Kenichiro Kusano

Histological changes of the pharynx and larynx in rats with chronic acid reflux esophagitis.

Conclusions: The histological changes of the pharynx and the larynx associated with surgically induced chronic acid reflux esophagitis were observed in rats. Chronic inflammatory change due to gastric acid reflux was found microscopically in the pharynx and larynx. This indicated that inflammatory changes due to gastric acid reflux are associated with the pathogenesis of laryngopharyngeal reflux disease (LPRD). Objective: To clarify the pathological mechanism of LPRD by studying the histological changes of the pharynx and the larynx in rats with chronic acid reflux esophagitis. Materials and methods: An experimental rat model of chronic acid reflux esophagitis was created surgically. The pharynx, larynx, trachea, lung, and esophagus of these rats were observed histologically every 2 weeks until 20 weeks after the operation. Results: At 8 weeks after the operation, mucosal thickening and inflammatory cell infiltration were observed in the hypopharynx of the rat model. Moreover, chronic inflammation with proliferation of fibroblasts, deposition of collagen fibers, and proliferation and dilatation of the capillaries were found as time progressed. However, little macroscopic change was observed in the hypopharyngeal mucosa. In addition, at 16 weeks post-operation, inflammatory cell infiltration was identified in the nerve cells around the thoracic esophagus, the arytenoid region, and the lung.

Olfactory neuroepithelioma: An immunohistochemical and ultrastructural study

Three cases of olfactory neuroepithelioma are presented in this report. Histologically, these tumors were composed of small cells with round to oval, relatively hyperchromatic nuclei and scanty cytoplasm. The tumor cells were occasionally observed in tubular formations or rosette‐like arrangements. Immunohistochemically, the tumor cells showed a positive reaction for cytokeratin AE1, cytokeratin CAM5.2, Ber‐EP4, antisynaptophysin and anti‐S100 protein in all cases. In two cases, LH‐RH was detected in the tumor cells. Ultrastructurally, the tumor cells had the differentiation features of olfactory epithelium. Olfactory neuroepithelioma is a rare occurrence and it can be very difficult to distinguish olfactory neuroepithelioma from small cell carcinoma, neuroendocrine carcinoma and so‐called “olfactory neuroblastoma” on the basis of hematoxylin and eosin stained sections alone. In controversial cases, a diagnosis of olfactory neuroepithelioma must be substantiated by ultrastructural and immunohistochemical findings, particularly regarding the detection of Ber‐EP4 and LH‐RH immunoreactivity.

Active neovascularization and possible vascular-centric development of gastric and periscapular elastofibromas

An elastofibroma is a benign and rare fibrous lesion that most commonly occurs in the periscapular region. A gastrointestinal elastofibroma is extremely rare. In the present study, six cases of elastofibromas including a case in the stomach were evaluated. The gastric case revealed widely distributed lesions in the submucosal layer with perivascular fibrotic lesions (PVFLs) and some PVFLs were distributed to the skip lesions of elastofibroma. These PVFLs were also observed in all five periscapular cases and invariably contained elastic fibers which showed various degree of maturation. CD34-positive stromal cells were observed not only in elastofibromas but also in PVFLs in each case. These findings suggested the possibility of the PVFLs were the primary lesions of elastofibroma and their vascular-centric development. The percentage of the CD105-positive vessels in elastofibroma group was significantly higher than in the control group. This result indicates active neovascularization in elastofibromas.

Innate immune reactions in locally limited tonsillar cancer.

Tonsillar cancers often present as locally limited tumors but with cervical metastases. When the primary tumors of tonsillar cancers with cervical metastases are as small as clinically occult, the clinical features are diagnosed as primary-unknown cervical metastases. However, little is known as to why small tonsillar cancers establish cervical metastases. The aim of this study was to investigate a possibility that innate immune reactions might suppress the growth of tumors arising in the palatine tonsils, because the palatine tonsils contain various immune effector cells. Infiltration of natural killer (NK) cells and macrophages, which are major innate immune cells, in surgically removed tumors from patients with locally limited tonsillar cancers and tongue cancers was immunohistochemically studied by using anti-CD57 and anti-CD68 antibodies. Phagocytosis of the tumor cells by macrophages was also studied by dual immunofluorescence labeling. The number of infiltrating CD57+ NK cells and CD68+ macrophages was significantly increased in locally limited tonsillar cancers in comparison to normal tonsils and tongue cancers. The phagocytosis of tumor cells by CD68+ macrophages was observed significantly more frequently in tonsillar cancers than in tongue cancers. These results indicated that the innate immune reactions were more strongly induced in locally limited tonsillar cancers than in tongue cancers, and might therefore suppress the growth of primary tumors in palatine tonsils. The innate immune reactions against cancers in palatine tonsils were suggested to be one of the possible etiologies for the developing of primary-unknown cervical metastases.

Innate Immune Reactions in Locally Early Tonsillar Cancer

Objective: The palatine tonsil contains innate immune cells such as natural killer (NK) cells and macrophages. Tonsillar cancers often present locally early tumors with cervical metastases. This study was performed to clarify the possibility that the growth of primary tumors might be inhibited by innate immune cells in the palatine tonsil. Method: NK cells and macrophages were immunohistochemically identified using anti-HNK-1 and anti-CD68 antibodies. The degree of the immune cell infiltration in tonsillar cancers, tongue cancers, and normal tonsils was estimated by counting the number of NK cells and macrophages in formalin-fixed, paraffin-embedded blocks. Phagocytosis of the tumor cells was also studied. Results: There was a significant increase in the number of NK cells in locally early tonsillar cancers (a median of 100 in 8 patients) in comparison to locally early tongue cancers (a median of 8 in 15 patients) and 5 normal tonsils (a median of 35; P < .0001). The number of macrophages was also significantly increased in tonsillar cancers (a median of 247) in comparison to tongue cancers (a median of 81) and normal tonsils (a median of 82; P < .0001). Phagocytosis of tumor cells by macrophages was observed significantly more frequently in tonsillar cancers than in tongue cancers (P < .01). Conclusion: The innate immune reactions were observed to significantly increase and they might therefore inhibit the growth of the primary tumor in locally early tonsillar cancer. In addition, these inhibitory immune reactions against the primary tumor in the palatine tonsil might be part of the etiology of developing primary-unknown cervical metastasis.