Lipoma of the adrenal gland

A rare case of a lipoma of the adrenal gland is reported with a review of the literature. The tumor was incidentally found at autopsy in a 50-year-old man who died from severe head trauma after a traffic injury. At autopsy, an oval-shaped, soft yellow nodule measuring 1.1 cm in diameter was found in the right adrenal cortex. Histological examination revealed a lesion consisting of mature adipose tissue partially surrounded by a thin fibrous capsule. On serial sections there was no evidence of hematopoiesis nor of adrenal medulla cells. To the best of our knowledge, this is the eighth case described in the English literature. With the increasing use and the high resolution of modern imaging techniques, these unsuspected adrenal masses may become more prevalent.     

Immunocytochemical distribution of the GABA(B) receptor splice variants GABA(B) R1a and R1b in the rat CNS and dorsal root ganglia

The anatomical distribution of the GABA_B receptor (GBR) splice variants GBR1a and 1b in the CNS has not previously been studied. In the present study, distribution of the splice variants was mapped using immunohistochemistry. Polyclonal antibodies against splice variant unique epitopes were raised in rabbits. Affinity purified antibodies were used according to routine immunohistochemical procedures in sections from the rat CNS or dorsal root ganglia (DRG). The staining intensity was high in the cerebral cortex but lower in basal ganglia and the hippocampus. In the cerebellum, there was a marked difference in the distribution of GBR1a- and 1b-like immunoreactivity (LI). GBR1a-LI was preferentially localised in the granule cell layer whilst GBR1b-LI was mostly found in Purkinje cells and in the molecular layer. Cell bodies of the deep cerebellar nuclei stained for the GBR1a antibody while terminals surrounding the cell bodies were strongly labelled with the GBR1b antibody. A similar pre- vs postsynaptic pattern was seen in several nuclei ventral or caudal to the cerebellum (e.g. the cochlear nucleus, the facial nucleus, the spinal cord) but not in regions rostral to the cerebellum. In the spinal cord, strong labelling for both antibodies was seen in the dorsal horn. The GBR1b but not the GBR1a antibody stained tanycytes in the epithelium of the 3rd ventricle and in the central canal at the brain stem level. DRG neurons were positive for both the GBR1a and 1b antibody, but the former stained the cells much more intensely. Satellite cells were labelled with the GBR1b antibody. The most important aspect of these findings is that in some nuclei, GBR1b may mediate inhibition of transmitter release while in the same regions, GBR1a may mediate postsynaptic inhibition. Further, the observations support previous findings that GBR1b is the predominant splice variant in Purkinje cells. Accepted: 16 July 1999     

Adenomatoid tumor of the adrenal gland with micronodular adrenal cortical hyperplasia

We report a case of an adenomatoid tumor (AT) of an adrenal gland with micronodular adrenal cortical hyperplasia (ACH). A 51-year-old man was found to have newly developed hypertension with clinical evidence of primary aldosteronism. A computerized tomogram of the abdomen revealed a solitary mass in the right adrenal gland. He underwent a right adrenalectomy for a presumptive clinical diagnosis of a solitary aldosterone-producing adrenal cortical adenoma. On histopathologic examination, the adrenal gland demonstrated an AT, diagnosed by the characteristic histological features, immunohistochemical stain results, and electron microscopic findings. The surrounding adrenal cortex showed multiple small hyperplastic cortical nodules. After the adrenalectomy, the patient's blood pressure normalized. Primary AT of the adrenal gland coexisting with micronodular ACH associated with hypertension has not been previously reported.     

Expression of miR‐155 and miR‐126 in situ in cutaneous T‐cell lymphoma

Recently, miR‐155 has been implicated in cutaneous T‐cell lymphoma (CTCL). Thus, elevated levels of miR‐155 were observed in skin lesions from CTCL patients as judged from qPCR and micro‐array analysis and aberrant, high miR‐155 expression was associated with severe disease. Moreover, miR‐155 promoted proliferation of malignant T cells in vitro. Little is, however, known about which cell types express miR‐155 in vivo in CTCL skin lesions. Here, we study miR‐155 expression using in situ hybridization (ISH) with a miR‐155 probe, a negative control (scrambled), and a miR‐126 probe as a positive control in nine patients with mycosis fungoides, the most frequent subtype of CTCL. We provide evidence that both malignant and non‐malignant T cells stain weakly to moderately positive with the miR‐155 probe, but generally negative with the miR‐126 and negative control probes. Reversely, endothelial cells stain positive for miR‐126 and negative for miR‐155 and the control probe. Solitary T cells with a malignant morphology display brighter staining with the miR‐155 probe. Taken together, our findings suggest that both malignant and non‐malignant T cells express miR‐155 in situ in CTCL. Moreover, they indicate heterogeneity in miR‐155 expression among malignant T cells.     

Hyperactivation of the hypothalamo‐pituitary‐adrenocortical axis in streptozotocin‐diabetic gerbils (Gerbillus gerbillus)

This study was designed to investigate the HPA‐axis impairment in the streptozotocin (STZ)‐diabetic gerbils (Gerbillus gerbillus). Twenty‐six male gerbils (body weight ~27 g) were divided into 3 groups: vehicle control (n = 10), 2 days of diabetes (n = 09) and 30 days of diabetes (n = 07). The latter 2 groups received an intraperitoneal injection of STZ (150 mg/kg of body weight). At 2 and 30 days of diabetes, streptozotocin‐diabetic gerbils underwent a retro‐orbital puncture for assessment of biochemical and hormonal parameters. Subsequently the animals were decapitated and the adrenal glands were removed, weighed and processed for light microscopy and stereology. Nondiabetic control gerbils that had been injected with citrate buffer were examined as a comparison. At 2 days of diabetes, STZ gerbils exhibited symptoms that are characteristic of human diabetes type 1. The adrenal gland showed significant increase in weight, associated with a larger cortex layer, hypertrophy of the fasciculate cells and a significant decrease in the nucleocytoplasmic index. These changes were associated with higher plasma ACTH and cortisol concentrations compared to nondiabetic controls. At 30 days postdiabetes, ACTH levels remained elevated, whereas cortisol levels decreased compared to the early stage of diabetes. Histological analysis revealed the existence of a band of connective tissue (collagen) that separates the cortical and medullary zones and is not present in humans or laboratory rodents, which represents a striking change seen throughout the disease. STZ‐induced diabetes mellitus in Gerbillus gerbillus resulted in hyperactivation of the HPA axis in the early stages of diabetes mellitus which did not persist into the final stages of the disease, suggesting a possible reduction in adrenocortical sensitivity over time.     

Gamma‐aminobutyric acid B Receptor Immunoreactivity in the Mouse Adrenal Medulla

The present study examined gamma‐aminobutyric acid B (GABA_B) receptor, GABA, choline acetyltransferase (ChAT), and neuronal nitric oxide synthase (nNOS) immunoreactivities in the mouse adrenal medulla. GABA_B receptor immunoreactivity was seen in numerous chromaffin cells and in a few ganglion cells of the adrenal medulla. By using a formaldehyde‐induced fluorescence (FIF) method, GABA_B receptor immunoreactivity was observed in numerous adrenaline (A) cells, but not in noradrenaline (NA) cells showing blue‐white fluorescence. This suggests that GABA_B receptors may be present in the A cells and be related to the secretory activity of A cells but not NA cells in the mouse adrenal medulla. GABA_B receptor immunoreactive ganglion cells were shown to be nNOS immunopositive by using a double immunostaining method. Weak GABA immunoreactivity was visible in some chromaffin cells and in the numerous nerve fibers of the medulla. By using the FIF method, weak GABA‐immunoreactive chromaffin cells were shown to be in the NA cells showing blue‐white fluorescence. GABA‐immunoreactive nerve fibers were in dense contact in A cells, but not NA cells. GABA‐immunoreactive nerve fibers closely contacted a few ganglion cells. Numerous GABA‐immunoreactive nerve fibers in the medulla showed ChAT immunoreactive. This result suggests that GABA and acetylcholine may be released from the same nerve fibers and may have a secretory effect on the A cells of the medulla. Anat Rec, 296:971–978, 2013. © 2013 Wiley Periodicals, Inc.     

Myelolipoma in adenoma of accessory adrenal gland.

A tumor was incidentally found at autopsy in the vicinity of the right adrenal gland of a 69-year-old man who had died of liver cirrhosis with hepatoma. Microscopic examination disclosed a myelolipoma associated with a cortical adenoma occurring in an accessory adrenal gland. No evidence of hormonal abnormalities was found in the clinical record of the patient. The association of myelolipoma with cortical adenoma occurring in an accessory adrenal gland seems very unusual, and the present case is believed to be the first reported of this type of association.     

Patency of Litomosoides sigmodontis infection depends on Toll‐like receptor 4 whereas Toll‐like receptor 2 signalling influences filarial‐specific CD4+ T‐cell responses

BALB/c mice develop a patent state [release of microfilariae (Mf), the transmission life‐stage, into the periphery] when exposed to the rodent filariae Litomosoides sigmodontis. Interestingly, only a portion of the infected mice become patent, which reflects the situation in human individuals infected with Wuchereria bancrofti. Since those individuals had differing filarial‐specific profiles, this study compared differences in immune responses between Mf⁺ and Mf^– infected BALB/c mice. We demonstrate that cultures of total spleen or mediastinal lymph node cells from Mf⁺ mice produce significantly more interleukin‐5 (IL‐5) to filarial antigens but equal levels of IL‐10 when compared with Mf^– mice. However, isolated CD4⁺ T cells from Mf⁺ mice produced significantly higher amounts of all measured cytokines, including IL‐10, when compared with CD4⁺ T‐cell responses from Mf^– mice. Since adaptive immune responses are influenced by triggering the innate immune system we further studied the immune profiles and parasitology in infected Toll‐like receptor‐2‐deficient (TLR2^?/?) and TLR4^?/? BALB/c mice. Ninety‐three per cent of L. sigmodontis‐exposed TLR4^?/? BALB/c mice became patent (Mf⁺) although worm numbers remained comparable to those in Mf⁺ wild‐type controls. Lack of TLR2 had no influence on patency outcome or worm burden but infected Mf⁺ mice had significantly lower numbers of Foxp3⁺ regulatory T cells and dampened peripheral immune responses. Interestingly, in vitro culturing of CD4⁺ T cells from infected wild‐type mice with granulocyte–macrophage colony‐stimulating factor‐derived TLR2^?/? dendritic cells resulted in an overall diminished cytokine profile to filarial antigens. Hence, triggering TLR4 or TLR2 during chronic filarial infection has a significant impact on patency and efficient CD4⁺ T‐cell responses, respectively.     

Different cytokine production and toll‐like receptor expression induced by heat‐killed invasive and carrier strains of Neisseria meningitidis

Neisseria meningitidis may cause severe invasive disease. The carriage state of the pathogen is common, and the reasons underlying why the infection becomes invasive are not fully understood. The aim of this study was to compare the differences between invasive and carrier strains in the activation of innate immunity. The monocyte expression of TLR2, TLR4, CD14, and HLA‐DR, cytokine production, and the granulocyte oxidative burst were analyzed after in vitro stimulation by heat‐killed invasive (n = 14) and carrier (n = 9) strains of N. meningitidis. The expression of the cell surface markers in monocytes, the oxidative burst, and cytokine concentrations were measured using flow cytometry. Carrier strains stimulated a higher production of inflammatory cytokines and oxidative burst in granulocytes than invasive strains (all p < 0.001), whereas invasive strains significantly up‐regulated TLR2, TLR4 (p < 0.001), and CD14 (p < 0.01) expression on monocytes. Conversely, the monocyte expression of HLA‐DR was higher after the stimulation by carrier strains (p < 0.05) in comparison to invasive strains. The LPS inhibitor polymyxin B abolished the differences between the strains. Our findings indicate different immunostimulatory potencies of invasive strains of N. meningitidis compared with carrier strains.     

Mesothelial cyst of the adrenal gland

A case of mesothelium-lined cyst of the adrenal gland is reported. Although more than 300 adrenal cysts have been reported in the literature, epithelial cell-lined cysts are rare and comprise only 9% of the cases. An adrenal cyst was found, the lining cells of which had features consistent with mesothelial cells. The inner surtace of the cyst was lined by a single layer of cuboidal cells, which showed alcian blue positive cellular outline. Immunohistochemically, the lining cells were positively stained for keratin, epithelial membrane antigen and CA-125. Electron microscopic examination revealed many long complex microvilli and desmosomes in the lining cells. There was a basal lamina beneath the cell layer. These morphological and immunohistochemical findings indicated that the lining cell is derived from mesothelium.     

Bilateral adrenal gland enlargement secondary to histoplasmosis mimicking adrenal metastases: Diagnosis with EUS‐guided FNA

While adrenal gland histoplasmosis has been previously diagnosed by fine needle aspiration utilizing the percutaneous approach, EUS‐FNA has not been employed in the diagnosis of this infection affecting both adrenal glands. We report a patient with massive bilateral adrenal enlargement due to histoplasmosis that was diagnosed by EUS‐FNA. Trans‐duodenal and trans‐gastric fine needle aspiration biopsy of both adrenal glands was performed. Rapid onsite cytopathologic evaluation (ROSE) revealed epithelioid histiocytes, singly and in clusters consistent with granulomas. Apparent intracytoplasmic inclusions suggestive of organisms were visible. A Gomori Methenamine Silver stain (GMS) revealed abundant small intracellular budding yeasts, morphologically consistent with Histoplasma; the patient was admitted for amphotericin B intravenous infusion. His fever abated on the second day after amphotericin B was started. His urine Histoplasma antigen was positive. Fungal cultures from both adrenal EUS‐FNA samples grew Histoplasma capsulatum. After a one week hospital stay, he was discharged home on itraconazole 200 mg po bid for one year. Four months after initiation of treatment, his urine Histoplasma antigen was undetectable. Nine months after initial diagnosis, the patient regained his energy level, and returned to work with complete resolution of his initial symptoms. This case highlights that EUS‐FNA with ROSE can be a highly effective tool in the diagnosis of uncommon infections of the adrenal glands. Diagn. Cytopathol. 2010. © 2009 Wiley‐Liss, Inc.     

Characterization of a new V gene replacement in the absence of activation‐induced cytidine deaminase and its contribution to human B‐cell receptor diversity

In B cells, B‐cell receptor (BCR) immunoglobulin revision is a common route for modifying unwanted antibody specificities via a mechanism called VH replacement. This in vivo process, mostly affecting heavy‐chain rearrangement, involves the replacement of all or part of a previously rearranged IGHV gene with another germline IGHV gene located upstream. Two different mechanisms of IGHV replacement have been reported: type 1, involving the recombination activating genes complex and requiring a framework region 3 internal recombination signal; and type 2, involving an unidentified mechanism different from that of type 1. In the case of light‐chain loci, BCR immunoglobulin editing ensures that a second V‐J rearrangement occurs. This helps to maintain tolerance, by generating a novel BCR with a new antigenic specificity. We report that human B cells can, surprisingly, undergo type 2 replacement associated with κ light‐chain rearrangements. The de novo IGKV‐IGKJ products result from the partial replacement of a previously rearranged IGKV gene by a new germline IGKV gene, in‐frame and without deletion or addition of nucleotides. There are wrcy/rgyw motifs at the ‘IGKV donor–IGKV recipient chimera junction’ as described for type 2 IGHV replacement, but activation‐induced cytidine deaminase (AID) expression was not detected. This unusual mechanism of homologous recombination seems to be a variant of gene conversion‐like recombination, which does not require AID. The recombination phenomenon described here provides new insight into immunoglobulin locus recombination and BCR immunoglobulin repertoire diversity.     

水通道蛋白4在大鼠脑垂体中的表达

目的：研究水通道蛋白4(AQP4)及其mRNA在脑垂体中的表达,探讨其在脑垂体激素分泌过程中的作用。方法：应用免疫组织化学和原位杂交技术,观察成年Wistar大鼠脑垂体中AQP4及其mRNA的正常分布。结果：AQP4及其mRNA在成年大鼠神经垂体的垂体细胞上表达呈阳性,分布在毛细血管窦周围的垂体细胞表达尤为强烈。腺垂体的所有细胞均有AQP4的表达,胞质中AQP4 mRNA表达呈阳性。中间叶所有细胞AQP4及其mRNA的表达呈弱阳性,其中滤泡星形细胞表达较内分泌细胞强烈。结论：AQP4广泛分布于脑垂体的各种组织细胞表面,可能在垂体激素的正常分泌过程中起重要的调节作用。     

Plasma membrane Toll‐like receptor activation increases bacterial uptake but abrogates endosomal Lactobacillus acidophilus induction of interferon‐β

Lactobacillus acidophilus induces a potent interferon‐β (IFN‐β) response in dendritic cells (DCs) by a Toll‐like receptor 2 (TLR2) ‐dependent mechanism, in turn leading to strong interleukin‐12 (IL‐12) production. In the present study, we investigated the involvement of different types of endocytosis in the L. acidophilus‐induced IFN‐β and IL‐12 responses and how TLR2 or TLR4 ligation by lipopolysaccharide and Pam3/4CSK4 influenced endocytosis of L. acidophilus and the induced IFN‐β and IL‐12 production. Lactobacillus acidophilus was endocytosed by constitutive macropinocytosis taking place in the immature cells as well as by spleen tyrosine kinase (Syk) ‐dependent phagocytosis but without involvement of plasma membrane TLR2. Stimulation with TLR2 or TLR4 ligands increased macropinocytosis in a Syk‐independent manner. As a consequence, incubation of DCs with TLR ligands before incubation with L. acidophilus enhanced the uptake of the bacteria. However, in these experimental conditions, induction of IFN‐β and IL‐12 was strongly inhibited. As L. acidophilus‐induced IFN‐β depends on endocytosis and endosomal degradation before signalling and as TLR stimulation from the plasma membrane leading to increased macropinocytosis abrogates IFN‐β induction we conclude that plasma membrane TLR stimulation leading to increased macropinocytosis decreases endosomal induction of IFN‐β and speculate that this is due to competition between compartments for molecules involved in the signal pathways. In summary, endosomal signalling by L. acidophilus that leads to IFN‐β and IL‐12 production is inhibited by TLR stimulation from the plasma membrane.     

Update on tumours of the adrenal cortex,phaeochromocytoma and extra‐adrenal paraganglioma

McNicol A M
(2011) Histopathology  58, 155–168
Update on tumours of the adrenal cortex, phaeochromocytoma and extra‐adrenal paraganglioma This review covers aspects of adrenal cortical tumours, phaeochromocytoma and extra‐adrenal paragangliomas. Relevant clinical and epidemiological information is included. It is now known that about 30% of paragangliomas occur in a familial setting and these new aspects of the genetic background are presented. The main diagnostic problem in both groups of tumours is the recognition of malignant potential. The uses and limitations of multifactorial histological assessment in diagnosis and prognosis are discussed. Finally, data on the molecular changes associated with tumorigenesis and tumour progression are highlighted, and how this information may contribute in future to diagnosis and prognosis.