Related Experiment Video
Updated: Sep 5, 2025
Identification of OTX1 and OTX2 As Two Possible Molecular Markers for Sinonasal Carcinomas and Olfactory Neuroblastomas
Published on: February 28, 2019
Rhino-Orbital-Cerebral Mycosis and Extranodal Natural Killer or/and T-Cell Lymphoma, Nasal Type
1Division of Dermatology and Mycological Lab, Peking University Third Hospital, Beijing, China.
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.
Insights
Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL-NT) and rhino-orbital-cerebral mycosis (ROCM) share similar symptoms and pathology. Fungal infections, particularly by Mucorales, may play a role in ENKTL-NT development, causing diagnostic confusion.
Area of Science:
- Pathology
- Infectious Diseases
- Oncology
Background:
- Extranodal natural killer/T-cell lymphoma, nasal type (ENKTL-NT) presents as destructive midface syndrome, often linked to Epstein-Barr virus.
- Fungal presence in ENKTL-NT is sometimes noted but often dismissed as secondary infection, despite cases showing recovery with antifungal therapy.
Purpose of the Study:
- To investigate the similarities and potential shared etiology between ENKTL-NT and rhino-orbital-cerebral mycosis (ROCM).
- To clarify the role of fungal infections in the pathogenesis of ENKTL-NT.
Main Methods:
- A systematic literature search of Medline for English-language case reports, letters, reviews, and clinical conferences from 1966 to 2022.
- Utilized MeSH terms for ENKTL-NT and fungal infections, as well as ROCM and fungal infections.
- Appraised 149 articles, extracting relevant themes and subcategories for comparative analysis.
Main Results:
- ROCM and ENKTL-NT exhibit similar clinical, radiological, and pathological features, including destructive facial ulcers, sinusitis, necrosis, and granuloma formation.
- ROCM is primarily caused by Mucorales fungi, while ENKTL-NT is associated with Epstein-Barr virus and sometimes fungi like *Mucor irregularis* and *Rhizopus arrhizus*.
- Both conditions show inflammation, necrosis, and granuloma pathologically; ROCM is defined by fungal detection, whereas ENKTL-NT is characterized by NK/T-cell markers and angioinvasion.
Conclusions:
- ENKTL-NT and ROCM share significant clinical, radiological, and histopathological similarities, suggesting a potential common etiology.
- Fungal pathogens, specifically *Mucor irregularis* and *Rhizopus arrhizus*, are implicated in both ENKTL-NT and ROCM, explaining diagnostic confusion.
- The findings highlight the crucial role fungi may play in the development of ENKTL-NT/ROCM diseases.
