Extranodal NK/T-cell lymphoma, nasal type.

Extranodal NK/T-cell lymphoma, nasal type (ENKTCL), previously known as lethal midline granuloma is a distinct clinico-pathological entity associated with Epstein-Barr virus that typically causes destruction of the midface, palatal and orbital walls. In addition, ENKTCL can involve the skin, soft tissue, testes, gastrointestinal and upper respiratory tract. ENKTCL neoplastic cells express some T-cell associated antigens, most commonly CD2 and cytoplasmic CD3epsilon and, in favour of an NK-cell origin, CD56. Early stage disease may respond to radiotherapy alone, however late stage disease does not respond well to any available therapies. Overall, patients with ENKTCL have a cumulative probability of survival at 5 years ranging from 37.9% to 45.3%.

Idiopathic midline destructive disease: fact or fiction.

The differential diagnosis of a progressive destructive lesion of the midface and upper airway region includes both neoplastic and non-neoplastic entities; of these, the majority of cases prove to be either Wegener's granulomatosis or lymphoma. Historically, these sorts of necrotizing midfacial lesions were diagnosed clinically, and as a consequence a variety of overlapping categories of disease sprang up. As pathologic examination of biopsy material became both more widespread and (particularly in the last several years) more sophisticated, many lesions previously thought to be of mysterious origins have proven to be examples of lymphoma (in particular, sinonasal natural killer cell or T cell [NK/T] lymphomas). At present, the evaluation of a patient with a progressive destructive process involving the midface region should include imaging studies (to delineate the extent of disease) as well as biopsy (with sampling of lesional tissue for application of sophisticated testing--including immunohistochemical studies, flow cytometry, or molecular studies as necessary--to exclude the possibility of a NK/T cell lymphoma). There remain occasional patients whose necrotizing midfacial lesions continue to be difficult to classify despite the application of extensive testing; such patients are sometimes described as suffering from the nebulous entity of "idiopathic midline destructive disease". While it remains to be seen whether such patients will ultimately be assigned to other diagnostic groups (as, for example, occult toxic injuries--as in the case of cocaine abusers who are not forthcoming with regard to their drug usage), it seems likely that "idiopathic midline destructive disease" is a diagnostic term of questionable validity which should be used only with extreme reticence in modern practice.

[Lethal midline granuloma]. / Letalni granulom sredine lica.

Lethal midline granuloma is a rare clinical syndrome. In clinical practice the destructive process of the facial midline may appear as a symptom of various infective, malignant or autoimmune diseases. A physician must have a good knowledge of the problem in order to make a rational approach to diagnosis. The present paper discusses the case of a 34-year old patient with destructive changes of midline, nose, perforating of palatal cleft and destruction of bone structure of nose, maxillary and ethmoid sinus. For histopathologic diagnosis of T-lymphoma it was necessary to make immunohistological study of the biopsy specimen. Irradiation therapy with total dose of 5600 cGy showed an extremely good therapeutic result. Three years after irradiation therapy the patient is still in a remission.

Midline lethal granuloma complicating pregnancy: case report.

A case of midline lethal granuloma in a 28-year- old female Nigerian patient is reported. Oral, ocular and nasal lesions were present and these preceded a spontaneous abortion of a three month old pregnancy. The clinical course of the disease and its similarity to other granulomatous diseases, which are generally classified as midline granuloma syndrome, are highlighted. The prognosis is poor but early diagnosis and treatment appears to improve a patient's condition

Centrofacial malignant T-cell lymphoma exhibiting recurrent fever and skin ulcer in a 3-year-old girl.

A rare case of undetermined fever and skin ulcers is reported. The patient had an 8-month history of recurrent fever, destructive ulceration of the midline facial tissue, and symmetrical skin ulcer in the cheeks and the back of the hand. Pathological examination revealed that the patient had lethal midline granuloma (centrofacial malignant T-cell lymphoma), which is very rare in childhood. Centrofacial malignant T-cell lymphoma should be considered as a differential diagnosis of unexplained fever and skin ulcer in children.

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

Lethal midline granuloma: report of three cases.

Lethal midline granuloma (LMG) is a rare clinical entity characterized by progressive relentless ulcerations and necrosis of midfacial structures. It occurs more frequently in Oriental than in Western populations with no demonstrable etiology. Treatment and outcome for cases differ, but their pathological distinction may not always be possible from routine biopsy specimens. The histological features often seen include widespread coagulative necrosis, heavy inflammatory infiltrates, and atypical pleomorphic cells. However, the paucity of these atypical cells in biopsy specimens and the degree of necrosis can make the diagnosis of a neoplastic lesion very difficult. Because of the progress in pathology methodology including immunohistochemistry, most cases have been proven to be malignant lymphomas of T-cell lineage. We present 3 patients for whom an initial clinical diagnosis of LMG was made. From their several oral biopsies and nasal specimens, difficulties were encountered in differentiating "midline granuloma" from other possible diseases using histomorphological criteria alone. After extensive evaluations, malignant T-cell lymphoma was the specific disease entity identified in only one case by cell membrane immunostaining technique. A literature review was carried out, and recent concepts of the etiology and pathogenesis of this disease are presented.

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.

Natural killer cell lymphoma/leukemia: pathology and treatment.

Malignancies arising from cells of putative natural killer (NK) cell origin have increasingly been recognized as distinct clinicopathological entities. These malignancies are marked by tumour cells with NK cell characteristics, including the immunophenotype of CD2+, surface CD3-, cytoplasmic CD3 epsilon+, CD7 +/-, and CD56+, and the genotype of germline T cell receptor gene. A consistent association with monoclonal Epstein-Barr virus infection in the tumour cell has been observed. These tumours are now regarded as putative NK cell lymphoma/leukemia. Pathologically, tumour cells show variable cytological appearances, with frequent angiocentricity and angioinvasion, associated with zonal necrosis. Clinically, most cases occur in the nasal area and upper aerodigestive tract. However, occurrence in non-nasal sites such as the skin, gastrointestinal tract and testis is also observed. A particularly aggressive form of NK lymphoma/leukemia presents fulminantly as disseminated disease sometimes with a leukemic phase. All types of NK lymphoma/leukemia have an extremely poor prognosis with a median survival of less than a year. New modalities of treatment, including the use of high dose chemotherapy and stem cell rescue may be needed to improve treatment outcome.

Midline granuloma presenting as orbital cellulitis.

BACKGROUND: Lethal midline granuloma usually presents with rhinorrhoea and redness of the skin above the nose. Early ocular symptoms are very rare. We here describe a patient who presented with acute orbital cellulitis. PATIENT: A 73-year-old woman had a 24-h history of severe pain around her left eye. We saw the typical clinical picture of orbital cellulitis. A CT scan revealed a diffuse infiltration of the left upper and lower lid, the anterior orbit and the ethmoidal sinuses. RESULT: On surgical exploration we found a granular, partly necrotic tumour. Histological examination revealed an angiocentric nasal T-cell lymphoma (midline granuloma). CONCLUSION: Midline granuloma should be included in the differential diagnosis of acute orbital cellulitis.

[Cases of lethal midline granuloma (polymorphic reticulosis) at our department in a recent 10-year period].

We had 18 patients (15 males and 3 females) with lethal midline granuloma (polymorphic reticulosis) in the period from 1981 to 1990. This number was about 5.6% of the total number of patients with malignant head and neck tumors that we encountered during this period. An average of 9.1 months separated the first appearance of disease and the beginning of treatment. Most of the 18 patients underwent both radiation therapy and chemotherapy (COP, CHOP, MACOP-B), but, since their disease had reached an advanced stage, 3 underwent radiation therapy only, 3 underwent chemotherapy only, and 1 received no radical therapy at all. Of the 18 patients, 13 died of the disease. In of 6 of these, the disease was confined to the local lesion. The 5-year cumulative survival rate was 15.7% (Kaplan-Meier). Fourteen autopsy studies revealed that tumor cells had invaded the liver (92.8%), lung (92.8%) and spleen (71.4%) and in all cases it was in leukemic patterns. Fifteen cases were studied for tumor surface marker phenotype, but none was found to be positive for L26, CD43, Leu M1 (CD15), or MAC 387. Five cases were positive for UCHL-1 (CD45RO) and 10 cases were positive for lysozyme. All cases were positive for Ki-1 (CD30).

[Midline granuloma. A clinical case report]. / Midline granuloma. Presentazione di un caso clinico.

Granuloma gangraenescens or "midline granuloma" (Stewart's malignant granuloma, idiopathic midline destructive syndrome) is a rare clinical syndrome. In clinical practice, the destructive process of the facial midline may appear as a symptom of various infective, malignant or autoimmune diseases. In addition to these cases, a number of cases have been reported in the literature since 1896 with the diagnosis of lethal midline granuloma. These subjects underwent a progressive and often fatal destructive process of unknown cause which generally initiated in a nasal cavity (or sometimes on the palate) in the form of a granulomatous lesion with a rapid tendency to necrosis. The lesion affects the nose, paranasal sinuses, palate and soft facial tissue. As it progresses, it involves soft tissue, cartilage and the bone structures of the aforesaid and adjacent areas. A number of systemic symptoms may be present. The age of patients ranges from a minimum of 15 to a maximum of 59 years old. Repeated biopsies are usually necessary before the syndrome is diagnosed. From a histological point of view, it has been reported that the tissues in the nasal cavities are affected by diffuse infiltration of lymphocytes and leukocytes and histiocytic-type cells. The disease lasts between 3 and 20 months and causes death due to secondary infection, hemorrhage caused by the erosion of major vessels in the head and neck, and cachexia. With regard to therapy, the majority of authors appear to agree that local high-dose radiations in the area of the lesion are the best method of treatment for this pathology.(ABSTRACT TRUNCATED AT 250 WORDS)

Centrofacial malignant granulomas. Clinicopathologic study of 40 cases and review of the literature.

An important problem in the treatment of centrofacial ulcerations is to establish a precise diagnosis, since similar clinical and microscopic findings can result from many different causes (as in the centrofacial malignant granuloma syndrome [CFMG]). A comprehensive surgical biopsy protocol (known as SNFMI/GMCF), involving microbiology, parasitology, immunology and pathology laboratories, allowed us to evaluate and to treat 40 cases of CFMG, who form the basis of this report. In 13 of them, specific diagnoses were found and curative treatments could be given. In the remaining 27, the optical microscopy pattern met the criteria for CFMG without identifiable origin or the presence of so-called lethal midline granulomas; however, a more precise evaluation with the help of immunofluorescence studies led to the recognition of malignant lymphoma (ulcerative lymphoma of the midface [ULM]). Most of these lymphomas belonged to the T cell lineage; the others were of B lymphoid origin, or, more rarely, of histiocytic origin. Patients with ULM received radiotherapy and chemotherapy with a response rate of 70.3%; however, the toxicity was significant, with frequent occurrence of chemotherapy-induced neutropenia followed by severe infectious facial cellulitis. Six patients were enrolled in a preliminary open trial of treatment with recombinant alpha-2b interferon with little success. Three patients were treated with radiation therapy only, and survived. Thus, CFMG is a syndrome with specific causes and treatments, requiring multiple extensive biopsies to make the correct diagnosis. The recognition of ULM as the cause of the previously called "lethal midline granulomas" leads logically to the use of chemotherapy with growth factors in order to ameliorate its bad prognosis.

[Long-term follow-up and therapeutic results of the protocol of the National Society of Internal Medicine in centrofacial malignant granuloma. Report of 40 cases]. / Suivi à long terme et résultats thérapeutiques du protocole de la Société Nationale de Médecine Interne sur les granulomes malins centro-faciaux. A propos de 40 cas.

We have studied 40 cases of mediofacial necrosis with no specific diagnosis on biopsy. After an exhaustive work-up we reached a specific diagnosis in 13 patients (Wegener's granulomatosis in 7, classical malignant lymphoma of the nose in 3, squamous cell carcinoma = "goundou" in 1, syphilis and tuberculosis in 1, aspergillosis in 1). Those patients received the appropriate treatments with good results. The remaining 27 patients, however, had ulcerative lymphomas of the midface (according to the immunofluorescence and molecular biology techniques). Their fate was worse since only 15% remain alive on the long-term, despite intensive treatments with chemotherapy, radiotherapy, interferon, artificial nutrition and antibiotics as needed. We present a new protocol with intensified chemotherapy and growth factor treatment in order to ameliorate the very poor prognosis of these patients.

[Midline granuloma and Wegener's granulomatosis]. / Il "granuloma centro-facciale" e la granulomatosi di Wegener. "Midline granuloma" and Wegener's granulomatosis.

Necrotizing lesions of upper respiratory tract have always been among the most enigmatic diseases of the head and neck region. Nowadays a great deal of nosographic confusion still remains along with numerous doubts concerning diagnostic and therapeutic strategies to be followed in dealing with many diseases often erroneously defined "midline granuloma". In fact, a large variety of diseases appear or may appear as midline destructive lesions in the upper respiratory tract. Each of these, including infections, immune and neoplastic disorders, obviously requires a different therapy. The clinician must have a very good knowledge of the problem in order to make a rational approach to diagnosis and therapy. Wegener's granulomatosis is quite different from "midline granuloma" and must be diagnosed promptly so that an appropriate therapy may be determined as soon as possible. Unlike in the case of "midline granuloma", a prompt therapy is often very effective and gives long periods of remission. In this disease, nevertheless, the etiopathogenesis of both diseases is unknown, precise protocols for diagnosis or treatment do not exist (every case must be considered separately) and prognosis is very poor. On the basis of their personal experience and of an accurate review of Literature, the Authors present a systemic and up-to-date monographic study focusing particular attention on the most recent diagnostic techniques, such as immunohistochemical techniques which utilize monoclonal antibodies, indispensable in the cases of "midline granuloma", and immunofluorescent techniques searching antibodies to cytoplasmic antigens of neutrophil granulocytes, of great value in dealing with Wegener's granulomatosis not only in establishing an initial diagnosis, but also in making prognosis and in controlling the evolution of the disease. The paper also discusses differential diagnosis of midline destructive disorders, highly important for a correct and rational initial approach in diagnosis. Every disease described in the section concerning differential diagnosis must be excluded in order to make an accurate diagnosis of "midline granuloma" in that no typical histopathologic or clinical signs of this particular, destructive disorder. Finally, the authors focus their attention on new etiopathogenetic hypotheses and their therapeutic implications. The most interesting of them are surely those that consider "midline granuloma" the manifestation of a malignant lymphoma as well as those that explain the recent success obtained in treatment of Wegener's granulomatosis using trimethoprim and sulfamethoxazole asserting a possible essential role of infections in the etiology of the disease.

[Lethal midline granuloma in Senegal. (Apropos of 15 cases)]. / Le granulome médio-facial au Sénégal (A propos de 15 observations).

African authors, other than senegalese, have not paid enough attention to lethal granuloma, a terrible disease. This series is about a series collected between 1975 and 1990. It is particularly high compared to other series in the world. If diagnosis is easy for the clinician, much care must surround the pathological answer. Those diagnosis problems and difficulties of treatment (represented by 11 deaths) are studied.