Abstract Background Hemosiderophages in bronchoalveolar lavage fluid (BALF) are commonly ascribed to exercise‐induced pulmonary hemorrhage (EIPH). Little information exists regarding the presence of these cells in horses that perform light or no work and that are referred for respiratory problems. Objectives Evaluate the presence of hemosiderophages in BALF of horses suspected of respiratory disease without history of or risk factors for EIPH and determine predictors of hemosiderophages in BALF in this population. Methods Observational retrospective cross‐sectional study using STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Bronchoalveolar lavage fluid cytology reports of 353 horses evaluated for respiratory disease between 2012 and 2022 at the Cummings School for Veterinary Medicine were reviewed retrospectively. Horses with a history or likelihood of having performed past strenuous exercise were removed, and the remaining 91 horses were divided into hemosiderin‐positive (HSD‐POS) and hemosiderin‐negative groups based on Perls' Prussian blue staining. Potential predictors for the presence of hemosiderophages in BALF (history, clinical evaluation, baseline lung function, airway reactivity, BALF cytology, and hemosiderin score) were compared between the 2 groups, using univariate and multivariate analyses. Results Horses with a diagnosis of severe equine asthma (sEA; odds ratio, 11.1; 95% confidence interval, 3.2‐38.5; P

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. 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. 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. 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. [Display omitted] • New concept of individually reconstructed diamagnetic and paramagnetic specific SWI images: Current clinical/commercially available SWI post-processing algorithms only create images which enhance the paramagnetic component of susceptibility (e.g. p-SWI specific susceptibility weighted images). • In this work we separately reconstruct diamagnetic and paramagnetic susceptibility weight images (d-SWI, p-SWI) and use these to better discriminate hemosiderin from calcification. • The algorithm is described pictorially in the attached diagram. • The phase masks were applied exponentially to the magnitude image, with exponent of 4 for p-SWI and 5 for d-SWI. [ABSTRACT FROM AUTHOR]

The serum level of ferritin, the protein synthesized in the spleen, bone marrow, liver, correlates with the body's iron deposits and total iron binding capacity (TIBC). Moreover, the blood concentration of ferritin is more sensitive and specific than sideremia and TIBC. Ferritin is an acute phase reagent, being increased in patients with acute or chronic liver disease, kidney disease, alcoholism, neoplasm, hyperthyroidism, infections and inflammation. The determination and correlation of the values obtained for ferritin with HLG, ESR, sideremia and other acute phase reactants (fibrinogen, C-Reactive Protein), allow the correct establishment of the diagnosis and an adequate treatment. [ABSTRACT FROM AUTHOR]

This article discusses two rare cases of intra-labral pigmented villonodular synovitis (PVNS) of the hip. The hip joint represents the second most common location of pigmented villonodular synovitis, second to the knee [1]. The majority of hip PVNS cases either diffusely involve the synovium or are focal lesions within the joint. The lesions and synovium show foci of low signal intensity related to hemosiderin deposition, a finding that differentiates PVNS from other causes of synovial proliferation. Our case report presents two rare manifestations of PVNS lesions localized within the hip labrum. This presentation could easily be mistaken for a cyst by imaging modality. Despite the rarity of this condition, we highlight the importance of questioning the possibility of intra-labral PVNS, when patients have persistent hip pain not responding to therapy and atypical imaging findings. Highlighting this rare presentation is crucial for establishing the correct diagnosis, guiding treatment, and obtaining the best clinical outcome. [ABSTRACT FROM AUTHOR]

Nailfold videocapillaroscopic alterations have been described in COVID-19, but their correlations with biomarkers of inflammation, coagulation and endothelial perturbation are still unclear, and no information is available on nailfold histopathology. Nailfold videocapillaroscopy was performed on fifteen patients with COVID-19 in Milan, Italy and the signs of microangiopathy were correlated with plasma biomarkers of inflammation (C reactive protein [CRP], ferritin), coagulation (D-dimer, fibrinogen), endothelial perturbation (Von Willebrand factor [VWF]) and angiogenesis (vascular endothelial growth factor [VEGF]) along with genetic drivers of COVID-19 susceptibility. Histopathological analysis of autoptic nailfold excisions was performed on fifteen patients who died for COVID-19 in New Orleans, United States. All COVID-19 patients studied with videocapillaroscopy showed alterations rarely seen in healthy individuals consistent with microangiopathy, such as hemosiderin deposits (sign of microthrombosis and microhemorrhages) and enlarged loops (sign of endotheliopathy). The number of hemosiderin deposits correlated both with ferritin and CRP levels (r = 0.67, p = 0.008 for both) and the number of enlarged loops significantly correlated with the levels of VWF (r = 0.67, p = 0.006). Ferritin levels were higher in non-O groups, determined by the rs657152 C > A cluster, (median 619, min–max 551–3266 mg/dL) than in the O group (373, 44–581 mg/dL, p = 0.006). Nailfold histology revealed microvascular damage, i.e., mild perivascular lymphocyte and macrophage infiltration and microvascular ectasia in the dermal vessels of all cases, and microthrombi within vessels in five cases. Alterations in nailfold videocapillaroscopy and elevated biomarkers of endothelial perturbation that match histopathologic findings open new perspectives in the possibility of non-invasively demonstrating microangiopathy in COVID-19. [ABSTRACT FROM AUTHOR]

ABSTRACT We report two cases of hemochromatosis-like disease in captive Brazilian tapirs, Tapirus terrestris in Pará state, Brazil. Both animals presented symptoms of chronic hepatopathy associated with marked accumulation of hemosiderin. The coloration of Perls demonstrated pronounced iron accumulation in macrophages in the portal space, Kupffer cells, and, to a lesser extent, in the hepatocytes of the periportal region. Marked portal fibrosis was evidenced by Masson’s trichrome. The pathological mechanisms of this disease in tapirs are not yet well established. It has been suggested that the species may have different mechanisms of iron absorption and elimination, rendering them sensitive to elevation in dietary levels of this metal. Two previous reports of this disease in T. terrestris exist from zoos in Australia and Scotland. This is the first report of this disease in tapirs in Brazil based on histopathological and histochemical findings.

Background: Hemosiderophages in bronchoalveolar lavage fluid (BALF) are commonly ascribed to exercise‐induced pulmonary hemorrhage (EIPH). Little information exists regarding the presence of these cells in horses that perform light or no work and that are referred for respiratory problems. Objectives: Evaluate the presence of hemosiderophages in BALF of horses suspected of respiratory disease without history of or risk factors for EIPH and determine predictors of hemosiderophages in BALF in this population. Methods: Observational retrospective cross‐sectional study using STROBE (Strengthening the Reporting of Observational Studies in Epidemiology) guidelines. Bronchoalveolar lavage fluid cytology reports of 353 horses evaluated for respiratory disease between 2012 and 2022 at the Cummings School for Veterinary Medicine were reviewed retrospectively. Horses with a history or likelihood of having performed past strenuous exercise were removed, and the remaining 91 horses were divided into hemosiderin‐positive (HSD‐POS) and hemosiderin‐negative groups based on Perls' Prussian blue staining. Potential predictors for the presence of hemosiderophages in BALF (history, clinical evaluation, baseline lung function, airway reactivity, BALF cytology, and hemosiderin score) were compared between the 2 groups, using univariate and multivariate analyses. Results: Horses with a diagnosis of severe equine asthma (sEA; odds ratio, 11.1; 95% confidence interval, 3.2‐38.5; P <.001) were significantly more likely to be HSD‐POS than horses with mild‐to‐moderate equine asthma. Conclusions and Clinical Importance: Hemosiderophages were found in the BALF cytology in a subset of horses that perform light or no work and presented for respiratory signs; these cells were found more frequently in horses with sEA. The link between hemosiderophages and sEA highlights previously unstudied pathology associated with this common disease. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Purpose: Clinical outcome of spinal cavernous malformation (SCM) varies because of its unclear natural history, and reliable prognostic prediction model for SCM patients is limited. The aim of the present study was to investigate potential factors that predict one-year neurological status in postoperative patients with SCM. Methods: This was a multicenter prospective observational study in consecutive patients with SCMs. SCMs treated microsurgically between January 2015 and January 2021 were included. Outcome was defined as the American Spinal Injury Association Impairment Scale (AIS) grade at one year after operation. Multivariable analyses were used to construct the best predictive model for patient outcomes. Results: We identified 268 eligible SCM patients. Neurological outcome had worsened from preoperative baseline in 51 patients (19.0%) at one year. In the multivariable logistic regression, the best predictive model for unfavorable outcome included symptom duration ≥ 26 months (95% CI 2.80–16.96, P < 0.001), size ≤ 5 mm (95% CI 1.43–13.50, P = 0.010), complete intramedullary (95% CI 1.69–8.14, P = 0.001), subarachnoid hemorrhage (95% CI 2.92–12.57, P < 0.001), AIS B (95% CI 1.91–40.93, P = 0.005) and AIS C (95% CI 1.12–14.54, P = 0.033). Conclusions: Admission size of the lesion, morphology, symptom duration, AIS grade and the presence of subarachnoid hemorrhage were strong outcome predictors regarding prognostication of neurological outcome in postoperative patients with SCMs. A decision to surgically remove a symptomatic SCM should be justified by systematic analysis of all factors potentially affecting outcome. [ABSTRACT FROM AUTHOR]

Hereditary hemochromatosis is an iron-overload disease most often arising from a mutation in the Homeostatic Fe regulator (HFE) gene. HFE organs become overloaded with iron which causes damage. Iron-overload is commonly detected by NMR imaging, but the spectroscopic technique is insensitive to diamagnetic iron. Here, we used Mössbauer spectroscopy to examine the iron content of liver, spleen, kidney, heart, and brain of 57Fe-enriched HFE(−/−) mice of ages 3–52 wk. Overall, the iron contents of all investigated HFE organs were similar to the same healthy organ but from an older mouse. Livers and spleens were majorly overloaded, followed by kidneys. Excess iron was generally present as ferritin. Iron–sulfur clusters and low-spin FeII hemes (combined into the central quadrupole doublet) and nonheme high-spin FeII species were also observed. Spectra of young and middle-aged HFE kidneys were dominated by the central quadrupole doublet and were largely devoid of ferritin. Collecting and comparing spectra at 5 and 60 K allowed the presence of hemosiderin, a decomposition product of ferritin, to be quantified, and it also allowed the diamagnetic central doublet to be distinguished from ferritin. Hemosiderin was observed in spleens and livers from HFE mice, and in spleens from controls, but only when iron concentrations exceeded 2–3 mM. Even in those cases, hemosiderin represented only 10–20% of the iron in the sample. NMR imaging can identify iron-overload under non-invasive room-temperature conditions, but Mössbauer spectroscopy of 57Fe-enriched mice can detect all forms of iron and perhaps allow the process of iron-overloading to be probed in greater detail. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

IntroductionEvidence suggests that toxic iron is involved in haemophilic joint destruction.AimTo determine whether joint iron deposition is linked to clinical and imaging outcomes in order to optimize management of haemophilic joint disease.MethodsAdults with haemophilia A or haemophilia B (n = 23, ≥ age 21) of all severities were recruited prospectively to undergo assessment with Hemophilia Joint Health Scores (HJHS), pain scores (visual analogue scale [VAS]) and magnetic resonance imaging (MRI) at 3T using conventional MRI protocols and 4-echo 3D-UTE-Cones sequences for one affected arthropathic joint. MRI was scored blinded by two musculoskeletal radiologists using the International Prophylaxis Study Group (IPSG) MRI scale. Additionally, UTE-T2* values of cartilage were quantified. Correlations between parameters were performed using Spearman rank correlation. Two patients subsequently underwent knee arthroplasty, which permitted linking of histological findings (including Perl's reaction) with MRI results.ResultsMRI scores did not correlate with pain scores or HJHS. Sixteen joints had sufficient cartilage for UTE-T2* analysis. T2* values for cartilage correlated inversely with HJHS (rs  = -0.81, P

BACKGROUND:Cerebral microhemorrhages (CMH) are commonly found in the aging brain. CMH are also the neuropathological substrate of cerebral microbleeds (CMB), demonstrated on brain MRI. Recent studies demonstrate the importance of systemic inflammation in CMH development, but the relationships among inflammation, aging, and CMH development are not well-defined. In the current study, we hypothesized that the pathogenesis of inflammation-induced CMH in mice differs by age. METHODS:We studied young (3 months, n = 20) and old (18 months, n = 25) C57BL/6 mice injected with low-dose lipopolysaccharide (LPS; 1 mg/kg, i.p.) or saline at 0, 6, and 24 h. Seven days after the first LPS/saline injection, brains were harvested, sectioned, and stained with hematoxylin and eosin (H&E) and Prussian blue (PB) to estimate acute/fresh and sub-acute CMH development, respectively. The relationships between microglial/macrophage activation (ionized calcium-binding adapter molecule-1), astrocyte activation (glial fibrillary acidic protein), blood-brain barrier (BBB) disruption (brain immunoglobulin G), aging, and CMH development were examined using immunohistochemistry. RESULTS:Aging alone did not increase spontaneous H&E-positive CMH development but significantly increased the number, size, and total area of LPS-induced H&E-positive CMH in mice. LPS- and saline-treated aged mice had significantly larger PB-positive CMH compared with young mice, but the total area of PB-positive CMH was increased only in LPS-treated aged mice. Aged mice had significantly increased microglial/macrophage activation, which correlated with H&E- and PB-positive CMH development. Aged mice treated with LPS had significantly increased astrocyte activation and BBB disruption compared with young LPS-treated mice. CONCLUSIONS:Aging makes the brain more susceptible to inflammation-induced CMH in mice, and this increase in CMH with aging is associated with microglial/macrophage activation.

Objective: To assess whether post‐stroke epilepsy (PSE) is associated with neuroimaging findings of hemosiderin in a case–control study, and whether the addition of hemosiderin markers improves the risk stratification models of PSE. Methods: We performed a post‐hoc analysis of the PROgnosis of POST‐Stroke Epilepsy study enrolling PSE patients at National Cerebral and Cardiovascular Center, Osaka, Japan, from November 2014 to September 2019. PSE was diagnosed when one unprovoked seizure was experienced >7 days after the index stroke, as proposed by the International League Against Epilepsy. As controls, consecutive acute stroke patients with no history or absence of any late seizure or continuing antiseizure medications at least 3 months after stroke were retrospectively enrolled during the same study period. We examined cortical microbleeds and cortical superficial siderosis (cSS) using gradient‐echo T2*‐weighted images. A logistic regression model with ridge penalties was tuned using 10‐fold cross‐validation. We added the item of cSS to the existing models (SeLECT and CAVE) for predicting PSE and evaluated performance of new models. Results: The study included 180 patients with PSE (67 women; median age 74 years) and 1,183 controls (440 women; median age 74 years). The cSS frequency was higher in PSE than control groups (48.9% vs 5.7%, p < 0.0001). Compared with the existing models, the new models with cSS (SeLECT‐S and CAVE‐S) demonstrated significantly better predictive performance of PSE (net reclassification improvement 0.63 [p = 0.004] for SeLECT‐S and 0.88 [p = 0.001] for CAVE‐S at the testing data). Interpretation: Cortical superficial siderosis was associated with PSE, stratifying stroke survivors at high risk of PSE. ANN NEUROL 2023;93:357–370 [ABSTRACT FROM AUTHOR]

Purpose: To investigate thrombus age and its association with clinical and procedural parameters in patients with acute ischemic stroke (AIS) due to anterior circulation occlusions. Methods: The thrombi of 107 consecutive AIS patients with occlusions in anterior circulation large-arteries were collected during mechanical recanalization. By hematoxylin–eosin staining analysis, thrombi were classified as fresh (< 3 days) or old (≥ 3 days) according to the hemosiderin positivity. Old thrombi were further classified as thrombi with focal hemosiderin or diffuse hemosiderin according to their predominant distribution. Neuro-interventional data and clinical outcomes were compared based on thrombus age. Results: We identified fresh thrombi in 29 patients and old thrombi in 78 patients. Compared with patients with fresh thrombi, patients with old thrombi were associated with (i) a longer mechanical recanalization time (p = 0.027), (ii) a higher percentage of fibrin/platelets and leukocytes (all p = 0.02) and a lower percentage of erythrocytes (p = 0.001), and (iii) less favorable clinical outcomes at discharge (p = 0.019) and 90 days later (OR = 2.76, 95% CI = 1.09–6.99, p = 0.032). Furthermore, 18 (16.8%) of all patients had focal hemosiderin in old thrombi, which was independently linked to a poor clinical outcome 90 days later (adjusted OR = 5.37, 95% CI = 1.14–25.28, p = 0.034). Conclusion: The presence of old thrombi, particularly those with focal hemosiderin, may aid in identifying patients with acute ischemic anterior circulation stroke who are at a higher risk of poor clinical outcome at 3-month follow-up. [ABSTRACT FROM AUTHOR]

Background: There is a broad spectrum of vulvar pigmented lesions that differ based on their histopathological and clinical features. Chronic vulvar purpura is a rare entity, associated with a broad morphological spectrum, from lichen aureus, Zoon's vulvitis, pigmented purpuric dermatosis and with lichen planus as in our case. Case presentation: In this article we discuss a case of an 86-year-old white woman with hyperpigmentation on her upper vulva, next to the introitus, with complaints of urine incontinence. Biopsy revealed subepithelial stromal lichenoid inflammatory infiltrate containing plasma cells, lymphocytes and some neutrophilic granulocytes as well as dilated and congested vessels. Hemosiderin deposits and erythrocyte extravasation were found. There was evidence of hyperkeratosis with hyper granulosis and erosions. Spongiosis was also noted. Few melanocytes were identified with no sign of malignancy. These findings correlate with the diagnosis of vulvar lichen planus. Conclusions: Chronic vulvar purpura is a clinical term used for different chronic inflammatory dermatoses presenting as red bluish or violaceous discolorations on the vulva, often associated with cayenne-pepper-like speckling. Considering a great overlap of possible diseases, the final diagnosis could be challenging. It is important to exclude a melanocytic tumour in these cases. [ABSTRACT FROM AUTHOR]

Exercise-induced pulmonary hemorrhage (EIPH) is a relevant respiratory disease in sport horses, which can be diagnosed by examination of bronchoalveolar lavage fluid (BALF) cells using the total hemosiderin score (THS). The aim of this study was to evaluate the diagnostic accuracy and reproducibility of annotators and to validate a deep learning-based algorithm for the THS. Digitized cytological specimens stained for iron were prepared from 52 equine BALF samples. Ten annotators produced a THS for each slide according to published methods. The reference methods for comparing annotator's and algorithmic performance included a ground truth dataset, the mean annotators' THSs, and chemical iron measurements. Results of the study showed that annotators had marked interobserver variability of the THS, which was mostly due to a systematic error between annotators in grading the intracytoplasmatic hemosiderin content of individual macrophages. Regarding overall measurement error between the annotators, 87.7% of the variance could be reduced by using standardized grades based on the ground truth. The algorithm was highly consistent with the ground truth in assigning hemosiderin grades. Compared with the ground truth THS, annotators had an accuracy of diagnosing EIPH (THS of < or ≥ 75) of 75.7%, whereas, the algorithm had an accuracy of 92.3% with no relevant differences in correlation with chemical iron measurements. The results show that deep learning-based algorithms are useful for improving reproducibility and routine applicability of the THS. For THS by experts, a diagnostic uncertainty interval of 40 to 110 is proposed. THSs within this interval have insufficient reproducibility regarding the EIPH diagnosis. [ABSTRACT FROM AUTHOR]

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The correction of leg telangiectasias is one of the most frequently performed interventions in the Western world. While sclerotherapy remains the gold standard of treatment, several studies have shown comparable efficacy and, in some situations, an even more favorable use of lasers as an alternative treatment option. The most frequent side effect of both treatment options is hyperpigmentation, which usually clears spontaneously in most cases but can be challenging to treat if it persists. The origin of this hyperpigmentation is not fully understood; small studies point to hemosiderin as the causative pigment, at least in post-sclerotherapy hyperpigmentation. More rare side effects of the treatment include ulcerations and scarring. Quality-switched (QS) Nd:YAG lasers have demonstrated good efficacy in treating hemosiderin depositions in the skin, post-inflammatory hyperpigmentation and atrophic scars. We present a case of post-inflammatory hyperpigmentation and scarring after laser treatment of leg telangiectasia with a long-pulsed Nd:YAG laser that was successfully treated using a QS Nd:YAG 1064 nm laser. This case suggests the QS Nd:YAG laser as a possible treatment option in cases of hyperpigmentation with various origins, including hemosiderin and melanin, and scarring after laser treatment of leg telangiectasias.

Differentiation of suprasellar xanthogranuloma (XG) from adult craniopharyngioma (CP) can be problematic in endoscopic extended transsphenoidal surgery. We reviewed the clinical data, preoperative imaging, intraoperative endoscopic findings, and intraoperative frozen section pathology in newly diagnosed adult CPs (19 patients) and XGs (6 patients). Intracystic signal intensity was often high on T1-weighted magnetic resonance images in the XGs but low in the CPs (P = 0.015). Capsular intensity was low on T2-weighted imaging in XGs but iso to high in CPs (P < 0.001). Capsular gadolinium enhancement was often seen in CPs and not in XGs (P < 0.001). CPs often had a solid component with contrast enhancement but none in XGs (P < 0.001). Intraoperative endoscopic observations frequently found a whitish solid component in the CPs but yellow to brown fibrous granulomatous lesions in XGs (P < 0.001). The tumor capsule was dark grayish and soft in CPs, whereas it was fibrously hard in XGs (P = 0.002). Yellowish hemosiderin deposits were seen in all XGs (P = 0.003). Intraoperative pathologic diagnosis of CP was all verified whereas no evidence of tumor was found in XGs (P < 0.001). Partial removal was performed in 4 patients with XGs. No recurrence was observed in these patients during the follow-up period (1.5–8 years). Careful interpretation of preoperative magnetic resonance imaging, intraoperative endoscopic findings, and intraoperative frozen section diagnosis may be important for the differential diagnosis between XG and CP. In endoscopic-extended transsphenoidal surgery, intentional partial removal can be effective for XG after careful diagnosis. [ABSTRACT FROM AUTHOR]

We report the largest case series to date of granulomatous pigmented purpuric dermatosis (GPPD), a rare variant of pigmented purpuric dermatoses (PPD). GPPD can cause diagnostic difficulties as it can be mistaken clinically and histopathologically with numerous inflammatory and infectious dermatoses or even cutaneous T‐cell lymphoma. We compared the histopathological findings of nine cases of GPPD with a control group consisting of 10 randomly selected PPD of other subtypes. GPPD seems to predominantly affect the lower extremities of adult male patients; a clear association with hyperlipidemia or other systemic conditions could not be confirmed. Histopathologically, GPPD is characterized by a dermal histiocyte‐rich interstitial infiltrate with or without granuloma formation, thickened capillaries, extravasated erythrocytes, and/or hemosiderin deposits. In contrast to other forms of PPD, the inflammatory infiltrate of GPPD can extend to the mid or deep dermis and the admixed lymphocytic infiltrate is mainly composed of CD8+ T‐cells. [ABSTRACT FROM AUTHOR]

Background: The dermoscopic features of classic patch stage mycosis fungoides (MF) have been described, but data on plaque and tumoral stage as well as rarer MF subtypes is limited. Objective: To evaluate dermoscopic morphology and dermoscopic‐pathological correlations of classic MF stages and investigate dermoscopic features of MF variants. Methods: Patients with histopathologically confirmed lesions of classic MF (patch, plaque and tumoral stage) or folliculotropic, erythrodermic and poikilodermatous MF were included. Standardized evaluation of dermoscopic pictures of the included MF variants and comparative analysis and dermoscopic‐pathological correlation assessment of different stages of classic MF were performed. Results: A total of 118 instances were included (75 classic MF, 26 folliculotropic MF, 9 erythrodermic MF and 8 poikilodermatous MF). Linear/linear‐curved vessels and white scales in the skin furrows were significantly associated with patch‐stage MF, while clustered dotted vessels were related to plaque‐stage MF and peripheral linear vessels with branches, ulceration and red globules separated by white lines to tumour‐stage MF. Moreover, patchy white scales were significantly more common in patches and plaques compared to tumours, whereas focal bright white structureless areas were related to plaque and tumoral stage. Vessels histopathologically corresponded to dilated vascular structures in the dermis, orange structureless areas to either dermal hemosiderin (patch/plaque stage) or dense cellular infiltration (tumours), bright white lines/structureless areas to dermal fibrosis and ulceration to loss of epidermis. The main dermoscopic findings of folliculotropic MF were lack of hairs, dilated follicles and follicular plugs, while erythrodermic MF was mainly characterized by linear/dotted vessels, patchy white scales and focal orange structureless areas and poikilodermatous MF by focal white and brown structureless areas, white patchy scales and brown reticular lines. Conclusion: Dermoscopy may allow a more precise characterization of classic MF and reveal clues suggestive of the main MF variants. [ABSTRACT FROM AUTHOR]

Objective Schamberg's disease is the most common type of pigmented purpuric dermatosis, characterized by a benign course with reddish-brown patches or macules with overlying purpuric spots resembling a cayenne pepper. It is not uncommon condition, but the available information regarding its epidemiological, clinical, and histopathological features are very limited. The objective of the study is to evaluate the clinical and histopathological features of Schamberg's disease trying to have more insight into its etiopathogenesis. Methods A descriptive cross sectional study was conducted in the Center of Dermatology and Venereology, Medical City, Baghdad, Iraq, during the period from October 2018 to March 2020. Fifty patients with clinical features of Schamberg's disease were included. The demographic features were recorded. Full history and dermatological examination were carried out. Results 50 patients were included with mean age of 47.22±11.8 years. 76% were males and 24% were females. The lesions were symmetrical and consisted of macules (44%), petechiae and macules (32%). Histopathological examination showed normal stratum corneum in 11 (100%), acanthosis in 18%, epidermal atrophy in 72%, spongiosis in 45%, rete ridges effacement in 45%, basal layer vacuolization in 27%. Many pathological changes in superficial dermis were observed like RBC extravasation, mostly around dilated and congested blood vessels was noted in 81%, variable perivascular lymphocytic infiltrates were seen in all 11 cases; 36% mild infiltrates, 36% moderate infiltrate and 27% extensive with fibriniod alterations in some of the sections. These changes were suggestive of lymphocytic vasculitis. Perls stained sections revealed dermal iron deposition (Hemosiderin) with in siderophages mainly in the upper dermis in 82% that was mild in 11%, moderate in 33% and extensive in 55% of the patients. Conclusion Schamberg's disease is a chronic, benign, asymptomatic disease affecting lower limbs in a symmetrical fashion with characteristic clinical and histopathological features that suggest lymphocytic vasculitis rather than capillaritis of dermis, leading into hemosiderin deposition as an outcome. These features with poor circulation do suggest that disease is a form of vasculitis that could be named stasis vasculitis as the main etiopathological finding. [ABSTRACT FROM AUTHOR]

Pulmonary hemorrhage (P-Hem) occurs among multiple species and can have various causes. Cytology of bronchoalveolar lavage fluid (BALF) using a 5-tier scoring system of alveolar macrophages based on their hemosiderin content is considered the most sensitive diagnostic method. We introduce a novel, fully annotated multi-species P-Hem dataset, which consists of 74 cytology whole slide images (WSIs) with equine, feline and human samples. To create this high-quality and high-quantity dataset, we developed an annotation pipeline combining human expertise with deep learning and data visualisation techniques. We applied a deep learning-based object detection approach trained on 17 expertly annotated equine WSIs, to the remaining 39 equine, 12 human and 7 feline WSIs. The resulting annotations were semi-automatically screened for errors on multiple types of specialised annotation maps and finally reviewed by a trained pathologist. Our dataset contains a total of 297,383 hemosiderophages classified into five grades. It is one of the largest publicly available WSIs datasets with respect to the number of annotations, the scanned area and the number of species covered. Measurement(s) Hemosiderin-Laden Macrophage • Hemosiderin-Laden Macrophage Technology Type(s) machine learning • visual observation method Sample Characteristic - Organism Homo sapiens • Felinae • Equus caballus [ABSTRACT FROM AUTHOR]

Background and purposeSilent microhemorrhage (hemosiderin) has been observed in resected brain arteriovenous malformations (bAVM) tissue and may represent a subgroup at increased risk for clinical hemorrhage. Previous studies suggest that ruptured bAVMs have faster flow and shorter mean transit time of contrast in blood vessels than unruptured bAVMs. We hypothesized that flow would be faster in unruptured AVMs with hemosiderin compared with those without hemosiderin.MethodsWe selected unruptured, supratentorial bAVMs >3.5 cc with pathology specimens. Hemodynamic features were evaluated using color-coding angiography, including contrast mean transit time of AVM nidus, time to peak (TTP) of feeding artery (FA) and draining vein (DV), and the ratio (TTP DV/FA). Characteristics of 9 cases with hemosiderin and 16 without hemosiderin were compared using 2-sample t tests and Fisher exact tests.ResultsNo difference in FA TTP and DV TTP was observed between groups. However, cases with hemosiderin had significantly shorter mean transit time compared with those without hemosiderin (1.11±0.28 versus 1.64±0.55 seconds; P=0.013) and a lower ratio of DV TTP/FA TTP (1.48±0.32 versus 1.94±0.61; P=0.045). Presence of venous varix was significantly associated with hemosiderin (P=0.003). No other clinical or angioarchitectural factors were associated with hemosiderin.ConclusionsShorter mean transit time through the AVM nidus, lower DV TTP/FA TTP, and the high prevalence of venous varices suggests that high flow is an important feature of unruptured bAVMs with hemosiderin.

BackgroundCerebral microhemorrhages (CMH) are tiny deposits of blood degradation products in the brain and are pathological substrates of cerebral microbleeds. The existing CMH animal models are β-amyloid-, hypoxic brain injury-, or hypertension-induced. Recent evidence shows that CMH develop independently of hypoxic brain injury, hypertension, or amyloid deposition and CMH are associated with normal aging, sepsis, and neurodegenerative conditions. One common factor among the above pathologies is inflammation, and recent clinical studies show a link between systemic inflammation and CMH. Hence, we hypothesize that inflammation induces CMH development and thus, lipopolysaccharide (LPS)-induced CMH may be an appropriate model to study cerebral microbleeds.MethodsAdult C57BL/6 mice were injected with LPS (3 or 1 mg/kg, i.p.) or saline at 0, 6, and 24 h. At 2 or 7 days after the first injection, brains were harvested. Hematoxylin and eosin (H&E) and Prussian blue (PB) were used to stain fresh (acute) hemorrhages and hemosiderin (sub-acute) hemorrhages, respectively. Brain tissue ICAM-1, IgG, Iba1, and GFAP immunohistochemistry were used to examine endothelium activation, blood-brain barrier (BBB) disruption, and neuroinflammation. MRI and fluorescence microscopy were used to further confirm CMH development in this model.ResultsLPS-treated mice developed H&E-positive (at 2 days) and PB-positive (at 7 days) CMH. No surface and negligible H&E-positive CMH were observed in saline-treated mice (n = 12). LPS (3 mg/kg; n = 10) produced significantly higher number, size, and area of H&E-positive CMH at 2 days. LPS (1 mg/kg; n = 9) produced robust development of PB-positive CMH at 7 days, with significantly higher number and area compared with saline (n = 9)-treated mice. CMH showed the highest distribution in the cerebellum followed by the sub-cortex and cortex. LPS-induced CMH were predominantly adjacent to cerebral capillaries, and CMH load was associated with indices of brain endothelium activation, BBB disruption, and neuroinflammation. Fluorescence microscopy confirmed the extravasation of red blood cells into the brain parenchyma, and MRI demonstrated the presence of cerebral microbleeds.ConclusionsLPS produced rapid and robust development of H&E-positive (at 2 days) and PB-positive (at 7 days) CMH. The ease of development of both H&E- and PB-positive CMH makes the LPS-induced mouse model suitable to study inflammation-induced CMH.

Abstract Background Macroscopic hematuria-associated acute kidney injury (AKI) is a well-known complication of immunoglobulin A (IgA) nephropathy. In such cases, intratubular obstruction by red blood cell (RBC) casts and acute tubular necrosis are mainly observed pathologically. Herein, we report the case of a patient with IgA nephropathy presenting with AKI following an episode of macrohematuria. The patient presented with severe renal tubular hemosiderosis and acute tubular necrosis and without any obvious obstructive RBC casts. Case presentation A 68-year-old woman, who was diagnosed with IgA nephropathy on renal biopsy 6 years ago, was admitted to our hospital after an episode of macroscopic glomerular hematuria and AKI following upper respiratory tract infection. Renal biopsy showed mesangial proliferation of the glomeruli, including crescent formation in 17 % of the glomeruli, and acute tubular necrosis without obvious hemorrhage or obstructive RBC casts. The application of Perls’ Prussian blue stain showed hemosiderin deposition in the renal proximal tubular cells. Immunofluorescence showed granular mesangial deposits of IgA and C3. Based on these findings, she was diagnosed with acute tubular necrosis with a concurrent IgA nephropathy flare-up. Moreover, direct tubular injury by heme and iron was considered to be the cause of AKI. She was treated with intravenous pulse methylprednisolone followed by oral prednisolone. Thereafter, the gross hematuria gradually faded, and her serum creatinine levels decreased. Conclusions IgA nephropathy presenting with acute kidney injury accompanied by macrohematuria may cause renal hemosiderosis and acute tubular necrosis without obstructive RBC casts. Hemosiderosis may be a useful indicator for determining the pathophysiology of macroscopic hematuria-associated AKI. However, renal hemosiderosis may remain undiagnosed. Thus, Perls’ Prussian blue iron staining should be more widely used in patients presenting with hematuria.