Yukitoshi Fukumatsu

Role of macrophages in ovarian follicular development

The effects of macrophages on granulosa cell proliferation were examined using gonadotropin-primed immature female rats and osteopetrotic (op/op) mice, a model defective in monocyte-macrophage lineage cells. Macrophages were found in the follicles at various developmental stages in rats and mice. The labeling index with [3H]thymidine of cultured rat granulosa cells was maximal when they were cultured with peritoneal macrophages at a macrophages:granulosa cell ratio of 0.01. This ratio was similar to those in rat preantral and antral follicles in vivo. In op/op mice, the number of developing follicles was markedly reduced, but increased after daily macrophage-colony-stimulating factor (M-CSF) administration. In the antral follicles of op/op mice, both granulosa cells and macrophages were significantly decreased in number but were increased after M-CSF treatment. Double immunohistochemical staining revealed that epidermal growth factor (EGF)-positive cells were macrophages in the developing rat follicles. These findings suggest that macrophages are located in the developing follicles and participate in promoting granulosa cell growth through a paracrine mechanism by secreting EGF and other cytokines.

Immunohistochemical and Morphological Observations of Macrophages in the Human Ovary

Macrophages have been identified within the corpus luteum of several species, including human (1–3). In addition to their well recognized phagocytic property, macrophages have been shown to exert other influences in luteal tissue. Recently, Kirsch et al. reported that macrophages secrete substances that stimulate luteal cell progesterone production in the mouse corpus luteum (4), and Halme et al. suggested that peritoneal macrophages may exert luteotropic effects on human granulosa-luteal cells (5).

Distribution and Cytological Properties of Macrophages in Human Fallopian Tubes

The macrophages in human Fallopian tubes of women in the reproductive and postmenopausal periods were examined with a focus on their morphological properties by immunohistochemical staining and transmission electron microscopy. The fine structure of the smooth muscle cells in the Fallopian tubes was also investigated during the reproductive period. For immunohistochemical staining, we used two monoclonal antibodies that were specific for human macrophages, namely PM-1K and PM-2K. PM-1K recognizes human monocytes/ macrophages corresponding to CD68, and PM-2K recognizes tissue macrophages. PM-1K-positive cells were always present and their numbers increased significantly during the menstrual and early to mid-secretory phases. In contrast, relative numbers of PM-2K-positive cells were small throughout the menstrual cycle. In the postmenopausal period, few PM-1K-positive cells were detected, but PM-2K-positive cells remained. The macrophages during the secretory phase in the endosalpingeal stroma had well-developed intracytoplasmic organelles, but relatively few cytoplasmic vacuoles and granules. In the same phase, many cells of the monocyte/macrophage lineage appeared in the vascular lumen of the endosalpingeal stroma. The macrophages during the menstrual phase had well-developed intracellular organelles, with cytoplasmic vacuoles and granules of various sizes and configurations. During the late secretory phase, just prior to menstruation, the smooth muscle cells contained few cytoplasmic filaments but electron-lucent or electron-dense lysosome-like bodies were seen. These findings suggested the presence of macrophages in human Fallopian tubes. It is possible that such macrophages might be involved in the physiological functions of the tubes during the reproductive period and moreover that they might participate in the reconstruction of the muscle layer of the tubes.

Malignant mesenchymal tumors of the ovary in three cases: Histology, immunohistochemistry, and ultrastructural observations

Primary ovarian sarcoma is a rare neoplasm. The diagnosis sometimes becomes difficult by light microscopic examination alone because of the rarity and heterogeneity of these tumors. Immunohistochemical and ultrastructural studies are very useful for diagnosis. Here, we describe two cases of ovarian sarcomas: fibrosarcoma and leiomyosarcoma, and a case of carcinosarcoma (homologous malignant mixed müllerian tumor). In addition to histological findings, immunohistochemical and ultrastructural observation was undertaken to make a final diagnosis. Clinical outcome was variable in the three cases. It was unlikely to be related to the disease stage or treatment, such as surgical excision or anticancer drugs, whereas the mitotic index may be an important prognostic indicator in ovarian sarcomas.

Endometrial adenocarcinoma following the conservative treatment of an atypical polypoid adenomyoma

We present a case of well differentiated endometrioid adenocarcinoma of the endometrium in a 29-year-old woman, developing 6 months after an atypical polypoid adenomyoma (APA) was diagnosed by curettage. Four cases of APA with coexistent endometrial adenocarcinoma were recently reported. To our knowledge, this is the first reported case of endometrioid adenocarcinoma following conservative treatment for an APA. Since APA may be associated with the development of adenocarcinoma, careful follow-up with hysteroscopy and endometrial sampling is recommended in a woman with APA who desires continued fertility.

High-dose oral tegafur-uracil maintenance therapy in patients with uterine cervical cancer

Objective The aim of this study was to determine the efficacy and toxicity of oral administration of tegafur-uracil (UFT) at a high dose, 600 mg/day, based on the tegafur dose, against uterine cervical cancer. Methods This study consisted of a retrospective analysis. From April 1986 to March 1997, 309 patients with uterine cervical cancer were registered. Oral UFT was administered to 162 patients for maintenance therapy after an initial treatment (the UFT group). The other 147 patients were not treated with UFT (the control group). The survival rate was calculated for both groups and statistically analyzed using the log-rank test. Adverse events were compared between the UFT and control groups. Results In the UFT group, 103 patients (63.6%) received UFT for ≥90 days. The drug dose was 600 mg/day for 137 patients (84.6%) and 300 to 400 mg/day for the remainder. The overall survival rate was significantly higher in the UFT group than in the control group (p<0.05). The prognosis was particularly favorable in stage III cases, in cases of squamous cell carcinoma, and in cases that were treated by radiotherapy. The most frequent side effects were nausea/vomiting (12.2%), appetite loss (10.1%), and leukopenia/neutropenia (5.8%). Conclusion High-dose oral UFT maintenance treatment prolonged the disease-free survival and overall survival of patients with uterine cervical cancer, particularly of those with advanced disease.

Squamous cell characteristics in small cell carcinoma of the uterine cervix: histological, immunohistochemical, and ultrastructural study in xenografted small cell carcinoma

Small cell carcinoma of the uterine cervix is a rare type of gynecological tumor that frequently expresses neuroendocrine differentiation. Its histological origin is unclear. We examined the histopathological characteristics of small cell cervical carcinoma in a patient with elevated serum adrenocorticotropin hormone. We then studied the morphological alteration in xenotransplanted tumors (passages 1–9) using immunohistochemistry and electron microscopy. The primary cervical tumor was characterized by a sheetlike arrangement of uniform small cells with hyperchromatic nuclei and a high nucleocytoplasmic ratio. A ribbon-like or trabecular pattern was also observed in a small area of the tumor. Neuron-specific enolase, chromogranin A, and S-100 were positive for the tumor cells, but cytokeratin was negative. Dense-core granules were detected by electron microscopy. In the xenografted tumor, a serial change from squamous cells to round-to-oval cells was observed. Cytokeratin was immunohistochemically stained in the squamous tumor cells but not in the other tumor cells. In contrast, chromogranin A was stained in some of the round-to-oval cells. Basal lamina underlaid the squamous tumor cells, and desmosome-like junctions were apparent. The cytoplasm was filled with well-differentiated organelles including electron-dense tonofilaments. Elliptical tumor cells resembled the primary carcinoma ultrastructurally. These findings suggest that small cell cervical carcinoma with neuroendocrine properties shares the characteristics of squamous cell carcinoma.

Isolation, growth, and characteristics of human ovarian surface epithelium

To isolate human ovarian surface epithelium (OSE) and studied its characteristicsin vitro, we used the scraping method with an enzymatic procedure. After incubation of the ovary in collagenase type 1 solution, the surface cells were removed by gentle scraping with surgical blade. Cells obtained as a cluster after unit gravity sedimentation with 5% bovine serum albumin in medium 199 were cultured in medium 199 containing 15% fetal bovine serum. The viable cell number in a single ovary was 0.1 to 2.7×106, and the cell population doubling time was between 7 to 10 days. Confluent monolayers were formed after 13–20 days and subcultured one to three times. The monolayers mostly had a cobblestone appearance, and fusiform or polygonal cells were also observed. By cytochemistry, immunocytochemistry and scanning and transmission electron microscopy, the cells in short-term culture were shown to have characteristics of mesothelial OSE cells.

Torsion of a Subserosal Uterine Myoma

The authors report a case of subserosal uterine myoma associated with acute abdominal pain due to torsion. A 28-year-old woman complained of severe low abdominal pain. Torsion of an ovarian tumor was strongly suspected, and conventional MRI was performed. The MRI showed a large mass adjacent to the anterior wall of the uterus, and the mass was connected to the uterus by a pedicle. Accordingly, torsion of a subserosal uterine myoma was strongly suspected, and emergency operation was performed. The mass was twisted about 180°, and it was successfully resected. Torsion of a subserosal uterine myoma is very rare, and it is difficult to diagnose immediately. MRI is a very useful examination for diagnosing intrapelvic lesions, as in this case.