Primary sclerosing encapsulating peritonitis.

Sclerosing encapsulating peritonitis also known as cocoon abdomen is a rare chronic inflammatory condition of the peritoneum in which the bowel loops are encircled by a membrane (cocoon formation) within the peritoneal cavity leading to intestinal obstruction. It can be primary (idiopathic) or secondary (chemotherapy, beta-blockers, peritoneal dialysis, shunts, tuberculosis, systemic lupus erythematosus, etc.). The symptomatology report includes recurrent episodes of abdominal pain and vomiting. We present here a case of a 32-year-old male who presented with complaints of being unable to pass stools, vomiting (3-4 times), and abdomen pain for 4 days. This case is considered worth mentioning due to its rarity, lack of identification of secondary causes, and diminutive mention of histopathological aspect.

Evaluation of tumor budding and its correlation with histomorphological prognostic markers in oral squamous cell carcinoma and its association with the epithelial-mesenchymal transition process.

Objective: To evaluate the association of tumor budding (TB) with prognostic histomorphological parameters in oral squamous cell carcinoma (OSCC) and to investigate the correlation of TB intensity with epithelial to mesenchymal transition (EMT). Material and Method: A total of 200 cases diagnosed as OSCC were selected and their TB status was reviewed using Hematoxylin and eosin (H and E) and Immunohistochemistry (IHC). Correlation with histomorphological prognostic parameters was done. Also, IHC for Vimentin and E-cadherin was performed to look for EMT. Results: On H and E examination, TB was observed in 154/200 (77%). About 88/154 (57.14%) cases showed a high TB (>5 TB/10 hpf) which increased to 100/154 (64.9%) cases on IHC staining. The intensity of TB was significantly associated with tumor grade and depth of invasion. It was also significantly associated with reduced expression for E-Cadherin and upregulation of Vimentin establishing a pathogenetic correlation between the TB and EMT. Conclusion: Therefore, our results suggest that TB is associated with poor prognosis and histologically represents EMT in OSCC which further adds to the aggressiveness of the tumor.

Spectrum of histopathological changes and its quantification using a scoring system in patients with gastroesophageal reflux disease.

Aim: The aim of this study was to evaluate the role of histopathological and histomorphometric features in oesophageal biopsy of patients presenting with symptoms of Gastroesophageal Reflux Disease (GERD). Material and Methods: Present study included 42 patients and 12 controls. Complete clinical evaluation followed by endoscopic examination of the patients was done and multipleoesophageal biopsies were taken. Biopsies were processed routinely and stained with Hematoxylin and Eosin and examined for any changes related to GERD. Morphometric assessment was done by using Leitz optical micrometer. The histological scoring was done based on the parameters: basal cell hyperplasia, stromal papillae elongation, cells with irregular nuclear contour (CINC), eosinophilic infiltrate, gastric and intestinal metaplasia. A numerical score was assigned to each parameter and sum of these scores represented the total score. Statistics: The statistical analysis was done using graph pad prism, Medcalc software and Windows MS office. P value and mean standard deviation (SD) was calculated. Results: The endoscopic findings of all the controls and 83.33% of patients were normal. Only 16.67% of patients had reflux associated changes of varying grades on endoscopy. Oesophageal biopsy of all patients had changes related to GERD on histology. Immunohistochemistry confirmed that cells with irregular nuclear contour were T- lymphocytes. The mean (SD) histological scoring of control and patients were 1.75 (0.62) and 5.66 (1.31) respectively. The difference was considered to be statistically significant (P < 0.001). Thus, it was suggested that a cut-off of histological score > 3 can be used to indicate GERD. Conclusion: Patients with gastroesophageal reflux symptoms can have normal endoscopic findings but can be diagnosed on the basis of histological changes in the squamous epithelium. Scoring of the histopathological parameters along with the cut-off value can give a definitive diagnosis of GERD.

Role of Immunohistochemistry and serology in subclassifying the Inflammatory Bowel Disease cases diagnosed as Inflammatory Bowel Diseases---unclassified on colonic biopsies.

Background: Inflammatory bowel diseases (IBDs) mainly consist of Crohn's Disease (CD) and Ulcerative Colitis (UC). These two categories have overlapping histopathological features and sometimes it is difficult to diagnose them into distinct category and such biopsies are categorised as Inflammatory Bowel Disease (IBD-U). Recently, there has been an increase in interest to discover new biomarkers of IBD to differentiate UC and CD and predict their prognosis. Method: In the present study, 273 non-neoplastic colonic biopsies with clinicoendoscopic features of IBD were studied and categorized into UC (88; 32.3%) and CD (03; 1.1%) but a major chunk remained in category of IBD-U (182; 66.6%). 161 (58.9%) of these biopsies were then subjected to IHC for RB protein and ß-catenin and Serology for pANCA and ASCA was done in only 85 (31.13%) of these selected cases for identification of UC and CD on colonic biopsies. Result: 161 biopsies that were subjected to IHC analysis included 57 cases of UC, 03 cases of CD, and rest 101 cases of IBD-U. Out of 101 cases of IBD-U, 87 (86.13%) cases were reclassified as UC (61; 60.3%) and CD (14; 13.86%) on the basis of results of IHC and Serology. Conclusion: The two major tools IHC for ß-catenin and RB protein and the assay of serum ASCA and p-ANCA along with proper history and clinical presentation can act as a good adjunct to conventional H and E in subclassifying cases of IBD-U into UC and CD.

Prevalence of precursor lesions (P53 signature, SCOUT, STIL, STIC) in fallopian tubes resected for non-neoplastic causes.

Background: High-grade pelvic serous carcinoma is a common cause of death in women worldwide and India. Recent evidence has clearly implicated the changes in the mucosa of the fimbrial end of the fallopian tube in its pathogenesis. Objective: 1) To study histopathology features of surgically resected specimens of fallopian tubes received with non-neoplastic lesions of the uterus and ovary for the presence of any precursor lesions [secretory cell outgrowth (SCOUT), serous tubal intraepithelial lesion (STIL), p53 signatures, and serous tubal intraepithelial carcinoma (STIC)]. 2) To confirm the findings with immunohistochemistry. 3) To correlate the prevalence of precursor lesions with clinical parameters and benign lesions of the uterus and ovaries. Materials and Methods: Assessment of histopathological changes in 100 specimens of distal fallopian tubes was done using the sectioning and extensive examination of the fimbrial end (SEE-FIM) protocol. H and E stain followed by immunohistochemistry for Bcl-2, p53, and Ki-67. The statistical significance of the difference in the mean values of precursor areas was evaluated by an unpaired t-test. Results: Among 100 specimens taken on H and E, precursor lesions were suspected in 49% of the cases. SCOUT, suspicious for STIC, suspicious for STIC with areas of SCOUT, and unequivocal for STIC with areas of SCOUT were seen in 8%, 4%, 33%, and 4% of the cases, respectively. However, on IHC, SCOUTS were confirmed in 45% of the cases, p53 signature in 2%, STIL in 9%, and STIC in 4% of the cases. Conclusion: Sectioning and extensive examination of the fimbrial end (SEE-FIM) should be routinely done as it provides the opportunity to detect the early malignant changes. It may help in evolving the strategies for early detection, management, and reducing mortality.

Role of C4d in the Diagnosis and Prognosis of Native Renal Diseases.

Introduction: C4d is a biomarker of the complement cascade and has a primary role in the diagnosis of antibody-mediated rejection in solid organ transplantation. The present study was undertaken to investigate the role of C4d in the diagnosis and prognosis of native renal diseases. Methods: An observational cross-sectional study was conducted in the Department of Pathology from September 2017 to September 2019. In this study, we applied C4d staining by immunohistochemistry in 51 native renal biopsies. Semiquantitative scoring was done on the basis of intensity of C4d staining along the glomerular capillary wall (0-3) and mesangium (0-3), tubules (0-3), and arteries (0-3). These individual scores were added to get the total C4d score (0-12) which was correlated with chronicity index, serum urea and creatinine levels. Glomerular C4d score was correlated with 24 h urinary protein as well as with immunofluorescence deposition of immunoglobulins and complements. Results: We found a linear positive correlation (P < 0.05) between the total C4d score and serum creatinine; tubular C4d score and serum creatinine; and glomerular C4d score along capillary wall and 24 h urinary protein. A positive correlation (P < 0.05) was found between glomerular C4d score along the capillary wall with immunofluorescence deposits of immunoglobulins and complements, suggesting the efficacy of C4d as a surrogate marker in the diagnosis of native renal diseases. Conclusions: C4d deposition is associated with a poor prognosis in renal diseases and an accelerated deterioration of renal function. It also plays a role as a surrogate marker in diagnosis of native renal diseases.

Expression of HER2/neu in gastric adenocarcinoma and its correlation with serum HER2/neu level and E-cadherin expression.

AIM: : To assess HER2/neu expressions and correlate with E-cadherin and Serum HER2 level in gastric carcinoma. METHOD: 31 gastric biopsies and 1 resected specimen were taken in the study with patient details and stained with H and E for histopathological details following Lauren's classification. Immunohistochemistry for HER2 and E-cadherin expression was conducted followed by serum HER2/neu ELISA. RESULT: Adenocarcinoma with 61% diffuse, 29% intestinal, and 10% other type were observed with predominant HER2 immunoexpression in intestinal-type than in diffuse-type adenocarcinoma. Other observations marked 44% as 3+/positive and 56% as 2+/equivocal in intestinal type while 26% cases as 3+/positive, 69% as 2+/equivocal, and 1% as 1+/negative were observed in diffuse type. The data presented 33% membranous positivity and 67% both membranous + cytoplasmic positivity in intestinal type while 2% showed membranous positivity, 47% both membranous + cytoplasmic, and 42% only cytoplasmic positivity in diffused type. On comparing the localization pattern of HER2 and E-cadherin, 25% of cases showed membranous staining while 50% of cases showed membranous with cytoplasmic staining for both. No cytoplasmic HER2 staining as well as no any staining for E-cadherin was shown by 6% cases. CONCLUSION: Thus, it can be concluded that cytoplasmic expression of HER2 in gastric adenocarcinoma (mainly diffuse type) may be due to shedding of its extracellular domain, leading to loss of membranous E-cadherin expression on immunohistochemistry. The loss of membranous expression of E-cadherin and increased serum HER2 ELISA were correlated well with these findings.

Ectopic thyroid in left parotid gland with an orthotopic thyroid gland: A rare case scenario.

Benign ectopic thyroid tissue within the parotid gland is very rare with only one case reported till date in the world literature. We report a case of ectopic thyroid in the left parotid gland with an orthotopic thyroid in an elderly female, who was presented to us with the simultaneous onset of right-sided thyroid swelling and left parotid swelling for 6 months. Fine-needle aspiration cytology (FNAC) was done from both the swellings and a diagnosis of Hurthle cell neoplasm metastasizing to the left parotid gland was initially made. However, histopathological examination along with the immunohistochemistry (IHC) panel proved it to be an ectopic thyroid in the parotid. The case is being documented here for its rarity as well as an unusual presentation so that the readers are aware of this entity and the complete workup required to prevent diagnostic pitfalls.

Evaluation and Quantification of Cytomorphometry in Conjunction with Visual Examination and Exfoliative Cytology in Early Diagnosis of Oral Premalignant and Malignant Lesions.

INTRODUCTION: Incidence of oral epithelial dysplasia and oral squamous cell carcinoma (SCC) is very high in south Asian countries as compared to western population owing to a greater use of tobacco in these regions. While visual examination and exfoliative cytology are the most common screening and diagnostic modalities at present, it is a subjective analysis. Quantitative analyses such as nuclear size, cell size, and nuclear-to-cytoplasmic ratio may provide an accurate diagnosis and improve reproducibility. The aim of the study was to evaluate the role of morphometry as a diagnostic adjunct to exfoliative cytology and to derive a significant cutoff to identify the population at risk for development of SCC among chronic tobacco users. MATERIAL AND METHODS: This was an outpatient-based prospective study done in a tertiary hospital over a period of 2 years. Hundred and fifty cases with a history of chronic tobacco use for a minimum period of 5 years were evaluated. Visual inspection using acetic acid was done. Oral scrapes were taken for cytological and morphometric analysis followed by incision biopsy for histopathological evaluation, wherever possible. RESULTS: On morphometrical analysis, mean nuclear area and nuclear:cytoplasmic (N:C) ratio increased, while the cytoplasmic area decreased from smears with normal cytology to oral dysplasia to SCC. Analysis of variance and post hoc Tukey's honest significant difference test showed a statistically significant difference among the 3 groups (p value <0.05). A cutoff value for a significant N:C ratio was calculated as ≥0.08 using Youden's index with a sensitivity and a specificity of 88% and 94%, respectively. CONCLUSION: In high-risk cases, morphometry can be a useful adjunct to exfoliative cytology and visual examination for an early and accurate diagnosis and timely intervention in oral potentially malignant and malignant lesions, thereby improving the prognosis.

Evaluation of Role of Visual Inspection Using Acetic Acid (VIA) and Exfoliative Cytology in Screening and Early Detection of Oral Premalignant Lesions and Oral Cancer.

OBJECTIVE: Oral cancer accounts for 50-70% of total cancer mortality. VIA screening has drastically changed the morbidity and mortality related to cervical cancer. In present study, we assessed the role of 5% Acetic Acid as a vital stain in oral mucosa of chronic tobacco chewers, to know if it can help in early diagnosis and improved prognosis of oral malignancies and to assess the sensitivity and specificity of VIA and exfoliative cytology for screening of Oral premalignant and malignant lesions in high risk population with limited health care infrastructure. METHODS: This was an outpatient department based prospective study done in a tertiary hospital over a period of two years. 150 cases with a history of chronic tobacco use were evaluated. Visual inspection (VI) followed by VIA using 5% Acetic acid was done. Oral scrapes were taken for cytological examination followed by biopsy for histopathological evaluation, wherever possible. RESULTS: Sensitivity, specificity, PPV, NPV and accuracy of VIA and Exfoliative cytology was 71%, 65%, 83%, 48%, 69% and 98%, 65%, 89%, 92%, 88% respectively keeping histology as gold standard. CONCLUSION: Acetic acid along with exfoliative cytology can be used as simple, cost effective and convenient methods for mass screening of OPMDs and OSCC in high risk population where biopsy is not possible.
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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.

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.

Portal hypertensive vasculopathy - An entity worth remembering with non-neoplastic gastrointestinal lesions.

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.

Artificial intelligence technologies empowering identification of novel diagnostic molecular markers in gastric cancer.

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.

Combined pancreatic and gastric heterotopia in small intestine presenting as intussusception-A rare congenital anomaly.

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.

Serum CA 19-9 and CA 125 as a diagnostic marker in carcinoma of gallbladder.

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.

Role of Hematological Indices as a Screening Tool of Beta Thalassemia Trait in Eastern Uttar Pradesh: An Institutional Study.

A large majority of microcytic hypochromic anemia have defects in cellular hemoglobin synthesis due to either iron deficiency or thalassemia trait; both differing in management and prognosis. HPLC and serum iron profile as confirmatory tests are unavailable at health care centers. Blanket therapy of iron supplements is therefore given in all such cases which may cause iron overload in thalassemia cases. Easy to use and cost effective screening methods are desirable. The present study was undertaken to evaluate the diagnostic accuracy of twelve indices to effectively screen cases of thalassemia trait and differentiate them from iron deficiency anemia. Routine samples from the hematology lab with Hb < 13 gm/dl, MCV < 80 fl and MCH < 27 pg were screened. Taking HPLC and serum ferritin as gold standard, out of total 1353 cases, 98 cases of thalassemia trait (HbA2 > 3.5 on HPLC) and 1102 cases of iron deficiency anemia (serum ferritin < 12 g/ml) were evaluated using discrimination indices. Diagnostic accuracy for each index was calculated. While few indices showed a sensitivity of 100%, their specificity was low which meant more number of false positive cases. Based on Youden's Index, which measures the diagnostic tests ability to balance sensitivity and specificity, the best three indices in the decreasing order of their efficacy in our study were Ricerca Index (RI), Green and King Index (GKI) and Mentzer Index (MI). MI is considered a reliable index by many clinicians since a long time, however RI and GKI were found to have a better diagnostic accuracy based on our study.

Guidelines for various laboratory sections in view of COVID-19: Recommendations from the Indian Association of Pathologists and Microbiologists.

Declared as a pandemic by WHO on March 11, 2020, COVID-19 has brought about a dramatic change in the working of different laboratories across the country. Diagnostic laboratories testing different types of samples play a vital role in the treatment management. Irrespective of their size, each laboratory has to follow strict biosafety guidelines. Different sections of the laboratory receive samples that are variably infectious. Each sample needs to undergo a proper and well-designed processing system so that the personnel involved are not infected and also their close contacts. It takes a huge effort so as to limit the risk of exposure of the working staff during the collection, processing, reporting or dispatching of biohazard samples. Guidelines help in preventing the laboratory staff and healthcare workers from contracting the disease which has a known human to human route of transmission and high rate of mortality. A well-knit approach is the need of the hour to combat this fast spreading disease. We anticipate that the guidelines described in this article will be useful for continuing safe work practices by all the laboratories in the country.

Association of different patterns of expression of beta-catenin and cyclin D1 with pathogenesis of breast carcinoma.

BACKGROUND: Beta-catenin and cyclin D1 have attracted considerable attention in recent studies as potential proto-oncogenes in many human cancers especially colonic cancer. Beta-catenin plays multiple roles within the cell such as canonical Wnt signaling where cyclin D1 has been identified as one of its target genes. The role of beta-catenin and cyclin D1 in breast cancer has been evaluated in many studies but not established yet. MATERIALS AND METHODS: The expression of beta-catenin and cyclin D1 was evaluated in 82 cases of breast carcinoma (BCa) and 32 cases of ductal carcinoma in situ(DCIS) by immunohistochemistry (IHC). Their relationship with clinicopathological features was also investigated. Statistical analysis was done to establish an association. RESULTS: Abnormal expression of beta-catenin (ABE) was seen in 80.2% cases of invasive ductal carcinoma (IDC) and 47% cases of DCIS, while the cyclin D1 positive expression rate was 60.9% and 50%, respectively. In the cases showing ABE, cyclin D1 positivity was 88.1%. ABE showed significant association with high-grade BCa. The most common pattern of ABE was loss of membrane with nuclear positivity which is associated with worst prognosis. In addition, ABE in cases of BCa and DCIS showed concordant patterns. CONCLUSION: Therefore, an association exists between ABE and cyclin D1 in BCa and its precursor lesions implying that Wnt/beta-catenin oncogenic pathway may have a definite role in breast carcinogenesis and can be used for targeted therapy. Also, different patterns of beta-catenin expression may have prognostic and predictive value.