[Non-invasive precursor lesions of penile carcinoma : Differential diagnosis and treatment]. / Nichtinvasive Vorläuferläsionen des Peniskarzinoms : Differentialdiagnose und Therapie.

Clinical diagnosis of preinvasive malignant lesions of the penis is difficult and there are numerous differential diagnoses. Recent decades have been witness to several changes in the terminology of histopathological diagnoses. In the current World Health Organization classification, penile intraepithelial neoplasia (PeIN) is defined, of which several subtypes exist. Just like in invasive carcinoma, the principal classification of PeIN subtypes corresponds with pathogenesis and includes human papilloma virus (HPV)-related and non-HPV-related forms. Subdivision is important for prognosis. Several therapeutic options exist, including surgical and nonsurgical procedures.

[Renal cell carcinoma diagnosis and prognosis within the context of the WHO classification 2016]. / Histopathologische Diagnose und Prognose des Nierenzellkarzinoms im Kontext der WHO-Klassifikation 2016.

BACKGROUND: Histological classification of renal cell carcinoma (RCC) has become more and more important for clinical management, but relatively few is known regarding the swiftness with which the 2016 World Health Organization (WHO) classification of RCC was adopted in the daily routine diagnostics. AIM: To retrospectively review the histological diagnosis of RCC within the context of 2016 WHO classification followed by survival analysis. MATERIAL AND METHODS: Retrospective register based analysis of RCC diagnosis between 1998 and 2017 and survival analysis. RESULTS: 1440 RCC cases were registered between 1998 and 1917. According to 2016 WHO classification, 77.7% clear cell RCC and 22.3% non-clear cell RCC were diagnosed. A total of 37 rare subtypes were recorded, among those 1% MiT family translocation RCC, 0.35% acquired cystic disease-associated RCC, 0.35% multilocular cystic renal neoplasm of low malignant potential, 0.35% collecting duct carcinoma, 0.3% mucinous tubular and spindle cell carcinoma, 0.1% clear cell papillary RCC and 0.1% RCC with (angio)leiomyomatous stroma. Cox regression analysis showed significant different overall survival and progression-free survival between the histological subtypes. DISCUSSION: The complexity of the 2016 WHO classification of RCC put high demands on histopathological diagnostics. At University Medicine Center Rostock morphological distinct RCC entities have been mostly diagnosed by conventional means via hematoxillin and eosin stained slides, but beyond immunohistochemistry additionally molecular techniques were established. The histologic subtyping of RCC according to 2016 WHO classification has prognostic significance and might have predictive significance for unique therapeutic approaches.

Optical coherence tomography and confocal laser scanning microscopy as non-invasive tools in the diagnosis of sinonasal inverted papilloma: a pilot study.

Optical coherence tomography (OCT) and confocal laser scanning microscopy (CLSM) are light-based imaging techniques that allow for a visualization of microscopic tissue properties in vivo. Our study was to examine whether they allow for differentiation of inverted papilloma (IP) from nasal polyps (NP). Five cases of IP and NP, respectively, were investigated intraoperatively with OCT and CLSM. Biopsies were taken of the investigated area and were analyzed ex vivo with OCT and CLSM and then underwent HE-staining for standard light microscopy. On OCT images, IP showed the characteristic inverted character of the epithelium, that was thicker with a high degree of variability of thickness compared to the thin and homogenous epithelium of NP. In addition, the characteristic stromal edema of NP could be visualized. On CLSM images, the typical epithelial invaginations of IP appeared as crypts, while in NP the highly organized cylindric epithelium could be visualized. In vivo, OCT acquired images of sufficient quality to visualize these characteristics, while CLSM did not. Our study demonstrates that OCT and CLSM can distinguish IP from NP. Further technical development is required to apply the techniques clinically to guide intranasal biopsies or even to make them dispensable.

[Pathology and histopathological evaluation of penile cancer]. / Pathologie und histopathologische Begutachtung des Peniskarzinoms.

BACKGROUND: Penile cancer is rare in Germany and in western European countries. Our understanding of the pathogenesis and pathology of this malignancy has increased considerably in recent years. OBJECTIVES: Clinical management has become more complex, with organ-preserving strategies being increasingly favored. Associated with these developments, the demands on the pathology reports of biopsies and surgical specimens from the penis have also increased. MATERIALS AND METHODS: According to guidelines and the relevant literature, this review outlines the most important aspects that must be considered in the classification and pathological reporting of penile cancer. RESULTS: Correct histological subtyping of penile cancer is important for prognostic and therapeutic considerations. There are also some peculiarities with the current TNM classification system of this tumor compared to other entities. CONCLUSION: Handling of specimens and histopathological typing must be performed by experienced pathologists according to recent developments in the pathogenesis, classification, and therapeutic strategies of penile cancer.

[Endometrioid borderline tumor of the testis. A rare cause of cystic neoplasia]. / Endometrioider Borderlinetumor des Hodens. Eine seltene Ursache für eine zystische Raumforderung.

Ovarian type surface epithelial carcinomas of the testis are rare and therefore mostly represent a surprising finding in diagnostic procedures. The most frequent is the serous subtype, while only a few cases of the endometrioid subtype have been reported in the literature. The case of a 73-year-old patient with an endometrioid type papillary cystic tumor of borderline malignancy is presented. The histopathological and immunohistochemical details of this rare tumor are discussed.

Reproducibility of histopathologic tumor grading in penile cancer--results of a European project.

Since reliable molecular prognostic parameters for inguinal lymph metastases in penile cancer are not available, tumor grading is often used as a surrogate prognostic tool for the indication of inguinal lymphadenctomy and has been integrated into the current TNM classification for penile cancer. The reliability of tumor grading is under discussion. We examined interobserver grading variability in 90 primary penile carcinomas, assessed by 12 different uropathologists from five European countries. Tumor grading, following the CAP scheme, was compared, and interobserver variability was calculated using kappa statistics. The interobserver variability was high as reflected by an overall low kappa coefficient (mean k = 0.34) and reached a moderate level only in 26.4 % of the cases (range 0.02-0.67). The percentage of G1 tumors assigned ranged from 8.6 to 52.5 %, G2 tumors from 27.1 to 72.6 % and G3 tumors from 11.7 to 48.7 %. Only some observers assigned G4 with a range of 0.6-21.9 %. Subdivision into low and high grade according to UICC and EAU classifications differed significantly (P < 0.001). Low reproducibility of grading in penile carcinomas with the favored method does not allow a reliable prognostication of tumor aggressiveness. Inclusion of histological grading into the TNM classification currently seems not to be a benefit.

[Non-neoplastic alterations of the prostate. Why should pathologists know them?]. / Nichtneoplastische Veränderungen der Prostata. Warum sollten Pathologen sie kennen?

Non-neoplastic changes in the prostatic gland include inflammatory, atrophic, hyperplastic and metaplastic reaction patterns of the glandular epithelium and the fibromuscular stroma. Furthermore, histoanatomical structures from outside the prostatic gland are sometimes included in biopsy material. Knowledge of the morphological appearance of benign, reactive lesions is important in order to differentiate them from malignancies. To this aim knowing the precise location of tissue sampling as well as ancillary immunohistochemical investigations are often useful or necessary.

Losses at chromosome 4q are associated with poor survival in operable ductal pancreatic adenocarcinoma.

Here we tested the prognostic impact of genomic alterations in operable localized pancreatic ductal adenocarcinoma (PDAC). Fifty-two formalin-fixed and paraffin-embedded primary PDAC were laser micro-dissected and were investigated by comparative genomic hybridization after whole genome amplification using an adapter-linker PCR. Chromosomal gains and losses were correlated to clinico-pathological parameters and clinical follow-up data. The most frequent aberration was loss on chromosome 17p (65%) while the most frequent gains were detected at 2q (41%) and 8q (41%), respectively. The concomitant occurrence of losses at 9p and 17p was found to be statistically significant. Higher rates of chromosomal losses were associated with a more advanced primary tumor stage and losses at 9p and 18q were significantly associated with presence of lymphatic metastasis (chi-square: p = 0.03, p = 0.05, respectively). Deletions on chromosome 4 were of prognostic significance for overall survival and tumor recurrence (Cox-multivariate analysis: p = 0.026 and p = 0.021, respectively). In conclusion our data suggest the common alterations at chromosome 8q, 9p, 17p and 18q as well as the prognostic relevant deletions on chromosome 4q as relevant for PDAC progression. Our comprehensive data from 52 PDAC should provide a basis for future studies with a higher resolution to discover the relevant genes located within the chromosomal aberrations identified.

[Allogeneic stem cell transplantation for acute myeloid leukemia and HIV infection--case 3/2012]. / Allogene Stammzelltransplantation bei Akuter Myeloischer Leukämie und HIV-Infektion--Fall 3/2012.

HISTORY AND ADMISSION FINDINGS: A 27-year-old male patient with a past medical history of HIV presented with acute myeloid leukemia for allogeneic hematopoietic stem cell transplantation (HSCT). Highly active anti-retroviral therapy suppressed the viral load below detection threshold. INVESTIGATIONS: There were no contraindications for allogeneic HSCT. TREATMENT AND COURSE: Myeloablative conditioning consisted of total body irradiation and cyclophosphamide. Anti-thymocyte globulin, tacrolimus and mycophenolate mofetil were used for immunosuppression. Combined anti-retroviral therapy (nucleoside and nucleotide analog reverse-transcriptase inhibitor, boostered protease inhibitor, maraviroc and raltegravir) was maintained for allogeneic HSCT and viral load remained below detection threshold. No graft-versus-host disease or serious infectious complications occurred. The patient showed good graft function with stable hematopoiesis. Localized Kaposi's sarcoma was diagnosed six months after allogeneic HSCT and treated successfully with surgical excision and reduction of immunosuppression. Almost one year after allogeneic HSCT, the CD4+ cell count is rising and viral load remains below detection threshold with combined anti-retroviral therapy. CONCLUSION: Allogeneic HSCT can be safely performed in HIV positive patients. Kaposi's sarcoma is a rare event after allogeneic HSCT and linked to strong immunosuppression.

Prognostic relevance of Bcl-2 overexpression in surgically treated prostate cancer is not caused by increased copy number or translocation of the gene.

BACKGROUND: Overexpression of anti-apoptotic Bcl-2 plays a role in prostate cancer progression, particularly in transformation to androgen-independent disease. Androgen-independent prostate cancers have been shown to harbor Bcl-2 gene copy number gains frequently suggesting that this genetic alteration might play a role in Bcl-2 overexpression. The relation of Bcl-2 overexpression and copy number gains or translocation of the BCL-2 gene in prostate cancer under hormone-naïve conditions is unknown. METHODS: Prostate cancers of 3,261 hormone-naïve patients undergoing radical prostatectomy were arrayed in a TMA with one tissue core (diameter 0.6 mm) per tumor. Bcl-2 immunohistochemistry, analyzed for Bcl-2 expression level (negative, low, and high), was correlated with clinical, histopathological and molecular (Ki67, p53) tumor features, and biochemical failure. Cancers with high-level Bcl-2 expression were evaluated for genetic aberrations by fluorescence in situ hybridization (FISH). RESULTS: Bcl-2 expression was significantly up-regulated in tumors with aggressive phenotype as indicated by high Gleason score (P < 0.0001), advanced stage (P < 0.0001), and high proliferation index (P = 0.0114). The different Bcl-2 expression levels translated into significantly different survival curves showing better outcome for patients with lower Bcl-2 levels. The prognostic information obtained from the anti-apoptotic Bcl-2 was independent from the proliferation index (Ki67) of the cancer. FISH analysis detected no copy number gains or translocation of the Bcl-2 gene. CONCLUSION: Bcl-2 overexpression in prostate cancers under hormone-naïve conditions is not associated with increased copy numbers of the gene. This suggests that these frequently detected genetic alterations in androgen-independent tumors occur late in prostate cancer progression.

Dural metastases from disseminated prostate cancer clinically mimicking a benign reactive condition of the dura: case report and review of the literature.

Dural spread from prostate cancer (PC) is exceedingly uncommon. We report on a 62-year-old man suffering from disseminated PC with osseous metastases who presented with a parietal skull metastasis along with a circumscribed nodular thickening of the adjacent dura. Magnetic resonance imaging findings suggested a benign reactive condition of the dura which, however, histologically turned out to be a dural metastasis. Therefore, the present case report stresses the notion that very rarely, disseminated PC might present with clinically unsuspected dural metastases radiologically mimicking a benign condition.

Schmincke's Tumor, Carcinoma of the Base of the Tongue c T1-2, cN2c M0 - A Case Report.

BACKGROUND: Lymphoepithelial tumors are the most common carcinomas of the nasopharynx. The non-differentiated tumor, also called Schmincke's tumor, is more prevalent in the African and Chinese population. The incidence of the tumor according to age peaks between 20 and 30 years of age, and after 60 years of age. The tumor is rarely located outside of the nasopharynx. Case Report: This report is about a 73-year-old female patient diagnosed with a tumor of the base of the tongue. The histological result shows a low-grade carcinoma of the squamous epithelium, a lymphoepithelial carcinoma. CONCLUSION: Despite the tumor's rare manifestation outside the nasopharynx, one must also consider the non-differentiated carcinoma of lymphoepithelial matrix. Especially due to the well-known early tumor spreading, cervical lymph node swelling on both sides can be recognized as a possible early symptom. First-line therapy consists of primary radiation of the tumor's primary region and its lymphoid draining channels. Concomitant chemotherapy can be applied. In case of cervical tumor spreading, a neck dissection reduces the risk of local recurrence.

[The significance of chronic prostatitis for the etiopathology of prostate cancer]. / Die Bedeutung der chronischen Prostatitis für die Pathogenese des Prostatakarzinoms.

Although prostate cancer is of crucial impact as a common disease of men, numerous relationships remain unknown, particularly concerning its pathogenesis. A novel approach regarding the origin and development of prostate cancer is a phenomenon that has already been investigated in other human cancers: cancerogenesis due to chronic inflammation. Hence, the present review introduces the current state of research concerning the relationship between chronic prostatitis and prostate cancer. In addition to histological and biochemical features, the latest discoveries are discussed, including the relationship between the pathogenesis of prostate cancer and infection by the novel gammaretrovirus XMRV, similar to cervical cancer associated with HPV.

[MicroRNA in uro-oncology : New hope for the diagnosis and treatment of tumors?]. / Mikro-RNA in der Uroonkologie : Neue Hoffnungen für die Diagnostik und Therapie von Tumoren?

MicroRNAs (miRNAs) are non-coding RNAs that regulate basic cellular processes and are associated with cancer characteristics. The aim of this review is to summarize the principles of miRNA biogenesis and function and to describe their contribution to tumor development, especially in uro-oncology. Therefore a PubMed search was conducted. Up to March 2009 approximately 4,500 miRNA-related articles were cited in this database. Studies of miRNA expression and functional analyses prove their impact in carcinogenesis and their potential as diagnostic or prognostic markers or as novel therapeutic targets. Only a few miRNA-related studies have been published in uro-oncology so far. Although tumor-specific miRNA expression has been shown for urological neoplasms, the contradicting data show that miRNA research is still in its infancy in this field. A systematic elucidation of characteristic miRNA abnormalities could decisively improve diagnostics as well as therapy of urological tumors.

Partin Tables cannot accurately predict the pathological stage at radical prostatectomy.

PURPOSE: The Partin Tables represent the most commonly used staging tool for radical prostatectomy (RP) candidates. The Partin Tables' predictions are used to guide the type (nerve preserving RP) and/or the extent (RP with wide resection) of RP. We examined the ability of the Partin Tables' predictions incorrectly assigning the stage at RP. METHODS: The testing of the Partin Tables (external validation) was based on 3105 patients treated with RP at a single European institution. Standard validation metrics were used (area under the receiver operating characteristics curve, AUC) to test the three endpoints predicted by the Partin Tables, namely the presence of extracapsular extension (ECE), seminal vesicle invasion (SVI), and lymph node invasion (LNI). RESULTS: Ideal predictions are denoted with 100% accuracy vs. 50% for entirely random predictions. For the 2001 version of the Tables the accuracy defined by the AUC was 79.7, 77.8, and 73.0 for ECE, SVI, and LNI, respectively. For the 2007 version of the Tables the corresponding accuracy estimates were 79.8, 80.5, and 76.2. The relationship between predicted probabilities and observed rates was poor. CONCLUSION: The Partin Tables are meant to guide clinicians about the safety of nerve bundle preservation at RP, about the need for seminal vesicle resection or for lymphadenectomy. Therefore, the use of the Partin Tables predictions may significantly affect the type and/or the extent of RP. In their present format the Partin Tables are not accurate enough to influence the pre-operative decision making regarding the type or extent of RP.

Transition zone cancers undermine the predictive accuracy of Partin table stage predictions.

PURPOSE: The Partin tables represent the most widely used predictor of pathological stage in men with localized prostate cancer (PCa). The accuracy and performance of the tables have been tested across different populations. However, to our knowledge the potential limitations that may stem from differences between transition zone (TZ) and peripheral zone (PZ) prostate cancers has not been explored. We tested the predictive accuracy and performance of the Partin tables according to TZ vs PZ tumor predominance. MATERIALS AND METHODS: Preoperative serum prostate specific antigen, clinical stage and biopsy Gleason sum data on 1,990 patients treated with radical retropubic prostatectomy were used to define the 2001 Partin probabilities of organ confinement and seminal vesicle invasion (SVI). Data on 1,320 patients who underwent staging pelvic lymphadenectomy and radical retropubic prostatectomy were used to define the probabilities of lymph node invasion (LNI) and organ confined disease (OC). ROC area under the curve was used to assess the predictive accuracy of the 2001 Partin tables relative to observed extracapsular extension (ECE), SVI, LNI and OC. Performance characteristics for each prediction were explored graphically with local regression, nonparametric smoothing plots. Results were compared between 222 TZ cancers and 1,768 PZ cancers. RESULTS: The 1,990 radical retropubic prostatectomy specimens demonstrated ECE in 689 cases (34.6%) (TZ in 58 or 27.1% and PZ in 631 or 35.8%) and SVI in 224 (TZ in 13 or 6.1% and PZ in 211 or 11.9%). The 1,320 lymphadenectomy specimens demonstrated LNI in 56 cases (TZ in 2 or 0.9% and PZ in 54 or 4.6%). OC was found in 784 cases (59.4%) (TZ in 95 or 69.9% and PZ in 689 or 58.2%). Predictive accuracy was for ECE 76.4% (TZ 69.0% and PZ 77.2%), 78.0% for SVI (TZ 73.5% and PZ 78.3%), 78.6% for LNI (TZ 44.5% and PZ 79.9%) and 79.4% for OC (TZ 73.8% and PZ 80.0%). CONCLUSIONS: The biological tumor characteristics of TZ PCa differ from those of PZ PCa. These differences appear to undermine the accuracy of pathological stage predictions.