Frequency of Expression of PD-1 and PD-L1 In Head And Neck Squamous Cell Carcinoma And their Association With Nodal Metastasis: A Cross-Sectional Study.

OBJECTIVE: The objective of this study was to determine the Immunohistochemical expression of PD- 1, PD-L1 and its association with nodal metastasis in head and neck squamous cell carcinoma. MATERIALS AND METHODS: A total of 66 cases were studied at Oral pathology/Histopathology, Armed forces Institute of Pathology (AFIP), Rawalpindi. The tissue sampling and processing yielded the formalin fixed, paraffin wax blocks. These blocks were cut into the thin sections (5 microns) by the microtome and then were mounted on the glass slides. This was followed by the routine H&E staining and then IHC staining (PD-1 and PD-L1) of these tissues mounted slides. For each case a definitive histological diagnosis was made. The two types of variables were analyzed. For qualitative variables frequencies and percentages were calculated whereas for quantitative variables means and standard deviations were analyzed. The Chi-square test then was applied to evaluate the significant difference and p-value of ≤0.05 was taken significant. RESULTS: This study was conducted at Histology department, Armed Forces Institute of Pathology, Rawalpindi over a period of one year from June 2019 to June 2020. It revealed male and female patients with 66.7% (44 Cases) and 33.3% (22cases) percentages respectively. The mean age was found to be 59.53 ± 13.637 (mean ± SD) and the mandible (37.9%) was the most commonly affected site. In total of 66 cases, 48 (72.7%) cases with metastasis of lymph nodes were presented. Out of 66 cases ,47 (71.2%) cases showed positive expression of PD-1 in the TILs seen among the primary tumor of the specimens, whereas, 40 (60.6%) cases showed positive PD-L1 expression in tumor cells of primary tumor.In comparison, as out of 66 cases ,48 (72.5%) cases showed lymph nodes metastasis, out of which 45 showed positive expression for PD-1 and 25 out of those 48 cases showed positive expression for PD-L1 in metastatic lymph nodes.The p-value turned to be significant for PD-1 IHC expression and PD-L1 IHC expression in the primary tumorand metastatic lymph nodes. CONCLUSION: A significant correlation was inferred among IHC expression of PD-1 and PD-L1 with lymph nodes metastasis. Accurate evaluation, analysis and precise management with aid of IHC markers results in initial and timely diagnosis and favorable treatment outcomes helping in the evaluation of disease course at preliminary diagnosis on incisional biopsies.

Diagnosis and Management of Diffuse Large B-Cell Lymphoma: Society of Medical Oncology, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology Joint Clinical Practice Guideline.

Diffuse large B-cell lymphoma (DLBCL) is the commonest non-Hodgkin lymphoma encountered by hematopathologists and oncologists. Management guidelines for DLBCL are developed and published by countries with high income and do not cater for practical challenges faced in resource-constrained settings. This report by a multidisciplinary panel of experts from Pakistan is on behalf of three major national cancer societies: Society of Medical Oncology Pakistan, Pakistan Society of Hematology, and Pakistan Society of Clinical Oncology. The aim is to develop a practical and standardized guideline for managing DLBCL in Pakistan, keeping in view local challenges, which are similar across most of the low- and middle-income countries across the globe. Modified Delphi methodology was used to develop consensus guidelines. Guidelines questions were drafted, and meetings were convened by a steering committee to develop initial recommendations on the basis of local challenges and review of the literature. A consensus panel reviewed the initial draft recommendations and rated the guidelines on a five-point Likert scale; recommendations achieving more than 75% consensus were accepted. Resource grouping initially suggested by Breast Health Global Initiative was applied for resource stratification into basic, limited, and enhanced resource settings. The panel generated consensus ratings for 35 questions of interest and concluded that diagnosis and treatment recommendations in resource-constrained settings need to be based on available resources and management expertise.

Childhood cancers: Analysis of 1279 cases at Armed Forces Institute of Pathology, Rawalpindi, Pakistan.

OBJECTIVE: To determine the clinicopathological pattern of childhood malignancies registered with a pathology-based tumour registry. METHODS: The descriptive retrospective study was conducted at the Armed Forces Institute of Pathology, Rawalpindi, Pakistan, and comprised data related to all the histologically diagnosed malignant childhood tumours in the institutional tumour registry from January 2009 to December 2018. Data was analysed using SPSS 20 for the site of involvement, age distribution and histological types of tumours. RESULTS: Of the total 37793 malignant tumours, 1279(3.38%) were in paediatric subjects aged <15 years. There were 820(64.1%) male subjects and 459(35.8%) were female. Lymph node malignancies were the commonest 261(20.4%), followed by eye tumours 251(19.6%), and brain 107(8.3%). CONCLUSIONS: Lymphomas and eye tumours were found to form the main bulk of childhood cancer.

Immunohistochemical Expression of CD10, BCL6 and MUM1 in Differentiating Diffuse Large B Cell Lymphoma Subtypes.

OBJECTIVE: To determine the immunohistochemical expression of CD10, BCL6 and MUM1 in differentiating diffuse large B cell lymphoma subtypes. STUDY DESIGN: Descriptive, cross-sectional study. PLACE AND DURATION OF STUDY: Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi, from November 2014 to May 2015. METHODOLOGY: Newly diagnosed cases of DLBCLon H&E stain as well as IHC markers, according to WHO blue book 2008, were included in the study. Patients' gender, age and site of lymphoma were noted. DLBCLsubtypes (GCB and activated type or non-GCB) were assessed based on IHC expression of CD10, BCL6 and MUM1 and the results were recorded. The data were analyzed by using computer software program SPSS version 20. Descriptive statistics, frequencies and percentages were calculated. RESULTS: Out of 96 patients, 79 (82%) were male and 17 (18%) were female. Mean age was 54.66 ±16.73 years. Thirty-six (37.5%) cases showed positivity for CD10 and BCL6 both (GCB type), whereas MUM1 was positive in 60 (62.5%) cases (non-GCB type or activated type). Asignificant statistical association was seen between expression of IHC markers (CD10, BCL6 and MUM1) and DLBCLsubtypes (GCB and non-GCB type, p<0.001). CONCLUSION: In Pakistani population, the frequency of non-GCB type expressing MUM1 is 62.5%, which is quite high as compared to western countries. It needs to be further explored, because it represents high-risk subsets in which alternative strategies for diagnosis and management should be planned.

Diagnostic utility of C-kit protein (CD117) expression in differentiating adenoid cystic carcinoma and polymorphous low grade Adenocarcinoma.

BACKGROUND & OBJECTIVE: To evaluate usefulness of immunohistochemical marker C-kit (CD117) in differentiating Adenoid cystic carcinoma (AdCC) from Polymorphous low-grade adenocarcinoma (PLGA) in patients of salivary gland carcinomas. AdCC is a malignant salivary gland neoplasm with poor prognosis. PLGA is a salivary gland malignancy with indolent growth pattern. Differentiating between the two entities is a diagnostic challenge. We evaluated the role of C-kit in differentiating the two. METHODS: This is a Cross sectional study. Samples of 19 tumors including 12 AdCC and 4 PLGA was evaluated at Department of Histopathology, Armed Forces Institute of Pathology, Rawalpindi from December 2015 to August 2016. Immunohistochemical techniques were used to analyze the level of c-kit expression in AdCC (n = 12), polymorphous low-grade adenocarcinoma (PLGA) (n = 6). Samples were stained using monoclonal antibody against C-kit. Statistical analysis of the data was done using SPSS version 21. RESULTS: Strong diffuse cytoplasmic reactivity was observed in more than 50% of the tumor cells of AdCC whereas less than 20% of cells showed negative to weak positivity in PLGA. Hence, the difference in the expression of c-kit between AdCC and PLGA was statistically significant (p value <0.002). CONCLUSIONS: CD117 expression itself can be used as a marker in differential diagnosis of salivary gland neoplasms. However, the percentage of the CD117 immunoreactive cells and the staining intensities appeared to be important factors in distinguishing AdCC from PLGA.

Immunohistochemical Expression of B Cell Lymphoma2 with Clinicopathological Correlation in Triple Negative Breast Cancers in Northern Pakistan.

BACKGROUND: Triple negative breast cancers (TNBCs) are high grade aggressive tumors generally with a poor prognosis, not responding to hormonal and anti Her2 Neu therapy. Expression of the antiapoptotic B cell lymphoma 2 gene (Bcl2) is associated with low grade, slowly proliferating hormone receptor positive tumors with improved survival. Anti Bcl2 agents can be used as alternative targeted therapy in triple negative cancers. MATERIALS AND METHODS: The objective of this study was to determine the immunohistochemical expression of Bcl2 in triple negative breast cancers and any correlation with clinicopathological variables in Northern Pakistan. RESULTS: All 52 patients were females, aged between 28 and 80 years(average 48.0±12.1). 28 cases (53.8%) were positive for Bcl2, this being associated with low grade invasive ductal carcinomas, lymph node metastasis and lymphovascular invasion. CONCLUSIONS: Bcl2 may be an important prognostic factor and its expression might be used for targeted therapy using Anti Bcl2 drugs.

Sarcoma-Like Mural Nodule in a Borderline Mucinous Tumour of Ovary.

A 37-year female presented with complaint of lower abdominal pain and amenorrhoea to the Military Hospital, Rawalpindi. Ultrasound of pelvis showed a right adnexal cystic lesion. On investigation, CA-125 was raised. Her MRI scan of pelvis revealed a right adnexal mass of fluid intensity measuring 15.2 x 12.9 x 9.2 cm. Right ovarian cystectomy was performed and the specimen was sent for histopathological examination. Grossly, the mass was cystic in appearance and measured 13.5 x 10 x 10 cm. On sectioning, it was unilocular and filled with turbid material. The cyst wall showed multiple papillary structures along with a nodule measuring 1.1 x 1 cm. Microscopically, the sections revealed borderline mucinous tumour with a sarcoma-like mural nodule composed of spindle shaped cells and epulis-like giant cells. Sarcoma-like mural nodules are rare nodules which are associated with mucinous tumours of the ovary. However, they have excellent prognosis and should not be interpreted as malignant.

Frequency of epstein-barr virus in classical hodgkin Lymphoma.

BACKGROUND: Epstein-Barr virus plays an important role in pathogenesis of Hodgkin lymphoma. The first patient with Epstein-Barr positive Reed Sternberg cells was described in 1985. Since then association between Epstein-Barr virus and Hodgkin lymphoma has been shown in many parts of the world and its occurrence shows significant variation from continent to continent and from country to country. METHODS: The study was carried out at department of histopathology, Armed Forces Institute of Pathology from 27th April 2013 to 10th March 2014. A total of 55 cases of classical Hodgkin lymphoma were included in the study. RESULTS: Out of 55 patients, 38 (69%) were male and 17 (31%) were female. The age of the patients ranged between 4-67 years with an average age of 29.4±21.72 years. Out of these, 44 cases (80%) were positive for latent membrane protein-1. Among positive cases 32 (72.72%) were male and 12 (27.28%) were female. Based upon histological subtypes MCHL was the commonest as a whole accounting for 87.3% as well as among both genders. Out of total 55 cases, 79.16% (38/48) of mixed cellularity Hodgkin lymphoma cases showed positivity for latent membrane protein-1 while 83.33% (5/6) cases of nodular sclerosis Hodgkin lymphoma and 100% (1/1) cases of lymphocyte depleted Hodgkin lymphoma showed positivity. No case of lymphocyte predominant classical Hodgkin lymphoma was diagnosed during the study. 80% of our classical Hodgkin lymphoma cases showed association with EBV expression. A total of 79.16% cases of mixed cellularity Hodgkin lymphoma showed LMP1 expression while 100% of lymphocyte depleted Hodgkin lymphoma showed LMP1 expression. CONCLUSIONS: The highest expression seen in lymphocyte depleted Hodgkin lymphoma subtype in contrast to mixed cellularity requires to be confirmed by a larger scale study comprising of substantial number of patients of lymphocyte depleted Hodgkin lymphoma and lymphocyte rich classical Hodgkin lymphoma.

SPECTRUM OF CENTRAL NERVOUS SYSTEM TUMOURS--A SINGLE CENTER HISTOPATHOLOGICAL REVIEW OF 761 CASES OVER 5 YEARS.

BACKGROUND: The incidence of central nervous system (CNS) tumours has rapidly increased over the past few years. There is no accurate nationwide CNS tumour epidemiology in Pakistan that makes policy making for tumour screening and early treatment difficult. The purpose of this study was to provide the spectrum of CNS tumours in a premier diagnostic and referral centre of Pakistan. METHODS: This cross-sectional study was carried out at Histopathology Department, Armed Forces Institute of Pathology over a period of 5 years. A total of 761 cases patients who were diagnosed with CNS tumours on histopathology, both benign and malignant, belonging to both genders, between the ages of 1-85 years, from 11.2009 to 31.12.2013 were included in the study. RESULTS: Seven CNS tumour categories were as follows; tumours of neuroepithelial tissue (56.0%), tumours of the meninges (28.3%), tumour of the sellar region (2.6%), germ cell tumour (0.1), tumour of cranial and paraspinal nerves (5.4%), lymphomas and haematopoietic neoplasm (2.4%), metastatic tumours (4.9%), where histological types by age and gender showed great variability. Astrocytic tumours were the commonest neuroepithelial tumours (69.4%). Glioblastoma multiform forming the largest subtype of neuroepithelial tumours (40.4%) with a mean age at diagnosis being 47.1 years. Overall, males exceeded females in number of most of the CNS tumour types, however meningeal tumours were more frequently noted in females. CONCLUSIONS: Neuroepithelial tumours are commonest tumour and comprise more than half of all operated CNS tumours in our setup, followed by meningeal tumours. Glioblastoma multiforme is largest subtype of neuroepithelial tumour, and comprising 40.4% of all.

Importance of clinical assessment in diagnosis of acute appendicitis and its role in decreasing negative appendicectomy rate.

BACKGROUND: Appendicitis is a common diagnosis, but is by no means a simple one to establish. It is impractical to have a definitive preoperative diagnosis, which leads to an appreciable rate of negative appendicectomy as reported in world literature varying from 20-40% with its morbidity around 10%. This retrospective study investigated the value of clinical assessment and medical imaging (ultrasonography) for patients with suspected appendicitis. Negative appendicectomy rate and appendiceal perforation with or without medical imaging were used as end points for this investigation. METHODS: This study reviewed all patients admitted in Sheikh Khalifa Bin Zaid Hospital with suspected acute appendicitis. The patient cohort was identified from the unit registry and review of medical records. The medical records were analysed, and the outcomes of patients were followed up. RESULTS: Between June 2010 to June 2012, 375 patients' medical records were audited. These included 56.3% males and 43.7% females. The negative appendicitis rate was 7.2% and appendiceal perforation rate was 5.3%. Ultrasound was done in 103 (27.4%) patients in whom diagnosis of appendicitis was doubtful. Medical imaging had a 50% prediction rate for acute appendicitis, 40% false-negative rate, and 10% false-positive rate. Overall, the prediction rate for appendicitis by clinical assessment supplemented by laboratory tests and medical imaging at clinician's discretion was 92.8%. CONCLUSIONS: Despite studies advocating routine use of medical imaging for patients with suspected acute appendicitis, this study showed that the clinical evaluation is still paramount to the management of patients with suspected acute appendicitis before considering medical imaging.