Mucormycosis (previously known as zygomycosis) encompasses infections caused by filamentous fungi of the order Mucorales, including Mucor, Rhizopus, Lichtheimia (previously known as Absidia), Cunninghamella, Apophysomyces, Rhizomucor and Saksenaea. Pulmonary involvement is common; a known risk factor is underlying hematologic malignancy. Rhino-orbito-cerebral mucormycosis is associated with underlying diabetes. Soft tissue infection and disseminated disease may also occur. Other risk factors for mucormycosis include solid organ transplantation, hematopoietic stem cell transplantation, immunosuppressive medications (including everolimus), COVID-19 (especially in India, where the incidence of mucormycosis is 70 times higher than the rest of the world) and trauma (for cutaneous infection). It has been suggested that prior treatment with voriconazole for other fungal infections predisposes to mucormycosis since voriconazole does not have activity against the Mucorales.

Imaging findings of pulmonary mucormycosis include the reverse halo sign (ground-glass opacity surrounded by consolidation), the halo sign, consolidation alone, pleural effusion, nodules, masses and cavitation. None of these features are specific for mucormycosis, and many of them also occur in pulmonary aspergillosis.

The diagnosis of mucormycosis is made by histology, cultures or PCR. Extensive necrosis and vascular invasion are common. In the lung, necrotizing granulomatous inflammation is most commonly caused by mycobacteria or fungal yeasts; it is not common with fungal hyphae but is well documented with certain forms of pulmonary aspergillosis, especially the semi-invasive or chronic necrotizing variants. A distinctive variant of pulmonary aspergillosis mimicking lung cancer characterized by PET-positive solid lung nodules in the upper lobes of smokers with emphysema has been described recently.

The treatment of choice for mucormycosis is liposomal amphotericin B, and surgery may also be required. Mortality ranges from low (in immunocompetent patients) to 40-50% in diabetes and hematologic malignancies, to as high as 76% in those with hematopoietic cell transplantation. 

Take home message for trainees:

Dermawan JK, Ghosh S, Mukhopadhyay S. Expanding the spectrum of chronic necrotizing (semi-invasive) aspergillosis: a series of 8 cases presenting as radiologically solid lung nodules mimicking malignancy. Histopathology 2020;76(5):685-697.