Makoto Gomibuchi

Mosaic-like distribution of endothelial cell antigens in capillaries and juxta-alveolar microvessels in the normal human lung

The distribution patterns of endothelial cell antigens, including thrombomodulin and von Willebrand factor (vWf), were studied in normal lung tissues obtained from distant areas of solitary nodules (seven adenocarcinomas and four hamartomas). By single immunoalkaline phosphatase and dual immunofluorescence stainings, the plasma membranes of alveolar capillary endothelium showed linear distribution of thrombomodulin, but their cytoplasm was rarely reactive for vWf (thrombomodulin‐dominant pattern). Microvessels with a diameter larger than 10 μm located in the connective tissue zones demonstrated band‐like reaction for vWf in their cytoplasm, and their plasma membranes often lacked reactivity for thrombomodulin (vWf‐dominant pattern). The juxta‐alveolar microvessels located along the borders between the alveolar‐ and connective‐tissue zones showed mosaic‐like pattern of distribution for these antigens. The pulmonary venules and peribronchial microvessels measuring up to 40 μm in diameter, demonstrated the expression of thrombomodulin along the plasma membrane, and that of vWf in the cytoplasm. Capillaries of the bronchial circulation were also characterized by mosaic‐like pattern of distribution. Both antigens were often expressed in a single cytoplasmic segment. The heterogeneous distribution pattern of these antigens suggests topographic difference in endothelial cell function to maintain coagulatory and anticoagulatory balance in the normal human lung.

Angiogenesis and phenotypic alteration of alveolar capillary endothelium in areas of neoplastic cell spread in primary lung adenocarcinoma.

Normal alveolar capillary endothelium is quiescent in nature and displays anticoagulant thrombomodulin (TM) on its surface. The cytoplasms of these endothelial cells are ultrastructurally non‐fenestrated type, and they barely express von Willebrand factor (vWf). Alveolar fibrosis is accompanied by a capillary endothelium reactive for vWf, and a loss of TM expression. In primary lung adenocarcinoma, neovascularization occurs in association with alveolar fibrosis. In order to study basic factors related to angiogenesis and phenotypic changes of the capillaries located in tumor‐bearing alveolar walls, we examined 37 primary lung adenocarcinomas with electron microscopy and confocal laser scanning microscopy with antibodies for TM, vWf, vascular endothelial growth factor (VEGF), and its receptors (KDR and Flt‐1), and proliferating markers (Ki‐67/proliferating cell nuclear antigen). Tissues microdissected specifically from alveolar walls were used for reverse transcription–polymerase chain reaction (RT–PCR) to assess expressions of mRNA isoforms of VEGF and its receptors. New capillary branching was found by ultrastructural study in the alveolar walls in 12% of the patients. Nuclei of the capillary endothelial cells were reactive for proliferating cell markers. Endothelial fenestrae were developed in 65% of the patients, TM reactivity was lost in the alveolar capillaries, and their cell cytoplasms obtained a reactivity for vWf through a transitional mosaic‐like distribution pattern of both antigens. Besides cytoplasmic VEGF expression in neoplastic cells, tumor‐bearing alveolar walls showed significant expression of mRNA of VEGF165 and KDR. These findings imply that angiogenesis and phenotypic changes of the alveolar capillaries are closely related to a higher expression of tumor‐associated VEGF165 and of KDR in the alveolar walls in primary lung adenocarcinoma.

Mediastinal yolk sac tumor in a woman

Abstract Primary endodermal sinus tumor (yolk sac tumor) of the mediastinum is uncommon and most patients are young and male. We report a yolk sac tumor with a mature teratoma of the anterior mediastinum in a 28-year-old woman with an intrathoracic mass. Four courses of combination chemotherapy were given and the tumor was resected. The patients serum alpha-fetoprotein (AFP) level was elevated, to more 100 000 ng/ml. To the best of our knowledge, this is the first report of serum AFP level exceeding 100 000 ng/ml in a yolk sac tumor with a mature teratoma.

MULTIPLE LUNG TUMORS FOUND 17 YEARS AFTER HYSTERECTOMY : A CASE OF BENIGN METASTASIZING LEIOMYOMA

The patient is a 50-year-old female who presented with cough. A chest X-ray showed bilateral multiple modular shadows. Even though a diagnosis of metastatic lung tumors was strongly suspected no primary lesion could be detected on close examination. Therefore, an exploratory thoracotomy, and histopathological examination of a specimen obtained from a resected tumor were carried out. The resected tumor revealed pathological proliferation of spindle cells without high cellularity or mitosis with nuclear atypism. The patient had a history of surgery for uterine leiomyoma at the age of 33. The histopathological characteristics of the resected lung tumors were remarkably similar to those of the previously resected uterine leiomyoma. In addition, the serum levels of sex hormones, including LH, measured after lung surgery, were within normal range suggesting the possibility of the lung tumors being metastatic. The residual lung tumors did not show any increase in size 26 months after surgery. Therefore, these lung tumors could be considered as lung metastases from a low grade malignant uterine leiomyoma (benign metastasizing leiomyoma).

Carcinoma positive for Epstein-Barr virus staining. Mediastinal lymph node origination?

A 44-year-old man undergoing radical excision of metastatic carcinoma of the mediastinal lymph node with unknown primary sites remains alive and disease-free 14 years after surgery. His cancer cells were positive for the Epstein-Barr virus, which may have been related to the oncogenesis of this tumor. This case is unique in the patients long, disease-free survival and its positive presence of the Epstein-Barr virus.

Bronchial mucoepidermoid carcinoma; Two cases report.

我々は最近, 稀な粘表皮癌の2例を経験した.症例1は20才男性, 左底幹から肺内に直接浸潤し左肺門リンパ節に転移を認め, 左肺全切除術一副ン・櫛享晴をおこなった.症例2は50才女性, 左上幹内に限局, 左上葉スリーブ切除術・縦隔りンパ節郭清をおこなった+占表皮癌は1ow maiignant potentialを有する腫瘍と考えられているが, 治療成績ほ必ずしも良好ではむいとの報告もあり, 手術術式は慎重に決定されるべきと考える.