© JAPI • may 2012 • VOL. 60 57 Case Report Primary Cryptococcal Prostatitis- Rare Occurrence Vinaya B Shah*, Pallavi A Patil**, Vipul Agrawal***, Harish K Kaswan*** Abstract Cryptococcosis is a well recognized infection in immunocompromised patients. Cryptococcal infection primarily involves the lung and is hematogeneously spread to other organs. Sometimes it might affect the genitourinary tract. The prostate gland is a rare site of primary infection due to cryptococcus neoformans. We report a case of granulomatous inflammation in the prostate as a result of crypyococcus neoformans infection in a 70 year old immunocompetent patient, a non diabetic, which was diagnosed by transrectal ultrasound guided biopsy. C Introduction ryptococcosis is a well recognized infection in immunocompromised patients. Cryptococcal infection primarily involves the lung and is hematogeneously spread to other organs. Sometimes it might affect the genitourinary tract and rare cases have been reported involving the prostate without systemic infection and still rarer occurrence in an immunocompetent patient. Case Report A 70 year old non diabetic, non hypertensive was admitted with complaints of frequency, dysuria and fever since 1 week. His general condition was satisfactory. His temperature was 39.5º C. The rest of the physical examination was unremarkable. His laboratory results showed a Hb of 14.2 gm%, total white cell count of 6x 109 /dl, platelet count of 185x 109/dl and ESR of 20mm/ hour. Urine microscopy showed 10-12 white blood cells per high power field, but urinary culture was negative. Ultrasound of prostate showed symmetrical prostatomegaly weighing 120 gms. Prostatic specific antigen (PSA) levels were high i.e 45ng/ml. Transrectal biopsy of prostate was done from both the lobes and sent for the histopathological examination, which showed total 4 linear bits which showed fibrous stroma with multiple foci of granulomatous inflammation comprising of lymphocytes, macrophages, epithelioid cells, histiocytes and multinucleate giant cells (Figure 1). High power revealed histiocytes and multinucleate giant cells with engulfed grey yeast forms surrounded by a clearing of surrounding tissue, a halo representing the capsular material (Figures 2a, 2b). prostatitis was made. He was treated with high dose of fluconozole 400mg/day and venous amphotericin at doses 0.4 mg/kg/day for 2-3 weeks. Discussion Cryptococcus infection is acquired through the respiratory route. In most hosts who encountered Cryptococcus neoformans the infection is contained or eliminated. Immunocompromised patients are at risk of systemic disease and dissemination. The clinical presentation of cryptococcosis varies depending on the site and host, but the dominant involved organ are the lungs and CNS. Early reports dated back to the 60`sand 70`s.1 Subsequently prostatic involvement were reported in patients immunocompromised by steroids.2 organ transplantation,3 human immunodeficiency syndrome (HIV) infection and Hodgkins lymphoma. 4 It is also described in apparently immunocompetent host.5 The prostate gland has also emerged as a potential site of relapse of cryptococcosis after apparently successful therapy of cryptococcal meningitis.6 Systemic spread from primary focus of cryptococcal infection commonly involves CNS, manifested as meningitis. Untreated meningitis are invariably fatal. Our patient was treated with high doses of fluconazole and recovered. We Gomori methenamine silver (GMS) very efficient to visualize the fungi and also advantageous since it stains old and nonviable fungal elements more efficiently as seen in (Figure 2c). Special stains like mucicarmine helped in delineating the capsule (Figure 2d). Diagnosis of granulomatous cryptococcal prostatitis was given. Subsequently the patient was investigated for any immunocompromised status. Patient was seronegative for HIV-I, HIV-II, HbsAg, VDRL. Culture from blood and cerebro spinal fluid(CSF) was negative for cryptococcus. X ray chest showed clear lung fields. Thus the diagnosis of primary cryptococcal Associate Professor, Pathology Department, **Resident Pathology, Pathology Department, ***Senior Resident, Urology Department, TNMedical College & BYLNair Hospital, Mumbai- 400034 Received: 18.06.2010; Revised: 29.03.2011; Accepted: 02.06.2011 * Fig. 1 : Prostatic tissue with fibrous stroma and multiple foci of granulomas. [Scanner view of Hematoxylin & Eosin(H & E) stain x 40] 58 © JAPI • may 2012 • VOL. 60 by histopathology).10 The cryptococcal CSF antigen had the best overall sensitivity (94.1%) followed by the serum antigen (93.6%).10 However, some differences were observed in the different categories of hosts, with lower sensitivity in AIDS and immunocompetent patients (92%) and higher sensitivity among the other immunocompromised hosts without HIV infection.10 Though our case had negative CSF culture, histopathological demonstration of the organism was done in the prostatic tissue which had multiple foci of granulomatous inflammation with the aid of special stains. In the needle biopsies of the prostate, if granulomas are observed on histology, then the usual common differential diagnosis include tuberculous, BCG induced idiopathic non specific granulomatous, malackoplakia, xanthogranulomatous, iatrogenic postsurgical induced and fungal etiology. Fig. 2 : (a) H & E stain x100 shows a granuloma comprising of lymphocytes, macrophages, multinucleate giant cells and (b) High power: H & E stain x400 shows grey yeast bodies of cryptococcus engulfed by the giant cell (arrow). Gomori methenamine silver (GMS) stained the fungus black and numerous such cryptococci were seen in (c) and Mucin stain: mucicarmine delineated the capsule by staining magenta pink (arrow) (d). feel that a persistent prostatic focus of infection needs to be scrutinized vigilantly. The rising incidence of cryptococcosis in India is posing a serious threat. Due to lack of sensitive methods for diagnosis, high morbidity and mortality are associated with the disease. Early diagnosis and institution of specific antifungal therapy are imperative to minimize the severity of infection. The laboratory diagnosis of cryptococcosis is based on direct demonstration, culture, and antigen detection by latex agglutination test (LAT). Histopathological examination of organisms on tissue biopsy is also a effective means of diagnosing cryptococcosis. Special stains include gomori`s silver and calcofluor white stain are sensitive means of identifying this organism in tissue. The mucicarmine stain is particularly helpful in that it stains the capsule of this organism, allowing the observer to make a presumptive diagnosis of cryptococcossis. Cryptococcossis is easily cultured on standard fungal media that do not contain cycloheximide. Large, cream to yellow colored colonies appear in 3-5 days when yeast is cultured on Saborauds dextrose agar. Encapsulated colonies are mucoid. Cryptococcus neoformans can be distinguished from most other species of cryptococcossis by its ability to produce melanin through phenol oxidase. Cultures may require several weeks for a positive result and these are not helpful in the immediate management of clinical patients. Microscopic methods and culture, though specific, show a sensitivity of 50–80 %.7 Also, culture takes time and requires more labour and large volumes of samples. Latex agglutination test (LAT) is more sensitive but suffers from the limitation of false positivity.8,9 The latex- Cryptococcus antigen test is simple, sensitive test capable of detecting C. neoformans polysaccharide antigens in serum and CSF and is superior to india- ink mount. Clinical studies established the prognostic value of aid in establishing a diagnosis when culture was negative.10,11 In one study, despite negative CSF culture, there was disseminated cryptococcal disease at autopsy (demonstrated To summarize, thorough histopathological examination for classic histologic clues and clinical history will aid in diagnosing most of the lesions considered in the differential diagnosis of granulomatous prostatitis. But in fungal prostatitis, histopathology is one of the major tools of diagnosis. The major advantages of histopathology are speed, low-cost, and the ability to provide a presumptive identification of the infecting fungus, as well as demonstrating the tissue reaction. A number of histologic stains are available that are routinely used to visualize fungi in tissue sections Gomori methenamine silver (GMS), Gridley’s fungus (GF), and periodic acid-Schiff (PAS) are special for and very efficient to visualize the fungi. Mucin stains, like Mayer’s mucicarmine, stain the mucopolysaccharide capsule of Cryptococcus neoformans which was done in our case. Conclusion Cryptococcosis can be easily misdiagnosed in uncompromised host both clinically and pathologically because of misconception that the disease affects only immunocompromised individuals. Hence, awareness and thorough histopathological examination of granulomatous lesion in a prostate would avoid misdiagnosis. References 1. Dreyfuss ML, Sommer RI. 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Whittier S, Hopfer R L and Gilligan P. Elimination of false-positive serum reactivity in latex agglutination test for cryptococcal antigen in human immunodeficiency virus-infected population. J Clin Microbiol 1994;32:2158–61. 10. Antinori S, Radice A, Galimberti L, Magni C, Fasan M, Parrvicini © JAPI • may 2012 • VOL. 60 C. The Role of Cryptococcal Antigen Assay in Diagnosis and Monitoring of Cryptococcal Meningitis. J Clin Microbiol 2005;43:5828-9. 59 11. Cunha BA. Central nervous system infections in the compromised host: a diagnostic approach. Infect. Dis Clin N Am 2001;15:567-590.
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