Radiological and pathological features of AIDS-related polypoid cholangitis

Clinical Radiology (1993) 48, 307 310

Radiological and Pathological Features of AIDS-Related Polypoid Cholangitis C. D. COLLINS, A. FORBES$, J. N. H A R C O U R T - W E B S T E R # , N. D. FRANCIS#, J. A. G L E E S O N and B. G. G A Z Z A R D *

Department of Radiology, *H I V Unit and #Department of Pathology, Chelsea and Westminster Hospital, London and ~St Mark's Hospital, London A review of the radiographs obtained at ERCP from 31 patients with AIDS-related sclerosing cholangitis (ARSC) demonstrated intraluminal polypoidal defects within the common bile duct and larger intrahepatic ducts in eight cases (26%). The radiologicai features from this subgroup are described and correlated with the microbiological and histological findings from biopsy specimens including two patients who underwent post-mortem examination. At microscopy the polypoid lesions were demonstrated to consist of granulation tissue. The presence of these polyps did not adversely affect the prognosis nor were they associated with any particular infective agent. We propose recognizing the existence of this entity by the term AIDS-related polypoid cholangitis (ARPC). Collins, C.D., Forbes, A., Harcourt-Webster, J.N., Francis, N.D., Gleeson, J.A. & Gazzard, B.G. (1993). Clinical Radiology 48, 307-310. Radiological and Pathological Features of AIDS-Related Polypoid Cholangitis

Accepted for Publication 20 May 1993 In the acquired immune deficiency syndrome (AIDS) biliary tract abnormalities are well recognized and may be manifest as cholecystitis, ampullary stenosis and/or cholangitis [1,2]. Cryptosporidium and cytomegalovirus (CMV), often in association, are the commonest infective agents but Campylobacter species have also been implicated [3-6]. Atypical mycobacteria (usually avium intracellulare) may rarely be found in the biliary tract, but more often are responsible for portal lymphadenopathy causing compression of the bile duct [7]. In the majority of cases biliary tract involvement presents with right upper quadrant pain; in some patients, diarrhoea and/or weight loss may predominate. The alkaline phosphatase levels are typically raised but serum bilirubin is often not significantly elevated and overt jaundice is infrequent [8]. In affected patients, imaging most frequently shows a distended gall-bladder with variably dilated intra- and extra-hepatic bile ducts sometimes associated with ampullary stenosis. In addition there may be beading of the same ducts as seen in sclerosing cholangitis [9]. No calculi are visualized although there may be an intraluminal sludge of necrotic cellular debris. In several of our patients with AIDS and biliary disease we have noticed apparent polypoidal filling defects in the duct system. Post-mortem examination in two patients and review o f biopsy specimens in the others allowed us to correlate the ERCP changes with the subsequent microbiological and histological findings and to offer a possible explanation for the ductal abnormalities. PATIENTS AND M E T H O D S The case records of 31 consecutive patients with AIDSrelated sclerosing cholangitis (ARSC) were reviewed together with the radiographs taken during ERCP. For this study the diagnosis of ARSC required HIV seroposit-

ivity to be confirmed by two separate methods and features on direct cholangiography that would otherwise meet diagnostic criteria for primary sclerosing cholangitis (PSC) [8]. Patients with established inflammatory bowel disease were excluded. All patients had standard haematological and biochemical analyses, an upper abdominal ultrasound scan and an ERCP. Their fundi were examined for CMV retinitis by an experienced ophthalmologist after mydriatics. Each patient was investigated for intestinal pathogens; concentrated samples of faeces were examined by direct microscopy for cysts, ova and parasites. At least three stools were cultured for organisms including mycobacteria, both typical (TB) and atypical forms. After concentration by the modified sucrose flotation method smears were stained by the Kinyoun modification of Ziehl-Neelsen for cryptosporidia [9]. Each patient underwent sigrnoidoscopy and during this a biopsy of the rectal mucosa was fixed in buffered formalin. Each patient underwent flexible gastrointestinal endoscopy (upper and lower tract) during which mucosal biopsies were obtained and fixed in buffered formalin. Sections were stained with haematoxylin and eosin (H and E), periodic acid Schiff (PAS) for fungi and Ziehl-Neelsen (ZN) for acid-alcohol fast bacilli; all biopsies obtained during the course of the investigation were reviewed. Post-mortem examinations were performed on two patients. In both cases multiple tissue blocks were taken from many sites, including the liver and gastrointestinal tract and fixed in a similar manner. Sections obtained were stained with H&E, Fouchet for bile, Gram for organisms, Martius Scarlet Blue for fibrin, PAS for fungi, Perls' for haemosiderin and Z N for acid-alcohol fast bacilli before examination. When CMV inclusion bodies were suspected they were confirmed by immunocytochemistry [10]. RESULTS

Correspondence to: Dr C. D. Collins, Department of Radiology, Royal Postgraduate Medical School, Hammersmith Hospital, London WI2 0HS.

Eight of these patients (26%) (one woman and seven homosexual men), aged between 31 and 44 years (median

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Table 2 - Incidence of infection within polypoid subgroup, n = 8 Cryptosporidia and cytomegalovirus Cryptosporidia Microsporidia

2 2 l

Total

Fig. 1 ERCP demonstrating a dilated common bile duct (CBD) containing intraluminal polypoidal defects within the upper CBD (arrow).

35 years) were found to have polypoidal filling defects within both the larger intrahepatic ducts and common bile duct (CBD) on ERCP (Fig. 1). These lesions were fixed and did not alter with position. Some of the defects had a stalk-like attachment to the duct wall giving a linear defect. Dilatation of the CBD and intrahepatic ducts was present in six patients. In three cases this was secondary to stenosis at the ampulla of Vater which was treated by sphincterotomy at the time of the diagnostic study. The outline of the CBD and intrahepatic ducts in all eight patients was seen to be irregular with beading of the intrahepatic ducts present in six. The smaller intrahepatic ducts were not visualized well in any patient. The cystic duct had an irregular mucosal pattern in five studies but

Table 1 - Incidence of infection within non-polypoid subgroup, n = 23) Cryptosporidiosis Cytomegalovirus (CMV) Cryptosporidia and CMV Cryptosporidia and microsporidia Microsporidia Adenovirus (rectum) Total

8 4 3 I 1 1 23

no evidence of filling defects in any case. Dilatation of the pancreatic and accessory duct was present in four studies. Ultrasound confirmed the presence of a dilated CBD and intrahepatic ducts in the same six patients as ERCP; the ductal wall was thickened in three patients with dilatation and in two patients with a normal calibre common bile duct. No calculi were identified in either the gall-bladder or CBD, although biliary sludge was present in four. No polypoid lesion was identified within the CBD or dilated larger intrahepatic ducts. The pancreatic duct was mildly dilated in two patients. N o other pancreatic abnormality was identified. At the time of the radiological investigations stool microscopy + / - intestinal biopsies identified the following pathogens. In the non-polypoid subgroup (n = 23), 18 patients (78%) had evidence of infection (Table 1). The majority, 14/18 (78%), had infection by a single organism. Three out of the remaining four patients had infection with cryptosporidium and CMV and one patient had infection with cryptosporidium and microsporidia. In the polypoid subgroup (n=8), five patients (62.5%) had evidence of infection (Table 2). A single organism was present in 3/5 (60%) patients and cryptosporidium and CMV were present in the remaining two patients. Four patients from the polypoid subgroup have died at a median of 8 months from the diagnosis of ARSC (range 1-15 months) and four remain alive; of the 23 remaining patients with ARSC, 20 have died at a median of 9 months (range 1-23 months). Two of the deceased (patients A and B) from the polypoid group underwent post-mortem examination (the terminal CD4 counts were 23 and 51 mm 3, respectively). The pathological findings in the two patients undergoing full post-mortem examination were as follows:

Macroscopy The intrahepatic bile ducts had thick sclerotic walls (up to 3 mm) with variable narrowing of the lumina throughout most of their length, up to the porta hepatis. Nodules of scarring (up to 15 mm across) were found close to the hilum and formed from coalescence of adjacent ducts. The larger of these ducts were lined by thickened bilestained mucosa with brown staining of the adjacent parenchyma. In some areas both the larger and smaller ducts had a folded mucosal lining. The liver in both cases retained a normal lobular architecture.

Microscopy Many larger ducts showed chronic inflammation with multifocally more acute changes, including abscess formation and mucosal destruction. Within the inflamed areas, solid polypoid protrusions of granulation tissue were found-within ducts or duct remnants (Fig. 2). In addition, small deposits of fibrin and bile were seen in the

AIDS-RELATED POLYPOID CHOLANGITIS

Fig. 2 A chronically inflamed bile duct with a polyp part covered by biliary epithelium (arrowhead) protruding into the lumen (arrow).

duct remnants and in the inflammatory foci, often cuffed by acute change. Granulomas and giant cells were not seen. In the smaller intrahepatic ducts the epithelium was normal or slightly folded. Elsewhere there was marked folding and bile duct proliferation (hyperplasia), particularly around the porta hepatis. Around some of the bile debris and occasionally within the abscesses were numerous organisms. These were predominantly Gram-positive cocci with lesser numbers of Gram-negative cocci and bacilli. No acid fast bacilli were found. Attempts to culture material taken at postmortem were unsuccessful (as had been the case with samples taken at ERCP). In both patients the extrahepatic (cystic and c o m m o n bile ducts) also showed thickened walls with folded mucosa and minimally patent lumina. Periductal fibrosis was present in almost all sites down to the ampulla of Vater, both of which had previously been subject to sphincterotomy. The gall-bladders showed normal mucosa with slightly thickened (3 ram) fibrous wall. There was no evidence of calculi or neoplasia. Pancreatic histology in both cases was normal. In patient 'A', CMV-infected cells (confirmed by immunocytochemistry) were seen in the chronically inflamed areas of the intra- and extrahepatic ducts and in the epithelial cells of non-inflamed areas (CD4 count 23 mm3). Occasional cryptosporidia were also seen throughout the same duct system. In patient 'B', cryptosporidia and C M V infection were not found (CD4 count 51 mm3). N o cysts, ova or other parasites were identified in any specimen from either patient.

DISCUSSION Polypoidal filling defects within the biliary system have been described previously on E R C P examinations in a minority o f patients with AIDS. Initially they were described as a plaque causing an irregular surface to the lumen [11] and subsequently as polypoidal defects in the wall [12] with no further comment being made. Similar changes in E R C P images have been illustrated elsewhere [5,13] but more often no such abnormality has been demonstrated [14 18]. This is the first series to demonstrate these lesions with pathological correlation in patients following comprehensive microbiological and

309

histologic.al investigations. No polyps were identified within the lumina on ultrasound but the radiographic appearances on E R C P were consistent with polyps. The polyps appear to represent one of the effects of diffuse, severe inflammation in the biliary system. Inflammatory polyps of the bile ducts are reported elsewhere in association with calculi in the common bile duct [19,20], but there was no evidence of calculi in any of our patients. However, it seems likely that biliary sludge visualized on ante-mortem ultrasound examination may reflect supersaturation b f s o m e bile components within the ducts. This is a further consequence of impaired drainage and a probable stimulant to hyperplasia of the biliary epithelium. Opportunistic infections of the gastrointestinal tract are frequent in the HIV-seropositive patient. C M V and protozoa are the commonest pathogens but m a n y bacteria, some fungi and other viruses are reported. In addition, microsporidia are being increasingly recognized as a possible pathogen. Direct damage to the small intestinal mucosa has been attributed to H I V infection alone and compared to graft-vs-host disease [21]. Furthermore, a Whipple's disease-like picture is seen with atypical mycobacteria, especially M. avium intracellulare complex [22]. The possibility of other still-unidentified enteric pathogens cannot be discounted. Ascending involvement of the biliary system might well be expected with such intestinal infections and especially where there is impaired drainage associated with involvement of the ampulla of Vater. Bacteraemia and dissemination via the liver to the bile ducts is also probable. Infective cholecystitis without calculi is well recognized in A I D S and combined studies of the biliary system by ERCP, and of the intestinal tract by endoscopy have confirmed the same polymicrobial infections. The threshold for performing E R C P in patients with cryptosporidial infection is low given the suggestion that many (or even all) patients with cryptosporidiosis have biliary involvement [23]. In this study, it was present in four from the polypoid subgroup and 12 from the nonpolypoid group. The other c o m m o n organism, CMV, was implicated in less than a third of cases overall with no significant difference in incidence between the polypoid and non-polypoid groups; 28% of patients in the polypoid group had no identifiable gastrointestinal infection/ infestation. It is possible that new organisms or occult infection are implicated and although unlikely given the absence of CD4 receptors on healthy biliary epithelium [24], H I V itself m a y damage the biliary tree. As regards prognosis, no difference was apparent between the two groups. In conclusion, the pathological findings confirmed the presence of polypoid lesions consisting of granulation tissue within the CBD and intrahepatic ducts. N o effect on prognosis or association with any particular intestinal pathogen was demonstrated.

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