SMALL INTESTINAL NEOPLASMS

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SMALL INTESTINAL NEOPLASMS
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Despite comprising 75 of the length and 90 of
the surface area of the GI tract, the small bowel
harbors relatively few primary neoplasms and
fewer than 2 of GI malignancies.
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WHY THIS LOW INCIDENCE ?
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1. Rapid intestinal transit limits contact time
to the mucosa.
2.Greater fluidity of chyme may dilute luminal
irritants.
3.Alkaline pH may play a role
4. Low bacterial counts make them less capable of
transforming potential procarcinogens to
carcinogens
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5.Higher levels of benzyl peroxidase (thought to
detoxify potential carcinogens) have been detected
6. Increased levels of immunoglobulin A
7.Widespread gut lymphoid tissue
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SMALL INTESTINAL NEOPLASMS COULD BE
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BENIGN ?GI stromal tumors (GIST) (45) ?
Adenomas (20-40) ? Lipomas (16) ?
Hemangiomas (13) ? Lymphangioma (5) ? Neuroma
(1) ? S.intestinal polyps
MALIGNANT ? Carcinoids (47) ?
Adenocarcinomas (25) ? Lymphomas (16) ?
Sarcomas or GIST (1) ? Metastasis (1)
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SMALL INTESTINE TUMORS
Benign Epithelial Tumors
Malignant Epithelial Tumors
Lympho- proliferative disorders
Mesenchymal Tumors
B cell
T cell
Brunner Gland Lesions
Benign Intestinal polypi

• Pr. ADC
• Metastasis.
• Carcinoid.

• Diffuse large cell lymphoma.
• Small non cleaved cell lymphoma.
• MALT cell lymphoma.
• Mantle cell lymphoma.
• Immuonoproliferative small cell disease

Enteropathy associated T-cell lymphoma

• Adenomas
• Hamartomas

Para gangl.
Smooth Ms tumors
GIST
Fatty tumors
Neural tumors
Vasc. tumors

• Lipoma
• Liposarcoma

• Leioyomayoma
• Leioyomayosarcoma

• Benign
• Malignant

• Gut autonoic tumor
• Schwannoma
• Neurofibroma
• Granular cell tumor

• Haemangioma
• Angiosarcoma
• Lymphangioma
• Kaposi sarcoma

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SYMPTOMS
Small bowel tumors are mostly ASYMPTOMATIC, but
in symptomatic cases there is lack of specific
identifying symptom no hallmark presentation has
been described.
? Abdominal pain This is generally nonspecific,
and epigastric in location. Pain is more commonly
associated with larger lesions. ? Constipation ?
Nausea ? Vomiting ? Early satiety ? Anorexia ?
Diarrhea ? Palpable mass ? Anemia? Melena
The interval from symptom onset to diagnosis
ranges from less than a month to more than a
year, with a mean duration of symptoms of 6
months.
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SI tumors may manifest primarily with
complications of their growth.
? Bowel obstruction the leading cause of
intussusception in adults. ? Volvulus from
serosal ependymal lesions ? GI bleeding occurs
in up to 38 of lesions. ? Perforation
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PHYSICAL EXAMINATION
? Usually unrevealing.? larger tumors (gt6 cm),
may manifest as a palpable abdominal
mass.? Tenderness on the mass may be elicited.
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DIAGNOSIS OF SMALL INTESTINAL NEOPLASMS
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LABORATORY STUDIES
Routine laboratory testing do not reveal
abnormalities in most patients.
CBC count may show mild anemia related to chronic
blood loss.
Liver function tests may reveal
hyperbilirubinemia, which may be related to
biliary obstruction from periampullary tumors.
Elevated transaminase levels also may be found in
the presence of liver metastases.
CEA levels may be elevated in malignant tumors.
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IMAGING
Large lesions may demonstrate signs of complete
or partial small bowel obstruction on plain films
(eg, dilated small bowel, air-fluid levels,
volvulus).
Barium contrast studies may demonstrate the
lesion in up to 29 of cases. The radiographic
appearance includes irregular mucosal surfaces,
barium-filled cavities (showing central lesion
necrosis), and dumbbell-shaped lesions
(indicating intraluminal and extraluminal growth)
Enteroclysis
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IMAGING (cont.)
CT scan demonstrate up to 27 of SI tumors
especially when larger than 2 cm.
Accurate size, evidence of ulceration and lesion
necrosis are often detected.
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IMAGING (cont.)
On arteriograms tumors are identified by
characteristic tumor blush . Additional clues
include multiple feeding arteries, irregular
draining veins, and venous pooling around the
lesion.
Arteriography may assist in differentiating
malignant from benign lesions ? Benign tumors
receive arterial supply from either the GD or SM
arteries. ? Malignant lesions often demonstrate
aberrant arterial inflow from renal arteries,
lumbar arteries, or both.
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IMAGING (cont.)
Ultrasound images may demonstrate larger tumors
(gt4 cm) giving a mass or target sign appearance.
US can help differentiate if the mass is
intraluminal, intramural, and extraluminal
exophytic growth patterns.
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IMAGING (cont.)
Luminal small bowel tumors may cause
intussusception giving rise to a mass with
layered appearance by US.
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IMAGING (cont.)
Also, EUS is valuable in smaller tumors.
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IMAGING (cont.)
MRI is useful to determine the extent of the
tumor in the abdomen although usually CT scans
are adequate.
It is also useful in looking for recurrence or
metastases.
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IMAGING (cont.)
PET has become one of the most useful tests for
spotting GIST tumors. Radioactive glucose is used
which is consumed much faster by the malignant
tissues.
It may be a useful test for staging the cancer
and for determining drug efficacy.
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ENDOSCOPY
Upper endoscopy has been employed successfully
for the detection of proximal lesions in 30 of
cases.
It allows biopsy of intraluminal lesions.
Polypectomy may be performed for small lesions.
Push enteroscopy may identify lesions in the
distal duodenum and jejunum.
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ENDOSCOPY (cont.)
Colonoscopy with retrograde ileoscopy may be
useful in identifying ileal tumors.
GISTs and lipomas cannot be removed via endoscopy
because of their deep intramural location and the
subsequent elevated risk of bowel perforation
during removal attempted.
In addition, some authors caution against
endoscopic biopsy because of increased risk of
shedding cells, which could lead to nests of
local tumor recurrence.
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ENDOSCOPY (cont.)
By capsule endoscopy both color video images and
transit time values can be analyzed for regional
mucosal abnormalities.
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In cases where all these investigations are
negative and the index of suspicion remains high,
then a laparotomy is indicated and if no lesion
is palpable, an intraoperative enteroscopy should
be done.
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ENDOSCOPY
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BENIGN SMALL INTESTINAL NEOPLASMS
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S.I.ADENOMAS
Three types of adenomas have been described
adenomatous polyps, Brunner gland adenomas, and
villous adenomas.
Histologically, they appear as intraluminal
extensions of the mucous membrane and submucosal
architecture with multiple acini supported on a
central fibrovascular core. Varying degrees of
differentiation are encountered across and within
tumors.
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Villous adenomas larger than 4 cm are at
particular risk for malignant transformation.
Tubular adenoma
Adenoma in duodenum
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S.I. LIPOMA
Small bowel lipomas are benign submucosal tumors
of mesenchymal origin.
Pathology includes collections of mature adipose
tissue and fibrous tissue strands.
Collections of adipose tissue may be found near
the ileocecal valve. These deposits may
clinically mimic other lesions, both
radiographically and endoscopically.
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S.I. HEMANGIOMA
Hemangiomas of the small bowel are rare vascular
tumors of 3 types capillary, cavernous (most
common), and mixed.
Hemangiomas may be solitary or multiple and may
account for up to 13 of small bowel lesions.
GI bleeding is a frequent complication. The blood
loss may be occult (resulting in chronic anemia)
or acute.
Preoperative arteriography or intraoperative
maneuvers, such as transillumination or
ultrasound, may be employed to increase
localization success.
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S.I. NEUROMA
Neurofibromatosis type 1 (von Recklinghausen
disease of nerve) affects the GIT in up to 25 of
cases, and in such cases is characterized by
multiple submucosal neurofibromas.
Also, all patients with MEN 2B have intestinal
neuromas.
Patholoy shows spindle cells in loose fibromyxoid
background, spindle cells may expand the lamina
propria and separate the crypts
Spindle cells stains with S100, chromogranin,
neuron specific enolase
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S.I. POLYPS
? Familial adenomatous polyposis ? Gardner's
syndrome. ? Lynch's syndrome. ? Turcot's
syndrome. ? Peutz-Jeghers syndrome. ?
Juvenile polyposis.
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MALIGNANT SMALL INTESTINAL NEOPLASMS
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EPIDEMIOLOGY
Prevalence prevalence is lower in less
industrialized countries. In addition, lymphomas
are predominant in less developed countries.
Race higher prevalence rates for blacks than for
whites
Sex Males have higher prevalence compared with
females, with a ratio of 1.41
Age The prevalence tends to increase with age
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RISK FACTORS
Familial adenomatous polyposis
Hereditary nonpolyposis colorectal cancer
Celiac disease
Crohns disease
Tobacco and alcohol
Diet animal fat, red meat and salt-cured or
smoked foods
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S.I. ADENOCARCINOMA
Epidemiologically, small-bowel adenocarcinomas
have a striking resemblance to large-bowel
adenocarcinomas
1. They share a similar geographic distribution.
2. They tend to co-occur in the same individuals,
with an increased risk of SI adenocarcinoma in
survivors of CRC and vice versa
3. SI adenocarcinoma arise from premalignant
adenomas both sporadically and in the context of
FAP.
4. K-ras mutation and p53 over-expression appear
to be as common in SI adenocarcinoma as in CRC.
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S.I. ADENOCARCINOMA (cont.)
Despite these similarities, SI adenocarcinomas
have differences from CRC
1. Small-bowel adenocarcinomas tend to cluster
away from the colon, toward the gastric end of
the small intestine.
2. Mutation of the APC tumor suppressor gene,
which is characteristic of colorectal carcinoma,
does not commonly occur in small-bowel
adenocarcinoma
3. The SMAD4/DPC4 gene, which is often mutated in
pancreatic and colorectal carcinomas, also
appears to be inactivated in small-bowel
adenocarcinomas
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S.I. ADENOCARCINOMA (cont.)
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S.I. CARCINIOD
Of patients with SI carcinoids, 40-50 experience
the syndrome.
Patients with SI carcinoids frequently have
symptoms for long periods ( 2-5 or more y) before
diagnosis is made.
In this group of patients, early diagnosis can
potentially lead to a cure by surgical resection
of the primary tumor.
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S.I. CARCINIOD (CONT.)
Obstruction in SI occurs due to ? Desmoplastic
reaction Invasion of the mesentery with scarring
and matting of loops. ? Mass effect.
Carcinoid syndrome is rarely observed in
association with appendiceal carcinoids, and does
not occur with rectal carcinoids, even when the
it is in an advanced stage and has metastasized.
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S.I. METASTASIS
SI is an uncommon site for metastasis. Primary
tumors include ? Melanoma, ? Carcinomas from
bronchus, breast, thyroid, colon, pancreas,
prostate, uterus, ovary and testicular
malignancy.
Metastatic deposits lie within the wall usually
within the submucosa. US shows a focal mural mass
which may or may not have a target sign.
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S.I. LYMPHOMA
Lymphoma represents approximately 20 of primary
malignancies of the small intestine
It is considered to be primary if the predominant
lesion is in the intestine and the initial
presenting symptoms are related to intestinal
involvement.
The ileum is the mostly affected location (more
lymphoid tissue)
Disorders that predispose patients to SI lymphoma
include previous extraintestinal lymphoma,
chronic lymphocytic leukemia, celiac disease, and
immunologic dysfunction, including AIDS
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S.I. LYMPHOMA (cont.)
Aneurysmal dilatation (seen by BMFT) is
pathognomonic of small-bowel lymphoma and refers
to a segmentally dilated lumen with associated
wall thickening and without proximal bowel
dilation
CT findings include mural infiltration of the
wall with homogenous, asymmetric wall thickening
(gt2 cm) and a nodular appearance of the mass.
On CT, lymphoma is softer and longer than
adenocarcinoma, and it has ill-defined, thickened
walls with irregular or complete loss of the
normal mucosal folds.
In addition, CT often reveals mesenteric or
retroperitoneal lymphadenopathy, a hallmark of
this disease.
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S.I. LYMPHOMA (cont.)
By US tumors appear as multiple well defined
hypoechoic masses in GI wall.
Extensive lymphomatous involvement of the
stomach create the pathological cochade
pattern.
Early stages present as localized thickening of
mucosa, while global wall thickening, destruction
of wall stratification, and visibility of
draining LN can be observed in later stages.
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TREATMENT OF SMALL INTESTINAL NEOPLASMS
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SURGERY
Surgical excision of small bowel tumors remains
the recommended therapy.
Both segmental resection and enterotomy/polypectom
y have been used for lesion removal.
If the pathology cannot be established at the
time of resection, full segmental resection with
adequate margins is recommended.
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CHEMOTHERAPY
No standard regimen demonstrates benefit in an
adjuvant or metastatic setting for small-bowel
adenocarcinoma.
Because of the similarity to CRC, a regimen
containing 5-FU with leucovorin may be used.
Newer agents as irinotecan and oxaliplatin, may
also be used with 5-FU.
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GASTROINTESTINAL STROMAL TUMORS (GIST)
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They are mesenchymal neoplasms derived from the
interstitial cells of Cajal in the GI tract.
GI STROMAL TUMORS
GI stromal tumors are the most common symptomatic
small bowel lesions. They have been found in all
areas of the small bowel, including within the
Meckels diverticulum.
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By US, GIST appear as well defined hypoechoic
masses arising from the GI wall, their shape is
variable ( often eccentrically oval), large
tumors may be circular. Large GIST may contain
cystic areas, have a pedicle and/or may be mobile
and change position, which makes it difficult o
define their site of origin. Small GIST can only
be detected by hydrosonography or EUS.
Pathology shows nests of spindle-shaped cells
located between the muscularis propria and
muscularis mucosa. These intramural lesions may
form intraluminal masses, extraluminal masses, or
transmural (dumbbell-shaped) lesions.
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While most GISTs are located in the stomach, 30
of GISTs are found in the small bowel.
Small-bowel GISTs tend to be more aggressive and
have a worse prognosis.
Previously, these tumors were classified as GI
leiomyomas, leiomyosarcomas, leiomyoblastomas, or
schwannomas as a result of their histologic
findings and apparent origin in the muscularis
propria layer of the intestinal wall.
With the advent of immunohistochemical staining
techniques and ultrastructural evaluation, GISTs
now are recognized as a distinct group of
mesenchymal tumors.
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GI STROMAL TUMORS (GIST) (CONT.)
Etiology
1.Sporadic GISTs a. Mutations of c-kit
receptor tyrosine kinase (KIT) gene b.
Mutations of PDGFR-alpha gene coding for
platelet-derived growth factor receptor Alpha 2.
NF-associated GISTs a. NF germline mutations
b. No KIT or PDGFRA mutations
Nearly all GISTs, unlike true sarcomas, express
mutations in c-kit that cause constitutive
tyrosine kinase activity and result in
uncontrolled cell proliferation
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GI STROMAL TUMORS (GIST) (CONT.)
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The exact definition of GISTs varies among
authors. Some use the term to describe any GI
submucosal mesenchymal tumor that is not myogenic
(eg, leiomyosarcoma) or neurogenic (eg,
schwannoma) in origin. Others are more
restrictive and use the term when specifically
referring to GI mesenchymal tumors that express
the CD117 and/or CD34 antigen.
The CD34 protein is a hematopoietic progenitor
cell antigen that occurs in a variety of
mesenchymal tumors. CD117 also is known as the
c-kit protein it is a membrane receptor with a
tyrosine kinase component. Mutations in the CD117
gene have been linked to malignant behavior in
GISTs
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GI STROMAL TUMORS (GIST) (CONT.)
Cytologically, GISTs can be classified into 2
broad categories ?Spindle cell GISTs are
characterized by a nuclear palisading or
prominent perinuclear vacuolization pattern. ?
Epithelioid GISTs may have either a solid pattern
or a myxoid pattern, with a possible
compartmental pattern.
The number of mitotic figures present can be used
to histologically grade GISTs. Unfortunately, no
standard exists for their classification.
? GISTs with less than 1 mitotic figure per 50
HPFs are benign ? 1-5 mitoses per 10 HPFs
suggests potential malignancy. ? more than 5 per
10 HPFs indicates malignancy. ? more than 10 per
10 HPFs denotes high-grade malignancy
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GI STROMAL TUMORS (GIST) (CONT.)
About 10-30 of GISTs have malignant behavior.
Major negative prognostic factors include large
size (gt5 cm), high mitotic index, and grossly
positive resection margins. Other factors with
poor prognosis include tumor rupture, distal
location, high cellularity, tumor necrosis,
presence of metastases or invasion, and mutation
in the c-kit gene
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TREATMENT OF GIST
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SURGERY
GISTs are resistant to cytotoxic chemotherapy.
However, patients with advanced disease may be
treated with Imatinib
CHEMOTHERAPY
GISTs are resistant to cytotoxic chemotherapy.
However, patients with advanced disease may be
treated with Imatinib
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Defining the structure of KIT allows molecular
targeting of specific kinase inhibitors.
IMATINIB selectively inhibits tyrosine kinase
activity of c-kit.
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GIST before and after Imatinib as seen by PET
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GIST before and after Imatinib as seen by CT
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(No Transcript)
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Survival of GIST patients treated with Imatinib
is good with stable disease
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