Molavi Chapter 8 - Colon and Appendix Flashcards
Can you diagnose tubular adenoma if the endoscopist did not see a polyp?
NO
The history and gross anatomy matters
Where should you vs should you not see Paneth cells
You should see Paneth cells in the ascending and transverse colon
You should NOT see Paneth cells in the descending colon.
Colonic tubular adenoma
Stand out at low power by looking blue.
Crypts are depleted of goblet cells and mucin and have cigar-shaped and/or pseudostratified hyperchromatic nuclei.
Dysplasia must extend all the way to the surface epithelium to qualify as an adenoma. If there are signs of maturation, it is more likely a reactive change.
“Tubular” adenoma
Smooth surface, parallel crypts, similar to the normal epithelium but with full-thickness low-grade dysplasia.
“Villous” adenoma
Covered in finger-like papillary projections
“Tubulovillous” adenoma
Has features of tubular and villous adenomas
Tubular adenoma with high grade dysplasia
Effectively equivalent to carcinoma in-situ.
Diagnosis made on the basis of architecture and cytology. Glands become cribriform, fused, or back-to-back. Cytologic features include total loss of nuclear polarity, significant pleomorphism, atypical mitoses, and large nucleoli.
Often for cases where “you are worried about carcinoma but can’t quite find any areas of invasion”
To diagnose invasive carcinoma in the colon, you must demonstrate cancer . . .
. . . crossing the basal lamina into the lamina propria
Clues to invasion include jagged interface with the lamina propria, individual infiltrating cells, desmoplastic response, and “pinking up” of the invasive cells
Invasive colonic adenocarcinoma
Note the poorly-formed glands clearly witihn the lamina propria.
Hyperplastic polyps
The surface shows a characteristic “frilly” appearance with hyperplastic mucinous epithelium. Deeper crypts how star-shaped (serrated) lumens.
Sessile serrated adenoma
Associated with the microsatellite instability cancer pathway.
Have a characteristic widening and horizontal branching at the base (“duck feet”, arrow). Epithelial cells may be more eosinophilic (less mucin) and pseudostratified than a typical hyperplastic polyp. The surface looks similar to a hyperplastic polyp though.
Clinically, these are treated as adenomas – not as hyperplastic polyps.
Inflammatory pseudopolyp
Polypoid structure consisting of granulation tissue or inflamed lamina propria with distorted crypts.
When adjacent to an ulcer, there may be significant reactive changes ressembling dysplasia – but surface maturation should still be visible.
Three pathways to adenocarcinoma in the colon
-
APC or “chromosome instability” pathway:
- APC is inactivated ⇒ KRAS and/or BRAF mutation ⇒ p53 mutation ⇒ carcinoma
-
“Microsatellite instability” pathway
- Mismatch repair mutations in areas of repeated sequences (microsatellites) ⇒ instability of microsatellite regions ⇒ carcinoma
-
CpG island methylator phenotype (CIMP) or “epigenetic instability” pathway
- Methylation of promoters of tumor suppressors or MMR genes ⇒ convergence with MSI or APC pathways ⇒ carcinoma
Colon tumor features that predict high microsatellite instability
- Arising from the right sided colon
- Mucinous, medullary, or signet-ring variants
- Prominent lymphocytic infiltrate
Medullary carcinoma of the colon
Distinct and rare variant associated with dense lymphocytic reaction, but a bland, almost neuroendocrine cytology.
When seen, medullary carcinoma suggests Lynch syndrome or a sporadic MSI-type tumor.
MSH2, MSH6, MLH1, PMS2
Mutations of the HNPCC (hereditary non-polyposis colon cancer) syndrome (specifically the Lynch syndrome subtype) family mutations. These mutations are associated with a high risk of MSI-type colon cancers (medullary, mucinous, signet ring) as well as endometrial cancer, ovarian cancer, and prostate cancer.
MSH = Mismatch Repair (involved in mismatch repair)
MLH = MutL Homolog (pairs with PMS2 to form a dimeric protein involved in regulating DNA repair response)
PMS = Postmeiotic segregation (pairs with MLH to form a dimeric protein involved in regulating DNA repair response)
The HNPCC umbrella
Well-differentiated neuroendocrine tumor (Carcinoid tumor)
The most common locations for a GI neuroendocrine tumor are the appendix and small bowel. They are often submucosal, and often present as SBO.
Well-differentiated NETs are characterized by a uniform, neuroendocrine-type cytology and trabecular, spindly, rosette-like architecture separated by ribbons of fibrovascular septa. Rarely they may appear to be pseudo-gland forming, so be doubly careful that you are not looking at a NET if you have an unusually bland and homogenous adenocarcinoma on your hands.
Low-grade appendiceal mucinous neoplasm
Tumors with bland or low-grade cytology, may extravasate mucinous epithelium (or just mucin) into the wall of the appendix all the way up to the serosa. The extent of mucin spread determines the tumor stage even in the absence of stromal invasion. May compress the lamina propria basically out of existence, as seen here.
High-grade appendiceal mucinous neoplasm
Mucinous tumors with high-grade dysplasia, but lacking usual colonic-type stromal invasion and desmoplastic response.
Like LAMN, may extravasate mucinous epithelium (or just mucin) into the wall of the appendix all the way up to the serosa. The extent of mucin spread determines the tumor stage even in the absence of stromal invasion.
Appendiceal mucinous adenocarcinoma
Note the full invasion of the stroma and fibrous, desmoplastic response.
Active colitis
Neutrophils are seen at the epithelium of the crypts (cryptitis) and there is an ulcerated surface epithelium (arrowhead).
Chronic inflammatory disease
There is loss of crypt density (atrophy), crypt distortion (1), elevation of crypts off of the muscularis mucosa (2), accompanied by a dense basal lymphocytic infiltrate and Panth cell metaplasia .
Basal plasmacytosis is the most reliable sign of chronic colon inflammation, since macrophages and lymphocytes are present in large numbers even in a health colon.
Paneth cells don’t belong in the left colon – if you see them here, they are a metaplastic response.
In a patient with known IBD and a sudden exacerbation, you may find ___ hiding within the ulcers.
In a patient with known IBD and a sudden exacerbation, you may find CMV infection hiding within the ulcers.
Crohn’s disease
Granuloma!
Ischemic colitis
Note the small, dark regenerative crypts (1), the hyalinization and fibrosis in the lamina propria (2), ulceration (3), and crypt dropout (4).
Crypt atrophy in ischemia is generally top-down, starting at the surface and appearing active and regenerative at the base.
Collagenous colitis - one of the two subtypes of microscopic colitis
There is a chronic lymphoplasmacytic infiltrate at the subepithelium and a heavy subepithelial layer of collagen. Clinically this will present as a chronic secretory diarrhea.
A trichrome stain confirms that this is indeed collagen and makes the diagnosis.
Lymphocytic colitis - one of the two subtypes of microscopic colitis
Note that there are more lymphocytes than usual in a colon (can be hard to discern) and, more importantly, there are lymphocytes within the epithelium, squeezing inbetween te epithelial cells where they do not belong.
This presents as a chronic secretory diarrhea clinically, often in young individuals.
This is the colon, and those are too big to be microvilli
This is intestinal spirochetosis, caused by Brachyspira pilosicoli
Pseudomembranous colitis
Classic. Know it.
Cryptosporidium colitis
Note that the protazoal forms are ~1/5 the size of a normal epithelial cell nucleus and how they appear to adhere to the epithelial surface.
Cystisospora colitis, aka cystisosporiasis
An infection by Cystisospora belli. This may occur in the colon, or may occur in the small intestine.
Common in tropical and subtropical areas and presents as a watery diarrhea. Acquired by ingesting contaminated food or water.
Note how the protozoa has several life cycle stages with distinct morphologies – sometimes looking like an invading epithelial lymphocyte and sometimes looking like a ring or cluster of smaller cryptosporidia within the epithelium.
Cyclospora colitis
An infection by the protazoa Cyclospora cayetanensis. Most common in the colon or proximal ileum, but can also occur in the more proximal small intestine.
Causes (sometimes explosive) watery diarrhea. Organisms enter your body when you consume contaminated food or water. Often associated with travel to developing countries or HIV/immunocompromise, but outbreaks have occurred in immunocompetent individuals as well in the case of contaminated crops.
Note the small intraepithelial inclusions that may contain between one and four organisms. These may occasionally occur in the lamina propria as well, and are much smaller than typical Cystisospora organisms.
Microsporidia colitis
An infection caused by the protazoa Enterocytozoon bieneusi and/or Encephalitozoon intestinalis.
The smallest of the pathogens that can cause protazoal colitis in an immunocompromised patient, as seen on Giemsa (H and E may not catch it). Appear as tiny grayish dots clustered within intraepithelial inclusions in the GI tract. Best visualized on Warthin Starry Silver stain.
Notably, E. bieneusi affects only enterocytes while E. inestinalis also affects MΦ, fibroblasts, and endothelial cells. This can be useful in distinguishing the two.
Comparing the four intestinal protazoa of HIV/AIDS
Adenoviral colitis
Typically occurs in immunocompromised patients, may co-exist with CMV colitis
Infects surface epithelial cells, especially goblet cells. Cowdry A bodies may be present, more rarely Cowdry B bodies too. There is usually necrotic cells, apoptotic bodies, and apoptotic dusting with a mononuclear infiltrate.
Infected epithelial cells may have eccentric nuclei with vacuolated cytoplasm, and “stick out” underneath the nice line of surface epithelial nuclei. Nuclei may have a “smudgy, glassy” appearance with a rim of darker chromatin.
On EM, there are readily aparent spherical nuclear inclusions with a regular, crystal lattice-like arrangement. (https://www.ncbi.nlm.nih.gov/pmc/articles/PMC495144/figure/F5/)
