1

Introduction

Blastomycosis is a fungal infection caused by the inhalation of conidia from the Blastomyces genus of fungi which are found in moist, acidic soil near sources of water. Blastomyces dermatiditis , the most frequently encountered human pathogen, is endemic to North America with most cases reporting from southeastern and south-central United States and in regions bordering the Great Lakes. Manifestations include subclinical infection, acute and chronic pulmonary infection, extrapulmonary infection including cutaneous, osteoarticular, central nervous system and genitourinary system infection (epididymo-orchitis, prostatitis). Initial infection of the lungs is common, leading to pulmonary symptoms several weeks after exposure, although as many as 50 % of patients remain asymptomatic. In 20–50 % of cases, the blastomycosis disseminates from the pulmonary system. Cutaneous lesions are typically due to hematogenous spread and classically present as a verrucous lesion with heaped edges but can also present as ulcerative lesions and subcutaneous nodules or abscesses. Culture from respiratory specimens or from a biopsy of affected tissue is the gold standard for diagnosis. Direct microscopy of clinical specimens may also indicate the presence of characteristic yeast cells with thick walls and single, broad-based buds. Polymerase chain reaction (PCR) can be used in conjunction with a culture to confirm presence of Blastomyces. Serological (antibody) assays are available but have a low sensitivity and specificity. ^, Severe infections are typically treated initially with intravenous amphotericin B, while mild to moderate infections can be treated with oral itraconazole alone. ^, These therapies are effective for infections that are localized or disseminated. We present a case of a male patient with blastomycosis infection based on a histopathological diagnosis that initially presented as a scrotal abscess. This unique case highlights the importance of considering a broad differential and obtaining a tissue culture in patients with draining or ulcerative scrotal lesions.

2

Case presentation

A man in his mid-fifties presented to the emergency room in November 2021 with a several week history of a painful lump in the right testicle. He had a mild cough, but no dyspnea and no constitutional symptoms. He travelled frequently and had previously visited Arizona, Europe and parts of Asia. He did not have any animal exposures. There was no recent camping, hiking or hunting and no obvious exposure to decaying organic matter. He was diagnosed with presumed right epididymo-orchitis and empirically treated by the emergency room physician with 10 days of ciprofloxacin. Urine culture drawn at the time returned negative and an ultrasound was highly suggestive of epididymo-orchitis. The patient reported a mild improvement in symptoms after ciprofloxacin, but due to refractory pain and a palpable fluctuance of the right hemiscrotum, he returned to hospital. Repeat ultrasound confirmed interval worsening of epididymitis and scrotal skin edema, with imaging being unable to rule out a defined scrotal wall abscess. An incision and drainage under local anesthetic produced a minimal amount of fluid, insufficient even for a swab. The patient was placed on a 21-day empiric course of sulfamethoxazole-trimethoprim to cover for a possible MRSA infection.

At outpatient follow-up 2 months later, the patient reported initial improvement after antibiotics. However, he then had an episode of a spontaneously draining abscess. Physical examination revealed active serosanguineous fluid from a draining sinus at the previous right scrotal wall incision and drainage site. He was placed on a 14-day course of levofloxacin. A repeat ultrasound demonstrated a complex structure, possibly an abscess, involving the right scrotal wall, likely associated with the epididymis. Short-term follow-up revealed significant interval improvement and the drainage had completely resolved.

Three months later the patient returned with complaints of recurrent serosanguineous drainage with well-controlled pain and edema. Repeat ultrasound showed a small tract measuring less than 1 cm in the subcutaneous tissues with a trace amount of fluid. The area was estimated at 3 × 9 mm, and the right testicle appeared normal. The chronically draining sinus tract was surgically dissected; at the time of the operation, no obvious purulence or infection was observed, and the right testicle remained uninvolved. Pathology confirmed a dermal sinus tract lined by inflammatory histiocytic lining. The working diagnosis was that a fistula to the epididymis was created at the time of the initial incision and drainage. Follow-up 2 months post-operatively once again confirmed complete resolution of symptoms and a completely healed scrotum.

Two months later, the patient developed a palpable abnormality of the left hemiscrotum which was initially painless and had the impression of a spermatocele. Ultrasound confirmed a 1.2 cm structure of decreased echogenicity with no vascularity. Shortly after the ultrasound the patient developed progressive pain and edema. Repeat urine culture was negative and he was empirically treated with a 14-day course of amoxicillin-clavulanate. Despite antibiotics, short-term reassessment demonstrated interval increase in the left hemiscrotal lesion. Ultrasound revealed: a new ill-defined area of decreased echogenicity in mid pole measured 0.8×0.5 × 0.5 cm, new right epididymal hypoechoic nodules measuring 1.1 × 1.5 cm and interval increase in the left epididymal lesion from 1.2 cm to 2.5 cm. Enhancing soft tissue nodules within the scrotum were also noted. A metastatic process involving the scrotum could not be ruled out. A CT chest, abdomen and pelvis showed tiny nonspecific scattered pulmonary nodules which statistically represented benign post inflammatory sequela however metastatic nodules weren’t entirely excluded. The CT also revealed nonspecific diffuse haziness of the omentum and mesentery with small volume pelvic free fluid. These findings could represent a sequela of inflammatory or infectious process however early carcinomatosis wasn’t excluded. There were no definite enlarged lymph nodes above or below the diaphragm, but a borderline enlarged left inguinal lymph node was identified. The case was reviewed at multidisciplinary rounds and a core biopsy of the left inguinal node was pursued to rule out malignancy.

The biopsy revealed occasional yeast with focal budding suggestive of Blastomyces species, background necrotizing granulomas, negative for acid-fast bacilli and CD20/CD3/CD5 compatible with reactive lymphoid infiltrate. The patient was initiated on itraconazole 200 mg PO twice daily immediately and referred for infectious disease consultation. His scrotal lesions rapidly subsided. He had no additional systemic symptoms. Additional investigations at that time revealed Cryptococcus serum antigen negative and non-reactive serology for Blastomyces and Histoplasma. Coccidioides serology was most consistent with prior exposure or a false-positive test. In an attempt to confirm the diagnosis, fungal PCR from the fixed specimen was requested from the mycology lab at the Hospital for Sick Children but returned negative for fungal DNA. A CT 6 months into treatment demonstrated only a few scattered subcentimeter mediastinal lymph nodes. No significant mediastinal, hilar, axillary, abdominal or pelvic lymphadenopathy was seen. Complete clinical and radiographic resolution was observed so itraconazole treatment was discontinued after 6 months and there have been no recurrent symptoms. Although not confirmed by culture or molecular methods, the clinical presentation with subtle pulmonary symptoms and pulmonary nodules as well as cutaneous scrotal lesions and epididymo-orchitis supports the histological diagnosis of blastomycosis.

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Discussion/conclusion

This case highlights the importance of considering endemic fungal infections in the differential diagnosis of ulcerative or draining scrotal lesions and epididymo-orchitis. Bacterial and viral infections are often the focus of urologists, but fungal and mycobacterial infections should remain on our differentials. Tissue culture for bacteria, fungi and mycobacteria is essential to diagnose such pathogens and greatly accelerates treatment.

CRediT authorship contribution statement

Duncan Petrik: Conceptualization, Writing – original draft, Writing – review & editing. Dylan Hoare: Conceptualization, Investigation, Writing – original draft, Writing – review & editing. Megan MacGillivray: Conceptualization, Writing – original draft, Writing – review & editing. Daniel Ricciuto: Conceptualization, Writing – original draft, Writing – review & editing.