Small intestinal cancers are rare but increasing in incidence. The four main subtypes are adenocarcinomas, neuroendocrine tumors, gastrointestinal stromal tumors, and lymphomas. Adenocarcinomas and carcinoid tumors are the most common. Risk factors include hereditary conditions and diseases like celiac disease and Crohn's. Tumors are staged using the TNM system and treated with surgery though chemotherapy may be used for lymphomas. Prognosis depends on factors like lymph node involvement and primary tumor location.

1. PATHOLOGY AND TREATMENT OF
SMALL INTESTINAL CANCERS
DR. OBIORA NWAFULUME
UNIVERSITY OF NIGERIA TEACHING
HOSPITAL, ITUKU-OZALLA.

2. Introduction:
• Although the small intestine makes up
75% of the length of the digestive tract and
90% of its mucosal surface area, cancer of
the small bowel is rare, accounting for 2%
of gastro-intestinal malignancies.
• Nonetheless, incidence has been
increasing owing to the widespread use of
endoscopy.

3. • Exact explanation for the low incidence of
cancer is unknown but probably are:
• The fluidy contents cause less mucosal
irritation, and reduce the intensity of
exposure to oral carcinogens.
• Rapid transit of intestinal contents through
it reduce contact time to carcinogens
• Its low bacterial count result in decreased
conversion of bile-acids into carcinogens

4. • The carcinogen benzpyrene is converted
to less toxic metabolites by benzpyrene
hydroxylase, present in high
concentrations in the small intestine.
• Lymphoid accumulations within the small
bowel wall may be protective.
• Efficient epithelial cellular apoptotic
mechanisms: Eliminates clones
harbouring genetic mutation

6. HISTOLOGICAL SUBTYPES
• Of the over 40 different subtypes
described, the 4 major subtypes of cancer
of the small intestine:
• adenocarcinomas
• neuroendocrine tumours,
• gastrointestinal stromal tumours (GISTs)
• lymphomas

7. ADENOCARCINOMAS
• 64% of all small-bowel tumors are
malignant and approximately 50% of these
tumors are adenocarcinomas.
• Followed by carcinoid tumours,
lymphomas, and GISTs.
• Half of all small bowel adenocarcinomas
are located in the duodenum.Probably due
to the higher concentration of bile (Note:
presence of the ampulla of Vater).

8. Adenocarcinomas
• Peak incidence: 7th decade of life with
slight male preponderance.
• Histologically resembles their more
common colon counterparts, but with a
higher proportion of poorly differentiated
tumours.2
• SEER program of the U.S. National
Cancer Institute for 1973–1982:
duodenum (48.4%), jejunum (32.5%) and
ileum (19.2%)

9. CARCINOID TUMOURS
• Arise from enterochromaffin cells in the
crypts of Lieberkuhn.
• GIT is the most common site; almost
always occur within the last 2 feet of ileum
• Other sites include lungs, tracheobronchial
tree, pancreas, biliary tract, and liver.
• Midgut carcinoids known for high serotonin
production

10. CARCINOID TUMOURS
• Seen in the 5th decade of life
• Malignant potentials directly related to site
of origin, size of tumour, and the depth of
penetration in the wall of the gut.
• Composed of multipotential cells able to
secrete numerous humoral agents such as
serotonin, substance P.

11. LYMPHOMA
• May involve the small intestine or as a
manifestation of disseminated systemic
disease
• Primary lymphomas arise within the lymphoid
tissue of the GIT and are most commonly
located in the ileum
• Predisposing factor are celiac disease and
immunodeficiency states
• Secondary lymphomas are brought to the
GIT from lymphomas primary arising
somewhere else

12. GASTROINTESTINAL STROMAL
TUMOURS (GISTs)
• Most common mesenchymal tumours of
the small bowel
• The small intestine is the 2nd most
common site
• No regional variation in its occurrence in
the small intestine
• Most have activating mutations in the c-kit
proto-oncogene

13. METASTATIC CANCERS
• Commoner than the primary cancers
• Commonly arises from intra-abdominal
organs eg uterine cervix, ovaries, kidneys,
colon, pancreas.
• Metastasis from extra-abdominal organs
rare but could occur in breast ca and lung
ca.
• Small intestinal involvement occur by
direct extension or implantation of tumour
cells.

14. EPIDEMIOLOGY
• The incidence of small bowel cancer is
increasing, particularly the incidence of
carcinoid tumours.
• US National Cancer Database: the
incidence rose from 11.8 cases/million
persons in 1973 to 22.7 cases/million
persons in 2004.
• Similar rise in incidence was also noted in
France in 1976 to 2001.

15. EPIDEMIOLOGY
• Geography:
• Higher in Northern America and Europe than in
African and Asian countries.
• Adenocarcinomas are the largest fraction in
western countries; lymphomas predominate in
other nations.
• Sex:
• 0.5-1.5/100,000 (males); 0.2-1.0/100,000
(females).
• Adenocarcinoma predominates in males as
compared to females (1.4:1)

16. EPIDEMIOLOGY
• Race:
• United States: blacks more than for whites at
2:1 (Adenocarcinoma)
• Age:
• Mean age at diagnosis of any small bowel
cancer is 65 but sarcoma and lymphoma tend
to present earlier than adenocarcinoma and
carcinoid tumours.
• The incidence rises after the age of 40 years
for all histological subtypes.

17. RISK FACTORS
• FAP: most have duodenal adenomatosis
• Small intestine adenomas: malignant
transformation greatest with villous
morphology, increasing size and dysplasia
• Hereditary non-polyposis colorectal cancer
(Lynch syndrome)
• Coeliac disease: T-cell non-Hodgkin’s
lymphoma and adenocarcinoma
• Small bowel Crohn’s disease:
adenocarcinoma.

18. RISK FACTORS
• Peutz-Jeghers syndrome
• MEN-1, von Hippel Lindau disease and NF type 1:
each carry increased risk of carcinoid tumours
• Cystic fibrosis
• Consumption of red meat or salt-cured/smoked
food
• Cigarette smoking
• Alcohol consumption
• Prior colon cancer
• Obesity: Inconclusive

19. PATHOGENESIS: Adenocarcinoma
• Like CRC, this arises from adenomatous
polyps and both cancers may share many
of the genetic changes of carcinogenesis.
• The adenoma-carcinoma sequence
described transformation of normal
intestinal epithelium to an adenoma and
ultimately to an invasive and metastatic
tumor.
• Mutations have been described in APC, b-
catenin, E-cadherin, K-ras, P-53.

20. • Through a stepwise accumulation of
genetic mutations, these adenomas
become dysplastic and progress to
carcinomas in situ and then to invasive
adenocarcinomas.
• SPREAD: via the lymphatics or portal
circulation to the liver, lung, bone, brain,
and other distant sites.

21. The adenoma-carcinoma sequence

22. PATHOGENESIS: GISTs
• Most GISTs are located in the stomach but
30% found in the small bowel.
• Originate from the interstitial cells of Cajal in
the muscularis propria with gain of function
mutations in the KIT proto-oncogene.
• This oncogene codes for the c-KIT molecule
which acts as a receptor for stem cell factor.
• Mutations in the gene result in activation of c-
KIT independent of stem cell factor, which
results in uncontrolled proliferation of cells

23. • GIST tumours are classified as either
spindle cell type, epithelioid type or mixed
type.
• The vast majority express c-kit, detected
by routine immunohistochemistry.
• Over 80% express the CD117 antigen,
part of the KIT transmembrane receptor
tyrosine kinase, a product of the c-kit
proto-oncogene.
• A small percentage have mutations in the
platelet derived growth factor receptor
alpha.

24. • They tend to grow extraluminally.
• Because they are highly vascular lesions
that commonly ulcerate.
• SPREAD: primarily via the hematogenous
route, commonly involving the liver and
lungs.
• GISTs also may invade adjacent organs
directly or spread via peritoneal seeding.
• Lymphatic metastases are rare.

25. PATHOGENESIS
• Lymphoma: Primary lymphoma is
generally divided into:
• immunoproliferative small intestinal
disease (IPSID) lymphoma,
• enteropathy associated T cell (EATL)
lymphoma
• other western-type non-IPSID lymphomas
(e.g. diffuse large B cell lymphoma, mantle
cell lymphoma, follicular lymphoma).

26. PATHOGENESIS
• Patients with coeliac disease are at
increased risk of enteropathy-associated
T-cell lymphoma, possibly due to the
chronic mucosal inflammatory response
following gliadin exposure.
• Similarly infections with Helicobacter pylori
cause chronic antigenic stimulation, a
possible predisposing factor for
lymphoma.

27. PATHOGENESIS
• Carcinoid tumours:
• Arise from the serotonin producing
enterochromaffin (Kulchitsky) cells,
predominantly located in the ileum.
• Chromosomal instability, point mutations,
methylation abnormalities and dysfunction
of tumour suppressor pathways including
p53 are responsible for this malignancy.

28. STAGING: TNM classification of small
intestine adenocarcinomas.

29. TNM classification of small intestine
adenocarcinomas.

31. STAGING: TNM classification of small
intestine carcinoid

32. Differential Diagnoses
• Ampullary carcinoma
• Benign neoplasm of the small intestine
• Bile duct tumours
• Colon cancer
• Crohn’s disease
• Gastric cancer
• Intestinal polypoid adenomas
• Pancreatic cancer Peptic ulcer disease

33. TREATMENT
Adenocarcinoma
• Wide local resection with its mesentery to
achieve regional lymphadenectomy
• Chemotherapy and radiotherapy: has no
proven efficacy in the adjuvant or palliative
treatment .
Lymphoma
• Localized: segmental resection with adjacent
mesentery
• Diffuse involvement: chemotherapy rather
than surgery is the primary treatment.

36. Carcinoid tumours

41. • Metastatic cancers: Consider
metastasectomy where feasible
• Melanoma: Palliative resection/ bypass +/-
systemic therapy

43. PROGNOSIS:
• Lymph-node invasion: the main prognostic
factor for adenocarcinoma. The number of
positive lymph nodes are of prognostic value.
• Duodenal primary tumour has a worse
prognosis than a jejunal or ileal primary
tumour.
• Advanced age, pT4 tumour stage, poorly
differentiated tumour, positive resection
margins, lymphovascular invasion and a
lymph node ratio of ≥10%