Recurrent sigmoid volvulus secondary to a large pedunculated colonic lipoma.

Symptomatic colon lipoma is a rare occurrence in clinical practice, and its association with sigmoid volvulus is even rarer. We present a case of a man in his 70s who presented to our emergency department with suspected intestinal obstruction. Upon examination, sigmoid volvulus was diagnosed and successfully treated endoscopically through decompression and detorsion. However, the patient experienced a recurrence, leading to the decision to perform sigmoid resection as a Hartmann's procedure. Subsequently, a prolapsed tumor was observed through the stoma, which was endoscopically resected, revealing a pedunculated submucous colonic lipoma. This case report highlights the potential association between sigmoid volvulus and the presence of a large colon lipoma. Thus, giant colonic lipoma should be considered as a differential diagnosis among the causes of colonic volvulus.

ERBB2 Amplification as a Predictive and Prognostic Biomarker in Upper Tract Urothelial Carcinoma.

Upper tract urothelial carcinomas (UTUCs) occur in about 5-10% of all urothelial carcinomas and are frequently discovered in high-stage disease. We aimed to evaluate human epidermal growth factor receptor 2 (ERBB2) protein expression immunohistochemically and ERBB2 amplification in UTUCs by fluorescence in situ hybridization, applying a tissue microarray technique. ERBB2 overexpression and ERBB2 amplification were defined according to the recommendations of the American Society of Clinical Oncology/College of American Pathologists (ASCO/CAP) for breast cancer and gastric carcinoma (GC), revealing scores of 2+ and 3+ in 10.2% and 41.8% of UTUCs, respectively. The performance parameters showed obviously higher sensitivity of ERBB2 immunoscoring according to the ASCO/CAP criteria for GC. ERBB2 amplification was detected in 10.5% of UTUCs. ERBB2 overexpression was more likely to be found in high-grade tumors and was associated with tumor progression. Univariable Cox regression analysis revealed a significantly lower progression-free survival (PFS) in cases with ERBB2 immunoscores of 2+ or 3+ according to the ASCO/CAP guidelines for GC. UTUCs with ERBB2 amplification showed a significantly shorter PFS in the multivariable Cox regression analysis. Irrespective of their ERBB2 status, patients with UTUC treated with platin showed a significantly lower PFS than UTUC patients who had not received any platin-based therapy. In addition, UTUC patients with a normal ERBB2 gene status who had not received platin-based therapy showed significantly longer overall survival. The results suggest that ERBB2 is a biomarker for progression in UTUCs and may define a distinct subgroup of UTUCs. As previously shown, ERBB2 amplification is infrequent. However, the small number of patients diagnosed with ERBB2-amplified UTUC might benefit from ERBB2-targeted cancer therapy. In clinical-pathological routine diagnostics, the determination of ERBB2 amplification is an established method in some defined entities and also successful in small samples. Still, the simultaneous use of ERBB2 immunohistochemistry and ERBB2 in situ hybridization would be important in order to record the low rate of amplified UTUC cases as completely as possible.

Comparing tumor microRNA profiles of patients with long­ and short­term­surviving glioblastoma.

Glioblastoma is one of the most frequent primary brain tumors with a poor prognosis. Nevertheless, some patients show a prolonged survival. The aim of the present study was to compare the expression profiles of tumor derived microRNA (miR) of long­term survivors with those of short­term survivors in order to identify differentially expressed miRs as well as their target genes, which may elucidate mechanisms that play a role in varying tumor progression and, therefore, may influence survival. Formalin­fixed paraffin­embedded samples of 23 patients with glioblastoma were classified according to overall survival. Profiles of miR expression were determined using Nanostring technology. Expression levels of potential target genes of differentially expressed miRs were assessed using immunohistochemistry. MiR profiles of long­term survivors differed from those of short­term survivors. A total of three prominent differentially expressed miRs were highlighted: MiR­130b­3p, which is downregulated in long­term survivors, and miR­146b­5p and miR­148a­3p, which are upregulated in long­term survivors. Known tumor suppressor genes are among targets potentially affected by miR­130b­3p, whereas targets of miR­146b­5p and miR­148a­3p consist of several genes known to have a role in tumor invasion and aggressiveness. In conclusion, it was revealed that a type of miR­signature was associated with short­ and long­term survival, potentially serving as biomarker for disease progression and providing a base for further functional studies.

Evaluation of the Cellular Dissociation Grading, Based on Tumor Budding and Cell Nest Size, in Squamous Cell Carcinoma of the Penis.

The "Cellular Dissociation Grade" (CDG) is based on tumor cell budding and cell nest size. Many studies have examined the CDG in squamous cell carcinomas of other organs such as the lungs, oral cavity, pharynx, larynx, cervix and esophagus. In this study, the CDG was examined in 109 cases of invasive penile squamous cell carcinoma that were treated at the University Medicine Rostock between 2014 and 2022. Furthermore, its correlation with the pathologic status of regional lymph nodes (pN) as the main prognostic factor was verified. Finally, cellular dissociation grading was compared with classic WHO grading. The results showed that pN in penile squamous cell carcinoma showed a highly significant association with the CDG and no statistically significant association with WHO grading. These results support the notion that cellular dissociation grading is an important prognostic factor for squamous cell carcinoma.

An Extremely Rare Cause of an Obstructive Jaundice in Adults: Limited Langerhans Cell Histiocytosis of the Extrahepatic Bile Duct.

Langerhans cell histiocytosis (LCH) is a rare group of idiopathic disorders (previously termed "histiocytosis X") which is characterized by the presence of cells with characteristics similar to bone marrow-derived Langerhans cells which infiltrate various tissues and organs. Like Langerhans cells located in the skin, they express histiocytic markers such as S100, CD1a, and CD68 and contain Birbeck granules, which are rod-shaped intracytoplasmic organelles best demonstrated in electron microscopy. LCH primarily affects the skeleton, but lung, skin, liver, and lymph node involvement may occur alike. Hepatic involvement is well recognized in children, with sclerosing cholangitis occurring in 10-15% of those with multisystemic involvement, whereas LCH confined to the liver appears to be very unusual in adults. Up to date, only one case of a solitary LCH affliction of the extrahepatic bile duct lacking liver involvement in adulthood has been reported on in the literature. We here report on a 60-year-old male patient with classical indolent progressive obstructive jaundice. The diagnostic workup revealed a tumorous lesion in the middle third of the common hepatic bile duct, initially being highly suspicious of an extrahepatic cholangiocarcinoma. CT scans further suspected an infiltration of the right portal vein, implicating a potentially extensive tumor growth, but a preoperative histological confirmation was not feasible. The serum tumor marker CA19-9 was 48 U/mL. The patient then underwent an explorative laparotomy with a pylorus preserving pancreaticoduodenectomy, as all frozen section tissue specimens revealed no tumor infiltration. The final result of the histopathological examination revealed an isolated LCH in the extrahepatic bile duct with a consecutive secondary sclerosing cholangitis. To complete the tumor staging, a thorax CT scan was performed and a generalized histiocytosis was ruled out, hence confirming the localized character of the disease. To the best of our knowledge and after a comprehensive literature review, we report on the second case globally, which describes a primary LCH limited to the extrahepatic bile duct in adulthood. A generalized sclerosing cholangitis in the liver was ruled out by radiological imaging. Preoperative histological affirmation of such findings is very confined due to the complexity and hence can only be diagnosed in the postoperative specimen. However, patients with nondisseminated sole findings, usually report a good prognostic outcome after surgical resection despite the paucity of corresponding data.

The miR-183/96/182 cluster is upregulated in glioblastoma carrying EGFR amplification.

Glioblastoma (GBM) is one of the most frequent primary brain tumors. Limited therapeutic options and high recurrency rates lead to a dismal prognosis. One frequent, putative driver mutation is the genomic amplification of the oncogenic receptor tyrosine kinase EGFR. Often accompanied by variants like EGFRvIII, heterogenous expression and ligand independent signaling render this tumor subtype even more difficult to treat, as EGFR-directed therapeutics show only weak effects at best. So EGFR-amplified GBM is considered to have an even worse prognosis, and therefore, deeper understanding of molecular mechanisms and detection of potential targets for novel therapeutic strategies is urgently needed. In this study, we looked at the level of microRNAs (miRs), small non-coding RNAs frequently deregulated in cancer, both acting as oncogenes and tumor suppressors. Comparative analysis of GBM with and without EGFR amplification should give insight into the expression profiles of miRs, which are considered both as potential targets for directed therapies or as therapeutic reagents. Comparison of miR profiles of EGFR-amplified and EGFR-normal GBM revealed an upregulation of the miR-183/96/182 cluster, which is associated with oncogenic properties in several tumor entities. One prominent target of this miR cluster is FOXO1, a pro-apoptotic factor. By observing FOXO1 downregulation in EGFR-amplified tumors, we can see a significant correlation of EGFR amplification, miR-183/96/182 cluster upregulation, and repression of FOXO1. Although no significant difference in overall survival is shown, these data may contribute to the molecular understanding of this tumor subtype and offer potential targets for miR-based therapies.

Surgery for Valvular and Nonvalvular Papillary Fibroelastomas.

Papillary fibroelastomas (PFE) are benign neoplasms, mostly located on valvular surfaces with high embolic potential. This study presents a 27-year single institutional experience on surgical treatment of PFE in an adult patient- cohort with long-term follow-up. This study was approved by the institutional review board. Date and number of IRB approval: 11/23/2017, Institutional Review Board approval number A2014-0149. The need for individual patient consent was waived. We retrospectively evaluated all patients who underwent cardiac surgery for suspected space-occupying lesions in the observation period between June 1991 and June 2018 at our hospital. Clinicopathological features, imaging characteristics, surgical procedures and disease outcome were analyzed. 120 patients were diagnosed with various primary/secondary cardiac tumors and histology confirmed 21 PFEs were found in 16 patients. There was no significant age difference between patients with valvular vs nonvalvular PFEs (P = 0.26). Valvular lesions were found in aortic valve (n = 6), mitral valve (n = 2) and tricuspid valve (n = 1). Nonvalvular PFEs were found in right atrium (n = 2), left ventricle (n = 2), left atrial appendage (n = 2) and aortic wall (n = 1). Valvular lesions were significantly smaller in size compared to non-valvular lesions (P = 0.0013). Left-side PFEs were associated with a high embolization episodes (10/13 patients, 77%) not related to the size. One patient died in-hospital. All other patients were discharged out of the hospital postoperative. Follow-up was performed regularly for a median of 2.8 years (range 0.1-11 years) postoperative. Nonvalvular PFE tended to be larger in size and at least when located on the left sided heart had equally high propensity to embolize compared to valvular PFE. We strongly advocate surgical excision in all left-sided PFE.

Papillary Fibroelastoma in Differential Diagnosis of Left Atrial Appendage Masses.

Papillary fibroelastomas are benign tumors that usually originate from cardiac valves but may have other endocardial origins. We report the cases of 2 patients in whom left atrial appendage masses were initially diagnosed as thrombus. They were treated for embolic stroke and their symptoms resolved; however, their left atrial appendage masses did not regress. After surgery, histologic analysis of the resected masses revealed papillary fibroelastoma in both cases. We discuss the diagnostic and therapeutic dilemmas encountered in patients with papillary fibroelastomas and cardiac masses other than thrombus.

Rare germline variants in the E-cadherin gene CDH1 are associated with the risk of brain tumors of neuroepithelial and epithelial origin.

The genetic basis of brain tumor development is poorly understood. Here, leukocyte DNA of 21 patients from 15 families with ≥ 2 glioma cases each was analyzed by whole-genome or targeted sequencing. As a result, we identified two families with rare germline variants, p.(A592T) or p.(A817V), in the E-cadherin gene CDH1 that co-segregate with the tumor phenotype, consisting primarily of oligodendrogliomas, WHO grade II/III, IDH-mutant, 1p/19q-codeleted (ODs). Rare CDH1 variants, previously shown to predispose to gastric and breast cancer, were significantly overrepresented in these glioma families (13.3%) versus controls (1.7%). In 68 individuals from 28 gastric cancer families with pathogenic CDH1 germline variants, brain tumors, including a pituitary adenoma, were observed in three cases (4.4%), a significantly higher prevalence than in the general population (0.2%). Furthermore, rare CDH1 variants were identified in tumor DNA of 6/99 (6%) ODs. CDH1 expression was detected in undifferentiated and differentiating oligodendroglial cells isolated from rat brain. Functional studies using CRISPR/Cas9-mediated knock-in or stably transfected cell models demonstrated that the identified CDH1 germline variants affect cell membrane expression, cell migration and aggregation. E-cadherin ectodomain containing variant p.(A592T) had an increased intramolecular flexibility in a molecular dynamics simulation model. E-cadherin harboring intracellular variant p.(A817V) showed reduced ß-catenin binding resulting in increased cytosolic and nuclear ß-catenin levels reverted by treatment with the MAPK interacting serine/threonine kinase 1 inhibitor CGP 57380. Our data provide evidence for a role of deactivating CDH1 variants in the risk and tumorigenesis of neuroepithelial and epithelial brain tumors, particularly ODs, possibly via WNT/ß-catenin signaling.

EGFR and BRAF mutations in inverted sinonasal papilloma - a more complex landscape?

Inverted (Schneiderian) sinonasal papilloma (ISP) is a neoplasm derived from mucosa of the sinonasal tract characterized by local aggressive growth, a tendency to recur and an association with sinonasal carcinoma. The etiology of ISP remains unclear. Recently, identical mutations in exons 19 and 20 of the oncogene EGFR were reported in ISP and ISP-associated sinonasal carcinoma. Nevertheless, it remains unclear whether recurring ISPs show identical EGFR mutations at different time points or whether these mutations are identical throughout the respective ISP sample. We used Sanger sequencing to test 60 formalin-fixed paraffin embedded ISP samples from 40 patients regarding mutations in exons 19 and 20 of EGFR-together with exon 15 of BRAF. Overall, 32 samples of 22 patients showed a mutation in EGFR exon 20, whereas 28 samples of 18 patients showed none. No mutation in EGFR exon 19 was found in any sample. Four samples of four patients showed a BRAF exon 15 mutation. Interestingly, samples of four patients exhibited genetic heterogeneity, enabling us to report this in ISP for the first time.

Histopathological Features and Ann Arbor Stage in Periocular Lymphoma.

BACKGROUND: To evaluate biodata, symptoms/signs, lymphoma type, localization, stage level, treatment choice and outcome of ocular adnexal lymphoma (OAL). PATIENTS AND METHODS: A single-center retrospective analysis of 56 patients with OAL was performed from 1998 to 2018. RESULTS: OAL involved the orbit in 44.6%, the conjunctiva in 32.1%, the lacrimal apparatus in 14.3% and the eyelid in 8.93%. Extranodal marginal zone B-cell lymphoma (EMZL) was found in 60.7%, follicular lymphoma (FL) in 21.4%, diffuse large B-cell lymphoma in 7.14%, mantle cell lymphoma in 5.36% and chronic lymphatic leukaemia in 5.36% patients. No relapse was seen in 76%. EMZL and FL had a significantly better overall survival compared to other lymphoma types (p=0.002). Patients with Ann Arbor stage IE had a significantly better prognosis than those with stages higher than IE (p=0.048). CONCLUSION: Our data suggest that clinicopathological features such as Ann Arbor stage influence survival.

Loss of Mismatch-repair Protein Expression and Microsatellite Instability in Upper Tract Urothelial Carcinoma and Clinicopathologic Implications.

BACKGROUND: Upper tract urothelial carcinoma (UTUC) may arise in the setting of hereditary non-polyposis colorectal cancer (Lynch syndrome [LS]) or sporadically. Variable frequencies of microsatellite instability (MSI) were found in UTUC. For advanced solid MSI tumors, targeted therapy with programmed death-ligand 1 inhibitors is available. Therefore, we aimed to determine the prevalence of mismatch repair (MMR) protein loss and MSI in UTUC using a tissue microarray approach and further molecular and correlation analysis. MATERIALS AND METHODS: We studied the immunohistochemical expression of MLH1, MSH2, MSH6, and PMS2 on tissue microarrays containing formalin-fixed, paraffin-embedded samples of 128 patients with UTUC. MSI analysis was performed in 79 cases with deficient MMR protein expression, and/or in patients aged 60 years and below, and/or other tumors possibly related to LS. RESULTS: Loss of MMR protein expression was seen in 24 (18.8%) of 128 cases. MSI analysis revealed MSI-high in 29, MSI-low in 7 cases. The Fisher exact test demonstrated significant differences between MSI and loss of MMR protein expression, clinically possible LS, tumor growth pattern, inverted growth pattern, and death (P < .001, P < .001, P = .002, P = .003, and P = .033, respectively). MSI does not appear to influence survival (overall and progression-free), but there was a significant shorter progression-free survival in MSI-high versus MSS patients who had received chemotherapy. CONCLUSION: The frequency of MSI in UTUC was 36 (28.1%) of 128 patients with a good accuracy of immunohistochemistry. In daily practice, MSI screening especially is recommended in patients with advanced UTUC and inverted papillary tumor growth pattern with the aim of screening patients for possible targeted therapy.

Circular RNAs in Clear Cell Renal Cell Carcinoma: Their Microarray-Based Identification, Analytical Validation, and Potential Use in a Clinico-Genomic Model to Improve Prognostic Accuracy.

Circular RNAs (circRNAs) may act as novel cancer biomarkers. However, a genome-wide evaluation of circRNAs in clear cell renal cell carcinoma (ccRCC) has yet to be conducted. Therefore, the objective of this study was to identify and validate circRNAs in ccRCC tissue with a focus to evaluate their potential as prognostic biomarkers. A genome-wide identification of circRNAs in total RNA extracted from ccRCC tissue samples was performed using microarray analysis. Three relevant differentially expressed circRNAs were selected (circEGLN3, circNOX4, and circRHOBTB3), their circular nature was experimentally confirmed, and their expression-along with that of their linear counterparts-was measured in 99 malignant and 85 adjacent normal tissue samples using specifically established RT-qPCR assays. The capacity of circRNAs to discriminate between malignant and adjacent normal tissue samples and their prognostic potential (with the endpoints cancer-specific, recurrence-free, and overall survival) after surgery were estimated by C-statistics, Kaplan-Meier method, univariate and multivariate Cox regression analysis, decision curve analysis, and Akaike and Bayesian information criteria. CircEGLN3 discriminated malignant from normal tissue with 97% accuracy. We generated a prognostic for the three endpoints by multivariate Cox regression analysis that included circEGLN3, circRHOBT3 and linRHOBTB3. The predictive outcome accuracy of the clinical models based on clinicopathological factors was improved in combination with this circRNA-based signature. Bootstrapping as well as Akaike and Bayesian information criteria confirmed the statistical significance and robustness of the combined models. Limitations of this study include its retrospective nature and the lack of external validation. The study demonstrated the promising potential of circRNAs as diagnostic and particularly prognostic biomarkers in ccRCC patients.

A Novel Predictor Tool of Biochemical Recurrence after Radical Prostatectomy Based on a Five-MicroRNA Tissue Signature.

Within five to ten years after radical prostatectomy (RP), approximately 15-34% of prostate cancer (PCa) patients experience biochemical recurrence (BCR), which is defined as recurrence of serum levels of prostate-specific antigen >0.2 µg/L, indicating probable cancer recurrence. Models using clinicopathological variables for predicting this risk for patients lack accuracy. There is hope that new molecular biomarkers, like microRNAs (miRNAs), could be potential candidates to improve risk prediction. Therefore, we evaluated the BCR prognostic capability of 20 miRNAs, which were selected by a systematic literature review. MiRNA expressions were measured in formalin-fixed, paraffin-embedded (FFPE) tissue RP samples of 206 PCa patients by RT-qPCR. Univariate and multivariate Cox regression analyses were performed, to assess the independent prognostic potential of miRNAs. Internal validation was performed, using bootstrapping and the split-sample method. Five miRNAs (miR-30c-5p/31-5p/141-3p/148a-3p/miR-221-3p) were finally validated as independent prognostic biomarkers. Their prognostic ability and accuracy were evaluated using C-statistics of the obtained prognostic indices in the Cox regression, time-dependent receiver-operating characteristics, and decision curve analyses. Models of miRNAs, combined with relevant clinicopathological factors, were built. The five-miRNA-panel outperformed clinically established BCR scoring systems, while their combination significantly improved predictive power, based on clinicopathological factors alone. We conclude that this miRNA-based-predictor panel will be worth to be including in future studies.

Correlation of Ki-67 Index with Volumetric Segmentation and its Value as a Prognostic Marker in Glioblastoma.

OBJECTIVE: Previous research has shown a strong correlation between the Ki-67 proliferation index and grade of malignancy in astrocytoma. Ki-67 has also shown encouraging results as a prognostic marker for patients' overall survival (OS). We focus on whether the index is linked to the appearance of glioblastoma on pretreatment magnetic resonance imaging (MRI) or to OS. METHODS: In our retrospective study, only isocitrate dehydrogenase IDH wild-type glioblastoma was included (n = 152). Ki-67 index was quantified via immunohistochemistry. On all pretreatment MRI, tumor compartments (tumor, necrosis, and edema) were volumetrically assessed. An OS subpopulation was filtered from the total cohort (residual tumor volume ≤2 cm3). In addition, a propensity score matching was executed. RESULTS: All volumetric assessed tumor volumes correlated with each other (P ≤ 0.011), although the Ki-67 index showed no correlation with any of the measured volumes. Concerning the OS, a cutoff value of 20% for the Ki-67 index showed a significant influence on patients' OS in multivariate analysis (P = 0.043). CONCLUSIONS: The unique appearance of every glioblastoma on MRI seems to be independent of the Ki-67 index. Furthermore, the Ki-67 index did show a distinct prognostic value for OS within our cohort at a cutoff value of 20% for Ki-67.

Pathologic Features of Tumor Activity and Stability in Uveal Melanoma Specimens after Fractionated CyberKnife Radiosurgery.

To evaluate uveal melanoma cell activity and pathologic features after stereotactic CyberKnife radiosurgery in specimens from five patients. Specimens from five patients treated by CyberKnife radiosurgery in three fractions were included in this study. Because of persistent retinal detachment in 3 patients, tumour endoresection was performed at four, seven and ten month after CyberKnife radiosurgery. At nine and twelve months after treatment, enucleation of the eye globe was performed in 2 patients because of secondary tumour bleeding and missing regression. After histomorphological analysis and determination of Ki67-proliferation index, DNA cytophotometry, fluorescence in-situ hybridization evaluation for chromosome 3 loss, GNA11and GNAQ mutation analysis were performed. Four of the five tumours included in this study showed variable radiation-induced morphologic changes in the form of enlargement of cells and nuclei, cytoplasmic vacuolisation and nuclear fragmentation. The DNA content of a large fraction of tumour cells was hypoploid. On the other hand, single strikingly hyperchromatic melanoma cells showed marked aneuploidy. The proliferation fraction in the three endoresected tumours was very low (<1%), but it was elevated in the enucleation cases. Monosomy 3 was detected in two of the endoresection cases, but none of the enucleation cases. None of the patients experienced a local tumour recurrence, but two of the patients developed liver metastasis. Many melanoma cells seemed to be vital within the first 6 months after CyberKnife radiosurgery, but obvious radiation-induced morphologic changes, including tumour necrosis, hypoploid DNA content plus low Ki-67 index could indicate sublethal cell damage.

Frequent and Yet Unreported GNAQ and GNA11 Mutations are Found in Uveal Melanomas.

Malignant melanoma of the uvea is the most common primary malignant tumor in the eye. We aimed to analyze GNAQ and GNA11 mutations in uveal melanomas using formalin-fixed, paraffin-embedded material and correlate the results with clinicopathological parameters. Tumor tissue was microdissected followed by amplification of GNAQ exon 4 and 5, GNA11 exon 4 and 5, and finally analyzed by Sanger sequencing. A total of 64.4 GNA11/GNAQ mutations, including ten yet unreported, were found. Two cases showed multiple mutations. Overall survival was significantly shorter in the uveal melanoma cohort with GNAQ exon 5 mutation. In concordance with previous studies, high frequencies of mutations in GNAQ or GNA11 were detected. Interestingly, in about 20% of UM, not yet reported mutations in GNAQ or GNA11 were seen. Rarely, uveal melanoma may harbor double mutations in GNAQ and/or GNA11. Recent data imply, that implementation of GNAQ/GNA11 mutation analysis in routine diagnostic procedures might be helpful for future therapeutic decisions.

Management of Congenital Clinical Anophthalmos with Orbital Cyst: A Kinshasa Case Report.

An early developmental lack of the optic vesicle can result in congenital anophthalmia, defined as a complete absence of the eye, which can be distinguished from congenital microphthalmos, where ocular rudiments are present. Here, a rare pediatric case of congenital clinical anophthalmos with orbital cyst in the left orbit is reported. The patient was a 14-month-old girl with no other congenital defects who underwent surgical and prothetic management in St. Joseph's Hospital Kinshasa, Democratic Republic of the Congo (DRC). Surgery was carried out under general anesthesia. The cyst was punctured and its wall fully excised. Near the orbital apex pigmented elements representing iris, ciliary body, and choroidal or retinal remnants were found. The specimens were fixed in formalin for histological examination. Surgical cyst removal including socket deepening for an artificial eye was performed. Postoperative wound healing was uneventful and a satisfactory cosmetic outcome was achieved in all follow-up examinations. Histological examination revealed rudimentary ocular structures similar to degenerated lens tissue with a typical, PAS-positive capsule. Additionally, pigmented epithelial structures, which seem to be of ciliary body, iris, and choroidal or retinal-type epithelium origin, could be detected, prompting the final diagnosis, microphthalmia with dominant cyst formation.

The Diagnosis and Treatment of Penile Cancer.

BACKGROUND: The incidence of penile cancer in Europe lies in the range of 0.9 to 2.1 cases per 100 000 persons per year. Carcinogenesis is associated with human papilloma virus (HPV) infection and with chronic inflammation. METHODS: This review is based on publications (2010-2017) retrieved by a selective search in PubMed and EMBASE and on the guidelines of the European Association of Urology, the European Society of Medical Oncology, the National Comprehensive Cancer Network, and the National Institute for Health and Care Excellence (NICE). RESULTS: 95% of cases of penile cancer are accounted for by squamous cell carcinoma, whose numerous subtypes have different clinical courses. Chronic preputial inflammation due to phimosis or lichen sclerosus is often associated with penile cancer. Circumcision lowers the risk of penile cancer (hazard ratio: 0.33). Maximally organ-preserving surgery with safety margins of no more than a few millimeters is the current therapeutic standard, because a local recurrence, if it arises, can still be treated locally with curative intent. Local radiotherapy can be performed in early stages. Lymphogenic metastasis must be treated with radical lymphadenectomy and adjuvant chemotherapy. Patients with clinically unremarkable inguinal lymph nodes nonetheless need invasive lymph node staging because of the high rate of lymphogenic micrometastasis. CONCLUSION: Penile cancer is curable in all early stages with the appropriate treatment, but its prognosis depends crucially on the proper management of the regional (i.e., inguinal) lymph nodes. In many countries, the treatment of this rare disease entity has been centralized.

Diagnostic and Prognostic Potential of MicroRNA Maturation Regulators Drosha, AGO1 and AGO2 in Urothelial Carcinomas of the Bladder.

Bladder cancer still requires improvements in diagnosis and prognosis, because many of the cases will recur and/or metastasize with bad outcomes. Despite ongoing research on bladder biomarkers, the clinicopathological impact and diagnostic function of miRNA maturation regulators Drosha and Argonaute proteins AGO1 and AGO2 in urothelial bladder carcinoma remain unclear. Therefore, we conducted immunohistochemical investigations of a tissue microarray composed of 112 urothelial bladder carcinomas from therapy-naïve patients who underwent radical cystectomy or transurethral resection and compared the staining signal with adjacent normal bladder tissue. The correlations of protein expression of Drosha, AGO1 and AGO2 with sex, age, tumor stage, histological grading and overall survival were evaluated in order to identify their diagnostic and prognostic potential in urothelial cancer. Our results show an upregulation of AGO1, AGO2 and Drosha in non-muscle-invasive bladder carcinomas, while there was increased protein expression of only AGO2 in muscle-invasive bladder carcinomas. Moreover, we were able to differentiate between non-muscle-invasive and muscle-invasive bladder carcinoma according to AGO1 and Drosha expression. Finally, despite Drosha being a discriminating factor that can predict the probability of overall survival in the Kaplan⁻Meier analysis, AGO1 turned out to be independent of all clinicopathological parameters according to Cox regression. In conclusion, we assumed that the miRNA processing factors have clinical relevance as potential diagnostic and prognostic tools for bladder cancer.