CTYTOLOGY & CYTOPATHOLOGY

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CYTOLOGY CYTOPATHOLOGYGI Tract Accessory
Organs

• Lecturer/Mentor Dr Guyah
• Student Seth Shikuku
• Msc. Medical Cytology Histology
• Maseno University

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Sampling Techniques-GI tract Cytology

• Brushing Cytology Superficial mucosal lesions,
  bile ducts and pancreas using endoscopy
• Transmucosal FNA Endoscopic Ultrasound guided.
  Allows sampling lymphnode, GI Tract, Liver and
  pancreas
• Salvage cytology processing materials present on
  forceps after biopsy
• Touch Imprint cytology

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Overview of GI Tract

• Four concentric layers Mucosa, Submucosa,
  Muscularis externa and serosa
• Mucosa Inner most(Epithelium, lamina propria,
  muscularis mucosae)
• Lamina propria A CT glands, blood vessels and
  lymph.
• Mucosae smooth muscle, movt of mucosa.
• Submucosa Dense, Fibroelastic CT, neural,
  vacular and lyphatic system. Meisssners
  submucosal nerve plexus
• Muscularis Externa Smooth muscle-circular
  longitudinal-contractions peristalysis
• Serosa Thin layer of CT, outermost. Simple
  squamous epithelium(mesothelium)

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Esophagus

• Esophagus Mucosanon-keratinized stratified Sq.
  epithelium.
• Submucosatubuloacinar (esophangeal glands
  proper)
• Muscularisskeletal and smooth muscle
• Serosa LCT, Mesothelial cells(Sq epthelial
• Convey boluses to the stomach

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INFECTIOUS ESOPHAGITIS

• Infections Candida, Herpes, CMV
• Repair
• Barrets Dysplasia (Low grade, High grade)
• Adenocarcinoma
• Squamous cell carcinoma

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Infectious Esophagitis

• A. Candida spp. esophagitis.
• The spaghetti and meat-balls appearance is very
  characteristic.
• Non-branching pseudohyphae, yeast forms, or a
  mixture of both.
• Necroinflammatory debris
• B. Aspergillus Esophagitis
• Aspergillus esophagitis. Compared with Candida,
  the hyphae of Aspergillus are thicker and
  cyanophilic, and show true septation and 45
  acute angle branching (Papanicolaou, HP
• C. Herpes simplex esophagitis.
• Squamous cells with increased cytoplasmic and
  nuclear volumes
• Intranuclear inclusion bodies surrounded by a
  halo and thickened nuclear membrane
• Ground-glass chromatin
• Multinucleation, nuclear molding.
• 
  
  Refer Comprehensive Cyto pg290

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Infectious Esophagitis

• CMV Esophagitis
• Marked nucleomegaly and cytomegaly
• Thick, irregularly marginated chromatin
• The diagnostic infected cell is enlarged compared
  with its uninfected compatriots.
• The nuclear inclusion resembles an owls eye
  with a large central dark area, surrounded by a
  zone of pallor, which is in turn surrounded by an
  irregularly thickened nuclear membrane (CC291)

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BARRETTS ESOPHAGUS, DYSPLASIA, AND ADENOCARCINOMA

• Columnar cell change/Columnar line Esophagus
  (CLE)
• Characterized by columnar cells in a honeycomb
  pattern with basally oriented nuclei and granular
  to vacuolar apical cytoplasm, filled with neutral
  mucin.
• Change is thought to represent the first step in
  the progression to adenocarcinoma of the
  esophagus
• Repair changes.
• Metaplastic cells are arranged in a streaming
  architecture that resembles a school of fish
  swimming.
• NC ratios can be moderately elevated.
• Chromatin is pale with prominent nucleoli.
  (P294)

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• Intestinal metaplasia.
• Thought to be the step after columnar-like
  epithelium in the progress towards esophageal
  adenocarcinoma.
• characterized by the presence of goblet cells in
  a background of columnar cell change.
• Goblet cellsbarrel-shaped with an eccentric
  nucleus pushed to one end of the cell by a large
  amount of mucin that also causes the cell
  membranes to bulge
• Esophageal adenocarcinoma.
• Loose clusters of cells and individually
  scattered cells with large pleomorphic nuclei
  with distorted membranes, nuclear overlap,
  hyperchromatic chromatin, and distinct nucleoli
• Diathesis presence background has a dirty
  appearance (P295)

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• Brushing cytology of gastroesophageal junction,
• Papanicolaou stain, 600.
• Benign glandular mucosa. (b) Barrett esophagus.
• (c) Low grade dysplasia. (d) High-grade dysplasia

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Histology of gastrointestinal junction,
hematoxylin-and-eosin (HE) stain, 400. (a)
Benign glandular mucosa. (b) Barrett esophagus.
(c) Low-grade dysplasia. (d) High-grade
dysplasia
Low grade dysplasia The presence of small
clusters or
acini of columnar cells with crowded, enlarged,
elongated, and hyperchromatic nuclei and
increased nuclear to cytoplasm ratio
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Key Features of Barretts Glandular Dysplasia and
Adenocarcinoma

• Reduced intercellular cohesion small cellular
  aggregates with frayed borders, individually
  dispersed abnormal cells
• Loss of polarity with irregular distribution of
  crowded, overlapped nuclei
• Indistinct cell borders
• Nuclei thickened membranes with contour
  irregularities, pleomorphism, hyperchromasia,
  large nucleoli nuclei tend to be rounder in
  carcinoma than in dysplasia
• Greater degrees of changes in carcinoma than in
  dysplasia, including increased numbers of single
  abnormal cells.

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Well differentiated Squamous Cell Carcinoma

• Intercellular cohesion is relatively well
  maintained
• sizeable aggregates of large tumor cells that
  have abundant dense appearing cytoplasm (
• With the Papanicolaou, many of the neoplastic
  cells may have orangeophilic cytoplasm.
• Nuclei are centrally positioned and have sharply
  angulated contours. The chromatin is very
  hyperchromatic and coarsely granular or almost
  pyknotic in quality.
• Keratin pearls, elongated cellular configurations
  (tadpole cells), and numerous anucleated squames
  may be present as well.

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Less differentiated Squamous Cell Carcinoma

• Smaller cellular aggregates and often numerous
  individually dispersed neoplastic cells,
  reflecting reduced cohesion.
• Cytoplasm remains dense but more frequently
  cyanophilic.
• Lower volumes of cytoplasm translate into higher
  NC ratios
• Pyknotic chromatin is less frequent as well
  rather, the chromatin appears finely to coarsely
  granular. Nucleoli are also more apparent

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Key Features of Squamous Cell Carcinoma

• Variability in cellular size and shape
• Optically opaque cytoplasm, varying from
  orangeophilic to cyanophilic well-defined cell
  borders
• Centrally positioned angulated nuclei
• Obviously hyperchromatic chromatin, typically
  coarsely granular to structureless
• Variable nucleoli
• Variable intercellular cohesion

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Neuroendocrine Carcinoma SCC LCC

• SMALL-CELL CARCINOMA
• Smears are typically hypercellular, leading to a
  characteristic 1 appearance on Diff-Quik
  stains of a solid sheet of purple almost allowing
  for a diagnosis by examining the slide with the
  naked eye.
• Microscopic examination reveals innumerable
  malignant cells, sometimes extending
  wall-to-wall on the cytologic slides.
• Loosely cohesive groups that readily fall apart
  into single cells
• Cell sizesmall, almost 2 to 3 times a quiescent
  lymphocyte
• Scanty cytoplasm that may occasionally contain
  perinuclear blue bodies
• Nuclear moldingappear to be so compressed into
  each other that they deform mold
• Nuclear features are an important diagnostic
  feature the nuclei should have powdery, stippled
  chromatin.

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Stomach

• Regions Cardia (short pits) with cardiac glands,
  Fundus-largest(Long glands short pits) ,
  Pylorus-pens to SI via pyloric sphincter
• Gastric epitheliumSecretion HCL, digestive
  enzymes and mucus for protection.
• Cells Mucous surface cells Line mucosa pits,
  Mucous neck cells Line entire gland in cardia
  pylorus, Parietal cells-fundusHCL gastric
  Intrinsic factor, Chief cells (zymogen)-base of
  fundic Pepsinogen and Lipase, Enteroendocrine
  cells.
• Simple columnar cells.

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BENIGN Gastric Mucosa

• Glandular epithelium is arranged in flat
  honeycombed sheets with peripheral palisading or
  a picket-fence arrangement (P299)
• H.pylori
• Cytologic and histologic preparations. They are
  curved to S-shaped rods that are 13 µm in
  length. Curving morphology has been compared to
  flying seagulls, especially the 13 µm in
  length.
• On cytologic preparations, the organisms are
  frequently not attached to the mucosal cells
  (Papanicolaou, HP). (P300)

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ADENOCARCINOMA

• Key Features of Adenocarcinoma, Intestinal Type
• Reduction of intercellular cohesion
• Reduction of polarity
• Enlarged nuclei with irregular contours and
  hyperchromatic chromatin
• Prominent nucleoli.

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Key features of Adenocarcinoma Signet-Ring Type

• Variable numbers of generally dispersed
  solitary tumor cells
• Rounded cells with clear to foamy cytoplasm, a
  single eccentric nucleus, and at times a low NC
  ratio
• Cytoplasmic mucin vacuoles displace and distort
  nucleus
• Hyperchromatic nuclei vary from bland to
  obviously malignant
• Contours may be sharply angulated or pointed
• Variable nucleoli.
  (p302)

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GASTROINTESTINAL STROMAL TUMORS

• GISTs) are thought to be derived from cells which
  are the precursors to the cells of Cajal
• Small proportion
• Variable cellularity
• Cohesive groups of spindled cells or epithelioid
  cells
• Variably stained, finely granular chromatin.
  (p304)

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Small intestine

• Duodenum-Brunners gland, jejunum-highly
  developed plicae circulares(main absorptive
  site), ileum-lymphoid follicles(payers patches)
  numerous goblet cells.
• Modificationsincrease surface area Plicae
  circulares, Villi, Microvilli
• Epithelium-absorptive columnar cells
  (enterocytes) interspersed goblet cells
• Villi project into lumen, crpts of
  Lieberkuhn(simple/tubular gland) project into
  lamina propria and open into villi.

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Duodenum

• Proximal of duodenum and terminal of ileum not
  anatomically accessible to sampling by endoscopy
• Secretion of alkaline fluid-neutrailize chime. If
  fails-malignancy
• CMV duodenitis-Most of the glandular cells have
  enlarged nuclei, each with a prominent nuclear
  inclusion surrounded by a broad halo and thick
  nuclear membrane. Multinucleation absent.
• Giardiais Giardia deudonelis-Giardia
  trophozoites have a characteristic pear shape
• Malignant lymphomas, adenocarcinoma, carcinoid
  tumour-less frequent

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Duodenum

• Marginal zone lymphoma of MALT.
• Cytologic hallmark is a monomorphic population of
  small lymphocytes with high NC ratios and ropey
  chromatin
• Benign lymphoid hyperplasia.
• Numerous dyshesive lymphocytes.
• Most are small and mature appearing.
• A fewer larger transformed lymphocytes with
  prominent nucleoli are present.
• The polymorphism is a clue to the benign nature
  of this process

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METASTATIC TUMOURS

• METASTATIC TUMORS
• Metastases may occur to any portion of the
  alimentary tract.
• Although malignant neoplasms arising almost
  anywhere in the body may spread to the tract,
• Most frequent ones include melanoma and
  carcinomas of the breast, ovary, and lung.

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Large Intestine

• Caecum, Colon, Rectum Anus
• Epithelium Columnar cells, without brush-border
  enzyme unlike SI.
• Anus- Near rectum changes from simple columnar to
  Non-keratinized stratified squamous and to
  Keratinized near external opening.
• Inflammatory bowel disease
• The most dreaded complication of inflammatory
  bowel disease (IBD) is the development of
  colorectal adenocarcinoma.
• Blood in stool, occult blood.
• Colonic adenocarcinoma.
• Loose cluster of malignant cells from colonic
  adenocarcinoma with focal signet and ring cells
  present (P

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Accessory Organs- Liver

• Liver Produce bile. Synthesis-plasma proteins,
  storage- glycogen, detoxification
• Encased in Glissons capsule CT, covered with
  visceral peritoneum. Porta hepatis Gate to the
  liver
• 4 Lobules Right, Left,
• Plates of liver cellshexagonal
  cellshepatocytes, nucleus centrally placed
  (epithelial cells) interspersed btn hepatic
  sinusoids (highly permeable capillaries-lined by
  Kupffer cells (Liver macrophages))
• Portal TriadRegion with branches of hepatic
  portal venules, hepatic arterioles bile
  ducts-exit livercuboidal cells, also nerves
  lymphatics.
• Bile canaliculi-channels within Liver
  plates-drain bile into bile ducts
• Space of Disse-spaces btn sinuisods-hosts Ito
  cells stores Vit A
• Liver acinus- Diamond shaped- Zone 1, 2, 3. Zone
  1 most perfused
• Gall bladder- Store Concentrates bile-Simple
  columnar with apical microvilli, joins pancrease
  through pancreatic duct

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BILIARY TRACT

• Right and left hepatic ducts fuse to form the
  common hepatic duct, which is jointed by the
  cystic duct, forming the common bile duct.
• Biliary duct system is lined by a simple tall
  columnar epithelium with small basally oriented
  nuclei.
• Benign/reactive bile ductal epithelium.
• Flat cohesive cluster sheet of highly uniform
  epithelial cells shows a well-demarcated smooth
  edge.
• cells exhibit polarity and are bland in
  appearance.
• Although the NC ratios are focally high, the
  cells are quite uniform. Note the absence of
  individual atypical epithelial cells
  (p313)
• Adenocarcinoma
• Majority of malignant neoplasms involving the
  extrahepatic biliary ductal system are
  adenocarcinomas. Quite uncommon tumor type.
• N/B- Hepatopancreatic biliary conditionsLiver
  pancreas

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Biliary duct Adenocarcinoma

• Key Features
• Atypical cells in tight, 3-dimensional groups
• Significant nuclear overlap and pleomorphism
• Increased NC ratios
• Clumpy chromatin with prominent nucleoli
  (p314)

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Pancreas

• Exocrine and Endocrine portions
• ExocrineSecrete pancreatic juice-enter duodenum
  via hepatopancreatic ampulla.
• Tubuloacinar glands acinar cells-produce
  enzymes, centroacinar-alkaline fluid and
  intercalated ducts-drain acinus are lined by
  centro acinar.
• Endocrine Islets of Langerhans alpha cells
  glucagon(glycogen into glucose), Beta
  cellsInsulin (Tissue glucose uptake), delta
  cellsSomatostatin
• Type 1 Diabetes Loss of Beta cells, inactitivty-
  No insulin secretion
• Type 2 Diabetes- Failure of tissues to utilize
  insulin being produced normally

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Pancreatitis

• Pancreatitis Clinical
• Progressive inflammatory disease of pancreas,
  caused by alcohol consumption in 70 of cases,
  idiopathic chronic pancreatitis (second most
  common type), gallstones.
• Most common in men.
• Characterized by a clinical triad diabetes,
  steatorrhea, radiographic evidence of
  calcification.
• Elevated risk for pancreatic adenocarcinoma.

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Pancreatic Ductal Adenocarcinoma

• Cellular specimen consisting of single cells,
  drunken honeycomb sheets, or loosely cohesive
  two- or three-dimensional glandular clusters of
  pleomorphic polygonal, cuboidal, or columnar
  cells with loss of polarity.
• The nuclei are enlarged and pleomorphic, show
  irregular and thickened nuclear membranes,
  hyperchromatic, coarse, or vesicular unevenly
  distributed chromatin and prominent nucleoli.
• The cytoplasm is delicate, vacuolated, or
  squamoid, is variable in amount, and may contain
  mucin.
• Bizarre cells, signet-ring cells, bi- or
  multinucleated cells, osteoclast-like giant
  cells, mitoses, necrosis, and mucin can be seen

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Acinar Cell Carcinoma

• Moderately cellular smears consisting of
  polygonal cells arranged in loosely cohesive
  irregularly shaped clusters, trabecular
  formations, acini, solid sheets, small glandular
  clusters, or as individual cells
• Cells with low nuclear cytoplasmic ratio,
  pleomorphic nuclei containing granular or
  coarsely clumped chromatin and one to two
  prominent nucleoli, and scant to moderate amounts
  of granular cytoplasm.
• Scattered, strikingly large tumor cells with
  giant nuclei, prominent mitoses, associated
  necrosis, and granular background are evident
• Atlas of cytopath p157-158