Pedunculated
Sessile

An All-inclusive Classification of Colonic Polyps
1. Developmental a. Juvenile b. Hamartomatous (Peutz-Jeghers)
2. Inflammatory “pseudo-”
3. Neoplastic a. Adenoma b. Carcinoma
4. The Serrated bunch including hyperplastic polyp
5. Recently named: transitional mucosal, fibroblastic
6. Mixed, hybrid, unclassifiable, pimples, etc.
7. Normal mucosa

A lot of the information for this discussion comes from the WHO
2010 book

Developmental Polyps
1. Juvenile
2. Peutz-Jeghers

Smooth, eroded surface
Lots of pink lamina propria
Cystic crypts

Expanded, inflamed lamina propria and crypt distortion: cystic, branched

Eosinophils are common

Normal or regenerative epithelium

Juvenile Polyps

Class: Hamartoma



Excess cellular lamina propria
Hardly any muscularis mucosae: a few branching fibers at the base
Distortion: budding, cystic tubules

(crypts or pits)
Distribution:
> small intestine & stomach

What are the minimal criteria for diagnosing the smallest juvenile polyp?
In fact, there are no diagnostic criteria for juvenile polyps of any size. Every definition is a description that seems to assume that we all know what juvenile polyps look like and how to diagnose them.

How do juvenile polyps develop?
The best place to look for the smallest changes is in the flat mucosa between the polyps in a colon from a patient with juvenile polyposis

Distorted crypts
Expanded lamina propria

1
Progressively larger polyps in Juvenile polyposis:
Even the smallest polyps have excess lamina propria and crypt distortion
3
2

Juvenile Polyposis
Definition: WHO (2010)
A familial cancer syndrome … autosomal dominant …characterized by multiple juvenile polyps of the GI tract, predominantly the colorectum , but also stomach, duodenum, biliary tree and pancreas.
(total cancer risk may be around 80%)

Juvenile Polyposis
Diagnostic criteria: WHO (2010)
1. More than 3-5 juvenile polyps of the colorectum or
2. Juvenile polyps throughout the GI tract or
3. Any number of juvenile polyps with a family history of JP
4. Other syndromes involving hamartomatous GI polyps should be ruled out clinically or by pathological examination (PJ, Cowden’s)

Some polyps are atypical lobulated or branched
Classic JP Atypical JP

Genetics of Juvenile Polyposis
Classic JP
Atypical JP
50-60% of JPS patients have mutations of SMAD4 or BMPR1A.
In the rest of the patients, the genetic changes are not known.

One JPS patient, 2 different types of polyps:
Typical juvenile polyp
Not sure of the genetic defect but may be
SMAD4 mutation
Dysplastic branched polyp

Developmental Polyps
1. Juvenile
2. Peutz-Jeghers

The Peutz-Jeghers Syndrome
Definition WHO (2010)
An inherited cancer syndrome (autosomal dominant) characterized by mucocutaneous melanin pigmentation and hamartomatous gastrointestinal polyposis , which preferentially affects the SI.
… extra-intestinal neoplasms …. include tumors of the ovary, uterine cervix, testis, pancreas, breast.

Mucocutaneous pigmentation

PJS Diagnostic Criteria (WHO, 2010)
1. 3 or more histologically confirmed PJ polyps, or
2. any number of PJ polyps with a family history of PJS, or
3. characteristic prominent mucocutaneous pigmentation with a family history of PJS, or
4. any number of PJ polyps and characteristic prominent mucocutaneous pigmentation

Peutz-Jeghers Polyps
 Class: Hamartoma
 Branched muscularis mucosae
 redundant, distorted mucosa
 normal or regenerative epithelium
 Genetics: mutation of LKB1/STK11 on 19p in the syndrome

> stomach and colon

The Peutz-Jeghers Syndrome
Definition WHO (2010)
An inherited cancer syndrome (autosomal dominant) characterized by mucocutaneous melanin pigmentation and hamartomatous gastrointestinal polyposis , which preferentially affects the SI
There are no specific written minimal criteria for diagnosing these hamartomatous polyps.

Peutz-Jeghers Syndrome
Cancer risk in LKB1/STK11 mutation carriers
All cancers:
63% by age 60
GI & Panc carcinomas:
42% by age 60
Lim, et al, Gastroenterol. 126:1788, 2004

A core of branching muscularis mucosae

Branching muscularis mucosae

The mucosa covering this branching muscle may be close to normal

Gastric P-J polyps usually have little branching smooth muscle, and they are composed mainly of cystic pits with hardly any glands.

Gastric polyp from a patient with the Peutz-
Jeghers syndrome

Colonic P-J polyps are not well characterized.
Some may have a muscle core covered by distorted mucosa

Colonic polyp from a patient with the Peutz-
Jeghers syndrome

Do sporadic PJ polyps exist?
Study from Hopkins: 3 patients with solitary typical SI polyps had clinical features suggesting the syndrome, but they didn’t meet the diagnostic requirements for the syndrome. However, 2 of 3 developed cancers like typical PJ syndrome patients.
So, if sporadic PJ polyps exist, they do not do so at Hopkins. I have never seen a case either.
Burkart, et al. Am J Surg Pathol. 31:1209, 2007

Multiple polyposis syndromes all have a high cancer risk, most of which is colorectal, but other GI and non-GI cancers also occur
Juvenile polyposis
Peutz-Jeghers syndrome
Familial adenomatous polyposis
Lynch Syndrome (Hereditary nonpolyposis colorectal carcinoma)
Serrated (hyperplastic) polyposis

Polypoid prolapsed diverticulosisassociated mucosal fold
(Kelly polyp)
The next slide is one of these

Thick distorted mucosa with prolapse changes

An endoscopic polyp composed of transitional mucosa: a transitional mucosal polyp

Not all GI polyps have names some are hybrids some don’t fit some are pimples some have obscure literature
These will make you crazy!
No polyp should take more than
30 seconds to be classified

Branching muscularis mucosae (like a P-J polyp) covered by redundant serrated mucosa (like a HP)

These have no name!
Polyps due to excess lamina propria

Colonic polyp with excess lamina propria and a coarse villous or nodular surface and striking crypt distortion
This one has no name!

If we can’t name things like this in 30 seconds, we make up a harmless name, most recently:

Or B U M P

Maybe 5-10% of endoscopic polyps contain histologically normal mucosa on the first cuts.

If we serial section them or turn the block around and start cutting from the back side, some of them will turn out to be something like…….

Normal
Start with normal mucosa. Many serial cuts later, a small hyperplastic polyp appears
Hyperplastic polyp

Normal
Adenoma
Start with normal mucosa. Many serial cuts later, a small adenoma appears

Dx: normal or no significant abnormality.
What made the polyp?
Who knows.
Most often,when we recut it, nothing changes.
It is still normal.

When we see normal mucosa in a biopsy of an endoscopic polyp, we do not do anything additional, and we just call it normal.
Our GI colleagues recognize that this happens, and they have neve disputed our interpretation in such cases.