A Multicenter Study of Clinical Presentations and Outcomes of Multiple Myeloma in Pakistan: The Real-World Analysis in a Resource-Constrained Country.

This is the first multicenter study from Pakistan exploring the prevalence, clinical presentations and treatment outcomes of Multiple Myeloma patients. This retrospective study involved data collection from hospital record system of four tertiary care referral hospitals of Pakistan including all patients diagnosed as having Multiple Myeloma from January 2014 to December 2018. The demographic details, clinical presentations, laboratory findings, treatment responses, and mortalities were evaluated. The progression-free survival and overall survival were analyzed considering relapse and mortality as the end points, respectively. For the progression-free survival, the Kaplan-Meier survival analysis and the log rank test were used to compare the survival function for chemotherapy followed by autologous stem cell transplant (ASCT) as opposed to chemotherapy alone (non-ASCT). The overall survival analysis was assessed by Kaplan-Meier survival analysis. This study identified 403 Multiple Myeloma patients in five years. The median age at presentation was 55 years. Bortezomib based drug regimens were the most commonly used initial treatments (57.5%). Forty three patients received ASCT. The progression-free survival median for ASCT and non-ASCT patients were 50 months (95% CI, 42-57.9 months) and 26 months (95% CI, 21.5-30.5 months), respectively. The cumulative probability of survival rate at 60 months was 80%. This study identified 403 Multiple Myeloma patients over 5 years in four tertiary care hospitals of Pakistan. It underscores the importance of autologous stem cell transplant in Myeloma patients and advocates improving its facilities in Pakistan.

Lung Biopsy in Coronavirus-19 Pneumonia: A Case Report and Review of Literature.

Pneumonia is one of the major manifestations of infection by the novel coronavirus (COVID-19) virus. CT scans are used as first line investigation in suspected cases. Biopsies are almost never done. The gross and microscopic pathology has been studied mostly on autopsy specimens in fatal cases. We present a case of a mildly symptomatic adult male, who was a chronic liver disease patient awaiting liver transplant. His lung biopsy was done for diagnosis of a lesion, suspected to be a fungal infection. He was tested for COVID-19 and was PCR-negative at the time. His biopsy showed patchy changes of viral pneumonia. One week later, he tested positive for COVID-19 on PCR. He became asymptomatic soon and the ground glass lung opacities cleared up within another week without any treatment in spite of having a serious comorbid condition.   Key Words: Viral pneumonia, COVID-19, Lung biopsy.

Early hematological indicators of severe COVID-19 disease in hospitalized patients: Data from a South Asian population.

INTRODUCTION: Outbreak of corona virus disease in 2019 (COVID-19) has resulted in significant morbidity and mortality worldwide. Our aim is to document hematological parameters of patients with COVID-19 during initial stage of diagnosis and to identify early hematological indicators of severe infection. MATERIALS AND METHODS: This retrospective study was conducted at Shifa International Hospital, Pakistan from April to November 2020. Patients hospitalized with COVID-19, diagnosed on RT-PCR and had a complete blood count (CBC) done within 48 hours of diagnosis were included. Data was analyzed using IBM® SPSS Statistics. RESULTS: A total of 425 patients were included in this study out of whom 272(64%) were males. The mean age was 55.61 ± 17.84 years. 95 patients (22.4%) had normal blood counts within 48 hours of COVID-19 diagnosis. Cytopenias were seen in 193(45.4%) patients. There were 75(17.6%) mortalities during the study period. Chi-square test showed that thrombocytopenia, lymphopenia and neutrophilic leucocytosis were significantly associated with mortality (P = .037, P < .001, P < .001 respectively) and need for ventilator (P = .009, P < .001, P < .001, respectively). Neutrophilia was also associated with development of Acute Respiratory Distress Syndrome (P < .001). On ROC analysis, Neutrophil-to-Lymphocyte Ratio yielded an area under the curve (AUC) of 0.693 and 0.660 for the outcomes mortality and need for ventilator, respectively. For a subset of 288 patients who had D-dimer levels checked within 48 hours of COVID-19 diagnosis, the AUC for mortality and ventilator need was 0.708 and 0.671, respectively. CONCLUSION: Hematological indices are vital indicators in the prognosis and risk stratification of COVID-19 during initial stages of disease.

Gastroenteropancreatic neuroendocrine tumours: Clinicopathological evaluation at Shifa International Hospital, Islamabad.

OBJECTIVE: 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. METHODS: The data of Shifa International Hospital, Islamabad was retrospectively analysed for pathologically confirmed GEP-NETs from January 2013 to March 2018. RESULTS: 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. CONCLUSIONS: 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.

Genetic Susceptibility to Chronic Liver Disease in Individuals from Pakistan.

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.

Role Of Immunohistochemistry In Subtyping Renal Cell Carcinomas With Overlapping Morphological Features.

BACKGROUND: 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. METHODS: 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 H&E.. 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. RESULTS: 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 H& E. 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. CONCLUSIONS: Although most RCC subtypes display a characteristic morphology on H&E, in a significant proportion of the cases there are considerable overlapping morphological features. Our study shows that a correct diagnosis cannot be made on H & E 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.

Interobserver variability in HER-2/neu reporting on immunohistochemistry in breast carcinomas.

OBJECTIVE: To evaluate human epidermal growth factor receptor 2 (HER2/neu) interobserver variability between specially trained and untrained general histopathologists. METHODS: 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. RESULTS: 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. CONCLUSION: 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.

The nested variant of urothelial carcinoma arising in a fibroepithelial polyp: Report of a case and review of literature.

The nested variant of urothelial carcinoma is a rare but very important histological entity due to its deceptively bland-looking appearance and aggressive behavior. We present a case of a 30-year-old man who was found to have a solitary polypoid growth in the bladder. It was resected and found to be a fibroepithelial polyp; a rare entity in itself, harboring the above tumor. The lesion also showed a second population of scattered bizarre stromal cells. To our knowledge, this is the first instance of a nested variant of urothelial carcinoma arising in a fibroepithelial polyp. The presence of atypical stromal cells has also not been described previously.

Yolk sac tumour arising in mature teratoma in the parapharyngeal space.

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.