Those red spots in the gastric fundus is what remains of the more normal gastric mucosa whilst most of the surrounding mucosa is atrophic. In contrast, the antrum is unremarkable, as is the duodenum.  This is an example of a 'body predominant' gastritis and your endoscopic diagnosis should be an autoimmune gastritis!   The antral G-cells, found deep within the antral pyloric glands are pumping out huge amounts of gastric which is leading to ECL cell hyperplasia and multiple small NET's.   In fact, most patients with type I gastric carcinoids have an autoimmune gastritis!  The anaemia was due to vitamin B12 deficiency.  ​

I removed this lesion without worrying too much about the subtle 'depressed' growth pattern and the small, round crypts in the centre of the lesion.  However, I was surprised to see the pathology report of a superficially invading adenocarcinoma, with poor differentiation to boot!!!   This finding makes the advice on 'further treatment' more complex.  As you know, in both the upper and lower GI tract, the finding of 'lymphovascular invasion' (LV) is probably the most 'ominous sign' that a patient needs surgery (or chemo-radiotherapy in case of the oesophagus).  Poor differentiation is 'bad', but less bad than LVI. 

​Depth of invasion is also important and in Barrett's you are 'allowed' invasion to about 500 microns below the muscularis mucosa.  The corresponding 'safe margin' in SCC's is only 200microns.  In this case the depth of invasion was only about 100 microns, leaving 'poor differentiation' as the only 'bad sign'.  The patient wasn't a surgical candidate and refused CRT.  This was 3 years ago and so far all is well!  

By the way, the histopathologists do have a more difficult job than you perhaps imagine, measuring the depth of invasion in Barrett's cancer.  This is because they often see several bands of muscularis mucosa, so called 'duplication of the muscularis mucosa'.  Elsewhere in the GI tract, the muscularis mucosa is a single band of smooth muscle.  They measure the depth of invasion from the top of the muscularis mucosa down the the deepest point of invasion.  However, if there are several bands of muscularis mucosa, which one do you measure from?!?    Below is an example to illustrate the dilemma.  

The surface appears villous in places and gyrate in other areas. The truth is that it is a bit of both - a 'Traditional Serrated Adenoma' (TSA), first described in 1990 by Longacre and Fenoglio-Preiser (Am J Surg Pathol 1990;14:524–37). TSA's  are usually less recognisable and usually somewhat 'cerebriform' (like an exaggerated TVA).

TSAs are the least common of the three serrated colonic polyps ('hyperplastic polyps', 'sessile serrated lesions' and TSA’s) and account for only about 5% of serrated polyps and less than 1-2% of all colonic polyps and are usually found in the distal colon.

Pathologists rely on three typical findings when diagnosing TSA’s: deeply eosinophilic cells, flat top luminal serrations and numerous ectopic crypt foci (all demonstrated in the histology slide below from the Journal of Clinical Pathology 2016;69:6-11). 

Genetically, TSA's are more like adenomatous polyps harbouring low-level microsatellite instability (MSI-L) or microsatellite stable (MSS) serrated colorectal adenocarcinomas. They usually contain KRAS mutations rather than  usual BRAF mutations which you find in the 'Serrated Pathway' to CRC associated with a high-level of microsatellite instability (MSI-H).   

Nevertheless, it’s thought that these precursor lesions give rise to serrated colorectal adenocarcinomas as part of the serrated (accelerated) pathway to cancer. 

There is no distinct edge to the 'polyp' and the crypts look normal, although a little splayed out and larger than normal, reminiscent of a serrated polyp.  In real life, I had the advantage of knowing that the patient had been sent for colonoscopy because of constipation. I low-risk indication of course.

There is no distinct edge to the 'polyp' and the crypts look normal, just a little splayed out and larger than normal. This 'polyp' is actually part of the "Mucosal prolapse syndrome", first described in 1983 by Du Boulay et al [J Clin Pathol. 1983;36:1264–8].

Obviously, this syndrome includes solitary rectal ulcers, inflammatory cloacogenic polyps but also rectal 'prolapse polyps' such as this. In addition, the 'Mucosal Prolapse Syndrome' includes those prolapsing mucosal folds in the sigmoid and perhaps most surprisingly - GAVE !

In a case like the above, a couple of superficial biopsies will usually reveal the true nature of the lesion as it's easy for pathologists to spot the fibromuscular hyperplasia with overlying epithelial crypt distortion rather than dysplasia.

You may be surprised to hear that the small nodule at 3 O'clock turned out to be an IMca! It was removed endoscopically. Of course, it's the question then arises; "Should we offer RFA".  The BSG recommends this for patients with Barrett's harbouring flat dysplasia.  However, in this case there is only a tiny, tongue of Barrett's in the 6 O'clock position! Actually, we just gave this a quick blast of APC (at a fraction of the cost of RFA) and it was gone.  However, the patient remains on annual surveillance! 

GIST's are extremely rare in the oesophagus whilst common in the stomach. In contrast, leiomyomas are common in the oesophagus and rare in the stomach. However, this looks odd and the previous biopsies had not been able to get to the bottom of the diagnosis. Are we missing a SCC? However, it looks like something from deeper layers were breaking through the mucosal surface. In contrast an SCC should start growing at the surface and in time invade deeper. The 'intrapapillary capillary loops (IPCL's) dilate up, become irregular and eventually completely disorganised in SCC's. At the same time the oesophageal wall takes on a brownish tint on NBI. 

I decided to remove it and it turned out to be a leiomyoma. I presume that it had got traumatised or perhaps by pressure necrosis ended up with a funny surface. Don't think that I have seen an oesophageal NET as yet. Presumably they are very rare in this location.

By the way, I've uploaded an example of a T2 mid-oesophageal SCC in the clip below.  The lesion looks smallish but is already beyond endoscopic cure and Lugol's shows up a large area of background dysplasia which looks orange rather than brown after Lugol's dye spray. 

My initial endoscopic diagnosis was that of a TVA. However, it looked a little "exaggerated". Actually it turned out to be a "traditional serrated adenoma" (TSA).

TSA's are rare and mysterious polyps. They only accounting for about 1% of colorectal polyps and are most common in the sigmoid and rectum. Endoscopically they can appear as “exaggerated” tubulo-villous adenomas or as villous adenomas.  In the image below, I've put four examples of TSA's together to illustrate how differently these can appear ! 

It has been proposed that because one-third of "serrated cancers" are found in the distal colon and perhaps these cancers arise from TSA’s!    However, genetically, TSA's are more like adenomatous polyps harbouring low-level microsatellite instability (MSI-L). They usually contain KRAS mutations rather than the BRAF mutations which you find in the 'Sessile Serrated Lesions'.  For this reason, it's perhaps unlikely that they contribute to the 'Serrated Pathway' to cancer. 

By the way, a recent paper has highlighted that patients with TSA's are also at greater risk of 'high risk polyps', elsewhere in the colon. 

Previous surveillance samples, 3 years earlier had not revealed any dysplasia. However, that red spot shouldn't be there! A reflux ulcer is unlikely as the Barrett's is there because it protects the food pipe from acid. Of course it does this by developing crypts with Goblet cells which secretes protective mucus (of course the pathologists call this process 'metaplasia'). Early texts usually stated that ulceration is common within Barrett's. In my experience, ulceration within Barrett's only happens when dysplasia develops.  With the arrival of dysplasia, you begin to see a disappearance of the Goblet cells and of course when the Goblet cells start to dwindle, so does the protective mucus. 

In the bottom zoom image you can see that there is a distinct surface crypt pattern at the site of the red spot. Therefore the cells can't be too disorganised, making cancer unlikely. 

Actually this turned out to be a spot of LGD. I would have guessed HGD/IMca (pathologists struggle to tell the difference) if there was a visible nodule at the site of the red spot. 

Isn't it interesting that even at the very earliest stage of dysplasia, the unstable cells signal the need for more oxygen to nearby vessels? 

Lets just state something from the start! A flat elevated polyp is of course a IIa type of lesion BUT when larger than 10mm in diameter is no longer referred to as a IIa lesion.  Now, it's a 'Laterally Spreading Tumour'!  
There are 4 types as follows:

• LST-G (granular type) – usually found in the rectum or caecum and are almost always TVA’s harbouring LGD only
• LST-NG (non-granular) – can be found anywhere in the colon and are always TA’s and usually harbour HGD (which should be your guess if the crypt openings are very small) or even cancer
• LST-M (mixed type) – these are usually LST-G’s which have developed a dominant nodule. Resect the nodule first because if there is cancer, it will be found at the site of the dominant nodule
• LST-D (depressed type) – this is the least common of all the LST’s are almost always TA’s in which early cancer has developed. 

I must admit to working from the crypt pattern and ‘backwards’ when deciding on the LST subtype.  Of course this is because the LST-G are always TVA’s with a gyrate crypt pattern whilst all the others are TA’s with slit-like crypts or small round crypts, usually found in LST-D's which usually harbour at least HGD.  This is because as the degree of dysplasia increase, the crypts wither, become smaller and more angular.   

In this case the crypts are gyrate, (type IV crypts), making it a TVA. Laterally Spreading Tumours with a gyrate crypt pattern are all TVA's and almost never harbouring more than LGD.  OK but it looks depressed in the centre doesn't it?  No, it isn't depressed in the centre!  It's simply they way the large lesion has folded itself. This is something of a 'trick question' as I deliberately didn't inflate the colonic lumen fully in the first image.   When the lumen is inflated, you can see the true shape of the lesion; a LST-G ! 

A meta-analysis in 2013 by Voorham et al. [Voorham QJM. AM J Gastro 2013;108(7):1042-] concluded that pedunculated polyps were more likely to harbour KRAS mutation and APC mutations than flat lesions, and that flat lesions were more likely to harbour BRAF mutations.  Depressed lesions and LST-NG’s were particularly unlikely to contain KRAS.  

Below are some examples of LST's

In most cases, I would say 'if it lifts it will shift'.  However, in this case I wouldn't bother with a test-lift.  The reason is that the thing is growing out of the terminal ileum. You don't get adenomatous polyps growing out of the TI!  This must be something else! In fact the true lesion may be larger than the red nipple-like polyp. 

Even though there are no large 'tell-tale' vessels running up it's side, the only thing of this size, growing out of the TI, is a NET!   A lymphoma was my second guess. 

TI NET's are often bad news and should be considered for surgical resection. There is another odd thing about NET's growing in the terminal ileum.  The WHO grading system doesn't seem to relate to the aggressiveness of the lesions behaviour ! 

This was only WHO grade I (proliferation index was only 1.8%) but on a full analysis after the right hemi-colectomy, the NET was found to be a invading into the muscle propria layer and with metastatic deposits in 2 out of 12 resected lymph nodes (T2,N1) as well as ulcerated deposits of NET in the nearby pericolic fat on the serosal surface.   The moral of the story?  In the terminal ileum, 'well differentiated NET' doesn't mean that it's well behaved! 

Well perhaps the crypts look a little like serrated crypt openings but somehow the rest of the polyp doesn't look like a typical serrated lesion.  Where is the covering mucus?!   Furthermore, the polyp definitely doesn't look adenomatous or malignant! 

Actually this has arisen as part of the 'Mucosal prolapse syndrome' which is the umbrella term for entities such as; solitary rectal ulcer syndrome and inflammatory cloacogenic polyps. 

Patients are often constipated or have difficulty with defaecation with straining on the toilet or undergo the sigmoidoscopy because of tenesmus, altered bowel habits or incontinence. Surprisingly, some patients don't have any straining-related complaints! 

Most pathologists would recognise the typical mild fibrosis, thickening of the muscularis mucosae and crypt irregularity (dilated, diamond shape crypts). The surface epithelium show regenerative changes.

I must admit that I don't like the current surveillance guidelines for patients with portal hypertension.  This is a good example why!  Although the LFT's had remained stable and the patient had remained abstinent, you could argue that there are 'red signs'. Of course, the presence of 'red signs' predicts progression of varices [J Hepatol 2003;38:266–72] and because the patient is already on a β-blocker, band ligation should now be started. The truth is that 'red signs' are common and have a poor agreement value between endoscopists. 

If you decide that there are no 'red signs', and that the varices are grade I only (which depends on the degree of inflation of the oesophagus), the recommendation is to offer surveillance in 1 year. 

Finally, if you decide that the varices are now grade II (or III), variceal band ligation would be the logical next step. 

Thus, you can make an subjective argument for any of the above three treatment options. Of course, what you decide will be judged in hindsight.  If you decide that these are not red signs and the patient re-presents with a bleed in 6 months time, you could be open to criticism for missing signs of progressive liver disease. 

Surely, in the modern era of FibroScans, it's possible to predict progression of portal hypertension non-invasively!!!   Five years ago, the BAVENO VI workshop only mentioned in passing, that surveillance endoscopies may be avoided in patients with elastography values <20 kPa and a platelet counts >150,000  as these patients are at low  risk of progression.  Similarly increasing size of the spleen is another warning sign and could be looked for when these patients attend for screening for HCC's.  

​The American guidelines  suggest that there is no need to offer patients with untreated viral cirrhosis a screening endoscopy to search for varices IF elastography is <20 kPa and the platelets are >150. They concede that annual elastography and platelet counts may be less predictive in other causes of cirrhosis. However, the American guidelines advice continued surveillance if varices have been found in the past, particularly if liver injury is ongoing. 

The next Baveno conference in October 2021 will hopefully recommend non-invasive monitoring rather than endoscopy.  It would be cheaper, less arduous for patients and offer less subjective findings! 

The now rather dated BSG guidelines are summarised in the graph below. 

Sadly, an intimate knowledge of the Kudo crypt patterns doesn't help you here! Adenomatous polyps should be covered with one of the following; 

• Small round crypts of a TA+HGD
• Slit-like crypts of a TA+LGD
• Gyrate crypts of a TVA

Of course, you have the 'villous adenomas' which are covered by finger-like extensions (and no crypt openings). 

In this case, the closest match is of a serrated polyp, which have wide open crypts with a somewhat jagged outline. However, apart from the crypt openings, there is nothing on this which looks like a serrated polyp!  

If you can't see a crypt pattern, the lesion is likely to be malignant. Conversely, if the lesion does have crypts but still doesn't look familiar, its either a hamartomatous polyp or, perhaps less likely, a 'Traditional Serrated Adenoma'.  

This lesion turned out to be a hamartomatous polyp. Why a 60 year old man would grow a hamartomatous colonic polyp remains a mystery !