Microsatellite instability in young patients with mucinous colorectal cancers – characterization using molecular testing, immunohistochemistry, and histological features

CONTEXT: The incidence of colorectal cancers (CRCs) in young Indian patients is higher than the international average. CRCs in young patients are commonly of mucinous type and show microsatellite instability (MSI). AIMS: To ascertain the MSI status of mucinous CRCs in patients ≤40 years of age by molecular testing and to correlate this with immunohistochemical (IHC) analysis and tumor histology. SUBJECTS AND METHODS: Archived formalin-fixed paraffin embedded tissue blocks of 30 young mucinous CRC patients were retrieved. MSI testing was done using two mononucleotide markers – BAT26 and NR24. IHC analysis was done using MLH1, MSH2, and MSH6. Histological features of all cases were studied. Data were analyzed using the SPSS software and the Pearson's chi-square test and Fisher's exact test. RESULTS: Eight out of 30 cases (26.7%) showed MSI by molecular testing. IHC identified seven of these cases. Histological features showing a statistically significant association with MSI were the presence of a well-differentiated adenocarcinoma component (P = 0.003), peritumoral lymphocytes (P = 0.002) and tumor budding (P = 0.021). CONCLUSION: The detection of defective mismatch repair (MMR) proteins using IHC for MLH1, MSH2, and MSH6 and molecular testing using BAT26 and NR24 appears to be a good protocol to detect CRCs with MSI. Histology could be useful in identifying cases that require screening for presence of MMR protein defects

Concerns with regard to an article

We have read with interest and concern the article titled “Consultations on human infection studies in India: Do people’s voices really count” by Sandhya Srinivasan and Veena Johari. The article expresses the opinions of 2 persons who have not visited CMC, nor have spoken to anyone concerned, to ascertain the authenticity of the information published or with regard to the purported research in CMC

The differentiation of amebic colitis from inflammatory bowel disease on endoscopic mucosal biopsies.

Background: Intestinal amebiasis is one of the important differential diagnoses of Inflammatory Bowel Disorders in areas where it is highly prevalent. Aim: Studies comparing the clinical, endoscopic and histological features of these disorders have never been done, so we undertook this study. Materials and Methods: A retrospective study comparing mucosal biopsies of 14 consecutive cases of intestinal amebiasis with 14 cases of Ulcerative colitis and 12 cases of Crohn’s disease. A total of 65 biopsies from patients with amebiasis, 56 biopsies from patients with Crohn’s disease and 65 biopsies of patients with Ulcerative colitis were reviewed. Results and Conclusions: Discrete small ulcers less than 2 cm in diameter in the cecum or rectosigmoid, with intervening normal mucosa, were the most common finding on endoscopy in patients with amebiasis. On histology, necrotic material admixed with mucin, proteinaceous exudate and blood clot lining ulcers, significant surface epithelial changes such as shortening and tufting adjacent to sites of ulceration, mild chronic inflammation extending into the deep mucosa and mild architectural alteration were features of amebiasis. Trophozoite forms of ameba were seen in the necrotic material lining sites of ulceration or lying separately, as well as over intact mucosa. Necrotic material lining ulcers was less common in IBD, but chronic inflammation, crypt abscess formation and architectural alteration were more severe.

Survey of ethical issues reported by Indian medical students: basis for design of a new curriculum.

Education in ethics is now a formal part of the undergraduate medical curriculum. However, most courses are structured around principles and case studies more appropriate to western countries. The cultures and practices of countries like India differ from those of western countries. It is, therefore, essential that our teaching should address the issues which are the most relevant to our setting. An anonymised, questionnaire-based, cross-sectional survey of medical students was carried out to get a picture of the ethical problems faced by students in India. The data were categorised into issues related to professional behaviour and ethical dilemmas. Unprofessional behaviour was among the issues reported as a matter of concern by a majority of the medical students. The survey highlights the need to design the curriculum in a way that reflects the structure of medical education in India, where patients are not always considered socio-culturally equal by students or the medical staff. This perspective must underpin any further efforts to address education in ethics in India.

Adherent Escherichia coli in colorectal mucosal biopsies: A histological and ultrastructural evaluation.

Background: Colorectal mucosal biopsies occasionally demonstrate the presence of bacteria adherent to the epithelium. This study evaluated the histological and ultrastructural correlates of such bacterial adherence. Materials and Methods: Rectal mucosal biopsies from eight patients in whom histopathological examination of biopsies had earlier demonstrated adherent bacteria were examined by electron microscopy and by bacterial culture. Colorectal biopsies of 69 patients with adherent bacteria detected histologically were retrospectively evaluated for histological changes at sites proximal and distant to adherent bacteria. Results: Escherichia coli of different serogroups were isolated from 7 of 8 rectal biopsies demonstrating bacterial adherence. All isolates showed diffuse or focal adherence to HEp-2 cell monolayers. Ultrastructural changes noted included microvillus damage, pedestal formation, actin web condensation, and protrusions of the apical cytoplasm of epithelial cells into the lumen towards the bacteria. Histological changes noted at light microscopy included reduction in epithelial cell height, focal epithelial cell degeneration, cryptitis and neutrophil infiltration at sites of bacterial adherence whereas these were usually absent at sites distant to adherent bacteria. Bacterial adherence was noted more often in biopsies from Crohn's disease patients than in patients without this diagnosis (P < 0.001). Conclusion: Adherent Escherichia coli in colorectal biopsies were associated with focal epithelial damage and showed an association with Crohn's disease.

Microvillous Inclusion Disease Diagnosed by Gastric Biopsy.

Protracted diarrhea in neonates is uncommon and usually requires an intestinal biopsy for etiological diagnosis. Gastric biopsy has not been used in the routine diagnosis of this condition. We report the first documented patient with microvillous inclusion disease from India, where the diagnosis was established by a gastric biopsy.

Environmental factors associated with Crohn’s disease in India.

Background The frequency of diagnosis of Crohn’s disease (CD) in India is increasing. This case-control study was designed to detect associations of environmental and dietary factors with the diagnosis of CD. Methods In 200 consecutive patients with CD and 200 control subjects without gastrointestinal disease, environmental hygiene exposures in childhood and in the past one year, and dietary preferences were recorded using a questionnaire. Univariate and multivariate analyses were done. Results In univariate analysis, CD showed positive association with urban residence (at birth and current), availability of protected drinking water (childhood and current), availability of piped water in the house (childhood and current), and strict vegetarian dietary habit, and negative association with regular fish consumption and presence of cattle in the house compound. Multivariate analysis showed that regular fish consumption (OR 0.52, 95% CI 0.33–0.80, p=0.003), and presence of cattle in the house compound currently (OR 0.57, 95% CI 0.35–0.92, p=0.023) were significant protective associations, whereas use of safe drinking water was positively associated (OR 1.59, 95% CI 1.02–2.47, p=0.042) with the disease. Conclusion Occurrence of CD was associated with dietary and environmental exposures, which indicate that diet and hygiene may influence the development of this disease.

Gastrointestinal lymphomas: Pattern of distribution and histological subtypes: 10 years experience in a tertiary centre in South India.

Background and Aim: Gastrointestinal tract (GIT) is one of the major sites of extra-nodal lymphomas constituting 10-15% of all non-Hodgkin's lymphoma cases and about 30-40% of extra-nodal lymphomas. Considerable variation exists in the literature with respect to incidence of the various histological subtypes and sites of involvement. This study was undertaken to ascertain the anatomic distribution, histological subtypes and sites of all GIT lymphomas presenting to a tertiary referral hospital in southern India. Materials and Methods: The histological material of 361 patients over a period of 10 years (2001-2010), with histopathological diagnosis of lymphoma involving the GIT (both primary and secondary), was analyzed retrospectively. All lymphomas were reclassified according to the World Health Organization 2008 classification. Results: These 361 cases include 336 primary and 25 cases of lymphomas, where the involvement was secondary. Primary lymphomas consisted of 267 males (79.64%) and 68 females (20.24%) with a male:female ratio of 3.93:1. The mean age was 45 years (range 3-88). Diffuse large B-cell lymphoma (DLBCL) was the commonest subtype (222 cases; 66.71%), followed by low-grade marginal zone lymphoma of the mucosa associated lymphoid tissue (MALT) type (34 cases; 10.12%) and Burkitt's lymphoma (35 cases; 10.48%). The commonest site was stomach (180 cases; 53.57%), followed by small intestine (79 cases; 23.51%) and large intestine (68 cases; 20.23%), respectively. There were some uncommon types of GIT lymphomas documented during the study. Conclusion: In this largest retrospective single centre study from India, we establish that the pattern of distribution of primary GIT lymphomas (PGLs) in India is similar to the western literature in that the stomach is the commonest site of PGL and DLBCL is the commonest histological subtype. Immunoproliferative small intestinal disease cases were seen in this study, which is uncommon in the west.

Clofazimine induced enteropathy--a case highlighting the importance of drug induced disease in differential diagnosis.

A patient on treatment for multibacillary leprosy for the past three years, presented with episodes of abdominal pain. Since the patient improved with conservative management, clofazimine induced enteropathy was considered as a remote possibility. A review of the mucosal biopsies showed macrophages with crystal-storing spaces consistent with clofazimine deposition in the duodenum. This case highlights the need to consider and investigate drug-induced disease as part of the differential diagnosis.