Highlights in Pathology: Gastrointestinal (GI) Pathology (January 2019)

Dr. Corwyn Rowsell, MD, FRCPC, FCAP, St. Michael's Hospital

Happy New Year!  As a new CPD initiative, I have been asked to summarize some GI literature of general interest from the past year.

I have selected the five articles below as they represent a variety of disease processes and GI sites, and address practical issues encountered by surgical pathologists.

It is by no means a ranking of which papers are best or most important - I would be delighted to hear from others which papers they would have chosen!

1. The histopathological classification, diagnosis and differential diagnosis of mucinous appendiceal neoplasms, appendiceal adenocarcinoma, and pseudomyxoma peritionei

Carr N,  et al. (2017) Histopathology 71, 847-858

Admittedly, I’m cheating a bit on this one as it is technically a December 2017 paper, but I figure it is close enough to 2018 and definitely worth a read!  

This review article is an excellent summary of the new classification of appendiceal neoplasia based on the consensus terminology adopted by the Peritoneal Surface Oncology Group International (PSOGI).  

If you are rushed for time, scanning the tables of terminology and histological features is still worthwhile.  

Here are a few of the highlights:

1. Defining histological features of low grade appendiceal mucinous neoplasms (LAMN).  
2. Introduction of the high grade appendiceal mucinous neoplasm (HAMN), which essentially has features of a LAMN but with high grade atypia.
3. Rejection of ‘adenoma’ terminology for appendiceal lesions, with the exception of colorectal-type adenomas.
4. Recommending the term ‘serrated polyp’ for serrated lesions of the appendix as opposed to colonic terminology such as ‘sessile serrated adenoma’.
5. The importance of signet ring cells as a defining feature of poorly differentiated mucinous adenocarcinoma.

There is also a summary of the new staging system, in which LAMNs are staged as pTis if they do not extend beyond muscularis propria, but are staged as pT3 if either mucin or neoplastic epithelium involves the subserosa or mesoappendix, and pT4 if mucin or neoplastic epithelium involves serosa/adjacent structures.

2. Findings in exudates can help distinguish benign gastric ulcers from ulcerated adenocarcinomas

Hissong E, Jessurun J, Yantiss R. (2018) Histopathology 73, 215-219

This paper might prompt us all to pay a little more attention to the debris we often see in biopsies of gastric ulcers.  

The authors examined 50 cases of ulcerated adenocarcinoma and 50 site-matched control cases of benign ulcer samples with respect to the contents of the debris.  

Amounts of inflammation or cellular debris were similar in both groups.

They found, however, that ulcerated adenocarcinomas were significantly more likely to be associated with non-Helicobacter bacterial colonies (76% of  ulcerated cancers vs 22% of benign ulcers). Furthermore, the finding of filamentous bacteria or fungi  in the exudate was highly specific for carcinoma (98%).  

Not surprisingly, intestinal metaplasia was more closely associated with carcinoma than benign ulcers, and the authors propose that it is the hypochlorhydria associated with atrophy and intestinal metaplasia that create a more permissive environment for diverse micro-organisms to grow.  

The bottom line – the finding of bacterial colonies in gastric ulcer debris should prompt a diligent search for evidence of malignancy on the slide, and perhaps a comment in cases where malignancy is not found, particularly in superficial or scant biopsy specimens.

3. Syphilis of the Aerodigestive Tract

Tse J, et al. (2018) Am J Surg Pathol  42, 472-478

Syphilis rates are on the rise in North America, and it is a disease that we can easily overlook if we are not alert to the histopathological patterns it may produce in extragenital sites.

Classically, we tend to think of plasma cells as a key histologic finding, but this paper describes three histologic patterns found in their evaluation of 12 cases of syphilis of the aerodigestive tract:

1. plasma-cell rich
2. lymphohistiocytic (+/- granulomata)  
3. lymphoma-like with an activated immune response and large, atypical lymphoid cells.  

The authors highlight some key differential diagnoses for each pattern (IgG4-related disease for pattern 1, fungal and mycobacterial infection for pattern 2, lymphoma for pattern 3).  

The authors also warn of the possibility of false negative silver stains (e.g. Steiner) for syphilis and recommend using immunohistochemistry.  

A word of caution (both from the paper and from my personal/institutional experience) – the Treponema antibody is not entirely specific and does cross-react with other spirochetes including Brachyspira, so serologic confirmation is still necessary even when the IHC is positive!

4. DALM, rest in peace: a pathologist’s perspective on dysplasia in the post-DALM era

Chiu K, Riddell RH, Schaeffer DF. (2018) Mod Pathol 31, 1180-1190

Are gastroenterologists and surgeons still asking you to distinguish between a DALM (dysplasia-associated lesion or mass) vs sporadic adenoma in inflammatory bowel disease patients?  

Add this useful review paper to your armamentarium!  

Challenges in histologically distinguishing sporadic adenomas from IBD-associated polypoid dysplasia as well as studies showing that polypoid IBD-associated dysplasia may be safely treated by complete endoscopic removal render the DALM concept less helpful in determining patient management.  

Also, advances in endoscopy such as high definition endoscopy and chromoendoscopy have likely rendered many previously ‘invisible’ flat dysplasia into endoscopically visible lesions.

The authors discuss the 2015 SCENIC consensus statement where DALM-related terminology was rejected in favour of descriptors based on the Paris classification.  

In a nutshell, dysplasia is divided into invisible (not seen on endoscopy; found on random mucosal biopsies) vs. visible (biopsy or endoscopic resection of a lesion seen on endoscopy).  

Visible dysplasia is further categorized as polypoid or non-polypoid, with polypoid lesions described as pedunculated or sessile, and non-polypoid lesions subdivided into superficial elevated, flat, or depressed categories.  

The paper also includes a helpful diagram showing treatment recommendations based on the type of lesion and degree of dysplasia.

5. The value of intramural venous invasion in colorectal cancer – a systematic review and meta-analysis

Knijn N, van Exsel U, de Noo M, Nagtegaal I. (2018) Histopathology 72, 721-728

We are accustomed to diligently searching for evidence of extramural venous invasion in our colorectal cancer resection specimens, but intramural venous invasion has garnered relatively little attention until recently.  

The authors of this paper have endeavoured to address the issue of the importance of IMVI via a systematic review and meta-analysis.  

They conclude that IMVI is underreported (the rate of IMVI was 17.6% in studies where slides were reviewed specifically for IMVI, vs studies that just relied on pathology reports), and that use of elastic stains results in increased detection over H&E alone.

IMVI was significantly associated with decreased cancer-specific survival, with a borderline significant effect on overall survival and local recurrence rates.  

Interestingly, the authors also concluded that there was no significant prognostic difference between EMVI and IMVI, suggesting that simply identifying venous invasion is more important than its location.