Endoscopy Practice and Safety
Editor: Peter B. Cotton
David N. Lewin
Fig. 1 Histological sections of well-oriented biopsies from various areas of the gastrointestinal tract. All reveal mucosa to the
muscularis mucosa (at the lower portion of the photomicrograph). (A) Esophageal (squamous mucosa). (B) Gastric fundic (or
oxyntic) type mucosa with a central parietal (pink cells) zone. (C) Gastric antral type mucosa with the basal mucous gland.
(D) Small bowel mucosa with finger-like villi; the gland-to-villus ratio should be at least 3:1. (E) Colon with a parallel
'test-tube' arrangement of the crypts.
Fig. 2 Histological sections of tangentially oriented normal mucosa from various areas of the gastrointestinal tract. (A) Esophageal
(squamous mucosa) with relative increased amount of basal cells (center) due to orientation. (B) Gastric fundic (or oxyntic)
type mucosa with increased amount of foveolar tissue due to poor orientation. (C) Small bowel mucosa in which it is very difficult
to assess the villus-to-crypt ratio. (D) Colonic mucosa with loss of the 'test-tube' arrangement and instead numerous small cross-sections of each crypt.
Fig. 3 Slide view of serial sections of four well-oriented biopsies in parallel.
Fig. 4 Slide view of numerous (greater than 10) biopsies placed in a single container. A few of the biopsies are of reasonable size;
however, some are not well represented.
Fig. 5 Section of colonic tissue with central fold (irregular dark line through the center of the biopsy). This artifact, if pronounced,
can make areas of the biopsy impossible to evaluate.
Fig. 6 Medium-power view of a tubular adenoma with a subtle shattering of the tissue. This is caused in the histology laboratory
by a dull microtome blade and causes linear lines through the tissue. This can cause interpretation problems.
Fig. 7 Slide view of a single well-oriented biopsy with multiple ribbons (sections) of the tissue on a single slide. This allows
the pathologist to follow suspicious areas through the depth of the tissue. This can be especially important when trying to
identify granulomas for the diagnosis of Crohn's disease.
Fig. 8 Crush artifact: a medium-power view of the edge of a duodenal biopsy with a carcinoid tumor. Crush is present in virtually
all biopsies to some degree. Lymphocytes and endocrine cells (as in this biopsy) are often most affected by the crush. The
cells lose their usual rounded appearance and become dark, elongated, and uninterpretable.
Fig. 9 Burn/cautery artifact: a medium-power view of a colonic biopsy with moderate cautery artifact. The cells and nuclei elongate and
the architecture of the lesion is distorted. Architecturally this polyp appears to be a hyperplastic polyp; however, differentiation
from a tubular adenoma or serrated adenoma due to the nuclear enlargement is impossible.
Fig. 10 Burn/cautery artifact: a high-power view of a colonic polyp to illustrate the elongation of the nuclei. The artifact gives the
suggestion of dysplastic nuclei; however, it is unclear if this represents an adenoma or not.
Fig. 11 Low-power view of a polypectomy specimen. The adenoma and focal invasive carcinoma are present in the tip at the lower right
portion of the specimen. The stalk is covered by normal colonic mucosa and has a loose (pale) fibrovascular core. The margin
is present at the other end.
Fig. 12 Low-power view of an endoscopic mucosal resection of a granular cell tumor of the esophagus. The surface (top of picture) is covered with squamous mucosa. There is a pink cellular lesion (granular cell tumor) in the center and the deep portion
represents the cauterized submucosal margin.
Fig. 13 High-power view of an EMR of a granular cell tumor. The deep surgical margin (inferior portion of picture) has been inked with black ink. There is an adjacent artery. The tumor is in the top right hand portion of the image.
Fig. 14 Medium-power view of a villous adenoma of the colon. The routine stain used in pathology is the hematoxylin and eosin (H&E)
stain. The nuclei stain blue with the hematoxylin and the cytoplasm has a pink (eosinophilic) appearance with the eosin.
Fig. 15 Slide view of a smear using a brush from a pancreatic duct brushing. The brush was smeared onto the slide, depositing cells,
the slide fixed in alcohol and stained with a Pap stain.
Fig. 16 Slide view of a smear made from a fine-needle aspiration. A drop of material was placed at the top of the slide and smeared
with a second slide to spread the cells. The material was allowed to air dry and stained with Romanovsky stain.
Fig. 17 Slide view of a ThinPrep. The material is placed into a fixative and transported to the lab. The ThinPrep machine creates
a monolayer of cells on a slide that are then stained with Pap stain.
Fig. 18 Medium-power view of Pap-stained slide. Image of a cluster of normal glandular epithelial cells. Similar to a H&E-stained
histology slide, the nuclei are stained blue (from hematoxylin). There are three cytoplasmic stains: light green (which stains
the majority of the cytoplasm in this image), eosin (a pink stain), and orange G.
Fig. 19 High-power image of a Romanovsky (metachromatic stain). These slides are allowed to air dry with subsequent enlargement of
the cells' cytoplasm and nuclei.
Fig. 20 High-power view of an air-drying artifact in a Pap-stained slide. The nuclei breakdown and the nuclear contours become indistinct.
There is irregularity to the cytoplasmic borders as well.
Fig. 21 Medium-power view of a cytological crush artifact. The cells can become spindled (as in this example) and may be mistaken
as a sarcoma. The nuclei become elongate and, if crushed enough, can be uninterpretable.
Fig. 22 High-power view of Pap-stained slide with cells on top of one another. The three dimensional nature of this preparation makes
it very difficult to evaluate the cytological features of each individual cell. The features are obscured by other cells on
top of one another.
Fig. 23 Medium-power view of Romanovsky-stained cytology slide with displaced epithelium. Squamous cells (the large purple cells with
centrally placed nuclei) are present in this aspirate from a lymph node. The squamous cells are picked up by the fine-needle
aspiration through the esophagus lined by squamous epithelium. This is not a significant problem in this case; however, aspirating
a lymph node through a malignancy is very problematic, as one may pick up malignant cells going through a tumor and get a
false positive lymph node.
Fig. 24 A medium-power view of an unsatisfactory smear (Romanovsky stain). In this case the thickness of the preparation makes it
impossible to render a cytological diagnosis.
Fig. 25 A medium-power view (Pap stain) of a benign aspirate of a pancreas. There is a cohesive group of cells present in a 'honeycomb-like' arrangement of cells. The nuclei are relatively homogenous and small. The cells respect each others borders.
Fig. 26 A medium-power view (Pap stain) of a reactive aspirate of the pancreas. Pancreatic ductal epithelial cells are present. The
nuclei are enlarged with single prominent nucleoli. These features are typically seen in inflammatory (reactive) conditions.
Fig. 27 A medium-power view (Pap stain) of an atypical smear of pancreatic ductal epithelial cells. The cells are clustered together;
however, there is nuclear enlargement and elongation of the nuclei. This is not definitive for malignancy; however, these
features are often seen in dysplasia and present in many malignant cases.
Fig. 28 A medium-power view (Pap stain) of a smear suspicious for malignancy. Two cell populations are present in this smear: the
inferior aspect of the picture has normal epithelial cells with a nice homogenous appearance. In the superior cluster, the
cells are larger. The nuclei are irregular and there is loss of the normal architecture. If this were all that were seen in
a smear, the diagnosis of suspicious would be used. The majority of these lesions are malignant; however, there are typically
too few diagnostic cells to feel comfortable with the diagnosis.
Fig. 29 A high-power view (Pap stain) of a malignant smear. The cells are enlarged. The nuclei are irregular with focal prominent
nucleoli. There are nuclear contour irregularities and loss of the typical architecture. Necrotic individual cells are present
Fig. 30 Summary of diagnostic features of malignancy.
Fig. 31 H&E images of reflux esophagitis. These are (A) low- and (B) medium-power images of the squamous mucosa in reflux esophagitis.
There is basal cell hyperplasia (expansion of the basal proliferative zone) and elongation of the rete papilla of the squamous
epithelium. In image B, a central eosinophil can be seen in the squamous mucosa.
Fig. 32 H&E image of eosinophilic esophagitis. There is some basal cell hyperplasia and elongation of the rete papilla (as seen in
reflux esophagitis); however, in contrast there are numerous eosinophils (typically greater than 20 per high-power field)
in the squamous mucosa.
Fig. 33 H&E image of marked elongation of the rete papilla (greater than 90% of the mucosal thickness) and basal cell hyperplasia.
Fig. 34 Low- and high-power H&E images of Barrett's esophagus. There is replacement of the normal squamous epithelial lining of the
esophagus by a glandular mucosa (typically gastric type with the presence of goblet cells). (B) is a high-power view of intestinal
metaplasia with numerous goblet cells.
Fig. 35 Combination Alcian blue at pH 2.5 and PAS stain on the same biopsy seen in Fig. 34. The goblet cells stain deep blue with
the Alcian blue stain, while the gastric-type epithelium with neutral mucins stains pink with the PAS stain. (A) is a low-power
view, while (B) is a high-power image.
Fig. 36 High-power images of candida in the esophagus. (A) An H&E stain. (B) A PAS stain. (C) A cytology specimen stained with Pap.
All show, with varying degrees of clarity, squamous epithelial cells and candidal spores and hyphae (pink on H&E, purple on
PAS, and red on Pap).
Fig. 37 Herpes esophagitis. (A) An H&E high-power view of the base of the epithelium adjacent to an ulcer. There are enlarged multinucleated
cells (representing the intranuclear inclusions of the virus). (B) An immunohistochemical stain, with the herpes infected
squamous cells staining brown.
Fig. 38 Cytomegalovirus esophagitis. (A) An H&E high-power view of the base of the ulcer. There are enlarged cells with single eosinophilic
intranuclear inclusions (representing the intranuclear inclusions of the virus). (B) An immunohistochemical stain, with the
CMV-infected endothelial cells staining brown.
Fig. 39 Invasive squamous cell carcinoma. (A) is a medium- and (B) a high-power H&E-stained slide. The lesion consists of infiltrating
nests of tumor cells. The cells have intercellular bridges and focal keratinization, characteristic of squamous differentiation.
Fig. 40 Adenocarcinoma of the esophagus. Medium-power H&E section with overlying squamous mucosa and infiltration of the lamina propria
and muscularis mucosa by a gland-forming tumor. The nests of tumor cells have enlarged hyperchromatic nuclei and irregular
Fig. 41 Poorly differentiated tumor of the esophagus. Medium-power H&E section of a poorly differentiated malignancy of the esophagus.
Immunohistochemical stains would be required to exclude sarcomas, lymphomas from carcinoma. No distinguishing elements (gland
or mucin formation for an adenocarcinoma or keratinization for a squamous cell carcinoma) are present.
Fig. 42 Reactive gastropathy. Medium-power H&E section of gastric antral type mucosa. There is elongation of the foveolar (surface
epithelium) with focal erosion and an inflammatory exudate. The inflammatory cells present are predominately neutrophils,
with a relative paucity of lymphocytes (chronic inflammatory infiltrates).
Fig. 43 H. pylori-associated chronic active gastritis. (A) Medium-power H&E section with a superficial infiltrate of lymphocytes and plasma
cells in the lamina propria (what was once called a superficial gastritis). (B) High-power H&E of the superficial foveolar
epithelium to illustrate some Helicobacter organisms. (C) High-power Giemsa stain of Helicobacter organisms (staining blue). (D) High-power silver stain (Steiner stain) where the Helicobacter organisms are black. (E) High-power H&E revealing the infiltration of the gastric epithelium by neutrophils (acute or active
gastritis). (F) Medium-power H&E revealing a lymphoid aggregate at the base of the epithelium, typical of Helicobacter infection.
Fig. 44 Medium-power PAS-stained section of an infiltrative signet ring carcinoma of the stomach. There is loss of the normal glandular
architecture. Residual normal surface epithelium (staining pink at the top) is present and there is an infiltration of single
malignant cells in the lamina propria. These cells are filled with mucin that stains pink with the PAS stain.
Fig. 45 Mucosal associate lymphoid tissue (MALT) lymphoma. H&E medium-power view with intense infiltration of the lamina propria by
a lymphoid infiltrate (blue) with associated parietal gland (pink) loss on the right hand portion of the image.
Fig. 46 Stomach with granuloma: H&E medium-power view with two large epithelioid granulomas at the base of the mucosa, surrounded
by a lymphoid aggregate in a Crohn's patient.
Fig. 47 Hyperplasic polyp: H&E low-power image of antral mucosa with surface erosion (top of image), foveolar hyperplasia, and glandular dilatation lined by mucinous cells.
Fig. 48 Fundic gland polyp. H&E low-power image of fundic-type mucosa with glandular dilatation lined by a mixture of parietal, chief,
and mucinous cells.
Fig. 49 Gastric adenocarcinoma. H&E medium-power image of an adenocarcinoma of the stomach. There is an increased number of glands
with enlarge nuclei and relatively little cytoplasm. The normal gastric glands are not present.
Fig. 50 Endocrine (carcinoid) tumor. H&E medium-power image with tumor comprised of nests and lobules of cells. Gland formation is
Fig. 51 Lymphoma. H&E medium-power image of a high-grade lymphoma. The cells are enlarged with prominent vesicular nuclei and prominent
nucleoli. Numerous mitotic figures are present.
Fig. 52 Gastrointestinal stromal tumor. H&E medium-power image of a spindle cell neoplasm with numerous admixed lymphocytes. There
is relatively little mitotic activity. Immunohistochemical stains are needed to subclassify this mesenchymal neoplasm. The
primary prognostic factors are tumor size and mitotic activity.
Fig. 53 Normal small bowel mucosal biopsies. H&E medium-power image. (A) has the normal gland-to-villus ratio of 3:1, while (B) is
a biopsy from the duodenal bulb with Brunner's glands and relative villous blunting, but no increased inflammatory infiltrate.
Fig. 54 Celiac sprue. This is a severe mucosal lesion with almost total villous atrophy ((A) medium-power H&E), an increased lymphoplasmacytic
infiltrate in the lamina propria, and increased numbers of intraepithelial lymphocytes ((B) high-power H&E).
Fig. 55 Whipple's disease. There is a lamina propria infiltration by histiocytes. Focal fat (clear spaces) are present as well. (A)
is a medium-power H&E, (B) a high-power H&E, and (C) a high-power PAS-stained section. The histiocytes are positive (pink)
with the PAS stain.
Fig. 56 Mycobacterium aviumintracellulare (MAI). Similar to Whipple's disease, there is a significant infiltration of histiocytes in the lamina propria. These are
filled with the organisms and can be identified on a modified acid fast stain (Fite). (A) medium-power H&E, (B) high-power
H&E, and (C) high-power fite stain.
Fig. 57 Giardia. High-power H&E of small bowel mucosa. The organisms can be seen in the lumen adjacent to the surface epithelium. They are
purple concave or pear shaped.
Fig. 58 Gastric metaplasia. (A) Medium-power H&E of duodenal mucosa with the typical goblet cells. In the center of the picture the
surface epithelium has the foveolar epithelium typically seen in gastric mucosa (gastric surface metaplasia). (B) Low-power
H&E of duodenal mucosa with gastric surface metaplasia and gastric fundic-type glands.
Fig. 59 Brunner's gland nodule. Low-power H&E image of surface duodenal mucosa and prominent submucosal Brunner's glands (endoscopically
a nodular appearance).
Fig. 60 Adenoma. (A) Low-power H&E image of an adenomatous polyp. The lesion is blue from low power due to the enlargement and hyperchromasia
of the epithelium (dysplasia). (B) Higher-power H&E of the dysplastic epithelium with enlargement and stratification of the
nuclei typical of adenoma (dysplasia, low grade in this instance).
Fig. 61 Abnormal endoscopy and biopsy findings in 205 patients with diarrhea.
Fig. 62 Normal colonic mucosa, H&E stains. (A) Low-power image of the right side of the colon and left side of colon. (B) The architecture
is similar with the crypts lined up as 'test tubes' in a rack. There is a difference in the inflammatory infiltrate, with more lymphocytes, plasma cells, and eosinophils typically
present on the right side of the colon. (C) There is some mild architectural distortion adjacent to this normal lymphoid aggregate
in the center of this biopsy.
Fig. 63 Collagenous colitis. (A) Low-power H&E view of a colonic biopsy in collagenous colitis. The architecture is similar to the
normal mucosa (Fig. 62A) with crypts arranged parallel to one another and extending to the base of the biopsy. There is a
mild increase in the lymphocytes in the lamina propria. A prominent acellular band is present below the surface epithelium.
This 'collagenous' expansion of the basement membrane is the characteristic finding in collagenous colitis. (B) High-power H&E view of the thickened
basement membrane. This basement membrane should be thicker than 15 µm (a normal lymphocyte is 7 µm, so at least the thickness of two lymphocyte nuclei). There are often entrapped lymphocytes and blood vessels in the collagen
band. Additionally there are increased numbers of lymphocytes, eosinophils, and plasma cells in the lamina propria. There
is focal epithelial detachment from the basement membrane and some epithelial apoptosis. (C) Medium-power trichrome stain
of normal colonic epithelium. The blue strip below the epithelium is the normal basement membrane thickness. This is to be
contrasted with (D), a trichrome stain in collagenous colitis that highlights the marked basement membrane thickening (blue)
below the surface epithelium.
Fig. 64 Lymphocytic colitis. (A) Medium-power H&E view of lymphocytic colitis. Similar to normal and collagenous colitis, the architecture
of the mucosa is intact, with parallel crypts that extend to the muscularis mucosa. There is an increased lymphocytic infiltrate
in the lamina propria, no thickening of the basement membrane, and a characteristic increase in the number of intraepithelial
lymphocytes (lymphocytes above the basement membrane and between the colonic epithelial cells). This increase in the number
of intraepithelial lymphocytes is best identified in (B), a high-power H&E view of the mucosa. There should be greater than
one lymphocyte per five epithelial cells.
Fig. 65 Crypt architectural changes in idiopathic inflammatory bowel disease. Medium-power H&E view of a biopsy from a patient with
ulcerative colitis. The normal crypt architecture is disrupted. There is crypt branching. Some of the crypts are markedly
expanded with the presence of neutrophils in the lumen (crypt abscess). A number of the crypts are foreshortened with the
base of the crypt not extending all the way to the muscularis mucosa at the base of the biopsy. The surface of the biopsy
has an undulating, almost villiform appearance, not the typical flat surface.
Fig. 66 Acute self-limited colitis (infectious colitis). A medium-power H&E view of colonic mucosa with an increase in the number
of lamina propria inflammatory cells. The majority of inflammatory cells are in the upper half of the lamina propria (as opposed
to the predominance of deep inflammatory cells in typical inflammatory bowel disease. There is no crypt architectural distortion.
Fig. 67 Crohn's disease. Medium-power H&E view of mucosa and superficial submucosa with an epithelioid granuloma, typical of that
seen in Crohn's disease. The granuloma is seen in the middle of the image, at the base of the crypts. There is an increase
in the number of inflammatory cells in the lamina propria and some crypt architectural distortion.
Fig. 68 Granuloma associated with a ruptured crypt. High-power H&E image of a ruptured crypt in the center of the image with an associated
granuloma composed of epithelioid histiocytes. These lesions can be seen in both ulcerative colitis and Crohn's disease and
are not the characteristic granuloma (Fig. 67) virtually diagnostic of Crohn's disease.
Fig. 69 Crohn's disease. Medium-power H&E view of colonic mucosa illustrating patchy microscopic inflammation typical of Crohn's disease.
In addition to the gross patchiness present on endoscopic examination, microscopic patchiness is also present. There is a
focus of inflammation on the left side of the image, while the right side of the image has a normal inflammatory component.
Fig. 70 Pseudomembranous colitis. Medium-power H&E view of colonic mucosa with pseudomembrane formation. There is a predominantly
neutrophilic (acute) inflammatory infiltrate present in the biopsy. The pseudomembrane is present on the right upper portion
of the image. There is a loss of the surface epithelium and the pseudomembrane is comprised of inflammatory cells and pink
Fig. 71 Ischemic colitis. Medium-power H&E view of colonic mucosa in ischemia. There is surface erosion and a pseudomembrane present
in the top right portion of the image. In contrast to Fig. 70, there is atrophy (loss) of the crypt glandular epithelium and the lamina propria has a pink hyalinized quality.
Fig. 72 Tubular adenoma. High-power H&E image of tubular adenoma. The top of the image has the adenomatous (dysplastic) epithelium
and is to be compared with the normal colonic mucosa in the lower portion of the image. The dysplasia is characterized by
a dark blue appearance to the tissue. This is secondary to the increased size of the nuclei, stratification of the nuclei,
and a loss of pale mucin.
Fig. 73 Tubular adenoma. Low-power H&E image of tubular adenoma. The extreme left portion of the image contains normal colonic mucosa
and the remainder of the darker glandular tissue is the (dysplastic) tubular adenoma. This image should be compared to Fig.
74, of a villous adenoma. The tubular adenoma is comprised of tubular forms of the dysplastic glands.
Fig. 74 Villous adenoma. Low-power H&E image of a dysplastic (adenomatous) epithelium with tall finger-like projections. The architecture
is similar to the villi present in small bowel mucosa (Fig. 53), however, there are increased nuclear atypia and enlargement.
Fig. 75 Flat adenoma. Low-power H&E view of colonic mucosa with dysplastic epithelium. On the far right of the image there are a couple
of normal crypts present. Unlike usual adenomatous polyps, there appears to be no protrusion of the dysplastic epithelium
above the normal mucosa (the lesion appears flat, or even depressed).
Fig. 76 Hyperplastic polyp. Medium-power H&E view of a typical hyperplastic polyp. There is an increased number of epithelial cells,
giving a serrated (saw-like) appearance to the surface epithelium and into the crypts. There is no increase in the nuclear
size (no dysplasia).
Fig. 77 Serrated adenoma. Medium-power H&E view of a lesion that has the architecture of the hyperplastic polyp (Fig. 76), but nuclear
atypia and hyperplasia (dysplasia) typically seen in a tubular adenoma (Fig. 72).
Fig. 78 Sessile serrated adenoma. Medium-power H&E view of a lesion with architecture of the hyperplastic polyp (Fig. 76), but more
architectural distortion (dilatation of the basal glands and arrangement of the glands parallel to the muscularis propria).
There should not be significant dysplasia (nuclear atypia) in contrast to a serrated adenoma (Fig. 77).
Fig. 79 Adenocarcinoma of the colon. Medium-power H&E view of a moderately differentiated invasive adenocarcinoma. The lesion is forming
glands (best seen in the top of the image). At the base of the image, the glandular cells are infiltrating into the lamina
propria. There is a characteristic desmoplastic response to the tumor, comprised of a fibroblastic response around the tumor
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