Figure 3.2 Normal small bowel, layers of the small intestine. This resection specimen illustrates the four main layers of the small bowel: mucosa, submucosa, muscularis propria, and serosa. The mucosa consists of epithelium (E), lamina propria (L), and muscularis mucosae (MM). The submucosa sits between the muscularis mucosae and the muscularis propria (MP) and it consists of loose fibroconnective tissue and lymphovascular channels. The MP consists of two muscle layers: an inner circular and outer longitudinal. The outermost layer is the serosa. Note the plicae circulares are composed of a reduplication of mucosa held together by a submucosa core.

Figure 3.3 Normal small bowel. The crypt to villous ratio in the normal small bowel ranges from 1:3 to 1:5. The epithelial cells lining the villi are tall columnar absorptive cells and are intermittently punctuated by goblet cells. The base of the crypts contains visible bright pink Paneth cells with scattered endocrine cells (unperceivable at this magnification).

Figure 3.4 Normal small bowel, lacteals. The core of the villi are composed of lamina propria containing migratory chronic inflammatory cells, blood vessels, lymphatic channels, and smooth muscle cells. This example shows dilated lacteals in the tips of the villi, a finding that indicates lymphatic blockage of lymphatic flow of unclear significance.

Figure 3.5 Normal small bowel, cross section of villous projection. Higher magnification of a villous core highlights a dilated lymphatic space containing pale eosinophilic serum. Separate capillary vessels contain red blood cells, and scattered chronic inflammatory cells are present in the supporting substance.

Figure 3.6 Normal small bowel, villous tip. The villous tip is lined by columnar cells with an absorptive brush border composed of microvilli. On H&E stain, this can be visualized as an eosinophilic “fuzzy” border. These absorptive columnar cells are punctuated by goblet cells (arrowhead), and small numbers of lymphocytes (arrows) may be seen traversing between them.

Figure 3.7 Normal small bowel, villous tips (PAS special stain). The microvillous brush border is crisp and deeply eosinophilic on a PAS special stain, which also highlights the goblet cells. Defective, broken, or smudgy brush borders should prompt consideration of microvillous inclusion disease, especially in infants. The cytoplasm of the columnar cells appears pale and homogeneous.

Figure 3.8 Normal small bowel, lipid “hang-up” (PAS special stain). This PAS stain of a villous tip reveals vacuolated cytoplasm of the absorptive columnar cells (compare to previous figure). This finding indicates lipid within the cytoplasm of the epithelial cells and is commonly seen among patients who have ingested food or drink prior to endoscopy. When severe, diffuse, or present in the pediatric population, it is worthwhile to consider a lipid transport disorder.

Figure 3.9 Normal small bowel, crypt base. Paneth cells (arrowheads) contain abundant brightly eosinophilic coarse granules that face the gland lumen. By comparison, enteroendocrine cells (arrows) have deeper red and smaller granules that face the basement membrane.

Figure 3.10 Normal small bowel, smooth muscle within villous core. Delicate tufts of smooth muscle (arrows) extend from the muscularis mucosae along the core of the villi. When cut in cross section (arrowheads), these can be mistaken for histiocytes, signet ring cell carcinoma, or infectious diseases (such as Mycobacterium avium intracellulare).

Figure 3.11 Normal small bowel, normal variant morphology in small intestine. Remember that the slide is a two-dimensional representation of three-dimensional tissues. Villi may be truncated if they extend out of the plane of section, as seen here. The adjoining long, slender villi reassure observers that there is not true villous atrophy.

Figure 3.12 Normal small bowel, normal variant morphology in small intestine. Villi may vary from slender and fingerlike to broad and leaflike depending on geographic region or specific diets. Other variations, such as bridging villi (seen here) may also be seen in healthy patients.

Figure 3.13 Normal small bowel, proximal duodenum with Brunner glands. Brunner glands are found exclusively in the proximal duodenum. Although their bulk lies in the submucosa, extension above the muscularis mucosae is not uncommon, even under normal conditions, as seen here.

Figure 3.14 Normal small bowel, Brunner glands. Brunner glands are lined by cuboidal to columnar cells with pale, uniform cytoplasm and oval, basally located nuclei.

Figure 3.15 Normal small bowel, crushed Brunner glands. Crushed Brunner glands may sometimes take on a neural appearance, raising the differential diagnosis of a neural tumor.

Figure 3.16 Normal small bowel, Brunner glands (PAS special stain). Brunner glands contain PAS positive and diastase-resistant cytoplasmic mucin. This staining pattern can be helpful in differentiating crushed Brunner glands from a neural tumor.

Figure 3.17 Normal small bowel, terminal ileum. Unencapsulated organized lymphoid nodules are found within the mucosa and submucosa of the terminal ileum. These Peyer patches are found exclusively in the ileum, which functions as an immunologic organ.

Figure 3.18 Dart game analogy. If it is difficult to remember the significance of BCL-2, BCL-6, and CD10 as they relate to normal lymphoid aggregate architecture, consider this dartboard analogy. In the game of darts, a player is awarded more points for landing a dart at the center bull’s eye as compared to the periphery of the dartboard. In this analogy, imagine the bull’s eye as a germinal center with the highest points awarded (BCL-6 and CD10). In contrast, the peripheral location is outside of the germinal center and fewer points are awarded for these less challenging shots (BCL-2).

Figure 3.19 Normal lymphoid aggregate, illustration. In a normal lymphoid aggregate, the germinal center is highlighted by BCL-6 and CD10 (analogous to a dartboard’s prized bull’s eye) and is negative for BCL-2. Recall, normal B lymphocytes in the mantle zone surrounding the germinal center and normal T lymphocytes express BCL-2 (analogous to a dartboard’s periphery). Therefore, interpretation of BCL-2 always requires concomitant interpretation of CD20 B lymphocyte marker and CD3 T lymphocyte marker.

Figure 3.20 Normal terminal ileum. The overlying villi of the terminal ileum are characteristically shorter than those seen in the duodenum and jejunum (Figs. 3.3 and 3.13). At low power, the prominent lymphoid aggregate is seen confined within the mucosa (arrowheads highlight the narrow wisp of muscularis mucosae). Although the crypts are not identical copies of each other (the crypts are variably sized with varying amounts of intervening lamina propria), these slight differences are due to the prominent lymphoid aggregate and are entirely within the spectrum of normal terminal ileum histology. The lymphoid aggregate gently pushes the crypts apart; there is neither acute inflammation actively destroying the epithelium nor features of chronic injury (such as pyloric gland metaplasia). As a result, the superficial epithelium could be theoretically pulled off the lymphoid aggregate since there is no destructive inflammatory injury tethering the epithelium to the lymphoid aggregate. See figures 3.64, 3.66–3.70 to contrast this normal architecture with features of established active chronic injury.

Figure 3.21 Normal terminal ileum. As this case illustrates, large lymphoid aggregates can occasionally extend below the muscularis mucosae (bracket) into the submucosa. Features in support of a benign process include variably sized lymphoid aggregates, germinal centers (arcs), tingible body macrophages (macrophages containing apoptotic debris in the cytoplasm, arrowheads), and a polymorphous lymphoid population (variably sized lymphocytes, best seen at high-power, Figures 3.29–3.30).

Figure 3.22 Normal terminal ileum. Note how the overlying epithelium could be theoretically “peeled” off the lymphoid aggregates since the large lymphoid aggregates are seen gently pushing aside the epithelium and not associated with active chronic inflammatory injury. Note the features of benignity: variably-sized lymphoid aggregates, germinal centers, and tingible body macrophages.

Figure 3.23 Normal terminal ileum. With such large prominent aggregates, the ever so slight scattered appearance to the crypts is entirely within the spectrum of normal terminal ileum architecture. Note that the overlying epithelium could be theoretically “peeled” off the lymphoid aggregates since there is no active chronic inflammatory injury linking the lymphoid aggregates to the epithelium.

Figure 3.24 Normal terminal ileum with variably sized lymphoid aggregates, germinal centers, and tingible body macrophages.

Figure 3.25 Normal terminal ileum. Crushed lymphoid tissue traversing the muscularis mucosae can raise concerns for a malignant hematolymphoid process (bracket). In this case, however, the intact lymphoid aggregate shows germinal centers (arc), tingible body macrophages (arrowheads), and a polymorphous lymphoid population, all features of a benign lymphoid process.

Figure 3.26 Normal terminal ileum. On higher power, a germinal center with tingible body macrophages is seen. Note that increased IELs are a normal finding in epithelium overlying lymphoid aggregates (brackets).

Figure 3.27 Normal terminal ileum. On higher power, the increased IELs are better appreciated (brackets). Recall, increased IELs are a normal finding in epithelium overlying lymphoid aggregates.

Figure 3.28 Normal terminal ileum. This high power view features a reactive germinal center with numerous tingible body macrophages (arrowheads). Tingible body macrophages harbor engulfed apoptotic debris, accounting for their characteristic cytoplasmic morphology.

Figure 3.29 Normal terminal ileum. This focus illustrates important features of a benign lymphoid aggregate: a germinal center (arc), tingible body macrophages (arrowheads), and variably sized lymphocytes (small, medium, and large lymphocytes).

Figure 3.30 Normal terminal ileum. The polymorphous nature of this benign lymphoid aggregate is best seen at high power (note the various sized and shaped lymphocytes). A rare mitotic body is seen (arrowhead), a feature not unusual for reactive lymphoid aggregates.

Figure 3.31 Normal terminal ileum. Prominent lymphoid aggregates can be alarming and, consequently, are a common source of consultation. Most typically, recognition of the key H&E features of benignity is sufficient to render a diagnosis of an unremarkable lymphoid aggregate: as in this case, germinal centers, tingible body macrophages, and variably sized lymphocytes are seen. Sometimes, however, a quick immunostain panel approach can be reassuring.

Figure 3.32 Normal terminal ileum (CD23 immunostain). A CD23 highlights the follicular dendritic cell meshwork surrounding the germinal centers, a feature of intact (normal) lymphoid aggregate architecture.

Figure 3.33 Normal terminal ileum (CD3 immunostain). A CD3 highlights T lymphocytes, which are predominantly seen surrounding the germinal center. On H&E, these lymphocytes were uniform and small, no atypical cytologic features were seen.

Figure 3.34 Normal terminal ileum (CD20 immunostain). A CD20 highlights B lymphocytes, which are the majority of the lymphoid constituents.

Figure 3.35 Normal terminal ileum (BCL-6 immunostain). Various artifacts occasionally make germinal centers difficult to discern. In such cases, BCL-6 and CD10 are equally helpful markers that highlight germinal centers.

Figure 3.36 Normal terminal ileum (CD10 immunostain). Like BCL-6, CD10 also highlights germinal centers. Of note, CD10 also highlights a crisp/intact brush border characteristic of normal small bowel mucosa (bracket). Defective, broken, or smudgy brush borders should prompt consideration of microvillous inclusion disease, especially in infants.

Figure 3.37 Normal terminal ileum (BCL-2 immunostain). Normal germinal centers are BCL-2 negative. If the germinal center is BCL-2 reactive, consider follicular lymphoma, which is characterized by the t(14;18) rearrangement of BCL-2 and the immunoglobin heavy chain (IgH). Importantly, recall that normal B lymphocytes in the mantle zone surrounding the germinal center and normal T lymphocytes express BCL-2. Therefore, interpretation of BCL-2 always requires concomitant interpretation of CD20 B lymphocyte marker, CD3 T lymphocyte marker, and a germinal center marker (BCL-6 or CD10).

Figure 3.38 Acute duodenitis pattern. Acute duodenitis refers to acute inflammation in the duodenal epithelium (arrowheads). In this particular example, infiltrating pancreatic adenocarcinoma (not shown) was identified lurking within the acute inflammation, underscoring the importance of recognizing seemingly bland clues, such as acute duodenitis, to help uncover critical diagnoses.

Figure 3.39 Acute duodenitis pattern, peptic injury. Acute duodenitis is an etiologically nonspecific injury pattern most commonly seen in the setting of peptic injury, infection, and medication injury. Neutrophils are seen in the epithelium (arrowhead) and lamina propria (asterisk).

Figure 3.40 Acute duodenitis pattern, peptic injury. Under oil immersion, the neutrophils are more easily seen in the epithelium (arrowhead) and lamina propria (asterisk). The cause of the injury is unknown.

Figure 3.41 Acute duodenitis pattern, Helicobacter pylori. This case of Helicobacter pylori duodenitis shows similar features to Helicobacter pylori gastritis. At low power, increased acute and chronic inflammation is seen, which is particularly prominent toward the superficial mucosa. Gastric foveolar metaplasia (bracket) provides a hospitable environment for Helicobacter and should always be carefully checked for organisms.

Figure 3.42 Acute duodenitis pattern, Helicobacter pylori. At higher power, intraepithelial acute inflammation (arrowheads) and prominent superficial plasma cells provide helpful red flags to the underlying Helicobacter infection. A rare Helicobacter organism is seen (arrow). Since this case had no corresponding stomach biopsy, the only opportunity to diagnosis and treat the infection stemmed from recognizing this injury pattern and carefully searching for the rare Helicobacter organisms.

Figure 3.43 Acute duodenitis pattern, Helicobacter pylori. This low power image shows features highly suspicious for a Helicobacter infection with a prominent superficial lymphoplasmacytic infiltrate, acute inflammation (not seen at this power), and gastric metaplasia (brackets). The organisms were seen in abundance on a Diff–Quik special stain (not shown) in the gastric metaplastic zones.

Figure 3.44 Acute duodenitis pattern, Helicobacter pylori. This low power image shows features reminiscent of those of exuberant Helicobacter gastritis. Note the prominent superficial lymphoplasmacytic infiltration and gastric metaplasia (brackets). Brisk acute inflammation and Helicobacter organisms were seen on higher power (not shown).

Figure 3.45 Acute duodenitis pattern, gastric foveolar metaplasia (PAS/AB). A PAS/Alcian blue pH 2.5 special stain highlights the neutral mucin characteristic of gastric foveolar metaplasia (bracket), similar to native stomach mucosa. In contrast, goblet cells display basophilia because of acidic mucin (arrowhead).

Figure 3.46 Acute duodenitis pattern, gastric foveolar metaplasia (PAS/AB). Gastric foveolar metaplasia appears eosinophilic because of neutral mucin (bracket); goblet cells are basophilic because of acidic mucin (arrowhead). Note the abundant superficial plasma cells with a sprinkling of acute inflammation, features suggestive of Helicobacter duodenitis (organisms not shown).

Figure 3.47 Acute duodenitis pattern, adenovirus infection. Prominent apoptotic bodies (arrowheads) and scattered intraepithelial neutrophils serve as helpful red flags to the characteristic adenovirus inclusions (bracket). Note the glassy and eosinophilic intranuclear inclusions typical for adenovirus. Since similar findings can be seen with degenerative change, a confirmatory adenovirus immunostain was performed and was reactive (not shown).

Figure 3.48 Acute duodenitis pattern, CMV infection. In this case, a smattering of acute inflammation and increased apoptotic bodies (arrowheads) serve as important clues to the diagnosis of CMV enteritis.

Figure 3.49 Acute duodenitis pattern, CMV infection. Careful inspection of the nearby mucosa revealed abundant Brunner epithelium with classic CMV viral cytopathic effect (arrowheads): cytolomegaly, prominent nucleoli, and both nuclear and cytoplasmic viral inclusions are seen. In the stomach and small bowel, viral cytopathic effect is often more conspicuous in the epithelium than the stromal and endothelial cells. These viral inclusions were diagnostic (a CMV immunostain was not required).

Figure 3.50 Acute duodenitis pattern, CMV infection. Higher power of another field shows classic CMV viral cytopathic effect with cytolomegaly and prominent nuclear and cytoplasmic viral inclusions (arrowheads). Although not included on the requisition, chart review revealed a history of febrile diarrhea, metastatic colorectal carcinoma, and concurrent chemotherapy. This case underscores the importance of recognizing this acute enteritis pattern, even when the history of immunosuppression is not apparent on the requisition.

Figure 3.51 Acute ileitis pattern. Acute ileitis refers to acute inflammation in the epithelium of the ileum (arrowheads). It is most commonly caused by medication, infection, and inflammatory bowel disease.

Figure 3.52 Acute ileitis pattern, aphthoid lesion. The diagnosis of acute ileitis implies the absence of chronic injury, as seen in this figure). Although the lymphoid aggregate is gently pushing apart the crypts, there is no chronic injury of the epithelium (note the epithelium could be theoretically peeled off the lymphoid aggregate since the epithelium is not tethered to the lymphoid aggregate by destructive inflammatory injury).

Figure 3.53 Acute ileitis pattern, aphthoid lesion. Higher power of previous case. An aphthoid lesion/ulcer refers to acute inflammation in the epithelium overlying a lymphoid aggregate. In the appropriate clinicopathologic context, an aphthoid lesion can lend support to the diagnosis of Crohn disease.

Figure 3.54 Acute ileitis pattern. A pocket of luminal neutrophils is seen (bracket) along with acute inflammation in the epithelium (arrowheads).

Figure 3.55 Acute ileitis pattern, prominent ulceration. Acute ileitis refers to a fairly wide range of mucosal injury patterns ranging from scattered neutrophils in the epithelium to deep penetrating ulcerations and fissures. In this example, a prominent ulceration is featured (arrowhead), while the background mucosa is essentially unremarkable at this power. The terminal ileum findings were attributed to the established history of excessive NSAID usage.

Figure 3.56 Acute ileitis pattern, backwash ileitis, ulcerative colitis. This ileal biopsy was taken from a patient with well-established ulcerative colitis.

Figure 3.57 Acute ileitis pattern, backwash ileitis, ulcerative colitis. Higher magnification of the previous figure reveals mild focal acute inflammation (arrowheads) that should not be mistaken for Crohn disease.

Figure 3.58 Granulomatous pattern (brackets), terminal ileum, sarcoidosis. This terminal ileum resection originated from a 58-year-old woman with an extensive history of sarcoidosis who presented with a small bowel obstruction. The background mucosa was unremarkable. AFB and GMS special stains were negative.

Figure 3.59 Acute ileitis pattern, granuloma, Crohn disease. This sneaky granuloma is almost miss-able on low power (arrowhead). This biopsy originated from a patient with a history of Crohn disease and scattered mucosal granulomata were seen throughout representative upper and lower gastrointestinal tract biopsies.

Figure 3.60 Acute ileitis pattern, granuloma, Crohn disease. On higher power, the granuloma is more easily spotted (arrowhead) as is the focal acute inflammation in the adjoining epithelium (bracket). AFB and GMS special stains were negative.

Figure 3.61 Acute ileitis pattern, erosive active chronic granulomatous ileitis, Crohn disease. Active chronic inflammation refers to acute injury (i.e., acute inflammation in the epithelium or crypt lumens, erosions, and or ulcerations) and chronic injury. In this case, an erosion is seen (arrowhead) along with an expansion of the lamina propria by a lymphohistiocytic inflammation (brackets).

Figure 3.62 Acute ileitis pattern, erosive active chronic granulomatous ileitis, Crohn disease. On intermediate power, a foreign body giant cell is more easily seen (arrowhead) in addition to vague granulomatous inflammation (brackets). Granulomata in Crohn disease are often poorly formed, as in this case.

Figure 3.63 Acute ileitis pattern, erosive active chronic granulomatous ileitis, Crohn disease. On highest power, the epithelioid morphology characteristic of granulomatous inflammation is seen (bracket). AFB and GMS special stains were negative.

Figure 3.64 Acute ileitis pattern, active chronic granulomatous ileitis, Crohn disease. At low power, crypt shortfall with basal lymphoplasmacytosis is seen: note that the crypts fall short of the muscularis mucosae (arrowheads) because of a basal layer of lymphoplasmacytic inflammation (bracket). Granulomata in Crohn disease (asterisk) can be notoriously difficult to appreciate in intensely inflamed specimens, as in this case. In contrast to normal terminal ileum architecture, note that it would be impossible to strip off the overlying epithelium in this case since the epithelium is inseparably melded to the associated active chronic inflammatory injury. Contrast this image with normal architecture (Figs. 3.20–3.25).

Figure 3.65 Acute ileitis pattern, active chronic granulomatous ileitis, Crohn disease. On higher power a granuloma with foreign body giant cells is more easily appreciated (bracket). AFB and GMS special stains were negative.

Figure 3.66 Acute ileitis pattern, active chronic ileitis, Crohn disease. Active chronic injury implies both acute and chronic inflammatory injury. Although acute inflammation is not apparent at this magnification, features of established chronic injury (chronicity) include pyloric gland metaplasia (best appreciated at higher power) and architectural distortion (note the variably sized crypts with variable intervening lamina propria). Also note the transmural fibrosis and chronic inflammation, and subserosal lymphoid aggregates (brackets), features compatible with the history of established Crohn disease.

Figure 3.67 Acute ileitis pattern, ulcerative active chronic ileitis, Crohn disease. This resection is from a patient with a history of terminal ileum-restricted Crohn disease. The image features both acute injury (ulceration (arrowhead) and acute inflammation in the epithelium (not shown)) and chronic injury (gastric foveolar metaplasia [brackets], pyloric gland metaplasia [asterisks], and slight architectural distortion with variably sized crypts, variable intervening lamina propria, minimal crypt shortfall, and basal lymphoplasmacytosis [arrows]).

Figure 3.68 Acute ileitis pattern, ulcerative active chronic ileitis, Crohn disease. Alternate field. Luminal ulcer debris is seen along with features of chronic mucosal injury (gastric foveolar metaplasia and architectural distortion).

Figure 3.69 Acute ileitis pattern, active chronic ileitis, Crohn disease. Alternate field. Architectural distortion is often best seen at low power: note the variably sized crypts with variable intervening lamina propria.

Figure 3.70 Acute ileitis pattern, active chronic ileitis, Crohn disease. Architectural distortion can also be appreciated on small bits of biopsy material, as this case. Note the central bizarrely shaped crypt with greater than seven branches, and the variable amount of intervening lamina propria throughout, both features of chronic mucosal injury. Acute ileitis was also seen (not shown).

Figure 3.71 Acute ileitis pattern, active (arrow) chronic (arrowheads) ileitis, Crohn disease.

Figure 3.72 Acute ileitis pattern, active chronic ileitis, Crohn disease. Pyloric gland metaplasia is evidence of chronic mucosal injury (brackets). Pyloric gland metaplasia of the ileum is histologically identical to the pyloric-type glands of the gastric cardia and antrum and to Brunner glands of the duodenum. These glands are composed of mucus secreting cells with abundant clear foamy cytoplasm and basally located nuclei. A PAS/AB special stain would highlight eosinophilic neutral mucin (not shown).

Figure 3.73 Acute ileitis pattern, active chronic ileitis, Crohn disease. Higher power of previous case.

Figure 3.74 Chronic inflammation, nonspecific. Not uncommonly, small bowel biopsies show a chronic inflammatory infiltrate without other specific features. Following systematic review of all tissue compartments for clues, and chart review for clinical correlates, some cases just remain “nonspecific.”

Figure 3.75 Chronic inflammation, nonspecific, duodenal giardiasis. Chronic inflammation in the small bowel is often nonspecific, but routine careful examination of all the tissue compartments may yield diagnostic findings. This example shows a prominent lymphoid aggregate and some dilated lacteals (arrow) in this duodenal biopsy. The tissue findings are nonspecific, but the diagnosis resides in the space between the villi (arrowhead).

Figure 3.76 Chronic inflammation, nonspecific, duodenal giardiasis Higher magnification of the indicated area in the previous figure reveals the protozoa Giardia.

Figure 3.77 Chronic inflammation, focally enhanced, duodenal Crohn disease. This biopsy shows a pattern of focally enhanced inflammation in a patient with duodenal Crohn disease. The findings are nonspecific and consist of localized inflammation, which should be interpreted in the proper clinical setting.

Figure 3.78 Chronic inflammation, nonspecific, duodenal Crohn disease. Higher magnification of the previous figure shows cryptitis (arrowheads) consistent with the patient’s known history of duodenal involvement by Crohn disease.

Figure 3.79 Crypt architectural disturbance pattern. This pattern encompasses the general features of “chronicity” including crypt distortion and branching (pictured here), crypt dropout, crypt shortfall, and pyloric metaplasia.

Figure 3.80 Crypt architectural disturbance, Crohn disease. The crypt architectural disturbances are evident at low magnification. Normally, the crypts rest directly on the muscularis mucosae. In this example, the base of a crypt falls short of touching the muscularis mucosae. This gap between the muscularis mucosae and the crypt is called “crypt shortfall” (arrow). Also, note the irregularly shaped crypts, or abnormal crypt configuration, in addition to areas of total glandular loss, or “crypt dropout.”

Figure 3.81 Crypt architectural disturbance, Crohn disease. Crypt architectural disturbances are seen with irregularly shaped crypts and bifid branching crypts (arrowhead). Note also the presence of cryptitis within this same crypt and the loosely-formed granuloma (arrow).

Figure 3.82 Crypt architectural disturbance, Crohn disease. Residual villous projections are present, but the major pattern here is crypt architectural disturbances, including crypt distortion, crypt shortfall, and crypt dropout. The lamina propria is expanded with increased chronic inflammation and prominent pyloric metaplasia (arrowheads) is present.

Figure 3.83 Crypt architectural disturbance, pyloric metaplasia. Pyloric-type glands are normally limited to the pylorus at the junction of the stomach and small bowel. When seen in the terminal ileum, these metaplastic glands indicate chronicity.

Figure 3.84 Crypt architectural disturbance, pyloric metaplasia. These pyloric glands have abundant foamy-to-clear cytoplasm and small, round or ovoid nuclei that may be flattened against the basement membrane.

Figure 3.85 Crypt architectural disturbance, pyloric metaplasia. Although pyloric metaplasia (arrowhead) indicates chronicity, it is not specific for Crohn disease, and can be found in other chronic conditions, such as diaphragm disease of the terminal ileum.

Figure 3.86 Crypt architectural disturbance, Crohn disease. This example shows crypt distortion and expansion of the lamina propria with an inflammatory infiltrate. Areas of pyloric metaplasia (arrow) are also present.

Figure 3.87 Crypt architectural disturbance, Crohn disease. Although chronic injury features are evident at low power, higher magnification is required to see areas of active inflammation (activity) indicated by neutrophils. Seen here are cryptitis (arrow) and lamina propria acute inflammation (arrowhead).

Figure 3.88 Diaphragm disease, endoscopic view. Chronic NSAID injury in the distal small bowel causes cycles of ulceration and healing that result in circumferential stenosing lesions (“diaphragms”) and can lead to obstruction.