Tumors of large intestine- both benign and most common malignant have been covered.

1. LARGE INTESTINAL
TUMORS
DR.Navleen kaur
3rd year Pathology resident
AIMSR, Bathinda

2. Lesson plan
 Anatomy of intestine
 Normal histology
 Classification
 Polyps
 Ca colon
 Other types
 Appendix

9. NORMAL HISTOLOGY OF COLON

10. Epithelium-lined by absorptive colonocytes, goblet cells, endocrine
cells and paneth cells.
Goblet cells

11. Fetal colon
meconium

12. NORMAL HISTOLOGY OF RECTUM
AND ANAL CANAL

13. Definitions of histological
abnormalities
 Normal colorectal crypts are straight, parallel
and extend from immediately above the
muscularis mucosae to the surface.
 Crypt distortion: implies non-parallel,
variable diameter or cystically dilated crypts
as opposed to the normal 'test-tube rack'
appearance.

14. WHO CLASSIFICATION OF TUMORS
OF COLON AND RECTUM
 EPITHELIALTUMORS
 Adenoma
Tubular
Villous
Tubulovillous
 Dysplasia(IEN), low grade
 Dysplasia, high grade

15.  Serrated lesions
Hyperplastic polyps
Sessile serrated polyp
Traditional serrated adenoma
 Hamartomatous
Cowden-associated polyp
Juvenile polyp
Peutz-Jeghers polyp

16. CARCINOMAS
 Adenocarcinoma
 Other types

17. MESENCHYMAL TUMORS
 Lipoma
 Leiomyoma
 Gastrointestinal stromal tumor
 Leiomyosarcoma
 Angiosarcoma
 Kaposi sarcoma

18. Lymphomas
 B-cell lymphoma,unclassifiable
 Burkitt lymphoma
 Diffuse large B-cell lymphoma
 Mantle cell lymphoma
 Marginal zone lymphoma of mucosa-
associated lymphoid tissue(MALT)
 Secondary tumors

19. POLYPS
 Definition:The term polyp refers to any
circumscribed mucosal growth either flat,
depressed, sessile or pedunculated.

20. adenomas
 Tubular adenoma – distributed regularly
throughout the large bowel with 40 % in right
colon, 40 % left colon and 20 % in rectum.
 Blacks>whites.
 Assymptomatic, but can result in bleeding.

21. Gross
 < 1cm.
 Sessile/peduncul
ated
 Single/multiple
 Knob-like
projections can
be seen.

22. Microscopy
 in number of
glands and cells
per unit area
confined to
normal mucosa.
 Disorganized
glands, Cells are
crowded,
enlarged with
hyperchromatic
nuclei

23. Villous adenoma
 Infrequent type
of polyp,single,
sessile, larger
than tubular.
 Very soft in
consistency, can
be missed on
DRE.

24. microscopy
 A villous adenoma is shown at its edge on the left,
and projecting above the basement membrane at
the right. The cauliflower-like appearance is due to
the elongated glandular structures covered by
dysplastic epithelium

25. Tubulovillous adenoma
 Polyps in which adenomatous and villous
components are present in approximately
equal amounts are referred to as
Villoglandular polyps,Tubullovillous
adenomas or papillary adenomas.
 TVAs are considered to have a higher risk of
malignant transformation than tubular
adenomas

27. tubular component - left of image,
villous component - right of image

28. HYPERPLASTIC POLYPS
 Colonic hyperplastic polyps are benign
epithelial proliferations that are typically
discovered in 6th and 7th decades of life.
 Site- most common in left colon and <5mm in
diameter.
 Pathogenesis- decreased epithelial turnover
and delayed shedding of surface epithelial
cells, leading to “piling up” of goblet and
absorptive cells.

29. Clinical significance
 They must be distinguished from sessile
serrated adenomas, which are histological
similar and have malignant potential.

30. Hyperplastic polyps
Gross- < 5 mm in diameter
left colon
small,sessile
 Microscopy- 1)mature goblet and absorptive cells.
 2)irregular tufting of epithelial cells.
 3)epithelial overcrowding serrated
architecture.

31. Hyperplastic polyp
GROSS
MICROSCOPY

32. Sessile serrated adenomas
 Histologically similar to hyperplastic polyp
but has malignant potential.
 Commonly found in right colon.
 Serrated architecture is present throughout
the full length of the glands, including crypt
base and leads to its dilatation.

34. Hamartomatous polyps
 1.juvenile polyps
 2.cowden associated
 3.peutz-jeghers polyp
 4.Bannyan –Riley syndrome
Hamartomas are tumor-like growth comprised
of mature tissues that are normally present at
the site in which they develop.

35. Juvenile polyps
 Sporadic/syndromic
 Site-rectum
 Age -<5 yrs
 C.F- Rectal bleeding
 Pathogenesis- associated with mutations in
SMAD 4 and also in BMPR1A.

36. GROSS
 <3 cm in diameter.
 Pedunculated, smooth, reddish lesion
 C/S –lattice like appearance

37. MICROSCOPIC PICTURE
 Surface ulceration
with granulation
tissue
 Beneath, cystically
dilated glands filled
with mucus,
inflammatory debris
 Inflammed &
edematous stroma

38. Cowden syndrome
 Autosomal dominant hamartomatous polyp
syndrome.
 Loss of function mutation in PTEN mutation
 Macrocephaly, intestinal hamartomatous
polyp,benign skin tumors.

39. Bannyan Riley Syndrome
 Similar to cowden syndrome
 But has mental deficiencies & development
delays
 Less incidence of neoplasia than cowden
syndrome.

40. Cronkhite Canada syndrome
 Non-hereditary sundrome
 >50 yrs
 Hamartomatous polyps of stomach, small
intestine & colorectum that are
histologically indistinguishable from juvenile
polyps.
 50 % cases are fatal

41. Peutz Jeghers syndrome
 Autosomal dominant syndrome
characterized by:
1) Multiple hamartomatous polyps
in the GI tract.
2) Muco-cutaneous pigmentation .
3) Increased risk of various GI and
non GI malignancies.

42. Pathogenesis
 Germline mutation in gene LKB1/STK11
 Site- most common in small intestine but can
occur in stomach and large intestine.
 Lobulated with dark head,absent stalk
 Size- 5-50mm

43. Microscopy- central core of smooth muscle
that shows tree like branching.

44. Familial adenomatous polyposis
(FAP)
 It is the most common adenomatous
polyposis syndrome.
 An autosomal dominant disorder
characterized by the early onset of
numerous adenomatous polyps throughout
the colon.

45.  Incidence- 1 per 7000 and 1 per 30,000
newborns.
 Age group- between 10 and 20 years
 Site- more common in sigmoid colon and
rectum
 Clinical features- obstruction and rectal
bleeding

48. A.Colectomyspecimensfrompatientswithfamilialadenomatouspolyposis.A Hundredsof
polyps of differentsize covertheentiremucosalsurface.
BMultipleadenomasindifferentstagesof development.
C Lateralviewof polyps.D Numeroussmall early (sessile)adenomas.

49. Pathophysiology
 90% of cases of classic FAP are caused by
germline mutation of APC.
 PC (adenomatous polyposis coli) is a tumor
suppressor gene involved in cell cycle control
and downregulation of beta-catenin through
theWnt signaling pathway
 The APC protein is normally involved in
apoptosis of colonic epithelial cells

50. APC-β Catenin pathway

51. Diagnostic criteria:
 100 or more colorectal adenomatous polyps, or
 Germline mutation in APC or
 Family history of FAP with colorectal adenomas
(age < 30) or
 Family history of FAP and presence of at least
one epidermoid cyst, osteoma or desmoid tumor

52.  Patients with a history of > 10 colorectal
adenomas, a family history of adenomatous
polyposis syndromes or a history of
adenomas with FAP type extracolonic
lesions should undergo assessment for
adenomatous polyposis syndrome.
 Histological confirmation requires
examination of several polyps.

53. Adenoma involving few crypts

54. Tubular adenoma polyp, FAP patient

55.  Colorectal adenocarcinomas develops
in 100% patients of untreated FAP patients,
often before age 30 and nearly always by age
50.

57. COLORECTAL CARCINOMA
 Adenocarcinoma – the most common
Gastro-intestinal malignancy
 Incidence(as shown in next slide)
 Age group - 60-70 years
 Males > females

59. Etiology
 Decrease in fibre diet.
 Decrease intake of vitamins- A,C,E.
 Increase in fat intake.
 Drugs like NSAID’s play a protective role

60. pathogenesis
 Ca Colon development = genetics!!!!
 It can arise in 2 settings
1) Mutations as seen in FAP, leading to
Adenocarinoma via APC-β Catenin pathway
2) MSI pathway leading to HNPCC.

61. 2) APC-β Catenin pathway

62. Pathogenesis

63. 2) Microsatellite instability pathway-
seen in patients with DNA mismatch repair
gene
Normally, when there is abnormal basepairing=
DNA repair genes come & try to correct the
mismatch
But when there is no mismatch repair gene
Accumulation of abnormal DNA
Carcinogenesis

64. Genes affected(DNA mismatch repair
are)-
 MLH1
 MSH2

65.  Clinical features – rectal bleeding
altered bowel habits
abdominal pain

66.  Anemia of chronic blood loss
 If a post-menopausal women or elderly
male comes with Iron deficiency anemia,
think of colorectal CA.
 INTESTINAL OBSTRUCTION -if left side
colon is involved.


68. MORPHOLOGY
 Common site- rectosigmoid region
 Types of growth-
 Right colon- polypoidal
 Left colon- napkin ring constriction
 c/s- grey white

71. MICROSCOPY
 Usually well or moderately differentiated
gland forming carcinoma with marked
desmoplasia, particularly at edge of tumor
 Glands often filled with necrotic debris ("dirty
necrosis"), in both primary and metastatic
sites
 Inflammatory cells and scattered
neuroendocrine cells are common

72.  Well differentiated:
 15% - 20% of all carcinomas
 Well formed glands or simple tubules with uniform,
basally oriented nuclei
 Somewhat resembles adenomatous epithelium
 Moderately differentiated:
 60% - 70% of all carcinomas
 Tubules may be simple, complex or slightly irregular
 Nuclear polarity lost
 Poorly differentiated:
 15% - 20% all of carcinomas
 Less than 50% gland formation
 Majority of tumor (excluding advancing edge) consists
of sheets of cells without gland formation
 Usually right sided

74. Moderately differentiatd
adenocarcinoma

76. Other microscopic types
 Cribriform comedo-type carcinoma
 Medullary carcinoma
 Micropapillary carcinoma
 Mucinous
 Serrated adenocarcinoma
 Signet-ring cell carcinoma
 Adenosquamous carcinoma

77.  Spindle cell carcinoma
 Squamous cell carcinoma
 Undifferentiated carcinoma
 Neuroendocrine neoplasms
 Neuroendocrine tumor(NET)
 Neuroendocrine Carcinoma
Large cell NEC
Small cell NEC
Mixed adenoneuroendocrine carcinoma

78. Immunohistochemistry

79.  Positive for
 MUC 1
 MUC3
 CK20
 CEA

80. MUC 3 POSITIVE/MUC 1 POSITIVE

81. CK20 POSITIVE

82. Dukes staging

83. TNM STAGING

84. Astler-Coller classification (not
currently used
 A: lesion limited to mucosa
 B1: lesion involves muscularis propria but does
not penetrate through it
 B2: lesion penetrates through the muscularis
propria
 C1: metastatic tumor in lymph nodes but the
tumor is still confined to the bowel wall
 C2: metastatic tumor in lymph nodes and tumor
has penetrated through the entire bowel wall

85. Prognostic factors
WORST PROGNOSIS IS SEEN IN
 1) young patients
 2) males
 3) Increased CEA levels
 4) Rectosigmoid region
 5) Left side colon-obstruction
 6) Perforation
 7) Infiltrating margins

86.  8)Vascular/perineural invasion
 9)Tumor angiogenesis
 10) APC>HNPCC
 11)Lymph nodes
 12) Stage C

87. Intestinal lymphomas
Most common site for Primary Extra Nodal
Lymphoma is GIT.
But more common in small intestine than Large
intestine
 T cell Lymphoma
 B cell Lymphoma

88.  T cell- malignancy of intra-epithelialT cells.
 Associated with Celiac disease.
 Common site- small intestine

89. B cell lymphoma
 MALTOMAS
 Solitary
 More common in small intestine(ileum)
 Gross- garden hose appearance/bulky
tumor

90. Important B cell lymphomas that
affect intestine are
 Α-HCD
 MALTOMA
 Follicular lymphoma
 Mantle cell lymphoma

91. this photomicrograph shows MALT lymphoma
extending from mucosa (top arrow) to the
subserosa (bottom arrow).

92. APPENDIX

93. Gross Anatomy
Extension of cecum

94. NORMAL HISTOLOGY OF APPENDIX

95. This is the appendix comprise of the mucosa
submucosa with prominent lymphoid
tissue beneath
which are the inner circular and the outer
longitudinal smooth muscle coats, all
surrounded by a serosa with
adjacent adipose tissue.
The lumen of the appendix is typically filled
with fecal material

96.  Gross- grey yellow
 Microscopy-Three histological subtypes
including classic, tubular, and goblet cell
types are recognized.
 classic carcinoid insular growth pattern of
solid islands of uniform polygonal cells with
minimal pleomorphism, retraction of
peripheral tumor cells from stroma

97. M.c- Carcinoid tumor

98. Conclusion
 Polyps – anywhere in the GI tract can be a
precursor to the malignancy.
 FAP has high chances of turning into
malignancy.
 Adenocarcinoma is the most common
malignancy of the COLON.

99. References
 Rosai and Ackerman
 Robbins & Cotran
 Wasington manual of surgical pathology
 Internet resources-
 Pathology outlines
 https://library.med.utah.edu/WebPath/GIHT
ML/GIIDX.html

100. THANK YOU