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Clinicopathological features of gastroenteropancreatic neuroendocrine tumours (GEP-NETs) have rarely been studied in Pakistani population. We investigated clinical characteristics of these tumours according to updated World Health Organization (WHO) 2010 classification.The data of Shifa International Hospital, Islamabad was retrospectively analysed for pathologically confirmed GEP-NETs from January 2013 to March 2018.One hundred and eighteen patients (mean age, 52.2± 16.4 years; Of these 65(55.1%) were males. Majority, 98(83.1%) of the patients were symptomatic including 6(5.1%) with functional tumours. Pancreas was the most frequent primary site noted in 33(28%) patients. The most common histologic type was well differentiated neuroendocrine tumour (WDNET) in 96(81.4%) patients followed by neuroendocrine carcinoma (NEC) in 11(16.1%) patients. Almost half the cases or 54(45.8%) of WDNET were grade 1, 32 (27.1%) were grade 2, and 10 (8.5%) were grade 3. Distant metastasis at the time of diagnosis was found in 18(15.3%) cases with 14,(77.7%) in liver as the most common metastatic site. Synaptophysin positivity was seen in 60 (96.8%) cases of grade 1, 32(27.2%) of grade 2 WDNET, 8(100%) cases of grade 3 WDNET and 12(92.3%) of NEC and chromogranin was positive in 49(94.2%) of grade 1 and grade 2 WDNET, 5 (83.3%) cases of grade 3 WDNET and 5 (45.4%) cases of NEC.GEP-NETs showed a wide clinicopathological spectrum. Pancreas is the most common site of involvement by the GEP-NET, however, grade 3 WDNET had a predilection for colon. Small cell carcinoma was commonly observed in the oesophagus.

Herpes simplex virus type 1 (HSV-1) is a structurally complex enveloped dsDNA virus that has evolved to replicate in human neurons and epithelia. Viral gene expression, DNA replication, capsid assembly, and genome packaging take place in the infected cell nucleus, which mature nucleocapsids exit by envelopment at the inner nuclear membrane then de-envelopment into the cytoplasm. Once in the cytoplasm, capsids travel along microtubules to reach, dock, and envelope at cytoplasmic organelles. This generates mature infectious HSV-1 particles that must then be sorted to the termini of sensory neurons, or to epithelial cell junctions, for spread to uninfected cells. The focus of this review is upon our current understanding of the viral and cellular molecular machinery that enables HSV-1 to travel within infected cells during egress and to manipulate cellular organelles to construct its envelope.

Chronic liver disease, with viral or non-viral etiology, is endemic in many countries and is a growing burden in Asia. Among the Asian countries, Pakistan has the highest prevalence of chronic liver disease. Despite this, the genetic susceptibility to chronic liver disease in this country has not been investigated. We performed a comprehensive analysis of the most robustly associated common genetic variants influencing chronic liver disease in a cohort of individuals from Pakistan. A total of 587 subjects with chronic liver disease and 68 healthy control individuals were genotyped for the HSD17B13 rs7261356, MBOAT7 rs641738, GCKR rs1260326, PNPLA3 rs738409, TM6SF2 rs58542926 and PPP1R3B rs4841132 variants. The variants distribution between case and control group and their association with chronic liver disease were tested by chi-square and binary logistic analysis, respectively. We report for the first time that HSD17B13 variant results in a 50% reduced risk for chronic liver disease; while MBOAT7; GCKR and PNPLA3 variants increase this risk by more than 35% in Pakistani individuals. Our genetic analysis extends the protective role of the HSD17B13 variant against chronic liver disease and disease risk conferred by the MBOAT7; GCKR and PNPLA3 variants in the Pakistani population.

Renal cell carcinoma (RCC), accounts for 2-3% of all new cancers diagnosed. Most renal tumours have characteristic histological features, which help in their sub classification. However, some cases do show overlapping morphology which pose a diagnostic challenge for the pathologists. Tumour ancillary studies such as immunohistochemistry (IHC) may play a significant role in segregation of these tumours. This study was undertaken to determine the role of IHC in diagnosing these tumours.December 2015. It was carried out in histopathology laboratory of Shifa International Hospital, Islamabad. A total of fifty-five (n=55) nephrectomy specimens having RCC subtypes were included. A specific morphological diagnosis was rendered in each case on HE.. A panel of six immunohistochemical markers CK7, CD10, CD117, CA IX, AMACR and Vimentin was then applied in each case and a final diagnosis considering both morphology and IHC was given. Statistical analysis was done using SPSS version 20.0. Mean and SD were calculated for quantitative variables where as frequencies and percentages were calculated for qualitative variables.Out of a total of 55 cases, 36 (65.55%) were males whereas 19 (34.5%) were females. The mean age of patients was 54.04±14.40 years. Clear cell RCC comprised 70.9% (n=39), Papillary RCC 14.5% (n=8), Chromophobe RCC 10.9% (n=6) and clear cell papillary RCC 3.6% (n=2) of cases on morphology. After application of IHC stains in all cases, 83.6% (n=46) of cases were found to have correct diagnosis on HE. However, 16.4% (n=9) of cases could not be correctly diagnosed on morphology alone and it was in these cases that IHC played a major role in reaching a final diagnosis.Although most RCC subtypes display a characteristic morphology on HE, in a significant proportion of the cases there are considerable overlapping morphological features. Our study shows that a correct diagnosis cannot be made on HE alone in a notable number of cases. Therefore, IHC should be applied in all cases to reach a final diagnosis, which has both prognostic and therapeutic implications.

To evaluate human epidermal growth factor receptor 2 (HER2/neu) interobserver variability between specially trained and untrained general histopathologists.The retrospective study cases of invasive breast carcinoma received at Shifa International Hospital, Islamabad, from June 2010 to December 2011, for assessment of HER2/neu status by immunohistochemistry which were retrieved from the files and, 30 consecutive cases each of score 0, 1+, 2+ and 3+ were selected for a total of 120 cases. Two groups of two histopathologists each examined the cases blindly. One group had attended a short course in Germany, while the other group comprised two qualified histopathologists who had not had any special training. Each histopathologist reported the cases independently according to standard guidelines. Kappa statistics were applied.The trained group of histopathologists showed agreement in 113 (94%) cases. Kappa value was calculated to be 0.96 which means 'perfect agreement. In contrast the untrained group showed agreement in 83 (69%) cases with a kappa value of 0.59 which means 'moderate agreement.Interobserver variability in immunohistochemical scoring of HER-2/neu in breast carcinoma is high among untrained general histopathologists. This may adversely affect the selection of patients with cancers who could benefit from Herceptin therapy.

Yolk sac tumour is germ cell tumour commonly found in children and infants under three years of age in its pure form with a good prognosis. The commonest location for the yolk sac tumour is gonads i.e. testis and gonads. Yolk sac tumour is rarely reported in extra- gonadal locations. Parapharyngeal space is an uncommon site for mature teratoma and very few cases have been reported in adults and children. Malignant transformation in a mature teratoma in the extragonadal sites has been reported but development of yolk sac tumour has not been reported so far in the world literature. We report to our knowledge, the only and first case of yolk sac tumour arising in a mature teratoma presenting as a parapharyngeal mass in a four year old male child.

Akylation reactions of the Mannich bases Viz: 3-diethylaminomethylindole and 3-(diethylaminomethyl)-2-methylindole with nitromethane, ammonium carbonate, levulinic acid, methylcyanide and acetamide in aqueous medium have been described.