Primary non-Hodgkin's lymphoma and malakoplakia of the vagina: a case report.

The vagina is a rare site for both primary non-Hodgkin's lymphoma and malakoplakia. We report a case of concurrent diffuse large B-cell lymphoma and malakoplakia of the vagina in a 67-year-old woman presenting with a vaginal discharge and a vaginal mass. The patient had two biopsy specimens reported as showing malakoplakia only, followed by a third biopsy specimen 10 months later which was diagnosed as diffuse large B-cell lymphoma. Review of the first two biopsy specimens showed areas of histiocytes with Michaelis-Gutman bodies merging with areas of cells with slightly larger nuclei and more amphophilic cytoplasm. Immunohistochemistry for the B-cell marker L-26 (CD20) and polymerase chain reaction analysis of the immunoglobulin heavy chain gene were helpful in retrospectively distinguishing the population of diffuse large B-cell lymphoma from the areas of malakoplakia. The third biopsy specimen showed sheets of large atypical lymphoid cells characteristic of a large cell lymphoma. Malakoplakia has been described in association with a variety of cancers, and this is only the second report of malakoplakia associated with non-Hodgkin's lymphoma. Considering the rarity of these two entities in the vagina, it is unlikely that the association in this case is coincidental, raising the possibilities of an unusual reaction to the presence of lymphoma or a common pathogenesis such as underlying chronic inflammation. Epstein-Barr virus DNA was detected in the second biopsy specimen, suggesting a possible role in the pathogenesis of this lymphoma.

Antigenicities of enteropathogenic Escherichia coli, lysozyme, and alpha-1-antichymotrypsin on macrophages of genitourinary malacoplakia.

Seven cases of genito-urinary malacoplakia were analyzed histologically, ultrastructurally and immunohistochemically in a comparison with two cases of xanthogranulomatous pyelonephritis. Immunohistochemically, von Hansemann cells and Michaelis-Guttmann bodies, both hallmarks for the diagnosis of malacoplakia, showed a common antigenicity for enteropathogenic Escherichia coli as cytoplasmic granules of varying sizes. These microscopic manifestations corresponded ultrastructurally to a series of phagolysosomal degradations of coliform bacilli. Serogroups against E. coli OK antigens, which were positive for malacoplakic cells, were not confined to a particular group. Macrophages of xanthogranulomatous pyelonephritis did not show the E. coli antigenicity. Antigenicity of lysozyme and alpha-1-antichymotrypsin on the von Hansemann cells was equivocal, but these enzymes were strongly positive on macrophages of xanthogranulomatous pyelonephritis. The macrophages of both malacoplakia and xanthogranulomatous pyelonephritis were positive for antihuman macrophage antibody. These results indicate that malacoplakia depends mainly on infection by a non-specific strain of enteropathogenic E. coli and may arise from defective digestive enzyme activity of infiltrating macrophages. Immunohistochemical analysis using antisera against E. coli OK antigens, lysozyme and alpha-1-antichymotrypsin was useful in identifying the prediagnostic stage of malacoplakia and in differentiating the lesion from xanthogranulomatous pyelonephritis.

Renal parenchymal malakoplakia: ultrastructural findings in different stages of morphogenesis.

Light microscopic and ultrastructural findings in five cases of renal parenchymal malakoplakia detected in renal biopsy specimens (four cases) or observed at autopsy (one case) are reported. The spectrum of ultrastructural changes ranging from lamellar and microvesicular phagolysosomal inclusions arranged in a biphasic pattern to fully developed Michaelis-Gutmann bodies is described. In three of the biopsy cases the lesions appeared to represent early stages of malakoplakia lacking classic Michaelis-Gutmann bodies. Especially in this phase of disease, ultrastructural investigation can distinguish between this condition and other histiocytic interstitial renal processes. The findings show that focal cytoplasmic degeneration and autophagolysosomal processes observed in macrophages could precede the disturbance in the process of bacterial breakdown that is responsible for the peculiar granuloma-like inflammatory histiocytic reaction.

Tenascin in inflammatory conditions and neoplasms of the urinary bladder.

Tenascin (Tn) is an extracellular matrix (ECM) glycoprotein strongly and widely expressed during embryogenesis. Tn is decreased in normal adult tissues but is reexpressed in numerous inflammatory, reparative and neoplastic processes. We immunostained samples of fetal and normal adult bladders and samples of bladder tissue from patients with chronic cystitis, detrusor hypertrophy, malakoplakia and transitional cell carcinomas (TCC) of all grades, with a monoclonal antibody (mAb) to Tn 143DB7. Sections of flat in situ carcinomas were also studied. In fetal bladders, strong and ragged Tn reactions were noted at the epithelial-stromal interface; in normal adult bladders, the reaction was delicate and less extensive. In chronic cystitis, Tn reactivity was enhanced particularly around prominent capillary blood vessels. In flat in situ carcinomas, Tn staining was stronger and more extensive than in normal mucosa but was often less extensive than in some examples of cystitis. In TCC I and II, Tn immunoreactivity was strong and predominated in the pericapillary stroma of the papillae; in infiltrating TCC II, comparatively limited Tn staining was noted. In deeply infiltrating grade III TCC with abundant stroma, Tn reaction was invariably strong and extensive, particularly around advancing tumor nests. The strongest Tn reactions were noted in invasive, high-grade TCC with abundant stroma. We conclude that in inflammatory-reactive processes, and in in situ carcinomas as well as in TCC, the extent and intensity of the Tn reaction correlates with the severity of the inflammatory infiltrate and with the extent of the stromal remodelling.

Morphogenesis of Michaelis-Gutmann bodies in cerebral malacoplakia. An ultrastructural study.

Malacoplakia was found in the brain biopsy specimen from the wall of a cystic lesion in a 4-month-old girl. Ultrastructural study of the Michaelis-Gutmann bodies revealed that the initial stage of calcification appeared to be the deposit of needle-shaped apatite crystals within intracytoplasmic membrane-bound vesicles of histiocytes. Accumulation of apatite crystals and coalescense of calcified vesicles resulted in the formation of large laminated calcospherules. Extracellular Michaelis-Gutmann bodies and apatite crystal-containing matrix vesicles were also noted. Calcified vesicles and the Michaelis-Gutmann bodies were not observed in the phagolysosomes. Bacteria and viral particles were not identified. These findings suggest that matrix and intracytoplasmic membrane-bound vesicles play an important role in the initial stage of the formation of Michaelis-Gutmann bodies and that a mechanism other than bacterial or viral infection may be involved in cerebral malacoplakia.

A case of fistulizated pelvic malacoplakia: cytohistologic, immunohistochemical and electron-microscopic study.

A case of malacoplakia with a tumor-like involvement of the pelvis is presented. It was characterized by a urine-trickling fistula from the bladder to the gluteal surface and by acute urinary retention. Examinations both cytologic of urine collected from urethra and from fistula, and histological of tissues from bladder and rectum were performed. Histiocytes with Michaelis Gutmann bodies were found in all specimens. The specimens were also studied from an immunohistochemical and electron-microscopic point of view. The case was found interesting because of the unusual fistulization and for the absence of other important associated diseases usually reported in the literature.

Prostatic malacoplakia. An ultrastructural and immunohistochemical study.

A case of malacoplakia of the prostatic gland associated with prostatic nodular hyperplasia from a 69 years old man was presented, and its light and electron microscopic and immunohistochemical features were discussed along with its pathogenesis. This lesion was incidentally found in a transurethral prostatectomy specimen, and consisted of large number of epithelioid cells in which were typical cytoplasmic inclusions known as Michaelis-Gutmann bodies. Ultrastructurally, these inclusions showed a dense, central calcified bodies of various developmental stages. Immunohistochemical study using antilysosomal antibody revealed no lysosomal activity. Based on these findings, we could suspect that main problem for this development of malacoplakia is altered intracellular digestion process of foreign biologic materials.

Prostatic malacoplakia. An ultrastructural and immunohistochemical study

A case of malacoplakia of the prostatic gland associated with prostatic nodular hyperplasia from a 69 years old man was presented, and its light and electron microscopic and immunohistochemical features were discussed along with its pathogenesis. This lesion was incidentally found in a transurethral prostatectomy specimen, and consisted of large number of epithelioid cells in which were typical cytoplasmic inclusions known as Michaelis-Gutmann bodies. Ultrastructurally, these inclusions showed a dense, central calcified bodies of various developmental stages. Immunohistochemical study using antilysosomal antibody revealed no lysosomal activity. Based on these findings, we could suspect that main problem for this development of malacoplakia is altered intracellular digestion process of foreign biologic materials.

The histochemical features of the Michaelis-Gutmann body and a consideration of the pathophysiological mechanisms of its formation.

The reactions to a number of histochemical stains by Michaelis-Gutmann (MG) bodies in 13 cases of malakoplakia are described. All MG bodies contained calcium and phosphate. Iron was present in six cases. Special stains failed to reveal the presence of micro-organisms. In six cases the MG bodies contained either lecithin or sphingomyelin and in three both phospholipids were present. There was no evidence of phospholipid of bacterial cell membrane derivation. Carbohydrate staining reactions suggested the presence of a neutral polysaccharide and an acidic non-sulphated polysaccharide (such as a sialoglycan). No histochemical evidence could be adduced to implicate bacterial cell membranes in the structure of the organic matrix of the MG body. The implications of these findings in the light of the association between clinical bacterial infection and malakoplakia are discussed.

Extravesical malacoplakia--possibly originated from a superficial part of the renal cortex.

A 61-year-old woman was found to have a right flank mass. Radiologically, the mass was thought to be of renal origin. Surgically, however, the tumorous lesion adhered tightly not only to the cortical surface but extended to the retroperitoneum and psoas muscle. Pathological examination confirmed the lesion to be malacoplakia which was characterized by the presence of von Hansemann cells and Michaelis-Gutmann bodies. Despite the effort made to focus on the initiating site of the tumor, it was considerably difficult to decide whether it originated from either an extremely superficial part of the renal cortex or renal capsule or retroperitoneum itself. Histochemical and electron microscopical investigations on the von Hansemann cells and Michaelis-Gutmann bodies were made. The pathogenesis of malacoplakia was briefly discussed with particular emphasis on its possible occurrence in the patients under various therapeutic regimes.

Malakoplakia of the skin. Ultrastructure and quantitative x-ray microanalysis of Michaelis-Gutmann bodies.

The etiologic agent in a case of malakoplakia of the skin was identified as Staphylococcus aureus from culture of the lesion and from ultrastructural observations. Ultrastructurally, electron-dense inclusions were observed in addition to membranous whorls and Michaelis-Gutmann (MG) bodies. These were labeled "precalcification formations" since they possessed an organic crystalline structure. These formations may act as nucleation centers for further incorporation of organic and inorganic material. Deposition of fine crystalline material in the outer region may occur as the structure becomes saturated with inorganic elements, thus completing formation of the MG body. Quantitative x-ray microanalysis of MG bodies demonstrated the presence of phosphorus, calcium, and iron, with average concentrations of 2.1%, 2.6%, and 0.7% by weight, respectively.

X-ray microprobe analysis of Michaelis-Gutmann bodies in human and experimental malakoplakia.

Using x-ray microprobe analysis, we studied Michaelis-Gutmann bodies (M-G bodies) in malakoplakia tissue samples from human kidney and testis as well as from lesions experimentally induced in the rat. In all the M-G bodies tested we could unambiguously detect calcium at both its Kalpha and Kbeta lines. The actual amount of calcium depended on the developmental state, ie, on the degree of calcification of the M-G body, In M-G bodies of rat kidney malakoplakia tissue fixed without osmium tetroxide, the phosphorus could also be detected unambigously. From the ratios of calcium and phosphorus percentages (w/w) we concluded that CaHPO4 was present. No difference was found between M-G bodies in malakoplakia tissues of human origin and those in experimentally induced malakoplakia.

Malakoplakia. Defect in digestion of phagocytized material due to impaired vacuolar acidification?

On the basis of light and electron microscopical findings in a case of malakoplakia of urinary bladder, (1) we concur with others that malakoplakia is a hyperplastic accumulation of histiocytes, and that the formation of Michaelis-Gutmann bodies is associated with incomplete digestion of phagocytized cell debris; (2) we hypothesize that digestion within phagolysosomes is impaired because of deficient acidification; and (3) we suggest that the defect in acidification in some cases may be related to treatment with drugs that affect the mechanism of phagocytic vacuolar acidification.

Malakoplakia of the prostate: a morphological and biochemical study.

A case of malakoplakia of the prostate is presented. Electron microscopic appearances support the origin of the Michaelis-Gutmann bodies from phagolysosomes in the histiocytes characteristic of the lesion. Biochemical analysis revealed the presence of muramic acid in the prostate with malakoplakia. This amino sugar is characteristic of bacterial cell walls and despite the absence of demonstrable bacteria in the affected tissues indicates the involvement of bacteria in the disease process.