Search

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.

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.

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.

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.

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.

Four cases of small cell carcinoma of the paranasal sinuses were studied histologically, ultrastructurally, and endocrinologically. All tumors showed features of undifferentiated carcinoma with alveolar patterns but without acinar or squamous differentiation and contained cells possessing endocrine-type small secretory granules, which were indistinguishable from non-neoplastic neurosecretory granules. The three cases also possessed a small number of microtubules, and in one of these fine cytoplasmic filaments were observed. One case showed elevated plasma levels of cortisol and adrenocorticotropic hormone associated with adrenocortical hyperplasia and Crooke's changes of the pituitary gland. Another case showed hypercalcemia with bone metastasis, hypercalcitonemia with a high content of calcitonin in the tumor tissue, calcitonin-positive tumor cells, and C-cell hyperplasia of the thyroid. It was concluded that all four cases should be called neuroendocrine carcinoma, which might be related to neoplasms derived from amine precursor uptake and decarboxylation cell series rarely encountered in the paranasal sinuses.

By immunoperoxidase histochemical staining of formalin-fixed paraffin-embedded sections, the production of alpha-fetoprotein(AFP), albumin(ALB), transferrin(TF), alpha-1-antitrypsin(AAT), and human chorionic gonadotropin(HCG) was examined in 35 operatively resected stomach cancers with elevated serum AFP levels (higher than 20 ng/ml as determined by radioimmunoassay). Cells positive for AFP were found in 19 cases (54%). In 29 cases (83%), some tumor cells contained normal serum proteins (ALB, TF, or AAT). All 19 tumors with AFP-positive cells also stained positively for two or three kinds of normal serum proteins. In some cases, AFP and normal serum proteins were localized in the same cells. There were two cases in which metastatic tumors produced AFP, whereas the primary sites did not. In nine cases (26%), HCG was present in tumor cells and HCG- and AFP-positive cells were coexistent in six tumors. Histologic examination of AFP-producing stomach tumors revealed medullary or papillotubular arrangements with marked nuclear atypia and eosinophilic granular or clear cytoplasms containing no glycogen or mucin. Some tumors with medullary patterns resembled liver cell carcinomas. Concordant phenotypic expression of AFP and normal serum protein production appears to be a general feature of AFP-producing tumors such as liver cell carcinoma, yolk sac tumor, and stomach cancer.