Malakoplakia is a rare granulomatous disorder, mostlyinvolving urinary tract. Few cases are reported about malakoplakia in gallbladder.It morphologically mimics other lesions like xanthogranulomatous cholecystitis aswell as malignancy 1.
We report a case of gall bladder wallthickness, clinically suspected to be carcinoma and then revealed as malakoplakia.We will discuss the condition in the context of other causes of gall bladderwall thickness.Case ReportA 65 year-old nondiabetic female patient, presented with a complaint of upperabdominal discomfort. Abdominal examination showed palpable non-tender mass inthe right hypochondrium.
Signs and symptoms of acute pancreatitis werenegative.Hemogram, liver function tests, and renal function tests, Serumamylase and serum lipase were within normal limits. Ultrasonography wholeabdomen revealed multiple stones and contracted gall bladder with wall thickeningand absence of pancreatic and peripancreatic tissue edema.
Clinically GB carcinoma was suspected. Open cholecystectomywas performed. Grossly, gall bladder specimen measured 10x6x4cm with thickened wall. Dissection showed greenish velvety mucosa with areas ofulceration.
obliteration of the cavity by diffuse nodules with yellowishdiscoloration and impacted three blackish stones FigureHPE was doneafter staining the paraffin blocks with hematoxylin and eosin. Sectionsexamined from gall bladder wall revealed subtotally denuded mucosal lining withthickening of the wall. Ulcerated area and lamina propria showed sheets offoamy macrophages with rounded, concentrically layered intracytoplasmicinclusions (Michaelis-Gutmann bodies) were detected Figure 2. Rokitansky-Aschoff sinus was alsonoted. There was no evidence of granuloma, polyps, dysplasia or malignancy .the characteristic Michaelis-Gutmann bodies were stained positively forperiodic acid-Schiff stain Figure 3.
The patient’s postoperative period was non-eventful. She was givenbroad-spectrum antibiotics. She is symptom free and on regular follow up.DiscussionMalakoplakia (fromGreek Malako “soft” + Plako “plaque”)is first described in 1902 by Michaelis and Gutmann as a rare chronicgranulomatous disorder most commonly affecting the urinary system1. However it was discovered also toaffect a wide range of tissues, extraurinary malakoplakia remains an occasional diagnosis2–4. There are few reported cases ofmalakoplakia in the gall bladder, wherein, it usually present as mass lesion orwall thickness and open cholecystectomy is indicated due to diagnosticsuspicion of carcinoma as in our case5.
Grossly,Malakoplakia specimens reveal a soft yellowish mass. On routine staining, microscopicexamination show aggregates of histiocytes with fine eosinophilic cytoplasmicgranules (von Hansemann cells) admixed with intracellular and extracellularbasophilic discrete inclusions with concentric laminations known as Michaelis-Gutmannbodies in a background of mixed inflammatory cells infilterating stroma. Thesebodies also demonstrate positive results using periodic acid–Schiff stain. Theystain with von Kossa stain for calcium and Perls Prussian blue stain for iron.Michaelis-Gutmann bodies are pathognomonic to Malakoplakia and thought to representremnants of phagosomes mineralised by calcium and iron deposits1.Although more than a century has passed since Malakoplakia’s originalrecognition, the exact pathogenesis has not been fully recognized.
Malakoplakia is thought to result from insufficient lysis of bacteria bymacrophages. Experimentalfindings suggest that the defective phagolysosomal activity may be due to decreasedintracellular concentration of cGMP which leads to deficient fusion oflysosomes with phagosome6. Partially digested bacteriaaccumulate in monocytes or macrophages and lead to the deposition of calciumand iron on residual bacterial glycolipid, resulting in accumulation ofinclusion structures in cytoplasm of histiocytes, the Michaelis–Gutmannbodies which are considered to bepathognomic of malakoplakia3,7.It issuggested that the defect may exihibit the expression of a genetic disorder or analtered immune system like that observed in in alcohol abuse, malnutrition,post organ transplant, intake of certain drugs such as steroids or cytotoxicagents, malignancy and chronic diseases such as diabetes mellitus, autoimmunedisease and sarcoidosis2.Malacoplakia has been described in association with several microorganisms:E.coliis usually seen in cases involving the urinary bladder, Rhodococcus aequi in patients with AIDS infection and lungmalacoplakia and Herpessimplex virus in young patients with cerebral malacoplakia. Other bacteria (i.
e. Proteus, Mycobacterium, Shigella, Klebsiella,Staphylococcus, Streptococcus, Pseudomonas), fungi (i.e.
Paracoccidiodes) andparasites have also been implicated6.Development of malakoplakia in chronic cholecystitis could be in the backgroundof otherwise a typical xanthogranulomatous cholecystitis, which is thought toresult due to unsuccessful phagocytosis of the bile material8.In our case patient, was nondiabetic female, free of any of reported risk factors,the matter which explains the possibility of multifactorial pathogenesis ofthis disorder.
Xanthogranulomatous cholecystitis and malakoplakia can present in a similarfashion and are thought to be part of spectrum of chronic inflammatorypathology, with difference being malakoplakia being more aggressive and showsthe presence of both intracellular and extracellular Michaelis–Gutmann bodiesas in our case. Gallbladder involvement in autoimmune pancreatitisas a part of IgG4-associated systemic disease is also common. In our case, thiswas excluded by lack of characteristic laboratory investigations and by theabsence of characteristic histopathological findings of this disease.Although malakoplakia is considered as a benign pathological process thatrequires local excision but it has been observed that many of these cases haveaggressive disease process including high disease recurrence with fistulisationand partial or failure to respond to antibiotics9.
More specifictherapy with antibiotics that concentrate in macrophages such as quinolone,trimethoprim-sulfamethoxazole, is associated with a high cure rate10. Bethanechol, a choline agonist, hasbeen used in combination with antibiotics and surgery with the concept thatBethanechol may correct the decreased cGMP levels that are believed tointerfere with complete bacterial killing. Ascorbic acid has been in used toincrease the cGMP and cyclic AMP levels in monocytes, which may represent aneffective strategy for therapy, though it is under trial11.Discontinuation of immunosuppressive drug therapy is usually needed to effectivelytreat malakoplakia12.The difficulty of distinguishing gall-bladder carcinoma, XGC and malakoplakiaradiologically would appear to support attempts at curative surgery in allcases.Conclusion:Owing todifference in postoperative management between malakoplakia and its mimickers, histopathologyis considered a must to differentiate these lesions, especially carcinoma gallbladder and xanthogranulomatous cholecystitis.Reporting malakoplakia in gall bladder is therefore of importance for surgeonsand histopathologist to recognize that this entity does exist also in thegallbladder, in order to install proper treatment and to avoid unnecessaryextensive surgery.