Flow cytometric and morphological studies of ovarian carcinoma cell lines and xenografts.

Human ovarian cancers of four different histological types have been cultured in vitro and in nude mice. Nineteen tumor specimens (11 solid tumors and eight malignant effusions) were obtained from 14 patients. Tumor lines from ten of these patients were established after several subpassages, and six xenograft lines have been grown, all of them from tumors of which a cell line exists in vitro. In all, 14 lines have been successfully cultured from the 19 tumor specimens. The morphology (studied by light and electron microscopy) of the established lines in vitro and in vivo resembles that of the original tumors in all cases. Flow cytometric studies of DNA content of the original tumor specimens and the cell culture and xenograft lines were performed. In all lines in both culture systems, aneuploid cells became predominant after the first to fourth passages, despite an aneuploid peak having been evident in only nine of the 19 initial specimens. Four of the original tumor specimens contained measurable estrogen receptors and five progesterone receptors, but none of the established cell lines expressed these hormone receptors. These results indicate that, while morphological features are similar in the initial tumor specimens and in the established lines in vitro and in vivo, flow cytometric and steroid hormone receptor data suggest selection of aneuploid and receptor-negative cells.

Bladder cancer xenografts: a model of tumor cell heterogeneity.

Twenty bladder biopsies from patients with primary transitional cell carcinoma were inoculated into nude mice. To date, eleven of these have grown as primary implants and three serially transplantable xenograft lines (UCRU-BL-12, UCRU-BL-13, UCRU-BL-14) have been established. The histological and ultrastructural features of human transitional cell carcinoma have been maintained in each line. Despite a relatively uniform histological appearance, several indices of occult tumor heterogeneity have been revealed. Immunocytochemical staining was negative for beta-subunit human chorionic gonadotrophin but positive for carcinoembryonic antigen only in areas of squamous differentiation. All three tumors bound peanut lectin. Flow cytometric DNA analysis of UCRU-BL-13 showed multiple aneuploid peaks, separate populations being demonstrated in different xenografts of the same generation. However, the morphologies of these tumors remained identical. On initial implantation UCRU-BL-12 and UCRU-BL-14 were near diploid but aneuploid populations became apparent with increasing passage number. Each xenograft line caused cachexia in the host mice. Treatment with the cisplatin analogue, isopropyl platinum, ameliorated the cachexia displayed by mice carrying UCRU-BL-14 but did not cause tumor regression. UCRU-BL-12, when tested with cisplatin, isopropyl platinum, and carboplatin, showed equivalent growth retardation with each drug. These xenografted human bladder cancers may be useful models for the study of heterogeneity of the tumor populations in bladder cancer and for the evaluation of new approaches to treatment.

Effects of hyperthermia therapy on the liver. II. Morphological observations.

Liver biopsy specimens obtained from three patients during treatment of advanced malignant disease by exogenous hyperthermia were studied by light and electron microscopy. In two patients the parenchymal cells showed either slight swelling or nuclear alterations by light microscopy and, at the fine structural level, large numbers of autophagic vacuoles, dilatation of Golgi elements and endoplasmic reticulum, and large cytoplasmic vacuoles. Similar changes, but in much more severe form together with parenchymal cell necrosis and cholestasis, were seen in the liver of case 3, who developed jaundice 24 hours after hyperthermia. The findings are discussed in relation to earlier accounts of liver changes following hyperthermia, and the functional implications are considered.

Morphological features in a neutral lipid storage disease.

The morphological changes in a patient with a generalized storage disease characterized by the intracellular deposition of neutral lipid are described. There is widespread accumulation of lipid in the cytoplasm of many cells and in occasional nuclei. Diagnosis may be facilitated by the recognition of clear vacuoles in the cytoplasm of granulocytes in blood films. In jejunal biopsies vacuolation of the epithelial cells may simulate the appearances of a-betalipoproteinaemia. The lipid inclusions consist largely of normal triglycerides and are free in the cytoplasm, unassociated with any organelle. The biochemical basis of the lesions is uncertain. Although there are lipoprotein abnormalities the primary defect appears to be intrinsic to the cell and may involve either a defective cytoplasmic lipase or an impaired uptake and utilization of fatty acids by mitochondria.

Intra-abdominal desmoplastic small round cell tumor.

A rarely encountered but distinctive type of aggressive malignant tumor of childhood and adolescence has been recently described as occurring predominantly or exclusively intrabdominally. It is characterized by a generally diffuse pattern of growth of small cells with hyperchromatic nuclei, scanty cytoplasm, patchy epithelial differentiation, immunohistochemical co-expression of keratin and desmin intermediate filaments and a focal but pronounced desmoplastic stromal component. It is regarded as yet another variant in the group of small round cell tumors (SRCT) of infancy and childhood. This case report of a mass in the greater omentum of a 15 yr-old girl adds to the 33 cases already described in the English literature.

Noncondylomatous wart virus infection of the postmenopausal cervix.

Noncondylomatous papilloma virus infection of the cervix is much more common than formerly realized. The majority of patients are young, but two cases are reported here in postmenopausal women.

Hyalinising spindle cell tumour with giant rosettes: report of a case with unusual features including original histological and ultrastructural observations.

Hyalinising spindle cell tumour with giant rosettes (HSCTGR) is an uncommon, recently described low-grade sarcoma which shares many histological features with low-grade fibromyxoid sarcoma (LGFMS). We report a case of HSCTGR occurring in the deep soft tissues of the thigh of a 46-year-old woman, that presented as a slowly growing, painless mass. Microscopically the tumour was composed of spindled stromal cells amongst which were scattered so-called collagen rosettes. The distinctive feature of this case was the previously unreported finding of lymphoid cells of T-cell phenotype admixed with fibrohistioctyic cells in the cellular cuff surrounding the collagenous core of the rosettes. The case was further unusual in that it included focal areas of increased cellularity with a mitotic count of up to three per 10 high-power fields. While the latter feature has been associated with increased recurrences and metastases in LGFMS, it is not known whether the significance is similar in HSCTGR. The spindled stromal cells showed ultrastructural features of poorly differentiated fibroblasts, while those at the edges of the rosettes showed features of altered fibroblasts, some with a fibrohistiocytic appearance. These findings support the interpretation that HSCTGR forms part of the spectrum of sarcomas showing fibroblastic differentiation.

Large parathyroid adenoma in a normocalcemic patient.

A large parathyroid adenoma was found in a patient who presented with a mass in the neck with, however, no overt evidence of hyperparathyroidism. The morphological features of this tumour are described.

"Rhabdoid meningioma" lacking malignant features. Report of two cases.

We report 2 cases of meningiomas with rhabdoid morphology but lacking histological features of malignancy. Both occurred in adult women, one arising from the superior surface of the tentorium and the other in the Sylvian fissure. The tumors showed light microscopic, immunohistochemical and ultrastructural evidence of meningothelial differentiation together with diffuse or focal areas exhibiting rhabdoid morphology. The rhabdoid areas were characterized by cells with large cytoplasmic eosinophilic inclusions and large eccentric nuclei. Both cases showed areas with sheet-like growth and one had macronucleoli and brain invasion. The same case showed areas of necrosis that most likely related to pre-operative arterial embolization. Unlike most cases reported in the literature, these "rhabdoid meningiomas" lacked significant mitotic activity or other atypical features. The diagnostic and prognostic significance of this tumor entity is discussed along with a review of the literature.

Phaeochromocytoma in two coatimundi (Nasua nasua).

Two unrelated coatimundi (Nasua nasua) had bilaterally enlarged adrenal glands at necropsy, and sections of the glands from both animals had histopathological features consistent with neoplasia. They were differentiated from an adrenal cortical tumour on the basis of their light microscopical morphology, immunoperoxidase staining and electron microscopic studies and a final diagnosis of phaeochromocytoma was made. To the authors' knowledge, these are the first reported cases of phaeochromocytoma in coatimundi.

Peritoneal desmoplastic small round cell tumors with divergent differentiation: a review.

Peritoneal desmoplastic small round cell tumors with divergent differentiation are recently described highly aggressive neoplasms with characteristic clinical, morphologic, and immunohistochemical features. This review covers 38 cases that have been reported in the literature. The average age of patients is 18.4 years, and males are affected twice as frequently as females. Tumors generally present as multiple peritoneal nodules without obvious organ involvement. Histology shows islands of small cells set in dense desmoplastic stroma. Immunohistochemical stains are usually positive for cytokeratins, epithelial membrane antigen, desmin, and vimentin. Many cases also stain for neuron-specific enolase but rarely for other neuroepithelial markers. Ultrastructural appearances range from undifferentiated small cells to larger epithelial elements. Paranuclear aggregates of intermediate filaments are characteristic. Dense-core granules and other neuroendocrine features have been described in a minority of cases. Some tumors respond to chemotherapy, but most patients die within months to a few years. The histogenesis of these tumors is uncertain.

Ground glasslike hepatocytes produced by glycogen-membrane complexes ("glycogen bodies").

A 54-year-old man developed liver disease 11 months after renal transplantation. Liver biopsy demonstrated hepatitis with numerous periodic acid-Schiff-positive, diastase-sensitive ground glass inclusions in parenchymal cells. Electron microscopy revealed that the inclusions consisted of parallel arrays of smooth surfaced cisternae separated by glycogen rosettes ("glycogen bodies"). The differential diagnosis of ground glass hepatocytes, the occurrence of glycogen bodies, and the possible etiological factors in the patient's liver disease are discussed.

Anemone cell tumor with neuroendocrine differentiation (presumed Merkel cell carcinoma).

A neuroendocrine tumor with ultrastructural "anemone cell" features in lymph nodes is reported. A primary tumor was not identified, but clinical and morphologic features suggested a metastatic Merkel cell carcinoma. The anemone cells were dissociated, lacked intercellular junctions, and contained cytoplasmic intermediate filament aggregates that immunohistochemically reacted with keratins, but they had only sparse neurosecretory granules. Where the tumor cells had infiltrated beyond the lymph nodes, however, they formed a trabecular pattern. A fine-needle aspirate from a later recurrence of the tumor lacked anemone cell features and was ultrastructurally typical of a Merkel cell carcinoma, with neurosecretory granules and intercellular junctions both being evident. The concept of anemone cell tumors and the morphologic variations determined by site are discussed.

Pleural mesothelioma with initial presentation as cervical lymphadenopathy.

A 41-year-old woman presented with a left neck mass. Light microscopy suggested metastatic large cell carcinoma, but subsequent electron microscopy demonstrated typical epithelial mesothelioma. Initial clinical investigations were negative and the primary pleural tumor remained inapparent for a further 8 months. The woman ultimately died from the effects of superior vena caval obstruction. Mesotheliomas frequently metastasize late in the course of the disease, but it is exceptional for them to present as a metastatic tumor of unknown primary origin.

"Normal" elimination of aberrant autoimmune clones.

Tetraparental mouse chimaeras formed by aggregation of early embryos have been utilised in the study of immunological mechanisms. Tolerance in chimaeras has proven somewhat controversial, but recent evidence has suggested the existence of "classic" tolerance and furthermore that this is achieved by elimination of cells potentially capable of fatal self in equilibrium self reactivity. Clonal elimination was also considered to be responsible for the "correction" of the autoimmune disease of NZB mice made chimaeric with a normal strain. It is now suggested that a similar mechanism may be responsible for the "normal" elimination of any aberrant autoimmune clone in both mouse and man.

A clinico-pathological survey of thyroid glands in old age.

A quarter of the thyroid gland obtained at post-mortem examination from a group of elderly inpatients were nodular. There was a significant preponderance of women with goitre, but no relationship to age. The incidence of hyperthyroidism was increased in patients with nodular glands. There was no correlation between the weight of the thyroid gland, the age of the patient and the free-thyroxine index. Histological examination of macroscopically normal glands showed tiny follicles, microscopic colloid nodules and fibrosis. Nodular glands had the features of long-standing colloid nodular goitre. Focal lymphocytic thyroiditis was observed in a fifth of the glands. Microscopic evidence of altered function was common but could not always be correlated with the results of the thyroid function studies.