The last two decades have seen considerable progress in the use of digital technology in histopathology. Digital photography of microscopic slides and the use of static images gave way to robotic microscopes. These technologies had their own limitations that precluded their widespread use. Creation of whole slide scanners that can produce digitized whole slide images (WSI) and the “comparable to conventional microscope” experience opened multiple avenues for their utilization not only in specific applications such as expert consults, quality assessment programs, education and archiving, but also for routine day-to-day reporting. Industry pressures driven by consumer requirements have led to great development in image quality, speed of scanning, size of stored files, and capital cost of scanners. User-friendly software and analytical algorithms have further enhanced user experience. Challenges that need to be either accepted or overcome would include capital expense not significantly yielding a return on investment, and management of storage space. This review attempts to take the reader through the evolution of WSI scanners and to share the author's experience with WSI for routine histopathology reporting, education, and external quality assessment along with a review of available literature.

Sudden death, a catastrophic event, falls within the purview of the forensic experts. It is often caused by cardiovascular diseases, which may be evident or occult. A vast majority of sudden cardiac deaths (to the extent of 90%) are due to ischemia of the working or conducting myocardial tissues consequent to coronary artery diseases. A heterogeneous group of nonischemic myocardial disorders, most producing structural abnormalities are responsible for the remainder; they predominantly represent various cardiomyopathies. This review, in two parts, covers sudden cardiac death in medicolegal autopsies with an approach to some common and uncommon nonischemic myocardial diseases that have a genetic and/or nongenetic basis.

Background: Salivary gland tumors bear uncanny characteristics of being different based on their morphological aspects rather than the presence of clear demarcation. This ambiguity in the spectrum from benign to malignant salivary gland neoplasms while categorizing the neoplasm is having inherent pitfalls. The present study was, therefore, designed to characterize benign and malignant salivary gland tumors based on their proliferative indices. Materials and Method: Study samples comprised of 97 cases of histopathologically confirmed benign and malignant salivary gland tumors. The cases were immunohistochemically assessed for MCM3 and Ki-67 expressions and the molecular characterization was performed based on the findings. Results: The majority of benign and malignant salivary gland tumors were from the parotid gland, (51.2%) and (42.4%), respectively. Overall mean labeling index of MCM3 was higher i.e., (5.60 ± 3.99) in comparison to Ki-67 i.e., (2.82 ± 3.14) with P = 0.05 using paired t-test. Besides, malignant salivary gland neoplasms represented a higher mean score of MCM3 and Ki-67 than benign neoplasms. Conclusion: The requirement of a novel marker has led to the use of MCM3 which has a characteristic role in the entire spectrum of the cell cycle. The present study highlighted the extrapolation of MCM3 over Ki-67 for diagnosis and for true characterization of biologic behavior of salivary gland pathologies which may, in turn, influence the treatment modality employed for such lesions.

Context: Tumor immune microenvironment (TIME) is heterogeneous and dynamic. It exerts bimodal pro and antitumor effects. Among the TIME contributors, TAMs and Tregs are condemned as cancer cells allies rather than enemies; however, such contribution is not universally equal in all tumors. Aims: We aimed to explore and compare TAMs and Tregs in various breast cancers and link such findings to pathologic prognostic indices. Settings and Design: This was a retrospective study. Methods and Materials: Archival blocks of 108 breast cancers were immunohistochemically studied for CD163 and FOXP3 in tumor stroma (TS) and specialized DCIS periductal stroma. FOXP3 was additionally evaluated in tumor cells. CD163 and FOXP3 expressions were compared with different histopathological prognostic categories for statistical analysis. Statistical Analysis Used: Analysis of data was done using the Chi-Square test. Results: Both CD163+ TAM and FOXP3+ Tregs. showed statistically significant association with high tumor grade, T stage, multifocality and hormone negativity. Synchronous expression was consistent for both markers in almost all compared parameters, dual high expression of both CD163 and FOXP3 yielded additional statistically significant association with lymphovascular invasion (LVI). Periductal stromal CD163 and FOXP3 high expression showed statistically significant association with DCIS. FOXP3 tumor cells expression was similar to TS FOXP3 but additionally showed significant association with LVI and N stage; moreover, Her-2 over-expressing breast cancer was significantly associated with low FOXP3+ tumor cells. Conclusions: Breast cancer TS TAMs and Tregs. abundance reflects unfavorable prognosis in various breast cancers particularly hormone negative cancers.

Background: In breast cancer, metastasis and recurrence is the main culprit in treatment failure. This study aimed to explore the role of E-cadherin/N-cadherin Switch in progression, spread and metastasis in breast invasive duct carcinoma. Materials and Methods: A cross-sectional study on 118 formalinfixed paraffinembedded mastectomy specimens of invasive breast duct carcinoma. Primary antibodies for E-cadherin (monoclonal, clone HECD-1; Zymed Laboratories; dilution 1:600) and N-cadherin (monoclonal, clone 3B9; Zymed Laboratories, Inc., Montrouge, France; dilution 1:200) were applied for all cases. The study revealed that E-cadherin high expression was significantly associated with advanced TNM clinical stage (P = 0.021), and nodal metastasis (P < 0.001). High expression of N-cadherin was significantly positively correlated with tumor sizes (P < 0.00), advanced clinical stage (P < 0.00), and nodal metastasis (P < 0.008). Mean OS was 39.99 months in cases with negative expression versus 41.8 months in cases with positive expression. Mean DFS in cases with positive E. cadh expression was 41.89 months was higher than mean DFS in cases with negative E. cadh expression which was 40.52 months, but it showed no statistical significance (P = 0.57). Conclusions/Significance: This study demonstrated that loss of E-cadherin and gain of N-cadherin promotes invasion, migration, and metastasis in invasive ductal carcinoma cells. Importantly, these findings may exploit new cancer therapies using N-cadherin antagonists.

Background: Oesophageal cancer both squamous cell [SCC] and adenocarcinoma have poor outcomes with high morbidity and mortality. Our hospital-based registry for year 2017–2018 showed that oesophageal cancer constituted 22.7% of annual case load. The main objective of this study was to determine the presence of HER-2 receptors in patients with oesophageal carcinoma in our region. Methodology: From September 2018 to September 2019, data regarding expression of HER-2 receptors was analysed in 133 patients of oesophageal carcinoma. Data were statistically described as frequencies (number of cases) and percentages where appropriate. Chi-square and Fischer's exact test was used to find out the association between categorical variables. A P value less than 0.05 was considered as statistical significant at 95% confidence interval. The statistical analysis was performed using SSPS [statistical package for the social sciences] software version 17.0. Results: A total of 133 patients were taken into study. Majority of patients were males (96) with mean age of 52 years. Squamous cell carcinoma was predominant histology. HER-2 receptor positivity was seen in 6.01% of patients. Patients with HER-2 receptor positivity presented in advanced stage with poor functional status and poor grades of differentiation. Statistically significant correlation of Her-2 expression was seen with stage (p = 0.001) and pathology of tumour (p = 0.0001). Conclusion: Squamous cell carcinoma of oesophagus still predominates in North-eastern part of India. For studying the role of effective targeted therapies knowledge of frequency of HER-2 receptor positivity is of utmost importance in our population, and our study aims to answer this question. The present study shows low prevalence of HER-2 neu overexpression in our community, probably due to disproportionately high incidence of SCC compared to adenocarcinoma. Patients with HER-2 receptor positivity presented in advanced stage with poor functional status and poor grades of differentiation.

Objective: Postoperative recurrence and metastasis of gastric cancer is still a difficult problem in medical field. About 60% of patients with advanced gastric cancer die from peritoneal metastasis, which has become one of the main causes of death of gastric cancer patients. To elucidate the molecular mechanism of peritoneal metastasis of gastric cancer can help us better early diagnosis and improve treatment measures. Methods: This project intends to validate the above hypothesis from three different levels of tissue, cell, and animal models by means of fluorescence quantitative PCR, Western blot, double Luciferase Report Analysis and immunohistochemical detection, and to further explore the molecular mechanism of peritoneal metastasis of gastric cancer. Results: Our previous studies have shown that PARK7 promotes peritoneal metastasis of gastric cancer through PI3K/Akt signaling pathway, but its specific regulatory mechanism remains unclear. Conclusion: Our preliminary study showed that the expression of microRNA-216b in gastric cancer tissues with peritoneal metastasis was significantly lower than that in patients without peritoneal metastasis, while the expression of PARK7 was the opposite.

Background: Gastric cancer is one of the most common cancers in the world and is responsible for over a million deaths. Gastric cancer broadly consists of two main histological types, diffuse and intestinal, and can be further classified as proximal (cardia) and distal (corpus and pylorus) cancers. The presence of Her2neu in certain cancers including gastric cancers has helped in throwing some light on the prediction of prognosis of the tumours. This study was carried out to assess and evaluate the role of Her2neu immunohistochemical expression in gastric cancers. Methodology: This study was carried out as a retrospective study on paraffin blocks of 70 gastrectomy specimens in the pathology department of our hospital. After the histological assessment and interpretation of data, appropriate blocks were chosen and sections of 3 micron thickness were cut and immunohistochemical staining of Her2neu was done and scoring was carried out. Results: We found that gastric cancer occurred predominantly in men as compared to women. Antrum was the most common site involved in gastric cancer (60%). In our study Grade 2 predominated (54%) than Grade 1 (4.2%) and Grade 3 (41%). According to the scoring system of Her2neu expression by immunohistochemistry in gastric cancer it was positive (3+) in 8 cases (11.4%), equivocal (2+) in 10 cases (14.3%) and negative (0+,1+) in 52 cases (74.3%). Her2neu was seen positive 13.7% of intestinal type tumours and in only 5.3% of diffuse type of tumours (P < 0.05). Conclusion: Her2neu testing in gastric adenocarcinomas especially in histologically identified early gastric carcinoma is recommended.

Background: Gall bladder carcinoma is endemic in North India along the Ganges belt. Most of the cases usually present in late stage when prognosis is poor. That mandates a necessity for proper screening in these areas for gall bladder lesions. Tumor markers CA 19-9 and CA 125 have been studied in various GI cancers and may also help in the screening, diagnosis and evaluation of gall bladder carcinoma. Aims: To assess serum CA19-9 and serum CA125 in patients with gall bladder lesions and find out a cut off value for diagnosis of carcinoma gallbladder. Methods and Material: Study included 118 cases, with female: male ratio of 4:1.Out of it, 91 (77 %) cases were benign and 27 (23 %) were malignant. Patients' sera was collected and analyzed for CA19-9 and CA 125 by CMIA method. Results: The Mean (SD) value of CA19-9 for benign and malignant cases was found to be 12.86 (17.54) and 625.35(186.52) U/ml. For CA 125 it was found to be 17.98(13.69) and 239.63(73.72) U/ml respectively. The difference was statistically significant (P< 0.001). When Mean - 2SD value of malignant lesions were taken as cut off a value of CA 19-9 and CA 125 were found be 252.31 U/ml & 92.19U/ml respectively, found to be significant to suggest /diagnose a case of carcinoma gall bladder along with clinicoradiological findings. Taking these value as cut off Sensitivity & Specificity for CA 19-9 and CA 125 in detecting malignant cases were found to be 100% & 98.90% and 100% & 94.50% respectively. Conclusions: It is concluded that both serum CA 19-9 and serum CA 125 may act as a good adjunct for diagnosis of cases of carcinoma gallbladder along with imaging studies. However, changes in CA19-9 are more significant than CA 125.

Introduction: The aim of this study was to evaluate the immunohistochemical expression of C4d in native renal biopsies of proliferative glomerular diseases, complement pathways in these diseases, and assess the relationship of C4d with histological and clinicopathological parameters, other complement proteins, and immunoglobulin markers. Methods: This cross-sectional study was conducted during the year 2018-19 involving 107 native renal biopsies with histologically diagnosed cases of proliferative glomerular diseases. C4d immunohistochemical evaluation of renal tissue sections was performed using polyclonal antihuman C4d as the primary antibody. Patients were classified as positive and negative groups based on their glomerular C4d deposition. Results: The overall prevalence of C4d positivity was 80.4% in proliferative glomerular diseases ranging between 60.0% in C3 glomerulonephritis to 92.9% in membranoproliferative glomerulonephritis. Mixed capillary and mesangial deposition were noted in all cases of proliferative glomerulonephritis. Classical pathway was dominantly involved in all glomerular diseases except C3 glomerulonephritis and IgA nephropathy. Multivariate logistic regression analysis revealed that glomerular IgG staining (aOR: 5.86, 95% CI: 1.26–27.14) and IgM staining (aOR: 3.90, 95%CI: 1.07–14.18) were significantly associated with C4d positivity. Conclusion: C4d staining along with immunoglobulin markers such as IgG and IgM and complement proteins can be useful in delineating different complement activation pathways in glomerular diseases and understanding the disease pathogenesis.

Context: Whole slide imaging (WSI) is an important component of digital pathology which includes digitization of glass slides and their storage as digital images. Implementation of WSI for primary surgical pathology diagnosis is evolving, following various studies which have evaluated the feasibility of WSI technology for primary diagnosis. Aims, Settings and Design: The present study was a single-center, observational study which included evaluation by three pathologists and aimed at assessing concordance on specialty-specific diagnosis and comparison of time taken for diagnosis on WSI and conventional light microscopy (CLM). Materials and Methods: Seventy prostate core biopsy slides (reported between January 2016 and December 2016) were scanned using Pannoramic MIDI II scanner, 3DHISTECH, Budapest, Hungary, at 20× and 40×. Sixty slides were used for validation study following training with 10 slides. Statistical Analysis Used: Intraobserver concordance for diagnosis between the two platforms of evaluation was analyzed using Cohen's κ statistics and intraclass correlation coefficient (ICC); observation time for diagnosis was compared by Wilcoxon signed-rank test. Results: Interpretation on WSI using 20× and 40× was comparable with no major discordance. A high level of intraobserver agreement was observed between CLM and WSI for all three observers, both for primary diagnosis (κ = 0.9) and Grade group (κ = 0.7-0.8) in cases of prostatic adenocarcinoma. The major discordance rate between CLM and WSI was 3.3%–8.3%, which reflected the expertise of the observers. The time spent for diagnosis using WSI was variable for the three pathologists. Conclusion: WSI is comparable to CLM and can be safely incorporated for primary histological diagnosis of prostate core biopsies.

Background and Objective: Bladder cancer is the ninth most common type of cancer worldwide. We aimed to investigate the relationship between tumor grade, lamina propria invasion, muscularis propria invasion, and lymphovascular invasion and human epidermal growth factor receptor 2 (HER-2), cyclin D1, and alpha-methyl-CoA racemase (AMACR) expressions in bladder cancer. Materials and Methods: The study included patients who underwent complete TURBT. In total, 72 cases of bladder cancer diagnosed by two pathologists were selected. AMACR, HER-2, cyclin D1 expressions were detected immunohistochemically. Results: The study population comprised 80% (57) males and 20% (15) females (mean age, 68 years). Further, 35 cases were noninvasive and 37 invasive urothelial carcinoma and 38 patients had low-grade tumor and 34 high-grade tumor. Intense immunostaining was observed with cyclin D1 for 75% tumors, AMACR for 39%, and HER-2 for 86%. High expressions of cyclin D1 and AMACR were observed in high-grade tumors (P < 0.05 and P < 0.005, respectively). High expression of HER-2 (2 and 3 positive) was found both at low- and high-grade tumors (84% and 88%, respectively). Conclusion: Cyclin D1, AMACR expressions were found to be significant predictive factors of high-grade tumors. High Her-2 expression in patients with bladder carcinoma may indicate that they are potential targets for treatment. These markers may be important in determining prognosis of tumors and may be valuable for guiding treatment options.

Context: Twelve-year retrospective study of surgically excised umbilical lesions received for histopathology in a pediatric tertiary care hospital. Aims: To study histopathology of the umbilical lesions and review pertinent literature on the embryological basis of these lesions. Subjects and Methods: We reviewed cases of umbilical lesions and classified them as “developmental” and “others.” Developmental cases were sub-classified based on the mechanism as those due to defect in the closure of body wall, defect in the closure of the umbilical ring, persistence of embryonic remnants, or failure of epithelization. Persistent embryonic remnants were subdivided into fistula, sinus, and cyst. Histology of all the cases was studied and the different types of tissue in omphalomesenteric ducts (OMD) remnants were identified. Statistical Analysis Used: Descriptive statistics were used as required. Results: Seventy-one cases in the age range of 1 day to 13 years were studied and male preponderance was noted. The developmental lesions included 4 omphalocele sacs with dense acute inflammation, 2 umbilical hernial sacs with fibrocollagenous tissue, 30 OMD remnants, 10 allantoic duct remnants, 19 umbilical granulomas, and 2 cases showing more than one developmental mechanism. Four cases were classified as “others” including 3 epidermal inclusion cysts and 1 skin tag. Among OMD remnants, sinuses (arising from the distal tract) were found to be the most common. Histological examination of the OMD remnants showed enteric (18), enteric and gastric (5), colonic (4), enteric and colonic (2), and pancreatic and enteric and gastric mucosae (1). Conclusion: Accurate diagnosis is essential for definite treatment of these lesions.

Background: Molecular confirmation of histologic diagnosis has become mandatory for the diagnosis of Ewing sarcoma family of tumors (ESFT). Aim: To validate the diagnosis made by morphology and immunohistochemistry (IHC) by fluorescence in-situ hybridization (FISH) for EWSR1 rearrangement on formalin fixed paraffin embedded (FFPE) tissues. Settings and design: A retrospective and prospective observational study. Material and methods: All patients who had FISH studies for EWSR1 rearrangement for small round cell tumors during 10 years period were included. Demographic, clinical and radiological details were obtained from medical records. Morphology was reviewed with IHC by CD99, FLI1 and others. FISH studies were performed using the break apart probe. Additional molecular studies and IHC were done to resolve the diagnosis in EWSR1 rearranged tumors. Final diagnosis was made by integrating clinical, morphology, IHC and molecular features. Results: There were 81 patients (M: F 45:36, median age 21 years) with 32 skeletal and 49 extra skeletal tumors. CD 99 was positive in 94.52%. FISH for EWSR1 were positive in 59, negative in 13 and failed in 9. The final diagnosis was made as ESFT in 67, angiomatoid fibrous histiocytoma in 3, desmoplastic small round cell tumor in 3, myxoid chondrosarcoma in 2, unclassified in one, synovial sarcoma in 3, and one each of lymphoma and small cell neuroendocrine carcinoma. FISH was positive for ESFT in 89.83% of EWSR1 rearranged tumors. FISH validated the diagnosis made on IHC in 79.10%. FISH resolved the diagnosis in 1.49% CD99 negative tumors. Conclusion: FISH is a reliable ancillary technique for the diagnosis of ESFT on FFPE tissues.

Background: An optimal core needle biopsy (CNB) is expected to balance between tissue diagnosis, the accuracy of negative sampling, and concordance with reports from resected specimens to select the appropriate treatment. Though various techniques for CNBs are available, no guidelines exist for processing CNB, with practices varying from lab to lab for transport and processing. This prospective study aims to design a cost-effective, user-friendly pre-embedding method for CNBs to yield intact cores. Objective: To compare the outcomes of CNBs by a conventional method with those processed by the modified pre-embedded processing protocol over 2 years. Material and Methods: Presurgical CNBs from SOL in various organs were subjected to the conventional free-floating method in formalin (control) for histopathology diagnosis. CNBs from the corresponding, freshly resected SOLs (test) were taken, inked with coloring inks if multiple, placed between two 2 × 2 cm polyurethane foam meshes fitted inside cassettes, fixed in formalin, and transported to the laboratory. The two CNB groups were coded and scored independently for intactness, tissue processing, ease of embedding, and ease of cutting sections. Data obtained were statistically analyzed. Results: Test CNB cores were better processed, intact, linear, and aligned, compared to control CNBs. With four CNBs in one block, the number of blocks and sections were cut-down by one-fourth. Conclusion: CNBs processed using polyurethane foam and coloring inks were superior and economical against conventional free-floating CNBs. This technique can be practiced by surgeons at the bedside.

Objective: To evaluate the clinical value of epidermal growth factor receptor (EGFR) detection in pleural effusion cell blocks among patients with non-small-cell lung cancer (NSCLC). Methods: From July 2016 to September 2018, EGFR gene mutations in 40 lung tumor tissue samples and pleural fluid samples from NSCLC patients in Jinhua Municipal Central Hospital were assessed by the amplification refractory mutation system method. The EGFR results of the two types of samples were compared using the paired Chi-square test, and the mutation positive rates in EGFR exons 18, 19, 20 and 21 were compared between the two types of specimens using the four-grid Chi-square test. Results: Among the 40 tissue samples and pleural effusion samples, 21 and 18 cases of EGFR mutations were detected, respectively, and the mutation positive rates were 52.5% and 45%, respectively. The κ value of the consistency test of the two specimens was 0.851. There were no significant differences in the mutation positive rates in EGFR exons 18, 19, 20, and 21 between the two types of specimens. Conclusion: The EGFR results of pleural fluid and tissue samples were in good agreement. Therefore, we can use pleural fluid samples to detect EGFR mutations to guide tyrosine kinase inhibitor treatment for NSCLC patients in whom tumor tissue samples cannot be obtained.

Background: Till date, SARS CoV2 (COVID-19) is a pandemic viral infection in the world with the main and strong impact on respiratory airway, but this virus can affect any system of the human body. Aims: This research is aimed to dictating the effect of SARS CoV2 infections on hematological, biochemical, and arterial blood gas parameters by using their mean values. Settings and Design: This retrospective study was included a total no. of 97 SARS CoV2 positive patients from 27 March to 15 May 2020. All positive patients were consented and took all the significant details. Materials and Methods: We review the total 97 COVID-19 positive patients after obtaining all the hematological and other relevant clinical data from laboratory and medical records. The subjects were tabulated into three categories named; admitted (Gp A), discharged (Gp B), and expired (Gp C) patients and compared their hematological, biochemical parameters, and arterial blood gas analysis by using blood or serum and processed by proper methods. Statistical Analysis: The data was cleaned, edited, checked for completeness, and processed then entered in SPSS version 20 statistical software. Results: Blood samples were collected of all positive patients. Most of the patients had X-ray changes. Blood parameters showed that patients who were expired (Gp-C) suffered from anemia, lymphopenia, leucoytosis, neutrophilia, and thrombocytopenia with high ALT, pCO₂ and low pO₂ than admitted and expelled patients. Conclusions: Result from this study provides that WBC count, absolute lymphocyte count, neutrophil count, and pO₂ were independently associated and an important forecaster of mortality from SARS CoV2. All healthcare provides to regularly monitor above parameters indicators of COVID-19 infected patients to improve their quality of life and to reduce the risk of mortality rate.

Context: Hemophilia A is classified as mild, moderate, and severe based on Factor VIII levels (FVIII). Clot-based assays only detect initiation of thrombin generation, hence FVIII levels may not accurately predict the bleeding risk in all hemophilia patients. The entire process of thrombin generation as measured by global hemostasis tests like activated partial thromboplastin time clot waveform analysis (APTT CWA) and thrombin generation test (TGT) may reflect the actual bleeding phenotype. Aims: To assess the utility of TGT and CWA as a screening tool to identify bleeders and to evaluate the bleeding phenotype in Hemophilia A. Settings and Design: Prospective, observational study of 147 consecutive patients referred for coagulation workup. Subjects and Methods: Bleeding assessment tool was used to identify bleeders. Patients were classified as severe and nonsevere bleeders based on clinical criteria. TGT was performed by calibrated automated thrombogram, CWA by photo-optical coagulometer and factor levels by one stage clot-based assays. Statistical Analysis Used: The Kruskal-Wallis test with post-hoc analysis was done to examine the difference in CWA/TGT parameters amongst hemophilia classified by FVIII levels. Receiver operating characteristic (ROC) analysis was performed to estimate the diagnostic accuracy of CWA and TGT in discriminating between clinically severe vs nonsevere bleeders. Results: Using ROC derived cut-offs of min1, min2 and peak height of thrombin (PH), the sensitivity (min1:91.67%, min2:91.67%, PH: 97.22%, FVIII: 86.11%) and specificity (min1:100%, min2:100%, PH: 90.91%, FVIII: 90.91%) of CWA/TGT was superior to FVIII to distinguish between clinically severe vs nonsevere bleeders. Phenotypic heterogeneity of bleeding severity was identified in our study population. Clinical severity correlated with CWA/TGT parameters instead of FVIII levels. Conclusions: CWA and TGT are more effective tools than conventional factor assays to identify clinically severe bleeders and tailor prophylaxis as per bleeding phenotype.

Background: In the laboratory, factor VIII can be measured by three different methodologies, such as one-stage clotting assay, two-stage clotting assay, and chromogenic assay. These assays differ in ease of use, variety of reagents available, sensitivity to mild hemophilia A, and interference from lupus anticoagulants (LACs). Certain factor VIII gene mutations can cause discrepancy in results between one-stage activated partial thromboplastin time (APTT) and chromogenic assays. Materials and Methods: The coagulometer for factor VIII assay is Sysmex CS-5100. All data were expressed as mean ± standard deviation (SD). Results: A total of 135 cases were studied. Of these, 100 cases were of mild hemophilia A diagnosed by molecular genetics and, 15 cases were positive for LAC, which were confirmed by dilute Russell Viper venom test. Clot-based one-stage APTT assay showed 65% sensitivity and 80% specificity in diagnosing mild hemophilia A cases and out of 15 LAC cases, it showed false positivity in five cases. Chromogenic assay showed 85% sensitivity and 90% specificity in diagnosing mild hemophilia cases and was 100% specific in excluding LAC cases. Conclusions: One-stage APTT assay is the most commonly used test for determining factor VIII levels but chromogenic assay are considered as the gold standard and recommended as the reference method by European Pharmacopoeia and ISTH subcommittee. Mild hemophilia A patients with missense mutations show discrepancy between the one-stage clot-based APTT assay and chromogenic assays for determination of factor VIII level and this can lead to misdiagnosis or misclassification of mild hemophilia A. Therefore, it is recommended that both the assays should be used in the evaluation of mild hemophilia cases.

Hepatoid adenocarcinoma of lung is a rare entity, accounting for 5% of all hepatoid adenocarcinoma. Distinguishing it from metastatic hepatocellular carcinoma is essential, but occasionally can be very challenging, especially with concurrent liver mass. A judicious immunohistochemical panel is warranted for accurate diagnosis and subsequent preservation of tissue for molecular testing. There is limited data on the mutational status, behavior and management strategies of this type of lung adenocarcinoma. We report largest series of six cases of hepatoid adenocarcinoma of lung citing the clinical, histopathological, immunohistochemical and molecular parameters including PD-L1 immunoexpression as a predictive biomarker for immunotherapy. None of the evaluated cases showed targetable mutation; however, four out of six cases showed significant PD-L1 expression. All the cases presented with advanced stage and received chemotherapy, however overall prognosis was dismal. In view of significant PD-L1 expression in these tumors and poor response to conventional chemotherapy, these cases might be considered for upfront immunotherapy.

Primary adenocarcinoma of the urinary bladder is a rare malignancy with a frequency of less than 2% of all urothelial malignancies. Colonic adenocarcinoma has a much higher prevalence and its infiltration/metastasis in the urinary bladder is a pertinent differential of primary adenocarcinoma of the urinary bladder. However, the distinction of infiltration by colonic adenocarcinoma from synchronous adenocarcinoma in the bladder and colon is not always easy. Here, we report a 42-year-old male, who initially presented with bladder symptoms and subsequently found to have growth in both bladder and colon. A diagnosis of adenocarcinoma was made from the biopsies from both bladder and colon. Further attempts to differentiate synchronous occurrence or secondary involvement from an adjacent organ was made by radiology, and by an immunohistochemistry panel. The loss of MLH1 and PMS2 coupled with histomorphology and radiology helped in the diagnosis of primary colonic adenocarcinoma infiltrating the urinary bladder.

Context: An audit aims to verify conformance to required processes, assess their implementation, and define the targets of quality control. Aims: To evaluate preanalytic and analytic phases of surgical histopathology in a tertiary healthcare center. Setting and Design: An observational retrospective and prospective study over 3 months each of year 2013 and 2014. Materials and Methods: Biopsy, small resections, large organ resections, bone marrow aspirate/biopsy (BMA/BMB), and frozen section samples received in surgical histopathology were categorized as I to V, respectively. A manual audit was done for preanalytical phase (adequacy of clinical information and grossing adequacy) and analytical phase [turnaround time (TAT) and tissue section quality]. Statistical Analysis: Qualitative data was assessed by Chi-Square test. Quantitative data was assessed using One-Way Analysis of Variance. Results: Among 3179 total cases, category I to V had 1558 (49%), 1099 (34.6%), 342 (10.8%), 124 (3.8%), and 56 (1.8%) cases, respectively. Category I had shortest TAT but maximum number of inadequately sent specimens and recuts. Category III had maximum cases with inadequate clinical history, grossing errors, additional sections, and longest TAT. Category IV had maximum cases with poor quality sections. Category V had maximum cases with inadequate demographic details and clinical investigations. BMB (114, 91.9%) was more useful than BMA for diagnosis. Mean TAT for fixed tissues and frozen tissues was 3.6 ± 1.8 days and 26.6 ± 11.2 min, respectively. Conclusions: Total 25% of annual workload was studied by an observational, manual audit. Quality indicators were achieved as per international norms despite limited resources. Remedial actions were suggested for technicians, clinicians, and pathologists to minimize errors.

Pituicytoma is a distinct sellar or supracellar tumor which originates from specialized glial cells of neurohypophyses and infundibulum known as pituicytes. Because of its sellar location patients present with headache, visual disturbance, and endocrine abnormalities. Pituicytoma is difficult to diagnose on neuroimaging as radiological features overlap with other more common tumors of this region. Thus, diagnosis is established by histopathology and immunohistochemistry of resected tumor only. Pituicytomas are composed of bipolar spindle cells arranged as fascicles and are immunoreactive for TTF-1, S100p, and vimentin. These tumors are extremely rare and only around 70 published cases are known in literature. We report a case of suprasellar SOL in a 58-year-old male who presented with headache and gradual visual deterioration in both eyes. He was diagnosed as a case of pituicytoma based on light microscopy findings and immunohistochemical expression of TTF-1, vimentin, S100p, and bcl-2.

Chronic lymphocytic leukemia/small lymphocytic lymphoma (CLL/SLL) is the most common adult leukemia. The coexistence of CLL and papillary thyroid carcinoma (PTC) is extremely rare. PTC sometimes shows microscopic vascular invasion but rarely cause a tumor thrombus in the internal jugular vein (IJV). It is also rare to find both differentiated and poorly differentiated types of thyroid cancer in the same metastatic location. We report a case of 63-year-old Turkish man with history of CLL who had CLL/SLL involvement and PTC metastasis in the same lymph node. Additionally, there was macroscopic metastasis to the IJV with poorly differentiated areas in the removed tumor thrombus. Patient was treated with total thyroidectomy, left radical neck dissection, resection of the left IJV segment that contained the tumor thrombus and radioactive iodine (RAI) therapy. Furthermore, metastatic lesions were found in the brain, lung and bone. Radiotherapy and chemotherapy were performed. However, our patient died approximately 12 months after thyroidectomy. To our knowledge, our present report is the first description with its current features.

Acute aortic syndromes comprise a heterogeneous group of life-threatening disorders, characterized by acute-onset chest or back pain with or without cardiovascular collapse. The major entities include acute aortic dissection, penetrating atherosclerotic ulcer, and intramural hematoma. Spontaneous rupture of the aorta is an additional, rare cause of this syndrome, which frequently leads to sudden cardiac death. This is a report of two cases of this uncommon entity with detailed pathological analysis.

Myoepithelial tumor of lung is a rare tumor; the histopathological findings resemble the myoepithelial tumors of the salivary gland. Distinguishing low-grade nonmetastatic myoepithelial carcinoma from benign myoepithelioma can be challenging both radiologically and histomorphologically. We present a case report of a low-grade myoepithelial carcinoma of lung with contralateral lung metastasis which was treated with low-dose external beam radiotherapy

Malignant peripheral nerve sheath tumor (MPNST) is a type of soft tissue sarcoma arising from peripheral nerves. They can be found in isolation, but about half of the cases are associated with neurofibromatosis type 1 (NF1), an autosomal dominant genetic disorder. They usually arise from the nerve plexus in extremities and trunk. MPNSTs arising from the viscera or internal organs are very rare. We hereby report a rare case of sporadic MPNST arising from pleural surface in a middle-aged male. The diagnosis of such a rare entity involved multimodal investigations with consideration of wide differential diagnosis.

A 60-year-old Chinese male with a hard mass, pressure pain, and ulcerous skin under his left axilla was first diagnosed with apocrine carcinoma, most likely metastasis from breast cancer. PET/CT scan detected multiple bone metastasis and enlarged lymph nodes at left axilla, mediastinal area 7, and left pulmonary hilus. Lumpectomy was performed to remove the mass followed by chemotherapy and radiotherapy against focal bone metastasis, left axillary lesion, and left subcutaneous chest wall. PET/CT examination showed progressive disease after the completion of the treatments. Two nontender hard nodules were noticed on the patient's left upper arm and multiple immobile nodules were palpated under his left axillary skin. Immunohistochemistry (HER2++, ER+, PR+, AR-) of the biopsy tissue combined with histopathology indicated invasive ductal carcinoma with neuroendocrine differentiation. Metastatic Luminal B subtype breast cancer was preferred. Anti-estrogen endocrine therapy was then performed and PET/CT scan showed partial remission after one month's fulvestrant administration. Two significant somatic mutations, AR R616H and GATA3 S408Afs*99, were detected in the biopsy tissue by next-generation sequencing. GATA3 is associated with estrogen receptor signaling and was identified as a driver gene of female breast cancer. However, the function of GATA3 in male breast cancer remains controversial. Report of this case hopefully will contribute to exploring the role of GATA3 mutation in molecular mechanisms and endocrine therapy of male breast cancer.

Strongyloides stercoralis is an intestinal nematode that infects humans, percutaneously and has a complex life cycle. We report a case of a thirty year old male presenting with chief complaints of profuse watery diarrhoea, abdominal fullness, loss of appetite, creepy abdominal pain and low-grade fever for the last one month. He was on corticosteroids for systemic sclerosis. Endoscopy showed thickened and oedematous duodenal folds with pinpoint areas of bleeding and multiple ulcerations on the duodenal mucosa. Histopathologial examination of duodenal biopsy revealed infestation by Strongyloides stercoralis in the duodenum, the duodenal mucosal glands were occupied by various parts of parasite. The patient was successfully treated and had uneventful recovery.

Lymphomas are hematological malignancies with a wide variety of histological subtypes, varied clinical manifestations and behaviour and have a wide range of organ involvement. About 40 per cent of lymphomas are extra nodal. The most common extra nodal site is gastrointestinal tract (GIT). In the GIT, stomach is the most common organ involved accounting for 50–60 per cent of the lesions. Colorectal lymphomas are rare and account for 15–20 per cent of GIT lymphomas. They constitute 1 per cent of colorectal malignancies. Most common histological type of lymphoma involving GIT is diffuse large B-cell lymphoma, followed by MALT lymphoma; T-cell lymphomas are very rare and have an incidence of 3 per cent of Non Hodgkins Lymphoma (NHL). We report a case of anaplastic large cell lymphoma in the caecum and ascending colon with review of literature.

Collision tumor consists of two tumors occurring in the same organ without intermixture of the two cell types. The most common type of collision tumor in ovary is between teratoma and surface epithelial tumor. A 38-year-old woman presented with complained of lower abdominal pain and tightness, and a solid partially cystic left ovarian mass with minimal ascites was detected. Left salpingo-oophorectomy was performed. The ovarian mass measured 15 × 12 × 7 cm with a pedunculated mass on its surface which measured 6 × 2.5 × 2.5 cm. Histologically, it was a collision tumor of fibroma and mature cystic teratoma. Fibroma becomes more edematous as their size increases, which is frequently accompanied by the escape of increasing quantities of fluid from the tumor surfaces. Ascites is often detected when the fibroma is more than a diameter of 10 cm. It is important to identify the different components of a collision tumor for proper management.

Adenocarcinoma admixed with neuroendocrine carcinoma of the uterine cervix is a rare malignancy with a poor prognosis. In the literature, there are few reported cases. Herein, we report a case of a 56-year-old Turkish woman with cervical adenocarcinoma admixed with small cell neuroendocrine carcinoma. Histological examination of endocervical curettage specimens revealed a tumor composed of almost equal areas of small cell neuroendocrine carcinoma and adenocarcinoma. Neuroendocrine differentiation was confirmed by immunohistochemistry for chromogranin-A, synaptophysin, and CD 56. After the adenocarcinoma and small cell neuroendocrine carcinoma association was detected in the curettage material, both cervicovaginal smear and then total abdominal hysterectomy and bilateral salpingo-oophorectomy resection material of the patient were submitted to our pathology department. Histological features of both curettage and resection material were determined by immunohistochemical studies.

A solitary fibrous tumor (SFT), although ubiquitous, is rarely documented in the female genital tract, especially confirmed by STAT6 immunostaining and underlying NAB2-STAT6 gene fusion. A 24-year-old female presented with a gradually increasing vulvar swelling in her right labia, which rapidly increased in size over 1-year duration. Radiologically, a subcutaneous, predominantly solid, lobulated mass, measuring 10 cm in the largest dimension was seen involving her right labia majora and perineum. She underwent tumor resection, elsewhere, where it was reported as a pleomorphic sarcoma. Histopathologic review revealed a cellular tumor comprising spindle cells, displaying mild nuclear variation, arranged diffusely and focally, in a hemangiopericytomatous growth pattern, within a collagenous stroma. Interspersed were blood vessels with perivascular hyalinization and few giant cells. By immunohistochemistry, tumor cells showed patchy immunostaining for CD34 and diffuse immunostaining for STAT6. Furthermore, the tumor displayed NAB2ex6-STAT6ex 17 fusion by RT-PCR technique. This case constitutes one of the few reported cases of vulvar SFT, confirmed by STAT6 immunostaining and the second such case, displaying NAB2-STAT6 gene fusion. Diagnostic and treatment implications are discussed herewith.

Endocrine mucin-producing sweat gland carcinoma (EMPSGC) is a rare adnexal tumor with a predilection for the skin of the eyelid. It has also been reported in other areas of the face. Extra facial location has rarely been reported. They are twice as common in the females as compared to men and frequently affect the elderly between 50 and 80 years of age. It is a low-grade carcinoma with no reported cases of metastases, although a few cases with recurrences have been reported. Since it was first described by Flieder et al. in 1997, fewer than 60 cases have been reported in the literature. We describe one such case of EMPSGC in an adult male occurring at an unusual location, the peno-scrotal junction with systemic metastases to bilateral inguinal and iliac lymph nodes, multiple bones, and pancreas. Unlike previously reported cases, our patient worsened rapidly and succumbed to the disease six months after initiation of chemotherapy and radiotherapy. To the best of our knowledge, this is the first reported case of its kind in modern published literature.

Primary cutaneous apocrine carcinomas are rare cutaneous adnexal neoplasm with less than 100 cases reported in the literature. The tumor arises in areas rich in apocrine glands particularly axilla, modified apocrine glands such as ceromucinous and Moll's glands. Most of these carcinomas are indolent and slowly growing but few rapidly progressive and extremely aggressive? cases have also been reported. Wide local excision with clear margins and sentinel lymph node biopsy is standard treatment of choice.This case was of much interest from the diagnostic point of view both microscopically as well as immunohistochemically. We report a case of 46-year-old man who presented to our hospital with an ulcerated painless nodular mass in his right axilla.With combined use of microscpic features, special stains and immunohistochemical examination the case was correctly diagnosed as primary cutaneous apocrine carcinoma.

Eccrine porocarcinoma is a rare malignant dermal appendageal tumor notorious for its varied morphology, both clinically and histologically; and it can pose a considerable diagnostic dilemma to both the dermatologist and the pathologist. Herein, we present a case of a 74-year-old woman with slow-growing nodular masses on both buttocks, reaching a fairly large size over a course of 3 years. Although atypical morphologic features posed significant diagnostic difficulty to both the surgeon and the pathologists, it was eventually diagnosed as eccrine porocarcinoma with focal squamoid features, using immunostains. To our knowledge, this is the second reported case of bilateral eccrine porocarcinoma which highlights the need for awareness of the morphological variations that this entity is capable of producing.

Chronic myelomonocytic leukemia is a clonal chronic hematopoietic disorder that has been classified under the category of Myelodysplastic syndrome/Myeloproliferative neoplasms (MDS/MPN). CMML has high chances of transforming to acute leukemia, however isolated CNS relapse in CMML has never been reported in literature. We report an extremely rare case of a 47 yearold female diagnosed to have CMML- 2 in remission, who developed an isolated central nervous system relapse after matched related allogeneic hematopoietic stem cell transplantation. To our knowledge this is the first report of isolated CNS relapse in CMML post allogeneic stem cell transplant.

Hemophagocytic lymphohistiocytosis (HLH) has been recognized as a potentially life-threatening syndrome. This is the first case of acquired HLH caused by dual infections with Candida albicans and reactivated EBV infections, which focuses on the importance of morphological awareness of peripheral blood and bone marrow because sometimes they are the only locations that HLH and fungal microorganisms can be diagnosed. A 29-year-old woman with a history of abdominal distension and 9 months of intermittent fevers ($38.8°C) was admitted to the hematology department with treatment for leukopenia and thrombocytopenia. Severe infection of bilateral pulmonary and marked hepatosplenomegaly were detected by computed tomography. EB virus-CA IgG, EB virus-NA IgG and EB virus-CA IgM were positive. Scattered yeast-like fungi were found on peripheral blood and bone marrow (BM) smears. BM smears indicated prominent hemophagocytosis. Cultures of bronchoalveolar lavage and BM confirmed the growth of C. albicans. A diagnosis of HLH caused by dual infections with Candida albicans and reactivated EBV infections was established based on the clinical features of the patient because 7 of the 8 diagnostic criteria were met. She was treated with etoposide, dexamethasone for HLH, as well as highly active antifungal and antiviral therapies for the underlying etiology of dual infections. The patient eventually recovered following the effective treatment. A timely and accurate diagnosis is crucial to the prognosis of the dangerous disease.

Desmoplastic small round cell tumor (DSRCT) is a rare, aggressive neoplasm of uncertain histogenesis that preferentially involves the abdominal and pelvic cavities. DSRCT mainly develops in adolescent and young adults with a strong male predominance; the male to female ratio is 4:1. Ovarian location is exceptional. DSRCT generally develops in the abdomen and have a tendency towards peritoneal spread, with subsequent metastasis to distant lymph nodes, liver and lungs. It is a poorly understood malignancy with a very characteristic morphology, immunophenotype, cytogenetic features, and poor prognosis. This tumor can co-express epithelial, neuronal, and mesenchymal markers. Despite intensive therapy, including surgery, radiotherapy and chemotherapy, and immunotherapy; the 5-year survival is less than 15%.