A 45-year-old woman consulted in May 2021 in the Emergency Department for a painless, stony breast lump in the right breast of two months of evolution. The tumor had about 4 cm in diameter, was located in the superoexternal breast quadrant and had no associated lymphadenopathies. It had ulceration to the skin and bleeding, some sloughing and grayish pustular exudate. The patient primary care physician requested a mammogram and referral to our breast pathology unit. The mammogram, which was completed with an ultrasound scan, showed a polylobulated nodule, BI-RADS 4C, 40 × 35 mm in diameter, without associated pathological axillary nodes, and ulcerated to the skin (Fig. 1). She consulted the day after the mammography, after starting with non-hematic telorrhea. She did not present fever, chills, nor data of general malaise or systemic involvement.
The patient was a native of Nigeria, with a history of hypertension, dyslipidemia, anemia with sickle cell trait and a history of malaria. She had a myomatous uterus, one full-term pregnancy and five miscarriages. Three years prior to the current episode, the patient had begun follow-up in our center for long-standing chronic kidney disease with no known etiology, and she has been on hemodialysis for 9 months, until receiving a cadaver transplant in May 2019. She develop a Diabetes Mellitus 2 in relation to the use of corticosteroids in immunosuppression scheme, requiring insulinization. The patient's immunosuppressive treatment at the time of this episode consisted of prednisone 5 mg daily, tacrolimus 9 mg at breakfast and 8.5 mg at dinner, mycophenolate 500 mg at breakfast and 250 mg at dinner. During the two years of evolution, she had not presented rejection, and as complications she had presented BK viruria, although without associated BK viremia.
In view of the ulcerated bleeding lesion and with the suspicion of a malign breast disease, a core needle biopsy was performed. The pathology study showed fibrinous and granulation tissue with intense chronic acute inflammatory component, granulomatous reaction, and abundant presence of fungal spores and hyphae, as well as eosinophils and multinucleated giant cells.
Given the high suspicion of fungal abscess, a sample of exudate from the lesion was taken and sent to the microbiology laboratory for culture. The sample was cultured in common and specific media for fungal growth (Saboureaud Agar + Chloramphenicol and Potato Glucose Agar—Becton Dickinson®) in aerobic atmosphere at 37 ºC and 30 ºC. Between 48 and 72 h later, growth of white filamentous colonies was observed on the front and back of the plate and, when stained with lactophenol blue, hyaline septate hyphae with chains of arthro-conidia and sessile microconidia were identified (Fig. 2). Preliminary identification was performed with Matrix-Assisted Laser Desorption/Ionization-Time Of Flight (MALDI-TOF)Bruker®and a score lower than 1.25 was obtained, so it was decided to perform molecular identification. It was identified by genomic amplification by polymerase chain reaction (PCR) of the internal transcription spacer region-2 (ITS-2) and, after sequencing, a percentage of similarity with sequences of Nannizziopsis obscura from GenBank of 98% was obtained. After that, the sample was sent to the Spanish National Center of Microbiology for microdilution fungigram according to the methodology described in: (a) de Hoog GS, Guarro J, Gené J, Ahmed S, Al-Hatmi AMS, Figueras MJ & Vitale RG (2020) Atlas of Clinical Fungi, 4th edition. Hilversum; and (b) Sutton, Deanna A.; Etc.; Fothergill, Annette W.; Rinaldi, Michael G. Guide to Clinically Significant Fungi), obtaining the MIC results described in Table 1. The sample was registered on GenBank with the code OQ001484.
The patient was scheduled for surgery of the lesion two weeks later. The preoperative blood test showed normal infectious and basic hematological parameters: 5160 leukocytes per microliter (2540 neutrophils per microliter, 1780 lymphocytes per microliter, 40 eosinophils per microliter), 13.1 g per liter of hemoglobin, 285,000 platelets per microliter, with C-reactive protein (CRP) of 8.9 mg/L. In terms of renal function, she had a creatinine of 1.39 mg/dL, equivalent to a Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) filtration rate of 46 ml/min.
A open biopsy of the lesion was performed without complete excision of the lesion, leaving external drainage through a Penrose catheter. Treatment with anidulafungin was started at that time, still pending definitive typing of the fungus, which at this time is known to be a non-conventional fungus without yeast characteristics, and choosing this option to avoid the possible nephrotoxicity of amphotericin B, which would have been the alternative broad-spectrum antifungal in this case; and to avoid azoles, which would have interacted increasing tacrolimus doses. A total of 14 days of intravenous treatment with anidulafungin 100 mg daily was completed, reducing the tacrolimus dose to reach a target level of 4–5 ng/ml, in agreement with the Nephrology Service. She presented a good evolution during the whole treatment, presenting a residual seroma in ultrasound. During the course of treatment, the fungus was definitively identified as Nannizziopsis obscura, with the antifungigram described in Table 1. Given the initial non-complete resection and the immunosuppression status, it was decided to maintain oral treatment for a prolonged period of time, switching to isavuconazole 600 mg for two days and a subsequent dose of 200 mg daily for a total of 14 more days, with good tolerance and acceptance and without side effects.
