Infiltration Of Foamy Macrophages Research Articles

Novel Insights into the Pathogenesis of Human Post-Primary Tuberculosis from Archival Material of the Pre-Antibiotic Era, 1931-1947.

Primary and post-primary tuberculosis (TB) are distinct entities. The aim of this study was to study the histopathology of primary and post-primary TB by using the unique human autopsy material from the pre-antibiotic era, 1931-1947. Autopsy data were collected from the autopsy journals, and the human tissue was collected from the pathology archives at the Department of Pathology, the Gades Institute. Histological presentations of TB lesions showed great diversity within a single lung. Post-primary TB starts as a pneumonia forming early lesions, characterized by the infiltration of foamy macrophages containing mycobacterial antigens within alveoli, and progressing to necrotic pneumonias with an increasing density of mycobacterial antigens in the lesions. These necrotic pneumonic lesions appeared to either resolve as fibrocaseous lesions or lead to cavitation. The typical granulomatous inflammation, the hallmark of TB lesions, appeared later in the post-primary TB and surrounded the pneumonic lesions. These post-primary granulomas contained lesser mycobacterial antigens as compared to necrotic pneumonia. Immunopathogenesis of post-primary TB is different from primary TB and starts as pneumonia. The early lesions of post-primary TB may progress or regress, holding the key to understanding how a host can develop the disease despite an effective TB immunity.

Whipple disease – an important cause of culture negative endocarditis

Whipple disease is a rare systemic disease caused by the bacterium Tropheryma whipplei with a range of clinical manifestations including diarrhoea, abdominal pain, arthralgia. There is increasing evidence that Whipple disease can present with isolated organ involvement, which may include culture negative endocarditis.1 We present a case of a 49-year-old female who presented with a prolonged history of progressive cardiac symptoms, found to have valve destruction and foamy macrophage infiltration of her aortic valve.

A rare cause of scrotal abscess: xanthogranulomatous epididymitis

Xanthogranulomatous epididymitis is a rare benign process with destruction of tissue and replacement by cellular infiltration of foamy macrophages, dense lymphocytes and plasma cells. Literature has very few case reports. We reported here a case of a 72 years old male who presented as scrotal abscess with bilateral hydrocele on ultrasound. On exploration he had normal right testis with abscess localized to epididymis underwent right epididymectomy with orchidopexy. Histopathology reported necrosis and abundant foamy macrophages and plasma cells findings suggestive of xanthogranulomatous epididymitis.

Toxic leukoencephalopathy with axonal spheroids caused by chemotherapeutic drugs other than methotrexate

BackgroundThe objective of this report is to share the clinicopathological features of chemotherapy-induced toxic leukoencephalopathy, which is a rare and under-recognized disease, clinically characterized by rapidly progressive cognitive loss that often leads to sudden death.Case presentationA 64-year-old woman and a 63-year-old man, who had both suffered from a rapid deterioration of consciousness, were autopsied under the clinical impressions of either the central nervous system graft versus host disease (CNS-GVHD), infectious encephalitis, or autoimmune encephalitis. Both patients had been treated with multiple chemotherapy regimens, including adriamycin, cytarabine arabinoside, daunorubicin, fludarabine, azacitidine, and allogeneic peripheral blood stem cell transplantation to treat hematological malignancies (acute myelogenous leukemia and myelodysplastic syndrome). Neuropathological findings at autopsy revealed rarefaction and vacuolar changes of the white matter with axonal spheroids, reactive gliosis, and foamy macrophage infiltration, predominantly in the visual pathways of the occipital and temporal lobes. Damaged axons exhibited immunoreactivity to beta-amyloid, consistent with axonopathy. However, there was no lymphocyte infiltration that suggested CNS-GVHD or any type of encephalitis.ConclusionThe neuropathology found in the presented cases had the characteristic features of toxic leukoencephalopathy (chemobrain). Our cases showed that toxic leukoencephalopathy can also be caused by chemotherapy drugs other than methotrexate.

The Phosphoinositide Kinase Pikfyve Regulates Lysosomal Biogenesis in Macrophages By Modulating the Transcription Factor EB (TFEB)

Macrophages are professional phagocytes that are essential for host defense and tissue homeostasis. Phagocytic functions critically depend on the proper membrane trafficking and degradative functions of the endolysosomal system. Membrane trafficking is modulated by several signaling molecules including phosphoinositides. Particularly, the endolysosomal trafficking involves the endosomal phosphoinositide phosphatidylinostol 3,5 bisphosphate [PI(3,5)P2], which is synthesized by the kinase PIKfyve. Studies using PIKfyve inhibitors or genetically modified mice demonstrate that PIKfyve is critical for lysosomal homeostasis. In this study, we analyzed the role of PIKfyve in macrophages as well as the potential mechanism by which PIKfyve regulates lysosomal homeostasis.Mice were genetically engineered to lack PIKfyve in their macrophages (PIKfyvefl/fl LysM-Cre). These mice develop diffuse tissue infiltration of foamy macrophages, hepatosplenomegaly, and a systemic inflammation response that is reminiscent of lysosomal storage disorders. Their macrophages were isolated from the spleen or bone marrow using F4/80 antibody and the biogenesis and function of their endolysosomes was analyzed. PIKfyve-null macrophages displayed an enlarged LAMP1-positive compartment by immunofluorescence microscopy. Moreover, the enlarged endolysosomes showed reduced proteolysis of endocytosed fluorogenic substrates demonstrating these cells have decreased lysosomal degradative activity. It is notable that the endolysosomal compartment was normally acidified in the PIKfyve-null macrophages. In addition, RT-PCR showed increased mRNA of lysosomal genes such as Cathepsin D and LAMP1 in the PIKfyve-null macrophages compared to WT macrophages. Immunoblotting confirmed increased expression of these lysosomal proteins in PIKfyve-null macrophages. Together, these findings indicate that PIKfyve is a critical regulator of the endolysosomal morphology, function, and biogenesis in macrophages.TFEB is the master transcription factor for lysosomal gene network. Activation and nuclear translocation of TFEB is inhibited by mTORC1-dependent and mTORC1-independent phosphorylation of TFEB. We hypothesized that the upregulation of lysosomal genes in the PIKfyve-null macrophages may be driven by activation of TFEB. Surprisingly, we found that both mRNA expression and protein expression of full-length TFEB were reduced in PIKfyve-null macrophages compared to WT macrophages. Interestingly, mTORC1 activity was reduced, and as expected, the phosphorylation of full-length TFEB was decreased in PIKfyve-null macrophages. However, significantly elevated protein expression of shorter variants of TFEB was also detected in PIKfyve-null macrophages. Given that these shorter forms of TFEB were not previously reported, we analyzed them by mass spectrometry. The shorter forms of TFEB were identified to be truncated at the N-terminus of TFEB upstream of Aa 71 or Aa 197. Since the canonical phosphorylation and inactivation sites of TFEB include serine 142 and serine 211, we postulate that truncated variants of TFEB function as active forms of TFEB that translocate into the nucleus and mediate transcription of the lysosomal gene network. Together, our data show that PIKfyve deficiency may upregulate the expression of lysosomal genes by reducing mTORC1 activity and generating truncated variants of TFEB.In conclusion, our study demonstrates that PIKfyve is a critical regulator of lysosome biogenesis and function in macrophages, and suggests a novel mechanism for the regulation of TFEB-mediated lysosome biogenesis. DisclosuresNo relevant conflicts of interest to declare.

Validation and application of OCT tissue attenuation index for the detection of neointimal foam cells

Neointimal infiltration with foamy macrophages is recognized as an early and important sign of de-novo atherosclerosis after stent implantation (neoatherosclerosis). Recent histopathological studies have proven that automated quantification of signal attenuation using intravascular optical coherence tomography (OCT) imaging allows for sensitive identification of macrophages in native atherosclerotic disease. Whether this is true for neointimal foam cells in the setting of neoatherosclerosis remains unknown. Autopsy samples of stented coronary arteries (n = 13 cases) were evaluated by histology and OCT. After co-registration with histology, the attenuation rate of emitted laser light was measured in regions with and without neointimal foamy macrophages relative to its peak intensity at the blood-tissue interface. Attenuation index was subsequently determined as slope of a regression curve fitted to individual data points. Receiver operating curve (ROC) analysis was used to establish an optimal cut-off for detecting foamy macrophages in homogenous and non-homogenous neointima, respectively. Finally, the tissue attenuation index was applied to confirm or exclude the presence of neointimal foamy macrophages in symptomatic patients presenting with in-stent restenosis and undergoing intravascular OCT imaging (n = 29 cases). Tissue attenuation index derived from post-mortem samples differed significantly between histologically confirmed regions with and without neointimal foamy macrophages (− 1.23 ± 1.42 vs. − 0.52 ± 1.79, p < 0.05). ROC analysis was able to distinguish neointima with foamy macrophage infiltration from neointima without (93% sensitivity, 73% specificity, cut-off − 0.79, AUC 0.87 for homogenous neointima and 40% sensitivity, 95% specificity, cut-off − 1.93, AUC 0.69 for non-homogenous neointima). In symptomatic patients presenting with in-stent restenosis after stent implantation and undergoing intravascular imaging with OCT, neointimal foamy macrophages were detected in 34.2% of homogenous and 43.6% of non-homogenous neointimal ROI’s evaluated. OCT-derived and histopathologically validated tissue attenuation index enables identification of neointimal foamy macrophages in stented coronary arteries. Such image-based post-processing software algorithm may help discern and triage subjects at increased risk for device-related events.

Are we curing one evil with another? A translational approach targeting the role of neoatherosclerosis in late stent failure.

Neoatherosclerosis is defined as foamy macrophage infiltration into the peri-strut or neointimal area after stent implantation, potentially leading to late stent failure through progressive atherosclerotic changes including calcification, fibroatheroma, thin-cap fibroatheroma, and rupture with stent thrombosis (ST) in advanced stages. Human autopsy as well as intravascular imaging studies have led to the understanding of neoatherosclerosis formation as a similar but significantly accelerated pathophysiology as compared to native atherosclerosis. This acceleration is mainly based on disrupted endothelial integrity with insufficient barrier function and augmented transmigration of lipids following vascular injury after coronary intervention and especially after implantation of drug-eluting stents. In this review, we summarize translational insights into disease pathophysiology and discuss therapeutic approaches to tackle this novel disease entity. We introduce a novel animal model of neoatherosclerosis alongside accompanying in vitro experiments, which show impaired endothelial integrity causing increased permeability for low-density lipoprotein cholesterol resulting in foam cell transformation of human monocytes. In addition, we discuss novel intravascular imaging surrogates to improve reliable diagnosis of early stage neoatherosclerosis. Finally, a therapeutic approach to prevent in-stent neoatherosclerosis with magnesium-based bioresorbable scaffolds and systemic statin treatment demonstrated the potential to improve arterial healing and re-endothelialization, leading to significantly mitigated neoatherosclerosis formation in an animal model of neoatherosclerosis.

The early onset and persistent worsening pulmonary alveolar proteinosis in rats by indium oxide nanoparticles

Workplace inhalation exposure to indium compounds has been reported to produce ‘indium lung disease’ characterized by pulmonary alveolar proteinosis (PAP), granulomas, and pulmonary fibrosis. However, there is little information about the pulmonary toxicity of nano-sized indium oxide (In2O3), which is widely used in various applications such as liquid crystal displays. In this study, we evaluated the time-course and dose-dependent lung injuries by In2O3 nanoparticles (NPs) after a single intratracheal instillation to rats. In2O3 NPs were instilled to female Wistar rats at 7.5, 30, and 90 cm2/rat and lung injuries were evaluated at day 1, 3, 7, 14, 30, 90, and 180 after a single intratracheal instillation. Treatment of In2O3 NPs induced worsening diverse pathological changes including PAP, persistent neutrophilic inflammation, type II cell hyperplasia, foamy macrophages, and granulomas in a time- and dose-dependent manner. PAP was induced from day 3 and worsened throughout the study. The concentrations of interleukin-1β, tumor necrosis factor-α, and monocyte chemoattractant protein-1 in bronchoalveolar lavage fluid (BALF) showed dose- and time-dependent increases and the levels of these inflammatory mediators are consistent with the data of inflammatory cells in BALF and progressive lung damages by In2O3 NPs. This study suggests that a single inhalation exposure to In2O3 NPs can produce worsening lung damages such as PAP, chronic active inflammation, infiltration of foamy macrophages, and granulomas. The early onset and persistent PAP even at the very low dose (7.5 cm2/rat) implies that the re-evaluation of occupational recommended exposure limit for In2O3 NPs is urgently needed to protect workers.

The inflammatory pseudotumor presenting periodic acid-Schiff-positive inclusions with acute unilateral facial nerve palsy

Although most acute peripheral facial palsies can be attributed to Bell’s palsy, other factors, such as infection, trauma, and neoplasm, can cause facial palsy as well. Among these, facial nerve tumors are rare but should be considered in the differential diagnosis of facial palsy. Palsies due to facial nerve tumors usually present with slow onset but occasionally present as acute episodes. In such cases, facial nerve decompression is the treatment of choice to allow the tumor room to grow without compressing the nerve or its blood supply. We describe a case of severe, acute facial palsy presenting with a spindle-shaped bone erosion on the mastoid portion of the facial canal. Although facial neuroma was suspected preoperatively, emergency decompression surgery revealed that an unusual inflammatory pseudotumor was responsible for the finding. Postoperative histological analysis revealed extensive destruction of the nerve fibers, with extensive infiltration of foamy macrophages containing characteristic, diastase-resistant, periodic acid-Schiff (PAS)-positive inclusions, which are hallmark of the uncommon bacterial infections. This was a case of facial palsy with an unusual etiology. The case shows the benefit of decompression surgery not only as treatment for the palsy but also as exploratory surgery in cases of facial nerve tumor.

Chronic liver disease in cattle associated with ingestion of Brachiaria spp.

ABSTRACT: One hundred and ninety livers condemned due to chronic disease (fibrosis) were evaluated in a bovine slaughterhouse over 12 months. Hepatic lymph nodes were also examined while still attached to livers. The major macroscopic lesion observed in the livers was moderate to severe atrophy of the left lobe associated with compensatory hypertrophy of the right lobe. Histologically, the main changes corresponded to sites of macroscopic lesions, and fibrosis was observed in all livers, along with bile duct hyperplasia and neovascularization. Masson's trichrome stain highlighted the fibrous connective tissue. Most of the livers analyzed had macrophages with foamy cytoplasm and a peripheral nucleus that infiltrated fibrotic areas. Immunohistochemistry (IHC) for macrophages with monoclonal antibody clone MAC 387 revealed that the cytoplasm of the foamy macrophages of the liver and of the hepatic lymph nodes were positively immunostained. These cells are frequently associated to the consumption of grasses of the genus Brachiaria. Although the liver gross lesions described in this study have not been previously reported in animals consuming Brachiaria , the associated changes observed histologically, such as fibrosis and infiltration of foamy macrophages, showed a new form of chronic liver disease probably associated with the consumption of this forage. The IHC technique was important to prove that the foam cells observed are macrophages.

Pathology of coronary atherosclerosis and thrombosis.

The process of early atherosclerotic plaque progression is characterized by the development of pathologic intimal thickening (PIT) with lipid pool that may transform into the necrotic core to form fibroatheroma, where infiltration of foamy macrophages plays a crucial role. The expansion of the necrotic core is also attributable to intraplaque hemorrhage. Thin-cap fibroatheroma (TCFA) is characterized by a relatively large necrotic core with an overlying thin fibrous cap measuring <65 µm typically containing numerous macrophages, and is considered to be the precursor lesion of plaque rupture which is the most common cause of coronary thrombosis. The second common cause of acute thrombosis is plaque erosion, while calcified nodules is known to be the least frequent cause of coronary thrombosis. Coronary thrombosis can occur without symptoms to form healed lesions, which contributes to an increase in plaque burden and luminal narrowing. The process of plaque progression is generally accompanied by the progression of calcification. An understanding of the histomorphological characteristics of coronary plaques should provide important insights into the pathogenesis, diagnosis, and treatment of atherosclerotic coronary disease for both basic and clinical researchers as well as for clinicians.

Spontaneous poisoning by Brachiaria decumbens in goats

Abstract: An outbreak of Brachiaria decumbens poisoning in goats in the state of Mato Grosso do Sul, Brazil, is described. Out of a herd of about 1,000 goats, seven goats died after showing photosensitivity (3 out 7 goats) and icterus (4/7). Other clinical signs included lethargy, dehydration and weight loss (7/7). At necropsy there was either hepatomegaly or liver atrophy; orange, yellow or gray discoloration - were observed in the liver of six goats. Two had accentuation of lobular pattern and punctate, linear or stellar fibrous depressions were randomly distributedover the capsular surface. Macroscopic changesattributedto liver failure consisting of hydropericardium (2/7) and ascites (2/7) were observed. Histologically, there was accumulation of refringent crystals in the bile ducts and infiltration of foamy macrophages in the liver of all goats. Foamy macrophages were also present in the hepatic and mesenteric lymph nodes of two goats. The diagnosis of B. decumbens poisoning was based on epidemiology, clinical signs, necropsy findings and histopathology.

Very, very late stent thrombosis triggered by in-stent neoatherosclerosis: optical coherence tomography findings.

A 64-year-old woman with dyslipidemia, hypertension and type 2 diabetes plus an existing 4.0-mm × 28-mm bare-metal stent (BMS; Multilink Penta, Abbott Vascular, US) deployed over 10 years ago in the right coronary artery (RCA) was admitted to our emergency department with inferolateral and posterior ST-segment elevation acute myocardial infarction. Coronary angiography showed occlusion and thrombotic plaque in the mid RCA at the site of the prior stent implantation. After thrombectomy, optical coherence tomography (OCT) documented the presence of in-stent neoatherosclerosis with lipid-laden plaque, mild calcification, clustered macrophages and a disrupted thin-cap fibroatheroma (TCFA), a pattern similar to the morphology seen with typical native atherosclerosis (Figure 1). Figure 1 RCA angiography in right anterior oblique view before (left) and after (middle) thrombus aspiration. The region between the arrows represents the region covered by the BMS implanted over a decade earlier. OCT (right) demonstrates that TCFA has developed ... In-stent restenosis has widely been considered a stable process, showing an early peak of intimal hyperplasia followed by a stationary period generally after 1 year following stent implantation [1]. More recently, pathologic and in vivo intravascular imaging studies have challenged this finding by showing that lipid-rich plaque with macrophage infiltration and a necrotic core may occur inside the stent. This process of in-stent neoatherosclerosis occurs within months to a few years, compared with the decades that it generally takes for native disease to develop [2, 3]. Previous autopsy studies have shown a higher incidence of neoatherosclerosis in lesions treated with first- and second- generation drug-eluting stents (DES) compared with BMS (31% vs. 30% vs. 16%, respectively) [2, 3]. Of note, neoatherosclerosis presentation occurred on average at ∼400 days after first-generation DES, ∼200 days after second-generation DES, and ∼2,000 days after BMS [2, 3]. Much like native coronary disease, the infiltration of foamy macrophages within the neointima could possibly cause thinning of the fibrous cap, leading to the development of a TCFA and complications of rupture with thrombosis, as seen in the present case. The present report describes an unusual case of very, very late stent thrombosis – occurring more than a decade after BMS at 3,710 days – with evidence of neoatherosclerosis. This case highlights the need for continuous and perpetual secondary prevention of coronary artery disease in patients receiving percutaneous coronary intervention. The permanent presence of metallic foreign material in the vessel wall might indefinitely remain a potential trigger for stent failure at extended follow-up.

18F-FDG PET and intravascular ultrasonography (IVUS) images compared with histology of atherosclerotic plaques: 18F-FDG accumulates in foamy macrophages

Intravascular ultrasonography (IVUS) and (18)F-FDG PET have been used to evaluate the efficacy of antiatherosclerosis drugs. These two modalities image different characteristics of atherosclerotic plaques, and a comparison of IVUS and PET images with histology has not been performed. The aim of this study was to align IVUS and PET images using anatomic landmarks in Watanabe heritable hyperlipidaemic (WHHL) rabbits, enabling comparison of their depiction of aortic atherosclerosis. Cellular (18)F-FDG localization was evaluated by (3)H-FDG microautoradiography (micro-ARG). A total of 19 WHHL rabbits (7 months of age) were divided into three groups: baseline (n = 6), 3 months (n = 4), and 6 months (n = 9). PET, IVUS and histological images of the same aortic segments were analysed. Infiltration by foamy macrophages was scored from 0 to IV using haematoxylin and eosin (H&E) and antimacrophage immunohistochemical staining, and compared with (3)H-FDG micro-ARG findings in two additional WHHL rabbits. IVUS images did not identify foamy macrophage deposition but revealed the area of intimal lesions (r = 0.87). (18)F-FDG PET revealed foamy macrophage distribution in the plaques. The intensity of (18)F-FDG uptake was correlated positively with the degree of foamy macrophage infiltration. Micro-ARG showed identical (3)H-FDG accumulation in the foamy macrophages surrounding the lipid core of the plaques. F-FDG PET localized and quantified the degree of infiltration of foamy macrophages in atherosclerotic lesions. IVUS defined the size of lesions. (18)F-FDG PET is a promising imaging technique for evaluating atherosclerosis and for monitoring changes in the composition of atherosclerotic plaques affecting their stability.

Oxidative stress and lung injury induced by short-term exposure to wood smoke in guinea pigs

Oxidative stress and lung injury induced by short-term exposure to wood smoke were evaluated in guinea pigs through cell profile, bronchoalveolar lavage (BAL), conventional histology and immunohistochemistry (4-hydroxynonenal, 3-nitrotyrosine, Mn-superoxide dismutase, heme oxygenase-1); malondialdehyde and 4-hydroxynonenal concentration, Mn-superoxide dismutase, glutathione reductase, glutathione peroxidase, and catalase activities in plasma, lung and BAL. Total cells increased in BAL, and the percentage of macrophages, neutrophils and lymphocytes augmented (72–96 h). Histopathological examination of lung tissues showed mild thickening of membranous bronchiole walls, infiltration of foamy macrophages and polymorphonuclear leukocytes in bronchial, bronchiolar and intraalveolar spaces. Goblet cell hyperplasia was also observed in bronchial and bronchiolar epithelia. Plasma malondialdehyde concentration was increased at all times, while 4-hydroxynonenal was increased only in plasma and BAL after 24 h. Plasma glutathione reductase activity increased at 24 and 72 h, BAL glutathione peroxidase activity decreased at 72 and 96 h, whereas catalase activity increased in plasma at 72 h, and decreased in BAL at 24 h. Immunostaining intensity to 4-hydroxynonenal, 3-nitrotyrosine, Mn-superoxide dismutase and heme oxygenase-1 was enhanced mainly in macrophages, bronchial/bronchiolar epithelial cells and type II pneumocytes after 72–96 h of wood smoke exposure. Overall, short-term exposure to wood smoke induces alterations in oxidative/antioxidant state in lung and airway injury, similar to those observed in humans with domestic exposure.

Avian Mycobacteriosis in Psittacines: A Retrospective Study of 123 Cases

One hundred and twenty-three cases of mycobacterioses were diagnosed in psittacine birds from a total of 9,241 submissions for necropsy examination or histopathology made to the California Animal Health and Food Safety Laboratory System between 1990 and 2007. The species affected most commonly were Amazon parrots (Amazona spp.)(n=32; 26%) and grey-cheeked parakeets Brotogeris pyrrophterus (n=23; 18.7%). The main gross findings on necropsy examination were enlarged and mottled pale livers and spleens and thickening of the small intestinal wall with numerous pale miliary nodules on the mucosa. Microscopical examination revealed infiltration of foamy macrophages and giant cells containing acid-fast bacteria in various organs. The gene encoding mycobacterial 65kDa heat shock protein (hsp65) was amplified by nested polymerase chain reaction (PCR) from DNA extracted from 22 cases. The species of Mycobacterium involved was determined by analysis of restriction endonuclease patterns of the PCR products. Mycobacterium genavense was detected in 19 cases and Mycobacterium avium in two cases. One parrotlet (Touit spp.) had a mixed infection of both species of mycobacteria. It is concluded that M. genavense is the primary cause of mycobacteriosis in psittacine birds and the potential for zoonotic disease should be considered, especially for immunocompromised owners.

Retroperitoneal schwannoma is characterized by a high incidence of cellular type and GFAP‐immunoreactivity

To clarify the clinicopathologic characteristics of retroperitoneal schwannomas, which are sometimes confused with other spindle cell tumors, 27 cases were studied microscopically and immunohistochemically. The 27 cases consisted of 17 females and 10 males, the ages of whom ranged from 31-79 (mean 57.4) years. Gross examination revealed well-demarcated, encapsulated tumors, 3-15 cm (mean 8 cm) in diameter. Microscopic review divided them into 13 cases of cellular/fascicular, 3 of conventional, 6 of intermediate, and 5 of ancient type. Cellular/fascicular schwannomas were composed of cellular fascicles of spindle cells, in which nuclear palisading, Antoni B area and cyst were unclear, while numerous foamy cells were intermingled. Immunohistochemical investigation revealed diffuse, strong positivity for S-100 protein and Sox10 in all tumors studied. In addition, glial fibrillary acidic protein (GFAP) was extensively expressed in 92% of the cellular/fascicular type, while it was less prominent in others. The present study suggests that retroperitoneal schwannoma often occurs in the middle-aged woman, grows to a large size, exhibits cellular/fascicular microscopic features in half of the cases, and may arise from GFAP-positive Schwann cells. The presence of hyalinized vessels and dense infiltration of foamy macrophages as well as diffuse immunoreactivity for S-100 protein and Sox10 are helpful for the differential diagnosis.

Alterações histológicas em fígados e linfonodos de búfalos (Bubalus bubalis) mantidos em pastagens de Brachiaria spp.

Infiltração por macrófagos espumosos e outras lesões podem ser encontradas em bovinos clinicamente sadios em pastagens de Brachiaria spp. Com o objetivo de determinar as alterações histológicas do fígado e linfonodos mesentéricos em búfalos no Pará foram estudadas as alterações histológicas de fragmentos desses órgãos de 142 búfalos da raça Murrah e de 15 bovinos da raça Nelore, coletados em frigoríficos. As coletas foram separadas em grupos de animais de acordo com sua origem e tempo de permanência na pastagem de Brachiaria spp., sendo o Grupo (G) 1 composto por 79 búfalos provenientes da Ilha de Marajó, criados em pastagens de campo nativo; o G2 composto por 17 búfalos mantidos desde o nascimento em pastagens de Brachiaria brizantha; o G3 composto por 29 búfalos adquiridos na Ilha do Marajó e introduzidos em pastagem de B. decumbens por aproximadamente 12 meses; o G4 composto por 17 búfalos adquiridos na Ilha de Marajó e introduzidos em pastagem de B. brizantha por aproximadamente 18 meses; e o G5 composto por 15 bovinos mantidos em pastagem de B. brizantha por aproximadamente 12 meses. Para avaliar a gravidade da lesão hepática foram estabelecidos graus de acordo com a quantidade e tamanho dos grupos de macrófagos espumosos, seguindo uma escala de 0 a 4. Nos animais do G1, provenientes da Ilha de Marajó, não foram observadas alterações histológicas significativas no fígado e linfonodos mesentéricos. Em todas as amostras dos grupos G2, G3 e G4 foram observados quantidades variáveis de macrófagos espumosos no fígado e linfonodos mesentéricos. Os animais dos grupos G2 e do G4, que permaneceram um período maior em pastagens de Brachiaria spp, apresentaram lesões mais acentuadas (P&lt;0,05) de macrófagos espumosos do que os animais do G3. Além da presença de macrófagos espumosos, foram observadas também, no fígado desses três grupos, tumefação, vacuolização e necrose de hepatócitos, principalmente da região centrolobular. Essas lesões eram mais acentuadas nas áreas onde havia maior infiltração de macrófagos espumosos. Havia fibrose capsular e as lesões dos hepatócitos nesta localização eram mais severas. Nos bovinos do G5 foram observados pequenos grupos de macrófagos espumosos nos linfonodos mesentéricos e ausência dessas células no fígado. Esses resultados sugerem que as lesões hepáticas observadas na histologia em búfalos sem sinais clínicos são ocasionadas pela ingestão de Brachiaria spp. A presença de lesões severas em búfalos sem sinais clínicos, bem mais graves do que as observadas em bovinos, assim como a ausência de surtos de intoxicação por Brachiaria nessa espécie, sugere sua resiliência à intoxicação por Brachiaria spp. Dentro de cada grupo não foi comprovada associação entre o peso ao abate e a gravidade das lesões. A presença de lesões severas no fígado de búfalos sem sinais clínicos alerta para o fato de que lesões semelhantes encontradas durante necropsias de búfalos mortos por outras causas possam levar ao diagnóstico errado de intoxicação por Brachiaria spp.

A Case of Osteoarthropathy Due to Erdheim-Chester Disease with Overlapping Langerhans' Cell Infiltration

Histiocytosis sometimes involves the joints, and is one of the important differential diagnoses of osteoarthropathy. A 31-year-old man presented with recurrent fever and bilateral knee arthritis two years prior to admission. He also showed the hypopituitary mass lesion and partial hypopituitarism. X-ray studies showed both osteosclerotic and osteolytic lesions near the large joints. Histological findings of bone biopsy revealed foamy macrophage infiltration, which were CD68+CD1a-S100-, and Erdheim-Chester disease was diagnosed. In addition, CD68+CD1a+ Langerhans' cells also aggregated in the same lesions, and we thought this case was a rare variant of Erdheim-Chester disease with overlapping histiocytic invasion.

Sebaceous carcinoma of the eyelids: Thirty cases from Japan

Sebaceous carcinoma of the eyelids is rare in Western countries but not uncommon in Asian countries. Diagnosis is difficult both clinically and histologically. Thirty cases of sebaceous carcinoma of the eyelids treated at Tokyo Medical University Hospital were reviewed to elicit characteristic features of pathological findings. The tumor cells were infiltrating in a lobular pattern that consisted mainly of large atypical germinative cells. Sebocytes seen in the lobules had conspicuous nucleolus associated with perinucleolar halo. In 17 cases (57%) there was foamy histiocyte infiltration in and around the tumor nests. Sebaceous duct differentiation, namely holocrine secretion indicating a specific type of coagulation necrosis maintaining a cellular framework or maintaining a bubbly cytoplasm associated with nuclear debris in the periphery, was seen in 24 cases (80%). Although unequivocal squamous differentiation was limited to only 11 carcinomas, scattered individual necrosis with nuclear debris in the background of germinative cells appeared in 29 cases (96.7%). Expression of epithelial membrane antigen, perilipin and adipophilin were detected in all cases. In conclusion, to detect sebaceous differentiation in sebaceous carcinoma, it would be helpful to focus on holocrine secretion, squamous differentiation and foamy macrophage infiltration, and to utilize immunohistochemistry involving anti-perilipin and anti-adipophilin stain.