Accelerated photocarcinogenesis and multifocal squamous cell carcinomas associated with voriconazole and human papillomavirus in HIV - case report.

Voriconazole is an antifungal with known side effects of phototoxicity and photocarcinogenesis. We present a case of HPV-related multifocal squamous cell carcinoma in a 68-year-old man with HIV, due to accelerated photocarcinogenesis associated with long-term use of voriconazole. Histology confirmed SCC with HPV-related features and he was found to have metastases. Multifocal SCC is unusual in association with voriconazole and HIV infection and only one other case has been reported. It is important for clinicians to be aware of the photocarcinogenic effects of voriconazole, especially in patients with HIV.

HIV-related Merkel cell carcinoma: A report of three cases from the UK.

Merkel cell carcinoma (MCC) of the skin is a rare, aggressive and often fatal neuroendocrine skin cancer. The incidence of MCC has significantly increased in the last decades. Factors that have been associated with the development of MCC include infection with Merkel Cell polyomavirus (MCPyV), ultraviolet exposure, hematologic malignancies and immunosuppression.We present three cases of patients living with HIV who were diagnosed with MCC. HIV cases associated with MCC have been rarely reported and to our knowledge, not yet before in the UK.

An unusual penile lesion.

We present an unusual case of an orange-brown penile lesion with a description of the histological findings. Click here for the corresponding questions to this CME article.

NeuroSAFE frozen section during robot-assisted radical prostatectomy: peri-operative and histopathological outcomes from the NeuroSAFE PROOF feasibility randomized controlled trial.

OBJECTIVES: To report on the methods, peri-operative outcomes and histopathological concordance between frozen and final section from the NeuroSAFE PROOF feasibility study (NCT03317990). PATIENTS AND METHODS: Between May 2018 and March 2019, 49 patients at two UK centres underwent robot-assisted radical prostatectomy (RARP). Twenty-five patient were randomized to NeuroSAFE RARP (intervention arm) and 24 to standard RARP (control arm). Frozen section was compared to final paraffin section margin assessment in the 25 patients in the NeuroSAFE arm. Operation timings and complications were collected prospectively in both arms. RESULTS: Fifty neurovascular bundles (NVBs) from 25 patients in the NeuroSAFE arm were analysed. When analysed by each pathological section (n = 250, average five per side), we noted a sensitivity of 100%, a specificity of 99.2%, and an area under the curve (AUC) of 0.994 (95% confidence interval [CI] 0.985 to 1; P ≤0.001). On an NVB basis (n = 50), sensitivity was 100%, specificity was 92.7%, and the AUC was 0.963 (95% CI 0.914 to 1; P ≤0.001). NeuroSAFE RARP lasted a mean of 3 h 16 min (knife to skin to off table, 95% CI 3 h 2 min-3 h 30 min) compared to 2 h 4 min (95% CI 2 h 2 min-2 h 25 min; P ≤0.001) for standard RARP. There was no morbidity associated with the additional length of operating time on in the NeuroSAFE arm. CONCLUSION: This feasibility study demonstrates the safety, reproducibility and excellent histopathological concordance of the NeuroSAFE technique in the NeuroSAFE PROOF trial. Although the technique increases the duration of RARP, this does not cause short-term harm. Confirmation of feasibility has led to the opening of the fully powered NeuroSAFE PROOF randomized controlled trial, which is currently under way at four sites in the UK.

Author Correction: Co-targeting PIM and PI3K/mTOR using multikinase inhibitor AUM302 and a combination of AZD-1208 and BEZ235 in prostate cancer.

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Co-targeting PIM and PI3K/mTOR using multikinase inhibitor AUM302 and a combination of AZD-1208 and BEZ235 in prostate cancer.

PIM and PI3K/mTOR pathways are often dysregulated in prostate cancer, and may lead to decreased survival, increased metastasis and invasion. The pathways are heavily interconnected and act on a variety of common effectors that can lead to the development of resistance to drug inhibitors. Most current treatments exhibit issues with toxicity and resistance. We investigated the novel multikinase PIM/PI3K/mTOR inhibitor, AUM302, versus a combination of the PIM inhibitor, AZD-1208, and the PI3K/mTOR inhibitor BEZ235 (Dactolisib) to determine their impact on mRNA and phosphoprotein expression, as well as their functional efficacy. We have determined that around 20% of prostate cancer patients overexpress the direct targets of these drugs, and this cohort are more likely to have a high Gleason grade tumour (≥ Gleason 8). A co-targeted inhibition approach offered broader inhibition of genes and phosphoproteins in the PI3K/mTOR pathway, when compared to single kinase inhibition. The preclinical inhibitor AUM302, used at a lower dose, elicited a comparable or superior functional outcome compared with combined AZD-1208 + BEZ235, which have been investigated in clinical trials, and could help to reduce treatment toxicity in future trials. We believe that a co-targeting approach is a viable therapeutic strategy that should be developed further in pre-clinical studies.

PEOPLE: PatiEnt prOstate samPLes for rEsearch, a tissue collection pathway utilizing magnetic resonance imaging data to target tumor and benign tissue in fresh radical prostatectomy specimens.

BACKGROUND: Over 1 million men are diagnosed with prostate cancer each year worldwide, with a wide range of research programs requiring access to patient tissue samples for development of improved diagnoses and treatments. A random sampling of prostate tissue is sufficient for certain research studies; however, there is growing research need to target areas of the aggressive tumor as fresh tissue. Here we set out to develop a new pathway "PEOPLE: PatiEnt prOstate samPLes for rEsearch" to collect high-quality fresh tissue for research use, using magnetic resonance imaging (MRI) to target areas of tumor and benign tissue. METHODS: Prostate tissue was sampled following robotic radical prostatectomy, using MRI data to target areas of benign and tumor tissue. Initially, 25 cases were sampled using MRI information from clinical notes. A further 59 cases were sampled using an optimized method that included specific MRI measurements of tumor location along with additional exclusion criteria. All cases were reviewed in batches with detailed clinical and histopathological data recorded. For one subset of samples, DNA was extracted and underwent quality control. Ex vivo culture was carried out using the gelatin sponge method for an additional subset. RESULTS: Tumor was successfully fully or partially targeted in 64% of the initial cohort and 70% of the optimized cohort. DNA of high quality and concentration was isolated from 39 tumor samples, and ex vivo culture was successfully carried out in three cases with tissue morphology, proliferation, and apoptosis remaining comparable before and after 72 hours culture. CONCLUSION: Here we report initial data from the PEOPLE pathway; using a method for targeting areas of tumor within prostate samples using MRI. This method operates alongside the standard clinical pathway and minimizes additional input from surgical, radiological, and pathological teams, while preserving surgical margins and diagnostic tissue.

Schistosomiasis-A Disobedient Ureter, a Disobedient Diagnosis.

Background: Schistosomiasis is rare in western countries, but remains a potentially serious disease. It is known to result in severe urogenital complications; prompt diagnosis can therefore significantly affect outcomes. Case Presentation: We report the case of a 41-year-old male with pleuritic chest pain and visible hematuria who had emigrated from Zimbabwe to the United Kingdom 20 years previously. CT imaging revealed a hydronephrotic right pelvicaliceal system, with a dilated ureter to its distal portion. Preliminary tests for schistosomiasis, including terminal urine microscopy and serology, were negative. An initial ureteroscopy was challenging owing to a tight ureteral stricture such that a retrograde stent insertion and not ureteroscopic visualization or biopsy was carried out. A relook ureteroscopy after 6 weeks revealed a dense distal ureteral stricture, biopsies were taken, the stricture was ablated with LASER, and a retrograde stent was placed. Microscopic examination of the biopsies confirmed Schistosomiasis haematobium. Treatment consisted of a divided dose of praziquantel and a reducing dose of steroids. At a third look ureteroscopy the stricture was ablated with LASER again, and the stent was removed. Subsequent renograms indicated recurrent obstruction despite LASER treatment and a retrograde ureteral stent was replaced. The patient ultimately had a Boari flap ureteral reimplant with good results. Conclusion: This case illustrates the clinical challenges of diagnosing and treating ureteral schistosomiasis. It shows that all the initial tests can be negative, but where the clinical picture points toward schistosomiasis it is worth persevering and a good tissue biopsy may be the only way to verify an otherwise elusive diagnosis.

Basal cell carcinoma arising from an epidermal cyst: when a cyst is not a cyst.

Malignant degeneration within epidermal cysts is very rare. However, these lesions may not be recognised clinically, and histological examination plays an important role in arriving at a correct diagnosis. Hence, we believe that benign-looking cystic lesions with a history of progressive growth should be surgically excised and submitted for histopathological assessment.

Multifocal peritoneal calcifying fibrous tumour: incidental finding at cholecystectomy.

Calcifying fibrous tumour (CFT) is a benign tumour of elusive aetiology and a potential for local recurrence. Despite its peculiar histological characteristics it can still be confused with interrelated differential diagnosis like inflammatory myofibroblastic tumour (IMT) or solitary fibrous tumours. The clinical differential diagnosis is however much wider. To date seven cases of multiple peritoneal CFTs are on record. The authors present a case discovered incidentally during laparoscopic cholecystectomy, with no previous history and no radiological diagnosis achieved despite having undergone magnetic resonance cholangiopancreatography (MRCP) and normal routine perioperative investigation. The patient is disease-free 12 months after diagnosis. The case report is followed by a detailed literature review.

Immunohistochemical pattern of protein P21, cyclin D1 and cyclin E in endometrial hyperplasia.

PURPOSE: In our research we investigated immunohistochemical expression of cell cycle proteins protein p21, cyclin D1 and cyclin E in physiological endometrium (n = 15), hyperplastic endometrium (n = 61), and post hormone replacement therapy endometrium (n = 24). MATERIAL AND METHODS: We performed immunohistochemical analysis of selected cell cycle proteins in 100 specimens of human endometrium. RESULTS: The average immunoexpression index scores in glandular endometrial cells (GES) and stromal endometrial cells (SEC) were respectively: for p21- GES: 11.8 +/- 17.19%; SEC: 9.31 +/- 17.15%; for cyclin D1- GES: 9.25 +/- 18.41%; SEC: 3.22 +/- 11.46%; for cyclin E: GES: 26.42 +/- 27.47%; SEC: 4.61 +/- 7.90%. Statistical analysis disclosed more intense p21 glandular immunoreactivity among women with endometrial hyperplasia in comparison to other subpopulations. In the case of assessment of cyclin D1 immunoreactivity, there was no statistical correlation between analysed parameters. The average cyclin E immunoreactivity in endometrial glandular cells was significantly higher (p = 0.003) in women with endometrial hyperplasia and correlated with age. CONCLUSIONS: Intensive immunoreactivity of cyclin E in glandular cells is typical for endometrial hyperplasia and can be treated as an objective indicator of this pathological process during histopathological diagnostic procedures. Immunoreactivity index of p21 and cyclin D1 is independent of the morphological pattern of human endometrium, patients' age and gynaecological history of patients.

Cyclin D1 expression in primary thyroid carcinomas.

OBJECTIVES: The aim of the study was to demonstrate and evaluate the expression of cyclin D1, a protein connected with a cell cycle, by means of the immunohistochemical method in malignant thyroid neoplasms. The purpose of the analysis of the results was to explain the relation between cyclin D1 in thyroid cells and neoplasm transformation. MATERIAL AND METHODS: The study was conducted on thyroid neoplasms from 35 patients who were diagnosed with the thyroid carcinoma (30 women and 5 men). Detection DAKO LSAB + system was applied with use of monoclonal antibodies against cyclin D1. The results of immunohistochemical reaction was described as an index (percentage of cells showing a characteristic brown color in 1000 counted cells). As a positive result of reaction an intensive brown color of carcinomas cellular nuclei was acknowledged. RESULTS: The mean value of cyclin D1 expression index in papillary carcinoma was 14.44% +/- 9.37, in medullary carcinoma 27.35% +/- 5.40, in nonpapillary carcinomas originating from A cells 18.0% +/- 10.20. The results were statistically analyzed. In medullary carcinoma the highest values of positive cells cyclin D1 index were revealed. CONCLUSIONS: The results obtained encourage continued studies on cyclin D1 expression in thyroid neoplasms and a more accurate analysis with a larger number of cases. Perhaps the index of this protein will become a recognized prognostic marker in thyroid neoplasms or an objective risk factor of the thyroid epithelial cells neoplastic transformation.

[Rare case of a respiratory epithelial adenomatoid hamartoma of the nasal cavity, maxillary sinus et ethmoid sinuses: a clinicopathologic study]. / Respiratory epithelial adenomatoid hamartoma jamy nosa, zatoki szczekowej i zatok sitowych: kliniczno-histopatologiczny opis przypadku.

A case of the respiratory epithelial adenomatoid hamartoma of the nasal cavity, maxillary sinus and ethmoid sinuses for the first time in the polish literature was reported. Characteristic clinical symptoms and histopathologic features, diagnosis and surgical intervention as well differential diagnosis were introduced.

[A study of human lens epithelial cells by light and electron microscopy and by immunohistochemistry in different types of cataracts]. / Ocena komórek nablonka soczewki w mikroskopie swietlnym i elektronowym oraz metodami immunohistochemicznymi w zacmach róznego typu.

PURPOSE: To evaluate the characteristics of cataract changes in lens epithelial cells (LECs), in different types of human cataract. MATERIAL AND METHODS: Anterior capsules for the study were obtained from patients with different types of cataracts during extracapsular cataract extraction, or phacoemulsification using continuous curvilinear capsulorhexis. LECs attached to the anterior capsules were analyzed for morphological changes by light and electron microscopy, and for cellular characteristics by immunohistochemistry. The reactivity to cytokeratins 5,6,8,17 and 19 (arker for epithelial cells) and to vimentin (arker for mesenchymal cells) was determined. RESULTS: The consecutive degenerative changes were observed in most of the cells: multilayered cells, nuclei of abnormal diameters and shapes, vacuolation of nuclei and cytoplasm. LECs were immunohistochemically positive for cytokeratin and vimentin, or only for vimentin in all types of cataract. Some of LECs showed morphological and immunohistochemical characteristics of mesenchymal cells. CONCLUSIONS: Lens epithelial cells show similar degenerative changes in different types of cataract and may have the ability to transdifferentiate into mesenchymal cells.