A Case of Recurrent Urinary Tract Infections With Neurogenic Bladder Due to Spinal Tumors.

Neuroblastic tumors are the most common extracranial solid tumors in children. They are manifested by different clinical presentations ranging from cord compression symptoms to asymptomatic cases. A 2.5-year girl with a history of vaginal delivery at 39 gestational weeks and low Apgar score presented by repeated episodes of urinary tract infections and progressive paraplegia started at the age of 8 months. Brain MRI and EEG were normal. Voiding cystourethrography revealed grade II vesicoureteral reflux in the left kidney. Lumbar MRI with and without contrast showed a dumbbell shape mass, the hyper signal in T2 -weighted image and low signal in T1 -weighted image, extramedullary, and intramural with mass effect on the cord. Microscopic examination of tissue obtained by surgery reported ganglioneuroma. Our case was interesting because of her presentation, neurogenic bladder associated with repeated episodes of urinary tract infections, and secondary paraplegia. Neurogenic bladder dysfunction is rarely reported in cases with ganglioneuroma.

Ki67 Frequency in Breast Cancers without Axillary Lymph Node Involvement and its Relation with Disease-free Survival.

BACKGROUND: Breast cancer prognosis is influenced by several histopathology and clinical factors including expression of Ki67 which may have a predictive role in lymph node negative breast cancer patients. The aim of this study was to assess Ki67 expression in breast cancers without axillary lymph node involvement and to evaluate its prognostic value with regard to disease-free survival. MATERIALS AND METHODS: Subjects were selected from non-metastatic invasive breast cancer patients who were referred to the oncology department of Ghaem hospital during 1 April 2001 to 1 April 2008. Ki67 levels were measured using immunohistochemistry (IHC) and compared with clinicopathological features. The relation of Ki67 expression with disease-free survival was also analysed. RESULTS: A total of 106 women with a mean age of 49 were examined. Some 94.3% were classified as having invasive ductal carcinomas and the mean tumour diameter at the time of diagnosis was 2.8 cm. Some 50.9% of cases were ER positive and 47.2% were PR positive. P53 expression was positive in 48.1% of the cases. According to the IHC results, only 8.5% of the patients were Her2/neu positive. Ki67 was positive in 66 (62.3%) with a significant relation to lower age (p=0.0229) and P53 positivity (p=0.005). After an average of 40-months follow up, 13 (12.3%) demonstrated recurrence, most commonly systemic. Of 13 cases with relapse, 10 patients (77%) were Ki67 positive. CONCLUSIONS: In our population Ki67 appeared to be an independent prognostic factor for three-year survival. However, we stress that a survival study with a bigger sample size would help to support this conclusion.

Hormone receptor expression and clinicopathologic features in male and female breast cancer.

BACKGROUND: Male and female breast cancers were investigated for variation in the clinicopathologic characteristics and expression of steroid hormone receptors in the northeast of Iran. MATERIALS AND METHODS: Tumor specimens of 17 males and 338 females with breast cancer were collected at the hospitals of Mashhad University of Medical Sciences. Immunohistochemical expression of hormone receptors and clinicopathologic features of breast cancer were compared between two groups. RESULTS: The mean age in men was 15 years higher than women (p=0.000). Males and females were mainly in stage II and III respectively (p=0.007). Although more than 60% of male and female patients were grade II, the respective figures for grade I and III were 25% and 12.5% in men but 7.1% and 27.2% in women respectively (p=0.025). ER was significantly more positive in men against women; 82.3% versus 53.4% (p=0.016). The related measures for PR was 58.8% and 50.3%, respectively (p=0.424). Males also showed significantly more ER expression than postmenopausal females; 82.3% versus 48.9% (p=0.010). CONCLUSIONS: Breast cancer in males and females contrasted in age at diagnosis, histological type, stage, grade and ER expression which emphasize they are separate diseases with different behaviors.

Lymphatic mapping and sentinel node biopsy in endometrial cancer--a feasibility study using cervical injection of radiotracer and blue dye.

BACKGROUND: The aim of this study was to evaluate the feasibility and accuracy of sentinel lymph node (SLN) detection using preoperative lymphoscintigraphy and intra-operative gamma probe/blue dye for endometrial cancer patients. MATERIAL AND METHODS: Twenty four consecutive patients with endometrial cancer were recruited. All patients underwent lymphatic mapping and sentinel node biopsy using combined intracervical radiotracer and blue dye injections. Pelvic lymph node dissection was performed for all patients. Para-aortic lymphadenectomy was done in high risk patients. All SLNs were examined by frozen section and Hematoxylin and Eosin (H&E) permanent sections. RESULTS: Pre-operative lymphoscintigraphy showed at least one SLN in 21/24 patients. Intra-operatively, at least one SLN could be harvested by gamma probe and/or blue dye methods. A total of 95 SLNs were detected. Four SLNs were detected only by blue dye, 42 only by radiotracer, and 49 were hot/blue. Median number of SLN per patient was 3. Three patients had positive pelvic lymph nodes. All of them had positive SLN (no false negative case). Frozen section could identify SLN involvement in two of three patients with positive pathology. CONCLUSION: Lymphatic mapping and sentinel node biopsy is feasible and accurate in endometrial cancer patients using combined radiotracer and blue dye methods. Frozen section accuracy was lower and underscores the importance of expert pathologists for SLN mapping technique.

Immunohistochemical expression of p16 protein in oral squamous cell carcinoma and lichen planus.

Epithelial carcinogenesis is a multistep process. Specific genetic events lead to malignant transformation of oral epithelium. Oral squamous cell carcinoma (OSCC) may be preceded by potentially malignant lesions such as oral lichen planus (OLP). The p16 protein functions as a negative regulator of the cell cycle progression. Altered pattern of p16 serves as a biomarker for oral mucosal dysplasia and malignant growth. The purpose of this study was to evaluate p16 expression in OSCC and OLP to determine whether it can be a useful marker for early detection of carcinogenesis. We examined p16 expression in 45 OSCCs (15 grade I, 15 grade II, and 15 grade III), 15 OLPs without dysplasia, and 8 normal mucosal specimens with immunohistochemistry. p16 was interpreted as positive if more than 70% of tumor cells showed brown nuclear and cytoplasmic staining. All of the OSCC and control group samples showed negative immunoreactivity, whereas 26.7% of OLP samples were positive for p16. Our findings suggest that p16 expression could not be used as a helpful marker for detection of development toward malignancy in OLP samples.

Immunohistochemical expression of apoptosis regulators in squamous cell carcinoma of the cervix and their association with human papillomavirus 16/18 subtypes.

BACKGROUND: Human papillomavirus (HPV) infection is an important aetiological factor in squamous cell carcinoma (SCC) of the cervix. Limited studies have been focused on the differences between carcinogenesis of SCCs with and without HPV infection. AIMS: The main goal of this study is to determine the expression of some of the apoptotic pathway regulators, including P53, Bax and Bcl2 in SCCs with and without high risk HPV 16/18 infection. STUDY DESIGN: Cross sectional study. METHODS: A total of 42 paraffin-embedded blocks with the histopathological diagnosis of invasive SCC with determined HPV 16/18 status were selected; half of them were HPV positive and the rest were negative. Afterwards, immunohistochemistry stained slides for p53, Bcl2 and Bax were evaluated with H-score, multiplicative and Additive Quick score by two pathologists; in cases of controversy about the results, the mean results were recorded. RESULTS: Mean results and percentage of expression of our three markers were significantly higher in the HPV 16/18 infected group than in uninfected individuals: Respectively, the mean score for Bcl2, Bax and p53 staining according to H-scoring method was 68.5, 234, 106.4 in the HPV 16/18 infected group and 4.5, 218.8, 5.07 in the uninfected group; and the Multiplicative Quick score was 4, 14.6, 8.2 in the HPV 16/18 infected group and 3, 12.3, 3.5 in the uninfected group. CONCLUSION: High risk HPVs possibly act in favour of apoptotic pathway inactivation. The significant difference in apoptotic pathway between SCCs with and without high risk HPVs suggests a different early carcinogenesis pathway.

Immunohistochemical expression of the proliferative marker Ki67 in hydatidiform moles and its diagnostic value in the progression to gestational trophoblastic neoplasia.

AIM: Considering that Ki-67 is a proliferative marker in molar pregnancies and the possible progression of these kinds of pregnancies to gestational trophoblastic neoplasia (GTN), we decided to evaluate the rate of expression of this marker in patients with uneventful hydatidiform moles and GTN. Moreover, we determined the predictive value of this factor for the progression of molar pregnancies to GTN. METHODS: In two groups of patients, including 30 patients with uneventful molar pregnancies and 30 patients with GTN, an immunohistochemical staining technique using the Envision method was performed. To evaluate nuclear immunoreactivity of trophoblastic cells for Ki67 on paraffin sections obtained from molar pregnancy products, the percentage of the stained cells was used. Semi-quantitative evaluation was also performed. Data were analyzed using Mann-Whitney tests and receiver operating characteristic curve analysis. RESULTS: The expression of Ki67 in cytotrophoblastic and syncytiotrophoblastic cells of patients with GTN was significantly more than for patients with an uneventful molar pregnancy (P<0.05). We considered a 12.5% cut-off value for Ki67 in cytotrophoblastic cells and a sensitivity of 90%, specificity 93%, positive predictive value of 93.1% and negative predictive value of 90.3% were obtained. Similarly, considering a cut-off value of 6% for Ki67 in syncytiotrophoblastic cells, results of 90% were obtained for all diagnostic indices. CONCLUSION: Our findings suggest that expression of the Ki67 oncogene in trophoblastic cells in patients with GTN are found far more frequently than in patients with an uneventful molar pregnancy, and demonstrate a high predictive value of progression to GTN.

Evaluation of osteopontin and CD44v6 expression in odontogenic cystic lesions by immunohistochemistry.

Odontogenic cysts are common lesions with different biological behavior. Odontogenic keratocysts (OKCs) and calcifying odontogenic cysts (COCs) with ameloblastoma-like epithelium are more aggressive than dentigerous cysts (DCs) and radicular cysts (RCs). Therefore, they were included in the list of odontogenic tumors by WHO. Osteopontin (OPN) is a calcium-binding glycoprotein present in many normal tissues. It plays a role in the migration and invasion of transformed epithelial cells. Binding of OPN to its receptor CD44v6 can enhance cell motility and migration. The purpose of this study was to compare the expression of these markers between odontogenic cysts of varying biological behavior. We examined OPN and CD44v6 expression in tissue sections of 14OKCs, 14COCs, 14RCs and 14DCs by immunohistochemistry. OPN and CD44v6 immunostaining was observed in all lining epithelial cells of the studied lesions with different degrees. The highest level of OPN and CD44v6 expression was found in OKCs, followed by COCs, RCs and DCs. Comparison of both markers among four groups revealed significant differences (P<0.001). Our findings suggest that higher level of OPN and CD44v6 expression in epithelial cells of some lesions such as OKC and COC can explain the local aggressive behavior of them.

Calretinin Immunohistochemistery: An Aid in the Diagnosis of Hirschsprung's Disease.

OBJECTIVES: Definite diagnosis of Hirschsprung's disease (HD) is based on histopathological study, but there are limitations associated with standard histology and histochemistry in this regard. The aim of this study was to investigate calretinin immunostaining patterns in both ganglionic and aganglionic HD intestinal specimens and to compare them with control specimens. MATERIALS AND METHODS: Specimens included 30 patients with histopathologic diagnosis of HD and 20 patients that underwent colectomy for other reasons (as control group). Eighty paraffin wax blocks of full thickness intestinal specimens (30 blocks of ganglionic segments, 30 blocks of aganglionic segments and 20 blocks of control group) were studied. Calretinin immunoreactivity and pattern of staining for ganglion cells (nuclear and cytoplasmic) and also nerve fibers in different layers of bowel were evaluated in IHC stained slides. RESULTS: There were positive immunostaining of nerve fibers in the lamina propria, submucosa and muscularis propria in control and patient group. There were also nuclear and cytoplasmic staining of ganglion cells in submucosa and muscularis propria in all specimens of both control group (100%) and ganglionic segments (100%). Calretinin immunoexpression of nerve fibers in muscularis propria of the aganglionic segments was negative in all but two cases (6.7%). This method had sensitivity of 93.3% and specificity of 100% for diagnosis of HD in full thickness specimens of intestinal wall. The positive predictive value was 100% and negative predictive value was 93.8%. CONCLUSION: Calretinin immunohistochemistry can be used on suction rectal biopsies as a reliable and adjunctive method to diagnose HD.

Endobronchial leiomyoma; report of a case successfully treated by bronchoscopic resection.

Bronchial leiomyoma is extremely rare. To date less than 60 cases have been reported in the world literature. The presented case here is a 30 year old woman who had been treated for bronchial asthma for several years. Her chest radiograph showed bulluos emphysematous changes in the right lung and computer tomography scan found the tumor in the right main bronchus near carina. Diagnosis was made by histological and immunohistochemical examination of the specimens obtained during bronchoscopy. The patient was treated by bonchoscopic resection of the 3 centimetre firm tumor and its removal through a tracheostomy incision.

P63 and Ki-67 expression in trophoblastic disease and spontaneous abortion.

BACKGROUND: Despite well-described histopathologic criteria, the distinction of spontaneous abortion from hydatidiform mole and complete hydatidiform mole from partial hydatidiform mole remains a problem because of interobserver and intraobserver variability. The aim of this study was to evaluate the value of two immunohistochemical markers in the differential diagnosis of subgroups of lesions of villous trophoblasts and spontaneous abortions. METHODS: Immunohistochemistry with the P63 and Ki-67 antibody was performed in formalin-fixed paraffinembedded samples of non hydropic abortion (n = 14), partial hydatidiform mole (n = 12), complete hydatidiform mole (n = 12) and choriocarcinoma (n = 12). The Ki-67 and P63 labeling index (number of positive nuclei/total number of nuclei) for villous stromal cells, cytotrophoblasts and syncytiotrophoblasts were evaluated separately by counting 100 cells of each population. Statistical analysis was carried out by χ(2) analysis, and the Mann-Whitney U test. Statistical significance was determined at p < 0.05 on the basis of 2-tailed tests. RESULTS: None of nonhydropic spontaneous abortions analyzed exhibited positive cytotrotrophoblastic and syncytiotrophoblastic cells for P63. The syncytiotrophoblastic cells were negative for p63 in all of choriocarcinomas. All of choriocarcinomas analyzed exhibited severe expression of Ki-67 in cytotrotrophoblastic cells. None of abortions and partial moles was diffusely labeled with Ki-67. CONCLUSIONS: Ki-67 labeling index in cytotrophoblastic cells is the best index to differentiate between abortion and subgroups of lesions of villous trophoblasts as well as between different subgroups of lesions of villous trophoblasts. Ki-67 is a better marker than P63 to attain this goal.

Increased microvessel density in involved organs from patients with HTLV-I associated adult T cell leukemia lymphoma.

Adult T-cell leukemia-lymphoma (ATLL) is a rapidly progressive lymphoproliferative disorder secondary to infection with the human T cell lymphotropic virus type I (HTLV-I). The role of angiogenesis in the development and prognosis of many hematologic malignancies is established. We have previously shown that ATLL derived cells secrete high levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF), induce endothelial tube formation in vitro and establish functional gap junction-mediated communication with endothelial cells. We also demonstrated that plasma from ATLL and tropical spastic paraparesis/HTLV-I associated myelopathy patients exhibit very high levels of VEGF and b-FGF. Recently, we showed that treatment with the combination of zidovudine and interferon alpha reduced both HTLV-I proviral load and importantly VEGF plasma levels suggesting a potential anti-angiogenic effect of this therapy. In this report, we evaluated microvessel density (MVD) in involved organs from 20 patients with ATLL, as compared to normal organs from matched controls. We show evidence of significantly increased MVD in all tested involved organs from ATLL patients, suggesting that angiogenesis plays an important role in the development or organ invasion of ATLL, and could represent a potentially interesting target for anti-angiogenic therapy of ATLL.

Evaluation of the relationship between human epidermal growth factor receptor-2/neu (c-erbB-2) amplification and pathologic grading in patients with breast cancer.

OBJECTIVE: The human epidermal growth factor receptor-2 (HER-2)/neu is a proto-oncogene that is amplified in 10-30% of breast cancers. It is known to be associated with a poor overall survival. We studied the relationship between its amplification and different histological gradings of breast cancer. METHODS: We studied 196 patients diagnosed with breast cancer in 2005 at the Omid and Ghaem Training Hospital, Mashhad Medical University, Iran. The HER-2/neu oncoprotein was measured by immunohistochemistry and the histological gradings were carried out according to the Bloom-Richardson Grading system. RESULTS: Sixty-seven (34.2%) cases were HER-2/neu positive and 129 (65.8%) cases were HER-2/neu negative. Overexpression of HER-2/neu was significantly higher in breast cancer patients <30 years (50% versus 33.3%, p=0.034). There was a non-significant statistical relationship between histological grading and overexpression of HER-2/neu oncogen (p=0.087). Twelve (17.5%) of HER-2/neu positive cases were metastatic and only 4 (3.1%) of HER-2/neu negative cases had metastasis (p=0.051). CONCLUSION: HER-2/neu gene amplification or its overexpression is detected in approximately 34.2% of breast cancer cases. Patients with HER-2/neu positive breast cancer have higher stage and grade diseases. This may help to use a better treatment for patients.