Cryptococcal Prostatitis Forming Caseous and Suppurative Granulomas Diagnosed by Needle Biopsy: A Case Report

Introduction

Granulomatous prostatitis accounts for 1% of benign inflammatory conditions of the prostate, and is classified as specific, nonspecific, or allergic inflammation. ¹ Granulomatous prostatitis following bacillus Calmette–Guerin (BCG) immunotherapy for bladder cancer is the most common type of specific inflammation. ² Cryptococcal prostatitis is exceedingly rare and related histological findings are not well documented in the literature.^2,3 It has been reported that granulomatous prostatitis associated with Cryptococcus infection can induce the development of suppurative granulomas. ⁴ Several studies have provided histologic evidence of necrosis.^3,5 However, to the best of our knowledge, no caseous granulomas (necrotizing granulomas) have been reported in cases of cryptococcal prostatitis. In addition, fungal prostatitis identified from a prostate needle biopsy is very rare. ³ Here we report a case of granulomatous prostatitis caused by Cryptococcus infection in which a core needle biopsy provided various histologic findings, including a caseous granuloma as well as a suppurative granuloma.

Case Report

The patient is an 81–year–old man who was diagnosed with rheumatoid arthritis 40 years ago and had been treated orally with methotrexate and prednisolone. He underwent a biopsy for an oropharyngeal ulcer and the pathological diagnosis revealed a methotrexate–related diffuse large B–cell lymphoma, not otherwise specified. Combined fluorine–18 fluorodeoxyglucose positron emission tomography and computed tomography for staging showed an abnormal uptake in the prostate, and magnetic resonance imaging detected a tumor–like mass. The prostate–specific antigen was at a normal level (1.072 ng/mL [normal range, 0.00-4.00 ng/mL]). The patient was clinically diagnosed with prostate cancer and underwent needle biopsies of the prostate.

Pathological Findings

Histologically, caseous and suppurative granulomas were found in the prostate tissue by employing hematoxylin–eosin (HE) staining (Figure 1A and D). In the caseous granulomas, epithelioid histiocytes collected around the caseous necrosis (Figure 1B). By contrast, in the suppurative granulomas, numerous neutrophils infiltrated the center of the granulomas and caseous necrosis was not observed (Figure 1D). Foreign–body–type and Langhans–type multinucleated giant cells were found (Figure 1E). Multiple round and oval organisms 5 to 7 µm in diameter were seen in both the caseous and suppurative granulomas (Figure 1B and E). In addition, the capsules of the observed organisms were capable of Grocott methenamine silver (GMS) staining (Figure 1C and 1F), which is compatible with Cryptococcus infection. Acid–fast bacilli were not detected in either caseous or suppurative granulomas by Ziehl–Neelsen staining. The pathological diagnosis was granulomatous prostatitis caused by Cryptococcus infection. A systemic survey revealed no findings suggesting Cryptococcus infection except in the prostate. The patient had no history of exposure to Cryptococcus and had not lived in an endemic area. Treatment with fluconazole, an antifungal drug, has reduced the size of the tumor-like mass in the prostate as observed with imaging. The oropharyngeal ulcer disappeared after methotrexate was discontinued.

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Figure 1.

Histological findings of granulomatous prostatitis due to Cryptococcus infection with caseous granuloma (A, B, C) and suppurative granuloma (D, E, F). (A) Extensive caseous necrosis surrounded by epithelioid histiocytes. (B) Translucent organisms (arrows) in caseous necrosis and epithelioid histiocytes. (C) Organisms stained with Grocott methenamine silver (GMS). (D) Focus of numerous neutrophilic infiltrations surrounded by epithelioid histiocytes and giant cells. Caseous necrosis is not shown. (E) Organisms (arrows) in epithelioid histiocytes and giant cells. (F) GMS stained positive organisms were observed. A and D, x200; B, C, E, and F, x400.

Discussion

Prostatitis induced by a fungal infection histologically shows granulomatous inflammation with fungal organisms. ³ Fungal granulomas have been reported to present a morphology of suppurative granuloma with prominent neutrophilic infiltration. ⁶ However, in this case, both caseous granulomas and suppurative granulomas were observed. In addition, yeast-type fungi, suspected from HE staining and confirmed from GMS staining, were found in both granulomas. Caseous granulomas often develop in the prostate after BCG immunotherapy for bladder cancer, ² although the possibility of fungal prostatitis, including Cryptococcus infection, should also be considered. The mechanism of caseous granulomas is considered to provide a strong acquired immunity against antigens, and a characteristic necrosis is formed by the death of granuloma component cells, including macrophages. ⁷ Gordon et al reported a peritoneal cryptococcal granuloma with a central caseous granuloma. ⁸ The possibility of Cryptococcus infection as well as tuberculosis infection after BCG immunotherapy should be considered for caseous necrosis, and organisms should be identified by GMS and Ziehl–Neelsen staining.

As shown in Table 1, including our case, there have been 14 case reports of cryptococcal prostatitis diagnosed by prostate core needle biopsy.^3–5,9–16 Of the 14 cases, granulomas were observed in prostate biopsy specimens in 8 cases. In previous reports, cryptococcal prostatitis has been mainly diagnosed from autopsy specimens, transurethral resection of prostate (TURP), prostatectomy, and prostatic fluid or urine cultures, and less often from a biopsy specimen. ¹⁶ It has also been reported that Cryptococcus infection is rarely diagnosed by a prostate biopsy. ³ Cryptococcus infection is known to develop granulomatous inflammation when the cell-mediated immunity is not impaired. ¹⁷ Although cryptococcal prostatitis is diagnosed by the presence of small encapsulated yeast cells in granulomatous lesions, especially in phagocytic cells, the small size and translucent nature of the small encapsulated yeast cells may make them difficult to find in HE-stained biopsy specimens. However, patients with cryptococcal prostatitis were more likely to have underlying immunosuppressive conditions such as immunosuppressive agent therapy including steroids, diabetes, liver cirrhosis, hematopoietic neoplasm, and human immunodeficiency virus infection, as in this case.^3,16 Clinical information about the patient, such as immunosuppressive status and no history of BCG therapy, might be useful in diagnosing cryptococcal prostatitis by means of a biopsy.

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Table 1.

Literature on Cryptococcal Prostatitis Diagnosed by Prostate Needle Biopsy.

Year	Author	Cases	Age	Predisposing condition	Pathological diagnosis
1965	Tillotson, et al 9	1	18	None	Inflammation
1972	Orr et al 10	1	70	Polycythemia vera	Abscess
1990	King et al 11	1	48	Hodgkin lymphoma	Fungal organism
1992	Adams et al 5	1	55	HIV infection	Inflammation
1992	Mamo et al 12	1	28	HIV infection	Abscess
1995	Fuse et al 4	1	55	Behçet's disease	Suppurative granuloma
2005	Siddiqui et al 13	1	51	Renal transplant recipient	Granuloma
2006	Seo et al 14	1	75	Alcoholic cirrhosis	Suppurative granuloma
2008	Wada et al 15	1	57	Diabetes mellitus	Suppurative granuloma
2017	Shah et al 16	1	62	Cardiac transplant recipient	Suppurative granuloma
2020	Epstein et al 3		56	Renal transplant recipient	Granuloma
			57	Rheumatoid arthritis	Granuloma
		3	47	HIV infection	Fungal organism
2021	Present case	1	81	DLBCL	Suppurative granuloma and caseous granuloma

Abbreviations: HIV, Human immunodeficiency virus; DLBCL, diffuse large B-cell lymphoma.

In a review by Shah et al, of 70 cases of cryptococcal prostatitis, 38 (54.3%) had infection foci in organs other than the prostate. ¹⁶ Here, fluconazole was administered because the patient was immunosuppressed, although no infection foci were found in other organs. No treatment for tuberculosis was given. In immunosuppressed patients, opportunistic infections may lead to a serious deterioration in general condition. It is better to accurately identify the pathogen and consider treatment without assuming that the patient is infected with tuberculosis, even if the patient is suffering from caseous necrosis.

We here presented a case of granulomatous prostatitis caused by Cryptococcus infection diagnosed by employing a prostate core needle biopsy. In cryptococcal granulomatous prostatitis, not only suppurative granuloma but also caseous granuloma might develop.