Recent application of artificial intelligence on histopathologic image-based prediction of gene mutation in solid cancers.

PURPOSE: Evaluation of genetic mutations in cancers is important because distinct mutational profiles help determine individualized drug therapy. However, molecular analyses are not routinely performed in all cancers because they are expensive, time-consuming and not universally available. Artificial intelligence (AI) has shown the potential to determine a wide range of genetic mutations on histologic image analysis. Here, we assessed the status of mutation prediction AI models on histologic images by a systematic review. METHODS: A literature search using the MEDLINE, Embase and Cochrane databases was conducted in August 2021. The articles were shortlisted by titles and abstracts. After a full-text review, publication trends, study characteristic analysis and comparison of performance metrics were performed. RESULTS: Twenty-four studies were found mostly from developed countries, and their number is increasing. The major targets were gastrointestinal, genitourinary, gynecological, lung and head and neck cancers. Most studies used the Cancer Genome Atlas, with a few using an in-house dataset. The area under the curve of some of the cancer driver gene mutations in particular organs was satisfactory, such as 0.92 of BRAF in thyroid cancers and 0.79 of EGFR in lung cancers, whereas the average of all gene mutations was 0.64, which is still suboptimal. CONCLUSION: AI has the potential to predict gene mutations on histologic images with appropriate caution. Further validation with larger datasets is still required before AI models can be used in clinical practice to predict gene mutations.

Association of hormone receptors and human epidermal growth factor receptor-2/neu expressions with clinicopathologic factors of breast carcinoma: a cross-sectional study in a tertiary care hospital, Kabul, Afghanistan.

BACKGROUND: Breast cancer (BC) is one of the major causes of death worldwide. It is the most common cause of death before the age of 70 years. The incidence and mortality of BC are rapidly increasing, posing great challenges to the health system and economy of every nation. METHODOLOGY: A cross-sectional analytical study was conducted at the Department of Pathology and Clinical Laboratory of the French Medical Institute for Mothers and Children (FMIC) to demonstrate the association of human epidermal growth factor receptor 2 (Her2/Neu) and estrogen receptor (ER)/ progesterone receptor (PR) with clinical as well as pathological parameters among women with BC. A consecutive nonprobability sampling method was used for this study over a span of one and a half years. RESULTS: One hundred twenty participants diagnosed with breast cancer were included in the study. The mean age at diagnosis was 44.58 ± 11.16 years. Out of the total patients, 68 (56.7%) were above 40 years old, 108 (90%) were married, 94 (78.3%) were multiparous, and 88 (73.3%) had a history of breastfeeding. 33.3% of cases were within the age range of menopause (40-50 years). The positive expression rates of ER, PR, and Her2/neu were found to be 48.8%, 44.6%, and 44.6%, respectively, and Her2/neu overexpression was found to be higher among ER/PR-negative cases. CONCLUSION: In our study, we demonstrated that among Afghan women, grade II invasive ductal carcinoma, not otherwise specified, was the most common type of BC and frequently affected women above the age of 40. We also revealed that the percentage of negative ER (50.4%), negative PR (54.4%), and concordant ER/PR-negative cases were high compared to other possibilities. Additionally, the study revealed that expression of Her2/neu was in contrast with the expression of ER and PR receptors. The findings of our study still support the importance of performing immunohistochemical stains for hormonal receptor classification in terms of better clinical outcomes and prognosis.

Tranilast treatment prevents chronic radiation-induced colitis in rats by inhibiting mast cells infiltration.

INTRODUCTION: Mast cells are the principal cells leading to acute and chronic colitis due to irradiation, radiation-induced colitis (RIC). Herein, we investigated whether pre-treatment with tranilast, mast cell inhibitor, could alleviate chronic RIC. METHODS: A total of 23 Sprague Dawley (SD) rats were randomly divided into three groups: control group (n=5, C), irradiation group (n=9, RG), and tranilast pre-treated irradiation group (n=9, TG). The rats in RG and TG were irradiated in the pelvic area (1.5cm from anus) with a single dose of 20 Gray under general anesthesia. Tranilast (100 mg/kg) was intraperitonially injected to mice of the TG for 10 days starting from the day of pelvic irradiation. Ten weeks after irradiation, the rats were euthanized. Rectal tissue samples were evaluated histologically for the total inflammation score (TIS) and mast cell count. Expression of MUC2, MUC5AC and matrix metalloproteinase 9 (MMP9) were also assessed immunohistochemically. RESULTS: Both TIS and some components of TIS, epithelial atypia, vascular sclerosis and colitis cystica profunda (CCP) were significantly higher in RG than in TG (P=0.02, 0.038, 0.025, 0.01, respectively). The number of infiltrating mast cells was significantly higher in the RG than in TG (20, 3-54 and 6, 3-25, respectively, P=0.034). Quantitatively, the number of MMP9-positive cells was significantly higher in the RG (23.67±19.00) than in the TG (10.25±8.45) (P<0.05). TIS and MMP9 exhibited strong associations (correlation coefficient r=0.56, P<0.05) Immunohistochemically, mucin-lake of CCP showed no staining for MUC5AX but positivity for MUC2. CONCLUSION: Tranilast pretreatment in RIC shows an anti-inflammatory effect on the RIC in association with the reduction of mast cell infiltration and MMP9 expression.

Secondary involvement of gallbladder by acute lymphoblastic leukemia presenting clinically as cholecystitis in a young patient: a case report.

BACKGROUND: Primary lymphoma of the liver, gallbladder, and extrahepatic bile ducts or secondary involvement of these organs by leukemia is exceedingly rare. Patients with primary lymphoma or leukemic involvement of the biliary tract and liver often present with symptoms and signs of biliary tract obstruction or inflammation. CASE PRESENTATION: We present a case of a 24-year-old male with biliary tract symptoms who underwent laparoscopic cholecystectomy. His precholecystectomy complete blood count performed on the same morning showed 72% lymphocytes while peripheral blood smears showed approximately 15% blasts. Surgeon went ahead with the procedure. Imaging done prior to surgery showed thickened gallbladder, while the liver, biliary tract, and pancreas did not show any thickening or mass lesion. However, the liver was enlarged. Grossly, the gallbladder wall did not show any stones or discrete mass involving the wall. Instead, there was subtle thickening of the gallbladder wall due to diffuse infiltration by the leukemic infiltrate. This lymphoid population reacted with PAX-5 and TdT immunohistochemical antibodies in a diffuse manner confirming precursor B-cell origin. This patient was found to have B-lymphoblastic leukemia involving his bone marrow on further clinical and diagnostic workup. Patient responded well to chemotherapy and is currently on maintenance treatment. He is well 1.5 years after his diagnosis. CONCLUSION: This case highlights a unique and rare scenario where a previously undiagnosed and unsuspected hematologic malignancy initially presented with clinical features of a chronic inflammatory condition involving an abdominal organ owing to secondary involvement by the malignant infiltrate.

Risk factors associated with esophageal cancers, diagnosed at tertiary level in Afghanistan: a descriptive cross-sectional study.

BACKGROUND: Worldwide, esophageal cancer (EC) is a common cancer in term of incidence and mortality and is the 4th common cancer in Afghanistan. Current study aimed to evaluate the profile of risk factors for EC among patients diagnosed at tertiary level in Afghanistan. METHODOLOGY: A descriptive cross-sectional study was carried out between January 2019 up to February 2021 including all esophageal cancers diagnosed at pathology department of French Medical Institute for Mothers and Children, Afghanistan. RESULT: 240 diagnosed cases were analyzed, in which 59.40% of squamous cell carcinoma and 41.07% Adenocarcinoma. Both histopathological type of were predominantly diagnosed in males. The majority of the patients were residents of rural areas. More than 80% of the patients were illiterate with only less than 2% completing higher education. Majority of the patients were laborers and farmers while less than 10% were employed. According to income assessment, more than 80% were from low-income household, the rest from middle-income and none from high-income family. Oral snuff consumption was noted in 33.9% of squamous cell carcinoma patients and 40% adenocarcinoma patients whereas, family history of esophageal cancer was observed in 37.8% and 36.7% in both types of carcinomas, respectively. More than 60% of both types of carcinomas patients were hot tea drinkers. CONCLUSION: Current study demonstrated that most patients diagnosed with esophageal cancers were male, uneducated, belongs to low-income groups, lives in rural areas. These findings suggest distribution of esophageal cancer in specific socioeconomic groups, clearly demonstrating the need further analytical study.

Perception of postgraduate medical residents regarding educational environment at French Medical Institute for Mothers and Children, Kabul Afghanistan.

OBJECTIVE: To assess the perceptions of postgraduate medical education residents regarding educational environment at a medical institution in Afghanistan. METHODS: The descriptive cross-sectional study was conducted from 2017 to 2018 at the French Medical Institute for Mothers and Children, Kabul, Afghanistan, FMIC, and comprised postgraduate medical residents. Dundee Ready Educational Environment Measure was administered to determine the perception of learning environment by the residents' perceptions related to learning, teachers, academic self-perception, atmosphere and social self-perceptions sub scales. Data was analysed using SPSS 22. RESULTS: Of the 63 subjects, 55(87.30%) were males and 42(66.66%) were married. The overall mean age was 30±4.38 years. There was no significant difference in mean subscales scores and overall scores in relation to participants' age, gender, type of specialty, province and year of training (p>0.05). There was a significant difference in students' perception of teachers in relation with the type of specialty (p<0.05). CONCLUSIONS: The educational environment at the medical institution in Afghanistan was perceived by the students of residency programme as conducive.

Risk factors of breast cancer among patients in a tertiary care hospitals in Afghanistan: a case control study.

BACKGROUND: Breast cancer is the second most common causes of women's death, worldwide. Data on risk factors associated with female breast cancer in the Afghan population is very limited. The aim of our study was to identifying risk factor associated with female breast cancer in Afghanistan. METHODS: A retrospective case-control study was conducted with inclusion of 201 cases and 201 controls. Patient information was collected by interviewing the patient through a structured questionnaire. Histopathological information was collected from the hospital integrated laboratory management system. The data was analyzed by using logistic regression with univariate and multivariable analyses to determine the association between breast cancer and predictors. RESULTS: The results of the current study showed that factors such as: age (OR = 1.02; 95%CI: 0.99-1.04; p-0.148); age at menarche (OR = 0.83; 95%CI: 0.72-0.92; p-0.008); age at first baby (OR = 1.14; 95%CI: 1.07-1.20; p- < 0.001); illiteracy (OR = 1.93; 95%CI: 1.16-3.22; p-0.011); smoking (OR = 2.01; 95%CI: 1.01-3.99; p-0.04) and family history of cancer (OR = 1.98; 95%CI: 1.18-3.32; p-0.009) were significantly associated with breast cancer. However, our study did not demonstrate any statistically significant correlation between breast cancer and some of the predictors that were previously highlighted in literature, such as: marital status, Body Mass Index (BMI), use of hormonal contraceptive, breastfeeding and exercise. CONCLUSION: Our study demonstrated that age at menarche, and age at first baby birth, illiteracy, smoking and family history of cancer were significant risk factors associated with development of breast cancer among women in Afghanistan. Health education of women regarding aforementioned predisposing factors are therefore, expected to be valuable in decreasing the burden of breast cancer with reduction of its burden on the healthcare system in Afghanistan.

Metastatic renal cell carcinoma to pancreas and gastrointestinal tract: a clinicopathological study of 3 cases and review of literature.

BACKGROUND: Renal Cell Carcinoma (RCC) metastasizes in approximately 20-30% cases. The most common sites for metastases are the lungs, bones, liver, and brain. Metastases of RCC in the gastrointestinal tract (GIT) are very rare. Metastatic RCC has a poor prognosis. We herein present a case series of three patients with metastatic disease in the colon, duodenum, and pancreas following complete resection of RCC. METHODS: Hematoxylin and Eosin and immunohistochemical slides of 3 cases of RCC metastatic to GIT were reviewed. These cases were diagnosed between 2002 and 2019 at French Medical Institute for Mothers and Children (FMIC), Kabul, Afghanistan, and Aga Khan University Hospital (AKUH), Karachi, Pakistan. We also present a detailed review of published literature. RESULTS: We reviewed cases of three patients, two females and one male, with a mean age of 57.3 years (range 40-67 years) who underwent nephrectomy for RCC. They developed metastases in the colon, pancreas, and duodenum, respectively 12-168 months (median time 156 months) following primary tumor resection. The patient with metastatic RCC in colon presented with abdominal pain and constipation. An ulcerated mass was found on colonoscopy 30 cm from the anal verge. Diagnosis of RCC with rhabdoid features was confirmed in both primary and metastatic tumors. The second patient developed a metastatic nodule in the head of pancreatic while the third patient developed metastatic nodules in the duodenum and pancreas which were detected by Computed Tomography (CT) scanning. Histopathological examination confirmed the presence of clear cell RCC in the metastatic nodules in both cases. CONCLUSION: Metastatic RCC should be considered in the differential diagnosis of mass in the gastrointestinal (including pancreaticobiliary) tract especially in presence of a past history of RCC. These patients should be screened thoroughly by physical examination and appropriate imaging studies.

Gliosarcoma in patients under 20 years of age. A clinicopathologic study of 11 cases and detailed review of the literature.

BACKGROUND: Gliosarcoma is a rare variant of IDH- wild type glioblastoma with both glial and mesenchymal differentiation. It accounts for approximately 2% of glioblastomas and has a poor prognosis similar to that of classic glioblastoma. It is seen mostly between 40 and 60 years of age with a mean age over 50 years. Pediatric gliosarcoma is even rarer than gliosarcoma in adults. We describe the clinicopathological features of gliosarcoma in patients under 20 years of age and determine whether there are significant differences from gliosarcoma in adults. We also present detailed review of published literature on pediatric gliosarcoma. METHODS: Slides of gliosarcomas in patients under 20 years of age were reviewed. Clinicopathological features were noted in detail and follow up was obtained. RESULTS: Eleven cases of gliosarcoma were reported in patients under 20 years of age. Ages ranged from three to 19 years (mean age 13 years). Frontal, parietal and temporal lobes were the commonest locations. Mean and median tumor size was six and five cm respectively. All 11 cases demonstrated the classic biphasic pattern. In 10 cases, glial component was astrocytic and was highlighted on GFAP. Sarcomatous component in most cases resembled fibrosarcoma and was high grade in 72.7%. Glial areas were reticulin poor while sarcomatous areas were reticulin rich. In over 45% cases, bizarre tumor giant cells were seen in the sarcomatous areas. In 1 case, sarcomatous areas showed extensive bone and cartilage formation. Other histologic features included hyalinized blood vessels, hemorrhage, infarction, gemistocytic cells, rhabdoid cells etc. Follow up was available in nine patients, five received chemoradiation post resection while three received radiotherapy only. Prognosis was dismal and eight patients died within one to 14 months following resection. CONCLUSIONS: Gliosarcomas in patients under 20 comprised 13% of all gliosarcomas reported during the study period. Frequency and mean age were higher compared to other published reports. Pathological features were similar to those described in literature. Clinicopathological features and prognosis of pediatric gliosarcomas were similar to adult gliosarcomas.

Concomitant bilateral mandibular cemento-ossifying fibroma and cementoblastoma: case report of an extremely rare occurrence.

BACKGROUND: Cemento-ossifying fibroma (COF) and cementoblastoma (CB) are rare benign odontogenic tumors with a predilection for the mandible. Cemento-ossifying fibroma is a fibro-osseous lesion that originates in the tooth bearing areas of jaw and shows cementum-like tissue in a fibrotic stroma. Cementoblastoma is classically related to roots of teeth with the presence of calcified cementum-like material. To date, only a single case of concomitant unilateral COF and CB has been reported in the literature. CASE PRESENTATION: We present an unusual case of a 37-year-old female who presented with two discrete bilateral swellings in the right and left mandible for 10 years. The larger tumor involved the left posterior mandible with extension anteriorly to the left and right anterior mandibles, and the smaller tumor was present in right posterior mandible. Radiology revealed two distinct lesions involving both sides of mandible. Histopathological examination showed characteristic features of cemento-ossifying fibroma in sections of the larger tumor and cementoblastoma in sections of smaller tumor. CONCLUSION: This case shows the very unique bilateral co-existence of COF and CB, the second case reported in literature to date.

Cancer prevalence in Pakistan: meta-analysis of various published studies to determine variation in cancer figures resulting from marked population heterogeneity in different parts of the country.

BACKGROUND: Pakistan's population is ethnically diverse with distinct ethnic groups inhabiting various parts of the country. Cancer statistics obtained from specific regions populated by distinct ethnic groups may vary considerably. There is no national cancer registry. To determine whether there are indeed significant statistical differences in cancer incidence and prevalence, data was recorded from different parts of Pakistan based on the ethnic composition of the population in those parts. METHODS: Ten papers (original articles) on cancer incidence and prevalence in Pakistan published in the last two decades were selected from PubMed and Google Scholar. Meta-analysis of findings of these studies was performed using Meta-analysis of Observational Studies in Epidemiology (MOOSE) checklist. χ2-based I2 test was used for evaluating heterogeneity and Forest plots were generated for calculating unadjusted prevalence estimates. Oral, gastric, prostate, breast, and colorectal cancers were selected for meta-analysis. I2 values of 75% or greater indicated high heterogeneity. RESULTS: All five types of cancer selected for meta-analysis (performed on studies carrying similar statistical weights) showed extremely high heterogeneity with I2 values of 99.7% for oral cancer, 98.6% for prostate cancer, 98.3% for gastric cancer, 99.8% for breast cancer, and 85.4% for colorectal cancer. p values for all cancers were highly statistically significant. CONCLUSIONS: Our findings show that the prevalence rates of different cancer types demonstrate marked variation in different studies depending on the place of origin of the study and dominant ethnic group in that region, and these variations are highly statistically significant. A national cancer registry needs to be established as soon as possible.

Hybrid peripheral nerve sheath tumors: report of five cases and detailed review of literature.

BACKGROUND: Hybrid peripheral nerve sheath tumors (PNSTs) have been recognized recently and were first included in the 4th edition of World Health Organization (WHO) Classification of Tumors of Soft tissue and Bone, published in 2013. These tumors show combined features of more than one type of conventional benign peripheral nerve sheath tumors. The most common combinations are those of schwannoma/perineurioma followed by combinations of neurofibroma/schwannoma and neurofibroma/perineurioma. A detailed literature review of published cases is presented. We have discussed the types and etiology, epidemiology and sites of localization, gross and microscopic appearances and immunohistochemical features of hybrid PNSTs and association of these tumors with tumor syndromes. CASE PRESENTATION: We have included five cases which were diagnosed in our department as we believe that publication of these new cases is relevant for the improved understanding of these specific tumors. Four of our five patients were males, mean age was 24 years. There was wide variation in the location of these tumors. Mean size of excised tumors was 5.5 cms in the greatest dimensions. Three out of five cases represented hybrid schwannoma/perineurioma histologically. No significant nuclear atypia, mitotic activity or necrosis seen. All five cases were completely excised. All five patients are alive and well at the time of writing with no recurrence. CONCLUSION: Hybrid PNSTs are distinct tumors and are usually benign. However, rare case reports have described local recurrence and at least two recent case reports have described malignant transformation in these tumors. Further studies on large number of cases are required to determine the exact pathogenetic basis of these tumors.

Poly (Adp-Ribose) Polymerase-1 (PARP-1) Is a Good Prognostic Marker for Pancreatic/Periampullary Cancers.

BACKGROUND: Periampullary cancer (PAC) is highly aggressive with no effective adjuvant therapy or prognostic markers. Recently, poly (ADP-ribose) polymerase-1 (PARP-1) has emerged as a target in solid cancers, and its relationship with epithelial-mesenchymal transition (EMT) has been observed. However, the relationship between PARP-1 and EMT in PAC has not explored well. MATERIALS AND METHODS: We assessed the prognostic significance of PARP-1 in 190 PACs patients and correlated it with EMT markers, including FGF8, FGFR4, MMP2, MMP3, Snail, and ZEB1. Immunohistochemistry for PARP-1 and EMT markers was performed using a tissue microarray. RESULTS: PARP-1 and FGF8 expression were associated with better survival unlike other solid cancers ( P = 0.006 and P = 0.003), and MMP3 and ZEB1 expression were associated with poor prognosis in multivariate and survival analyses ( P = 0.009 and P < 0.001). In addition, PARP-1 is related negatively to Snail but not related with other EMT markers, implying an independent mechanism between PARP-1 and EMT in PACs. PARP-1 and FGF8 are independent good survival markers in PACs unlike other solid cancers. CONCLUSIONS: PARP-1 and FGF8 in PACs could not be related to the EMT pathway but must be rather understood in light of similar cancer-protective roles. Further studies are required on EMT-associated immune markers in PACs.

Primary synovial sarcoma in anal canal: Report of a very rare case.

Extensive studies are required to understand the behavior as well as prognosis of SS in the colorectal region. IHC staining is essential for the accurate diagnosis when a lesion is encountered at an unusual site.

Artificial-Intelligence-Assisted Detection of Metastatic Colorectal Cancer Cells in Ascitic Fluid.

Ascites cytology is a cost-effective test for metastatic colorectal cancer (CRC) in the abdominal cavity. However, metastatic carcinoma of the peritoneum is difficult to diagnose based on biopsy findings, and ascitic aspiration cytology has a low sensitivity and specificity and a high inter-observer variability. The aim of the present study was to apply artificial intelligence (AI) to classify benign and malignant cells in ascites cytology patch images of metastatic CRC using a deep convolutional neural network. Datasets were collected from The OPEN AI Dataset Project, a nationwide cytology dataset for AI research. The numbers of patch images used for training, validation, and testing were 56,560, 7068, and 6534, respectively. We evaluated 1041 patch images of benign and metastatic CRC in the ascitic fluid to compare the performance of pathologists and an AI algorithm, and to examine whether the diagnostic accuracy of pathologists improved with the assistance of AI. This AI method showed an accuracy, a sensitivity, and a specificity of 93.74%, 87.76%, and 99.75%, respectively, for the differential diagnosis of malignant and benign ascites. The diagnostic accuracy and sensitivity of the pathologist with the assistance of the proposed AI method increased from 86.8% to 90.5% and from 73.3% to 79.3%, respectively. The proposed deep learning method may assist pathologists with different levels of experience in diagnosing metastatic CRC cells of ascites.

Single cell view of tumor microenvironment gradients in pleural mesothelioma.

Immunotherapies have shown great promise in pleural mesothelioma (PM), yet most patients still do not achieve significant clinical response, highlighting the importance of improving understanding of the tumor microenvironment (TME). Here, we utilized high-throughput, single-cell RNA-sequencing to de novo identify 54 expression programs and construct a comprehensive cellular catalogue of the PM TME. We found four cancer-intrinsic programs associated with poor disease outcome and a novel fetal-like, endothelial cell population that likely responds to VEGF signaling and promotes angiogenesis. Throughout cellular compartments, we observe substantial difference in the TME associated with a cancer-intrinsic sarcomatoid signature, including enrichment in fetal-like endothelial cells, CXCL9+ macrophages, cytotoxic, exhausted, and regulatory T cells, which we validated using imaging and bulk deconvolution analyses on independent cohorts. Finally, we show, both computationally and experimentally, that NKG2A-HLA-E interaction between NK and tumor cells represents an important new therapeutic axis in PM, especially for epithelioid cases.

Expression of adiponectin receptor 1 is indicative of favorable prognosis in non-small cell lung carcinoma.

Lung cancer is a major cause of cancer-related death worldwide. It is believed that obesity-related malignancies such as breast, endometrial, colorectal, and kidney carcinomas have lower plasma level and/or tissue expression of adiponectin receptors. However, the association between adiponectin receptors and lung cancer, a non obesity-related malignancy, is still unknown. We evaluated the tissue expression of adiponectin receptor (AdipoR) 1 and AdipoR2 in 83 cases of non-small cell lung carcinoma (NSCLC) and matched non-neoplastic lung tissues by immunohistochemistry and real-time polymerase chain reaction (PCR). Clinicopathological data, including smoking history, smoker's bronchiolitis, emphysema, lymph node metastasis, and T-stage were collected and evaluated. Expression of immunohistochemically stained AdipoR1 and AdipoR2 was observed in all samples of non-neoplastic lung tissues. Both receptors showed higher mRNA expression in non-neoplastic than neoplastic tissues (p < 0.05). In NSCLC tissues, AdipoR1 immunohistochemical expression was not observed in most of patients with squamous cell carcinoma and current smoking history (31/42, p = 0.04 and 25/29, p = 0.003, respectively). Additionally, AdipoR1 mRNA expression was significantly lower in patients with lymph node metastasis (p = 0.05). Meanwhile, AdipoR2 immunohistochemical stain expression was inversely correlated with T-stage (p = 0.05) and AdipoR2 mRNA expression was significantly lower in patients with smoker's bronchiolitis (p = 0.01) and emphysema (p = 0.03). Patients with expression of AdipoR1 had longer overall survival. AdipoR2 expression was not correlated with patients' survival. In conclusion, we suggest that expression of AdipoR1 is indicative of favorable prognosis and may be used as prognostic marker in NSCLC.

A suggested way forward for adoption of AI-Enabled digital pathology in low resource organizations in the developing world.

Low- and middle-income countries (LMICs) represent a big source of data not only for endemic diseases but also for neoplasms. Data is the fuel which drives the modern era. Data when stored in digital form can be used for constructing disease models, analyzing disease trends and predicting disease outcomes in various demographic regions of the world. Most labs in developing countries don't have resources such as whole slide scanners or digital microscopes. Owing to severe financial constraints and lack of resources, they don't have the capability to handle large amounts of data. Due to these issues, precious data cannot be saved and utilized properly. However, digital techniques can be adopted even in low resource settings with significant financial constraints. In this review article, we suggest some of the options available to pathologists in developing countries which can enable them to start their digital journey and move forward despite resource-poor health system.

Events in CNS Tumor Pathology Post-2016 WHO CNS: cIMPACT-NOW Updates and Other Advancements: A Comprehensive Review Plus a Summary of the Salient Features of 2021 WHO CNS 5.

Introduction: The 2016 World Health Organization Classification (WHO) of Tumors of the Central Nervous System (CNS) represented a major change. It recommended an "integrated diagnosis" comprising histologic and molecular information facilitating a more precise diagnosis of specific CNS tumors. Its goal was to provide greater diagnostic precision and reproducibility resulting in more clinical relevance and predictive value, ultimately leading to better patient care. Advances in molecular classification, mostly resulting from DNA methylation array profiling of CNS tumors, were occurring at a very rapid pace and required more rapid integration into clinical practice. Methods: cIMPACT-NOW updates and other recent papers plus salient features of 2021 WHO CNS5 in this comprehensive write-up were reviewed. Results: CNS tumor classification needs to be updated at a rapid pace and mechanisms put into place to guide diagnosticians and clinicians in the interim period if major changes in the classification of tumor types came to light. Recognizing the need to integrate these into clinical practice more rapidly and without inordinate delay, the International Society of Neuropathology (ISN) 2016 sponsored an initiative called cIMPACT-NOW. Discussion and/or Conclusion: Goal of cIMPACT-NOW was to provide clarification regarding contentious issues arising in the wake of the 2016 WHO CNS update as well as report new advancements in molecular classification of CNS tumors and new tumor entities emerging as a result of these advancements. cIMPACT-NOW updates: It thus laid the foundation for the 5th edition of the WHO Classification of CNS tumors (2021 WHO CNS 5). We have discussed cIMPACT updates in detail in this review. In addition, molecular diagnostics including DNA methylation-based classification of CNS tumors and the practical use of molecular classification in the prognostication and treatment of CNS tumors is discussed. Finally, the salient features of the new CNS tumor classification are summarized.

Hybrid odontogenic lesions: A case series of a rare entity.

Background: The occurrence of hybrid odontogenic lesions with two or more morphologically distinct components is a rare phenomenon and poses a diagnostic challenge. We aimed to study the clinical, radiological, and pathological features and behavior of hybrid odontogenic lesions, to enhance awareness about these rare lesions. Method: Hematoxylin and Eosin slides of hybrid odontogenic lesions diagnosed between January 01, 2012 and December 31, 2020, were reviewed. Demographic and radiological information were obtained from the patient's medical records. Results: 8 cases were diagnosed with a mean age of 19.1 years and male to female ratio of 1:1.7. Involvement of mandible was more common (n = 5) as compared to maxilla (n = 3). All patients presented with swelling for an average of 9.75 months (3-25 months) duration. Bleeding, loose teeth, pain and facial asymmetry were reported in 5,3, 3, and 2 cases, respectively. Radiologically, 7 cases were well demarcated, 75% cases (n = 6) were radiolucent, and average radiological size was 4.8 cm. All patients were managed with surgery alone. 5 cases (62.5%) underwent enucleation and curettage, while local excision, en-block resection and segmental mandibulectomy were performed in 1 case each. Histologically, ossifying fibroma/cemento-ossifyiong fibroma were the most lesion, occurring in 5 cases (62%), followed by giant cell granuloma like lesions (GCG) i.e., central and peripheral giant cell granuloma (n = 3), Adenomatoid Odontogenic tumor (AOT) (n = 2), and DC (n = 2), ameloblastic fibroma (AF) (n = 1), Ameloblastoma (n = 1), calcifying odontogenic cyst (COC) (n = 1), and complex odontoma (n = 1). No evidence of recurrence was noted after 4-99 months of surgery (mean: 32.9) in cases with available data (n = 7). Long-term complaints included facial asymmetry (n = 2) and pain (n = 1). Conclusion: Most hybrid odontogenic lesions affect young females in the second decade of life and commonly show COF and OF as hybrid components. A conservative approach to management appears adequate.