A combined immunohistochemical and histochemical approach on the differential diagnosis of giant cell epiphyseal neoplasms

The histological similarities and the common localization are the main causes of difficulties concerning the differential diagnosis between giant cell tumor of bone and chondroblastoma. The purpose of the present study was to detect whether histochemistry and/or immunohistochemistry could help to make the distinction between these two entities easier. The study was based on cases of chondroblastoma and giant cell tumor of bone from patients in the 2nd and 3rd decades of life. Histochemical detection of special intracellular and extracellular components (glycogen, glycosaminoglycans) as well as immunohistochemical investigation using various tumor markers (S-100, NSE, a-1-ACT, lysozyme, fibronectin) were performed on parallel paraffin sections. The presence of abundant intracytoplasmic glycogen granules and the immunoreactivity of the cells of chondroblastoma with S-100 and NSE, together with the presence of acidic sulfated glycosaminoglycans in the stroma, could help the differential diagnosis of this tumor from giant cell tumor of bone.     

The favourable prognostic value of oestrogen receptor beta immunohistochemical expression in breast cancer

AIMS: Oestrogen receptor beta (ERbeta) is present in breast tumours, although its prognostic and pathophysiological roles remain to be established. METHODS: Standard immunohistochemistry with a specific monoclonal antibody was performed on paraffin wax embedded sections; 10% of strongly immunostained carcinoma cells was used as the cutoff point to classify tumours as ERbeta positive. Statistical correlations were sought with clinicopathological variables (including hormone receptor status) and disease free (DFS) and overall survival (OS) in a well documented series of 181 invasive breast carcinomas. Cell proliferation was assessed immunohistochemically by topoisomerase IIa (TopoIIa) index; p53 protein accumulation and c-erbB-2 oncoprotein expression were also taken into account. RESULTS: ERbeta immunoreactivity was detected in most specimens (71.2%); it was positively linked to ERalpha immunoreactivity and increased TopoIIalpha index, and inversely to c-erbB-2 overexpression. There were no correlations with p53 immunostaining or other clinicopathological parameters. A significant favourable impact of ERbeta immunopositivity emerged with regard to DFS and OS in both univariate and multivariate analysis; ERbeta immunopositivity retained its favourable significance with regard to DFS in the subgroups of stage I and II patients when they were examined separately. Progesterone receptor expression also had an independent favourable influence on survival, albeit with less significance. In contrast, survival was not significantly influenced by ERalpha status. CONCLUSIONS: Because of the positive association between ERbeta immunoreactivity and TopoIIalpha expression, the presence of ERbeta in breast cancer cells could be considered an indication of increased proliferation. Nevertheless, ERbeta immunoreactivity emerges as a valuable, independent indicator of favourable prognosis.     

Shifting towards an Opt-Out System in Greece: A General Practice Based Pilot Study

New legislation in Greece towards presumed consent for organ donation, effective as of June 2013, has come at a critical moment. This pilot study aims to explore awareness, specific concerns and intentions about the new organ donation framework among patients attending Greek general practices in a rural and urban setting. Only 2.6% of respondents had a donor card, a mere 9.6% was aware of new legislation, whereas only 3.8% considered that the public had been adequately informed. Higher income respondents were more likely to be aware that they would be considered organ donors upon death, unless declared differently. Urban practice respondents were less likely to have previously discussed with a significant other their intentions in regards to presumed consent. One quarter of all respondents (22.4%) intended to carry out their right to prohibit organ removal upon death. Survey results reveal that organ donation reform has yet to be disseminated by the Greek society, underscoring the urgency for targeted information campaigns.     

Routine application of a novel MLPA-based first-line screening test uncovers clinically relevant copy number aberrations in haematological malignancies undetectable by conventional cytogenetics

Objective

The presence of numerical and/or structural chromosomal abnormalities is a frequent finding in clonal hematopoietic malignant disease, typically diagnosed through routine karyotyping and/or fluorescent in situ hybridization (FISH) analysis. Recently, the application of array comparative genomic hybridization (aCGH) has uncovered many new cryptic genomic copy number imbalances, most of which are now recognized as clinically useful markers of haematological malignancies. In view of the limitations of both FISH and aCGH techniques, in terms of their routine application as a first line screening test, we designed a new multiple ligation-dependent probe amplification (MLPA) probemix for use in addition to classic karyotype analysis.

Methods

A novel MLPA probemix was developed to interrogate copy number changes involving chromosomal regions: 2p23-24 (MYCN, ALK), 5q32-34 (MIR145A, EBF1, MIR146A), 6q21-27, 7p12.2 (IKZF1), 7q21-36, 8q24.21 (MYC), 9p24 (JAK2 V617F point mutation), 9p21.3 (CDKN2A/2B), 9p13.2 (PAX5), 10q23 (PTEN), 11q22.3 (ATM), 12p13.2 (ETV6), 13q14 (RB1, MIR15A, DLEU2, DLEU1), 17p13.1 (TP53), and 21q22.1 (RUNX1/AML1) and was applied to DNA extracted from 313 consecutive bone marrow patient samples, referred for routine karyotype analysis.

Results

More than half of the samples originated from newly investigated patients. We discovered clinically relevant genomic aberrations, involving a total of 24 patients (8%) all with a normal karyotype, which would have remained undiagnosed.

Discussion

Our data clearly indicate that routine application of this MLPA screening panel, as an adjunct to karyotype analysis, provides a sensitive, robust, rapid and low-cost approach for uncovering clinically important genomic abnormalities, which would have otherwise remained undetected.     

The prognostic value of vascular endothelial growth factors (VEGFs)-A and -B and their receptor, VEGFR-1, in invasive breast carcinoma

OBJECTIVES: Vascular endothelial growth factors A and B (VEGF-A and VEGF-B) play a major role in angiogenesis and activate VEGF receptor 1 (VEGFR-1). However, the clinicopathologic and clinical value of VEGF-B and VEGFR-1 in invasive breast carcinoma remains unclear. METHODS: We immunohistochemically examined the expression pattern of VEGF-A, VEGF-B and VEGFR-1 in 177 invasive breast carcinomas in relation to clinicopathological parameters, p53, c-erbB2 proteins expression and patients' survival. RESULTS: VEGF-A, VEGF-B and VEGFR-1 were immunodetected predominantly in the cytoplasm of the malignant cells. None of the studied markers correlated with any of the clinicopathological parameters, other than stromal VEGFR-1 which inversely correlated with PR (p=0.021). Cancerous VEGF-A and stromal VEGFR-1 were positively related to p53 (p=0.016 and p=0.033, respectively). Cancerous VEGF-B was positively associated with c-erbB-2 (p=0.045) and was found to exert an unfavorable impact on both disease-free and the overall survival of the node-positive patients (p=0.05 and p=0.029, respectively). Cancerous VEGFR-1 was recognized as being an independent poor prognostic indicator (p=0.037). CONCLUSION: These findings suggest that, while VEGF-B seems to be useful as a prognostic indicator only in node-positive patients, VEGFR-1 may be an independent poor prognosticator in patients with invasive breast carcinoma.     

Laparoscopy in the evaluation of women with unexplained ascites: an invaluable diagnostic tool

STUDY OBJECTIVE: To assess whether laparoscopy is a reliable technique for the investigation of women presenting with ascites and in whom the diagnosis remains obscure. DESIGN: Prospective nonrandomized clinical study (Canadian Task Force classification II-2). SETTING: University Departments of a tertiary referral center. PATIENTS: Women presenting in our institution with ascites in whom the diagnosis remained obscure after an extensive nonoperative diagnostic work-up. INTERVENTION: Undiagnosed cases were submitted to laparoscopy, and selective biopsy specimens were taken for histologic study. MEASUREMENTS AND MAIN RESULTS: Over a 3-year period, 73 patients were admitted to our institution with diffuse ascites. In 9 patients (12.3%), the diagnosis remained obscure, and these patients were further investigated with laparoscopy. Selective biopsy specimens obtained at laparoscopy clarified the specific cause of the ascites in all 9 patients. Peritoneal carcinomatosis was responsible in 5 patients (a metastatic gastrointestinal tumor in 1 patient, a malignant mesothelioma of the peritoneum in 1 patient, and a serous papillary carcinoma of the peritoneum and of the ovary in 2 and 1 patients, respectively). Three patients were found with miliary peritoneal tuberculosis, and the last patient had an unusual peritoneal reaction to methylene blue after laparoscopic adhesiolysis. CONCLUSION: Laparoscopy is a valuable means of assessing the peritoneal cavity in patients with unexplained ascites, where the primary cause remains unclear. The diagnosis can be accurately made with selective biopsy specimens, and appropriate treatment can be instituted without delay.     

Management of childhood diseases during the Byzantine period: V − Hydrocephalus

Hydrocephalus was a recognizable medical problem during the Byzantine period. In the medical texts of the time it was attributed to the pressure that was applied on the newborn's head during labour. The suggested treatments focused on the relief of the symptoms only and surgical methods were believed to be helpful in very rare cases.