Malacoplakia of Gall Bladder: Casereport and review.Introduction Malakoplakia(MP) is a rare granulomatous disorder,mostly involving urinary tract.
Few cases are reported about malakoplakia in gallbladder(GB). It morphologically mimics other lesions like xanthogranulomatouscholecystitis as well 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 nondiabeticfemale patient, presented with a complaint of upper abdominal discomfort.Abdominal examination showed palpable non-tender mass in the righthypochondrium. Signs and symptoms of acute pancreatitis were negative.
Hemogram,liver function tests, renal function tests, Serum amylase and serum lipase werewithin normal levels. Ultrasonography whole abdomen revealed multiple stones, contractedgall bladder with wall thickening and excluded presence of pancreatic andperipancreatic tissue edema.Clinically Gall bladder carcinoma was suspected. Open cholecystectomy was performedand gall bladder specimen was referred to histopathological examination (HPE).Grossly, GB specimen was measured 10x6x4 cm with thickened wall. Dissectionshowed greenish velvety mucosa with areas of ulceration. obliteration of thecavity by diffuse nodules with yellowish discoloration and impacted three blackishstones Figure 1.HPE 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) Figure 2. Rokitansky-Aschoff sinus wasalso noted.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”) wasfirst 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 of malakoplakia in the gall bladder, wherein, itis usually presented as wall thickness as in our case or mass lesion and opencholecystectomy is indicated due to diagnostic suspicion of carcinoma as in ourcase5.Grossly,Malakoplakia specimens reveal a soft yellowish mass.
On routine staining, microscopicexamination shows aggregates of histiocytes with fine eosinophilic granularcytoplasm (von Hansemann cells) admixed with intracellular and extracellularbasophilic discrete inclusions with concentric laminations known as Michaelis-Gutmannbodies in a background of mixed inflammatory cells infiltrating stroma. Thesebodies also demonstrate positive results using periodic acid–Schiff stain. Theystain with von Kossa stain for calcium and Perls Prussian blue stain for iron1.HPE isnecessary to differentiate MP from its mimickers; Xanthogranulomatous cholecystitisand malakoplakia that can present in a similar pattern.
Both are thought to bepart of spectrum of chronic inflammatory pathology, with difference thatmalakoplakia is more aggressive and shows the presence of both intracellularand extracellular Michaelis–Gutmann bodies as in our case. Gallbladder involvement in autoimmune pancreatitisas a part of IgG4-associated systemic disease is also a common mimicker. In ourcase, this was excluded by lack of characteristic laboratory investigations andby the absence of characteristic histopathological findings of this disease.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 results in 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.Anotherexplanation suggested that the defect may exihibit the expression of a geneticdisorder or an improper immune response like that observed in alcohol abuse,malnutrition, post organ transplant, immunosuppressive drugs such as steroidsor cytotoxic agents, malignancy and chronic diseases such as diabetes mellitusand autoimmune disease2.
Malacoplakia has been described also in association with several microorganisms:E. coliis usually seen in cases of urinary MP, Rhodococcus aequi in patients with AIDS infection and pulmonary MP and Herpes simplexvirus in young patients with cerebral MP. Other bacteria (i.e. Proteus, Mycobacterium, Shigella, Klebsiella,Staphylococcus, Streptococcus, Pseudomonas), fungi (i.e. Paracoccidiodes) andparasites have also been reported6.
Development of malakoplakia in chronic cholecystitis could be observed in thebackground of xanthogranulomatous cholecystitis, which is thought to result fromunsuccessful phagocytosis of the bile material8.In our case patient, was nondiabetic female, free of any of reported risk factors,the matter which refers to the possibility of multifactorial pathogenesis ofthis disorder.Although malakoplakia is considered as a benign pathological process thatrequires local excision, it has been observed that many of these cases haveaggressive course including high disease recurrence with fistulisation and poorresponse to antibiotics9.More specific therapy with antibiotics that concentratein macrophages such as quinolone and trimethoprim-sulfamethoxazole isassociated with a high cure rate10. Bethanechol, a choline agonist, has been recommendedin combination with antibiotics and surgery with the principle that Bethanecholmay correct the decreased cGMP levels that are believed to interfere with successfulphagolysosomal activity. Ascorbic acid has been used also to increase the cGMPand cAMP levels in monocytes, which may offer an effective strategy fortherapy, though it is still under trial11.Discontinuation of immunosuppressive drug therapy is usually needed to treatmalakoplakia effectively12.Attempts of curative surgery would appear to be supported in all cases of gallbladder MP and its mimickers; gall bladder carcinoma and xanthogranulomatouscholecystitis due to the difficulty of distinguishing them radiologically.