Mucormycosis (zygomycosis) is a globally invasive fungal infection that rarely occurs in immunocompetent but frequently in immunocompromised patients and is associated with high morbidity and mortality [1-4]. The biopsy is the preferred method of diagnosis but may not be an option in the early course of the disease, resulting in delayed diagnosis and increased mortality [5]. Herein, we presented a case of disseminated rhinoorbital-cerebral mucormycosis (ROCM) in mixed phenotype acute leukemia (MPAL) with Philadelphia (ph) chromosome positive and shared the therapy to it.
A 48-year-old woman who presented with painlessness and fever for 1 week was admitted to People’s Hospital of Xinghua City (Jiangsu province, China) on December 6, 2017. Physical examination was negative. Her complete blood-cell-count (CBC) data (with references ranges in parentheses) were as follows: white blood cells (WBC), 180.7 (4.0–10.0) ×109/L; hemoglobin (HGB), 123 (110–150) g/L, and platelets (PLT), 53 (100–300) ×109/L. Bone marrow (BM) biopsy showed hypercellularity with 83.5% blast cells. Eosinophilia was not evident in either peripheral blood or BM. Flow cytometry analysis showed that the blast cells, which accounted for 95.2% of bone marrow karyocytes, were strongly positive for CD34, CD19, CD13, CD33, CD 11B, CD64, MPO, and CD79a. The chromosomal analysis of bone marrow cells revealed t (9;22) (q34; q11) translocation. Molecular genetics showed BCR/ABL (e1a2) fusion gene. According to the World Health Organization (WHO) 2016 criteria, the patient was diagnosed with Ph+MPAL. The patient was treated with imatinib (400 mg/day) and ALL-like chemotherapy (VDP: vincristine 2 mg/qwx4, daunorubicin 30 mg/m2 d1–3, prednisone 60 mg/m2 d1–28) on December 9, 2017. Also, preventive treatment was given with voriconazole (4 mg/kg, q12h). On December 12, 2017, the patient’s body temperature reached 38.6 ℃ and skin lesions developed on the right nasal that spread rapidly to the whole right nasal. Chest computed tomography (CT) examination was negative, and serum β-D-glucan, galactomannan tests, and blood culture examinations were negative. Skin biopsy revealed hyphae consistent with mucormycosis. Wound secretion culture was positive for Rhizomucor species (Fig. 1). After the diagnosis of mucormycosis, according to the guidelines of the Infectious Diseases Society of America (IDSA), we administered liposomal amphotericin B (L-AMB) at 5 mg/kg on December 15, 2017. On December 17, 2017, the patient’s temperature returned to normal, and the mucormycosis infection was controlled successfully. She achieved complete remission from Ph+MPAL on February 10, 2018. The patient died of intracranial hemorrhage after 1 year.
Mucormycosis is a severe and rapidly progressing fungal infection caused by members of the genera Mucor, Rhizopus, Rhizomucor, and Lichtheimia (formerly Absidia) in the order Mucorales [6]. The present case demonstrates a progressive ROCM in Ph+MPAL during induction therapy. Mucormycosis in patients with diabetes mainly causes rhino-cerebral and sino-orbital infections [7]. As observed in the current case, ROCM infection usually originates from the paranasal sinuses, with bone destruction and subsequent invasion of the orbit, eye, and brain [8]. Unilateral facial edema, proptosis, and palatal or palpebral fistula developing into necrosis may be observed. In our case, after the diagnosis of mucormycosis infection, the patient was treated with liposomal amphotericin B and the disease was controlled. We hope that this case can provide a new perspective for the clinical diagnosis and treatment of Ph+MPAL.