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Introduction Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma and is the most common type of non-Hodgkin's lymphoma (NHL) worldwide. The World Health Organization (WHO) classification of hematopoietic tumors has recognized three morphological variants of DLBCL: centroblastic, immunoblastic, and anaplastic. Some studies have shown that the anaplastic variant of DLBCL is associated with aggressive clinicopathological features. Anaplastic DLBCL is rare, and the clinicopathological characteristics of this subtype of DLBCL are not widely studied in our population. Therefore, in this study, we evaluated the frequency of the anaplastic variant of DLBCL and its association with other clinicopathological parameters. Methods A retrospective study was conducted in the Department of Histopathology at the Liaquat National Hospital and Medical College over a period of six years, from January 2015 to December 2020. All cases diagnosed as DLBCL based on morphology and immunohistochemical (IHC) profile were included in the study. The diagnosis of anaplastic DLBCL was rendered based on morphology (large bizarre pleomorphic cells in a cohesive or sheet-like growth pattern), combined with CD30 IHC expression. Results The mean age of the patients was 52.90 ±16.42 years, and the mean Ki67 index was 73.18 ±16.52%. Of the 220 cases of DLBCL, 47.3% cases were germinal center B-cell (GCB) subtype, and 59.1% cases were nodal. BCL-2, BCL-6, MUM1, c-MYC, and CD10 positivity were noted in 60%, 45.5%, 40.9%, 44.1, and 38.6% cases, respectively. Only 14 cases (6.4%) were recognized as anaplastic variants of DLBCL according to the previously defined criterion. The only significant association of anaplastic-variant DLBCL was noted with a lack of BCL-2 expression. No significant association of anaplastic-variant DLBCL was noted with age, gender, Ki67 index, DLBCL subtype, or any other IHC marker expression. Conclusion We found a low frequency of the anaplastic variant of DLBCL in our study. No significant association of this DLBCL variant was noted with any of the clinicopathological parameters, except for the lack of BCL-2 expression. Alternatively, from a pathological perspective, it is important to recognize this variant of DLBCL as it often mimics other CD30-positive lymphoma and undifferentiated carcinoma.

Introduction Invasive ductal carcinoma (IDC) is the most common histological subtype of breast cancer. Conversely, many special types of breast carcinoma were described with varying prognosis and hormone receptor status. Mucinous carcinoma (MC) is a rare special subtype of breast cancer, and only a few studies have evaluated the clinicopathological and hormone receptor profile of this type of breast cancer. Therefore, in this study, we compared the clinicopathological characteristics of MC with IDC in our population. Methods A retrospective observational study was conducted in the Department of Histopathology, Liaquat National Hospital and Medical College, from January 2013 till December 2020, for eight years. During this period, 38 cases of MC were diagnosed and 1268 cases of IDC were identified. All specimens were grossed according to standard protocols and representative sections were submitted from tumors, resection margins, and lymph nodes. Slides were examined by histopathologists to determine tumor type and grade. Immunohistochemical (IHC) stains were applied to evaluate estrogen receptor (ER), progesterone receptor (PR), Ki67, and human epidermal growth factor receptor 2 (HER2/neu) statuses. Results The mean age of the patients with MC was 56.47±13.90 years, and most of the patients were above 50 years of age. The mean tumor size was 34.89±19.70 mm. Most tumors were grade 1 (68.4%) with a low mean Ki67 index (15.21±14.06%). Axillary metastasis was present in 31.6% of cases and all of them were nodal (N)-stage N1. ER, PR, and HER2/neu positivity were noted in 94.7%, 78.9, and 10.5% cases, respectively. Compared with IDC, a significant association of MC was noted with age, Ki67 index, tumor (T)-stage, N-stage, and tumor grade. MC cases had a higher mean age than IDC cases. Comparative analysis revealed that MC had a lower frequency of axillary metastasis, a lower mean Ki67 index, and a lower tumor grade than IDC. About biomarker status, MC was noted to have a higher frequency of ER and PR expression, and a lower frequency of HER2/neu expression than IDC. Conclusion MC is a rare subtype of breast cancer. However, it is important to recognize this subtype of breast cancer as it is associated with a prognostically better pathological profile, such as lower tumor grade and Ki67 index, lower frequency of axillary metastasis, higher expression of ER and PR, and lower expression of HER2/neu.

Introduction The two broad subcategories of neuroendocrine neoplasms (NENs) are well-differentiated neuroendocrine tumors (WDNETs) and poorly differentiated neuroendocrine carcinomas (PDNECs), based on tumor architecture and cytology. Grade 3 WDNETs are a subset of WDNETs that not only are high grade by mitotic activity or proliferative index but exhibit a well-differentiated histology. In this study, we evaluated the clinicopathological features of primary neuroendocrine tumors of the gastrointestinal (GI)/pancreatobiliary tract with emphasis on high-grade WDNETs, as it is a newly defined entity. Methods We conducted a retrospective observational study, including a total number of 122 cases of primary GI and pancreatobiliary tract NENs. Slides and blocks of all cases were retrieved from the departmental archives. Immunohistochemical stains including Ki67 were applied to selected tissue blocks of all cases. Tumors were then evaluated for their histological differentiation and tumor grade. Results Our results showed that the mean age of patients was 46.8 ± 17.1 years. Majority of the NENs were GI tract origin (86.9%). The most common site of tumor in gastroenteropancreatic tract was the small bowel (31.1%), followed by the stomach (26.2%). Ninety five percent of the tumors were WDNETs, of which the most common grade was G2. The mean Ki67 index was 15.8 ± 23.8. Grade 3 WDNETs were noted to have an older mean age than grades 1 and 2 WDNETs. Ten out of 102 (9.8%) WDNETs of GI tract were grade 3, compared with four out of 14 (28.6%) of pancreatobiliary tract. Conclusion In this study, we found that high-grade (grade 3) WDNETs were more frequent in pancreatobiliary tract than GI tract. Moreover, high-grade WDNETs were associated with a higher mean age than low-grade (grade 1-2) WDNETs. It is extremely important to recognize this subset (high grade) of WDNETs and to distinguish it from PDNECs, as the latter are known to be associated with a worse overall survival. Despite high mitotic rate/proliferative index, high-grade WDNETs are characterized by organoid architecture and monomorphic cell population.

Introduction Diffuse large B-cell lymphoma (DLBCL) is an aggressive B-cell lymphoma. The 2016 World Health Organization (WHO) update on hematopoietic tumors suggested that all DLBCL cases should be subtyped into germinal and non-germinal center phenotypes. Ki67 immunohistochemistry is a maker of cell proliferation and thus is used as a prognostic and predictive marker in various tumors of human body. Only a few studies evaluated the proliferative index of DLBCL subtypes in our population. Therefore, in this study, we evaluated the frequency of subtypes of DLBCL in our population and K67 index in each subtype. Methods A retrospective observational study was conducted in the Department of Histopathology, Liaquat National Hospital and Medical College, from January 2018 till December 2020, over a period of three years. A total of 101 cases with a histopathological diagnosis consistent DLBCL were included in the study. Immunohistochemical (IHC) stains CD10, B-cell lymphoma 6 (Bcl-6), and multiple myeloma oncogene 1 (MUM1) were applied for the further sub-categorization of DLBCL into germinal center B-cell-like (GCB) and non-GCB subtypes according to the Hans algorithm. The Ki67 index was interpreted in hot spots of the tumor and reported as an average percentage. Results Out of 101 DLBCL cases, 47.5% of DLBCL were GCB, while 52.5% were non-GCB subtypes. Bcl-2, Bcl-6, MUM1, c-Myc, CD10, and CD30 expression were noted in 62.4%, 45.5%, 42.6%, 44.6%, 39.6%, and 7.9% cases, respectively. The mean Ki67 index was 72.94±16.69%. The mean Ki67 index in non-GCB-type DLBCL was 77.67±14.80%, which was significantly higher than the mean Ki67 index in GCB-type DLBCL (67.70±17.22%) with a significant p-value (p=0.002). Cervical lymph node was the most common site of DLBCL, while the stomach was the most common extra-nodal site. A significant association of Ki67 index was noted with subtypes of DLBCL. A higher proportion of non-GCB-type DLBCL exhibited greater than 80% Ki67 index than GCB subtype DLBCL. Moreover, a significant association Ki67 index was noted with c-Myc positivity. A higher proportion of c-Myc-positive DLBCL had greater than 80% Ki67 index. Conclusion We found that non-GCB-type DLBCL had a higher Ki67 index than GCB subtype DLBCL, portending a poor prognostic significance of non-GCB subtype of DLBCL. Moreover, c-Myc expression was associated with a higher Ki67 index.

Introduction Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease, the spectrum of which is increasing with time. The 2016 World Health Organization (WHO) update on hematopoietic tumors recognized a prognostic subgroup of DLBCL called double-expressor DLBCL. Double-expressor DLBCL is defined by the co-expression of c-MYC and BCL-2 by using immunohistochemical (IHC) studies. To our knowledge, very few studies have looked into the pathological features of this newly defined prognostic category of DLBCL; therefore, in this study we evaluated the frequency of the double-expressor phenotype of DLBCL and its association with other clinicopathological parameters. Methods We conducted a retrospective observational study in the Department of Histopathology, Liaquat National Hospital and Medical College, from November 2017 till December 2020. Pathological and clinical records were retrieved from departmental archives. All cases diagnosed as DLBCL were included in the study. More than 40% c-MYC expression in the presence of more than 50% BCL-2 expression was defined as double-expressor DLBCL. Results The mean age of the patients was 52.1±16.9 years. The mean Ki67 index was 73.0±17.0%. A total of 48.6% cases were of germinal center B-cell-like (GCB) subtype, and 59.6% cases were nodal. Double-expressor phenotype was noted in 35.8% of DLBCL cases. A significant association of double-expressor phenotype was noted with age, gender, Ki67 index and subtype of DLBCL. Double-expressor DLBCL had a higher mean age than non-double-expressor DLBCL. Similarly, double-expressor DLBCL had a higher Ki67 index. Moreover, double-expressor phenotype was associated with non-GCB subtype DLBCL. Conclusion We found a high proportion of double-expressor phenotype DLBCL in our population. Moreover, double-expressor phenotype DLBCL was associated with female gender, higher age, higher Ki67 and non-GCB subtype. The association of double-expressor DLBCL with a high Ki67 index and non-GCB subtype confers a poor prognostic significance of this variant of DLBCL, requiring more aggressive therapy.

Introduction The Killip classification system was introduced for clinical assessment of patients with acute myocardial infarction (MI). It stratifies individuals according to the severity of their post-MI heart failure. This system provides effective stratification of long-term and short-term outcomes in patients with acute MI and influences the treatment strategies. Revalidation of Killip class in our local population is mandatory. We planned this study to increase cardiologist's readiness to tackle the risks associated with increased mortality in each class post ST-segment elevation MI (STEMI). Objectives were to determine the frequency of Killip classes I, II, III, and IV and in-hospital mortality in each Killip class in patients with left ventricular failure secondary to STEMI. Methods A retrospective cross-sectional study was conducted in the Department of Cardiology, Jinnah Hospital, Lahore, over a period of three years. Patients with STEMI were stratified using Killip classification, and validation was performed by determining the within 15 days in-hospital mortality in each Killip class. Results The frequency (percentage) of patients with STEMI in each Killip class from I to IV was 395 (81.4%), 46 (9.5%), 27 (5.6%), and 17 (3.5%), respectively, while the in-hospital mortality in each Killip class came out to be 39 (9.9%), 4 (8.7%), 25 (92.6%) and 17 (100%), respectively. The presence of diabetes, history of smoking, and body mass index (BMI) of more than 30 kg/m2 were significant contributors to mortality, along with higher Killip class and age of presentation. Conclusions It is concluded that the Killip classification system is a valid tool for risk stratification for patients after STEMI, especially in resource-limited countries.

Objectives: International Society of Urologic Pathology (ISUP) grade grouping of prostatic adenocarcinoma was introduced to simplify gleason score-related categories of prostatic adenocarcinoma. Prognostic reproducibility of ISUP/WHO grade grouping was not well studied in our population, therefore in this study, our aim was to evaluate the association of ISUP/WHO grade groups with various pathological prognostic parameters.Results: This retrospective cross-sectional study was done in Liaquat National Hospital, Department of Histopathology from February 2011 to January 2018, over a period of seven years. A total of 172 patients were included in this study. The mean age of patients was 66.97±10.51 years. In this study we noted, 27 (15.7%) cases of grade group 1, 22 (12.8%) of grade group 2, 30 (17.4%) of grade group 3, 40 (23.3%) of grade group 4 and 53 (30.8%) of grade group 5. A significant association of tumor grade with perineural invasion (p=0.005) and tumor volume (tumor quantification was noted. In this study, we found a high frequency of grade group 4 and 5 in prostatic adenocarcinoma. Moreover, a significant association of grade groups was noted with perineural invasion and tumor volume, signifying prognostic significance of grade grouping in prostatic adenocarcinoma.

Introduction Neuroendocrine neoplasms (NENs) are a heterogeneous group of tumors with histological features varying from well-differentiated neuroendocrine tumors (WDNETs) to poorly differentiated neuroendocrine carcinomas (PDNECs). In this study, we investigated the clinicomorphological spectrum of NENs including tumor grade, site of origin, and metastasis. Methods We retrospectively studied 125 cases of NENs (at the Department of Histopathology, Liaquat National Hospital and Medical College, Karachi) between the years 2014 and 2020. Slides of these cases were retrieved from the departmental archives and were evaluated for the tumor type, grade, and site of origin. Results The mean age of the patients was 51.25±16.10 years. Overall, the liver was the most common site of the tumor (27.2%), followed by the small bowel (15.2%). Grade 2 was the most common tumor grade (40.8%), and most of the tumors were primary (68.8%). A total of 84.8% of the tumors were WDNETs/carcinoids, while 15.2% were PDNEC. The small bowel was the most common site of primary NENs, followed by the stomach and lung. Among primary neuroendocrine tumors, patients with PDNEC were significantly noted to have a higher mean age than WDNET/carcinoid. Similarly, PDNEC had a higher ki67 index than WDNET/carcinoid. For metastatic NENs, the liver was the most common site of metastasis (71.8%) with the GI/pancreatobiliary tract being the most common primary site of origin (51.3%). Tumors with primary lung origin were found to have a higher tumor grade than primary GI/pancreatobiliary tract origin NENs (p

Introduction Solid papillary carcinoma (SPC) is a distinct rare subtype of breast tumour that often exhibits a neuroendocrine differentiation. Due to the rarity of these tumours, few studies have assessed the clinicopathological features of these tumours. Therefore, in this study, we evaluated the clinical and pathological profiles of SPC and compared the pathologic features with conventional invasive ductal carcinoma (IDC) in our population. Methods It was a retrospective cross-sectional study conducted at Liaquat National Hospital and Medical College from January 2013 until December 2019 over seven years. Cases with histological diagnosis of SPC and IDC were included in the study, and clinicopathological characteristics were compared. Results We included 39 cases of SPC in our study diagnosed during the study period. During the same timeline, 634 cases of IDC were reported and therefore included in the study for comparison. The mean age of the patients with SPC was 53.97 ± 12.15 years, and the mean tumour size was 3.42 ± 1.87 cm. Axillary metastasis was noted in 15.4% of cases. 94.9% of cases of SPC were invasive. Estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor-2 (HER2/neu) and synaptophysin positivity was seen in 84.6%, 87.2%, 10.3%, and 59% respectively. Recurrence was noted in 10.3% of cases with 94.9% survival rate. Cases of SPC had significantly lower grade (grade I + II), tumour (T) and nodal (N) stage than IDC. Moreover, the frequency of hormonal receptor expression (ER and PR) was higher, and the frequency of human epidermal growth factor receptor 2 (HER2/neu) expression was lower compared to IDC. Conclusion SPC is a distinct variant of malignant papillary breast tumours with overall better prognostic parameters than IDC. Therefore, it is essential to recognize the histological features of this rare breast tumour.

Introduction Endometrial cancers (ECs) are the most common gynecological malignancies. Based on morphology and pathogenesis, ECs are segregated into type 1 and 2 ECs. Types 1 ECs are those tumors that are estrogen-driven, whereas type 2 ECs are more aggressive and are independent of hormonal status. In the proposed study, we evaluated the clinicopathological parameters of type 2 ECs and its comparison with type 1 ECs. Methods We retrospectively analyzed seven-year data from archives of pathology, Liaquat National Hospital, from January 2013 to December 2019. All patients underwent radical surgeries for diagnosed EC on endometrial biopsy. All specimens were of total abdominal hysterectomy with bilateral salpingo-oophorectomy, omentectomy, and peritoneal sampling, along with pelvic lymphadenectomy. Records regarding tumor type, grade, depth of myometrial invasion, and ovarian, omental, nodal, and parametrial involvement were assessed. Results A total of 129 cases of ECs were included in the study. The mean age of the patients was 57.6 ± 9.3 years. Majority of the cases were type 1 ECs (82.2%). The most common histological type of EC was endometrioid (82.2%) followed by serous carcinoma (10.1%). Most of the tumors were grade 1 (42.6%) and the International Federation of Gynecology and Obstetrics (FIGO) stage I (72.8%). Nodal metastases were present in eight cases (6.2%) and adnexal involvement was present in 12 cases (9.3%). We found a significant association of the type of EC with lymphovascular invasion, nodal metastasis, and adnexal involvement, whereas no significant association of EC type was seen with other clinicopathological characteristics. Conclusions Type 1 EC was the most frequent subtype of EC in our study. On the other hand, type 2 EC was significantly associated with nodal metastasis, lymphovascular invasion, and adnexal involvement, signifying the poor prognostic significance of this group of EC.

Introduction Urothelial carcinoma (UC) is the most common bladder cancer. The most censorious pathological aspect of UC is deep muscle invasion and tumor grade. In this study, we assessed the prognostic implications of tumor grade and deep muscle invasion in UC. Methods It was a retrospective cross-sectional study conducted at the Department of Histopathology, Liaquat National Hospital, from July to December 2019. The data were collected over five years from January 2014 till December 2018. Records from archives of the anatomic pathology were searched, clinical characteristics were recorded, and histopathological slides were reviewed. Histological parameters, including tumor grade and muscle invasion, were evaluated. Records of patient follow-up were assessed by reviewing clinical records. Recurrence of UC and overall survival was also recorded. Multivariate binary logistic regression was applied for variables that were significant on univariate logistic regression. Survival analysis was performed using the Kaplan-Meier method. Results The mean age of the patients was 63.39 ± 14.1 years. More than half (53%) cases were of low-grade papillary UC. Disease recurrence was observed in 53 (39.1%) patients, whereas the mortality rate was 16.6%. In our study, 49 (32.5%) patients were found to have deep muscle invasion. By multivariate analysis, we found that the deep muscle invasion was significantly associated with male gender and grade. In addition, a significant association of high-tumor grade with survival status of the patients was noted. Conclusions A high proportion of UC cases in our study were found to have deep muscle invasion and high-tumor grade. Moreover, a significant association of deep muscle invasion with tumor grade and an association of tumor grade with survival signify the prognostic value of these factors in UC.

Introduction Lupus nephritis is one of the most important secondary glomerulopathy and a significant cause of chronic renal failure. Early diagnosis is key to improved prognosis. The International Society of Nephrology/Renal Pathology Society (ISN/RPS) classification stratifies renal biopsy evaluation in different classes that correlates with clinical renal outcome. In the current study, we aimed to evaluate the proportion of patients in each class of lupus nephritis in our population. Methods We evaluated renal biopsies of 128 patients that fulfilled the clinical and serologic criteria of lupus nephritis. The histologic classification was done according to the ISN/RPS classification, and immunofluorescence studies were performed. Active and chronic lesions were assessed on renal biopsy, and association of different histopatholgic parameters with lupus classes was done. Results The mean age was 28.85±12.24 years. Most of the patients were from age group ≤25 years (48.4%). Active lesions were seen in 66 (51.6%) patients, with endocapillary hypercellularity being the most common active lesion type, i.e. 81.8%. Chronic lesions were noted in 42 (32.8%) patients, with glomerular sclerosis being the most common chronic lesion type, i.e. 69%. Majority of the patients belonged to class IV (46.9%). Females were more likely to present at advanced lupus stage compared to males, and older patients (>50 years) had a higher chance to present at a late stage (class IV and higher). Active lesions were significantly found more frequently in classes III and IV, while chronic lesions were more likely to present in classes III to V. Conclusion We found that a significant proportion of patients of lupus nephritis in our population presents at an advanced stage as more than 60% patients were of class IV or higher. This signifies lack of appropriate clinical surveillance of patients and assessment of renal functions early in disease course. This also necessitates revision of our locoregional protocols to manage lupus nephritis patients and a need to perform a renal biopsy early in disease course.

Background p16 is a tumor suppressor gene, over expression of which is considered as a surrogate marker of oncogenic human papillomavirus (HPV) infection. Moreover, p16 over expression correlates with good prognosis in head and neck squamous cell carcinoma (HNSCC). In the present study, we aimed to evaluate the frequency of p16 overexpression in HNSCC in our setup and its association with clinicopathologic parameters. Methods We performed p16 immunohistochemistry (IHC) on 144 cases of HNSCC. Association of p16 overexpression with various clinicopathologic parameters including T-stage, N-stage, grade, recurrence status, and risk factors was evaluated. Results p16 over expression was noted in 22.9% (33 cases), while 21.5% (31 cases) were focal positive and 55.6% (80 cases) were negative for p16 over expression. On the basis of percentage of expression; > 70% p16 expression was noted in 4.9% (7 cases), 9% (13 cases) showed 51% - 70% p16 expression, 9% (13 cases) revealed 11%-50% p16 expression, while 77.1% cases revealed no expression or < 10% p16 expression. Significant association of p16 expression was noted with nodal metastasis and extranodal spread while no significant association of p16 was noted with other prognostic parameters and risk factors. Conclusion Our data revealed that high expression (> 50%) of p16 is low in oropharyngeal squamous cell carcinoma in our setup. These finding suggest a low prevalence of HPV as a cause of HNSCC in our population. Moreover, p16 expression was found to be associated with some good prognostic parameters like lack of nodal metastasis, however, no significant association was noted with overall disease-free survival.

Objectives Ki67 is the most commonly used marker to evaluate proliferative index in breast cancer, however no cutoff values have been clearly defined for high ki67 index. Cancer management should be according to loco-regional profile; therefore, we aimed to determine ki67 index in 1951 cases of intrinsic breast cancer subtypes and its association with other prognostic parameters in our set up. Results Triple negative breast cancers showed highest ki67 index (mean 50.9 ± 23.7%) followed by Her2neu (mean 42.6 ± 21.6%) and luminal B cancers (mean 34.9 ± 20.05%). Metaplastic and medullary breast cancers significantly showed higher ki67 index as compared to ductal carcinoma, NOS. No significant association of ki67 index was noted with any of the histologic parameters in different subtypes of breast cancer expect for tumor grade. Although, ki67 index is a valuable biomarker in breast cancer, however no independent prognostic significance of ki67 could be established in our study.