Diverticular disease of the sigmoid colon is one of the commonest diseases seen at sigmoidoscopy/colonoscopy and yet biopsies are not often taken from the colon afflicted by this disease. Indeed, biopsies are often contraindicated in acute diverticulitis because of the risks of perforation. Nevertheless, there is increasing understanding that the disease is associated with luminal mucosal pathology, namely diverticular colitis, which is a close histological mimic of chronic inflammatory bowel disease. Indeed, there is a close relationship between the diseases and there are occasional cases where diverticular colitis is followed, in due course, by the onset of true chronic inflammatory bowel disease, specifically ulcerative colitis. The disease is also associated with characteristic mucosal polypoid change. Often mucosal biopsies show similar inflammatory changes to those seen in classical diverticular colitis but the pathology of mucosal prolapse may also be seen. The latter features may occur in many different situations, although all show the same characteristic morphological appearances. Such situations include stomas, both ileal and colonic, in association with ‘cap polyposis’, in solitary ulcer (mucosal prolapse) syndrome in the rectum, and at the anorectal junction in so-called inflammatory cloacogenic polyp. Several other conditions can produce mimicry of chronic inflammatory bowel disease in mucosal biopsies, having in common the ability to produce underlying mass lesions that result in ‘secondary colitis’ in the mucosa. These conditions include endometriosis, pneumatosis coli, primary and secondary tumours and, inevitably, intramural and extramural suppuration associated with diverticular disease itself.
Diverticular disease is one of the most common diseases of the gastrointestinal tract, especially in Western populations. It is most prevalent in the sigmoid colon but can affect the entire colon, although notably it spares the rectum. It particularly affects the elderly population, resulting in considerable morbidity and some mortality. It often coexists with a second intestinal pathology and it behoves the practising diagnostic pathologist to be aware of the potential diagnostic overlaps of the inflammatory complications of diverticular disease. Diagnostic conclusions should very rarely be based solely on the histological assessment of biopsies, and correlation with clinical, endoscopic, and radiological information is paramount. While mechanical forces are largely responsible for the genesis of diverticulosis, the disease is particularly complicated by inflammatory pathology, especially in and around the diverticula themselves, but it is the luminal mucosal inflammatory pathology that causes significant pathological diagnostic issues. This chapter will concentrate on the mucosal pathology of diverticular disease, seen in biopsies, but will also consider other conditions, notably mucosal prolapse and endometriosis, which can result in perplexing, part-inflammatory pathology in intestinal biopsies.
The frequency of diverticular disease in Western populations has risen over the past two decades1, 2 and epidemiological data indicate that diverticulosis afflicts more than 50% of adults over the age of 60 and 65% over the age of 80.3–5 There is evidence of a slight female preponderance in those over 50.2, 3, 6–8 When presenting in the young, the condition tends to be male-predominant, has more rapid progress and is more likely to require urgent surgery.7, 9 Obesity has been proposed as an important aetiopathogenetic factor, especially in the young,7, 10, 11 but a definite causative link has not been demonstrated.12 Diverticular disease has widely been associated with a Western diet and lifestyle.3, 4, 9, 13, 14 Data from South Africa and Singapore demonstrate a positive correlation between diverticular disease and a higher socio economic status. 15, 16 A study from Australia showed diverticulosis in 45% of consecutive autopsy patients,10 while an endoscopy study from Saudi Arabia showed a frequency of only 7.4%.17 A large population study in Sweden found a lower proportion of diverticular disease in newly arrived non-Western immigrants and demonstrated a positive correlation of frequency with duration of residency.18 The same group reported an overall 10-year mortality rate of 0.003%, which is low but significant, given the prevalence of the disease. Mortality figures for admissions with complicated diverticular disease rise to 3%.6, 19
Diverticulosis of the right colon is more common in an East Asian population, including those in Japan and Hawaii,20–22 and is seen in this anatomical location in 70% of affected patients.11, 20 Isolated diverticula are not unusual: in 30% of cases there is a solitary diverticulum. If multiple, up to 15 may be present while more than 15 is rare.16, 20 Although there are similarities with its generalised colonic counterpart, including a common pathogenesis of an abnormal intraluminal pressure and motility, a thickened muscularis propria is not a characteristic feature of such isolated diverticula. 20, 23 Right colonic diverticular disease is mostly asymptomatic, although it can cause significant morbidity and a modest mortality due to secondary inflammation.
Although not specifically encountered during the assessment of biopsy material, it is appropriate to consider briefly the subject of appendiceal diverticular disease, as we now recognise that this is associated with very specific pathology and significant diagnostic issues. It is present in up to 2% of surgical appendicectomy specimens, is more common in males and, as with diverticulosis of the right colon, is usually asymptomatic.24–28 Congenital diverticula of the appendix are rare: they are true diverticula surrounded by a conspicuous layer of muscularis propria. Acquired diverticula are commoner, and the mucosa of the acquired diverticulum is subtended by only a small amount of smooth muscle, reflecting the attenuated muscularis mucosae. Diligent examination will reveal parts of the out pouching in the distal third of the appendix, at either the mesenteric or the anti-mesenteric border (Figure 26.1). The site of protrusion is often the window of appendicular vessels penetrating the muscularis propria (Figure 26.1). Secondary inflammation and local tissue necrosis may obliterate most of the features, but careful inspection and awareness of the condition will reveal remnants of diverticula. In our experience, acquired appendiceal diverticulosis is the most common reason for the pathologist to be able to give a specific cause of acute appendicitis. Diverticula are usually acquired rather than congenital, and thus the acute appendicitis complicating appendiceal diverticulosis occurs in the older patient. Characteristically it causes a notably focal acute inflammatory pathology, closely related to one or more appendiceal diverticula. Perhaps more importantly, inflammation and obstruction of one or more appendiceal diverticula can lead to the combination of mucocoele(s) and hyperplasia and/or attenuation of the epithelium, and this combination causes close mimicry of low-grade appendiceal mucinous neoplasms (LAMNs).27, 29, 30 While the latter is associated with a significant risk of pseudomyxoma peritonei, the former is not associated with pseudomyxoma. Therefore, it is imperative that pathologists recognise the characteristic features of this complication of appendiceal diverticulosis.30
This chapter is concerned primarily with the biopsy pathology of diverticular disease and with a discussion of other related pathological entities that may, in particular, lead to biopsy mimicry of chronic inflammatory bowel disease (IBD). One of these is mucosal prolapse but it is important to understand that diverticulosis and mucosal prolapse often coexist. Although the pathological features of mucosal prolapse represent a broad church, with the features occurring in several different clinical entities in the small intestine and in the colon and rectum,31 in the sigmoid colon a distinctive form of mucosal prolapse may occur in association with diverticulosis. In fact, mucosal prolapse is a regular finding in mucosal biopsies taken from the mucosal redundancy and/or polypoid change that complicates diverticulosis of the sigmoid colon (Figure 26.2). The mucosal pathology is probably a result of excessive intraluminal pressure, associated with hypertrophy of the muscularis propria and luminal narrowing, leading to inflamed crescent-shaped folds of mucosa with inflammatory changes and mucosal prolapse evident at endoscopy, an appearance that has been termed crescentic fold disease.32, 33
Figure 26.2 A histological image of a colon with diverticulosis. Two large and redundant mucosal folds are seen in association with the characteristic thickening of the muscularis propria that is so typical of diverticulosis.
Luminal inflammation related to diverticular disease requires further comment, especially as it is amenable to endoscopic biopsy. Diverticular colitis limited to segments of colon afflicted by diverticulosis is well described. However, it is not a clear-cut entity as some patients may subsequently develop true chronic IBD.32, 34 The exact inter relationship between diverticular disease, diverticular colitis and chronic IBD remains uncertain and is a major consideration in this chapter. For instance, whilst some earlier studies have suggested that diverticulosis and Crohn’s disease coexist more often that might be expected, there is now general acceptance that the frequency of cases with both diverticular disease and Crohn’s disease does not exceed the cumulative natural occurrence of both conditions. 35–37
Pathogenesis and Macroscopic Appearances of Diverticulosis
To gain a better understanding of the pathological changes that may occur, both in biopsies and in resections specimens, it is appropriate that we now consider the pathogenesis of diverticulosis and its macroscopic appearances. The diverticula themselves arise because the difference between the intraluminal and intra peritoneal pressures, between the colonic circular smooth muscle rings, forces the mucosal out-pouchings into the subserosa. The resulting sac is outlined by a retained thin layer of smooth muscle. It is not surprising that obesity, leading to weakening of abdominal muscles, and connective tissue disorders, such as Marfan’s syndrome and Ehlers–Danlos syndrome, predispose to this process.38, 39 The sites of diverticula correspond to points of perforating vasa recta that supply the mucosa. This has important implications as, during diverticular inflammation, these substantial vessels are prone to rupture resulting in significant haemorrhage, accounting for considerable morbidity and some mortality of diverticular disease.
The underlying pathogenetic mechanism is gross thickening of the muscularis propria with, collaterally, a greater strain on the taeniae coli and an increase in elastin fibres.40, 41 This results in a gradual shortening of the afflicted intestine, so called myochosis. The mucosa becomes proportionally excessive compared to the length of the segment, producing polypoid mucosal folds (Figure 26.3), which become irritated and inflamed by the firm faeces that characterise diverticulosis, resulting in the endoscopic appearance of crescentic fold disease. Although these muscular and neural changes have been recognised for many years,31, 42 there has been very little progress in our understanding of the cellular pathogenesis of diverticular disease, although a recent study has suggested that an increase in serotonin-producing cells may be an important part of the pathogenesis.43
Figure 26.3(A) A sigmoid colonic resection specimen showing the classic features of complicated diverticular disease. There is stricturing, fibrosis, and tracking suppuration.
(B) A histological wholemount of diverticulosis. Chronic inflammation is confined to the diverticula themselves.
Therefore, the cardinal and most consistent feature of diverticular disease is gross thickening of the muscularis propria, seen throughout the affected segments and being particularly evident in the sigmoid colon10, 43, 44 (Figure 26.3). The cut surface of the muscle exhibits a firm, grey, myxoid, almost cartilaginous quality. Interestingly, several studies have demonstrated no definite evidence of either smooth muscle hyperplasia or hypertrophy.40, 44, 45 The characteristic radiographic appearances are produced by disproportionately greater thickening of the circular smooth muscle layer. When only the pathological changes of the muscularis propria, without the formation of diverticula, are observed, the term ‘pre-diverticular syndrome’ is used. Such a condition, namely the muscular changes of diverticular disease but without formation of diverticula, may be particularly prevalent in a somewhat younger Western population and may result in some morbidity. However, the disease has been little studied, a situation that requires resolution.34
Older studies of diverticulosis have suggested that thickening of collagen fibrils in the left colon is greater than in the right colon46 and that there is increased cross-linking of collagen and smooth muscle remodelling in the sigmoid colon, leading to lower compliance compared with the proximal colon.47, 48 Although the connection between diverticular disease and dietary fibre is well documented, it has lately come under greater scrutiny.49–51 Studies have shown disparity between primary and secondary prevention in diverticular disease. High fibre intake was purported to be beneficial for symptomatic relief only and is not curative.51 There is also a weaker correlation between a fibre-rich diet and right-sided diverticulosis.52 Nevertheless, the evidence points to an inverse relationship between a fibre-rich diet and the development of diverticular disease.4 Cellulose and other insoluble fibres derived from fruit and cereal seem protective,53, 54 while red meat and a low fruit and vegetable but potato-rich diet has been demonstrated to be diverticulogenic.8, 55 Dietary fibre appears to have no influence on right-sided diverticular disease.56 Reduction of stool bulk leads to decreased transition time and faecal stasis, adding to the effect of intraluminal pressures.4, 8
In summary, while there have been many studies on the causes of diverticular disease and the factors at play in its development, ultimately we still have much to learn about the pathogenesis of this common disease and its complications.
The Inflammatory Complications of Diverticular Disease
Diverticulitis is the most common inflammatory complication of diverticulosis, affecting between 1% and 4% of the population.1, 12, 55, 56 Of these, 2%–5% are below 40 years of age and, when presenting acutely, the majority will require surgical treatment.57, 58 Inspissated faecal material becomes entrapped in the blind diverticular sacs and cannot be expelled through the narrow neck. This causes localised pressure effects, inducing mucosal ischaemia, abrasion, ulceration, bacterial overgrowth, and inflammation. Compression of the vasa recta in the diverticular neck, at the level of the weakened muscularis propria, causes further perfusional insult to the misplaced mucosa. The inflammation typically starts at the tip of diverticula and spreads into the surrounding subserosal tissues as peridiverticulitis. Invariably there is a break in the continuity of the diverticular mucosa leading to the formation of a peridiverticular abscess. Ongoing inflammation may produce an abscess pocket between the muscular wall and extramural fat which often extends along that plane, cuffing and encircling the external muscle layer, which we refer to as ‘tracking suppuration’ (Figure 26.3). It is important to appreciate that mucosal biopsies are not often taken in this acute situation, as this may increase the propensity to colonic perforation. Even so, the luminal mucosa adjacent to afflicted diverticula may show a combination of active inflammation and ischaemia, preceding ulceration.
It is important to appreciate that, in acute diverticulitis, acute peritonitis is not necessarily the result of full thickness perforation (despite what surgeons tell us at the time of the surgery) but is more usually due to rupture of one or more peridiverticular abscesses and the tracking suppuration that is so characteristic of the disease (Figures 26.4 and 26.5). Regardless of the mechanisms of its initiation, such ‘perforation’ is the most severe complication of diverticular disease and results in most of the mortality from the disease.10 A 7% mortality has been quoted for such perforation, with systemic sepsis the dominant factor leading to death.59 Pelvic abscesses, pelvic inflammatory phlegmon and obstruction are among other acute outcomes. Severe haemorrhage is rare. The use of steroids correlates positively with perforation. Sixteen per cent of patients with diverticulitis will develop a diverticular abscess and between 1% and 20% develop one or more fistulae.60–62 Fistulation to the bladder is commonest, reported in two-thirds of all cases, with colo-vaginal, colo-uterine and colo-enteric fistulae less common.60, 61, 63
Figure 26.4 A sigmoid resection specimen with diverticulosis. Tracking suppuration is apparent just outside the muscularis propria. To the left, the tracking suppuration reaches the peritoneal surface resulting in ‘perforation’.
Figure 26.5 The histological appearances of tracking suppuration. There is a complete split in the subserosal tissues caused by the tracking suppuration, whilst the mucosa above shows focal ischaemic changes.
Mucosal biopsies taken from an area of diverticular disease may show no specific features or minimal inflammation with mucin depletion and an increase in lymphocytic exocytosis. More prominent changes of chronic active inflammation may include intraepithelial polymorphs and crypt abscess formation but there is also often granulation tissue and ulcer debris. Non-necrotising granulomas may be present and can be present in the inflamed diverticular mucosa and throughout the thickness of the intestine. Granulomatous reaction can also be seen within adjacent reactive lymph nodes.64 The granulomas are not necessarily indicative of Crohn’s disease, particularly in the absence of other features of chronic IBD. Notwithstanding this, it has been previously intimated that Crohn’s disease may exacerbate diverticular disease by inducing diverticulitis.65 One of the distinctive histological features of complicated diverticulosis is the radiation of lymphoid follicles away from the inflamed diverticulum, contrary to Crohn’s disease where lymphoid aggregates are distributed in a ‘rosary’-like fashion on the external surface of the muscularis propria (Figure 26.6), a feature initially recognised by our friend and colleague, the late Professor Bryan Warren.
Figure 26.6 A histological image of complicated diverticular disease. Lymphoid aggregates radiate away from the inflamed diverticulum unlike the classical rosary of inflammation seen in Crohn’s disease. There is a reactive lymph node in the mesocolic tissue (lower right).
In the authors’ experience, 40% of sigmoid colonic cancers coexist with diverticular disease.66 Although there is no documented correlation between diverticular disease and carcinoma, they do share the same aetio-pathogenetic factors, particularly a low-fibre diet and obesity.67, 68
The luminal mucosa of the sigmoid colon, not that lining the diverticula, may develop chronic active inflammatory change.69 This disorder has been given various appellations.70 ‘Diverticular disease-associated chronic colitis’ implies a strict relationship with inflammation of diverticula. ‘Segmental colitis associated with diverticulosis’ (SCAD) erroneously omits the fact that diverticula may not be present in the segment affected by diverticular disease, which is primarily a disease of smooth muscle. Other terms lack specificity. The term ‘diverticular-associated colitis’ has been widely promulgated. However, the association with an adjective (rather than a noun) means that this term is not etymologically correct. The authors of this chapter use the term ‘diverticular colitis’, which is most appropriate. It emphasises the inflammatory component, associating it with the established symptomatic process that is diverticular disease. This complication of diverticulosis is poorly recognised both by clinicians (especially endoscopists) and pathologists. The former often interpret the segmental inflammation as representing Crohn’s disease while pathologists often interpret the diffuse chronic active inflammatory pathological changes on mucosal biopsy as ulcerative colitis (UC), ignoring the fact that rectal biopsies, taken contemporaneously, are, by definition, normal.
Given the preponderance of diverticular disease, it is not surprising that diverticular colitis is common. Furthermore, up to 25% of colons resected for the disease bear the changes of diverticular colitis.34 Few such diagnoses are made prior to surgery because the disease may show patchy distribution, but misdiagnosis as chronic IBD after assessment of endoscopic biopsies is not uncommon. Consequently, the true frequency of the disease has been difficult to determine but three older studies have reported a prevalence of between 1% and 2% in unselected flexible sigmoidoscopic and colonoscopic series32, 71, 72 while more recent publications report a lower prevalence of about 0.4%.73, 74 Although these figures may seem low, the overall numbers are appreciable given the volume of flexible sigmoidoscopy and colonoscopy that is undertaken currently in Western countries. Diverticular colitis mostly affects elderly patients and, more commonly, males. It traditionally presents with haematochezia but diarrhoea and abdominal pain also occur and the duration of symptoms extends from weeks to years.32, 71 The numbers reported in the literature to date are relatively scarce but are presented in Table 26.1.
|Year||Study||Case number||UC-like pattern||UC later||Treatment|
|1984||Sladen and Filipe116||5||3||1||sulph and steroids|
|1992||Gore et al.32||34||11||3||sulph and steroids|
|1992||Peppercorn79||8||8||0||sulph and steroids|
|1993||Polit117||1||1||0||sulph and steroids|
|1995||Hart et al.118||14||5||0||sulph|
|1996||van Rosendaal and Andersen119||2||2||0||5-ASA and abs|
|1996||Makapugay and Dean71||23||23||3||abs, sulph and steroids|
|1998||Pereira84||3||3||1||medical and surgical|
|2002||Gupta and Shepherd75||7||7||0||surgery|
|2002||Evans et al.120||4||2||0||sulph, steroids and surgery|
|2005||Koutroubakis at al74||23||4||0||mesalazine, abs and surgery|
|2006||Imperiali et al.73||15||15||0||mesalazine and surgery|
|2008||Freeman121||24||24||0||sulph, steroids and surgery|
|2009||Mulhall et al.82||3||3||3||medical and surgical|
|2010||Tursi et al.72a||92||34||N/A||N/A|
abs, antibiotics; IBD, inflammatory bowel disease; sulph, sulphasalazine; UC, ulcerative colitis.
a Numbers from this study not included in the total score.
Pathogenesis of Diverticular Colitis
The pathogenesis of diverticular colitis is unclear and may well be multifactorial. The severity of the disease varies from mild inflammatory changes to IBD-like inflammation and appearances that are indistinguishable from UC. Previous publications suggest the role of mucosal redundancy and mucosal prolapse in diverticulosis (Figure 26.7).33, 66, 75 The putative pathogenic mechanisms are relative ischaemia, alteration of bacterial flora, and local toxin production.32 Some have suggested a role for tumour necrosis factor-alpha (TNF-α) overexpression, which could account for the response by some patients with diverticular colitis to immunosuppressive therapy.76 The picture is further complicated by a proportion of patients in whom diverticular colitis appears secondary to diverticulitis and pericolic abscess formation.35, 66, 75 This discrepancy has profound implications for treatment because immunosuppressive therapy, including steroids, is an absolute contraindication for such acute inflammatory pathology.
Figure 26.7 The macroscopic appearances of a diverticular stricture causing a mass-like lesion. The concertina-like nature of the colonic shortening with stricturing and mucosal redundancy is easily appreciated. The patient had a known history of diverticular colitis.
Endoscopic and Macroscopic Appearances
The cardinal macroscopic feature of diverticular colitis is the presence of luminal mucosal changes within a segment of colon, usually the sigmoid colon, afflicted by diverticular disease. The latter implies pathologically thickened muscularis propria. Ironically, diverticula themselves may not be present. Such diverticular colitis associated with pre-diverticular syndrome has been seriously neglected as a concept and merits further research.
The spectrum of mucosal changes seen at endoscopy is wide-ranging from subtle to severe (Figure 26.8). There may be mucosal oedema, congestion, granularity, mucosal haemorrhage, friability, and surface exudates. Figure 26.7 demonstrates the macroscopic appearance of a resected specimen from a patient diagnosed with diverticular colitis. There is shortening and stricturing of the segment with a relative increase of the mucosal folds. In severe forms of the disease, ulceration and fissures may mimic chronic IBD.77, 78 One of the more characteristic manifestations is the development of crescentic mucosal folds that protrude into the lumen and are susceptible to intraluminal trauma (Figure 26.7). The edges of the folds undergo haemorrhagic change and show patchy brown to orange discolouration due to haemosiderin deposition (Figure 26.7). Crucially, one feature that distinguishes diverticular colitis from classical chronic IBD is the absence of disease in the colon and rectum unaffected by diverticular disease (Fact Sheet 26.1).
Figure 26.8 The endoscopic appearances of relatively severe diverticular colitis. Here it is the mucosal crescents that show pronounced congestion and inflammation, so-called crescentic fold disease. The brown discolouration of the mucosal folds at the edges of the intense inflammation is a result of haemosiderin deposition.
Common complication of diverticulosis
Inflammation of mucosa within diverticula
Usually starts at tip of diverticulum
May extend into subserosal layer of bowel, with or without abscess
Biopsies rarely taken
Synonyms: diverticular disease-associated chronic colitis; segmental colitis associated with diverticulosis; diverticular-associated colitis (not advised)
Affects non-diverticular mucosa within the diverticular segment(s)
Occurs occasionally in the absence of diverticula (‘pre-diverticular syndrome’)
Poorly recognised by clinicians and pathologists
The histopathological findings corroborate the spectrum of changes seen endoscopically. Most importantly, the microscopic assessment should focus on low-power observation of sequentially obtained biopsies, which will demonstrate the characteristic distribution of the disease (Figure 26.9). In serially orientated biopsies, the left-sided colonic biopsies show prominence of inflammation, which spares the proximal colon and the rectum (Figure 26.9). A mucosocentric process, including surface epithelial sloughing, cryptitis, crypt abscess formation, chronic inflammation in the lamina propria, and ulceration may be present and may resemble UC. There is usually little significant crypt distortion, probably because the disease is, perhaps, less chronic than classical UC, although absence or mildness of crypt changes is not an absolute feature32, 34, 71, 79 (Figures 26.10 and 26.11). Lymphoid follicles at the base of crypts are common but they may not be present in superficial biopsies.71 Chronic inflammatory cells, including plasma cells and eosinophils, expand the lamina propria. The chronicity is manifested by a villiform architecture and Paneth cell metaplasia. If crescentic folds are present, the microscopic changes include typical features of prolapse with characteristic haemosiderin deposition in the submucosa (Fact Sheet 26.2).
Figure 26.9 A colonoscopic series of biopsies showing inflammation restricted to two penultimate biopsies (at right), representing the inflamed mucosa of the sigmoid colon afflicted by diverticulosis and ‘diverticular colitis’. The last biopsy (at right) is from the rectum and is notably normal.
Figure 26.10 The histological appearances of relatively mild diverticular colitis. There is minor crypt distortion, moderate chronic inflammation and minimal active inflammation.
Figure 26.11 The histological appearances of severe diverticular colitis. There is more pronounced crypt distortion, moderate chronic inflammation, and prominent active inflammation, including crypt abscesses. The histological mimicry of chronic inflammatory bowel disease, especially ulcerative colitis, is palpable.
Usually sigmoid colon
Sparing of rectum
Sparing of right colon in most cases
Distribution apparent in anatomically sequential biopsies
Chronic inflammatory cells, including plasma cells and eosinophils, expand the lamina propria
Lymphoid follicles at the base of crypts
Crypt abscess formation
Surface epithelial sloughing and ulceration
Crypt distortion usually minimal or mild but may be severe
Villiform surface change may occur
Paneth cell metaplasia
May resemble ulcerative colitis
Features of prolapse may occur if crescentic folds are present
Chronic IBD demonstrates a second prevalence peak in the elderly population71, 80 and the high prevalence of diverticular disease in the same patient cohort infers that many patients will be diagnosed with both conditions. The evidence implies a more intricate interrelationship of the conditions than would be expected by pure coincidence. 35,81,82 Diverticular colitis can manifest in three morphological patterns and, according to a recent study, most will display an endoscopic crescentic fold-like pattern demonstrating characteristic leaf-like mucosal flaps. There are also an UC-like pattern, with confluent mucosocentric inflammation, and a Crohn’s disease-like pattern with patchy inflammation and fissuring, which may be associated with the formation of granulomas.72 Further, the pathologically altered mucosa of diverticular disease is susceptible to secondary infections and may also be susceptible to the pathological effect of drugs and chemotherapeutics. Pathogens, such as Salmonella spp. and Shigella spp., may occasionally cause mucosal inflammation and crypt distortion resembling UC.83 Non-steroidal anti-inflammatory drugs (NSAIDs) may produce similar inflammation and ulceration, particularly in the terminal ileum83 but also in the sigmoid colon afflicted by diverticulosis.71 Thus, accurate clinical information is paramount in the pathological assessment of these biopsies, as there is such a complex interaction between diverticular disease, chronic IBD, drugs and infective pathology.82
Diverticular Disease and Ulcerative Colitis
The diagnoses of diverticular disease and UC are governed by strict criteria. Nonetheless, clinical and pathological features of both conditions widely overlap and may be indistinguishable when presented with a single biopsy of an affected area. The sparing of the rectum in diverticular colitis is THE distinguishing feature and it is essential that the clinician/endoscopist understands this and ensures that rectal biopsies are always taken, even if the rectum appears endoscopically normal. However, the pathologist must also be mindfully cautious, as up to 13% of cases diagnosed as diverticular colitis will progress, in time, to classical UC.32, 71, 84 Table 26.1 demonstrates the publications illustrating this relationship. There is even one recent case in the literature whereby ‘diverticular colitis’ of the ascending colon has preceded the onset of classical UC.85 Caution is also appropriate, as relative sparing of the rectum in UC, not just after treatment, is now fully recognised.86 The latter study compared biopsies of 56 patients with subsequent resection specimens. The biopsies showed rectal sparing in 30% of cases and discontinuous disease in 25%. The same features were present in 5% and 11% of resection specimens.
It has been proposed that the putative common denominators for the development of diverticular colitis and UC are faecal stasis and alteration in bacterial flora.77 The dynamic immunological interconnection between the bacterial flora and the mucosa may result in the protective effect of short-chain fatty acids.49, 70, 87 In terms of the pathogenesis of UC, it is notable that the one consistent factor is that UC occurs at sites of relative faecal stasis. Thus the rectum is the classical and most prevalent site for the disease but ‘focal’ UC is also seen, at sites of faecal stasis, in the sigmoid colon afflicted by diverticular disease, in the caecum, as the ‘caecal patch lesion’, and in the appendix. These observations suggest that faecal stasis and alterations in bacterial flora may be powerful factors in the generation of UC itself.35, 70, 87, 88
Diverticular Disease and Crohn’s Disease
In the elderly population, Crohn’s disease is more likely to present in the colorectum and may preferentially involve sites of diverticular disease.35, 81 Relative ischaemia and alterations in the bacterial flora have been postulated as putative stimuli.89 Vulnerable segments of the intestines may be susceptible to involvement by Crohn’s colitis, including sites subject to previous surgical manipulation. Initial reports of patients with Crohn’s disease and coexistent diverticular disease facing a poorer outcome have been reviewed and the current consensus is that this is less likely and that the association of Crohn’s disease and diverticular disease truly coinciding, only in the sigmoid colon, has been overcalled.35, 37, 64, 80, 90 Further, it is now thought that Crohn’s disease inducing diverticulitis in patients with diverticular disease has also been overcalled.65, 90 Complications of diverticular disease, leading to inflammation and shortening of the sigmoid colon, can lead to encasement of the segment by adipose tissue, subserosal fibrosis, fissures, mucosal cobblestoning and fistulation, common features of Crohn’s disease and leading to mimicry of Crohn’s disease in complicated diverticular disease alone.35, 64, 89, 90 Fissures do occur in complicated diverticular disease but, in diverticulitis, these are mostly found related to diverticula themselves rather than away from diverticula.89
Three studies, all published within two years of each other, are important when considering the possible joint diagnosis of diverticular disease and Crohn’s disease. 64, 89, 90 All three studies examined resection specimens in which a putative diagnosis of the coincidence of diverticular disease and Crohn’s disease, restricted to the sigmoid colon, had been made previously. In the great majority of patients, the pathological changes could be attributed firmly to mimicry of Crohn’s disease rather than true Crohn’s disease, with, critically, only a very small proportion of patients showing any evidence of Crohn’s disease at a site other than the sigmoid colon. This is strong evidence that one should only make a diagnosis of the coincidence of diverticular disease and sigmoid colonic Crohn’s disease with profound caution and that the astute clinician and pathologist should always seek evidence of Crohn’s disease elsewhere before making the joint diagnosis (Fact Sheet 26.3).66