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. 2022 Jun 17:9:851208.
doi: 10.3389/fmed.2022.851208. eCollection 2022.

Rhino-Orbital-Cerebral Mycosis and Extranodal Natural Killer or/and T-Cell Lymphoma, Nasal Type

Dong Ming Li  1 , Li De Lun  2
Affiliations

Rhino-Orbital-Cerebral Mycosis and Extranodal Natural Killer or/and T-Cell Lymphoma, Nasal Type

Dong Ming Li et al. Front Med (Lausanne). .

Abstract

Background: Extranodal natural killer/T-cell lymphoma, nasal type is a syndrome of middle face destruction with an association to Epstein-Barr virus. Fungi have been recovered from the diseased tissue now and then but were often seen as a lymphoma-associated secondary infection. However, there are ENKTL-NT cases with the recoveries of fungi and complete recovery with antifungal therapy, which are quite similar to rhino-orbital-cerebral mycosis (ROCM) that often confuses the physicians.

Methods: We searched Medline for English-language manuscripts limited to "human" and "case reports," "letters," "reviews," and "clinical conferences" from 1966 to 2022. We used MeSH terms "lymphoma, extranodal nk-t-cell" [MeSH Terms] or "lethal midline granuloma" [MeSH Terms], in combination with MeSH terms "microbiology" [subheading] or "microbiology" [all fields] or "fungi" [all fields] or "fungi" [MeSH Terms] for ENKTL-NT with infections. We used MeSH terms "Mycoses" in combination with "Nose" [Mesh] OR "Orbital Diseases" [Mesh] for rhino-orbital-cerebral fungal infections.

Results: We appraised 149 included articles and extracted references related to ENKTL-NT and/or ROCM. Themes and subcategories were subsequently derived. Our findings revealed that ROCM and ENKTL-NT are characterized by progressive and destructive ulcers in the midline face or rhino-orbital structures. ROCM is mainly caused by fungi in the order of Mucorales, and ENKTL-NT is usually associated with Epstein-Barr virus and sometimes fungi. Radiologically, both are characterized by non-specific features of sinusitis, soft tissue infection, and necrosis. Pathologically, ROCM and ENKTL-NT share the same characteristics of inflammation, necrosis, and granuloma. ROCM is characterized by the detection of fungi in tissue, while ENKTL-NT is typically positive for NK/T-cell markers and cytotoxic granule-associated proteins, proliferation, and vascular damage of angioinvasion, which could be incited by Mucor irregularis and Rhizopus arrhizus in patients and mice.

Conclusion: ENKTL-NT and ROCM share many similarities in clinical presentations, radiology, and histopathology, and might have the same etiology. This may explain why the two diseases are tangled together in the reported cases, and suggests the role that the fungi may play in the development of these ENKTL-NT/ROCM diseases. The reason why ENKTL-NT and ROCM are sometimes confused is that the main pathogens of ROCM, Mucor irregularis and Rhizopus arrhizus, are the fungal causative agents of ENKTL-NT.

Keywords: Rhizopus arrhizus; extranodal nK/T-cell lymphoma; facial destruction; lethal midline granuloma; mucor irregularis; nasal type; rhino-orbital-cerebral mycosis.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
“Extranodal natural killer/T-cell lymphoma, nasal type/rhino-orbital-cerebral mycosis.” Mucor irregularis angioinvasion and angiodestruction (H&E, original magnification ×100).
FIGURE 2
FIGURE 2
“Extranodal natural killer/T-cell lymphoma, nasal type/rhino-orbital-cerebral mycosis.” Broad thin-walled hyphae of Rhizopus arrhizus (H&E, original magnification ×400).
FIGURE 3
FIGURE 3
Numerous spores of Aspergillus sydowii in the artery lumen and artery wall in rhino-orbital-cerebral mycosis (periodic acid-Schiff staining, original magnification ×1,000).
FIGURE 4
FIGURE 4
Branched and septate hyphae of Penicillium sp. in the cavernous sinus of rhino-orbital-cerebral mycosis (periodic acid-Schiff staining, original magnification ×400).
FIGURE 5
FIGURE 5
Aspergillus heads in the cavernous sinus of rhino-orbital-cerebral mycosis (periodic acid-Schiff staining, original magnification ×400).
FIGURE 6
FIGURE 6
“Extranodal natural killer/T-cell lymphoma, nasal type-orbital-cerebral mycosis.” Distorted, broken, and disintegrated hyphae of Mucor irregularis (H&E, original magnification ×400).
FIGURE 7
FIGURE 7
“Extranodal natural killer/T-cell lymphoma, nasal type-orbital-cerebral mycosis.” Mucor irregularis-induced atypical hyperplasia (H&E, original magnification ×200).
FIGURE 8
FIGURE 8
“Extranodal natural killer/T-cell lymphoma, nasal type/rhino-orbital-cerebral mycosis.” Mucor irregularis-induced angioinvasion (H&E, original magnification ×200).
FIGURE 9
FIGURE 9
“Extranodal natural killer/T cell lymphoma, nasal type/rhino-orbital-cerebral mycosis.” Rhizopus arrhizus-induced positive expression of KI67 from granulomatous tissues (envision method, original magnification ×200).
FIGURE 10
FIGURE 10
Extranodal natural killer/T cell lymphoma, nasal type/rhino-orbital-cerebral mycosis.” Rhizopus arrhizus-induced positive expression of CD2 from granulomatous tissues (envision method, original magnification ×200).
FIGURE 11
FIGURE 11
Extranodal natural killer/T cell lymphoma, nasal type/rhino-orbital-cerebral mycosis.” Rhizopus arrhizus-induced positive expression of CD3 from granulomatous tissues (envision method, original magnification ×200).
FIGURE 12
FIGURE 12
Extranodal natural killer/T cell lymphoma, nasal type-orbital-cerebral mycosis.” Rhizopus arrhizus-induced positive expression of CD8 from granulomatous tissues (envision method, original magnification ×200).
FIGURE 13
FIGURE 13
Extranodal natural killer/T cell lymphoma, nasal type-orbital-cerebral mycosis.” Rhizopus arrhizus-induced positive expression of GZMB from granulomatous tissues (envision method, original magnification ×200).
FIGURE 14
FIGURE 14
Extranodal natural killer/T cell lymphoma, nasal type/rhino-orbital-cerebral mycosis.” Rhizopus arrhizus-induced positive expression of TIA1 from granulomatous tissues (envision method, original magnification ×200).
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