Determination of apoptosis, proliferation status and O6-methylguanine DNA methyltransferase methylation profiles in different immunophenotypic profiles of diffuse large B-cell lymphoma.

OBJECTIVE: Our aim was to investigate the expression of apoptosis-associated proteins (bcl-2, bcl-xl, bax, bak, bid), apoptotic index (AI) and proliferation index (PI) in germinal center B-cell-like immunophenotypic profile (GCB) and non-GCB of diffuse large B-cell lymphoma (DLBCL). METHODS: The methylation status of the promoter region of O6-methylguanine-DNA yerine O6-methylguanine-DNA methyltransferase (MGMT) gene and its relation with immunophenotypic differentiation of DLBCLs were also investigated. 101 cases were classified as GCB (29 cases) or non-GCB (72 cases). Apoptosis-associated proteins and PI were determined by IHC, and TUNEL method was used to determine AI. MGMT methylation analysis was performed by real-time PCR. RESULTS: The PI was significantly higher in GCB compared with non-GCB (p=0.011). Percentage of cells stained with bcl-6 was positively correlated with the percentage of cells expressing bcl-2 (p=0.023), AI (p=0.006) and PI (p<0.001), while a significant negative correlation was observed with the percentage of cells expressing bax (p=0.027). The percentage of cells stained with MUM1 showed a significantly positive correlation with the percentage of cells expressing bcl-xl (p=0.003), bid (p=0.002), AI (p<0.001), and PI (p=0.001). MGMT methylation analysis was performed in 95 samples, and methylated profile was found in 31 cases (32.6%). GCB was found in 6 cases (22.2%) and non-GCB was determined in 25 cases (36.8%) out of 31 with MGMT methylated samples. There was no significant association between MGMT methylation status and immunophenotypic profiles (p=0.173). CONCLUSION: These results suggest that bcl-6 protein expression may be responsible for the high PI in GCB. Additionally, we found that apoptosis-associated proteins were not significantly associated with immunophenotypic profiles.

Chorangiosis: the potential role of smoking and air pollution.

Chorangiosis is considered to be strongly associated with various fetal, maternal, and placental disorders, including pre-eclampsia, diabetes, hypertension, and major congenital anomalies, and has been found to correlate with increased fetal morbidity and mortality. In this study, we investigated the pathologic effects of maternal smoking and air pollution on the pathogenesis of chorangiosis. We investigated 92 placentas macroscopically and microscopically over a 3-month period (March 2006-May 2006) at Denizli State Hospital to identify the frequency of chorangiosis and the potential role of maternal smoking and air pollution. Placental changes were examined by light microscopy after hematoxylin and eosin (H&E) staining and immunohistochemical evaluation of CD 34 and CD 68; muscle-specific actin was used to confirm the diagnosis. Among the 92 mothers included in the study, 33 were smokers (group I), 31 were thought to have been exposed to air pollution (group II), and 28 were living in rural areas free of air pollution and maternal smoking (group III). Chorangiosis was found in 14% (13/92) of all placentas: 7 (53.8%) cases were assigned to group I, 5 (38.5%) to group II, and 1 (7.7%) to group III. Vascular changes were found mainly in the smoking and air pollution groups. There appeared to be no correlation of these vascular changes with placental weight, parity, gestational age, major congenital anomalies, and maternal factors, including diabetes and pre-eclampsia. We presume that smoking and air pollution may contribute to the development of chorangiosis. We suggest that chorangiosis may be an adaptive response to maternal hypoxia, and studies addressing the role of smoking and air pollution in chorangiosis may provide new insights into the pathogenesis of this condition.

Secondary involvement of the breast in T-cell non-Hodgkin lymphoma, an unusual example mimicking inflammatory breast carcinoma.

Non-Hodgkin lymphoma of the breast is a rare malignancy and present with almost equal frequency either as a primary or a secondary disease. Survival is poor in most cases of secondary breast lymphoma because of their advanced stage. We report a 35-year-old woman presenting with dyspnea as well as swelling, tenderness, and ruddiness in the left breast with non-cyclic pain for several months and maculopapular skin eruption in the same breast. Physical examination revealed fixed lymphadenopathies in both axillary regions. Radiologic evaluations (bilateral mammaograpy and ultrasonography) showed skin thickening in the left breast, asymmetrical densities in both breasts, and confirmed lymphadenopathies in the axillary regions. Excisional biopsies were performed to the left axillary lymph nodes and the breast skin eruptions. The histologic and immunohistochemical features were diagnosed as an ALK (-) anaplastic large cell lymphoma. A Computed Tomography examination was performed for staging the lymphoma and then chemotherapy was started. Thirty months after the diagnosis, the patient is still alive with disease. Because of the presence of systemic symptoms such as skin involvement and generalized lymphadenopathies (mediastinal, axillary or cervical), T cell lymphoma cases with breast involvement could mimic the clinical presentation of inflammatory breast carcinoma. Pathologic examination is needed for the correct diagnosis.

A prenatally detected case of congenital hepatoblastoma.

Hepatoblastoma is a rare tumor of childhood and its incidence in the first year of life is about one in a million. Forty-two congenital hepatoblastoma cases were reported so far. Among 42 congenital hepatoblastoma patients, only seven cases have been detected in the prenatal period. Here we report a rare case diagnosed before birth and confirmed by postmortem autopsy.

The effects of air pollution and smoking on placental cadmium, zinc concentration and metallothionein expression.

This study is designed to determine the placental zinc (Zn) and cadmium (Cd) levels in mothers who were smokers, mothers who were thought to be exposed to air pollution, and mothers who were non-smokers and to investigate the relationship between the expression of placental metallothionein (MT) binding these metals and blood progesterone level. Placental Zn and Cd levels were measured by atomic absorption spectrometry. Presence of placental MT was determined immunohistochemically. Placental changes were examined by light microscope after H&E and PAS staining. Immunohistochemical MT staining of syncytiotrophoblastic and villous interstitial cells were scored as positive or negative. Among the 92 mothers included in the study, 33 were smokers (Group I), 29 had been exposed to air pollution (Group II) and 30 were non-smoker rural residents who had never been exposed to air pollution (Group III). Mean off-spring birth weight of 3198.62+/-380.01 g and mean placenta weight of 561.38+/-111.55 g of Group II were lower when compared with those of other two groups. In Group I, mean placental Cd and Zn were 0.063+/-0.022 microg/g and 39.84+/-15.5 microg/g, respectively, being higher than in other groups. In Group II, mean placental Cd and Zn levels were higher than those of Group III. Blood progesterone levels of subjects in Group I (121 ng/ml) were the lowest of all groups. While the mean count of villi was the highest in Group III; the highest mean count of syncytial knots was in Group II. Thickening of vasculo-syncytial membrane was most prominent in Group I. Similarly, MT staining was positive and very dense in 72.7% (24/33) of cases in Group I (p

Primary neuroendocrine carcinoma of the breast: a case report.

Primary neuroendocrine carcinoma of the breast is an extremely rare tumor. We present our experience of primary neuroendocrine carcinoma of the breast in a 76-year-old woman. Surgical biopsies from breast and axillary lymphadenopathy showed a neuroendocrine carcinoma. Immunohistochemical staining of tumor cells with GCDFP15, NSE and chromogranin were positive. Computed tomography scans of the chest and abdomen showed no lesion for metastasis or another primary origin. Adjuvant hormone therapy was given, since the tumor was immunohistochemically receptor positive.

Gallium-67 citrate scintigraphy and marginal zone lymphoma of the mucosa-associated lymphoid tissue. Ocular MALT.

We describe marginal zone lymphoma of the mucosa-associated lymphoid tissue (MALT) and especially MALT lymphoma occurring in the conjunctiva. Tumors of the conjunctiva and cornea are grouped into two major categories of congenital and acquired lesions. Lymphoid tumors of the conjunctiva are acquired tumors and can occur as an isolated lesion or can be a manifestation of systemic lymphoma. Primary lymphomas of the conjunctiva are extremely rare usually originate from extranodal marginal zone B-cell non-Hodgkin's lymphomas of MALT and occur among older adults with a mean age of 61 years. In the last decade it has been reported that MALT lymphomas may develop in various extraintestinal locations, sometimes even without the presence of a mucosa. Half of MALT lymphomas occur in the gastrointestinal tract. MALT lymphomas of the eye are rare and originate from the conjunctiva and the lacrimal glands. Studies evaluating the clinical impact of 67Ga-C scintigraphy for MALT-type lymphomas imaging are rare, based on small numbers, heterogenous groups of patients. Clinical examination, excisional biopsy, histopathology and immunohistochemical studies, computerized tomography and magnetic resonance imaging are also used for the diagnosis of cunjunctival MALT disease. A case of ours gives reason for further discussion. Treatment and follow-up of MALT lymphoma is described.

Callus formation of the tibial hallux sesamoid mimicking a bone tumor.

Sesamoid tumors of the hallux are rare, and their incidence and differential diagnosis have not been well described. We present a case with a bizarre callus formation of the medial sesamoid of the hallux that mimicked a bone tumor. After excision of the mass and related sesamoid, the patient remained asymptomatic during 3 years of follow-up.

Reproducibility of the 1998 World Health Organization/International Society of Urologic Pathology classification of papillary urothelial neoplasms of the urinary bladder.

OBJECTIVES: This study assessed the diagnostic agreement and intra- and inter-observer reproducibility of the World Health Organization/International Society of Urologic Pathology Consensus Classification of Urothelial Neoplasms (1998 WHO/ISUP classification) and the 1973 WHO classification. METHODS: A teaching set with 5 slides of each papillary neoplasm of low malignant potential, low-grade papillary carcinoma, high-grade papillary carcinoma, and a guideline, as well as a study set of 30 slides containing ten cases of each category, were sent to participants. Six pathologists expert in urological pathology reviewed the 30 slides of non-invasive papillary urothelial tumors in the study set. Diagnostic accuracy and reproducibility were evaluated using intra- and inter-rater techniques (kappa statistic). RESULTS: A moderate to substantial intra- and inter-observer reproducibility was achieved for both the 1998 WHO/ISUP and 1973 WHO classification. The results of the two classification systems were not different statistically ( P>0.05). Reproducibility was lower in low-grade tumors for both classifications. CONCLUSIONS: The new proposed classification system for non-invasive urothelial neoplasms does not increase the reproducibility. There is still a need for uniformity in grading in order to compare the different studies and therapies and to provide more accurate information for management.

The effects of postmenopausal Vitamin D treatment on vaginal atrophy.

OBJECTIVES: To evaluate the efficacy of Vitamin D for relieving vaginal atrophy. METHODS: In our cross-sectional study, 60 eligible women were consecutively identified among patients who were followed in physical medicine and rehabilitation's outpatient clinic, during the period March June 2001. The sample consisted of 30 postmenopausal women on 1,25-dihydroxy Vitamin D (calcitriol) treatment, 30 postmenopausal women taking neither hormone replacement nor osteoporosis treatment. Vaginal atrophy was determined by symptoms, physical examination and maturation index (MI). RESULTS: The mean physical findings score in Vitamin D treatment (VDT) group was significantly lower than the mean physical findings score in the group without treatment. Symptom scores were lower in both groups and there was not significantly difference between two groups. As maturation indices: in VDT group, superficial cells proportion was significantly higher and basal, parabasal cells proportion was lower than in the group without treatment. CONCLUSION: The results of current study seem to indicate that vaginal tissue may be a new target organ for therapeutically applied Vitamin D analogues.

Effects of intraoperative sponge mitomycin C and 5-fluorouracil on scar formation following strabismus surgery in rabbits.

PURPOSE: To investigate the influence of 5-fluorouracil (5-FU) and mitomycin C (MMC) on the postoperative adhesions following strabismus surgery in rabbits. METHODS: Twenty-one New Zealand white rabbits were used in this prospective, masked, controlled trial. Both eyes of 20 animals underwent 3-mm recession of the superior rectus muscle (SRM). In group I (io animals), one eye of each animal received topical application of MMC (0.2 mg/ml) for 5 minutes and the other eye (control eye) was treated with balanced salt solution (BSS) using an intraoperative sponge. In group II (10 animals), a randomly chosen eye of each animal was treated with 5-FU soaked sponges (50 mg/ml) for 5 minutes and the fellow eye (control eye) with BSS. Two eyes of a rabbit were included as unoperated controls. Four weeks after the surgery, conjunctival vascularity and postoperative adhesions between the SRM Tenon's capsule (TC) and SRM sclera (scl) were assessed. Additionally, eyes were enucleated and evaluated histopathologically for evidence of scarring, granuloma formation, and muscle tissue changes under a light microscope. RESULTS: MMC-treated eyes had a higher rate of avascular conjunctiva compared to both controls and 5-FU-treated eyes. Mean adhesion scores, particularly between the SRM-scl, were lower in eyes treated with antiproliferative agents compared to controls. The difference was statistically significant in MMC-treated eyes for the adhesions between SRM-scl (p = 0.03). Histopathological examination revealed less scarring and granuloma formation in MMC- and 5-FU-treated eyes compared to their control eyes. CONCLUSIONS: MMC, and to a lesser extent 5-FU, are shown to be effective in reducing postoperative scarring following strabismus surgery in rabbits. It seems reasonable to suggest that antimetabolites should be used for cases having an increased risk of postoperative adhesions.

The value of diffusion-weighted MRI for prostate cancer detection and localization.

PURPOSE: The aim of this study was to evaluate the role of prebiopsy T2-weighted imaging (T2WI), quantitative diffusion-weighted imaging (DWI), and the combination of these magnetic resonance (MR) techniques (T2WI+DWI) in the detection and localization of peripheral zone prostate cancer. MATERIALS AND METHODS: T2WI and DWI (b value = 800 s/mm2) with an endorectal coil at 1.5 T were performed prospectively in 43 consecutive male patients with suspicion of prostate cancer before a systematic 12-core prostate biopsy. The peripheral zone of the prostate was evaluated after dividing it into sextants (n = 258). Minimum apparent diffusion coefficient (ADC) values of each sextant in the peripheral zone were measured. Two core biopsies were obtained from each sextant under transrectal ultrasound guidance. RESULTS: The mean minimum ADC values of the malignant sextants were significantly lower than that of noncancerous tissue, with a significant negative correlation between the ADC value and the Gleason score. The sensitivity, specificity, and area under the receiver operating characteristic curve for the detection and localization of prostate cancer within the peripheral zone were 71%, 77%, and 0.741 for T2WI alone; 84%, 82%, and 0.830 for quantitative DWI alone; and 81%, 92%, and 0.863 for T2WI+DWI, respectively. The use of quantitative DWI, alone or combined with T2WI, improved diagnostic performance in prostate cancer detection and localization compared with T2WI alone (P = 0.020 and P = 0.001, respectively). CONCLUSION: Prebiopsy DWI is valuable in detecting, localizing, and grading prostate cancer within the peripheral zone, and the lowest ADC values can indicate the regions to be biopsied.

IMP3 expression in urothelial carcinomas of the urinary bladder.

OBJECTIVE: Superficial tumors including Ta, Tis, and T1 make up 75% of urothelial carcinomas of the bladder. While the behavior of these superficial urothelial cancers is relatively benign, invasive tumors have a significant mortality rate. However, Ta and T1 tumors might display different biological behavior. There is therefore a great need for biomarkers that can accurately distinguish the behavior of urothelial carcinomas in addition to tumor grade and stage. Our aim was to determine the immunohistochemical expression profile of insulin like growth factor II mRNA binding Protein 3 (IMP3) and its correlation with tumor stage and grade in benign urothelium and bladder urothelial carcinomas. MATERIAL AND METHOD: The expression of IMP3 in 91 patients with benign urothelium (20 cases), low grade invasive (17 cases) / noninvasive (20 cases) urothelial carcinoma and high grade invasive (20 cases) / non-invasive (14 cases) urothelial carcinoma was evaluated by immunohistochemistry in this study. RESULTS: IMP3 was not expressed in benign urothelium, low-grade non-invasive urothelial carcinoma and high grade non-invasive urothelial carcinoma. Expression of IMP3 was found in 11.76% of low-grade invasive urothelial carcinomas and 55% of high grade invasive urothelial carcinomas. Statistical analysis including chi2 tests showed that IMP3 expression of invasive urothelial carcinomas was statistically significant (p < 0.000). CONCLUSION: The detection of IMP3 only in invasive carcinomas although some of them were low grade showed that the expression of IMP3 may be related to aggressive behavior of urothelial carcinomas.

Histologic grading of urothelial papillary neoplasms: impact of combined grading (two-numbered grading system) on reproducibility.

The clinical management of tumor patients is often strongly influenced by the tumor grade. The presence of heterogeneity is well recognized in a variety of tumors. Overall grade is based on highest grade area identified within a tumor. Urothelial carcinoma often contains different histological grades within the same tumor. This study investigates the impact of a combined grading system on the reproducibility of papillary urothelial neoplasms. A set prepared for an earlier study consisting of ten cases of each category (papillary urothelial neoplasm of low malignant potential (PUNLMP), LGPUC, and HGPUC) was used. Agreement between pairs of pathologists was evaluated using κ statistics for the combined scoring system. Interobserver agreement was fair to substantial as reflected by κ values ranging from 0.24 to 0.74 (mean κ = 0.43). The combined scores of 2 and 3 which included PUNLMP showed the lowest degree of agreement and when this category was excluded from the analysis, interobserver agreement increased significantly (mean κ = 0.65; ranging from 0.43 to 0.92) in terms of combined scores of 4, 5, and 6. PUNLMP has been shown to be the least reproducible component of a combined scoring system even among experienced observers. Exclusion of PUNLMP from grading scheme seems to improve interobserver variability.

Ectopic pancreas of the gastric antrum contiguous to a gastrointestinal stromal tumor manifesting as upper gastrointestinal bleeding: report of a case.

A 54-year-old woman was referred to us for investigation of recurrent episodes of melena. Gastroduodenal endoscopic examination revealed a hemorrhagic, polypoid tumor, about 3 cm in diameter, in the posterior wall of the gastric antrum, near the greater curvature. The lesion had a smooth surface with ulceration, and was fixed to the sublying planes. The source of the bleeding was the mucosa overlying the tumor. We performed a distal subtotal gastrectomy with Roux-en-Y anastomosis. Histopathological examination of the resected specimen revealed an ectopic pancreas and a gastrointestinal stromal tumor contiguous to the ectopic pancreatic tissue in the gastric antrum. The patient was discharged after an uneventful postoperative course and has not experienced any recurrence of symptoms since.

Immunohistochemical expression of beta-catenin, E-cadherin, cyclin D1 and c-myc in benign trichogenic tumors.

BACKGROUND: beta-catenin gene mutations have been reported in vast majority of pilomatrixomas (PMXs). beta-catenin, a component of the adhesion molecules of the cytoskeleton, is degraded at the cytoplasm. Excess cytoplasmic beta-catenin enters into the nucleus and activates the transcription of several genes encoding c-myc, cyclin D1 and others. Sublocation of beta-catenin has been demonstrated by immunohistochemistry. The aim of this study was to determine the role of beta-catenin-related proteins in various benign trichogenic tumors. METHODS: We investigated the expression of beta-catenin, E-cadherin, c-myc and cyclin D1 immunohistochemically, and the expression of these molecules were compared between two groups consisting of 12 PMXs and 12 other benign trichogenic tumors (OBTTs). RESULTS: In PMX group, nuclear and/or cytoplasmic expression of beta-catenin was associated with a loss of membranous expression of E-cadherin (p = 0.002). In OBTT group, a membranous expression of E-cadherin and beta-catenin was observed, and there was a stronger nuclear immunoreactivity of cyclin D1 compared with PMX group (p = 0.006). CONCLUSIONS: In PMX, nuclear and/or cytoplasmic beta-catenin expression of tumoral cells is not related with beta-catenin-related gene expressions (c-myc or cyclin D1). The molecular behaviour of OBTTs is clearly different from that of PMXs in terms of to E-cadherin and beta-catenin expression.

PCNA expression in chronic gastritis due to Helicobacter pylori*.

BACKGROUND/AIMS: It has been reported that cases of Helicobacter pylori (H. pylori) gastritis, those with epithelial hyperproliferation, have potential for malignant transformation. This study was planned to determine the effects of H. pylori on gastritis and the gastric epithelial cell proliferation. METHODS: In this study, we re-evaluated biopsy samples obtained from 331 cases of chronic gastritis according to Sydney criteria, retrospectively. We examined the gastric epithelial cell proliferation with proliferating cell nuclear antigen in the proliferating zone, in the whole mucosa of intestinal metaplasia and in areas of regenerative atypia, separately. RESULTS: The relationship between H. pylori colonization density and chronic active gastritis was statistically significant. We did not see any relationship between the presence and density of H. pylori in gastric mucosa via proliferating cell nuclear antigen indices. In the presence of lymphoid follicles, we noted a significant expression of proliferating cell nuclear antigen in the areas of whole gastric mucosa and regenerative atypia. CONCLUSIONS: In the presence of lymphoid follicles, proliferating cell nuclear antigen expression was observed in the areas of whole gastric mucosa and regenerative atypia, but we did not see any relationship between the presence and density of H. pylori in gastric mucosa via proliferating cell nuclear antigen indices. This observation suggests the role of chronic inflammatory cells in gastric epithelial cell proliferation rather than the bacterium itself.