Journal of Cytology
Home About us Ahead of print Instructions Submission Subscribe Advertise Contact e-Alerts Login 
Users Online:995
  Print this page  Email this page Small font sizeDefault font sizeIncrease font size


 
 Table of Contents    
ORIGINAL ARTICLE  
Year : 2019  |  Volume : 36  |  Issue : 3  |  Page : 165-168
von Hansemann cells from fresh urine sediment samples in the diagnosis of malakoplakia


1 Departamento de Bioquímica Clínica, Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Area Citología, Córdoba 2351 (1120) C.A.B.A., INFIBIOC, Argentina
2 Departamento de Patología, Universidad de Buenos Aires, Hospital de Clínicas, Córdoba 2351 (1120) C.A.B.A, Argentina

Click here for correspondence address and email

Date of Web Publication18-Jun-2019
 

   Abstract 


Background: Malakoplakia is characterized by the presence of plaques with macrophages containing inclusion bodies. The diagnosis of this disease is carried out by biopsy of the lesion. The objective of this paper was to assess the value of fresh urine sediment in the diagnosis of malakoplakia. Materials and Methods: Five suspected cases of malakoplakia that showed macrophages with inclusions called bodies of Michaelis-Gutmann (von Hansemann cells) in unstained urine sediment were processed with Papanicolaou, Giemsa, and periodic acid-Schiff (PAS) stains. Four of the five patients had a history of cystitis and had developed antibiotic resistance. The other patient had the characteristics cells in a routine urinalysis. Results: Papanicolaou stain revealed intracytoplasmic eosinophilic or basophilic bodies, single or multiple in macrophages. Such bodies were stained deep red with PAS technique. Giemsa stain showed these bodies with a faint basophilic coloration, sometimes with a central core. Bladder biopsies established the definitive diagnosis, showing bodies within and outside macrophages, with a concentric “birds-eye” or “owl-eye” (targetoid) appearance. Conclusions: Finding of von Hansemann cells in fresh urine sediment of patients with cystitis and a history of resistance to antibiotic scan leads to the diagnosis of malakoplakia. Giemsa stain can show in some cases the characteristic central core of Michaelis-Gutmann bodies. Malakoplakia is probably the result of an acquired defect in macrophage function causing impairment of bactericidal activity. A correct diagnosis is important because the spread to ureters with bilateral stenosis and obstruction can lead to kidney failure.

Keywords: Fresh urine sediment, malakoplakia, von Hansemann cells

How to cite this article:
Guerra F, Rocher AE, Angeleri A, Juarez M, Coliva G, Palaoro LA. von Hansemann cells from fresh urine sediment samples in the diagnosis of malakoplakia. J Cytol 2019;36:165-8

How to cite this URL:
Guerra F, Rocher AE, Angeleri A, Juarez M, Coliva G, Palaoro LA. von Hansemann cells from fresh urine sediment samples in the diagnosis of malakoplakia. J Cytol [serial online] 2019 [cited 2019 Jul 20];36:165-8. Available from: http://www.jcytol.org/text.asp?2019/36/3/165/251100





   Introduction Top


Malakoplakia is a rare chronic inflammatory reaction that usually affects the urinary tract in association with E. coli infection. The extravesical extension is usually rare and more aggressive. The term malakoplakia was coined by von Hansemann in 1903 and is derived from the Greek words malakos (soft) and plakos (plaque).[1] A year before the publication of the paper of von Hansemann, Michaelis and Gutmann published similar results, and therefore, these two authors are associated with this disease, almost forgetting von Hansemann.[2]

Malakoplakia, in the urinary bladder, is detected commonly as oval, yellowish plaques with central umbilication. Histologically, these plaques show numerous macrophages, called von Hansemann cells, with many bodies within and outside these cells, called Michaelis-Gutmann bodies (MGB). The bodies have a concentric “birds-eye” or “owl-eye” (targetoid) appearance because of the development of a central hydroxy-apatite core. Almost 95% of the bodies are of organic material, the rest being iron, calcium, phosphorous, chloride, and sulphur.[3] These structures, pathognomonic of malakoplakia, are positive for von Kossa stain (calcium), Perls' stain (iron), and periodic acid-Schiff (PAS) stain.[4] So far, Giemsa stain was not tested in these bodies.

The urinary tract is the most common site for malakoplakia, and 80%-90% of patients have a persistent coliform infection.[5]

However, malakoplakia may be associated with infection with microorganisms other than E. coli including other bacteria, mycobacteria, and fungi.[6]

The disease was also reported, to a lesser extent, in retroperitoneum, gastrointestinal tract, lung, lymphatic nodules, tongue, etc.[7],[8] Malakoplakia is also associated with immunodeficiency states and hematopoietic malignancies.[9] The association of malakoplakia with immunosuppression comes from the finding of patients with a history of prolonged treatment with chemotherapeutic or immunosuppressive agents.


   Materials and Methods Top


We present 5 cases of malakoplakia, detected in fresh urine sediments. The smears were stained with Papanicolaou, Giemsa, and PAS stains. In 3 patients, bladder biopsy samples were taken.

Ethics statement

The patients have given their informed consent for participation in the research study.

This study was approved by the Institutional Review Board at the Faculty of Biochemistry, Buenos Aires University. (Chairperson: Dr Luis Palaoro - N° 09032016-26 -Approval March 9th, 2016).

The researchers respect the Declaration of Helsinki in its latest version (World Medical Association Declaration of Helsinki 2013).


   Results Top


The first patient, a woman 65-year-old, had a history of repeated cystitis with culture positive for E. coli, Klebsiella, and Proteus who developed resistance to the antibiotics used. Fresh urine sediment (undyed) showed abundant macrophages, epithelial squamous cells, and abundant bacilli. Macrophages had cytoplasmic inclusions of round, oval, and elongated bodies. Sometimes the bodies had irregular forms, similar to worms (“wormy” shapes) [Figure 1]. These inclusions are similar to those that Koss[10] published in urine samples stained with the Papanicolaou method in cases of Malakoplakia. Papanicolaou, Giemsa, and PAS stains were carried out in the urine samples. Papanicolaou stain revealed intracytoplasmic eosinophilic bodies, sometimes basophils, single or multiple in macrophages. Such bodies were stained deep red with PAS technique. Giemsa stain showed these bodies with a faint basophilic coloration, with net limits, and sometimes with a central core. Bladder biopsy confirmed the presumptive diagnosis [Figure 2]. The other 4 patients (60, 55, 52, and 32 years old) were studied in the same way as the first, confirming the disease in all cases. None of the cases presented had a history of immunosuppression. The youngest patient had no history of cystitis, but malakoplakia was suspected by observation of macrophages with inclusions in the urinary sediment.
Figure 1: von Hansemann cells in fresh urine sediment. (a): Abundant von Hansemann cells in fresh urine sediment (Fresh urine sediment-400×). (b): von Hansemann cell with a big M-G body in fresh urine sediment (Fresh urine sediment-400 × x)

Click here to view
Figure 2: Stained von Hansemann cells in urine sediment and in biopsy. (a): Big MGD into a macrophage. (b): Macrophage with MGD showing strongly stained edge and central core. (c): PAS stain in a von Hansemann cell. (d): Biopsy of malakoplakia of the bladder. A round  Michaelis-Gutmann body More Details (arrow) is observed in foam cells. (a: Papanicolaou stain 400×; b: Giemsa stain 400×; c: PAS stain 400×; d: Hematoxylin and eosin 400×)

Click here to view



   Discussion Top


Malakoplakia of the bladder is a rare disease. Probably, the low number of reported cases are because there is no simple primary diagnosis but is detected in patients with histories of antibiotic resistance, in the biopsies taken from their typical lesions of the bladder.

We studied, for several years, the correlation between cells of the urinary sediments in fresh, colored with Papanicolaou/Giemsa and their corresponding bladder biopsies and were able to demonstrate the usefulness of the observation in fresh as primary diagnosis of various diseases.[11]

Taking advantage of this knowledge, we could detect von Hansemann cells (pathognomonic of malakoplakia) in fresh urine sediments, which were confirmed by various methods. Fresh urinary cytology in Malakoplakia suggests this pathology, but confirmation should be made with the described colorations, especially that of Giemsa, which shows the central core.

Malakoplakia is probably the result of an acquired defect in macrophage function causing impairment of bactericidal activity. It is now believed that the disease may be related to abnormal microtubular assembly. Microtubules are responsible for normal invagination and degranulation of lysosomes, which are important in the destruction of bacteria in phagocytosis. cGMP stimulates while cAMP inhibites the assembly of microtubules. However, lysosomal function also depends on the enzyme -glucuronidase and the redox state of the cell.[12] Alteration in the redox state, with the reduction in the ratio of cGMP/cAMP could be the triggers in malakoplakia.

Supporting this theory, monocytes with intracytoplasmic lysosomal inclusions, abnormal release of the enzyme β-glucuronidase, low intracellular levels of cyclic GMP, and depressed bactericidal activity have been reported in retroperitoneal malakoplakia.[13]

Therefore, treatments with bethanechol, agonist cholinergic drug, aim to increase the concentration of intracellular cGMPc.

Some antimicrobials, capable of intracellular penetration such as trimethoprim-sulfamethoxazole were used with some success. In addition, there were cases of malakoplakia successfully treated by ciprofloxacin.[14]

So far, as we know, it is the first report of the detection of MGB in fresh urine samples. The biopsies showed MGB often exhibiting a targetoid appearance with a central core. The targetoid appearance may not be apparent if the plane of section does not pass through the dense central core. The central core could be observed in some cells of fresh urine sediment. Moreover, Giemsa stain, performed for the first time in the urine cells from malakoplakia, showed in some cases the characteristic central core of MGB. These bodies must be differentiated from other inclusion bodies: Melamed-Wolinska bodies (MWB)[15] and eosinophilic inclusions of urothelial necrotic cells (EIUC). MWB were reported in urothelial cells of patients with urothelial carcinoma, mainly. Although they have a certain morphological similarity with MGB, their origin is different because the latter are observed in macrophages of patients with a history of resistance to antibiotics. The Giemsa stain allows to differentiate between MWB and MGB because the latter show the typical central core. EIUC are observed especially in viral infections, as small eosinophilic bodies of varying size, inside necrotic urothelial cells[16] [Table 1].
Table 1: Differential diagnosis between inclusion bodies in urine cells

Click here to view


By electron microscopy, the inclusions have crystalline structure with a central dense body, an intermediate halo, and a peripheral laminated ring. Moreover, there is material that reminds bacterial debris in the center of the inclusion.[17] In four of our patients, their urines contained numerous bacilli, according to their histories of resistance to antibiotics. Malakoplakia is difficult to diagnose from the symptoms alone, although in retrospect most patients are found to have a urinary tract infection. The bladder involvement is associated with irritative urinary symptoms and hematuria; a correct diagnosis is important because the spread to ureters with bilateral stenosis and obstruction can trigger kidney failure.[18]


   Conclusion Top


Finding of von Hansemann cells in fresh urine sediment of patients with cystitis and a history of resistance to antibiotics can lead to the diagnosis of malakoplakia. Giemsa stain can show in some cases the characteristic central core of Michaelis-Gutmann bodies. So far, as we know, this paper is the first report of the presence of these cells in urine undyed and the value in diagnosing malakoplakia.

The dissemination of these results could help to detect more cases in patients with cystitis and history of antibiotic resistance, which could then be treated with other drugs, avoiding future complications such as kidney failure.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form the patient(s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initials will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.



Financial support and sponsorship

The work was financed by own funds. We thank Dr. Mabel Lardo for her technical support.

Conflicts of interest

There are no conflicts of interest.



 
   References Top

1.
von Hansemann D. UberMalakoplakie der Harnblase. Virch Arch Path Anat 1903;173:302-8.  Back to cited text no. 1
    
2.
Dasgupta P, Womack C, Turner AG, Blackford HN. Malacoplakia: von Hansemann's disease. Review. BJUInt 1999;84, 464-9.  Back to cited text no. 2
    
3.
Sencer O, Sencer H, Uluoglu O, Torunoǧlu M, Tatlicioǧlu E. Malakoplakia of the skin. Ultrastructure and quantitative x-ray microanalysis of Michaelis-Gutmann bodies. Arch Pathol Lab Med 1979;103:446-50.  Back to cited text no. 3
    
4.
Kohl SK, Hans CP. Cutaneous malakoplakia. Arch Pathol Lab Med 2008;132:113-7.  Back to cited text no. 4
    
5.
Stanton JM, Maxted W. Malacoplakia: Astudy of the literature and current concepts of pathogenesis, diagnosis and treatment. J Urol 1981;125:139-46.  Back to cited text no. 5
    
6.
Velásquez López JG, Vélez Hoyos A, Uribe Arcila JF. Malacoplaquia en urología: Aportación de seis casos y revisión de la literatura. Actas UrolEsp 2006;30:610-8.  Back to cited text no. 6
    
7.
Shimizu S, Takimoto Y, Nimura T, Kaya H, Yamamoto T, Kawazoe K, et al. A case of prostatic malacoplakia. J Urol 1981;126:277-9.  Back to cited text no. 7
    
8.
Alvarez Gomez GJ, Martin Botero ML, HenaoCalle CA, Duque Serna FL. Malacoplakia: Case report in tongue and review of the literatura. Med Oral Patol Oral Cir Bucal 2008;13:E352-4.  Back to cited text no. 8
    
9.
Matsuda I, Zozumi M, Tsuchida YA, Kimura N, Liu NN, Fujimori Y, et al. Primary extranodal marginal zone lymphoma of mucosa-associated lymphoid tissue type with malakoplakia in the urinary bladder: Acase report. Int J Clin Exp Pathol 2014;7:5280-4.  Back to cited text no. 9
    
10.
Koss LG. Diagnostic Cytology and its Histopathologic Bases. 3rd ed. Philadelphia: J.B. Lippincott Company; 1979.p. 735.  Back to cited text no. 10
    
11.
Palaoro L, Angerosa M. Correlation between the cytology of urine sediment in fresh samples and smears stained by Papanicolaou and Giemsa Methods. J Cytol 2014;31:25-31.  Back to cited text no. 11
    
12.
Zurier RB, Weissman G, Hoffstein S, Kammerman S, Tai HH. Mechanisms of lysosomal enzyme release from human leukocytes. II. Effects of cAMP and cGMP, autonomic agonists, and agents which affect microtubule function. J Clin Invest 1974;53:297-309.  Back to cited text no. 12
    
13.
Abdou NI, NaPombejara C, Sagawa A, Ragland C, Stechschulte DJ, Nilsson U, et al. Malakoplakia: Evidence for monocyte lysosomal abnormality correctable by cholinergic agonist in vitro and in vivo. N Engl J Med 1977;297:1413-9.  Back to cited text no. 13
    
14.
van Furth R, van'tWout JW, Wertheimer PA, Zwartendijk J. Ciprofloxacin for treatment of malakoplakia. Lancet 1992;339:148-9.  Back to cited text no. 14
    
15.
Ayra P, Khalbuss WE, Monaco SE, Pantanowitz L. Melamed-Wolinska bodies. Diagn Cytopathol 2012;40:150-1.  Back to cited text no. 15
    
16.
Palamas M, Rocher AE, Sardi-Segovia M, Harriet LA, Palaoro LA. Symptomatic BK virus infection in an immunocompetent child diag nosed on urine cytology. Cytopathology 2012;23:274-5.  Back to cited text no. 16
    
17.
Kern WF, Silva GF. Atlas of Renal Pathology. Philadelphia: W. B. Saunders Company; 1999.p. 147.  Back to cited text no. 17
    
18.
Steele B, Vade A, Lim-Dunham J. Sonographic appearance of bladder malacoplakia. Pediatr Radiol 2003;33:253-5.  Back to cited text no. 18
    

Top
Correspondence Address:
Prof. Luis A Palaoro
Avda Forest 13184º B - (1427) C.A.B.A.
Argentina
Login to access the Email id

Source of Support: None, Conflict of Interest: None


DOI: 10.4103/JOC.JOC_45_17

Rights and Permissions


    Figures

  [Figure 1], [Figure 2]
 
 
    Tables

  [Table 1]



 

Top
 
 
  Search
 
  
    Similar in PUBMED
 Related articles
    Email Alert *
    Add to My List *
* Registration required (free)  


    Abstract
     Introduction
   Materials and Me...
     Results
     Discussion
     Conclusion
    References
    Article Figures
    Article Tables

 Article Access Statistics
    Viewed208    
    Printed12    
    Emailed0    
    PDF Downloaded29    
    Comments [Add]    

Recommend this journal