Programmed death ligand-1 (PD-L1) immunohistochemical assessment using the QR1 clone in muscle-invasive urothelial carcinomas: a comparison with reference clones 22C3 and SP263.

Programmed death ligand-1 (PD-L1) immunohistochemical (IHC) status is used to predict which patients with metastatic urothelial carcinoma (UC) will respond to immunotherapy. We aimed to compare QR1(Quartett), 22C3 (Dako), and SP263 (Ventana) detection of PD-L1 expression in muscle-invasive UCs and determine the best scoring algorithm for assessment of PD-L1 expression when using the QR1 clone. Our study included 69 UCs. For SP263 and 22C3, PD-L1-positive tumor cell (TC) and/or immune cell (IC) percentages (TC%/IC%) and the Combined Positive Score (CPS) were assessed, respectively (positivity cut-offs of ≥ 25% and ≥ 10). For QR1, both interpretation systems were evaluated. The concordances between assays were calculated. PD-L1 IHC staining characteristics were comparable between QR1, 22C3, and SP263 in both conventional and variant histology UCs. We demonstrated strong or very strong correlations between clones; the strongest correlation for TCs was between QR1 and SP263 (r = 0.92; p = 0.001) and for ICs was between QR1 and 22C3 (r = 0.85; p = 0.001). Our comparative analysis of the scoring algorithms revealed very good concordances among the three assays (range 0.791-0.878); the highest concordance was between QR1 and SP263 when CPS was used as the scoring algorithm for QR1 (0.878; p < 0.001). Our study is the first to demonstrate that the QR1 clone can be used to evaluate PD-L1 status in UCs, with a very good agreement rate with the reference clones. QR1 appeared to be more similar to the SP263 clone. With regard to the scoring algorithm, when evaluating PD-L1 expression using QR1 clone, CPS performed better compared with the TC%/IC% score.

Fascin-1 and its role as a serological marker in prostate cancer: a prospective case-control study.

AIM: This study aims to investigate any modification of serological FSCN1 in prostate cancer patients compared with patients without neoplasia. MATERIAL & METHODS: Clinical data and blood specimens from patients with and without prostate cancer were obtained. A quantitative sandwich ELISA method was used to determine serological values of FSCN1. RESULTS: Although serum values of FSCN1 were dissimilar in the two cohorts of patients (6.90 vs 7.33 ng/ml), the difference was not statistically significant (p = 0.20). Serum values of FSCN1 stratified for Gleason score groups were not significantly distinguishable (p = 0.65). A negative correlation (rho = -0.331; p = 0.009) was reported between FSCN1 and age. CONCLUSION: Further studies are required to evaluate a possible diagnostic role of FSCN1 in prostate cancer.

PD-L1 Expression in Muscle Invasive Urothelial Carcinomas as Assessed via Immunohistochemistry: Correlations with Specific Clinical and Pathological Features, with Emphasis on Prognosis after Radical Cystectomy.

In the present study, we analyzed Programmed Death Ligand-1 (PD-L1) expression in radical cystectomy (RC) specimens from patients with muscle-invasive urothelial carcinoma (UC), in order to assess any correlations with specific clinicopathological features and its potential prognostic value. A multi-institutional study was performed within the departments of urology and pathology at the Mureș County Hospital, Romania, and Centre Hospitalier Lyon Sud, France. Sixty-nine patients with MIBC were included, for whom tumor histology (conventional versus histological variant/differentiation), tumor extension (T), lymph node involvement (N), and distant metastases (M) were recorded. PD-L1 immunostaining was performed using the 22C3 clone and was interpreted using the combined positive score (CPS) as recommended (Dako Agilent, Santa Clara, CA, USA). Positive PD-L1 immunostaining was more prevalent among UCs with squamous differentiation compared to conventional UCs and trended towards an improved OS (p = 0.366). We found the T stage to be a risk factor for poor survival in PD-L1-positive patients (HR 2.9, p = 0.021), along with the N stage in PD-L1-negative patients (HR 1.98, p = 0.007). No other clinicopathological factor was found to be significantly associated with PD-L1 positivity. Thus, we confirm the need for PD-L1 immunostaining prior to initiating immune checkpoint inhibitor therapy for a more accurate assessment of the patients' chances of responding to treatment.

Evaluation of a DNA Extraction and Purification Protocol Using Archived Formalin-fixed Paraffin-embedded Tissues for BRAF Mutations Analysis in Papillary Thyroid Microcarcinomas.

The isolation of good quality genomic DNA from formalin-fixed, paraffin-embedded tissues is challenging, especially in cases of small tissue specimens. The aim of our study was to evaluate a DNA extraction protocol using formalin-fixed, paraffin-embedded tissues in our laboratory and apply this method to a series of papillary thyroid microcarcinomas (PTMCs). A total of 25 PTMCs and 3 papillary thyroid carcinoma control cases were included in the study. We assessed a DNA extraction protocol on the basis of a precipitation method (MasterPure DNA purification kit, Epicentre), according to the manufacturer's instructions. All PTMCs were subject to real-time polymerase chain reaction (PCR) amplification targeting the BRAF gene and a housekeeping gene (GAPDH). BRAF gene mutations were then assessed by high-resolution melting analysis and confirmed by sequencing of the PCR products. Using this extraction method, we produced good yields of DNA (mean concentration, 147.4±77.8 ng/µL), in addition to high levels of purity (mean A260/A280 ratio: 1.63±0.1). We successfully assessed the BRAF mutation status in 24 cases (16 BRAF-negative; 8 BRAF positive), although 1 case revealed an inconclusive pattern following high-resolution melting analysis and sequencing of the PCR products. We observed no differences in the tumor size (P=0.693), storage period of the tumor block (P=0.282), DNA concentration (P=0.243), DNA purity (P=0.458), CpGAPDH (P=0.173), or CpBRAF (P=0.217) values between the BRAF-mutated and nonmutated group of PTMCs. Our findings demonstrate the importance of a reliable, reproducible DNA extraction technique for efficient PCR amplification, uniformly applied to all cases in this study, regardless of the BRAF mutation status.

Histopathological and perioperative factors influencing the length of hospital stay and patients' outcome after radical cystectomy for urothelial carcinoma.

INTRODUCTION: Length of hospital stay (LOS) is considered as a key factor in estimating outcomes after radical cystectomy (RC) in urothelial carcinoma (UC) patients. We aimed to assess whether clinical perioperative (age, gender, type of urinary diversion technique) and histopathological factors [UC variant, primary tumor, node, metastasis (pTNM) staging] could be a determining factor for LOS, as well as its influence on overall survival (OS) in a single institution, retrospective cohort study. PATIENTS, MATERIALS AND METHODS: We included a total of 69 UC patients that had RC performed in our Department during November 2011 and October 2018. Regular LOS was considered arbitrarily up to 12 days. All factors were analyzed in relation to LOS, using the chi-square and the Mann-Whitney tests. Impact of LOS on survival was assessed using the Kaplan-Meier and the Cox regression methods. RESULTS: Age was associated to increased LOS (p=0.042), as well as the type of urinary diversion (p=0.003). Patients with complex diversion were found more frequently in the prolonged LOS group (ileal conduit p=0.006, Mainz pouch p=0.15, Camey neobladder p=0.517). Histopathologically, N stage had a significant association to LOS (p=0.044). Survival analysis showed decreased survival in the prolonged LOS group (p=0.653). Cox regression found no influence of LOS (p=0.653), advanced age (p=0.518) or type of urinary diversion on OS. CONCLUSIONS: Advanced age, the complexity of urinary diversion and lymph node involvement were found as associated factors for prolonged LOS in RC patients. The impact of LOS on survival is uncertain, requiring larger, in-depth studies.

Histopathological predictive factors for the overall survival rate in patients with urothelial carcinoma of the bladder treated by radical cystectomy: a Romanian cohort study.

INTRODUCTION: Urothelial carcinoma (UC) variants are considered as having a more aggressive behavior and a more advanced stage at presentation than conventional UC. However, the evidence supporting the role of UC variants on overall survival (OS) is conflicting. We aimed to assess the impact of demographic factors (age at surgery, gender) and tumor characteristics [conventional∕variant UC, associated carcinoma in situ (CIS), associated papillary component, Tumor, Node, Metastasis (TNM) staging, positive surgical margins] on OS in a series of patients treated for UC in our Department. PATIENTS, MATERIALS AND METHODS: We performed a retrospective, cohort study and included 69 UC patients treated by radical cystectomy (RC) in our Department over an eight-year period, with complete follow-up information. Associations of UC variants as well as demographic and morphological factors with OS were assessed using univariable and multivariable Cox analysis. RESULTS: Our data showed that UC variants were statistically significantly associated with the presence of distant metastases (p=0.036) and positive surgical margins (p=0.009), but had no influence on OS (p=0.504). Further on, we demonstrated that age at surgery (p=0.045), tumor stage (p=0.012), lymph node involvement (p=0.009), and presence of positive surgical margins (p=0.002) had a statistically significant influence on OS both by univariable and multivariable Cox analysis. CONCLUSIONS: Age, tumor stage and lymph node involvement, as well as positive surgical margins represent prognostic factors in RC patients. UC variants were more likely to be associated to metastases and positive surgical margins but had no influence on OS.

Morphological features predictive for BRAF(V600E) mutation in papillary thyroid microcarcinomas.

BACKGROUND: The B-Raf proto-oncogene serine∕threonine kinase (BRAF) V600E (BRAF(V600E)) mutation represents a very specific marker for papillary thyroid carcinoma (PTC), including microcarcinomas (PTMCs). However, assessment of the BRAF(V600E) mutational status is expensive and not available in all pathology laboratories. AIM: We aimed to evaluate if we can identify those morphological features that could predict the presence of the BRAF(V600E) mutation in a series of PTMCs. MATERIALS AND METHODS: Nineteen PTMCs with analysis of 25 tumor foci were included. The following histological features were evaluated: size of the tumor, multifocality, extrathyroidal extension, tumor's border, characteristic PTC nuclear features, tumor-associated stromal reaction and histological variant. All PTMCs foci were subject to real-time polymerase chain reaction (RT-PCR) amplification targeting the BRAF gene. BRAF(V600E) mutation was assessed by high resolution melting (HRM) analysis and confirmed by Sanger sequencing. Morphological features associated with BRAF(V600E) positive and BRAF(V600E) negative PTMCs were compared using the two-tailed Fisher's exact test, with α set at ≤0.05. RESULTS: Out of the 25 PTMC foci, 16 (64%) were BRAF(V600E) negative, whereas nine (36%) were BRAF(V600E) positive. Our data showed that subcapsular localization (p=0.013), conventional histological type (p=0.05) and tumor-associated stromal reaction (moderate∕extensive fibrosis) (p=0.032) were significantly associated with the mutation. CONCLUSIONS: We have demonstrated the value of several morphological features in predicting a BRAF(V600E) mutation profile in PTMCs. All these parameters should be documented in the histopathological report, as they seem to be associated with this mutation and could serve as a risk stratification tool in the selection of patients in need for adjuvant post-surgery therapy.

XRCC3 Thr241Met and XPD Lys751Gln gene polymorphisms and risk of clear cell renal cell carcinoma.

INTRODUCTION: In the last decade, an increasing number of polymorphisms in DNA repair genes have been identified and their involvement in carcinogenesis was studied. Despite the fact that XRCC3 and XPD DNA repair genes association with several types of cancer was widely studied, their role in the development of clear cell renal cell carcinoma (CCRCC) has not been established in the European population. OBJECTIVE: The objective of this study was to investigate the association of XRCC3 Thr241Met and XPD Lys751Gln gene polymorphisms with the risk of CCRCC and the association between these genotypes and CCRCC histopathological prognostic factors (pathologic stage, Fuhrman grade, tumor diameter). METHODS: This study included 73 patients with CCRCC and 100 healthy individuals without cancer. We used the PCR-RFLP method to determine XRCC3 and XPD genotypes. RESULTS: The XPD 751 variant genotype (Lys/Gln) was more frequent in CCRCC patients than in healthy individuals (OR = 2.92, 95%CI: 1.47-5.79, p= 0.001). Regarding the XRCC3 Thr241Met/XPD Lys751Gln combined genotypes a significant difference was found between patients and controls for Thr/Thr+Lys/Gln (OR = 5.44, 95%CI: 2.09-14.15, p= 0.0003) and for Thr/Met+Gln/Gln (OR = 11.2, 95%CI: 1.95-100.4, p= 0.01).No association was found between any of the studied genotypes and histopathological prognostic factors of CCRCC. CONCLUSIONS: Our findings indicate that XPD Lys751Gln polymorphism may be a risk factor for CCRCC. Regarding the XRCC3 Thr241Met polymorphism, an association with CCRCC was found only in XRCC3 Thr241Met/XPD Lys751Gln combined genotypes.

The storage period of the formalin-fixed paraffin-embedded tumor blocks does not influence the concentration and purity of the isolated DNA in a series of 83 renal and thyroid carcinomas.

Optimal recovery of nucleic acids from formalin-fixed paraffin-embedded (FFPE) tissues is highly dependent on a series of pre-extraction steps, mainly related (but not limited) to fixation. The aim of our study was to investigate if the storage period of the FFPE blocks had a significant effect on the isolated DNA. We examined the quantity and purity of the isolated DNA from 83 FFPE blocks, corresponding to malignant thyroid (n=28) and renal (n=55) carcinomas that had been stored in our department for up to eight years. The DNA extraction protocol was based on a precipitation method (MasterPure™ DNA Purification Kit, Epicentre), in accordance to the manufacturer instructions, optimized in our laboratory. A spectrophotometer was used to determine the yield (A260) and purity (A260/A280 ratio) of the isolated DNA. We successfully isolated good DNA quantity and purity from all our study cases (mean concentration: 223.4 ± 104.16 ng/µL; mean A260/A280 ratio: 1.68 ± 0.09). Moreover, no statistically significant differences were observed between tumor blocks stored for 2-3 years and 7-8 years, respectively, both in terms of DNA quantity (p=0.196) and purity (p=0.663). In conclusion, we successfully validated an efficient, reproducible DNA extraction technique that provided a good range of DNA concentrations and purity, regardless the type of tissue (thyroid or kidney). Moreover, we demonstrated that the storage period of the FFPE blocks does not have a significant influence on the DNA quantity and purity.

Cyclooxygenase-2 and matrix metalloproteinase-9 expressions correlate with tissue inflammation degree in periodontal disease.

INTRODUCTION: Cyclooxygenase-2 (Cox-2) and matrix metalloproteinase-9 (MMP-9) have synergistic effects in the degradation of the extra-cellular matrix. OBJECTIVE: The aim of our study was to correlate the intensity of inflammation with MMP-9 and Cox-2 expression in the periodontal tissue of patients with chronic inflammatory disease (gingivitis and chronic periodontitis) in order to determine the role of these two biomarkers in the progression of periodontal disease. MATERIALS AND METHODS: To conduct this study we analyzed the gingival biopsies taken from patients clinically divided into three study groups: Group I (control): Patients free of periodontal disease (seven biopsies); Group II: Patients with gingivitis (10 biopsies); Group III: Patients with chronic periodontitis (10 biopsies). In these three groups, we graded the intensity of inflammation in the lamina propria and the immunohistochemical expression of MMP-9 and Cox-2. RESULTS: The presence of a large number of inflammatory cells in the lamina propria in patients with gingivitis or chronic periodontitis (Groups II and III) correlated with the clinically diagnosed inflammation of the gingival tissue. The expression of MMP-9 was higher in patients with chronic periodontitis than in those with gingivitis, showing a trend towards statistical significance (p=0.07, Mann-Whitney U-test). The expression of Cox-2 in periodontitis was also higher compared to gingivitis (p=0.05, Mann-Whitney U-test) and to controls (p=0.001, Mann-Whitney U-test).The inflammation score could be positively correlated to the MMP-9 and Cox-2 expression scores at the overall study group, but not separately on gingivitis and periodontitis patients. CONCLUSIONS: The presence of an intensive inflammatory infiltrate is characteristic both for periodontitis and gingivitis. MMP-9 and Cox-2 show higher expression in periodontitis, than in gingivitis and healthy controls, but MMP-9 and Cox-2 expression scores cannot be directly correlated to the grade of inflammatory infiltrate in the two different disease entities. As biomarkers of chronic inflammation activity, angiogenesis, and degradation of the extracellular matrix, MMP-9 and Cox-2 can be used in clinical practice for the detection of patients with chronic periodontitis risk, at whom treatment with Cox-2 and MMP-9 inhibitors may be considered.

Micropapillary urothelial carcinoma: an aggressive variant of urothelial carcinoma.

Micropapillary urothelial carcinoma (MPC) is a rare variant of urothelial carcinoma (UC) with an aggressive clinical course, an advanced stage at first presentation and a high metastatic potential. The aim or our study is to present five illustrative cases of MPC, diagnosed among the 21 patients with UC treated by radical cystectomy in the Department of Urology, County Hospital of Tirgu Mures, Romania, between January 1, 2011 and December 31, 2013. The morphological and immunohistochemical features of this rare and aggressive variant of UC, as well as a brief review of the literature are all presented. All five cases were associated with lymph node metastases with micropapillary features, regardless of the microscopic aspect of the tumor on the surgical specimens [transurethral resection (TUR) or cystectomy]. Three of them had a micropapillary component in the TUR, on the cystectomy specimen, or in both, along with lymph nodes metastases. In two cases, the MPC features were present only in the lymph node metastasis, with a conventional UC on the TUR and on the cystectomy. Immunohistochemical staining demonstrated that both micropapillary and associated conventional UC were positive for CK7 and CK20. Ki67 was expressed in 40% of tumor cells and CD34 was positive in the endothelial cells and negative in the flattened spindled cells lining the retraction spaces around tumor cell nests. MPC is a highly aggressive variant of UC with specific morphological characteristics. Any amount of micropapillary component found in UC is significant, and should be reported because it encompasses an aggressive clinical behavior and a poor prognosis.

Morphological aspects and distribution of interstitial cells of Cajal in the human upper urinary tract.

OBJECTIVE: The mechanism by which the ureter propels urine towards the bladder has a myogenic origin, through peristaltic contractions. This pyeloureteral autorhythmicity is generated by specialized, electrically active cells, the interstitial cells of Cajal, located in the proximal regions of the upper urinary tract. The aim of this study was to describe the exact location and the distribution of interstitial Cajal cells in the human upper urinary tract and to analyze their normal number and morphology. This is a preliminary study, which will allow the study of these cells in different urinary tract pathologies. MATERIAL AND METHOD: Urinary tract fragments were sampled at different levels, from 13 autopsy cases. Cases with clinical evidence of renal disease, and with histological changes in the kidney or in the urinary tract tissue samples, visible in hematoxylin-eosin staining, were excluded. The interstitial Cajal cells were highlighted with anti-CD117 antibody, immunohistochemically. RESULTS: Cajal cells were indirectly highlighted by the presence of a finely granulated cytoplasm indicating immunoreactivity. These cells were spindle-shaped or stellate, with cytoplasmic extensions at one or both poles of the cell and large oval nucleus. We found that interstitial Cajal cells were located at all upper urinary tract levels, with a higher predominance in the calyces and pyelon. Interstitial Cajal cells were observed mostly between the two layers of the muscularis, but also between the muscle bundles. Most often, these cells were parallel to the muscle fibers. CONCLUSION: Our study describes the method of detection of interstitial Cajal cells in normal human urinary tract. These results can be used to analyze the number, morphology and the location of these cells in different congenital pathologies, such as vesicoureteral reflux, pyeloureteral junction obstruction or primary obstructive megaureter.

Diagnostic value of HBME-1, CD56, Galectin-3 and Cytokeratin-19 in papillary thyroid carcinomas and thyroid tumors of uncertain malignant potential.

AIM: We aimed to evaluate four immunohistochemical markers (HBME-1, Galectin-3, Cytokeratin-19 and CD56) used alone or in panels in a series of papillary thyroid carcinoma (PTC) and thyroid tumors of uncertain malignant potential (TT-UMP) cases. MATERIALS AND METHODS: We performed an immunohistochemical analysis on a tissue micro-array of 11 PTCs [six classic (CPTC), five follicular variant (FVPTC)] and 31 TTs-UMP. A control group of 11 benign thyroid lesions/tumors was also included. RESULTS: CD56, whose expression is reduced or absent in thyroid carcinomas, was the most sensitive marker (81.8%), showing a "malignant" profile in 5/6 CPTCs and 4/5 FVPTCs. It was followed by HBME-1 (63.6% sensitivity). Cytokeratin-19 and Galectin-3 were the least sensitive antibodies (45.6%), but the most specific ones (100%). Three panels consisting of CD56 and/or Cytokeratin-19/Galectin-3 and HBME-1 and/or CD56 reached the highest sensitivity (90.9%) and the highest negative predicting value (87.5 and 83.3, respectively). In TTs-UMP, Cytokeratin-19, Galectin-3, HBME-1 and CD56 stained negatively in most of the cases (90.3%, 83.9%, 87.1% and 61%, respectively) and no statistically significant differences compared to the benign thyroid lesions' immunoprofile could be observed. CONCLUSIONS: New panels of antibodies, consisting of CD56 and/or Cytokeratin-19/Galectin-3 and CD56 and/or HBME-1 that were found to be highly sensitive for PTC in our study, are reported. Applying these panels to TTs-UMP seems also useful. Our results showed that these tumors have an immunoprofile similar to the benign thyroid lesions, suggesting that they are most likely to have a benign rather than a malignant biological behavior.

The place of prostate rebiopsy in the diagnosis of prostate cancer.

AIM: To highlight the role of prostate rebiopsy in the diagnosis of prostate cancer (PCa) in cases with an atypical small acinar proliferation (ASAP) diagnosis on the initial biopsy. MATERIALS AND METHODS: A retrospective study on 1525 patients who underwent prostate needle biopsy (PB) over a period of four years (2009-2012) was performed. For each patient the following were analyzed: age, prostate volume, digital rectal examination (DRE), serum total prostate specific antigen (tPSA), number of the cores taken. All PB were examined in HE staining and in difficult cases, immunohistochemistry (IHC) for basal cell markers was performed in order to establish a correct diagnosis. According to morphological criteria and IHC results, all PB were classified into four category of diagnosis: PCa, ASAP, high-grade prostate intraepithelial neoplasia (HGPIN) and benign (including normal tissue, inflammatory lesions, and prostatic atrophy). In ASAP cases, a rebiopsy was performed. RESULTS: PCa detection on the first biopsy was 69.77%, with a 3% incidence of ASAP and 1% of HGPIN, values similar with those in the literature. After rebiopsy the overall detection rate of PCa was improved to 71.01%, with a detection rate of 41.17% on the second biopsy. CONCLUSIONS: PCa diagnosis is the result of a complex algorithm including DRE, tPSA, transrectal ultrasound (TRUS) examination and TRUS-guided prostate biopsy. TRUS-guided prostate biopsy is the key step of this algorithm; it confirms the diagnosis of PCa and must be repeated in cases with a solid clinical suspicion of PCa, whenever histopathological features are inconclusive even after IHC staining.

Fibro-hyaline involution of a papillary thyroid carcinoma metastasis in a lymph node, consecutive to radioiodine therapy, mimicking a parathyroid adenoma. A case presentation.

OBJECTIVE: The aim of the study is to present the unusual changes that a lymph node metastasis of papillary thyroid carcinoma (PTC) underwent after radioiodine therapy, leading to the confusion with a parathyroid adenoma (PA). PATIENT AND METHODS: Eight years after a total thyroidectomy and radioiodine ablation with 73.35 mCurie 131I for PTC, a 67-year-old female presented with an enlarged, painless, nodular mass in the left lateral neck region. Clinical examination revealed a firm nodule located on the site of the left inferior parathyroid gland. Elevated serum parathyroid hormone level (120 pg/mL) and parathyroid scintigraphy led to a suspicion of PA. A minimally invasive surgical procedure was performed to remove the mass, which was sent to the Department of Pathology, Emergency County Hospital, Tirgu Mures, Romania, as left PA. It was fixed and processed for microscopic evaluation. RESULTS: On macroscopic examination, the surgical specimen was oval; it had 13 mm at the largest diameter and weighted 2 g. On microscopy, the lesion appeared as a fibro-hyaline, intensely acidophilic, acellular mass, with calcifications. It was limited by a delicate capsule in which one typical psammoma body was present. At the periphery, on one single level, a small mass of cells of indefinite origin was noticed. Immunohistochemistry (IHC) was done to ascertain the origin of these cells: they were negative for Pan-Cytokeratin AE1/AE2, Parathormone and Thyroglobulin antibodies, but positive for Leukocyte Common Antigen (LCA) antibody, proving that they were lymphocytes, most likely residual from a lymph node. CONCLUSIONS: These IHC data, together with the microscopic feature, the presence of the psammoma body and the patient's history, excluded a PA and led to a diagnosis of fibro-hyaline involution of a PTC metastasis in a lymph node, consecutive to radioiodine therapy. Without careful microscopic examination and accurate clinical information, this lesion could represent a real diagnostic challenge.

Bilateral primary fallopian tube carcinoma: a case report.

Primary cancer of the fallopian tube is a very rare tumor nowadays, accounting for approximately 0.14-0.3% of all tumors of the female genital tract. From these, bilateral primary cancer is found in less than 25% of all cases. We report here a case of bilateral primary cancer of the fallopian tube in a 48-year-old woman, associating uterine fibromatosis.

Pseudobenign prostate carcinomas: causes of false-negative biopsy results.

Prostate carcinomas are continuously surprising the pathologists through their multitude of variants and histological subtypes, some of them being recently described and characterized. Among these are individualized: atrophic carcinoma, foamy gland, pseudohyperplastic, microcystic, certain subtypes of ductal adenocarcinoma and hormone-treated adenocarcinoma, which because of minimal architectural and/or cytological atypia are often under-diagnosed, especially in small tissue fragments. This paper presents the morphological criteria, including information provided by some immunohistochemical markers for positive and differential diagnosis of these variants/subtypes of prostate adenocarcinoma with which the pathologist should be familiar and avoid their confusion with a series of similar histological structures or benign/premalignant lesions.

Histopathological and immunohistochemical features of gastrointestinal stromal tumors.

Gastrointestinal stromal tumors (GISTs) are the most frequent mesenchymal tumors of the gastrointestinal tract. Major advances in their definition and classification and the understanding of their molecular mechanisms have recently been made. These advances have become a model of targeted therapy in oncology. The diagnosis of GISTs relies on histological arguments - proliferation of spindle cells, seldom of epithelioid cells or both spindle and epithelioid cells - and on immunohistochemical arguments - expression of CD117 usually associated with CD34 expression. The evaluation of the prognosis is essential and based on a simple algorithm using two prognostic parameters, tumor size and mitotic index. The aim of this paper is a complex histopathological assessment, using both classic and modern (immunohistochemistry) techniques, of the GISTs comprised in the study. GISTs occur mainly in older adults (median age 60-69 years), anywhere along the gastrointestinal tract but also retroperitoneal. Most of them were nodular (75%), tumor necrosis and mucosal ulceration being the most frequent encountered secondary alterations; these modifications proved to be significantly correlated with large tumor size and high malignancy. Immunohistochemical evaluation revealed that 77 (97%) cases of GISTs presented a positive reaction for CD117, 50 (63%) cases were positive for CD34, 19 (24%) were positive for SMA and only 10 (13%) were positive for S100. Immunohistochemical evaluation remains an important tool of pathology in the diagnosis of GISTs, in the differential diagnosis from other gastrointestinal mesenchymal tumors and represents the gold standard for diagnosis of these tumors and an eligibility criterion for imatinib therapy.

Retroperitoneal seminoma as a first manifestation of a partially regressed (burnt-out) testicular germ cell tumor.

Regressed (burnt-out) testicular germ cell tumors (TGCT) are rare clinical situations that are clinically difficult to recognize. This 43-year-old patient was admitted because of a suspicion of prostatic carcinoma, which eventually was followed by transrectal ultrasonography and a CT scan, both of which revealed a large retroperitoneal mass. Surgery showed extensive ureteral and vas deferens infiltration. Pathology was consistent with a classical seminoma. Eventually, testes were normal on palpation but ultrasonography only revealed areas of fibrosis and microcalcifications in the left testis, which was followed by a left orchidectomy. Microscopically, there were extensive areas of fibrosis and only a 2 mm area of seminoma was demonstrated. The few areas of uninvolved testicular tissue lacked lesions of intratubular germ cell neoplasia (IGCNU). Retroperitoneal germ cell tumors are rare in the male and consequently, an origin from an occult testicular tumor should always be discarded by image analysis and eventually a biopsy. Immunologic response may be responsible for tumor involution.

Predictive preoperatory variables of the prostate tumor volume.

Prostate cancer (PCa) is the second most frequent malignant tumor in men worldwide and the most common form of cancer in men over 50-year-old. The adequate preoperative estimation of tumor volume in order to identify small tumors that lack a short-term aggressive behavior and do not necessitate a forthwith-radical prostatectomy (RP) is the subject of various recent studies and numerous debates. In this study, that included 128 cases, we attempted to evaluate some of the common preoperative variables (patient's age, total prostate volume determined on ultrasound examination, serum PSA, the number of positive biopsies and tumor size, the percentage of tumor length and the Gleason score) that could predict the tumor volume on the final RP. Based on these correlations, we develop a scoring system that combines only the Gleason score, the number of positive biopsies and the percentage of tumor length and that has been statistically proved to be correlated and predictive for the tumor volume. Our study brings additional and practical information about a true and effective prospective evaluation of the volume of the PCa.