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COLON AND RECTUM

TUMOURS
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del corso Integrato Malattie dellapparato Gastroenterico e
Infettive.

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Buon studio

Achille PICH
Colon and rectum tumours
WHO Histological classification
Epithelial tumours
Benign
Malignant
Non-epithelial tumours
Benign
Malignant
Malignant lymphomas
Secondary tumours
Polyps
Adenoma
WHO histological classification
Epithelial tumours
Tubular
Villous
Tubulovillous
Intraepithelial neoplasia (dysplasia)
associated with chronic inflammatory diseases
- Low-grade glandular intraepithelial neoplasia
- High-grade glandular intraepithelial neoplasia
Serrated
Epithelial tumours
Carcinoma
Adenocarcinoma
Mucinous adenocarcinoma
Signet-ring cell carcinoma
Small cell carcinoma
Squamous cell carcinoma
Adenosquamous carcinoma
Medullary carcinoma
Undifferentiated carcinoma
WHO histological classification
Epithelial tumours
Carcinoid (well differentiated endocrine neoplasm)
EC-cell, serotonin-producing neoplasm
Others
L-cell, glucagon-like peptide and
PP/PYY producing tumour
Mixed carcinoid-adenocarcinoma
Others
WHO histological classification

Lipoma
Leiomyoma
Gastrointestinal stromal tumour
Leiomyosarcoma
Angiosarcoma
Kaposi sarcoma
Malignant melanoma
Others
Non-epithelial tumours
WHO histological classification
Malignant Lymphomas
Marginal zone B-cell lymphoma of MALT type
Burkitt lymphoma
Others
Diffuse large B-cell lymphoma
Burkitt-like / atypical Burkitt-lymphoma
Mantle cell lymphoma
WHO histological classification
Secondary tumours
Polyps
Hyperplastic (metaplastic)
Peutz-Jeghers
Juvenile
WHO histological classification
Adenoma
Colon and rectum tumours
WHO Histological classification
Epithelial tumours
Benign
Tubular
Villous
Tubulovillous
Serrated
POLIPI
DEL GROSSO INTESTINO
1. ADENOMA TUBULARE (POLIPO ADENOMATOSO)
Predisposizione familiare.
Unico o multiplo. Peduncolato o sessile.
Spesso (30%) con aree villose.
Probabilit di cancerizzazione: 5%.
Grado di atipia: lieve, moderata, grave (ca. in situ)
2. POLIPOSI FAMILIARE
Ereditaria, Dominante (Mutazione di APC sul cromosoma
5q21).
Interessa anche lo stomaco e/o ileo.
Il numero dei polipi (adenomatosi) > 100.
Elevata attivit proliferativa della mucosa intestinale.
Probabilit di cancerizzazione: altissima (quasi sempre).
Tv. associata ad epatoblastoma, MEN, angiofibroma
rinofaringeo, e ad aumentato rischio di ca. tiroideo e/o
pancreatico.
3. SINDROME DI GARDNER
Malattia familiare.
Polipi adenomatosi multipli (tv. anche nello stomaco e/o ileo)
+ Osteomi multipli + Cisti cornee + Fibromatosi.
Probabilit di cancerizzazione: altissima (quasi sempre).
4. SINDROME DI TURCOT
Polipi adenomatosi + tumori cerebrali (glioblastoma).
Trasmissione ereditaria recessiva.
Mutazione del gene APC o del mismatch-repair gene.
Adenoma
Colon and rectum tumours
WHO Histological classification
Epithelial tumours
Benign
Tubular
Villous
Tubulovillous
Serrated
5. ADENOMA VILLOSO
- Sessile
- Tv. Perdita di proteine (sindrome
proteinodisperdente)
- Probabilit di cancerizzazione: 30-70%
Adenoma
Colon and rectum tumours
WHO Histological classification
Epithelial tumours
Benign
Tubular
Villous
Tubulovillous
Serrated
Colon and rectum tumours
WHO Histological classification
Polyps
Hyperplastic (metaplastic)
Peutz-Jeghers
Juvenile
6. POLIPO IPERPLASTICO (METAPLASTICO)
Sessile
Piccolo (per lo pi < 5mm)
Molto frequente: nel 30-50% degli adulti.
Non una neoplasia.
Colon and rectum tumours
WHO Histological classification
Polyps
Hyperplastic (metaplastic)
Peutz-Jeghers
Juvenile
7. POLIPO GIOVANILE (DA RITENZIONE)

Solitario
Nei bambini
Tv. autoamputazione
Non una vera neoplasia
7c. SINDROME DI CRONKHITE - CANADA
Non ereditaria.
Polipi giovanili multipli + alopecia, atrofia ungueale, e/o
iperpigmentazione.
Possono insorgere adenomi tubulari e carcinomi colo-rettali.
7b. POLIPOSI GIOVANILE MULTIPLA
Pu essere rischiosa per la vita.
Pu associarsi ad adenomi tubulari ed adenocarcinomi dello
stomaco, duodeno, grosso intestino e pancreas.
Colon and rectum tumours
WHO Histological classification
Polyps
Hyperplastic (metaplastic)
Peutz-Jeghers
Juvenile
9. SINDROME DI COWDEN
Malattia autosomica dominante (mutazione gene PTEN/MMAC1).
Polipi amartomatosi multipli + trichilemmomi faciali, cheratosi
acrale, papillomi orali.
Elevata incidenza di neoplasie in varie sedi.
8. POLIPO DI PEUTZ - JEGHERS
Amartoma.
Nella forma multipla (poliposi di Peutz-Jeghers) pu interessare
anche lo stomaco e il piccolo intestino.
Cancerizzazione dei polipi
Relationship with carcinoma
1) Solitary hyperplastic polyps (which represent the large
majority of epithelial colonic polyps), retention polyps,
and Peutz-Jeghers polyps do not become malignant.
2) Patients with any type of polyposis syndrome are at
increased risk for the development of large bowel
carcinoma. This incidence is extremely high (nearly 100%)
in familial polyposis and Gardner's syndrome; it is lower,
but still increased, in patients with Peutz-Jeghers
syndrome, juvenile polyposis, and hyperplastic polyposis.
3) Villous adenomas can become malignant, in a high
proportion of cases (29% to 70%).
4) Adenomatous polyps can become malignant in about 5%.
The malignant transformation of polyps (so-called
adenoma-carcinoma sequence) has been carefully
documented with chemically induced colorectal tumors
in animals by the demonstration that the morphologic
progression from adenomatous polyp with mild to
moderate to severe atypia ("carcinoma in situ") and to
invasive and metastatic carcinoma is accompanied by
(and presumably caused by) a series of molecular
alterations.
These alterations include the mutational activation of
oncogenes and the inactivation of tumor-suppressor
genes.
It is thought that mutations in at least four or five
genes are required to produce a fully malignant
phenotype. These include activational mutation of the ras
oncogene, mutations of the p53 gene (located on
chromosome 17), deletion of the dcc ("deleted in colonic
carcinoma") gene (located on chromosome 18), and
possibly mutations of the mcc ("mutated on colonic
carcinoma") gene (located on chromosome 5).
In familial polyposis, an additional (and very early)
change is a mutation of the apc (adenomatous polyposis
coli) gene (located on chromosome 5).
Treatment
1) Solitary juvenile polyps. Simple removal is sufficient.
2) Familiar polyposis. Since all untreated patients
eventually develop carcinoma of the colon, colectomy is
indicated even though the patient is young.
3) Villous adenomas. Should be removed in toto; colon
resection is sometimes necessary.
4) Adenomatous polyps. Solitary adenomatous polyps are
routinely removed endoscopically. When several polyps
are present, the patient can be safely managed by
removing these polyps individually rather than performing
a partial or total colectomy.
5) Adenomatous polyp with area of carcinoma.
a) The carcinomatous glands may be present only in the
mucosa and lamina propria above the muscularis mucosae
("carcinoma in situ").
This situation has never been found associated with lymph
node metastases
simple polypectomy
b) They may extend beyond the muscularis mucosae but
not invade the stalk of the polyp ("focal carcinoma")
The incidence of lymph node metastasis is less than 1%.
simple polypectomy (unless the lesion is undifferen-
tiated or is accompanied by obvious vascular invasion).
c) They may extend to the base of the stalk or beyond
("focal carcinoma with stalk invasion").
The possibility of lymph node metastases, although still
relatively low, is probably high enough to justify a

formal bowel resection, especially when the carcinoma
is found in the submucosa of the underlying colonic wall
and/or when it is present at the surgical margin.
Colon and rectum tumours
WHO Histological classification
Epithelial tumours
Malignant
Carcinoma
Adenocarcinoma
Mucinous adenocarcinoma
Signet-ring cell carcinoma
Small cell carcinoma
Squamous cell carcinoma
Adenosquamous carcinoma
Medullary carcinoma
Undifferentiated carcinoma
EPIDEMIOLOGIA
Circa 875.000 casi di carcinoma del colon-retto nel 1996,
rappresentanti l 8.5% di tutti i nuovi carcinomi.

Incidenza (nuovi casi per 100.000 per anno):

- 44 (USA, Australia: et media 62 anni)
- 35.6 Europa occidentale
- 28 Argentina,Cile
- 24.8 Europa orientale ed ex URSS
- 17.5 Brasile
- 13.3 Cina
- 5.7 Africa
- 2.7 Medio Oriente, India, Asia Sud Orientale
EZIOLOGIA
1) Dieta e stile di vita
Fattori di rischio: Alimentazione ipercalorica e vita
sedentaria
Consumo di carne
Fumo e alcool
Fattori protettivi: Consumo di vegetali
Antiinfiammatori non-steroidei
Terapia sostitutiva estrogenica
Attivit fisica
Dieta ricca di fibre (?)
2) Infiammazioni croniche
Colite ulcerosa (incidenza: x20)
Malattia di Crohn (incidenza: x3)

3) Pregressa irradiazione pelvica
4) Pregressa uretero-sigmoidostomia
5) Fattori genetici
elevatissima predisposizione per il carcinoma nella
Poliposi familiare (100%)
Sindrome di Lynch (50%)
Sindrome di Torre-Muir
LOCALIZZAZIONE
About 50% of all carcinomas occur in the rectosigmoid
area, although their relative incidence seems to be
decreasing.
A shift in location toward the proximal colon during the
past few decades has been noted. Right-sided tumors are
said to be more common in the elderly, in blacks, and in
patients with diverticular disease.
Multicentric carcinomas are found in 3% to 6% of the
cases.

ASPETTO MACROSCOPICO
Most colorectal carcinomas can be described as either
polypoid or ulcerative/infiltrating.
Polypoid: a bulky mass with well defined, rolled
margins and a sharp dividing line with the normal bowel.
Ulcerative/infiltrating: has a less elevated
surface and is centrally ulcerated.
A particular variant of this tumor type is referred to as
"flat" or "depressed" carcinoma and is thought to arise de
novo rather than through malignant transformation of an
adenoma.
ASPETTO MICROSCOPICO
Usually is a well to moderately differentiated
adenocarcinoma secreting variable amounts of mucin.
The tumor cells represent a combination of columnar
and goblet cells, with occasional participation of
endocrine cells and the exceptionally Paneth cells.
Often there is an inflammatory and desmoplastic
reaction, particularly prominent at the edge of the tumor.
Most of the inflammatory cells are T lymphocytes, but B
lymphocytes, plasma cell, histiocytes, and S-100
proteinpositive dendritic cells may also be present.
The tumor may be seen invading all the layers of the
bowel and extending into the pericolic fat, permeating
perineurial spaces, and invading veins.
HISTOLOGICAL GRADING
G1
G2
G3
Well differentiated
(glandular structures in >95%)
Moderately differentiated
(glandular structures in 50-95%)
Poorly differentiated
(glandular structures in 5-50%)
G4 Undifferentiated
(glandular structures in <5%)
Mucinous and signet ring cell type
Medullary type
Carcinomas of the large bowel may present with
rectal bleeding, changes in bowel habits (such as
diarrhea alternating with constipation), anemia resulting
from chronic blood loss, and vague abdominal pain.
Intestinal obstruction is common when the tumor is
situated in the left colon and rare for tumors in the cecum
or ascending colon.
One of four cecal carcinomas will present with
signs suggestive of appendicitis.
Perforation may rarely occur, either at the site of
the carcinoma or in the cecum as a result of distention
caused by an obstructing rectosigmoid carcinoma.
Unfortunately, the previously mentioned symptoms
are often indicative of advanced disease.
CLINICAL FEATURES
To detect tumors at an earlier stage,

one can
perform appropriately timed proctosigmoidoscopic
examinations of both men and women over 40 years of
age; such examinations should detect about 50% of the
cases.

Whether routine examination of the entire large
bowel with the fiberscope will prove rewarding as a
screening method remains to be seen.
Routine barium enemas are too expensive and not
entirely without risk.
Guaiac stool examination for occult blood is an
efficient and inexpensive way of detecting cases of early,
asymptomatic carcinoma.
DIAGNOSIS
Carcinoembryonic antigen (CEA) has been
detected in the serum of 72% to 97% of patients with
colorectal carcinoma. It disappears after resection of the
tumor and reappears in the event of recurrence or
metastases. Higher values are found in tumors that have
spread beyond the bowel wall, in poorly differentiated
neoplasms, and in tumors associated with blood vessel,
lymphatic, and perineural invasion.


Elevated circulating levels of CEA also occur in
carcinomas of the stomach, pancreas, breast, and
prostate gland.
Unfortunately, the test is often negative during the
early stages of colorectal carcinoma and is therefore not
a good screening procedure. Its main utility has been in
the monitoring of therapy and in the early detection of
metastases.
CEA can also be detected in the tumor tissue by
immunocytochemistry, radioimmunometric assay, or
enzyme immunometric assay; its ability to discriminate
between normal and carcinomatous tissue is higher than
that of CA 19-9, CA 125, and CA 195, these being other
antigens that have been found to be associated with
colorectal carcinoma.

A novel and very promising screening approach is
that of searching for ras oncogene mutations in the
stools; unfortunately, the test does not distinguish polyps
from carcinoma.
Cytology is of little practical value. In 87 patients
with carcinoma the malignancy was correctly identified in
seventy (80%); the incidence of false positives in 438
patients was 0.45%; however, the technique employed to
obtain the specimenwhich involves extensive cleansing
of the colon followed by a diagnostic enema with
manipulation of the patienthas led to an unenthusiastic
response from clinicians.
Low-lying rectal lesions can be easily sampled.


Brush cytology can also be performed via the
fiberoptic scope. It is a sensitive technique, but it has not
yet found widespread acceptance.
Cytology
A positive biopsy should always be obtained before
radical surgery for colorectal carcinoma is undertaken. It
is imperative that sufficient representative material be
taken.
In large lesions, it is advisable to perform
several biopsies from diverse areas.
Lesions below the peritoneal reflection should be
removed in toto wherever possible to facilitate their
orientation for section by the pathologist. Sometimes is
more difficult (but just as critical) to ascertain the position
and extent. Close communication with the endoscopist
and surgeon, intact biopsy of an adequate size and depth,
and proper orientation of the specimen are essential
requisites for this determination.
Biopsy
IMMUNOISTOCHIMICA
Keratin
Colorectal adenocarcinomas are invariably positive for
keratin (positivity for CK 20 and negativity for CK 7).
CEA
Reactivity for CEA is also the rule; as a matter of fact,
failure to demonstrate CEA in an adenocarcinoma makes
it unlikely that the tumor is primary in the large bowel.
There is good correlation of the immunohistologic pattern
with the serum levels but not with tumor staging or degree
of differentiation.
Tumor-associated glycoprotein (TAG-72), recognized by
MoAb B72.3, is present not only in 100% of invasive
colorectal carcinomas but also in the majority of
hyperplastic and adenomatous polyps and even in normal
mucosa, but with variable pattern of expression.
Another tumor-associated antigen, large external
antigen (LEA), has been identified in the tumor tissue and
sera of colorectal carcinoma cases.
Carcinomas of the large bowel often show loss of blood
group isoantigens and of HLA-A, B, and C expression,
particularly if poorly differentiated and acquire reactivity for
blood group substance H.
Immunoreactivity for the secretory component of
immunoglobulin is seen in about 50% and is particularly
strong in the well-differentiated tumors.
p53 mutations have been detected by molecular
techniques in the majority of colorectal carcinomas. About
half of the tumors show positive staining; regardless of
site, differentiation, or DNA ploidy.
Mutations of the ras oncogene have been found in a
minority of colorectal carcinomas, particularly those in the
metastatic group.
Enhanced expression of the c-myc oncogene occurs in
about 90% of colorectal carcinomas.
The proliferative activity of colorectal carcinoma can be
measured by S-phase determination, staining for Ki-67 or
PCNA, and AgNOR counts. None of these determinations
correlate very closely with microscopic grade, and they
may carry prognostic implications of their own.
Villin, a cytoskeletal protein associated with the axial
microfilament bundles of brush border microvilli, is
consistently expressed regardless of differentiation.
Increased expression of cathepsin B (a lysosomal
cysteine proteinase) is also a feature of these tumors,
particularly in advanced stages of the disease.
Expression of the epithelial-specific adhesion
molecule E-cadherin is closely related to the degree of
tumor differentiation.
A high percentage of colorectal carcinomas are
immunopositive for HCG, particularly mucinous and
poorly differentiated tumors.
Placental alkaline phosphatase (PLAP) has been
detected in about 10% of all colorectal carcinomas.
TNM Clinical Classification
TX
Primary tumour cannot be assessed
T0
Submucosa
T2
Muscularis propria
T3
Tumour invades subserosa or into non-
peritonealized pericolic or perirectal tissues
T4
Tumour directly invades other organs or structures
and/or perforates visceral peritoneum
T4a Tumour perforates visceral peritoneum
T4b directly invades other organs or structures
T - Primary Tumour
No evidence of primary tumour
T1
Tis
Carcinoma in situ: intraepithelial or invasion
of lamina propria
TNM Clinical Classification
N0 No regional lymph node metastasis
N1
Metastasis in 1 to 3 regional lymph nodes
N - Regional Lymph Nodes
NX Regional lymph nodes cannot be assessed
N1a Metastasis in 1 regional lymph node
N1b Metastasis in 2-3 regional lymph nodes
N1c Tumour deposit(s) (satellites) in the
subserosa or in non-peritonealized
pericolic or perirectal soft tissue without
regional lymph node metastasis
TNM Clinical Classification
M0
No distant metastasis
M1
M - Distant Metastasis
MX
Distant metastasis cannot be assessed
N2
Metastasis in 4 or more regional lymph nodes
N2a Metastasis in 4-6 regional lymph nodes
N2b Metastasis in 7 or more regional lymph nodes
Distant metastasis
M1a Metastasis confined to one organ (liver,
lung, ovary, non-regional lymph node(s))
M1b Metastasis in more than one organ or the
peritoneum
STAGE GROUPING(1)
Stage I
Stage II
Stage IIC
T1,T2
T3,T4
T3
T4b
N0
N0
N0
N0
M0
M0
M0
M0
Stage 0
Tis N0 M0
Stage IIA
T4a N0 M0
Stage IIB
STAGE GROUPING(2)
Stage IIIA
Stage IIIB
Stage IIIC
Stage IVA
T1,T2
T1
T3,T4a
T2,T3
T4a
Any T
N1
N2a
N1
N2a
N2a
Any N
M0
M0
M0
M0
M0
M1a
Stage III Any T N1,N2 M0
T4b N1,N2 M0
T1,T2 N2b M0
T3,T4a N2b M0
Stage IVB Any T Any N M1b
Flat carcinomas have a greater tendency for deep
stromal invasion with lymphovascular permeation than
the more common polypoid types.
The most common sites of metastatic involvement
of colorectal carcinoma are regional lymph nodes and
liver. Lymph node metastases are more common in the
tumors showing poorly differentiated areas and a highly
infiltrative pattern of growth.
Liver metastases are more common in the tumors
showing evidence of blood vessel invasion. Other
relatively common metastatic sites include peritoneum,
lung, and ovaries.
Rare metastatic sites include central nervous
system, bone, testis, uterus, and oral cavity.
SPREAD AND METASTASIS
The standard therapy for colorectal carcinoma is
surgical resection:

- ileocolectomy (carcinoma of the cecum or ascending
colon),
- abdominoperineal resection (tumour located below the
peritoneal reflection)
- anterior resection (tumors in other areas)

The current resectability rate for colorectal
carcinoma is 92%, and the operative mortality for
resections for cure is 2%.
TREATMENT
Fulguration, endoscopic transrectal resection, and
fullthickness local excision are acceptable alternative
procedures for rectal carcinomas if the tumor is small,
superficial, and well differentiated and/or if the patient is a
poor candidate for abdominoperineal resection.

The possible role of preoperative or postoperative
irradiation and/or chemotherapy for operable carcinoma
of the large bowel is still questionable.
The 5-year crude survival rate after curative
resection for colorectal carcinoma ranges between
40% and 60% in most large series. Local recurrence
and/or regional lymph node metastases occur in over
90% of the failure cases, and they represent the only
site of tumor in about half of them. A total of 71% of
the recurrences are evident within the first 2 years
and 91% by 5 years.
PROGNOSIS
PROGNOSTIC FACTORS
1. Age. Tumors occurring in very young and very old
patients are associated with a poor prognosis.
2. Sex. The prognosis is significantly better for females
than for males.
3. Location. This factor remains controversial.
4. Multiplicity of tumors. The survival rate for patients
with synchronous or metachronous malignancy of the
large bowel is similar to that for patients with solitary
colorectal carcinoma.
5. Local extent.
6. Size: is not a reliable prognostic indicator.
7. Obstruction.
8. Perforation: is linked to a poor prognosis.
9. Microscopic type and grade. There is a definite
relationship between the microscopic grade of the tumor
and its prognosis. Among the microscopic subtypes,
mucinous carcinoma, small cell carcinoma, and signet
ring carcinoma have a worse prognosis than the ordinary
type of adenocarcinoma.
10. HLA-DR expression. Tumors having strong HLA-DR
expression have the best survival, even within the same
Dukes' stage.
11. Tumor margins. Carcinomas having pushing margins
and an inflammatory infiltrate (plasma cells and
lymphocytes) have a better prognosis.
12. Inflammatory reaction.
13. Vascular and perineurial invasion: negative prognosis.
14. Lymph node involvement.
15. Dukes' staging. The 5-year survival rates are 90% or
higher for Dukes' A, 50% to 65% for Dukes' B, and 15%
to 25% for Dukes' C.
16. DNA ploidy: several studies have shown a correlation
between aneuploidy and risk of recurrence or survival.
17. Cell proliferation.
18. Allelic loss of chromosome 18q: negative prognostic
significance.
19. Oncogene expression. K-ras mutations and
overexpression of the ras p21 protein are associated with
recurrent disease. p53 overexpression was found to be an
independent predictor of survival. Expression of the c-myc
oncogene has been found to correlate with the degree of
differentiation of the tumor.
Colon and rectum tumours
WHO Histological classification
Epithelial tumours
Malignant
Carcinoma
Adenocarcinoma
Mucinous adenocarcinoma
Signet-ring cell carcinoma
Small cell carcinoma
Squamous cell carcinoma
Adenosquamous carcinoma
Medullary carcinoma
Undifferentiated carcinoma
Large lakes of extracellular mucin, mixed with
collections of tumor cells, that constitute at least half of the
tumor mass.
Mucinous tumors usually have an exophytic shape,
comprise 15% of colorectal carcinomas and occur most
commonly in the rectum. In 31% were associated with
villous adenomas, 7% with ulcerative colitis, 8% with colitis,
and 5% with prior pelvic irradiation. Mucinous carcinomas
are also more frequently associated with adenomas and
tend to present at a more advanced stage.


Their prognosis is somewhat worse than for the
conventional type of adenocarcinoma, at least when they are
located in the rectum and/or if they are stage B lesions.
Mucinous carcinoma
Colon and rectum tumours
WHO Histological classification
Epithelial tumours
Malignant
Carcinoma
Adenocarcinoma
Mucinous adenocarcinoma
Signet-ring cell carcinoma
Small cell carcinoma
Squamous cell carcinoma
Adenosquamous carcinoma
Medullary carcinoma
Undifferentiated carcinoma
Rare form of colorectal malignancy that usually
affects young patients.
It usually presents grossly as a diffuse infiltration of
the wall. Microscopically, the tumor grows in a diffuse
fashion, with little if any glandular formation. Most or all of
the mucin is intracellular and displaces the nucleus with a
typical signet ring configuration of the cells.
Metastases tend to develop in lymph nodes, the
peritoneal surface, and the ovary rather than the liver. The
pattern of spread is mainly in the form of peritoneal
dissemination. The prognosis is extremely poor.

The possibility of the colorectal lesion representing a
metastasis from a gastric primary lesion should always be
investigated.
Signet-ring cell carcinoma
Colon and rectum tumours
WHO Histological classification
Epithelial tumours
Malignant
Carcinoma
Adenocarcinoma
Mucinous adenocarcinoma
Signet-ring cell carcinoma
Small cell carcinoma
Squamous cell carcinoma
Adenosquamous carcinoma
Medullary carcinoma
Undifferentiated carcinoma
Tumor having a microscopic appearance similar to
that of its pulmonary homonym, with few M.E. dense-core
secretory granules in the cytoplasm, and IHC positivity
for neuron-specific enolase and other endocrine markers,
such as synaptophysin.


The entire tumor may have this appearance, or
there may be foci of glandular or squamous. Most small
cell carcinomas of the large bowel are located in the right
colon.
The prognosis is poor, with early metastases to
lymph nodes and liver.
Small cell carcinoma
Colon and rectum tumours
WHO Histological classification
Epithelial tumours
Malignant
Carcinoma
Adenocarcinoma
Mucinous adenocarcinoma
Signet-ring cell carcinoma
Small cell carcinoma
Squamous cell carcinoma
Adenosquamous carcinoma
Medullary carcinoma
Undifferentiated carcinoma
Colon and rectum tumours
WHO Histological classification
Epithelial tumours
Malignant
Carcinoma
Adenocarcinoma
Mucinous adenocarcinoma
Signet-ring cell carcinoma
Small cell carcinoma
Squamous cell carcinoma
Adenosquamous carcinoma
Medullary carcinoma
Undifferentiated carcinoma
Squamous differentiation may be present in
colorectal carcinoma; this is more common in cecal
neoplasms but may be seen in any other area of the large
bowel.
In most instances, the squamous component is
associated with glandular elements (adenosquamous
carcinoma) but occasionally it is seen in a pure form
(squamous cell carcinoma).
An association has been noted between squamous
changes in colorectal carcinoma and ulcerative colitis. For
the squamous tumors located in the low rectum, the
alternative possibility of upward extension or submucosal
metastasis from a carcinoma of the anal canal should be
considered.
Adenosquamous carcinoma
Colon and rectum tumours
WHO Histological classification
Epithelial tumours
Carcinoid
EC-cell, serotonin-producing neoplasm
Others
L-cell, glucagon-like peptide and
PP/PYY producing tumour
Mixed carcinoid-adenocarcinoma
Others
(well differentiated endocrine neoplasm)
Carcinoids are more common in the rectum.
In the colon they tend to be large, extend
deeply through the wall of the bowel, and involve the
regional lymph nodes.
In the rectum, they are often located in the
anterior or lateral wall. Most measure less than 0.5
cm in diameter. Only very few, larger than 2 cm, are
associated with lymph node metastases. Rectal
carcinoids have been reported in bowels affected by
ulcerative colitis or Crohn's disease and were
multicentric. They have also been reported in
association with ovarian carcinoid.
Colorectal carcinoids are practically never
associated with the carcinoid syndrome.

Grossly, carcinoid may appear as a flat and
slightly depressed plaque or as a polypoid lesion.
One of its most distinctive features is the yellow
color that it acquires after formalin fixation.
.
Microscopically, invasion of the stroma by
small uniform cells growing in a ribbon or festoon
fashion is seen. A minor tubular and/or acinar
component associated with mucin production may
also be present.
Argentaffin and argyrophil reactions are said
to be usually negative, but consistently positive
Grimelius stain has been reported by several
authors.
Immunocytochemically, they stain for the
panendocrine markers (neuron-specific enolase
(NSE), chromogranin, synaptophysin) and for a variety
of peptide hormones. The most common are
somatostatin, glucagon, substance P, and peptide YY
(usually absent in other sites), but gastrin-
colecystokinin, calcitonin, pancreatic poly-peptide,
and motilin have also been demonstrated.
Many of the tumors are polyhormonal.
Rectal carcinoids may also be positive for
CEA, HCG, and prostatic acid phosphatase (PAP).
The PAP positivity is of practical importance
because metastatic prostatic carcinoma may be
suspected; however carcinoid is consistently
negative for prostatic specific antigen.
Rectal carcinoid tumors smaller than 2 cm and
limited to the mucosa or submucosa are best treated by
local excision; those of larger size and/or exhibiting
invasion of the muscularis externa need radical surgery,
in view of their propensity for lymph node involvement.
In one study, all of the 19 nonmetastasizing
carcinoid tumors showed a diploid pattern by flow
cytometry, whereas all three metastasizing tumors were
aneuploid. If this remarkable correlation is confirmed,
DNA ploidy analysis may become important in this
situation to decide on the extent of the operation.
TREATMENT AND PROGNOSIS
ASPETTI CLINICI DELLA SINDROME DA
CARCINOIDE
1. Disturbi vasomotori
Flushes cutanei e cianosi evidente (nella maggior parte dei pazienti)
2. Ipermotilit intestinale
Diarrea, crampi, nausea, vomito (nella maggior parte dei pazienti)
3. Attacchi asmatici broncocostrittivi
Tosse, sibili, dispnea (in un terzo dei pazienti)
4. Epatomegalia
nodulare, correlata a metastasi epatiche (in alcuni pazienti)
5. Fibrosi sistemica

Interessamento cardiaco
Ispessimento e stenosi valvolare tricuspidale e polmonare
Fibrosi endocardiaca, principalmente nel ventricolo destro
(nei carcinoidi bronchiali interessato quello sinistro)
Fibrosi retroperitoneale e pelvica
Placche collagene della pleura e dellintima
dellaorta

Leiomyoma
Gastrointestinal stromal tumour
Leiomyosarcoma
Angiosarcoma
Kaposi sarcoma
Malignant melanoma
Others
Non-epithelial tumours
Colon and rectum tumours
WHO Histological classification
Lipoma

Lipoma

Gastrointestinal stromal tumour
Leiomyosarcoma
Angiosarcoma
Kaposi sarcoma
Malignant Melanoma
Others
Non-epithelial tumours
Leiomyoma
Colon and rectum tumours
WHO Histological classification

Lipoma
Leiomyoma
Gastrointestinal stromal tumour

Angiosarcoma
Kaposi sarcoma
Malignant Melanoma
Others
Non-epithelial tumours
Leiomyosarcoma
Colon and rectum tumours
WHO Histological classification

Lipoma
Leiomyoma
Gastrointestinal stromal tumour

Angiosarcoma
Kaposi sarcoma
Malignant melanoma
Others
Non-epithelial tumours
Leiomyosarcoma
Colon and rectum tumours
WHO Histological classification

Lipoma
Leiomyoma
Gastrointestinal stromal tumour

Angiosarcoma
Kaposi sarcoma
Malignant Melanoma
Non-epithelial tumours
Leiomyosarcoma
Colon and rectum tumours
WHO Histological classification
Others
Colon and rectum tumours
WHO Histological classification
Malignant Lymphomas
Marginal zone B-cell lymphoma of MALT type
Burkitt lymphoma
Others
Diffuse large B-cell lymphoma
Burkitt-like / atypical Burkitt-lymphoma
Mantle cell lymphoma
Malignant lymphomas are less frequent than in
the small bowel or stomach. Some of the cases of
large bowel lymphoma have been seen in renal
transplant recipients or in patients with ulcerative
colitis. These tumors can occur at any level of the
colorectum.
Grossly, they may produce prominent
mucosal folds, prominent ulceration, a large mass,
or a solitary polyp, multiple small polyps distributed
throughout the colorectum that may also extend to
the small bowel ("lymphomatous polyposis").
The regional lymph nodes are involved in
about half of the cases.
They are nearly always of non-Hodgkin's type;
the large cell and small cell types are the
predominant varieties.
The low-grade tumors have features similar to
the group of MALT lymphomas. They often show
evidence of plasmacytic differentiation; when this is
extensive and associated with abundant
immunoglobulin production (and occasionally also
with amyloid deposits), the designation of
plasmacytoma has sometimes been used for them.
The MALT concept
Mucosa-associated lymphoid tissue (MALT) is the
term proposed by Isaacson et al. for the component of
the immune system that has evolved to protect the
freely permeable surface of the gastrointestinal tract
and other mucosal membranes directly exposed to the
external environment.
This comprises lymphoid nodules (which in the
ileum form the Peyer's patches), lymphocytes and
plasma cells in the lamina propria, and intraepithelial
lymphocytes.
The lymphomas arising from it ("MALTomas") have
propensity to involve other mucosal sites, which has
been explained by the normal homing pattern of MALT
lymphocytes.
Lymphomatoid polyposis, which is nearly
always composed predominantly of small cleaved
cells and represents the colorectal manifestation of
mantle cell lymphoma, may evolve into a high-grade
lymphoma.
Other reported types of colorectal
hematolymphoid malignancies include mantle cell
lymphoma, anaplastic large cell lymphoma, AILD like
lymphoma, and true histiocytic lymphoma.
Colon and rectum tumours
WHO Histological classification
Secondary tumours
Metastatic tumors occur as a part of a disse-
minated process.
These tumors form disk-like areas in which
there is a central area of ulceration; the normal
mucosa extends to the ulcer, giving indirect
evidence that the metastatic focus began in the
submucosa. This phenomenon is particularly
common in malignant melanoma and primary
carcinoma of the lung.
Prostatic carcinoma can extend into the
rectum and simulate a primary rectal neoplasm.
PSA positive immunostaining in prostate
carcinoma allows the differential diagnosis.