GATA3 expression and its relationship with clinicopathological parameters in invasive breast carcinomas.

GATA3, as a transcription factor, is associated with estrogen receptor (ER) expression and necessary for luminal cell differentiation in mammary glands. Association of GATA3 expression with clinicopathological parameters, molecular subtypes of tumors, disease free survival (DFS) and overall survival (OS) for breast carcinoma patients were evaluated in this study. We immunohistochemically stained GATA3, CK5/6, EGFR, CK14 and vimentin on tissue microarray blocks of 457 invasive breast carcinomas. Tumors are sub-classified as luminal A, luminal B, HER2 expressing, basal-like and null type according to their hormonal status with cerbB2, CK 5/6 and EGFR expressions. Follow-up data for 254 cases were obtained. 215/457 (47%) tumors were GATA3 positive. GATA3 expression was inversely correlated with mitotic count (p<0.0001), nuclear grade (p=0.001), histological grade (p=0.001), tumor necrosis (p=0.001), stromal lymphocytic response (p<0.01), nipple invasion (p=0.01), metastasis (p=0.03), vimentin (p=0.0003), EGFR (p=0.015) and CK14 (p=0.001) expressions; and directly associated with ER (p<0.0001) and progesterone receptor (PR) (p<0.0001) expressions. Luminal A carcinomas had the highest frequency for GATA-3 (140/245), however basal-like carcinomas had the lowest (1/42) (p<0.0001). None of the medullary and metaplastic carcinomas expressed GATA3. GATA3 was associated with good DFS and OS (p=0.001 and p=0.0009) and was an independent prognostic factor for OS. GATA3 expression, regardless of the subtype, may have a prognostic significance for breast carcinomas through its ability to promote the differentiation of luminal progenitor cells.

Intrasellar plasmacytoma: an unusual presentation of multiple myeloma.

INTRODUCTION: Plasmacytomas are unusual causes of a sellar mass. Occasionally, they can be misdiagnosed as a nonfunctioning adenoma because of radiological and clinical similarities. LITERATURE REVIEW: We reviewed the pertinent literature and discuss here in the light of an illustrative case of our own. DISCUSSION: A 70-year-old woman presented with a recurrent hypophysial mass. Initial diagnosis of a nonfunctioning pituitary adenoma was later overruled by a repeat biopsy, which showed a plasmacytoma. The tumor stained positively for CD138 and kappa light chain. Further studies confirmed the diagnosis of multiple myeloma. The patient was successfully treated with radiotherapy followed by systemic chemotherapy. Because they have different therapeutic implications, extramedullary plasmacytomas involving pituitary gland should be considered in the differential diagnosis of a nonfunctioning pituitary mass.

Retrorectal hemangiopericytoma: a case report.

Hemangiopericytoma is a rare, vascular soft tissue tumour originating from the pericytes, the contractile cells that surround capillaries. A case of retrorectal hemangiopericytoma in a 49-year-old woman is reported. With a posterior sagittal approach, the tumour was completely removed. Pathological examination, including immunohistological stains, was consistent with a hemangiopericytoma. A step-by-step approach to a retrorectal tumour is exemplified, and a very rare pathological entity is added to the spectrum of retrorectal masses.

Megacystis secondary to myenteric plexus pathology. Presentation of two cases.

Herein, 2 cases of megacystis secondary to myenteric plexus pathology are reported. Unlike the entity of visceral myopathy, there was ganglion cell loss both in the bladder and in the colon of these 2 cases. Moreover, they did not present any gastrointestinal symptoms. Megacystis was the common pathology in these patients, whereas 1 of them suffered from unilateral vesicoureteral reflux. We could not find any similar report dealing with this phenomenon up to this time in the literature.

Cerebriform fibrous proliferation vs. proteus syndrome.

Proteus syndrome is a rare, congenital hamartomatous syndrome that presents with a wide range of abnormalities. Regardless of different manifestations found in different patients, there exists three mandatory criteria for the diagnosis of this syndrome: a mosaic distribution of the lesions, a progressive course, and sporadic occurrence. When these criteria are met, the presence of additional connective tissue nevi, which are encountered mostly on the plantar surface of the feet, suffices for the diagnosis of Proteus syndrome. The authors present a 48-year-old woman who had been evaluated for a lesion on the plantar aspect of her left foot that was diagnosed as keloid and was treated unsuccessfully. In the light of the literature and with the help of histopathological reevaluation, the authors thought this unique lesion may be a localized form of Proteus syndrome.

Non-specific inflammation and bone marrow depletion due to intramedullary porous hydroxyapatite application.

Calcium hydroxyapatite (HA) ceramics are widely used in orthopaedic surgery and are known to be biocompatible, biodegradable, and osteoinductive. Recent studies of HA have identified early stage inflammatory reactions and third-body wear following hip replacement surgery. The aim of this study was to investigate the early stage inflammatory response toward HA by means of conventional radiography, histopathology, and scanning electron microscopy (SEM). HA was implanted into the medullary area of the tibiae of rabbits and followed from one week to six months. Radiography revealed local osteoporosis on Week 6 and Month 6 in some, but not, all rabbits. SEM presented favorable bonding between the implant and the cortical bone. Eosinophilic deposition, non-specific local inflammation, and bone marrow depletion were the histopathological findings. Multinuclear cells were identified in the inflammation area. Although bone ingrowth into the pores of the HA was demonstrated, there is no doubt that HA may cause an early inflammatory reaction in the bone marrow. This inflammatory reaction is followed by bone marrow depletion and may be the early sign and the cause of HA-coated implant failure.

P53 and proliferating cell nuclear antigen (PCNA) expression in non-tumoral liver diseases.

The tumor suppressor gene p53 is known to be involved in the negative regulation of cell growth. Proliferating cell nuclear antigen (PCNA), which is a nuclear protein and a component of the DNA replication process, is also involved in growth regulation. Both have been studied as progression markers in various tumors including hepatocellular carcinoma. In the present study, the aberrant p53 protein and PCNA expressions in non-tumoral liver diseases were investigated. Using monoclonal antibodies anti-p53 (D07-DAKO) and anti-PCNA (PC10-DAKO), 149 samples were stained, including 10 normal and 10 tumoral control liver tissues. p53 Overexpression was detected in 52 specimens (35%) whereas PCNA positivity was found in 96 (64%). There were 21 different pathological entities but most of the positive samples could be grouped into four types of diseases; namely, non-specific reactive hepatitis, steatohepatitis, chronic hepatitis and cirrhosis. Statistical analyses performed on these groups revealed that p53 positivity was found to be significantly higher in steatohepatitis (P < 0.05), while PCNA positivity did not show any statistical significance. The number of samples showing both p53 and PCNA positivity was 42 but their coexistence was not found to be significant. Certain cytological alterations like nuclear pleomorphism, steatosis and cholestasis, in addition to necroinflammatory activity, were evaluated for their possible impact on p53 and/or PCNA positivity. Necroinflammatory activity in steatohepatitis and steatosis in chronic hepatitis was found to be significant for p53 positivity (P < 0.05). In contrast, nuclear pleomorphism in non-specific reactive hepatitis was found to be significant for PCNA positivity (P < 0.05).

The effect of EGb 761 on the doxorubicin cardiomyopathy.

Doxorubicin (Dx) is used to treat a number of types of cancer. The drug produces many toxic reactions and cardiomyopathy. Many drugs have been used to prevent this myocardial damage caused by peroxidative alterations. EGb 761 is being used to prevent arrhythmias in ischemic myocardium. We decided to establish the tissue protective effect of EGb 761 against myocardial toxic effects of Dx in three groups of rats. Cardiotoxicity signs of Dx were found to be dose-related, beginning at 30 mg/kg dose and being apparent at 45 mg/kg dose. 48 hr after a single i.v. injection, myocardial tissues showed a marked edema, vacuolization and fragmentation. We compared the changes in heart tissue biochemically and histopathologically among the control, Dx treated and EGb 761 (100 mg/kg/d.x 4, i.p.) + Dx treated groups. Biochemical results of CK-MB and MDA values showed a significant decrease in Dx + EGb 761 group when compared with Dx treated group. Histopathologically, myocardial tissues of Dx + EGb 761 treated group were found to have diminished vacuolization and fragmentation. These results suggest that EGb 761 might have the same therapeutic potential in Dx related cardiomyopathy.

Unusually high frequency of a 69-bp deletion within the carboxy terminus of the LMP-1 oncogene of Epstein-Barr virus detected in Burkitt's lymphoma of Turkish children.

Burkitt's lymphoma (BL) in Turkish children is commonly associated with Epstein-Barr virus (EBV) infection. The C-terminus of the latent membrane protein 1 (LMP-1) of EBV is essential for transformation and the 30-bp deletion detected in this region has been implicated to be associated with a more aggressive malignant phenotype. To understand the molecular mechanisms underlying EBV pathogenesis in BL of Turkish children, we analyzed 30-bp deletion and 33-bp variable repeat regions of the LMP-1 gene from paraffin-embedded tumor tissues of 30 BL patients (mean age 5.9 years). Primer pairs spanning the 30-bp deletion and 33-bp repeat regions were designed for amplification by polymerase chain reaction (PCR). The PCR-amplified products were analyzed by gel electrophoresis, Southern blot hybridization, and DNA sequencing. Twenty-eight (93%) of 30 BL biopsy samples were EBV positive as determined by PCR. Variable copy numbers (ranging from 4.5 to 7) of the 33-bp repeat of LMP-1 gene were detected in these EBV-containing tumor samples. To determine the frequency of the 30-bp deletion of the LMP-1 gene, we sequenced the amplimers encompassing this region. Analyses of DNA sequence of 28 Turkish BLs have disclosed four patterns: the first (32% (9/28)) is identical to B95-8 with no deletion, the second (11% (3/28)) is identical to Asian NPC CAO strain with 30-bp deletion, the third (46% (13/28)) is prevalent in Turkish BLs with a longer deletion (69 bp), and the fourth (11% (3/28)) consists of a mixture of 30-bp and 69-bp deletion. The occurrence of high frequency of the 69-bp deletion appears to have no correlation with the disease site. Mutations found in the CAO strain were also detected in the Turkish BL clustering at the amino acids 322, 334, 338 and 342; whereas mutations specific for Turkish BL were clustered at amino acids 326, 352 and 361. To assess the EBV genotype with the changes in C-terminus of LMP-1 gene, we performed genotyping by PCR to differentiate type A and B strain. All 28 patients were infected by type A EBV. Such a high frequency of the larger size (69 bp) deletion has never been reported. Ascertaining the role of this deletion in BL pathogenesis will require further study.

Long-term outcome of a patient with intrascrotal extratesticular malignant schwannoma.

We have the opportunity to present a rare case of late local recurrence after treatment of intrascrotal extratesticular malignant schwannoma with rhabdomyoblastic features in an adult man. As our case is the first in the literature, we want to inform the reader about the long-term follow-up of our patient and suggest that these tumors may have a long survival and late recurrences may occur even after 5 years postoperatively.

Hodgkin's disease in 82 Turkish children diagnosed over a 10-year period: epidemiological, clinical, and histopathologic features and prognosis with prolonged chemotherapy.

In this study, 82 Turkish children with Hodgkin's disease (HD) between 1 and 14 years of age and diagnosed over a 10-year period were evaluated retrospectively. More than half of the patients (54%) presented with advanced stages of HD. Mixed cellularity (MC) was the most frequent (56.1%) histopathologic type, which was followed by nodular sclerosing (NS, 18.3%) in frequency. None of the patients received radiotherapy as initial treatment. In 67 children the COPP regimen alone and in 15 the ABVD regimen alternating with COPP were started, to be given as a total of 12 courses. In the patients who presented with stage I-II HD the overall survival (OAS) rate and 5-year event free survival (EFS) rate were 92.3% and 77.8%, respectively. In the patients with advanced disease (stage III-IV) OAS and 5-year EFS were estimated to be 89.5% and 67.4%, respectively. No serious toxicity of chemotherapy was detected during the follow-up. In this group, clinical, epidemiological and histopathologic features of the disease showed a special pattern close to the type I pattern of HD. Regarding the survival rules and occurrence of low toxicity in our patients, results of prolonged chemotherapy alone seem to be encouraging in most of the children with HD. However, the follow-up duration is not yet sufficient to declare a clear conclusion related to the late complications.

Early phase alterations in endothelium dependent vasorelaxation responses due to aneurysm clip application and related manipulations.

Mechanically induced vasoconstriction observed throughout surgery and in the immediate postoperative period was investigated to assess the effects of various microsurgical manipulations. Factors such as the type of aneurysm clip, duration of temporary clipping and peri-adventitial tissue stripping were the variables in this study. Microsurgical clips were applied on guinea pig "cervical carotid arteries" in which peri-adventitia had been removed microsurgically. Arterial rings were removed immediately after surgery. Endothelium dependent relaxations were measured and morphological investigations were performed using light microscopy. It was observed that as the clip application period increased, relaxation responses decreased. Peri-adventitial tissue stripping caused a marked decrease in the relaxation responses in all types of the clips. Microvascular clips, in spite of their lower closing forces, had the greatest deleterious effect on relaxation responses of the vessel, in both normal and peri-adventitial tissue stripped. When the peri-adventitial tissue of the vessel had been stripped, convolutions of the lamina elastica interna were found to be lost in parallel with the decreased tonus of the artery. In the vessels subjected to clipping endothelial denudation and cracking took place. As a conclusion it can be stated that both peri-adventitial tissue stripping and microvascular clip application have deleterious effects in the early postoperative period. While choosing clips from minimal occlusion force tables, care must be taken to choose clips with less width; and while performing microvascular anastomosis, temporary clips with a lesser width must be used in place of microvascular clips. Adventitial stripping must not be unnecessarily generous during microvascular anastomosis.

Pharmacological and pathophysiological effects of periadventitial stripping on immediate and subacute postoperative vasoconstriction in guinea pigs.

Mechanically induced vasospasm observed in the immediate post-operative period was investigated, and the effect of factors such as temporary clip applications and post-operative intervals were studied. Guinea pig "cervical internal carotid arteries" were used and temporary clips, chosen according to the diameter of the artery and systolic pressure, were applied for a standard period. The same procedure was applied on arteries in which periadventitial tissue had been removed using appropriate microsurgical techniques. On postoperative days 1, 5, and 10, arterial rings were removed while the animals were still alive and Endothelium Dependent Relaxations were measured using a bioassay system. Morphological investigations were also performed using light microscopy on the same arterial preparations. We observed no difference between perioperative and first day postoperative results. The relaxations were minimum. The most striking pathological changes were observed on postoperative day 5, and the relaxation responses began to rise on day 10 together with morphological improvement. It was also found that periadventitial tissue stripping could be used to prevent subacute post-operative vasoconstriction, since its effect was marked on postoperative day 5 and began to resolve on day 10.

Rete testis adenocarcinoma recurring in the inguinal lymph nodes. A case report.

Adenocarcinoma of the rete testis is a rare neoplasm with 41 reported cases in the literature till 1994. In most of the reported cases, the neoplasm presents as a scrotal mass with diffuse enlargement. The aetiology is unknown and the clinical course of the tumour is not very well defined. In six of the reported cases metastatic spread of the tumour to inguinal lymph nodes was demonstrated in the follow-up. We report herein a distinctive case of rete testis adenocarcinoma presenting as an isolated inguinal recurrence one year after radical orchiectomy.

Burkitt's lymphoma in 63 Turkish children diagnosed over a 10 year period.

Sixty-three Turkish children with Burkitt's lymphoma (BL) diagnosed over a 10-year period in a single institution were retrospectively analyzed. Burkitt's lymphoma included 41.7% of non-Hodgkin's lymphomas and 17.2% of all childhood malignant solid tumors diagnosed in our department in this duration. The patients studied with BL were aged between 3 and 14 years (mean 5.9 years), with a male of female ratio of 2:1. While the age distribution in our patients was similar to that in African BL (endemic), the predominance of abdominal involvement and the frequency of bone marrow infiltration and pleural effusion were reminiscent of American BL (sporadic). The incidence of jaw involvement (15.9%) in our group was higher than in American BL, however, and was not a high as in African BL. Most of the patients were of a lower socioeconomic status. Significant growth retardation was found in the children with BL compared with 40 age-matched children without malignancy, nor chronic or endocrinologic disorders, who were of a similar socioeconomic status. A serological study for Epstein-Barr virus (EBV) was performed in 18 children, and the IgG-type antibody to the viral capsid antigen of EBV was found to be positive in all of them. As a result, BL seems to include a considerable proportion of all childhood malignant solid tumors in Turkey. The epidemiological and clinical presentation and course indicate that BL appears in Turkish children in a form that is between the African and American types of the disease. Further molecular and chromosomal studies in Turkish children with BL are needed.

Tween 80 and endothelium: functional reduction due to tissue damage.

The effects of Tween 80, a surface active agent which is frequently used for dispersion of water-insoluble substances, on endothelial function in rabbit aorta, were investigated in a cascade superfusion bioassay system by using a deendothelized precontracted rat aorta ring as a bioassay tissue. Prior incubation of rabbit thoracic aorta segments with higher concentrations of Tween 80, caused total inhibition of acetylcholine-induced endothelium derived relaxing factor (EDRF) release, while moderate concentrations had no significant effect. Perfusion of the donor aortae segments with 10 (-1) - 10 (-3) ml/1 Tween 80 also inhibited the EDRF release from donor aorta dose-dependently. Histopathological examination of the vasculary wall and endothelial structures revealed a significant desquamation of vasculary endothelium with the highest concentration of Tween 80 used in this study. These data suggest that the mechanism underlying the reduction in the release of EDRF from donor aorta segments may be the destruction by Tween 80 of endothelial lining.

Intestinal endotoxins as co-factors of liver injury in obstructive jaundice.

The concept of endotoxin-mediated rather than direct liver injury in biliary obstruction was investigated using the experimental rat model of bile duct ligation (BDL) and small bowel bacterial overgrowth (SBBO). Small identical doses of intravenous endotoxin (bacterial LPS) caused a significantly more severe liver injury in rats with BDL, compared with sham-operated rats, suggesting the possible contribution of LPS in this type of liver damage. BDL was then combined with surgically created jejunal self-filling blind loops, which resulted in SBBO. Plasma LPS level increased significantly, and once again a more severe liver injury, determined by liver histology and serum gamma-glutamyl transpeptidase levels, was observed compared with the control group of rats with BDL+self-emptying blind loops. The data presented suggest that small amounts of exogenous LPS and/or the ordinarily innocous amounts of LPS constantly absorbed from the intestinal tract may be critical in the hepatic damage caused by obstruction of the biliary tract.

Retroperitoneal malignant teratoma. A case report.

Retroperitoneal teratomas are rare in adults. These tumours may be benign or malignant and are composed of multiple tissues foreign to the part in which they arise. We report a malignant teratoma of retroperitoneal space. In searching the literature, we have been able to find 39 cases reported since 1937. Of the forty cases reported (including this case), only ten (25%) were malignant.

Critical tricuspid regurgitation secondary to ruptured chordae tendineae mimicking a mass on the tricuspid valve in a newborn.

Tricuspid regurgitation (TR) due to chordal rupture is a rare condition in newborns. We present a newborn with critical TR. Cross-sectional echocardiography demonstrated a dense, mobile mass localized at the tricuspid valve and resembling an atrial thrombus or myxoma. At operation, ruptured chordae tendineae of the tricuspid valve were found, forming a tangled mass. Histopathologic examination revealed collagen degeneration and calcification in the ruptured chordae, producing the hyperechoic image. It should be emphasized that ruptured chordae of the tricuspid valve might mimic a tricuspid valve myxoma or a thrombus on cross-sectional echocardiography.