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.

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.

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.

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.

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.

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)".

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.

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.

CD1a-positive dendritic cell density predicts disease-free survival in papillary thyroid carcinoma.

OBJECTIVES: Dendritic cells are common in inflammatory processes and in papillary thyroid carcinoma (PTC). Previous studies of the predictive value of S100-positive dendritic cell density for PTC outcome yielded inconsistent results. This study investigated the association of dendritic cell density and PTC recurrence based on CD1a expression. METHODS: Representative slides from 56 consecutive specimens of PTC were immunostained with anti-CD1a antibodies, and dendritic cell density was analyzed by disease-free survival. RESULTS: Dendritic cells were abundant in the tumoral tissue and sparse in the normal peritumoral tissue. Peritumoral dendritic cell density >1.1 cells/HPF was inversely associated with the risk of recurrence. Similar results were obtained with tumoral dendritic cell density (>12 cells/HPF), although the statistical significance was marginal. CONCLUSIONS: High CD1a-positive dendritic cell density is associated with improved disease-free survival in PTC. The specificity of anti-CD1a immunostain for activated dendritic cells may explain the better outcome prediction in this study than in studies using S100 protein.

A new Ki-67 / E-cadherin cocktail reduces inter-observer variation of the calculated proliferative index.

The proliferative index in breast carcinoma is usually calculated by the percentage of the Ki-67 positive cells out of the total number of malignant cells. In order to reduce the inter-observer variability of the calculated proliferative index a cocktail of antibodies against E-Cadherin and Ki-67 (Ki/Cad Cocktail) is presented. The cocktail was applied on 59 cases of infiltrating duct carcinoma of breast and compared to the consecutive slides stained for Ki-67 alone. The Ki/Cad cocktail has the advantage that by adding the anti E-Cadherin antibody, all the malignant epithelial cells are highlighted and can be differentiated from other proliferating cells. Statistical analysis proved that the cocktail increases the inter-observer agreement from 89 % to 97 % as compared to the Ki-67 alone and also reduces the overlap between the cancer grades.

The role of s100-positive dendritic cells in the prognosis of papillary thyroid carcinoma.

Dendritic cells are potent antigen-presenting cells, common in inflammatory processes. We sought to investigate dendritic cell expression in papillary thyroid carcinoma and the relationship of dendritic cell density with the extent of thyroiditis and prognosis. Specimens from 69 consecutive patients with papillary thyroid carcinoma were immunohistochemically stained for the S100 protein, and the number of positive dendritic cells was counted. Cells were sparse in normal thyroid tissue and common in areas of thyroiditis and papillary carcinoma. Dendritic cell density in papillary carcinoma correlated with the thyroiditis grade and dendritic cell density in surrounding areas of thyroiditis. High-grade thyroiditis (42% of patients) was inversely associated with 3-year recurrence. Dendritic cell density was not associated with disease-free survival. The lack of prognostic value of dendritic cell density is not compliant with the only other relevant study in the literature, and further research is required.

Expression of cyclin E in stage III colorectal carcinoma.

Carcinogenesis is characterized by an abnormal regulation of the cell cycle. Regulators of the cell cycle such as cyclin E play an important role in neoplasia and may be correlated with prognosis. The clinical significance of the expression of cyclin E in stage III colorectal carcinoma has not yet been investigated. The expression of cyclin E was evaluated in 49 patients. Using a multivariate analysis, the expression of cyclin E in the tumor at diagnosis was compared with various clinicopathological variables, including age, gender, tumor site, tumor size, tumor differentiation and lymph node involvement. There were more node-positive cases in the cyclin E-negative group than in the cyclin E-positive group (P=0.003). However, there was no correlation between the degree of cyclin E expression and the clinical data. In conclusion, our data suggest that overexpression of cyclin E does not predict the clinical outcome in colorectal cancer stage III. Negative cyclin E staining may be associated with lymph node involvement.

Expression of estrogen receptor ß1 in colorectal cancer: correlation with clinicopathological variables.

Colorectal cancer (CRC) is a common malignancy in both genders with a high death rate, accounting for about 56,000 each year in the USA only. In this study we examined the differences in CRC between the genders. We also looked for differences in the staining of the tumors and adjacent colonic mucosa to estrogen receptor ß1 and its possible prognostic value. Fifty-five specimens from patients who underwent resection of colon cancer in our institute were sectioned and stained for estrogen receptor ß1. The histopathological slides were evaluated for positive staining in the tumor and the normal colonic mucosa as well. The results were statistically analyzed. Positive estrogen receptor ß1 stain was found in the nuclei of the tumor cells. We noted positive stain also in the cytoplasm of the tumor cells. Similar findings were observed in the normal colonic mucosa. Statistically significant differences were found regarding the positivity of the staining between the deceased and surviving patients, men/women and those who had metastases vs. the non-metastatic ones. Our data suggest that there is an estrogen influence on the development and progression of colon cancer. Furthermore, it was found to be higher in the more severe cases.

Thyroid gland involvement in advanced laryngeal cancer: association with clinical and pathologic characteristics.

BACKGROUND: Indications for thyroidectomy during laryngectomy are controversial. We examined whether clinicopathologic features can predict thyroid gland involvement, and the prognostic effect of thyroid gland involvement in patients undergoing total laryngectomy. METHODS: The study set out to review preoperative assessment, operation findings, pathologic findings, and follow-up data. RESULTS: Thyroid gland involvement was found in 11 of 53 patients (21%) undergoing total laryngectomy and thyroidectomy. Preoperative work-up failed to predict thyroid gland involvement. Thyroid gland involvement was associated with salvage procedures (p = .025), paratracheal metastases (p = .003), and poor overall survival (hazard ratio = 2.74, p = .008). CONCLUSIONS: Thyroid gland involvement in patients undergoing total laryngectomy is frequent and is associated with poor prognosis. Preoperative assessment failed to predict thyroid gland involvement. We believe that thyroidectomy should be considered in cases with paratracheal lymphatic spread irrespective of tumor location within the larynx.

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.

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.

Female urethral diverticulum: a pathological insight.

INTRODUCTION AND HYPOTHESIS: In this study, we define the histopathological features of female urethral diverticula and attempt to elucidate its pathogenesis and etiology. METHODS: We analyzed 22 clinical records of women diagnosed with urethral diverticula. We collected clinical, surgical, and pathological data. Pathological re-assessment was performed using hematoxylin-eosin and van Gieson stains. RESULTS: The predominant epithelial types were squamous (41.9%), columnar (31.8%), combined squamous and columnar (18.2%), and cuboidal (13.6%). There was no case of the transitional type. Epithelial ulcerations were present in nine cases. The diverticular wall was composed only of fibrous collagen tissue in all cases. Inflammatory signs were noted in 77.3% of specimens. CONCLUSIONS: Histopathological features of female urethral diverticula match the criteria for paraurethral cysts. Concomitant use of synthetic meshes should be avoided due to the possibility of an infectious etiology. Transvaginal excision of the sac is recommended, while transurethral procedures are contraindicated.

T1 glottic carcinoma involving the posterior commissure.

OBJECTIVES/HYPOTHESIS: The posterior commissure is an uncommon site of glottic carcinoma. The aim of the study was to compare the clinical and prognostic characteristics of glottic carcinoma of the posterior commissure and the vocal cords. STUDY DESIGN: Retrospective case control study. METHODS: The study group consisted of 40 patients aged 32 to 84 years (mean, 62.7 +/- 10.7) diagnosed with T1 glottic carcinoma involving the posterior commissure from 1960 to 2008. Data on clinical features and outcome were collected from the medical files and compared with the data for 42 patients aged 30 to 87 years (mean, 64.4 +/- 11.8) with T1 vocal cord carcinoma. RESULTS: : There were no significant differences in clinical characteristics between the groups except for the higher rate of smokers among the patients with vocal cord carcinoma (95% vs. 65%, P = .01). All patients were treated primarily with radiotherapy. Disease-free survival in the posterior commissure carcinoma group was 76.1% after 5 years and 72.3% after 10 years, and in the vocal cord carcinoma group, 95% after 5 and 10 years (P = .012). The risk of recurrence was higher when the tumor involved the posterior commissure (hazard ratio, 8.78; 95% CI, 1.12-68.5, P = .038). CONCLUSIONS: T1 glottic carcinoma involving the posterior commissure has a more aggressive biological behavior and a worse prognosis than T1 glottic carcinoma of the vocal cords. Smoking, which is an important pathogenetic factor in vocal cord carcinoma, plays a lesser role in posterior commissure carcinoma. Laryngoscope, 2009.

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 human DNA Topoisomerase II-alpha in squamous cell carcinoma of the larynx and its correlation with clinicopathologic variables.

The aggressiveness of laryngeal squamous cell carcinoma (SCC) is unpredictable. Topoisomerase (Topo) II-alpha is an essential nuclear enzyme; its expression rises at the end of the S-G2/M phase and drops at completion of mitosis. This study sought to determine if Topo II-alpha expression can serve as a prognostic factor in laryngeal SCC. Specimens from 56 consecutive patients were immunohistochemically stained for Topo II-alpha, and the number of positive cells in the areas of highest staining was counted in 3 highpower fields (X400) (Topo II-alpha index). Differences in the Topo II-alpha index by the presence or absence of recurrence, tumor stage and grade, and disease course were analyzed statistically. On multivariate Cox regression analysis, the Topo II-alpha index (>70 or < or =70) (P = .008) and tumor grade (P = .034) independently predicted disease-free survival. These findings suggest that high Topo II-alpha expression may be a useful indicator of tumor aggressiveness and poor outcome in laryngeal SCC.