Accurate diagnose and management of advanced nasal type extranodal nk/t cell lymphoma. a case report

ABSTRACT Extranodal natural killer (NK)/T-cell lymphoma, nasal type, is a rare entity in otorhinolaryngology. Its management requires skilled physicians in order to suspect this disease and making a proper diagnosis at early stages. This paper reports the case of a 31-year-old male patient, with one month of nasal obstruction, recurrent sinusitis, palatal ulceration and a necrotizing lesion. Histopathology reported lymphoid infiltrate polymorph angiocentric growth pattern and extensive areas of necrosis. Immunohistochemistry confirmed the phenotype for T/NK cells: positive CD3, BCL2, CD4 and CD56. IgG for Epstein-Barr virus was also positive. The initial staging was T4, N1, M0, Eastern Cooperative Oncology Group (ECOG) scale was 1, with intermediate risk, and low International Prognostic Index (IPI); based on this results, the patient was referred to oncology to initiate treatment. After a ten-month follow-up, the patient's condition improved, with complete remission of nasal and palate injuries; no relapse has occurred to date. This case is a clear example of the importance of early diagnostic through multiple biopsies in order to establish a specific treatment to decrease complication rates and improve prognosis.

Síndrome do granuloma letal da linha média: um dilema diagnóstico / Lethal midline granuloma syndrome: a diagnostic dilemma

A rara síndrome do granuloma letal da linha média apresenta difícil diagnóstico, em razão da grande variedade de doenças que podem causá-la e um desconhecimento pela maioria da classe médica. No presente artigo relatamos caso de paciente com esta doença, provocada por carcinoma epidermoide, chamando a atenção para os diagnósticos diferenciais e aspectos clínico-radiológicos que podem auxiliar no diagnóstico.

The rare lethal midline granuloma syndrome is difficult to diagnose because of the wide array of related diseases and lack of knowledge by the majority of physicians. In the present report, the authors describe the case of a patient with this disease, caused by squamous cell carcinoma, drawing attention to differential diagnoses and to clinical and radiological findings that may be useful to define the diagnosis.

Lesões destrutivas da linha média induzidas por cocaína com ANCA positivo mimetizando a granulomatose de Wegener / Cocaine-induced midline destruction lesions with positive ANCA test mimicking Wegener's granulomatosis

O uso crônico de cocaína por inalação pode causar lesões destrutivas de linha média (LDLMIC), que podem ser difíceis de distinguir das lesões da granulomatose de Wegener (GW) nos ouvidos, nariz e garganta. Descrevemos o caso de uma paciente de 43 anos admitida com história de dois anos de obstrução nasal e rinorreia. Ela havia recebido o diagnóstico de GW há cinco meses e estava em tratamento com prednisona e ciclofosfamida. Ao exame físico apresentava perfuração de septo nasal e palato. Exames de laboratório mostraram elevação das proteínas de fase aguda e teste p-ANCA positivo. Ensaios ELISA antiproteinase 3 e mieloperoxidase foram negativos. Tomografia computadorizada (TC) dos seios paranasais mostrou destruição de septo nasal e palato, bem como sinusite maxilar bilateral. TC de tórax resultou normal. Biópsia da mucosa nasal revelou infiltrado inflamatório sem granuloma ou vasculite. Quando questionada, admitiu ser usuária de cocaína há cinco anos. Os imunossupressores foram suspensos e a paciente não mais fez uso da droga. Ela está sendo monitorada há seis meses e não desenvolveu novas lesões ou sintomas de outros órgãos. O diagnóstico diferencial em pacientes com LDLMIC pode ser desafiador. A avaliação deve incluir pesquisa de uso intranasal de cocaína. Embora o teste de ANCA não diferencie claramente o ANCA encontrado em alguns pacientes com LDLMIC daqueles em pacientes com GW, o envolvimento localizado e os achados de biópsia não típicos de vasculite granulomatosa de pequenos vasos devem ser reconhecidos como características das lesões induzidas por cocaína.

Chronic use of cocaine by inhalation may induce midline destructive lesions (CIMDL), which can sometimes be difficult to distinguish from the ear, nose and throat lesions of Wegener's Granulomatosis (WG). We describe the case of a 43-year-old female patient admitted with a two-year history of nasal obstruction and rhinorrhea. She had been diagnosed with WG for five months, being on prednisone and cyclophosphamide. On her physical examination, perforation of her nasal septum and palate was observed. Laboratory tests showed elevated acute phase proteins and a positive p-ANCA test. ELISA assays anti-proteinase 3 and myeloperoxidase were negative. The paranasal sinus computed tomography (CT) showed destruction of the nasal septum and palate, in addition to bilateral maxillary sinusitis. Chest CT was normal. Nasal mucosal biopsy revealed an inflammatory infiltrate, with neither granuloma nor vasculitis. When questioned, she admitted being a cocaine user for five years. Medical therapy and cocaine use were withdrawn. She has been followed up for six months and no other lesion or other organ symptoms occurred. Differential diagnosis in patients with midline destructive lesions can be very challenging. Evaluation should include enquiry about intranasal use of cocaine. Although ANCA testing does not clearly differentiate the ANCA found in some patients with CIMDL from those found in WG patients, the localized involvement and the biopsy findings non-characteristic of small vessel granulomatous vasculitis should be recognized as features for cocaine-induced lesions.

Extranodal NK/T cell Lymphoma, nasal type: clinical, radiological, histological features for early diagnosis

Primary nasal type natural killer (NK)/T cell (NKTC) lymphoma, a specific form of malignant lymphoma, has a higher geographic incidence in Oriental, Mexican, and South American populations than the Western population. In Koreans, it comprises 9-12% of all cases of non-Hodgkin's lymphoma. This type of lymphoma has also been named as angiocentic lymphoma and lethal midline granuloma because the most common site is the upper airway area and its clinical aggressiveness presents with a necrotic and destructive pattern. NKTC lymphoma can also be detected in different organs (testis, spleen, parotid gland, skin, gastroinstinal tract, central nervous system, lungs, bone marrow, etc.) other than the upper airway including the oral cavity. The lymphoma detected in the oral cavity shows various destructive and inflammatory changes, similar to the signs of inflammation and infection from periodontitis and pulpal disease, making a diagnosis difficult with just the clinical signs. For early detection, clinical, radiological, and pathological examinations are required. This report describes the clinical, radiological and histological characteristics with a case report for the early detection of NKTC lymphoma in the oral cavity.

A case of nasal-type NK/T cell lymphoma with cutaneous and ocular involvement / 대한내과학회지

Natural killer (NK)/T cell lymphoma is a lethal midline granuloma that produces necrotic and granulomatous lesions in the upper respiratory tract, especially in the nasal cavity. This tumor affects the nose and midface, but can also arise in the skin, gastrointestinal tract, testes, central nervous system, lungs, salivary glands, bone marrow, and larynx. Five to eight percent of extranodal lymphomas involve the orbit, and 1.3~2.0% of these present as primary orbital tumors. The skin can also be the primary site of NK/T cell lymphomas. Aside from affecting the nasal and facial skin, the tumor can involve the skin of the postauricular area, back, trunk, and upper and lower extremities. We present the case of a 37-year-old woman who had a nasal NK/T cell lymphoma with cutaneous and ocular involvement.

Nasal NK/T cell lymphoma presenting as a lethal midline granuloma.

Nasal NK/T cell lymphomas are aggressive, locally destructive, midfacial, necrotizing lesions. The nonspecific clinical symptoms constitute a major stumbling block in the early diagnosis and management of these lymphomas. We report here a case of probable nasal NK/T cell lymphoma in an apparently healthy male that progressed rapidly in a short span of time and was managed subsequently with chemotherapy and external beam irradiation with which the lesion regressed.

Linfoma Nasal: Reporte de un caso y revisión de la literatura / Nasal Lymphoma: A case report and literature review

Los tumores de la nariz y de los senos paranasales no son comunes. Constituyen el 0.2% de todas las neoplasias humanas y solo el 3% de los tumores malignos del tracto respiratorio superior, la sospecha clínica debe tenerse ante un paciente con sintomatología de larga evolución caracterizada por síntomas de obstrucción nasal o sinusitis quienes deben ser candidatos a biopsia amplia y estudio histopatológico minucioso. Presentamos un caso de linfoma angiocéntrico de células T (antes conocidas como granuloma letal de la línea media) diagnosticado en un paciente de 40 años de edad que acudió a la consulta externa del HVQ, con sintomatología de obstrucción nasal de larga evolución.

Tumors of the nose and sinuses are not common. They constitute 0.2% of all human neoplasms and only 3% of malignant tumors of the upper respiratory tract, clinical suspicion should be taken in a patient with long-standing symptoms characterized by symptoms of nasal obstruction or sinusitis who should be candidates for biopsy. comprehensive and detailed histopathological study. We present a case of angiocentric T-cell lymphoma (formerly known as lethal midline granuloma) diagnosed in a 40-year-old patient who attended the HVQ outpatient clinic, with symptoms of long-standing nasal obstruction.

Granuloma maligno medio facial / Medial facial malignant granuloma

Ingresó en el Servicio de O.R.L. del Hospital Provincial Universitario Camilo Cienfuegos una paciente femenina R.O.R. de raza negra, de 51 años de edad, por presentar lesiones en la orofaringe y síndrome general, que al examinársele la orofaringe se aprecia lesión ulcerada del pilar anterior y posterior de la amígdala derecha, úlcera que se extiende al pilar anterior y posterior de la amígdala izquierda, con fondo limpio, bordes rosados, tejido friable y fetidez intensa. Remiten las lesiones posteriores al uso de esteroides y es egresada con tomas de biopsias con células inflamatorias. Reingresa dos meses después con desaparición anatómica de la orofaringe, úvula amputada, ausencia de ambos pilares. Fallece en shock hipovolémico por epistaxis severa, diagnosticándosele días antes Granuloma maligno medio facial por L.N.H. de alto grado de malignidad.[AU]

Survivin expression in midline T-cell lymphoma in relation to Epstin-Barr virus infection / 中国实验血液学杂志

To investigate the expression of survivin gene and its relationship with Epstin-Barr virus (EBV) infection in midline T-cell lymphoma (MTL), immunohistochemistry staining method was used to examine the expression of survivin and EBV-latent membrane protein (LMP-1) in the 41 cases. In situ hybridization (ISH) was used to detect EBV-encoded RNA (EBER1/2). The results showed that the expression of survivin was positive in 26 cases of midline T-cell lymphoma, but no positive was detected in 10 cases of reactive lymphoid tissues. The positive expression ratio of survivin was 12.5% in cases of MTL with low grade of malignancy, and was 75.76% in cases of MTL with middle and high grades of malignancy, the significant difference was found between these two groups (chi(2) = 8.55, P < 0.01). Positive expression ratios of EBER1/2 and LMP-1 were 70.73% and 41.46% respectively. Survivin expression was not significantly different between EBER1/2 positive and negative cases (P > 0.05). It is concluded that survivin expression is up-regulated in MTL, and survivin positive expression rate is associated with the degree of malignancy. Survivin may play a role in the pathogenesis of the MTL by influencing cell apoptosis. EBV infection is not significantly associated with survivin expression in the MTL.

A Case of Duodenal Relapse of Epstein-Barr Virus-positive, CD56-negative Extranodal NK/T-cell Lymphoma, Nasal Type / 대한소화기내시경학회지

Mature T-cell and natural killer-cell neoplasms account for 10 to 15% of all non-Hodgkin's lymphomas. Of the various subtypes of mature T-cell and NK-cell lymphomas, extranodal NK/T-cell lymphoma, nasal type (nasal type NK/T-L) is relatively more common among Asians including Koreans. Nasal type NK/T-L is an aggressive, Epstein-Barr virus-associated lymphoma with characteristic expression of NK-cell antigen CD56. In this report, we present an unusual case of EBV(+), CD56(-) NK/T-L of oropharynx which recurred in duodenum after the period of complete remission lasting for 10 years. A 58-year-old woman presented with 3 months history of abdominal pain. Gastroduodenoscopy showed the diffuse wall thickening with multiple ulcerations in bulb and proximal second portion of the duodenum. Pathological examination revealed the infiltration of atypical lymphocytes, which was positive for CD3, CD4, CD5, TIA-1, and EBV and was negative for CD15, CD20, and CD56, consistent with NK/T-L of mature T-cell origin. The past medical history included the presence of oropharyngeal mass 10 years earlier, which was diagnosed as polymorphic reticulosis. The mass resolved completely after the radiation therapy, and she remained free of the disease for 10 years. Upon review, the oropharyngeal biopsy showed an identical morphology and immunophenotype with duodenal lesion. In conclusion, we experienced an unusal case of NK/T-cell lymphoma, nasal type recured in the duodenum.

Midline lethal granuloma--a clinical enigma.

Midline Lethal granuloma is characterized by progressive destruction of nose, paranasal sinuses and palate. Till date, the diagnosis of this mutilating process remains as enigma due to the non specific histological and systemic findings. However, over the years the clinicians have been able to divide the "Lethal midline granuoloma syndrome" into clinical entities: Idiopathic midline destructive disease, Wegener's granulomatosis, polymorphic retiaculosis and Non-Hodgkins lymphoma. This article attempts to distinguish between these disease entities in the light of 2 case reports of Idiopathic midline destructive disease.

Granuloma letal da linha média: relato de um caso clínico / Lethal granuloma of the medium line: clinical case report

O presente trabalho tem como objetivo o relato de um caso clínico de granuloma letal de linha média, descrevendo suas características clínicas e histopatológicas diferenciais mais frequentes, bem como tratamento e prognóstico

Granuloma letal de línea media: experiencia con un paciente / Midline lethal granuloma: experience with a patient

Se realizó el estudio retrospectivo de una paciente extranjera con granuloma letal de línea media, diagnósticada en la Clínica Central "Cira García", durante el año 1998. En esta enfermedad, tiene lugar un proceso granulomatoso y necrótico, en forma progresiva, que destruye la nariz, senos perinasales y otras estructuras faciales; esta enfermedad es poco frecuente y puede ser producida por diferentes enfermedades infecciosas neoplásicas, autoinmunes e idiopáticas. La mayoría de los pacientes portadores de ésta, hacen una evolución a corto plazo. Valoramos los aspectos en que podríamos ayudar con un tratamiento médico con vistas a mejorar la calidad de vida de los pacientes y alargar, si es posible, la vida de estos. Por ser una enfermedad poco conocida y tener la oportunidad de brindarle atención, pudimos identificar los problemas que afectan el bienestar físico y serios trastornos del autoconcepto. El objetivo fundamental de nuestro trabajo consiste en demostrar la significativa atención con respecto a la atención que recibió esta paciente y sus familiares por parte del personal de enfermería(AU)

A retrospective study of a foreign patient with midline lethal granuloma diagnosed at the "Cira García" Central Clinic, in l998, was conducted. A granulomatous and necrotic process takes place progressively in this disease that destroys the nose, the perinasal sinuses and other facial structures. This is an uncommon disease and may be produced by different infectious neoplastic, autoimmune and idiopathic diseases. Most of the patients carriers of this disease had a short-term evolution. We assessed the aspects in which we could help with a medical treatment in order to improve the quality of life of the patients and to extend, if possible, their life. As it is a little known disease and we had the opportunity to give it attention, we were able to identify those problems affecting physical well -being, as well as serious problems of selfconcept. The main objective of our paper is to show the significant nursing care received by these patients and their relatives(AU)

Immunohistochemical Classification and Clinical Evaluation of Nasal Malignant Lymphoma

BACKGROUND AND OBJECTIVES: Polymorphic reticulosis (PMR), a type of lethal midline granuloma, has characteristics of necrosis, angiocentricity, and angiogenesis, which is also known as nasal T-cell lymphoma. In this study, we classified PMR and nasal lymphoma using immunohistochemical staining and investigated the clinical characteristics of nasal malignant lymphoma including survival rates with treatment modalities. MATERIALS AND METHODS: Twenty-six patients previously diagnosed with PMR or nasal lymphoma from May 1992 to April 1997 were included in this study. We performed immunohistochemical staining with CD3, CD56 and CD79a for classification and reviewed the patients' clinical characteristics and survival rates, retrospectively. RESULTS: Of twenty-six patients, twenty-five patients were classified as having angiocentric lymphoma and only one patient with B-cell lymphoma. Higher mortality rates were observed in patients receiving chemotherapy alone than in those receiving chemotherapy and radiation therapy and in advanced stage. CONCLUSIONS: Early detection and combined treatment could improve the survival rate of patients with nasal malignant lymphomas.

Linfoma centrofacial: un análisis retrospectivo, clínico, patologíco y terapeutico de 10 casos / Centrofacial linfoma: a therapeutic pathological clinical retrospective analysis of ten cases

Se comunican 10 casos de linfoma centrofacial estudiados de manera retrospectiva entre 1995 y 1999, que correspondieron a 6.6 por ciento de todos los linfomas diagnosticasos durante este periodo; cuatro de los 10 pacientes fueron del sexo masculino, con mediana de edad de 59 años 89 a 87 años). En dos pacientes se localizó en el paladar, en dos se afectaron antro nasal y senos paranasales, En otros dos casos se afectaron paladar y nariz, y en dos más al maxilar; uno se localizó en el párpado y el tabique nasal y otro en el paladar y la amígdala derecha. Todos se mostraron como lesiones expansivas, mayores de 4 cm de diámetro (4.5 a 7 cm). Histopatológicamente, tres fueron de alto grado de malignidad (angiocéntricos) y siete de grado intermedio. En un caso se relacionó con infección por VIH. Según su estadio clínico al momento del diagnóstico, siete fueron estadio I; dos estadio II y uno estadio IV por infiltración asintomática de médula ósea. Todos recibieron quimioterapia combinada con ciclofosfamida, doxorrubicina, vincristina y prednisona cada 21 a 28 días, durante seis ciclos. Se logró respuesta completa en cuatro de los pacientes, respuesta parcial en dos y no hubo respuesta en cuatro enfermos. Fallecieron cuatro pacientes: dos por infección grave uno por actividad tumoral y uno por toxicidad a quimioterapia. La supervivencia libre de enfermedad es de 39 por ciento y la supervivencia total de 56 por ciento a 36 meses. Nuestros resultados terapéuticos son similares a lo informado en la literatura; consideramos que ante un linforma centrofacial es obligado realizar fenotipo inmunológico de las células linfomatosas y análisis exhaustivos para detectar genoma de virus linfotrópicos en el tejido tumoral, en virtud de sus implicaciones pronósticas, y un mayor número de estudios prospectivos y controlados que permitan conocer las características clínicas, inmunofenotípicas y de asociación con infecciones virales en pacientes mestizos mexicanos y establecer el mejor esquema terapéutico para las particularidades de nuestro país

Granuloma letal da linha média: abordagem clínica e terapêutica de três casos / Lethal midline granuloma: clinical management of three cases

Objetivo. Relato de três casos do GLLM acompanhados pela Disciplina de Hematologia e Hemoterapia da Unifesp-EPM que tiveram boa resposta à terapêutica e evoluçao favorável. Métodos. Após confirmaçao histológica e histoquímica, os pacientes foram submetidos à tratamento quimio e radioterápico com boa resposta terapêutica. Resultados. Atualmente estes pacientes encontram-se em remissao total da doença, com sobrevida média de 45 meses. Conclusao. Levando-se em consideraçao nossa pequena experiência, acreditamos que o tratamento radioterápico e a abordagem quimioterápica inicial agressiva sao fundamentais para uma boa evoluçao deste tipo de linfoma.

Importancia de un signo diagnóstico clínico diferencial de los granulomas crónicas nasales / Importancy of the clinic diagnostic differential of the nasal chronic granulomas

The author calls the attention on a sign that can be useful in the defferencial clinical diagnosis among the chronic granulomatosis of the nose. He has observed a typical infiltrative edema in the orbital region of four cases of lethal midline granuloma of the face (Pathergic Granulomatosis), but has not observed in the other chronic infectious disease (scleroma, leishmaniasis, mycosis, etc.) or neoplastic tumors

Clinical Characteristics of Angiocentric Immunoproliferative Lesions in Head and Neck / 대한이비인후과학회지

BACKGROUND AND OBJECTIVES: The histologic features of polymorphic reticulosis are identical to those of sinonasal "angiocentric immunoproliferative lesions" (AILs) which are characterized by angiocentric and angioinvasive lymphoid infiltrates with a wide range of cytologic atypia. 1) This report was conducted to further define the clinicopathological nature of this lesion and evaluate the important prognostic factors and therapeutic strategies. MATERIALS AND METHODS: The clinical features and therapeutic outcomes of 22 patients with AILs were reviewed. Histologic grading was performed by using previously reported criteria (Grade I-III).2) To clarify the cell origin of AIL, immunohistochemical studies were performed in 21 cases. RESULTS: On the slide review, 10 cases were Grade II and 12 cases were grade III which showed characteristic histologic features similar to those of peripheral T-cell lymphoma. On immunohistochemical studies, neoplastic cells of all patients had a T-cell phenotype. The difference in primary treatment results according to the histologic grade, clinical staging and therapeutic modalities was not significant statistically. The overall 5 year survival rates were 58%. CONCLUSION: Our results suggest strongly that quite a significant portion of AIL may be in fact T-cell lymphoma. The only significant prognostic factor that predicts better survival is the achievement of initial complete response.