PMC9248758_01
PMC9248758_02
"Extranodal natural killer/T-cell lymphoma, nasal type/rhino-orbital-cerebral mycosis." Mucor irregularis angioinvasion and angiodestruction (H&E, original magnification x100).
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F1
Angioinvasive, angiocentric, and angiodestructive infiltration is a well-known pathological feature of ENKTL-NT and ROCM (Figures 1-3). Sometimes, hyphae and spores were seen growing in the artery lumens, on the artery walls, and in the tissues along the destructed arteries (Figures 1-3). Angioinvasion, angiocentricity, angiodestruction, and onion-skin lesions could be observed involving destroyed artery, and sometimes hyphae could be seen on the artery wall (Figures 1-4). If branched and septate hyphae are present, the fungus is non-Mucorales, likely an Aspergillus sp., Alternaria spp., and other non-Mucoralean fungi (Figures 1-6).
"Extranodal natural killer/T-cell lymphoma, nasal type/rhino-orbital-cerebral mycosis." Broad thin-walled hyphae of Rhizopus arrhizus (H&E, original magnification x400).
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F2
Angioinvasive, angiocentric, and angiodestructive infiltration is a well-known pathological feature of ENKTL-NT and ROCM (Figures 1-3). Sometimes, hyphae and spores were seen growing in the artery lumens, on the artery walls, and in the tissues along the destructed arteries (Figures 1-3). Angioinvasion, angiocentricity, angiodestruction, and onion-skin lesions could be observed involving destroyed artery, and sometimes hyphae could be seen on the artery wall (Figures 1-4). If branched and septate hyphae are present, the fungus is non-Mucorales, likely an Aspergillus sp., Alternaria spp., and other non-Mucoralean fungi (Figures 1-6).
Numerous spores of Aspergillus sydowii in the artery lumen and artery wall in rhino-orbital-cerebral mycosis (periodic acid-Schiff staining, original magnification x1,000).
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F3
Thrombosis of the cavernous sinus, visible as an enhanced mass or filling defect, is the striking feature in ROCM that can be seen in ENKTL-NT (Supplementary Figure 3). Angioinvasive, angiocentric, and angiodestructive infiltration is a well-known pathological feature of ENKTL-NT and ROCM (Figures 1-3). Sometimes, hyphae and spores were seen growing in the artery lumens, on the artery walls, and in the tissues along the destructed arteries (Figures 1-3). Angioinvasion, angiocentricity, angiodestruction, and onion-skin lesions could be observed involving destroyed artery, and sometimes hyphae could be seen on the artery wall (Figures 1-4). If branched and septate hyphae are present, the fungus is non-Mucorales, likely an Aspergillus sp., Alternaria spp., and other non-Mucoralean fungi (Figures 1-6).
Branched and septate hyphae of Penicillium sp. in the cavernous sinus of rhino-orbital-cerebral mycosis (periodic acid-Schiff staining, original magnification x400).
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F4
Angioinvasion, angiocentricity, angiodestruction, and onion-skin lesions could be observed involving destroyed artery, and sometimes hyphae could be seen on the artery wall (Figures 1-4). If branched and septate hyphae are present, the fungus is non-Mucorales, likely an Aspergillus sp., Alternaria spp., and other non-Mucoralean fungi (Figures 1-6). By comparing multiple specimens of biopsied samples obtained from the edge of newly infected tissues with those obtained from necrotic tissues that were infected for a long period, we found that typical hyphae could be seen clearly only in the newly infected tissues but were hardly recognized in the necrotic tissues (Figures 4-7, 13).
Aspergillus heads in the cavernous sinus of rhino-orbital-cerebral mycosis (periodic acid-Schiff staining, original magnification x400).
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F5
Fungal thromboses and artery inclusion were seen in the newly involved tissues, some of which were ischemic necrosis (Figures 5, 6). If branched and septate hyphae are present, the fungus is non-Mucorales, likely an Aspergillus sp., Alternaria spp., and other non-Mucoralean fungi (Figures 1-6). By comparing multiple specimens of biopsied samples obtained from the edge of newly infected tissues with those obtained from necrotic tissues that were infected for a long period, we found that typical hyphae could be seen clearly only in the newly infected tissues but were hardly recognized in the necrotic tissues (Figures 4-7, 13).
"Extranodal natural killer/T-cell lymphoma, nasal type-orbital-cerebral mycosis." Distorted, broken, and disintegrated hyphae of Mucor irregularis (H&E, original magnification x400).
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F6
Fungal thromboses and artery inclusion were seen in the newly involved tissues, some of which were ischemic necrosis (Figures 5, 6). If branched and septate hyphae are present, the fungus is non-Mucorales, likely an Aspergillus sp., Alternaria spp., and other non-Mucoralean fungi (Figures 1-6). By comparing multiple specimens of biopsied samples obtained from the edge of newly infected tissues with those obtained from necrotic tissues that were infected for a long period, we found that typical hyphae could be seen clearly only in the newly infected tissues but were hardly recognized in the necrotic tissues (Figures 4-7, 13).
"Extranodal natural killer/T-cell lymphoma, nasal type-orbital-cerebral mycosis." Mucor irregularis-induced atypical hyperplasia (H&E, original magnification x200).
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F7
Granulation with atypical hyperplasia with high Ki-67 expression is usually seen in ENKTL-NT that could either represent neoplastic proliferation (Figures 7-9) or as a marker of activated NK and/or T cells in host defense against pathogens. Recently, we reported the inducement of proliferation in ENKTL-NT patients with M. irregularis or R. arrhizus infection (Figures 7-9). By comparing multiple specimens of biopsied samples obtained from the edge of newly infected tissues with those obtained from necrotic tissues that were infected for a long period, we found that typical hyphae could be seen clearly only in the newly infected tissues but were hardly recognized in the necrotic tissues (Figures 4-7, 13).
"Extranodal natural killer/T-cell lymphoma, nasal type/rhino-orbital-cerebral mycosis." Mucor irregularis-induced angioinvasion (H&E, original magnification x200).
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F8
Granulation with atypical hyperplasia with high Ki-67 expression is usually seen in ENKTL-NT that could either represent neoplastic proliferation (Figures 7-9) or as a marker of activated NK and/or T cells in host defense against pathogens. Recently, we reported the inducement of proliferation in ENKTL-NT patients with M. irregularis or R. arrhizus infection (Figures 7-9). In both M. irregularis and R. arrhizus related ROCM/ENKTL-NT cases, T-cell and NK-cell infiltration were observed (Figures 8-12).
"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 x200).
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F9
Granulation with atypical hyperplasia with high Ki-67 expression is usually seen in ENKTL-NT that could either represent neoplastic proliferation (Figures 7-9) or as a marker of activated NK and/or T cells in host defense against pathogens. Recently, we reported the inducement of proliferation in ENKTL-NT patients with M. irregularis or R. arrhizus infection (Figures 7-9). In both M. irregularis and R. arrhizus related ROCM/ENKTL-NT cases, T-cell and NK-cell infiltration were observed (Figures 8-12).
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 x200).
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F10
In both M. irregularis and R. arrhizus related ROCM/ENKTL-NT cases, T-cell and NK-cell infiltration were observed (Figures 8-12).
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 x200).
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F11
In both M. irregularis and R. arrhizus related ROCM/ENKTL-NT cases, T-cell and NK-cell infiltration were observed (Figures 8-12).
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 x200).
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F12
In both M. irregularis and R. arrhizus related ROCM/ENKTL-NT cases, T-cell and NK-cell infiltration were observed (Figures 8-12).
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 x200).
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F13
By comparing multiple specimens of biopsied samples obtained from the edge of newly infected tissues with those obtained from necrotic tissues that were infected for a long period, we found that typical hyphae could be seen clearly only in the newly infected tissues but were hardly recognized in the necrotic tissues (Figures 4-7, 13).
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 x200).
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F14
In M. irregularis or R. arrhizus cases, the proliferation was measured using the Ki-67 labeling index which was observed to be as high as 50%, accompanied by high loads of fungal elements (Figure 14).