Difficulties in diagnostics of lung tumours in biopsies: an interpathologist concordance study evaluating the international diagnostic guidelines.

AIMS: Accurate and reliable diagnosis is essential for lung cancer treatment. The study aim was to investigate interpathologist diagnostic concordance for pulmonary tumours according to WHO diagnostic criteria. METHODS: Fifty-two unselected lung and bronchial biopsies were diagnosed by a thoracic pathologist based on a broad spectrum of immunohistochemical (IHC) stainings, molecular data and clinical/radiological information. Slides stained with H&E, thyroid transcription factor-1 (TTF-1) clone SPT24 and p40 were scanned and provided digitally to 20 pathologists unaware of reference diagnoses. The pathologists independently diagnosed the cases and stated if further diagnostic markers were deemed necessary. RESULTS: In 31 (60%) of the cases, ≥80% of the pathologists agreed with each other and with the reference diagnosis. Lower agreement was seen in non-small cell neuroendocrine tumours and in squamous cell carcinoma with diffuse TTF-1 positivity. Agreement with the reference diagnosis ranged from 26 to 45 (50%-87%) for the individual pathologists. The pathologists requested additional IHC staining in 15-44 (29%-85%) of the 52 cases. In nearly half (17 of 36) of the malignant cases, one or more pathologist advocated for a different final diagnosis than the reference without need of additional IHC markers, potentially leading to different clinical treatment. CONCLUSIONS: Interpathologist diagnostic agreement is moderate for small unselected bronchial and lung biopsies based on a minimal panel of markers. Neuroendocrine morphology is sometimes missed and TTF-1 clone SPT24 should be interpreted with caution. Our results suggest an intensified education need for thoracic pathologists and a more generous use of diagnostic IHC markers.

Real-World Diagnostic Accuracy and Use of Immunohistochemical Markers in Lung Cancer Diagnostics.

OBJECTIVES: Accurate and reliable diagnostics are crucial as histopathological type influences selection of treatment in lung cancer. The aim of this study was to evaluate real-world accuracy and use of immunohistochemical (IHC) staining in lung cancer diagnostics. MATERIALS AND METHODS: The diagnosis and used IHC stains for small specimens with lung cancer on follow-up resection were retrospectively investigated for a 15-month period at two major sites in Sweden. Additionally, 10 pathologists individually suggested diagnostic IHC staining for 15 scanned bronchial and lung biopsies and cytological specimens. RESULTS: In 16 (4.7%) of 338 lung cancer cases, a discordant diagnosis of potential clinical relevance was seen between a small specimen and the follow-up resection. In half of the cases, there was a different small specimen from the same investigational work-up with a concordant diagnosis. Diagnostic inaccuracy was often related to a squamous marker not included in the IHC panel (also seen for the scanned cases), the case being a neuroendocrine tumor, thyroid transcription factor-1 (TTF-1) expression in squamous cell carcinomas (with clone SPT24), or poor differentiation. IHC was used in about 95% of cases, with a higher number of stains in biopsies and in squamous cell carcinomas and especially neuroendocrine tumors. Pre-surgical transthoracic samples were more often diagnostic than bronchoscopic ones (72-85% vs. 9-53% for prevalent types). CONCLUSIONS: Although a high overall diagnostic accuracy of small specimens was seen, small changes in routine practice (such as consequent inclusion of p40 and TTF-1 clone 8G7G3/1 in the IHC panel for non-small cell cancer with unclear morphology) may lead to improvement, while reducing the number of IHC stains would be preferable from a time and cost perspective.

Impact of the 2014 International Society of Urological Pathology Grading System on Concept of High-Risk Prostate Cancer: Comparison of Long-Term Oncological Outcomes in Patients Undergoing Radical Prostatectomy.

Objective: To investigate the relationship between the new International Society of Urological Pathology (ISUP) grading system, biochemical recurrence (BCR), clinical progression (CP) and cancer related death (CRD) after open radical prostatectomy (RP) and determine whether the 2014 ISUP grading system influences the concept of high-risk prostate cancer (HRPCa). Patients and Methods: A total of 1,754 men who underwent RP from 2005 to 2017 were identified from a database at a single tertiary institution. Histopathology reports were reassessed according to the 2014 ISUP grading system. All preoperative, pathological, and clinical follow-up data were obtained. Univariable and multivariable Cox regression, Kaplan-Meier and log-rank analyses were performed. Results: At a median (quartiles) follow-up of 83 (48-123) months, 446 men (25.4%) had BCR, 77 (4.4%) had CP and 39 (2.2%) died from cancer. Grade groups 1, 2, 3, 4, and 5 were detected in 404 (23%), 931 (53.1%), 200 (11.4%), 93 (5.3%), and 126 (7.2%), respectively. 10-year biochemical progression free survival difference between Grade group 3 and 4 was minor but significant (log-rank p = 0.045). There was no difference between Grade groups 3 and 4 comparing 10-year clinical progression free and 10-year cancer specific survival: p = 0.82 and p = 0.39, respectively. Group 5 had the worst survival rates in comparison with other groups (from p < 0.005 to p < 0.0001) in all survival analyses. Pathological stage (hazard ratio (HR) 2.6, p < 0.001), positive surgical margins (HR 2.2, p < 0.0001) and Grade group (HR 10.4, p < 0.0001) were independent predictors for BCR. Stage and Grade group were detected as independent predictors for CP-HR 6.0, p < 0.0001 and HR 35.6, p < 0.0001, respectively. Only Grade group 5 (HR 12.9, p = 0.001) and pT3b (HR 5.9, p = 0.001) independently predicted CRD. Conclusions: The new ISUP 2014 grading system is the most significant independent predictor for BCR, CP, and CRD. Grade group 3 and 4 had similar long-term disease progression survival rates and could potentially be stratified in the same risk group. High-risk cancer associated only with group 5.

Association of Ki-67 Labelling Index and IL-17A with Pituitary Adenoma.

The aim of the present study was to determine if the Ki-67 labelling index reflects invasiveness of pituitary adenoma and to evaluate IL-17A concentration in blood serum of pituitary adenoma patients. The study was conducted in the Hospital of Lithuanian University of Health Sciences. All pituitary adenomas were analysed based on magnetic resonance imaging findings. The suprasellar extension and sphenoid sinus invasion by pituitary adenoma were classified according to Hardy classification modified by Wilson. Knosp classification system was used to quantify the invasion of the cavernous sinus. The Ki-67 labelling index was obtained by immunohistochemical analysis with the monoclonal antibody, and serum levels of IL-17A were determined by enzyme-linked immunosorbent assay (ELISA). Sixty-nine PA tissue samples were investigated. Serum levels of IL-17A were determined in 60 patients with PA and 64 control subjects. Analysis revealed statistically significantly higher Ki-67 labelling index in invasive compared to noninvasive pituitary adenomas. Median serum IL-17A level was higher in the pituitary adenoma patients than in the control group. Conclusion. IL-17A might be a significant marker for patients with pituitary adenoma and Ki-67 labelling index in case of invasive pituitary adenomas.

Atypical Teratoid/Rhabdoid Tumor After In Vitro Fertilization: Illustrative Case Report and Systematic Literature Review.

OBJECTIVE: In vitro fertilization (IVF) is increasingly used for the treatment of infertile couples worldwide. The association between IVF and cancer risk in offspring is conflicting. We present a case of atypical teratoid/rhabdoid tumor (AT/RT) in a girl conceived by IVF and present results of systematic review of literature of primary intracranial neoplasms diagnosed in children conceived by IVF. METHODS: A systematic review of literature was conducted on April 12, 2017, to identify previously published reports of intracranial brain tumors in patients conceived after IVF. RESULTS: A 21-month-old girl born after IVF and uneventful pregnancy presented with progressive nausea, vomiting, irritability, and right-side weakness. Magnetic resonance imaging demonstrated large heterogeneous contrast enhancing left frontotemporoparietal tumor. The operation was aborted due to asystole after subtotal tumor removal. The patient passed away on postoperative day 3. Histologic examination demonstrated AT/RT. We identified 7 previously published case reports of intracranial neoplasms in children conceived by IVF. Patient age at brain tumor diagnosis ranged from 31st week of gestation to 3 years of age. The most common histological diagnosis was AT/RT (3 cases), followed by glioblastoma multiforme, gliosarcoma, medulloblastoma, craniopharyngioma, and choroid plexus papilloma. Three of five operated patients died during perioperative period. Outcomes were dismal in 7 patients. CONCLUSIONS: IVF-associated brain tumors are usually malignant and associated with high mortality. Future studies investigating possible causal relationship between IVF and brain tumor risk are encouraged.

Long-Term Oncological Outcomes for Young Men Undergoing Radical Prostatectomy for Localized Prostate Cancer.

Aim. The aim of this study was to describe PCa characteristics and long-term outcomes in young men aged ≤55 years after radical prostatectomy (RP) and to compare them with older men cohort. Methods. Among 2,200 patients who underwent RP for clinically localized PCa at our centre between 2001 and 2015, 277 (10.3%) men aged ≤55 years were identified. All preoperative and pathological parameters were compared between groups. Biochemical progression free survival (BPFS) and disease progression free survival (DPFS) were assessed at 5 and 10 years. Results. Men aged ≤55 years had similar pathological tumor characteristics and biochemical recurrence rate (BCR) compared to their older counterparts. Disease progression rate 2.5% versus 0.4% was higher in older patients (p = 0.026). BPFS rate was not different in both study groups. Estimated 10-year DPFS was 98.8% in younger men compared to 89.2% in their older counterparts (p = 0.031). Multivariate Cox regression showed that Gleason score lymph-nodes and surgical margins status were significant predictors for disease progression. Conclusions. In our cohort, men aged ≤55 years had similar pathological PCa characteristics and BCR rate in comparison with older men. RP can be performed with excellent long-term DPFS results in men with localized PCa at ≤55 years of age.

Dutasteride for the prevention of prostate cancer in men with high-grade prostatic intraepithelial neoplasia: results of a phase III randomized open-label 3-year trial.

PURPOSE: High-grade prostatic intraepithelial neoplasia (HGPIN) is a potential precursor of prostate cancer (PCa), and patients with HGPIN are at high risk for PCa development. Objective of our study was to evaluate the efficacy of dutasteride 0.5 mg in PCa prevention among men with isolated HGPIN on biopsy. METHODS: This prospective, randomized, phase III, open-label 3-year trial assessed dutasteride versus active surveillance in patients with HGPIN. Patients were randomized to dutasteride 0.5 mg daily or active surveillance. Per-protocol prostate biopsies were performed at 6, 12, 24, and 36 months until cancer detection or study end. The primary end point was cancer-free survival (CFS). An intention-to-treat analysis was done for patients who underwent at least one per-protocol biopsy. An efficacy analysis was done for patients who completed the study. CFS was evaluated using Kaplan-Meier and log-rank analysis. RESULTS: In total, 220 men were randomized (dutasteride, n = 107; surveillance, n = 113). PCa was detected in 47.6: 49.1 % in the surveillance group and 45.9 % in the treatment group (p = 0.66). The detected PCa differentiation by Gleason score (GS) was GS 6 in 76.9 %, GS 7 in 19.8 %, and GS ≥ 8 in 3.3 %, with no difference between groups. The 3-year PCa-free survival was 43.6 % in the surveillance and 49.6 % in the dutasteride group (log rank p = 0.57). Limitations include a relatively high non-adherence rate, open-label design, and baseline sextant biopsy scheme. CONCLUSIONS: Dutasteride 0.5 mg for 3 years did not lower the PCa detection rate but did not worsen detected PCa characteristics in men with HGPIN.

Sporadic Creutzfeldt-Jakob disease with unusual initial presentation as posterior reversible encephalopathy syndrome: a case report.

BACKGROUND: Creutzfeldt - Jakob disease (CJD) is a rapidly progressive and fatal neurodegenerative prion disease. MRI findings are included in diagnostic criteria for probable CJD, giving a sensitivity and specificity more than 90%, but the atypical radiological presentations in the early stage of the disease could cause the diagnostic difficulties. CJD can be definitively diagnosed by histopathological confirmation, brain biopsy or at autopsy. CASE PRESENTATION: We present a case of 53-year-old woman with a history of a rapidly progressive dementia with symptoms of visual impairment, increased extrapyramidal type muscle tonus, stereotypical movements and ataxic gait resulting in the patient's death after13 months. The clinical symptoms deteriorated progressively to myoclonus and akinetic mutism already on the 14th week. The series of diagnostic examinations were done to exclude the possible causes of dementia. Initial MRI evaluation as posterior reversible encephalopathy syndrome (PRES) on the 9th week after the onset of symptoms created us a diagnostic conundrum. Subsequent MRI findings of symmetrical lesions in the basal ganglia (nucleus caudatus, putamen) on the 13th week and EEG with periodic sharp wave complexes (PSWC) in frontal regions on the 18th week allowed us to diagnose the probable sCJD. The histopathological findings after brain biopsy on the 14th week demonstrated the presence of the abnormal prion protein deposits in the grey matter by immunohistochemistry with ICSM35, KG9 and 12 F10 antibodies and confirmed the diagnosis of sCJD. CONCLUSIONS: In this article we focus our attention on a rare association between radiological PRES syndrome and early clinical stage of sCJD. Although concurrent manifestation of these conditions can be accidental, but the immunogenic or neuropeptide mechanisms could explain such radiological MRI findings. A thorough knowledge of differential diagnostic of PRES may be especially useful in earlier diagnosis of sCJD.

Evaluation of D'Amico criteria for low-risk prostate cancer.

OBJECTIVE: The aim of the study was to identify the risk of unfavourable disease (≥ pT3 and/or Gleason score ≥ 7) in radical prostatectomy (RP) specimens and biochemical progression-free survival (BPFS) after RP in patients with low-risk prostate cancer detected by D'Amico criteria before surgery. MATERIAL AND METHODS: Between 2004 and 2007, 690 men underwent prostate biopsy and RP at a single university hospital. Of those, 248 patients (35.9%) had low-risk prostate cancer criteria. The endpoints of the study were detection of low-risk (pT2 and Gleason score ≤ 6) or unfavourable (≥ pT3 and/or Gleason score ≥ 7) prostate cancer, and BPFS. The risk of progression was analysed using multivariate Cox regression model and BPFS was established using Kaplan-Meier analysis. RESULTS: The median follow-up was 60 months (1-112 months). pT3 was detected in 14.1%, and Gleason score ≥ 7 in 32.7% of patients. Unfavourable prostate cancer was detected in 37.5% of patients. Overall biochemical relapse rate was 13.6%. The estimated probability of 3-, 5- and 8-year BPFS for all study patients was 90.6%, 88.1% and 77.9%, respectively. Eight-year BPFS was 83.3% for low-risk prostate cancer and 68.2% for unfavourable prostate cancer (p = 0.007). Positive surgical margins (p = 0.0001) and postoperative Gleason score (p = 0.023) were the most significant predictors of biochemical relapse in Cox regression analysis. CONCLUSIONS: The D'Amico criteria may underestimate potentially aggressive prostate cancer in up to 37.5% of patients. Consequently, caution is recommended when the decision concerning the treatment modality is based on D'Amico criteria alone.

Comparison of long-term results after nephron-sparing surgery and radical nephrectomy in treating 4- to 7-cm renal cell carcinoma.

OBJECTIVE: The aim of our study was to compare long-term oncological outcomes following nephron-sparing surgery (NSS) and radical nephrectomy (RN) for renal cell carcinoma (RCC) 4 to 7 cm in diameter. MATERIAL AND METHODS: The study included patients who underwent RN or NSS for RCC 4 to 7 cm in diameter between 1998 and 2009. The studied groups were compared with respect to the patients' age, sex, physical status according to the American Society of Anesthesiologists Physical classification, histological type, stage, tumor size, grade, duration of the operation, and complications. Survival was established using the Kaplan-Meier method. The risk factors for survival were analyzed using a multivariate Cox regression model. RESULTS: During the study, 351 patients underwent surgery: 317 patients (90.3%) underwent RN, and 34 (9.7%), NSS. The compared groups differed with respect to tumor size (P=0.001) and stage (P=0.006). The overall estimated 12-year survival was 53.7% after RN and 55.2% after NSS (log-rank test P=0.437). The 12-year cancer-specific survival in the RN and NSS groups was 69.6% and 80.6%, respectively (log-rank test P=0.198). Pathological stage and patients' age were the major factors affecting both overall and cancer-specific survival. The type of surgery (NSS or RN) had no effect on survival. CONCLUSIONS: Our study showed that nephron-sparing surgery is a safe technique compared with radical nephrectomy that ensures good oncological control in the treatment of renal cell carcinoma measuring 4 to 7 cm and may be proposed as the treatment of choice for renal tumors not only up to 4 cm, but also 4 to 7 cm in size.

A primary primitive neuroectodermal tumor of the central nervous system in a 51-year-old woman: a case report and literature review.

Primitive neuroectodermal tumors are a group of rare, aggressive, and highly malignant embryonal tumors of unknown etiology of the central and peripheral nervous systems. It is a term for a group of small round cell tumors thought to be derived from fetal neuroectodermal precursor cells. Primitive neuroectodermal tumor is usually described as a tumor of children younger than 15 years and is very rare in adults. The article presents a short literature review and a rare case of a primary primitive neuroectodermal tumor of the central nervous system diagnosed in a 51-year-old woman.

Factors predicting Gleason score 6 upgrading after radical prostatectomy.

OBJECTIVES: Prostate cancer Gleason score 6 is the most common score detected on prostatic biopsy. We analyzed the clinical parameters that predict the likelihood of Gleason score upgrading after radical prostatectomy. METHODS: The study population consisted of 241 patients who underwent radical retropubic prostatectomy between Feb 2002 and Dec 2007 for Gleason score 6 adenocarcinoma. The influence of preoperative parameters on the probability of a Gleason score upgrading after surgery was evaluated using multivariate logistic regression and ROC curves. RESULTS: Gleason score upgrade was found in 92 of 241 patients (38.2%). Multivariate logistic regression analysis showed that only percentage of cancer in dominant lobe and prostate weight were significant predictors for Gleason score upgrading (p = 0.043 and p = 0.006, respectively). ROC curves showed that prostate weight and PSA density were only two independent significant parameters for prediction of upgrade (AUC - 0.634, p <0.0001 and 0.604, p = 0.006, respectively). Gleason score upgrading was observed to be accompanied by significantly higher rates of extra prostatic extension (p <0.001) and seminal vesicle invasion (p = 0.002). CONCLUSIONS: Almost forty percent of tumors graded Gleason 6 at biopsy are Gleason 7 at surgery. Upgraded tumors significantly associated with adverse pathological features. The probability of Gleason score upgrade can be predicted using prostate weight and PSA density as independent parameters.

Outcome of surgery in locally advanced pT3a prostate cancer.

INTRODUCTION: The aim of this study is to present the oncologic outcomes and to determine prognostic parameters of overall (OS), cancer specific survival (CSS), disease progression free survival (DPFS) and biochemical progression free survival (BPFS) after surgery for pT3a prostate cancer (PCa). MATERIAL AND METHODS: Between 2002 and 2007, a pT3a stage after radical prostatectomy was detected in 126 patients at our institution. Kaplan-Meier analysis was used to calculate OS, CSS, DPFS and BPFS. Cox regression was used to identify predictive factors of survival. RESULTS: Five-year OS, CSS, DPFS and BPFS rates were 96%, 98.7%, 97.3% and 60%, respectively. Among patients with prostate specific antigen (PSA) <10 ng/ml and PSA >20 ng/ml the 5-year OS was 98.8% and 80%, respectively, whereas 5-year BPFS was 66% and 16.6%, respectively. Survival was different when comparing surgery Gleason score ≤7 and ≥8. 5-year OS and BPFS were 98% vs. 80%, and 62.6% vs. 27.3%, respectively. Specimen Gleason score and preoperative PSA were significant predictors of BPFS. The risk of biochemical progression increased up to 2-fold when a Gleason score ≥8 was present at final pathology. CONCLUSIONS: In locally advanced pT3 PCa, surgery can yield very good cancer control and survival rates especially in cases with PSA <10 ng/ml and Gleason score ≤7. PSA and Gleason score after surgery are the most significant predictors of outcomes after radical prostatectomy.

The role of high-grade prostatic intraepithelial neoplasia for biochemical relapse of prostate carcinoma after radical prostatectomy.

UNLABELLED: The objective of the study was to evaluate the relationship between high-grade intraepithelial neoplasia diagnosed after radical retropubic prostatectomy and the clinical and pathological characteristics of prostate cancer, and to evaluate the time to biochemical relapse of the disease within the groups of high-grade prostatic intraepithelial neoplasia (HGPIN) and non-HGPIN patients. MATERIAL AND METHODS: Patients, clinically diagnosed with local prostate carcinoma at the Clinic of Urology, Kaunas University of Medicine, during 2003-2007 and treated with radical retropubic prostatectomies, were distributed into two groups according to the HGPIN detected in the postoperative material: HGPIN and non-HGPIN. The two groups were compared in terms of preoperative and postoperative characteristics. The patients who were followed up for at least 12 months were included into the study. The biochemical relapse of prostate cancer was determined if there were two consecutive rises of prostate-specific antigen (PSA) level above 0.2 ng/mL or according to the attending physician's opinion, there was a need for adjuvant treatment even with onetime rise of PSA level above 0.2 ng/mL. RESULTS: There was no significant difference between the HGPIN and non-HGPIN groups in terms of time to biochemical relapse and frequency of biochemical relapses, time before surgery, the timing of the HGPIN diagnosis, age, or PSA level. After radical prostatectomy, patients in the HGPIN group were found to have significantly more often poorer cancer cell differentiation according to the Gleason score (≥7 vs. <7; P=0.001) and higher TNM stage (T3a,b vs. T2a,b,c; P=0.001). Fewer positive resection margins were diagnosed in the HGPIN group (P=0.05). The groups did not differ in terms of the degree of differentiation according to the Gleason score or perineural invasion (P=0.811 and P=0.282, respectively). CONCLUSIONS: HGPIN was more often associated with the characteristics of the poor prognosis for relapse of prostate cancer: poorer tumor cell differentiation according to the Gleason score and more cases of higher TNM stage. HGPIN did not have any influence on biochemical relapse of the disease during the short-term follow-up.

Histology of human glioblastoma transplanted on chicken chorioallantoic membrane.

Glioblastoma is the most malignant tumor in the range of cerebral astrocytic gliomas. A lot of experimental models are used to evaluate various properties of glioblastoma. Chicken chorioallantoic membrane model is one of them. OBJECTIVE. To evaluate histology and survival of glioblastoma tumors taken immediately from operating theatre and transplanted on chicken chorioallantoic membrane. MATERIALS AND METHODS. Glioblastoma samples obtained from 10 patients were transplanted onto 200 eggs. Overall, we used 15 tumors; only 5 of them were not glioblastomas as it was revealed later. RESULTS. The transplanted tumors survive up to 6 days. Transplants do not survive longer because during embryo's development the nourishing membrane dries. Transplanted glioblastomas exhibited the same features as original glioblastomas - necrosis, endothelium proliferation, cellular polymorphism - while transplanted glioblastomas also showed glial fibrillary acidic protein (GFAP), vimentin, Ki67, S100 protein, neurofilament immunoreactivity, and infiltration of macrophages (CD68) and T cells (CD3(+), CD8(+)). Transplanted glioblastomas did not show any immunoreactivity of p53. Invasion of vessels from the chicken into transplanted tumor is not observed. Chicken erythrocytes did not appear within the transplants, and tumor cells invade chicken tissue at the minimum. CONCLUSION. Our data show that transplanted pieces of glioblastoma survive with all cytological features. The presence of macrophages (marker CD68) and T cells (markers CD3(+) and CD8(+)) can be registered in the transplant. The data revealed that transplanted glioblastoma remains as insulated unit, which survives from nourishment of the chorioallantoic membrane apparently only by diffusion. The features of original tumor-host reaction of the patient remained too.

Lichen sclerosus et atrophicus in pediatric and adult male patients with congenital and acquired phimosis.

Lichen sclerosus et atrophicus is a chronic inflammatory sclerotic and atrophic disease of unknown cause that predominantly affects male and female genital skin. This study was designed to evaluate histological characteristics of congenital and acquired phimoses among pediatric (n=60) and adult (n=60) male patients who were admitted for circumcision to the Clinics of Urology and Pediatric Surgery of Kaunas University of Medicine Hospital between 2000 and 2003 and to determine the rate of lichen sclerosus et atrophicus and other histological diagnoses among them. This study demonstrates that 45.1% of congenital and 62.3% of acquired phimoses show histological signs of lichen sclerosus et atrophicus. The rate of lichen sclerosus et atrophicus was statistically significantly higher among patients with acquired than congenital phimosis. Boys with acquired narrowing of prepuce were statistically significantly 3.9 times more likely to develop lichen sclerosus et atrophicus than those with congenital phimosis. There were no statistically significant differences between rates of lichen sclerosus et atrophicus and other dermatological diagnoses among pediatric and adult male patients if the type of phimosis (acquired or congenital) was considered. Histological features of lichen sclerosus et atrophicus and other histological diagnoses in boys and men with phimosis were detected with equal frequency irrespective the age of the subjects. The rate of lichen sclerosus et atrophicus was similar among all boys (56.7%) and men (53.3%) treated for phimosis. Only the type of phimosis had a statistically significant influence on the rate of lichen sclerosus et atrophicus and other histological diagnoses.

A 10-month-old boy with a large pineal tumor.

February 2005. Case report of a 10-month-old boy with a large tumor located in the pineal gland, consisting of glia, ganglion cells, pigmented neuroepithelium and striated muscle, without immature components. The combination of neuroectodermal and mesenchymal constituents includes entities as pineal anlage tumor (melanotic neuroectodermal tumor of infancy, MNTI), ectomesenchymoma, medullomyoblastoma, and teratoma in the differential diagnosis. Lack of immature elements in this case, however, eliminates ectomesenchymoma and medullomyoblastoma from the differential diagnosis. Retinal anlage tumors, to be considered as MNTI at the site of the pineal gland, usually harbor immature components as well. Therefore, the present case does not match strict criteria of any of the categories mentioned and therefore we have designated it as a "pineal anlage tumor (without immature components)".

Improvement of liver histopathology in patients with hepatitis C after interferon and ribavirin combination therapy.

UNLABELLED: Aim of the study was to evaluate the effect of interferon and ribavirin combination therapy on liver histopathological outcomes. MATERIAL AND METHODS: Pre-treatment and post 24-week treatment liver biopsy specimens were available in 68 naive patients, 37 nonresponders and 18 relapsers after interferon monotherapy. For all patients paired liver biopsies (6-month interval) were assessed for necroinflammation (according to the method by K. Ishak), fibrosis (according to METAVIR score) and steatosis at the end of 24-week treatment. RESULTS: Virological end-of-treatment response was: 36.8% in naive patients, 24.3% in nonresponders and 22.2% in relapsers. Out of 38 patients, who achieved virological end-of-treatment response, sustained virological response was in 65.8%. There was obvious drop of histological activity features scores in all treated patients at the end of 24-week treatment period. According to the baseline findings, only confluent necrosis was found to be significantly lower in patients, who achieved virological end-of- treatment response (p<0.05). The fibrosis and steatosis has not been influenced at least by 24-week treatment success. But in patients, who achieved sustained virological response, fibrosis was lower at baseline and after 24-week of interferon and ribavirin therapy (p<0.001). In conclusion, assessment of liver histopathology has real value in the evaluation of therapeutic response. Grade of pre-treatment confluent necrosis could predict virological end-of-treatment response. Lower stage of fibrosis both at baseline and after 24-week treatment period seems to be a predictor of sustained virological response.

Interferon alpha-2b in combination with ribavirin for the treatment of chronic hepatitis C: assessment of virological, biochemical and histological treatment response.

UNLABELLED: Aim of the study is to establish the efficacy of treatment of chronic hepatitis C with interferon alpha-2b and ribavirin in treatment-naive patients, in non-responders to interferon monotherapy, in relapsers after interferon monotherapy, and to evaluate the possible predictors of treatment response. MATERIAL AND METHODS: One hundred thirty one patients with chronic hepatitis C were included and assigned to 24-week course of interferon alpha-2b with ribavirin. At the end of 24-week combination therapy biochemical, histological, virological and complete end-of-treatment responses were evaluated. Patients with virological end-of-treatment response were treated with interferon alpha-2b and ribavirin for further 24 weeks and followed-up for the next 6 months after stopping therapy. RESULTS: End-of-treatment response was assessed in 119 patients: 57.1% were treatment-naive, 28.6% were non-responders, and 14.3%--relapsers. Overall virological end-of-treatment response rate was 35.3%, biochemical--64.7%, histological--80.9% and complete--33.3%. Treatment-naive patients have better end-of-treatment response than non-naive patients in all dimensions, but statistical significance is reached only evaluating histological end-of-treatment response. Sustained virological response of overall 119 patients was in 23.6%. There was no statistically significant difference in sustained virological response rate among all patient groups. None of pre-treatment demographic, clinical, biochemical and morphological parameters was found as possible response predicting factors. Hepatitis C virus genotype was assessed in 40 patients. Hepatitis C virus genotype 1 was found in 34 (85%), genotype 2 in 3 (7.5%), and genotype 3 in 3 (7.5%) patients. In conclusion, in our studied population with high prevalence of hepatitis C virus genotype 1 (85%), there is low sustained virological response rate (23.6%) to interferon alpha-2b in combination with ribavirin therapy.

Impact of morphology and biology on the prognosis of patients with gliomas.

Gliomas are the most common type of primary intracerebral neoplasm. They carry a dismal prognosis. The main prognostic factors are patient age, performance status and malignancy grade. Because patients with the same histologic diagnosis have variable outcomes, there is a need to develop better prognostic markers with the aim of predicting tumor behaviour and response to therapies. This paper reviews different morphological, genetic, molecular factors and their association with survival. Tumor associated morphological features such as predominant cell type, cellularity, cytological atypia, proliferation activity, microvascular proliferation, necrosis and apoptosis are discussed in some detail.