Double-Expressor Phenotype (BCL-2/c-MYC Co-expression) of Diffuse Large B-Cell Lymphoma and Its Clinicopathological Correlation.

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.

Ki67 Proliferation Index in Germinal and Non-Germinal Subtypes of Diffuse Large B-Cell Lymphoma.

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.

Recurrence and Disease-Free Survival in Head and Neck Squamous Cell Carcinoma After Margin-Free Resection on Frozen Section: An Institutional Perspective.

Introduction The most important factor determining survival in patients with head and neck squamous cell carcinoma (HNSCC) is a disease recurrence. A high rate of recurrence was noted in previous studies conducted in Pakistan; however, these studies did not consider margin status as inadequate margin clearance leads to disease recurrence. In this study, we determined cancer recurrence in patients with HNSCC after nullifying this factor. Methods This cross-sectional observational study was conducted in Liaquat National Hospital (LNH) for a duration of three years. Data collection period was from January 2015 to December 2017. A total of 150 patients that underwent surgery at LNH for HNSCC with margin-free frozen sections were included in the study. Pathological tumor characteristics such as tumor type, size, depth of invasion and nodal status were determined. Results The mean age of the patients was 50.31±12.90 with mean tumor size of 3.38±1.76. Nodal metastases were present in 45.3% cases with 17.3% showing extranodal extension. Recurrence was observed in 66% of cases with median disease-free survival of 12 months and perineural invasion was noted in 12% cases. We found a significant association of disease recurrence with larger tumor size, depth of invasion and extranodal extension. Moreover, younger age (<30 years) and older age (>50 years) groups showed higher rates of recurrence than the middle age group (30-50 years). Similarly, univariate and multivariate analyses revealed that tumors with ≥1 cm depth of invasion and the presence of extranodal extension were more likely to have disease recurrence than tumors with <1 cm depth of invasion and without extranodal extension. Survival analysis using the Kaplan-Meier method for HNSCC revealed a significant difference in disease-free survival in patients with more than 2 cm tumor size and ≥1 cm depth of invasion than cases with ≤ 2cm tumor size and <1 cm depth of invasion. Conclusion A high rate of disease recurrence for HNSSC was noted in our study, despite margin-free primary tumor resection. Apart from tumor size and depth of invasion, extranodal extension was significantly associated with disease recurrence in HNSCC. This signifies a need for margin evaluation of neck dissection specimen in cases with extranodal extension.

Solid Papillary Carcinoma of Breast: Clinicopathologic Comparison With Conventional Ductal Carcinoma of Breast.

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.

Encapsulated Papillary Carcinoma of Breast: Clinicopathological Features and Prognostic Parameters.

Introduction Encapsulated papillary carcinoma (EPC) is a rare malignant papillary breast tumor that, despite a lack of distinct myoepithelial layer, is considered an in situ carcinoma unless associated with a frank invasive component. Data regarding clinicopathologic features of rare breast tumors like EPC are especially scarce. Therefore, in this study, we evaluated the clinicopathologic features of EPC and performed a clinicopathological comparison with conventional invasive ductal carcinoma (IDC). Methods It was a retrospective study conducted in the Department of Pathology, Liaquat National Hospital and Medical College, from January 2013 to December 2019 over a period of seven years. During this period, 16 cases were diagnosed as EPC, and 634 cases were labeled as IDC. Estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2/neu) immunohistochemical (IHC) stains were performed on both EPC and IDC cases. Moreover, myoepithelial IHC stains were performed on all cases of EPC. Clinicopathologic features of EPC were compared with IDC. Results The mean age of the EPC patients was 51.81±13.94 years, with a mean tumor size of 2.97±2.46 cm. The majority of cases were grade II, and axillary metastasis was present in 18.8% of cases. About 56.3% of cases were in situ, and 43.8% showed foci of invasion in the form of IDC. Recurrence was noted in 12.5% of cases with a survival rate of 93.8%. ER, PR, and HER2/neu positivity was noted in 81.3%, 75%, and 12.5% cases, respectively. EPC was significantly noted to have lower tumor grade and pathological T-stage than IDC. Similarly, a lower frequency of axillary metastasis was noted in EPC than IDC.  Conclusion EPC is a rare distinct subtype of papillary breast tumors with overall good survival and low recurrence rate. Compared to IDC, we found EPC to be associated with better prognostic parameters such as lower tumor grade and T-stage and lower frequency of axillary metastasis.

Morphological Spectrum and Pathological Parameters of Type 2 Endometrial Carcinoma: A Comparison With Type 1 Endometrial Cancers.

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.