Most 'laterally spreading TVA's are of course LST-G's.  However, this doesn't have the usual cobblestoned appearance of a 'laterally spreading tumour of the granular type'.  It's rather 'chunky' in fact. That's because its harbouring HGD!  A rare beast indeed as almost all laterally spreading TVA's only harbour LGD. 

​You've seen a few examples now of the 'mucosal prolapsing conditions' which include solitary rectal ulcer syndrome and inflammatory cloacogenic polyps. First described in 1985 [GIE 1985;31:196–9] they are usually said to be rare. However, experienced endoscopists know that these are common in the sigmoid.  I've never seen a mucosal prolapse polyp outside of the sigmoid and would actually not make this diagnosis elsewhere in the colon. 

Histology is usually said to be the way to "confirm the diagnosis and rule out cancer".  However, for me it's an endoscopic diagnosis.  But I do understand that these lesions do look alarming. For this reason, I sometimes take it upon myself to resect the tip of the lesion, proving to all those of little faith, that the lesion is absolutely innocent. 

However, I'm not sure that my surgical colleauges are always reassured by the histology which usually rambles on about 'distorted elongated branched crypts, with fibromuscular obliteration of lamina propria with lots of intramucosal haemorrhages and a splayed and hypertrophied muscularis mucosae". However, the bottom line of that pathology report will read; 'No dysplasia'.  

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. 

Must admit that I didn't like the look of this polyp. Sure, it does have an organised crypt pattern. I think that I can see short slits, making it a TA. This would fit with the fact that it probably is a LST-NG type of lesion (which are always TA's). 

However, it also looks, 'chunky' and it's the 'thickness' of the lesion which made me suspicious. For this reason I was not surprised to find the non-lifting sign. As there is no lifting what-so-ever, I suspect that the lesion will turn out to be T2 at least. 

Actually, the red bit of the polyp was composed of a tubulovillous adenoma and the rest was a serrated polyp!  In other words, a mixed serrated/adenomatous polyp.  Clearly the famous "three pathways to colorectal cancer": the APC mutation pathway (50%-70%); the mutator “Lynch syndrome” route (3%-5%); and the serrated pathway (30%-35%) can sometime get mixed up !!!

​I couldn't stop myself!  After yesterday's case of a rectal 'prolapse polyp, part of the 'Mucosal Prolapse Syndrome', I had to show an example of a sigmoid mucosal 'traction polyp' (my nomenclature). The mucosa at the apex of this sigmoid fold is traumatised and inflamed but not actually adenomatous!  Histologically these lesions also appear somewhat bashed up. This is where pathologists may see 'pseudo-invasion' which is actually movement of crypts due to trauma and inflammation. 

The sigmoid colon is the most 'powerful' part of the colon developing the force needed to go to the toilet. Presumably this is the reason that diverticular disease first develop in the sigmoid. The force can also create these pseudo-polyps from patches of inflammation which I presume gets tugged along with each peristaltic wave.  The end result is that this is the most difficult part of the colon to make head an tail of polyps.  

These are common lesions and if you are a 'therapeutic endoscopist', you will be refer these lesions.   In these cases, I don't go overboard by placing a snare far down the 'pseudo-stalk'.  If you did, you will find that it's taking a long time to cut through all that healthy sigmoid mucosal fold and you run the risk of a perforation (early or late).

Instead, I just catch the tip of the fold and ask my assistant to close the snare as quickly as possible. Of course, you don't need to worry about a type of chunky central vessel which you may find in an adenomatous polyp.  Analysis of a small piece of mucosal apex confirmed a normal mucosa. Hopefully this was enough for everyone to relax ... 

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 call this a "flat elevated lesion with a central depression (IIa+IIc lesion) or simply a depressed lesion (IIc lesion). Frankly it doesn't matter because both a part of the same 'family' of evil little b.....ds.

They are always TA's and the small, round crypts (Kudo type IIIs crypt pattern) tells you that the lesion harbours HGD. This is because as dysplasia progresses from low to high grade, crypts get smaller and more withered. Of course they eventually disappear altogether as the lesion develops into a cancer which no longer follows any 'instructions' to form organised crypts. 

However, the crypt pattern is still discernible in the centre AND the lesion lifts well. Both of these tells you that the lesion is likely to still be benign. 

Ultimately, the pathologists called it a TA+HGD. However, there was mucinous differentiation in the centre of the lesion. Could these little shits be the early stage of mucinous colonic cancers?  Quite likely!    Imagine how easily they are missed when hiding behind a fold or below a shallow puddle !!!

​This is a LST-NG type of lesion (laterally spreading tumour of the non-granular type). They are always TA's (tubular adenomas) and often (but usually not), harbour HGD or cancer. I guess that we can't really be sure about the crypt pattern as this is a non-magnified image. However, looking at the histology slide with narrow crypts, I expect that the crypt pattern is probably IIIs (small round crypts) which goes with TA+HGD. Must admit that I was surprised to find invasive cancer and LVI (lymphovascular invasion) in a small lesion such as this! The last image shows clusters of malignant cells within lymphatics. Of all the 'markers' to suggest that the patient needs surgery, LVI is the most important!

Actually, this patient had collagenous colitis! I suspect that the acute injury are linear tears in the mucosa which then granulate as in the images above. Finally, you are left with linear scars as in the image below. Pure speculation but seems logical ! 

At colonoscopy, the mucosa is often unremarkable but there may also be mild, patchy erythema or linear cracks. Histology reveals the typical thickening of the subepithelial collagen layer from the normal 3-6 μm to more than 10 μm as well as lymphocytic infiltration of the epithelium and the lamina propria. 

Rectal biopsies are not sufficient to make the diagnosis as normally the collagen layer is particularly thin here.  Samples from the rectum and sigmoid confirms the diagnosis is more than 90% of cases. 

Interestingly, patients with eosinophilic oesophagitis may also develop some fibrosis in the lamina propria which also 'cracks' in a spectacular way when a dilatation is carried out.

Endoscopically it can be difficult to recognise a villous adenoma. Unless you submerge the lesion to see the villi rise up like the arms of a sea anemone.  Apparently, they are quite difficult to 'process' by the pathology lab as well. They are fragile and those beautiful villi, easily become damaged. 

Of course, villous adenomas are regarded as 'high risk lesions'.  The other high risk findings often used as surrogate markers for cancer in guidelines are: having 3 or more adenomas, polyps 10mm or larger, and polyps harbouring high-grade dysplasia.  

However, if you have to make a choice of the two strongest predictors of future cancer risk, a study in Gastroenterology found that it would be;  finding a polyp 2cm or larger and resecting a polyp found to harbour HGD [Gastroenterology 2019;158(4);875-83]. 

The polyp looks very suspicious but did seem to lift and I therefore decided to go ahead and removed it using a stiff, large snare.  It took a little longer than expected for the snare to cut through. Of course, the mucosal defect should be blue. In this case it's yellow!  The polyp was malignant, invading about 1mm into the submucosa and you are looking at the 'desmoplastic' reaction generated by the cancer.   

Apart from the sometimes deceptive 'non-lifting sign', there are two further signs that a lesion may be malignant. First, it may look smaller and smaller as you inject below the lesion (see example below).  Another sign is that your blue sub-mucosal injection appears to lift the lesion until you retrovert and have a look at the other side. If you then find that it hasn't actually 'crossed the mid-line', there is fibrosis below the lesion preventing the fluid to disperse evenly. 

I was not entirely surprised to learn that the patient declined surgery. After all, he was 86 years old!  He lived another 7 years and never developed any sign of bowel cancer. 

By the way, there is a theoretical risk of tumour seeding if the lesion is perforated during resection. However, when the perforation is done with a red-hot tool such as a knife or snare, the risk of seeding is surprisingly low. I have perforated a handful of cancers but have never had a case of late disseminated peritoneal disease. My Japanese colleagues (off the record), agree that the risk is there (some have seen it) but is low. 

If you decide to sample a suspicious looking polyp, you shouldn't use the same forceps to sample another lesion.  This is because if cancer cells become lodged in the biopsy forceps, which are then used to sample another location and them become stuck in the biopsy, the histopathologist will diagnose cancer in TWO locations when in fact, there is only a single cancer.

Some would say; "if you can remove the lesion in that colitic colon, then 'do it'!  The problem is that nothing may appear "irresectable" giving plenty of time, determination and poor judgement. 

Many studies looking at outcomes of polypectomy in UC, excluded polyps >1-2cm or flat polyps.  Other studies have included polyps arising outside of the colitic field or only have a short follow up period of a few years.

Actually, most are coming to believe that when dysplasia develops in the colitic colon, it's not a 'random' case of bad luck. It can be the result of a long process of progressive DNA damage!  At some stage we will be able to have a look at the state of the stem cell DNA in patients with conditions such as Barrett's, Colitis and atrophic gastritis.  I think that we are in for a surprise !

In addition, did you spot the small focus of invasive cancer in the 2-3 O'clock position?  Surprisingly, this was only T1 disease!

Did you spot that cancer has developed on the right side of this tubular adenoma (TA). On the left side, the crypts are slit-like whilst on the right hand side, the crypt pattern has been destroyed (Kudo type V crypt pattern). The Haggitt stage was I and I took particular care in removing the polyp with a large margin. The cancer was only 4mm in diameter. Perhaps the smallest adenocarcinoma of the colon you will ever see ?

The first EMR was piecemeal and histology could of course not confirm that the resection had been complete. Indeed the 'index histology' reads oddly mentioning "frequent mitotic figures" and "back to back glands". To a gastroenterologist these words does not sound particularly alarming. 

However, the pathologist was trying to say "this looks like cancer but I can't actually make that diagnosis" !!!  Indeed this doesn't look like a normal EMR scar! The whole area is indurated as if there is an infiltrative process below the mucosa. Histology was reassuring mentioning some distorted crypts only. 

Sadly, the endoscopist was content with the reassuring repeat histology and did not reflect on the worrying endoscopic appearances. He did NOT organise a second round of post-EMR samples and the patient returned 2 years later with an advanced cancer. 

The take home messages from this sad story? 

1. Always make an endoscopic diagnosis! 
   This does NOT look like a normal scar and therefore you don't histology at face value.  If the histology does not tally with your endoscopic diagnosis, then you stick with your endoscopic diagnosis and act accordingly. In the above case, the patient should at least have had more samples urgently obtained with or without staging CT's.
2. Give the pathologists your endoscopic diagnosis!
   In the above case, if I had seen the scar, I would have written; "At least intramucosal cancer removed 6 month ago and now the EMR site appears indurated and infiltrated presumably by a malignant process. Eight Jumbo samples taken for confirmation" 
   
   As you know Western pathologists are not 'allowed' to make a diagnosis of intramucosal cancer in the colorectum.  it's not a recognised diagnosis in the colorectum according to the Vienna classification.  Naturally,  a UK pathologists would NEVER make that diagnosis.  But as I'm not a pathologists, I don't feel that I have to adhere to the Vienna classification (which I think should be updated) ! 

The head of the lesion is clearly of concern.  There are 'horns' on it!   Of course, the devil has horns but as it was arising from a stumpy stalk. I went ahead and removed it. Somewhat surprising our pathologists called the lesion TA+HGD! 

Admittedly, there was disagreement between our histopathologists and 2 out of 5 believed that it was an invasive cancer. Endoscopically, the lesion is clearly malignant and at the very least it's an intramucosal cancer (IMca).  Of course, our UK histopathologists are unable to make the diagnosis of Intramucosal cancer in the colorectum because this is not a diagnosis recognised by the 'Vienna classification'.  Elsewhere in the GI tract, intramucosal cancer is  a diagnosis which our pathologists are 'free' to make.  It makes no sense whatsoever to me ! 

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. 

These peculiar things are post-inflammatory polyps found in a patient with quiescent colitis. They are an endoscopic diagnosis and taking a sample will only reveal 'normal colonic mucosa'.  In patients with more 'recent' inflammation, the polyps appear more red as in the example below! 

​In this case, an image tells the story of a thousand words. A single zap in the centre made the whole thing go away!  

Actually, this isn't a case of haemorrhoids or an anal fissure. Histology reported; " Within hyperkeratotic epidermis there are scattered individual highly atypical infiltrating malignant cells with frequent apoptosis and moderate clear cytoplasm.  There is no ulceration or significant inflammation."  

Actually, this is a case of Perianal Paget's disease, - a VERY rare condition!!!   You'll remember that a 'puckering' of the skin around the breast areola is associated with underlying breast cancer. This was first reported by Sir James Paget in 1874.  However, a few years later, the same phenomenon was described elsewhere, so called "extramammary Paget's disease".  In descending order of frequency, this has been described at; the skin of the vulva, perineal skin, perianal skin and the skin of the scrotum.  

Paget's disease, is usually NOT a primary cancer of the apocrine glands of the skin. It's almost always secondary to a nearby cancer of the rectum, anus or prostate.  In this particular case, further imaging revealed a nearby prostate cancer! ! 

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

The learning point of this video clip is the EMR defect; it's white (image A) !!!  Perhaps the picture below explains it better. Normally my EMR defects are blue (because I mix indigo carmine dye into the submucosal mix). In 'image B' below, the white arrow in the second image shows you what a 'healthy EMR defect should look like. IF you cut too deep, you can see the white, linear fibres of the muscle propria layer (red arrow). Of course this is a warning sign that you MUST carefully close the defect with lots of clips. Actually, next to the tip of the red arrow you can see a black 'micro-perforation' where the full thickness of the muscle layer has been breeched. Naturally, this is were your first clips goes! 

Anyway, the mucosal defect in the video clip is just - white, without any linear muscle fibres. This is fibrosis! I have seen fibrosis like this below large sigmoid polyps which have been yanked about with the forceful sigmoid peristalsis. However, the more usual reason for this appearance is that you are looking at the fibrous tissue below a cancer, called 'desmoplasia'.  

Consequently, if I see a fibrous tissue in the base of the lesion I would do the following: 
Place clips (because I always do)
Fast-track the histology
Organise an MRI 
Request staging CT (chest+abdomen+pelvis)

The ultimate diagnosis?  Histology confirmed that the polyp was malignant and the imaging (of course requested at the time of the resection), confirmed a T2, N1 carcinoma. A week later, we had a full diagnosis.  Unfortunately, the patient turns out not to be a surgical candidate.   There is rarely unbridled joy after the endoscopic removal of a CRC ... 

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.