Case Presentation: A 46-year-old Hispanic male with a history of acute myelocytic leukemia (AML) presents with subjective fever of three-day duration after one week of induction chemotherapy with fludarabine, cytarabine, filgrastim (FLAG), and venetoclax. Otherwise, the patient denies cough, shortness-of-breath, diarrhea, abdominal pain, or dysuria. Vitals signs showed a temperature of 37.6C, pulse of 87, blood pressure of 108/50 and SpO2 of 94% on room air. On physical exam, the lungs were bilaterally clear to auscultation and heart sounds demonstrated regular rate and rhythm. A chest radiograph showed right upper lobe atelectasis(Figure 1). A complete blood count showed a white blood cell count of 1700, an absolute neutrophil count(ANC) of near 0, hemoglobin 8.9, and platelets of 402. Covid and influenza tests were negative. The patient had no history of tuberculosis and three sets of sputum acid fast bacilli smears and tuberculosis PCR was negative. Fungitell and Galactomannan tests were negative. The patient was started on prophylactic levofloxacin, acyclovir, voriconazole, and Bactrim until ANC recovered to above 500. While urine cultures were negative, blood cultures were positive for streptococcus mitis. The patient was initially started on ceftriaxone to cover S.Mitis and was transitioned to oral linezolid upon discharge. However, the patient returned in one week complaining of persistent subjective fevers. He continued to deny any shortness-of-breath or cough. Vital signs were stable with a temperature of 37.2C. The ANC has recovered to 260 and other labs were mostly consistent with previous encounter. A decision was made to perform a CT scan of the chest, abdomen, and pelvis to assess for possible infectious, malignant, or structural causes. This revealed a 2x3cm soft tissue mass in the right upper lung lobe. A subsequent bronchoscopy with endobronchial ultrasound-guided biopsy and bronchioalveolar lavage (BAL) was performed. The BAL showed numerous inflammatory cells. The PAS and GMS stains were positive for fungal organisms and biopsy showed the presence of Aspergillus spp, confirming the diagnosis of aspergilloma. The patient was subsequently referred for surgical removal while continuing voriconazole therapy.
Discussion: Aspergillomas most commonly arise in patients with pre-existing pulmonary cavities, such as those with a history of pulmonary tuberculosis. However, as evident in this case, it is also possible to develop aspergilloma in an immunocompromised, neutropenic setting without a prior history of known pulmonary cavities[1]. Notably, the patient also denied cough, hemoptysis or respiratory symptoms that are considered classical for aspergillosis. Furthermore, most diagnostic tests employed up until the bronchoscopy with biopsy were unremarkable, including a chest radiograph, blood culture, Fungitell, and Galactomannan tests[2]. Here, it is important to consider that the sensitivity of the Fungitell and Galactomannan tests for detecting aspergillosis are 80% and 71% respectively, with chest radiographs and blood cultures having even lower sensitivities[3].
Conclusions: Aspergillosis can have an insidious presentation in immunocompromised, neutropenic patients. Diagnostic tests can often fail to detect the presence of aspergillosis. The absence of respiratory complaints and negative diagnostic tests should not preclude the possibility of aspergillosis as a key differential in high-risk patients.
