2nd Edition – 2018

I picked up some articles that I found useful when I had a difficulty or while preparing for a talk. I have given my own thoughts but also provided abstracts in some. They are numbered but the order does not reflect any particular order of importance. I have focused on the articles published during April and June 2018 as suggested. Enjoy!

1 -Features of Adult Autoimmune Enteropathy Compared With Refractory Celiac Disease. Clinical Gastroenterology and Hepatology 2018;16:877–883

A problem that we seem to encounter, infrequently though are biopsies of patients with clinic-pathological features that raise the possibility of Adult Autoimmune Enteropathy. I found the recent article in Clinical Gastroenterology and Hepatology by Sharma et al quite useful. The microscopic comparison with refractory coeliac disease is quite nice!

In a retrospective study of 30 patients with AIE, followed for a median 28 months, they found this disease to have distinct demographic, clinical, and histologic characteristics compared to refractory celiac disease type 1. Most patients with AIE (85%) have a clinical response to budesonide, all of whom were unsuccessfully treated with conventional therapies.

 

 

 

On histologic analysis, there was no significant difference in degree of villous atrophy in intestinal tissues from patients with AIE vs controls (P [ .68). However, a greater proportion of patients with RCD had increased intraepithelial lymphocytes (>40 per 100 epithelial cells in 100%) compared with patients with AIE (in 50%) (P [ .003).

2 – Inflammatory and infectious manifestations of immunodeficiency in the gastrointestinal tract. Modern Pathology. Volume 31, pages844–861 (2018).

A somewhat related theme in Modern Pathology by Nicole Panarelli and Rhonda Yantis cover some useful information on infectious manifestations of immunodeficiency in the gastrointestinal tract. This review discusses the gastrointestinal manifestations of primary and acquired immunodeficiency, chemotherapy-related injury, and infections that show a predilection for immunocompromised patients. Key histologic features and relevant differential diagnoses are emphasized.

3 – Tumor budding as a standardized parameter in gastrointestinal carcinomas: more than just the colon. Modern Pathology. Volume 31, pages862–872 (2018).

A good summary of various studies on tumour budding in the gastrointestinal tractas a whole is presented in this article.

4 – Hepatotoxicity of immune checkpoint inhibitors: a histology study of seven cases in comparison with autoimmune hepatitis and idiosyncratic drug-induced liver injury. Modern Pathology. Volume 31, pages965–973 (2018)

A very useful article as we have started to witness the tsunami of gastrointestinal pathology resulting from immune checkpoint inhibitors! Liver biopsies of patients treated withimmune checkpoint inhibitors are seen by many of us in the setting of high incidence of Melanoma in Australia and New Zealand. Histologically, all biopsies showed predominantly lobular hepatitis with milder portal inflammation. Centrilobular confluent necrosis and plasmacytosis were observed in a single case, and were markedly less common and milder than those in autoimmune hepatitis (p = 0.017 and p < 0.001, respectively). Bile duct injury, micro-abscesses, and extramedullary hematopoiesis were also found in one case each.

They confirm that liver injury caused by cancer immunotherapy shares some features with injury of autoimmune hepatitis although there are obvious differences between the two conditions.

5 – Mutational landscape of goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids of the appendix is distinct from typical carcinoids and colorectal adenocarcinomas. Modern Pathology Volume 31, pages 989–996 (2018) and;

6 – Appendiceal goblet cell carcinoids and adenocarcinomas ex-goblet cell carcinoid is genetically distinct from primary colorectal-type adenocarcinoma of the appendix. Modern Pathology volume31, pages 829–839 (2018)

The interest in “goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids” of the appendixis continuing. Our colleagues from Boston together with our own Masato (President, AGPS 2018) assert that the overlapping molecular alterations suggest that goblet cell carcinoids and adenocarcinoma ex goblet cell carcinoids are best considered as two grades of differentiation of the same tumour rather than two distinct histological types.Two articles on “goblet cell carcinoids” and “adenocarcinoma ex goblet cell carcinoids” describe the molecular alterations that support the notion. The unique mutational profile also explains the poor chemosensitivity in these tumours and highlights the need for developing new targeted therapies. The German study suggests that appendiceal goblet cell carcinoids and adenocarcinomas ex-goblet cell carcinoid constitute a morpho molecular entity, histologically and genetically distinct from appendiceal colorectal-type adenocarcinomas and its colorectal counterparts. Altered Wnt-signaling associated genes, apart from APC, may act as potential drivers of these neoplasms. The absence of KRAS/NRAS mutations might render some of these tumours eligible for anti-EGFR directed therapy regimens.
These two articles are good reads as we all await the NEW WHO 2018 terminology and classification of gastrointestinal neuroendocrine tumours to be published.

7 – Intramucosal lipomas of the colon implicate Cowden syndrome. Mod Pathol 2018 Apr 1;31(4):643-651. Epub 2017 Dec 1.

We often do not think of the implications of a gastrointestinal lipoma. The finding by Bronner and her colleagues provide evidence that intramucosal lipomas are important harbingers of Cowden syndrome. The intramucosal lipoma was the index diagnostic lesion in some of the cases of Cowden syndrome in the series. On the other hand, that two-thirds of intramucosal lipomas are sporadic.

8 – Identification of clinically relevant cytomegalovirus infections in patients. Modern Pathology volume31, pages527–538 (2018).

Evidence of the presence of CMV infection in endoscopic biopsies brings in the challenging issue of distinguishing clinically relevant infection from other. This study demonstrates a viral load threshold, predictive for clinical relevance concerning antiviral therapy response and they assert that immunohistochemistry is insufficient to reliably identify antiviral therapy responders. This is interesting and should be discussed with our clinical colleagues.

9 – Comparison of dysplastic fundic gland polyps in patients with and without familial adenomatous polyposis. Histopathology. 2018 Jun;72(7):1172-1179.

A large series of dysplastic fundic gland polyps has confirmed some useful findings. Identification of recurrent dysplastic fundic gland polyps in younger age group should alert to the possibility of syndromic polyps. The also conclude FAP and non-syndromic patients developed non-gastric cancers at similar rates, and even suggested that d-FGPs may portend a general increased risk of carcinogenesis in non-syndromic patients!

10- Prognostic value of pathological lymph node status and primary tumour regression grading following neoadjuvant chemotherapy – results from the MRC OE02 oesophageal cancer trial. Histopathology. 2018 Jun;72(7):1180-1188. doi: 10.1111/his.13491. Epub 2018 Mar 25.

Interestingly, lymph node status in resectable oesophageal cancers treated with Neoadjuvant chemotherapy irrespective of tumour regression grade (TRG) was found to be the most important prognostic factor. We must try even harder to find those ‘hard to find’ nodes. TRG is less important according to them.

11 – Improved diagnostic stratification of digitised Barrett’s oesophagus biopsies by p53 immunohistochemical staining. Histopathology 2018, 72, 1015–1023.

A Dutch group has shown improvement of grading of Barrett’s oesophagus biopsies by using ofp53 immunohistochemistry. This is a much discussed issue with no clear international consensus, although the British Society of Gastroenterology (BSG) recommends the use of p53. Talking to GI pathologists, it appears that everyone would use p53 when they want some help! This article provides scientific evidence for this practice.This is a good read.

12 – Gastric pyloric gland adenoma: a multicentre clinicopathological study of 67 cases. Histopathology. 2018 May;72(6):1007-1014.

A large series of Gastric pyloric gland adenomas has been studied by an international group including our own Australian GI pathologists and international colleagues. This is a very good evaluation of clinicopathological and immunohistochemical characteristics. They conclude that the risk of HGD increases with the size of PGA, tubulovillous architecture and the presence of AIG as well as mixed immunophenotype. As the overall local recurrence rate is less than 10%, PGAs may be treated conservatively, but they should be excised completely if possible, particularly if they are large or show high-grade features.

13 – Colorectal Carcinomas With Isolated Loss of PMS2 Staining by Immunohistochemistry . Arch Pathol Lab Med. 2018;142:523–528

Isolated loss of PMS 2 staining is an uncommon finding in colorectal carcinoma. It is rare, seen approximately 4% of MSI tumours. Wendy Frankel and her team is of the opinion that unusual clinicopathologic features observed in colorectal carcinomas with isolated PMS2 loss are likely related to the high proportion of cases caused by germline mutations. Isolated PMS2-loss tumours may demonstrate more aggressive behaviour than other tumours with microsatellite instability. A multi institutional large study may be required to investigate this assertion further.

14 – Update on Fecal Microbiota Transplantation in Patients With Inflammatory Bowel Disease. Gastroenterol Hepatol (N Y). 2018 May; 14(5): 319–322.

Faecal transplantation for patients in inflammatory bowel disease is something old but new. The article in gastroenterology and hepatology is very interesting! We do not know whether this will alter mucosal pathology!