Clinical case
A 32-year-old male without any previous medical history initially presented to our outpatient hematology department with a 1-month history of progressive weakness, dyspnea, and intermittent fever. Physical examination revealed petechiae on the upper extremities and thorax. The peripheral blood cell count showed the following results: white blood cell count (WBC), 75.8 × 109/l with 42% blast cells, hemoglobin level of 7.2 g/dl, and a platelet count of 54 × 109/l. Subsequent bone marrow aspiration revealed a hypercellular bone marrow with a significant increase in cells displaying morphological features consistent with myeloblasts (fig. 1). Larger cells with more abundant basophilic cytoplasm and scattered granules were also observed, suggestive of monocytic differentiation. A diagnosis of AML, subtype M4 (Acute Myelomonocytic Leukemia) by the French-American-British (FAB) classification, was established.
Standard induction chemotherapy was initiated with an anthracycline-based 7+3 regimen containing doxorubicin and cytarabine. After the first cycle, repeat bone marrow aspiration showed no blast cells, and the complete blood count (CBC) revealed a hemoglobin level of 10.6 g/dl, platelet count of 204 × 109/l, and WBC count of 6 × 109/l with a normal differential, indicating complete remission with hematologic recovery. Additionally, a lumbar puncture (LP) was performed due to the high WBC count at diagnosis and signs of monocytic differentiation serving as additional risk factors for CNS involvement. The cerebrospinal fluid (CSF) analysis was unremarkable for signs of disease.
Post-remission therapy consisted of three additional consolidation cycles of the same regimen, followed by monthly surveillance. After approximately 16 months of CR, the patient presented to a local otolaryngology department with complaints of left-sided otalgia, hearing loss and fever. Otoscopic examination revealed a narrowed left external auditory canal with ipsilateral hyperemia and purulent otorrhea obscuring the tympanic membrane. Examination of the right side was unremarkable, with an intact external auditory canal and tympanic membrane. Bilateral mixed hearing loss was confirmed by audiometry. At the time, the CBC results did not show any signs of systemic AML, except for a slight leukocytosis with a left-shift deviation suggestive of an inflammatory process. Likewise, the CSF examination indicated no evidence of leukemic cells. Based on presentation and symptoms, a presumptive diagnosis of acute otitis media and externa was made, and the patient was prescribed oral antibacterial therapy. However, after one week of treatment, there was no symptomatic improvement.
A computed tomography (CT) scan was conducted (fig. 2), revealing a narrowed left external auditory canal and non-specific bilateral opacification of the middle ear cavities and the mastoid cells with increased soft tissue density, which was particularly notable on the left side. Importantly, the mastoid structure appeared intact, with no apparent areas of bone destruction and distinct masses. Taking into account the clinical presentation and imaging findings, a provisional diagnosis of acute bilateral otomastoiditis was made. Due to the worsening of the symptoms and refractoriness to conservative therapy, a left-sided mastoidectomy was performed with a curative intent (fig. 3). On visual inspection, the mastoid fragment contained no soft tissue.
The subsequent pathological review of the mastoid structure demonstrated extensive effacement with a homogeneous population of atypical cells, characterized by irregular nuclei, fine chromatin, prominent nucleoli, and scant cytoplasm (fig. 4). Importantly, these findings were at odds with the absence of leukemic cells in the blood, bone marrow and CSF. An initial diagnosis of Burkitt’s lymphoma was considered; however, further immunohistochemistry profiling showed positive staining for myeloperoxidase, CD34, TdT, CD117, CD68, and negative staining for CD3, CD20, PAX5, ALK, and Desmin. These results were consistent with the presence of blast cells of the myeloid lineage. Consequently, a final diagnosis of relapsed AML presenting as an isolated myeloid sarcoma of the temporal bone was confirmed.
Following the surgical intervention, the patient made a full recovery with significant symptom relief. Approximately 3 months have passed since the initial presentation, during which neither the CBC, nor the bone marrow examination showed signs of leukemic involvement. As such, combined treatment with local radiation (28 Gy) and intrathecal chemotherapy with cytarabine, methotrexate and dexamethasone was attempted.
However, by the end of radiation therapy, the patient presented once again with fever and progressive weakness. The CBC revealed a hemoglobin level of 12.4 g/dl, platelet count of 74 × 109/l and a WBC count of 4.2 × 109/l with 8% blast cells. Subsequent bone marrow aspiration confirmed systemic relapse, with 56% blast cells. Reinduction was attempted using the previously successful induction regimen; however, after two cycles, the patient failed to achieve remission.