Differential cyclin-E1 expression in CIC-rearranged sarcoma.

CIC-rearranged sarcoma (CRS) is a group of high-grade undifferentiated small round cell sarcomas examined as a separate entity in the current WHO classification; since it shows more aggressive clinical behavior and distinct morphological and molecular features compared to Ewing sarcoma (ES). As CCNE1 expression is associated with tumor growth in CIC::DUX4 sarcomas, we aimed to demonstrate the value of cyclin E1 expression in CRS. Cyclin E1 immunohistochemistry and break-apart FISH for EWSR1 and CIC gene rearrangements were performed on 3-mm tissue microarrays composed of 40 small round cell tumors. Five cases were classified as CRS, whereas 22 were ES and 13 were unclassified (EWSR1-/CIC-). Among all three diagnostic groups, we found cyclin E1 expression level to be higher in CRS (80 %) and unclassified groups (61.5 %) compared to ES (4.5 %, p < 0.001). In addition, high cyclin E1 expression levels were associated with higher mean age at diagnosis, presence of atypical histology and myxoid stroma, low CD99 expression, and presence of metastasis at diagnosis. The sensitivity and specificity of high cyclin E1 expression in detecting non-ES cases were 95.5 % and 66.7 %, respectively. However, the correlation between cyclin E1 expression level and survival was not statistically significant. This is the first study that shows cyclin E1 immunohistochemical expression in EWSR1-negative undifferentiated small cell sarcomas, particularly CRS.

Effect of LigaSure™, Monopolar Cautery, and Bipolar Cautery on Surgical Margins in Breast-Conserving Surgery.

BACKGROUND: We compared the differences in thermal damage at the surgical margin between monopolar cautery, bipolar cautery, and LigaSure™ in breast cancer lumpectomy specimens and assessed the effect of these techniques on the evaluation of the surgical margins. METHODS: 30 patients scheduled for breast-conserving surgery for breast cancer were included in this study. During lumpectomy, each of the superior, inferior, lateral, and medial borders of the tumour was excised using one of the following: a scalpel, monopolar cautery, bipolar cautery, and LigaSure technology. The surgical margins of frozen and paraffin-embedded tissue sections of the lumpectomy specimen were evaluated. Thermal damage was defined as the maximum depth of thermal damage (in mm) from the surgical margin, and the level was categorized as none, low (≤1 mm), or high (>1 mm). RESULTS: There was no statistically significant difference between monopolar cautery, bipolar cautery, and LigaSure in terms of thermal damage. There was no thermal damage at the surgical margin in tissues dissected by scalpel. CONCLUSION: Thermal damage due to the excision method may cause false-negative and false-positive results in the surgical margin evaluation of lumpectomy specimens. More research is needed on the effects of different energy modalities on surgical margin evaluation in breast-conserving surgery.

Tamoxifen-Related Thrombosis: An Experimental Study in Rat Venous Microvascular Anastomosis Model.

Tamoxifen is an estrogen receptor modulator and has been shown to increase risk for microvascular flap complications. This study aimed to investigate the clinical and histopathological effects of tamoxifen use in venous microvascular anastomosis model in rats. The role of vitamin E combination therapy and discontinuing tamoxifen therapy preoperatively were also evaluated.Forty rats were equally divided into 4 groups as follows: group 1 was given saline by oral gavage, group 2 was given tamoxifen citrate, group 3 was given tamoxifen citrate and vitamin E, and in group 4, tamoxifen citrate was given everyday except between days 12 and 16. In each group, femoral veins were dissected in each side and end-to-end anastomosis was performed in one side. Clinical and histopathological evaluations were performed. The ratio of total endothelial area to total vein area in a cross-sectional view of the vein was evaluated and compared.All veins with anastomosis in postoperative 15 minutes were found to be patent. In postoperative 1 week in groups 1 to 4, visible thrombus were present in 1, 3, 2, and 3 samples, respectively. Vitamin E group showed similar histopathological findings with control group. The ratio of endothelial layer to total vein cross-sectional area was increased in groups 2 and 4 in all samples. The increase was statistically significant between groups 2NA and 3NA (P = 0.023) and 2A and 1A (P = 0.006).Chronic tamoxifen consumption in the presence of anastomosis have led to prominent endothelial proliferation in rat femoral veins. Vitamin E combination therapy reversed this endothelial proliferation and should be focused in future studies.

Lichen striatus and pityriasis lichenoides chronica in an 11-year-old girl: An etiologic relationship?

Lichen striatusis a rare linear papulardermatosis that primarily occurs in children. The lesions have a linear distribution following Blaschko's lines. Pityriasis lichenoides is an uncommon benign skin disorder with two major variants: acute and chronic.Herein, we report the case of an 11-year-old girl with concurrent pityriasisli chenoides chronica and lichen striatus, a previously unreported association. Although it remains unclear whether there is an aetiological relationship between the two diseases or whether their coexistence was coincidental in our patient, but some common mechanisms may be involved in the two diseases.

New hemostatic agent: the effect of Ankaferd Blood Stopper on healing wounds in experimental skin incision model.

AIM: To conduct a histopathological evaluation of the effects of Ankaferd Blood Stopper (ABS) on healing wounds in a rabbit skin incision model. MATERIALS AND METHODS: Incisions were performed on the backs of rabbits. The first incision was allowed to undergo normal secondary healing. ABS (1 mL) was applied to the second incision, which was subsequently allowed to undergo secondary healing. The third incision was sutured. ABS (1 mL) was applied to the fourth incision, which was subsequently sutured. During the wound healing period, the histopathologic signs of ulceration, inflammation, the proliferative phase, and the extent of early remodeling were comparatively evaluated by performing biopsies on days 5, 10, and 30. RESULTS: For all of the ABS-treated wounds, the appearance of the cavities during the early stage and the disappearance of the cavities during the late stage were observed. In addition, on days 5-10, the inflammatory granulation tissue in the ABS-treated wounds was less than in the normal wounds. By day 30, all of the wounds had achieved the same symptomatic state. CONCLUSION: As ABS does not exert any negative effects on wound healing, this agent is a secure and effective method for achieving hemostasis.

Effect of anti-vascular endothelial growth factor antibody during early fetal development in rats.

OBJECTIVE: To examine the effect of anti-vascular endothelial growth factor (VEGF) antibody Bevacizumab during early fetal development in rats. METHODS: Presumed-pregnant rats received single intraperitoneal injection of Bevacizumab (0-20 mg/kg) on gestational day (GD) 3, 7, and 14 (n = 2 rats/group). After Study 1 (dose range finding study), Study 2 performed with intraperitoneal 20 mg/kg bevacizumab or saline on GD 7 (n = 6 rats/group including the Study 1). Blood samples were collected 3 and 7 d after the injection. Uterus and ovarian tissues were obtained 7 d after the injection. Number of gestational sacs (GS), size of GS and fetus, serum rat ß chorionic gonadotropin (ß-CG), and platelet endothelial cell adhesion molecule (PECAM) for immunohistochemical assessment of angiogenesis were evaluated. RESULTS: Number of GS, size of GS, and fetus were lower in the study group than the control group. Serum rat ß-CG levels were significantly increased in the control group and significantly decreased in the study group. Staining densities for PECAM in vascular structures in both corpus luteum and placenta were lower in the study group than the control group. CONCLUSION: Anti-VEGF antibody has an inhibitory effect on pregnancy development and caused litter death.

Completely infarcted smooth muscle tumor of the placental membrane.

Non-trophoblastic tumor of the placenta is rare, and so is placental smooth muscle tumor. We report leiomyoma of the placental membrane, which was discovered on cesarean section. Histologically, the tumor was a benign leiomyoma with complete necrosis, and this finding was confirmed immunohistochemically. Only six cases of smooth muscle tumors of the placenta have been reported to date. This is the third report of leiomyoma involving the placental membrane.

Invasive lobular carcinoma with extracellular mucin as a distinct variant of lobular carcinoma: a case report.

The differences between invasive lobular and ductal carcinomas affect the diagnostic and therapeutic management for patients with breast cancer. In most cases, this can be accomplished because of distinct histomorphologic features. However, occasionally, this task may become quite difficult, in particular when dealing with the variants of infiltrating lobular carcinoma. Lobular carcinoma has been considered a variant of mucin-secreting carcinoma with only intracytoplasmic mucin. The presence of extracellular mucin is a feature of ductal carcinoma. Herein is presented a case of lobular carcinoma with extracellular and intracellular mucin in a 43-year-old female patient, and confirmed by immunohistochemistry. Up to the present, infiltrating lobular carcinoma displaying extracellular mucin has not been described in the literature except two case. Virtual slides: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1839906067716744.

The value of CDX2 and cytokeratins 7 and 20 expression in differentiating colorectal adenocarcinomas from extraintestinal gastrointestinal adenocarcinomas: cytokeratin 7-/20+ phenotype is more specific than CDX2 antibody.

BACKGROUND/OBJECTIVE: Metastatic adenocarcinoma from an unknown primary site is a common clinical problem. Determining the cytokeratin (CK) 7/CK20 pattern of tumors is one of the most helpful procedures for this purpose since the CK7-/CK20+ pattern is typical of colorectal adenocarcinomas. CDX2, a critical nuclear transcription factor for intestinal development, is expressed in intestinal epithelium and adenocarcinomas. In the present study, we compared the sensitivity and specificity of CDX2 expression and the CK7-/CK20+ phenotype in differentiating colorectal adenocarcinomas from pancreatic and gastric adenocarcinomas. METHODS: CK7/CK20 staining pattern and CDX2 expression were evaluated in 118 cases of colorectal, 59 cases of gastric, and 32 cases of pancreatic adenocarcinomas. The sensitivity, specificity, and positive and negative predictive values of the CK7-/CK20+ phenotype and of CDX2 expression were analyzed. RESULTS: The CK7-/CK20+ immunophenotype was expressed by 75 of 118 (64%) colorectal and 3 of 59 (5%) gastric tumors and was not observed in any pancreatic adenocarcinomas. The CK7+/CK20+ immunophenotype was expressed in 24/118 (20%) of colon, 28/59 (48%) of gastric and 7/32 (22%) of pancreatic adenocarcinomas. The CK7+/CK20- expression pattern was observed in only 2% (2 of 118) of colorectal carcinomas. CDX2 was expressed in 114 of 118 (97%) colorectal, 36 of 59 (61%) gastric, and 5 of 32(16%) pancreatic adenocarcinomas. There was no significant association between CDX2 expression and tumor differentiation in colorectal carcinomas. In gastric carcinomas, CDX2 expression was more common in intestinal type tumors than in diffuse type carcinomas. The CK7-/CK20+ phenotype showed a specificity of 96.7% in predicting colorectal adenocarcinomas, which was superior to that of CDX2 expression. CDX2 expression at both cut-off levels (> 5% and > 50%) had a higher sensitivity (96.6% and 78%) than the CK phenotype. CONCLUSIONS: Both the CK7-/CK20+ phenotype and expression of the antibody CDX2 are highly specific and sensitive markers of colorectal origin. CDX2 expression should be a useful adjunct for the diagnosis of intestinal adenocarcinomas, particularly when better established markers such as CK7 and CK20 yield equivocal results. The CK7-/CK20+ phenotype is superior in its specificity and positive predictive value and might be preferred. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/4851011866354821.

To determine of the prevalence of Bacterial Vaginosis, Candida sp, mixed infections (Bacterial Vaginosis + Candida sp), Trichomonas Vaginalis, Actinomyces sp in Turkish women from Ankara, Turkey.

OBJECTIVE: To determine of the prevalence of Bacterial Vaginosis, Candida sp, mixed infections (Bacterial Vaginosis + Candida sp), Trichomonas Vaginalis, Actinomyces sp in Ankara, Turkey and analyze whether there is seasonal variation in these infectious agents. METHODS: A retrospective study on the results of 23298 cervical cytology examinations of patients which were performed in Fatih University Faculty of Medicine, Pathology Laboratory in Ankara, Turkey from January 2007 to July 2011. Patients were included in the study if a Pap smear was performed for any reason. RESULTS: The prevalence of Bacterial Vaginosis, Candida sp, mixed infections (Bacterial Vaginosis + Candida sp), Trichomonas Vaginalis, Actinomyces sp was 7.76%, 2.81%, 0.32%, 0.13%, and 0.27%, respectively A seasonal variation was not observed in the prevalence of any of the infectious agents (p>0.05). CONCLUSION: We conclude that cervical cytology is well suited for diagnosis of cervical infections. Bacterial vaginosis appears to be the predominant cause of vaginitis.

Helicobacter pylori and histopathological findings in patients with dyspepsia.

BACKGROUND/AIMS: Although Helicobacter pylori infection has been reported to be more frequent in patients with dyspepsia, whether it should be treated in dyspepsia remains controversial. This study was carried out to compare the histopathological changes in Helicobacter pylori-positive and -negative dyspepsia patients. METHODS: A total of 461 patients with Helicobacter pylori-positive dyspepsia seen in our institution were enrolled in the study. The control group was formed from 100 Helicobacter pylori-negative dyspepsia patients. Subjects underwent an upper gastrointestinal endoscopy, and biopsy specimens were taken from the gastric antrum and corpus. All of the cases were evaluated according to the Sydney classification, and the relation of Helicobacter pylori with chronic inflammation, atrophy, intestinal metaplasia, and activity was investigated by two pathologists. RESULTS: Activity, inflammation and intestinal metaplasia were found in 10 (10%), 70 (70%) and 10 (10%) of Helicobacter pylori (-) patients, respectively, and the numbers increased with increasing Helicobacter pylori intensity when compared with Helicobacter pylori (+) patients (p<0.01, p<0.01 and p<0.05, respectively). Atrophy was found in 27 (5.5%) of all cases (in 10 Helicobacter pylori (-) patients and in 17 Helicobacter pylori (+) patients), but no significant relation was found with increasing Helicobacter pylori intensity (p>0.05). There was no significant difference between corpus alone or antrum alone Helicobacter pylori (+) and both corpus/antrum (+) patients in regards to the presence of activity, inflammation, intestinal metaplasia, and atrophy (p>0.05). CONCLUSIONS: Determination of the degree of morphological changes accompanying Helicobacter pylori infection in dyspepsia is important in the follow-up and treatment of patients. As activity, inflammation and intestinal metaplasia increase with increasing Helicobacter pylori intensity in dyspepsia patients, Helicobacter pylori eradication treatment can be recommended in these patients.

Predictive value of pathological and immunohistochemical parameters for axillary lymph node metastasis in breast carcinoma.

BACKGROUND/OBJECTIVE: While several prognostic factors have been identified in breast carcinoma, the clinical outcome remains hard to predict for individual patients. Better predictive markers are needed to help guide difficult treatment decisions. Axillary lymph node metastasis (ALNM) is one of the most important prognostic determinants in breast carcinoma; however, the reasons why tumors vary in their capability to result in axillary metastasis remain unclear. Identifying breast carcinoma patients at risk for ALNM would improve treatment planning. This study aimed to identify the factors associated with ALNM in breast carcinoma, with particular emphasis on basal-like phenotype. METHODS: Breast carcinoma patients (n = 210) who underwent breast conserving surgery and axillary lymph node dissection (ALND) (level I and II) or modified radical mastectomy were included in this study. Pathological and immunohistochemical data including individual receptor/gene status was collected for analysis. The basal phenotype status was ascertained using the basal cytokeratin markers CK5, CK14, CK17 and EGFR. RESULTS: ALNM was found in 55% (n = 116) of the patients. On univariate analysis, multicentric disease, large tumor size (>2 cm), vascular and lymphatic invasion, epithelial hyperplasia, necrosis, in situ carcinoma and perineural invasion were associated with higher risk for ALNM, whereas CK5, CK14, EGFR positivity and basal-like tumor type were associated with lower risk. On multivariate analysis, CK5 positivity (OR 0.003, 95%CI 0.000-0.23, p = 0.009) and lymphatic/vascular invasion (OR 17.94, 95%CI 4.78-67.30, p < 0.001) were found to be independent predictors. CONCLUSIONS: Although the value of complete ALND has been questioned in invasive breast cancer patients, treatment decisions for breast carcinoma have been influenced by many parameters, including lymph node status. Since histopathologic characteristics and expression of biological markers varies among the same histologic subtypes of breast carcinoma, specific clinical and histopathologic features of the primary tumor and ALN status like sentinel node might be used to tailor the loco-regional and systemic treatment in different clinical settings.

Cytokeratin 7 and cytokeratin 20 expression in colorectal adenocarcinomas.

Cytokeratin 7 (CK7) and cytokeratin 20 (CK20) are low molecular weight cytokeratins. The expressions of CK7 and CK20 have been studied in various primary and metastatic carcinomas. Their expression patterns may help to distinguish the site of origin of metastatic carcinomas. We investigated the expressions of CK7 and CK20 in 196 cases of colorectal carcinoma. Paraffin sections of 196 colonic adenocarcinomas were randomly selected, retrieved, and immunostained for CK7 and CK20 with a standard avidin-biotin complex method. CK7 was expressed in 34/196 (17.3%) and CK20 in 159/196 (81.1) cases of colorectal adenocarcinoma. CK7-/CK20+ had the greatest proportion (65.8%) in colorectal carcinomas. The CK7+/CK20+ immunophenotype was identified in 30/196 (15.3%), CK7-/CK20- in 33/196 (16.9%), and CK7+/CK20- in 4/196 (2%) colon adenocarcinomas. The CK7 and CK20 expression patterns were different in colorectal carcinomas according to histological grade, location of the tumor, and lymph node metastasis. CK20 positivity was more common in low grade carcinomas than in high grade carcinomas (85.1% versus 47.6%) and in rectal and sigmoid carcinomas than in proximal colon carcinomas (88.2% versus 63.2% and 88.9% versus 63.2%, respectively). Furthermore, CK7 expression was more common in tumors with lymph node metastasis than in non-metastatic tumors (25.3% versus 11%). In conclusion, a considerable number of colorectal carcinomas showed reactivity to CK7 (17.3%) or no reactivity to CK20 (18.9%). Therefore, CK7 positivity or CK20 negativity does not rule out a colorectal origin of metastatic carcinoma.

Foreign body granuloma: a mimic of breast carcinoma.

Foreign body granuloma of the breast may cause diagnostic controversy when they present with neoplasia-like imaging findings. A 70-year-old woman presented with a mass in the lower outer quadrant of the right breast measuring 3 x 2 cm with a history of breast biopsy from her right breast a year ago. Mammography was performed and the mass was diagnosed as malignant. A wide excision was performed. The mass was diagnosed histologically as a foreign body granuloma. The patient was discharged and her postoperative recovery was uneventful. Clinicians and radiologist should be aware of this type of breast lesion which may be misinterpreted as breast carcinoma (Fig. 2, Ref. 8).

Protective effects of monoclonal antibody to intercellular adhesion molecule-1 in venous ischemia-reperfusion injury: experimental study in rats.

Flaps with venous occlusion have a decreased survival rate compared with arterial occlusion. It seems that several factors are involved in the etiology of total venous occlusion, including free radicals, edema, thrombosis, and reperfusion injury. In the present study, the authors evaluated the blockage of polymorphonuclear leukocyte endothelial adhesion by using a monoclonal antibody to the intercellular adhesion molecule 1 (ICAM-1) ligand to prevent venous ischemia-reperfusion injury in rat epigastric island flaps. A skin flap (3 x 4 cm) supplied by the superficial epigastric artery and vein was harvested unilaterally in 40 male Wistar rats. Total venous occlusion of the skin flap was achieved. Arterial inflow was left intact. Rats were randomly divided into four groups (n = 10). In Group 1; rats were intravenously pretreated with 0.5 ml of 0.9 percent normal saline 15 min before applying a venous clamp, and the flaps were subjected to 6 hr of venous ischemia. In Group 2; rats were intravenously pretreated with 0.05 mg of monoclonal antibody to the intercellular adhesion molecule 1 (0.20 mg/kg) in 0.5 ml of 0.9 percent normal saline 15 min before applying the venous clamp, and the flaps were subjected to venous ischemia as in Group 1. In Group 3; rats were pretreated as in Group 1, and the flaps were subjected to 8 hr of venous ischemia. In Group 4; rats were pretreated as in Group 2, and the flaps were subjected to 8 hr of venous ischemia. The flaps were assessed histologically and by measuring viable and non-viable areas on postoperative day 7. Flap measurements revealed that blocking the action of ICAM-1 IN VIVO by administering monoclonal antibody significantly attenuated ischemic injury after 6 or 8 hr of venous occlusion.

Effect of vitamin A on the CD44 expression in the small intestine of rats with obstructive jaundice.

HYPOTHESIS: In this study, the influence of obstructive jaundice on the CD44 expression in the rat small intestine and the alterations of this CD44 expression by vitamin A given intraperitoneally (200 IU/g/day) are evaluated. MATERIALS AND METHODS: In a prospective animal model study, 32 Sprague-Dawley rats were randomized into four groups: group A rats (n = 8) underwent sham operation and were given daily saline intraperitoneally for 2 weeks (sham + saline); group B animals (n = 8) underwent sham operation and were given daily vitamin A intraperitoneally for 2 weeks (sham + vitamin A); group C rats (n = 8) underwent common bile duct ligation and were given daily saline intraperitoneally for 2 weeks (obstructive jaundice + saline), and group D animals (n = 8) underwent common bile duct ligation and were given daily vitamin A intraperitoneally for 2 weeks (obstructive jaundice + vitamin A). After 2 weeks, standardized jejunum and ileum segments were harvested from all animals. The expression of CD44 on the cell surface was evaluated immunohistochemically. Comparisons among the four groups were done. RESULTS: The plasma bilirubin, aspartate transaminase, alanine transaminase, alkaline phospatase, and gamma-glutamyltransferase levels in groups C and D (obstructive jaundice groups) were higher than those in groups A and B (sham groups; p < 0.05). There was no difference between groups A and B (sham groups) with regard to the number of cells expressing surface CD44 in jejunum and ileum. When groups A and B were compared with group C (obstructive jaundice + saline) animals, the number of cells expressing surface CD44 was significantly decreased in both jejunum and ileum in group C. The difference between sham groups (A and B) and group C was found to be significant (p < 0.05). When group D (obstructive jaundice + vitamin A) was compared with group C (obstructive jaundice + saline), the number of cells expressing surface CD44 was significantly increased in jejunum and ileum in group D animals (p < 0.05), higher than in the sham groups (A and B). The difference between group D and sham groups (A and B) was found to be significant (p < 0.05). CONCLUSION: Obstructive jaundice for 2 weeks significantly decreased the CD44 expression in the rat small intestine. We found that daily intraperitoneal administration of vitamin A in rats with obstructive jaundice for 2 weeks significantly restored the impaired CD44 expression.