Splenic Sinuses Research Articles

Benign Lesions of the Spleen—Are They Really So Benign? A Report of Two Cases

Primary angiosarcoma of spleen is a rare and aggressive tumour arising from the endothelial lining of the splenic sinuses, with very poor outcome. Due to similarity in clinical and radiological features, they are often mistaken for benign splenic lesions and misdiagnosed. We present two cases where they were misdiagnosed as splenic haemangioma and splenic abscess. Both patients ultimately underwent splenectomy but succumbed to this aggressive disease.

Typhlohepatitis and Amyloidosis Associated with High Mortality in Chukar Partridges (Alectoris chukar)

Twelve chukar partridges (Alectoris chukar) from a farm experiencing poor uniformity and increased mortality of up to 65% were submitted for diagnosis. Several birds had mild to moderate multifocal white foci or multifocal petechial hemorrhages throughout the liver. Livers and spleens of older birds were moderate to severely diffusely enlarged. In addition, some birds had caseous cores mixed with blood within the ceca as well as segmentally thickened cecal walls. Histopathology showed acute, multifocal, severe, often coalescing foci of necrosis with accumulation of fibrin and/or fibrinosuppurative inflammation in livers and spleens. Scattered within exudate were protozoa that were spherical or round and measured 12-20 µm in diameter. In the ceca, acute necrosis of the mucosa was observed, often with ulceration and fibrinosuppurative inflammation. Immunohistochemistry using an antiserum against Tritrichomonas foetus revealed round protozoa in ceca, small intestines, liver, spleen, and lung. Quantitative PCR to detect DNA of Histomonas meleagridis was negative. Non-species-specific PCRs amplifying the partial rDNA, the internal transcribed spacer (ITS) region, and the partial beta-tubulin gene yielded products of the expected size. Sequences of the PCR products had the highest homology to sequences of Tetratrichomonas gallinarum and less homology to sequences of H. meleagridis. In addition there was accumulation of amyloid in the space of Disse in the liver, splenic sinuses, and walls of the blood vessels. The typhlohepatitis and other inflammatory processes that were diagnosed might be the underlying cause of the amyloidosis. Other findings were clusters of Clostridium perfringens associated with the lesions in the ceca; multifocal granulomas in the lungs, occasionally associated with fungal hyphae; hyperkeratosis associated with bacteria and Candida sp. cells in the crop; mild infection of the bursal mucosa with Cryptosporidium.

Tumour necrosis factor receptor-1 is dispensable for the migration of marginal metallophilic macrophages into the B-cell zone of the mouse spleen.

The spleen is the only blood filter in the organism which removes foreign antigens and effete cells from circulation. The significant role in capturing, transporting and presentation of antigens to immune cells is executed by a special subset of splenic macrophages called marginal metallophilic macrophages. Upon stimulation with lipopolysaccharide, these cells promptly migrate from their preferential location at the inner aspect of the splenic marginal sinus into the B-cell lymphoid follicles. This migration is executed via CXC chemokine ligand 13 in a lymphotoxin-dependent fashion. However, the role of tumour necrosis factor-α/tumour necrosis factor receptor-1 signalling axis has not been studied, despite its critical role in the formation of B-cell lymphoid follicles, follicular dendritic cell networks and germinal centres. Here, we show that signalling via tumour necrosis factor receptor-1 is not required for the migration of marginal metallophilic macrophages into the B-cell zone and that the presence of organized B-cell lymphoid follicles is not a prerequisite for their dislocation.

Comparison of histological characteristics and expression of CD3 and CD79a among the hemal nodes, lymph nodes and spleens of yaks (Bos grunniens).

This experiment compared the histological characteristics and distribution of CD3 and CD79a among yak lymph nodes, hemal nodes and spleen. The three organs from ten clinically healthy newborn and adult yaks were studied using histology and immunohistochemistry. The yak hemal nodes, which consisted of blood sinuses, lymphoid follicles, diffuse lymphoid tissue and lymphoid cords, appeared to share the histological characteristics of the spleen and lymph nodes: the lymphoid follicles of the hemal nodes were much like those of the lymph nodes, which were not surrounded by the central artery and periarteriolar lymphoid sheath. The lymphoid cords of the hemal node, which contained many erythrocytes, were much like the splenic cords. The sinuses of the hemal nodes had a similar structure to the lymph sinuses of the lymph nodes but were engorged with erythrocytes rather than lymph as in the lymph nodes. Interestingly, the splenic sinuses of yak were of two different types: the sinuses with obvious endothelial cells or those consisting of reticular cells. The CD3+ cells were mainly located in the paracortex area and medulla of the lymph nodes, the diffuse lymphoid tissues of the hemal nodes, and the periarteriolar lymphoid sheaths and red pulp of the spleen. Most CD79a+ cells were mainly detected in the lymphoid follicles of all examined lymphoid organs. The results suggested that although the three organs had specific characteristics, in some respects, they had similar organizational structural characteristics and immune functions. These may be useful to better understand the relationship between the morphology and function of these organs and provide useful references for normal yak lymphoid organs.

Distribution of non-myelinating Schwann cells and their associations with leukocytes in mouse spleen revealed by immunofluorescence staining.

The nervous system and the immune system communicate extensively with each other in order to maintain homeostasis and to regulate the immune response. The peripheral nervous system (PNS) communicates specifically with the immune system according to local interactions, including the “hardwiring” of sympathetic/parasympathetic (efferent) and sensory nerves (afferent) to lymphoid tissue and organs. To reveal this type of bidirectional neuroimmune interaction at the microscopic level, we used immunofluorescent staining of glial fibrillary acidic protein (GFAP) coupled with confocal microscopy/3D reconstruction to reveal the distribution of nonmyelinating Schwann cells (NMSCs) and their interactions with immune cells inside mouse spleen. Our results demonstrate i) the presence of an extensive network of NMSC processes in all splenic compartments including the splenic nodules, periarteriolar lymphoid sheath (PALS), marginal zone, trabecula, and red pulp; ii) the close association of NMSC processes with blood vessels (including central arteries and their branches, marginal sinuses, penicillar arterioles and splenic sinuses); iii) the close “synapse-like” interaction/association of NMSC processes with various subsets of dendritic cells (DCs; e.g., CD4+CD11c+ DCs, B220+CD11c+ DCs, and F4/80+ CD11c+ DCs), macrophages (F4/80+), and lymphocytes (B cells, CD4+ T helper cells). Our novel findings concerning the distribution of NMSCs and NMSC-leukocytes interactions inside mouse spleen should improve our understanding of the mechanisms through which the PNS affects cellular- and humoral-mediated immune responses in a variety of health conditions and infectious/non-infectious diseases.

Littoral cell angioma with splenic rupture in pregnancy

Abstract Splenic rupture in pregnancy is a rare event. It is generally due to trauma or an underlying splenic pathology. Timely diagnosis and intervention of splenic rupture is essential given the high rates of associated maternal and fetal morbidity and mortality. This case illustrates a 38 year old lady in the third trimester of pregnancy who presented with maternal collapse and a non-reassuring foetal heart rate tracing following a fall at home one week previously. A massive hemoperitoneum was identified at caesarean section and a splenectomy was performed. Histological examination revealed a littoral cell angioma of the spleen. This vascular tumour arising in the splenic red pulp sinuses is a rare entity and specific immunophenotypic features help distinguish it from other vascular tumours of the spleen. Both trauma and an underlying splenic pathology led to splenic rupture in this unique case.

Multifocal capillary hemangioma (hemangiomatosis) of the spleen.

The spleen is mainly affected by benign tumors that originate from the vascular endothelium. The most common is hemangioma, which presents as a small, localized lesion. Isolated diffuse hemangiomatosis of the spleen is a rare entity in which the entire splenic parenchyma is replaced by a proliferation of neoplastic blood vessels. Here we illustrate the case of a 26-year-old man presenting with splenomegaly due to diffuse hemangiomatosis of the white pulp who underwent a splenectomy. Representative samples of the spleen were stained with hematoxylin and eosin, and immunohistochemical analysis was performed for Mib-1, CD20, CD30, CD15, CD34, CD31, CD8, factor VIII, D2-40, CD68PGM1, and LMP1. Macroscopically, the splenic parenchyma contained multiple, red-brown nodules ranging from 0.4 to 1.5 cm. Microscopically, the nodules were roundish and confluent with an angiomatoid appearance and high positivity for CD34 and factor VIII, while they were negative for D2-40. The differential diagnosis of splenic tumors includes lymphangioma, lymphangiomatosis, peliosis, littoral cell angioma, hemangioendothelioma, hamartoma, angiomatoid transformation of the spleen, and angiosarcoma. It is debated whether diffuse hemangiomatosis is a malformation of the postsinusoidal venous system or a slowly growing neoplasm arising from the splenic sinuses. The positivity of the cavernous vessels for CD8 seems to be in favor of the malformative nature of the tumor.

Supersonic Shear Wave Imaging of the Spleen for Staging of Liver Fibrosis in Rats

The goal of the work described here was to explore the cause of spleen stiffness (SS) in hepatic fibrogenesis and evaluate the value of SS in liver fibrosis (LF) staging. LF was induced with carbon tetrachloride (CCl4) in rats (n = 40). Supersonic shear wave imaging and contrast-enhanced ultrasound were performed to determine liver stiffness (LS), SS and splenic hemodynamics. SS, LS and free portal pressure exhibited moderate correlations with fibrosis stage (r = 0.744–0.835, p < 0.001). Time–intensity curves of contrast-enhanced ultrasound for the spleen were presented as decreasing peak intensity and slope of decrease, and increasing time to peak. Splenic sinus dilation and congestion were observed on histopathologic analysis. The area under the receiver operating characteristic curve of SS was higher than that of LS for differentiating LF stages 0–2 from stages 3–4 (Z = 2.293, p = 0.02). SS is a reliable diagnostic marker for the assessment of LF in the CCl4 model, especially for severe fibrosis. Elevated portal pressure is the cause of increasing SS.

Endoscopic Ultrasound-Guided Fine Needle Aspiration Diagnosis of Intrapancreatic Accessory Spleen

Introduction: Accessory spleen (AS) is a rare congenital anomaly in which there is failure of fusion between a portion of the developing splenic tissue and the main body of the spleen. The majority of cases occur at the splenic hilum, while the second most common site is the tail of the pancreas. Intrapancreatic accessory neoplasm (IPAS) cytopathology findings include heterogeneous small lymphocytes along with traversing small vessels. Immunohistochemical staining for CD8 is a useful tool that specifically highlights the endothelial cells of the splenic sinus. Here report an additional case of IPAS diagnosed by endoscopic ultrasound (EUS) guided fine needle aspiration (FNA). Case presentation: A 20 year old Caucasian female presented as a referral to the gastroenterology department for an EUS evaluation after she had an elevated liver function test postpartum. An magnetic resonance cholangiopancreatography (MRCP) revealed an obstruction in the common bile duct and a small solid mass at the tail of the pancreas measuring 11 mm in size. She underwent an Endoscopic Retrograde Cholangiopancreatography (ERCP) with common bile duct stone removal. Endoscopic ultrasound (EUS) with FNA was performed and revealed a single hypoechoic oval welldemarcated 11.4 mm x 8.9 mm pancreatic solid mass at the tail of the pancreas. Cytopathology revealed a benign intrapancreatic accessory spleen. Cell block sections displayed branching thin walled blood vessels surrounded by lymphoid cells that shows positive immunoreactivity for CD8. Immunohistochemical stains were positive leukocyte lymphoid antigen. Conclusion: IPAS is a benign congenital anomaly that may mimic a pancreatic neoplasm. FNA can be performed for diagnosis. The use of a combination of common cytomorphologic features, immunohistochemical stains and radiologic findings will enable an accurate diagnosis and prevent unnecessary surgical procedures.

Reversible host cell remodeling underpins deformability changes in malaria parasite sexual blood stages

The sexual blood stage of the human malaria parasite Plasmodium falciparum undergoes remarkable biophysical changes as it prepares for transmission to mosquitoes. During maturation, midstage gametocytes show low deformability and sequester in the bone marrow and spleen cords, thus avoiding clearance during passage through splenic sinuses. Mature gametocytes exhibit increased deformability and reappear in the peripheral circulation, allowing uptake by mosquitoes. Here we define the reversible changes in erythrocyte membrane organization that underpin this biomechanical transformation. Atomic force microscopy reveals that the length of the spectrin cross-members and the size of the skeletal meshwork increase in developing gametocytes, then decrease in mature-stage gametocytes. These changes are accompanied by relocation of actin from the erythrocyte membrane to the Maurer's clefts. Fluorescence recovery after photobleaching reveals reversible changes in the level of coupling between the membrane skeleton and the plasma membrane. Treatment of midstage gametocytes with cytochalasin D decreases the vertical coupling and increases their filterability. A computationally efficient coarse-grained model of the erythrocyte membrane reveals that restructuring and constraining the spectrin meshwork can fully account for the observed changes in deformability.

Differentiated localizations of phosphorylated focal adhesion kinase in endothelial cells of rat splenic sinus.

The splenic sinus endothelium adhering via adherens junctions and tight junctions regulates the passage of blood cells through the splenic cord. Focal adhesion kinase (FAK) regulates the focal adhesion complex in the basal part of endothelial cells and is an integrated component of cell-cell adhesion, depending on its phosphorylation status. The objectives of this study are to assess the localization of FAK phosphorylated at tyrosine residues and the related proteins of integrin β5, talin, paxillin, p130Cas, vinculin, RhoA, Rac1, Rac2, Cdc42 and VE-cadherin, in the sinus endothelial cells of rat spleen and to examine the roles of FAK in regulating endothelial adhesion and the passage of blood cells. Immunofluorescence microscopy of tissue cryosections revealed that FAK was localized in the entire circumference of sinus endothelial cells and FAK phosphorylated at Try397 residue (pFAKy397) and pFAKy576 were precisely localized in the adherens junctions of the endothelial cells, whereas pFAKy925 was localized in the basal part of the endothelial cells. Paxillin and vinculin were prominently localized in the basal part of the endothelial cells. Integrin β5, talin and p130Cas were colocalized with FAK in the entire circumference of sinus endothelial cells. RhoA, Rac2 and Cdc42 were localized in the entire circumference of sinus endothelial cells close to FAK, stress fibers and cortical actin filaments. Immunogold electron microscopy revealed that pFAKy397 and pFAKy576 were colocalized with VE-cadherin, RhoA, Rac2 and Cdc42 in the adherens junctions of the endothelial cells. Possible functional roles of FAK in splenic sinus endothelial cells are also discussed.

Variation of subsets of myeloid derived suppressor cells and their ratio in septic mice

To investigate the dynamic variation of subsets of myeloid derived suppressor cells (MDSC) and their ratio in septic mice, and to discuss their role in the development of sepsis. Male C57BL/6 mice were randomly divided into sepsis model group and sham group according to random number table. Polymicrobial sepsis was induced by using cecal ligation and puncture (CLP), while mice in sham group only underwent laparotomy and laparorrhaphy without CLP. Thirty mice in each group were used to observe living condition, and the 20-day survival rate was compared between the two groups. In addition, subsets of MDSC in peripheral blood, spleen and bone marrow were analyzed with flow cytometry for other 60 mice (12 mice at each time point, as 0, 3, 7, 12 and 20 days). Spleens were harvested at 7 days for weighing, and single cell suspension of spleen tissue was prepared for splenocyte counting. Histopathologic changes in spleen tissue and liver tissue were observed under light microscope after hematoxylin and eosin (HE) stain. (1) No mice died in sham group within 20 days after the operation. On the other hand, 10 mice in model group died within 20 days, and the difference in survival rate between the two groups was statistically significant (100.0% vs. 66.7%, χ(2) = 11.861, P = 0.001). (2) The spleens in model group showed obvious enlargement and significantly outweighed as compared with those in sham group (mg: 413.33±41.63 vs. 111.67±17.56, t = 11.564, P = 0.000), and the total count of splenocytes was significantly higher than that in sham group (×10(9)/L: 21.20±2.43 vs. 1.87±0.06, t = 13.578, P = 0.005). (3) Pathological sections with HE staining showed that the liver tissue and spleen tissue remained normal in sham group. In model group, the hepatic tissue showed acute inflammatory reaction, including tissue disruption, capillary congestion, infiltration of neutrophils, marked edema of hepatocytes and focal hepatocellular necrosis. Abnormalities were also found in the spleen tissue: the red pulp and white pulp were disordered, splenic sinus was congested with numerous red cells, the splenic capsule thickened, immature myeloid cells with circular nuclei proliferated in the subcapsular region and perivascular region, splenic cord and splenic sinus were infiltrated with a large number of hematopoietic cells. (4) No significant changes in the monocytic MDSC (M-MDSC) and granulocytic MDSC (G-MDSC), and their ratio were found in peripheral blood, spleen and bone marrow at every time point in sham group. On the other hand, in model group, the ratio of M-MDSC and G-MDSC was continuously increased in peripheral blood, spleen and bone marrow, and M-MDSC only slightly decreased at 20 days. On the other hand, the ratio of M-MDSC/G-MDSC rose at first followed by a decrease. The ratio of M-MDSC/G-MDSC in peripheral blood was higher than 1 from 3 days after the operation, reaching the peak at 12 days (compared with 0 day: 4.16±0.53 vs. 0.79±0.11, P < 0.05), while the ratio of M-MDSC/G-MDSC in spleen and bone marrow after CLP were lower than 1 at all time points, reaching the peak on 7 days after the operation (compared with 0 day: 0.70±0.06 vs. 0.25±0.02 in spleen, 0.39±0.06 vs. 0.11±0.01 in bone marrow, both P < 0.05), and then gradually decreased afterwards. Subgroups of MDSCs were continuously aggregated in the peripheral blood, spleen and bone marrow, and their ratio rose first and decreased afterwards along with the development of sepsis, and the changes may reflect the change of immune status at different stages of sepsis.

Marginal Zone B Cell Depletion Prevents Factor VIII Inhibitor Development in Model of Hemophilia

Background While Factor VIII (fVIII) therapy can provide a life saving intervention in patients with hemophilia A, patients receiving fVIII can develop anti-fVIII antibodies. These antibodies, otherwise known as fVIII inhibitors, often prevent the therapeutic impact of fVIII. As a result, hemophilia A patients with fVIII inhibitors often experience increased morbidity and mortality. Given the unique role of the splenic marginal sinus in the immune response to blood borne antigens, we hypothesized that key immunological constituents within the marginal zone (MZ) likely play a critical role in the initiation and development of anti-fVIII antibodies in hemophilia A recipients.Methods: To deplete MZ B-cells, complete F8 gene knockout mice (TKO mice) received two initial 100 µg intraperitoneal injections of MZ B-cell depleting antibodies (anti-CD11a and anti-CD49d) or isotype controls on days -4, -2, 10 and 20. Additional mice that received MZ B cell depleting antibodies were examined for MZ B cell depletion efficacy and specificity on days 0, 7, 14, 21 and 28 by staining splenocytes with CD3, CD4, CD8, CD11b, CD11c, NK1.1, B220, CD21 and CD23. Starting on day 0, mice received 4 weekly retro-orbital injections of 2 µg of B-domain deleted human fVIII (BDD hfVIII). At 6 weeks, mice received a 4 µg "boost" dose of BDD hfVIII. At eight weeks, mice were then re-challenged with 4 weekly doses of 2 µg of BDD hfVIII. At each interval (pre-boost, post-boost, and after re-challenge) mice were bled and ELISA and inhibitor titers were determined.Results: As the development of detectable anti-fVIII antibodies often requires repeat fVIII exposure, we examined whether repeat injection of MZ B cell depleting antibodies could sustain MZ B cell depletion. Injection of MZ B cell depleting antibodies on days -4, -2, 10 and 20 completely prevented MZ B cell localization within the spleen for 28 days, while failing to alter follicular B cell, NK cell, CD4 T cell, dendritic cell and macrophage numbers. Injection of isotype controls failed to alter MZ B cell numbers when evaluated in parallel. Weekly injection of BDD hfVIII during the first four weeks completely failed to induce an anti-fVIII antibody response in MZ B cell depleted recipients (p<0.0015, Mann Whitney), while isotype control treated recipients developed inhibitors at the same rate as non-treated controls. However, following MZ B cell reconstitution at day 35, recipients previously treated with the MZ B cell depletion regiment developed an immune response that closely resembles naive hemophilia A recipients.Conclusion: These results demonstrate that marginal zone constituents, in particular MZ B cells, play a critical role in the initiation and development of fVIII inhibitors. While MZ B cell depleted recipients failed to generate anti-fVIII antibodies following fVIII exposure, MZ B cell reconstitution after fVIII exposure readily induced anti-fVIII antibodies, suggesting that transient removal of MZ B cell may provide a unique mechanism to prevent fVIII antibody formation without permanently altering host immunity. As a result, MZ B cells and additional unique targets within the marginal sinus may be used to develop specific strategies to prevent anti-fVIII antibody formation in patients with hemophilia A. [Display omitted] DisclosuresNo relevant conflicts of interest to declare.

Restoration of cerebral and systemic microvascular architecture in APP/PS1 transgenic mice following treatment with Liraglutide™.

Cerebral microvascular impairments occurring in AD may reduce Aβ peptide clearance and impact upon circulatory ultrastructure and function. We hypothesized that microvascular pathologies occur in organs responsible for systemic Aβ peptide clearance in a model of AD and that Liraglutide (Victoza(®)) improves vessel architecture. Seven-month-old APP/PS1 and age-matched wild-type mice received once-daily intraperitoneal injections of either Liraglutide or saline (n = 4 per group) for eight weeks. Casts of cerebral, splenic, hepatic, and renal microanatomy were analyzed using SEM. Casts from wild-type mice showed regularly spaced microvasculature with smooth lumenal profiles, whereas APP/PS1 mice revealed evidence of microangiopathies including cerebral microanuerysms, intracerebral microvascular leakage, extravasation from renal glomerular microvessels, and significant reductions in both splenic sinus density (p = 0.0286) and intussusceptive microvascular pillars (p = 0.0412). Quantification of hepatic vascular ultrastructure in APP/PS1 mice revealed that vessel parameters (width, length, branching points, intussusceptive pillars and microaneurysms) were not significantly different from wild-type mice. Systemic administration of Liraglutide reduced the incidence of cerebral microanuerysms and leakage, restored renal microvascular architecture and significantly increased both splenic venous sinus number (p = 0.0286) and intussusceptive pillar formation (p = 0.0129). Liraglutide restores cerebral, splenic, and renal architecture in APP/PS1 mice.

Neuroinflammation, mitochondrial defects and neurodegeneration in mucopolysaccharidosis III type C mouse model.

Severe progressive neurological paediatric disease mucopolysaccharidosis III type C is caused by mutations in the HGSNAT gene leading to deficiency of acetyl-CoA: α-glucosaminide N-acetyltransferase involved in the lysosomal catabolism of heparan sulphate. To understand the pathophysiology of the disease we generated a mouse model of mucopolysaccharidosis III type C by germline inactivation of the Hgsnat gene. At 6-8 months mice showed hyperactivity, and reduced anxiety. Cognitive memory decline was detected at 10 months and at 12-13 months mice showed signs of unbalanced hesitant walk and urinary retention. Lysosomal accumulation of heparan sulphate was observed in hepatocytes, splenic sinus endothelium, cerebral microglia, liver Kupffer cells, fibroblasts and pericytes. Starting from 5 months, brain neurons showed enlarged, structurally abnormal mitochondria, impaired mitochondrial energy metabolism, and storage of densely packed autofluorescent material, gangliosides, lysozyme, phosphorylated tau, and amyloid-β. Taken together, our data demonstrate for the first time that deficiency of acetyl-CoA: α-glucosaminide N-acetyltransferase causes lysosomal accumulation of heparan sulphate in microglial cells followed by their activation and cytokine release. They also show mitochondrial dysfunction in the neurons and neuronal loss explaining why mucopolysaccharidosis III type C manifests primarily as a neurodegenerative disease.

Experimental splenosis in the liver and lung spread through the vasculature.

To demonstrate that intra-organ splenosis can engraft and develop after being distributed through the vasculature, tiny fragments of splenic tissues were injected into the inferior vena cava or the portal vein to induce intrapulmonary and intrahepatic splenosis in rats. After 1 month, splenic autograft structures in the lung and liver were assessed for structure by histology, for immunologic compartments by immunohistochemistry, for phagocytic function by carbon uptake and for vascular formation by Microfil (a silicon rubber compound) injection. Intrapulmonary and intrahepatic splenoses were indeed able to spread through the vasculature. The intrapulmonary splenic autografts were trapped and spread out in the interstitium, without forming a capsule. White pulp was markedly developed, showing lymphocyte aggregations that consisted in B cells surrounding the dilated vessel. Splenic sinuses were not definitively observed. Although macrophages were detected by immunohistochemistry, they showed no indication of having phagocytized carbon particles from the vessels, implying a closed circulation. In contrast, intrahepatic splenic autografts formed well-developed capsules, trabeculae and red pulp with splenic sinuses. Macrophages detected by immunohistochemistry were observed capturing carbon particles, which clearly revealed an open system circulation, as seen in normal rat spleen. The development of white pulp was poor and lymphocytes consisting in B cells aggregated in the peripheral margins. These results demonstrate that intra-organ splenosis can spread through the vasculature and that the morphologic and immunologic structures formed in these regenerated autografts are influenced by the organ vasculature and extracellular matrix wherein the tissue fragments settled.

Enhanced CT and FDG PET/CT Findings of Splenic Hamartoma

Splenic hamartomas are very rare benign vascular tumors. A 67-year-old man was referred after an incidental detection of a splenic lesion. Abdominal-enhanced CT showed a splenic lesion with progressive enhancement. This lesion showed intense FDG uptake with an SUVmax of 9.2. The patient underwent splenectomy. Splenic hamartoma was confirmed by pathologic evaluation. In this tumor, the disorganized splenic sinus contained a large amount of lymphocytes and plasma cells, which may contribute to the intense FDG uptake. This case indicates that splenic hamartoma should be included in the differential diagnosis of focal FDG accumulation along with tumor and nontumor conditions.

Assessment of immune cells and function of the residual spleen after subtotal splenectomy due to splenomegaly in cirrhotic patients

BackgroundThe spleen is thought to be central in regulating the immune system, a metabolic asset involved in endocrine function. Overwhelming postsplenectomy infection leads to a mortality rate of up to 50%. However, there is still controversy on performing subtotal splenectomy as treatment of splenomegaly due to portal hypertension in cirrhotic patients. In the present study, immunocytes and the indexes of splenic size, hemodynamics, hematology and immunology in the residual spleen were analyzed to support subtotal splenectomy due to splenomegaly.ResultsIn residual spleen, T lymphocytes mainly were focal aggregation in the periarterial lymphatic sheath. While B lymphocytes densely distributed in splenic corpuscle. In red pulp, macrophages were equally distributed in the xsplenic cord and adhered to the wall of splenic sinus with high density. The number of unit area T and B lymphocytes of splenic corpuscle and marginal zone as well as macrophages of red pulp were obviously increased in the residual spleen, while the number of macrophages didn’t be changed among the three groups in white pulp. While there were some beneficial changes (i.e., Counts of platelet and leucocyte as well as serum proportion of CD3+ T cells, CD4+ T cells, CD8+ T cells were increased markedly; serum levels of M-CSF and GM-CSF were decreased significantly; The proportion of granulocyte, erythrocyte, megakaryocyte in bone marrow were changed obviously; But serum IgA, IgM, IgG, Tuftsin level, there was no significant difference; splenic artery flow volume, portal venous diameter and portal venous flow volume, a significant difference was observed in residual spleen) in the clinical indices.ConclusionAfter subtotal splenectomy with splenomegaly due to portal hypertension in cirrhotic patients, the number of unit area T and B lymphocytes, and MØ in red pulp of residual spleen increased significantly. However, whether increase of T, B lymphocytes and MØs in residual splenic tissue can enhance the immune function of the spleen, still need further research to confirm.

Peripheral prion disease pathogenesis is unaltered in the absence of sialoadhesin (Siglec-1/CD169).

Prions are a unique group of pathogens, which are considered to comprise solely of an abnormally folded isoform of the cellular prion protein. The accumulation and replication of prions within secondary lymphoid organs is important for their efficient spread from the periphery to the brain where they ultimately cause neurodegeneration and death. Mononuclear phagocytes (MNP) play key roles in prion disease pathogenesis. Some MNP appear to facilitate the propagation of prions to and within lymphoid tissues, whereas others may aid their clearance by phagocytosis and by destroying them. Our recent data show that an intact splenic marginal zone is important for the efficient delivery of prions into the B-cell follicles where they subsequently replicate upon follicular dendritic cells before infecting the nervous system. Sialoadhesin is an MNP-restricted cell adhesion molecule that binds sialylated glycoproteins. Sialoadhesin is constitutively expressed upon splenic marginal zone metallophilic and lymph node sub-capsular sinus macrophage populations, where it may function to bind sialylated glycoproteins, pathogens and exosomes in the blood and lymph via recognition of terminal sialic acid residues. As the prion glycoprotein is highly sialylated, we tested the hypothesis that sialoadhesin may influence prion disease pathogenesis. We show that after peripheral exposure, prion pathogenesis was unaltered in sialoadhesin-deficient mice; revealing that lymphoid sequestration of prions is not mediated via sialoadhesin. Hence, although an intact marginal zone is important for the efficient uptake and delivery of prions into the B-cell follicles of the spleen, this is not influenced by sialoadhesin expression by the MNP within it.

Unusual Cause of Abdominal Pain

Question: A 24-year-old man visited our gastroenterology clinic due to intermittent, dull, left upper abdominal pain for 6 months. He had an unremarkable medical history and no history of abdominal trauma or surgery. He denied any weight loss. Physical examination revealed a palpable mass in the left upper abdomen. Laboratory examinations were within normal limits. Abdominal computed tomography (CT) and magnetic resonance imaging (MRI) were subsequently performed to clarify the nature of the lesion (Figures A and B). What are the findings of the abdominal CT and what is the diagnosis? Look on page 1609 for the answer and see the Gastroenterology web site (www.gastrojournal.org) for more information on submitting your favorite image to Clinical Challenges and Images in GI. Abdominal CT revealed a large, cystic lesion of the spleen with partial calcification of the wall (Figure A, arrow). T2WI MRI revealed a 14-cm, homogeneous, hyperintense, cystic lesion without contrast enhancement. The patient underwent laparoscopic splenectomy for the symptomatic tumor (Figure C). On histologic examination, the splenic cyst was lined by mature squamous cells and walled by fibrotic tissues with inflammation (Figure D). A diagnosis of splenic epidermoid cyst was made. Cystic lesions of the spleen are uncommon.1Chen Y.Y. Shyr Y.M. Wang S.E. Epidermoid cyst of the spleen.J Gastrointest Surg. 2013; 17: 555-561Crossref PubMed Scopus (18) Google Scholar, 2Dan D. Bascombe N. Harnanan D. et al.Laparoscopic management of a massive splenic cyst.Asian J Surg. 2010; 33: 103-106Abstract Full Text PDF PubMed Scopus (20) Google Scholar, 3Fan H. Zhang D. Zhao X. et al.Laparoscopic partial splenectomy for large splenic epidermoid cyst.Chin Med J (Engl). 2011; 124: 1751-1753PubMed Google Scholar Acquired splenic cysts are caused by trauma, pancreatitis, parasite infection, or neoplasm. Congenital splenic and epidermoid cysts are rare, comprising <10% of all nonparasitic splenic cysts; only 78 cases were reported in a recent review from 1950 to 2012.1Chen Y.Y. Shyr Y.M. Wang S.E. Epidermoid cyst of the spleen.J Gastrointest Surg. 2013; 17: 555-561Crossref PubMed Scopus (18) Google Scholar Epidermoid cysts are lined by keratinizing and nonkeratinizing epithelium that may be squamous or cuboidal.1Chen Y.Y. Shyr Y.M. Wang S.E. Epidermoid cyst of the spleen.J Gastrointest Surg. 2013; 17: 555-561Crossref PubMed Scopus (18) Google Scholar The etiology is believed to be congenital and proposed as mesothelial inclusion with squamous metaplasia and fetal squamous epithelium in the cyst or metaplasia in the cells lining the splenic sinus. Patients with splenic epidermoid cysts usually present with cysts at a young age, with a median age of 19 years; there is a slight female predominance. The most common symptoms presented are left upper abdominal pain or a palpable mass. In patients with splenic epidermoid cysts, 90% are uniloculated and uncomplicated. Complications from cysts are uncommon, but can include infection (6.8%), rupture (9.8%), or bleeding (2.7%).1Chen Y.Y. Shyr Y.M. Wang S.E. Epidermoid cyst of the spleen.J Gastrointest Surg. 2013; 17: 555-561Crossref PubMed Scopus (18) Google Scholar On imaging studies, uncomplicated cysts are a solitary, well-defined cystic lesion, occasionally with plaque-like wall calcification. The treatment for symptomatic cysts is open or laparoscopic splenectomy.2Dan D. Bascombe N. Harnanan D. et al.Laparoscopic management of a massive splenic cyst.Asian J Surg. 2010; 33: 103-106Abstract Full Text PDF PubMed Scopus (20) Google Scholar, 3Fan H. Zhang D. Zhao X. et al.Laparoscopic partial splenectomy for large splenic epidermoid cyst.Chin Med J (Engl). 2011; 124: 1751-1753PubMed Google Scholar Conservative therapy, such as aspiration or sclerotherapy, is associated with a high recurrence rate and a risk of bleeding or infection; it is therefore not recommended.