Preface

Agam is a group of budding medicos, who are currently doing their under graduation in
various Medical Colleges across Tamil Nadu and Pondicherry. The group was initiated on 18th
November 2017, in the vision of uniting medicos for various social and professional causes.

We feel delighted to present you Agam Pathology notes prepared by Agam Divide and Rule
2020 Team to guide our fellow medicos to prepare for university examinations.

This is a reference work of 2017 batch medical students from various colleges. The team
took effort to refer many books and make them into simple notes. We are not the authors of the
following work. The images used in the documents are not copyrighted by us and is obtained from
various sources.

Dear readers, we request you to use this material as a reference note, or revision note, or
recall notes. Please do not learn the topics for the 1st time from this material, as this contain just the
required points, for revision.
Acknowledgement

On behalf of the team, Agam would like to thank all the doctors who taught us Pathology.
Agam would like to whole heartedly appreciate and thank everyone who contributed towards the
making of this material. A special thanks to Vignesh M, who took the responsibility of leading the
team. The following are the name list of the team who worked together, to bring out the material in
good form.

• Neelavathi S
• Pavithra Devi K
• Prasanna Sri P
• Rajath B
• Santhiya K
• Shalika G
• Shenbhaga Praveen N
• Sowmya T D
• Vijayalakshmi K
• Snaha M
• Projatna Chaudhuri
• Krishna Priyaa S
• Vennmadhi Vellentina D
• Varshaa A S
• Subhashree Karishma Choudhury
• Yashwantha Elumalai Jagadeesan
• Vignesh. M
 THE GASTROINTESTINAL TRACT
ESSAY
1. Ulcerative colitis
2. Ulcerative lesion of SI and LI
3. Crohn's disease
4. Peptic Ulcer

SHORT NOTES:
1. Etiopathology of Duodenal Ulcer
2. H.pylori gastritis
3. Barett's esophagus
4. Early gastric Carcinoma
5. APUD cell tumours
6. Celiac sprue
7. Neoplastic polyps of Large Intestine
8. Hirshsprung Disease
9. Gross and microscopic features of colorectal Carcinoma
10.Amoebic dysentry colon
11.Carcinoid syndrome
12.Zollinger Ellison syndrome

SHORT ANSWERS
1. Microscopic intestinal changes in malabsorption syndrome
2. Morphological hallmarks of Whipple's disease
3. Peutz-Jagger syndrome
4. Linitis plastica
5. Cobble-stone appearance
6. FAP syndrome
7. Sites of Peptic Ulcer Disease
8. Helicobacter pylori
9. Microscopic appearance of appendicitis
10.Difference between UC and Crohn's disease
11.Gross difference between benign and malignant ulcers of stomach
12.Morphology of 2 types of hiatal hernia

UPDATES

PATHOLOGY AGAM
ESSAY
1. ULCERATIVE COLITIS
 Chronic ulcerating inflammation extending into mucosa and submucosa.
 Limited to colon and rectum
 Inflammatory bowel disease.
 Associated with HLA-DR2
 CD4 Th2 cells are involved
 Associated with IL-10 gene polymorphism
 IL-13 increased

EPIDEMIOLOGY:
 Common in women
 Typically during adolescence
 It is related to hygiene hypothesis
 More common in developed countries

PATHOGENESIS:
 Results from a combination of defects in host interactions with intestinal microbiota,
intestinal epithelial dysfunction and aberrant mucosal immune responses and altered
composition of the gut microbiome.
 Genetic factors are less dominant.

MORPHOLOGY:
 Ulcerative colitis is a disease of continuity with no skip lesions and is diffusely ulcerated.
 It involves rectum and extends proximally to involve the entire colon in a retrograde
fashion (pancolitis).
 Disease is limited to the rectum or rectosigmoid (ulcerative proctitis or ulcerative
proctosigmoiditis)
 Distal ileum may also show some mild mucosal inflammation (backwash ileitis)
 Grossly;
 Colonic mucosa is reddened, granular, extensive broad-based ulcers and friable with
Pseudopolyps.
 There can be ulceration or atrophic and flattened mucosa.
 Inflammation and inflammatory mediators damage the muscularis propria and disturb
neuromuscular function leading to colonic dilation and toxic megacolon

AGAM PATHOLOGY
 Microscopically;
 Mucosal inflammation is diffuse and generally limited to the mucosa and superficial
submucosa.
 They will have crypt abscesses, ulceration, chronic mucosal damage, glandular
architectural distortion and atrophy
 There are no fissures, aphthous ulcers and granulomas and malignant potential.

CLINICAL FEATURES: Intermittent attacks of

 Lower Abdominal pain and cramps
 Bloody mucoid stools
 Fever
EXTRA INTESTINAL MANIFESTATIONS:
 Uveitis  Sacroiliitis
 Iritis  Primary sclerosing cholangitis
 Ankylosing spondylitis  Pyoderma gangrenosum
 Clubbing  Erythema nodosum
 Migratory polyarthritis

IMPORTANT FEATURES OF UC: (Mnemonic: Ulcerative COLITIS)

 Ulcerative – Ulcers in mucosa and sub mucosa (muscle layer not effected)
 C – Continuous retrograde involvement (no skip lesions)
 O– Originates in rectum
 L – Lead pipe appearance (radiological appearance)
 I – Increased chances of cancer
 T – Toxic megacolon (due to involvement of transverse colon)
 I – Increased growth from the mucosa (pseudopolyps)
 S – Symptoms are severe

TREATMENT:
 Sulfasalazine (5-aminosalicylic acid is the principal therapeutic moiety)
 Infliximab (TNF – α antagonist)
 Steroids

PATHOLOGY AGAM
2. ULCERATIVE LESIONS OF SMALL AND LARGE INTESTINE
These include;
 Infectious enterocolitis (typhoid, T.B, amoebic ulcers)
 Inflammatory bowel disease (Ulcerative colitis, Crohn’s disease)

INFECTIOUS ENTEROCOLITIS:
Enteric fever (typhoid)
 Caused by Salmonella species
 Most commonly affects the terminal ileum, jejunum and colon
 Children and adolescents are most commonly affected
 Humans are the only reservoirs and transmission is most commonly through
contaminated food and water
 Infection cause marked expansion of payer’s patches (terminal ileum) and draining nodes.
 Terminal ileum will show longitudinal ulcers (oval ulcers with long axis along the ileal
long axis)
 Liver shows typhoid nodules consisting of macrophage aggregates and focal hepatocyte
necrosis
 Peripheral blood will show leucopenia with neutropenia and relative lymphocytosis
 It will show erythrophagocytosis which means macrophage will phagocytose RBC and
bacteria
 Perforation and hemorrhage are common complications, whereas fibrosis and stricture
are rarely seen.
 Clinically, the patient develops
 Step-ladder pyrexia
 Rose spots
 Splenomegaly
 Abdominal pain
 Vomiting
 Bloody diarrhea
 Blood culture – mainstay of diagnosis
 Widal test –for measuring the antibody titer
 Treatment
 DOC –ciprofloxacin/ceftriaxone
 For carriers –ampicillin + probenacid

AGAM PATHOLOGY
Tuberculosis (T.B)
 Primary infection
 It occurs due to mycobacterium bovis (due to intake of infected milk) and results in
the development of hyperplasic tuberculosis
 Most common site is ileocecal region
 Fibrosis and stricture are seen commonly and perforation is rare
 Tabes mesenterica -mesentric lymph nodes are enlarged; matted and caseous
 Clinical features
 Acute abdominal pain
 Diarrhea
 Malabsorption
 pulled up caecum (widening of ileocaecal angle) on barium radiography
 Secondary infection
 caused by mycobacterium tuberculosis
 ileum will show transverse ulcers
 Multiple granulomas with caseous necrosis.
 Clinical features:
 weight loss
 intermittent diarrhea
 Filling defect in the ileum, caecum and ascending colon – barium radiography.
 Treatment: Antitubercular therapy or surgical resection of the affected part of intestine

Amoebiasis
 it is caused by protozoa E. histolytica by Fecal-oral route of transmission
 most common site of amoebiasis is caecum and ascending colon
 ulcers are seen up to the mucosa and the submucosa only, it never reaches up to the
mucularis propria
 flask-shaped ulcers (narrow neck and broad base are characteristic )
 anchovy sauce pus in liver abscess, formed by the mixture of hemorrhagic and necrotic
debris
 Clinical features
 Weight loss
 Abdominal pain
 Bloody diarrhea
 Occasionally acute necrotising colitis and megacolon can occur
 DOC – metronidazole
PATHOLOGY AGAM
3. CROHN’S DISEASE
 Aka Regional enteritis / terminal ileitis / granulomatous COLITIS
 It is a chronic granulomatous disease which can affect any part of gut from oesophagus
to the large intestine but the most commonly affected part is small intestine particularly
ileum.
 It is associated with HLA –DR1
 CD4 Th1 cells are involved (reason for granuloma formation)
 TH17 cells also are contributory
 IL -23 receptor polymorphisms is protective
 It is a chronic non-caseating transmural granulomatous inflammation
 Most common site is terminal ileum and rectum is usually spared
 Location: May occur in any part of GIT but more commonly occurs in Terminal Ileum,
Ileocecal valve, Caecum.
 Wall involvement: Entire thickness of wall (Transmural inflammation)
 Epidemiology: Early age, Females, Western countries
 Pathogenesis:
 Abnormal immune responses to enteric flora
 Genetic factors
 Environmental factors
 Altered composition of gut microbiome

Crohn’s Disease

Abnormal immune Genetic factors Environmental Deranged

responses to factors microbiota
 1st degree relatives
enteric flora  NSAIDs  Frequent use of
 Higher chance in
 Def. regulation monozygotic twins  Psychological antibiotics
of immune  Disease predisposing factors  Antibodies
suppression loci 16  Smoking against bacterial
 Activated CD4+  HLA Types proteins
T cells  NOD 2 ,ATG16L1 AND
IRGM gene mutation

AGAM PATHOLOGY
MORPHOLOGY:
 Gross:
 Skip lesions-multiple, separate, sharply delineated areas
 Earliest lesion is punched out mucosal aphthous ulcers, coalescing into longitudinal
serpentine ulcers
 Cobblestone appearance - alternative normal and ulcerated mucosa
 Creeping fat-Mesentric fat around inflamed serosa
 Bowel wall is thick and rubbery and often strictured - Due to Transmural edema,
inflammation, submucosal fibrosis, hypertrophy of muscularis propria.
 Fissures and fistula tracts are common
 Fibrosis, serositis, lymphoid reaction are marked.

 Microscopic:
 Ulceration
 Distortion of Mucosal architecture-bizarre branching of crypts
 Pseudopyloric metaplasia
 Metastatic crohn disease-nodules formed by cutaneous granulomas
 Mucosal inflammation and ulceration with intraepithelial neutrophils and crypt
abscesses
 Transmural inflammation and Transmural noncaseating granuloma formation with
lymphoid aggregates in submucosa, muscle wall and subserosal fat.
 Distortion of mucosal architecture, Paneth cell metaplasia in the left colon
 Noncaseating granulomas occurs throughout the gut even in uninvolved segments.

CLINICAL FEATURES:
 Alternative periods of active disease and non-symptomatic period is seen
 Intermittent attacks of mild diarrhea, fever, abdominal pain
 Extensive crohn’s disease can lead to
 Malabsorption and malnutrition
 Loss of albumin
 Perianal fistula (in colonic disease).
 Iron-deficiency anemia and vitamin B 12 deficiency
 Extra intestinal manifestations
 Migratory polyarthritis  Uveitis
 Sacroiliitis  Cholangitis
 Ankylosing spondylitis  Amyloidosis
 Erythema nodosum

PATHOLOGY AGAM
 Minor symptoms: Serum protein loss, Right lower quadrant pain
 Complications: Fibrosing strictures, Fistulae, Perforations, Peritoneal abscess
 Screening test - Presence of ASCA (anti-saccharomyces cerevisiae antibody)
 Diagnosis is confirmed by endoscopy and biopsy
 There is ↑ risk of colonic adenocarcinoma in pts. with long standing colon involvement.
IMPORTANT FEATURES OF CROHN’S DISEASE (Mnemonic-SISTER)
 S - Skip leions
 I - Ileum (most commonly affected)
 S - Saccharomyces cerevisae antibody present
 T - Transmural involvement
 E - Extra fibrosis and fistula formation
 R - Radiological sign-string sign of Kantor, Rectum is usually spared

4. PEPTIC ULCER DISEASE

 Chronic solitary mucosal ulceration affecting stomach/duodenum
 Types:
 Gastric ulcer (10%)
 Duodenal ulcer (90%)
 Epidemiology:
 Decreasing H.pylori infection in developed countries----decreased PUD
 Increased NSAID use above 60 years of age----increased PUD
 Pathogenesis:
 Results from imbalances between mucosal defense mechanisms & damaging factors
that cause chronic gastritis.
 Chronic gastritis develops to Peptic ulcer
CAUSES:
 H.pylori infection
 Cigarette use (synergizes with H. pylori for gastric PUD )
 Chronic obstructive pulmonary disease
 Illicit drugs, e.g. cocaine , that reduce mucosal blood flow
 NSAIDs (potentiated by corticosteroids)
 Alcoholic cirrhosis (primarily duodenal PUD)
 Psychological stress (can increase gastric acid secretion)
 Endocrine cell hyperplasia (stimulate parietal cell growth and gastric acid secretion)
 Zollinger-Ellison Syndrome (PUD of stomach, duodenum, and jejunum)
 Viral infection (CMV, herpes simplex virus)

AGAM PATHOLOGY
MORPHOLOGY:
 Gross:
 Most commonly found locations:
 Anterior wall of proximal duodenum near the pyloric valve (Duodenal ulcer)
 Lesser curvature near the interface of body and Antrum (Gastric ulcer)
 Size:
 Diameter <0.3 cm-shallow ulcers
 >0.6 cm-deeper ulcers
 Shape: Round/Oval “sharply punched out defect”
 Microscopic: (from outside to inside) - 4 zones:
 A thinlayer of Fibrinoid debris
 Neutrophilic inflammatory infiltrate.
 Granulation tissue infiltrated with mononuclear leukocytes
 A fibrous or Collagenous scar forms the ulcer base.

CHARACTERISTICS:
 Base of ulcer is smooth and clean (due to peptic digestion of exudate)
 Depth of ulcer is limited by: Thick Gastric muscularis propria /pancreas/omental fat/liver
 Hemorrhage and fibrin depositions are often seen on Gastric Serosa
 Benign ulcer: smooth edged and mucosal margin may overhang the base.
 Malignant ulcer: Heaped up margins.
 Perforation into peritoneal cavity → surgical emergency → identified by free air under
diaphragm on radiograms
 Malignant transformation of peptic ulcer is rare (gastric carcinoma > duodenal
carcinoma)
CLINICAL FEATURES:
 Major: Epigastric burning /aching pain
 Minor: iron deficiency anemia, hemorrhage, perforation, obstruction(by edema/scarring)
 With penetrating ulcers, the pain is occasionally referred to back, the left upper quadrant
of the chest.
 Pain: 1-3 hours after meal
 Day > night
 Relieved by- Alkali, Food
 Other symptoms: Nausea, Vomiting, Belching and Bloating.
TREATMENT:
 Proton pump inhibitors---decreases gastric acid secretion
 Offending agents to be withdrawn (H.pylori infection, NSAIDs, COX-2 inhibitors)
 Surgical intervention- Antrectomy / Vagotomy (Not in use now a Days)

PATHOLOGY AGAM
SHORT NOTES:
1.. ETIOPATHOGENISIS OF DUODENAL ULCER
 Part of duodenum affected: anterior wall
 Strongly associated with H.pylori
 Acid hypersecretion is the main reason for occurrence of duodenal ulcer
 Clinical manifestations:
 Epigastric pain  Bloating
 Vomiting  Belching
 Consumption of food reduces epigastric pain, rather in gastric ulcer food consumption
causes (food consumption triggers alkaline secretions in intestine), and so patient tend
to eat more resulting in weight gain.
 Investigations: Biopsy: increase in size of Brunners gland (hypertrophy)
 Complications:
 Bleeding due to rupture of gastroduodenal artery
 Perforation causing pancreatitis and perotinitis- reason for mortality of patients
 Gastric outlet obstruction (increased fibrosis as a process of healing ulcer)
 Malena  Hypokalemia
 Hypochloremia  Aciduria
 Metabolic acidosis

2. H. PYLORI GASTRITIS
 90% of patients suffering from chronic gastritis are H. PYLORI infected
 Antral gastritis with acid hypersecretion
 Location: antrum
 Pathogenesis:
 Features linked to virulence of H.pylori :
 Urease -produce ammonium ions which irritates mucosa
 Cag A/ vac A - cytotoxins causing gastric mucosal inflammation
 Flagella
 Adhesins
 Complications:
 Duodenal ulcer (hypersecretion of acid )
 Gastric adenocarcinoma
 Reactive T-cells causing polyclonal proliferation – Maltoma

AGAM PATHOLOGY
 Investigations:
 Serology: antibodies to H.pylori
 Rapid urease test
 Bacterial culture
 PCR
 Treatment: Antibiotics and proton pump inhibitors

3. BARRET ESOPHAGUS
 The replacement of normal stratified squamous epithelium of esophagus with columnar
epithelium due to chronic GERD.
 Cause: Long standing gastric esophageal reflux disease (GERD)
 MORPHOLOGY:
 Gross: Patches of Red – Velvety mucosa extending from gastroesophageal junction up
to esophagus.
 Microscopy
 The squamous epithelium of esophagus is replaced by intestinal columnar
epithelium.
 Goblet cells with mucous vacuoles is indicative of Barrett esophagus.
 The length of barrett esophagus correlates with risk of dysplasia.
 SUB BARRETT ESOPHAGUS CLASSIFICATION:
 Long segment –more than 3cm
 Short segment –less than 3cm
 COMPLICATION:
 Ulceration
 30 -40 increase in risk of esophageal carcinoma
 TREATMENT:
 Proton inhibitors
 Antacids
 H2 receptor antagonist

PATHOLOGY AGAM
4. EARLY GASTRIC CARCINOMA
 The invasive cancer which is limited to sub mucosa and mucosa layer without
involvement of lymph node metastases is called early gastric carcinoma.
 The early gastric carcinoma is confined to epithelial surface
 Absence of metastasis.
 Sites:
 Pylorus and antrum ( most common)
 Cardiac part (25%)
 Body and fundus (15%)
TYPES:
 TYPE – I: Exophytic Type
 The solid tumour protrudes into lumen as polypoid or nodular mass.
 TYPE – II:
 This is a superficial or flat lesion without nodular mass, they may be elevated or
depressed or flat type.
 Subtypes:
 TYPE-II a - Elevated Type
 TYPE-II b - Flat Type
 TYPE-II c - Depressed Type
 TYPE – III: Excavated Type
 This is characterised by shallow depression in wall of the stomach (mucosal layer)
which resembles chronic peptic ulcer. (Mucosal surface surrounding the ulcer
becomes firm and appears in nodular form).

5. APUD TUMOURS
 APUDomas is the term used to describe an embryologically related group of tumours of
endocrine organs.
 Amine Precursor Uptake and Decarboxylation cells are neuroendocrine cells and are part
of the Diffuse Endocrine System.
 These are otherwise called as ‘Neuroendocrine Gastroenteropancreatic Tumours’.
 APUDomas include carcinoid tumours of the gut and pancreatic endocrine tumors

AGAM PATHOLOGY
CARCINOID TUMOUR:
 Carcinoid tumours arise from the diffuse components of the endocrine system.
 Now, they are called as well-differentiated neuroendocrine tumours.
 Most are found in the GIT – 40% in the small intestine; tracheobronchial tree and lung are
2nd most common sites.
 Gastric carcinoid tumours may be associated with
 Autoimmune chronic atrophic gastritis
 MEN-I
 Endocrine cell hyperplasia
 Zollinger Ellison Syndrome

MORPHOLOGY:
 Grossly, carcinoids are intramural or submucosal masses that create small polypoid
lesions.
 In the intestines, the tumours invade deeply to involve the mesentery.
 Yellow or tan in colour; Very firm as a result of an intense desmoplastic reaction – can
result in kinking and obstruction of bowel.
 Histology – islands, trabeculae, strands, glands, or sheets of uniform cells with scant,
pink granular cytoplasm and a round to oval stippled nucleus.
 IHC stains are typically positive for endocrine granule markers such as synaptophysin and
chromogranin A.

CLINICAL FEATURES:
 Peak incidence : 6th decade
 Symptoms are determined by the hormones produced.
 Gastrin-producing tumours: Zollinger-Ellison Syndrome; Ileal tumours: Carcinoid
Syndrome.
 Carcinoid syndrome occurs in fewer than 10% of patients with ileal carcinoid tumours.
 Location is the most important prognostic factor for GI carcinoid tumours.
 Foregut Carcinoid tumours: Rarely metastasize and are generally cured by resection.
 Midgut Carcinoid tumours: Aggressive; Greater depth of local invasion, increased size
and the presence of necrosis and mitosis – associated with a worser outcome.
 Hindgut Carcinoid tumours: Typically discovered incidentally; Those in the appendix
are generally located in the tip and are almost always benign; Rectal carcinoid tumours
produce polypeptide hormones and rarely metastasize.

PATHOLOGY AGAM
6. CELIAC SPRUE
 Also known as celiac disease or gluten sensitive enteropathy.
 It is an immune-mediated enteropathy triggered by the ingestion of gluten-containing
foods in genetically predisposed individuals.
 PATHOGENESIS:
 The alcohol-soluble fraction of gluten, gliadin, contains most of the disease-producing
components.

Gluten → α-gliadin (by Luminal & Brush border enzymes)

Induces epithelial cells to express IL-5

NKG2D-expressing intraepithelial lymphocytes attack enterocytes

that have been induced to express MIC-A

Activation and proliferation of CD8+ intraepithelial lymphocytes that express

NKG2D, an NK cell marker and receptor for MIC-A

Epithelial Damage

Passage of other gliadin peptides into lamina propria

Gliadin → Deamidated gliadin (by Tissue Trans- glutaminase in Lamina Propria)

Deamidated gliadin peptides interact with HLA-DQ2 or HLA-DQ8 on APCs

1
Stimulates CD4+ T cells → Production of Cytokines
S

Tissue damage

 Almost all people with celiac disease carry the class II HLA-DQ2 or HLA-DQ8 allele.
 Other genetic factors include polymorphisms of genes involved in immune regulation
and epithelial function.

AGAM PATHOLOGY
 MORPHOLOGY:
 Biopsy specimens from 2nd portion of duodenum or proximal jejunum are used for
diagnosis.
 Histopathology is characterized by intraepithelial lymphocytosis, crypt hyperplasia
and villous atrophy.
 Other features include increased numbers of plasma cells, mast cells and eosinophils,
especially within the upper part of the lamina propria.
 Adherence to a gluten-free diet typically results in resolution of symptoms, decreasing
titers of anti-tissue transglutaminase or other celiac disease-associated antibodies and
restoration of normal or near normal mucosal histology within 6-24 months.

 CLINICAL FEATURES:
 In adults, celiac sprue is common between the ages of 30 and 60. Detected twice as
frequently in women.
 Adult patients may also have silent celiac disease (+ve serology & villous atrophy;
asymptomatic) or latent celiac disease (+ve serology without villous atrophy).
 Celiac disease is mostly asymptomatic.
 Maybe associated with chronic diarrhoea, bloating, anemia, chronic fatigue.
 Pediatric celiac disease affects males and females equally.
 Classic symptoms: Begins after introduction of gluten diet between the ages of 6 /7 24
months; irritability, abdominal distension, anorexia, chronic diarrhoea, failure to
thrive, weight loss or muscle wasting.
 Non-classic symptoms: Older ages; Abdominal pain, nausea, vomiting, bloating or
constipation, delayed puberty, short stature.
 Only treatment currently available is gluten-free diet.
 For diagnosis, most sensitive test is measurement of IgA antibodies against tissue
transglutaminase.
 Individuals with celiac disease have a higher than normal rate of malignancy, most
commonly enteropathy-associated T-cell lymphoma and small intestinal
adenocarcinoma.

PATHOLOGY AGAM
7. NEOPLASTIC POLYPS OF LARGE INTESTINE
 Intra epithelial neoplasm ranging from small, pedunculated to large, sessile polyps
 M/c- adenomas; benign polyps with malignant potential
 Male predominance
 Regular survelliance and polyp removal required for those have familial history
 Classification: Depending on
 Growth pattern:  Architecture:
 Pedunculated  Tubular
 Sessile  Tubulovillous
 FLAT or depressed  Villous
Pedunculated adenomas have thin fibromuscular stalks containing prominent blood
vessels derived from the submucosa.
 Morphology:
 Size: Range from 0.3 to 10 cm in diameter
 Site: Almost 50% - rectosigmoid region; remaining 50% -evenly distributed throughout
the rest of the colon.

MICROSCOPY
 Low-grade dysplastic lesions-the epithelial dysplasia may be classified as mild, moderate
and severe dysplasia.
 Nuclear hyperchromasia,stratification and elongation is seen
 Eosinophilic cytoplasm
 Reduction in no of goblet cells
 Tubular Adenomas
 Constitute two-third of the adenomas of large intestine
 Appear as small, smooth-surfaced, pedunculated polyps usually less than 2 cm in
diameter
 Tubular adenoma over 2 cm have higher risk of invasive carcinoma.
 Villous Adenomas
 One tenth of colonic adenomas, predominantly found in the rectosigmoid region.
 Large, broad-based, sessile, elevated lesions
 Sometimes produce hypoprotemic hypokalemia
 Increased risk of developoing carcinoma.

AGAM PATHOLOGY
 Tubulovillous Adenomas
 Mixture of both tubular and villous elements.
 Polyps with more than 25% and less than 75% villous component are called as
tubulovillous.
 Sessile serrated adenomas
 overlap histologically with hyperplastic polyps
 more commonly found in the right colon
 lack typical cytologic features of dysplasia but have malignant potential.
 Histologic criteria: serrated architecture throughout the full length of the glands,
including the crypt base, crypt dilation, and lateral growth
 Intramucosal carcinoma
 dysplastic epithelial cells breach the basement membrane to invade the lamina propria
 have little or no metastatic potential- no functional lymphatic channels
 complete polypectomy is generally curative
 Invasion beyond the muscularis mucosae-invasive adenocarcinoma and carries a risk of
spread to other sites.

8. HIRSHSPRUNG DISEASE
 congenital aganglionic megacolon
 Prevalence – 1:500
 Pathogenesis:
 Failure of migration of neural crest cells into bowel
 Leading to absence of nitric oxide releasing ganglionic cells
 Resulting in sustained contraction
 Failure of peristalisis as it lacks both meisenner and myenteric plexus
 Downregulation of RET gene and Downs syndrome
 If short segment of colon gets affected - short segment hirschprung
 If entire colon gets affected - long segment hirschprung
 Most common site: rectum and proximal part of colon to rectum
 Clinical manifestations:
 Constipation - failure of passage of meconium
 Distension of colon proximal to constriction
 Investigations: Rectal biopsy findings:
 Aganglionosis
 Increased acetylcholinesterases
 Absence of calretenin

PATHOLOGY AGAM
9. GROSS & MICROSCOPIC FEATURES OF COLORECTAL CARCINOMA
GROSS PICTURE
 Right (proximal) colon:
 Large polypoid, exophytic masses (cauliflower like) projecting into the lumen
 Rarely causes obstruction
 Left (distal) colon:
 Annular lesions producing napkin ring constriction and luminal narrowing.
 The tumours are firm.
 Associated with intestinal obstruction
 Flattening of mucosal folds
GROSS FEATURES:
 They can occur in any part of the colon.
 Frequency: Rectum (60%)>Sigmoid and descending colon (25%)>caeaum and ileocaecal
valve (10%), hepatic and splenic flexure (5%), least in transverse colon.
 Proximal bowel-more liquid- allow large growth
 Distal bowel- less liquid- growth more into the wall
 Other morphological patterns include:
 Diffuse/ tubular tumours- diffuse flattening and thickening of the colon. Initially
involving mucosa then involve the entire wall of intestine.
 Ulcerating tumours: -Raised, irregular edges with central ulcerated area which
infiltrate the deep layers of the bowel wall.
MICROSCOPY:
 Right and left-sided colonic adenocarcinomas are similar.
 Character:
 tall columnar cells that resemble dysplastic epithelium found in adenomas
 Strong stromal desmoplastic response is responsible for firm consistency.
 Well or moderatley differentiated:
 glands of variable size and configuration separated by moderate amount of stroma
 Abundant mitotic figures
 lumen filled with inspissated eosinophilic mucus and nuclear and cellular debris
(“dirty” necrosis)
 Poorly differentitated: form few glands
 Others may produce abundant mucin; these are associated with poor prognosis.
 Tumors may also be composed of signet ring cells similar to those in gastric cancer or
may display features of neuroendocrine differentiation.
AGAM PATHOLOGY
10. AMOEBIC DYSENTERY
 Caused by Entamoeba histolytica.
 Spread by fecal-oral transmission.

PATHOGENESIS:
 E. histolytica cysts have a chitin wall and four nuclei and are resistant to gastric acid.

Acid-resistant E. histolytica cysts pass through stomach unharmed

Cysts colonize the epithelial surface of the colon

Trophozoites are released and they reproduce under anaerobic conditions

Amoebae attach to the colonic epithelium

Amoebae include apoptosis and invade crypts

Burrow laterally into lamina propria

Tissue damage

Flask-shaped ulcer with a narrow neck and broad base

Dysentery

 In 40% of patients with, parasites may penetrate splanchnic vessels and embolize to the
liver to form abscesses.
 Amoebae may also spread to the kidneys and brain via the bloodstream.

CLINICAL FEATURES:
 Patients present with abdominal pain, bloody diarrhea or weight loss.
 Occasionally, acute necrotizing colitis and megacolon occur; associated with significant
mortality.
 Metronidazole is the most effective treatment for the systemic disease.

PATHOLOGY AGAM
MORPHOLOGY:
 Amoebiasis affects the cecum and ascending colon most often; sigmoid colon, appendix
and rectum can also be involved.
 Histologic diagnosis is difficult since amoebae are similar to macrophages in size and
general appearance.
 Amoebic liver abscess – can exceed 10 cm in diameter– scant inflammatory reaction at
margins and shaggy fibrin lining.
 Abscess persists after the acute intestinal illness has passed; may spread to heart and
lung.

11. CARCINOID SYNDROME

 Carcinoid tumours arise from the diffuse components of the endocrine system.
 Now, they are called as well-differentiated neuroendocrine tumours.
 Most are found in the GIT – 40% in the small intestine; tracheobronchial tree and lung are
2nd most common sites.
 Ileal carcinoid tumours may cause carcinoid syndrome.
MORPHOLOGY:
 Grossly, carcinoids are intramural or submucosal masses that create small polypoid
lesions.
 In the intestines, the tumours invade deeply to involve the mesentery.
 Yellow or tan in colour; Very firm as a result of an intense desmoplastic reaction – can
result in kinking and obstruction of bowel.
 IHC stains are typically positive for endocrine granule markers such as synaptophysin and
chromogranin A.
CLINICAL FEATURES:
 Carcinoid syndrome occurs in fewer than 10% of patients with ileal carcinoid tumours.
 Characterized by cutaneous flushing, sweating, bronchospasm, colicky abdominal pain,
diarrhea and right-sided cardiac valvular fibrosis.
 Caused by vasoactive substances secreted by the tumour into the systemic circulation.
 Mostly, the released vasoactive substances are inactivated by ‘first pass’ metabolism in
the liver.
 Strongly associated with metastatic disease in the liver because bioactive products can be
released directly into systemic circulation.

AGAM PATHOLOGY
12. ZOLLINGER – ELLISON SYNDROME
 Zollinger Ellison syndrome is caused by the triad of hypergastrinemia, increased acid
production and peptic ulcer.
 They are commonly found in chronic diarrhoea or duodenal ulcers.

PATHOGENESIS:
Gastrinoma = ↑ Gastrin levels

Stimulates enterocytes in S.I Stimulates G receptor in Parietal cell

↑ Secretion of fluid in lumen ↑ Parietal cell mass

Diarrhoea ↑ HCl production

TUMOUR DISTRIBUTION:
 80% is seen in case of duodenal ulcer, pancreatic ulcer and other extra pancreatic sites
 20% is seen in MEN I syndrome (multiple endocrine neoplasia type 1).
 Duodenal Ulcer
Peptic Ulcer
 Duodenal Ulcer → ↑HCl secretion Inactivates pancreatic enzymes
Damage to epithelial surface
 It finally leads to Malabsorption and Maldigestion
 Men 1 syndrome:
 Occurs mainly in three sites:
 Pituitary gland
 Pancreas
 Parathyroid

TREATMENT:
 Proton pump inhibitors
 Somatostatin analogues

PATHOLOGY AGAM
SHORT ANSWERS:
1. MICROSCOPIC INTESTINAL CHANGES IN MALABSORPTION SYNDROME
 Loss of villi and microvilli in the small bowel is the anatomic basis for Malabsorption
Syndrome.
 Scalloping or flattening of duodenal folds. Fissuring over the folds. Mosaic pattern of the
mucosa in the folds
 These damages are caused by presentation of gluten derived peptide Gliadin by HLA
molecules of helper T cells.
2. MORPHOLOGICAL HALLMARKS OF WHIPPLE DISEASE
 Dense accumulation of distended, foamy macrophages in the lamina propria of the small
intestine.
 The villous expansion caused by the dense macrophage infiltrate imparts a shaggy gross
appearance to the mucosal surface.
 Bacteria laden macrophages can accumulate within mesenteric lymph nodes, synovial
membranes of affected joints, cardiac valves & the brain.
3. PEUTZ – JEGHERS SYNDROME
 Etiology - Loss of function mutation of STK11 gene (Autosomal Dominant).
 Presented with multiple GI hamartomatous polyps (benign) and mucocutaneous
hyperpigmentation.
 Most common site - Small intestine
 Histology - Arborizing network of connective tissue, smooth muscle, lamina propria &
glands lined by normal-appearing intestinal epithelium.
 Associated with markedly increased risk of several malignancies.

4. LINITIS PLASTICA
 In diffuse gastric cancer, a mass may be difficult to appreciate but when it's an infiltrative
tumor it often evokes a desmoplastic reaction that stiffens the gastric wall.
 So when there are large areas of infiltration, diffuse rugal flattening & a rigid, thickened
wall may impart a leather bottle appearance termed Linitis Plastica.
 This is a valuable diagnostic clue for gastric adenocarcinoma.
5. COBBLE STONE APPEARANCE
 Sparing of interspersed mucosa, a result of the patchy distribution of Crohn's disease,
resulting in a coarsely textured Cobblestone appearance in which diseased tissue is
depressed below the level of normal mucosa.
AGAM PATHOLOGY
6. FAMILIAL ADENOMATOUS POLYPOSIS (FAP)
 Autosomal dominant disorder in which patients develop numerous colorectal adenomas
in teenage.
 Etiology - Mutation of APC (Adenomatous Polyposis Coli) gene.
 Diagnostic criteria - at least 100 polys are necessary.
 Complication - Colorectal adenocarcinoma develops in 100% untreated FAP patients
early at the age of 30 yrs or always at 50 yrs.
 Treatment - Prophylactic Colectomy.

7. SITES OF PEPTIC ULCER DISEASE

 Proximal duodenum (Most Common)
 Along the lesser curvature, near the interface of the body and antrum.(Common)
 Esophagus, Gastric fundus or body, anterior and posterior wall, greater curvature. (Less
common)
 Margins of gastroenterostomy (stomal ulcer)
 Duodenum, stomach or jejunum - of patients with Zollinger Ellison Syndrome.
 Within or adjacent to Meckel's diverticulum.

8. HELICOBACTER PYLORI
 Nearly all peptic ulcers are associated with H.pylori infection.
 The most common form of peptic ulcer within the gastric antrum or duodenum occurs as
a result of chronic H.pylori - induced antral gastritis.
 So treatment of peptic ulcer is aimed at eradication of H.pylori & neutralization of gastric
acids using Proton Pump Inhibitors.
9. MICROSCOPIC APPEARANCE OF APPENDICITIS
 Neutrophilic infiltration of muscularis propria is the most important diagnostic feature.
 Early stages-associated with congestion and edema of the appendiceal wall
 Later stages-Mucosa gets sloughed off
 Wall becomes necrotic
 Blood vessels get thrombosed
 Neutrophilic abscess in the wall
 Impacted foreign body may be seen in both the cases.

PATHOLOGY AGAM
10. DIFFERENCE BETWEEN ULCERATIVE COLITIS AND CROHN’S DISEASE
Feature CROHNS UC
Any part of g.i tract, usually the ileocaecal
Affects any part of colon
Location region, small intestine or colon. Rectum
Continuous lesion
spared. Skip lesion
Transmural inflammation luminal Mucosal and submucosal
Gross
narrowing common inflammation only.
morphology
Mucosal Cobblestone appearance Luminal narrowing is rare
Lymphocytic infiltrate, Non caseating Crypt abscess, ulcers,
Microscopy
granuloma, fibrosis No granuloma
Intestinal
Diarrhea-bloody or non-bloody Bloody diarrhea
manifestation
Incidence of secondary malignancy low
Increased incidence of colon
Complications Fissures/fistula seen, Malabsorption
cancer
common, Kidney stone formation
Treatment Corticosteroids, antibiotics, azathioprine Mesalamine, 6 mercapto purine
Recurrence
Commonly observed Not observed
after surgery

11. MORPHOLOGY OF TYPES OF HIATAL HERNIA

 Sliding Hernia: The upward movement of entire gastroesophageal junction which results
in protusion of gastric fundus into thorax.
 Paraesophageal Hernia: Here, the gastroesophageal junction remains in the same place,
whereas the fundic part of the stomach slides against the esophagus.

12. GROSS DIFFERENCE BTW BENIGN AND MALIGNANT ULCERS OF STOMACH

FEATURE BENIGN ULCER MALIGNANT ULCER
Site Lesser curvature Greater curvature
Morphology Mucosal base is clear with Necrotic base
mucosal rugae radiating out Mucosal rugae is absent
Margin Overhanging margins Everted margins
Peristalisis Preserved absent
Healing Duration 8-10 days Never heals

AGAM PATHOLOGY
UPDATES
OMPHALOCELE
 Omphalocele occurs when the extraembryonic gut fails to return to the abdominal cavity
and closure of the abdominal musculature is incomplete.
 As a result, abdominal viscera (including the liver) herniate ventrally into a membrane
covered by amnion and peritoneum separated by Wharton jelly.
 Omphalocele is associated with other birth defects as well as chromosomal abnormalities.

GASTROSCHISIS
 Gastroschisis involves all the layers of the abdominal wall, from the peritoneum to the
skin, is usually limited to the intestine, and occurs as an isolated defect without other
abnormalities.
 The incidence of gastroschisis is rising, possibly due to environmental factors including
smoking and exposure to agricultural chemicals.
HIRSCHSPRUNG DISEASE AND DOWN SYNDROME:
 The association between Down syndrome and Hirschsprung disease may be linked to the
Down syndrome cell adhesion molecule gene on chromosome 21, overexpression of
which leads to neural defects.
 In patients without trisomy 21, germline mutations in several genes that are required for
normal gut innervation have been implicated, the most common of which involve RET and
EDNRB or EDN3 (which encode a receptor-ligand pair).
 These proteins appear to participate in signaling pathways that regulate development of
the enteric nervous system.
MORPHOLOGY OF VIRAL GASTROENTERITIS
 Include villous shortening, epithelial vacuolization, crypt hypertrophy, and lamina propria
infiltration by neutrophils, lymphocytes, and monocytes
 The microvillus brush border is also compromised, and reduced expression of digestive
enzymes can lead to mild steatorrhea and carbohydrate malabsorption.
PATHOLOGY OF EARLY ONSET IBD
 Very early onset IBD can be driven by mutations in single genes required for epithelial ion
transport, immune signaling, or host defense.
 Macrophages produce excessive IL-1β in infants with IL-10 receptor mutations (the most
common mutation in very early onset IBD).
 These patients have benefited from IL-1 receptor antagonist treatment

PATHOLOGY AGAM
MICROBES AND IBD
 Microbes express proteins and other molecules and generate metabolites that can
protect against or promote IBD
 Specific examples include Clostridia species, which stimulate development of regulatory T
cells, and Bifidobacterium, which promote Th17 differentiation.
 In addition, multiple species produce butyrate, whose activities include enhancement of
mucosal barrier function, increased epithelial proliferation, and immune regulation.
ONE LINERS
 The risk of dysplasia in inflammatory polyps ranges from 1% to 20% and increases sharply
in pedunculated polyps greater than 1 cm in diameter.
 Peri-appendiceal lymphoid hyperplasia, e.g., after viral infection, and the resulting
appendiceal compression has also been proposed as a mechanism of venous and luminal
obstruction in acute appendicitis
 VACTERL (vertebral, anal, cardiac, tracheoesophageal, renal, and limb defects)
 TACRD (tracheal agenesis/atresia, complex congenital cardiac abnormalities, radial ray
defects, and duodenal atresia)
 Diffuse esophageal spasm is also known as corkscrew esophagus due to the appearance
on barium swallow
 Environmental enteric dysfunction / environmental enteropathy / tropical enteropathy /
tropical sprue.
 Albumin loss, which can approach 10 g/day, across the gastric mucosa characterize
Ménétrier disease.
 Enteroaggregative Escherichia coli. EAEC has a unique “stacked brick” morphology when
bound to epithelial cells.
 Some individuals are naturally resistant to norovirus infection due to mutations that
inactivate galactoside 2-alphaL-fucosyltransferase, FUT2, which contributes to the
glycosylation of proteins destined for the cell surface in the Golgi complex.
 AMP-activated protein kinases (AMPK) control cell polarization and act as a brake on
growth and anabolic metabolism (mutated in Peutz-Jeghers Syndrome)
 The ATG16L1 mutation that is linked to Crohn disease promotes ATG16L1 degradation,
thereby limiting autophagy in IBD

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