Arzu Saglam

Correlation of clinicopathological parameters with HGF, c-Met, EGFR, and IGF-1R expression in uveal melanoma.

This study evaluated the expression profile of hepatocyte growth factor (HGF), c-Met, epidermal growth factor receptor (EGFR), insulin-like growth factor-1 receptor (IGF-1R), and vitreal and serum EGF, HGF, IGF-1 levels in patients with uveal melanoma and assessed their correlation with the clinicopathological parameters. Forty patients with uveal melanoma were included in the study. Clinicopathological parameters were evaluated with hematoxylin–eosin staining. HGF, c-Met, EGFR, and IGF-1R expressions were evaluated immunohistochemically. HGF, EGF, and IGF-1 levels were measured with enzyme-linked immunosorbent assay in vitreous and serum specimens taken at enucleation and 6 months after the enucleation. HGF, c-Met, IGF-1R, and EGFR expressions were detected in 57.5, 20, 20, and 12.5% of cases, respectively. IGF-1R expression was significantly correlated with the degree of pigmentation, necrosis, and lymphocyte infiltration (P=0.013, 0.04, and 0.017). EGFR expression was significantly correlated with the mitosis rate (P=0.02). Vitreal EGF and serum IGF-1 levels were significantly higher in patients with scleral invasion (15.72±29.13, 199.01±154.01 pg/ml, respectively) when compared with the patients without invasion (0.56±1.05, 33.01±36.52 pg/ml) (P=0.03 and 0.015). When the preoperative and postoperative serum growth factor levels were compared, the serum EGF level was found to be lower (125.93±62.84, 100.02±31.19 pg/ml, P=0.007) and the serum IGF-1 level (165.81±153.6, 301.35±131.24 pg/ml, P<0.001) was found to be higher in the postoperative 6-month specimens. Uveal melanomas express HGF, c-Met, EGFR, and IGF-1R. Vitreal growth factor levels and expression of EGFR and IGF-1R are correlated with some clinicopathological parameters. IGF-1 and EGF may have a role in the development and progression of uveal melanoma.

The presence of Epstein–Barr virus (EBV) in diffuse large B-cell lymphomas (DLBCLs) in Turkey: special emphasis on ‘EBV-positive DLBCL of the elderly’

Uner A, Akyurek N, Saglam A, Abdullazade S, Uzum N, Onder S, Barista I, Benekli M. The presence of Epstein–Barr virus (EBV) in diffuse large B‐cell lymphomas (DLBCLs) in Turkey: special emphasis on ‘EBV‐positive DLBCL of the elderly’. APMIS 2011; 119: 309–16.

Immunohistochemical expression of multidrug resistance proteins in mature T/NK-cell lymphomas.

Multidrug resistance (MDR) is defined as resistance of tumor cells to a wide spectrum of structurally and functionally unrelated drugs. One of the most important mechanisms in mediating MDR is that involving cellular drug efflux transporters. Drug resistance is a common and formidable obstacle to therapy in mature T/NK‐cell lymphomas and the MDR phenotype is thought to be one of the contributing mechanisms. In this study we assessed the immunohistochemical expression of P‐gp (P‐glycoprotein), MRP‐1 (multidrug resistance associated protein 1), BCRP (breast cancer resistance protein) and LRP (lung resistance protein) in 45 mature T/NK‐cell lymphomas diagnosed at our hospital. We detected P‐gp expression in 31% (13/42), MRP‐1 expression in 74% (31/42), BCRP in 78% (32/ 41) and LRP in 59% (26/44) of the cases. These findings show that our T/NK‐cell lymphoma cases display high frequency of MDR protein expression.

Urgent liver transplantation for Amanita phalloides poisoning.

Abstract:  Amanita phalloides is a deadly wild mushroom causing severe damage in man ranging from diarrhea to organ dysfunction. If not treated, mortality is as high as 80%. Treatment includes supportive measures, inactivation of the toxin and if liver failure occurs liver transplantation. The indications for transplantation are debatable.

PTEN and p27 expression in mature T-cell and NK-cell neoplasms

PTEN is a tumor suppressor gene located on chromosome 10q23 and is amongst the most commonly mutated genes in human cancers. The lipid phosphatase activity of Pten enables it to dephosphorylate PIP3, thereby antagonizing growth factor stimulated PI3-kinase signaling mediated by AKT/PKB. The growth inhibition effect of PTEN has been shown to be mediated by p27 which is one of the important effector molecules downstream of the AKT pathway. Recently the importance of the Pten and AKT pathway in the regulation of the immune system and development of hematological malignancies has been shown. Loss of Pten and p27 expressions were examined immunohistochemically in 45 patients with peripheral T- and NK-cell lymphoma. Partial or complete loss of Pten was detected in 66.7% of the cases of anaplastic large cell lymphoma (ALCL) compared to only 12.5% of all other mature T-/NK-cell lymphomas combined. Loss of p27 was identified in 64.9% of cases, which showed a positive correlation with Pten loss. In this study, we showed that loss of Pten is more frequent in ALCL as compared to other mature T-/NK-cell lymphomas, which strongly correlates with the loss of p27 expression. Our findings provide further evidence for the importance of the deregulation of the PI3K-AKT pathway in ALCL.

Reproducibility of endometrial intraepithelial neoplasia diagnosis is good, but influenced by the diagnostic style of pathologists

Endometrial intraepithelial neoplasia (EIN) applies specific diagnostic criteria to designate a monoclonal endometrial preinvasive glandular proliferation known from previous studies to confer a 45-fold increased risk for endometrial cancer. In this international study we estimate accuracy and precision of EIN diagnosis among 20 reviewing pathologists in different practice environments, and with differing levels of experience and training. Sixty-two endometrial biopsies diagnosed as benign, EIN, or adenocarcinoma by consensus of two expert subspecialty pathologists were used as a reference comparison to assess diagnostic accuracy of 20 reviewing pathologists. Interobserver reproducibility among the 20 reviewers provided a measure of diagnostic precision. Before evaluating cases, observers were self-trained by reviewing published textbook and/or online EIN diagnostic guidelines. Demographics of the reviewing pathologists, and their impressions regarding implementation of EIN terminology were recorded. Seventy-nine percent of the 20 reviewing pathologists’ diagnoses were exactly concordant with the expert consensus (accuracy). The interobserver weighted κ values of 3-class EIN scheme (benign, EIN, carcinoma) diagnoses between expert consensus and each of reviewing pathologists averaged 0.72 (reproducibility, or precision). Reviewing pathologists demonstrated one of three diagnostic styles, which varied in the repertoire of diagnoses commonly used, and their nonrandom response to potentially confounding diagnostic features such as endometrial polyp, altered differentiation, background hormonal effects, and technically poor preparations. EIN diagnostic strategies can be learned and implemented from standard teaching materials with a high degree of reproducibility, but is impacted by the personal diagnostic style of each pathologist in responding to potential diagnostic confounders.

Primary Signet-ring Cell Carcinoma of the Cervix: Case Report and Review of the Literature

Mucinous adenocarcinoma of the cervix has 5 subtypes: endocervical, intestinal, signet-ring cell, minimal deviation, and villoglandular. There are only rare reports of primary signet-ring cell carcinoma of the cervix in the literature. Herein we report a 53-year-old woman with cervical adenocarcinoma with signet-ring cell morphology. Thorough systemic examination did not reveal another primary focus. DNA extraction from paraffin-embedded tissue revealed the presence of human papilloma virus (HPV) type 18, which supports the cervical origin of the tumor. Signet-ring cell morphology can be observed in both benign and malignant lesions of the uterine cervix. Most of the malignant lesions are metastatic. Histological features and immunohistochemical profiles are discussed, and a review of signet-ring cell morphology in the uterine cervix is included.

Four synchronous female genital malignancies: the ovary, cervix, endometrium and fallopian tube.

AbstractObjectiveTo present a unique case of a 63 year-old woman with coexistent adenocarcinoma of the ovary, endometrium, cervix and fallopian tube.Materials and methodsA case report from a tertiary health center.ResultsA woman presenting with postmenopausal bleeding and abdominal distantion was assessed by endometrial biopsy and explorative surgery. The frozen section of the mass on the right adnex revealed malign mucinous carcinoma of the ovary. As usual, optimal debulking was performed as initial surgical staging procedure of ovarian cancer. The microscopic examination of the right ovary revealed a typical mucinous cystadenocarcinoma. Furthermore, the focal endometrial irregularity at the left uterine cornus turned out to be a well differentiated endometrial carcinoma of the endometrioid type with <1/3 myometrial invasion. The pale infiltrative lesion in the cervix also turned out to be an adenocarcinoma of the endocervical type with deep stromal invasion and areas of diffuse glandular dysplasia and in-situ glandular neoplasia at the periphery. Besides, several sections from the left fallopian tube uncovered diffuse dysplasia in the lining epithelium and a focus of adenocarcinoma with papillary and cribriform pattern.DiscussionWhen compared with patients having metastatic lesions, most synchronous female malignancies are accompanied with early stage and low-grade with a more favorable prognosis. However, there is paucity of data for the exact criterion to distinguish primary tumors from metastatic lesions. In such cases, the validity of immunohistochemical and cloning studies are not clear.

Pituitary adenoma with gangliocytic component: report of 5 cases with focus on immunoprofile of gangliocytic component

IntroductionPituitary adenomas with gangliocytic component are rare tumors of the sellar region that are composed of pituitary adenoma cells and a ganglion cell component. Their histogenesis and hence nosology is not yet resolved because of the small number of cases reported and lack of large series in the literature.MethodsHerein we report five cases of pituitary adenoma with gangliocytic component to add knowledge to this rare neoplasm.ResultsThree cases are functional mammosomatotroph adenomas, one case is functional sparsely granulated somatotroph adenoma and the other is functional corticotroph adenoma. Gangliocytic component showed immunohistochemical expression of hormones in three cases. The ganglion cells were prolactin immunoreactive in case 1, GH and TSH immunoreactive in case 5 and showed expression of prolactin, TSH, ACTH and FSH in case 4. Three cases had undergone more than one surgery of which two had gangliocytic cells only in the recurrent tumors whereas the third case showed gangliocytic cells only in the initial tumor.DiscussionThe cases are discussed with clinical and histological features and a brief review of the literature considering the histogenesis is included.

Epstein-Barr virus frequency in primary central nervous system lymphomas in Turkey

Primary central nervous system (CNS) lymphomas are rare neoplasms which are usually not associated with Epstein‐Barr virus (EBV) in immunocompetent patients. The aim of this study was to investigate the incidence of EBV in primary CNS lymphomas in the Turkish population. Thirty‐two primary CNS lymphomas diagnosed according to the WHO 2008 criteria were included in this study. The presence of EBV small ribonucleic acids was investigated by in situ hybridization using EBV encoded small RNA oligonucleotides. The expression of CD10, Bcl‐6, MUM‐1/IRF‐4, Bcl‐2, and Ki‐67 were evaluated using immunohistochemistry. The patient cohort included 20 male patients and 12 female patients with a median age of 53.5 years (range 13–75). Seven (22%) of cases were classified as germinal center (GC) and 25 (78%) cases as non‐GC phenotype according to the Hans criteria. Twenty‐six (81%) of the cases showed strong Bcl‐2 expression and the median Ki‐67 index was 78%. EBV expression was observed in four primary CNS lymphoma cases (12.5%). Most primary CNS lymphomas show non‐GC phenotype with high Bcl‐2 expression and high proliferative rate. The incidence of EBV in primary CNS lymphomas from Turkey appears to be higher than that observed in the Western countries.