Introduction/Background:Fuhrman nuclear grade is the most important histological parameter to predict prognosis in a patient of renal cell carcinoma (RCC). However, it suffers from inter-observer and intra-observer variation giving rise to need of a parameter that not only correlates with nuclear grade but is also objective and reproducible. Proliferation is the measure of aggressiveness of a tumour and it is strongly correlated with Fuhrman nuclear grade, clinical survival and recurrence in RCC. Ki-67 is conventionally used to assess proliferation. Mini-chromosome maintenance 2 (MCM-2) is a lesser known marker of proliferation and identifies a greater proliferation faction. This study was designed to assess the prognostic significance of MCM-2 by comparing it with Fuhrman nuclear grade and Ki-67.Material and Methods:n=50 cases of various ages, stages, histological subtypes and grades of RCC were selected for this study. Immunohistochemical staining using Ki-67(MIB-1, Mouse monoclonal antibody, Dako) and MCM-2 (Mouse monoclonal antibody, Thermo) was performed on the paraffin embedded blocks in the department of Morbid anatomy and Histopathology, University of Health Sciences, Lahore. Labeling indices (LI) were determined by two pathologists independently using quantitative and semi-quantitative analysis. Statistical analysis was carried out using SPSS 20.0. Kruskall-Wallis test was used to determine a correlation of proliferation markers with grade, and Pearson's correlate was used to determine correlation between the two proliferation markers.Results:Labeling index of MCM-2 (median=24.29%) was found to be much higher than Ki-67(median=13.05%). Both markers were significantly related with grade (p=0.00; Kruskall-Wallis test). LI of MCM-2 was found to correlate significantly with LI of Ki-67(r=0.0934;p=0.01 with Pearson's correlate). Results of semi-quantitative analysis correlated well with quantitative analysis.Conclusion:Both Ki-67 and MCM-2 are markers of proliferation which are closely linked to grade. Therefore, they can act as surrogate markers for grade in a manner that is more objective and reproducible.

Objective CYP11A1 mutations cause P450 side-chain cleavage (scc) deficiency, a rare form of congenital adrenal hyperplasia with a wide clinical spectrum. We detail the phenotype and evolution in a male sibship identified by HaloPlex targeted capture array. Family study The youngest of three brothers from a non-consanguineous Scottish family presented with hyperpigmentation at 3.7 years. Investigation showed grossly impaired glucocorticoid function with ACTH elevation, moderately impaired mineralocorticoid function, and normal external genitalia. The older brothers were found to be pigmented also, with glucocorticoid impairment but normal electrolytes. Linkage studies in 2002 showed that all three brothers had inherited the same critical regions of the maternal X chromosome suggesting an X-linked disorder, but analysis of NR0B1 (DAX-1, adrenal hypoplasia) and ABCD1 (adrenoleukodystrophy) were negative. In 2016, next-generation sequencing revealed compound heterozygosity for the rs6161 variant in CYP11A1 (c.940G>A, p.Glu314Lys), together with a severely disruptive frameshift mutation (c.790_802del, K264Lfs*5). The brothers were stable on hydrocortisone and fludrocortisone replacement, testicular volumes (15–20 mL), and serum testosterone levels (24.7, 33.3, and 27.2 nmol/L) were normal, but FSH (41.2 µ/L) was elevated in the proband. The latter had undergone left orchidectomy for suspected malignancy at the age of 25 years and was attending a fertility clinic for oligospermia. Initial histology was reported as showing nodular Leydig cell hyperplasia. However, histological review using CD56 staining confirmed testicular adrenal rest cell tumour (TART). Conclusion This kinship with partial P450scc deficiency demonstrates the importance of precise diagnosis in primary adrenal insufficiency to ensure appropriate counselling and management, particularly of TART.

Melanosis of the bladder, also known as melanosis vesicae, refers to presence of pigment in bladder mucosa. A rare phenomenon, however, it can be confused with the primary or metastatic melanoma of the bladder. Therefore, knowledge of the entity can prevent over diagnosis of this benign entity.We are reporting a case of melanosis of bladder in a 69 year old male with prolonged history of LUTS and bladder diverticulae. Cystoscopic examination showed black patches and biopsy revealed pigmentation in the epithelium and underlying lamina propria. Special stains identified the pigment to be melanin. No malignant cells were identified.

Background Fine needle aspiration cytology has been established as a minimally invasive, non-tumour seeding investigation of choice in the initial diagnostic pathway of parotid lesions. The purpose of this study was to compare the accuracy of fine needle aspiration cytology performed with and without ultrasound to determine whether one method should be preferred to the other. A retrospective review of all patients undergoing fine needle aspiration cytology with and without ultrasound for parotid masses in a large district general hospital between 2012 and 2016 was performed. Specificity, sensitivity, accuracy, positive and negative predictive value, percentage of inconclusive fine needle aspiration cytology and percentage of second fine needle aspiration cytology were determined for each group. Results A total of 397 fine needle aspiration cytology results were available for analysis. The numbers performed with ultrasound guidance and free-hand were roughly equal (208 (52.3%) versus 189 (47.7%)). The number of inconclusive fine needle aspiration cytology reports was significantly higher in the free-hand group (65/189 (34.4%)) than the ultrasound group (25/208 (12%)) (p < 0.0001). A significantly higher number of repeated fine needle aspiration cytology were undertaken in the free-hand group vs ultrasound group (43 vs 15, p < 0.0001); overall 7.2% of ultrasound-guided fine needle aspiration cytology required a second fine needle aspiration cytology, compared to 22.8% in the free-hand group. The sensitivity, specificity, positive and negative predictive values were all higher in the ultrasound group versus the free-hand group. Conclusions Ultrasound-guided fine needle aspiration cytology is superior to free-hand fine needle aspiration cytology in the investigation of parotid tumours. There is a significant benefit in reducing the number of inconclusive results and repeat fine needle aspiration cytology, and a potential benefit in improving the sensitivity and positive predictive value, when immediate cytology assessment of the sample quality is not performed.