Mucopolysaccharidosis

* Although malakoplakia of the genitourinary tract and colon is reported frequently in the literature, malakoplakia that occurs primarily in the liver is rare, and only 4 cases have been described thus far. To our knowledge, this is the first case of malakoplakia of the liver diagnosed by a needle core biopsy. This case occurred in a 19-year-old man with small bowel ileus following Klebsiella pneumonia.

(Arch Pathol Lab Med. 2002;126:372-374)

PATHOLOGIC FINDINGS

Histologic sections of the liver needle core biopsy Specimen showed cirrhotic hepatic parenchyma with bile ductular proliferation and portal inflammatory infiltrates composed of lymphocytes, neutrophils, and a few scattered eosinophils. Rare isolated bile ductules were associAted with neutrophils consistent with cholangitis. Scattered within periportal and portal regions were small, round-to-oval targetoid structures consistent with Michaelis-Gutmann bodies (Figure, A). These stained positively with periodic acid-Schiff (with and without diastase) (Figure, B), Von Kossa calcium (Figure, Q, and colloidal iron stain (with and without hyaluronidase) (Figure, D), but were negative for copper and otl-antitrypsin. Immunohistochemistry with CD68 (Figure, E) demonstrated these targetoid bodies within scattered histiocytes and Kupffer cells. Electron microscopy confirmed the presence of Michaelis-Gutmann bodies (Figure, F) within histiocytes and failed to show any evidence of mucopolysaccharidosis. The hepatocyte cytoplasm was neither pale nor reticulated as would be expected in mucopolysaccharidosis.

COMMENT

Malakoplakia, a Greek term meaning soft (malako) plaque (plakia), is an unusual inflammatory process. It was originally described in the early 1900s. Although the original article was published by Michaelis and Gutmann in 1902, its discovery is best attributed to their senior colleague, Von Hanseman, even though his article was published a year later5

Malakoplakia was first reported and is most commonly seen in the bladder. It has since been described in other locations, such as the colon, upper and lower genitourinary tract, gynecologic regions, upper and lower respiratory tract, spleen, joints, and brain. It has rarely been reported to occur in the liver. This case is the fifth reported case of malakoplakia of the liver and the first to be diagnosed by a needle core biopsy (Table). Two other cases involved the liver through extension from the kidney and urinary tract.

Malakoplakia is usually associated with Klebsiella and Escherichia coli, although gram-negative and gram-positive cocci and acid-fast bacilli have also been identified. Recently, malakoplakia has been reported to occur in association with unusual organisms such as Rhodococcus equi and paracoccidioidomycosis infection.6

There is usually an underlying systemic disease in malakoplakia. Some of the reported associated systemic diseases include systemic lupus erythematosus, diabetes mellitus, myotonic dystrophy, and chronic active hepatitis. Immunosuppression is also common, but malakoplakia is not as common as one would expect in acquired immunodeficiency syndrome, which may be due to a relative or selective preservation of antimicrobial function of monocytes.

Malakoplakia has a distinct gross and microscopic appearance. In urothelial and colonic mucosa, where they are frequently seen, lesions of malakoplakia are characterized by variably sized yellow-to-brown plaques that are usually soft, often with central erosion and peripheral hyperemia.7 The lesions of malakoplakia may be solitary, multifocal, or present as a large mass.

Microscopically, malakoplakia is characterized by aggregates of histiocytes, the Von Hanseman cells, with Michaelis-Gutmann calcospherites. Surrounding inflammatory cells usually consist of lymphocytes and plasma cells. There are 3 phases in the histopathologic evolution of malakoplakia, as described by Smith.8 The early phase consists of Von Hanseman histiocytes and plasma cells in an edematous stroma. The granulomatous phase displays many lymphocytes and plump histiocytes with typical Michaelis-Gutmann calcospherites. The fibrosing or healing phase is characterized by interwoven fibroblasts and strands of thickened collagen admixed with histiocytes. Michaelis-Gutmann bodies are sparse.

The most plausible pathogenetic explanation for the development of malakoplakia centers on the defective function of macrophages that phagocytose the bacteria but are unable to kill or digest them. Intracytoplasmic phagolysosomes continue to enlarge and coalesce with subsequent degenerative change of both matrix and limiting membrane. The deposition of crystals within this enlarged phagolysosome leads to the development of the characteristic, concentrically laminated Michaelis-Gutmann inclusions.9

Other authors propose that the defect in malakoplakia may be due to low levels of cyclic guanosine monophosphate in mononuclear cells, resulting in deficient lysosomal bacterial degradation and the inability of cells to release the lysosomal enzymes. Correction of this defect with cholinergic agonists would correct the lysosomal deficiency and prove therapeutically beneficial.10

In summary, this case occurred in a 19-year-old man with a cirrhotic liver of uncertain origin, who subsequently developed malakoplakia of the liver following sepsis that resulted from Klebsiella lobar pneumonia. It is the fifth reported case in the medical literature of malakoplakia that occurred primarily in the liver and, to our knowledge, the first to be diagnosed by a needle core biopsy. A surgical procedure, which comparatively has more potential for complications than a needle core biopsy, may be avoided in some cases. Complete workup and diagnosis of malakoplakia are possible even in specimens as small as those obtained with a needle core biopsy.

We acknowledge Raoul Fresco, MD, who interpreted the material that was submitted for electron microscopic studies and for his translation of a French text. We also acknowledge Elena Roukhadze, MD, for her translation of a Russian text.

References

1. Boucher L, Makoto A, Lee E, Cibull M. Malakoplakia of liver associated with perforated colonic diverticulum: a case report and review of the literature. Clin GastroenteroL 1994;19:318-320.

2. Robertson S, Higgins R, Powell C. Malakoplakia of liver: a case report. Hum Pathol. 1991;22:1294-1295.

3. Moldavski M, Rustamov I. Multichamber pseudocyst of the liver with malakoplakia [in Russian]. Klin Khir. 1984;9:64-65.

4. De Saint-Maur P, Gal lot D. Malakoplakie hepatique compliquant one polykystose [letter]. Ann PathoL 1990;10:50-51.

5. Damjanov I, Mori her Katz S. Malakoplakia [review]. Pathol Ann. 1981;16(pt 203-126.

6. Rocha N, Suguiama EH, Maia D, et al. Intestinal malakoplakia associated with paracoccidioidomycosis: a new association. Histopathology. 1997;30:7983.

7. Stanton M, Maxted W. Malakoplakia: a study of the literature and current concepts of pathogenesis, diagnosis, and treatment [review]. J Urol. 1981;125: 139-146.

8. Smith B. Malakoplakia of the urinary tract: a study of twenty-four cases. Am Clin Pathol. 1965;43:409-417.

9. Lou T, Teplitz C. Malakoplakia: pathogenesis and ultrastructural morphogenesis: a problem of altered macrophage phagolysosomal response. Hum PathoL 1974;5:191-207.

10. Abdou N, Napombiyare C, Sagawa A, et al. Malakoplakia: evidence for monocyte lysosomal abnormality correctable by cholinergic agonist in vitro and in vivo. N Engl J Med. 1977;297:1413-1419.

Grace Hartman, MD; Sherri L. Yong, MD; Gregorio Chejfec, MD

Accepted for publication August 3, 2001.

From the Department of Pathology, Loyola University Medical Center, Maywood, III. Dr Yong is now with Northwest Community Hospital, Arlington Heights, III. Dr Chejfec is now with the University of Illinois at Chicago.

Reprints: Grace Hartman, MD, Department of Pathology, Loyola University Hospital, 2160 S First Ave, Maywood, IL 60153 (e-mail: ghartma@lumc.edu).

Copyright College of American Pathologists Mar 2002
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