Carcinoma Showing Thymus-Like Differentiation (CASTLE): A Rare Tumor of the Thyroid

Carcinoma showing thymus-like differentiation (CASTLE) is a rare neoplasm of the thyroid or the adjacent tissues in the neck. It was first described by Miyauchi et al. in 1985 as an intrathyroidal epithelial thymoma. In 1991 Chan and Rosai classified these tumors into four types including CASTLE. World Health Organization (WHO) declared it as an independent clinicopathologic entity in 2004. The tumor arises from ectopic thymus tissue or remnants of branchial pouch. Both sexes are affected similarly with a slight female dominance. It is usually encountered in the fourth and fifth decades of life. It does not have specific symptoms or radiologic findings which makes preoperative diagnosis difficult. It has a higher tendency to be located in the lower poles of thyroid lobes. Immunohistochemistry helps differentiate it from other malignant neoplasms, CD5 being an important marker. The tumor is negative for thyroid specific markers as thyroglobulin, TTF-1 or calcitonin. Surgery is considered the mainstream therapy. Radiotherapy may be reserved for gross disease or recurrence. The role of chemotherapy is unclear. The prognosis of CASTLE is favourable.

Morphofunctional characterization of rat thymus mast cells after administration of magnesium orotate mechanically activated forms

Relevance. The topicality of the work is determined by the wide spread of hypomagnesemia among the people, which makes it necessary to correct it. The aim of the work is to elucidate the cell-mediated response of the thymus mastocytic link to magnesium deficiency and its correction by the mechanoactivated form of magnesium orotate. Materials and Methods . Animals with drug-induced magnesium deficiency (administration of furosemide 30 mg/kg for 14 days) were administered either the initial preparation Magnerot (Magnerot, Vervag Pharma, Germany), or its mechanoactivated form. The level of magnesium in the blood was determined by test systems ARKREY (Japan). The concentration of magnesium in the thymus tissue was determined by the method of emission spectroscopy with inductively coupled (argon) plasma on an atomic emission spectrometer. Density of mastocytes and the indices of degranulation and granulolosis were calculated on paraffin sections of the thymus after coloration with toluidine blue. Results and Discussion . It was shown that furosemide administration the amount of magnesium decreased in the blood (from 1,750,08 to 0,9020,18 mmol/l, p0,05), but increased in the thymus (from 1,60,6 in the control to 3,71,2 mg/l); in the gland tissue, the number of mastocytes of morphotype A decreased and the number of mastocytes of morphotype D, after active degranulation, increased (by 7,1 times, p0,05). The type of mastocyte secretion in hypomagnesemia is represented by the merocrine variant. The administration of the initial magnesium orotate led to an increase in the concentration of magnesium in the blood to 1,150,25 mmol/l, which is 65,7% of the initial level, the amount of magnesium in the thymus remained elevated (3,41,1 mg/l), the number of actively degranulating cells (morphotype D) was increased. Mechanoactivated magnesium orotate restored the concentration of Mg2+ in the blood to 89,1% (1,560,18 mmol/l, p0,05) and decreased in the thymus (to 2,30,7 mg/l), restored the subpopulation of mastocytes saturated with heparin (type A), reduced the number of mastocytes of morphotype D. Conclusion . The mechanoactivated form of magnesium orotate has a normalizing effect on the population of thymic mastocytes, shows pronounced immunomodulatory activity, which allows us to consider it as a potential therapeutic agent for clinical testing in the complex therapy of hypomagnesemia and associated immunodeficiency.

A novel activity on thymocytes cells exerted by the rattlesnake (Crotalus durissus cumanensis) venom

Introduction: The thymus is active mainly during the neonatal and pre-adolescent periods.Objective: To test naïve thymocytes proliferation and monocytes stimulation.Materials and methods: We collected fresh thymus tissue from neonate mice after surgery. Suspension cells were coated onto Ficoll-Hypaque support. The obtained cells (thymocytes) were cultured measuring the proliferation of naïve T cells stimulated by Crotalus durissus cumanensis (Cdc) venom at sub-lethal doses (20 ng). Then, we supplemented the wells with AlamarBlue™ and incubated them for 5 h to test their proliferation. Mononuclear cells from mice peripheral blood were collected and layered onto the support of the Ficoll-Hypaque solution. We added the thymocytes actively dividing (25 x 105 cells) from cultures stimulated with Cdc venom at 20 ng/well to cultured monocytes freshly obtained from the Ficoll-Hypaque separation. Both cell populations were incubated for 36 h until monocytes matured to macrophages.Results: The naïve thymocytes rapidly proliferated after stimulation with the Cdc venom (NTCdc) and these successively induced the maturation and function of monocytes progenitor cells to mature macrophages, which ingested Chinese ink.Conclusions: The naïve thymocytes proliferated by stimulation with the Cdc venom and subsequently the NT/Cdc induced the rapid maturation and function of monocytes progenitor cells becoming mature macrophages with their phenotypic characteristics.

Thyroid carcinoma with thymus-like differentiation (CASTLE) tumor: а сase report

Thyroid carcinoma with thymus-like differentiation (Carcinoma Showing Thymus-Like Differentiation, CASTLE) is an extremely rare disease. It arises from the thymus tissue ectopic into the tissue of the thyroid gland, usually in patients 40–50 years old. In this work, we present an observation of the development of CASTLE in a patient at a young age. A 21-year-old woman was admitted to our clinic with a volumetric education in the projection of the left lobe of the thyroid gland. Ultrasound revealed a 5-centimeter thyroid tumor. Surgery was performed in the scope of thyroidectomy, selective cervical dissection (level VI). Morphological and immunohistochemical studies showed that cancer has a thymus-like differentiation (CASTLE). After 32 months, she recurred to the lymph nodes of the neck (level IV on the left). She underwent repeated surgery, after which she was observed without signs of relapse for 120 months. The rarity of the pathology leads to difficulties in establishing a diagnosis at the preoperative stage and in choosing the optimal treatment tactics during treatment and further follow-up.

Non-sebaceous Lymphadenoma of the Thymus: a Case Report

Background: non-sebaceous lymphadenoma (NSL) is a rare benign tumor with a predominant lymphoid background within which is embedded solid or duct-like structures squamous epithelial nests, lacking of sebaceous differentiation. Non-sebaceous lymphadenoma most commonly arises within the salivary glands. However, Non-sebaceous lymphadenoma arises in the thymus have not been reported.Case presentation: A 53-year-old female patient, computed tomography (CT) scan of the chest for patient showed a nodular (19 ×13 × 16-mm) in the anterior mediastinum, and with mild homogeneous enhancement on contrast-enhanced CT. The patients underwent total thymectomy with removal of the anterior mediastinal nodule by thoracoscope via below the costal margin of the Xiphoid process. Microscopically, the tumor was composed of epithelial nests and prominent lymphoid stroma, with a capsule and clearly demarcated from the surrounding thymus tissue. The epithelial nests are arranged in solid nests or duct-like structures, lacking of sebaceous differentiation and cytological atypia. The pathological diagnosis was lymphadenoma, non-sebaceous type. There were no signs of recurrence 6 months after the surgery.Conclusions: There are very few reported cases of non-sebaceous lymphadenoma occurred in thymus in the medical literature. So accurate understanding of the histopathologic diagnosis of this rare tumor is important to avoid unnecessary overtreatment.

Analyses of Gnai3-iresGFP reporter mice reveal unknown Gαi3 expression sites

Inhibitory G proteins (Gi proteins) are highly homologous but play distinct biological roles. However, their isoform-specific detection remains challenging. To facilitate the analysis of Gαi3 expression, we generated a Gnai3- iresGFP reporter mouse line. An internal ribosomal entry site (IRES) was inserted behind the stop-codon of the Gnai3 gene to initiate simultaneous translation of the GFP cDNA together with Gαi3. The expression of GFP was confirmed in spleen and thymus tissue by immunoblot analysis. Importantly, the GFP knock-in (ki) did not alter Gαi3 expression levels in all organs tested including spleen and thymus compared to wild-type littermates. Flow cytometry of thymocytes, splenic and blood cell suspensions revealed significantly higher GFP fluorescence intensities in homozygous ki/ki animals compared to heterozygous mice (+/ki). Using cell-type specific surface markers GFP fluorescence was assigned to B cells, T cells, macrophages and granulocytes from both splenic and blood cells and additionally blood-derived platelets. Moreover, immunofluorescent staining of the inner ear from knock-in mice unraveled GFP expression in sensory and non-sensory cell types, with highest levels in Deiter’s cells and in the first row of Hensen’s cells in the organ of Corti, indicating a novel site for Gαi3 expression. In summary, the Gnai3- iresGFP reporter mouse represents an ideal tool for precise analyses of Gαi3 expression patterns and sites.

Preconceptional Immunization Can Modulate Offspring Intrathymic IL-17-Producing γδT Cells with Epigenetic Implications Mediated by microRNAs

The mechanisms through which maternal immunization can modulate offspring thymic maturation of lymphocytes are not fully understood. Here, we aimed to evaluate whether maternal OVA-immunization can inhibit the maturation of IL-17-producing γδT cells in offspring thymus, and if this mechanism has epigenetic implications mediated by microRNAs (miRNAs) expression. Wild-type (WT) C57BL/6 females were immunized with OVA in Alum or Alum alone and were mated with normal WT males. Evaluating their offspring thymus at 3 or 20 days old (d.o.), we observed that maternal OVA immunization could inhibit the thymic frequency of offspring CD27- and IL-17+ γδT cells at the neonatal and until 20 days old. Furthermore, we evaluated the expression of function-related γ and δ variable γδTCR chains (Vγ1, Vγ2, Vγ3, Vδ4, and Vδ6.3), observing that maternal OVA-immunization inhibits Vγ2 chains expression. The small RNAs (sRNAs), particularly miRNAs, and messenger RNAs (mRNA) expression profiles by pools of thymus tissue samples (from 9 to 11 mice) from offspring OVA-immunized or Alum-immunized mothers were analyzed via Illumina sequencing platform and bioinformatics approaches. Using a fold change >4, our results showed that seven miRNAs (mmu-miR-126a-3p, 101a-3p, 744-3p,142-5p, 15a-5p, 532-5p, and 98-5p) were differentially expressed between both groups. Ten target genes were predicted to interact with the seven selected miRNAs. There were no enriched categories of gene ontology functional annotation and pathway enrichment analysis for the target genes. Interestingly, four of the identified miRNAs (mmu-miR-15a, mmu-miR-101 mmu-miR-126, and mmu-miR-142) are related to IL-17 production. Our data is of significance because we demonstrate that maternal immunization can modulate offspring thymic maturation of IL-17-producing γδT cells possibly by an epigenetic mechanism mediated by miRNAs.

Mouse Surgery – Transplantation of human thymus into the kidney capsule of NSG mice v1

This protocol details our minimally invasive approach for implanting human thymus tissue under the kidney capsule of NSG mice. In contrast to our open abdominal approach, this approach is from the dorsal aspect of the mouse and requires only two interrupted sutures and 1-2 staples to close the incision. The technique can be applied to other strains of mice, though we have found the NSG kidney capsule to be more delicate, and thus more challenging to manipulate during surgery.