Expression of MMP-1 in invasive well-differentiated thyroid carcinoma.

The objective of this study is to examine the expression of matrix metalloproteinase 1 (MMP-1) in invasive well-differentiated thyroid carcinoma (WDTC) and its relation to clinicopathological features. This retrospective case study group included 26 patients with invasive WDTC who were treated at our center between January 1985 and May 2007. Clinical data were collected from the medical files. MMP-1 expression was tested in samples from paraffin-embedded tumor by immunohistochemical staining. MMP-1 expression correlated with laryngotracheal invasion (p = 0.032), multifocality of the tumor (p = 0.044), and presence of regional (p = 0.034) and distant metastases (p = 0.048). In conclusion, the expression of MMP-1 in invasive WDTC is consistent with tumor aggressiveness, manifested by laryngotracheal invasion, multifocality, and regional and distant metastases. MMP-1 expression may serve as a prognostic marker and an indicator for the need for more aggressive surgical treatment.

Leiomyosarcoma of the inferior vena cava. Our experience and a review of the literature.

Leiomyosarcoma (LMS) of the inferior vena cava (IVC) is a rare malignant tumor, accounting for 2% of all LMSs. Less than 400 cases have been reported in literature. Computed tomography (CT) is the most accurate imaging method in assessing the location of the tumor within the IVC and magnetic resonance imaging (MRI) accurately identifies its extent and the potential for surgical resection. We present the case of a patient with inferior vena cava leiomyosarcoma (IVCL), for whom the pathological diagnosis was different from the initially expected one, the tumor appearance on pre-operative imaging mimicking renal cell carcinoma. The intraoperative difficulty of approaching renal hilum and IVC was a factor suggesting the vascular origin of the tumor, which was confirmed at pathological analysis. The extensive defect in the IVC after tumor excision led to the decision of complete transverse suturing of IVC, as significant collateral venous circulation was already present. Because IVCL is a rare disease, there is scarce data regarding the prognosis and treatment options. Long-term survival depends on the extent of the surgery. The need of vascular reconstruction is not always mandatory. Despite high recurrence rates, no consensus regarding adjuvant treatment exists yet. A multidisciplinary approach including surgical oncologists and vascular surgeons is mandatory to achieve the best patient outcomes. Perioperative planning, coordination and adherence to oncological techniques are critical.

Histopathological changes of the nasal mucosa induced by smoking.

Changes in the histopathology of the respiratory epithelium in response to cigarette smoking have been studied in depth in the lungs, but data on the nasal lining are lacking. The aim of the present retrospective study was to investigate the histological changes that occur in the nasal mucosa of smokers compared with non-smokers. The study group included 47 patients who underwent partial resection of the inferior turbinates. Archival nasal tissue samples were collected and examined by light microscopy: the number of goblet cells was counted, and the degree of inflammation, congestion, and edema was graded as mild, moderate, or severe. Epithelial thickness was measured as well. Findings were compared between smokers (n = 21) and non-smokers (n = 26). On statistical analysis, significant differences were found between the smokers and non-smokers in mean number of goblet cells in the nasal epithelium, 43.43 +/- 16.80 vs. 16.23 +/- 5.65 respectively (p < 0.0001), mean edema grade, 2.43 +/- 0.75 vs. 1.12 +/- 0.33 respectively (p < 0.0001), and mean epithelial thickness, 111.9 +/- 25.8 microm vs. 60.4 +/- 18.4 microm respectively (p < 0.0001). The corresponding mean values of congestion were 2 +/- 0.71 and 1.27 +/- 0.67 (p < 0.001), and of inflammation, 1.81 +/- 0.60 and 1.81 +/- 0.85 (NS). In conclusion, the histopathological findings in the nasal mucosa of smokers resemble reported findings in the bronchial respiratory epithelium. The main differences from non-smokers are greater goblet cell hyperplasia and thicker epithelium.

Cholesterol granuloma in thyroglossal cysts: a clinicopathological study.

Thyroglossal duct cyst (TDC) is a congenital anomaly caused by retention of epithelial remnants from the descent of the thyroid gland during embryological development. Cholesterol granuloma represents a granulomatous reaction to precipitates of cholesterol crystals in tissue, usually related to middle-ear disease. The association of TDC with cholesterol granuloma has hardly been reported. This study describes five patients with TDC and cholesterol granuloma over a 16-year-period. The treatment consisted of excision of the TDC and the mid-portion of the hyoid bone and excision of a core of tissue between the hyoid bone and the foramen cecum (Sistrunk procedure). We speculate that the pathogenesis of cholesterol granuloma in TDC resembles that in the paranasal sinuses, as both sites provide a closed, poorly ventilated hollow structure with slow drainage. Our five patients accounted for 13% of all patients with TDC treated in our center during the same period, indicating that cholesterol granuloma in TDC may not be as rare as previously thought.

Expression of epithelial cell adhesion molecule in gallbladder carcinoma and its correlation with clinicopathologic variables.

Gallbladder carcinoma is rare and fatal, and conventional therapies have been disappointing. Epithelial cell adhesion molecule (EpCAM) serves as a prognostic marker in various carcinomas and is a target of antibody-based therapies. Our purpose was to examine the expression of EpCAM in gallbladder carcinomas in relation to tumor grade, disease stage, and patient survival. Gallbladder carcinoma tissue specimens from 25 patients attending our center between 1991 and 2004 were immunohistochemically stained for EpCAM. The intensity and extent of staining were analyzed, and the specimens were classified accordingly: (1) weak, weak or no EpCAM expression in less than 10% of the selected area; (2) moderate, moderate expression in 10% to 49% of the selected area; or (3) strong, heavy staining in 50% or more of the selected area. The correlation between EpCAM expression and clinicopathologic variables was analyzed statistically.EpCAM overexpression predicted decreased survival (P = .005), but EpCAM expression did not correlate with tumor grade (P = .28) or disease stage (P = .10). EpCAM expression in gallbladder tumors may serve as a prognostic factor for poor survival. Its detection may help clinicians select patients likely to benefit from novel molecular therapies.

A Novel Technique to Improve the Processing of Minute Ureteroscopic Biopsies.

To examine the ability of a new specimen handling technique to improve histopathological yield of ureteroscopic biopsies, performed in patients with suspected upper tract urothelial carcinoma (UTUC). In a bi-center retrospective study we compared the results of the new tissue handling technique (group 1) with the standard technique (group 2). In the new technique, to achieve maximal tissue preservation, the specimen is mounted on filter paper prior to embedding in paraffin. Multivariate analysis was performed to determine which factors are associated with optimal histological results. We further compared the biopsies with the final specimen in a subgroup of patients who underwent nephroureterectomy (NU). Of 55 ureteroscopic biopsies, 1 biopsy from group 1 (new technique) and 3 biopsies from group 2 (standard technique) were inadequate for pathological examination. 51 UTUC specimens were analyzed. Tumor grade and stage were determined in 85% and 63% of the patients in group 1 and in 83% and 25% of group 2 (p=0.85 and p=0.007). Orientation was preserved in 82% of group 1 and 42% of group 2 (p=0.003). On multivariate analysis biopsy technique and biopsy diameter were found to predict stage determination (p=0.01 and p=0.007) and tissue orientation (p=0.005 and p=0.04). Among patients who underwent NU, stage concordance between the biopsy and final pathology was observed in 56% and 27% of the patients in group 1 and 2, respectively. The new processing technique for small UTUC forceps biopsies decreases the rate of biopsies with insufficient material and improves biopsy interpretation.

Endoscopic laser surgery for subglottic stenosis in Wegener's granulomatosis.

PURPOSE: Wegener's granulomatosis (WG) is a rare multisystem inflammatory disease, which infrequently involves the subglottic area and trachea. Treatment usually involves the use of immunosuppressive agents with corticosteroids. Some patients, however, continue to have symptoms of airway obstruction after clinical remission following the standard therapeutic regimen. OBJECTIVE: To investigate laser treatment for subglottic stenosis in five patients suffering from WG. MATERIALS AND METHODS: We endoscopically treated 5 patients with subglottic stenosis due to WG and airway obstruction by Nd:YAG and CO2 lasers. One of the patients had preoperative tracheostomy and after treatment was decannulated and could not breathe without dyspnea. Another patient required stenting of the subglottic area. RESULTS: All five patients were able to breathe without dyspnea after the treatment. Three patients were treated with an Nd:YAG laser but needed repeated laser treatment every four to six months, whenever they complained of dyspnea. The other two patients were treated with a CO2 laser; one of these patients had preoperative tracheostomy and was treated twice by CO2 laser and decannulated, with no further difficulty in breathing. The follow-up period was 1-5 years. CONCLUSIONS: Nd:YAG and CO2 lasers are recommended in the treatment of subglottic stenosis (SS) due to WG, particularly when the stenosis is in continuity or close proximity to the vocal cords.

Activin betaA in term placenta and its correlation with placental inflammation in parturients having epidural or systemic meperidine analgesia: a randomized study.

STUDY OBJECTIVE: To investigate the immunohistochemical localization of betaA subunit of activin A in human term placenta, as a marker for placental infection/inflammation and elevated temperature, in parturients laboring during two analgesic regimens. DESIGN: Prospective, randomized controlled study. SETTING: Delivery room. PATIENTS: 56 healthy, ASA physical status I and II primiparous women in labor. INTERVENTIONS: Parturients were assigned to receive patient-controlled epidural analgesia (PCEA) with 0.2% ropivacaine or patient-controlled intravenous analgesia PCA with meperidine. MEASUREMENTS: Histologic and immunohistochemical placental evaluation for white blood cell infiltration and activin betaA staining were made. Maternal temperature elevation above 37.6 degrees C and leukocytosis above 15,000/microL were recorded. MAIN RESULTS: Temperature was not significantly increased in parturients receiving PCEA over those who received (PCA) with meperidine (31% vs 11%, respectively; P = 0.1). There was also no association between temperature elevation during epidural analgesia and increased white blood cell count (>15,000/microL) or presence of polymorphonuclear and/or lymphocyte aggregation in the placenta. Immunohistochemical staining with antisera against the betaA subunit of activin was present mainly in the placental cytotrophoblast, syncytiotrophoblast, and vascular endothelium, and was not associated with an increase in maternal temperature. No significant difference was noted between the two analgesic techniques with regard to maternal temperature elevation. Intrapartum temperature elevation was not associated with histologic signs of placental inflammation or with expression of activin betaA in the placenta. CONCLUSION: Other mechanisms may be involved in the etiology of temperature elevation during labor.

Seminal Tract Amyloidosis: Synchronous Amyloidosis of the Seminal Vesicles, Deferent Ducts and Ejaculatory Ducts.

Senile Seminal Vesicle Amyloidosis (SSVA) increases with age. Involvement of the whole seminal tract, i.e. the seminal vesicles, ejaculatory and deferent ducts was first reported by us in the International Symposium on Amyloidosis 1998. Since then we encountered four more cases of SSVA. In all these cases the ejaculatory and deferent ducts were also involved by amyloid. The amyloid was located mostly sub-epithelially, stained positively with Congo red, gave green birefringence under polarized light and was permanganate sensitive, slightly positive for lactoferrin immunostaining and negative for all known amyloid types. In recent years the amyloid was found to be derived from Semenogelin I, a major constituent of the seminal fluid which is present in the epithelial cells of the seminal vesicle and vas deference. This would explain the deposition of amyloid not only in the seminal vesicles but also in the deferent an ejaculatory ducts which transport the seminal fluid. In a review of the literature we found three more articles on SSVA in which the amyloid was not limited to the seminal vesicles alone. We propose to designate this type of amyloid as "Senile seminal Tract Amyloidosis" (SSTA) instead of "Senile Seminal Vesicle Amyloidosis (SSVA)".

Morphological changes in peri-prostatic sympathetic ganglion cells in aging males.

A significant part of morbidity in elderly male patients involves the pelvic organs and their autonomic neural regulation. The aim of the current study was to report the histopathological changes in the peri-prostatic ganglia in elderly males. The sympathetic ganglia from 36 prostatectomy specimens, 26 due to carcinoma of the prostate and 10 prostates from total cystectomies for transitional cell carcinoma, were examined. The age range was 54-88 years. A total of 5,075 ganglion cells were counted in all the specimens. Pathological changes were identified in 1,696 neuron cells as follows: Neuronophagia in 746 neuron cells, neuron cell vacuolization (330 cells), satellite cells vacuolization (423 cells), cell pyknosis (148 cells) and nageotte nodules (49 cells). A number of these changes increased with age. All the changes were more marked in the peri-prostatic ganglion cells of patients with prostatic adenocarcinoma compared with those with benign prostate hyperplasia, which may be due to local environmental changes associated with the presence of malignancy.

Expression of Topoisomerase II-α protein in salivary gland tumors.

Salivary glands give rise to approximately 30 histological distinct tumor types, which results in a diagnostic challenge for the pathologist. The present retrospective, immunohistochemical study aimed to evaluate the expression of Topoisomerase II-α, a nuclear enzyme, as a diagnostic and prognostic marker in benign and malignant salivary gland tumors, including leomorphic adenoma, mucoepidermoid carcinoma, acinic cell carcinoma and carcinoma ex-pleomorphic adenoma. A total of 59 cases of benign and malignant salivary gland tumors were included in the present study. Representative paraffin-embedded sections were immunostained for Topoisomerase II-α (Topo II-α). The expression level was semi-quantified for each case and then correlated with the histological diagnosis using hematoxylin and eosin-stained slides, grade of tumor and total survival. Significant differences were revealed between the expression level of Topo II-α in pleomorphic adenoma and mucoepidermoid carcinoma (P<0.001), carcinoma ex-pleomorphic adenoma (P<0.001), acinic cell carcinoma (P=0.005) and a group composed of all the malignant tumors (P<0.001). Cancer-specific survival rates were insignificantly increased in tumors expressing low levels of Topo II-α (P=0.464). Thus, the present study demonstrated different expression levels of Topo II-α in benign and malignant salivary gland tumors. These differing expression levels may act as valuable biomarkers for the correct histological diagnosis. Further studies conducted on a larger scale may lead to even more conclusive results.

Gastritis in patients undergoing sleeve gastrectomy: Prevalence, ethnic distribution, and impact on glycemic.

Laparoscopic sleeve gastrectomy (LSG) is a therapeutic option in severely obese patients. The aim of this study was to evaluate the presence of Helicobacter pylori (HP) gastritis and non-Helicobacter gastritis in the gastrectomy specimens, and its association to other variables.One hundred six sleeve gastrectomy specimens were examined histopathologically for the presence of gastritis and its relation to other factors like ethnicity, glycemic control, and postoperative complications.Twelve patients had HP gastritis, 39 had non-HP gastritis, and 55 had normal mucosa. There was a statistical difference between the Arab and Jewish Israeli patients in our study. Twenty-eight of the Arab patients had HP gastritis and 48% had non-HP gastritis. In the Jewish population 6% had HP gastritis and 34% had non-HP gastritis. The preoperative glycemic control was worse in the gastritis group with a mean HbA1c of 8.344% while in the normal mucosa group the mean HbA1c was 6.55. After operation the glycemic control reverted to normal in most the diabetic patients. There were few postoperative complications however, they were not related to HP.There is a high incidence of gastritis in obese patients. The incidence of gastritis in the Arab population in our study was higher than that in the Jewish population. The glycemic control before surgery was worse in patients with gastritis than in the normal mucosa group. HP bares no risk for postoperative complications after LSG and does not affect weight loss. However a larger cohort of patients must be studied to arrive at conclusive results.

Use of Er:YAG laser to improve osseointegration of titanium alloy implants--a comparison of bone healing.

PURPOSE: The objective of this study was to compare the osseointegration of implants in rats in sites prepared with an Er:YAG laser with osseointegration in sites prepared using a conventional drill by assessing the percentage of bone-implant contact (BIC). MATERIALS AND METHODS: Osteotomies were prepared with an Er:YAG laser in the tibiae of 18 rats (the test group) and drill-prepared with a 1.3-mm-wide surgical implant drill at 1,000 rpm with simultaneous saline irrigation in the tibiae of another 18 rats (the control group). Acid-etched titanium alloy implants (2 x 8 mm) were placed in the tibiae, engaging the opposite cortical plate. The Er:YAG laser was used with a regular handpiece and water irrigation (spot size, 2 mm; energy per pulse, 500 to 1,000 mJ; pulse duration, 400 ms; and energy density, 32 J/cm2). Nine animals from each group were sacrificed after 3 weeks of unloaded healing; the remainder were sacrificed after 3 months. The tissues were fixed and prepared for histologic and histomorphometric evaluation. RESULTS: Statistical analysis showed significant differences between the 2 groups at both 3 weeks and 3 months. After 3 weeks of unloaded healing, the mean BICs (+/- SD) were 59.48% (+/- 21.89%) for the laser group and 12.85% (+/- 11.13%) for the control group. Following 3 months of unloaded healing, the mean BICs (+/- SD) were 73.54% (+/- 11.53%) for the laser group and 32.6% (+/- 6.39%) for the control group. DISCUSSION: Preparation of the implant sites with the Er:YAG laser did not damage the interface; the healing patterns presented were excellent. CONCLUSIONS: Based on the results of this study, it may be concluded that the Er:YAG laser may be used clinically for implant site preparation with good osseointegration results and bone healing and with a significantly higher percentage of BIC compared to those achieved with conventional methods.

Visualization of Grossly Undetectable Breast Tumors by Refixation in Lymph Node Revealing Solution.

Introduction Breast lesions might be missed by the traditional method of inspection, palpation, and sectioning of the specimen. Lymph node revealing solution (LNRS) was first introduced by us as a fixative that enhances the retrieval of lymph nodes in breast carcinoma and other malignancies. This is a preliminary report of our experience with the use of LNRS in order to visualize malignant breast tumors that were not detected by the traditional method. Material and Methods Eight post-chemoradiation-treated tumors, 6 relumpectomy specimens, and 1 post mammotome lumpectomy with no grossly detectable residual tumor and 2 mastectomy specimens with multifocal tumors which were missed by the first inspection were postfixed in LNRS for 24 hours and sectioned. Results In some of the cases, small tumors up to 0.5 cm were visualized as white gray lesions. Carcinoma has been confirmed by histopathologic examination and the final diagnosis had to be changed. Conclusion Postfixation in LNRS enhances the visualization of grossly undetectable breast lesions and it is worthwhile to use it in problematic cases in order to arrive at a more accurate diagnosis.

The predictive value of dendritic cells in early squamous cell carcinoma of the tongue.

OBJECTIVES: The aim of this study was to evaluate the relationship between dendritic cell density in early squamous cell carcinoma (SCC) of the tongue and patients' clinical outcome. METHODS: Representative samples of low-risk SCC of the tongue (T1-2,N0,M0) from a homogeneous group of 18 patients following local complete excision and elective selective neck dissection, were immunostained with antibodies against S100 and CD1a. Dendritic cell density was analyzed by outcome. RESULTS: Mean dendritic cell densities were 17 cells/HPF for tumoral S100 and CD1a counts, and 10 cells/HPF for peritumoral S100 and CD1a counts. Better disease-free survival was associated with low peritumoral S100- and CD1a- positive cell counts (p=0.006 and p=0.004, respectively), and with low tumoral S100- and CD1a- positive cell counts (p=0.037 and p=0.04, respectively). Lymphocytic response was decreased in tumors with high dendritic cell density (p=NS). There was no association of dendritic cell density with patient age, tumor size and depth of invasion. CONCLUSIONS: These results may suggest an association between dendritic cell accumulation and functional immunologic impairment.

Human DNA topoisomerase II-alpha expression in laparoscopically treated renal cell carcinoma.

To investigate whether the expression of Topoisomerase II-alpha (TII-alpha) can serve as a prognostic factor in renal cell carcinoma (RCC), histological sections from 27 renal tumors were stained immunohistochemically for TII-alpha expression. The percentage of positive cells in the area of greatest staining was recorded as the TII-alpha index. TII-alpha nuclear staining was positive in all the samples except one. The mean TII-alpha index was 12.5 for grade 1, 44 for grade 2 and 113 for grade 3 tumors. The mean TII-alpha index was 22.3 in tumors which did not recur and 81 for tumors which recurred during the follow-up period. In this study, a higher TII-alpha index correlated with more aggressive tumor behaviour. However, a large cohort of patients should be assessed before drawing definitive conclusions.

Expression of p53, Ki-67 and Bcl-2 in parathyroid adenoma and residual normal tissue.

The aim of this study was to investigate the expression of Ki-67, bcl-2 and p53 in parathyroid adenomas and their residual rim of normal parathyroid tissue. Specimens from 26 parathyroid adenomas were studied by immunohistochemical analysis for Ki-67, bcl-2 and p53 expression. Positive findings were noted for p53 in 4 (15%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.055); for Ki-67 in 15 (56%) adenomas and none of the residual rims of normal parathyroid tissue (p = 0.00002); and for bcl-2 in 19 (73%) adenomas and 8 (31%) residual rims of normal parathyroid tissue (p < 0.01). The high rate of Ki-67 expression may indicate susceptibility of parathyroid adenomas to clonal proliferation. The weak immunoreactive expression of p53, combined with a relatively strong expression of bcl-2, may contribute to the characteristic slow progression of these tumors.

Mucinous adenocarcinoma of posterior urethra. Report of a case.

Primary carcinoma of the male urethra accounts for less than 1% of malignancies in males. Mucinous adenocarcinoma of the urethra is extremely rare, and its biologic behavior is not well known. We report a case of mucinous adenocarcinoma showing the histologic features of colloid adenocarcinoma that appears to have evolved either by neoplastic degeneration of goblet cells found in the urethral epithelium or by malignant degeneration of persistent glandular elements of uretheritis cystica and glandularis.

An improved technique for mitosis counting.

Mitosis counting remains one of the most valuable prognostic indicators in tumor pathology; however, as currently carried out it is time consuming and not reproducible. In this study, 6 different pathologists, using different microscopes, arrived at widely different mitotic counts on the same slide, ranging from 4 to 16. These differences were mainly due to the different field areas of the various microscopes used and the method used for counting and recording. In evaluating the most active 10 HPF, the count ranged from 10 to 19. Instead, when an average of 40 fields was recorded, the range was 4-11. Using the mitosis/volume index, which expresses the number of mitotic figures per mm2 of viable tumor, the counts ranged from 8 to 10, a marked improvement. However, this method is complicated and not "user-friendly.'' We suggest a variation of the technique by which a 2 mm2 rectangle is drawn on a cover slip and mounted under the microscope, centered on the most mitotically active area of the tumor. The mitoses in that area are counted (=n) and the percent of viable tumor (=x%) is estimated under low magnification. The number of mitoses per mm2 of viable tumor (cs-MAI) is then calculated according to the formula Cs-MAI=100n/2x. Using this modified method, the range of mitoses counted by the different observers was very narrow (9 to 11), and the time required for the counting was only 5-10 minutes.

Transthoracic needle biopsy in the diagnosis of large-cell neuroendocrine carcinoma of the lung.

To determine the effect of cytological diagnosis, fine-needle aspiration and brush cytology on lung tumors and core-needle biopsy, we retrospectively reviewed 11 cases of large-cell neuroendocrine carcinoma (LCNEC) found in our archives between the years 1997 and 2004. The preoperative cytological diagnosis of LCNEC is challenging because of the broad histologic similarity to other neuroendocrine tumors of the lung. The original cytologic diagnosis was LCNEC in nine of the cases while the remaining two were misdiagnosed as small-cell lung carcinoma. Smears were composed of clusters of intermediate-size cells with amphophylic cytoplasm, some with large nuclei and prominent nucleoli. In two of the cases there was discordance between the cytological findings and the immunohistochemical results. The cytological findings were correlated with histopathological observations.