Case Report: Rhizopus arrhizus Rhino-Orbital-Cerebral Mycosis and Lethal Midline Granuloma: Another Fungal Etiological Agent

Objective: Both rhino-orbital-cerebral mycosis and lethal midline granuloma (LMG) may result in midline destruction. LMG has now been generally considered as a natural killer/T cell lymphoma, nasal type (ENKTL-NT) with an association of EBV. Fungi have been detected from the diseased tissues now and then but are often considered as lymphoma-associated infections. We previously reported an ENKTL-NT case with Mucor irregularis, which played a causal role in the disease and was involved in the overexpression of Ki67 and CD56 in the mouse experiment. The present study describes a chronic Rhizopus arrhizus infection with immunological parameters that are closely similar to LMG. We aim to explore the relationship of another Mucorales fungus, R. arrhizus, and LMG in a patient and in mice.Methods: Case study and mouse infection modules were designed for our observation. A 35-year-old man with midline face ulcers which was clinically suspected as LMG was selected. Biopsy specimens were sent for lymphoma diagnosis and microbiological detection. The isolated fungus was tested in an ICR mouse model for mycological and histological analyses.Results: Five tissue samples yielded Rhizopus arrhizus. In the pathology, characteristic inflammation, necrosis, and granulation with thin-walled hyphae are observed. Immunohistochemistry showed NK/T cell infiltration (CD3+, CD8+, TIA1+, GZMB+, PRF+, individual CD56+) with hyperplasia (Ki67+) and angioinvasion. The patient recovered completely with amphotericin B. In the murine experiment, R. arrhizus caused angioinvasion with NK/T cell infiltration (CD3+, CD56+, TIA1+, GZMB +, PRF+) with proliferation (Ki67+) and was re-isolated from the infected host.Conclusions: We here describe a mid-face destruction patient, which was diagnosed by the top pathologists in China according to the current criteria of NK/T cell lymphoma, with a negative result for EBV and positive result for R. arrhizus. With a then developed mouse experiment, the R. arrhizus in the diseased lesions was responsible for the NK/T cell infiltration (CD3+, CD8+, CD56+, TIA1+, GZMB+, PRF+), proliferation (Ki67+), and angioinvasion, suggesting another fungal etiological agent for LMG, which could be eradicated with amphotericin B.Limitations: The sample size is not sufficient for statistical analysis. However, our findings are suggestive for the role fungus plays in LMG.

Lethal Midline Granuloma in a 15-Year-Old Girl: A Diagnostic Dilemma

Objective: To report a case of lethal midline granuloma and discuss the diagnostic and treatment dilemma, and management. Methods Design: Case Report Setting: Tertiary Government Hospital Patient: One Results: A 15-year-old girl under treatment for pulmonary tuberculosis presented to the Emergency Room for epistaxis and a nasopalatine lesion. She was managed as a case of nasopalatine osteomyelitis for one month and discharged on antibiotics. She returned due to bleeding after being lost to follow up for 3 more months. Hemostasis, debridement and biopsy yielded atypical cells, possibly lymphoma. Immunohistochemistry confirmed the diagnosis of NK-cell lymphoma. Unfortunately, she expired prior to initiation of chemotherapy. Conclusion: Clinicians must have a high index of suspicion for lethal midline granuloma in chronic, non-healing midline lesions. Multiple biopsies confirm the diagnosis, and earlier initiation of treatment may improve prognosis. Keywords: Granuloma, lethal midline; Lymphoma, extranodal NK-T-cell

Midline Granuloma

<p><strong>Pendahuluan</strong><strong>:</strong></p><p><em>Midline granuloma</em> atau<em> nasal type extranodal T/NK-cell non-Hodgkin’s lymphoma </em>sering menimbulkan berbagai permasalahan.</p><p><strong>Pembahasan</strong><strong>:</strong></p><p><em>Midline granuloma</em> adalah kelainan bagian tengah wajah dengan ciri khas destruksi dan ulserasi yang progresif, meliputi hidung, sinus paranasal, palatum, mata, serta jaringan lunak wajah.Etiologi dan patofisiologi belum jelas antara reaksi radang dan tumor.<em> Midline granuloma</em> termasuk dalam penyakit granuloma hidung berdasarkan pemeriksaan biopsi, sedangkan<em>The Revised European American Lymphoma</em> (REAL) / <em>Wordl Health Organization</em> (WHO) mengelompokkan <em>midline granuloma</em> dalam <em>extranodal </em><em>T/NK-cellnon-Hodgkin’s lymphoma</em> berdasarkan pemeriksaan imunohistologi. Infeksi virus Epstein-Barr (EBV) 90-100% terlibat dalam proses pembentukan tumor.Diagnosis sulit dan diagnosis banding luas, sehingga diperlukan anamnesis dan pemeriksaan yang lengkap, terutama biopsi, imunohistologi, dan sitogenetik didapatkan gambaran nekrosis disertai destruksi dan ulserasi pembuluh darah, radang dengan infiltrat sel pleomorfik, CD56+, CD3+, protein sitotoksik+, dan EBV+. Penatalaksanaan dengan radioterapi, kemoterapi, transplantasi sumsum tulang, dan imunoterapi. Komplikasi dapat terjadi lokal maupun sistemik dengan penyebaran ke sirkulasi darah tepi, jaringan lunak, paru-paru, hati, kulit, saluran pencernaan, testis, saraf pusat, dan sumsum tulang. Prognosis buruk, hanya kurang dari 50% penderita yang berespon lengkap setelah kemoterapi dan radioterapi. Prognosis dapat dinilai dengan <em>International Prognostic Index</em> (IPI).</p><p><strong>S</strong><strong>impulan:</strong></p><p>Diagnosis<em>Midline granuloma</em>sulit, penatalaksanaan sering terlambat, sedangkan sifatnya yang progresif menimbulkan berbagai komplikasi, sehinggasemakin memperburuk prognosis.</p><p><strong> </strong></p><strong>Kata Kunci: midline granuloma, EBV, biopsi, imunohistologi, sitogenetik</strong>

Linfoma de células T/Natural Killer extranodal, tipo nasal

Introducción: El linfoma de células T/Natural Killer (T/NK) extranodal, tipo nasal, es un linfoma extra-ganglionar poco frecuente, con extensión a lo largo de la línea media facial, rápidamente progresivo, catastrófico y de mal pronóstico, por lo que también se le conoce como “granuloma letal de la línea media”. Objetivo: El propósito de este artículo es revisar la literatura disponible y actualizada sobre el linfoma de células T/NK extranodal, tipo nasal: manifestaciones clínicas, estándares de enfoque, diagnóstico, pronóstico y tratamiento. Diseño: Revisión Narrativa de la literatura. Metodología: Revisión de la literatura mediante búsqueda selectiva por términos MeSH: Extranodal Natural Killer /T cell lymphoma, nasal type, lethal midline granuloma, de las bases de datos: MEDLINE, Current Contents, Cochrane, Pubmed y Scielo, entre los años 2000 y 2014. Resultados: Se revisaron 36 artículos según los requerimientos de los objetivos. El linfoma de células T/NK es una neoplasia rápidamente progresiva, destructiva y de mal pronóstico excepto en los casos donde el diagnóstico ha sido oportuno. Conclusiones: El diagnóstico y tratamiento tempranos del linfoma de células T/NK extranodal, tipo nasal, son las únicas herramientas para mejorar el mal pronóstico y gran afectación en la calidad de vida de los pacientes con esta enfermedad.