Extramedullary plasmacytoma, a report of five cases diagnosed by FNAC

Objective:  To review cytological findings and diagnostic challenges in the use of fine needle aspiration in the diagnosis of extramedullary plasmacytoma.
Methods:  Five cases of extramedullary plasmacytoma that were initially diagnosed on fine needle aspiration cytology over a period of two years in Sir Ganga Ram Hospital were reviewed.
Results:  The cytological findings were similar in all five cases. The smears were cellular and composed of plasmacytoid cells arranged singly and in clusters, with varying pleomorphism, bi- and multinucleation and mitotic figures. Presence of anaplasia, increased plasmablasts, numerous naked nuclei and unusual location of the tumour were some of the challenges faced during the cytological evaluation.
Conclusions:  Extramedullary plasmacytoma may occur either as an initial presentation or as a secondary involvement by multiple myeloma. Fine needle aspiration is a reliable technique for its rapid diagnosis.     

Treatment of multiple solitary plasmacytomas with cytokine-induced killer cells

Background aimsCurrently available treatment methods for advanced plasmacytoma include surgery, chemotherapy, radiotherapy, immunomodulatory agents, hematopoietic stem cell transplantation and donor lymphocyte infusion. We report a case of advanced refractory multiple solitary plasmacytomas in a 68-year-old Asian man with multiple bone lesions, in whom autologous cytokine-induced killer (CIK) cells were administered in an effort to eliminate residual tumor lesions.MethodsCIK cells were infused monthly for 21 courses.ResultsThe patient has survived 63 months since the first hospital visit without disease progression for 40 months.ConclusionsThis case represents the first report of autologous CIK cell immunotherapy used successfully to suppress multiple solitary plasmacytomas and resolve bone lesions.     

Impact of bone events on survival in solitary bone plasmacytoma

BackgroundAlthough much studied in multiple myeloma, bone events (BE) can also cause important morbidity in bone plasmacytoma patients. To our knowledge, the effect of BE on overall survival (OS) and progression to multiple myeloma free-survival (MPFS) also has never been studied.Patients and MethodsFifty-nine patients treated from 2008 to 2017 were retrospectively assessed. All patients had histological proof of disease and were treated with radical radiotherapy (RT). Available clinical information for at least 6 months follow-up or until death had to be available. BE were described as one of the following events in the index bone: fractures, osteomyelitis, chronic pain, surgery or loss of limb function after RT.ResultsMean age at diagnosis was 57.3 years (18–80); most male (67.8%). Mean OS, bone event free-survival (BEFS), local progression-free survival (LPFS) and MPFS were 41, 36, 37 and 19 months, respectively. There were 15 deaths. BEFS (p = 0.008) and age>55y (p = 0.044) were associated with MPFS. Only BEFS correlated with OS (p = 0.029). BE was independently associated with both MPFS and OS in multivariate analysis.ConclusionBE and survival end-points were correlated. BE should be investigated in prospective trials.     

Osteogenic potential of rat spleen stromal cells

Evidence is mounting that an increasing number of cell populations in the adult organism already committed and/or differentiated retain the ability to reprogram themselves and give rise to a different phenotype. Bone marrow stromal cells have long been recognized as early progenitor cells for osteoblasts, chondrocytes, hematopoietic-supportive fibroblasts and adipocytes. Recent reports though have demonstrated a potential of cell populations outside the bone marrow environment to sustain bone formation under specific circumstances. The formation of bone nodules in the spleen of IL-5 transgenic mice has been recently reported (Macias et al. (2001): J. Clin. Invest. 107, 949 - 959). We thus postulated that a cell population exists in the spleen that under particular microenvironmental conditions is able to reprogram itself and pursue a fate other than the tissue-specific one. Therefore we isolated and expanded in vitro spleen-derived stromal cells. After expansion, these cells were challenged with culture conditions designed to induce osteogenic differentiation. We hypothesized that the combination of a proliferating factor (fibroblast growth factor 2) and a differentiating hormone (dexamethasone) would allow us to induce spleen-derived stromal cells to proliferate and at the same time to express osteoblast-specific genes. Thus, spleen-derived stromal cells were isolated from rat spleen and expanded in the presence of fibroblast growth factor 2 and dexamethasone. Once primary cultures reached confluence they were either switched to an osteo-inductive medium or implanted in immunodeficient mice. Although no bone formation was observed in in vivo experiments, in vitro spleen-derived stromal cells were able to deposit a mineralized matrix. Gene expression, as revealed by RT-PCR analysis, evidenced that the deposition of a mineralized matrix was concomitant with the expression of CBFA1 and osteocalcin, along with alkaline phosphatase and bone sialoprotein. Our data suggest that rat spleen-derived stromal cells can undergo osteogenic differentiation in a permissive microenvironment.     

Electron microscopic studies of the innervation of the human spleen

Summary The innervation of four normal human spleens was investigated by electron microscopy. Unmyelinated nerve fibers accompanied the arterial vascular system up to the arterioles of the red pulp. Neither myelinated nerve fibers nor ganglion cells were seen in the splenic hilum or in the splenic tissue itself. The nerve fibers terminated against the smooth muscle cells of the blood vessels in a manner that is typical of the autonomic nervous system. The terminal axons contained small and large granular vesicles and thus were adrenergic nerve fibers. In contrast to the results of previous studies using silver impregnation methods innervation of the red or white pulp could not be demonstrated. The findings on human spleens agree with those on mammalian spleens obtained by other authors using ultrastructural and fluorescence histochemical methods.We are indebted to Prof. Dr. K. Unsicker for his help in discussing the results     

TPA induces apoptosis in MPC-11 mouse plasmacytoma cells grown in serum-free medium

Apoptotic-like events could be rapidly induced by the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) in cells of the mouse plasmacytoma cell line MPC-11 grown in serum-free medium. Indicators for apoptosis were morphological changes visualized by light and electron microscopy, such as chromatin condensation and the formation of cellular buds and fragments, as well as biochemical indices like the appearance of the so-called ‘DNA ladder’. Additionally, in these cells which are usually devoid of significant amounts of cytoplasmic intermediate filament (cIF) proteins, synthesis and accumulation of the cIF protein vimentin was rapidly induced by TPA treatment and almost all cells became vimentin-positive. Later on, substantial amounts of vimentin and lamin B degradation products appeared, and an increasing fraction of cells displayed low or even undetectable quantities of intact vimentin. This subpopulation was characterized via microscopy to be in the late stages of apoptosis. We suggest that in MPC-11 cells undergoing apoptosis in response to TPA treatment vimentin as well as lamin B are degraded, leading to a rearrangement and eventual loss of their respective filament networks.     

Ultrastructure of human spleen in transmission and scanning electron microscope

Despite new information concerning functional morphology of spleen, there are still some inaccuracies mostly regarding the spleen blood circulation. Billroth’s (splenic) cords are formed from three-dimensional network of fibroblastic reticular cells located among branched sinuses. Results from our study using scanning electron microscopy confirm an intimate contact between adjacent reticular cells and erythrocytes. Arterial terminals can be observed in the Billroth’s cords. The wall of sinuses reminds a sieve and it is lined with a special type of endothelium. In electron microscope, endothelial cells look like rods oriented parallel to the longitudinal axis of sinuses. Based on our observations fibroblastic reticular cells change to fixed phagocytes under no circumstances, hence they do not participate in phagocytosis. They may have a recognition function for cells circulating around them. According to our opinion, the open and the closed blood circulation are present in the human spleen simultaneously. Blood flowing in the closed circulation can help “absorption” of extra-vascular liquid and the blood elements into the vascular lumen. Due to sporadic occurrence of smooth muscle cells in the capsule and trabeculae, we assume that human spleen is not a blood reservoir, unlike the spleen in some other animals.     

Characterization of the effect of LPS on dendritic cell subset discrimination in spleen

The Gram‐negative bacterial endotoxin lipopolysaccharide (LPS) is a potent inflammatory mediator and a leading cause of bacterial sepsis. While LPS is known to activate antigen‐presenting cells, here we find that LPS down‐regulates expression of CD11c and CD11b on splenic dendritic cell subsets, thus confounding the ability to identify these subsets following treatment. This has implications with regard to tracking the response to LPS in terms of the cell subsets involved, and should be considered whenever such studies are undertaken.     

The antitumor action of seminal ribonuclease tested with the plasmacytoma spleen colonization assay

The antitumor action of bovine seminal ribonuclease was evaluated with a quantitative assay based on the production of tumor foci in the spleens of mice injected with plasmacytoma cells. The antitumor action depended on the integrity of the catalytic site, and on the dimeric structure of the enzyme. A working hypothesis is proposed, based on these results, and on previous results obtained studying the antitumor action of seminal RNAase in vitro on cell cultures. According to this hypothesis, the antitumor action is based on the ability of seminal RNAase to interact at specific receptor sites on the tumor cell membrane, as well as on its RNA degrading ability.     

The role of the spleen in protective immunity against Angiostrongylus cantonensis in rats: Splenectomy and passive spleen cell transfers

Splenectonuzed rats infected with Angiostrongylus cantonensis had more and longer worms and lower anti-A. cantonensis antibody titres compared to intact and sham operated rats. Splenectomy, however, had no effect on the capacity of rats to mount a cell-mediated immune response, as assessed by the in vitro uptake of tritiated thymidine by peripheral blood lymphocytes following stimulation by PHA and adult worm antigen. Adoptive protection and antibody production against A. cantonensis could be transferred with immune spleen cells. This protection was strongly dose and time dependent. Protection was adoptively conferred with 3 × 10⁹ spleen cells transferred 7 days before infection.     

The development of the human spleen

Summary Splenic tissue of human fetuses from the 14^th to the 24^th week of gestation (menstrual age) were investigated by light- and electron microscopy to describe the development of the red and white pulp in close relationship to the differentiation of the vascular tree. Special interest is focussed on the differentiation of the T-cell- and the B-cell regions and their specific stationary cells.The preliminary stage, here called the primary vascular reticulum, lasts up to the 14^th gestational week (gw). Numerous erythrocytes, normoblasts and macrophages are seen among a network of mesenchymal cells and argyrophilic fibers. Hematopoiesis, especially erythropoiesis, can be recognized.The characteristic organ structure becomes established during the subsequent transformation stage of the fetal spleen, beginning with the 15^th gw. Splenic lobules begin to form during the 15^th to 17^th gw. They consist of a central artery, surrounded by a sheath of lightly stained stationary cells which resemble myofibroblasts. At the periphery of these lobules the red pulp forms. Initially mobile cells are distributed throughout the reticulum. Soon they begin to accumulate in the venous sinuses, which develop from lacunae among the reticular network and come into contact with the venous system. The endothelial wall of these sinuses remains discontinuous, confirming the theory of the open vascularization of the spleen. The development of the larger veins is correlated with the differentiation of the splenic trabeculae.The development of the white pulp is correlated with the stage of lymphoid colonization within the spleen, beginning around the 18^th gw. An accumulation of lymphocytes around the central arteries can be recognized during the 19^th and 20^th gw. These lymphoid cells show morphological and immunohistochemical characteristics of T-precursor cells. Within the now assembling periarterial lymphoid sheath (PALS) a few precursors of interdigitating cells (IDC) are recognizable, giving evidence for the differentiation of the T-cell region.Around the 23^rd gw the assemblage of primary follicles is discernible at the periphery of the PALS. Precursors of the follicular dendritic reticulum cell (FDRC), the specific stationary cell of the B-cell region, have been recognized. This observation leads to the conclusion that the small primary follicles represent the beginning formation of the B-cell region.The significance of the vascular system for the differentiation of the specific splenic organization is discussed.This investigation was supported by grants from the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 111)The authors appreciate the contribution of human fetal material from Dr. von Hollweg and Dr. Körner from the Hospital Heidberg, Hamburg, and the excellent technical assistance of Mrs. H. Hansen, Mrs. I. Knauer, Mrs. M.v. Kolszynski, Mrs. J. Quitzau, Mrs. H. Siebke and Mrs. H. Waluk     

Immune complex-trapping cells in the spleen of the chicken

Summary By means of immunohistoperoxidase techniques and the use of HRP-anti-HRP complexes, follicular dendritic cells in chicken spleen can be characterized both at the light-microscopical and ultrastructural level. In contrast to findings in mammals follicular dendritic cells in chicken spleen exhibit evident acid-phosphatase activity and possess considerable numbers of primary lysosomes. After intravenous injection of immune complexes a transient immune complex-trapping occurs in the peripheral parts of the Schweigger-Seidel sheath. The immune complextrapping cells in the Schweigger-Seidel sheath and germinal centre show an identical enzyme histochemical pattern and only minor differences in ultrastructural characteristics.Shortly after intravenous injection of immune complexes and carbon particles these compounds show an identical distribution pattern; however, in the following days these distribution patterns become divergent.     

Altered histology of the thymus and spleen in contaminant-exposed juvenile American alligators

Morphological differences in spleen and thymus are closely related to functional immune differences. Hormonal regulation of the immune system has been demonstrated in reptilian splenic and thymic tissue. Spleens and thymus were obtained from juvenile alligators at two reference sites in Florida, USA: Orange Lake and a National Wildlife Refuge, Lake Woodruff, as well as from a contaminated lake, Lake Apopka. Lake Apopka has been extensively polluted with agricultural pesticides. Tissues were prepared for histological analysis to determine if previously detected endocrine abnormalities associated with contaminant exposure might also be reflected in morphological differences in splenic and thymic structures important for immunological response. Similar tissues were taken from captive-raised juvenile female alligators (3 years old) that were hatched from eggs collected on Lake Woodruff and Lake Apopka. Differences in thymic ratios (medulla/cortex) were found among alligators collected from the two lakes (P = 0.0051). Alligators from Lake Apopka had smaller thymic ratios than animals from either reference lake. Males from Lake Woodruff had significantly smaller lymphocyte sheaths in the spleen than females (P = 0.0009), indicative of a normal sexual dimorphism. Lymphocyte sheath width differed among females obtained from the three lakes, with females from Lake Apopka having the smallest sheath width and those from Orange Lake having the largest. Malpighian body area was largest in alligators from Orange Lake, intermediate in Lake Woodruff, and smallest in Lake Apopka. In contrast to that observed for wild-caught animals, no difference was found in the thymic medulla/cortex ratio of captive-raised female alligators (P = 0.378). Captive-raised female alligators from Lake Apopka and Lake Woodruff displayed lake-associated differences in lymphocyte sheath width as observed in wild animals; Lake Apopka alligators had smaller lymphocyte sheath width compared to Woodruff alligators (P = 0.0396). In contrast to wild-caught animals, area of the Malpighian bodies did not differ by lake in the captive-raised female alligators (P = 0.066). The enlarged thymic cortex suggests a change in T-lymphocyte maturation within the thymus of alligators from a contaminated environment, Lake Apopka. The results point to alterations in the histology of the thymus and spleen. Further studies are required to examine the functional significance of these observations.     

Analysis of magnetic material in the human heart, spleen and liver

Isothermal remanent magnetization (IRM) acquisition and alternating field (A.F.) demagnetization analyses were performed on human heart, spleen and liver samples resected from cadavers. The magnetic properties of the samples were measured both at 77K and at 273K. A.F. demagnetization was performed at 273K. Results from the analyses of the tissue indicate the presence of ferromagnetic, fine-grained, magnetically interacting particles which, due primarily to magnetic properties, are thought to be magnetite and/or maghemite. The presence of superparamagnetic particles can be inferred from the increase in saturation IRM values when measured at 77K compared with measurements at 273K and the decay of remanent magnetization upon warming from 77K. The concentration of magnetic material (assuming it is magnetite or maghemite) in the samples varies from 13.7 ng g-1 to 343 ng g-1, with the heart tissue generally having the highest concentration. The presence of magnetic material in these organs may have implications for the function of biogenic magnetite in the human body.     

Tight junction of sinus endothelial cells of the rat spleen

The fine structure of the tight junctions between sinus endothelial cells of the rat spleen and the permeability of such sinus endothelial cells were examined by transmission electron microscopy, using freeze-fracture, triton extraction, and lanthanum-tracer techniques. In freeze-fracture replicas, the segmented strands and grooves of the tight junctions were frequently observed on the basolateral surfaces of the sinus endothelial cells irrespective of the location of the ring fiber. There were one or two wavy-strands or grooves which were, for the most part, oriented parallel to the long cell axis thus forming networks at places. In addition, some strands or grooves were discontinuous while some networks of the junctional strands were not closed. These strands also occasionally lacked intramembranous particles in the tight junctions. The junctional strands run apicobasically at certain sites. In the vertical sections of the sinus endothelial cells treated with lanthanum nitrate, although no tight junctions were observed wherever the endothelial cells were apposed, most of them were situated on the basal part of the lateral surfaces of the adjacent endothelial cells. Several fusions of the junctional membranes were observed in a vertical section of the lateral surfaces of the adjacent endothelial cells. The intercellular spaces of the adjacent endothelial cells except for the fusion of the junctional membranes, were electron dense and the infiltration of lanthanum nitrate was found not to be interrupted by these tight junctions. Based on these observations, the molecular 'fence' and paracellular 'gate' functions of the tight junctions in the sinus endothelial cells are discussed.     

Fine needle aspiration biopsy of the spleen in pyrexia of unknown origin

To evaluate the diagnostic utility, value and potential risk of fine needle aspiration biopsy of spleen (sFNAB) in patients with splenomegaly in pyrexia of unknown origin (PUO), a retrospective analysis of medical records and cytological material of 31 patients on whom FNAB was performed between April 1994 and October 1997 was done. The patients were HIV- and presented with PUO. All other relevant investigations were negative. The spleen was either palpable or detected to have space-occupying lesions on ultrasonography (USG). The splenic aspirates showed tuberculosis in 11 patients (35.4%) and inconclusive or reactive changes in nine patients (25.8%). One case out of this group proved to be Kaposi's sarcoma on autopsy. The other diseases encountered were leishmaniasis (n = 3), non-Hodgkin's lymphoma (n = 4), fungal infections (n = 2), Hodgkin's lymphoma (n = 1). The patients who were diagnosed as having tuberculosis had epithelioid cells, giant cells, necrosis and inflammatory cells in various combinations. AFB positivity was 63.6%. The other cases which showed granulomas but no AFB were diagnosed on empirical grounds and all responded to the anti-tuberculosis therapy. No complications were encountered with the procedure. Therefore the authors conclude that sFNAB is rewarding in patients where all other non-invasive modalities of diagnosis have failed.     

A quantitative and histochemical study on melano-macrophage centres in the spleen of the teleost fish Diplodus annularis L.

The incidence and histochemical features of melano-macrophage centres in the spleen of the teleost fish D. annularis were studied with respect to starved and fed fish. Tissue catabolism following complete starvation appears to induce formation of new centres containing melanin and lipofuscin pigments. However, a change in the amount of melano-macrophages was also recorded in fed fish, suggesting that some other factor(s), internal to fish, may affect the presence of such structures within the spleen of D. annularis .     

大豆异黄酮对电离辐射小鼠脾脏细胞周期、凋亡与增殖的影响

目的：研究大豆异黄酮对辐射小鼠免疫器官脾脏的影响。方法：90只雄性昆明小鼠,随机分为正常组、对照组和补充0．5％大豆异黄酮组,喂养两周后,4．0Gyγ射线照射;于照射后12、24h和一周、两周杀死部分小鼠取脾脏,测定小鼠的脾脏指数、脾脏细胞周期、细胞增殖指数及细胞凋亡率等指标。结果：辐射使小鼠脾脏明显萎缩。脾脏细胞凋亡率和G0-C1期细胞百分比明显增加（P〈0．05）,脾脏细胞S期的百分比及细胞增殖指数明显降低（P〈0．01）;补充大豆异黄酮,可使上述指标更接近正常组水平,使脾脏细胞G0-C1期百分比较辐射对照组明显减少（P〈0．05）,脾脏细胞的C2-M期百分比和细胞增殖指数较辐射对照组明显增加（P〈0．05）。结论：大豆异黄酮可对脾脏起到辐射防护的作用。     

Stimulation of rat spleen cells by staphylococcal enterotoxins

Abstract There is much interest in staphylococcal enterotoxins as T cell mitogens in humans, mice and rabbits. Rat spleen cells were shown to proliferate in response to staphylococcal enterotoxins A and B and toxic shock syndrome toxin-1 at concentrations (5 to 500 ng ml⁻¹) which also stimulate mouse spleen cells. The proliferative response to all these enterotoxins was inhibitted by cyclosporin A, indicating the response to be predominantly that of T cells. These results indicate that the rat provides another convenient model for the analysis of T cell responses to enterotoxins.