The role of R21 expression in differential diagnosis of melanocytic lesions.

Background: Cyclic adenosine monophosphate (cAMP) is an intracellular signal transmitter involved in the regulation of melanocyte growth, proliferation, and melanogenesis. R21 is a monoclonal antibody against the soluble adenylyl cyclase (sAC) protein. Various nuclear and cytoplasmic R21 expression patterns in melanocytic lesions have been previously reported. Pan-nuclear staining was defined as specific for melanoma and was found supportive in the assessment of surgical margins. Aims: The aim of this study is to evaluate the different expression patterns of R21 immunostain and investigate its effectiveness in the differential diagnosis of cutaneous malignant and benign melanocytic lesions. Settings and Design: Fifty invasive cutaneous melanoma and 50 benign melanocytic proliferation were included in the study. Materials and Methods: Paraffin blocks that best reflected tumor morphology were studied via immunohistochemical staining for R21. For all patterns, the cases showing staining in 25% or more tumor cells were considered as positive. Statistical Analysis used: Yates' Chi-square, Pearson Chi-square exact test, Spearman correlation were used. Results and Conclusions: Dot-like Golgi staining was characteristic for nevi (12/50) and seen only in one melanoma. Pan-nuclear staining was striking for melanoma (36/50). This pattern was observed in 2 dysplastic and 3 common melanocytic nevi too. None of the Spitz nevi expressed R21 in pan-nuclear pattern. For the diagnosis of melanoma, sensitivity and specificity of the pan-nuclear expression were 72% and 90%, respectively. Positive and negative predictive values were found as 87% and 76%. R21, a second-generation immunohistochemical marker, can be used in the differential diagnosis of benign and malignant melanocytic lesions.

Immunohistochemical evaluation of IL-1ß, IL-6, TNF-α and IL-17 cytokine expression in peripheral giant cell granuloma and peripheral ossifying fibroma of the jaws.

OBJECTIVE: To examine and compare the immunohistochemical expressions of IL-1ß, IL-6, IL-17 and TNF-α in peripheral giant cell granuloma (PGCG) and peripheral ossifying fibroma (POF). DESIGN: The study included 20 POF and 20 PGCG cases diagnosed at the Pathology Department of Eskisehir Osmangazi University Medical Faculty. Hematoxylin & Eosin-stained slides obtained from each biopsy specimen were re-evaluated, and IL-1ß, IL-6, IL-17 and TNF-α antibodies were investigated immunohistochemically. While staining in stromal cells was examined in POF cases, staining in both stromal spindle cells and multinucleated giant cells was evaluated in PGCG cases. An immunoreactivity score was established for each case by evaluating the staining percentage and intensity for each individual case. The significance level was set at 5% (p < 0.05). RESULTS: The level of IL-6 and TNF-α expressions in the multinucleated giant cells in PGCG lesions was found higher than that in stromal cells (p < 0.005 and p < 0.000, respectively). In PGCG lesions, there was no significant difference between giant cells and stromal cells in terms of IL-1ß and IL-17 expression levels. There was no significant difference between PGCG and POF lesions in terms of IL-1ß and IL-6 expression. TNF-α expression levels were significantly higher in spindle cells of PGCG lesions than that of POF lesions (p < 0.00). However, IL-17 expression levels were significantly lower in PGCG lesions than in POF lesions (p < 0.05). CONCLUSION: The study results showed that TNF-α expression was significantly higher in PGCG lesions and IL-17 expression in POF lesions. IL-1ß, IL-6, IL-17 and TNF-α are involved in the pathogenesis of both PGCG and POF lesions.

CD105 (endoglin) expression as a prognostic marker of angiogenesis in squamous cell cervical cancer treated with radical radiotherapy.

INTRODUCTION: Increased levels of endoglin may represent a new reagent of active neovascularization and angiogenesis process in various cancer types. The prognostic value of tumor CD105 (endoglin) expression in cervical squamous cell cancer (CSCC) patients treated with radical radiotherapy (RT) ± chemotherapy was investigated. MATERIALS AND METHODS: CD105 (endoglin) expression was assessed by immunohistochemical methods in seventy patients, who were treated with radical RT ± chemotherapy for CSCC. The prognostic effects of CD105 on patient and treatment characteristics, local-regional control, and survival were assessed. RESULTS: The median follow-up was 24 (5-99) months for the whole cohort. The median CD105 microvessel density was 55.5 (range; 12-136). Age (≤61 vs. >61 years; P = 0.015), lymph node metastasis status (absent vs. present; P = 0.028), International Federation of Gynecology and Obstetrics stage (Ib-IIa vs. IIb-IVa; P = 0.036), cycles of concurrent chemotherapy (1-3 vs. 4-6 cycles; P = 0.001), and hemoglobin levels (≤10 g/dL vs. >10 g/dL; P = 0.006) appeared to associate significantly with overall survival on univariate analysis. DISCUSSION: No correlation was identified between the tumor CD105 (endoglin) expression and survival in CSCC patients treated with radical RT ± chemotherapy.

High nucleostemin expression has a favorable prognostic effect on gastric carcinomas

Background/aim: Nucleostemin is a nuclear protein that maintains stem cell features and plays a role as a cell proliferation marker. It also participates in cell cycle regulation by interfering with other intracellular proteins. Recent reports have indicated that this protein plays a role in ribosomal biogenesis and genome protection. High expression level of nucleostemin has been reported in some cancer patients. However, the importance of nucleostemin in gastric cancer needs to be addressed. The aim of this study was to investigate nucleostemin expression in gastric cancer and the effects of this expression on prognosis. Materials and methods: Nucleostemin expression was assessed in 103 patients with gastric carcinomas via immunohistochemistry. Subsequently, relationships between nucleostemin expression and clinicopathological features and prognosis were evaluated. Results: In this study, there were 33 and 70 cases involving high and low nucleostemin expression, respectively. Nucleostemin expression was negatively correlated with lymphovascular invasion, the number of metastatic lymph nodes, extracapsular extension, and T stage. Disease-free survival and overall survival were markedly longer in patients with high nucleostemin expression. Conclusion: We suggest that nucleostemin is a favorable prognostic marker for gastric cancer patients. Our results are in conflict with prior studies. The prognostic effect of nucleostemin in gastric cancer remains to be solved.

Prognostic Significance of CD24 in Clear Cell Renal Cell Carcinoma.

The role of cancer stem cells in the initiation and progression of cancer has become a well-studied area of emerging research, and stem cells with different surface markers have been identified in various types of cancer. CD24 is a membrane protein that acts as the ligand for P-selectin and has been defined as a stem cell marker of colonic cancer. The immunohistochemical expression of CD24 is associated with worse patient outcomes in small cell lung cancer, hepatocellular carcinoma, breast cancer, and colon cancer. In this study, we used immunohistochemistry to determine CD24 expression in clear cell, papillary and chromophobe renal cell carcinoma and investigated its relationship with other clinicopathological parameters and prognosis. A total of 108 cases of clear cell, 12 papillary and 13 choromophobe renal cell carcinoma were examined. Clinicopathological features including age, gender, vascular invasion, tumor necrosis, and T stage were recorded. Clinical stage and overall survival and disease-free survival times were recorded. The immunohistochemical expression of CD24 was classified as low or high based on the percentage and intensity of positive staining. CD24 expression was associated with both tumor grade and recurrence rates. The survival analysis revealed that patients with high CD24 expression exhibited significantly lower overall and disease-free survival. Increased expression of CD24 is related to the prognosis of clear cell renal cell carcinoma. This is the first study identifying a strong association between CD24 expression levels and survival. Thus, CD24 expression may aid in predicting prognosis in clear cell renal cell carcinoma.

Tumor deposits: Prognostic significance in gastric cancer patients.

PURPOSE: Tumor deposits (TDs) are defined as satellite peritumoral nodules in the peritumoral adipose tissue of a primary carcinoma without histologic evidence of residual lymph node in the nodule. We aimed to investigate the relation between TDs and clinicopathological characteristics of gastric cancer and to evaluate the effect of TDs on prognosis. METHODS: One hundred and seven non-metastatic gastric cancer patients were enrolled. The relationships between positive and negative TDs with respect to clinicopathological characteristics, as well as disease free survival (DFS) and overall survival (OS), were analyzed. RESULTS: TDs were detected in 28 patients (26.2%). Advanced pT stage and pN stage were significantly higher in TDs-positive compared to TDs-negative patients (p=0.015 and p=0.037, respectively). No significant differences were identified between the groups in other clinicopathological variables such as gender, lymphovascular and perineural invasion. Recurrence and mortality rates were higher in the TDs-positive patients during follow-up of both groups (22/78.6% vs 38/48.1%, p=0.010 for relapse; 20/71.4% vs 3/38%, p=0.005 for mortality). The univariate analysis demonstrated shorter DFS and OS for TDs-positive compared to TDs-negative patients. In multivariate analysis, TDs-positive patients had 1.75-fold higher likelihood to develop recurrence, while the likelihood of death increased 1.99-fold (p=0.041 and p=0.020, respectively). CONCLUSION: TDs-positive gastric cancers demonstrate a more aggressive clinical course compared to TDs-negative. More effective treatment methods should be necessary for management of this subgroup of gastric cancer.

Perforated mixed carcinoid-adenocarcinoma in transverse colon and at gastroenterostomy site: case report.

Goblet cell carcinoid of the large intestine is a rare neoplasm, usually located in ascending colon and rectum. A 60-year-old male patient underwent surgery after the diagnosis of acute abdomen. Exploratory laparotomy revealed perforation with a diameter of 1 cm at the site of the previously performed gastroenterostomy and dilatation of the right colic flexure, secondary to a solid obstructive mass located in the mid-portion of transverse colon. Histopathological investigation of the biopsies, taken from the gastroenterostomy site and the tumor, revealed mixed carcinoid-adenocarcinoma with carcinoid component, predominantly composed of goblet cells. Three cycles of FOLFOX-4 protocol was administered. Following respiratory distress secondary to pulmonary metastasis, the patient's condition deteriorated and subsequently died in the fourth postoperative month. Our aim with this paper is to point out that more cases should be reported for more effective diagnosis, histopathological study, clinical investigation, treatment and prognosis of this specific neoplasm.

Malignant myoepithelioma of the palate: a case report with review of the clinicopathological characteristics.

A malignant myoepithelioma is one of the rarest salivary gland neoplasms which may either arise de novo or develop within a preexisting pleomorphic adenoma or benign myoepithelioma. The parotid gland is the most common primary site and the palate the most common intra-oral site of occurrence. Herein is present a case of a malignant myoepithelioma arising in the hard palate of a 79-year-old woman. The lesion had been examined by biopsy at another hospital, and diagnosed as a poorly differentiated squamous cell carcinoma. The patient underwent a wide local tumor resection. Examination of the resection specimen showed the characteristic histopathological and immunohistochemical features of a malignant myoepithelioma. Five months after the operation, the patient was well without evidence of recurrence or metastasis.

Autoerythrocyte sensitization syndrome (Gardner-Diamond syndrome) associated with cutaneous vasculitis.

Autoerythrocyte sensitization syndrome (ASS) (Gardner-Diamond syndrome) is characterized by painful ecchymotic lesions affecting mostly women with emotional stress. Although it is widely accepted as a non-inflammatory disease, ASS can be accompanied by some autoimmune diseases. In this case report, we present a case with ASS associated with cutaneous vasculitis. We also briefly discuss the possible inflammatory features of ASS.

[Efficiency of coenzyme Q(10) at experimental spinal cord injury]. / Deneysel spinal kord yaralanmasinda koenzim Q10'un etkinligi.

BACKGROUND: In this study, we aimed to compare the efficacy of methylprednisolone, coenzyme Q(10) and combined methylprednisolone and coenzyme Q(10) treatments on experimental spinal cord injury. METHODS: Thirty-two male Sprague-Dawley rats (200-250 g) were divided into four groups. Spinal cord injury (SCI) was performed by placement of an aneurysm clip, extradurally at the level of T4-5. After the trauma, group K (control group) received soybean oil, group M (methylprednisolone group) received 30 mg.kg-1 methylprednisolone and 5.4 mg.kg.hour-1 maintenance dose of methylprednisolone, group Q (coenzyme Q(10) group) received 10 mg.kg-1 coenzyme Q(10), group MQ (methylprednisolone and coenzyme Q(10) group) received 30 mg.kg-1 methylprednisolone and 5.4 mg.kg.hour-1 maintenance dose of methylprednisolone and 10 mg.kg-1 coenzyme Q(10) intraperitoneally. Twenty-four hours after the trauma spinal cord samples of the rats were obtained and tissue samples had been harvested for both biochemical and histopathological evaluation. RESULTS: In histopathological examination, the edema pattern was significantly more severe in group K than the group M, group Q and group MQ (p<0.001). There was no statistically significant difference between group M, group Q and group MQ regarding edema and bleeding (p>0.05). Mean superoxide dismutase (SOD) scores were significantly low while comparing the group K with all remaining groups and the group MQ comparing with the group M (p<0.05). Mean malondialdehyde (MDA) scores were low in the group M, Q and MQ in comparison with the group K, but there was no statistically significant difference between all groups (p>0.05). CONCLUSION: Methylprednisolone, coenzyme Q(10) and combined methylprednisolone and coenzyme Q(10) treatments were found to be effective as they decrease the edema and coenzyme Q(10) could be effective for prevention of secondary injury at experimental SCI.

Plasmacytoid myoepithelioma of the soft palate: a review of the literature and report of a case with immunohistochemical findings.

Myoepitheliomas of salivary glands are rare neoplasms, accounting for less than 1% of all salivary gland tumors. They are classified into four cell types: epithelioid, spindle, clear, and plasmacytoid. Among them, the plasmacytoid cell type appears to have a predilection for the oral cavity, especially the palate. We presented a 32-year-old man with plasmacytoid myoepithelioma arising in the soft palate, together with a brief discussion of the clinicopathologic features and differential diagnosis in the light of the literature.

Protective effect of leptin against ischemia-reperfusion injury in the rat small intestine.

BACKGROUND: The small intestine is extremely sensitive to ischemia-reperfusion (I/R) injury and a range of microcirculatory disturbances which contribute to tissue damage. Previous studies have shown that leptin plays an important physiological role in the microvasculature. The aim of this study was to evaluate the protective effects of leptin in I/R--induced mucosal injury in the small intestine. METHODS: Forty rats were divided into 5 groups (n = 8). Group I was subjected to a sham operation. Following mesenteric ischemia in group II (control); physiologic saline 1 cm3, in group III; leptin 100 microg/kg, and physiologic saline 1 cm3, in group IV; NG-L-arginine methyl ester (L-NAME) 20 mg/kg, and physiologic saline 1 cm3, in group V; leptin 100 microg/kg, L-NAME 20 mg/kg, and physiologic saline 1 cm3 were given intra-peritoneally. In these groups, an I/R procedure was performed by occlusion of the superior mesenteric artery for 45 min followed by 120 min reperfusion. After reperfusion, the small intestines were resected for malondialdehyde (MDA) and nitric oxide (NO) concentration and histopathologic properties. Mucosal lesions were scored between 0 and 5. Tissue MDA and NO concentration and histopathologic grades were compared statistically. RESULTS: Tissue MDA level significantly increased (P < 0.05), tissue NO level significantly decreased in group V animals, compared to group III animals respectively (P < 0.001). Histopathologically, intestinal injury significantly decreased in the leptin treated ischemic group. CONCLUSION: Leptin can be used safely in mesenteric occlusive diseases, since it induces NO formation and release in mesenteric vessels.

Epithelioid angiomyolipoma of the kidney.

Epithelioid angiomyolipoma is a recently recognized variant of angiomyolipoma, which is characterized by the presence of polygonal cells with densely eosinophilic cytoplasm and varying degrees of nuclear atypia. Only a relatively small number of cases of epithelioid angiomyolipoma of the kidney have been reported in the literature. We report a case of epithelioid angiomyolipoma of the kidney that occurred in a 38-year-old woman. The tumor was composed of diffuse sheets of epithelioid cells, adipocytes and only scattered thick-walled blood vessels. The epithelioid cells had pleomorphic and hyperchromatic nuclei with densely eosinophilic cytoplasm. Hemorrhage, necrotic foci and clusters of foamy macrophages were present. HMB-45, CD117 (c-kit) and CD68 were detected in the epithelioid cells. There was no expression of cytokeratin, epithelial membrane antigen or desmin. The patient showed no evidence of recurrence or metastatic disease 9 months after nephrectomy.

Conn's syndrome (primary hyperaldosteronism) simulating polymyositis.

A 44-year-old woman presented with typical polymyositis findings associated with hypokalemia. Abdominal CT as well as plasma renin and aldosterone levels showed a right surrenal adenoma secreting aldosterone. Unilateral adrenalectomy was performed and resolved all the clinical and laboratory manifestations. Hypokalemia should be considered in the differential diagnosis of polymyositis, even in the face of inflammatory cell infiltration in the muscle biopsy.

Successful ivermectin treatment of hepatic strongyloidiasis presenting with severe eosinophilia.

A 49-year-old, previously healthy nurse presented with hepatic lesions and severe peripheral eosinophilia due to strongyloidiasis. Imaging studies of the abdomen showed predominantly peripheral, confluent hepatic lesions. The hepatic lesions and eosinophilia did not show any improvement with albendazole, but completely resolved with ivermectin treatment. Our findings suggest that Strongyloides stercoralis can present with isolated focal hepatic lesions and severe eosinophilia, and resolves with ivermectin treatment.

Prognostic significance of Ki-67 expression for patients with laryngeal squamous cell carcinoma primarily treated by total laryngectomy.

The aim of this study was to determine the prognostic value of Ki-67 immunostaining in laryngeal squamous cell carcinomas. Ki-67 labeling was quantified in 63 laryngeal squamous cell carcinomas by counting at least 1,000 tumor cells in the most immunoreactive area in each sample, and the Ki-67 labeling index was calculated as a percentage. The antigen expression was compared with clinical factors, histopathological grading and prognosis. The Ki-67 mean proliferation index for all patients was 25.44% ( range, 2-75%). A significant correlation was found between Ki-67 mean proliferation index and patient age ( P<0.05), T-stage ( P<0.05), nodal metastasis ( P=0.001) and recurrence ( P<0.001). There was no significant association between the Ki-67 mean proliferation index and tumor site or histologic grade. A univariate analysis showed that the Ki-67 labeling index >21% ( P<0.001), T-stage ( P<0.001) and nodal metastasis ( P=0.001) are determinants of recurrence. In the multivariate analysis, the Ki-67 labeling index >21% ( P<0.001), T-stage ( P<0.001) and nodal metastasis ( P<0.05) were independent predictors of recurrence. Kaplan-Meier plots of survival in patients with Ki-67 values above and below the median (21%) of the general study population showed that a high Ki-67 labeling index correlated with a shorter disease-free survival ( P<0.0001). The analysis of the Ki-67 labeling index at the time of initial surgery may be a powerful prognostic marker for patients with laryngeal squamous cell carcinoma and may be useful for selecting subgroups of patients who should be treated with more aggressive therapies.

The effects of sodium phosphate and polyethylene glycol-electrolyte bowel preparation solutions on 2,4,6-trinitrobenzenesulfonic acid-induced colitis in the rat.

The aim of the present study is to evaluate the effects of sodium phosphate (NaP) and polyethylene glycol-electrolyte (PEG-EL) colon cleansing solutions on histopathology of 2,4,6-trinitrobenzene sulfonic acid (TNBS) and ethanol (E)-induced colitis in the rat and normal rat colon. The presence of hyperemia, inflammation and ulcer was evaluated to score of macroscopic morphologic damage. The microscopic criteria including ulceration, mucus cell depletion, crypt abscesses, inflammatory cysts, mucosal atrophy, edema, inflammatory cell infiltration, and vascular dilatation were evaluated to determine the extent of inflammatory reaction. Colitis findings were determined on the rats which were administered TNBS-E. Aphthoid lesions were seen 30% and 20 % of rats, respectively, by NaP and PEG-EL solutions in healthy group. Microscopic examination of aphthoid lesions revealed edema within the lamina propria and lymphoid hyperplasia in the mucosa and submucosa without erosion, ulceration and inflammatory cell infiltration. No significant difference was statistically found either macroscopically or microscopically in terms of the effects of saline, NaP and PEG-EL solutions in healthy rats and rats with colitis (p > .05). Under the present conditions, we concluded administration of NaP and PEG-EL solutions did not cause evident morphological changes on the rectal mucosa macroscopically and microscopically, although in a proportion of rats aphthoid lesions seem as a marker of mucosal damage macroscopically.

Effects of the anti-ICAM-1 monoclonal antibody, allopurinol, and methylene blue on intestinal reperfusion injury.

PURPOSE: The aim of this study was to evaluate the effect of allopurinol, methylene blue, and a monoclonal antibody to the adhesion molecule ICAM-1 in intestinal ischemia and reperfusion injury. METHODS: The rats were divided into 5 groups. CG (n = 8) was untreated controls, SISG (n = 11) received sterile isotonic saline solution, ICAMG (n = 12) received a monoclonal antibody to rat ICAM-1, ALLOG (n = 12) received allopurinol, and MBG (n = 14) received methylene blue. Intestinal ischemia was performed for 60 minutes followed by 60 minutes of reperfusion. The agents were injected 10 minutes before the reperfusion to animals. After 60 minutes of reperfusion, the plasma samples for myeloperoxidase (MPO) activity, tumor necrosis factor alpha (TNF-alpha) and uric acid levels, and the intestinal biopsies of ileum and jejunum for histopathologic examination were taken. RESULTS: The mucosal damage was attenuated, and TNF-alpha level significantly decreased in ALLOG and ICAMG compared with SISG. The MPO activity was the lowest in ICAMG, and uric acid level was significantly decreased in ALLOG compared with the other groups. Methylene blue decreased TNF-alpha response to reperfusion injury but significantly increased the grade of the mucosal damage and the MPO activity. CONCLUSIONS: This study shows that prereperfusion application of allopurinol and monoclonal antibody to the adhesion molecule ICAM-1 may attenuate the damage caused by intestinal ischemia and reperfusion, but the different time-points for application, the effects observed in the different ischemia and reperfusion durations, and the long-term results also should be investigated in the same experimental model before the final conclusion. Methylene blue was not effective to prevent or attenuate the intestinal tissue injury, but because this was the first study examining the effect of methylene blue on intestinal reperfusion injury, further studies with the different doses, ischemic duration, and application times will be needed.

Supratentorial hemangioblastoma: a case report and review of the literature.

Central nervous system hemangioblastoma is a histologically benign tumor that usually occurs in the cerebellum. Supratentorial hemangioblastomas are exceedingly rare tumors. We present a case of cerebral hemangioblastoma, review the literature on supratentorial hemangioblastoma, and discuss the histologic characteristics and diagnostic difficulties associated with such lesions.