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Professor, Consultant Pathologist, American Board Certified Pathologist, Fellow College of American Pathologists. Areas of interest Fine Needle Aspiration Cytology, Cytology, Cancer, Ethics, Islam, Humanity

Editorial: Pathologists as Clinicians!

Modern day management of patients is a multi-disciplinary team (MDT) job and pathologist is an important member of the team. However, there are gross misconceptions about the role of pathology and pathologists in patient management. Perception about role of pathologist varies indifferent societies. While in scientifically developed countries misconceptions are not that great, in underdeveloped countries there exist serious misconceptions. Some even think pathologists are not real physicians! Some consider that pathologists are confined to do the autopsies; whatever they do is too little and too late. Even regulatory authorities like Pakistan Medical & Dental Council (PMDC) has bracketed discipline of Pathology into basic sciences in contrast to radiology which is regarded a clinical discipline! The fact is that pathology is equal if not more clinical subject than radiology. Pathologists render specific diagnoses of the diseases than radiologists whose diagnoses often require pathological confirmation. An eminent pathologist described this difference aptly as “While radiology is study of shadows, pathology is study of substance”! We have no objection on radiology being included in clinical subject, but pathology must also be classified as clinical subject which indeed it is.

Prognostic Factors in Uterine Sarcomas: A Clinicopathologic and Immunohistochemical Study

Abdul Mohsen Al Kushi*, Ahmad Omair***, Haitham Arabi,** and Motasim Badri,****

*College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.**Dept. of Pathology, King Abdulaziz Medical City, National Guard Health Affairs, Riyadh, Saudi Arabia.***Dept. of pathology, College of Science and Health Professions, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia.****Department of Epidemiology & Biostatistics, College of Public Health & Health Informatics, King Saud bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia

ABSTRACT

Background: Uterine sarcomas are rare malignant tumors histologically categorized into high-grade and low-grade sarcomas (HGS & LGS).

Objective: To examine the prognostic relevance of clinicopathological and immunohistochemical features for this rare group of tumors.

Methods: Clinicopathological data including age, follow-up, parity, tumor cell type, lymphovascular invasion, nuclear grade, stage and mitotic index was obtained for 28 cases treated at our institute. HGS (n=22) included 11 each of leiomyosarcoma (LMS), and carcinosarcoma (CS). LGS (n=6) included 3 each of Müllerien adenosarcoma (MAS) and endometrial stromal sarcoma (ESS). Sections were immunostained with antibodies for p53, Bcl-2, ER, HER-2 and c-Kit. The data was statistically analyzed for association between these factors and disease-free survival.

Results: Twelve (42.9%) patients with HGS died of the disease and none died among LGS. Descriptive analysis revealed a statistically significant association between death and HGS (p=0.024), sarcomas with nuclear grade 3 (p=0.029), mitotic index > 60 (p=0.016) and presence of lymphovascular invasion (p=0.028). More than 80% of the patients with recurrence were diagnosed with HGS. Median overall survival time was 70 months. The2, 5- and 10-year survival rates were 65%, 58% and 43% respectively. No statistically significant association was observed between survival times and histologic types of sarcoma (p=0.204) but stage 1 and 2 had a better survival compared to stage 3 and 4. Over expression of P53 was only found in 4 cases of CS; and complete membranous staining for Her-2 was also only observed in CS tumors (n=6). ER positive staining was found in all MAS and ESS tumors only. C-kit positive expression was observed in 8 cases, 7 of which were from HGS group.

Pseudothrombocytopenia in Asymptomatic Outdoor Patients Presenting with Low Platelet Counts

Jamila Farid, Muhammad Idris and Nasreen Gul

Department of Pathology, Ayyub Medical College, Abbottabad, Pakistan

ABSTRACT

Background: Pseudothrombocytopenia is spuriously low platelet count seen in complete blood count performed on an automated hematology analyzer. It may lead to unnecessary investigations& management. It has been postulated to be caused by an anticoagulant namely Ethylene-Diamine-Tetra Acetic-Acid (EDTA) and has been reported in physiological as well as disease conditions with variable frequency. No significant research has been done on this important clinical entity in our country.

Objective: To see the prevalence of pseudothrombocytopenia in our settings.

Methods: EDTA based hematology analyzer method was used as the initial test for blood counts. Patients showing thrombocytopenia were screened for pseudothrombocytopenia by Giemsa stained blood film examination. Those with platelet aggregates were labeled as pseudothrombocytopenia and were studied further by doing manual platelet count (ammonium oxalate method) and repeat automated platelet count on a citrate based fresh blood sample. Manual platelet count was also performed on blood samples not showing platelet aggregates, as a second security check, after which, those with low platelet count were labeled as true asymptomatic thrombocytopenia.

Results: Out of 385 patients, 30 revealed pseudothrombocytopenia, eight patients were male and 22 females, female to male ratio was 2.75:1. Ten patients were less than twenty five years old; 15 patients were 25 to 50 years and five patients aged more than 50 years. Mean age of the patients was 32.7±16.5 years. Machine generated blood report using EDTA blood, revealed platelet count <50 ×103/µl in 16(53.4%), 40-100×103/µl in 12(40%) & 100-149×103/µl in 2 (6.7%) patients respectively. Mean platelet count was 50±25×103/µl. No patient had platelet count of >150×103 /µl by this method. Platelet count using sodium citrate revealed platelets >150 ×103 /µl in 25(83.4%) and 100-149×103/µl in 5(16.6%) patients. By manual method none of patients had platelets lower than 150 ×103/µl.

Tranexamic Acid and Blood Loss During and After Cesarean Section: A Prospective Randomized Study

Noshina Shabir, Hina Pirzada, Shafaq Hanif and Rubina Rafique

Abbas Institute of Medical Sciences, Muzaffarabad, Azad Kashmir, Pakistan

Abstract:

Background: Incidence of cesarean sections is on the rise. This has increased incidence of associated complications, especially the Postpartum hemorrhage (PPH). Tranexamic acid is a potent antifibrinolytic agent. Efficacy and safety of the drug has not been assessed in patients from Muzaffarabad, as of yet.

Objective: To find out the effectiveness and safety of tranexamic acid in the reduction of blood loss during and after the cesarean section.

Methods: A prospective, randomized, placebo controlled, study was directed on 100 women experiencing lower segment cesarean segment (LSCS) at Department of Obstetrics and Gynecology, Combined Military Hospital Muzaffarabad over 6 months from May 2018 to October 2018.  Fifty of them were given tranexamic acid preceding LSCS were contrasted and 50 control group who got IV placebo. Blood loss was collected and estimated during two periods. The study group got IV tranexamic acid and the control group got IV placebo. Following delivery, all participants got 10 units of oxytocin in 500 mL of normal saline. Hemoglobin, urine examination, liver and renal functions were checked in both the groups.

Results: Tranexamic acid essentially decreased the quantity of blood loss from the finish of LSCS to 2 hours postpartum: 60.96±13.4 ml in the investigation group versus 112.02±13.46 mL in the control group (p=0.001). It additionally essentially reduced the amount of blood loss– Intraoperative 500.62±111.20 mL in the study group, versus 696.85±196.32 ml in the control group. (P<0.001). No serious complication or reactions were accounted for in either group.Conclusion: Tranexamic acid essentially decreased the quantity of blood loss during and after the lower segment cesarean segment and its utilization was not associated with any serious reactions or side effect like thrombosis. TXA can be utilized as safe and effective in participants undergoing LSCS and useful for anemic women or the individuals who refuse blood transfusion.

Hepatitis C Virus Genotype 3a: Association of Core Gene Mutations with Treatment Response among Patients of Peshawar

Amina Gul*, Naheed Gul**, Maria Khan***, Ijaz Ali****, Jawad Ahmed***** and Shahina Mumtaz*

*Department of Pathology, Khyber Medical College, Peshawar, Pakistan, **Department of Medicine, Shifa College of Medicine, Islamabad, ***Armed Forces Institute of Pathology, Rawalpindi, Pakistan, ****COMSATS Institute of Information Technology, Islamabad, Pakistan, *****Institute of Basic Medical Sciences (IBMS), Khyber Medical University (KMU), Peshawar, Pakistan, *Khyber Medical College, Peshawar, Pakistan

ABSTRACT

Background: Genome of Hepatitis C Virus (HCV) reveals a high degree of genetic diversity that could be associated with differential response to Interferon based antiviral therapy. Therapeutic response against chronic HCV infection depends on viral genetic mutations in various sub-genomic regions of HCV including Core gene. Identification of these mutations will help guiding individualized treatment regimens that will result in better treatment outcomes as well as future vaccine development against the virus.

Objective: To determine the association of Core gene mutations with response to conventional Interferon and Ribavirin combination therapy among chronically infected HCV genotype 3a patients of Peshawar.

Methods: This observational study was conducted in Institute of Basic Medical Sciences, Khyber Medical University Peshawar from November 2015 to December 2016 and comprised 100 HCV genotype 3a infected patients that received conventional INF and RBV combination therapy for 24 weeks. Core gene was amplified using qualitative nested PCR followed by cloning and sequencing. Viral gene sequences were analyzed for mutations among patients with Sustained Virological Response (SVR) and Non-responder (NR) patients using MEGA 6 software. Statistical analysis was carried out using SPSS version 20.

Results: Comparison of amino acid sequences among patients who achieved SVR and those who turned out to be non-responders against HCV 3a reference sequence (Isolate NZL1; BAA04609) revealed no specific amino acid changes that were associated with either resistance or favorable response to antiviral therapy. No significant differences were observed between the amino acid sequences of patients with SVR and NR (p-value≥0.05).Conclusion:Core protein of HCV genotype 3a was highly conserved among the studied isolates. Observed mutations in the amino acid sequence of Core gene had no significant effect on treatment response of chronic HCV infected patients.

Audit of Gastric Cancer Histopathology Reports – A Systematic Step Forward

Humaira Nasir, Naima Tariq and Uzair Latif

Histopathology Department, Shifa International Hospital, Islamabad, Pakistan

ABSTRACT

Background: Gastric cancer is the second most common cause of cancer-related mortality worldwide. Surgical resection remains the mainstay for treatment. Histopathology reports of these surgically resected specimens play an important part in deciding prognosis as well as future treatment options.

Objective:  This audit was carried out principally to assess adherence of histopathology reporting of gastric cancer cases in our hospital to minimum datasets by Royal College of Pathologists. The essential aim was to promote this practice and improve the standard of reporting in our country as well as health centers across the region.

Methods: This study was carried out from 1st January 2008 to 30th January 2016. Data for audit was collected from computer records using Oracle software. Only gastric epithelial malignancies were included. Criteria from the core and noncore dataset items were marked as either present or not present. After the presentation of the initial audit, deficiencies in reporting were highlighted and a re-audit was carried out.

Results: The mean percentage of completion of reports was 86.47 ±8.267.Tumor size, histological differentiation, lymph node status, proximal and distal resection margins were mentioned in all (100%) cases. Reporting of circumferential resection margin was most inconsistent and there were 32 (37.6%) cases in which pathologists failed to mention this core data item. Noncore data items were poorly represented. Re-audit showed marked improvement in reporting standards with circumferential and lymphovascular invasion missing in only 01 (5.6%) case.Conclusion: In our opinion, standard typed performas are necessary for improving pathological reporting. Moreover, audits should be a regular part of histopathological reporting in our part of the world similar to that seen in West as this is the only way to evaluate ourselves and allows continuous improvement.

Association of Inosine Triphosphatase Polymorphysims rs7270101 and rs1127354 with the occurrence of Anemia in Hepatitis C patients receiving Pegylated Interferon and Ribavirin

Inayat Ur Rahman*, Sami Siraj**, Munnaza Aqeel***, Muhammad Tariq Masood Khan* and Ayaz Hussain****

*Department of Pharmacology, Northwest School of Medicine, Peshawar, **Department of Pharmacology, Institute of Basic Medical Science, Khyber Medical University, Peshawar, ***Department of Pharmacology, Foundation University Medical College, Rawalpindi, ****Department of Medicine, Peshawar Medical College, Peshawar

Background: HCV presents major health care problem in Pakistan. Hepatitis C patients if not well treated may progress to liver cirrhosis and cancer. Currently recommended directly acting antiviral drugs produces better cure rate and less adverse effects than earlier drugs peg-interferon and ribavirin. Peg-interferon and ribavirin combination therapy produces anemia in hepatitis C patients which is the main reason for treatment discontinuation or dose reduction. Anemia due to peg-interferon and ribavirin therapy is associated with ITPA polymorphism.

Abstract:

Objective: To find the association of ITPA polymorphisms rs7270101 and rs1127354 with occurrence of anemia in hepatitis C patients receiving peginterferon and ribavirin combination therapy.

Methods: DNA was extracted from blood samples of treatment naïve hepatitis C patients. Two SNPs of Inosine triphosphatase rs7270101 and rs1127354 were genotyped by means of allelic inhibition of displacement activity method. Complete blood count of the patients was carried out first before starting interferon and ribavirin therapy and then after three months of therapy.

Results: 20 out of 115 patients had more than 3gm/dl reduction in hemoglobin level after 3 months of anti-HCV therapy. At rs1127354, 69 patients showed the presence of CC genotype, 38 were found to have CA and 3 patients had AA genotype. The minor allele A at rs1127354 was found to be protective against anemia due to peg interferon and ribavirin combination therapy in hepatitis C patients (Odds ratio=0.275, C.I= [0.081-0.938], Chi2=4.77, p=0.02889) while the major allele C at rs1127354 was found to be associated with anemia in HCV patients receiving interferon and ribavirin combination therapy (Odds ratio=3.638, C.I= [1.066-12.409],Chi2=4.77, p=0.02889).At rs7270101 all the patients showed AA genotype.

In-vitro Antimicrobial Activity of Fosfomycin Tromethamine against Urinary Extended Spectrum Beta Lactamase producing Escherichia coli and Klebsiella pneumoniae

Mumtaz Ahmad Khan*, Mohsin Shakil** and Rubina Rafique***

*Pathology Department, **Department of Urology, ***Department of Medicine

AJK Medical College, Muzaffarabad, Azad Kashmir, Pakistan

ABSTRACT

Background: Escherichia coli and Klebsiella pneumonia are the most common infecting organisms in patients with uncomplicated Urinary tract infections. Resistance against most of the commonly used antibiotics is increasing. Fosfomycin tromethamine is still effective in UTIs especially in extended spectrum beta lactamase (ESBL) producing bacteria.

Objective: To determine in vitro antimicrobial activity of fosfomycin tromethamine in extended spectrum beta lactamase producing E coli and Klebsiella pneumoniae causing urinary tract infections.

Methods: This was a descriptive cross-sectional study carried out at Abbas Institute of Medical Sciences, AIMS, Muzaffarabad from January 2017 to December 2017.

Urine specimens from suspected cases of UTI were inoculated on cysteine lactose electrolyte deficient (CLED) agar and incubated aerobically at 35oC ± 2 for 16-18 hours. After identification of Gram-negative rods; the isolates were screened for ESBL with cefotaxime 30 μg disc by Kirby-Bauer disc diffusion technique. The isolates with cefotaxime zone diameter equal to or less than 27 mm were further confirmed for ESBL by phenotypic confirmatory test applying cefotaxime and clavulanic acid 30/10 μg combination disc (double disc synergy). The inoculums of bacterial suspensions were plated on Mueller-Hinton agar with subsequent application of Fosfomycin tromethamine disc 200 μg. Plates were incubated overnight aerobically. Subsequently, resulting zone diameters were interpreted according to Clinical &Laboratory Standards Institute guidelines.

Results: Out of 84 ESBL producing Gram negative isolates, 81% (n=68) were identified as E coli and 19% (n= 16) as Klebsiella peumoniae. The age of the patients in ESBL producing urinary isolates ranged from 1 to 80 years, with larger numbers around 60 years of age. According to the study results, 82% (n=79) of E. coli and 75% (n =18) of Klebsiella peumoniae were susceptible to Fosfomycin tromethamine.

Conclusion: Fosfomycin has shown good sensitivity against ESBL producing E coli and Klebsiella pneumoniae emphasizing its role to be used in empirical therapy for simple lower urinary tract infections caused by these uropathogens.

Cutaneous Metastasis of Gestational Trophoblastic Neoplasia on the Face

Ruqaiya Shahid, Batool Huzaifa Husain and Rubina Gulzar

Department of Pathology, Dow International Medical College,

Dow University of Health Sciences, Karachi, Pakistan

ABSTRACT

Background: Choriocarcinoma is a malignant tumor of trophoblastic origin which is highly sensitive to chemotherapy and has a 95-98 % 5-year survival rate even after metastasis.

Objective: We report a rare site of cutaneous metastatic choriocarcinoma in a 30 years old lady who presented with multiple bleeding nodules on her face.

Case Report: The patient had a history of vaginal delivery one and a half year back and presented to the hospital with abnormal uterine bleeding for three months. The skin biopsy revealed a tumor showing dual cell population of cytotrophoblasts and syncytotrophoblasts with extensive hemorrhage and necrosis. Tumor cells were positive for immunohistochemical stains cytokeratin and beta Human Chorionic Gonadotrophin (β HCG) confirming the trophoblastic origin. Her β HCG level was 31,550mIU/ml. Metastatic Gestational Trophoblastic Neoplasia (GTN) occurs in 4 % of patients after evacuation of complete hydatidiform mole and very infrequently after other pregnancies. Lung (80%), vagina (30%), brain (20%) and liver (10%) are common sites of metastasis.

Conclusion: Cutaneous metastasis in GTN has been reported in only 13 other patients till 2015. Our report highlights the importance of histo-pathological input in determining site of primary malignancy. Overall cutaneous metastasis is a poor prognostic indicator for survival.Keywords: Cutaneous Metastasis, Trophoblastic Neoplasia, Gestational Choriocarcinoma

History of Medicine: Ishaq bin Ali al-Rohawi: Pioneer in Medical Ethics

Ethics is the foundation of all healthy developments and human progress in all spheres. Truth is life, and lie is death said the Prophet Muhammad ﷺ. When the world was in dark ages the Islamic world had glittering civilization and there was a big bang in all fields of science and humanities. The human uplift occurred at jet speed and was complete and comprehensive. Almost all modern sciences were founded in that era. It’s no exaggeration although it may seem so. A glance at Wikipedia will give you the names of hundreds of great scientists in that era. Islam instilled highest moral and ethical values as well as intense love for research with utmost honesty. Few people know that Khalifa Waleed predecessor of Khalifa Haroon Rashid had pioneered the medical licensing. Khalifa himself used to preside over the board of highly competent physicians of that time in competence examination of the clinicians before granting them license to practice. When Muslims downfall began in Spain, the medical licensing was taken over by the Italians.