A 32-year-old woman presented with acute-onset shortness of breath and chest pain for 4 days. She also complained of cough with some small amounts of phlegm and occasional low-grade fever, but no night sweat, rash, hemoptysis, loss of weight, joint swelling, or any other discomfort. Her medical history included hypotension, hypoglycemia and bile reflux gastritis. She was also a hepatitis B virus carrier and once arranged for an interventional operation for spontaneous intracerebral hemorrhage at the age of 20. Luckily, no sequela was found after that operation. Her home medications included itopride, sucralfate and famotidine. She was a lifelong non-smoker and had no history of recent travel, wild animal contacts or sick contacts. She lived in Guangdong province in China. She had no known allergies.
After admission to hospital, physical examination revealed the following: blood pressure was 92 mmHg systolic and 65 mmHg diastolic, respiratory rate was 21 breaths/min, heart rate was 122 beats/min, body temperature was 99.7 F, arterial oxygen saturation on room air was 95%. She had coarse breath sounds on auscultation without any wheezing, rhonchi or crackles. The remainder of the physical examination produced normal results.
Laboratory results suggested white blood cell count of 14,360 cells/mm (3) [normal value, 3,500-9,500 cells/mm(3)], neutrophil count of 10,820 cells/mm(3) [normal value, 1,800-6,300 cells/mm(3)], lymphocyte count of 1,960 cells/mm(3) [normal value, 1,100-3,200 cells/mm(3)], monocyte count of 850 cells/mm(3) [normal value, 100-600 cells/mm(3)] and procalcitonin level of 0.594 ng/ml (normal value, < 0.1 ng/ml). Blood gas analysis, NT-proBNP, D-dimer, cardiac enzymes were normal. T-Spot test suggested positive while other blood tests showed negative for blood culture, cryptococcal antigen latex agglutination test, candida galactomannan antigen test, (1-3)-beta-D glucan antigen test, tumor-associated antigens and HIV antibodies. In terms of immune-related examinations, blood level of immunoglobulin G turned out 20.8 g/L, slightly above the normal value (8.6-17.4 g/L), while levels of immunoglobulin A, immunoglobulin M, immunoglobulin E, complement 3 and complement 4 were within normal range. Blood levels of 6 types of cytokines, TNF-alpha, IFN-gamma, IL-2, IL-4, IL-6, and IL-10 were also normal. Moreover, no abnormal results were obtained on lymphocyte subset counts test, anti-extractable nuclear antigen antibodies test, antinuclear antibody test and vasculitis-associated autoantibodies test. Sputum culture and an electrocardiogram showed no obvious abnormalities. Initial chest radiograph indicated bilateral pneumonia. The contrasted chest CT demonstrated a 4.0 x 3.6 cm non-uniformly enhanced middle mediastinal mass with compression of lower trachea and superior vena cava (Figure 1A). Enlarged intramediastinal lymph nodes were appreciated, as well as right middle lobar infiltration (Figure 1D).
To obtain an accurate diagnosis, bronchoscopy, bronchoalveolar lavage (BAL), conventional transbronchial lung biopsy (TBLB) and endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) were performed on the 4th day of hospitalization.
Bronchoscopy revealed severe trachea compression stenosis caused by an extratracheal neoplasm anterior to the lower trachea (Figure 2A), along with bronchial inflammation and airway secretion. Mixed bacteria were found yet indistinguishable by BALF smear and BALF culture. mNGS of BALF detected T. marneffei with 15 sequence reads identified out of 84 total reads. TBLB showed acute inflammation, negative for Acid-fast, PAS and GMS stains, and no tumor cells were seen (Figure 3A). Whereas, with the technology of EBUS-TBNA, we were able to observe the ultrasonogram of the extratracheal neoplasm (Figure 2B) and obtain the needle aspirates of the mass. On the 9th day of admission, culturing on Sabouraud dextrose agar medium at 25 C confirmed T. marneffei in the biopsied mass with colonies showing characteristic red-pigmented fungal colonies from the needle aspirates (Figure 2D). Under the microscope, the mold form of T. marneffei was also observed in imprint smear obtained from cultured samples of needle aspirates at 25 C on the background of lactophenol cotton blue staining (Figure 2C). On the same day, histopathologic picture of needle aspirates demonstrated acute exudative inflammation and focal necrosis, where yeast cells with characteristic transverse septa were identified through PAS and GMS staining (Figures 3C,D). Based on the evidence above, we finally proved the diagnosis was acute Talaromyces marneffei mediastinitis.
We initially treated the patient with intravenous moxifloxacin (dose: 400 mg/d), but the broad-spectrum antibiotic seemed to make little effect on her. Her shortness of breath and chest pain continued, while the cough and fever were even exacerbated. We changed the treatment into intravenous amphotericin B deoxycholate (AmBd) (initial dose: 0.1 mg/kg/d) immediately on the day when the diagnosis was confirmed. However, the patient experienced hypotension (BP: 70/43 mmHg) and refused to continue the therapy after the first infusion. Therefore, on the 10th day of hospitalization, she was treated with inhaled AmBd (dose: 0.7 mg/kg/d). As expected, the patient's symptoms were gradually alleviated during the therapy. She was eventually discharged with imaging improvement (Figures 1B,E) after 2-week treatment of nebulized AmBd. At 3-month follow-up, the patient was still stable with subsequent therapy of oral itraconazole (dose: 400 mg/d) and CT scan uncovered significant improvement (Figures 1C,F).