Re-irradiation of a second localization of idiopathic midline destructive disease in the head and neck area.

Idiopathic midline destructive disease is a rare disease, characterized by a progressive ulceration and destruction of midline facial structures. We report a case with localization on the palate for which she received radiotherapy. Later she developed a second localization on the posterior pharyngeal wall for which she was re-irradiated, without severe sequels. Twice a complete regression was observed.

Lethal midline granuloma-nasal natural killer/T-cell lymphoma.

PURPOSE: The purpose of this paper is to discuss lethal midline granuloma (LMG)-nasal natural killer (NK) T-cell lymphoma (LMG-NTL). METHODS: Literature review. RESULTS: LMG is a rare entity that usually arises in the nasal cavity, exhibits a male preponderance, and has a wide age range. The majority of LMGs are LMG-NTLs. The optimal treatment of LMG-NTL is unclear and is most likely moderate-dose radiotherapy. The prognosis for patients with LMG-NTL is significantly worse than for patients with other types of head and neck non-Hodgkin lymphomas (NHL). The 5-year survival rate is approximately 20% but may be higher, depending on whether patients with less aggressive forms of NHL are included. Initial local-regional disease progression is the predominant pattern of treatment failure. Late failures after 5 years are uncommon. CONCLUSIONS: LMG-NTL is a rare nasal NK/T-cell lymphoma that can be difficult to distinguish from other benign and malignant entities. Its clinical course, however, is extremely aggressive. The patterns of failure suggest a role for more aggressive local-regional treatment, as well as more effective chemotherapy.

Lethal Epstein-Barr virus associated NK/T-cell lymphoma with primary manifestation in the conjunctiva.

BACKGROUND: Lethal midline granulomas (LMG) are very rare angiocentric NK/T-cell lymphomas in association with Epstein-Barr virus. LMG are reported mainly in East Asia occurring in immune compromised patients. HISTORY AND SIGNS: A 41-year old male patient presented with a conjunctival swelling of his upper left eyelid. The lesion had increased over a period of 2 months despite topical corticosteroid treatment. Conjunctival biopsy revealed a highly malignant, CD3 + and BCL2 + extranodal T-cell lymphoma with features of an NK/T-cell origin (CD56 +, TIA + TCR-rearrangement: germline). All lymphoma cells were positive for Epstein-Barr virus RNA. The proliferation rate was highly elevated at 100 %. THERAPY AND OUTCOME: Systemic 1 (st) cycle chemotherapy with cyclophosphamide, doxorubicin, vincristin and prednisone resulted in a complete remission of the swelling within 4 days. However, one week later a massive conjunctival tumour reappeared with only partial regression after combined chemo- and radiotherapy. The patient died within a month because of untreatable pancytopenia due to malignant bone marrow infiltration. CONCLUSIONS: LMG is a rare but highly malignant Epstein-Barr virus associated NK/T-cell lymphoma that can occur in healthy, immune competent Caucasians. This is the first reported case of an LMG in an immune-competent Caucasian patient with primary ocular manifestation. The LMG has a high mortality rate despite systemic treatment and can be lethal within a few months or even weeks.

Lethal midline granuloma starting as granuloma laryngis.

We report a case of lethal midline granuloma in a 34-year-old male patient. The patient was referred to our hospital because of long-lasting hoarseness. He was treated for granuloma laryngis. After two years nasal obstruction developed followed by ulceration of the hard palate and destruction of part of the nose and the upper lip. A biopsy demonstrated polymorphic infiltrate consisting of small lymphocytes, plasma cells, macrophages, atypical lymphoid cells and eosinophils. Radiotherapy was very effective and led to long-term remission. The different etiological aspects of this syndrome are discussed.

[Nasal T-cell lymphoma of the lethal midline type. Case report and current aspects in the literature]. / Nasales T-Zell-Lymphom-Typ letales Mittelliniengranulom. Kasuistik und aktuelle Aspekte zur Literatur.

A case of nasal T-cell lymphoma as a cause of lethal midline granuloma in a 41-year-old woman is described. Primary chemotherapy as management failed, and tumor control was achieved thereafter by local radiotherapy to a dose of 52 Gy. Fourteen months after diagnosis the patient died in multiorgan failure with involvement of her skin, lung and liver. Present studies give strong evidence that lethal midline granuloma is very often a type of T-cell lymphoma that might be caused by Epstein-Barr virus. According to the literature our findings support the hypothesis that tumors are best treated by local high-dose irradiation.

Treatment of lethal midline granuloma type nasal T-cell lymphoma.

Nasal T-cell lymphoma of the LMG type (LMG-NTL) is characterized by progressive, unrelenting ulceration, and necrosis of the nasal cavity and midline facial tissues. The clinical behavior of this tumor in 16 patients is compared with that of a nasal lymphoma of non-LMG-NTL type (non-LMG-NTL) in 8 patients and a paranasal sinus lymphoma (PSL) in 6 patients. All patients had stage I or II disease. Fourteen of the 16 patients with LMG-NTL received chemotherapy before and/or after radiotherapy. Cause-specific 5-year survival rates for patients with LMG-NTL, non-LMG-NTL, and PSL were 22%, 75%, and 67% respectively. Seven patients with LMG-NTL, had complete response, although 3 recurred, whereas it was incomplete in 9 patients. The data indicates that it is desirable to deliver 50 Gy or more to achieve in-field control of LMG-NTL.

[A case of "midline granuloma" in a 29-year-old patient]. / Fall eines "Mittelliniengranuloms" bei einem 29jährigen Patienten.

The term "(lethal) midline granuloma" originates from the disease's clinical presentations, including various granulomatous, inflammatory and destructive changes as well as necrosis of the midface. The present paper discusses the case of a 29-year-old woman with a midline granuloma involving the left palatal cleft and affecting the nose and naso-maxillary sinus. In terms of the currently available literature the difficulties are shown in diagnosing "midline granuloma" from other possible diseases using histomorphological criteria. Various therapies are discussed, including those used in the present case.

Experience of radiotherapy in lethal midline granuloma with special emphasis on centrofacial T-cell lymphoma: a retrospective analysis covering a 34-year period.

Lethal midline granuloma (LMG) is characterized by progressive ulceration and destruction of the midfacial tissue. It occurs more frequently in Oriental than in Western populations. Because of the progress in clinical pathology and immunohistochemistry, most cases have been proven to be malignant lymphomas, especially of T-cell lineage. We describe 92 cases of lethal midline granuloma or centrofacial malignant lymphoma in the period 1959-1993. All received complete courses of radiotherapy. Twenty of them also received combination chemotherapy. Thirty-six cases had specimens available for immunohistochemical study; 25 (69%) of these had a T-cell phenotype, and 6 (17%) were of B-cell lineage. The dose to the nasal region was in the range of 3000-7500 cGy in 11-58 days, and to the neck 3000-6400 cGy in 11-48 days. The overall survival rate for the LMGs was 59.5% at 5 years and 56.2% at 10 years (Kaplan-Meier). Combined chemotherapy seemed not to improve the overall survival in this study (p = 0.63), but the patient number was too small to make a firm conclusion. Based on the results of this study, we recommend a dose of 4500-5000 cGy to the midfacial region, since a higher dosage did not improve the treatment results (p = 0.88). Irradiation has a definite role in good locoregional control of this disease. The recent clarification of the disease nature and the recognition of the background clinicopathological features should provide valuable information for future patient management and prospective studies.

Reticulosis letal de la línea media. Manejo con radiaciones y consideraciones histopatológicas / Lethal midline granuloma. Radiotherapy and pathology

Entre 1973 y 1990 se han tratado 24 pacientes portadores de Reticulosis Letal de la Línea Media (RLLM) mediante el empleo de radiaciones ionizantes en el Departamento de Radioterapia del Instituto Nacional de Enfermedades Neoplásicas en Lima, Perú. Los autores realizan una revisión descriptiva y retrospetiva de dichos casos así como una revisión de la literatura referente a este tipo de neoplasia. Todas las láminas provenientes de las biopsias han sido revisadas para confirmar el diagnóstico de RLLM. Todos los pacientes recibieron tratamiento con radiaciones ionizantes y 12 de ellos algún tipo de quimioterapia durante el tratamiento con radiaciones. La relación según sexo masculino-femenino ha sido de 5:3, la edad promedio de 29:33 años y el rango de edad entre los 6 y 84 años de edad. Los síntomas de presentación más comunes han sido: obstrucción de fosa nasal (45.83 por ciento), aumento de volumen de la fosa nasal (33.33 por ciento), rinorrea (29.16 por ciento) y alza térmica constante mayor de 38.5ºC (29.16 por ciento), principalmente. No se ha podido establecer una dosis de referencia para el tratamiento con radiaciones puesto que las dosis han variado desde 732 cGy hasta 7095 cGy; sí hemos podido observar que todos aquellos que recibieron menos dosis de la planificación fue porque fallecieron durante el tratamiento ya que acudieron con enfermedad muy avanzada y en mal estado general. Asimismo, se ha podido corroborar que si la dosis administrada fue de 50 cGy ó más se obtuvo mejor control local aunque por el número de casos no se ha podido demostrar estadísticamente. Al evaluar la sobrevida se observa que ésta disminuye considerablemente durante el primer año de seguimiento pero a partir del segundo año se mantiene constante (33.33 por ciento); esto en relación al estado en que acudió el paciente a recibir tratamiento. Concluimos que en este tipo de neoplasias el empleo de radiaciones ionizantes juega un rol importante en el control local de la enfermedad pero también es importante la extensión de la misma

Combined therapy for angioimmunoproliferative lesions.

43 patients with a diagnosis of angioimmunoproliferative lesions (AIL) entered onto a prospective clinical trial to evaluate the use of combined therapy as a primary therapeutic approach. Patients were treated initially with involved field radiotherapy 40-55 Gy (40 patients received 45 Gy) followed by six cycles of chemotherapy which consisted of CEOP-Bleo (cyclophosphamide, epirubin, vincristine, prednisone and bleomycin). Complete response was achieved in 41 cases (95%). At a median follow-up of 40 months, 40 patients (91%) remain in first complete remission. 2 patients died during radiotherapy secondary to sepsis and tumour progression. Treatment was well tolerated. The treatment of AIL remains controversial. Our results show that combined therapy appears to be the best therapeutic approach in patients with this type of malignant lymphoma. More studies are necessary to define the role of combined therapy in patients with AIL.

[Difficulties in recognition and treatment of lethal midline granuloma and otolaryngologic and radiotherapeutic practice]. / Uber die Schwierigkeiten bei der Erkennung und Behandlung des "Lethal midline granuloma" in der otolaryngologischen und strahlentherapeutischen Praxis.

The authors report on two cases of a "lethal midline granuloma". The first patient was treated by irradiation and chemotherapy. He lives for the last three and a half years in complete remission. The established diabetes did not affect the healing process. In the second case only a palliative irradiation was practicable because of the extreme tumour propagation, but the result was nevertheless good.

Nasal peripheral T-cell lymphoma: a 20-year review of cases treated in Scotland.

The nasal peripheral (post-thymic) T-cell lymphoma is an important cause of the midline granuloma syndrome (MGS), in which ulceration and destruction of the tissues of the nose and paranasal sinuses occurs. We reviewed the histology of 9 cases of the MGS treated with radiotherapy, and, using immunocytochemistry, showed 8 cases to be peripheral T-cell lymphomas (PTCL) and 1 a B-cell lymphoma. All patients received radiotherapy and 2 died shortly after treatment from unrelated causes. Two patients with T-cell lymphoma and the solitary case of B-cell lymphoma achieved long-term disease-free survival. The 4 remaining cases of T-cell lymphoma relapsed locally at a median interval of 3.5 months despite megavoltage irradiation of 45-50 Gy (in 3 cases) and inclusion of uninvolved paranasal sinuses and the nasopharynx in the field (in 2 cases). All patients with local relapse achieved, and remain in, remission after treatment with alkylating agents and prednisolone. The disappointing response of some cases of nasal T-cell lymphoma to radiotherapy has been reported by others, and this may be due partly to the heterogeneity of nasal lymphomas. We are unable to provide clear guidelines for treatment but suggest that a role exists for initial treatment with oral alkylating agents and steroids in newly diagnosed cases.

Lethal midline granuloma: impact of imaging studies on the investigation and management of destructive mid facial disease in 13 patients.

In 13 patients presenting as lethal midline granuloma (LMG), computed tomography proved essential for determining the extent of the disease, guiding biopsy and planning radiotherapy. Magnetic resonance imaging (MRI) was also helpful for the latter, because it could distinguish fluid retained within the paranasal sinuses from solid masses and tumour from granulation tissue; it was of little value for detecting bone lysis. Eight of the 13 patients proved to have T-cell lymphoma, two had Crohn's disease, in one the lesion was factitious and two had granulomas without diagnostic histological features.

[Idiopathic form of lethal midline granuloma. Case report]. / Idiopatyczna postac ziarniniaka srodkowej czesci twarzy (midline lethal granuloma). Opis przypadku.

A case of the idiopathic form of facial midline granuloma is described in a man aged 35 years. Good result was obtained after radiotherapy, cobalt radiotherapy and chemotherapy. After 4 years no relapse or generalization of changes were noted.

[Is Stewart's malignant midline granuloma a peripheral T-cell lymphoma? Apropos of 5 cases]. / Le granulome malin centro-facial de Stewart est-il un lymphome T périphérique? A propos de 5 observations.

Midline granuloma includes diverse clinicopathological entities, such as Wegener granulomatosis, polymorphic reticulosis, lethal midline granuloma and conventional malignant lymphoma of the nose usually of B-cell origin. The authors describe five patients with LMG clinically and pathologically typical. Using an extensive panel of monoclonal antibodies, they demonstrate an "activate" T-cell phenotype observed on the initial lesion of the face in one patient, similar to that found in two patients with LMG but studied after dissemination in peripheral T-cell lymphoma. Furthermore, many atypical cells were found in LMG, and stained with the Ki-67 monoclonal antibody, a marker of proliferating cells. These findings support the view that LMG is closely related to T-cell malignancies. Two of them were treated with recombinant Interferon alpha 2a followed by a response rapidly objective. Immunohistologic studies are very important for confirming the T-cell origin of such a disease and for selecting patients to be treated with Interferon alpha.

Treatment of "idiopathic midline destructive disease" by irradiation. A case report.

An unusual case with an aggressive destructive granulomatous lesion of the maxilla is reported. Although the possibility of infection and neoplasm could be ruled out, a definite diagnosis could not be established even by repeated biopsies which showed the lesion to be a non-specific inflammatory process. Since Wegener's granulomatosis was most unlikely, the patient was treated by radiotherapy which caused rapid remission of the lesion with no sign of recurrence after 4 years. The clinical and histological findings as well as the responsiveness to the treatment were most indicative of idiopathic midline destructive disease. Effective management of lethal midline granuloma of unknown aetiology is discussed.