1. Gastric Polyps & Tumors
• Introduction to Polyps
• Classification of Polyps
• Gastric Carcinoma
• Endocrine Tumors
• Gastric Lymphomas
• Mesenchymal Tumors
By : Dr. Karan Arora

2. GASTRIC POLYPS

3. Introduction
• Gastric polyps are defined as luminal lesions
projecting above the plane of the mucosal
surface
• Develop as a result of epithelial/stromal cell
hyperplasia, inflammation, ectopia or neoplasia
• A gastric polyp has the potential to become
cancerous – most will remain benign but in a
minority of cases it will progress into cancer

4. Classification
• Enlarged Mucosal folds are also included because there
is some clinical overlap between prominent folds and
polyposis
• Although histologic examination is the key to differential
diagnosis, much practical diagnostic help can also be
obtained by determining
▫ If a biopsy comes from a discrete polyp / from a prominent
mucosal fold
▫ Whether a polyp is sessile/pedunculated
▫ Whether polyps are present in other parts of GI tract
▫ Whether the surrounding mucosa is normal

6. Peutz-Jeghers Syndrome
• Also known as Hereditory Intestinal Polyposis Syndrome
• Autosomal dominant genetic disease, characterised by
development of hamartomatous polyps in GI tract and
hyperpigmented macules on the lips and oral mucosa
• Caused by : Mutation of the serine/ threonine kinase
gene(STK11/LKB1)
• Commonly present in childhood / adolescence
• Size : 1-3 cms.
• Surface : Coarsely lobulated with short, broad stalk

7. • Histologically :
▫ The most useful diagnostic feature is : presence of a
core of finely arborizing branches of smooth muscle
from muscularis mucosae
▫ The core is covered with abundant mucosa, identical
with that of stomach, but often disorganized.
▫ Predominantly, consist of surface and foveolar
epithelium, although occasional antral glands and
small cysts may be found
▫ Inflammation is usually not prominent
▫ Low risk of developing into carcinoma

8. A 21-year-old female was referred to the
department of surgery as an emergency
with the complaints of abdominal pain and
bilious vomiting for the past 14 days
F/H : Similar lesions in family
G/E : mucocutaneous macules noted on
lips
On Operating table, intussusception of the
bowel was seen. A firm mass was palpable
in the lumen of the bowel. A segmental
resection was done as the mass was
completely obstructing the lumen and a
polypoidal mass was found. It was sent for
histopathological examination.

9. Fig 1(Left Upper) : Note the
arborizing smooth muscle
architecture unique to PJS-type
polyp
Fig : 2 (Rt Lower) : Low power
microscopic view of a PJS-type
polyp with pseudo-invasion

10. Juvenile Polyps
• Also called retention polyp
• Surface : Rounded, smooth-surfaced lesion
• Size : 1-2 cm in diameter
• Occurs due to mutation of SMAD4
gene(chromosome 18) / PTEN
gene(chromosome 10)

11. • Histologically :
▫ Consists of principally lamina propria which contains
irregularly shaped cysts lined by normal gastric
epithelium
▫ Repeated episodes of torsion may produce stromal
hemorrhage, surface ulceration, and secondary
chronic inflammation
• Small, but definite risk of colorectal cancer & gastric
cancer with patient with juvenile polyposis

12. Hyperplastic Polyps
• Also called regenerative/ hyperplaseogenous polyp
• Common in both children & adults(Most common
b/w 5th & 6th decade)
• Occurs mostly at junction of pyloric & corpus
mucosa
• Multiple, avg. size 1.4 cms
• Surface : coarsely lobulated
• Small polyp : Sessile, Large : short, broad stalk

13. • Presumed histiogenesis : Exagerrated
regenerative response to mucosal damage
• Adjacent non polypoid mucosa shows chronic
atrophic gastritis
• Rarely undergo malignant change(2%)
• Malignant change confined to lesions greater
than 2cms

14. • Histologically
▫ Elongated, distorted & branched gastric foveolae
▫ Often abundant lamina propria, which may be
inflammed & edematous
▫ Frequently foveolar cells are hypertrophic with excess
superficial cytoplasm with/without intestinal
metaplasia
▫ Nuclei are typically bland(resemble normal gastric
pit) but in areas of heavy inflammation , regeneration
can produce nuclear enlargement with prominent
nucleoli

15. Irregular Epithelial proliferation, cyst formation, and excess of lamina propria

16. Fig A : Hyperplastic Polyp showing cork screw shaped
foveolar gland
Fig B : Polyp with Ulceration

17. Fundic Gland Polyp
• Accounts for 50% of all gastric polyps
• Occur as isolated sporadic lesion that are usually of
little clinical significance
• However, fundic gland polyposis(10 or more polyps)
has been described in two clinical situations
▫ Following drug therapy for gastric acid suppression
▫ In Familial adenomatous polyposis(FAP) where many
hundred’s of polyp are present

18. • In FAP
▫ The polyps are true neoplastic lesions, showing
mutation in APC gene
▫ 25-50% prevalence of dysplasia in the foveolar
epithelium
▫ May rarely give rise to adenocarcinoma

19. • In sporadic & drug therapy related polyps
▫ They are non dysplastic
▫ Do not show APC mutation
▫ May have point mutation of beta-catenin
(CTNNB1) gene

20. • Macroscopically : Minute mucosal bumps : 1-
16mm in diameter, occur in gastric body &
fundus
• Microscopically :
▫ Single/ small groups of cystically dilated fundic
glands, lined by attenuated but otherwise normal
layer of chief cells, parietal cells & mucous neck
cells
▫ Inflammation is typically minimal/ absent

21. Consists of dilated gland lined by an attenuated , but otherwise normal epithelium

22. Adenomas
• Comprise 7-10 % of all gastric polyps
• Most are sessile & grow in tubulo villous / pure villous pattern
• Pure pedunculated tubular lesions are rare
• Usually Solitary lesions < 2cms
• Histologically : Two types of lesion
▫ Adenomas showing intestinal differentiation(goblet cells &/or
paneth cells)
▫ Adenomas showing gastric differentiation(columnar cells
containing neutral mucin)

23. • Polyps larger than 2cms & those with intestinal
differentiation have significant chance of becoming
malignant(Overall, carcinoma may be present upto
30% of gastric adenomas)
• Adenomas
▫ With intestinal differentiation , arise in background
mucosa that shows intestinal metaplasia
▫ With gastric differentiation , arise in mucosa that is
either normal/shows minor inflammatory feature

24. • By definition, all GI adenomas have epithelial dysplasia
that is classified as low/high grade
• Both grades include :
▫ Enlargement, elongation & hyperchromasia of epithelial
cell nuclei
▫ Epithelial crowding
▫ Pseudostratification
• High grade dysplasia includes more cytologic atypia with
irregular artitecture, including glandular budding &
gland within gland or cribriform structures

25. Villous adenoma of stomach

26. Zollinger -Ellison Syndrome
• Triad of
▫ Gastric acid hypersecretion
▫ Severe peptic ulceration
▫ Non beta cell islet tumor of pancreas(gastrinoma)
• Increase in mass of body glands with normal
sized antral glands & gastric foveolae(d/t excess
production of gastrin)
• Excess gastrin has trophic effect on parietal
cells, causing them to enlarge & proliferate

27. • Gross :
▫ Mucosal folds in gastric body are enlarged & thrown
into cerebriform pattern
• Histologically
▫ Gland thickness is expanded approx 2 times of normal
▫ Glands consist of hypertrophied & hyperplastic
parietal cells that appear to crowd out chief & mucous
neck cells
▫ Gland lumen may be dilated , producing small cysts
▫ Hyperplastic endocrine cells may also be present in
the corpus glands

28. Menetrier Disease
• Poorly defined entity
• Diagnosis criteria for this disease (Given by
Appleman) includes
▫ Giant Mucosal folds involving the corpus & possibly
antrum
▫ Low acid production, even after stimulation
▫ Mucosal protein loss
▫ Histologic findings of corpus foveolar hyperplasia &
glandular atrophy

29. • Histologic features :
▫ Elongation of gastric foveolae on the surface of
folds & may have cork screw appearance
▫ Often cystically dilated with mucus accumulation
▫ Cysts extends into deeper mucosal layer & even
occasionally the submucosa, with resulting corpus
gland atrophy

30. Menetriers disease showing foveolar hyperplasia & cyst formation

31. GASTRIC TUMORS

34. GASTRIC CARCINOMA
• Majority of gastric cancers are adenocarcinoma
• Definition of W.H.O
▫ “A malignant epithelial tumor of stomach mucosa with
glandular differentiation”
• Early symptoms resemble those of chronic gastritis,
including dyspepsia, dysphagia & nausea
• As a result these tumors are often discovered at
advanced stages, when symptoms such as weight
loss, anorexia etc. trigger further diagnostic
evaluation

35. Epidemiology
• Geographical Distribution
▫ In Japan & eastern europe, the incidence is upto 20 fold higher than in
north america & south east asia
• Time Trends
▫ Decline in incidence has been observed worldwide from past few decades
▫ Reason : Decrease consumption of dietary carcinogen such as : N-
Nitroso compounds & benzo(a) pyrene
• Age & Sex Distribution
▫ Rare in age < 30 yrs., highest in old age groups
▫ Intestinal type : Male> Female
▫ Diffuse type : Affects young females more(d/t hereditary characterstics :
germline mutation of CDH1 gene)

36. Aetiology
• Diet
▫ Increased Risk
 Smoked or cured meats or fish, pickeled vegetables, chilli
peppers
 Exposure to nitrosamines, alcohol, tobacco & Inorganic
dusts
▫ Decreased Risk
 Fruits, vegetables, carotenoids, folates etc.
• Bile Reflux
▫ Increased Risk after 5-10 yrs. Of gastric surgery
(Bilroth II) which increases Bile reflux

37. • Helicobacter Pylori Infection
▫ Strong association with the organism
▫ Induces the phenotypic change & leads to
formation of adenocarcinoma
▫ Sequential Steps involved
 Chronic gastritis
 Multifocal atrophy
 Intestinal metaplasia
 Intraepithelial neoplasia

39. • Precursor lesion
▫ Gastritis & Intestinal metaplasia
▫ Intraepithelial neoplasia(dysplasia)
• Location
▫ Most frequent site of sub cardial stomach cancer is
the distal stomach i.e the antro-pyloric region,
more on lesser curvature than greater curvature

40. • Classification
• Two widely used : Lauren & WHO
▫ Lauren
 List three histologic types
 Intestinal
▫ These form recognizable glands that range from well differentiated to
moderately differentiated tumors, sometimes with poorly differentiated
with advancing margin.
▫ Typically arise on background of intestinal metaplasia
 Diffuse
▫ Consist of poorly cohesive cells diffusely infilterating the gastric wall with
little / no gland formation.
▫ The cells appear round & small arranged as single/clustered in
abortive, lacy gland like/reticular formation. These tumor resemble signet
ring type as classified in WHO classification
▫ Most cases of LEATHER BOTTLE STOMACH(linitis plastica) is classified
as diffuse
▫ Mitotic rate is lower in diffuse than intestinal type
▫ Desmoplasia is more pronounced
▫ Inflammation is less evident
 Mixed

41. Leather bottle stomach

42. Adenocarcinoma of stomach & intestinal metaplasia

43. Intestinal type adenocarcinoma of stomach. Well formed glands with lack of cytoplasmic mucin

44. Diffuse carcinoma of stomach. Shows submucosal infiltration by single cells & small strings of cell

45. Diffuse carcinoma , showing multiple signet ring cells

46. • W.H.O classification
▫ Tubular
 Consist of prominent dilated/slit like & branching
tubules varying in their diameter; acinar structures
may be present
 Tumor cells are columnar, cuboidal or flattened by
intraluminal mucin
 Clear cells may also be present
 Cytologic atypia varies from low to high grade
 Poorly differentiated variant is sometimes called
solid carcinoma
 Tumors with prominent lymphoid stroma are
sometimes called medullary carcinoma/ carcinomas
with lymphoid stroma

47. ▫ Papillary
 Well differentiated exophytic carcinomas with finger
like processes lined by cylindrical/ cuboidal cells
supported by fibro vascular connective tissue cores
 Cells maintain their polarity
 Invading tumor edge is usually sharply demarcated
from surrounding structures from surrounding
structures
 May be infilterated by acute & chronic inflammatory
cells

48. ▫ Mucinous
 By definition >50% tumors consists of extracellular
mucinous pools
 Two major growth pattern
 Glands lined by a columnar mucous secreting
epithelium together with interstitial mucin
 Chains or irregular cell clusters floating freely in
mucinous flakes
 Signet ring cells when present do not dominate the
picture

50. ▫ Signet ring cell carcinoma
 >50 % of tumor consist of isolated/small groups of
malignant cells containing intracytoplasmic mucin
 Tumor cells have 5 morphologies
1. Nuclei push against cell membranes creating a classical
signet ring cell appearance d/t an
expanded, globoid, optically clear cytoplasm. These contain
acid mucin & stain with Alcian blue at pH 2.5
2. Other diffuse carcinomas contain cells with central nuclei
resembling histiocytes & show little/no mitotis
3. Small, deeply eosinophilic cells with prominent but
minute, cytoplasmic granules containing neutral mucin
4. Small cells with little/ no mucin
5. Anaplastic cells with little/ no mucin

51. ▫ Signet ring cell carcinoma(contd.)
 Special stains :
Mucin detection : PAS, mucicarmine, Alcian blue
IHC : Cytokeratin
 Several Condition which mimic Signet Ring
carcinoma :
 Signet ring lymphoma
 Lamina propria muciphages
 Xanthomas
 Detached/dying cells associated with gastritis

53. Rare variants of carcinoma
• Adenosquamous
• Undifferentiated carcinoma
• Mixed adenocarcinoma-carcinoid
• Small cell carcinoma
• Parietal cell carcinoma
• Endodermal sinus tumor
• Hepatoid carcinoma

54. Early gastric cancer
• Carcinoma limited to mucosa / mucosa &
submucosa regardless of nodal status
• Lesions may be categorised as :
▫ Flat
▫ Elevated
▫ Depressed
▫ Excavated
▫ Combined forms
• Most tumors are 2cms or less in diameter
• Importance of correctly identifying early gastric
cancer lies in excellent result of surgical treatment

55. Grading
• Well differentiated
▫ An adenocarcinoma with well formed glands, often resembling
metastatic intestinal epithelium
▫ >95% consist of glands
• Moderately differentiated
▫ Intermediate between well & poorly differentiated
▫ 50-95% consist of glands
• Poorly differentiated
▫ Adenocarcinomas consisting of irregular glands recognised with
difficulty/single cells that remain isolated or/are arranged in small/large
clusters with mucin secretion or acinar structures
▫ 49% or < consist of glands

56. Endocrine tumors
• Definition of W.H.O
▫ “Most endocrine tumors of stomach are well
differentiated, non functioning enterochromaffin-
like(ECL) cell carcinoids arising from the oxyntic
mucosa in the corpus /fundus”
• Three types
▫ Type I : associated with autoimmune chronic
atrophic gastritis
▫ Type II : associated with MEN-I & Z.E syndrome
▫ Type III : sporadic

58. • Type I
▫ Most common(74%)
▫ Average age of onset is 63 yrs.
▫ Sex : F>M(2.5 :1)
▫ Underlying cause : CAG from pernicious anemia
▫ Associated with achlorhydria, antral G cell hyperplasia &
hypergastremia
▫ Pathogenesis :
 Gastrin is trophic for ECL, which proliferate resulting in initially in
simple hyperplasia and later into nodular hyperplasia & finally
into neoplasia

59. • Type I(contd.)
▫ Histologically :
 Carcinoid tumor appear as small cluster/ribbons of
cells at base of mucosa
 Individual cells are regular, with rounded nuclei
having diffuse chromatin pattern
 Cytoplasm is grayish & not obviously granular
 Immunopositive : Chromogranin , synaptophysin

60. • Type II
▫ Constitute 6 % of all gastric endocrine tumors
▫ Mean Age : 50 yrs.
▫ Sex : M=F
▫ Morphology :
 Almost same as type I, occasionally may become large &
metastasize to regional nodes
 Background mucosa shows parietal cell hyperplasia

61. • Type III
▫ Constitute 13% of all gastric endocrine tumors
▫ Mean Age : 55 yrs.
▫ Sex : M>F(2.8:1)
▫ Not accompanied by hypergastrinemia/atrophic
gastritis/pernicious anemia
▫ Commonly found in corpus
▫ Behave in malignant fashion if lesion is > 2cms/show
angio invasion/deep muscle invasion

62. GI carcinoid tumor (neuroendocrine carcinoma).
A, Gross cross-section of a submucosal tumor nodule.
B, Microscopically the nodule is composed of tumor cells embedded in dense fibrous tissue.
C, In other areas, the tumor has spread extensively within mucosal lymphatic channels.
D, High magnification shows the bland cytology of carcinoid tumors. The chromatin texture, with fine and
coarse clumps, is frequently described as a "salt and pepper" pattern. Despite their innocuous appearance,
carcinoids can be extremely aggressive clinically.
E, Electron microscopy reveals cytoplasmic dense core neurosecretory granules

63. Extreme endocrine cell hyperplasia is present, resulting in microcarcinoid nodules in gastric mucosa

64. GASTRIC LYMPHOMAS
• Definition of WHO
▫ “Primary gastric lymphomas are defined as lymphomas
originating from the stomach & contiguous lymph nodes”
• Lymphomas at this site is considered as primary if the
main bulk of disease is located in stomach
• Majority of gastric lymphomas are high grade B-cell
lymphomas, some of which have developed through
progression from low grade lyphomas of mucosa
associated lymphoid tissue(MALT)
• The low grade lesions are exclusively B-cell MALT
lyphomas

65. • 40% NHL arise in extranodal site, out of which GI
tract is the most commonest
• Constitutes over 10 % of all gastric malignancy
• Age : Common in >50 yrs
• Sex : M=F
• Etiology
▫ H. Pylori
▫ Immunosuppression

66. MALT Lymphomas
• Pathogenesis
▫ The normal gastric mucosa contains scattered
lymphocytes & plasma cells but is devoid of organised
lymphoid tissue
▫ First step in development of primary gastric
lymphoma is acquisition of organised lymphoid tissue
from which lymphoma can arise
▫ In most cases it is associated with H.Pylori
▫ H. Pylori do not directly stimulate MALT lymphoma
cells but cause secretion of IL-2 from adjacent T cells
& induce IL-2 receptors on tumor cells themselves

67. • MALT lymphoma is low grade lymphoma
• It may transform to high grade i.e DLBCL
• Five cardinal histologic features of MALT lymphoma
▫ An infilterate of small lymphocyte & small cleaved
follicle centre(Centrocyte-like - CCL) cells
▫ Lymphoid follicles
▫ Neoplastic plasma cells
▫ Lymphoepithelial lesions
▫ Dutcher bodies(PAS-positive intranuclear inclusion)

68. ▫ Lymphocytic infiltrating the epithelium of the
stomach is highly characteristic of MALT
lymphomas, but can also be present in
lymphocytic gastritis
▫ To be suggestive of lymphoma, the infiltrate must
be present as a lymphoepithelial lesion(a
discrete cluster of three/more lymphocyte)
▫ In lymphocytic gastritis , the lymphocytes(Which
are T cells rather than B cells) are usually present
as single cells within the epithelium

69. ▫ Immunophenotype
 Positive : CD20
 Negative : CD5,CD10, Bcl-6, Cyclin D1
 Note : CD5 negativity is useful in differentiating
from other small cell lymphoma

70. MALT lymphoma producing expansion of submucosa in an ill defined nodular pattern & showing follicular colonization

71. Predominantly intermediate sized cells(cleaved cells) with less larger cells

72. Lymphoepithelial lesion from MALT lymphoma

73. Diffuse Large Cell B-cell Lymphomas
▫ Most high grade gastric lymphomas are DLBCL
▫ Major diagnostic challenge is to separate DLBCL
from poorly differentiated carcinoma
▫ Lymphoma cells tend to infiltrate widely in the
lamina propria in a sheet like fashion, but they
often spare existing gastric pits & glands
▫ In contrast to MALT lymphomas, lymphoepitheial
lesion is not a common finding

74. DLBCL(Contd.)
▫ Carcinomas tend to destroy mucosal structures as
they infiltrate
▫ Cells of lymphoma are totally non cohesive with
no tendency to form clumps/cords
▫ Nuclei of DLBCL are characteristically vesicular
with prominent nucleoli & nuclear membrane

75. DLBCL of stomach

76. Other B-Cell lymphomas
▫ Mantle Cell Lymphoma
▫ Follicular Lymphoma
▫ Burkitt Lymphoma

77. MESENCHYMAL TUMORS
• Definition of WHO
▫ “Most gastrointestinal mesenchymal neoplasms are
GIST/smooth muscle types”
• Previously the term GIST was applied to
mesenchymal tumors of all type
• At, present the diagnosis should be restricted to
neoplasm arising from Interstitial cells of Cajal(GI
pacemaker cells)
• Tumors arising from smooth muscle should be
called leiomyoma/leiomyosarcoma & thise arising
from the nerves should be called
shwannoma/neurosarcoma

79. GIST(Gastrointestinal Stromal Tumor)
• Accounts for 2% of all malignant gastric tumors
• Typically defined as “tumors whose behaviour is
driven by mutations in Kit gene/PDGFRA gene
and may/may not stain positive for kit”
• Age : B/w 5th & 8th decade
• Sex : M=F

80. GIST(Contd.)
• Pathophysiology
▫ Thought to arise from interstitial cells of cajal(ICC)
▫ What is ICC ?
 The Interstitial cell of Cajal (ICC) is a type of interstitial
cell found in the gastrointestinal tract that serves as a pacemaker
which creates the basal electrical rythym leading to contraction of
the smooth muscle(peristalsis)
▫ Most of GIST arise because of mutation of c-kit gene
▫ C-kit/CD117 is expressed in ICC
▫ Most are sporadic, some are hereditary

81. GIST(Contd.)
• Gross
▫ Solitary rounded or lobulated lesions with a clearly
defined margin
▫ Primarily involve the muscularis propria & submucosa
▫ Larger tumor bulge into gastric lumen & have attenuated
mucosa covering their surface
• C/S
▫ Flat, whorled appearance with tumor substance usually
firm with foci of necrosis/hemorrhage
▫ Large tumors may be cystic in middle

82. GIST(Contd.)
• Eight different histologic subtypes
▫ Spindle(4) & Epithelioid(4)
▫ Spindle type
 20% of all stromal tumor
 Subtypes :
 Sclerosing(most common)
 Palisading vacuolated
 Hypercellular
 Sarcomatous

83. GIST(Contd.)
▫ Spindle type(contd.)
 Sclerosing
▫ Composed of interlacing fascicles & whorls of uniform elongated
cells, with cigar-shaped vesicular nuclei & eosinophilic cytoplasm
 Palisading
▫ Close resemblance to schwannoma
 Hypercellular
▫ Tightly packed uniform spindle cell without significant
atypia/mitotic activity
 Sarcomatous
▫ Significant mitotic activity & pleomorphism

84. GIST(Contd.)
▫ Epithelioid type
 Involve the corpus & antrum
 Subtypes
 Sclerosing
▫ Syncytial pattern, composed of round cells with clear/lightly eosinophilic
cytoplasm
▫ Clearing of cytoplasm is result of fixation artefact
▫ Sometimes vacuolation in cytoplasm is eccentric giving false impression of
signet ring cells
 Dyscohesive variant
▫ Epithelioid cells surrounded by lacunar spaces
 Hypercellular
 Sarcomatous

85. • Immunophenotype : 95% positive for CD117
• Prognosis
▫ Four broad group depending upon gross size & mitotic activity/50 hpf
 Very Low malignant potential
 Less than 2cms with <5 mitoses/50 hpf
 Low malignant potential
 2-5cms with <5 mitoses/50 hpf
 Intermediate malignant potential
 <5cms with 6-10 mitoses/50 hpf
▫ Or
 5-10cms with <5 mitoses/50 hpf
 High malignant potential
 >5cms with >5 mitoses/50 hpf
▫ Or
 >10cms with any number of mitoses
▫ Or
 Any size with >10 mitoses/ hpf

86. Low grade spindle cell GIST composed of interlacing fascicles of cells with cigar
shaped nuclei

87. Epitheloid GIST with rounded nuclei & clear cytoplasm

88. Malignant Epitheloid GIST. Note : cellularity, pleomorphism & mitoses

89. References
• Robbins : 8th Edition
• Sternberg : 5th Edition
• WHO classification of tumors
• Internet