Lethal midline granuloma (peripheral T-cell lymphoma) after lymphomatoid papulosis.

A Japanese woman with an 8-year history of lymphomatoid papulosis (LP) had lethal midline granuloma (LMG) develop at the age of 51 years. There were histologic similarities between LP and LMG seen in this patient. Surface phenotypic studies on nasal and cutaneous lesions demonstrated a population of T-cells expressing CD2, CD4, CD25, CD30, and histocompatibility antigen-DR (HLA-DR). Genotypic analyses of nasal and skin biopsy specimens disclosed a clonal rearrangement of the beta T-cell receptor gene with the same rearrangement pattern. These data indicate that this patient had LMG characterized by clonal peripheral T-cell lymphoma, which probably resulted from progression of the LP.     

Nasal T-cell lymphoma as a type of so-called "lethal midline granuloma"

Six cases were described in which an initial clinical diagnosis of "rhinitis gangrenosa progressiva" or lethal midline granuloma was made. The histological examinations of their surgical and autopsy specimens proved that their nasologic diseases could all be identified as malignant lymphoma arising from the nasal cavity, showing the general histologic characteristics reported for T-cell lymphomata derived from peripheral T-cells. This histologic observation was then confirmed by immunofluorescence studies using various antisera directed toward either human T- or B-cell-surface antigens. These studies clearly demonstrated that their malignant cells bore human Ly-l-like antigen but lacked human TL-like and Ia-like antigens as well as surface-bound immunoglobulins, indicating their peripheral T-cell origin. These data may suggest that so-called "rhinitis gangrenosa progressiva" or lethal midline granuloma contains at least two distinct disease categories, one of which is Wegener's granulomatosis, and the other of which is nasal T-cell lymphoma as described herein.     

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.     

Implication of surfactant apoprotein in otitis media with effusion

A two-site simultaneous immunoassay using monoclonal antibodies against human surfactant apoprotein (SAP) was used to measure SAP in middle ear effusions (MEEs). In 130 MEE samples from children with otitis media with effusion, SAP was detected in 54 samples (SAP-positive cases, 41.5%). In the remainder, the SAP concentration was below the sensitivity of the immunoassay (SAP-negative cases, 58.5%). A significant difference in periods of observation was found between the SAP-positive cases (17.3 +/- 16.8 months) and the SAP-negative cases (26.2 +/- 22.5 months) (p less than .01). The percentage of positive cases was highest in the serous MEE group (81.2%) and decreased in the purulent MEE group (57%), the mucoid MEE group (30%), and the hyperviscous MEE group (13.6%), in that order. In the purulent MEE group and the mucoid MEE group, the period of observation was significantly shorter in the SAP-positive cases (18.3 +/- 20.4 months and 20.2 +/- 19.4 months) than in the SAP-negative cases (35.9 +/- 24.5 months and 25.4 +/- 18.7 months) (p less than .05). These results suggest that SAP is present in the middle ear cleft and may be a good prognostic predictor of otitis media with effusion in children.     

Immunohistological identification of the activated lymphocytes in human palatine tonsil

Employing various monoclonal antibodies and immunoperoxidase technique, we studied the distribution of the activated lymphocytes in human tonsillar tissue. Both the activated T-cells positive for IL2-receptor (IL2-R) and the activated B-cells defined by L29 were seen in the interfollicular area. Vast majority of the lymphocytes in the germinal center was stained with the L29, the anti-transferrin-receptor antibody, and the Ki-67 antibody which reacts with cycling cells in G1, S, or G2 + M phase. On the other hand, scarcely any cells in the mantle zone were stained with those. The Ki-67 positive cells in the germinal center were identified as two types of staining pattern, i.e., with strong nucleolar staining found in the dark zone and with nuclear staining found in the light zone. Small number of IL2-R positive cells was found in the mantle zone. The cell number per unit area of the activated lymphocytes in the interfollicular area as well as in the germinal center was decreased as the increment of patients' age. From these results, the immunological activation system of T- and B-cells in the tonsils was discussed.     

Metastatic squamous cell carcinoma of the paranasal sinuses from a primary squamous cell carcinoma of the urinary bladder

Metastatic tumours of the paranasal sinuses from primary lesions of the urogenital tract are rare, with about 50 cases so far being reported in the literature. The most frequent primary lesions is a renal carcinoma. We have experienced a case of paranasal sinus malignancy. There were no symptoms of urinary tract carcinoma preceding those in the paranasal sinuses. This case was later revealed at autopsy to be a metastasis from a diverticulum of the urinary bladder.     

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.     

Nasal responsiveness to methacholine stimulation in allergic rhinitis patients

Summary We examined the nasal responsiveness to topical methacholine application in allergic rhinitis and non-allergic chronic rhinitis patients, and in control subjects. Methacholine responsiveness was significantly higher in allergic rhinitis patients than in non-allergic patients and control subjects. In perennial rhinitis, methacholine responsiveness correlated with the severity of daily nasal symptoms and those provoked by specific allergen challenge tests. Among nasal symptoms, hyper-rhinorrhoea was found to be closely related to methacholine responsiveness. As a result of these findings, the possibility of cholinergic hyper-reactivity in allergic rhinitis patients is discussed.     

Synthesis of prostaglandin E2 and F2 alpha in human tonsillar lymphocytes

Although prostaglandins (PGs), especially PGE2 and PGF2 alpha, are thought to be associated with inflammation, there have been no papers dealing with the synthesis of PGE2 and PGF2 alpha in human tonsillar lymphocytes. The features of PG synthesis in lymphocytes were investigated by incubating cells with radiolabelled precursors. Synthesis of PGE2 was greater than that of PGF2 alpha in tonsillar lymphocytes. PGE2 was the predominant product in the tonsillar lymphocytes of the recent infection group. There was no significant difference between T and B lymphocytes in the ratio of PGE2 and PGF2 alpha formed. A significant increase in PGE2 formed with bradykinin was found in the tonsillar hypertrophy group. The possible role of PGs in the pathogenesis and mechanism of releasing free fatty acid PG precursors from cell membranes was discussed.