Human immunodeficiency virus (HIV) and Epstein-Barr virus (EBV) related lymphomas, pathology view point.

The contribution of Epstein Barr virus (EBV) and Kaposi sarcoma herpes virus (KSHV) to the development of specific types of malignant lymphomas occurring in the human immunodeficiency virus (HIV) setting has been extensively studied since the beginning of the HIV epidemic 35 years ago. The introduction of highly active antiretroviral therapies (HAART) in 1996 has changed dramatically the incidence of HIV-related malignancies. Nevertheless, malignant lymphomas continue to be the major group of malignances observed in HIV infected individuals, and the most common cause of cancer related-deaths. Common features of the predominant B-cell lymphomas in the HIV+ setting are the frequent plasmacytoid morphology of the neoplastic cells, advanced stage, aggressive disease and frequent extranodal involvement. In this article, we review the evolving concepts and definitions of the various EBV-associated lymphomas in HIV+ patients, including diffuse large B-cell lymphoma, Burkitt lymphoma, classical Hodgkin lymphoma, plasmablastic lymphoma and primary effusion lymphoma. The current knowledge regarding the pathogenesis of these malignancies, the interplay between HIV and EBV co-infection in the development of certain HIV related lymphomas, and the emerging paradigm that suggests that HIV may play a direct role in lymphomagenesis are explored as well.

Hydatid Cyst of Parotid Gland: An Unusual Case Diagnosed by Fine Needle Aspiration Biopsy.

Hydatid disease is a zoonotic disease caused by the parasite Echinococcus granulosus. This infection frequently infects the liver and the lung and even in endemic regions rarely occurs in the head and neck region. This is also true for the parotid gland. The diagnosis relies on imaging techniques and the medical history. Another method that is helpful in the diagnosis is serological tests. Fine-needle aspiration biopsy is usually not recommended due to the potential risk of anaphylactic shock or spreading of daughter cysts. The preferred treatment method of hydatid cysts in the salivary gland is surgical excision. We introduce a rare case of hydatid cyst in the parotid gland diagnosed preoperatively by fine-needle aspiration biopsy and discuss the differential diagnosis.

Sinonasal inflammatory myofibroblastic pseudotumor (plasma cell granuloma).

Inflammatory myofibroblastic pseudotumor (plasma cell granuloma) is a soft tissue lesion consisting of myofibroblasts, mature lymphocytes, histiocytes, plasma cells, eosinophils, and extracellular collagen. Various sites in the body may harbor these lesions. Lungs, omentum, intestines, mesentery, and urinary system are the most susceptible areas. It is usually seen in children and young adults. The lesion is rarely detected in the head and neck region. The orbit and the upper respiratory system are the most common localizations in the head and neck region. Sinonasal tract is a rare site of involvement. The differential diagnosis includes squamous cell carcinoma (spindle cell variant), inflammatory fibrosarcoma, leiomyosarcoma, schwannoma, and nonspecific inflammation. Our patient who had a sinonasal mass showed a benign tumor consisting of spindle tumor cells and inflammatory cells histopathologically. This case was presented due to its rare existence to this site.

Prognostic value of increased HER2 expression in cancers of pancreas and biliary tree.

Increased HER2 expression has a prognostic, and predictive value in many solid cancer types, predominantly in breast cancer. However the effects of HER2 on survival from cancers of pancreas, gall bladder, cholangiocellular, and ampullary region are not known. In this study, the effects of increased HER2 expression on these types of cancer have been analyzed. Immunohistochemical HER2 staining was performed in 31 (44.9 %) female, and 38 (55.1 %) male patients with a mean age of 65 ± 10 years, and various parameters, mostly survival rates of patients with pancreas (n = 30; 43.5 %), gall bladder (n = 17; 24.6 %), cholangiocellular (n = 12; 17.4 %), and ampullary region (n = 10; 14.5 %) carcinomas were evaluated. Strong (3 +) membranous staining for HER2 was observed in 2 patients with gall bladder cancers (11.76 % of all gall bladder cancers). In 2.90 % of all cases strong membranous staining (2+ or 3+) was observed. Weak (1+) membranous staining was noted in one (3.33 %) pancreatic, and one cholangiocellular (8.33 %) cancer patient, and in none of the ampullary region patient membranous staining for HER2 was observed. Since only scarce number of patients demonstrated membranous staining for HER2, survival analysis was not performed on these patients. Based on cytoplasmic HER2 staining scores, the patients were divided into weakly (0-3 pts; n = 17 patients; 24.66 %), moderate (4-5 pts; n = 22; 31.88 %), and strongly (6-7 pts; n = 30; 43.46 %) stained groups. Patients whose specimens demonstrated borderline statistical significant (p = 0.052) low staining for HER2 had higher survival rates when compared with other cases. Increased HER2 expression has no prognostic, and predictive value in cancers of pancreas, biliary tract, and ampulla vateri. If HER2 will be evaluated in these types of cancer, membranous, as well as cytoplasmic staining properties should be taken into account.

Two rare entities in the same palate lesion: hyalinizing-type clear cell carcinoma and necrotizing sialometaplasia.

Hyalinizing clear cell carcinoma is a low-grade malignant epithelial neoplasm of the salivary glands. The tumor has epithelial cells and lacks myoepithelial cells. Necrotizing sialometaplasia is a benign, self-limiting lesion of the salivary glands. The clinical and histologic features mimic those of mucoepidermoid carcinoma or squamous cell carcinoma. The importance of these entities are the rarity of both of them and their potential to be misdiagnosed as other lesions. Pathologists and clinicians should be aware of these entities to prevent misdiagnosis. This is the first clinical report of 2 rare and consecutive different entities of the same location on the hard palate to our knowledge.

[Osteoblastoma in the os hamatum: a rare case report]. / Hamatum kemiginde osteoblastom: Nadir bir olgu sunumu.

Osteoblastoma in the os hamatum is rarely seen. Although curettage and grafting seems to be disadvantageous, it offers advantages in the functional protection in the treatment of carpal bone-located osteoblastoma. In a 39-year-old housewife who was admitted with painful left wrist through all day for the past one year, physical examination revealed painful hypothenar region with the wrist adduction to the ulna. Radiography showed radial inclination of the wrist, ring appearance in the scaphoid bone, and slight radiolucency in the hamatum and adjacent bones. Computed tomography demonstrated an expanded lesion which separated the surrounding tissue with a thin edge layer and perforated the cortex mildly. Intralesional curettage was performed. The pathological examination of the specimen obtained was consistent with osteoid osteoma or osteoblastoma. Curettage and grafting were performed in case of recurrence. In this article, we present a rare case of carpal bone and hamatum-located osteoblastoma. The patient was free of pain with normal wrist functions at 16 months postoperatively.

[Effects of abdominal adhesion-preventing 4% icodextrin solution on healing of bowel anastomoses]. / Karin içi adezyon önleyici %4'lük ikodekstrin solüsyonunun gastrointestinal sistem anastomozlari üzerine etkisi.

BACKGROUND: We aimed to introduce the efficiency of 4% icodextrin solution on preventing adhesions and its effect on anastomotic healing, together with biochemical parameters. METHODS: In total, 40 rats were divided into four groups of 10 rats each as Group A (abrasion+icodextrin), Group B (abrasion), Group C (anastomosis+icodextrin), and Group D (anastomosis). Adhesion grade, anastomotic bursting pressure, histopathological analysis, tissue hydroxyproline level, and serum myeloperoxidase (MPO), nitric oxide (NO), and malondialdehyde (MDA) values were examined. RESULTS: Adhesion score was significantly lower in Group A than in Group B and significantly lower in Group C than in Group D (p=0.003577, p=0.001612). No difference in anastomoses healing was determined between Group C and Group D (p=0.816). Hydroxyproline level was significantly higher in Group A than in Group B and significantly higher in Group C than in Group D (p=0.001, p=0.0001). There were no differences in NO and MDA levels between Group A and Group B, but values were significantly lower in Group C than in Group D (p=0.434, p=0.001, p=0.116, p=0.018). MPO level was significantly lower in Group A than in Group B and significantly lower in Group C than in Group D (p=0.0001, p=0.0001). CONCLUSION: Based on our results, 4% icodextrin solution evidently decreased the formation of adhesion without negatively affecting the anastomotic healing. We also reported herein the biochemical and histopathological results and adhesion scores.

Contribution of DOG1 expression to the diagnosis of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GIST) are the most common mesenchymal tumors of the gastrointestinal tract, and the majority contain KIT or PDGFRA-activating mutations. However, up to 10% of GISTs are c-kit-negative. Antibodies with increased sensitivity and specificity for the detection of c-kit-negative GIST cases may be of value, especially because some of these cases may also benefit from tyrosine kinase inhibitor therapy. Hematoxylin and Eosin sections of 33 GISTs were re-examined in order to define histopathological criteria used in risk assessment of these tumors. Immunohistochemistry with a panel of antibodies [c-kit, DOG1 (discovered on GIST 1), CD34, smooth muscle actin (SMA), Desmin, S100 and Ki67] was performed on 5µm-thick paraffin sections of all tumors. Statistical analysis of immunohistochemical studies showed that DOG1 and CD117 were the most sensitive and specific antibodies in the diagnosis of GISTs. Other antibodies were unhelpful in confirming a diagnosis of GIST, but were particularly useful in the differential diagnosis. Reactivity for DOG1 may aid in the diagnosis of GISTs, which fail to express c-kit antigen, and lead to appropriate treatment with imatinib mesylate, an inhibitor of the KIT tyrosine kinase.

Follicular dendritic cell sarcoma of the tonsil.

Follicular dendritic cell sarcoma (FDCS) is an uncommon tumour within the spectrum of histiocytic and dendritic cell neoplasms that can occur at nodal and extra-nodal sites. Besides being rare, these tumours are difficult to diagnose. A 72-year-old man with a painless mass in the right tonsil was admitted to the Mersin University Hospital. Tonsillectomy was performed. Microscopically, the tumour consisted of spindle-shaped cells with large oval to polygonal nuclei. Lymphocytes were scattered among the tumour cells. Immunohistochemically, the cells were positive for CD23 and vimentin. The tumour was diagnosed as FDCS with histological and immunohistochemical findings. Recognition of extranodal FDCS requires knowledge of this entity and to consider it during the diagnosis. Confirmatory immunohistochemical staining is essential for diagnosis. Correct characterisation of this neoplasm is important because of its potential for recurrence and metastasis.

Ovarian hilus-cell hyperplasia and high serum testosterone in a patient with postmenopausal virilization.

OBJECTIVE: To describe a woman with postmenopausal virilization and hirsutism caused by hilus-cell hyperplasia. METHODS: We present a case report including laboratory, radiographic, and pathologic findings in a patient with postmenopausal hirsutism and virilization caused by ovarian hilus-cell hyperplasia as well as a brief review of the literature. RESULTS: A 60-year-old postmenopausal woman presented with extensive hirsutism, male-pattern hair loss, and clitoromegaly. The patient's plasma testosterone levels were very high, but computed tomography showed the adrenal glands to be normal in size. Pelvic ultrasonography revealed a cystic lesion in the left ovary. After bilateral salpingo-oophorectomy, histologic examination demonstrated a diffuse pattern of hilus-cell hyperplasia in the ovarian hilum. CONCLUSION: In the differential diagnosis of postmenopausal virilization, hilus-cell hyperplasia, although rare, should be considered.

Quantitative mRNA expression analysis of co-stimulatory molecules in sequential biopsies from heart allografts.

Allograft-specific T-cell activation requires two signals, "signal one" via the T-cell receptor and "signal two" via costimulatory pathways. Animal models provide promising data that blockade of costimulatory signals can lead to T-cell anergy and tolerance. We analyzed 72 formalin-fixed and paraffin-embedded sequential heart allograft biopsies from 22 patients by quantitative real-time reverse transcriptase-polymerase chain reaction for the mRNA expression of the costimulatory molecules CD28, CD80, CD86, CD40, and CD154. mRNA expression levels were correlated to histological grade and time-point of rejection. mRNA expression of costimulatory molecules predominantly expressed by antigen-presenting cells (CD80, CD86, CD40), correlated with histological grade of cell-mediated acute rejection. Costimulatory molecules were up-regulated not only during rejection episodes early after transplantation, but also at late occurring rejection. The present results suggest a simultaneous and long-term therapeutical blockade of more than one costimulatory pathway for the prevention of repetitive T-cell mediated acute rejection episodes after heart transplantation.

Local complement C3 expression is upregulated in humoral and cellular rejection of renal allografts.

Evidence on the role of the complement system in transplantation pathology has been accelerated by the discovery of C4d as an in situ marker of antibody-mediated rejection. However, a local or systemic source of complement expression during acute rejection is under discussion. Thus, we quantitatively analyzed local RNA expression of complement component C3 as a pivotal molecule in active humoral and cellular rejection of renal allografts. After laser microdissection, real-time RT-PCR was performed for C3 using RNA extracted from tubuli and glomeruli of 68 paraffin-embedded renal allograft biopsies. Protocol and indication biopsies with signs of humoral and/or cellular rejection were investigated. Quantitative expression analysis of cytokines (IFN gamma, MCP-1, IL2, IL8) potentially influencing local C3 expression was performed. We observed a significant increase in median expression level of C3 mRNA in tubuli of C4d-positive indication biopsies, and in tubuli from indication biopsies with signs of T-cell-mediated cellular rejection. Highest expression levels were found in C4d-positive indication biopsies with signs of cellular rejection. Biopsies with upregulated C3 showed increased IFN gamma expression, suggesting allograft-infiltrating T-cells as potential stimulus for local C3 expression. Therefore, locally synthesized complement component C3 contributes to both humoral and cellular rejection, with tubular epithelial cells being a major source.

Distribution of Bcl-2 gene expression and its prognostic value in non-small cell lung cancer.

The aim of this study was to determine the expression of Bcl-2 gene and prognostic importance of Bcl-2 expression in paraffin embedded blocks of patients diagnosed with non-small cell lung cancer (NSCLC). This study included the retrospective analysis of overall 46 patients diagnosed with NSCLC in our clinic between 1996 and 1999. In 16 (34.8%) patients, the diagnosis was made on biopsy of bronchial mucosa and in 30 (65.2%) patients, on materials obtained by surgical resection (lobectomy and pneumonectomy). We reviewed the sections 4-6 microns in size and stained with Hemotoxylin-Eosine (HE) obtained from paraffin embedded blocks and fixed by 10% formalin. These sections are transferred on to slides covered with poly-L-lysine, then de-paraffinization was made. In all cases, immunohistochemical staining with Bcl-2 antibodies was performed. Positive staining was observed in 9 (19.6%) patients, but not in 37 (80.4%) patients. Out of 32 cases with squamous cell tumor, 8 (25%) were observed to have positive staining in their sections, but 24 (75%) were not so. No staining was observed in 11 cases whose cell type was adenoma and two cases whose cell type was adenosquamos (100%). Staining was present in the section of one case with large cell (100%). Median survival time was 36.6 months in cases in which staining was observed and 6.10 months in cases in which staining was not observed, with a significant difference (p< 0.05). In conclusion, the rate of survival was higher in cases in which staining was present.

Aberrant expression of insulin-like growth factor-2 (IGF-2) in Philadelphia chromosome negative chronic myeloproliferative disorders.

Philadelphia chromosome negative chronic myeloproliferative disorders (Ph- CMPD) comprise haematopoietic stem cell disorders with currently unknown underlying molecular defect. Insulin-like growth factor 2 (IGF-2) is an imprinted gene that is known to be involved in the regulation of normal cell growth and that is overexpressed by a variety of tumors. The expression of IGF-2 in bone marrow cells is largely unknown. In order to elucidate gene expression level, protein expression pattern, and a potential role of IGF-2 in the pathogenesis of Ph- CMPD, we quantitatively analyzed the expression of the IGF-2 gene in bone marrow cells of 69 cases with Ph- CMPD and 31 control cases by applying real-time RT-PCR. IGF-2 gene expression in idiopathic myelofibrosis (IMF) was significantly increased by up to 11-fold as compared to the control group (P < 0.0001). IMF also expressed higher IGF-2 gene level as compared to essential thrombocythaemia (ET) and polycythaemia vera (PV) (P < 0.0001, P = 0.005, respectively). Paranuclear IGF-2 protein could be demonstrated in IMF, ET, and PV exclusively in megakaryocytes and myeloid progenitor cells in contrast to undetectable IGF-2 protein in control cases. We conclude that overexpression of the IGF-2 gene is a pathogenic feature in IMF. In addition, an abundant translational and post-translational processing could explain the accumulation of IGF-2 protein detectable in all Ph- CMPD entities in contrast to non-neoplastic haematopoiesis. We conclude that IGF-2 represents a new molecular target for evaluation of underlying fundamental pathomechanisms in Ph- CMPD.

N-acetylcysteine in intestinal reperfusion injury: an experimental study in rats.

BACKGROUND: The aim of the present study was to investigate the effect of N-acetylcysteine on intestinal reperfusion injury. METHODS: Forty Sprague-Dawley rats were divided into four groups (n = 10): sham, sham + N-acetylcysteine, reperfusion, and reperfusion + N-acetylcysteine. Thirty minutes of ischaemia +/- 30 min of reperfusion was performed under 100 mg/kg N-acetylcysteine or placebo, administered 30 min before the operation in the groups where appropriate. Ileum samples were resected for histopathologic evaluation and tissue malondialdehyde and super oxide dismutase level determination. RESULTS: The mean mucosal injury score and malondialdehyde level of the reperfusion and reperfusion + N-acetylcysteine groups were significantly higher than that of the control and control + N-acetylcysteine group (P < 0.01, P < 0.05, respectively). Mean super oxide dismutase level of the control + N-acetylcysteine group was significantly higher than that of the other groups (P < 0.05). CONCLUSION: N-Acetylcysteine did not prevent intestinal reperfusion injury by means of histopathologic findings and malondialdehyde level.

Aberrant expression of beta-catenin discriminates acute myeloid leukaemia from acute lymphoblastic leukaemia.

The role of beta-catenin in epithelial neoplasms has been widely studied whereas current knowledge regarding beta-catenin gene and protein expression in bone marrow cells derived from normal haematopoiesis and clonal haematological disorders is lacking. beta-Catenin gene expression was quantitatively investigated in bone marrow cells derived from clonal haematological disorders [acute myeloid leukaemia (AML), acute lymphoblastic leukaemia (ALL), Philadelphia chromosome-positive chronic myeloid leukaemia (Ph+ CML], Ph- myeloproliferative disorders, n = 96) compared with non-neoplastic haematopoiesis (n = 33) by real-time reverse transcription polymerase chain reaction. Cellular localization of beta-catenin protein was detected by immunocytochemistry. beta-Catenin gene expression was significantly increased in AML compared with ALL cases (P < 0.0001), Ph+ CML (P < 0.0001) and non-neoplastic haematopoiesis (P = 0.019). Immunocytochemistry revealed that, in non-neoplastic haematopoiesis, the granulopoietic lineage as well as megakaryocytes showed membranous and cytoplasmic staining to various degrees along with unlabelled nuclei. Besides haematopoiesis, beta-catenin prominently marked bone marrow vascularity and diverse stroma cells. beta-Catenin gene was inversely expressed in AML and ALL with a lack of protein expression in neoplastic cells in ALL. In contrast, the other haematological disorders under study, except for Ph+ CML, did not show significant alterations of overall beta-catenin gene expression compared with normal bone marrow. These data suggest different regulatory mechanisms in the expression and function of beta-catenin in haematopoietic cells.

Different expression levels of the telomerase catalytic subunit hTERT in myeloproliferative and myelodysplastic diseases.

Telomerase is the enzyme required for the addition of telomeric repeats to the ends of chromosomes and thus for chromosome stability. Most somatic human cells lack telomerase activity because they do not express the telomerase reverse transcriptase (hTERT) gene. In contrast, in almost every neoplasia, cancer cells express hTERT and therefore prevent progressive telomere shortening during each cell division. Consecutively, cancer cells obtain the ability to divide without limits and overcome replicative senescence. Gene expression level of the telomerase catalytic subunit hTERT in normal and neoplastic haematopoiesis has not yet been described. Using a quantitative real-time RT-PCR assay, we analysed the level of hTERT expression in various haematologic stem cell disorders and normal bone marrow. We could demonstrate that hTERT is differentially expressed in various haematologic stem cell disorders with significant higher levels in refractory anemia (RA) and chronic myeloid leukemia (CML) compared to other haematopoietic stem cell disorders and non-neoplastic haematopoiesis which may be used as a prognostic indicator in these entities.

Thrombopoietin receptor (Mpl) expression by megakaryocytes in myeloproliferative disorders.

The thrombopoietin receptor (Mpl) is involved in the pathogenesis of chronic myeloproliferative disorders (CMPD). In this study, we determined Mpl expression by bone marrow cells and megakaryocytes in CMPD by applying laser microdissection, real-time RT-PCR, and immunohistochemistry. Mpl mRNA expression was significantly increased up to 9-fold in total bone marrow cells (p < 0.001) and up to 4-fold in megakaryocytes in chronic myeloproliferative disorders (n = 73) compared to normal controls (n = 26, p = 0.01). Immunohistochemistry revealed heterogeneous Mpl expression by megakaryocytes in CMPD with a stronger accentuation in idiopathic myelofibrosis (IMF) in comparison to polycythaemia vera (PV) and essential thrombocythemia (ET). In addition to megakaryocytes, the erythropoietic lineage was prominently labelled by Mpl antiserum, with considerably stronger staining in polycythaemia vera. We conclude that, in CMPD, megakaryocytes and erythroid cells exhibit increased Mpl expression levels which may contribute to the sustained proliferation of both cell lineages in CMPD.

Predictable and efficient retroviral gene transfer into murine bone marrow repopulating cells using a defined vector dose.

OBJECTIVE: Current protocols of retroviral gene transfer into murine hematopoietic stem cells (HSC) result in variable gene transfer efficiency and involve various procedures that are not clinically applicable. We developed and evaluated a reliable transduction protocol that is more related to clinical methods. MATERIALS AND METHODS: HSC were enriched from steady-state bone marrow by magnetic cell sorting (lineage depletion) and cultured in defined serum-free medium containing an improved growth factor cocktail (Flt3-ligand, stem cell factor, interleukin-3, interleukin-11). Cell-free ecotropic retroviral vector particles, generated by transient transfection of human 293T-based packaging cells, were preloaded at defined titers on CH296-coated tissue culture plates, thus largely avoiding serum contamination. These conditions were evaluated in 17 experiments involving 29 transduction cultures and 185 recipient mice. RESULTS: After two rounds of infection, the gene marking rates in cultured mononuclear cells and stem/progenitor cells (Lin(-)c-Kit(+)) were 15 to 85% (53.7%+/-21.7%, n=23) and 30 to 95% (69.8%+/-20.4%, n=17), respectively. Even after one round of infection, gene transfer was efficient (31.2%+/-15.1%, n=12). Using identical conditions, gene transfer rates were highly reproducible. Average transgene expression in reconstituted animals correlated well with pretransplant data. Using a moderate multiplicity of infection, the majority of transduced cells carried less than three transgene copies. In addition, coinfection was possible to establish two different vectors in single cells. CONCLUSION: The protocol described here achieves efficient retroviral transduction of murine bone marrow repopulating cells with a defined gene dosage, largely avoiding procedures that decrease stem cell output and repopulating capacity. This protocol may help to improve the predictive value of preclinical efficiency/toxicity studies for gene therapeutic interventions and basic research.