Esofagite

General
• Definite ca leziuni ale mucoasei si inflamatie
• 10-20% incidenta in USA, incidenta crescuta in
N Iran si China.
• Cea mai frecventa cauza – esofagita de reflux
(reflux continutului gastric in esofagul inferior)
• Alte cauze: intubatie gastrica prelungita
• Uremie
• Ingestia de subst corozive sau iritante
• Chimioterapie si radiatii
• Modificarile histologice pot fi severe sau
(eroziune, ulcer) sau discrete
Esofag normal
 Esofagita de reflux

• Cea mai frecventa cauza de esofagita.

• Data de refluxul gastric sau duodenal in
esoofagul
• Afecteaza 3-4% din populatie,
• De obicei usoara sau moderata displazie
• De obicei adulti peste 40 ani, ocazional
copii.
• Poate fi eroziva sau neeroziva.
Cauze:
• alcool
• Medicamente antidepresive
• Hipotiroidism
• Intubare nasogastrica
• Sarcina
• Fumat
Simptome:
arsuri, disfagie;severitatea simptomelor nu
are legatura cu aspectul histologic; durere
severa retrosternala ( mimeaza infarct
miocardic)
.
• Ma: hiperemie cu hemoragie focala.
• Consecinte : sangerari, strictura, esofag
Barrett.
• Mi: eozinofile in straturile epiteliale, asociate
sau nu cu neutrofile
– Hiperplazia zonei bazale
– Alungirea papilelor din lamina propria

Neutrofilele intraepiteliale – marker de leziune

severa
 Gastroesophageal Reflux with Ulceration
A common pattern of reflux are longitudinal ulcers arising from
the gastroesophageal junction
Medium power view (10x) of reflux esophagitis (micro biopsy). Hyperplastic
squamous mucosa with elongated vascular papillae, intraepithelial eosinophils and
reactive epithelial changes
Medium power view (10x) of reflux esophagitis (micro biopsy). Hyperplastic epithelial
changes including hyperplastic squamous mucosa, basal layer and vascular papillae.
 Esofag Barrett
• Norman Barrett, un chirurg de la Spitalul St.
Thomas a descris pentru prima datã, în 1950,
esofagul Barrett
• Definitie: inlocuirea mucoasei scuamoase distale
de catre epiteliu columnar metaplaziat
• Epiteliul columnar poate fi rezistent la acizi,
pepsina si bila
• Risc major pt adenocarcinom
• In general la barbati, dupa 50 ani, rar la copii cu
fibroza chistica sau dupa chimioterapie
Cauze :

• Reflux gastroesofageal cronic (esofag

Barrett este prezent in 3-12% din pacientii
cu boala de reflux);
• Asociat frecvent cu hernie hiatala, strictura
esofageala, chimioterapie, reflux biliar,
ulcer peptic
Macro:

• mucoasa rosie catifelata printre

mucoasa scuamoasa alb-gri
These two endoscopic views demonstrate Barrett esophagus areas of mucosal
erythema of the lower esophagus, with islands of normal pale esophageal squamous
mucosa.
• Micro: epiteliul scuamos esofageal este
inlocuit de epiteliu de tip intestinal (gastric,
intestin subtire, colon) cu celule goblet
Section from gastro-esophageal junction showing BE with goblet cells, H&E.
Esofag Barrett - displazia de esofag

• Leziunile displazice care apar la nivelul

esofagului Barrett pot fi precursoare de
cancer
• High grade dysplasia: 15-50% risk of
invasive adenocarcinoma.
• Low grade dysplasia: se poate
transforma in displazie de grad inalt sau
carcinom in decurs de aprox 10 ani.
High grade dysplasia
Low-Grade Dysplasia
• Modificari arhitecturale
minime
• Descreste secretia de
mucus
• Pseudostratificare
nucleara
• Pleomorfism nuclear
scazut
• Mitoze ocazional
High grade dysplasia

• Scade secretia de
mucus
• Marcat pleomorfism
• Stratificare nucleara
• Frecvente mitoze
• Arhitectura nu se
pastreaza
 Carcinoamele esofagiene
• Cele mai frecvente:
• Cc scuamos
• Adenocarcinomul

• In USA– adulti peste 50 ani

• 3:1 barbati/femei
• 2% din cauzele de moarte
• Mai afectati barbatii negri
• In China, Iran – 100 la 100.000 cazuri
• 20% din cauzele de moarte
 Carcinoamele esofagiene
– general
• De obicei asimptomatic, se ajunge in
stadii tardive sau cu metastaze

• Supravietuire peste 5 ani – 14% din

cazuri sau 47% dupa rezectie

• Metastaze in ficat, plaman, pleura

 Cc scuamos
– Etiologie-
• 90% sunt atribuite fumatului si alcoolului
• Esofagite prelungite
• Deficit de vitamine (A, C)
• Ingestia cronica de lichide si alimente fierbinti
• Expunerea profesionala la azbest sau cauciuc;
• Nitriti si nitrozamine
• Deficienta de zinc, molibden
• Infectia cu papilomavirusuri umane tip 16-l8
• Predispozitia genetica (tilosis- hiperkeratoza palmara)
 Cc scuamos
• Cea mai ridicata incidenta a carcinomului epidermoid se
inregistreaza in unele regiuni de pe coasta marii
Caspice, Iran, China si Africa de Sud;
• Romania face parte dintre tarile cu incidenta redusa a
cancerului esofagian, cu rata standardizata a mortalitatii
pentru B/F de 1,6/0,3 la 100 000 (4).
• Incidenta este maxima in decada a 6-a si a 7-a, riscul
este triplu la barbati fata de femei.
• Studiile epidemiologice efectuate in regiuni cu incidenta
ridicata au identificat factorii de risc ce actioneaza ca
promotori ai carcinogenezei
 Cc scuamos
– Semne si simptome
• Disfagie
• Pierderea greutatii
• Durere retrosternala si epigastrica
• Regurgitatii
Cc scuamos
• De obicei apare in
portiunea mijlocie si
1/3 inf a esofagului
• Polipoid, plat,
ulcerativ, infiltrativ
• Metastazeaza in
limfoganglionii
regionali, plaman si
ficat
Cc scuamos
The normal squamous epithelium at the left merges into the squamous cell
carcinoma at the right, which is infiltrating downward. The neoplastic squamous
cells are still similar to the normal squamous cells, but are less orderly. This is a
well-differentiated squamous cell carcinoma.
Here is a moderately differentiated squamous cell carcinoma in which some, but
not all, of the neoplastic cells in nests have pink cytoplasmic keratin. In general,
neoplasms with less differentiation are more aggressive, growing more quickly,
invading, or metastasizing.
Infiltrative growth pattern with individual tongues and nests and intense
lymphocytic infiltrate.
CC scuamos
Adenocarcinomul esofagian

• 40-50% din cancerele primare esofagiene

• Incidenta crescuta in ultimii 20 ani
• 1/3 inf a esogagului pe esofag Barrett
• Peste 50 ani, 80% la barbati
• Rar poate apare pe mucoasa ectopica
gastrica
• Factori de risc : alcool, fumat, istoric
familial
 Simptome:
• disfagie, pierdere in greutate
• Supravietuire 5 ani 15-25%, peste 80% cu
leziuni superficiale si rezectie
• Pot fi plate, ulcerate, polipoide ,pot avea
adiacent mucoasa Barrett.
• Infiltreaza local prin peretele esofagului
• Metastaze – mediastin, arbore traheo-
bronsic, plaman, aorta, pericard
Nodular
tumor in
lower
esopha
gus
Polypoid tumor
 Micro
• De obicei moderat – bine
diferentiat, poate produce
mucina, poate avea arii de
diferentiere scuamoasa sau
endocrina
• Rar celule in inel cu pecete,
structuri papilare
Well
differentiated
papillary
adenocarcinoma
 Gastritele
Features to report
Sydney system
Biopsies
• Recommended to take 5 biopsy specimens, 2
from antrum (both at 2 to 3 cm from the pylorus,
1 from lesser and 1 from greater curvature), 2
from corpus (both at 8 cm from the cardia, from
lesser and greater curvature), 1 from the
incisura angularis;
• all samples should be identified and studied
separately; 5 biopsies appears to be adequate,
although site is often misidentified
• Reprezinta inflamatia mucoasei gastrice
• Acute sau cronice
• La biopsie se raporteaza :
– Localizarea, gastritelor (antrum, fundic,
cardia, difuza)
– Tipul : activa, cronica sau limfocitica,
granulomatoasa, eozinofilica
– Prezenta Helicobacter pylori, inflamatiei,
atrofiei glandulare, metaplaziei intestinale
 Alternative reporting:
• Antral predominant, corpus predominant
or pangastritis.
• Focal or diffuse.
• Superficial or full thickness.
• Atrophy: present or absent.
• Metaplasia: present or absent.
• Inflammation: active, chronic or both.
• H. pylori present or absent.
Gastrita activa
• Proces inflamatoriu acut de obicei tranzitoriu
• Asociat cu hemoragie locala sau eroziuni
• in cazuri severe de eroziune - cauza de sangerare
gastrointestinala
• Se asociaza cu:
– Medicamente antiinflamatorii nesteroidiene (aspirina)
– Alcool
– Fumat
– Chimioterapie
– Uremie
– Infectii sistemice (salmonela)
– Stress
– Ischemie si soc
– Ingestie de acizi si alcaloizi
– Trauma mecanica ( intubare nasogastrica)
– Dupa gastrectomie
 Simptome: nesemnificative sau, durere or pain,
greata, voma

Micro:
• moderata: edem moderat in lamina propria,
congestie vasculara minima, cateva neutrofile
• severa: eroziune si hemoragie in mucoasa

• Eroziunea: pierderea epiteliului superficial pana

la muscularis mucosa, cu infiltrat inflamator
acute si exudat fibrinopurulent in lumen
This is acute gastritis or the so-called acid indigestion, which is caused by irritating foods,
over-ingestion of alcohol or aspirin or poisons. Here the mucosa is edematous and there are
punctate submucosal hemorrhages.
This is a more typical acute gastritis with a diffusely hyperemic gastric mucosa.
Histologic appearance of Helicobacter associated active gastritis. Note the neutrophilic
infiltration of the lamina propria as well as neutrophils within glands (yellow arrows).
At high power, gastric mucosa demonstrates infiltration by neutrophils. This is acute gastritis.
Helicobacter organisms may be tested for urease activity. Staining of the gastric biopsy
shows the characteristic curved rods embedded in the mucin layer of the stomach.
Rod-shaped organisms are present along the luminal surfaces of the epithelium and in the luminal mucus.
They do not invade the mucosa. The bacteria are small and in H&E stain have a pale eosinophilic
appearance. They are best seen on giemsa stain, where they stain bluish-purple.
The rods are seen here with a methylene blue stain.
Neutrophils infiltrating foveolar epithelium in a case of active H. pylori gastritis.
 Ulcer
ulcer peptic
• Ulcer: Reprezintă o pierdere de substanţă la nivelul
peretelui gastric până la nivelul muscularei propria, datorită
hipersecretiei gastrice acide
• Ulcer peptic : cronic, de obicei solitar
• Localizare : duodenum, antrum, GE jonctiune, pe marginile
unei gastoenterostomii, in / adiacent unui diverticul Meckel
ce contine mucoasa gastrica ectopica

• Incidenta in USA: 4 million, 350,000 new cases/year; 3,000

deaths; affects 10% of American men, 4% of women (M/F =
3:1 for duodenal ulcers, 1.5-2:1 for gastric ulcers)
• Incidenta in scadere pt ulcer duodenal, nu si gastric
• Cauze:
– Leziuni ale mucoasei date de HP
– Medicamente antiinflamatorii nesteroidiene
(aspirina)
– Alcool
– Fumat
– Sindrom Zollinger-Ellison
– Ischemie
– Reflux de suc biliar si pancreatic
 Ulcer peptic cronic

• 10-20% din indivizii cu HP dezvolta ulcer peptic

• Media de varsta 50 ani, dar poate apare si la
copii

• Simptome: arsuri , durere mai ales noaptea, la

1-3 ore dupa mese,

• Complicatii: perforatie, hemoragie, obstructie,

• Macroscopic, leziunea apare
rotund/ovalară, cu margini netede în ulcerul
acut şi cu margini rigide în ulcerul cronic şi
un detritus alb-gălbui, hemoragic.
• Pliurile gastrice sunt convergente catre
marginile ulcerului, iar mucoasa din jurul
eroziunii este edemaţiată.
• Fundul ulceratiei- tesut de granulatie
The edges of
the ulcer are
heaped up
due to
epithelial
regeneration.
The ulcer
base is
smooth
and contains
only
granulation
tissue.
Ulcer
 Ulcer
• Microscopic se observă 4 straturi:
– Primul strat e reprezentat de un exsudat fibrino-
leucocitar amestecat cu detritus celular
– Al doilea strat e format din necroză de tip fibrinoid
– Al treilea strat este format din ţesut de granulaţie
– Al patrulea strat apare doar în cazul ulcerului
cronic, fiind un strat de fibroză.
Histologic section through the ulcer shows layers of acute inflammatory exudate including
fibrin, acute inflammation, chronic inflammation, and fibrosis.
 Carcinoma-general
• 22K cases/year in US; overall rates declining due to lower rates
of intestinal type; diffuse rates unchanged.
• 90% of all malignant tumors in stomach are carcinomas.
• High incidence in Japan, Chile, Italy, China, Portugal, Russia;
kills more people worldwide than lung cancer.
• 2/3 men; associated with lower socioeconomic groups
• In young patients, associated with radiation therapy or
chemotherapy for other malignancies.
• 5 year survival - 20% or less; 95% for surgically treated early
gastric carcinoma.
• Nodal involvement may not alter survival.
• Usually asymptomatic until late; weight loss, abdominal pain,
nausea, vomiting, altered bowel habits.
• Japan: mass endoscopy programs led to 35% early gastric
cancers vs. 10% in US.
• Well differentiated tumors may grow very slowly.
• Rarely occurs in gastric stump after partial gastrectomy for
ulcer.
• Minute (< 5 mm) poorly differentiated tumors may show no
gross features.
• Phenotypes: intestinal (arises from complete-type intestinal
metaplasia) and gastric (arises directly from gastric foveolar
epithelium, poorer prognosis)
• Pattern of allelic loss resembles colon carcinoma (c-met, K-ras,
HER2 [5-15%], p53 [50%])
• Microsatellite instability phenotype cancers (10% prevalence)
are associated with fewer lymph node metastases, borderline
significant improved survival; minimal dysplasia; patients with
gastric and colorectal cancers often (18%) have this phenotype)
• Site: pylorus and antrum > cardia; lesser > greater curvature
• Depth of invasion most important prognostic factor
• Metastases to supraclavicular nodes (Virchow’s node,
Trousseau’s sign) may be first clinical manifestation
• Death due to widespread seeding of peritoneum and lung/liver
metastases; also distant metastases to adrenal gland,
peritoneum, ovary, spleen (#2 cause of splenic metastases)
• Locally invades esophagus (proximal carcinomas), duodenum
(distal carcinomas), omentum, colon, pancreas, spleen
 Carcinomul gastric
• Radiologic poate apare
“nisa in lacuna” sau
aspect “in palnie”
• Macroscopic se pot
decela 3 forme ale
carcinomului gastric:
– forma vegetantă
conopidiformă
– forma ulcerată,
– forma infiltrativă sau
stenozant – infiltrativă.
• Kruckenberg tumor: metastases to one or
both ovaries; rarely has tubular pattern.
• Early: confined to submucosa, regardless of
perigastric nodal metastases
• Advanced: muscularis propria invasion
• Exophytic: protrudes into lumen
• Flat/depressed: no obvious tumor in
mucosa
• Excavated: erosive crater in stomach wall;
resemble peptic ulcers, but advanced
cancers have heaped up, beaded margins
and shaggy, necrotic bases
• Treatment: gastrectomy
• Poor prognostic factors: younger age (usually
diffuse histology, more advanced disease),
proximal half of stomach, deep invasion,
infiltrative margin, diffuse histologic type, positive
surgical margins (predicts local recurrence),
lymph node metastases, reduced neutrophilic
infiltration (women in high risk area in Italy)
• Mucosal lymphangiectasia common, and
associated with nodal metastases.
• Positive stains: CDX2, CK7 (71%), CK20
(41%)
• Negative stains: CD44 , EBV (except for
lymphoepithelioma-like carcinomas and rarely
classic carcinomas.
 Intestinal type adenocarcinoma
• Bulky tumors composed of glandular structures
• Mean age 55, 2/3 men
• Incidence has declined in last 50 years
• Risk factors: diet (nitrates, smoked and salted foods, pickled
vegetables, lack of fresh fruit and vegetables [green leafy
vegetables, citrus fruit]), low socioeconomic status, cigarette
smoking [RR: 1.5-3.0 x]
• Host factors: chronic gastritis (achlorhydria favors
Helicobacter pylori growth, intestinal metaplasia is a precursor
lesion), H pylori infection, autoimmune gastritis, partial
gastrectomy (favors reflux), gastric adenomas, Barrett’s
esophagus
• Genetic: slightly increased risk with blood group A, family
history, hereditary nonpolyposis colon cancer syndrome

•
• Not risk factors: alcohol, antacids,
occupational exposure
• Micro: neoplastic intestinal glands
resembling colonic adenocarcinoma;
contain apical mucin vacuoles; variable
calcification, endocrine cells, rare Paneth
cells
• Well differentiated: columnar cells that
secrete mucin, rarely are ciliated
• Poorly differentiated: solid pattern
• Positive stains: acid mucins (Alcian Blue,
colloidal iron), p53 (usually)
 Early gastric
adenocarcinoma
The adenocarcinoma is
small and confined to
the gastric mucosa.
Ulcerated adenocarcenoma. A yellow arrow points to malignant glandular structure with intestinal
features.
The tumor are cells arranged in variable sized glands; some of the glands show papillary projections,
others are branching. In their lumen, necrotic debris and nuclear fragments are frequently present.
Note invasion of the muscle layer.
Microscopically, invading adenocarcinoma can be seen here. Normal gastric epithelium at the left merges
with the carcinoma at the right, and irregular neoplastic glands infiltrate downward into the submucosa.
A moderately differentiated gastric adenocarcinoma is infiltrating up and into the submucosa below the
squamous mucosa of the esophagus. The neoplastic glands are variably sized.
At higher magnification, the neoplastic glands of gastric adenocarcinoma demonstrate mitoses, increased
nuclear/cytoplasmic ratios, and hyperchromatism. There is a desmoplastic stromal reaction to the
infiltrating glands.
 Diffuse type adenocarcinoma
• Infiltrative growth of poorly differentiated discohesive malignant
cells
• Aka linitis plastica or signet ring adenocarcinoma
• Mean age 48, M=F; more common in gastric cancers in the
young
• No reduction in incidence over past 50 years
• Appears to arise without dysplastic precursor, possibly through
primary involvement of genes affecting cell-cell and cell-matrix
junctional proteins
• No known risk factors
• Linitis plastica: broad region of gastric wall or entire stomach
is extensively infiltrated by malignancy, creating a thickened,
rigid, leather bottle-like stomach; may cause pyloric obstruction
•
 Linitis plastica
The wall of the stomach is thickened and rubbery hard due to an extensive infiltration with signet
ring cells.
Stomach carcinoma, linnitus plastica type. A yellow arrow denotes a thickened wall.
The mucosa has areas of hemorrhage, but is without a mass.
Gastric Carcinoma, linnitus plastica type -- A purple arrow points out a white, thickened wall, representing
diffuse infiltrating carcinoma. Grossly the stomach usually has a "leather bottle" appearance. The yellow
arrow points to uninvolved stomach.
This is an example of linitis plastica, a diffuse infiltrative gastric adenocarcinoma which gives the
stomach a shrunken "leather bottle" appearance with extensive mucosal erosion and a markedly
thickened gastric wall. This type of carcinoma has a very poor prognosis. The endoscopic view of this
lesion is shown below, with extensive mucosal erosion.
This cancer presented in a 40-year-old woman complaining of abdominal pain. Endoscopically it was a
"very suspicious" ulcer. Biopsy showed diffusely infiltrating signet ring cell adenocarcinoma. These are
gross photos of the subtotal gastrectomy specimen. The photo above is asen face view of the ulcer. The
pyloric margin is to the left. The ulcer is on the lesser curvature.
• Micro: gastric-type mucus cells, usually do
NOT form glands, infiltrate as individual cells
or small clusters, may be transmural; appear to
arise from middle layer of mucosa; intestinal
metaplasia usually not present; numerous
signet ring cells seen (mucin pushes nucleus
to periphery); submucosal fibrosis present,
variable mucosal ulceration; hypertrophic
muscularis propria; may have marked
desmoplastic and inflammatory reaction.
• Positive stains: mucicarmine, Alcian
blue-PAS, CEA, EMA, keratin, villin.
• Negative stains: TTF-1, p53 (usually).
• DD: metastases from breast, lung;
reactive epithelial atypia associated with
chemotherapy or otherwise; xanthoma;
lymphoma with artifactual signet ring cells
due to cytoplasmic shrinkage.
Gastric carcinoma, signet ring cell type. Yellow arrows points to a classic "signet ring " cells. This is a
large round cell with clear mucinous cytoplasm that causes the nucleus to be pushed to the edge of the
cell. One cell is circled in yellow.
At high power, this gastric adenocarcinoma is so poorly differentiated that glands are not visible. Instead,
rows of infiltrating neoplastic cells with marked pleomorphism are seen. Many of the neoplastic cells have
clear vacuoles of mucin.
This is a signet ring cell pattern of adenocarcinoma in which the cells are filled
with mucin vacuoles that push the nucleus to one side, as shown at the arrow.
Higher magnification shows the fairly uniform tumor cells with abundant intracytoplasmic mucin which pushes the
nuclei to the side, giving the cells their typical "signet-ring" appearance