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Malakoplakia of the Gall-bladder: Imaging and Histological Features
Clinical Radiology (2001) 56: 326±337 doi:10.1053/crad.1999.0279, available online at http://www.idealibrary.com on
Case Reports Malakoplakia of the Gall-bladder: Imaging and Histological Features G E O F F R E Y H ID E, S R I D E S A I, C L I V E A . B LO X HA M* Department of Radiology, Dryburn Hospital, Durham City, U.K. and *Department of Pathology, Bishop Auckland General Hospital, County Durham, U.K.
Malakoplakia is an uncommon, granulomatous disorder most frequently involving the urinary tract. Malakoplakia of the gall-bladder is rare and the imaging features have never previously been described. We report a case and discuss the condition in the context of other causes of gallbladder wall thickening.
CASE REPORT A 76-year-old male insulin-dependent diabetic was referred for transabdominal ultrasound by his general practitioner with a history of upper abdominal discomfort. A mass was palpable in the right upper quadrant. Sonographic examination showed irregular thickening of the gall-bladder wall with heterogeneous increased re¯ectivity and a small, central, highly re¯ective focus with posterior acoustic shadowing, which was thought initially to be a calculus (Fig. 1). The liver appeared normal. Computed tomography (CT) was performed because of the complex sonographic appearances (Fig. 2). This con®rmed the wall thickening with irregularity and extension into surrounding fat. A small locule of gas was shown within the fundus which corresponded to the highly re¯ective focus identi®ed with ultrasound. No calculi were
Fig. 1 ± Longitudinal sonogram showing irregular thickening of the gall-bladder wall with more central heterogenous re¯ectivity and a highly re¯ective focus in the fundus with posterior acoustic shadowing. Author for correspondence: Dr I. G. Hide, Department of Radiology, Freeman Hospital, Freeman Road, High Heaton, Newcastle upon Tyne NE7 7DN, U.K. Fax: 44 191 223 1168. 0009-9260/01/040326+12 $35.00/0
Fig. 2 ± (a) Non-enhanced CT con®rming irregular gall-bladder wall thickening and demonstrating a locule of low attenuation in the fundus with a Houns®eld value consistent with gas. (b) Enhanced CT demonstrating uniform enhancement of the gall-bladder wall. # 2001 The Royal College of Radiologists
CASE REPORTS
327
identi®ed within the gall-bladder. After intravenous contrast medium, the gall-bladder wall enhanced uniformly. No liver abnormality was shown. A diagnosis of presumed gall-bladder malignancy was made and the patient was referred for surgical resection. At laparotomy, extensive omental adhesions were found obscuring the gall-bladder. The liver surface contained no metastases and the surgical impression was of an in®ltrative gall-bladder malignancy. An extended cholecystectomy was performed with considerable diculty as it was impossible to de®ne a dissection plane. On pathological examination of the resected specimen, the typical histological features of malakoplakia were demonstrated (Fig. 3), replacing almost the entire gall-bladder wall and in®ltrating adjacent fat. No calculi were present in the specimen nor was a ®stula identi®ed. The patient had an uneventful early post-operative recovery but subsequently developed a deep venous thrombosis 5 weeks following surgery; this was treated by anticoagulation. He remains well with no symptoms of locally recurrent disease.
DISCUSSION
Only a handful of reports of malakoplakia of the gallbladder have been published, all in pathological texts [1,2]. Malakoplakia was originally described by Michaelis and Gutmann in 1902 [3], and further by von Hanseman in 1903 [4]. On gross examination, specimens contain soft, yellowbrown plaques and the term derives from the Greek `malakos' (soft) and `plakos' ( plaque). Microscopically, dense aggregates of macrophages (von Hanseman phagocytes) are present with both intra- and extracellular Michaelis±Gutmann (MG) bodies in a stroma in®ltrated by in¯ammatory cells. MG bodies are discreet, well demarcated structures usually 5±10 mm in diameter, frequently demonstrating a concentric, `target' appearance. Although not essential to the diagnosis, as they may be absent early in the disorder, these bodies are pathognomonic and thought to originate from phagolysosomes [5]. Although the exact pathogenesis is unclear, many investigators have found bacilliform structures or fragments of bacilli within MG bodies and it is generally believed that they arise from the mineralization of partially degraded bacteria which have overloaded the digestive capacity of phagocytes. A strong correlation between infection of urine with coliform bacilli, especially Escherichia coli, and malakoplakia of the bladder has been established [6]. Gram-negative infection is common and the question of why only small numbers of patients develop MP is unclear. Associations with immune de®ciency, either pharmacological or inherent, concurrent malignancy and other systemic disorders have been described and disruption of phagocytic function in the host may be to blame. In our case, the history of insulin-dependent diabetes mellitus may be signi®cant since there is evidence that high blood glucose levels are associated with impaired phagocytosis. Malakoplakia of the urinary tract is more common in females but this sex bias is not found in MP of other sites. The condition has been reported in patients aged 4 weeks to 85 years but is commonest in those in the sixth to eighth decades. Malakoplakia most commonly aects the urinary tract but has been described in a number of other sites. Although `benign', it may behave aggressively and be associated with considerable morbidity and mortality when involving vital
Fig. 3 ± Sheets of macrophages showing the presence of Michaelis± Gutmann bodies (arrow). H&E 400.
organs. The prognosis of malakoplakia is variable depending on the organ system involved. MP of the lower urinary tract has been considered self-limiting but MP of the gastrointestinal tract is particularly aggressive and has a high correlation with malignancy [7]. The imaging features of malakoplakia of the gall-bladder have not previously been described. Our case demonstrated non-speci®c wall thickening on both ultrasound and CT, which also showed in®ltration of surrounding fat. Gallbladder carcinoma, aggressive in¯ammation and xanthogranulomatous cholecystitis (XGC) can produce similar appearances. XGC has been the subject of recent interest and a study by Chun et al. [8] reviewed the imaging features in comparison with those of gall-bladder carcinoma. Substantial overlap was found, with no features enabling reliable exclusion of gall-bladder malignancy. The accompanying editorial [9] emphasized the non-random association of XGC and biliary malignancy. Even if a radiological diagnosis of XGC could be established, the surgeon would be left with compelling reasons to perform an extended cholecystectomy to cure a potentially malignant condition. In our case, the imaging features of gallbladder wall thickening with a complex heterogeneous mass on ultrasound and in®ltration of adjacent fat planes on CT suggested gall-bladder malignancy was the most likely diagnosis and resection recommended. At surgery, the lesion was felt to be tumour, emphasizing the diculty in distinguishing malignancy from these tumefactive in¯ammatory processes. The presence of a gas locule within the gall-bladder lumen was initially considered likely to indicate a ®stula with bowel. This may occur in gall-bladder malignancy [10] or in¯ammation. No ®stula was identi®ed on pathological examination however. In the absence of a history of previous instrumentation, we consider infection with gasproducing organisms to be the most likely cause of this ®nding. A number of organisms are known to be responsible for gas production in emphysematous cholecystitis, including E. coli. Electron microscopy of malakoplakia specimens reveals abnormalities in von Hanseman phagocytes and MG bodies, which bear a striking resemblance to intracytoplasmic membranes found in
328
CLINICAL RADIOLOGY
certain strains of E. coli. These features reinforce the evidence implicating this bacterium in the aetiology of malakoplakia of the gall-bladder. Emphysematous cholecystitis, whilst typically acute and rapidly progressive, may be indolent and it is therefore feasible that malakoplakia and emphysematous cholecystitis could co-exist. Both may be associated with diabetes mellitus. Gall-bladder carcinoma and xanthogranulomatous cholecystitis both exhibit strong associations with the presence of gallstones. The limited number of reported cases of malakoplakia of the gall-bladder are insucient to determine if a similar association exists. The absence of visualized calculi on CT in our case was not considered to be inconsistent with the diagnosis of probable carcinoma since up to 25% of calculi may be undetectable by CT (generally those with Houns®eld values below 30). It is unlikely that the presence or absence of calculi would represent a useful diagnostic discriminator in similar cases. Renal parenchymal malakoplakia is commonly confused on imaging studies with malignancy or xanthogranulomatous pyelonephritis. It has been postulated that malakoplakia and xanthogranulomatous pyelonephritis represent dierent degrees of the same process although the majority of investigators believe they are separate disease entities. It is unsurprising that malakoplakia of the gall-bladder and XGC have many features in common. Both are chronic granulomatous disorders with similar radiological and macroscopic appearances. Yellow±brown nodules are seen in each condition and in XGC; these may be identi®ed on CT [8]. We did not observe such lesions in our case. Malakoplakia appears to be a chronic in¯ammatory response to the incomplete breakdown of bacterial constituents and XGC has been thought to arise secondary to the unsuccessful phagocytosis of cholesterol deposits in the gall-bladder wall following the extravazation of bile from ruptured Rokitansky±Ascho sinuses or mucosal ulceration.
It is currently unclear whether malakoplakia, with its distinct histological characteristics, represents a disease entity separate to xanthogranulomatous cholecystitis or whether the two lie on the same spectrum within the gamut of chronic in¯ammatory disorders of the gall-bladder, manifesting dierent features as a result of the diering substances resisting phagocytosis in their evolution. The diculty of distinguishing gall-bladder carcinoma, XGC and malakoplakia radiologically would appear to support attempts at curative surgery in all cases. We consider that when imaging features of marked gall-bladder wall thickening and pericholecystic changes are found, malakoplakia should be considered among the dierential diagnoses alongside XGC and gall-bladder carcinoma.
REFERENCES 1 Charpenter P, Prade M, Bognel C, et al. Malakoplakia of the gallbladder. Hum Pathology 1983;14:827±828. 2 El Mezni F, Dziri CH, Kechrid H, et al. La malacoplasie resiculaire, une cause rare de cholecystite aigue alithiasique. Ann Pathol 1993;13:270±274. 3 Michaelis L, Gutmann C. Uber einschlusse in blasentumoren. Z Klin Med 1902;47:208±215. 4 von Hanseman D. Uber malakoplakie der harnblase. Virchows Arch (Pathol Anat) 1903;173:302±308. 5 Stanton MJ, Maxted W. Malakoplakia: a study of the literature and current concepts of pathogenesis, diagnosis and treatment. J Urol 1981;125:139±146. 6 McClure J. Malakoplakia of the prostate: a report of two cases and a review of the literature. J Clin Path 1979;32:629±632. 7 Sanusi ID, Tio F. Gastrointestinal malakoplakia: report of a case and review of the literature. Am J Gast 1974;62:356±366. 8 Chun KA, Ha HK, Yu ES, et al. Xanthogranulomatous cholecystitis: CT features with emphasis on dierentiation from gallbladder carcinoma. Radiology 1997;203:93±97. 9 Ros PR, Goodman ZD. Xanthogranulomatous cholecystitis versus gallbladder carcinoma. Radiology 1997;203:10±12. 10 Adson MA. Carcinoma of the gallbladder. Surg Clin N Am 1973;53:1203±1216.
doi:10.1053/crad.1999.0277, available online at http://www.idealibrary.com on
Percutaneous Transhepatic use of the Hydrolyser Thrombectomy Catheter to Re-canalize an Occluded Biliary Wallstent I . J . M c CA F F E R T Y, J . R . FE R R A N D O , H . T H O M S O N * Departments of Radiology and *General Surgery, Heartlands NHS Trust, Birmingham, U.K.
Self-expendable metallic stents now have an established role in the palliation of malignant biliary obstruction. The main Author for Correspondence: Dr I. J. McCaerty, Department of Radiology, Queen Elizabeth Hospital, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham B15 2TH, U.K.
complication, is recurrent jaundice, re-intervention is required and it is encountered following metallic stent placement. The causes include tumour ingrowth and overgrowth [1], stent migration [2] and choledocholithiasis. We describe the use of the hydrolyser to re-canalize an occluded Wallstent.
Case Reports Malakoplakia of the Gall-bladder: Imaging and Histological Features G E O F F R E Y H ID E, S R I D E S A I, C L I V E A . B LO X HA M* Department of Radiology, Dryburn Hospital, Durham City, U.K. and *Department of Pathology, Bishop Auckland General Hospital, County Durham, U.K.
Malakoplakia is an uncommon, granulomatous disorder most frequently involving the urinary tract. Malakoplakia of the gall-bladder is rare and the imaging features have never previously been described. We report a case and discuss the condition in the context of other causes of gallbladder wall thickening.
CASE REPORT A 76-year-old male insulin-dependent diabetic was referred for transabdominal ultrasound by his general practitioner with a history of upper abdominal discomfort. A mass was palpable in the right upper quadrant. Sonographic examination showed irregular thickening of the gall-bladder wall with heterogeneous increased re¯ectivity and a small, central, highly re¯ective focus with posterior acoustic shadowing, which was thought initially to be a calculus (Fig. 1). The liver appeared normal. Computed tomography (CT) was performed because of the complex sonographic appearances (Fig. 2). This con®rmed the wall thickening with irregularity and extension into surrounding fat. A small locule of gas was shown within the fundus which corresponded to the highly re¯ective focus identi®ed with ultrasound. No calculi were
Fig. 1 ± Longitudinal sonogram showing irregular thickening of the gall-bladder wall with more central heterogenous re¯ectivity and a highly re¯ective focus in the fundus with posterior acoustic shadowing. Author for correspondence: Dr I. G. Hide, Department of Radiology, Freeman Hospital, Freeman Road, High Heaton, Newcastle upon Tyne NE7 7DN, U.K. Fax: 44 191 223 1168. 0009-9260/01/040326+12 $35.00/0
Fig. 2 ± (a) Non-enhanced CT con®rming irregular gall-bladder wall thickening and demonstrating a locule of low attenuation in the fundus with a Houns®eld value consistent with gas. (b) Enhanced CT demonstrating uniform enhancement of the gall-bladder wall. # 2001 The Royal College of Radiologists
CASE REPORTS
327
identi®ed within the gall-bladder. After intravenous contrast medium, the gall-bladder wall enhanced uniformly. No liver abnormality was shown. A diagnosis of presumed gall-bladder malignancy was made and the patient was referred for surgical resection. At laparotomy, extensive omental adhesions were found obscuring the gall-bladder. The liver surface contained no metastases and the surgical impression was of an in®ltrative gall-bladder malignancy. An extended cholecystectomy was performed with considerable diculty as it was impossible to de®ne a dissection plane. On pathological examination of the resected specimen, the typical histological features of malakoplakia were demonstrated (Fig. 3), replacing almost the entire gall-bladder wall and in®ltrating adjacent fat. No calculi were present in the specimen nor was a ®stula identi®ed. The patient had an uneventful early post-operative recovery but subsequently developed a deep venous thrombosis 5 weeks following surgery; this was treated by anticoagulation. He remains well with no symptoms of locally recurrent disease.
DISCUSSION
Only a handful of reports of malakoplakia of the gallbladder have been published, all in pathological texts [1,2]. Malakoplakia was originally described by Michaelis and Gutmann in 1902 [3], and further by von Hanseman in 1903 [4]. On gross examination, specimens contain soft, yellowbrown plaques and the term derives from the Greek `malakos' (soft) and `plakos' ( plaque). Microscopically, dense aggregates of macrophages (von Hanseman phagocytes) are present with both intra- and extracellular Michaelis±Gutmann (MG) bodies in a stroma in®ltrated by in¯ammatory cells. MG bodies are discreet, well demarcated structures usually 5±10 mm in diameter, frequently demonstrating a concentric, `target' appearance. Although not essential to the diagnosis, as they may be absent early in the disorder, these bodies are pathognomonic and thought to originate from phagolysosomes [5]. Although the exact pathogenesis is unclear, many investigators have found bacilliform structures or fragments of bacilli within MG bodies and it is generally believed that they arise from the mineralization of partially degraded bacteria which have overloaded the digestive capacity of phagocytes. A strong correlation between infection of urine with coliform bacilli, especially Escherichia coli, and malakoplakia of the bladder has been established [6]. Gram-negative infection is common and the question of why only small numbers of patients develop MP is unclear. Associations with immune de®ciency, either pharmacological or inherent, concurrent malignancy and other systemic disorders have been described and disruption of phagocytic function in the host may be to blame. In our case, the history of insulin-dependent diabetes mellitus may be signi®cant since there is evidence that high blood glucose levels are associated with impaired phagocytosis. Malakoplakia of the urinary tract is more common in females but this sex bias is not found in MP of other sites. The condition has been reported in patients aged 4 weeks to 85 years but is commonest in those in the sixth to eighth decades. Malakoplakia most commonly aects the urinary tract but has been described in a number of other sites. Although `benign', it may behave aggressively and be associated with considerable morbidity and mortality when involving vital
Fig. 3 ± Sheets of macrophages showing the presence of Michaelis± Gutmann bodies (arrow). H&E 400.
organs. The prognosis of malakoplakia is variable depending on the organ system involved. MP of the lower urinary tract has been considered self-limiting but MP of the gastrointestinal tract is particularly aggressive and has a high correlation with malignancy [7]. The imaging features of malakoplakia of the gall-bladder have not previously been described. Our case demonstrated non-speci®c wall thickening on both ultrasound and CT, which also showed in®ltration of surrounding fat. Gallbladder carcinoma, aggressive in¯ammation and xanthogranulomatous cholecystitis (XGC) can produce similar appearances. XGC has been the subject of recent interest and a study by Chun et al. [8] reviewed the imaging features in comparison with those of gall-bladder carcinoma. Substantial overlap was found, with no features enabling reliable exclusion of gall-bladder malignancy. The accompanying editorial [9] emphasized the non-random association of XGC and biliary malignancy. Even if a radiological diagnosis of XGC could be established, the surgeon would be left with compelling reasons to perform an extended cholecystectomy to cure a potentially malignant condition. In our case, the imaging features of gallbladder wall thickening with a complex heterogeneous mass on ultrasound and in®ltration of adjacent fat planes on CT suggested gall-bladder malignancy was the most likely diagnosis and resection recommended. At surgery, the lesion was felt to be tumour, emphasizing the diculty in distinguishing malignancy from these tumefactive in¯ammatory processes. The presence of a gas locule within the gall-bladder lumen was initially considered likely to indicate a ®stula with bowel. This may occur in gall-bladder malignancy [10] or in¯ammation. No ®stula was identi®ed on pathological examination however. In the absence of a history of previous instrumentation, we consider infection with gasproducing organisms to be the most likely cause of this ®nding. A number of organisms are known to be responsible for gas production in emphysematous cholecystitis, including E. coli. Electron microscopy of malakoplakia specimens reveals abnormalities in von Hanseman phagocytes and MG bodies, which bear a striking resemblance to intracytoplasmic membranes found in
328
CLINICAL RADIOLOGY
certain strains of E. coli. These features reinforce the evidence implicating this bacterium in the aetiology of malakoplakia of the gall-bladder. Emphysematous cholecystitis, whilst typically acute and rapidly progressive, may be indolent and it is therefore feasible that malakoplakia and emphysematous cholecystitis could co-exist. Both may be associated with diabetes mellitus. Gall-bladder carcinoma and xanthogranulomatous cholecystitis both exhibit strong associations with the presence of gallstones. The limited number of reported cases of malakoplakia of the gall-bladder are insucient to determine if a similar association exists. The absence of visualized calculi on CT in our case was not considered to be inconsistent with the diagnosis of probable carcinoma since up to 25% of calculi may be undetectable by CT (generally those with Houns®eld values below 30). It is unlikely that the presence or absence of calculi would represent a useful diagnostic discriminator in similar cases. Renal parenchymal malakoplakia is commonly confused on imaging studies with malignancy or xanthogranulomatous pyelonephritis. It has been postulated that malakoplakia and xanthogranulomatous pyelonephritis represent dierent degrees of the same process although the majority of investigators believe they are separate disease entities. It is unsurprising that malakoplakia of the gall-bladder and XGC have many features in common. Both are chronic granulomatous disorders with similar radiological and macroscopic appearances. Yellow±brown nodules are seen in each condition and in XGC; these may be identi®ed on CT [8]. We did not observe such lesions in our case. Malakoplakia appears to be a chronic in¯ammatory response to the incomplete breakdown of bacterial constituents and XGC has been thought to arise secondary to the unsuccessful phagocytosis of cholesterol deposits in the gall-bladder wall following the extravazation of bile from ruptured Rokitansky±Ascho sinuses or mucosal ulceration.
It is currently unclear whether malakoplakia, with its distinct histological characteristics, represents a disease entity separate to xanthogranulomatous cholecystitis or whether the two lie on the same spectrum within the gamut of chronic in¯ammatory disorders of the gall-bladder, manifesting dierent features as a result of the diering substances resisting phagocytosis in their evolution. The diculty of distinguishing gall-bladder carcinoma, XGC and malakoplakia radiologically would appear to support attempts at curative surgery in all cases. We consider that when imaging features of marked gall-bladder wall thickening and pericholecystic changes are found, malakoplakia should be considered among the dierential diagnoses alongside XGC and gall-bladder carcinoma.
REFERENCES 1 Charpenter P, Prade M, Bognel C, et al. Malakoplakia of the gallbladder. Hum Pathology 1983;14:827±828. 2 El Mezni F, Dziri CH, Kechrid H, et al. La malacoplasie resiculaire, une cause rare de cholecystite aigue alithiasique. Ann Pathol 1993;13:270±274. 3 Michaelis L, Gutmann C. Uber einschlusse in blasentumoren. Z Klin Med 1902;47:208±215. 4 von Hanseman D. Uber malakoplakie der harnblase. Virchows Arch (Pathol Anat) 1903;173:302±308. 5 Stanton MJ, Maxted W. Malakoplakia: a study of the literature and current concepts of pathogenesis, diagnosis and treatment. J Urol 1981;125:139±146. 6 McClure J. Malakoplakia of the prostate: a report of two cases and a review of the literature. J Clin Path 1979;32:629±632. 7 Sanusi ID, Tio F. Gastrointestinal malakoplakia: report of a case and review of the literature. Am J Gast 1974;62:356±366. 8 Chun KA, Ha HK, Yu ES, et al. Xanthogranulomatous cholecystitis: CT features with emphasis on dierentiation from gallbladder carcinoma. Radiology 1997;203:93±97. 9 Ros PR, Goodman ZD. Xanthogranulomatous cholecystitis versus gallbladder carcinoma. Radiology 1997;203:10±12. 10 Adson MA. Carcinoma of the gallbladder. Surg Clin N Am 1973;53:1203±1216.
doi:10.1053/crad.1999.0277, available online at http://www.idealibrary.com on
Percutaneous Transhepatic use of the Hydrolyser Thrombectomy Catheter to Re-canalize an Occluded Biliary Wallstent I . J . M c CA F F E R T Y, J . R . FE R R A N D O , H . T H O M S O N * Departments of Radiology and *General Surgery, Heartlands NHS Trust, Birmingham, U.K.
Self-expendable metallic stents now have an established role in the palliation of malignant biliary obstruction. The main Author for Correspondence: Dr I. J. McCaerty, Department of Radiology, Queen Elizabeth Hospital, University Hospital Birmingham NHS Trust, Edgbaston, Birmingham B15 2TH, U.K.
complication, is recurrent jaundice, re-intervention is required and it is encountered following metallic stent placement. The causes include tumour ingrowth and overgrowth [1], stent migration [2] and choledocholithiasis. We describe the use of the hydrolyser to re-canalize an occluded Wallstent.