Genotypic analysis of lethal midline granuloma]

So-called lethal midline granuloma is of great clinical and theoretical interest. The etiology of lethal midline granuloma is unknown and the pathogenesis is variable, with debate as to precise classification and natural history. In this study, we reported genotypic and immunopathological features in 3 cases of lethal midline granuloma. The histopathological diagnosis of their biopsy specimens was initially polymorphic reticulosis/midline malignant reticulosis. Immunohistologic study of the specimens revealed that immature or atypical cells had phenotypes of T-cells, CD2, CD3, CD4 (Case 1), CD4 (Case 2), and CD2, CD3 (Case 3). Those cells were also found to be positive for HLA-DR, which indicated that they were activated T-cells. Immunohistology in T-cells, however, was not able to give a similar clue to clonarity as it was possible within B-cell neoplasms by immunophenotyping the light chains. With the establishment of cDNA probes for the T-cell receptor genes it was possible to analyze neoplasms of lymphocyte origin for lineage and clonality. The Southern blot analysis of 3 cases showed rearrangement of TCR gene, TCR beta and TCR gamma chain (Cases 1 and 2) and TCR beta and TCR delta chain (Case 3), whereas none of them showed rearrangement of immunoglobulin heavy chain. These findings represented conclusive evidence for a monoclonal T-cell proliferation within lethal midline granuloma. On the ground of immunohistological and genotypic studies, lethal midline granuloma histologically diagnosed as polymorphic reticulosis/midline malignant reticulosis are proven to be a T-cell lymphoproliferative disorder.     

Immunopathology of polymorphic reticulosis of the larynx

We treated a 28-year-old woman with initial symptoms of hoarseness. At biopsy, atypical lymphoid cells infiltrate was observed in the submucosa of the larynx and polymorphic reticulosis was diagnosed. Immunohistochemical examination of the laryngeal material obtained at autopsy revealed a strong reaction of lymphoid cells to the monoclonal antibody to human T lymphocytes. The possibility that polymorphic reticulosis is a transitional form of peripheral T cell lymphoma was confirmed.     

Is Stewart's malignant midline granuloma a peripheral T-cell lymphoma? Apropos of 5 cases

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.     

Midline peripheral T-cell lymphoma--an immunohistochemical and electron microscopy study

Twenty-six cases of nasal/nasopharyngeal midline peripheral T-cell lymphomas were studied clinically and pathologically with immunohistochemical markers and electronmicroscopy. A clearer understanding of the nature of midline malignant reticulosis has obtained. Immunohistochemical markers confirmed that except 5 small specimens which failed to show the monoclonal growth, 18 cases had peripheral T-cell lymphomas, 15 had TH, 3 Ts and 2 B-Cell lambda light chain and 1 HC. Morphological observations showed that 24 cases out of 26 exhibited middle and small polymorphic T-cells. This tumor had distinctive clinical features and was characterized by midfacial progressive necrosis, slow growth, local invasion and rarely metastasis, often with prominent granulomatous and vascular proliferation. Therefore, a discrimination of this disease from midline malignant reticulosis and midfacial destructive lesions is absolutely necessary.     

Association of Epstein-Barr virus with polymorphic reticulosis

Summary We report a case of polymorphic reticulosis (PR) associated with pharyngeal replication of Epstein-Barr virus (EBV). A 78-year-old man with necrotic inflammatory granulations in the nasal cavities and ulcerative tissue of the tonsils was found to have PR after an initial diagnosis of lethal midline granuloma and was found to have high antibody titers to EBV. EBV-determined nuclear antigen (EBNA) was demonstrated in pharyngeal biopsy specimens by the anti-complement immunofluorescent technique, following which dual immunofluorescence staining, EBNA and T-cell antigen analysis were performed, using a wide variety of monoclonal antibodies. All of the EBNA-positive lymphocytes in the pharyngeal biopsy specimens were found to have exclusively T-cell antigens. This case strongly suggests that some of the cases of PR related to T-cell lymphomas may be closely associated with active EBV infection.     

The protean clinical features of polymorphic reticulosis (lethal midline granuloma)

Confusion surrounds the entity known as “lethal midline granuloma.” Partly responsible is the lack of specificity in this term. “Polymorphic reticulosis” has been used as a term to describe the morphology of the disease. Thirty-two cases illustrate the protean features of this disease. Although it commonly presents in the head and neck, other sites such as the lungs, kidneys, skin, and gastrointentinal tract may be involved, either alone or in conjunction with lesions of the head and neck. Clinically, it is easily confused with Wegener's granulomatosis. Histopathologic differentiation, however, is both feasible and important. Wegener's granulomatosis is treatable with steroids with or without cyclophosphamide; polymorphic reticulosis confined to one site responds to irradiation. In polymorphic reticulosis, the best results of treatment are obtained in localized lesions of the upper airway treated early with irradiation; a poorer outcome is associated with multifocal involvement, which necessitates systemic therapy.     

The tonsils as MALT (mucosa-associated lymphoid tissue) of the nasal mucosa

One of the most effective defense mechanisms of the nasal mucosa is its immune response leading to the synthesis of antibodies directed against inhaled antigens. In order to understand the immunology of the upper respiratory tract it is essential to know whether this response takes place within the mucosa itself or within regional lymphoid organs. The authors investigated cell populations involved in immune processes within the mucosa and as a model of a lymphoid organ, in the tonsil. Using a range of monoclonal cell surface markers, the authors concentrated on antigen-presenting cells, the B-cell differentiation, and T-cell subpopulations and their corresponding activation markers. The findings demonstrate that the normal mucosa has no organized lymphoid structures and few or no early, maturing, or activated B-lymphocyte stages. The antibody-producing plasma cells found within the mucosa can therefore not be regarded as locally formed. On the contrary, the palatine tonsils demonstrate a typical lymphoid structure and contain all activation and differentiation stages of B-lymphocytes from premature to plasma cells. This would suggest that the human nasal mucosa is not capable of providing a local immune response, but is dependent on lymphoid organs like the tonsil, as the regional "mucosa-associated lymphoid tissue" (MALT).     

Limited parotidectomy: the role of extracapsular dissection in parotid gland neoplasms

OBJECTIVE: Surgical techniques for parotid gland neoplasm removal have been shaped over the years by the importance of the gland's relationship with the facial nerve, histologic behavior of parotid tumors, and recurrence rates from specific techniques. Parotidectomy with facial nerve dissection has become the procedure of choice in removal of parotid gland neoplasms because of the resulting low recurrence rate. However, these more comprehensive dissections can cause significant postoperative complications, some cosmetically devastating. We propose that a more limited dissection yields a similar low recurrence rate but with less risk of complications. STUDY DESIGN: Retrospective case series. METHODS: A retrospective review of the clinical outcomes and pathology of 27 patients who underwent extracapsular dissection for parotid gland neoplasms. RESULTS: All tumors were located in the superficial lobe of the parotid gland and size of the masses ranged from 4.0 to 1.0 cm (mean 2.4 cm) in diameter. Pathology of the parotid tumors consisted of 11 pleomorphic adenomas, six Warthin's tumors, six benign epithelial cysts, one sarcoid lesion, two lymphoid hyperplasia, and one Kaposi's sarcoma. There were no cases of capsular rupture. There was no temporary or permanent facial paralysis and no incidence of Frey's syndrome. One patient developed a sialocele, which was aspirated and resolved after 3 months. There were no recurrences with follow-up times between 5 months and 6 years (mean 41 mo). CONCLUSION: We advocate extracapsular dissection for benign parotid neoplasms because of the acceptable recurrence rates with limited complications as compared to superficial parotidectomy.     

Unusual presentations of lymphoma of the head and neck in childhood

Lymphoma of the head and neck in children can pose a significant diagnostic problem, especially when histologic analysis indicates non-Hodgkin's lymphoma and the initial site of involvement is extranodal. This report describes 15 pediatric cases of lymphoma seen from 1981 to 1987 with an initial presentation in the head and neck. Cervical lymph nodes represented the initial site of involvement in 10 of the cases. The other five cases presented with disease in the tonsillar fossa; maxillary sinus and mandible; parotid; pharyngeal wall; trachea and thyroid gland; and ethmoid sinus, sphenoid sinus, and anterior fossa. The histologic type was non-Hodgkin's lymphoma in 12 cases and Hodgkin's lymphoma in 3 cases. Our experience has shown that lymphoma of the head and neck in children presents a confusing clinical picture and was initially confused with inflammatory disease, polymorphic reticulosis, and other neoplasms such as rhabdomyosarcoma. In one patient, Epstein-Barr virus infection and an inherited immunodeficiency state probably played a role in the pathogenesis of the lymphoma.     

微切割喉鳞状细胞癌9p13-23区域微卫星杂合性缺失的研究

目的探讨喉鳞状细胞癌(简称鳞癌)在9p13-23区域微卫星(microsatellite)发生杂合性缺失(1ossofheterozygosity,LOH)的热点.方法采用显微切割法从病理切片中挑取肿瘤组织,选取位于9p13-23区域的13个高多态性微卫星引物对42例喉鳞癌组织进行聚合酶链反应和变性凝胶电泳.结果①42例喉鳞癌在9p13-23区域等位基因LOH的总发生率是97.6%(41/42).在13个微卫星引物中,LOH发生率最高者是位于9p22-23的D9S162(89.5%),其次是位于9p21的D9S171(80.0%).与p16基因紧密连锁的D9S1748的LOH发生率仅50.0%.②等位基因缺失作图分析发现42例喉鳞癌组织在9p13-23上存在2个明显的LOH较小区域,分别位于99211的D9S161～D9S171之间和9p22-23的IFNA和D9S162之间.结论喉鳞癌在9p13-23区域除抑癌基因p16以外可能还存在2个或2个以上候选抑癌基因,这些候选抑癌基因也许和p16一样与喉鳞癌的发生、发展密切相关.     

An unusual complication of polymorphic reticulosis: a case presentation

The authors present a case of polymorphic reticulosis which responded to radiotherapy, but had a fatal complication with the development of a tracheoesophageal fistula.     

微切割喉鳞状细胞癌9p13—23区域微卫星杂合性缺失的研究

目的：探讨喉鳞状细胞癌（简称鳞癌）在9p13-23区域微卫星（microsatellite)发生杂合性缺失（loss of heterozygosity,LOH)的热点。方法：采用显微切割法从病理切片中挑取肿瘤组织,选取位于9p13-23区域的13个高多态性微卫星引物对42例喉鳞癌组织进行聚合酶链反应和变性凝胶电泳。结果：（1）42例喉鳞癌在9p13-23区域等位基因LOH的总发生率是97．6％（41／42）。在13个微卫星引物中,LOH发生率最高者是位于9p22-23的D9S162（89．5％）,其次是位于9p21的D9S171（80．0％）,与p16基因紧密连锁的D9S1748的LOH发生率仅50．0％,（2）等位基因缺失作图分析发现42例喉鳞癌组织在9p13-23上存在2个明显的LOH较小区域,分别位于9p21的D9S161－D9S171之间和9p22-23的IFNA和D9S162之间。结论：喉鳞癌在9p13-23区域除抑癌基因p16以外可能还存在2个或2个以上候选抑癌基因,这些候选抑癌基因也许和p16-一样与喉鳞癌的发生,发展密切相关。     

Mucosa-associated lymphoid tissue in individuals with AIDS

Vestibular folds (VF) protect upper airways, but contain fewer immune cells in AIDS patients, which affects the structure of lymphoid follicles (LF).ObjectiveTo characterize fibrosis and immunoglobulin production in vestibular fold lymphoid tissues of AIDS patients with or with no infection and malnutrition.Materials and MethodsA retrospective study of 71 adult vestibular fold autopsy specimens. The morphological analysis was done using the picrosirius staining method. Immunohistochemical methods consisted of anti-IgA, anti IgG, and anti IgM antibodies.ResultsFibrosis was less intense in AIDS patients compared to subjects without AIDS; the same applied to patients with infection or malnutrition. IgA and IgG titers were higher in AIDS patients; IgM titers were higher in cases with infection.ConclusionThis study helps understand variations in lymphoid follicle components of AIDS patients; it also shows the influence of architectural changes and the effect of associated respiratory infection and malnutrition on lymphoid follicle function.     

Klassifikation maligner Lymphome des Halsbereiches: Kombinierte morphologische,immunzytologische, serologische und Zellkultur-Untersuchungen

Summary 81 untreated malignant lymphomas of the neck were classified morphologically according to the German Kiel classification and to the American classification of Rappaport and Berard and these tumors were typed immunologically as to their T- or B-cell nature. Cells from 16 of these patients were subsequently grown in tissue culture for periods up to seven months. Tissue culture cells were monitored as to spontaneous variations in the morphologic cell type and to the expression of T- or B-cell surface determinants. In addition in 10 patients sera were tested for anti-Epstein-Barr virus (EBV) antibodies. The results of these investigations were correlated with the course of the individual neoplastic disease. Significantly elevated titers against EBV antigens were detected primarily in 8 of 10 patients, mainly in lymphocytic lymphomas respective lymphoplasmacytoid immunocytomas. All such neoplasms belonged immunologically to B-cell lymphomas and were readily grown in tissue culture. The morphological cell type and the expression of B-cell determinants showed some variation during the culture period.In contrast, lymphomas of EBV-negative patients or patients with low EBV-titers grew poorly in tissue culture and remained morphologically more stabile. Immunocytologically they belonged to tumors with B- and T-cell deficiency and were classified primarily as histiolytic lymphomas and as Hodgkin's lymphomas.The clinical course in slow proliferating tumors seemed to be disadvantageous.     

Burkitt's lymphoma: historical background and recent insights into classification and pathogenesis

In this paper, the authors evaluate the historical evolution of the definition of Burkitt's lymphoma (BL) and of its clinicoepidemiological (endemic, sporadic, and acquired immunodeficiency syndrome-associated BL) and morphological variants. On the basis of the morphological, immunologic, genetic, and clinical characteristics of these tumors, the authors also emphasize the importance of precise disease definitions for biological and epidemiological studies. These principles were used in accordance with the Revised European-American classification of lymphoid neoplasms (REAL), which proposed that disease entities should be defined by a constellation of pathobiological and clinical features.     

Diagnostik und Therapie von Pseudotumoren der Orbita

Orbital pseudotumor is a nonspecific inflammatory process of unknown etiology that can be divided histopathologically into three basic types: granulomatous, lymphoid, and sclerosing. Between 1995 and 1998, 12 patients with pseudotumor orbitae were treated in the ENT Department of the University of Saarland. Histopathological examination showed granulomatous type of pseudotumor in six, lymphoid in three, and sclerosing in three patients. In seven cases the pseudotumor orbitae were medially located and in four cases laterally. In one patient nearly all orbital structures were infiltrated. Diagnostic biopsy was taken endonasally in six cases, via medical orbitotomy in two cases, and via lateral orbitotomy in four cases. Due to their good delimitation lymphoid and sclerosing tumors were extracted completely during diagnostic biopsy and patients were free of complaints after a few weeks. The six patients with granulomatous pseudotumor were treated primarily with steroids after the diagnosis had been definitely confirmed by histology. In three of those six cases a second course of steroid therapy had to be given, with positive results in two cases. Follow-up was between 6 and 28 months (mean 16 months). There were no postoperative complications. The clinical and radiographic presentation of the pseudotumors can vary greatly. Therefore, the differential diagnosis of specific infections or neoplasms can only be established through diagnostic biopsy. Different rhinosurgical approaches provide clear biopsy results and in some cases the pseudotumor is even completely removed.     

Centrosome hyperamplification in head and neck squamous cell carcinoma: a potential phenotypic marker of tumor aggressiveness

OBJECTIVES/HYPOTHESIS: There is currently no single histological or genotypic marker that reliably predicts the biological behavior of head and neck squamous cell carcinoma (HNSCC). While multiple genetic mutations have been investigated, no single genotypic alteration has consistently correlated with tumor aggressiveness. Phenotypic markers may prove more predictive, because they can represent many different genetic alterations. We investigated the frequency of centrosome hyperamplification in HNSCC and examined its usefulness as a marker for tumor recurrence. STUDY DESIGN: Analysis of archived paraffin blocks using immunohistochemistry. METHODS: Eighteen patients who underwent resection of oral cavity squamous cell carcinoma were reviewed. Ten patients had cancers that recurred locally within 1 year of resection, and 8 patients were tumor free at 5 years. The amount of centrosome hyperamplification in the cancer specimens and all surgical margins was graded as follows: 0, none; 1+, rare hyperamplification; 2+, greater than 10% of cells per high-powered field; and 3 +, greater than 20% of cells per high-powered field. RESULTS: Centrosome hyperamplification was found in 17 of 18 tumors (94%). Grade 2+ or 3+ hyperamplification was found more in cancers that recurred (9 of 10) than in those that did not (3 of 8) and was more prevalent in the histologically normal margins of patients with recurrence (8 of 10) than in those without recurrent cancer (3 of 8). CONCLUSIONS: Our results demonstrate the extremely frequent occurrence of centrosome hyperamplification in HNSCC. Centrosome hyperamplification is a phenotypic marker for HNSCC and can reflect multiple genotypic changes. Its presence in histologically normal margins suggests that it may be useful for analysis of primary tumors and tumor margins.     

Solitary fibrous tumor with pseudo-lipoblasts involving the sublingual gland: report of a case and review of the literature

Solitary fibrous tumors (SFTs) are mesenchymal neoplasms uncommonly occurring in the salivary glands. In rare instances, SFTs can contain mature fat, atrophic fat, or vacuolated cells previously termed ‘pseudo-lipoblasts’, which may be misinterpreted as a feature of malignancy. We report an unusual tumor with pseudo-lipoblasts occurring in the sublingual gland. The tumor exhibited a prominent hemangiopericytic pattern, bland cytology, and immunohistochemical and morphologic features consistent with that of an SFT. A review of 15 cases of SFTs of the salivary glands is presented. Emphasis is laid upon the histologic differential diagnosis and the clinical features of these tumors.     

Treatment of granulomatous disorders of the nose and paranasal sinuses

The granulomatous disorders discussed in this review are Wegener's granulomatosis (WG), lymphomatoid granulomatosis (polymorphic reticulosis) and "idiopathic midline granuloma". The treatment of choice of WG is combined therapy with corticosteroids and cyclophosphamide. Severely ill patients may be treated with intravenous bolus infusions of cyclophosphamide. Otherwise oral administration is used. Therapy must be adjusted according to leucocyte and thrombocyte counts. After clinical remission cyclophosphamide must be continued for at least a year under hydration sufficient to cause nycturia in order to protect the bladder mucosa. Corticosteroids can be withdrawn 9-10 months after clinical remission. Relapse of WG can be identified by clinical and laboratory (ESR, CRP, HB, urinary sediment) findings, including detection of anti-neutrophil cytoplasm antibodies (ANCA). Alternate treatment with azathioprine or trimethoprim/sulfamethoxazole may be used in patients with localized or smoldering disease. Furthermore trimethoprim/sulfamethoxazole may be used as adjunctive treatment. Lymphomatoid granulomatosis appears to be a T-cell lymphoma and should be treated aggressively with combination cytotoxic therapy and irradiation of localized manifestations. "Idiopathic midline granuloma" does not seem to exist but appears to be either WG or lymphomatoid granulomatosis when repeated biopsies are examined with monoclonal antibodies and/or serum examined for ANCA.     

Laryngeal plasmacytoma presenting as amyloid tumour: a case report

Laryngeal amyloidosis can be secondary to an underlying lymphoid neoplastic process and in view of this concept; the cases of localized laryngeal amyloidosis should be carefully examined and investigated for the presence of a lymphomatous process. The study design is case report. We report the case of a 64-year-old man with progressive hoarseness. A biopsy showed histological findings consistent with an extramedullary plasmacytoma associated with localized amyloidosis involving the right hemilarynx (ventricular band, arytenoids and true cord). Immunohistochemical studies showed that the tumour cells of the plasmacytoma were monoclonal (lambda-restricted). PCR analysis of the IgH gene demonstrated a clonal band confirming B-cell clonality. The amyloid deposits were also shown to be reactive with lambda immunoglobulin light chain, suggesting the pathogenetic relationship between the plasmacytoma and amyloid deposition in the larynx. There was no other evidence of malignancy or amyloidosis elsewhere. The majority of the cases reported of amyloid deposition with plasmacytoma, the lesions were found in the nasopharynx, in contrast to our case in which the lesions were sited in the larynx and with the peculiarity of being multiples. Moreover, amyloid and plasmacytoma were clearly delimitated and the amyloid tissue was more extensive than the tumour tissue. This case supports the concept that localized laryngeal amyloidosis may be a manifestation of low-grade B-cell neoplasms.