Cytomorphometry and morphology analysis of human papillomavirus type 16 in liquid-based cervical cytology samples.

BACKGROUND: Human papillomavirus (HPV) is the main causal factor of cervical carcinoma. HPV 16 is one of the most prominent oncogenic types. We aimed to evaluate the cytomorphometric and morphological alterations caused by HPV 16 in liquid-based cytology (LBC). METHODS: The Cobas 4800 HPV system was used for the detecting and typing HPV DNA in cervical specimens. In this study, 30 HPV 16 positive and 30 HPV 16 negative cervical samples were evaluated for micronuclei (MN), nonclassical cytologic abnormalities, and the nuclear-to-cytoplasmic ratio. Nuclear and cellular areas were evaluated using image analysis software and the nuclear-to-cytoplasm ratio was calculated. All analyses were performed blinded to the patients' HPV status. Statistical evaluation was carried out using the χ2 and Fisher test; P-values < .05 were considered significant. RESULTS: The frequencies of micronucleated cells and koilocytes were higher in the HPV 16 infected group (P < .05). Cells with perinuclear halo in control group were higher than the HPV 16 infected group (P < .05). The mean nuclear-to-cytoplasm ratio in HPV 16 patients was higher than the control value, but the difference was not statistically significant. CONCLUSION: LBC can be used to detect morphological and morphometric changes. HPV 16 induces the formation of MN and koilocytosis. The evaluation of MN could provide additional information in monitoring genomic instability and of koilocytes could provide information about damage to the cytoskeleton filaments in HPV infection. Further studies are needed to investigate the effects of HPV-18 and other high-risk HPV types on the cell size and nucleus-to-cytoplasm ratio.

Biological importance of podoplanin expression in chorionic villous stromal cells and its relationship to placental pathologies.

Podoplanin, a reliable marker of lymphatic endothelium, is a mucin-type transmembrane protein. Although the human placenta is devoid of a lymphatic system, chorionic villous stromal (CVS) cells express podoplanin. In this study, the pattern of podoplanin expression in normal and pathological placental tissues and the biological role of podoplanin were investigated. In total, 198 placental tissues belonging to 184 patients, seen at the Department of Pathology of Bulent Ecevit University Education and Research Hospital, Zonguldak, Turkey, were evaluated histopathologically and determined to meet the study criteria. The tissues were assigned to control, cisternal placental disorders, inflammation and hypoxic-ischemic pathology groups. Podoplanin expression in CVS cells was graded from 0 to 3 depending on the staining intensity, as determined by an immunohistochemical evaluation of chorionic villi in the most intensively stained tissue region. Podoplanin levels in control CVS cells increased in parallel with placental maturation, whereas in molar pregnancies podoplanin expression was lower than in control tissues. In the acute placental inflammation group, podoplanin immunoreactivity was similar to that in the control group, whereas in the preeclampsia group, podoplanin expression was higher than in all other groups. Our study showed an increase in podoplanin expression in CVS cells during pregnancy. In preeclamptic patients, the increase in podoplanin expression may be a response to hypoxic-ischemic conditions, whereas in molar pregnancies the decrease in podoplanin levels may cause villous swelling by disrupting intercellular fluid homeostasis.

Bacterial cellulose as a new graft model for the Turkish delight technique in rhinoplasty: An experiment in 20 rats.

We conducted an experiment to investigate the effectiveness of bacterial cellulose, a new graft material, in correcting and preventing dorsal nasal disorder in rhinoplasty. The experiment was performed on 20 Wistar albino rats. The rats were evenly divided into two groups: a fascia group and a cellulose group. In the fascia group, grafts from the conchal cartilage were removed, shredded, and then wrapped in temporal muscle fascia. In the cellulose group, shredded cartilage was wrapped in the bacterial cellulose. These shredded gristle grafts, which were also placed in a subcutaneous area at the back of the rats, were excised after 60 days. We then performed histopathology to compare the health and integrity of the cartilage and the degree of vascularization, fibrosis, and chronic inflammation in the two groups. We found a significantly greater degree of vascularization (p = 0.004) and fibrosis (p = 0.005) in the fascia group and a significantly greater degree of chronic inflammation (p = 0.023) in the cellulose group. We found no statistically significant difference between the two groups in terms of cartilage health and integrity. Our results suggest that bacterial cellulose grafting may play a role as an alternative to fascia grafting for the wrapping of shredded cartilages in Turkish delight grafting, but further investigation is needed.

Relationship of mast cell density with lymphangiogenesis and prognostic parameters in breast carcinoma.

In many cancers, mast cell density (MCD) in the tumor microenvironment is associated with tumor progression and, to a greater extent, angiogenesis. Our study was designed to investigate the correlation between MCD, tumor lymphangiogenesis, and several well-established prognostic parameters in breast cancer. One hundred and four cases of invasive breast carcinoma diagnosed in our clinic between 2007 and 2011 were included. Mast cells and lymphatic vessels were stained with toluidine blue and D2-40, respectively, and their densities were calculated in various areas of tumors and lymph nodes. The variables of MCD and lymphatic vessel density (LVD) were compared using prognostic parameters as well as with each other. As tumor size and volume increased, MCD increased comparably in metastatic lymph nodes; intratumoral and peritumoral LVD also increased. Lymphovascular invasion, lymphatic invasion, perineural invasion, and estrogen receptor positivity were positively related to intratumoral MCD. The relationship between peritumoral MCD and nontumoral breast tissue MCD was statistically significant. Stage was correlated with MCD in metastatic lymph nodes. Metastatic lymph node MCD and intratumoral MCD were also significantly related. Stage, lymphatic invasion, perineural invasion, lymphovascular invasion, and metastatic lymph node MCD were all correlated with intratumoral and/or peritumoral LVD. As nuclear grade increased, intratumoral LVD became higher. In breast carcinoma, MCD, depending on its location, was related to several prognostic parameters. Notably, mast cells may have at least some effect on lymphangiogenesis, which appears to be a predictor of tumor progression.

Clinicopathological features and pituitary homeobox 1 gene expression in the progression and prognosis of cutaneous malignant melanoma.

The evidence that PITX1 (pituitary homeobox 1) is a significant tumor suppressor in human cancer remains largely circumstantial, but it clearly warrants further study as little is known about the tumor-inhibitory roles of PITX1 in cutaneous malignant melanoma. The aims of this study were to investigate PITX1 gene expression in patients with cutaneous malignant melanoma and to evaluate its potential relevance to clinicopathological characteristics and tumor cell proliferation. Clinicopathological findings of patients with cutaneous malignant melanoma were analyzed retrospectively. PITX1 and Ki-67 expression were detected by immunohistochemistry in malignant melanoma and healthy tissue samples from each patient. Labeling indices were calculated based on PITX1 gene and Ki-67 expression. The correlation between PITX1and Ki-67 expressions was analyzed in cutaneous malignant melanoma cases. The relationship between PITX1 expression intensity and clinicopathological characteristics was also analyzed. PITX1 expression was observed in all (100%) normal healthy skin tissue samples. In addition, PITX1 expression was found in 56 (80%) and was absent in 14 (20%) of the 70 cutaneous malignant melanoma cases. Ki-67 positive expression was only detected in the 14 (20%) PITX1-negative cases. PITX1-positive tumor cells were observed on the surface, but Ki-67 positive tumor cells were observed in deeper zones of the tumor nests. PITX1 expression was downregulated in human cutaneous malignant melanoma lesions compared with healthy skin tissue, but Ki-67 expression was upregulated in concordance with the progression of cutaneous malignant melanoma. PITX1 expression may be involved in tumor progression and is a potential tumor suppressor gene and prognostic marker for cutaneous malignant melanoma.

T-cell/histiocyte-rich large B-cell lymphoma of stomach.

T-cell/histiocyte-rich large B-cell lymphoma is an unusually encountered lymphoid neoplasm of stomach with aggressive course, and is an uncommon morphologic variant of diffuse large B-cell lymphoma. An ulcerated mass, 7x5x1 cm in size was observed within the gastrectomy specimen of a 76-year-old female patient. In cross sections, besides mature lymphoid cells displaying T-cell phenotype, a neoplastic formation composed of large, pleomorphic atypical lymphoid cells with, prominent nucleoli, vesicular nuclei and abundant eosinophilic cytoplasm displaying B-cell phenotype were observed. Meanwhile, histiocyte-like mononuclear cells and Reed-Sternberg-like multinuclear cells expressing CD68 and Mac387 were also observed. The diagnosis of the case was T cell/histiocyte-rich large B-cell lymphoma. This rarely encountered neoplasm should be kept in mind in the differential diagnosis of primary gastric lymphomas.

A rare pattern of angiogenesis in meningiomas: glomeruloid microvascular proliferation.

Glomeruloid microvascular proliferation (GMP) is a localized proliferation of vascular endothelial cells resembling a renal glomerule. The nature of cells participating in the formation of these structures remains unclear. While it is a characteristic feature of glioblastoma, it is rarely seen in other solid tumors. Presence of diffuse GMP in meningiomas is characterized by peritumoral edema and an atypical contrast uptake in radiological imaging. Due to its rare nature, a case of spinal meningioma comprising distinct GMP was presented in this study in company with literature data. Also provided a discussion on the pathogenesis of this unusual pattern of angiogenesis and its relationship with tumors biological behavior.

Cavernous hemangioma-like kaposi sarcoma: histomorphologic features and differential diagnosis.

Aim. Cavernous hemangioma-like Kaposi sarcoma is a rare morphologic type of Kaposi sarcoma. So far there are no cases in the literature defining the histological features of this morphologic spectrum in detail. In this study we presented two classical-type cutaneous Kaposi sarcoma cases with histologic findings resembling cavernous hemangioma in company with clinical and histopathological data. Cases. One hundred and eighty-five classical-type cutaneous Kaposi sarcoma lesions in 79 patients were assessed retrospectively in terms of histopathological features. Findings of two cases showing features of cavernous hemangioma-like Kaposi sarcoma whose clinical data could be accessed were presented in accompany with the literature data. Both cases were detected to have bluish-purple, protruded, irregularly bordered cutaneous lesions. Histopathological examination revealed a lesion formed by cavernous hemangioma-like vascular structures organized in a lobular pattern that became dilated and filled with blood. Typical histological findings of early-stage KS, consisting of mononuclear inflammation, extravasated erythrocytes, and a few immature vascular structures in superficial dermis, were observed. All cases were serologically HIV-1 negative. A positive reaction with HHV-8, CD31, CD34, and D2-40 monoclonal antibodies was identified at both cavernous hemangioma-like areas and in immature vascular structures. Results. Cavernous hemangioma-like Kaposi sarcoma is a rare Kaposi sarcoma variant presenting with diagnostic challenges, that may be confused with hemangioma. As characteristic morphological features may not be observed in every case, it is important for diagnostic purposes to show immunohistochemical HHV-8 positivity in this variant.

Inducible nitric oxide synthase expression in gastric adenocarcinoma: impact on lymphangiogenesis and lymphatic metastasis.

BACKGROUND: Lymphatic metastasis is the most important parameter in the spread of gastric carcinomas. Nitric oxide (NO) is a signaling molecule that plays an important role in inflammation and carcinogenesis. In this study, the possible link between inducible nitric oxide synthase (iNOS) expression with lymphangiogenesis and the clinicopathological parameters of gastric carcinomas was investigated. METHODS: In this study, iNOS expression and D2-40 (lymphatic endothelium-specific marker monoclonal antibody) reactivity were examined immunohistochemically in 41 gastric adenocarcinoma and 20 non-neoplastic gastric tissues. iNOS expression was scored semiquantitatively in the tumor parenchyma and stroma. D2-40-positive lymphatic vessels were used in the determination of lymphatic invasion and intratumoral and peritumoral lymphatic vascular density. RESULTS: iNOS expression was higher in gastric carcinoma tissue compared with non-neoplastic tissue. Particularly, iNOS expression in tumor cells was found to be closely related to lymphangiogenesis and lymphatic metastasis. The density of lymphatic invasion as well as intratumoral and peritumoral lymphatic vascular density were positively correlated with lymph node metastasis. CONCLUSIONS: Our results suggest that iNOS-mediated NO formation plays an important role in gastric carcinogenesis, tumor lymphangiogenesis, and the development of lymphatic metastases. Inhibition of the NO pathway may be an alternative treatment of gastric carcinomas. VIRTUAL SLIDES: The virtual slides for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1713572940104388.

Effects of statins in an indomethacin-induced gastric injury model in rats.

BACKGROUND/AIMS: Statins have additional pleiotropic effects beyond their lipid-lowering effects. In this study, the effects of statins were evaluated in an indomethacin-induced gastric injury model in rats. MATERIALS AND METHODS: Animals were divided into eight groups. Distilled water (control group), omeprazole (30 mg/kg), atorvastatin (20 and 40 mg/kg), simvastatin (20 and 40 mg/kg), and rosuvastatin (20 and 40 mg/kg) were given orally (gavage). Thirty minutes later, indomethacin (25 mg/kg) was administered orally to all groups. Six hours later, the animals were sacrificed by decapitation. The mean ulcer indexes for each group were calculated, and the stomachs were evaluated histopathologically. RESULTS: The ulcer indexes were as follows: control 1.72 ± 0.16, omeprazole 0 ± 0.00, and atorvastatin, simvastatin and rosuvastatin (at 20 and 40 mg/kg doses, respectively) 4.28 ± 0.39, 4.99 ± 0.96, 1.72 ± 0.73, 1.90 ± 0.48, 1.85 ± 0.26, and 1.67 ± 0.18. Atorvastatin significantly increased the indomethacin-induced ulcer index at both doses and the erosion score at 40 mg/kg dose. Although the 20 mg/kg dose of simvastatin inhibited mononuclear leukocyte infiltration, the 40 mg/kg dose induced hyperemia. Rosuvastatin did not decrease mononuclear leukocyte or neutrophil infiltrations at 20 mg/kg dose, and only neutrophil infiltration at the 40 mg/kg dose. CONCLUSIONS: In patients with gastric discomfort, statins must be used carefully. If statin therapy is needed, we recommend to avoid using atorvastatin and to use the other statins only in the minimum effective dose.

Histopathological analysis of vesicular and bullous lesions in Kaposi sarcoma.

BACKGROUND: In this study, the clinical and morphological features of vesiculobullous lesions observed in Kaposi sarcoma are analyzed, and the features of bullous Kaposi sarcoma cases are emphasized. METHODS: A total of 178 biopsy materials of 75 cases diagnosed as classic-type cutaneous Kaposi sarcoma were reviewed. Twenty-five cases showing vesiculobullous features were included in the study. Tumor, epidermis, dermis, and clinical data regarding these cases was evaluated. RESULTS: Vesicular changes were observed in 21 (12%) out of 178 lesions of the 75 cases, while bullous changes were present in only 4 (2%). In all cases where vesicular and bullous changes were detected, tumor, epidermis, and dermis changes were similar. All cases were nodular stage KS lesions, whereas hyperkeratosis and serum exudation in the epidermis, marked edema in the dermis, and enlarged lymphatic vessels and chronic inflammatory response were observed. CONCLUSIONS: Our findings suggest that changes in vascular resistance occurring during tumor progression are the most important factors comprising vesiculobullous morphology. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/1646397188748474.

Clinicopathological significance of fascin and CD44v6 expression in endometrioid carcinoma.

BACKGROUND: Fascin and CD44v6 may have significant roles as biomarkers in tumour progression and metastasis. In endometrioid carcinomas, the fascin expression profile is less defined, and the significance of CD44v6 is uncertain. We aimed to investigate the expressions of both fascin and CD44v6 in endometrioid carcinomas and to evaluate their inter-relation with clinicopathological parameters. METHODS: Fascin and CD44v6 expressions were evaluated, individually and in combination, in a series of 47 endometrioid carcinomas and 10 proliferative endometrium samples. The staining extent and intensity of both markers in tumour cells were scored semiquantitatively. The relationship between immunoexpressions and clinicopathological variables was assessed. RESULTS: The expression rates of fascin and CD44v6 in endometrioid carcinoma were 72.34% and 46.80%, respectively. Although these expression rates were higher than those in proliferative endometrial samples, fascin expression showed a statistically significant difference from the normal group (p = 0.02), but CD44v6 did not differ (p = 0.54). Fascin expression was significantly correlated with tumour grade (p = 0.003) and neural invasion (p = 0.036) in a univariate analysis. In contrast, no significant correlation was found between CD44v6 and any of the clinicopathological parameters. CONCLUSIONS: Our findings suggest that fascin might be an independent prognostic indicator in the different steps of extracellular matrix invasion. On the other hand, CD44v6 was not a predictive factor in endometrioid cancer. VIRTUAL SLIDES: The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/8511594927206899.

Placental chorangiosis: the association with oxidative stress and angiogenesis.

BACKGROUND/AIMS: Chorangiosis is considered to be strongly associated with fetal, maternal, and placental disorders, and has been found to be correlated with increased fetal morbidity and mortality. In this study, it is aimed to investigate the association of angiogenesis and oxidative stress with the pathogenesis of chorangiosis. METHODS: Expressions of heat shock protein 70 (HSP70), vascular endothelial growth factor-A (VEGF-A) and basic fibroblast growth factor (b-FGF), which are investigated with avidin-biotin-peroxidase method in formalin-fixed, paraffin-embedded sections from placental tissues diagnosed as no chorangiosis (n = 18) and chorangiosis (n = 18), have been evaluated in a semiquantitative manner. RESULTS: There were significant differences between chorangiosis and no chorangiosis cases with respect to birth weight, birth length, and Apgar scores (p < 0.001). Statistically significant (p < 0.001), diffuse and strong expressions with HSP70, VEGF-A and b-FGF were observed in the villous tissue of placental chorangiosis cases when compared with no chorangiosis cases. CONCLUSION: The majority of the chorangiosis cases had an accompanying poor perinatal outcome, and also those with accompanying angiogenesis and increased oxidative stress demonstrated diffuse and strong expressions of HSP70, VEGF-A and b-FGF. The interaction of maternal, placental, and fetal factors with increased oxidative stress and angiogenesis may possibly contribute to this arising pathologic change.

Role of angiotensin and endothelin in testicular ischemia reperfusion injury.

OBJECTIVES: To determine whether angiotensin and endothelin have any role in testicular ischemia reperfusion injury by investigating the effects of the angiotensin converting enzyme inhibitor enalapril, selective non-peptide angiotensin-II type I blocker losartan and dual endothelin receptor blocker bosentan. METHODS: Rats were anesthetized with thiopental sodium (50 mg/kg i.p.) before the operation. The left testicular artery and vein of rats were occluded for 1 h; before the bilateral orchiectomy, the organ was allowed to reperfuse for 3 h or 24 h. Enalapril (20 mg/kg i.p.), losartan (30 mg/kg i.p.), bosentan (10 mg/kg i.p.) or vehicle (saline) were given 30 min before reperfusion. Malondialdehyde level was measured in testicular tissue after 3 h of reperfusion. Histological examination was carried out after 24 h of reperfusion. RESULTS: Ischemia reperfusion caused a significant increase in malondialdehyde level of ipsilateral testis, and histopathological injury in both ipsilateral and contralateral testes. Enalapril, losartan and bosentan treatments prevented the ischemia reperfusion-induced augmentation in malondialdehyde levels. Only bosentan treatment ameloriated ischemia reperfusion-induced histopathological alterations. CONCLUSIONS: Endothelin might play a more important role in pathogenesis of testicular ischemia reperfusion injury when compared with angiotensin.

Can lymphatic vascular density be used in determining metastatic spreading potential of tumor in invasive ductal carcinomas?

Regional lymph node status is the primary parameter determining treatment strategies and prognoses in breast cancer. Lymphatic vessels in primary tumor tissue play a significant role in lymphatic metastasis. The aim of this study was to investigate the correlation of intra- and peritumoral lymphatic microvessel densities (LVD) with prognostic parameters in breast cancer, including lymphatic invasion (LI). Lymphangiogenesis was investigated using D2-40 monoclonal antibody in 69 invasive ductal carcinoma cases who underwent mastectomy and axillary lymph node dissection. Positively stained microvessels were counted at 400× in dense lymphatic vascular foci (hotspots). Tumor LI was established when at least one neoplastic cell cluster was clearly visible inside a D2-40-positive lymph vessel. Relationships were sought between clinicopathological parameters and mean LVD and LI in primary tumor tissue. Peritumoral LVD was markedly higher than intratumoral LVD (p < 0.001). No significant relationship was found between intratumoral LVD and clinicopathological parameters (p > 0.05). However, significant relationships were detected between peritumoral LVD and LVI [H&E] (p = 0.04), number of lymphatic invasion [n/mm2, D2-40] (p = 0.001), tumor size (p = 0.01), lymph node status (p = 0.03), and tumor stage (p = 0.04). The immunohistochemical determination of LI and LVD can contribute to the prediction of a tumor's biological behavior in invasive ductal carcinomas. Peritumoral LVD in primary tumor tissue is closely related to parameters influencing the prognosis of a tumor.

Primary intestinal diffuse large B-cell lymphoma forming multiple lymphomatous polyposis.

Multifocal and skip involvement is quite a rare developmental pattern for primary gastrointestinal lymphomas. A 25-year-old male patient with diffuse large B-cell lymphoma of the small intestine, with macroscopic features and clinical aspects imitating Crohn's disease and attracting attention with cobblestone-like appearance, is presented herein together with the clinical and pathological features.Multiple ulcerated lesions were also observed infiltrating the serosa with polypoid appearance, 2.5 cm in largest diameter, within the resected jejunoileal specimen, which displayed patchy, healthy-appearing mucosal areas. In microscopic examination, a tumoral infiltration was observed comprised of pleomorphic, atypical lymphoid cells with abundant eosinophilic cytoplasm, marked nucleoli and vesicular nuclei. A B-cell phenotype immunoreaction was observed by vimentin, LCA, CD20, and CD79a in those atypical cells. The diagnosis of the case was diffuse large B-cell lymphoma.The possibility of the presence of this disorder, although rare, is emphasized here for patients applying to the hospital with the signs and symptoms of Crohn's disease.

Effect of coenzyme Q10 on ischemia and neuronal damage in an experimental traumatic brain-injury model in rats.

BACKGROUND: Head trauma is one of the most important clinical issues that not only can be fatal and disabling, requiring long-term treatment and care, but also can cause heavy financial burden. Formation or distribution of free oxygen radicals should be decreased to enable fixing of poor neurological outcomes and to prevent neuronal damage secondary to ischemia after trauma. Coenzyme Q10 (CoQ10), a component of the mitochondrial electron transport chain, is a strong antioxidant that plays a role in membrane stabilization. In this study, the role of CoQ10 in the treatment of head trauma is researched by analyzing the histopathological and biochemical effects of CoQ10 administered after experimental traumatic brain injury in rats. A traumatic brain-injury model was created in all rats. Trauma was inflicted on rats by the free fall of an object of 450 g weight from a height of 70 cm on the frontoparietal midline onto a metal disc fixed between the coronal and the lambdoid sutures after a midline incision was carried out. RESULTS: In the biochemical tests, tissue malondialdehyde (MDA) levels were significantly higher in the traumatic brain-injury group compared to the sham group (p < 0.05). Administration of CoQ10 after trauma was shown to be protective because it significantly lowered the increased MDA levels (p < 0.05). Comparing the superoxide dismutase (SOD) levels of the four groups, trauma + CoQ10 group had SOD levels ranging between those of sham group and traumatic brain-injury group, and no statistically significant increase was detected. Histopathological results showed a statistically significant difference between the CoQ10 and the other trauma-subjected groups with reference to vascular congestion, neuronal loss, nuclear pyknosis, nuclear hyperchromasia, cytoplasmic eosinophilia, and axonal edema (p < 0.05). CONCLUSION: Neuronal degenerative findings and the secondary brain damage and ischemia caused by oxidative stress are decreased by CoQ10 use in rats with traumatic brain injury.