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ESOPHAGUS AND STOMACH DISEASES - Coggle Diagram
ESOPHAGUS AND STOMACH DISEASES
normal histology of the GI
lamina propria
muscularis mucosae
submucosa
tunica muscularis
(circular and longitudinal)
adventitia
changes in the mucosa are due to different functions of the tract
when there is cancer, it is important to define which layer is affected by the tumor
ESOPHAGUS
mucosa: similar to the one of the oral cavity; consisting of non-keratinized stratified squamous epithelium, looking pink, thin, bright and translucent
muscularis mucosa: quite thin
submucosa: containing lymphatic vessels
(possible entry point for cancer)
STOMACH
mucosa: orange, translucent, rough
in the cardias, the mucosa is rich in mucus and WBCs (stained with Alcian blue)
the antral mucosa is similar to the cardias'
in the fundus and body, the mucosa is quite pink
different cells with different functions
muciparous cells --> producing mucin and bicarbonate
mucopeptic cells --> producing mucus and pepsinogen; located in the neck
parietal cells --> producing HCl
chief cells --> producing pepsinogen and gastric lipase
neuroendocrine cells --> producing gastrin
esophageal diseases
VARIX
located in lower and median ⅓ of the esophagus
they can bleed
typical patient: cirrhosis with portal hypertension
CONGENITAL ANOMALIES
interruption of the continuity of the esophagus
ATRESIA
type A: only the upper part is present
type B: both upper and lower parts are present, the middle portion is instead missing
FISTULA
quite serious: food may go to the lungs
(--> pneumonia)
when there is the connection of the lower part of the esophagus with the trachea, there may be the reflux of HCl from the stomach
EA/TEF is common in some aneuploidy syndromes (trisomy 21, trisomy18, trisomy 13, trisomy X)
CONTRACTILE DYSFUNCTIONS
ACHALASIA
it causes dysphagia
absence of peristalsis of the esophagus
failure to release the LES in response to swallowing
etiology is not clear
maybe chronic infection/aberrant autoimmune response causing ganglionitis or loss of neurons, in the end interfering with the normal activity of the enteric plexus
DIVERTICULA
"FALSE": they only involve mucosa and submucosa
types:
Zenker's esophageal pharyngeal diverticulum
alterations of the peristalsis
common in old patients
found in areas of weakness
mandatory surgical intervention
signs:
regurgitation
halitosis
hoarse voice
persistent cough
alteration of peristalsis causes outpouching of the posterior pharyngeal wall, just above the upper esophageal sphincter
longitudinal muscle originates as two bands from cricoid cartilage that incompletely difitate and leaves a bare V-shaped region (area of Laimer), that exposes the underlying circular muscle and creates areas of weakness
epiphrenic and
peribronchial diverticulum
traction due to secondary fibrosis
caused by mediastinal inflammation (LN TBC) and by diffuse esophageal spasm
SCHATZKI RING
hypertrophy of the muscular component of the esophagus wall, slighttly above the cardia
caused by GERD
no specific surgery to correct this alteration
MALLORY WEISS SYNDROME
uaually caused by severe vomiting due to alcoholism, bulimia or food poisoning
typical sign: hematemesis
signs: lacerations of the mucosa (longitudinal, due to increase of pressure at the junction between the stomach and the esophagus)
ESOPHAGITIS
frequently due to Candida infections, typical of immunocompromised pts;
in elderly, dissection of the mucosa may happen due to pill intake with little water
eosinophilic esophagitis
clinical presentation different on the basis of the pt's age:
feeding difficulty, nausea, vomiting and heartburn are typical of children
dysphagia and food impaction episodes are found in adults
chronic reflux symptom is a common finding
rare, but most common diagnosis in children
cause
allergen-mediated disease, in which eosinophils are recruited
aeroallergens, food, environmental factors
consequence: stricture formation with proximal dilation and longitudinal shearing
at endoscopy: rings
histology
thin and polylobulated nuclei in the mucosa (eosinophilic cells)
it is important to count cells:
at least 15 HPF must be present
characteristic, but not pathognomonic
basal hyperplasia, lamina propria fibrosis
reflux esophagitis
(GERD)
inflammation of the esophageal mucosa secondary to GERD
NERD: non-erosive disease
--> no erosions on endoscopy
ERD: erosive reflux disease
--> symptoms + erosions
causes of GERD:
transient imperfect relaxation of the LES after meals
hiatal hernia
obesity
age
pregnancy
hiatal hernia
sliding in 95% of cases: the fundic part goes up through the mediastinum
paraesophageal: rolling of part of the stomach, which goes in the mediastinum, parallel to the esophagus
at biopsy
bleeding (red areas, in the place of pink)
sclerotic areas due to previous ulceration
orange colour of the mucosa ( = stomach)
for the diagnosis:
thickness of the basal cell layer
(cells are not compact)
increased length of papillae
(they should be flat)
intraepithelial inflammation
(eosinophils, lymphocytes, granulocytes)
intracellular edema (spongiosis)
longstanding and untreated patients develop peptic strictures, chronic inflammation and Barrett metaplasia
ulceration of the mucosa
glandular epithelium development
pink-to-orange mucosa transformation
BARRETT'S ESOPHAGUS
condition in which a metaplastic intestinal type columnar/glandular mucosa replaces the squamous esophageal mucosa damaged by GERD
it confers predisposition to cancer
F:M = 3:1; 55 y
orange mucosa at endoscopy (no longer squamous epithelium (pink)
types
short segment BE
more sensitive to acid exposure for a short duration; <3 cm above the cardiac sphincter
long segment BE
mucosa goes up to the esophageal mucosa >3 cm; long duration of reflux, present both in standing and supine positions
diagnosis
histology
the pathologist has to identify which gland is present
columnar epithelium of the intestine, with high risk of transformation
gastric fundus and cardias have no risk and low risk of transformation respectively
specialized columnar epithelium, characterized by acid mucin-containing goblet cells (INTESTINAL METAPLASIA)
specific staining: Alcian blue; important to be capable of staining goblet cells (in blue)
endoscopy
visualization of columnar lined epithelium arising circumferentially at least 1 cm above the GEJ, with intestinal metaplasia on histological investigation of biopsies
also useful for surveillange through systematic biopsies, necessary to exclude the presence of dysplasia
pathologist pathway
presence of intestinal metaplasia
presence of dysplasia
in the cas of dysplastic metaplasia, it is important to look at the location of dysplasia and at the mitosis
normally, mitosis occurs in the crypt of the glands, but in the case of dysplastic metaplasia it is SUPERFICIAL
risk of transformation into adenocarcinoma
low in BE without dysplasia
10% in BE with low-grade dysplasia
40% in BE with high-grade dysplasia
dysplasia grades
low-grade
no large architectural alterations
mitoses in depth of crypts
high-grade
large architectural alterations
mitoses in higher part of crypts
association with TP53 mutation
(protein hyperexpression)
pathogenesis
of metaplasia
due to pluripotent cells at the base of the esophagus: during reflux esophagitis, the esophagus undergoes ulceration
pluripotent cells change because of possible mutations of TP53
clonal transformation: cells become similar to the ones of glandular intestine
SQUAMOUS CARCINOMA
the most common cancer in the GI, in particular in Eastern regions
causes
smoking (7x)
diet (low intake of fruits and vegetables
nitrosamines and precursors (metabolic action of bacteria and fungi
alcohol (nutritional deficiencies or direct action as a promoter
--> 40x when combined with smoking)
smoking and chewing opium residues
Plummer-Vinson syndrome (iron deficiency anemia, genetic factors and nutritional deficiencies)
sites
where there is bifurcation of the vessels, that may be due to narrowing of the mucosa of the esophagus
1/3 median 50%
1/3 lower 30%
1/3 upper 20% (F>>M)
diagnosis
endoscopic biopsy
mass screening in China
(cytology and XR)
at endoscopy, dishomogeneous lesions are observed: flat areas, bright and thicker than the normal one
MULTIPLE BIOPSIES ARE RECOMMENDED
(mucosectomy, to prevent purulent mediastinitis)
it is important to say whether the cells are poorly- or well- differentiated
well-differentiated tumors are reproducing the cornea pearl structures
staging
T1: lamina propria and submucosa
T2: muscular tunica
T3: adventitia
T4: adjacent structures
precursor
intraepithelial esophageal neoplasm
chronic inflammation together with DNA damages (TP53 mutations) may lead to an intraepithelial neoplasia delimited into the lamina propria
dysplastic cells + parakeratotic cells
high mitosis
intact lamina propria
dysplasia grade
low-grade
thickening of the basal layer, atypical cells
high-grade
the cancer may pass through the mucosa and become true infiltrating cancer
the treatment for both Barrett's esophagus and Invasive squamous carcinoma is based on neoadjuvant chemotherapy and radiation therapy
(2/10: complete regression)
surgery is generally performed after CT and RT
diffusion contiguity
purulent mediastinitis
fistulas in the bronchi, trachea, aorta
pericardial-heart infiltration
vertebrae, pleura
lymph vessels --> mediastinal lymph nodes
macroscopic appearance
plaque --> erosion, mucosal thickening --> annular infiltration or vegetation
polypoid appearance 60%
ulcerated 25%
infiltrating / stenosing 15%
ESOPHAGEAL TUMORS
benign
PAPILLOMA: warty surface, inferior thirs, fibrovascular axis with typical epithelium
LEYOMYOMAS (most frequent) / NEURINOMAS or NEUROFIBROMAS
LEIOMYOMATOSIS: terminal esophagus with muscle hyperplasia
malignant
rare: MUCOEPIDERMOID, ADENOSQUAMOUS, UNDIFFERENTIATED, LEIOMYOSARCOMA, GIST
frequent: SQUAMOUS CARCINOMA (90%) and ADENOCARCINOMA (10% - increasing)
gastric diseases
CONGENITAL ANOMALIES: congenital pyloric stenosis; white, M:F = 4:1; vomiting in th e3rd week of life; micro: increase in thickness of smooth muscle layer of pyloric sphincter
FOREIGN BODY: bezoar hairs of plant fibers administered for therapies
INVAGINATION: rare, from pedunculated tumor dragging the wall
VOLVULUS: rare, transverse or longitudinal
GASTRITIS
frequent
epigastric pain
at least 30 biopsies are needed
ACUTE
etiology
cortison
NSAIDs
aspirin
histology
infoammatiion within the crypts of the cells
edema
congestion
foveolar hyperplasia with aboundant mucus
CHRONIC
etiology
(not very clear)
infectious
autoimmune
drug
eosinophilic
granulomatous
OLGA classification
atrophy score at the level of the antrum and of the corpus
basic principles for diagnosis
topography
five biopsies are taken from different locations
three biopsies from region A (antrum and lower third of the body)
two biopsies from region B (upper half of the body and fundus)
in the case of H. Pylori infection, the chronic inflammation starts in the antrum and then it may move to the body and fundus, leading to complete atrophy of the mucosa
in the case of AI gastritis, it starts from the fundus and in the upper part of the body (atrophy is only in the upper part)
etiology
in the suspect for H- Pylori infection,
use Giemsa staining
micro-organism of 3-4 microns, located on the surface of the epithelium or in the foveoles;
this bacterium lives in an acidic environment, therefore it is usually absent in glands eith intestinal metaplasia
in the case of H. Pylori infection, therapy is based on long-term antibiotics, PPIs and a new biopsy after 6 months
urea breath test can be used to get the diagnosis
H. Pylori infection may affect children and, if not recognized, it may lead to lymphoma and carcinoma
morphology
elementary lesions
there are lymphocytes (small numbers, usually) and granulocytes (possibly associated with H. Pylori
look at the atrophy of glands
(both at the body and at the antrum)
in normal conditions they are quite close, while in case of atrophy they start disappearing
atrophy refers to the disappearance of glands, which are replaced by sclerosis and fibrosis or intestinal metaplasia
fibrotic expansion of the lamina propria, resulting in a reduced glandular mass with no change in the native glandular phenotype
AUTOIMMUNE METAPLASTIC ATROPHIC GASTRITIS (AMAG)
caused by the presence of anti-parietal cells antibodies (--> hypochloridria)
the cells producing gastrin increase their activity --> hypergastrinemia and atrophy
mainly affecting the fundic and gastric body
other etiologies: drugs, XR, granulomatous diseases, eosinophilia
the damage of these cells also induce deficiency of intrinsic factor and vitamin B12, leading to pernicious anemia
hypergastrinemia causes a reduction in the number of glands, but an increase in their size
PSEUDOATROPHY
of parietal glands
G cells start becoming more hypertrophic
increased production of histamina
hyperplasia of enterochromaffin cells
development of neuroendocrine tumors
at biopsy
alterations and intestinal metaplasia
on the crypts, bluish cells stained with chromogranin A
gastric mucosa atrophy
loss of specialized functions of the chief cells oxyntic mucosa
decrease of acid production by the parietal cells
loss of inhibition of feedback on gastrin producing ECL
antral G cell hyperplasia
hypergastrinemia and iincreased gastric secretion, in turn leading to parietal cell pseudo-hypertrophy
ECL cells increase histamin production, resulting in global ECL cell hyperplasia --> NE tumor
two types of G cell hyperplasia
(both happening when PPIs are taken for a too long period of time)
linear
nodular
it may lead to an endocrine tumor,
e.g. endocrine carcinoma
HYPERPLASTIC GASTRITIS
aka MENETRIER DISEASE
probably due to excessive TGFalpha with increased EGFR signalling
gastric folds are hypertrophic
M:F = 3:1
average age: 30-50
children: uncommon
chronic and severe
often pt affected by CMV and peripheral eosinophilia
peripheral edema due to loss of proteins
low HCl production even after stimulation
macroscopically and radiologically similar to Zollinger Ellison syndrome
GASTRIC ULCERS
STRESS ULCERS
small ulcers are found in the fundus of the stomach
they can be asymptomatic or cause a severe hemorrhagic ulcer
causes
mechanical ventilation for >48h
anti-inflammatory drugs
stress
hypotension
sepsis
liver failure
stress-related
PEPTIC ULCERS
lesions of the gastric / duodenal mucosa (acid-peptic action of gastric juice)
disruption of the balance between organic defenses and aggressive agents
association with renal failure and hyperPTH
forms
acute form
causes
trauma, surgery, sepsis, burns, intracranial injuries, Zollinger-Ellison syndrome
etiology
possibly, prostaglandin inhibition with reduced mucosal blood flow
chronic form
clinically, recurrent course
histologically, sclerotic lesions
etiology
hyperacidity, hypergastrinemia, smoking, alcohol, diet, drugs, H. Pylori
macro
continuous round/oval solution with raised and sclerotic edges and debris bottom
evolution:
40% healing, but never restitutio ad integrum (flat whitish scar)
complications:
stenosis
perforation
hemorrhage
diagnosis
(by looking at all 4 layers)
loss of mucosa with necrotic debris
layer of inflammation
new vessels
scar and fibrosis (granulation tissue and fibrotic layer)
duodenal mucosa is more frequently involved than the stomach mucosa and it shows the same features
DD with cancer ulcerating the mucosa
in peptic ulcers, the edges are thick and roundish / oval, while in cancer, edges are stellate
ZOLLINGER-ELLISON SYNDROME
rare, 1% of pt with PU
numerous PUs in the stomach/duodenum/ intestine, typically rsistant to therapy
GERD and chronic diarrhea
caused by gastrin-secreting tumor (GASTRINOMA, possibly associated with MEN1)
frequently localized in the pancreas (90%), duodenum (7%) and other sites, resulting in the increased stimulation of acid-secreting cells of the stomach
GASTRIC TUMORS
benign
epithelial and connective tissues involvement
(both can have polypous appearance)
polyps found in 2-6% of gastroscopies
HAMARTOMATOUS POLYPS
(Peutz-Jegher syndrome)
autosomal dominant disease (STKII/LKBI mutation, related to TGFbeta pathway)
usually, in children or adolescents
M=F
rarely, associated with dysplasia and rare-onset of carcinomas
mucocutaneous pigmentation (black spots), multiple polyps of the GI, more frequent in the small intestine, 20% in the stomach
HYPERPLASTIC /REGENERATIVE POLYPS
90% of all polyps
elongated foveole
hyperplast + edema
ADENOMAS
(rare)
LEYOMYOMAS, NEURINOMAS, NEUROFIBROMAS, GISTs
malignant
CARCINOMA
(95%)
gastric carcinoma is an ADENOCARCINOMA
decreasing; M>F (2:1)
geographical distribution: more common in Eastern countries (H. Pylori, diet, microbiota, family history)
when you detect metaplasia in a biopsy, it is important to assess the dysplasia and the localization of mitosis
if mitosis is deep, it is associated with low grade dysplasia with preserved architecture
if mitosis is more superficial, architecture is not preserved and there are stratified cells
precursors
adenomas (rare)
pernicious anemia (6x risk)
gastric resection
peptic ulcer ?
hypertrophic gastropathy of Menetrier
atrophic gastritis (BUT NOT ALONE -->
intestinal metaplasia is fundamental)
european guidelines to manage pts with PREMALIGNANT GASTRIC LESIONS
diagnosis
conventional white light endoscopy cannot accurately differentiate and diagnose pre-neoplastic gastric conditions
but metaplasia in the esophagus can be recognized due to changes in colour
for assessment of premalignant gastric lsions, diagnostic upper GI endoscopy should include gastric biopsy sampling from antrum and corpus
systems for histopathologic stagins may be useful for categorization of risk of progression to gastric cancer
surveillance
pts with extensive atrophy and/or intestinal metaplasia should receive surveillance with an interval of 3 ys
pts with low-grade dysplasia in the absence of endoscopically defined lesions should receive follow-up within 1 y after diagnosis
pts with high-grade dysplasia in the absence of endoscopically defined lesions should undergo immediate endoscopic reassessment with endoscopic biopsy sampling and surveillance at 6-12 month intervals
pts with endoscopically visible high-grade dysplasia or cancer should undergo staging and adequate management
treatment
H. Pylori eradication is recommended and heals non-atrophic gastritis, but does not appear to reverse intestinal metaplasia
EARLY GASTRIC CANCER
limited to mucosa and submucosa
mass screening in Japan
all cancers begin as intramucosal lesions
site: antrum or pylorus (50-60%), small curve (40%), cardias (28%), big curve (12%)
mucosectomy is performed in the case endoscopy is not enough
look at all mucosal layers!
there may be the possibility of LN metastases
if the cancer is only in the mucosa: 3%
if the cancer is also in the submucosa: 23.5%
flat, polypoid, excavated
different from the advanced form, which is characterized by a deeper, vegetating, ulcerated and infiltrating pattern
LINITIS PLASTICA
complications of invasive carcinoma
stenosis
perforation
hemorrhage
(BAD PROGNOSIS)
histological classification
WHO
papillary, tubular, mucinous, signet ring, undifferentiated
Lauren
intestinal 53%, diffuse 14%
DIFFUSE GASTRIC CANCER
diagnosis can be quite difficult due to the presence of cells which are signet ring cells, that are full of mucus, transparent and can infiltrate without forming glands
aka "signet ring carcinoma" or "isolated cell-type carcinoma"
inherited CDH1 mutations account for 40% of HDCG
other genes associated with hereditary gastric cancer are: CTNNA1, BRCA2, PALB2 and TP53
germline mutations of e-cadherin!!!
some of these tumors express HER2
(negative prognostic factor)
the patient may be treated with anti-HER2
Trastuzumab
HER2 expression is more frequent in the tumor of junction (Barrett's esophagus) and in the small curve, while it is lower in the signet ring tumor (diffuse)
diffusion may occur by contiguity into lymph nodes, peritoneum and ovary
signet ring carcinoma may metastasize to the ovary, giving origin to Krukemberg tumor
some tumors of breast may metastasize unti the stomach and the in the ovary
stage
T1: mucosa and submucosa
T2: tunica muscolaris and subserosa
T3: serosa
T4: adjacent structures
N1-N2
LYMPHOMA
(3%)
3% of all gastric cancers
likely to mimic diffuse carcinoma by diffuse infiltration of the DD wall non-neoplastic lymphoid hyperplasia, e.g. pseudo-lymphoma
LEIOMYOSARCOMA /LEIOMYOBLASTOMA
30-70 ys
wall mass
lifts the mucous membrane
malignancy diagnosis based on cellularity and mitosis (>5/10 x10 HPF)
atypia has nothing to do with it
leiomyoblastoma is epithelioid
CARCINOIDS
(3%)
polypoid or infiltrating
single or multiple
argyrophils
spectrum of precursor lesions in NE cells