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   Table of Contents - Current issue
Coverpage
June 2021
Volume 64 | Issue 5
Special Issue 1
Page Nos. 1-187

Online since Monday, June 7, 2021

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EDITORIALS  

Hepatitis C Nobel Prize: The exhumation p. 1
Ranjan Agrawal
DOI:10.4103/ijpm.ijpm_176_21  PMID:34135131
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Applicability and interpretation of HER2/Neu & PD-L1 stains in gastrointestinal tract tumours Highly accessed article p. 2
Prasenjit Das, Lalita Mehra
DOI:10.4103/ijpm.ijpm_260_21  PMID:34135132
The luminal gastrointestinal tract carcinomas are one of the major causes of cancer-related deaths. To improve overall survival, the current trend is to combine targeted therapeutic agents with conventional chemotherapies. Major trials have shown survival benefits with this approach and many more trials are being undertaken. However, pathologists often get perplexed by different methods of interpretation and reporting of these stains, vital for deciding therapeutic approaches.
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Evolving significance of liver pathology p. 4
Puja Sakhuja
DOI:10.4103/ijpm.ijpm_363_21  PMID:34135133
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Pancreatic pathology: Emerging issues p. 6
Vatsala Misra
DOI:10.4103/0377-4929.317938  PMID:34135134
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GASTROINTESTINAL PATHOLOGY - GUIDELINE PAPER Top

Best practices of handling, processing, and interpretation of small intestinal biopsies for the diagnosis and management of celiac disease: A joint consensus of Indian association of pathologists and microbiologists and Indian society of gastroenterology Highly accessed article p. 8
Prasenjit Das, Kim Vaiphei, Anjali D Amarapurkar, Puja Sakhuja, Ritambhra Nada, Roopa Rachel Paulose, Rachana Chaturvedi, Anuradha Sekaran, Usha Kini, Archana Rastogi, Niraj Kumari, Anna Pulimood, Mala Banerjee, Prateek Kinra, Lavleen Singh, AmarenderSingh Puri, Ganesh Pai, Rakesh Kochhar, Gopal Krishna Dhali, BS Ramakrishna, Ajit Sood, Uday Chand Ghoshal, Vineet Ahuja, Siddhartha DattaGupta, Govind K Makharia, Vatsala Misra
DOI:10.4103/IJPM.IJPM_1405_20  PMID:34135135
The Indian Association of Pathologists and Microbiologists (IAPM) and Indian Society of Gastroenterology (ISG) decided to make a joint consensus recommendation for handling, processing, and interpretation of SI biopsies for the diagnosis and management of celiac disease (CD) recognizing the inhomogeneous practice of biopsy sampling, orientation, processing, and interpretation. A modified Delphi process was used to develop this consensus document containing a total of 42 statements and recommendations, which were generated by sharing the document draft, incorporating expert's opinion, followed by three cycles of electronic voting as well as a full-day face-to-face virtual ZOOM meeting and review of supporting literature. Of the 42 statements, 7 statements are on small intestinal (SI) biopsy in suspected patients of CD, site and the number of biopsies; 7 on handling, fixative, orientation, processing, and sectioning in pathology laboratories; 2 on histological orientation; 13 statements on histological interpretation and histological grading; 3 on the assessment of follow-up biopsies; 2 statements on gluten-free diet (GFD)-nonresponsive CD; 4 on challenges in the diagnosis of CD; 2 statements each on pathology reporting protocol and training and infrastructure in this area. The goal of this guideline document is to formulate a uniform protocol agreed upon both by the experienced pathologists and gastroenterologists to standardize the practice, improve the yield of small bowel biopsy interpretation, patients' compliance, overall management in CD, and generate unified data for patient care and research in the related field.
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GASTROINTESTINAL PATHOLOGY - REVIEW ARTICLES Top

Portal hypertensive vasculopathy – An entity worth remembering with non-neoplastic gastrointestinal lesions p. 32
Vatsala Misra, Ranjan Agrawal, Sri Praksh Misra
DOI:10.4103/ijpm.ijpm_201_21  PMID:34135136
Portal hypertensive vasculopathy (PHV) represents an increase in the pressure in the portal circulation. This increased pressure leads to changes in the mucosa that can be appreciated endoscopically as well as histopathologically. Lesions can be observed in the entire gastrointestinal tract (GIT) including stomach, duodenum, jejunum and colon. The histological changes are appreciated mainly in the mucosal and submucosal blood vessels. A knowledge of these lesions as well as the changes helps in separating them from other close differentials with specific treatment to be instituted. The pathogenesis of the hemodynamic changes is not well-understood. The underlying factor is increased portal pressure. Studies indicate, that besides increased portal pressure other factors in combination led to the observed changes. Portal hypertensive gastropathy (PHG) is seen in the gastric body and fundus, while varices are noted in the cardia and fundus. Changes may be seen in the small intestine and throughout the colon with anorectal varices. Histopathological changes include dilated, congested and ectatic capillaries and edema in the lamina propria besides a large spectrum of other histopathological changes. Mucosal capillaries with thick irregular wall show absence of red blood cells in the lumen. Thickening of the vessel wall serves as a better marker than the vascular diameter when portal hypertension (PHT) is considered. Long standing cases may show fibrosis in lamina propria. At times, these changes may lead to occult gastrointestinal bleeding. Important differentials need to be ruled out in all the cases as the treatment and the outcome of all differs. Endoscopically or histopathologically if the mucosal changes are observed they should not be overlooked and a detailed work-up must be carried out.
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Molecular targets in GI malignancies – A pathologist's perspective p. 43
Satyajit Pawar, Atul Sharma
DOI:10.4103/IJPM.IJPM_1239_20  PMID:34135137
Newer molecular diagnostics and improved understanding of cancer pathogenesis have identified multiple pathways that can be potentially targeted with the use of novel therapeutics in development. These developments have ushered cancer therapeutics in newer era of personalized medicine. Same is reflected on current management strategies for advanced gastrointestinal malignancies. Molecular profiling for BRAF and RAS is standard for colorectal cancer while Her2 and PDL1 status is needed for planning therapy of advanced gastroesophageal cancers. Tissue agnostic markers like MSI, TMB and NTRK are making headways in therapeutic armamentarium. While newer targeted therapies against FGFR, EGFR, PI3K-AKT, DDR pathways are showing promising results in initial studies. Here we review traditional as well as upcoming molecular markers in field of GI malignancies, methods of testing and evidence for rational use in clinical practice.
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Cell culture techniques in gastrointestinal research: Methods, possibilities and challenges p. 52
Gaur Preksha, Rajendran Yesheswini, Chittur V Srikanth
DOI:10.4103/IJPM.IJPM_933_20  PMID:34135138
Cell culture is one of the most valuable tools which is being applied in both fundamental and applied gastrointestinal research. The cells are isolated from their natural location (in vivo) and further propagated in vitro or artificial environment and studied. Over the years, several methods have been devised to isolate animal cells derived from the gut and culture them in vitro to study the functions and biology in the context of complex gastrointestinal diseases. This mini-review briefly describes the types and methods of cell culture covering the simplest monoculture models to more recent 3D organoid models, highlighting its importance in personalized precession medicine and other aspects of translational research. It also throws light upon the major challenges and outlines the future directions for using cell culture as a model system.
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Murine models for studying immunopathogenesis in gastrointestinal lesions: How to go about it p. 58
Neharika Jain, Priya Sharma, Dhiraj Kumar
DOI:10.4103/IJPM.IJPM_802_20  PMID:34135139
Gastro-intestinal (GI) lesions are common outcome to diverse etiological agents affecting the GI tract. It requires significant expertise to accurately diagnose the fundamental cause and treat accordingly. A better understanding of the immunological underpinning of these lesions is of great importance to ensure their successful management. Availability of specific animal models allows us to understand the subtle differences among diverse disease conditions and help decide upon the treatment trajectories. Since murine models are best suited for studying the immunopathogenesis of any disease, we will restrict our discussions here to the available murine models and their applications to study gastrointestinal lesions. In this review, we have systematically examined and compared the variety of mice models that are routinely used to study Inflammatory Bowel disease (IBD) and also how they can be leveraged to address specific questions relating to IBD.
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Artificial intelligence technologies empowering identification of novel diagnostic molecular markers in gastric cancer p. 63
Ishan Pandey, Vatsala Misra, Aprajita T Pandey, Pramod W Ramteke, Ranjan Agrawal
DOI:10.4103/IJPM.IJPM_950_20  PMID:34135140
In recent clinical practice the molecular diagnostics have been significantly empowered and upgraded by the use of Artificial Intelligence and its assisted technologies. The use of Machine leaning and Deep Learning Neural network architectures have brought in a new dimension in clinical oncological research and development. These algorithm based software system with enhanced digital image analysis have emerged into a new branch of digital pathology and contributed immensely towards precision medicine and personal diagnostics. In India, gastric cancer is one of the most common cancers in males as well as in females. Various molecular biomarkers are associated with gastric cancer development and progression of which HER2 protein, a transmembrane tyrosine kinase (TK) receptor of epidermal growth factor receptors (EGFRs) family is of prime importance. The EGF receptor expression in gastric cancer is linked with its prognostics and theragnostics. These expressions are assessed by immunohistochemistry (IHC) and molecular techniques such as Fluorescence in-situ hybridization (FISH), as per recommendations for HER2 targeted immunotherapy. These have motivated the software giants like Google Inc. to produce innovative state of art technologies mimicking human traits such as learning and problem solving skill sets. This field is still under development and is slowly evolving and capturing global importance in recent times. A literature search on PubMed was performed to access updated information for this manuscript.
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GASTROINTESTINAL PATHOLOGY - ORIGINAL ARTICLES Top

Histomorphological analysis of gastric polyps p. 69
Anjali D Amarapurkar, Kshitija M Kale, Leena P Naik, Akash P Shukla
DOI:10.4103/IJPM.IJPM_118_20  PMID:34135141
Introduction: Incidence of gastric carcinoma and gastric polyps is on rise all over the world. Chronic atrophic gastritis to intestinal metaplasia progressing to adenocarcinoma has been documented pathway for gastric carcinogenesis. Another pathway for gastric carcinoma is adenoma carcinoma sequence similar to colon cancer. Aim: To study prevalence, endoscopic, and histomorphological features of gastric polyps. Methods and Material: This was retrospective analysis of gastric polyps from 2012 to 2019 in consecutive 10,800 upper gastrointestinal endoscopies. Demographic, endoscopic, and histopathological data were obtained from hospital records. All gastric polyps were classified as per standard histologic criteria. Additional histological features noted were presence of dysplasia, focus of adenoma, or malignancy. Results: The prevalence of gastric polyps was 434 (4%) of 10,800 upper gastrointestinal endoscopies. Majority of polyps were found in the last 4 years (277: 63.8%). Mean age was 55.4 years with male to female ratio 1:1.2. Most of the polyps (94.9%) were less than 1 cm, located in gastric antrum. Multiple polyps were seen in 20.9% cases. On histopathology, fundic gland polyps were most common (147: 33.8%), followed by hyperplastic (128: 29.4%) polyps. Adenomatous polyps were nine (2%); of these, two cases of hyperplastic polyps and one each of fundic gland polyp and benign epithelial polyp showed adenomatous foci. Conclusion: Fundic gland polyps were the most common polyps. With rising incidence of gastric carcinoma, identification of gastric polyps on endoscopy with biopsy can prevent progression to carcinogenesis.
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Diagnostic utility of multiple site duodenal biopsies in celiac disease p. 73
Vikarm Narang, Akriti Jindal, Aminder Singh, Bhavna Garg Varun Mehta, Neena Sood, Ajit Sood
DOI:10.4103/IJPM.IJPM_797_20  PMID:34135142
Background: Celiac Disease involves the small intestine patchily affecting more frequently the proximal small bowel but the histological changes have been observed till terminal ileum. Of late in addition to D2, the duodenal bulb (D1 region) biopsies have been found helpful in identifying a small group of patients with CD. Therefore, multiple site biopsies are recommended as histological changes are not uniform throughout small intestine. Methods: During this present 1.5 years prospective study, we evaluated 84 cases of suspected celiac disease with respect to the light microscopy (D1, D2, and D3 biopsy) and serology (anti tTg and or EMA). Histological examination was done according to Modified Marsh grading system. Results: Out of 84 cases with raised anti tTg, the segmental biopsies significantly increased the diagnostic accuracy from 39/44 cases (88.6%) to 43/44 cases (97.7%) and 44/44 cases (100%) when D2 alone, D1 + D2 and D1 + D2 + D3 biopsies were evaluated, respectively. Of the suspected cases of celiac disease patients (tTg > 10 ULN and associated weight loss, diarrhea), additional D3 biopsy increased the diagnostic yield by 2.1%, compared to D1, D2 region biopsy and 6.38% compared to standard D2 biopsy alone. Of the 28 cases (tTg > 10 times ULN + EMA positive and associated weight loss, diarrhea), the potential celiac disease (histologically Type 1/Normal) cases reduced from 28.5% (standard D2 region alone) to 21.4% and 17.8% when additional biopsies were taken from D1 region and D3 region, respectively, and additional D3 biopsy increased the diagnostic yield by 10.8% (compared to standard D2 biopsy alone) and 3.7% (compared to D1 and D2 biopsy). Conclusion: We believe multiple sites duodenal biopsies including D3 region biopsies might increase the diagnostic accuracy of adult celiac disease in addition to sensitive and specific serologic tests.
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Loss of YY1 expression predicts unfavorable prognosis in stage III colorectal cancer p. 78
Hyunsung Kim, Seongsik Bang, Seungyun Jee, Seongeon Park, Yeseul Kim, Hosub Park, Kiseok Jang, Seung Sam Paik
DOI:10.4103/IJPM.IJPM_96_20  PMID:34135143
Background: Yin Yang 1 (YY1), the multifunctional transcription factor, has recently been assigned biological properties related to human malignancies. YY1 can facilitate both tumor suppression and tumor growth. The conflicting role of YY1 in human malignancies is not yet fully explained. Objective: In this study, we determined the clinicopathologic significance and prognostic role of YY1 in stage III colorectal cancer (CRC). Materials and Methods: YY1 expression was evaluated immunohistochemically in tissue microarray from 345 CRCs. YY1 expression was scored by the proportion of tumor cells with nuclear staining into 4 scores (0, none; 1+, ≤10%; 2+, 10 to ≤25%; 3+, >25%). A score of 0 and 1 were considered as loss of expression. Results: Loss of YY1 expression was observed in 49 (14.2%) out of 345 CRCs and was associated with larger tumor size (P = 0.004), tumor deposit (P = 0.008), and higher pathologic tumor (pT) stage (P = 0.004). In stage III group, loss of YY1 expression was associated with larger tumor size (P = 0.027) and tumor deposit (P = 0.011). Kaplan–Meier survival curves revealed no significant difference between patients with YY1 loss and patients with intact YY1 in both cancer-specific survival and recurrence-free survival (P = 0.330 and P = 0.470, respectively). In American Joint Committee on Cancer (AJCC) stage subgroup, loss of YY1 expression was associated with poor recurrence-free survival in AJCC stage III CRC (P = 0.038). Conclusion: Loss of YY1 expression was significantly associated with aggressive phenotypes and poor patient outcome in AJCC stage III CRC.
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GASTROINTESTINAL PATHOLOGY - BRIEF COMMUNICATION Top

Malignancy-induced hemophagocytic lymphohistiocytosis in a case of signet ring cell carcinoma of the stomach p. 85
Subramaniam Ramkumar
DOI:10.4103/IJPM.IJPM_896_19  PMID:34135144
Hemophagocytic lymphohistiocytosis (HLH) is a rare and potentially life-threatening condition associated with high mortality and can be classified into primary (familial) and secondary HLH. Primary HLH is an inherited, autosomal recessive disorder associated with defects in perforin function, whereas secondary HLH is associated with infections, especially Epstein–Barr virus infection, malignancies, and autoimmune disorders. Patients with malignancy-associated secondary HLH experience symptoms that overlap with those described for other HLH types, which is associated with an increased incidence of misdiagnosis and mortality. Here, we report the case of a patient with secondary HLH associated with a solid malignancy (signet-ring cell carcinoma of the stomach).
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GASTROINTESTINAL PATHOLOGY - CASE REPORTS Top

Malignant gastrointestinal stromal tumor in association with Russell body gastritis—A case report p. 89
Desislava M Bozhkova, Maria S Koleva-Ivanova, Veselin T Belovejdov, Dorian I Dikov
DOI:10.4103/IJPM.IJPM_842_19  PMID:34135145
Russell body gastritis (RBG) is an unusual form of chronic inflammation characterized by accumulation of plasma cells containing Russell bodies (RB) in the gastric mucosa. Although its pathogenesis has not been fully evaluated, there is evidence to support a strong association with Helicobacter pylori infection. Only four cases of RBG in association with malignant epithelial gastric tumors were reported. We report the first case of RBG in peritumoral mucosa of a malignant gastrointestinal stromal tumor in association with coccoid form of Helicobacter pylori and a follow-up.
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Multifocal colorectal non-Hodgkin's lymphoma in a patient with ulcerative colitis: A case report p. 92
Sagar Walinjkar, Ashish Kumar, Praveen Sharma, Pallav Gupta, Naresh Bansal, Vikas Singla, Shrihari A Anikhindi, Anil Arora
DOI:10.4103/IJPM.IJPM_654_19  PMID:34135146
A case of multifocal non-Hodgkin's (Diffuse large B cell type) lymphoma of colon in a patient with ulcerative colitis is described. The patient was a 69-year old male treated with azathioprine and methotrexate for ulcerative colitis for 2 years. He was admitted with loose stools and hematochezia. Colonoscopy revealed two deep ulcers in ascending colon and a large ulcer in rectum. Biopsy from both the sites revealed atypical large lymphoid cells, which were CD20 positive. A whole body PET-CT scan showed disease localized to colon with bone marrow examination showing no evidence of lymphoma. The patient was given chemotherapy cycles and recovered well.
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GASTROINTESTINAL PATHOLOGY - IMAGES Top

Immature gastric teratoma in an infant: A rare entity with review of literature p. 95
Pragati Sathe, Mona Agnihotri, Roopali Manudhane, Swati Shinde
DOI:10.4103/IJPM.IJPM_297_20  PMID:34135147
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Helicobacter heilmannii associated gastritis: Report of a rare case p. 97
Rishila Majumder, Pritinanda Mishra, Subash C Samal, Sunil J Bhat, Susama Patra
DOI:10.4103/IJPM.IJPM_629_20  PMID:34135148
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GASTROINTESTINAL PATHOLOGY - LETTERS TO EDITOR Top

Sarcinia ventriculi, an incidental bacteria in gastric obstruction? Can it be a clue to underlying malignancy in endoscopic biopsy p. 100
Kaushik Saha, Arpita Saha, Kundan Kumar, Dipendu Majumder, Minakshi Mishra
DOI:10.4103/IJPM.IJPM_992_19  PMID:34135149
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Uncommon pathological presentation of colonic biopsy in a patient with inferior mesenteric venous thrombosis p. 102
I-Wei Chang
DOI:10.4103/IJPM.IJPM_46_20  PMID:34135150
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HEPATOBILIARY PATHOLOGY - REVIEW ARTICLES Top

Liver biopsy in the quantitative assessment of liver fibrosis in nonalcoholic fatty liver disease p. 104
Gwyneth Shook Ting Soon, Aileen Wee
DOI:10.4103/IJPM.IJPM_947_20  PMID:34135151
Nonalcoholic fatty liver disease/nonalcoholic steatohepatitis (NAFLD/NASH) is a major cause of liver fibrosis/cirrhosis and liver-related mortality. Despite emergence of noninvasive tests, liver biopsy remains the mainstay for the diagnosis and assessment of disease severity and chronicity. Accurate detection and quantification of liver fibrosis with architectural localization are essential for assessing the severity of NAFLD and its response to antifibrotic therapy in clinical trials. Conventional histological scoring systems for liver fibrosis are semiquantitative. Collagen proportionate area is morphometric by measuring the percentage of fibrosis on a continuous scale but is limited by the absence of architectural input. Ultra-fast laser microscopy, e.g., second harmonic generation (SHG) imaging, has enabled in-depth analysis of fibrillary collagen based on intrinsic optical signals. Quantification and calculation of different detailed variables of collagen fibers can be used to establish algorithm-based quantitative fibrosis scores (e.g. qFibrosis, q-FPs) in NAFLD. Artificial intelligence is being explored to further develop quantitative fibrosis scoring methods. SHG microscopy should be considered the new gold standard for the quantitative assessment of liver fibrosis, reaffirming the pivotal role of the liver biopsy in NAFLD, at least for the near-future. The ability of SHG-derived algorithms to intuitively detect subtle nuances in liver fibrosis changes over a continuous scale should be employed to redress the efficacy endpoint for fibrosis in NASH clinical trials. The current decrease by 1-point or more in fibrosis stage may not be realistic for the evaluation of therapeutic response to antifibrotic drugs in relatively short-term trials.
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An update on subtypes of hepatocellular carcinoma: From morphology to molecular p. 112
Monika Vyas, Dhanpat Jain
DOI:10.4103/IJPM.IJPM_751_20  PMID:34135152
The morphologic spectrum of hepatocellular carcinoma (HCC) is quite broad. While in about one-third of cases, the neoplasms can be categorized into meaningful subtypes based on morphology, a vast majority of these neoplasms are morphologically heterogeneous. With extensive tumor profiling, data has begun to emerge which can correlate specific morphologic features with underlying molecular signatures. A true morphologic subtype not only has reproducible H & E features, further supported by specific immunohistochemical or molecular signatures, but also has specific clinical implications and prognostic associations. Eight such morphologic subtypes are recognized by the 2019 WHO classification of tumors with a few more additional subtypes described in the literature. The goal of this review is to familiarize the reader with the morphologic subtypes and elaborate on the clinical and molecular associations of these neoplasms.
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An approach to grossing of hepatectomy specimens p. 121
Archana Rastogi
DOI:10.4103/IJPM.IJPM_870_20  PMID:34135153
Liver resections are performed for acute and chronic end stage liver failure, primary and secondary liver malignancies as well as for several other neoplastic and non-neoplastic conditions. Hepatectomy specimens can be total, partial, or wedge resections. These specimens are relatively rare and complex. Meticulous handling, orientation, dissection, margin assessment, and reporting as per the latest guidelines, often require a multidisciplinary approach. This article discusses the approach to grossing of hepatectomy specimens, and the most important macroscopic considerations for specific conditions.
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HEPATOBILIARY PATHOLOGY - ORIGINAL ARTICLE Top

Histological analyses of trucut liver biopsies from patients with noncirrhotic portal fibrosis and extra-hepatic portal vein obstruction p. 127
Archana George Vallonthaiel, Vandana Baloda, Lavleen Singh, Rajni Yadav, Ragini Kilambi, Sudha Battu, Vishnubhatla Sreenivas, Sujoy Pal, Subrat K Acharya, Siddhartha DattaGupta, Shalimar , Prasenjit Das
DOI:10.4103/IJPM.IJPM_387_20  PMID:34135154
Background: Both noncirrhotic portal fibrosis (NCPF) and extrahepatic portal venous obstruction (EHPVO) are important causes of noncirrhotic portal hypertension (PH) in the Asian region. In this study, we analyzed the histopathological changes of liver needle-core biopsies from patients with NCPF and EHPVO. Patients and Methods: The patients were diagnosed as per the Asia Pacific Association for the Study of Liver (APASL) criteria. Minimum adequacy criteria for liver core biopsies were defined, and finally, 69 liver biopsies from patients with NCPF and 100 liver biopsies from patients with EHPVO were analyzed. All histological parameters were predefined, and three experienced pathologists analyzed the biopsies after reaching consensus. Institute ethics committee clearance was taken. Results: Although some histological features were overlapping, phlebosclerosis of intra-hepatic branches of the portal vein (PV), periportal aberrant vascular channels, remnant portal tracts, and hepatic fibrosis beyond the portal tracts without the formation of complete hepatic nodules (P < 0.001 for all) were common histological characteristics of NCPF on core-needle liver biopsies; while maintained lobular architecture, nonspecific dilatation of PV branches, absence of intra-hepatic PV phlebosclerosis, aberrant vascular channels, and significant fibrosis were characteristics of EHPVO. Conclusions: Despite the considerable histological overlap between NCPF and EHPVO, careful histological evaluation, supplemented by clinical features, radiological and biochemical findings can help in making a conclusive diagnosis. Patients with NCPF and EHPVO with clinical jaundice show transaminitis, high serum alkaline phosphatase level, more variceal bleed, and histological evidences of nodular regenerative hyperplasia.
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HEPATOBILIARY PATHOLOGY - CASE REPORTS Top

Primary Ewings sarcoma in liver - A rare case report with review of literature p. 136
Anjali Sharma, Neha Sethi, Shashikant Saini, Kirti Pandia, Ritu Jangir
DOI:10.4103/IJPM.IJPM_288_19  PMID:34135155
Ewing's sarcoma family of tumours include both peripheral primitive neuroectodermal tumour (PNET) and Ewing's sarcoma including both intraosseous and extra osseous sites. Rarest of all is the involvement of liver as primary site, of which only 4 case reports have been published. We report a very rare case of 4 year old male child with primary Ewing's Sarcoma in the liver along with review of literature. The child presented with pain abdomen and low grade fever and hepatomegaly. On putting extensive IHC panel on liver SOL biopsy the small round cells were positive for FLI-1 & CD99 & were immunonegative for OCH, LCA, AFP, WT1, NSE, MYOGENIN, B-catenin & glypican 3. The histopathological and immunohistochemical profile was suggestive of Ewing's Sarcoma. To our knowledge, this is the fifth reported case of Ewing's Sarcoma occurring in liver as primary & first case to be present in a young boy of 4 years age.
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Primary hepatic adenosquamous carcinoma: A rare case report p. 140
Dong Wei, Liu Lu, Chen Ying, Kang Qingsong, Li Dongbo, Li Feibo
DOI:10.4103/IJPM.IJPM_785_18  PMID:34135156
Primary hepatic adenosquamous carcinoma (ASC) is an extremely rare primary hepatic malignant tumor, which is easily misdiagnosed as hepatocellular carcinoma before surgery. It has both the histologic features—adenocarcinoma and squamous cell carcinoma. Primary hepatic ASC incidence rate in intrahepatic cholangiocarcinoma is 2% to 3%.[1] Patients with hepatic ASC may experience recurrence or metastasis after surgery. The epidemiology, clinical diagnosis, etiology, and treatment of the disease remain challenging. It is important to improve the recognition of hepatic ASC because of its bad prognosis. Here, we report a man who had complained of an upper stomachache for 2 months and was diagnosed with primary hepatic ASC by histology and immunohistochemistry (IHC) after laparoscopic hepatectomy. The patient remained asymptomatic and survived well for 2 years post surgery and long-term follow-up was continued till now. In addition, we offer a brief discussion about the histopathological features, clinical behavior, and treatment of hepatic ASC and review the relevant literature.
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Epithelioid hemangioma of liver—The first reported case p. 143
Adrienn Biro, László Ternyik, Veronika Czoma, Géza Hegedűs, István Bálint, Dezső Tóth, Zsolt Káposztás
DOI:10.4103/IJPM.IJPM_148_20  PMID:34135157
Epithelioid hemangioma, otherwise known as angiolymphoid hyperplasia with eosinophilia, is a rare benign vasoproliferative disease with an unknown etiology. We report the case of a 42-year-old man with routine bloods test showing mildly elevated serum bilirubin level. CT scan revealed a lesion in the left liver lobe not typical of FNH. PET/CT scan and a dynamic liver MRI were consistent with a malignant mass. Surgical resection was performed. Histopathology of the 45 mm mass reported well-defined, slightly lobular proliferations of capillary-sized vessels around several central muscular vessels. Although the endothelial cells revealed a “hobnail” appearance, none of them showed pleomorphism or mitotic activity. Endothelial cells showed reactivity for the endothelial markers (CD34, CD31) and smooth muscle was detected in the blood vessel walls via immunohistochemistry. Despite its benign nature, epithelioid hemangioma of the liver can lead to a diagnostic and therapeutic dilemma due to the malignant looking features on imaging modalities.
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Benign recurrent intrahepatic cholestasis - 2 (BRIC-2)/ABCB11 deficiency in a young child – Report from a tertiary care center in South India p. 146
KV Kalaranjini, Jinu A Glaxon, Sheela Vasudevan, ML Arunkumar
DOI:10.4103/IJPM.IJPM_254_20  PMID:34135158
ABCB11 deficiency, formerly benign recurrent intrahepatic cholestasis (BRIC) is a very rare hereditary disorder characterized by the recurrent and intermittent episodes of cholestasis, jaundice, and pruritus. We report the case of a 12-year-old boy presenting with recurrent episodes of jaundice and severe pruritis since childhood. An extensive workup was done to rule out all the possible etiologies. Liver biopsy was done and histopathology was consistent with intrahepatic cholestasis. Immunohistochemistry, enzyme studies, and genetic testing confirmed the diagnosis. The patient was treated with Ursodeoxycholicacid and is on regular follow-up. We report this case due to the rarity of the disease in South India and to highlight the importance of genetic testing, which is the gold standard for diagnosis as well as for the classification of the disease. These patients should be under regular follow-up as those with fibrosis progression are at a risk for cholangiocarcinoma and hepatocellular carcinoma.
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PANCREATIC PATHOLOGY - REVIEW ARTICLE Top

Autoimmune pancreatitis: Current perspectives p. 149
Surbhi Goyal, Puja Sakhuja
DOI:10.4103/ijpm.ijpm_59_21  PMID:34135159
Over the last two decades, our knowledge and understanding regarding the pathogenesis and biology of autoimmune pancreatitis (AIP) have improved tremendously. Type 1 AIP or IgG4-related pancreatitis (IgG4-RP) is now believed to be the prototype of the multisystemic IgG4-related disease. In view of clinical features like obstructive jaundice and mass-forming lesions in the pancreas in elderly men, type 1 AIP often mimics pancreatic cancer. IgG4-related sclerosing cholangitis concomitantly involving the extrahepatic and intrahepatic biliary tree is the most common extrapancreatic involvement seen in up to 80% of these patients, which needs to distinguish from cholangiocarcinoma. Histology is characterised by lymphoplasmacytic inflammation, abundant IgG4 positive plasma cell infiltration, storiform fibrosis and obliterative phlebitis. Apart from histology, high serum IgG4 levels, pancreatic parenchymal and duct imaging findings and other organ involvement aid in diagnosis especially in cases where definitive histology is not evident. Also, these parameters lay the foundation of various diagnostic criteria proposed over last few years. On the contrary, histology alone is the mainstay for establishing diagnosis of idiopathic duct-centric pancreatitis (IDCP) as it lacks any specific serological marker or imaging. Since both types of AIP respond dramatically to corticosteroid treatment, a biopsy is crucial to establish the preoperative diagnosis and to exclude malignancy so as to avoid unnecessary surgery. This review discusses the morphologic spectrum, treatment and prognosis of IgG4-RP and IDCP with an emphasis on approach to diagnosis with relevant histologic features, differential diagnoses and the challenges faced during biopsy interpretation.
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PANCREATIC PATHOLOGY - ORIGINAL ARTICLE Top

Expression patterns and prognostic significances of RRM1 and ERCC1 in pancreatic carcinoma and cholangiocarcinoma p. 160
Khushbu Khetan, Ranjit K Sahoo, Vandana Baloda, Shalimar , Sreenivas Vishnubhatla, Anoop Saraya, Nihar Ranjan Dash, Atul Sharma, Siddhartha DattaGupta, Prasenjit Das
DOI:10.4103/IJPM.IJPM_537_19  PMID:34135160
Background: Aggressive pancreatobiliary tumors often require oxaliplatin-based therapies, instead of standard gemcitabine-based therapy and biomarker studies at diagnosis to decide the appropriate therapeutic regimen. The ribonucleotide Reductase catalytic subunit M1 (RRM1) and excision repair cross-complementing gene-1 (ERCC1) are related to DNA synthesis and repair and essential in this regard. However, apart from the therapeutic benefit, their prognostic implication is controversial. Methods: In this retrospective study, paraffin-embedded tissue from 51 cases of pancreatic cancer and 29 cases of cholangiocarcinoma were evaluated for RRM1 and ERCC1 expression by immunohistochemical technique along with 18 control pancreatic and biliary tissues. The semiquantitatively H score was calculated based on stain distribution and stain intensities. Results: Both RRM1 and ERCC1 expression were high in tumor epithelium than in controls (RRM1: the difference was statistically significant in cholangiocarcinoma (P = 0.008); ERCC1: the difference was statistically significant both in pancreatic and cholangiocarcinoma (P < 0.05)]. However, no correlation was noted between RRM1 and ERCC1-low and high tumors with histological markers of prognosis and overall survival in these patients. Conclusions: The present study adds further evidence against the controversy that if RRM1 and ERCC1 expression in pancreatic and biliary carcinomas have any prognostic significance apart from their proven therapeutic benefits in these tumors.
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PANCREATIC PATHOLOGY - CASE REPORTS Top

Benign macrocystic serous cystadenoma of the pancreas p. 166
Selma Erdogan Duzcu, Nur Tunc
DOI:10.4103/IJPM.IJPM_945_19  PMID:34135161
Serous cystadenoma is a rare benign cystic lesion of pancreas. They are mostly known as benign cystic tumors of pancreas but malign transformation as serous cystadenocarcinoma is also reported. It is more commonly observed in women with the mean age of onset is 62 years. The majority of patients present nonspecific symptoms such as abdominal pain, weight loss, nausea, vomiting, fever, and melena. One-third of the patients are asymptomatic. A 60-year-old woman presents with abdominal pain and nausea for 1 month was admitted. Physical and laboratory findings were normal. Abdomen computed tomography scan confirmed a large number of millimetric cysts of 45 × 47 × 50 mm in size at the head of the pancreas. Due to patient's symptoms and mass effect, Whipple procedure was performed. In the gross examination, a nodular area of 5 × 5 × 4 cm was observed in the head of the pancreas. The microscopic examination of the material revealed cystic structures with fibrous stroma dotted with single layered cuboidal epithelium in the pancreatic tissue. The pathology report confirmed benign macrocystic serous cystadenoma. Serous cystadenomas are rare benign cystic lesions of the pancreas. Although they are benign lesions, it is crucial to differentiate them from other cystic lesions of the pancreas and malignant serous cystadenocarcinomas.
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Calcifying fibrous tumor of the pancreas: A case report p. 169
Mustafa Kösem, Gupse Turan, Metin Ercan, Ebru Tezcan
DOI:10.4103/IJPM.IJPM_664_18  PMID:34135162
A calcifying fibrous tumor (CFT) is a rare benign mesenchymal tumor characterized by a hypocellular fibroblastic proliferation with associated chronic inflammation and variably prominent calcification. Gastrointestinal (GI) tract is the most common predilection site of CFT. English-language literature reveals approximate 50 such reports of GI-CFTs. In addition, the most frequently identified sites of the GI tract are stomach, small bowel, and colon. However, CFT has not been reported in the pancreas. In addition, we present the first pancreatic-CFT in this case report.
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Pancreatic collision tumor of ductal adenocarcinoma and neuroendocrine tumor—A rare case report p. 172
Prajna Das, Ranjita Panigrahi, Prita Pradhan, Urmila Senapati, Mihir Kumar Mohapatra
DOI:10.4103/IJPM.IJPM_735_19  PMID:34135163
A collision tumor is composed of two adjacent histological distinct neoplasms without the histological admixture of cell types in the same organ or tissue. It is rare in pancreas. Herein we report an unusual case of a mixed malignant neuroendocrine tumor (NET) and ductal adenocarcinoma of pancreas in a 24 year old male who presented with history abdomen pain. A clinicoradiological diagnosis of chronic calcific pancreatitis with carcinoma body of pancreas was made. Distal pancreaticosplenectomy specimen showed a grey white, nodular growth measuring 2 x 2 x 1.2 cm on the cut surface of pancreas. Histopathology revealed a composite tumor consisting of ductal and neuroendocrine origin. Immunohistochemistry showed complementary staining for CK7 in adenocarcinoma and chromogranin A in NET areas confirming a collision tumor. Accurate evaluation of the radiologic pointers, histomorphologic evaluation to recognize and quantitate the individual components, appropriate immunohistochemical evaluation and correlation is essential for diagnosis.
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PANCREATIC PATHOLOGY - IMAGE Top

Combined pancreatic and gastric heterotopia in small intestine presenting as intussusception—A rare congenital anomaly p. 175
Tejasvita Singh, Sonal Tripathi, Shatakshee Tewari, Kachnar Varma, Vatsala Misra
DOI:10.4103/IJPM.IJPM_662_20  PMID:34135164
Pancreatic and gastric heterotopias are rare congenital anomalies which have been reported throughout the length of the gastrointestinal tract. Combined gastric and pancreatic heterotopias, although very rare, have been described mainly in the duodenum followed by jejunum with ileum being a rare site. The reported incidence of this combined heterotopias is low, ranging from <1% to 13%. Extensive literature search has revealed that only Four cases of combined pancreatic and gastric heterotopias have been reported in the small intestine till date. Hence, we report this case for its rarity and unusual presentation as intussusception in a young male.
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PANCREATIC PATHOLOGY - LETTERS TO EDITOR Top

Heterotopic pancreatic tissue in the gallbladder: A rare incidental finding p. 178
Deepika Gupta, Devender Singh Chauhan, Swati Rao
DOI:10.4103/IJPM.IJPM_829_19  PMID:34135165
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Acute pancreatitis as a presenting feature in a child with systemic polyarteritis nodosa p. 180
Sunil V Kapur, Jitendra S Oswal
DOI:10.4103/IJPM.IJPM_804_20  PMID:34135166
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Primary squamous cell carcinoma of the common bile duct p. 182
Lin Zhong, Wenjing Qi, Fengming Tao, Lizhi Zhang, Jienan Kong
DOI:10.4103/IJPM.IJPM_633_20  PMID:34135167
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Primary non hodgkin lymphoma and Ewing's sarcoma/PNET: Two rare pancreatic round cell tumors with diverse clinical outlook p. 184
Neha Bakshi, Shashi Dhawan, Sunita Bhalla, Ritu Verma
DOI:10.4103/IJPM.IJPM_730_19  PMID:34135168
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