Akikatsu Kataura

Nasal T-cell lymphoma causally associated with Epstein-Barr virus : Clinicopathologic, phenotypic, and genotypic studies

The authors have previously demonstrated nasal T‐cell lymphoma (NTL) associated with Epstein–Barr virus (EBV). The detailed clinical, phenotypic, and genotypic features and the role of EBV in lymphomagenesis remain to be clarified.

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 la‐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 Wegeners granulomatosis, and the other of which is nasal T‐cell lymphoma as described herein.

The effect of adenotonsillectomy in children with OSA

Adenotonsillar hypertrophy and abnormal facial morphology are thought to be important for the occurrence of obstructive sleep apnea syndrome (OSA). We evaluated the effects of adenidectomy and/or tonsillectomy and the relationship between the treatment results and facial morphology in 134 children with OSA. Significant improvements in apnea-hypopnea indes (AHI) and lowest blood oxygen saturation (SaO2) were noted and 78.5% of the patients improved after adenoidectomy and/or tonsillectomy. Additional operations were needed in two out of 13 cases of the adenoidectomy group and two out of four cases of the adeno-monotonsillectomy group. In the adenotonsillectomy group, the unimproved children tended to have smaller tonsils, narrower epipharyngeal airspace, and more poorly-developed maxillary and mandibular protrusion than the improved children.

Non-Hodgkin's lymphoma of Waldeyer's ring and nasal cavity. Clinical and immunologic aspects

Twenty‐nine cases of non‐Hodgkins lymphoma of Waldeyers ring (W‐NHL) and nasal cavity or paranasal sinus (N‐NHL) were studied for tumor‐surface marker phenotype and histopathologic correlation with clinical features. Immunostaining procedures on tissue sections by using xenoantisera and monoclonal antibodies to human B‐ and T‐cells enabled the authors to demonstrate precise surface marker phenotypes of tumor cells and, moreover, the histologic localization of normal or neoplastic B‐ and T‐cells in preserving the original structure of lymphoid organs or tumor tissues. In 22 cases of W‐NHL, 19 (86%) had B‐cell markers and 3 (14%) had T‐cell markers, whereas 6 of 7 cases (86%) of N‐NHL had T‐cell markers. Tumor cells in T‐cell iymphomas in W‐NHL and N‐NHL reacted with antibodies to peripheral T‐cells except one case of W‐NHL. Rappaport “histiocytic” subtype was heterogeneous with respect to both surface marker characteristics and morphologic features, i.e., seven had B‐cell markers and four had T‐cell markers, and they were all subdivided into “large cell” or “large cell, immunoblastic” in Working Formulation and “large cell” or “pleomorpphic” in Lymphoma Study Group classification. The actuarial survival curve for all T‐cell lymphoma patients was characterized by a rapid initial decline and a subsequent plateau, which contained two of the long survivors. In contrast, the B‐cell lymphoma group had a more graded decline. The median and actuarial survivals of the T‐cell lymphoma group were far inferior to those for the lymphoma group that expressed B‐cell markers.

Effects of thromboxane A2 receptor antagonist (Bay u 3405) on nasal symptoms after antigen challenge in sensitized guinea pigs.

To define the role of thromboxane A2 (TxA2) in allergic rhinitis, we examined the effects of the TxA2 receptor antagonist Bay u 3405 (1, 3 and 10 mg/kg, orally) on nasal symptoms, changes in total airway resistance (TAR), histamine hypersensitivity and eosinophil infiltration into the nasal mucosa induced by topical antigen challenge in actively sensitized guinea pigs. Nasal symptoms (number of sneezes and scratches) were significantly inhibited by pretreatment with Bay u 3405, in a dose-dependent manner. We noted a biphasic increase in TAR after antigen challenge. The first peak response of TAR (177.5 +/- 6.1%, mean +/- SE) was partially but significantly inhibited by Bay u 3405 at 10 mg/kg (142.8 +/- 4.3%, p < 0.01). The second peak response of TAR (181.0 +/- 13.4%) was also inhibited by Bay u 3405 at 3 mg/kg (120.3 +/- 3.1%) and 10 mg/kg (125.2 +/- 9.4%) (both, p < 0.01). The histamine hypersensitivity induced by antigen was inhibited by Bay u 3405 at 15 mg/kg (p < 0.05). Moreover, the mean eosinophil infiltration into the nasal mucosa induced by antigen (644.1 +/- 202.6/both sides of the nasal septum) was inhibited to 137.8 +/- 69.0 by Bay u 3405 at 10 mg/kg (p < 0.05). In conclusion, our results suggest that TxA2 may play an important role in allergic rhinitis in guinea pig models.

Evaluation of the Role of Adenotonsillar Hypertrophy and Facial Morphology in Children with Obstructive Sleep Apnea

We evaluated the role of adenotonsillar hypertrophy and facial morphology in children with obstructive sleep apnea (OSA) and compared these data with an age-matched control group. We performed cephalometric analysis to evaluate facial morphology using lateral facilal roentgenograms. Adenotonsillar and maxillary hypertrophy was remarkable in OSA children. Maxillary protrusion was significantly smaller in the OSA group than in the control group in older children (5-9 years old). Mandibular protrusion was significantly smaller in the OSA group even at younger ages (1-2 years old). The hyoid bone was significantly lower in the OSA group than in the control group at age 3-6 years. Both environmental factors due to upper airway obstruction and genetic factors are suspected as causes of abnormal facial morphology in OSA children.

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.

Radiotherapy for Kimura's disease: the optimum dosage.

PURPOSE To evaluate retrospectively the optimum dosage of irradiation for Kimuras disease. METHODS AND MATERIALS Twenty patients with Kimuras disease were treated with radiotherapy. The sex ratio was 19 males to 1 female. The mean ages at onset, initial treatment, and radiotherapy were 26.2, 29.5, and 32.2 years, respectively. Radiotherapy was mainly applied for residual or recurrent tumors. The eosinophil count increased by more than 10% in 18 of the 20 patients. In most instances, irradiation was given through a single field with dosages ranging from 20 to 44 Gy. RESULTS At the completion of radiotherapy, a marked response in tumor size was noted in all cases. The minimum follow-up was 48 months. Local control was obtained in 23 of 31 lesions (74.1%). At dosages of < or =25 Gy, 26-30 Gy, and > 30 Gy, local control was obtained in 2 of 8 (25.0%), 9 of 10 (90.0%), and 12 of 13 sites (92.3%), respectively. CONCLUSIONS Radiotherapy is an effective treatment for Kimuras disease. This strongly suggests that no surgical procedure other than a biopsy should be carried out. The radiation field should be limited to the lesion and swelling of the adjacent lymph nodes as much as possible, with a optimum dosage of 26-30 Gy regardless of tumor size.

Midfacial T cell lymphoma: characterization by monoclonal antibodies.

Three cases of so-called lethal midline granuloma were studied immunologically, using monoclonal antibodies against T cell subsets, and electron microscopically. Immunofluorescence and immunoperoxidase studies of their surgical and autopsy specimens proved that the tumor cells showed positive stainings with anti-Leu 1 and anti-Leu 3a antibodies, and negative staining with anti-Leu 2a, anti-HLA-DR, and anti-immunoglobulin antibodies. These data might indicate that the tumor cells of the three cases had a similar surface antigen phenotype to that of peripheral helper-inducer T cells. The histopathological and ultrastructural examinations of the tumors showed general characteristics reported for T cell lymphomata derived from peripheral T cells.

Cellular immune response of adenoidal and tonsillar lymphocytes to the P6 outer membrane protein of non-typeable Haemophilus influenzae and its relation to otitis media.

Cellular immune responses to the P6 outer membrane protein of non-typeable Haemophilus influenzae (NTHi) were determined in vitro by measuring immunoglobulin (Ig) secreting cells and lymphocyte proliferation in adenoidal and tonsillar lymphocytes from 19 children. Preliminary tests showed that P6 did not stimulate naive cells such as cord blood lymphocytes, but did stimulate sensitized cells in adenoids and tonsils. Cellular proliferation was significantly higher in adenoidal lymphocytes than in tonsillar lymphocytes (median: quadratile of stimulation index = 3.7:2.3-5.5 vs. 1.2:1.0-2.1, p < 0.02). A comparison between children with or without otitis media revealed that proliferative responses to P6 of adenoidal lymphocytes from children with otitis media were significantly decreased (2.0:1.8-3.6 vs. 3.7:2.3-5.5, p < 0.04). P6-specific antibody secreting cells were identified in a total of 14 adenoids and the number of cells secreting IgA was decreased in the otitis media group compared to controls (median: quadratile/10(6) cells = 435:359-499 vs. 755:593-1870, p < 0.05). Cultivation with P6 stimulated IgA secretion in children without otitis media, while no response was seen in children with otitis media (median: quadratile/10(6) cells = 1323:915-2410 vs. 2240:1900-2830, p < 0.02). These preliminary data demonstrate that lymphocytes from adenoids and tonsils recognize P6 as a specific antigen and that the adenoid is the more reactive of the two organs. Impaired P6-specific cellular immune responses of adenoids in children with otitis media may explain the recurrent nature of otitis media due to NTHi in the otitis prone population.