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.

A Retrospective Evaluation of the Epithelial Changes/Lesions and Neoplasms of the Gallbladder in Turkey and a Review of the Existing Sampling Methods: A Multicentre Study.

OBJECTIVE: As there is continuing disagreement among the observers on the differential diagnosis between the epithelial changes/lesions and neoplasms of the gallbladder, this multicentre study was planned in order to assess the rate of the epithelial gallbladder lesions in Turkey and to propose microscopy and macroscopy protocols. MATERIAL AND METHOD: With the participation of 22 institutions around Turkey that were included in the Hepato-Pancreato-Biliary Study Group, 89,324 cholecystectomy specimens sampled from 2003 to 2016 were retrospectively evaluated. The numbers of adenocarcinomas, dysplasias, intracholecystic neoplasms/adenomas, intestinal metaplasias and reactive atypia were identified with the review of pathology reports and the regional and countrywide incidence rates were presented in percentages. RESULTS: Epithelial changes/lesions were reported in 6% of cholecystectomy materials. Of these epithelial lesions, 7% were reported as adenocarcinoma, 0.9% as high-grade dysplasia, 4% as low-grade dysplasia, 7.8% as reactive/regenerative atypia, 1.7% as neoplastic polyp, and 15.6% as intestinal metaplasia. The remaining lesions (63%) primarily included non-neoplastic polypoids/hyperplastic lesions and antral/pyloric metaplasia. There were also differences between pathology laboratories. CONCLUSION: The major causes of the difference in reporting these epithelial changes/lesions and neoplasms include the differences related to the institute's oncological surgery frequency, sampling protocols, geographical dissimilarities, and differences in the diagnoses/interpretations of the pathologists. It seems that the diagnosis may change if new sections are taken from the specimen when any epithelial abnormality is seen during microscopic examination of the cholecystectomy materials.

Metastatic chordoma of the tongue: Case report.

Chordomas are rare bone tumors that arise from notochord remnants. They most commonly occur in the sacrum, but they also can be seen in the skull base, cervical spine, and thoracolumbar vertebrae. Chordomas account for 1 to 4% of all primary skeletal tumors. They are usually indolent, locally growing tumors. Distant metastasis has been reported in 3 to 48% of cases. When metastasis occurs, it is usually observed in the lung, bone, and liver. To the best of our knowledge, no case of a chordoma metastasis to the tongue has been previously reported in the literature. We report such a case in a 61-year-old man.

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.

The effects of tadalafil and pentoxifylline on apoptosis and nitric oxide synthase in liver ischemia/reperfusion injury.

The aim of this study was to investigate the effects of tadalafil (TDF) and pentoxifylline (PTX) on hepatic apoptosis and the expressions of endothelial and inducible nitric oxide synthases (eNOS and iNOS) after liver ischemia/reperfusion (IR). Forty Wistar albino rats were randomly divided into five groups (n=8) as follows: sham group; IR group with ischemia/reperfusion alone; low-dose and high-dose TDF groups received 2.5 mg/kg and 10 mg/kg TDF, respectively; and PTX group received 40 mg/kg PTX. Blood was collected for the analysis of serum alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, uric acid, malondialdehyde (MDA), and total antioxidant capacity (TAC). MDA and TAC also were measured in liver tissue. Histopathological examination was performed to assess the severity of hepatic injury. Apoptosis was evaluated using the apoptosis protease-activating factor 1 (APAF-1) antibody; the expressions of eNOS and iNOS were also assessed by immunohistochemistry in all groups. Serum alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase, uric acid, MDA, and TAC, tissue MDA and TAC levels, hepatic injury, and score for extent and for intensity of eNOS, iNOS, and apoptosis protease-activating factor 1 were significantly different in TDF and PTX groups compared to the IR group. High dose-TDF and PTX have the best protective effect on IR-induced liver tissue damage. This study showed that TDF and PTX supplementation may be helpful in preventing free oxygen radical damage, lipid peroxidation, hepatocyte necrosis, and apoptosis in liver IR injury and minimizing liver damage.

Cytomorphometric and Morphological Analysis in Women with Trichomonas vaginalis Infection: Micronucleus Frequency in Exfoliated Cervical Epithelial Cells.

OBJECTIVES: The aim of this study was to explore the cytomorphometric and morphological effects of Trichomonas vaginalis in exfoliated epithelial cells. STUDY DESIGN: Ninety-six Pap-stained cervical smears were divided into a study group and two control groups as follows: T. vaginalis cases, a first control group with inflammation, and a second control group without inflammation. Micronucleated, binucleated, karyorrhectic, karyolytic, and karyopyknotic cells and cells with perinuclear halos per 1,000 epithelial cells were counted. Nuclear and cellular areas were evaluated in 70 clearly defined cells in each smear using image analysis. RESULTS: The frequencies of morphological parameters in the T. vaginalis cases were higher than the values of the two control groups, and the difference among groups was found to be significant (p < 0.05). The nuclear and cytoplasmic areas of epithelial cells were diminished in patients with trichomoniasis. The mean nucleus/cytoplasm ratio in T. vaginalis patients was higher than the value in the control groups, and the difference between the study group and control group 1 was significant. However, there was no statistically significant increase between the study group and control group 2. CONCLUSIONS: T. vaginalis exhibited significant changes in the cellular size and nuclear structure of the cells. The rising frequency of micronuclei, nuclear abnormalities, and changing nucleus/cytoplasm ratio may reflect genotoxic damage in trichomoniasis.

Evaluation of Micronuclei, Nuclear Anomalies and the Nuclear/Cytoplasmic Ratio of Exfoliated Cervical Epithelial Cells in Genital Candidiasis.

OBJECTIVE: Candida is the most common cause of fungal infections. The aim of this study was to fill the gaps in the current knowledge on the frequencies of micronuclei and nuclear anomalies, and the nucleus/cytoplasmic ratio in genital candidiasis. STUDY DESIGN: A total of 88 Papanicolaou- stained cervical smears, which comprised Candida spp. (n = 44) and control cases with no infectious agent (n = 44), were studied. In each smear, cells with micronuclei and nuclear anomalies were counted in 1,000 epithelial cells and also nuclear and cellular areas were evaluated using image analysis software at a magnification of ×400. RESULTS: The frequencies of micronucleated and binucleated cells and cells with perinuclear halos, and the nucleus/cytoplasmic ratio of epithelial cells were higher in the Candida-infected group compared with the control group (p < 0.05). CONCLUSIONS: Genital candidiasis is able to induce changes in the size and shape of epithelial cells. The nuclear/cytoplasmic ratio and the frequency of micronuclei may reflect the DNA damage in the cervical epithelium. Micronucleus scoring could be used to screen the genomic damage profile of epithelial cells in candidiasis.

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.

Comparison of the effects of bupivacaine, lidocaine, and tramadol infiltration on wound healing in rats.

BACKGROUND AND OBJECTIVES: The aim of this study was to investigate the effects of saline solution, bupivacaine, lidocaine and tramadol infiltration on wound healing in rats. METHOD: Thirty-two male Wistar Albino rats were randomly separated into four groups, receiving 3 mL saline solution in control group (Group C, n=8), 3 mL of 2% lidocaine in lidocaine group (Group L, n=8), 3 mL of 0.5% bupivacaine in bupivacaine group (Group B, n=8), and 3 mL of 5% tramadol in tramadol group (Group T, n=8). Breaking-strength measurements, collagen bundle counting, and histopathologic evaluation were evaluated in the tissue samples taken from the rats. RESULTS: Comparing the control group with the groups where bupivacaine and lidocaine were used for wound infiltration, collagen production was lower, breaking-strength measurements showed reduced resistance while significantly high edema, vascularity, inflammation scores were found (p<0.0125). Between the control and the tramadol group there were no significant differences in collagen production, breaking-strength measurements, and edema, vascularity, inflammation scores (p>0.0125). CONCLUSION: In our study, we found bupivacaine and lidocaine reduced the collagen production, wound breaking strength, and caused significantly high scores for edema, vascularity, and inflammation when compared to the control group. There was no significant difference between the control and the tramadol group. Results of this experimental preliminary study on rats support the idea that tramadol can be used for wound infiltration anesthesia without adverse effect on the surgical healing process. These results need to be verified in humans.

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.

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.

Lymphatic differentiation in classic Kaposi's sarcoma: patterns of D2-40 immunoexpression in the course of tumor progression.

The recent development of lymphatic endothelium-specific immuno-indicators has given rise to research on the histogenesis of Kaposi sarcoma (KS), specifically focusing on its lymphatic root and differentiation. D2-40 is a new lymphatic marker that recognizes podoplanin and is easily applied to formalin-fixed paraffin-embedded human tissues. This study examined D2-40 immunoexpression in 178 classical KS lesions using immunohistochemical methods. D2-40 immunoexpression was also examined in 63 non-KS soft tissue lesions to test the reliability of D2-40 monoclonal antibody in the pathological diagnosis of KS. D2-40 immunoreactivity was detected at all of the KS lesions and in lymphangioma and nonneoplastic lymphatic endothelium. There was no significant relationship between the extent of D2-40 staining and histopathological stage; however, there was a positive correlation between the staining intensity and histopathological stage in KS cases. D2-40 immunoreactivity was detected at all histopathological stages of KS and may be added to the routine immunohistochemical panel used for the differential diagnosis of KS. Widespread D2-40 protein expression is evidence of a lymphatic origin or the differentiation of neoplastic cells in KS, and D2-40 expression increases with tumor progression.

Malignant melanoma associated with congenital melanocytic nevus and diagnosed with intestinal metastases: Two case reports.

Congenital melanocytic nevi are hamartomatous lesions that develop from the neural crest and arise during odontogenesis. In this report, we present two malignant melanoma cases developed from congenital melanocytic nevi and revealed by gastrointestinal system metastases. The first case was a 71-year-old female who presented with pleural and peritoneal effusion and underwent biopsy due to detection of nodular lesions in the duodenum by endoscopic examination. The second case was a 36-year-old male patient who presented with abdominal pain in whom segmental ileal resection was performed due to mass lesions causing invaginations in the ileum. Histopathological examination of the lesions showed a diffuse neoplastic infiltration comprising the entire mucosal layers. In neoplastic cells having a marked atypia and pleomorphism, immunoreactions with S-100, HMB-45, and Melan A were detected. Both cases were diagnosed as malignant melanoma. Abdominal skin in the first case and the femoral region in the second case exhibited congenital melanocytic nevi, and those lesions were determined to show a transformation towards malignant melanoma in the histopathological studies. Malignant melanoma development in gastrointestinal system may have a primary or metastatic character. Definitive diagnosis always requires detailed clinical, histopathological and immunohistochemical analyses.