Peutz-Jeghers

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Polyp
A protrusion
from a surface
Polyps
of the
Gut
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:

colon> small intestine & stomach
What are the minimal criteria for
diagnosing the smallest juvenile polyp?
There are none!
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
2
1
Progressively larger polyps
in Juvenile polyposis:
Even the smallest polyps
have excess lamina propria
and crypt distortion
3
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 (P-J, 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
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


SI
> 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 typical small
intestinal PeutzJeghers polyp
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 PeutzJeghers
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 PeutzJeghers
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)
Polyps due
to excess
lamina
propria
These have
no name!
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 BUMP
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…….
Start with normal
mucosa. Many
serial cuts later, a
small hyperplastic
polyp appears
Normal
Hyperplastic polyp
Start with normal
mucosa. Many
serial cuts later, a
small adenoma
appears
Normal
Adenoma
Most often,when
we recut it,
nothing changes.
It is still normal.
Dx: normal or no
significant
abnormality.
What made the
polyp?
Who knows.
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.
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