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!

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).

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.

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

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.

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.

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.

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.

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!

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.

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.

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

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.

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!

1st Edition - 2017

This period saw an unprecedented number of review articles in GIT pathology. Hence, this inaugural edition of journal watch concentrates on these reviews.

Review Articles

Surgical Pathology Clinics

The December 2017 issue was in tightly devoted to luminal gastrointestinal tract disease. These articles are amongst the most comprehensive of any review Journal and are therefore recommended to members of the society.

I particularly enjoyed the following four articles

Diagnostic Histopathology

The December 2017 issue of this journal was devoted to gastrointestinal and hepatic pathology. The articles are well written and succinct, covering the core elements of the various subjects. The reviews on low-grade appendiceal mucinous neoplasms and vascular disorders of the liver are particularly recommended.

Advances in Anatomic Pathology

Two highly recommended articles appeared in the January 2018 addition of this journal.

Christophe’s article could be read in concert with a concurrently published clinical review on the same subject:  Hereditary Colorectal Polyposis and Cancer Syndromes: A Primer on Diagnosis and Management Am J Gastroenterol 2017; 112:1509–1525; doi: 10.1038

Virchows Archive

A series of great reviews (I am biased of course) dealing with inflammatory diseases of the luminal GIT.  


Neuroendocrine tumors of the colon and rectum. Dis Colon Rectum 2017; 60: 1018–1021.

This is a nice and brief review of the clinical staging and treatment implications for neuroendocrine tumours found in the colon and rectum. The review includes a nice algorithm predicting prognosis.

Non-review Articles

1 - Clinical Outcome of Patients with Raised Intraepithelial Lymphocytes with Normal Villous Architecture on Duodenal Biopsy. Digestion 2017;95:288–292.

This was a retrospective review of the outcome of duodenal biopsies with a pattern of intraepithelial lymphocytosis but normal villous architecture from a single centre in Dublin Ireland. 1.8% of 6244 adult patients (youngest 19 years) with a duodenal biopsy display this pattern. >25 intraepithelial lymphocytes /100 epithelial cells was used as the diagnostic threshold 65% at follow-up, with 32% of these eventually diagnosed as coeliac disease. This is higher than previous studies although given that it is unlikely that the one third of patients lost follow-up did not have coeliac disease, the true figure would appear to be closer to 20%. Factors associated with an eventual diagnosis of coeliac disease included female gender and higher intraepithelial lymphocytes count (typically>40/100 epithelial cells).

2 - 'Head Invasion’ Is Not a Metastasis-Free Condition in Pedunculated T1 Colorectal Carcinomas Based on the Precise Histopathological Assessment. Digestion 2016;94:166–175.

A paper examining the outcome of malignant colorectal polyps. The main interest is the finding of four cases of invasive malignancy confined to the head of a pedunculated polyp (Haggitt level I) that were associated with lymph node metastases. All four cases had high risk features such as poor differentiation and vascular invasion. This paper highlights a situation that the author of this overview has also witnessed several times. That is, invasion into the head of a pedunculated polyp cannot be regarded as innocuous if high risk features are present, in particular poor differentiation, tumour budding or vascular invasion.

3 - The Apoptotic Crypt Abscess- An Underappreciated Histologic Finding in Gastrointestinal Pathology. Am J Clin Pathol December 2017;148:538-544

This paper looks at causes of a relatively common, but to date not formally examined, finding in colonic biopsy specimens. Broadly apoptotic crypt abscesses were defined as “collections of at least three fragments of pleomorphic cellular debris/sloughed viable cells with crypt lumens”. Additional features are described in the paper. The distinction was drawn with neutrophil crypt abscesses which are much more frequently encountered. Common states in which this process is identified include graft vs host disease (GVHD), acute cellular rejection (ACR), autoimmune enteropathy, viral infections such as cytomegalovirus (CMV) enteritis, and injury by certain drug agents such as mofetil. The authors presented evidence that apoptotic crypt abscess is able to be separated from neutrophil crypt abscess.

4 - Lesions of All Types Exist in Colon Polyps of All Sizes. Am J Gastroenterol advance online publication, 12 December 2017; doi: 10.1038/ajg.2017.439

A retrospective review of the pathology of just over 550,000 polyps. 80% were <10mm diameter. Advanced adenoma features (villosity, high grade dysplasia or invasive carcinoma) was found in 0.6% of 1–5 mm polyps and 2.1% of 6–9 mm polyps and 13.4% of polyps ≥10 mm or larger. 25% of all the advanced adenomas were <10mm in size.

This study should prompt caution for those advocating a resect and discard approach to polyps <10mm diameter (although only 1 in 1000 of the polyps<10mm diameter harboured an invasive adenocarcinoma).

5 - Backwash Is Hogwash: The Clinical Significance of Ileitis in Ulcerative Colitis. Am J Gastroenterol 2017; 112:1211–1214; doi: 10.1038/ajg.2017.182.

A critical review of the literature by Rob Odze and colleague on ‘backwash ileitis’. The conclusions are that many of the early descriptions of patients with backwash ileitis actually had Crohn’s disease of the ileum and colon. While true ileitis in patients with UC does exist, it probably has multiple possible causes. Some of these include “drugs (particularly NSAIDs), infections, alcohol, or even bowel preparatory agents”.

The authors propose the term “UC-associated ileitis” be used instead.