Malakoplakia is a rare granulomatous disorder, mostly
involving urinary tract. Few cases are reported about malakoplakia in gallbladder.
It morphologically mimics other lesions like xanthogranulomatous cholecystitis as
well as malignancy 1.
We report a case of gall bladder wall
thickness, clinically suspected to be carcinoma and then revealed as malakoplakia.
We will discuss the condition in the context of other causes of gall bladder
A 65 year-old nondiabetic female patient, presented with a complaint of upper
abdominal discomfort. Abdominal examination showed palpable non-tender mass in
the right hypochondrium. Signs and symptoms of acute pancreatitis were
Hemogram, liver function tests, and renal function tests, Serum
amylase and serum lipase were within normal limits. Ultrasonography whole
abdomen revealed multiple stones and contracted gall bladder with wall thickening
and absence of pancreatic and peripancreatic tissue edema.
Clinically GB carcinoma was suspected. Open cholecystectomy
Grossly, gall bladder specimen measured 10x6x4
cm with thickened wall. Dissection showed greenish velvety mucosa with areas of
ulceration. obliteration of the cavity by diffuse nodules with yellowish
discoloration and impacted three blackish stones Figure
HPE was done
after staining the paraffin blocks with hematoxylin and eosin. Sections
examined from gall bladder wall revealed subtotally denuded mucosal lining with
thickening of the wall. Ulcerated area and lamina propria showed sheets of
foamy macrophages with rounded, concentrically layered intracytoplasmic
inclusions (Michaelis-Gutmann bodies) were detected Figure 2. Rokitansky-Aschoff sinus was also
noted. There was no evidence of granuloma, polyps, dysplasia or malignancy .
the characteristic Michaelis-Gutmann bodies were stained positively for
periodic acid-Schiff stain Figure 3.
The patient’s postoperative period was non-eventful. She was given
broad-spectrum antibiotics. She is symptom free and on regular follow up.
Greek Malako “soft” + Plako “plaque”)
is first described in 1902 by Michaelis and Gutmann as a rare chronic
granulomatous disorder most commonly affecting the urinary system1. However it was discovered also to
affect a wide range of tissues, extraurinary malakoplakia remains an occasional diagnosis2–4.
There are few reported cases of
malakoplakia in the gall bladder, wherein, it usually present as mass lesion or
wall thickness and open cholecystectomy is indicated due to diagnostic
suspicion of carcinoma as in our case5.
Malakoplakia specimens reveal a soft yellowish mass. On routine staining, microscopic
examination show aggregates of histiocytes with fine eosinophilic cytoplasmic
granules (von Hansemann cells) admixed with intracellular and extracellular
basophilic discrete inclusions with concentric laminations known as Michaelis-Gutmann
bodies in a background of mixed inflammatory cells infilterating stroma. These
bodies also demonstrate positive results using periodic acid–Schiff stain. They
stain with von Kossa stain for calcium and Perls Prussian blue stain for iron.
Michaelis-Gutmann bodies are pathognomonic to Malakoplakia and thought to represent
remnants of phagosomes mineralised by calcium and iron deposits1.
Although more than a century has passed since Malakoplakia’s original
recognition, the exact pathogenesis has not been fully recognized.
Malakoplakia is thought to result from insufficient lysis of bacteria by
findings suggest that the defective phagolysosomal activity may be due to decreased
intracellular concentration of cGMP which leads to deficient fusion of
lysosomes with phagosome6. Partially digested bacteria
accumulate in monocytes or macrophages and lead to the deposition of calcium
and iron on residual bacterial glycolipid, resulting in accumulation of
inclusion structures in cytoplasm of histiocytes, the Michaelis–Gutmann
bodies which are considered to be
pathognomic of malakoplakia3,7.
suggested that the defect may exihibit the expression of a genetic disorder or an
altered immune system like that observed in in alcohol abuse, malnutrition,
post organ transplant, intake of certain drugs such as steroids or cytotoxic
agents, malignancy and chronic diseases such as diabetes mellitus, autoimmune
disease 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 lung
malacoplakia and Herpes
simplex virus in young patients with cerebral malacoplakia. Other bacteria (i.e. Proteus, Mycobacterium, Shigella, Klebsiella,
Staphylococcus, Streptococcus, Pseudomonas), fungi (i.e. Paracoccidiodes) and
parasites have also been implicated6.
Development of malakoplakia in chronic cholecystitis could be in the background
of otherwise a typical xanthogranulomatous cholecystitis, which is thought to
result 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 of
Xanthogranulomatous cholecystitis and malakoplakia can present in a similar
fashion and are thought to be part of spectrum of chronic inflammatory
pathology, with difference being malakoplakia being more aggressive and shows
the presence of both intracellular and extracellular Michaelis–Gutmann bodies
as in our case.
Gallbladder involvement in autoimmune pancreatitis
as a part of IgG4-associated systemic disease is also common. In our case, this
was excluded by lack of characteristic laboratory investigations and by the
absence of characteristic histopathological findings of this disease.
Although malakoplakia is considered as a benign pathological process that
requires local excision but it has been observed that many of these cases have
aggressive disease process including high disease recurrence with fistulisation
and partial or failure to respond to antibiotics9.
therapy with antibiotics that concentrate in macrophages such as quinolone,
trimethoprim-sulfamethoxazole, is associated with a high cure rate10. Bethanechol, a choline agonist, has
been used in combination with antibiotics and surgery with the concept that
Bethanechol may correct the decreased cGMP levels that are believed to
interfere with complete bacterial killing. Ascorbic acid has been in used to
increase the cGMP and cyclic AMP levels in monocytes, which may represent an
effective strategy for therapy, though it is under trial11.
Discontinuation of immunosuppressive drug therapy is usually needed to effectively
The difficulty of distinguishing gall-bladder carcinoma, XGC and malakoplakia
radiologically would appear to support attempts at curative surgery in all
difference in postoperative management between malakoplakia and its mimickers, histopathology
is considered a must to differentiate these lesions, especially carcinoma gall
bladder and xanthogranulomatous cholecystitis.
Reporting malakoplakia in gall bladder is therefore of importance for surgeons
and histopathologist to recognize that this entity does exist also in the
gallbladder, in order to install proper treatment and to avoid unnecessary