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Objectives: The consensus conference of the International Society of Urological Pathology (ISUP), held in 2012, made recommendations regarding prognostic parameters of renal tumors. There was a strong consensus that tumor morphotype, pathologic tumor stage, and tumor grade are prognostic indicators of poor outcome. It was also agreed upon that prognostic significance of tumor necrosis is in evolution, and both microscopic and macroscopic tumor necrosis should be documented in percentages. The aim of our study was to explore the impact of tumor necrosis on metastasis-free survival in clear cell renal carcinomas (ccRCCs) in Pakistani patients.Methods: We retrieved 318 consecutive in-house cases of ccRCC resections from 2014 to 2020 through hospital archives. Histologic slide review was done for assessment of tumor necrosis, tumor stage, and World Health Organization/ISUP grade. The follow-up data to assess metastasis-free survival were available in hospital archives.Results: In multivariable analysis performed by logistic regression model, tumor necrosis was an independent poor prognostic indicator (P = .0001): group 1 (reference group), 0% necrosis; group 2, 1% to 10% necrosis (adjusted odds ratio [AOR], 8.71; 95% confidence interval [CI], 3.62-20.98); and group 3, more than 10% necrosis (AOR, 9.48; 95% CI, 3.99-22.725).Conclusions: Tumor necrosis is an independent predictor of poor outcome in ccRCCs. [ABSTRACT FROM AUTHOR]

The infiltration of T‐lymphocytes in the stroma and tumour is an indication of an effective immune response against the tumour, resulting in better survival. In this study, our aim was to explore the prognostic significance of tumour‐associated stroma infiltrating lymphocytes (TASILs) in head and neck squamous cell carcinoma (HNSCC) through an AI‐based automated method. A deep learning‐based automated method was employed to segment tumour, tumour‐associated stroma, and lymphocytes in digitally scanned whole slide images of HNSCC tissue slides. The spatial patterns of lymphocytes and tumour‐associated stroma were digitally quantified to compute the tumour‐associated stroma infiltrating lymphocytes score (TASIL‐score). Finally, the prognostic significance of the TASIL‐score for disease‐specific and disease‐free survival was investigated using the Cox proportional hazard analysis. Three different cohorts of haematoxylin and eosin (H&E)‐stained tissue slides of HNSCC cases (n = 537 in total) were studied, including publicly available TCGA head and neck cancer cases. The TASIL‐score carries prognostic significance (p = 0.002) for disease‐specific survival of HNSCC patients. The TASIL‐score also shows a better separation between low‐ and high‐risk patients compared with the manual tumour‐infiltrating lymphocytes (TILs) scoring by pathologists for both disease‐specific and disease‐free survival. A positive correlation of TASIL‐score with molecular estimates of CD8+ T cells was also found, which is in line with existing findings. To the best of our knowledge, this is the first study to automate the quantification of TASILs from routine H&E slides of head and neck cancer. Our TASIL‐score‐based findings are aligned with the clinical knowledge, with the added advantages of objectivity, reproducibility, and strong prognostic value. Although we validated our method on three different cohorts (n = 537 cases in total), a comprehensive evaluation on large multicentric cohorts is required before the proposed digital score can be adopted in clinical practice. © 2021 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland. [ABSTRACT FROM AUTHOR]

Background: Diabetes mellitus has become a major emerging health concern. Its burden, estimated to be 451 million in 2017, has been projected to rise to 693 million by 2045. This will bring a rise in the prevalence of its associated complications. There is a wide spectrum of nondiabetic renal disease (NDRD) known to be present in diabetic patients with variable prevalence. However, the majority of diabetes mellitus (DM) patients with renal disease are yet not biopsied and the diagnosis of diabetic nephropathy (DN) is presumed on clinical grounds. Methods: It is a retrospective cross-sectional study. We selected a total of 126 cases of renal biopsies with a history of type 2 diabetes mellitus. Demographic data was collected from the medical records and pathology reports while all cases were evaluated by reviewing the archived slides. Results: Patients were categorized into group 1 with isolated NDRD, group 2 showing NDRD mixed with DN and group 3 with isolated DN. Thirty-four (27%) cases had isolated NDRD (group 1), 14 (11%) had NDRD mixed with DN and 78 (62%) patients had isolated DN. NDRD, either alone or in combination with DN, was found to be present in 48 patients with an overall prevalence of 38%. Conclusion: Our study concludes that NDRD is frequent in type 2 diabetes mellitus patients. Renal biopsy remains the key diagnostic tool in such cases, providing crucial information for proper management of the underlying pathology. [ABSTRACT FROM AUTHOR]

Objective: To assess the patterns of myoinvasion of endometrial endometrioid adenocarcinoma, their frequencies in our hospital and to correlate these patterns with survival. Study Design: Retrospective observational study. Place and Duration of Study: Department of Pathology, Shaukat Khanum Memorial Cancer Hospital & Research Centre, Lahore, from Aug 2019 to Apr 2020. Methodology: All cases of endometrial endometrioid adenocarcinoma between 2015 and 2017 were retrieved from the archives, independently reviewed by two researchers, all key reporting parameters recorded in addition to the pattern of myoinvasion as per their operational definitions described by Cole and Quick. The follow-up of 3-5 years was obtained from archives and through telephonic contact for outside hospital patients. Disease free survival and relapse-associated mortality were represented through Kaplan-Meier curves. Results: Eighty cases of myoinvasive endometrial endometrioid adenocarcinoma were reviewed. We found that infiltrating irregular gland pattern was the most frequent in all the age groups. Thirty-five (43.75%) cases showed this type of invasion, followed by broad front pattern 23 (28.75%), Microcystic Elongated and Fragmented (MELF) pattern 15 (18.75%) and adenomyotic pattern 6 (7.5%). One case showed a combination of the last two patterns, whereas adenoma malignum pattern was not seen. Follow-up of these patients showed 8 (10%) patients with relapse related mortality including 5 (62.5%) infiltrating irregular glands, 2 (25%) adenomyosis-like and 1 (12.5%) broad front pattern of myoinvasion. Seventy-two (90%) patients had recurrence free survival. Conclusion: Frequency of infiltrating irregular pattern of myoinvasion in endometrial endometrioid adenocarcinoma is high and associated with recurrence related mortality. Recognition of these patterns is important as their impact on overall management and prognosis is, however, unknown, and further studies are required to determine the importance of these patterns. [ABSTRACT FROM AUTHOR]

Background: The 2013 World Health Organization (WHO) classification of soft tissue and bone tumours recognizes benign entities such as lipoma and four major liposarcoma subtypes: atypical lipomatous tumour/well differentiated liposarcomas (ALT/WDL), dedifferentiated liposarcomas (DDL), myxoid liposarcoma and pleomorphic liposarcoma. This classification of atypical and malignant adipocytic tumours has evolved significantly over the past few decades owing to contributions from cytogenetics, molecular genetics and Immunohistochemical correlates. Most ALT/WDLs can be diagnosed on histology; however, some of the biopsies may be underdiagnosed due to focal atypia or limited nature of tissue for the biopsy. Fluorescence in situ hybridization (FISH) for MDM2 (located at 12q14-15) gene amplification has emerged as gold standard for diagnosis in cases with limiting histological factors. Methods: We studied MDM2 amplification by FISH in 55 such problematic adipocytic tumours with overlapping morphological features and a retrospective analysis was made against their corresponding histological features. Results: MDM2 amplification correctly identified 11 of 17 ALT/WDLs (64.71% concordance) and 8 of 10 Lipomas (80% concordance). We were able to differentiate liposarcomas from other high grade sarcomatous lesions and sub-classified these lesions into pleomorphic and dedifferentiated types. Conclusion: FISH for MDM2 amplification should be used as a gold standard in adjunction with morphology and immunohistochemistry for problematic adipocytic neoplasms [ABSTRACT FROM AUTHOR]

Background: Secretory carcinoma of the salivary gland (SC) is a new entity that harbours a specific ETV6 gene rearrangement. The clinical behaviour of this tumour is not well-known as it is a relatively new entity but it is generally considered as a tumour of low malignant potential. The objective of the study was to find out the frequency of ETV6 translocation in cases diagnosed based on histology and immunohistochemistry, to study morphological features and immunohistochemical findings of our cases and to determine the survival and disease-free status of our patients. Methods: Twenty-five diagnosed cases of SC were retrieved from the archives of SKMCH and RC. Diagnosis was made primarily based on morphology and immunohistochemistry. Immunohistochemistry includes S100, p63, mammaglobin, DOG 1, GCDFP-15, TTF-1, GATA3, SMA, AMA, and AR. The diagnosis was further confirmed by molecular testing, i.e., Fluorescence in situ hybridization (FISH) studies to observe specific ETV6 gene break. Follow up of the patients was done by developing a questionnaire. Statistical analysis of the data was done using SPSS-23.0. Results: The mean age of diagnosis was 41±17.4 and the male to female ratio was 1.5:15. The mean size of the tumour was 45.48±27.35. The most common site of the tumour was parotid gland (60%). On morphology, SC showed a wide range of morphological patterns, most common being the tubular, microcystic, intraductal, and papillary. Immunohistochemical stains mammaglobin (22/22), GCDFP-15(15/15) and GATA3 (10/10) showed 100% positive result. However, all cases were negative for p63 (0/18) and DOG 1(0/11). ETV6 break was seen in 17/17 cases (100%). The mean disease-free survival was 75 months and the overall survival was 51.90±2.80 months. Conclusion: This study highlights the presence of specific molecular alteration in all cases, which were diagnosed based on morphology and immunohistochemistry. [ABSTRACT FROM AUTHOR]

Purpose. Clear cell sarcoma of the kidney (CCSK) is an uncommon malignant renal tumor. It is the second most common renal pediatric renal malignancy after Wilms tumor. It exhibits a heterogeneous morphology, with overlapping features with its close differentials, which results in diagnostic challenges. There was no specific immunohistochemical marker in the past, to help in this regard. BCOR antibody has recently been suggested to be helpful in the differential diagnosis. We aim to study the utility of the BCOR antibody in the diagnosis of CCSK. Methods. We selected a total of 27 cases of CCSK (n = 12), Wilms tumor (n = 12), and congenital mesoblastic nephroma (n = 3). All cases were evaluated for the extent and intensity of nuclear labeling for BCOR antibody by immunohistochemistry (IHC). Results. We found that BCOR IHC was positive in 11 out of 12 cases with diffuse and strong staining in 8 of the cases. None of the cases of Wilms tumor and congenital mesoblastic nephroma were positive. Only 2 cases of Wilms tumor showed minimal and weak staining in <5% of cells. Conclusion. Diffuse and strong nuclear staining for the BCOR antibody is highly specific for CCSK among common pediatric renal malignancies. Our study confirms that BCOR IHC is a good IHC marker for the diagnosis of CCSK. [ABSTRACT FROM AUTHOR]

Objective: To evaluate the use of Ki67 as a surrogate marker for Mitotic Karyorrhectic Index (MKI) in Neuroblastoma. Study Design: Cross-sectional study. Place and Duration of Study: This was a retrospective study conducted at Department of Histopathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan. 41 cases of neuroblastoma from 2010 to 2014 were retrieved. Methodology: Forty one cases of neuroblastoma were evaluated. Clinical and morphological features like age, gender and subtype of tumor were quantified. For each case, Mitotic Karyorrhectic Index was calculated and categorized as low, intermediate and high. This was followed by immunostaining for Ki67 on each case. Using linear regression model an equation was derived to calculate ki67 from Mitotic Karyorrhectic Index. The equation was as follows: Mitotic Karyorrhectic Index = (Ki67 x 0.115) ± 1.355. Using this equation, the cut-off values for low, intermediate and high Ki67 were <5.60%, 5.60% - 23.0% and >23.0% respectively. Results: Twenty four cases had low Mitotic Karyorrhectic Index and in 18/24 cases, Ki67 was also low. There were 5 cases with intermediate Mitotic Karyorrhectic Index with two cases showing correspondingly intermediate Ki67 index. There were 12 cases with high Mitotic Karyorrhectic Index and 10/12 cases showed a high Ki67 index as well. Conclusion: Ki67 is a useful technique and may be used as an adjunct to Mitotic Karyorrhectic Index for better evaluation of cases. [ABSTRACT FROM AUTHOR]

Objective: To stratify diffuse gliomas into subtypes including diffuse astrocytomas, oligodendrogliomas and glioblastomas based on recent molecular updates and assess their frequencies in our local subpopulation. Study Design: Cross-sectional study. Place and Duration of Study: Department of Histopathology, Shaukat Khanum Memorial Cancer Hospital and Research Centre, Lahore, Pakistan, from Jun 2015 to Jul 2017 Methodology: Two hundred and fourteen (n=214) cases of adult diffuse gliomas were evaluated. Clinical and morphological features like age, gender and type of tumor were quantified. Molecular studies including IDH 1 by antibody and PCR, ATRX by antibody and 1p/19q co-deletion by FISH were tested. Gliomas were subcategorised based on WHO 2016 guidelines. Results: Mean age of presentation was 39 years. Overall n=146/214 (68.2%) of the cases were completely classifiable including Diffuse Astrocytomas, Oligodendrogliomas and Glioblastomas. Out of the glioblastomas (n=81), 67/81(n=82.7%) were IDH Wild type and 14/81 (17.3%) were IDH Mutant. Conclusion: In this study, glioblastomas are the most frequent gliomas as categorized by current WHO molecular guidelines followed by diffuse astrocytomas. Oligodendrogliomas are the least common. [ABSTRACT FROM AUTHOR]

Background: The objective of the study is to analyze the expression of androgen, estrogen and progesterone receptor in different types of endometrial carcinomas and to correlate the androgen receptor expression with estrogen and progesterone receptor and the clinicopathological parameters like lymphovascular invasion, grade of the tumour, size of tumour and extent of myometrial invasion. Methods: It is a cross-sectional analytical study design with a simple random sample of a total of 54 cases of different types of endometrial carcinomas from the year 2017. Immunohistochemical stains androgen receptor, estrogen receptor, and Progesterone receptor were applied in all the cases. The Pearson Chi-square test of independence was applied to measure association and P-value is calculated to check the significance of the results. Results: Androgen receptor expression was observed in 73% of low-grade endometrioid carcinomas, 62.5% of high-grade endometrioid carcinomas, 62% of serous, 20% of clear cell and 18% of carcinosarcomas, respectively. Androgen positive tumours were also positive for estrogen and progesterone in most of the cases, except 3 serous carcinomas and one low-grade endometrioid carcinoma. However, no significant relation was observed between androgen expression and prognostic parameters like the lymphovascular invasion, size of the tumour and myometrial invasion. Conclusion: Maximum expression of androgen receptor was observed in endometrioid and serous carcinomas, while carcinosarcomas and clear cell carcinomas showed minimum expression with no significant correlation between androgen receptor expression and clinicopathological parameters. [ABSTRACT FROM AUTHOR]

We report a novel 1,2-catechol based radioiodinated precursor for radioiodination of bicyclo[6.1.0]nonyne (BCN) installed biologically active molecules using a strain-promoted oxidation-controlled cyclooctyne–1,2-quinone cycloaddition reaction (SPOCQ) under ambient conditions. Compared to the reported methodologies, the new strategy demonstrates some clear advantages, including high in vitro and in vivo stability, high radiochemical yield, and exceptionally fast reaction kinetics at micro-molar concentration. [ABSTRACT FROM AUTHOR]

Objective: To assess the expression of GATA-3 among epithelial tumors of four organs including invasive mammary carcinoma, prostatic adenocarcinoma, colorectal carcinoma and high grade serous carcinoma of ovary. Study Design: Case series study. Place and Duration of Study: The study was performed at Shaukat Khanum Memorial Cancer Hospital and Research Center, from Jul 2017 to Dec 2017. Methodology: Twenty cases of each of these tumors were collected and stained with ready to use GATA-3 immunohistochemical stain (Cell marque (L50-823) mouse monoclonal antibody) using BOND III Leica automated immunostainer. The expression of the antibody was assessed by two histopathologists. Diffuse nuclear staining in more than 30% of tumor cells was considered as positive. Results: All the breast carcinomas showed diffuse strong positivity in tumor cells, while all the cases of prostatic adenocarcinoma showed negative staining. Aberrant and focal staining was observed in a few cases of high grade serous and colorectal carcinomas. Three cases of high grade serous carcinoma showed weak nuclear staining in 10% of cells. Only one case of colorectal carcinoma showed weak nuclear blush in 10 to 20% of tumor cells. Conclusion: GATA-3 was found a sensitive and specific marker for mammary carcinomas. It is a useful diagnostic tool and should be included in a panel of immunohistochemical markers when working on a metastatic tumor of unknown origin. [ABSTRACT FROM AUTHOR]