Lethal Midline Granuloma Research Articles

An Unusual Presentation of Midline Lethal Granuloma.

Extranodal natural killer T-cell lymphoma, nasal type (ENKTCL), is a rare form of non-Hodgkin lymphoma that is strongly related to Epstein-Barr Virus (EBV) infection and commonly presents as "midline lethal granuloma." Herein, we report a middle-aged lady who presented with a two-week history of fever, sore throat and constitutional symptoms. Intraoral examination revealed a lacerated soft palate with an ulcerated uvula. A diagnosis of ENKTCL was confirmed through deep biopsies under general anaesthesia supplemented with a positive serum EBV genome. Unfortunately, she succumbed due to disease progression with left frontal brain metastasis with concurrent pulmonary tuberculosis before treatment was completed. The recommended treatment is multimodality with L-asparaginase-containing regimes chemotherapy in an advanced stage, relapsed, or refractory ENKTCL for better outcomes. The quantification of circulating plasma EBV deoxyribonucleic acid (DNA) is helpful as the baseline of tumour load and a biomarker for monitoring treatment response and prognostication. We advocate repeated and deeper core tissue biopsies.

NASAL NECROSIS ASSOCIATED WITH POSITIVE P-ANCA: A DIAGNOSTIC AND MANAGEMENT CHALLENGE

A 33-year-old woman developed necrosis in the left nostril. Granulomatosis with polyangiitis, tuberculosis, lymphoma, lethal midline granuloma, and vasculitis were the diagnostic hypotheses. Lymphoma and tuberculosis were ruled out after a normal blood count exam, negative nasal bacilloscopy, and positive p-ANCA. Multiple biopsies were performed in the left nostril at different locations and intervals. Histopathologic analysis ruled out malignancy, and clinically, the hypothesis of unspecified vasculitis with positive p-ANCA was sustained. To treat the disease and relieve pain, cyclophosphamide, haloperidol, morphine, methadone, and carbamazepine were prescribed. Despite therapeutics, there was a progression of nasal necrosis and infection, with intense pain, tooth mobility, and negative pulp thermal test of the upper anterior teeth. Thus, the patient started receiving radiotherapy and was prescribed methotrexate, prednisone, venlafaxine, and gabapentin. Approximately 2 years after the initial manifestation, the patient had persistent pain, increased nasal necrosis, and evolution of visual and auditory changes despite the therapeutic protocol. Nonspecific p-ANCA-positive maxillofacial lesions are infrequently reported in oral medicine literature and represent a multiprofessional diagnosis and therapeutic challenge.

Clinical spectrum of a syndromic diagnosis: Lethal midline granuloma

Clinical spectrum of a syndromic diagnosis: Lethal midline granuloma

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

BackgroundExtranodal 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.MethodsWe 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.ResultsWe 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.ConclusionENKTL-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.

A rare case of lethal midline granuloma posing a diagnostic challenge in COVID times and the response to chemotherapy

A rare case of lethal midline granuloma posing a diagnostic challenge in COVID times and the response to chemotherapy

A Fatal Ulceration of the Palate

Palatal necrosis seen clinically often has a differential diagnosis, such as necrotizing sialometaplasia, extranodal natural killer/T-cell lymphoma (ENKL), primary adenocarcinoma, squamous cell carcinoma, subacute necrotizing sialadenitis (SANS), and secondary syphilis. This case report will discuss and explore the unique disease of extranodal natural killer/T-cell lymphoma (ENKL), formerly known as midline lethal granuloma. ENKL is a rare mature and aggressive neoplasm that accounts for less than 1% of cutaneous lymphomas.2 It is more common in males than females, appears as an ulcerated nodule, and median survival rate is usually between 6-30 months.2ENKL is strongly associated with Epstein Barr Virus and usually seen in Asia and South and Central America with rarity in North America.1 Clinically, rapidly progressive inflammation and necrosis are observed and, on histology, CD56 and CD3 are expressed on malignant cells.1 Prognosis is generally poor, manifests mostly in the nasal and oral region, but can also be seen in dermis, intestines and testis.1,2The authors report a case of a 36-year-old Hispanic male presenting to the emergency room with a 3-month history of an ulcerated palate, which has progressively worsened. Excisional biopsy was completed that returned positive for ENKL.

HISTOPLASMOSIS IN YOUNG MAN WITH HIV/AIDS: CASE REPORT

Histoplasmosis is a fungal systemic infectious disease, which affects humans, caused by Histoplasma capsulatum. We report a case of a male with HIV/AIDS, 28 years old, feoderma, referred to the stomatology center with complaining of several lumps in his mouth. The patient was under severe immunosuppression and not adherent to HIV-treatment. Intraoral examination showed a tumor with papillary surface reaching all extension of palate presenting a painful ulcerated lesion in the middle, which has perforated the palate. The clinical diagnosis hypotheses were Paracoccidioidomycosis and Lethal midline granuloma. An incisional biopsy and histopathological specimens, stained with HE, and special colorations with Giemsa (Negative) and PAS (Positive) had led to the diagnosis of histoplasmosis. The patient was referred to treatment with an infectious disease specialist with good follow-up. This case reinforces the importance of stomatology professional in diagnosis and direction of treatment cases of systemic diseases with exclusive presentation in the mouth. Histoplasmosis is a fungal systemic infectious disease, which affects humans, caused by Histoplasma capsulatum. We report a case of a male with HIV/AIDS, 28 years old, feoderma, referred to the stomatology center with complaining of several lumps in his mouth. The patient was under severe immunosuppression and not adherent to HIV-treatment. Intraoral examination showed a tumor with papillary surface reaching all extension of palate presenting a painful ulcerated lesion in the middle, which has perforated the palate. The clinical diagnosis hypotheses were Paracoccidioidomycosis and Lethal midline granuloma. An incisional biopsy and histopathological specimens, stained with HE, and special colorations with Giemsa (Negative) and PAS (Positive) had led to the diagnosis of histoplasmosis. The patient was referred to treatment with an infectious disease specialist with good follow-up. This case reinforces the importance of stomatology professional in diagnosis and direction of treatment cases of systemic diseases with exclusive presentation in the mouth.

Lethal midline granuloma

Lethal midline granuloma is a syndrome with ulcerative vegetative lesion destructing nose, paranasal sinus and palate. Nasal type T-NK cells Lymphoma is often related with this syndrome and without treatment the mortality tax is around 100%. There is association with systemic infection with Epstein Barr Virus. The treatment is the association of radiotherapy and chemotherapy. A 70-year-old male patient presented nose congestion and bleeding with fast growing of an ulcerative lesion in the nose. The computer tomography showed destruction of nose septum and right sinuses. The biopsy diagnosis was nasal type T-NK cells lymphoma.

Lethal Midline Granuloma: An Enigma in Diagnosis-A Rare Case Report.

Lethal midline granuloma is a rare disease, characterised by progressive unrelenting necrosis and mutilation of nose, midline facial tissues and other respiratory passages. This particular type of disease is heterogeneous in its pathogenesis, non-specificity of symptoms obscures timely and correct diagnosis and is responsible for delay in of treatment which can be detrimental as this disease calls for immediate intervention. We present a case report of 60year old female who gave short one-month history of clinical symptoms.

Extranodal nasofacial natural killer/T-Cell lymphoma often missed by clinician

Aim: This study aims to review the current literature and to focus on etiopathogenesis, clinical profile, diagnosis, and treatment of extranodal nasofacial natural killer (NK)/T-cell lymphoma. Materials and Methods: It is based upon the available literatures from PubMed, Scopus, and Google scholar with the keywords: etiopathogenesis, clinical pictures, diagnostic methods, and current treatment of extranodal nasofacial NK/T-cell lymphoma from 2002 to 2017. Results: Primary nasofacial lymphoma is a rare form of malignancy in head and neck area. Extranodal nasofacial NK/T-cell lymphoma is an unusual clinical entity, which is an aggressive entity of non-Hodgkin's lymphoma with distinct clinicopathological pictures. It is possibly associated with Epstein–Barr virus infection. It is highly aggressive disease with poor prognosis. Nasofacial NK/T-cell lymphoma or lethal midline granuloma is often associated with destruction of midface and surrounding areas such as orbit, paranasal sinuses, and palate. The clinical picture is highly variable, often missed by clinician and depends on location and histopathological type of the lesion. Histopathological and immunohistochemistry are important tools for diagnosis of nasofacial NK/T-cell lymphoma. Histopathological picture shows angiocentric and angiodestructive pattern of tumor cells which often mimic vasculitis. Radiotherapy is the treatment of choice which improves quality and longevity of life whereas addition of chemotherapy gives additional benefit to the patients. Conclusion: Practicing physicians and otorhinolaryngologist need to be aware of this nonspecific presentation of lesion to prevent delay in diagnosis. Early diagnosis and intervention prolongs the survival of the patients.

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

Extranodal NK/T-Cell Lymphoma, Nasal Type, Presenting as Refractory Pseudomonas aeruginosa Facial Cellulitis.

Extranodal natural killer T-cell lymphoma, nasal type (ENKL), formerly called lethal midline granuloma or angiocentric T-cell lymphoma, is a predominantly extranodal non-Hodgkin lymphoma characterized by vascular damage, necrosis, and an association with Epstein-Barr virus. In the United States, it is more frequently seen in Asian, Asian Pacific Islander, and Hispanic descent populations and is more prevalent in males in their fifth decade. Clinical presentation of NK nasal lymphoma most commonly involves epistaxis; obstruction; discharge; destructive mass in sinuses, palate, and nose; and skin ulceration. These symptoms can mimic invasive fungal infections and other sinonasal disorders. Furthermore, ENKL has a broad cytologic spectrum and induces a mixture of inflammatory cells, causing difficulty in establishing the diagnosis, especially in initial biopsies. We present a case of refractory Pseudomonas aeruginosa facial cellulitis in a young woman whose treatment course was complicated by septic shock and resistance to multiple antibiotics, resulting in a delayed diagnosis of ENKL nasal type.

Lethal midline granuloma: a case report

The rarity of lethal midline granuloma and lack of knowledge by the majority of clinicians about this disease makes this disease a difficult entity to diagnose. Nonspecific symptoms of this disease present obstacles in correct diagnosis and lead to a delay in proper treatment. Surgeons play a limited role in this condition. We present a case report of a 38-year-old man with this rare condition.

Nasal NK/T-cell lymphoma: A tragic case

IntroductionNasal NK/T-cell lymphoma is a rare clinicopathological entity, formerly called midline lethal granuloma. Following progress in histology and the routine use of immunohistochemistry, nasal NK/T-cell lymphoma was recognized as a distinct entity by WHO in 2001. Case reportThe authors report the case of a 22-year-old, insulin-dependent diabetic woman, who presented with mid-facial inflammatory swelling following facial trauma, initially diagnosed and treated as cellulitis of the face. The subsequent course was rapidly progressive and fatal, with the development of midline destructive disease. Histological examinations concluded on NK/T-cell lymphoma. DiscussionThe various differential diagnoses of NK/T-cell lymphoma include gangrenous cellulitis, invasive mycotic rhinosinusitis, Wegener's granulomatosis, actinomycosis, and facial T-cell lymphoma. The clinical presentation of this case was atypical, resulting in delayed diagnosis and treatment. Treatment is based on radiotherapy and chemotherapy, but the prognosis remains very poor even when treatment is rapidly initiated.

Lethal Midline Granuloma: A Diagnostc Dilemma

ABSTRACTLethal midline granuloma (Stewart's syndrome, midline reticulosis) earlier was a name given to all progressive destructive lesions involving the nose, paranasal sinuses, hard palate, face, orbit, and upper airway. With the advent of immunohistochemistry, it is evident that it comprises a heterogenous group of disorders including non-Hodgkin lymphoma, Wegener's granulomatosis, and various granulomatous conditions which can often be encountered with dilemma of diagnosis.How to cite this articleMittal P, Singh I, Gupta D. Lethal Midline Granuloma: A Diagnostc Dilemma. Int J Otorhinolaryngol Clin 2016;8(2):60-61.

Imaging Case: NK/T-Cell Lymphoma, Nasal Type.

Peripheral T-cell lymphomas are a group of heterogeneous disorders and according to WHO classification, are categorized into nodal and extranodal forms. NK/T-cell lymphoma, nasal type, is a subtype of extranodal peripheral T-cell lymphoma and commonly presents as a midfacial destructive lesion. This disorder is more prevalent in Asia and South America and has a strong association with Epstein Barr Virus infection. Invasion of vessel walls by lymphoid cells, which is known as angiocentricity, is characteristic of nasal type NK/T-cell lymphoma. The tumor cells express CD2 and CD56 antigens; but not CD3. The nasal cavity is the mostly frequently affected site. Other commonly affected sites include palate and upper airways. On cross sectional imaging, the nasal involvement is seen as a diffuse sheet-like mucosal thickening along the nasal turbinates and septum or as a destructive midline mass (Figs 1,2). The latter form was previously described as a lethal midline granuloma or polymorphic reticulosis. The mass frequently extends into subcutaneous tissues of nasal ala and buccinator space (Fig.3). Regional lymphadenopathy is usually not seen. The radiological differential diagnoses for a midline nasal cavity mass include squamous cell carcinoma, minor salivary gland tumor, Wegener’s granulomatosis, and fungal infections. The imaging appearances of NK/T-cell lymphoma are often indistinguishable from the above mentioned conditions. However, predilection to involve both sides of the nasal cavity and tendency to spread as a diffuse thin sheet-like soft tissue along the walls of the nasal cavity enveloping the nasal turbinates and nasal septum favour the diagnosis of NK/T-cell lymphoma. Contiguous extension into the nasopharynx, palate, upper airways, and subcutaneous tissues can also suggest the possibility of NK/T-cell lymphoma, nasal type (Fig.4). T-cell lymphoma, compared to B-cell lymphoma, has an aggressive course and poor prognosis. The median survival was reported to be 12 months, even in patients showing a localised disease. Extranodal NK/T-cell lymphoma is sensitive to both chemo- and radiotherapy. Methotrexate and anthracycline based chemotherapy regimen (SMILE protocol) with infield radiotherapy is the recommended protocol for treatment of NK/T-cell lymphoma.

Midline lethal granuloma: Case report and review of literature

Lethal midline granuloma syndrome is a clinical term used generally to describe a rare clinical entity, of unknown aetiology, characterized by progressive destruction of face, nose, para-nasal sinuses, and palate, oral and para-oral structures. Diagnosis is often difficult and requires expert clinical and histopathological examination of the lesion. A case of advanced high–grade lymphoma is reported as it was misdiagnosed and not treated properly for several months. After final diagnosis, a combined radio and chemotherapy were offered to the patient, but unfortunately the patient died because there was no response to treatment.

NK/T Cell Lymphoma, Nasal Type

NK/T cell lymphoma of the nasal type is an aggressive lymphoma commonly presenting as a destructive process of the facial midline, often demonstrating clinical and histologic features of necrosis and angioinvasion. It was initially categorized as an angiocentric lymphoma in the Revised European-American Lymphoma (REAL) classification. It has been recategorized as extranodal NK/T cell lymphoma in the World Health Organization classification of lymphoid neoplasms. Historically these tumors were considered part of “midline lethal granuloma.” This entity frequently arises in extranodal regions, especially the nasal or paranasal sinuses.

The Serum Spectrum Of Cytokines In Patients With NK/T-Cell Lymphoma and Its Cilincial Significance In Survival

BackgroudNatural/killer T-cell lymphoma (NK/TCL) was previously named as lethal midline granuloma. Most patients presented with inflammatory symptoms such as fever and necrosis, which was associated with poor survival. It is still unclear what exactly the role of severe inflammation on the pathogenesis and development of NK/TCL, and there has been few report about the serum cytokines profile and its clinical significance in patients with NK/TCL. Patients and MethodsFrom January 2005 to December 2012, the serums and paraffin embed tissues of 59 patients with NK/TCL in Sun Yat-sen University Cancer Center were collected. The Human Cytokine 25-Plex Panel kits (Invitrogen) were used to detect the serum level of the cytokines. And the real-time quantitative polymerase chain reaction (RT-PCR) was employed for detection of the plasma EBV-DNA copies. ResultsOverall, fifty-nine patients with NK/TCL were analyzed. There were 44 male patients. The median age was 39 years (range 10-69 years). There were 37, 5 and 17 patients diagnosed as stage I, II and IV disease, respectively. Forty-one patients had B symptoms and ten patients were diagnosed hemophagocytic syndrome. Fifty-eight patients were followed up, the median follow-up time was 25 (0.2¨C70) months. Comparing with the 12 normal control cases, there were high proinflammatory cytokines and chemokines detected in most patients with NK/TCL(without hemophagocytic syndrome, HPS), including, interleukin-6 (IL-6)(2.56 (0.00-22.29) pg/ml), IL-1ra(88.98 (0.00-1210.05) pg/ml),interferon-¦Ã(IFN-¦Ã)(2.78 (0.00-61.60) pg/ml), IP-10 (41.85 (0.00-1057.41) pg/ml),MIG(49.90 (0.00-799.00) pg/ml), IL-10(0.43 (0.00-13.48)pg/ml), sIL-2R(168.82 (0.00-1916.61) pg/ml),IL-15(0.00(0.00-443.76) pg/ml)(datum express the median serum concentration of cytokines and their range). The serum levels of these cytokines and chemokines mentioned above dramatically increased in 10 patients with hemophagocytic syndrome. The serum concentration of these proinflammatory cytokines and chemokines was notably higher in patients with fever, advanced stage, and microenvironment NF-kB alternative pathway (P52) activation. In patients with P52 activation, the concentration of these cytokine were higher in those plasma EBV-DNA copies ≥103copy/ml (P≤¼0.05). Multivariate analysis showed that the Korean Prognostic Index (KPI)(P=0.003), the serum concentration of IL-6 (P=0.035) and IL-2R(P=0.044) were independent prognostic factors. High serum IL-6 and IL-2R correlates with poor survival. Twenty-nine patients with serum IL-6 level≤3.97pg/ml, had better survival, with 68.0±8.8% of 3-year overall survival (OS); while 3-year OS of the higher serum IL-6 group was 21.3±8.1% (P=0.001). Conclusion≤°Our study indicate that patients with NK/TCL had special serum proinflammatory cytokines and chemokines profile, and these cytokines were notably higher in those with fever, advanced stage, the NF-kB alternative pathway activation in microenvironment, and EBV-DNA copies ≥103copy/ml. Moreover, high serum concentration of IL-6 and IL-2R were correlated with poor survival. [Display omitted] [Display omitted] [Display omitted] Disclosures:No relevant conflicts of interest to declare.

A Rare Condition with a Common Presentation: NK/T-Cell Lymphoma Presenting as Recurrent Sinusitis and Facial Cellulitis

Journal of Case Reports in Medicine,2013,2,1,1-4.Published:April 2013Type:Case ReportAuthors:Danny K. C. Wong, Angus Shao, and Michael Davison Author(s) affiliations:Danny K. C. Wong, Angus Shao, and Michael Davison Department of Otolaryngology – Head and Neck Surgery, Northshore Hospital, Private Bag 93503, Takapuna 0622, Auckland, NEW ZEALAND. Abstract:Extranodal natural killer (NK)/T-cell lymphomas are rare tumors that account for 1.5% of all non-Hodgkin-type lymphomas in the United States and almost 7–10% of all non-Hodgkin’s lymphomas in Asia and South America. The nasal type commonly presents with facial cellulitis, nasal obstruction or proptosis. Occasionally, local extension from the nasal cavity causes destruction of the hard palate, previously known as “lethal midline granuloma.” We present a case of a 37-year-old male who presented with recurrent right-sided facial swelling, periorbital cellulitis and sinusitis. There was some delay in confirming the diagnosis but he was eventually diagnosed with stage 1e NK/T-cell lymphoma (nasal type). Disease diagnosed at an early stage confers a very favorable curative remission rate. Therefore, clinicians should be aware of the possibility of an NK/T-cell lymphoma when facing a presentation of recurrent sinusitis associated with atypical presentation such as periorbital cellulitis. Keywords:NK/T-cell lymphoma; Nasal type; Periorbital cellulitis; Sinusitis; Facial swellingView:PDF (1.11 MB) PDF Images Figure 2: Coronal CT scan of patient representing with recurrent right sided facial cellulitis and predominantly right sided sinusitis on the 2nd presentation.