A minute focus of extranodal marginal zone B-cell lymphoma arising in Hashimoto thyroiditis diagnosed with PCR after laser capture microdissection: a case report

<p>Abstract</p> <p>Background</p> <p>Primary thyroid gland lymphomas are uncommon tumours that occur in the setting of lymphocytic thyroiditis or Hashimoto's disease in almost all cases. In this condition a distinction between an inflammatory lymphoid infiltrate and a low grade lymphoma may be extremely difficult and precise criteria are necessary for a correct diagnosis.</p> <p>Patient and methods</p> <p>We report a case of a minute focus of primary extranodal marginal zone B-cell lymphoma (EMZBCL), incidentally discovered in a 63-year-old man with Hashimoto thyroiditis (HT) and diagnosed by means of polymerase chain reaction (PCR) after laser capture microdissection.</p> <p>The histological examination of surgical specimen confirmed the diagnosis of HT and showed a minute focus of dense lymphoid infiltrate (less than 4 mm in diameter), composed by centrocyte-like cells forming MALT balls. Immunoistochemistry was not useful. A microscopic focus of EMZBCL was suspected on the basis of morphological features. PCR assays revealed the rearrangement of the heavy chain of immunoglobulins only in the microdissected suspicious area, confirming the diagnosis of EMZBCL.</p> <p>Conclusion</p> <p>Our finding suggests that in cases of autoimmune thyroiditis a careful examination of the thyroid specimen is warranted, in order to disclose areas or small foci of lymphomatous transformation. Furthermore, in difficult cases with doubtful immunohistological findings, ancillary techniques, such as molecular studies, are necessary for a conclusive diagnosis.</p

Krox-20 inhibits Jun-NH2-terminal kinase/c-Jun to control Schwann cell proliferation and death

The transcription factor Krox-20 controls Schwann cell myelination. Schwann cells in Krox-20 null mice fail to myelinate, and unlike myelinating Schwann cells, continue to proliferate and are susceptible to death. We find that enforced Krox-20 expression in Schwann cells cell-autonomously inactivates the proliferative response of Schwann cells to the major axonal mitogen β–neuregulin-1 and the death response to TGFβ or serum deprivation. Even in 3T3 fibroblasts, Krox-20 not only blocks proliferation and death but also activates the myelin genes periaxin and protein zero, showing properties in common with master regulatory genes in other cell types. Significantly, a major function of Krox-20 is to suppress the c-Jun NH2-terminal protein kinase (JNK)–c-Jun pathway, activation of which is required for both proliferation and death. Thus, Krox-20 can coordinately control suppression of mitogenic and death responses. Krox-20 also up-regulates the scaffold protein JNK-interacting protein 1 (JIP-1). We propose this as a possible component of the mechanism by which Krox-20 regulates JNK activity during Schwann cell development

A rare case of endometriosis in Turner's syndrome

Endometriosis is defined by the presence of functional endometrial tissue outside the uterine cavity and musculature. It has a prevalence rate as high as 35e50% in women experiencing pain or infertility [1] and sometimes has a peculiar and rare onset [2,3]. Endometriosis is a common disease in menstruating women [4,5] but has also been reported in postmenopausal or surgically castrated women on hormone replacement therapy (HRT) [6]. The common denominator of all such cases is exposure to female hormones [7]. However, endometriosis, a common and important clinical problem in women of reproductive age, has rarely been described in prepubertal girls. In patients with Turner's syndrome or other ovarian dysgenesis, endometriosis is very rare. Some cases are subclinical, and endometriosis is an incidental finding during routine examination. Although endometriosis was described in the medical literature at the end of the 19th century, and the first theories regarding its hystogenesis were developed at the beginning of the 20th century, the real pathogenesis of endometriosis remains unknown. Most studies about the etiology of endometriosis claim that the main possible causes of endometriosis are probably multifactorial. Three theories of histogenesis have been proposed. (1) The metastatic theory [8] proposes the transplantation of endometrial tissue via retrograde menstrual implantation, vascular/lymphatic spread, and intraoperative implantation. (2) The coelomic metaplastic theory [9] suggests that the germinal epithelium of the ovary can be transformed by metaplasia into endometrium. This theory, which initially explained only ovarian endometriosis, has since been extended to the peritoneal serosa, as embryologic studies have indicated that Mullerian ducts, th

Soils of the Aversa plain (southern Italy)

The Aversa plain is one of the most important agricultural areas of the Campania region, combining the presence of very fertile soils, sites of great archaeological interest and growing residential urbanization. In this paper, the soil map (1:50,000 scale) of the Aversa plain is presented. Three main land systems (coastal, alluvial and foothill plains) characterized by different soil types (Andosols, Phaeozems, Cambisols, Vertisols, Arenosols, Histosols, Luvisols) have been identified. However, Andosols are the most widespread soil type (9768 ha) and, along with part of the Phaeozems and Cambisols, represent the most fertile soils of the Aversa plain (first and second classes of the land capability classification). In order to evaluate recent intense soil sealing, its impact over land capability classes was assessed during the last 60 years. Results show that soil sealing in the Aversa plain affected mainly the most fertile first- and second-class soils

Schwann cells ER-associated degradation contributes to myelin maintenance in adult nerves and limits demyelination in CMT1B mice

In the peripheral nervous system (PNS) myelinating Schwann cells synthesize large amounts of myelin protein zero (P0) glycoprotein, an abundant component of peripheral nerve myelin. In humans, mutations in P0 cause the demyelinating Charcot-Marie-Tooth 1B (CMT1B) neuropathy, one of the most diffused genetic disorders of the PNS. We previously showed that several mutations, such as the deletion of serine 63 (P0-S63del), result in misfolding and accumulation of P0 in the endoplasmic reticulum (ER), with activation of the unfolded protein response (UPR). In addition, we observed that S63del mouse nerves display the upregulation of many ER-associated degradation (ERAD) genes, suggesting a possible involvement of this pathway in the clearance of the mutant P0. In ERAD in fact, misfolded proteins are dislocated from the ER and targeted for proteasomal degradation. Taking advantage of inducible cells that express the ER retained P0, here we show that the P0-S63del glycoprotein is degraded via ERAD. Moreover, we provide strong evidence that the Schwann cell-specific ablation of the ERAD factor Derlin-2 in S63del nerves exacerbates both the myelin defects and the UPR in vivo, unveiling a protective role for ERAD in CMT1B neuropathy. We also found that lack of Derlin-2 affects adult myelin maintenance in normal nerves, without compromising their development, pinpointing ERAD as a previously unrecognized player in preserving Schwann cells homeostasis in adulthood. Finally, we provide evidence that treatment of S63del peripheral nerve cultures with N-Acetyl-D-Glucosamine (GlcNAc), known to enhance protein quality control pathways in C.elegans, ameliorates S63del nerve myelination ex vivo. Overall, our study suggests that potentiating adaptive ER quality control pathways might represent an appealing strategy to treat both conformational and age-related PNS disorders. Author summary Charcot-Marie-Tooth neuropathies are a large family of peripheral nerve disorders, showing extensive clinical and genetic heterogeneity. Although strong advances have been made in the identification of genes and mutations involved, effective therapies are still lacking. Intracellular retention of abnormal proteins has been recently suggested as one of the pathogenetic events that might underlie several conformational neuropathies. To limit the toxic effects of accumulated mutant proteins, cells have developed efficient protein quality control systems aimed at optimizing both protein folding and degradation. Here we show that ER-associated degradation limits Schwann cells stress and myelin defects caused by the accumulation of a mutant myelin protein into the ER. In addition, we also describe for the first time the importance of Schwann cells ERAD in preserving myelin integrity in adult nerves, showing that genetic ERAD impairment leads to a late onset, motor-predominant, peripheral neuropathy in vivo. Effort in the design of strategies that potentiate ERAD and ER quality controls is therefore highly desirable

Endometrial Carcinoma and Bisphenol A:A Pilot Case-Control Study

Female cancers represent one of the major causes of morbidity and mortality in the adult population

Levofloxacin to prevent bacterial infection in patients with cancer and neutropenia.

BACKGROUND: The prophylactic use of fluoroquinolones in patients with cancer and neutropenia is controversial and is not a recommended intervention. METHODS: We randomly assigned 760 consecutive adult patients with cancer in whom chemotherapy-induced neutropenia (<1000 neutrophils per cubic millimeter) was expected to occur for more than seven days to receive either oral levofloxacin (500 mg daily) or placebo from the start of chemotherapy until the resolution of neutropenia. Patients were stratified according to their underlying disease (acute leukemia vs. solid tumor or lymphoma). RESULTS: An intention-to-treat analysis showed that fever was present for the duration of neutropenia in 65 percent of patients who received levofloxacin prophylaxis, as compared with 85 percent of those receiving placebo (243 of 375 vs. 308 of 363; relative risk, 0.76; absolute difference in risk, -20 percent; 95 percent confidence interval, -26 to -14 percent; P=0.001). The levofloxacin group had a lower rate of microbiologically documented infections (absolute difference in risk, -17 percent; 95 percent confidence interval, -24 to -10 percent; P<0.001), bacteremias (difference in risk, -16 percent; 95 percent confidence interval, -22 to -9 percent; P<0.001), and single-agent gram-negative bacteremias (difference in risk, -7 percent; 95 percent confidence interval, -10 to -2 percent; P<0.01) than did the placebo group. Mortality and tolerability were similar in the two groups. The effects of prophylaxis were also similar between patients with acute leukemia and those with solid tumors or lymphoma. CONCLUSIONS: Prophylactic treatment with levofloxacin is an effective and well-tolerated way of preventing febrile episodes and other relevant infection-related outcomes in patients with cancer and profound and protracted neutropenia. The long-term effect of this intervention on microbial resistance in the community is not known

Notch controls embryonic Schwann cell differentiation, postnatal myelination and adult plasticity

Notch signaling is central to vertebrate development, and analysis of Notch has provided important insights into pathogenetic mechanisms in the CNS and many other tissues. However, surprisingly little is known about the role of Notch in the development and pathology of Schwann cells and peripheral nerves. Using transgenic mice and cell cultures, we found that Notch has complex and extensive regulatory functions in Schwann cells. Notch promoted the generation of Schwann cells from Schwann cell precursors and regulated the size of the Schwann cell pool by controlling proliferation. Notch inhibited myelination, establishing that myelination is subject to negative transcriptional regulation that opposes forward drives such as Krox20. Notably, in the adult, Notch dysregulation resulted in demyelination; this finding identifies a signaling pathway that induces myelin breakdown in vivo. These findings are relevant for understanding the molecular mechanisms that control Schwann cell plasticity and underlie nerve pathology, including demyelinating neuropathies and tumorigenesi