Pitfalls in the histological diagnosis of inflammatory …downloads.hindawi.com/journals/cjgh/1990/970436.pdfPitfalls in the histological diagnosis of inflammatory bowel disease on

IBO: DIAGNOSIS

Pitfalls in the histological diagnosis of inflammatory bowel

disease on colorectal biopsies

DA MAI ATJALIAN, M[)

ABSTRACT: Histopathological examination of appropriate colorectal biopsy specimens a llows accurate identification of chronic inflammatory bowel disease in the majority of cases. Pitfalls, however, appear because overlapping histological features occur among the various forms of colitis or because a specific fom1 of colitis may exhibit incomplete expression of its characteristic features. Pitfalls can be minimizeJ if the histological findings are considered in the context of all other clinical and investigative data. Can J Gastroenterol l 990;4(7):336-340

Key Words: Histological diagnosis, Inflammatory bowel disease, Pathology

Ecueils clans le diagnostic histologique des maladies inflammatoires de l'intestin d'apres les biopsies colorectales

RESUME: L'examen histopathologiquc des prelevements biopsiques colorectaux pennec de diagnostiquer correctement la majorice des cas d'entcropathies inflammatoircs chroniques. Les erreur~ surviennent toutefois, a cause Ju chevauchement des caracteristiques histologiques que parcagent Ji verses formes de colites ou parce que certains types de colite ne manifestent qu'une partie de leun; caracteristiques propres. II est toutefois possible de minimiser ces ecueds si les rcsultats histolog1qucs soot examines dans Le contexte Jc routes lcs autres donnees cliniques et de la recherche.

Victoria General Hospital, l-lal1fax Nova Scotia Correspondence and re/mms: Dr DA Mala[Jal1an, Vicwria Genenil I fos/>1uil, 1278 Tower

Road, 1/alifax, Nova ",,mia 133H 2Y9

T l IE TERM INFLAMMATORY ROWEL

Jiscase (IBD) convent ionally refers to ulcerative colitis anJ Crohn'I disease, both of which are of uncertain etiology anJ run a ch ronic course ( 1,2). There are other forms of colit is which can mimic IBD clinically, encloscop1· cally and radiologically (Table I). Mo11 of these have specific eriolog1cs and the ir differentiation from IBD 1s J

TABLE 1 Differential diagnosis of colitis

Inflammatory bowel disease Acute self-limited colitis Pseudomembranous colitis lschemic colitis Parasitic infections

Amebiasis Schistosomiasis

Drug-induced colitis Radiation colitis Solitary rectal ulcer syndrome Behc;:et' s syndrome Microscopic and collagenous colitis Other

136 CAN J GA:,,·RuLNTERl)L VOL 4 Nt) 7 NlWI.Ml\lR 1990

TABLE 2 Causes of pitfalls in the histological evaluation of colorectal biopsies in colitis

Limited morphological expression of Inflammation ~ Overlapping histological features

Incomplete expression of response to disease ~ Absence of discriminating histological features

Lock of pathognomonlc changes Occurrence of 'indeterminate colitis'

great therapeutic and prognostic significance.

Histological evaluation of co lo rec cal mucosa[ biopsy specimens 1s an important parameter in the evaluation and management of patients with colitis (3-7). Biopsies are of value when there is a clinical need to confinn the presence or absence of IBD. to recognize other forms of colitis, to distinguish between ulcerative colitis and Crohn's disease, to determine the extent of disease and to detect dysplasia and carcinoma which may complicate longstanding IBO.

While the h istopathological fearures of IBO are characteristic,

Figure 1) Rectal mucosa/ biopsy from a pacient wich ulcerative proctitis. Noce rhe heavy mononuclear inflammatory cell infiltrate in the lamina /)ropria, the irregularicy of crypt archaeccure, the depletion of goblet cell mucin and the crypc abscesses (arrows). Irregularity of crypt architecture is highly characceristic of inflammatory bowel disease. especially ulcerative colitis

Pathology of 180

TABLE 3 Acute self-limited colitis (ASLC) versus inflammatory bowel disease (IBD) (distinguishing features in colorectal biopsies)

ASLC 180 Crypt abscesses Superficial Tronsmucosol Goblet mucus depletion Mild Marked Inflammatory infiltrate Polymorphonucleor leukocytes Mononuclear cells Pseudovillous mucosa Absent Crypt architecture Preserved Crypt atrophy Absent Paneth cell metaplasia Absent Epithelioid granulomas Absent

problems leading to pitfalls may occur in the histological differentiation between IBO and other forms of colitis on one hand, and between ulcerative coli tis and Crohn's disease on the other (Table 2). Difficulties often orcur because the colon possesses limited morphological expression of inflammatory response~ which often shows overlap among a variety of conditions. In addition, a specific type of colitis may exhihit incomplete expression of its characteristic histological features, rendering it difficult co recognize. D ifficulties also arise because of the occurrence of indeterminate col itb with overlapping histological findings, which may be impossible to diagnose accurately.

Present Distorted Present Present Crohn's disease

Two conJirions often consiJered in the differential diagnosis of patients with acute onset colitis are IBO and acute self-limited coli us (ASLC) (8.9). ASLC refers to acute transient colitis caused by a known bacterial agent (infectious col itis) and coliti<les where no cnteropathogcnic microorganisms are identified on stool culture, hut hy all other criteria would be considered acute infectious-type colitis. Acute onset IBD may be mdistmgui~hable clinically from ASLC. Conversely, severe forms of ASLC can mimic lBD even to the extcnc of causing toxic dilation of the colon. The histological differentiation between I BO and ASLC is, therefore, of considerable importance (Table3).

Figure 2) Rectal mucosa/ biopsy from a patient with dmg-induced (gold salt thera/ry for rheumawid arthritis) acute colitis. As in Figure 1 , there is marked goblet cell mucin depletion and focal cryptitis (arrow). In contrast to inflammatory bowel disease ( Figure I), the crypt architecture is well preserved. A repeal biopsy after wichdrawal of the drug demonstrated entirely normal mucosa, a f eacure common co all forms of acwe self-limited colws

CAN J GASTROENTEROL VOL 4 No 7 NOVEMBER 1990 337

MALATJALIAN

Figure 3) Colonic mucosa! biopsy from a patient with ulcerative colitis. Note the heavy lymphocyte and plasma cell infilrrate m the lamina propria. The cryptitis is caused by polymorphonuclear cells (arrow) . Also nor.e distortion of normal crypt architecture

Figure 4) Colonic mucosa! biopsy demonsrrating the pseudovillou.s patr.em of the mucosa/ surface. This is seen in abom 20% of cases of inflammatory bowel disease and is a highly characteristic histological finding. It does not occur in acur.e self-limir.ed colitis. Also note the heavy mononuclear cell infiltrate in the lamina propria and the focal Pane th cell metaplasia ( arrow)

338

Figure 5) Colonic mucosa from a case of quiescenc ulcerative colitis demonstrating m11cosal atrol>h,, crypt distortion and focal Pane th cell metaplasia. Note sparse mflammatory cell infiltrate in the lamina propria. The absence of crypwis and crypt abscesses are features of inactive ulcerative colitis

Figure 6) Colome mucosa/ biopsy from a patient with Crohn's disease. Note the mucosa! and submucosal epithelioid granulomas ( arrows) and the presence of mucosa! and submucosal mononuclear inflammatory cell infiltrate. The crypts appear relatively well preserved but their goblet cell mucin 1s depleted

Cryptitis, crypt abscesses and depletion of goblet cell mucin (Figures 1,2) are shared by all forms of acute or active colitis regardless of etiology. These nonspecific features are reversible upon recovery or during remission of the

Figure 7) Colonic mucosa! biopsy from a patient with Crohn's disease showing isolated intramucosal Langhans' giant cell ( arrowheads)

colitis. On the other hand, there are characteristic histological features which help distinguish chronic IBO and ASLC. These include: predominantly lymphocytic infiltrate in the lamina propria (Figure 3 ); villiform (pseudovillous) pattern of the mucosa! surface (Figure 4 ); distorted and/or atrophic crypts (Figure 5 ); Paneth cell

CAN J GASTROENTEROL VOL 4 No 7 NOVEMBER 1990

Figure 8) Foreign body granuloma wich a mulrmucleared giam cell (arrow) m the superficial pare of che mucosa from a pauem wlLh ulcerative colitis. These granulomcLs may cause confusion wlLh Crohn's disease. In Crohn's disease, the characteriscic epichelioid granulomas are found deep m rhe mucosa and submucosa ( see Figure 6)

metaplasia (Figures 4,5); anJ epitheli

oid granulomas with or without Langhans' giant cells (Figures 6,7). These

changes are typically absent in ASLC. Since the above characteristic his

ropathological fea tures of IBO are related to the chronicity of inflammation , they may be absent in the early stages of IBD, thus posing a problem in differentiating it from ASLC. When the histological findings arc equ ivocal, examination of fo llow-up biopsies

TABLE 4

Figure 9) Bio/Jsy of signw,d colun fmm a /iauenr with d1verticulosis. The granuluma found Jeep in the mucosa ( am1wheads) caused imcial m1sd1agnos1s of Crohn's d1seme. Onl'I af1er dee/Jer secnon.s of the btoJ)sy JcmomrmreJ 1he /)resence of foreign material (arrow) , che true nature of 1hi~ foreign body granuloma was recogrnzed

taken six m e ight weeks later may yield more d iagnostic findings. If continued inflammation or crypt architectural abnormalities a re found in fo llow-up biopsies, the d iagnosis of lBD 1s established. On the orher hand, if fol low-up biopsies demomtrate normal mucosal histology, a diagnosis of ASLC wtiuld be more likely.

It is important to pomr out thc'lt while there are histological feature~ characteristic of IBD, none of these i~

Helpful features for distinguishing ulcerative colitis from Crohn's disease in colorectal biopsies

Features Inflammation

Crypt abscesses Crypt distortion Mucosal atrophy

Goblet mucln depletion Poneth cell metaplasia

Epithelloid granulomas and/or Langhans· giant cells

Ulcerative colitis Diffuse. mucosal

Frequent

Mild to severe Common Marked Common

Absent

CAN J GASTROENTEROI VOL 4 Nn 7 N\ WEMBER 1990

Crohn's disease Patchy. mucosal and

submucosal Few Mild Rare and slight Slight Rare Diagnostic

Pathology of IBD

pathognomonic. Crypt Jisrorcion and

Paneth ce ll metaplas1a may also occur in other forms of chronic colitis such as ischemic col1us ( 10), radiation c.olirb and soli tary rectal ulcer syndrome.

Epithelio1d granulom::is are s ine qua non for the diagnosis ofCrohn's disease (11-13). Unforrunately they me found

111 only about 15% of colorectal biopsies from patients with proven Crohn's disease. Less frequently isolated Langhans' giant cells, with the same

diagnostic significance as epithelio1d granulomas, may he found (Figure 7).

Epithelioid granulomas in Crohn'h disease are characrerisrically found

deep in the mucosa and submucosa and need to be differentiated from foreign body granulomas (Figures 8,9). The lat

ter tenJ co occur superficially in the mucosa but occasionally 111 the submucnsa. Foreign hody granulnmas m.1y

he found in ulcerauve col1m, ASLC ,mJ other forms of col1t1s. Granulomas also occur in sc.histosomiasis anJ rarely in cryptornccmb (14).

The differentiat ion between ulcerative colitis and Crohn\ disease is important because of therapeutic and prognostic implications (Table 4). W hile most pauents can he catcgonzed

as having ulcerative minis or Crohn\ disease without Jifficulty, m some the

diMinction between the two condit ions 1s uncertain. In such instance~. col,irectal biopsies may be ()fhelp, pamcularly when correlated with clinical, enJo

scopic and rndiolog1ca l findmgs. A normal hiopsy as evidence of a spared rectum or ocher skip areas, patchy muco~al and suhmucosal mflammauon

and an ep rt hcl roid granuloma \)r Langham.' giant cell favour Croh n's col it is, whereas diffuse in flammat 1011, marked goblet cell Jeplction and a significant degree of crypt destruction,

crypt architectural distonion or atrophy suggest ulcerative colitis.

Aphthous ulcers in seemingly normal mucosa are a characteristic endoscopic feature of Crohn 's disease anJ arc bel ieved to represent early lesions of Crohn's Jisease (15,16). However, aph thous ulcers may occur in other

forms of colilis including Behi;:et's synJrome (17) and amebiasis ( 18).

In about 7'Yc, of patients with acute

3 'l9

MALA TJALIAN

fulminant colitis, differentiation be·tween ulcerative colitis and Crohn's disease may not be possible even when a colectomy specimen becomes available for gross and microscopic examination. Such cases are best classified as 'indeterminate colitis' until subsequent clinical course and followup biopsies make a more precise classification possible (19).

In spite of certain limitations, microscopic examination of colorectal biopsies plays a major role in the diagnosis of colitis. To minimize pitfalls, the colorectal biopsy specimen should be appropriate and sectioned serially for a thorough microscopic examination (20). The hisropathological findings need to be interpreted in the context of clinical and other investigative c.lata.

REFERENCES I. Tawile NT, Priest RJ, Schuman BM.

Colonoscopy m mflammatory bowel Jiscasc. Gastrliintcst Endosc l 975;22: l 1- 3.

2. Farmer RG. Inflammatory bowel disease. Clin Gastroenteml 1980;9:229. (Incro)

3. Gear EV Jr, Dobbins WO Ill.

340

Rectal biopsy: A review of its diagnostic usefulness. Gastroenterology 1968;55:522-44.

4. Morson BC. The technique and interpretation of rectal biopsies in inflammatory bowel disease. Pathol Annu l 974;9:209-30.

5. Goodman MJ, Kirsner J-B, Riddell RH. Usefulness of rectal biopsy in inflammacory bowel disease. Gastroenterology l 977;72:952-6.

6. Yardley JH, Donowitz M. Colo-rectal biopsy in inflammatory bowel disease. In: Yardley JH, Morson BC, Abell MR, eds. The Gastrointestinal Tract. Baltimore: Williams and Wilkins, 1977:50-94.

7. Whitehead R. Mucosa! Biopsy of the Gastrointestinal Tract, 2nd edn. Philadelphia: WB Saunders, 1979.

8. Kumar NB, Nostrant TT, Appleman HD. The h1stopathologic spectrum of acute self-luniting colitis (acute infectious-type colitis). Am J Surg Pathol 1982;6:523-9.

9. Surawicz CM, Belie L. Rectal biopsy helps to distinguish acute self-limited colitis from idiopathic inflammatory bowel disease. Gascroencerology 1984;86:l 04-13.

10. Marston A. Intestinal !schemta. Chicago: Year Book Medical Publishers Inc, 1977.

l l. Morson BC. PathologyofCrohn's disease. Clin Gascrocnterol l 972; I :265-77.

12. Rotterdam H, Korelitz Bl, Sommers SC. Microgranulomas m grossly normal rectal mucosa in Crohn's disease.

AmJ Clin Pathol 1977;67:550-4. 13. Hamilcon SR, Bussey HJR, Morson

BC. En face histologic technique co demonstrate mucosa! inflammatory lesions in macroscopically uninvolved colon ofCrohn's disease resection specimens. Lab Invest 1980;42:121.

14. Hutto JO, Bryan GS, Greene FL, et al. Cryptococcosis of the colon resembling Crohn's disease in a patient with the hyperimmunoglobulinemia E-recurrenc infection (Job's) syndrome. Castro· enterology l 988;94:808-12.

15. Rickert RR, Carter HW. The 'early' ulcerative lesion ofCrohn's disease: Correlative light and scanning electron microscopic study. J Clin Gastroenterol l 980;2: 11.

16. Lusk LB, Reichen J, Levine JS. Aphthous ulceration in diversion colitis: Clinical implications. Gastroenterology 1984;87: 171-3.

17. Lee RO. The colitis of Beh~eL's syndrome. Am J Surg Pathol 1986;10:888-93.

18. Tucker PC, Webster PD, Kilpatrtck ZM. Amebic colitis mistaken for in

flammatory bowel disease. Arch Intern Med !975;135:681-5.

19. Price AB. Overlap in the spectrum ot non-specific inflammatory bowel du;ease - 'Colitis indeterminate'. J Clin Pathol 1978;3 L :567-77.

20. Surawicz CM. Sena! sectiomng of a portion of a rectal biopsy detects more focal abnormalities. A prospective study of patients with inflammacory bowel dll>l."'\Se.

Dig Dis Sci l 982;27:434-6.

CAN j GASTROENTEROL Vl1L 4 NO 7 NOVEMBER 1990

Submit your manuscripts athttp://www.hindawi.com

Stem CellsInternational

Hindawi Publishing Corporationhttp://www.hindawi.com Volume 2014


MEDIATORSINFLAMMATION

of


Behavioural Neurology

EndocrinologyInternational Journal of



Disease Markers


BioMed Research International

OncologyJournal of



Oxidative Medicine and Cellular Longevity


PPAR Research

The Scientific World JournalHindawi Publishing Corporation http://www.hindawi.com Volume 2014

Immunology ResearchHindawi Publishing Corporationhttp://www.hindawi.com Volume 2014

Journal of

ObesityJournal of



Computational and Mathematical Methods in Medicine

OphthalmologyJournal of


Diabetes ResearchJournal of



Research and TreatmentAIDS


Gastroenterology Research and Practice


Parkinson’s Disease

Evidence-Based Complementary and Alternative Medicine

Volume 2014Hindawi Publishing Corporationhttp://www.hindawi.com

Documents

Pitfalls in the histological diagnosis of inflammatory …downloads.hindawi.com/journals/cjgh/1990/970436.pdfPitfalls in the histological diagnosis of inflammatory bowel disease on