Testicular malakoplakia in a middle-aged Han Chinese male: a case report and review of the literature

Abstract

Background

Testicular malakoplakia (MP) is an extremely rare chronic granulomatous inflammatory lesion. It lacks specific clinical or imaging features and is highly prone to misdiagnosis as a testicular tumor. To our knowledge, no reports have described the contrast-enhanced ultrasound (CEUS) manifestations of this condition. Herein, we present a case with the aim of improving the understanding of testicular MP and reducing unnecessary misdiagnosis and oversight.

Patient presentation

A 41-year-old Han Chinese male presented with unexplained right scrotal swelling for more than 20 days, accompanied by intermittent fever, chills, and dysuria, along with mild distending pain in the enlarged testicle. CEUS revealed that the right affected testicle had rapid high enhancement and slow washout. Computed tomography (CT) and magnetic resonance imaging (MRI) showed marked enlargement of the right testicle and altered parenchymal density, suggestive of a neoplastic lesion. Urine culture confirmed a bacterial infection with Escherichia coli (E. coli). Treatment with ceftriaxone and other antimicrobial agents yielded no significant improvement. Subsequently, a right orchiectomy was performed, and pathological examination confirmed the diagnosis of testicular MP. The patient’s urinary symptoms gradually resolved postoperatively. During the 3-month follow-up, no recurrence was observed, and inflammatory markers remained within the normal range.

Conclusions

The clinical and imaging presentations of testicular MP are nonspecific, posing a significant challenge for preoperative diagnosis. Definitive diagnosis still relies on pathological examination. Therefore, clinicians should increase their awareness of this rare disease to avoid misdiagnosis. To our knowledge, this report represents the first description and analysis of CEUS manifestations in a case of testicular MP.

Introduction

Malakoplakia (MP) is a rare chronic granulomatous inflammatory disorder that most commonly affects the bladder, ureter, and kidney, while testicular involvement is exceedingly rare [1]. Testicular MP accounts for less than 0.1% of all testicular space-occupying lesions (including both neoplastic and non-neoplastic entities), testicular MP typically presents as a firm, painless mass or swelling with ill-defined margins and slow progression over several months to years [2, 3]. Due to its low incidence and nonspecific clinical and imaging features, it is frequently misdiagnosed as a testicular tumor or tuberculosis. Currently, diagnosis can only be confirmed by pathological biopsy, supported by special stains [e.g., calcium, Periodic Acid–Schiff stain (PAS) and iron staining] to identify Michaelis–Gutmann (M–G) bodies within histiocytes [4]. This report describes a case of testicular MP and documents its detailed clinical characteristics. The aim is to contribute to the limited understanding of this condition and to assist clinicians in recognizing the disease and formulating appropriate treatment strategies for future cases.

Case presentation

A 41-year-old Han Chinese male presented with recurrent fever, right scrotal swelling (accompanied by mild distension and pain), and dysuria. Initially treated at a local hospital with antibiotics, including cephalosporins (ceftriaxone 2 g IV q12h for 7 days) and terbinafine (250 mg orally once daily for 10 days), he showed no significant improvement. The patient had a 3-month history of diabetes, which was well controlled with regular insulin therapy (HbA1c 6.2% measured one month prior to admission). He denied any history of infectious disease or sexually promiscuous behavior. No immediate family members had a history of diabetes, malignancy, or urinary system diseases.

Physical examination revealed marked enlargement of the right scrotum compared to the left. The right testicle was palpably enlarged, firm, well-defined, and tender, without obvious erythema or swelling of the overlying skin. The left scrotum and bilateral spermatic cord regions were unremarkable. No significantly enlarged lymph nodes were palpated in either inguinal region. There was no tenderness or percussion pain over the bilateral renal areas, and no abnormal protrusions were noted in the pubic region.

Laboratory tests revealed leukocytosis (a white blood cell count 16.17×10⁹/L ↑, reference range 3.5–9.5×10⁹/L) with neutrophilia (85% ↑, reference range 40–75%), lymphocytopenia (10.1% ↓, reference range 20–50%), and eosinopenia (0.1% ↓, reference range 0.4–8.0%). Inflammatory markers were elevated, including C-reactive protein (CRP 91.40 mg/L ↑, reference range < 5 mg/L), the interleukin-6 (IL-6 30.42 pg/mL ↑, reference < 7 pg/mL), and procalcitonin (PCT 0.06 ng/mL ↑, reference < 0.046 ng/mL). Antinuclear antibody, beta-human chorionic gonadotropin (β-hCG), and serum tumor marker—alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), and lactate dehydrogenase (LDH)—were all within normal limits. Urinalysis showed pyuria (25 white blood cells/μL, 1 +), and urine culture was positive for E. coli, which was sensitive to ceftriaxone, ciprofloxacin, and trimethoprim–sulfamethoxazole.

Color Doppler ultrasonography revealed an enlarged right testicle with homogeneous hypoechoic parenchyma measuring approximately 65 × 46 × 50 mm, whereas the left testicle measured 39×20×26 mm. Although no discrete mass was identified, the right testicle exhibited marked hypervascularity with significantly increased blood flow signals relative to the contralateral side (Fig. 1). Contrast-enhanced ultrasound (CEUS) of the right testicle was performed using SonoVue (Bracco, Italy) administered as a 2.4 mL bolus injection followed by 5 mL normal saline flush, with real-time perfusion monitoring. CEUS demonstrated rapid and intense enhancement, with wash-in commencing at 15 s—significantly earlier than on the left side. The time to peak enhancement was 29 s, followed by a slow washout phase. At 2 min and 51 s, persistent contrast retention was observed in the affected testicle, whereas the left (normal) testicle had already completely cleared the agent. These perfusion features are suggestive of a neoplastic process (Fig. 2).

Fig. 1.

Color Doppler ultrasound of the bilateral testes. A Markedly increased vascularity in the right (affected) testicle. B Normal vascularity of the left (uninvolved) testicle

Fig. 2.

Contrast-enhanced ultrasound (CEUS) of the bilateral testes. A Right testicle shows early wash-in at 15 s, significantly earlier than the left. B Peak enhancement of the right testicle is reached at 29 s. C Slow washout with persistent mild enhancement at 2 min and 51 s

Contrast-enhanced computed tomography (CT) of the scrotal demonstrated an enlarged right testicle (maximum cross-sectional size of approximately 48 × 45 mm), showing uniformly reduced density with clear boundaries and heterogeneous enhancement, findings consistent with a tumorous lesion (Fig. 3). Magnetic resonance imaging (MRI) revealed right testicular enlargement (approximately 63 × 45 × 47 mm). The lesion appeared iso- to slightly hyperintense on T1-weighted images (T1WI), slightly hyperintense on T2-weighted images (T2WI), hyperintense on diffusion-weighted imaging (DWI), and hypointense on the apparent diffusion coefficient (ADC) map, with relatively uniform enhancement on post-contrast sequences (Fig. 4). No enlarged lymph nodes or effusion were observed in the pelvic cavity, further supporting the impression of a neoplastic process.

Fig. 3.

Contrast-enhanced computed tomography (CT) of the scrotum. A Non-contrast image demonstrating marked enlargement and decreased attenuation of the right testicle. B Contrast-enhanced image revealing heterogeneous enhancement of the right testicle

Fig. 4.

Magnetic resonance imaging (MRI) of the scrotum. A T1-weighted image (arrow indicates the enlarged right testicle). B T2-weighted image (arrow indicates the enlarged right testicle). C Diffusion-weighted image (DWI) (arrow indicates the enlarged right testicle). D Apparent diffusion coefficient (ADC) map (arrow indicates the enlarged right testicle)

The patient underwent a right radical orchiectomy via an inguinal approach. Intraoperatively, the right testis and epididymis were found to be enlarged (approximately 60 × 50 mm) and firm in consistency. The cut surface exhibited solid, grayish-yellow tissue. Histopathological examination showed extensive infiltration of eosinophilic histiocytes, accompanied by chronic inflammatory cells, within the testicular parenchyma. Immunohistochemical staining results were as follows: CD68 ( +), CD163 ( +) (confirming histiocytic origin), and special stains (calcium, iron, PAS) identified M–G bodies. The following markers were negative: inhibin, MART-1, S-100, HMB45, pan-cytokeratin (PCK), epithelial membrane antigen (EMA), SALI4, OCT3/4, leukocyte common antigen (LCA), IgG4, and BRAF (V600E). CD30 showed focal weak positivity ( ±), and the Ki-67 proliferation index was low (1–3%). These findings helped exclude other neoplasms such as germ cell tumors, lymphoma, and melanoma. The final pathological diagnosis was testicular MP (Fig. 5). A concise timeline summarizing the patient’s key clinical events, investigations, and interventions is provided in Table 1.

Fig. 5.

Histopathological findings diagnostic of testicular malakoplakia (MP). A Hematoxylin and eosin (H&E) staining (40 ×) showing pathognomonic Michaelis–Gutmann (M–G) bodies: round to oval, well-demarcated intracytoplasmic inclusions with a characteristic “owl’s eye” morphology (arrow). B Histochemical stain confirming positive calcium deposition within these bodies. C Periodic acid–Schiff (PAS) stain demonstrating intense magenta coloration of the inclusions

Table 1.

Timeline of patient’s key clinical course

Time point	Clinical events, findings, and interventions
T = 0 (Day 1)	Initial presentation to our hospital with right scrotal swelling, fever, and dysuria
T = 3 days	Laboratory tests (complete blood count, inflammatory markers, tumor markers) and imaging (color Doppler ultrasound, CEUS, CT, MRI) performed
T = 3–17 days	Preoperative antibiotic treatment (ceftriaxone + terbinafine) with no improvement
T = 20 days	Right radical orchiectomy via an inguinal approach
T = 1 month (follow-up)	Urinary symptoms completely resolved; inflammatory markers (WBC, CRP, ESR) returned to normal
T = 3 months (follow-up)	No recurrence of scrotal swelling/fever; abdominal ultrasound showed normal left testicle and pelvic lymph nodes

Postoperative follow-up: The patient’s fever subsided within 48 h after surgery. Dysuria and scrotal discomfort resolved completely within one week. Based on the urine culture sensitivity, he was prescribed oral ciprofloxacin (500 mg twice daily) for a total of 4 weeks. At the 3-month outpatient follow-up, he remained asymptomatic. A scrotal ultrasound showed a normal appearance of the left testicle and no recurrence in the surgical bed.

Discussion

Pathogenesis of malakoplakia

Malakoplakia (MP) is a rare chronic granulomatous inflammatory disease first described by von Hansemann in 1903. Its pathological hallmarks include extensive infiltration of von Hansemann cells and the presence of intracellular or extracellular calcified structures with concentric laminations, known as M–G bodies, the latter being considered pathognomonic. Although the urinary system—particularly the bladder—is most commonly affected site, testicular MP is exceptionally rare, accounting for less than 0.1% of all testicular space—occupying lesions [3]. Owing to its nonspecific clinical and imaging features, testicular MP is frequently misdiagnosed as a testicular tumor, tuberculosis, or other granulomatous conditions, presenting a significant challenge for preoperative diagnosis [5]. This study reports a case of pathologically confirmed testicular MP and provides the first detailed description of its CEUS characteristics, aiming to improve the imaging understanding of this disease and offer new perspectives for its clinical differential diagnosis.

Although the pathogenesis of MP remains incompletely understood, it is widely considered to be associated with impaired host immune function and chronic bacterial infection [6]. An immunocompromised state can lead to defective phagocytosis and lysosomal digestion within macrophages, resulting in the incomplete elimination of ingested bacteria—particularly Gram-negative bacilli such as E. coli [6, 7]. Undigested bacterial debris then undergoes abnormal mineralization within lysosomes, combining with calcium, iron, and other ions to eventually form the characteristic M–G bodies [8]. Diabetes mellitus is an important risk factor for MP, as it induces systemic immune dysfunction and weakened macrophage phagocytic ability, which promotes persistent infection and the formation of M–G bodies. Consistent with this theory, our patient had a history of diabetes mellitus, a known cause of immune dysfunction. Urine culture confirmed an E. coli infection, further supporting the role of chronic bacterial infection. These clinical features align with the established risk factors for MP, suggesting that this diagnosis should be considered in patients with similar backgrounds (e.g., diabetes, organ transplantation, or long-term immunosuppression) who present with a testicular mass [9, 10].

Imaging features and diagnostic challenges

The imaging appearance of testicular MP is variable and nonspecific, leading to a high rate of preoperative misdiagnosis. On conventional ultrasound, it may present as diffuse testicular enlargement with decreased echogenicity or as a focal, ill-defined hypoechoic or mixed-echogenicity mass with abundant internal blood flow [3, 11]. In the present case, conventional ultrasound revealed diffuse right testicle enlargement with uniformly reduced parenchymal echogenicity and significantly increased blood flow, resembling acute or subacute orchitis. However, diffuse infiltrative malignancies such as lymphoma or leukemia could not be excluded.

Both CT and MRI findings are also nonspecific. In our case, CT revealed decreased density with heterogeneous enhancement, while MRI revealed an iso- to slightly hyperintense signal on T1WI images, a slightly hyperintense signal on T2WI, restricted diffusion (hyperintensity on DWI and hypointensity on ADC maps), and relatively uniform enhancement. Restricted diffusion typically reflects high cellular density, a feature commonly associated with malignant [12]. This constellation of imaging findings, especially the hypervascularity observed on contrast-enhanced studies, often leads radiologists and clinicians to suspect malignant tumors such as seminomas or non-seminomatous germ cell tumors. Previous reports on testicular MP have similarly emphasized its significant imaging overlap with malignancy, making pathological examination of the resected specimen necessary for definitive diagnosis in nearly all cases [5, 13].

CEUS features in context of differential diagnosis

To our knowledge, this report provides the first detailed description of CEUS findings in testicular MP. CEUS enables real-time, dynamic assessment of tissue microvascular perfusion and has demonstrated significant value in differentiating testicular pathologies [14, 15]. In our case, CEUS revealed a pattern of rapid, intense hyperenhancement followed by slow washout. Specifically, contrast arrival (wash-in) in the lesion was observed at 15 s, with a rapid rise to peak enhancement at 29 s—significantly higher than in the contralateral testicle—followed by a slow washout phase. At 2 min and 51 s, marked contrast retention persisted in the affected testicle, while the contrast agent had completely washed out from the normal side. We compared this perfusion pattern with those of common testicular malignancies:

Seminoma: typically exhibits “fast-in-fast-out” enhancement (rapid wash-in and rapid washout) due to arteriovenous shunts in tumor tissue [14]. In contrast, our case showed slow washout, which may reflect inflammatory lesion hemodynamics.

Embryonal carcinoma: often presents with heterogeneous enhancement due to central necrosis, whereas testicular MP shows relatively uniform enhancement (consistent with diffuse inflammatory infiltration without necrosis).

We analyzed the CEUS enhancement pattern as follows:

First, rapid and intense enhancement reflects a rich and disorganized microvascular network within the lesion. The pathology of MP involves infiltration of inflammatory cells (notably histiocytes) and granuloma formation, processes that are accompanied by reactive neovascularization. These newly formed vessels are often immature and hyperpermeable, permitting rapid and abundant contrast filling [14, 16]. This pattern closely mimics that of many testicular malignancies (e.g., seminomas and embryonal carcinomas), which also demonstrate high perfusion due to tumor angiogenesis. Therefore, rapid, high-grade enhancement alone is insufficient to distinguish MP from a malignant tumor.

Second, slow washout may hold greater value for differential diagnosis. Typically, malignant tumors often contain arteriovenous shunts, leading to “fast-in, fast-out” kinetics with relatively rapid washout [14]. In our case, the observed slow washout may better reflect the hemodynamics of an inflammatory lesion: increased capillary permeability allows contrast microbubbles to extravasate into the interstitium, while inflammatory edema and cellular infiltration increase tissue pressure, thereby impairing venous return and delaying contrast clearance. The “slow washout” pattern seen here, potentially attributable to inflammatory hyperpermeability and interstitial contrast retention, could serve as an imaging clue when considering MP in the differential diagnosis of a testicular mass. Nonetheless, this interpretation is based on a single case and must be viewed cautiously. The specificity and diagnostic utility of this feature require validation through prospective studies with larger patient cohorts.

Treatment considerations

Given that testicular MP is nearly indistinguishable from malignancy preoperatively, radical orchiectomy remains the standard diagnostic and therapeutic approach [3, 5], a principle followed in the present case. Since multiple imaging modalities strongly suggested a tumor, orchiectomy was both a reasonable and necessary intervention, providing a definitive diagnosis and complete removal of the lesion.

Although MP is fundamentally an inflammatory condition, medical management alone is generally not advisable for an initial testicular mass, as the inability to rule out malignancy could lead to a dangerous delay and potential tumor progression. However, antimicrobial therapy may be considered if a pathological diagnosis is secured preoperatively via biopsy or if MP has been diagnosed in another site. Recommended regimens include long-term antibiotics capable of penetrating macrophages, such as fluoroquinolones (e.g., ciprofloxacin) or trimethoprim–sulfamethoxazole, administered for several months to years [7, 17]. Adjunctive therapies like cholinergic agonists (e.g., carbachol) and ascorbic acid (vitamin C), have also been reported to potentially improve macrophage function although evidence supporting their use remains limited [18–20].

Following complete surgical excision and pathological confirmation, there are no unified guidelines on the necessity of adjuvant antibiotic therapy. Nevertheless, given the frequent association with bacterial infection—in this case, a concurrent E. coli urinary tract infection—targeted anti-infective treatment is warranted. For our patients, preoperative antibiotics were empirical, aimed at the urinary infection. Postoperatively, based on culture sensitivities, therapy was transitioned to a long-term, macrophage-penetrating antibiotic (ciprofloxacin) for 4 weeks to address the presumed infectious etiology of MP and to prevent recurrence.

Conclusion

MP is an extremely rare chronic inflammatory disorder. Its clinical and imaging features closely mimic those of testicular malignancies, rendering preoperative diagnosis highly challenging. To our knowledge, this study is the first to report and analyze the CEUS manifestations in testicular MP, characterized by a pattern of “rapid and high enhancement followed by slow washout”. This finding adds a new perspective to the imaging assessment of this condition. While the observed “slow washout” feature may in the future offer a clue for differentiating testicular MP from malignant tumors, it requires validation through studies with larger case series. At present, for a testicular mass with suspicious imaging findings, radical orchiectomy remains the standard of care to establish a definitive diagnosis and ensure effective treatment.

Abbreviations

AFP

Alpha-fetoprotein

β-hCG

Beta-human chorionic gonadotropin

CEA

Carcinoembryonic antigen

CT

Computed tomography

CEUS

Contrast-enhanced ultrasound

CRP

C-reactive protein

E. coli

Escherichia coli

G–M bodis

Michaelis–Gutmann bodis

IL-6

Interleukin-6

LDH

Lactate dehydrogenase

MP

Malakoplakia

MRI

Magnetic resonance imaging

PCT

Procalcitonin

PAS

Periodic Acid–Schiff stain

Author contributions

ZQR and YC participated in the writing of the paper and obtained the patient’s consent. XJM, JJZ and BYM participated in the revision of the paper and provided imaging images. All the authors reviewed and approved the final version of the paper.

Funding

1·3·5 projects for artificial intelligence (ZYAI24056 and ZYAI24035), West China Hospital, Sichuan University. Sichuan Science and Technology Program (No. 2024NSFSC0660).

Data availability

Available data is presented in the article and its supplementary materials.

Declarations

Ethics approval and consent to participate

The handling of this case was carried out in accordance with the Declaration of Helsinki. All programs were conducted in accordance with the ethical standards of the Clinical Research Ethics Committee of West China Hospital of Sichuan University. Informed consent was obtained from the patient.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and any accompanying images. A copy of the written consent is available for review by the Editor-in-Chief of this journal.

Competing interests

The authors declare that they have no competing interest. The authors have no association with financial or nonfinancial organizations.