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.

[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.

[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.

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.

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.

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.

[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.

[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.

Simultaneous tumour-like, atypical basal cell hyperplasia and acinar adenocarcinoma of the prostate: a comparative morphological and genetic approach.

Basal cell tumours of the prostatic gland are rare, and the classification is difficult. In the present case report, a large, tumour-like proliferation of atypical basaloid cells was found incidentally in a prostatectomy specimen that otherwise contained a conventional acinar adenocarcinoma. The basaloid cells displayed a solid or adenoid-cystic growth pattern and strongly expressed high-molecular-weight cytokeratins and bcl-2. A high Ki-67 index was recorded within the atypical basaloid cells, by far exceeding the one counted in the conventional adenocarcinoma. However, there were no definite criteria for a malignant behaviour of the basal cell tumour. Comparative genomic hybridisation from microdissected tumour cells yielded losses at the short arms of chromosomes 8 and 12 in the conventional adenocarcinoma and a normal karyotype in the basal cell tumour. The pathological findings favoured the diagnosis of an atypical basal cell hyperplasia.

Ifosfamide and ACNU in experimental allogeneic bone marrow transplantation.

We have tested ifosfamide and ACNU for their effectiveness in preventing graft rejection following allogeneic bone marrow transplantation. The engraftment-promoting potency of both was compared to that of the standard agent cyclophosphamide. LEW rats received a lethal dose (35 mg/kg) of busulfan followed by injection of 1 x 10(8) (CAP x LEW) F1 marrow cells, which are unable to induce a graft vs host reaction in LEW recipients. Rejection of the marrow graft was assessed by monitoring haematocrit and granulocyte count either until death of the animal or until day 80. Surviving animals received a donor-type skin graft to confirm the persistence of allogeneic haematopoiesis. Because of its weak immunosuppressive properties, busulfan by itself is unable to allow engraftment of allogeneic marrow. Therefore, ifosfamide and ACNU and cyclophosphamide as the standard agent could be tested for their capacity to prevent marrow graft rejection. The following rejection rates were observed: cyclophosphamide: 30 mg/kg 100%, 60 mg/kg 60%, 90 mg/kg 20%, 120 mg/kg and 180 mg/kg 0%; ACNU: 3, 5, 7, and 10 mg/kg 100%, 15 mg/kg 45%, 20 and 30 mg/kg 0%; ifosfamide: 60-120 mg/kg 100%, 180 mg/kg 68%, 240 and 360 mg/kg 0%. Thus, 240 mg/kg ifosfamide or 20 mg/kg ACNU is nearly equivalent to the standard dose of 120 mg/kg cyclophosphamide in engraftment-promoting potency in allogeneic bone marrow transplantation.

Numerical chromosomal aberrations in papillary renal cortical tumors: relationship with histopathologic features.

Previous studies have indicated that a combined trisomy of chromosomes 7 and 17 is a constant finding in papillary renal cortical adenomas and that papillary renal cell carcinomas are marked by additional trisomies such as trisomy 12, 16, and 20. The aim of our study was to compare this cytogenetic classification of papillary renal cortical tumors with conventional histopathologic classification. We performed interphase cytogenetics with enumeration probes for chromosomes 7, 12, 16, 17, and 20 on 41 papillary tumors found in 21 nephrectomy and 10 autopsy kidneys. A total of 38 tumors harbored gains of chromosomes 7 or 17, and most of these showed a trisomic signal distribution. The three tumors with normal copy numbers for chromosomes 7 and 17 were a papillary grade-2 carcinoma, a small adenoma (both with distinctive oxyphilic cytoplasm), and a papillary carcinoma with focally clear cells. Gains for chromosomes 12, 16, or 20 were found in 21 tumors and were significantly associated with the presence of histologic criteria of malignancy ( P<0.0001). Histopathologic and cytogenetic features of malignancy were found in eight tumors smaller than 10 mm. There is a good agreement of cytogenetic and histopathologic criteria of malignancy in papillary renal cell tumors. Interphase cytogenetics might give useful additional information in cases of doubt or when only small biopsy specimens are available.

Expression of 17-1A antigen and complement resistance factors CD55 and CD59 on liver metastasis in colorectal cancer.

Despite radical surgery, the prognosis for colorectal cancer patients with liver metastases has not changed markedly. Furthermore, no standard adjuvant therapeutic regimen has been developed. Adjuvant therapy with monoclonal antibodies (e.g., against 17-1A), which has been shown to be effective in preventing metastatic relapse in patients with Dukes' C colorectal cancer, might be a promising approach for these patients. However, the cytotoxic effects of monoclonal antibodies can be blocked by coexpression of complement resistance factors that inhibit antibody-dependent complement-mediated cytotoxicity. We therefore analyzed immunohistochemically the expression of 17-1A and the membrane-bound complement resistance factors CD55 and CD59 on metastatic tumor cells in the livers of 71 patients with colorectal carcinoma who had undergone resection of their metastases with curative intent. In 67 (94%) of 71 patients, liver metastases with homogeneous expression of 17-1A was seen. Heterogeneous expression of 17-1A was seen in four patients (6%). Heterogeneous expression of CD55 or CD59 was observed in 8 (11%) of 71 patients and 4 (6%) of 71 patients, respectively. None of the patients showed homogeneous expression of either CD55 or CD59. All patients with CD55 or CD59 expression showed homogeneous 17-1A expression, whereas none of the four patients with heterogeneous 17-1A expression was positive for CD55 or CD59. Our data indicate that 17-1A is widely expressed on liver metastases of patients with colorectal carcinoma. Therefore patients with completely resected liver metastases might be suitable candidates for adjuvant therapy with and-17-1A antibody since only a few of these lesions showed coexpression of complement resistance factors.

Microsatellite alterations at chromosomes 9p, 13q, and 17p in nonmuscle-invasive transitional cell carcinomas of the urinary bladder.

The clinical behavior of bladder cancer is difficult to predict and prognostic markers applicable to routinely processed tumor specimens clearly are needed. We screened 40 primary Ta and T1 bladder cancers for microsatellite alterations at 9p, 13q, and 17p with PCR, using nine polymorphic microsatellite markers. DNA was prepared after microdissection of paraffin-embedded transurethral resection specimens. PCR products were separated on sequencing gels, and allelic loss as well as band shifts was assessed by comparing alleles of control and tumor tissue. The results were correlated with grade, stage, and clinically documented tumor recurrence. Overall, allelic loss at 9p, 13q, and 17p was present in 35.1%, 25%, and 27.5% of cases, respectively. Whereas the frequency of allelic loss at 9p was nearly equally distributed throughout all tumor grades and stages, the occurrence of allelic loss at 13q and 17p correlated statistically significantly with higher grades and stage. Band shifts were observed in three cases. Of the 40 patients, 16 had tumor recurrence during a follow-up period of 3-49 months (median, 23 months). Kaplan-Meier analysis did not show any statistically significant correlation between allelic loss at either locus and tumor recurrence. The results confirm the role of alterations at 13q and 17p in the progression of bladder cancer. Allelic loss at 9p seems to be an early event in tumor development. However, the detection of alterations at the three chromosomal loci studied did not have any prognostic value regarding tumor recurrence in this group of patients.

Pathological and clinical characteristics of large prostate cancers predominantly located in the transition zone.

Prostate carcinomas located in the transition zone are suspected to behave differently from the more frequent peripheral zone cancers. In this study, large transition zone prostate cancers were investigated for pathological and clinical features. From 365 consecutive radical prostatectomy specimens, 73 cases were disclosed with tumours larger than 10 cm(3). Of these, 14 were predominantly (>70% tumour area) located in the transition zone. Pathological investigations included a complete histological work-up, immunohistochemistry for p53 and bcl-2, and interphase cytogenetics for chromosomes 7, 8, 17, and X. Despite large tumour volumes and high preoperative prostate specific antigen (PSA)-values, most tumours showed quite favourable pathological features. Only two of these patients suffered from a postoperative PSA-recurrence during a median follow-up of 50 months. For comparison, 36 cases that contained tumours predominantly located in the peripheral zone mostly displayed adverse prognostic signs and 68.8% of these patients suffered from postoperative PSA-recurrence. We conclude that the peculiar pathological and clinical characteristics of large prostate cancers in the transition zone might be important for prognostic considerations.

Numerical chromosomal changes in high-grade prostatic intraepithelial neoplasia (PIN) and concomitant invasive carcinoma.

Prostatic intraepithelial neoplasia (PIN) is regarded as a precursor lesion of at least some prostatic cancers. Using interphase cytogenetics, an in situ hybridization technique with chromosome specific probes, we investigated 15 prostatectomy specimens containing both invasive carcinoma and PIN for the presence of numerical changes of chromosomes 7, 8, 10, 17 and X. The results were correlated with tumor stage and Gleason grade as well as with morphological features of PIN. Of the 15 carcinomas, four were disomic, five displayed at least focal chromosomal gains and six were found to be aneusomic. A non-disomic chromosomal status correlated well with a higher tumor stage and grade. Although the majority of PIN glands showed an eusomy, focal chromosomal gains within single glands or parts of a gland could be observed in 12 of the 15 cases. All but one specimen with non-disomic carcinomas also harboured areas of PIN with numerical chromosomal aberrations, often laying directly adjacent to tumorous glands. Additionally, focal non-disomies of PIN could also be detected in two cases with eusomic cancer. With regard to numerical changes in PIN and cancer, no significant preponderance could be observed for the five chromosomes tested. We conclude that numerical chromosomal aberrations are a frequent, but mostly focal event in PIN. This karyotypic instability is further evidence for the premalignant nature of this lesion.

[Mucinous adenocarcinoma of the urachus. Case report and review of the literature]. / Muzinöses Adenokarzinom des Urachus. Fallbericht und Literaturübersicht.

We report on a 44-year-old man with the rare case of a mucin-positive carcinoma of the urachus. We performed extended partial cystectomy with regional staging lymphadenectomy of the obturator lymph nodes. Histological investigation revealed a mucin-positive carcinoma of the urachus with negative lymph nodes. For this case, we present symptoms, a plan for diagnosis, and treatment of these tumors.

[Prognostic markers for prostate cancer]. / Prognosefaktoren des Prostatakarzinoms.

Careful consideration of therapy for prostate cancer needs an accurate analysis of prognostic markers to estimate success and benefit for the patient. Prognosis of prostate cancer is determined by the proportion of high grade cancer, many usually utilized prognostic characteristics were rejected by multivariate analysis as no independent prognostic information was delivered. For planning therapy it is crucial to estimate the proportion of high grade cancer as exact as possible. A standardized biopsy technique combined with a quantified analysis of the biopsy cores is most helpful to achieve this goal. The prognostic value of molecular biological and other factors is object of research, only a combination of some of these factors could be demonstrated so far to be superior to the estimation of the proportion of high grade cancer. However, at present their routine use in daily practise is precluded by a high technical and financial expense.

[Can nomograms derived in the U.S. applied to German patients? A study about the validation of preoperative nomograms predicting the risk of recurrence after radical prostatectomy]. / Sind statistische Vorhersagemodelle aus den USA auf deutsche Patienten übertragbar? Eine Validierungstudie präoperativer Nomogramme zur Vorhersage des Rezidivrisikos nach radikaler Prostatektomie.

In patients suffering from prostate cancer, preoperative nomograms, which predict the risk of recurrence may provide a helpful tool in regard to the counselling and planning of an appropriate therapy. The best known nomograms were published by the Baylor College of Medicine, Houston and the Harvard Medical School, Boston. We investigated these nomograms derived in the U.S. when applied to German patients. Data from 1003 patients who underwent radical prostatectomy at the University-Hospital Hamburg were used for validation. Nomogram predictions of the probability for 2-years (Harvard nomogram) and 5-years (Kattan nomogram) freedom from PSA recurrence were compared with actual follow-up recurrence data using areas under the receiver-operating-characteristic curves (AUC). The recurrence free survival after 2 and 5 years was 78% and 58%, respectively. The AUC of the Harvard nomogram predicting 2-years probability of freedom from PSA recurrence was 0.80 vs. Kattan-Nomogram 5-years prediction of 0.83. Thereby, the Kattan nomogram showed a significant higher predictive accuracy (p=0.0274). For that reason preoperative nomograms derived in the U.S. can be applied to german patients. However, we would recommend the utilization of the Kattan nomogram due to its higher predictive accuracy.