ISOLATED SPHENOIDAL HISTOPLASMOSIS IN A NEUTROPENIC PATIENT WITH ACUTE MYELOID LEUKEMIA: A DIAGNOSTIC AND THERAPEUTIC CHALLENGE

Invasive fungal infections (IFIs) are a major cause of morbidity and mortality in patients undergoing intensive chemotherapy for acute myeloid leukemia (AML). Histoplasma capsulatum, a dimorphic fungus, usually causes pulmonary disease after inhalation. Isolated sphenoidal involvement without pulmonary manifestations is exceedingly rare and diagnostically challenging. We report a case of sphenoidal histoplasmosis presenting as invasive fungal sinusitis during AML induction in a neutropenic patient. A 37-year-old woman was diagnosed with acute myeloid leukemia with monocytic differentiation (AML-M5) and started induction chemotherapy with the 7+3 regimen (cytarabine and daunorubicin) in April 2023. During medullary aplasia, she developed febrile neutropenia, managed with broad-spectrum antibiotics and amphotericin B due to high suspicion of invasive aspergillosis, with further clinical and radiologic improvement. Later during hospitalization, she developed a new febrile episode of unknown origin, along with progressive frontal headache, facial edema, and purulent rhinorrhea. Paranasal sinus CT revealed pansinusitis and sphenoidal bone erosion, suggestive of fungal sinusitis. Endoscopic sphenoidal biopsy was performed without complications. Histopathology revealed numerous intracellular yeast-like organisms staining positively with PAS and Grocott-Gomori methenamine silver, consistent with Histoplasma spp. No necrosis, granulomas, or leukemic infiltration were seen. Fungal cultures were negative. A diagnosis of localized sphenoidal histoplasmosis was established, and oral itraconazole was initiated, with progressive clinical improvement. The patient remained under close infectious surveillance, with full resolution of symptoms. She later received reinduction chemotherapy with the MITO-FLAG protocol (mitoxantrone, fludarabine, high-dose cytarabine) without recurrence of fungal disease. She ultimately progressed to refractory leukemia and died of multiorgan failure, unrelated to the resolved infection. Localized histoplasmosis of the paranasal sinuses is exceptionally rare, particularly in immunocompromised patients with hematologic malignancies. Sphenoidal involvement with bone erosion typically raises suspicion for Aspergillus spp. or Mucorales, more common causes of invasive fungal sinusitis. In contrast, H. capsulatum rarely causes isolated sinonasal disease, and sphenoidal presentation without lung involvement (as in this case) is highly atypical. Diagnosis is challenging due to nonspecific symptoms, overlapping radiologic features, and frequent negative cultures. Histopathology with fungal-specific stains was essential for definitive diagnosis in this case. This report underscores the need for clinical vigilance regarding uncommon fungal presentations in AML, especially when empiric antifungal therapy fails. Although fungal culture is the standard reference, tissue histopathology may be the only reliable diagnostic method in localized histoplasmosis. Therefore, isolated sphenoidal histoplasmosis, though rare, should be considered in neutropenic patients with refractory sinonasal symptoms, particularly in endemic areas. Given the low sensitivity of cultures and nonspecific imaging, histopathologic confirmation remains critical. This case highlights the diagnostic value of early endoscopic evaluation and broad differential consideration in immunosuppressed hosts.