Morphology combined with ancillary techniques: An algorithm approach for thyroid nodules.

INTRODUCTION: Several authors have underlined the limits of morphological analysis mostly in the diagnosis of follicular neoplasms (FN). The application of ancillary techniques, including immunocytochemistry (ICC) and molecular testing, contributes to a better definition of the risk of malignancy (ROM) and management of FN. According to literature, the application of models, including the evaluation of ICC, somatic mutations (ie, BRAFV600E ), micro RNA analysis is proposed for FNs. This study discusses the validation of a diagnostic algorithm in FN with a special focus on the role of morphology then followed by ancillary techniques. METHODS: From June 2014 to January 2016, we enrolled 37 FNs with histological follow-up. In the same reference period, 20 benign nodules and 20 positive for malignancy were selected as control. ICC, BRAFV600E mutation and miR-375 were carried out on LBC. RESULTS: The 37 FNs included 14 atypia of undetermined significance/follicular lesion of undetermined significance and 23 FN. Specifically, atypia of undetermined significance/follicular lesion of undetermined significance resulted in three goitres, 10 follicular adenomas and one NIFTP whereas FN/suspicious for FN by seven follicular adenomas and 16 malignancies (nine non-invasive follicular thyroid neoplasms with papillary-like nuclear features, two invasive follicular variant of papillary thyroid carcinoma [PTC] and five PTC). The 20 positive for malignancy samples included two invasive follicular variant of PTC, 16 PTCs and two medullary carcinomas. The morphological features of BRAFV600E mutation (nuclear features of PTC and moderate/abundant eosinophilic cytoplasms) were associated with 100% ROM. In the wild type cases, ROM was 83.3% in presence of a concordant positive ICC panel whilst significantly lower (10.5%) in a negative concordant ICC. High expression values of MirR-375 provided 100% ROM. CONCLUSIONS: The adoption of an algorithm might represent the best choice for the correct diagnosis of FNs. The morphological detection of BRAFV600E represents the first step for the identification of malignant FNs. A significant reduction of unnecessary thyroidectomies is the goal of this application.

Pituitary-tumour-transforming-gene 1 expression in testicular cancer.

Genomic instability is a feature of germ cell tumours. The pituitary-tumour-transforming-gene 1 (PTTG1) is the major effector of chromosome segregation during mitosis, protecting the cell from aneuploidy. The protein expression of this gene has been evaluated in testicular tumours by immunohistochemistry. Formalin-fixed and paraffin-embedded specimens of testicular tissues from 83 patients undergoing therapeutic orchidectomy for seminomas (n = 53), embryonal carcinoma (n = 10), yolk sac tumour (n = 10) and teratoma (n = 10) were examined. Seminoma was associated with in situ carcinoma (CIS) in 23 samples. PTTG1 immunostaining was performed using rabbit anti-PTTG1 as a primary antibody. In CIS, only isolated cells showed nuclear staining for PTTG1. In the peripheral area of seminoma, PTTG1 was mostly detected as localised in the nucleus; in the central area of seminoma, PTTG1 staining was more intense in cytoplasm. PTTG1-positive cells were also present in the areas of seminoma infiltration. On the other hand, in embryonal carcinoma, cells had a diffuse positive immunostaining, mainly cytoplasmatic, while we did not observe an expression of PTTG1 in yolk sac tumour and mature teratoma. We firstly identified the PTTG1 expression pattern in normal testis, CIS and testicular cancer. Further investigation is needed to clarify the functional activity of PTTG1 in testicular oncogenesis.

A systematic review and meta-analysis of CK20, CD44, Ki67 and p53 as immunohistochemical markers in bladder carcinoma in situ.

BACKGROUND: Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive atypia is often difficult based only on histological features. The integration of histological findings with immunohistochemistry is used in routine practice to make a diagnosis of CIS and, for this purpose, the immunohistochemical markers CK20, CD44, Ki67 and p53 are used to supplement histology. In this work, we aimed to assess CK20, CD44, Ki67 and p53 as immunohistochemical markers in patients with CIS through a systematic review and meta-analysis. MATERIALS AND METHODS: A systematic review was performed by searching electronic databases for English-language studies published from January 2010 to April 2021. Studies were considered eligible if they evaluated the CK20, CD44, Ki67 and p53 expression in CIS. RESULTS: In total, 15 references were suitable for quantitative review. The overall rate of CK20, CD44, Ki67 and p53 expression in CIS was 43%, 31%, 44%, 38%, respectively. CONCLUSIONS: Our study supports the 2014 International Society of Urologic Pathology consensus that histological assessment remains the gold standard to diagnose urothelial CIS and suggests that a very close correlation between morphological, immunohistochemical and clinical data is essential to provide the best management for patients with bladder carcinoma.

Do we really need fine-needle biopsy needle for an ultrasound-guided biopsy of pancreatic adenocarcinoma? A retrospective study.

OBJECTIVE: Endoscopic ultrasound (EUS)-guided FNB was not demonstrated to be better than EUS fine-needle aspiration (FNA) to obtain adequate samples for diagnosis of pancreatic tumors. We report our experience using a 22-gauge needle aspiration to obtain both cytologic and histologic samples. PATIENTS AND METHODS: In a total of 232 patients (51% men), 22-gauge needles (Cook Medical) were used to obtain a cytological sample (between 2008 and 2016, Cohort A) and a cytologic and a histologic sample (between 2016 and 2019, Cohort B) to evaluate the usability of this needle to collect material for cytologic and histologic examination. MOSE was used. RESULTS: Pancreatic adenocarcinoma was diagnosed in 76/113 (68%) patients in Cohort A and in 88/119 (74%) in Cohort B. Non-diagnostic sampling occurred in 30/113 (26%) patients in Cohort A and in 25/119 (21%) in Cohort B. The median number of passages was three in both cohorts. Lesions were in the head/uncinated process 57% vs. 51% and body/tail 43% vs. 49% in Cohorts A and B, respectively; the mean tumor size was 34.5 mm (SD 10.7) in Cohort A and 35.4 mm (SD 14.7) in Cohort B. CONCLUSIONS: FNA needle (22-gauge) with adequate passes, MOSE determination and adequate processing of specimens, provided FNA and FNB specimen collection.

Regulation of PDE5 expression in normal prostate, benign prostatic hyperplasia, and adenocarcinoma.

BACKGROUND: Type 5 phosphodiesterase (PDE5) expression in the normal and pathological prostate is controversial. OBJECTIVES: This study aimed at identifying the cell type/s, if any, expressing PDE5 in human healthy or pathological prostate sections in order to further validate the rationale of PDE5 inhibitor (PDE5i) treatment of benign prostatic hyperplasia (BPH) and their safety in the treatment of erectile dysfunction following prostate cancer (PCa) surgery. MATERIALS AND METHODS: By immunohistochemical analysis, we studied PDE5 expression in tissue microarrays containing sections obtained from healthy, BPH, and PCa samples. RESULTS: Our results showed that PDE5 is barely expressed in the epithelial or stromal compartment of normal human prostates, but it is highly expressed in the stromal compartment of BPH sections. We also found that a low but significant number of PCa samples (22%) expressed PDE5 in the epithelial cancer cells but not in stromal cells and that such expression was not correlated with the tumor aggressiveness, according to their Gleason score. DISCUSSION AND CONCLUSION: PDE5 overexpression in the stromal compartment of BPH samples supports the rationale of PDE5 as a target in lower urinary tract symptoms of BPH. PDE5 expression in a significant percentage of PCa samples but the lack of correlation with the Gleason score suggests that this enzyme is not correlated with tumor aggressiveness; however, a role of PDE5 in the minimal residual disease of PCa cannot be excluded.

Mesenchymal differentiation of glioblastoma stem cells.

Glioblastoma multiforme is a severe form of cancer most likely arising from the transformation of stem or progenitor cells resident in the brain. Although the tumorigenic population in glioblastoma is defined as composed by cancer stem cells (CSCs), the cellular target of the transformation hit remains to be identified. Glioma stem cells (SCs) are thought to have a differentiation potential restricted to the neural lineage. However, using orthotopic versus heterotopic xenograft models and in vitro differentiation assays, we found that a subset of glioblastomas contained CSCs with both neural and mesenchymal potential. Subcutaneous injection of CSCs or single CSC clones from two of seven patients produced tumor xenografts containing osteo-chondrogenic areas in the context of glioblastoma-like tumor lesions. Moreover, CSC clones from four of seven cases generated both neural and chondrogenic cells in vitro. Interestingly, mesenchymal differentiation of the tumor xenografts was associated with reduction of both growth rate and mitotic index. These findings suggest that in a subclass of glioblastomas the tumorigenic hit occurs on a multipotent stem cell, which may reveal its plasticity under specific environmental stimuli. The discovery of such biological properties might provide considerable information to the development of new therapeutic strategies aimed at forcing glioblastoma stem cell differentiation.

Meckel's diverticulum findings on Tc-99m red blood cell scintigraphy in a bleeding leukemic patient confirmed by Tc-99m pertechnetate scintigraphy.

A 25-year-old Caucasian woman with a medical history of acute promyelocytic leukemia presented to the emergency department with massive gastrointestinal bleeding. A bone marrow biopsy excluded hemorrhagic leukemia. Esophagogastroduodenoscopy, colonoscopy, emergency abdominal angiography, abdominal CT scan, and wireless capsule endoscopy were performed but no source of bleeding could be detected. Tc-99m RBC scintigraphy was consistent with a small bowel bleeding focus. The persistent and focal images in the right abdomen were suggestive of Tc-99m RBC trapping in the lumen of a Meckel diverticulum (MD). In accordance with this suspicion, successive Tc-99m pertechnetate scintigraphy was performed after 3 days, consistent with the diagnostic hypothesis. Due to the persisting severe bleeding (with a drop in baseline hemoglobin from 10.4 to 7.1 g/dL), despite 8 units of blood transfusion, emergency surgery was performed. Through a minilaparotomy a segmental small bowel resection, including Meckel diverticulum, was performed. The postoperative course was uneventful.

Value of combined approach with thallium-201 single-photon emission computed tomography and Epstein-Barr virus DNA polymerase chain reaction in CSF for the diagnosis of AIDS-related primary CNS lymphoma.

PURPOSE: To determine the diagnostic capability of thallium-201 (201Tl) single-photon emission computed tomography (SPECT) combined with Epstein-Barr virus DNA (EBV-DNA) in CSF for the diagnosis of AIDS-related primary CNS lymphoma (PCNSL). PATIENTS AND METHODS: All human immunodeficiency virus (HIV)-infected patients with focal brain lesions observed between June 1996 and March 1998 underwent lumbar puncture and 201Tl SPECT. Each CSF sample was tested with polymerase chain reaction (PCR) for EBV-DNA. RESULTS: Thirty-one patients were included, 13 with PCNSL and 18 with nontumor disorders. In 11 PCNSL patients, EBV-DNA was positive. Thallium-201 uptake ranged from 1.90 to 4.07 in PCNSL cases (mean, 2.77; 95% confidence interval [CI], 2.35 to 3.19) and from 0.91 to 3.38 in nontumor patients (mean, 1.62; 95% CI, 1.30 to 1.94) (P<.0002). Using a lesion/background ratio of 1.95 as cutoff, a negative SPECT was found in one PCNSL case and 16 nonneoplastic cases. A cryptococcoma and a tuberculoma showed highly increased 201Tl uptake. Epstein-Barr virus DNA was never detected in nonneoplastic patients. For PCNSL diagnosis, hyperactive lesions showed 92% sensitivity and 94% negative predictive value (NPV), whereas positive EBV-DNA had 100% specificity and 100% positive predictive value. The presence of increased uptake and/or positive EBV-DNA had 100% sensitivity and 100% NPV. CONCLUSION: Combined SPECT and EBV-DNA showed a very high diagnostic accuracy for AIDS-related PCNSL. Because PCNSL likelihood is extremely high in patients with hyperactive lesions and positive EBV-DNA, brain biopsy could be avoided, and patients could promptly undergo radiotherapy or multimodal therapy. On the contrary, in patients showing hypoactive lesions with negative EBV-DNA, empiric anti-Toxoplasma therapy is indicated. In patients with discordant SPECT/PCR results, brain biopsy seems to be advisable.

Epstein-Barr virus infection is predictive of CNS involvement in systemic AIDS-related non-Hodgkin's lymphomas.

PURPOSE: This study aimed at correlating Epstein-Barr virus (EBV) infection of systemic AIDS-related non-Hodgkin lymphomas (AIDS-NHL) with the development of a CNS localization of the tumor. PATIENTS AND METHODS: Demographic, epidemiologic, clinical, histologic, and virologic features were collected for all systemic AIDS-NHL patients included in the study (n = 50). Pathologic specimens were classified according to the working formulation for NHL and the Revised European-American Lymphoma classification. EBV infection in tumor tissue samples was studied by EBV small encoded RNA in situ hybridization; EBV-DNA detection in CSF was carried out by nested polymerase chain reaction using Epstein-Barr nuclear antigen-1-specific primers. In addition, selected EBV-positive lymphomas were subjected to a detailed characterization of EBV molecular heterogeneity. RESULTS: Eleven patients had a CNS involvement at some point during their clinical history (four at diagnosis and seven at relapse). Thirty patients (11 with CNS involvement and 19 without) harbored EBV infection of the tumor. Sensitivity, specificity, and positive and negative predictive values of EBV-DNA detection in CSF for CNS involvement by lymphoma were 90%, 100%, 100%, and 97.6%, respectively. Factors significantly predictive of CNS involvement were EBV infection of the tumor (P=.003), an extranodal disease at diagnosis other than CNS (P=.006), and a non-CNS relapse (P=.01). In four cases of CNS involvement, EBV-DNA in CSF preceded any other sign of disease by a mean of 35 days. CONCLUSION: These results show that EBV infection of the tumor clone significantly increases the risk of CNS involvement by systemic AIDS-NHL, without regard of specific molecular features. The detection of EBV-DNA in the CSF of AIDS-NHL patients may select cases with higher risk of CNS involvement and, therefore, may prove useful in the therapeutic stratification of these tumors.

Primary malignant melanoma of the gallbladder in dysplastic naevus syndrome.

A case of gallbladder involvement by malignant melanoma in a 57-year-old woman is reported. The gallbladder, resected for cholelithiasis, harboured a pedunculated polypoid dark mass, which histologically revealed sheets and nests of epithelioid cells with hyperchromatic nuclei in the lamina propria and at the junctional level. These cells were pigmented (with positive reaction with Schmorl's stain and bleaching with peroxide) and showed immunohistochemical positivity for S-100, gp 100 antigen (HMB-45 antibody) and vimentin. The patient, affected by dysplastic naevus syndrome, had a melanoma in situ excised from the scalp 8 years earlier. The features of the investigated lesion address towards a diagnosis of primary gallbladder melanoma. Furthermore, this is the first time that the existence of such a controversial entity is sustained by the ultrastructural investigation of melanosomes, demonstrating the presence of two melanocitary populations, a typical one exclusively junctional and an atypical one both at the junctional level and in the lamina propria.

Evidence for telomerase involvement in the angiogenesis of astrocytic tumors: expression of human telomerase reverse transcriptase messenger RNA by vascular endothelial cells.

OBJECT: Evidence from recent in vitro studies indicates that reactivation of telomerase, the enzyme that synthesizes the telomere ends of chromosomes, is a crucial event in the unlimited clonal expansion of endothelial cells that precedes the neoplastic conversion of these cells. It is known that high-grade gliomas express telomerase and that, in these neoplasms, proliferating endothelial cells may undergo transformational changes with development of sarcomatous components within the primitive tumor. To assess whether telomerase is involved in the endothelial cell proliferation that characterizes brain tumor angiogenesis, the authors investigated at the single-cell level the expression of messenger (m)RNA for the human telomerase catalytic subunit human telomerase reverse transcriptase (hTERT) by vascular cells of astrocytic tumors. METHODS: The in situ hybridization (ISH) method was performed by processing histological sections with specific riboprobes for hTERT and for c-myc, an oncogene that is known to upregulate hTERT. Results of the ISH studies were compared with proliferative activity, as estimated by Ki-67 immunostaining. The expression of hTERT mRNA by vascular endothelial cells was related to the histological grade of the tumor because it was detected in five (29%) of 17 low-grade astrocytomas, nine (56%) of 16 anaplastic astrocytomas, and 19 (100%) of 19 glioblastomas multiforme (GBMs). Expression of c-myc mRNA was strictly correlated with that of hTERT mRNA. In low-grade astrocytomas and anaplastic astrocytomas, a dissociation was noted between hTERT mRNA expression and the proliferation rate of endothelial cells. Conversely, GBMs displayed a significant correlation between the level of hTERT mRNA expression and endothelial cell proliferation. Data from an in vitro assay in which human umbilical vein endothelial cells were stimulated to proliferate by adding vascular endothelial growth factor and an ISH study of newly formed vessels surrounding brain infarcts confirmed that expression of hTERT mRNA does not merely reflect the proliferative status of endothelial cells but represents a specific feature of brain tumor neovascularization. CONCLUSIONS: The results of this study are consistent with a role of telomerase in the angiogenesis of astrocytic tumors. Expression of hTERT mRNA by tumor vascular cells is an early event during the progression of astrocytic tumors, which precedes endothelial cell proliferation and may represent a first sign of dedifferentiation. Other than elucidating the mechanisms of tumor angiogenesis, these results encourage research on antitelomerase drugs for the treatment of malignant gliomas.

Spontaneous partial fibrotic regression of a primary renal carcinoma: a case report.

Spontaneous regression of non metastatic renal carcinoma is a very unusual finding in daily urologic practice. Furthermore this is the first case of a partial primary renal cancer remission documented by hystopathological specimens. Current hypothesis were discussed.

Revisión sistemática y metaanálisis sobre CK20, CD44, Ki67 y p53 como marcadores inmunohistoquímicos en el carcinoma in situ vesical / A systematic review and meta-analysis of CK20, CD44, Ki67 and p53 as immunohistochemical markers in bladder carcinoma in situ

Introducción: La displasia urotelial y el carcinoma in situ (CIS) están relacionados con la recurrencia y la progresión del carcinoma urotelial. Diferenciar el CIS y la displasia de la atipia reactiva suele ser difícil sobre la base de las características histológicas. La integración de los hallazgos histológicos con la inmunohistoquímica se utiliza en la práctica habitual para realizar el diagnóstico del CIS y, para ello, se utilizan los marcadores inmunohistoquímicos CK20, CD44, Ki67 y p53 como complemento al estudio histológico.En este trabajo, nos propusimos evaluar CK20, CD44, Ki67 y p53 como marcadores inmunohistoquímicos en pacientes con CIS, mediante una revisión sistemática y un metaanálisis.Materiales y métodosSe realizó una revisión sistemática con búsqueda en bases de datos electrónicas de estudios en inglés publicados desde enero de 2010 hasta abril de 2021. Se consideraron elegibles los estudios que evaluaban la expresión de CK20, CD44, Ki67 y p53 en el CIS.ResultadosEn total, 15 referencias fueron aptas para la revisión cuantitativa. La tasa global de expresión de CK20, CD44, Ki67 y p53 en el CIS fue del 43%, 31%, 44% y 38%, respectivamente.ConclusionesNuestro estudio apoya el consenso de la Sociedad Internacional de Patología Urológica de 2014 sobre la evaluación histológica como método de referencia para diagnosticar el CIS urotelial, y sugiere que una correlación muy estrecha entre los datos morfológicos, inmunohistoquímicos y clínicos es esencial para proporcionar el mejor manejo de los pacientes con carcinoma vesical. (AU)

Introduction: Urothelial dysplasia and carcinoma in situ (CIS) are related to recurrence and progression of urothelial carcinoma. Differentiating CIS and dysplasia from reactive atypia is often difficult based only on histological features. The integration of histological findings with immunohistochemistry is used in routine practice to make a diagnosis of CIS and, for this purpose, the immunohistochemical markers CK20, CD44, Ki67 and p53 are used to supplement histology.In this work, we aimed to assess CK20, CD44, Ki67 and p53 as immunohistochemical markers in patients with CIS through a systematic review and meta-analysis.Materials and methodsA systematic review was performed by searching electronic databases for English-language studies published from January 2010 to April 2021. Studies were considered eligible if they evaluated the CK20, CD44, Ki67 and p53 expression in CIS.ResultsIn total, 15 references were suitable for quantitative review. The overall rate of CK20, CD44, Ki67 and p53 expression in CIS was 43%, 31%, 44%, 38%, respectively.ConclusionsOur study supports the 2014 International Society of Urologic Pathology consensus that histological assessment remains the gold standard to diagnose urothelial CIS and suggests that a very close correlation between morphological, immunohistochemical and clinical data is essential to provide the best management for patients with bladder carcinoma. (AU)

Silencing of GSTP1, a prostate cancer prognostic gene, by the estrogen receptor-ß and endothelial nitric oxide synthase complex.

We recently identified in prostate tumors (PCa) a transcriptional prognostic signature comprising a significant number of genes differentially regulated in patients with worse clinical outcome. Induction of up-regulated genes was due to chromatin remodeling by a combinatorial complex between estrogen receptor (ER)-ß and endothelial nitric oxide synthase (eNOS). Here we show that this complex can also repress transcription of prognostic genes that are down-regulated in PCa, such as the glutathione transferase gene GSTP1. Silencing of GSTP1 is a common early event in prostate carcinogenesis, frequently caused by promoter hypermethylation. We validated loss of glutathione transferase (GST) P1-1 expression in vivo, in tissue microarrays from a retrospective cohort of patients, and correlated it with decreased disease-specific survival. Furthermore, we show that in PCa cultured cells ERß/eNOS causes GSTP1 repression by being recruited at estrogen responsive elements in the gene promoter with consequential remodeling of local chromatin. Treatment with ERß antagonist or its natural ligand 5α-androstane-3ß,17ß-diol, eNOS inhibitors or ERß small interference RNA abrogated the binding and reversed GSTP1 silencing, demonstrating the direct involvement of the complex. In vitro, GSTP1 silencing by ERß/eNOS was specific for cells from patients with worse clinical outcome where it appeared the sole mechanism regulating GSTP1 expression because no promoter hypermethylation was present. However, in vivo chromatin immunoprecipitation assays on fresh PCa tissues demonstrated that silencing by ERß/eNOS can coexist with promoter hypermethylation. Our findings reveal that the ERß/eNOS complex can exert transcriptional repression and suggest that this may represent an epigenetic event favoring inactivation of the GSTP1 locus by methylation. Moreover, abrogation of ERß/eNOS function by 3ß-adiol emphasizes the significance of circulating or locally produced sex steroid hormones or their metabolites in PCa biology with relevant clinical/therapeutic implications.

Application of liquid-based preparation to non-gynaecologic exfoliative cytology.

Thin-layer cytology (TLC) is an automated method for processing cells harvested in a liquid solution and collected onto a single slide. The leftover material can be used for other techniques such as immunocytochemistry, molecular biology and flow cytometry. TLC has been applied with good results in exfoliative cytology of pulmonary, urinary, gastrointestinal and oral districts as well as in the evaluation of serous effusions. The main advantages of TLC over conventional techniques (CS) are: (a) simplification of the sampling technique; (b) decrease in cellular artefacts leading to a lesser amount of inadequate diagnoses; and (c) applicability of additional investigations. The limits of TLC are: (a) changes in the morphologic picture of some lesions; (b) increase of the workload for technical staff; and (c) increased cost. The application of TLC to non-gynaecologic specimens favours many innovative developments and can be regarded as an appropriate substitute for CS.

Polymorphism in cytokine genes as prognostic markers in Hodgkin's lymphoma.

BACKGROUND: In Hodgkin's lymphoma (HL), the production of cytokines by Reed-Sternberg cells and the surrounding tissue is thought to contribute to the biology of the disease. Cytokine expression can be altered by common single nucleotide polymorphisms (SNPs) in the 5'-promoter regions. PATIENTS AND METHODS: We studied polymorphic allele variants of the cytokine genes interleukin (IL)-10 (T-3575A, G-2849A, C-2763A, A-1082G and C-592A), IL-6 (G-174C) and tumor necrosis factor-alpha (C-863A and G-308A) in 184 patients with HL, and analyzed for associations with treatment outcome. RESULTS: Carriers of the IL-10-592AA and the IL-6-174GG genotypes had a significantly lower probability of freedom from treatment failure (FFTF) with adjusted hazard ratios (HRs) for failure of 2.92 [95% CI (confidence interval) 1.58-5.41, P = 0.001] and of 1.75 (95% CI 1.04-2.92, P = 0.03), respectively. Reconstructing haplotypes from the five SNPs in the IL-10 promoter revealed that homozygous carriers of the IL-10.4 haplotype (T-G-C-A-A) had a worse FFTF (HR, 2.35; 95% CI 1.2-4.6, P = 0.01). In the Cox multivariate analysis, the IL-10-592AA, the IL-6-174GG genotypes and stage were independent prognostic factors. CONCLUSIONS: Our study indicates that cytokine genotypes predict clinical outcome in patients with HL and points to the importance of the genetic background of the host for treatment response.

Effects of sodium selenite on vascular smooth muscle reactivity.

The effects of sodium selenite (Na(2)SeO(3)) on the vascular smooth muscle reactivity of rabbit aorta were studied. In isolated rabbit aorta, Na(2)SeO(3) inhibited contractile response to phenylephrine and developed a lasting contracture in the vascular tissue. Relaxation in phenylephrine-precontracted aortic rings induced by sodium nitroprusside and 8-bromo-guanosine 3':5'-cyclic-monophosphate was also inhibited. Preliminary data obtained with ascorbic acid suggested a partial involvement of an oxidative mechanism. Excluding the possibility that Se damages actin or modifies its distribution (immunohistochemical evaluation), results indicate that Se alters vascular smooth muscle reactivity by inhibiting both its contracting and relaxing properties. Calcium-dependent mechanisms appear to be primarily involved and an interference with calcium re-uptake by sarcoplasmic reticulum as a possible site of Se vascular action could be hypothesized.

Leiomyoma of the testis.

Testis leiomyoma is a very rare neoplasm. It is very difficult to perform an exact preoperative diagnosis; only histological examination can prove the presence of a leiomyoma. In our case radical orchidectomy was performed because of complete substitution of normal parenchyma, the extreme rarity at long-term follow-up of a reported benign intratesticular neoplasm, and the imperfect sensitivity of the extemporary histological examination.

Bax mutations are an infrequent event in indolent lymphomas and in mantle cell lymphoma.

BACKGROUND AND OBJECTIVES: The Bax gene is one of the most important genes involved in apoptosis regulation. Recently, it has been proposed that inactivating mutations of this death agonist may contribute to the pathogenesis of human tumors. This study was aimed at defining the status of the Bax gene in indolent lymphomas. DESIGN AND METHODS: Fifty paraffin-embedded biopsies from indolent lymphomas (10 small lymphocytic lymphomas, 5 immunocytomas, 20 follicular lymphomas and 15 marginal zone lymphomas) and 10 mantle cell lymphomas ( MCL ) were studied. All six exons of the Bax gene, together with their flanking sequences, underwent mutational analysis by PCR-SSCP followed by direct sequencing of positive cases. Moreover, Bax protein expression was investigated in all samples by immunohistochemical analysis. RESULTS: All analyzed cases showed wild type Bax gene alleles and variable levels of Bax protein expression. INTERPRETATION AND CONCLUSIONS: This study indicates that deregulation of apoptotic control in indolent lymphomas and MCL is not caused by Bax mutations and that other molecular mechanisms must, therefore, be involved.