Benign tumors of the large intestine

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Benign tumors of the large intestine

• Barbara Górnicka

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WHO histological classification of the colon
tumours

• Epithelial
• Benign
• adenoma (tubular, villous, tubolovillous,
  serrated)
• intraepithelial neoplasms (low grade, high grade)
• Malignant
• carcinoma
• endocrine neoplasms (carcinoids)
• carcinomas with endocrine differentiation
• Nonepithelial

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Polyp

• The term polyp designates only characteristic
  shape of tumor. These are tumours projecting into
  the lumen of the gut
• non-neoplastic polyps are formed as a result of
  abnormal maturation, inflammation or architecture
• neoplastic polyps as the result of proliferation
  and dysplasia within the epithelium
• Some polyps are caused by submucosal or mural
  tumors

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Non-neoplastic polyps

• 90 of all epithelial polyps in large
  intestine are found in more than 50 of all
  people over 60 years of age
• Hyperplastic (metaplastic) polyps
• Hamartomatous polyps
• -Juvenilie polyps
• -Peutz-Jeghers polyps
• Reactive polyps
• -Inflammatory polyps
• -Lymphoid polyps

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Hyperplastic (metaplastic) polyps

• The focus of epithelial dysmaturation (neither
  the term hyperplastic nor metaplastic are
  entirely suitable)
• Migration of maturing cells from the
  proliferative zone is slowed down and the crypt
  cells show premature or inappropriate
  cytoplasmatic maturation
• Ras mutation

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Hyperplastic (metaplastic) polyps

• The commonest polyps in the colon (more than half
  of them in the rectosigmoid)
• Small (usually lt5mm), smooth, nipple-like
  protrusion, often multiple
• Histological def mucosal excrescence
  characterized by elongated, serrated crypts lined
  by non-neoplastic epithelial cells, most of them
  show mature goblet-cell and absorbtive cell
  differentiation. The luminal surface of such
  crypts has a saw-tooth outline

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Hyperplastic polyp

• Mi Large, irregular, elongated crypts lined by
  crowded epithelial cell. Small, regular, round
  nuclei located at the base of the cells.
  Prominent mucin vacuoles in the cytoplasm
  (usually larger than in normal goblet cells).
  Proliferative zone shows increased cellularity
  and mitotic activity without dysplasia/atypia

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Hyperplastic polyp
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Hyperplastic polyp

• Non-neoplastic with no malignant potential
• Within large polyps (rarely) we can find
  dysplastic foci (adenomatous changes) serrated
  adenoma.

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Hyperplastic polyposis

• At least 5 HP proximal to the sigmoid colon of
  which 2 are greater than 10mm
• Any number of HP proximal to the sigmoid colon in
  an individual who has a first degree relative
  with hyperplastic polyposis
• More than 30 HP of any size distributed
  throughout the colon

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Hyperplastic polyposis

• Some polyps can contain foci of intraepithelial
  neoplasia serrated adenomatous polyposis
  precancerous lesion
• We see synchronicity of hyperplastic polyposis
  and colorectal carcinoma

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Non-neoplastic polyps

• Hyperplastic (metaplastic) polyps
• Hamartomatous polyps
• -Juvenile polyps
• -Peutz-Jeghers polyps
• Reactive polyps
• -Inflammatory polyps
• -Lymphoid polyps

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Hamartomatous polypsJuvenile polyp

• Hamartoma focal overgrowth of cells or tissues
  native to the organ in which it occurs. Although
  the cellular elements are mature and identical to
  those found in the normal organ, they do not
  reproduce the normal architecture of the
  surrounding tissue.
• Juvenile polyp non-neoplastic epithelial polyp
  composed of tissues indigenous to the site of
  origin, but arranged in a haphazard manner

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Juvenile polyp

• Children lt5, mostly in the rectum. In colon in
  adults retention polyps
• Ma Solitary, large (1-3cm in diameter), smooth
  or slightly lobulated, with a red head and a
  narrow stalk, often eroded, the cut surface
  typically shows mucin containing cystic spaces
• Clinical signs bleeding, autoamputation and
  prolapse through the anus

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Juvenile polyp

• Mi Dilated or cystic tubules lined with normal
  epithlium (with mucin production) embedded in an
  excess of lamina propria. Ulceration. Within the
  stroma purulent inflammation. Without
  dysplasia.
• No malignant potential
• DD Inflammatory polyps, reactive changes due to
  inflammation may be easily confused with dysplasia

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Juvenile polyposis syndrome

• Autosomal dominant inheritance
• Numerous polyps of the juvenile type in the large
  bowel, sometimes in the small bowel and stomach
• Rare form occurs in infancy
• May be associated with congenital defects
  including abnormalities of the cranium and heart,
  cleft palate, polydactyly and malrotation
• Can show dysplasia 30 mild, 15 moderate, 2
  severe
• Malignant transformation?

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Cowdens syndrome

• A variant of juvenile polyposis
• Gastrointestinal and cutaneous hamartomas
• Proliferative lesions of the breast. Women have a
  30 to 50 risk of developing breast cancer by
  the age of 50
• Proliferative lesions of the thyroid especially
  follicular carcinoma

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Cronkhite-Canada syndrome

• Gastrointestinal polyposis (hamartomatous or
  inflammatory). Mi polypoid hypertrophy of the
  mucosa without ulceration, lamina propria is very
  oedematous but shows only a small increase in
  inflammatory changes, glands are dilated and
  lined with flat epithelium (without dysplastic
  changes) with excessive production of mucin
• This hyperproduction of mucin is the cause of
  excessive protein loss and severe electrolyte
  disturbances
• Ectodermal changes alopecia, hyperpigmentation
  of the skin, atrophy of the nails

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Hamartomatous polypsPeutz-Jeghers polyp

• Single or multiple in the Peutz-Jeghers syndrome
• Ma large (up to 5cm in diameter), pedunculated
  with a firm lobulated contour
• Mi a central core of smooth-muscle that shows
  tree-like branches covered by the normal mucosa.
  Lack of cytological atypia and presence of all
  the normal cell types

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Peutz-Jeghers polyp
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Peutz-Jeghers syndrome PJS

• Is inherited with an autosomal dominant pattern
• Gastrointestinal polyps (anywhere in the gut but
  most commonly in the small intestine) and
  hyperpigmentation (typically around the mouth
  other locations fingers, palms and feet, buccal
  mucosa and the anal region)

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Peutz-Jeghers syndrome PJS

• The question whether or not the PJS is a
  precancerous lesion? is difficult to resolve.
• Intraepithelial neoplasia (though uncommon) has
  been described in PJS
• Carcinomas of the gut (particulary in gastric and
  duodenal polyps) may occur in contiguity with PJ
  polyps
• A predisposition to cancer of other organs
  ovary, uterine cervix, testis, pancreas, breast,
  lung

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Non-neoplastic polyps

• Hyperplastic (metaplastic) polyps
• Hamartomatous polyps
• -Juvenilie polyps
• -Peutz-Jeghers polyps
• Reactive polyps
• -Inflammatory polyps
• -Lymphoid polyps

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Inflammatory polyps (pseudopolyposis)

• In any chronic inflammatory diseases CD, UC,
  ischaemic bowel diseases, schistostomiasis.
• Ma multiple finger-like projection or solid
  masses
• Mi varying proportions of reactive epithelium,
  inflamed granulation tissue and fibrous tissue

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Lymphoid polyps

• These result from aggregates of reactive
  mucosa-associated lymphoid tissue with
  conspicuous germinal centres located in the
  mucosa and submucosa
• It is a normal variant because the mucosa
  contains intramucosal lymphoid tissue

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Neoplastic polyps

• Adenomas
• Tubular
• Villous
• Tubulovillous
• Serrated
• Dysplasia (intraepithelial neoplasia) is
  necessary to diagnose adenomas
• 20-30 before the age of 40, 40-50 after the age
  of 60

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Precursor lesions

• Aberrant crypt foci ACF only in microscopic
  examination. One single crypt is enlarged lined
  with thickened epithelium with reduced mucin
  content. Cells are dysplastic. Progression from
  ACF through adenoma to carcinoma characterizes
  carcinogenesis in the large intestine

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Aberrant crypt focus
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Adenomas

• Adenomas arise as a result of epithelial
  proliferative dysplasia, which may range from
  mild to so severe as to constitute carcinoma in
  situ. Furthermore such lesion can lead to
  invasive colorectal adenocarcinoma
• Adenomas are precusor lesions for
  adenocarcinomas

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Adenomas

• Macroscopic picture
• Elevated from pedunculated with a long stalk to
  those that are sessile
• Without polypoid lesion (flat or depressed) foci
  with dysplastic changes

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Tubular adenomas

• 50 single
• Rather small lt2cm
• Ma sessile or pedunculated
• Polypoid lesion with proliferation of dysplastic
  glandular structures
• Various degrees of dysplasia

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Villous adenoma

• Larger, up to 10cm in diameter
• Ma cauliflower-like masses projecting to the
  lumen
• Mi villiform projection covered by dysplastic
  epithelium and dysplastic proliferation of glands.

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Pedunculated villous adenoma
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Villous adenoma
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Adenomas/carcinomas

• The malignant risk is depended on polyp size,
  histologic type and severity of epithelilal
  dysplasia
• Cancer is rare in tubular adenoma lt1cm
• High risk of cancer in sessile villous adenomas
  gt4cm
• Severe dysplasia is connected with high risk of
  malignant transformation and often is found in
  villous adenomas

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Adenoma/carcinoma

• Severe dysplasia (high grade intraepithelial
  neoplasia, ca in situ) has no ability to
  metastasize and is still benign lesion
• Because lymphatic channels are absent in lamina
  propria of the mucosa intramucosal carcinoma has
  little or no metastatic potential
• By crossing the muscularis mucosae into he
  submucosal layer invasive adenocarcinoma is a
  malignant lesion with metastatic potential

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Adenoma/carcinoma
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Familial adenomatous polyposis FAP

• Autosomal dominant disorder caused by germline
  mutation in APC gene located on the long arm of
  chromosome 5 (5q21-22)
• 100-2500 adenomas in colon and elswhere in the
  gut
• Mostly tubular, some villous

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FAP macroscopic picture
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Familial adenomatous polyposis FAP

• Almost always progression of one or more
  colorectal adenomas to cancer
• The mean age of cancer development about 40 (but
  it can be in younger people, even in children)
• Cancer preventive treatment Prophylactic
  colectomy

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Variants of FAP

• Gardner syndrome FAP multiple osteomas,
  epidermal cysts and fibromatosis. Less frequent
  abnormality in teeth, higher frequency of
  duodenal and thyroid cancer
• Turcot syndrome FAP tumours of central nervous
  system, mostly gliomas

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Malignant tumors of the large intestine

• Barbara Górnicka

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WHO histological classification of the colon
tumours

• Epithelial
• Benign
• adenoma (tubular, villous, tubolovillous,
  serrated)
• intraepithelial neoplasms (low grade, high grade)
• Malignant
• carcinoma
• endocrine neoplasms (carcinoids)
• carcinomas with endocrine differentiation
• Nonepithelial

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Colorectal carcinoma

• Def The malignant epithelial tumor of the colon
  or rectum
• It is one of the most common form of malignant
  disease

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Histopathology

• Def Carcinoma with invasion the submucosa
• Only tumors that have penetrated through
  muscularis mucosae into submucosa are considered
  malignant
• Lesions with the morphological characteristic of
  adenocarcinoma confined to the epithelium (ca in
  situ) or invade the lamina propria alone
  (intramucosal carcinoma) have virtually no risk
  of metastasis

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Histopathology

• High-grade intraepithelial neoplasia is more
  appropriate term than adenocarcinoma in situ
• Intramucosal neoplasia is more appropriate term
  than intramucosal adenocarcinoma
• Use of this term helps to avoid overtreatment

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Adenoma/carcinoma
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Epidemiology

• About 875 000 cases of new cancer worldwide in
  one year
• 8.5 of all new cancer
• The incidence varies greatly around the world
  high rates in developed countries of Europe,
  North and South Americe, Australia and lower
  rates in developing coutries of Asia or Africa

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Epidemiology

• In USA the incidence rate increase by 18 in
  period 1973 87 and in last 20 years is
  relatively constant. In Singapore, by contrast,
  thie rate is rising rapidly (probably due to the
  acquisition of a western lifestyle)
• MgtF
• Incidence increase with age

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Etiology

• Diet and lifestyle highly caloric food rich in
  animal fat, meat consumption, smoking alkohol,
  lack of vegetables, sedentary lifestyle
• Chronic inflammation
• -UC risk to develope carcinoma 15 (more than
  half of the colon with UC), 5 - left side
  colitis. Ulcerative poctitis is not associaed
  with an increased carcinoma risk
• -CD The risk appears to be 3 fold above
  normal
• -Irradiation

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Precursor lesions

• Aberrant cryt foci
• Adenomas (villous, gt4cm, with high grade
  dysplasia), FAP

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Precursor lesions

• Peutz-Jeghers polyposis
• Ulcerative colitis
• Crohn disease
• Genetic syndromes FAP, Hereditary nonpolyposis
  colorectal cancer HNPCC (Lynch syndrome),
  Li-Fraumeni syndrome

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Hereditary nonpolyposis colorectal cancer HNPCC
(Lynch syndrome)

• Autosomal dominant disorder
• High risk developing colorectal carcinoma
  (70-85) in an early age, often multifocally
• 50 of patients have endometrial carcinoma
• 15 have other cancers renal pelvis/ureter,
  stmach, small bowel, ovary, brain, hepatobiliary
  tract, sebaceous tumors (Muir-Torre syndrome).

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Localization

• 38 - cecum and ascending colon (right side)
• 35 - sigmoid (left side)
• 18 - transverse colon
• 8 - descending colon
• 1 - multiple sites

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Clinical features

• Asymptomatic for years
• Clinical signs depends on the location and size
• Left side cancers growth with annular pattern and
  produce obstructive syndrome may produce occult
  bleeding, changes in bowel habit,
  left-lower-quadrant discomfort
• Right side cancers growth exophytic (the lumen of
  cecum has large caliber) obstructive syndrome
  are rare. Occult bleeding iron-deficiency
  anemia, weakness and weght loss.

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• IRON DEFICIENCY ANEMIA IN AN OLDER MAN MEANS
  GASTROINTESTINAL CANCER UNTIL PROVEN OTHERWISE

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Macroscopic picture

• Exophytic/intraluminal growth (proximal colon)
• Endophytic/ulcerative intramural growth
  (transverse and descending colon)
• Diffuse infiltrative, annular growth with
  circumferential involvement of corectal wall and
  constriction the lumen (sigmoin cancers)

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Histopathological types

• Adenocarcinoma intestinal type
• Mucinous adenocarcinoma (with pools of
  extracellular mucin)
• Signet ring cell carcinoma
• Adenosquamous carcinoma
• Medullary carcinoma (with prominent infiltration
  by intraepithelial lymphocytes)
• Undifferentiated carcinoma
• Small-cell carcinoma (endocrine)

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Adenocarcinoma intestinal type
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Grading

• Colorectal adenocarcinomas are
  gradedpredominantly on basis of the extent of
  glandular appearances
• G1 well differentiated glandular structures
  ingt95 of the tumor
• G2 moderatly differentiated glandular structures
  in 50-95 of the tumor
• G3 poorly differentiated glandular structures in
  5-50 of the tumor
• G4 undifferentiated glandular structures in lt5
  of the tumor

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Staging T
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Prognostic factors

• Prognosis is depended on
• Type of growth (sessile and ulcerated)
• Depth of invasion
• Histological type
• Grading
• Nodal metastases
• Distant metastases

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Prognosis

• The most important prognostic factor is the
  extent of he tumor at the ime of diagnosis
• Staging systems TNM, Astler Coller, Dukes.

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Endocrine tumors of the colon

• Most common in rectum (more than 50)
• Age gt70years
• Non specyfic clinical syndrome, only 5 of
  patients have carcinoid sydrome
• Potentially malignant tumors behavior cerrelates
  depth of penetration and size

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Endocrine tumors

• Well differentiated endocrine neoplasm (tumor)
  monotonously similar cells with scant cytoplasm
  and oval to round nuclei. Minimal atypia. Cells
  may form islands, trabecules, strands, glands or
  sheets

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Well differentiated endocrine neoplasm
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Endocrine tumors

• Endocrine carcinoma (large cell) with
  histological features of malignancy (atypia,
  mitoses)
• Small cell carcinoma (poorly differentiated
  endocrine carcinoma) like in the lung