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We investigated the relationship between radiological findings and the nature of the cyst fluid and histological findings of six Rathke's cleft cysts. The results show that the majority (five of six cases) of symptomatic Rathke's cleft cysts exhibit no enlargement of the sella turcica on plain x-rays, which may be helpful in differentiating cystic pituitary adenoma in the radiological diagnostic process. Three cases with large cysts showing high-intensity T1-weighted magnetic resonance images harbored abundances of cholesterol crystal and hemosiderin pigment in the cyst walls. The high signal intensity in magnetic resonance images of Rathke's cleft cysts may be explained by hemorrhage and a deposition of cholesterol crystal and may be considered in certain cases of Rathke's cleft cyst, especially when they are large.

Thyroglobulin (Tg) is believed to be iodinated immediately after secretion of Tg into the follicular lumen. In recent years, however, Tg has reportedly been suggested to be iodinated in follicle cells on the basis of biochemical studies. We encountered a boy with goiter diagnosed at the age of 5.5 years, the pathogenesis of which was considered to be Tg deficiency because of Tg secretion failure in blood.

A pulmonary blastoma in a 52-year-old Japanese man was serially transplanted into athymic nude mice. This report emphasizes the characteristics of the neoplasm seen on light and electron microscopic examination. The original tumor consisted of branching tubular structures and primitive mesenchymal components with a few smooth-muscle cell bundles, and resembled fetal lung tissue. Electron microscopic examination revealed that the immature stromal cells resembled epithelial cells. After serial passages in nude mice, the stromal element of the tumor disappeared, and the epithelial element showed squamous metaplasia and occasional mucus production. Endocrine-type granules were observed in a few tumor cells. Histogenetic considerations, including a suggestion that the tumor was derived from entodermal cells, are presented.

Ultrastructural characterization of human corticotrophs (ACTH cells) was performed by 'superimposition technique', which enabled detailed ultrastructural observation of immunoreactive ACTH cells in adjacent semi-thin light microscopic immunoperoxidase and routine electron microscopic sections. The human corticotrophs were large and round or polygonal and were not stellate. They had scanty rough endoplasmic membranes and were packed with numerous large secretory granules measuring from 250 to 500 nm in diameter. The sizes of secretory granules in 6 human pituitaries were 448 ± 128, 344 ± 86, 448 ± 117, 244 ± 65, 316 ± 76, and 340 ± 93 nm, respectively. The granules were not seen in a single row along the plasma membrane as is the case in the rat. They possessed somewhat irregular outlines with a rarely discernible halo. Different densities of granule matrices were occasionally found. The cells often contained a few large heterogeneous vacuoles. From these findings, the human ACTH cells were recognized to be remarkably different in cell shape and size, properties of secretory granules and cytoplamic inclusions from those of the rat pituitary gland. In respect to secretory granule properties, the human ACTH cells are similar to those of some other mammals (fox, young pig, and lerot). More data is required to elucidate the relationship between human ACTH cell morphology and functional state.

A gastric choriocarcinoma cell line capable of producing human chorionic gonadotropin (HCG) was studied by sc transplantation and serial passages into nude mice fed under specific pathogen-free (SPF) conditions. The tumor-take rate at the serial heterotransplantation in SPF mice was high (greater than 95%), in contrast with a low rate in coventional animals (35%). The restoration of morphology and function of the original neoplasm were exclusively verified in SPF mice. Multiple lung metastases were found in 2 animals. The production, storage, and excretion of HCG by tumor cells were confirmed by its high content in serum and cystic fluid in tumors and by its intracellular localization. The tumor cells also contained a specific placental alkaline phosphatase in their membranes. The cells were various trophoblastic types ranging from primitive cytotrophoblasts to typical syncytial cells. The hormone effects of the tumor on sex organs of tumor-bearing animals were evident.

Peripheral lung cancers frequently possess a fibrotic focus or scar in their center or beneath the pleura. We reexamined 58 cases of peripheral lung cancer of less than 3 cm in diameter (48 adenocarcinomas, two large cell carcinomas and eight squamous cell carcinomas) which were removed surgically between June 1962 and July 1973. Analyses of the cases revealed that in adenocarcinoma with increased collagenization or hyalinization in the fibrotic focus, the degree of pleural invasion and incidence of lymph node metastasis and blood vessel invasion were greater and thus the prognosis of the patient was poorer than in cases with no or slight collagenization. The results also indicate that the characteristics of the central fibrotic focus are probably more important than the size of the tumor for estimating the prognosis of patients with peripheral adenocarcinoma of less than 3 cm in diameter. The same might be said of peripheral large-cell carcinoma. However, the prognostic importance of the fibrotic focus was not confirmed in cases of peripheral squamous-cell carcinoma. Although the central or subpleural scar has long been the basis of the scar cancer concept, alternate explanations were considered, namely, that scar formation occurred along with tumor development, rather than before, in the case of adenocarcinomas.

Clinical symptoms, endocrinological findings, neuroradiological findings, and the results of treatments were studied in 24 patients with pituitary adenoma with hyperprolactinemia (over 30 ng/ml). The excised tumor tissues were examined light-microscopically and electron-microscopically, and hormones in the tumor culture medium were measured. The subjects in this study were 19 female and 5 male patients. All of the female patients had had amenorrhea and 14 of them had shown galactorrhea. Nine of the 24 patients had had visual disturbance and 2 had had diplopia or blephaloptosis. These 24 patients were classified into 3 groups according to the prolactin (PRL) values and the neuroradiological findings. The first group consisted of 4 patients who were rather aged (mean age, 44.5 years) and had low PRL values ranging from 30 to 112 ng/ml. The tumor showed suprasellar extension, and all the 4 patients had had visual disturbance. Electron microscopy and immunological staining did not yield confirmation of PRL-productive pituitary adenoma. The second group consisted of 12 patients who had high PRL values ranging from 116 to 1, 040 ng/ml. The tumor was intrasellarly localized. PRL value returned to normal after surgery in 18% of the patients. Menstruation started again in 27% of them. After administration of CB154 the PRL value was restored to normal in 75% of them, and menstruation started again in all of the 12 patients. The third group consisted of the remaining 8 patients where the tumor showed parasellar extension. Sufficient effects could not be obtained by surgery alone. Even after administration of CB154, the PRL value was restored to normal in only 2 of the 8 patients, and menstruation and pregnancy were observed in only 1 of the 4 female patients. Thus, patients who belong to the second and third groups with PRL-productive pituitary adenoma should be treated as follows: In patients with PRL-productive intrasellarly localized pituitary adenoma, the tumor should be totally excised. In patients with PRL-productive pituitary adenoma which invades the cavernous sinus and so cannot be totally excised, CB154 should be administered after surgery.

A case of large cell carcinoma of the lung which produced eosinophil colony stimulating factor and eosinophil chemotactic factor was reported. A 52-year-old Japanese man with a tumor in the left upper lobe of the lung underwent left pneumonectomy. Marked eosinophilia persisted especially after recurrence, with a maximum peripheral leukocyte count of 161,000/mm3, of which 78% consisted of eosinophils. The patient died of pulmonary insufficiency 18 months after surgery. At autopsy, metastatic tumor tissues and almost all organs were markedly infiltrated with eosinophils, especially the spleen, and there was marked proliferation of eosinophils in the bone marrow. Eosinophil colony stimulating factor production by the transplanted tumor in a nude mouse was confirmed by use of a human bone marrow culture assay system. Eosinophil chemotactic factor production by metastatic tumor tissue also was proved by a modified micro-filter technique.

A carcinoid tumor of the peripheral lung producing gastrin-releasing peptide (GRP), a peptide hormone known to be present in the endocrine cells of fetal bronchial epithelium, is reported. Brain-gut peptide hormones in this tumor were assayed by radioimmunoassays, localized by immunohistochemistry and characterized by gel filtration. Electron microscopic study revealed that tumor cells resembled P-cells of normal human fetal bronchial epithelium. While GRP-containing cells were predominant in this tumor, calcitonin-containing cells were also found in some areas. Difference in distribution of hormones according to histologic features was noted in the tumor. A greater portion of the tumor showed spindled cells that predominantly contained GRP, and a smaller portion of the tumor showed cells arranged in tubular or trabecular patterns that mainly contained calcitonin. The gel-filtration pattern of the tumor extracts consisted of two peaks, one of these corresponded to the synthetic replicate of porcine GRP, and another was considered to correspond to C-terminal fragments of the peptide.

Enzyme histochemical and ultrastructural studies of a "dexamethasone-suppressed" virilizing adrenocortical adenoma and the attached cortex revealed that tumor cells showed little activities of some lysosomal enzymes and scarcity of lipofuscins and dense bodies of lysosomal type, forming a marked contrast to the cells of zona reticularis and the virilizing adenomas previously reported. The other findings of tumor cells, such as a pattern of activities of dehydrogenases including 3beta-hydroxysteroid dehydrogenase and the morphology of mitochondria, were those of reticularis cells. The findings showed that scantiness of lipofuscins did not rule out the possibility of adenoma producing adrenal androgen, dehydroepiandrosterone. Most of the tumor cells as well as reticularis cells were positive for alkaline phosphatase, the activity of which was interpreted as the effect of ACTH stimulation.

✓ Ependymoblastoma is considered to be a primitive malignant glioma with ependymal differentiation. This rare tumor occurs in very early life and shows rapid growth and a diffuse infiltration through the leptomeningeal space. The tumor cells are highly immature, with numerous mitoses and multilayered ependymal rosettes. The ependymoblastoma described in this report was found in a 17-year-old girl. In spite of detailed clinical and postmortem examinations, no definite primary site was identified in the neuraxis. The lesion spread predominantly throughout the leptomeningeal space. Histological analysis strongly suggested that this tumor originated from a heterotopic glial nest in the subarachnoid space. The absence of immunohistochemical neural tissue markers, glial fibrillary acidic protein, S-100 protein, neuron-specific enolase, and neurofilaments ruled out neuronal or glial differentiation. The authors were unable to find any previous report of primary leptomeningeal ependymoblastoma.

The cellular localization of alpha-, beta- and gamma-subunits of enolase isoenzyme was studied immunohistochemically in various human brain tumors, retinoblastomas and pituitary adenomas (total, 91 cases). The alpha-subunit was found in almost all brain tumors except in medulloblastoma cases. A case of medullomyoblastoma contained beta-subunit-positive myoblastic cells, which was also positive for human myoglobin. The gamma-subunit was frequently observed in medulloblastomas, retinoblastomas and pituitary adenomas. However, gamma-subunit was also present in some non-neuronal brain tumors such as astrocytomas and oligodendrogliomas. Enzyme immunoassay technique also confirmed the presence of gamma-subunit in a medulloblastoma and two retinoblastomas.

Immunoreactive gastrin-releasing peptide (IR-GRP) was found to be present in medullary carcinoma of the thyroid (MCT) by use of a radioimmunoassay (RIA) specific for the carboxyl-terminal portion of GRP. Immunohistochemical studies revealed IR-GRP in the MCT tumor cells, indicating that the tumor cells produce IR-GRP. Immunoreactive GRP was also detected in macroscopically normal thyroid tissue of patients with multiple endocrine neoplasia type II (MEN II, or Sipple's syndrome) and in areas of C cell hyperplasia and micronodules in the thyroids of patients with MCT. When these tissue extracts were examined with a bombesin RIA that recognizes bombesin but not GRP, no IR-bombesin was detected, suggesting that the IR-GRP detected in these tissues is more similar to GRP than to bombesin. IR-GRP was also undetectable in normal thyroid tissues. Plasma IR-GRP was also undetectable in normal thyroid tissues. Plasma IR-GRP was elevated to 130 to 780 pg/mL (normal: undetectable, < 62.5 pg/mL) in three patients with metastatic MCT, and both calcium and tetragastrin increased the plamsa levels of IR-GRP. Sephadex G-50 gel filtration of the MCT extracts revealed two peaks, one coeluted with porcine GRP (1–27) and the other eluted just after its carboxyl-terminal (14–27) fragment. There was a significant correlation (P < 0.01) between the concentration of IR-GRP and that of IR-calcitonin in MCT tumor tissue and in macroscopically normal portions of thyroid tissue from two patients with MEN II, although the concentration of IR-GRP was only about 0.1% of that of IR-calcitonin. These data suggest that there may be some relationship between the mechanisms by which these two hormones are produced in MCT.

In order to explore the relationship between the expression of cancer-associated glycolipids such as sialylated Lex (SLEX) and sialylated Lea (SLEA) and the histological subtypes of lung cancers, 30 cases of small cell carcinoma (SCC) and 47 cases of non-small cell carcinoma (non-SCC) were examined immunohistochemically using monoclonal antibodies reacting with SLEX and SLEA. The forty-seven cases of non-SCC included 20 cases of adenocarcinoma, 20 of squamous cell carcinoma and 7 of large cell carcinoma. Tumour cells of most non-SCCs expressed SLEX and SLEA. In adenocarcinomas, the number of tumour cells having SLEX and SLEA was more than that of squamous cell carcinomas, large cell carcinomas and SCC. In SCC, 14 of the 30 cases were found to be positive for both antigens. Although the cancer cells of 11 cases of 17 intermediate cell type SCC had both antigens, the cells of only 3 of 13 oat cell tumours expressed SLEX and SLEA. The present study shows that SLEX and SLEA are useful markers for lung adenocarcinomas, that most cases of intermediate cell type of SCCs have characteristics similar to non-SCC but that many oat cell tumours lack them.

Forty-nine biopsy specimens of nasopharyngeal carcinoma and 20 biopsy specimens of nasopharyngeal mucosa obtained from non-cancer patients were studied for the presence of T-zone histiocytes (Langerhans' cells and their precursors) and macrophages by immunohistochemical methods with the use of antibodies against S-100 protein and lysozyme (lys), respectively. Patients with dense infiltration of T-zone histiocytes in the primary sites survived longer than those without such infiltration (mean survival times, 8, 39, and 72 months in the patients with the density of -, +, and ++, respectively; P less than 0.005). In contrast, there was no relationship between patient prognosis and density of lys+ macrophages in the tumor tissue (P = 0.33). The distribution of T-zone histiocytes in the tumor tissue was different from that of macrophages. T-zone histiocytes may play an important role in the immune reaction against cancer, probably acting through mechanism different from that of macrophages.

Endocrine and immunohistochemical studies were performed in a patient with lung cancer associated with gynecomastia. Elevated level of human chorionic gonadotropin (hCG) in plasma and mild hyperadrenocorticism were demonstrated by hormone assays. Postmortem examination proved the existence of anaplastic small cell carcinoma of the lung mixed with a feature of chorioepithelioma. The presence of significant amounts of adrenocorticotropic hormone (ACTH), beta-melanocyte stimulating hormone (beta-MSH), calcitonin, gastrin, hCG, hCG-alpha, hCG-beta and human chorionic somatomammotropin (hCS) in tumor tissues was demonstrated by radioimmunoassays, bioassay and immunohistochemical techniques. We present here a unique case of multiple hormones producing tumor elaborating both hormones of amine precursor uptake and decarboxylation (APUD) series (ACTH, beta-MSH, calcitonin and gastrin) and of placental origin (hCG, hCG-alpha, hCG-beta and hCS).

Two cases of intrathoracic tumor, different in histology and accompanied by hyperamylasemia, were studied ultrastructurally, histochemically, and biochemically. The ultrastructure of the tumor cell cytoplasm showed many zymogen granules in case 1 and smaller cored granules in addition to zymogen granules in case 2. Both tumors contained not only a large amount of amylase, which was electrophoretically of saliva type with three components, but also significant amounts of immunoreactive ACTH and beta-MSH. Starch film and immunofluorescence showed that the tumor cells stored amylase. It was concluded from these findings that the tumor cells ectopically producing amylase, which showed differentiation toward the cells with zymogen production, could differentiate toward the cells of ACTH-MSH system at the same time.

症例は48才,男性で,左側腹部痛で発症した.画像検査と内分泌学的検査で左副腎褐色細胞腫と診断した.血中カルチトニンが868pg/mlと高値であつたが甲状線髄様癌の合併は認められなかつた.摘出腫瘍組織内にはカルチトニン,ソマトスタチンをはじめ多種のペプチドが検出され,免疫組織化学的にもその存在が確認された.また術前高値であつた血中カルチトニン,ソマトスタチンは術後は正常に復した.本症例のように多種のペプチドホルモンを血中で測定し,同時に腫瘍組織内含量測定と免疫組織化学的検索をし,その存在を確認しえた報告はないので貴重な症例と考えここに報告した.

This study was designed to identify 11 different antigens including calcitonin (CT), calcitonin gene-related peptide (CGRP), gastrin-releasing peptide (GRP), and carcinoembryonic antigen (CEA), in the tumors of 36 patients with medullary thyroid carcinoma (MTC) using immunoperoxidase staining techniques. In addition, clinical features of MTC patients were compared with the immunohistochemical findings to establish factors influencing prognosis. MTC was found to contain various products in many patients and CT and CEA were positive in all patients. CGRP and GRP showed positive staining in 96.6% and 82.9% of MTC patients, respectively, suggesting that CGRP and GRP are novel tumor markers for MTC. In tumor cells, CT, CGRP, and GRP were often revealed in identical cells. Familial patients showed more multiple substances than sporadic patients. In the 2 inoperable patients with extremely aggressive progression, tumors showed undifferentiated histology and poor staining for peptide hormones, suggesting that specific qualities such as neuroendocrine tumor had been lost. These 2 patients particularly revealed an inverse relationship between CT and CEA distribution such that small amounts of CT were present in cells which have homogenous staining for CEA. This study suggests that CGRP and GRP, in addition to CT and CEA, may be a histologically potential tumor marker for MTC. CT and CEA may be possible markers for differentiating patients with high malignancy from those with ordinary malignancy.

The presence of nervous tissue specific S100 protein was studied immunohistochemically in 47 cases of malignant melanoma and 25 pigmented nevi of various types of peroxidase-antiperoxidase immunoenzyme method on routine paraffin sections of the surgical specimens. Of 47 cases of malignant melanoma, 44 were positively stained for S100 protein. The intensity of S100 protein immunostaining was suggested to be inversely proportional to the amount of melanin pigment. In ten cases of 12 amelanotic melanomas, the immunoreaction for S100 protein in tumor cells was stronger than that of normal Bergmann glial cell in human cerebellum. Intradermal nevi and juvenile melanomas were strongly positive for S100 protein, but blue nevi contained little or no S100 protein. Our results suggest that S100 protein is widely distributed among melanotic tumors and is also a very useful diagnostic indicator for malignant melanoma, especially of the amelanotic type.

The current study was undertaken on 25 cases of thyroid medullary carcinoma to compare the diagnostic value of calcitonin with other peptides including PDN-21, the C-terminal flanking peptide of human calcitonin within the calcitonin precursor, and calcitonin gene-related peptide, CGRP. Antiserum raised to chromogranin, an acidic protein of 68,000 daltons, was also used to compare its diagnostic value as a general marker for neuroendocrine neoplasia with neuron-specific enolase (NSE) and Grimelius' argyrophil silver staining. Immunocytochemistry was performed using the peroxidase-antiperoxidase method at the light microscopic level and the immunogold staining procedure at the ultrastructural level. All tumors were reactive to calcitonin and CGRP antisera, whereas PDN-21 was present in 23 cases. It was also found that these peptides were colocalized in the majority of C-cells. The intensity and specificity of CGRP and PDN-21 immunoreaction was comparable to and in some cases even better than that obtained with calcitonin antiserum. In the majority of tumors, somatostatin and bombesin immunoreactivity was either absent, weak, or variable in intensity and distribution. The current study thus demonstrates that together with calcitonin, PDN and, in particular, CGRP antisera may be applied to corroborate immunocytochemical diagnosis in medullary carcinoma of the thyroid. With regard to general neuroendocrine markers, Grimelius' and chromogranin provided the most consistent results. NSE isoenzyme immunoreactivity, on the other hand, was more variable, probably reflecting the metabolic state of the tumor cells.

肺腫瘍手術例683例中に2例の気管支腺原発唾腋腺型混合腫瘍があった. 1例は典型的な “良性混合腫瘍” の像を呈する末梢発生, 結節性腫瘍で他の1例は, B10b+c原発で気管支腔内に樹枝状に増殖する悪性混合腫瘍で, 共に腫瘍性の筋上皮細胞を有し, 転移はなく, 術後26, 53ヶ月健在である. 文献の展望と唾液腺混合腫瘍に関する経験から, 本腫瘍は一見良性にみえても悪性の潜在能を有する腫瘍として治療すべきであると結論した.

The cell source of peptide hormone production and the morphological differentiation were investigated in 18 adenocarcinomas of the lung by immunohistochemistry and/or by electron microscopy. These tumors were found by radioimmunoassay of tumor extracts to contain either one or more of 7 peptide hormones, i.e. adrenocorticotropin (ACTH), beta- and gamma-melanocyte stimulating hormones (MSH), somatostatin (SS), vasoactive intestinal polypeptide (VIP), gastrin releasing peptide (GRP) and calcitonin (CT). In a combined adeno- and small cell carcinoma, a considerable number of small tumor cells were positively stained for ACTH, beta- and gamma-MSHs and GRP. In a poorly differentiated adenocarcinoma with mucin and CT production, these products were localized in some single cells. Electron microscopy revealed secretory granules indistinguishable from exocrine or endocrine types. In another mucin-positive adenocarcinoma with high SS and CT contents, some tumor cells were stained for SS and/or CT. Two distinct exocrine and endocrine type secretory granules were found in the same cells. In tumors with 100 ng or less of the peptides/g tissue, most tumor cells were not stained for the peptides but a small number showed morphological endocrine differentiation. In conclusion, a considerable proportion of the adenocarcinomas of the lung may show heterogeneous differentiation in both endocrine and exocrine directions.

Nine pancreatic endocrine tumours of patients with watery diarrhoea hypokalaemia achlorhydria (WDHA) syndrome were examined by immunohistochemistry and electron microscopy. All cases revealed neoplastic proliferation of VIP (vasoactive intestinal peptide)-immunoreactive (IR) cells. Immunoreactivity to a novel peptide hormone PHM-27, which is processed from a common big precursor peptide of VIP (prepro VIP/PHM-27), was identified in VIP-IR cells of 8 tumours. VIP-PHM-IR cells had secretory granules measuring about 130 to 220 nm in diameter. Radioimmunoassay of tumour tissue extracts showed high VIP and PHM contents in proportional amounts in most cases. According to the results of immunostaining, the 8 tumours fell into two large groups; 5 with PP (pancreatic polypeptide)-IR cells and 3 with CT (calcitonin)-IR cells. The former group demonstrated VIP cells and PP cells intermingled in various proportions, including one tumour in which coexistence of PP-IR and VIP-IR in the same cells was demonstrated. Cell heterogeneity of the tumours and possible relationships of VIP, PP and CT cells were discussed.

The appearance of S-100 protein-positive Langerhans cells was studied in 90 cases of various lung cancers by an immunohistochemical method. S-100 protein-positive dendritic cells were frequently observed in many adenocarcinomas, especially in those subclassified as bronchiolar cell or type II alveolar cell type. However, no S-100 protein-positive cells were found in "goblet cell type" adenocarcinoma. In some cases of squamous cell carcinoma and large cell carcinoma, these dendritic cells were also observed though they were fewer in number. In all cases of small cell carcinoma, however, S-100 protein-positive dendritic cells were rare. Electron microscopic study of two adenocarcinomas clearly demonstrated many Birbeck granules in the cytoplasm of S-100 protein-positive dendritic cells and confirmed that S-100 protein-positive cells in lung cancer were identical with Langerhans cells.

The contents of three subunits (α, β and γ) of enolase isoenzymes of various human tumors, especially of neuronal and neuroendocrine tumors, were determined by a highly sensitive enzyme immunoassay system. A high level of γ-subunit was detected in neuronal and neuroendocrine tumors, including small cell carcinomas of the lung. The level of α-subunit was generally higher in all tumors and varied according to the tumor. The β-subunit level was elevated in rhabdomyosarcomas. Furthermore, analyzing the relationship between the contents of each enolase subunit among the tumors, the α-/γ-subunit ratios were the lowest in neuronal tumors and increased in order of neuroendocrine and non-neuroendocrine tumors. This result suggested that the α-/γ-subunit ratio is an important indicator to evaluate neuronal and neuroendocrine differentiation of the tumor rather than the amount of γ-subunit of enolase itself.

左上葉に発生した約1.5cm大の細気管支肺胞上皮癌巣内に, 病因不明の類上皮性肉芽腫が合併した1症例を報告する. 腫瘍中心部に癌による癩痕巣があり, これを囲んで微小な壊死巣を伴う粟粒大の類上皮性肉芽腫と癌巣が混在していた. この肉芽腫は, 癌に対するsarcoid like lesionと考えたが, 結核等の感染症の可能性を否定しきれなかった. 症例報告に併せ癌と瘢痕の問題, sarcoid like lesionについても若干の文献的考察を加えた.

Using 3H-TdR pulse labelling, the cell kinetics of four, serially transplantable, human tumors were studied in athymic nude mice. Squamous cell carcinoma of the lung, tongue and esophagus showed relatively similar cell kinetic parameters. The growth of an oat-cell carcinoma was initially very slow in mice and its growth fraction was unexpectedly small with a relatively low labelling index. Its postmitotic phase was very short. It was concluded that the nude mice/human tumor system may be useful for cell kinetic studies of human tumors from the standpoint of tumor biology and therapy.

Two permanent cell lines, designated LU-65 and SK-Luci-6, were established from large-cell anaplastic lung cancers of two patients. Both cell lines grew as solid tumors in nude mice. The histologic pattern of the tumors in the nude mouse resembled that of the primary lung cancers in that the xeno-transplanted tissues showed no distinctive features indicative of cell type, a finding consistent with origin from a large-cell anaplastic lung cancer. Cells from both lines formed clones in semisolid agar. Flow cytometric analysis of SK-Luci-6 showed a hypertriploid stemline with a very high RNA-index. Line LU-65 had a hyperdiploid stemline evolving into a hypertriploid stemline with a high RNA-index. Chromosome analysis showed aneuploidy with abnormalities and marker chromosomes in both tumor cell lines. The isoenzyme pattern of LU-65 and Sk-Luci-6 indicated that they were of human origin and distinct from HeLa cells or another common contaminating line. Both cell lines released biologically active agents that could have caused the neutrophilia and hypercalcemia seen in the patients.

A 53-year-old male with Cushing's syndrome due to ectopic ACTH production from medullary carcinoma of the thyroid was reported. The clinical course and results of detailed endocrinological studies and immunohistochemical findings about the cancer tissue were described. An abnormally high concentration of calcitonin, ACTH and beta-MSH in both plasma and cancer tissue (thyroid, lymph nodes and liver) were documented by radioimmunoassay. Urinary 17-OHCS was as high as 38.4 mg/day and showed no supression following dexamethasone 8 mg/day administration. ORAL METYRAPONE (3 G/DAY) CAUSED NO RESPONSE IN URINARY 17-OHCS. Parallel increments in plasma calcitonin, ACTH and beta-MSH were observed following calcium and gastrin loading. Total thyroidectomy with modified radical neck dissection caused minimal changes of plasma levels of calcitonin, ACTH and beta-MSH and no improvement in the clinical manifestations of Cushing's syndrome. An aortogram revealed metastatic tumors in the liver. A second operation, total adrenalectomy, resulted in an improvement of the clinical and laboratory findings such as hypokalemia, high blood pressure, muscle atrophy and moon face. Immunofluorescent study showed different distribution patterns in calcitonin- and ACTH-positive cells in the primary focus but similar patterns in the liver metastasis.

Ninety-one human tumors, including various common carcinomas, low-grade malignant tumors, and benign tumors, were transplanted into athymic nude mice. Tumor take was confirmed histologically for 22 neoplasms at the initial transplantation, and 14 serially transplantable tumors were established, including some hitherto unestablished or unreported, such as lung and hepatic cell carcinomas. Among the 91 tumors were 21, 14, and 13 carcinomas of the lung, stomach, and breast, respectively. Transplantability was highest in lung carcinomas (10/21), followed by gastric carcinomas (2/14) and breast carcinomas (1/13). Morphology of original tumors was retained well in most transplanted tumors, but desmoplastic or scirrhous tumors, such as gastric and breast carcinomas, tended to become medullary with a decrease in amount of tumor stroma. The ability to produce mucin in gastric carcinomas or melanin in malignant melanoma was maintained in serially transplantable tumors. In addition, ectopic production of adrenocorticotropin and beta melanocyte-stimulating hormone continued in a transplanted small cell carcinoma of the lung. Preliminary results were obtained on hormone dependency of the transplantable breast carcinoma and on alpha1-fetoprotein in the transplantable hepatic cell carcinoma.

During the past 15 years, 274 patients (pts) have been operated on for primary lung cancer at Kitasato University Hospital, 204 men and 70 women. The histological diagnosis was adenocarcinoma (Ad) in 135, squamous cell carcinoma (Sq) in 101, small cell carcinoma in 12, large cell carcinoma in 9, adenosquamous carcinoma in 7, adenocystic carcinoma in 2, and others in 8.Staging was stage I in 117, stage II in 22, stage IIIa in 82 Mb in 26 and stage IV in 24 pts.The 5-year survival rates were 41.5% in the group of 274 pts, 57% in stage I, 43.8% in stage II, 20.7% in stage III (a+b) and 36.4% in stage IV.There was no statistically significant difference in the 5-year survival rates between Ad (39.6%) and Sq (46.6%), but among the pts who were classified as stage III (a+b), those with Sq had significantly better 5-year survival rate than those with Ad (Sq : 35.5%; Ad : 10.6%, p< 0. 05).Pts who underwent lobectomy had a better 5-year survival rate than those who underwent pneumonectomy (lobectomy : 51.6%; pneumonectomy : 20.6%, p

アスベスト曝露の既往があり, 剖検にて肺にアスベスト小体が認められ, 胃壁への転移がみられた胸膜中皮腫の一例を経験した.症例は64歳男性.左側肩・肘・腰部の激痛を訴え, 胸部X線上左肺尖部・左S10の腫瘤影および右胸水貯留を認めた.左肺底部腫瘤と右胸膜の生検所見は同一で, 臨床的に胸膜中皮腫の対側播種が強く疑われ, 剖検にて確診された.また, 経過中好酸球増多を伴う等, 稀有なる一例と考えられた.

Fifteen cases of pituitary adenoma, 14 of which were associated with hyperprolactinemia, were studied by observation and granule morphometry of electron micrographs, immunohistochemistry and sequential observation of in vitro release with regard to hormone production, storage and secretion. Adenoma cells of 6 cases with marked elevation of plasma prolactin were sparsely granulated, showed characteristic ultrastructures including the presence of small secretory granules, well developed Golgi and rough membranes, misplaced exocytosis, and positive or negative immunostaining for prolactin. These adenomas also showed vigorous release of the hormone into the circulation and/or culture medium. In vitro studies showed that negative immunostaining of adenoma cells did not preclude the production and secretion of the hormone. One densely granulated adenoma containing cells with numerous lactotroph type granules showed moderate release of prolactin into the circulation. In an acromegalic case associated with both high plasma growth hormone and prolactin, some cells were shown by immunohistochemistry to store both hormones There were 4 adenomas which could not be shown to produce, store and secrete prolactin by any method available.

Both histochemical and electron microscopic findings confirmed that thymic lymphoid follicles were identical in structure with lymphoid follicles in peripheral lymphoid tissues and not related to thymic epithelial cells. Histochemical demonstration of β-glucuronidase and other acid hydrolases showed that thymic medulla around the lymphoid follicles was infiltrated with the lymphocytes of the peripheral type corresponding to recirculating lymphocytes in paracortical areas of lymph nodes. Reticular cells around the thymic germinal center showed the same activity of alkaline phosphatase as those in lymph nodes.Electron micrographs revealed that the thymic germinal center contained reticular cells connected to each other with prominent interdigitation and desmosome-like structures. These cells differ from thymic epithelial cells in the absence of typical desmosomes, abundant tonofilaments and basement membranes.It could be assumed that reticular cells of thymic lymphoid follicles arise from mesenchymal cells of the perithymic tissue, and that the lymphocytes of the peripheral type occur in the thymus by mutation of thymic lymphocytes or by immigration of circulating lymphocytes.