Šukrija Krvavac


Women's Health Center Sarajevo, Gynecological Service Stari Grad Sarajevo


Research paper




Because of the striking similarity between histopathological pictures of a chronic trichomonal cervicitis uteri, the tissue reaction after subcutaneous inoculation of trichomonas culture in experimental animals and female breast diseased by fibrocystic mastopathy, the detection of Trichomonads was undertaken in surgically removed diseased breast parts.


In 12 FCM patients, subjected to segmental breast resection, the imprint smears were prepared from dissected specimens and after supravital staining, immediately examined by light microscopy.

The mucous content from dilated ducts was inoculated in the culture media. The dissected tissues had been further histologically analyzed by standard method. In 9 out of 12 examined FCM cases, direct microscopy revealed aflagellary, pseudocystic leucocytoid form of Trichomonads. The cultures were positive in 4 cases; in 3 patients Thrichomonas tenax was identified, and in the last one T vaginalis. Histopathological findings in all 12 examined cases had shown the changes characteristic for FCM.

On the basis of accumulated knowledge about pathogenic capacity of Trichomonads, it can be with great certainty claimed, that these protozoa, even in their pseudocystic form, are able to cause all the appearances characteristic for FCM.

This first report about Trichomonas infection in the middle of FCM process gives the unexpected hope in solving of its etiology and a new insight into antitrichomonal host reaction which is frequently associated with epithelial dysplasia and unrarely with precancerous lesions as earlier observed in cervix uteri.

Key words: Trichomonas infection, Etiology, Fibrocystic mastopathy.




In literature there are many reports on trichomoniasis about atypical locations of this infection (1) but as a rule, the parasite presence in pathologic materials is considered to be a second colonization. In liquid environment and on wet epithelial surfaces, sufficiently far from the host immune forces, these protozoa take flagellary form with expressed morphological characteristics according to which they are classified into 3 human Trichomonas species. On the contrary, the hiperosmotic environment, medicaments and immune forces cause biologic regression of the parasites into pseudocystic aflagellary form which, by its size and shape mimic undifferentiated leucocytes in various secretions and pathologic materials. These Trichomonas pseudocysts, similarly to thropozoites, also secrete pathogenic proteinases (2) which obligatory elicit host immune reaction.


Pathologic process of female breast, characterized by the cyst formation, pericystic and periductal fibrosis, the mucus accumulation in dilated drain channels, the wide spectrum of dysplasia of duct epithelium (3), including even the precancerous lesions, is known as fibrocystic mastopathy.

This histopathologic description of FCM strongly corresponds to the microscopic picture of a chronic trichomonal cervicitis uteri in women and to tissue reacting after subcutaneous inoculation of trichomonas culture in various mammals (4). It seemed logical to search for a single-celled parasite in breast which is affected with fibrocystic disease, particularly because of the fact that this author had earlier discovered aflagellary Trichomonads in other pathologic processes with similar if not even identical pathoanatomic picture (5,6).




Randomly recruited 12 women with a long history of FCM and with a real need for segmental breast resection, due to the clinical worsening, were included into the study. Before fixing of the the surgical specimens for a standard histopathologic analysis, the imprint smears were prepared from the surfaces of dissected specimens and from the mucous content, which was squeezed from the visible channels. Wet smears were stained in a conventional manner and promptly examined by light microscopy. The rests of ductal secretion and squeezed excudat were inoculated in modified Diamond’s TYM medium (7). In culture positive cases the species identification was determined by light microscopy of cooled fresh preparation. The breast tissues were histopatologically analyzed using conventional procedure.




In 9 out of 12 examined cases, direct microscopy revealed the infection with aflagellary Trichomonads. Cultures were positive in 4 cases on the basis of morphological characteristics of thropozoites, in 3 cases Trihomonas tenax was identified and in the last one Trichomonas vaginalis. Histopathological findings in all 12 cases had shown the changes characteristic for FCM.




Trichomonads from atypical locations more rarely grow in available culture media then from typical ones. Because of the antigenic diversity of such strains, the commercial immunodiagnostics also frequently fail (8). In such circumstances the direct microscopy of supravitally stained wet smears remains the quickest and reliable detection method. After staining of wet smear only the live parasites, prophozoites and their pseudocysts remain uncolored during several minutes so distinguishing from the leucocytes.


Figure 1. Intraductal secretion by fibrocystic mastopathy. Wet smear stained by Haematoxilin. In the center, 5 unstained pseudocystic trichomonads and around polymorphonuclear leucocytes, 80x.              



The intracystoplasmic motility (“Brown’s motion”) is visible under higher magnification in aflagellary pseudocysts by light microscopy, probably due to the activity of internalized flagella (9), which appearance is never visible in leucocytes or in flagellated trophozoides. It is commonly accepted the causal relation between parasitic infections and fibrosis, which considers as the defensive demarcating host reaction. Such a relation was also in human and experimentally caused Trichomonas infection in animals (4). Also, often is observed a close relation between various parasitoses and cystic tissue alteration, the accumulation of pathologically changed mucus (11) and epithelial dysplasia of draining system of the colonized gland, especially in generally immunocompromized (12) and stressed (13) hosts. According to literature, trichomonal proteinases cause local pathogenic reaction of epithelial and mesenchymal tissues and the response of immune neutralization of the parasites resulting in their expulsion, thereupon the wide spectrum of epithelial damages in span of its desquamation with duct obliteration and cyst formation to precancerous lesions of draining system, and finally perifocal or periductal fibrosis as a defensive barrier around non-expelled protozoa or their metabolites.


After direct contamination of the nipple, Trichomonads can invade the breast by transductal ascension and through lymph ways from (peri) areolar ulcers. Eventually, associated bacteria, particularly piogenic, enhance the invasiveness of Trichomonads and can cause a dramatic course, while the infection by Trichomos strains wit low pathogenic potential and without bacteria can have a long subclinical course. The presence of Trichomonads can explain the beneficial effect of Metronidazole in the initial phase of puerperal breast inflammation (personal unpublished observations), so not just through commonly accepted inhibition of anaerobic bacteria.


Insatiable appetite of Trichomonads for glycogen in non-lactating breast and for milk remnants in lactation can explain their affinity to this gland. In the ulcers of intensely pigmented areola, the established Trichomonads may adopt more pathogenic characteristics, which can intensify the pathogenic process as earlier suggested (14).

As in 3 of 4 culture positive cases it was identified Trichomonas tenax (oralis), which usually inhabits the upper organs of digestive and sometimes respiratory tract, it can suppose the mother-to-suckling-to-mother’s breast transmission, similarly to well known bacterial transfer. Although the direct pathogenicity of Trichomonas tenax has not been solved yet, nevertheless it is well known by its immunogenicity. Therefore, it may suppose an allergic reaction to extrafocal Trichomonas infection. Spreading of this oral Trichomonas is nowadays facilitated by deep kissing promiscuity, which enables polystrain sensation with consecutive immunity erosion.


Frequent postlactational FCM process characteristically follows the retrograde course of drain channels, indicating probable parasites ascension. The coincidence of breast (micro) trauma and short lasting trichomonaemia, the existence of which is periodically being reported (15, 16, 17,18,19) but yet with obscure significance (20), enable parasites extravasation with their extra drain nesting and consecutive host non-cystic reaction. Therefore, the presence of Trichomonas vaginalis in the breast could be explained not only by direct external contamination, but also by internal parasitaemic way as a consequence of mucosal ulceration or partial laceration of infected genitals, especially by immunocompromized and stressed women. In women population such coincidence of conditions is not a rare event.  


Sometimes incriminated emotional stress as a cofactor in pathogenesis of FCM not only depresses functioning of the immune apparatus through the mediation of the central nervous system, but also the reactive adrenalinaemia may rise the virulence of Trichomonads, as noticed in vitro experiments.


The influence of estrogens on breast trichomoniasis in women could be similar to the influence on vaginal infection: by stimulating parasite multiplication through better saturation of gland by glycogen and by enhancing of parasite adherence to the cell surface. Contrarily, the progesterone has protective functions in women including the antimicrobial one. It has proved its antitrichomonal effect in experimental animals (21).

High incidence of vaginal trichomoniasis in pregnant women (up to 25%) could be a consequence of unprotected coitus and partly because of translocation of latent cervical to manifest vaginal infection. Similar inhibitory effect of progesterone on Amoeba Naegleria in vitro (22) might speak on behalf of this mechanism.


This hormones/Trichomonas interplay could also explain the clinical observations that FCM most frequently appears during decline of the ovary function in periods of relative progesterone insufficiency, i.e. when the decrease of progesterone level precedes the fall of estrogens.


In addition, the old experiences that pregnancy very effectively clears the FCM possibly is due to antitrichomonal activity of progesterone and chloriogonadotrophin, as noticed in experimental animals, suggestively support the above proposed pathogenic mechanism.


Finally, as a historical reflection, if we should consider the normal menses as a natural opportunity that woman’s blood be cleaned from periodically present Trichomonads, then Hippocrates’s opinion, that the breast diseases are due to the menstrual residua and milk remnants, would be completely in accordance with the above mechanism.




The inherent and acquired parasite virulence, the innate and acquired host immune forces, the variable hormonal status, particularly suboptimal progesterone/estrogens coefficient can affect the initiating, propagation, duration and the final result of both parasites colonization and FCM reaction. Though in small series, the first report about Trichomonas infection in the middle of the FCM process, after many decades, provides an unexpected hope for solving of the FCM etiology.




  1. Henigberg BM. Trichomonads found outside the urogenital tract of humans. In: Trichomonas parasite in humans. Honigberg BM (ed.), Springer Verlag, NewYork-Berlin-Heidelberg-London-Paris-Tokyo-Hong Kong, 1989: 342-93.


  1. Scot DA, North MJ and Coombs GH. Trichomonas vaginalis: amoeboid and flagellated form synthesize similar proteinases. Experim parasitol, 1995;Mar,80(2): 345-8.


  1. Kontrogerorgos G, Bouropolou V and Anastassiades DT. Mucous metapalsia of epithelial cells in fibrocystic disease of the breast. A histochemical study. Pathol. Res Prac. 1983;177(1): 1-5.


  1. Honigberg BM. Comparative pathogenicity of Trichomonas vaginalis and Trichomonas gallinae in mice. I. Grosspathology, quantitive evaluation of virulence and some factors affecting pathogenicity. JParasito., 1961;47:545-71.


  1. Krvavac Š. Aflagellary forms of Trichomonas species as etiologic agent of cystic fibrosis. In: XIIth World Gyn./Obst. Congress, Rio de janeiro, Abstracts, 1988;681-2


  1. Krvavac Š. Trichomoniasis and cystic fibrosis. Postgrad Med. J. 1990: 155-6.


  1. Diamond LSThe establishment of various Trichomonads of animal and man in axenic culture. J Parasitol. 1957; 43:488-98


  1. Teras J. Experimental infections of man by Trichomonadidae. Acta Univ Carol Biol (Prague), 1986;39: 459-68.


  1. Mattern CF, Honigberg BM and Daniel WA. Fine-structural changes associated with pseudocyst formation of Trichomitus (syn.Trichomonas) batrachorum. J parasitol, 1973;22:222-9.


  1. Jenny JH. Diagnostische Probleme. Gynaek Rundschau, 1982;22 (suppl): 12-22.


  1. Kreier JH. Parasitic protozoa, New York-San Francisco-London, Academic press, 1979.


  1. Gupta JP and Frost JK; Cythopathology and histopathology of the female genital tractin Trichomonas vaginalis infection. In: Honigberg BM(ed.) as in reference 1, pp. 274-90.


  1. Ader R. Psychoneuroimmunology. New York: Academic Press 1981.


  1. Krvavac Š.  Pre-existing chronic infraepithelial Trichomonas invasion with consecutive immunodepression enables progression of human immunodeficiency virus:A new concept of acquired immunodeficiency syndrome pathogenesis.Medical Hypotheses,1992;39:225-8.


  1. Pentimalli F. Flagellati del genere “Trichomonas” nel sangue circulante dell’uomo. Annali D’Igiene, 1233;33: 309-15.


  1. Wagner O. and Hees E. Cultural finding of Trichomonas vaginalis and other Trichomonas species. Zentalbl Bakt (Abt.I). 1935: 310-7.


  1. Coutts WE, Silva-Inunza E. and Tallman JB. Genitourinary complications of non-gonococcal urethritis and Trichomoniasis in males. Urol Int, 1959;9: 189-208.


  1. Korte W. and Sanft HH. Pathology and clinic of Trichomona vaginalis infection by humans. Hippokrates, 1976;47: 103-22.


  1. Krvavac Š. And Rustembegović A. Possible correlation between high eruytrocyte sedimentation rate and trichichomonaemia in rheumatic diseases. In: 3rd Interscience world Conference on Inflammation, Antirheumatics, Analgesics, Immunomodulators, Monte Carlo, Abstracts, 1989: 274.


  1. Piekarski G. Introduction. In: Trichomonads Parasitic in Humans. (BM Honigberg, ed.) Springer-Verlag, NewYork-Berlin-Heidelberg-London-Paris-Tokyo-Hong Kong, 1989:1.


  1. Combescot Ch. Pestre M. and domenech A. Action de la progesterone sur l’infestation experimental da la Ratta albinos par Trichomonas vaginalis. CR Seances Soc Biol Ses Fil, 1967;151:332-4.


  1. Pearson JL. And Willmer EN. Some observations on the action of steroids on the metaplasia of the amoeba Naegleria Gruberi. J Exp Biol, 1963;40: 493-515.




I thank to professor Dr. O. Durić, Director and surgeon from Department of surgery, University Hospital Sarajevo, for permission to prepare the smears; to Dr. H. Kulenović, Professor of physiology and Vice-Dean of Faculty of Medicine Sarajevo for his constructive criticism; to Drs. B. Udovičić, A. S. Softić and Š. Spahović for their consultative parasitological, endocrinological and cytological advices and to A. Krvavac for help in the manuscript preparation.


Notice: A short draft of this article was presented at the 8th International Congress on Infectious Diseases held from 15th-18th May 1998, in Boston, USA.