Rajkumar Vajpeyi

International study group on rectal cancer regression grading : interobserver variability with commonly used regression grading systems

The aim of this study was to ascertain the level of concordance among gastrointestinal pathologists for regression grading in rectal cancers treated with neoadjuvant chemoradiation. Seventeen gastrointestinal pathologists participated using the Mandard, Dworak, and modified rectal cancer regression grading systems to grade 10 representative slides that were selected from 10 cases of rectal cancer treated with long-course neoadjuvant chemoradiation. The slides were scanned with a whole-slide scanner generating dynamic digitized images. The results showed very little concordance across the 3 grading systems, with κ values of 0.28, 0.35, and 0.38 for the Mandard, Dworak, and modified rectal cancer regression grading systems, respectively. In only 1 of 10 study cases was there unanimous grading concordance using the modified rectal cancer regression grading system. It was felt that these systems lacked precision and clarity for reproducible, accurate regression grading. The study concluded that there was a need for a simple, reproducible regression grading system with clear criteria, a cumulative or composite score taking into account all sections of the tumor bed that is sampled rather than the worst section (highest grade), and there should be a uniform method of sampling of these specimens.

Hernia sacs: is histological examination necessary?

The hernia sac is a common surgical pathology specimen which can occasionally yield unexpected diagnoses. The College of American Pathologists recommends microscopic examination of abdominal hernias, but leaves submission of inguinal hernias for histology to the discretion of the pathologist. To validate this approach at a tertiary care centre, we retrospectively reviewed 1426 hernia sacs derived from inguinal, femoral and abdominal wall hernias. The majority of pathologies noted were known to the clinician, including herniated bowel, lipomas and omentum. A malignancy was noted in three of 800 inguinal hernias and seven of 576 abdominal wall hernias; five of these lesions were not seen on gross examination. Other interesting findings in hernia sacs included appendices, endometriosis, a perivascular epithelioid cell tumour, and pseudomyxoma peritoneii. All hernia sacs should be examined grossly as most pathologies are grossly visible. The decision to submit inguinal hernias for histology may be left to the discretion of the pathologist, but abdominal and femoral hernias should be submitted for histology.

A multi-centre pathologist survey on pathological processing and regression grading of colorectal cancer resection specimens treated by neoadjuvant chemoradiation

To ascertain the approach and degree of consensus of pathologists in the handling and regression grading of colorectal cancer resection specimens treated with neoadjuvant chemoradiation, a ten-part questionnaire was circulated to 18 gastrointestinal pathologists in eight countries. The questions were specific and addressed pertinent issues related to colorectal cancer with neoadjuvant chemoradiation. There is a lack of consensus on how to handle the specimen, number of sections taken, correlation with pre- and post-operative radiological imaging, and especially, regression grading schema employed. Consensus in the form of guidelines is required so that the pathological assessment of these specimens will provide clinically relevant information for patient management, irrespective of location.

Psammomatous melanotic schwannoma presenting as colonic polyps.

Psammomatous melanotic schwannoma is an uncommon neoplasm that usually occurs in the setting of Carney’s complex. They can occur in the gastrointestinal tract with preferential location in the stomach. A 43-year-old female presented with two colonic polyps at routine endoscopy. The patient was asymptomatic and did not have features of Carney’s complex. Both polyps were composed of melanin-containing epithelioid and spindle cells with several psammoma bodies. There was no evidence of cytological atypia or necrosis. The tumor was diffusely positive for S-100, and focally for HMB-45 and melan-A. The differential diagnosis includes melanoma, GIST, pigmented neuroendocrine tumor, and epithelioid leiomyoma. The lack of malignant features separates this lesion from melanoma while the immunophenotype of the other lesions is characteristic.

Gastric Biopsies: The Gap between Evidence-Based Medicine and Daily Practice in the Management of Gastric Helicobacter pylori Infection

BACKGROUND Many consider histology to be the gold standard for Helicobacter pylori detection. Because the number and distribution of H pylori organisms vary, particularly in patients taking proton pump inhibitors (PPIs), the American Gastroenterological Association recommends discontinuing PPIs two weeks before endoscopy, and taking biopsies from both the body and antrum. OBJECTIVE To assess the influence of clinical practice on the histopathological detection of H pylori infection. METHODS Electronic patient records were evaluated for the sites of gastric sampling and PPI use at endoscopy. One hundred fifty cases with biopsies taken from both antrum and body were randomly selected for pathological re-review with special stains. The gastric regions sampled, H pylori distribution and influence of clinical factors on pathological interpretation were assessed. RESULTS Between 2005 and 2010, 10,268 biopsies were taken to detect H pylori. Only one region was sampled in 60% of patients (antrum 47%, body 13%). Re-review of biopsies taken from both antrum and body indicated that the correct regions were sampled in only 85 (57%) patients. Of these, 54 were H pylori positive and 96 were H pylori negative. H pylori was present in the antrum in only 15% of the patients and body only in 21%. Of 96 H pylori-negative patients, two were reinterpreted as positive. Forty-seven per cent of patients were taking PPIs at endoscopy, contributing to both false-negative and false-positive diagnoses. CONCLUSION Despite national and international guidelines for managing H pylori infection, the American Gastroenterological Association guidelines are infrequently adhered to, with PPIs frequently contributing to false diagnosis; sampling one region only increases the likelihood of missing active infection by at least 15%.

Pathological grading of regression: an International Study Group perspective

In this issue of the Journal of Clinical Pathology , MacGregor, Maughan and Sharma1 discuss the value and utility of pathological grading of regression from an oncologists point of view. Neoadjuvant chemoradiotherapy is now a well-accepted treatment for locally advanced rectal cancer (cT3/T4 or lymph node-positive rectal cancers). However, neoadjuvant therapy affects the histopathological reporting of resected specimens by virtue of the host response to treatment, which occurs in the majority of patients. Pathological complete responses ranging from 9% to 29% have been reported,2 ,3 but the clinical significance of ‘incomplete’ regression and, more importantly, its role in determining postoperative treatment, is not clear. Pathological complete response has been associated with good patient outcomes.4–7 However, tumour regression grade (although having prognostic value for survival and recurrence by univariate analyses) has not been established to be an independent prognostic value that is superior to ypTNM in predicting clinical outcome.6 ,7–13 On the contrary, Min et al 11 demonstrated that regression grading is a good prognostic factor in patients with lymph node negative locally advanced rectal cancer. Therefore, regression grading may be a useful parameter for monitoring patient response and also as a potential prognostic factor. Several grading systems have been proposed and used, the most popular one being the Mandard and Dworak systems.14 ,15. We, an ‘International …

Primary cystic peritoneal masses and mimickers: spectrum of diseases with pathologic correlation

AbstractCystic lesions within the peritoneum have been classified classically according to their lining on histology into four categories—endothelial, epithelial, mesothelial, and others (germ cell tumors, sex cord gonadal stromal tumors, cystic mesenchymal tumors, fibrous wall tumors, and infectious cystic peritoneal lesions). In this article, we will proceed to classify cystic peritoneal lesions focusing on the degree of radiological complexity into three categories—simple cystic, mildly complex, and cystic with solid component lesions. Many intra-abdominal collections within the peritoneal cavity such as abscess, seroma, biloma, urinoma, or lymphocele may mimic primary peritoneal cystic masses and need to be differentiated. Clinical history and imaging features may help differentiate intra-abdominal collections from primary peritoneal masses. Lymphangiomas are benign multilocular cystic masses that can virtually occur in any location within the abdomen and insinuate between structures. Ultrasound may help differentiate enteric duplication cysts from other mesenteric and omental cysts in the abdomen. Double-layered wall along the mesenteric side of bowel may suggest its diagnosis in the proper clinical setting. Characteristic imaging features of hydatid cysts are internal daughter cysts, floating membranes and matrix, peripheral calcifications, and collagenous pericyst. Non-pancreatic psuedocysts usually have a fibrotic thick wall and chylous content may lead to a fat-fluid level. Pseudomyxoma peritonei appears as loculated fluid collections in the peritoneal cavity, omentum, and mesentery and may scallop visceral surfaces. Many of the primary cystic peritoneal masses have specific imaging features which can help in accurate diagnosis and management of these entities. Knowledge of the imaging spectrum of cystic peritoneal masses is necessary to distinguish from other potential cystic abdominal mimicker masses.

Vasculopathic Changes, a Somatostatin-Producing Neuroendocrine Carcinoma and a Jejunal Gastrointestinal Stromal Tumor in a Patient with Type 1 Neurofibromatosis

A 36-year-old male with neurofibromatosis type 1 (NF-1) presented with symptoms of obstructive jaundice. Imaging showed a periampullary mass, which on endoscopic retrograde cholangiopancreatography biopsy proved to be a somatostatinoma. A Whipple’s procedure was performed and a somatostatinoma of the duodenum was confirmed. In addition, the patient had a gastrointestinal stromal tumor (GIST) of the jejunum with accompanying hyperplasia of interstitial cells of Cajal. The somatostatinoma was histologically characteristic with pseudoglandular and solid patterns together with psammoma bodies and lymphovascular invasion. The GIST did not display mutations in c-kit or platelet-derived growth factor receptor genes. The novel finding in this case was the presence of several vessels in the submucosa and muscularis propria of the duodenum displaying prominent intimal hyperplasia and in keeping with so-called neurofibromatosis-associated vasculopathy. These abnormal vessels were within and close to the somatostatinoma only and were not found away from the tumor. It is thought that the vasculopathy is related to NF-1 with abnormal neurofibromin possibly playing a role.

The first report of a previously undescribed EBV-negative NK-cell lymphoma of the GI tract presenting as chronic diarrhoea with eosinophilia

A 74-year-old man presented with a 2-month history of watery diarrhoea. His complete blood count showed lymphopaenia and marked eosinophilia. Investigations for common infectious causes including Clostridium difficile toxin, stool culture, ova and parasites were negative. Endoscopy revealed extensive colitis and a CT of the abdomen identified numerous large abdominal lymph nodes suspicious for lymphoma. Multiple tissue samples were obtained; colon, mesenteric lymph node and bone marrow biopsy, as well as pleural fluid from a rapidly developing effusion, confirmed the presence of metastatic lymphoma with an immunophenotype most consistent with an aggressive variant of Epstein-Barr virus (EBV)-negative natural killer (NK)-cell lymphoma. The patients clinical condition rapidly deteriorated and he died shortly following diagnosis. To the best of our knowledge, this is the first case report of a primary gastrointestinal EBV-negative NK-cell lymphoma, and its clinical presentation highlights the importance of a broad differential in the management of chronic diarrhoea.

Regression grading in neoadjuvant treated pancreatic cancer: an interobserver study

Aim Several regression grading systems have been proposed for neoadjuvant chemoradiation-treated pancreatic ductal adenocarcinoma (PDAC). This study aimed to examine the utility, reproducibility and level of concordance of three most frequently used grading systems. Methods Four gastrointestinal pathologists used the College of American Pathologists (CAP), Evans, MD Anderson Cancer Centre (MDA) regression grading systems to grade 14 selected cases (7–20 slides from each case) of neoadjuvant chemoradiation-treated PDAC. A postscoring discussion with each pathologist was conducted. The results were entered into a standardised data collection form and statistical analyses were performed. Results There was little concordance across the three systems. The Kendall coefficient of concordance agreement scores were: CAP: 2-poor, 2-fair; Evans: 1-fair, 1-moderate, 2-good; MDA: 1-poor, 2-moderate, 1-good. Interpretation in all three grades in the CAP grading system was a source of discrepancy. Furthermore, using fibrosis as a criterion to assess regression was contentious. In the Evans system, quantifying tumour destruction using arbitrary percentage cut-offs (ie, 9% vs 10%; 50% vs 51%, etc) was imprecise and subjective. Although the MDA system generated greatest concordance, this was due to ‘oversimplification’ surrounding wide, arbitrarily assigned thresholds of 5% of tumour. Conclusions All systems lacked precision and clarity for accurate regression grading. Presently the clinical utility and impact of histological regression grading in patient management is questionable. There is a need to re-evaluate regression grading in the pancreas and establish a reproducible, clinically relevant grading system.