A clinicopathological study of pulmonary mucormycosis in cancer patients: Extensive angioinvasion but limited inflammatory response
Introduction
Filamentous fungi of the order Mucorales have recently emerged as important pathogens in patients with hematologic malignancies.1, 2 In many cancer centers, mucormycosis is now the second most common invasive mold infection in hematologic cancer patients; in this population, mucormycosis typically presents as a sinopulmonary infection, and is associated with a mortality rate of 66%.1, 3
The clinical immunobiology of pulmonary mucormycosis (PMM) remains undefined. Recent studies of invasive pulmonary aspergillosis, a more common pulmonary mycosis, demonstrate that the pattern of tissue injury and immune response depend on the type of immunosuppression in the host.4, 5, 6, 7 Specifically, patients with neutropenia induced by cytotoxic drugs have numerous hyphal elements and frequent angioinvasion but scant inflammatory infiltrates in their lungs.4, 5, 6, 7 In contrast, non-neutropenic patients who are immunosuppressed with corticosteroids have a low pulmonary fungal burden and extensive tissue infiltration by polymorphonuclear leukocytes.4, 5, 6, 7
To our knowledge, no studies have evaluated the clinicopathological characteristics of PMM in patients with different forms of immunosuppression. Herein, we correlate the patterns of tissue injury and pulmonary inflammatory responses with different immunologic backgrounds among cancer patients with mucormycosis.
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Study design
We identified patients with proven PMM who had undergone pulmonary biopsies or autopsies at The University of Texas M. D. Anderson Cancer Center (Houston, TX) between January 1990 and December 2007. Hyphae were considered typical of Mucorales if they were broad (10–25 μm), non-septated or pauci-septated, and ribbon-like in appearance and/or displayed right-angle branching. Cases with evidence of pulmonary fungal or bacterial coinfection were excluded from the final analysis.
Slides of pulmonary
Results
Twenty patients with PMM were identified. The median patient age was 52 years (range, 15 to 79 years); 14 patients (70%) were male. All but 1 patient (95%) had hematologic malignancies. Thirteen patients (65%) were neutropenic at the time of diagnosis, and 14 (70%) had received high-dose corticosteroids. Six patients (30%) were allogeneic hematopoietic stem cell transplantation (HSCT) recipients; all HSCT recipients had graft-versus-host disease (GVHD) and were receiving calcineurin inhibitors.
Discussion
Clinicopathologic studies may offer insights into the pathobiology of invasive mycoses. Such studies have helped elucidate the host–pathogen interactions of invasive pulmonary aspergillosis by demonstrating divergent patterns of tissue damage and inflammation in neutropenic versus non-neutropenic hosts.4, 5 However, histopathologic data about PMM in patients with different forms of immunosuppression is lacking. We studied the histopathologic features of PMM in 20 cancer patients. Angioinvasion,
Conflict of interest
The authors have no conflict of interest.
Acknowledgements
We dedicate this work to the memory of Dr. Mario Luna, a pioneer in the study of the histopathologic characteristics of fungal infections in cancer patients.
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