Showing papers in "Pathology Research and Practice in 1990"

WHO International Histological Classification of Tumours. Tentative Histological Classification of Salivary Gland Tumours.

Abstract: The principles of the proposed modified WHO Histological Typing of Salivary Gland Tumours are based on the following: 1) The classification of tumours is oriented to the routine work of the practicing surgical pathologists, those who do not see tumours of the salivary glands very often. The inclusion of rare, but clearly defined tumour entities should be helpful to surgical pathologists consulting with clinical specialists. 2) The different types of carcinomas must be distinguished not only by precise histopathological definitions, but also considering differences in prognosis and treatment. For example, the polymorphous low-grade adenocarcinoma and the epithelial-myoepithelial carcinoma are characterized by a relatively good prognosis in contrast to the salivary duct carcinoma. 3) Special points of discussion are: subclassification and grading of carcinomas (e.g. acinic cell carcinoma, mucoepidermoid carcinoma and adenoid cystic carcinoma), the classification of basal cell tumours (basal cell adenoma, basal cell carcinoma, solid type of adenoid cystic carcinoma), malignant tumours in pleomorphic adenomas and the differential diagnosis between primary tumours and metastases.

The consequences of tubulo-interstitial changes for renal function in glomerulopathies. A morphometric and cytological analysis.

Abstract: In recent years it has become recognized to an increasing extent that a wide range of inflammatory and non-inflammatory glomerular diseases may be complicated with varying frequency by disease in the region of the post-glomerular intertubular capillaries Thus we found additional disease of the tubulo-interstitial system in 40 – 695% of patients with the diseases listed in Table 1 Amongst these diseases, accompanying inflammation of the renal cortical interstitium occurs least often in endocapillary glomerulonephritis and most often in diabetic glomerulosclerosis Amongst the glomerulonephritides, interstitial inflammation leading to fibrosis is observed most frequently in rapidly progressive glomerulonephritis and membranoproliferative glomerulonephritis Interstitial inflammation is found relatively often in glomerular amyloidosis As a result of investigations we have undertaken in the last three years, it has been possible to demonstrate that the character of the inflammatory interstitial changes that accompany glomerular diseases is always the same, no matter what the glomerulopathy may be The cells most predominantly involved in the inflammatory process are T lymphocytes, macrophages, fibroblasts and fibrocytes Thus dense foci of T lymphocytes and macrophages are seen not only in Table 1 Survey of the incidence of intertubular inflammation associated with interstitial fibrosis in various glomerulopathies Various Glomerulopathies And The Occurrence Of Interstitial Inflammation And Interstitial Fibrosis Total Number Of Casas Cases With Interstitial Fibrosis (%) 1) Endocapillary GN 137 40 2) Minimal Changes With NS 470 85 3) Focal Sclerosing GN 469 341 4) Mesangioproliferative GN 805 230 a) Immunologically Negative GN 238 139 b) IgA Nephritis 369 233 c) Non-lgA Nephritis 198 333 5) Chronic Idiopathic Membranous GN 642 238 6) Membranoproliferative GN Type I 259 410 7) Rapidly Progressive GN 208 567 8) Perireticular Amyloidosis 443 480 9) Diabetic Glomerulosclerosis 406 695 mesangioproliferative glomerulonephritis, but also in the interstitial inflammation that complicates renal amyloidosis The tubulo-interstitial inflammation of diabetic glomerulosclerosis is also characterized by T lymphocytes, macrophages, fibroblasts and fibrocytes

Chronic Myeloproliferative Disorders in Bone Marrow Biopsies

Abstract: Summary This Diagnostic Seminar intends to announce that CMPDs can be classified from BMB histologically by a rather simple system, which can be applied by interested histopathologists successfully. The rationale of this classification is to stay within the groups of diseases which are outlined by clinical findings including the peripheral blood and bone marrow smears. The concept of traditional classification as given by the WHO and textbooks, however, has to be revised as follows (1) Primary diseases of CMPDs must be distinguished from advanced disorders. Primary diseases are CML, P. vera, Thrombocythemia, CMGM, and unclassifiable CMPD. (2) Idiopathic, primary myelosclerosis of the bone marrow is a reactive feature consecutive to neoplastic transformation of hematopoiesis, i.e. myeloproliferation. (3) Advanced disorders comprise (3.1.) excess of blasts and blast crisis, and (3.2.) early myelosclerosis, myelosclerosis and myelofibrosis, advanced myelofibrosis. Advanced disorders are designated by a composed term classifying them among the groups of primary disease and specifying the advanced stage by a suffix, so that the underlying disease remains coining the term, even in unclassifiable cases in which only CMPDs can be applied. (4) The CML group must be subtyped into CML of common type versus that with increase or predominance of megakaryocytes. By this system of classification, it seems possible to classify and type the spectrum of variations occurring among CMPDs to a satisfying result.

Prognostic significance of nucleolar organizing regions (NORs) in carcinomas of the sigmoid colon and rectum.

Abstract: The prognostic significance of silver-binding nucleolar organizing regions (AgNORs) has been evaluated in tissue sections of biopsies taken from 70 primary adenocarcinomas of the colon sigmoid (n = 25) and rectum (n = 45) prior to their curative resection. A significant correlation between five-year survival rate and the mean AgNOR number per tumour cell (p less than 0.001) and the mean size of silver stained dots (p less than 0.05) was found according to the univariate Kaplan-Meier survival analysis. There was no significant relationship between AgNOR content and grade of malignancy, pT categories or pN categories. Multivariate survival analysis of covariates (Cox regression model) revealed a set of five variables that significantly influenced the patients' outcome: pN categories, AgNOR content, pT categories, maximum grade of malignancy and number of inflammatory cells. From the clinical and pathological parameters studied, pN and pT categories as well as the mean AgNOR number were the most important variables predicting death from colorectal carcinoma. Since the analysis of AgNORs can be performed on routinely processed paraffin-embedded tissue, this method may be of potential use in pretherapeutic assessment of the biologic aggressiveness of the disease.

Histological grading of breast cancer. Interobserver, reproducibility and prognostic significance.

Abstract: A study was conducted to assess the reproducibility and prognostic significance of the histopathological grading by using the criteria of Bloom and Richardson. 166 breast carcinomas of the invasive ductal type (NOS - not otherwise specified) according to the WHO criteria, selected from the biopsy material of the years 1980 to 1988 were investigated. 85 of the patients presented axillary lymph node metastases in the mastectomy specimens. A satisfactory correlation of histopathological grades assessed by three pathologists was found in 72.3% of all cases. Fifteen cases (9%) were over- and 31 cases (18.7%) were underestimated compared with an expert's grade. A disagreement of two grades occurred in one case only. In comparison of grade 1 and grade 3 tumours as well as of grade 2 and grade 3 tumours significant differences in the overall survival could be found. Irrespective of statistically significant differences between the three grades in actuarial survival, the histopathological grading is of rather low value for the prediction of prognosis of individual patients.

Cytophotometry in tumor pathology. A critical review of methods and applications, and some results of DNA analysis.

Abstract: Summary In tumor pathology the quantitation of cellular substances can be of diagnostic value. Microscope cytophotometry and digital image analysis and, on the other hand, flow cytometry are supplementary methods for measuring, each with a typical spectrum of application. The methods are predominantly used for DNA analysis: Static and image cytophotometry are applicable to cytologic and histologic slides preferably for identifying stem lines in tumors of heterogenous morphology and in merely circumscribed lesions (e.g., precancerous lesions). On the other hand, sampling errors due to preselection, and the often low number of cells actually measured, may preclude the possibility of exact cell cycle analysis. This is, in fact, an important additional option of flow cytometry resulting from the high resolution of DNA histograms, which is explained by the large number of cells that can be measured in a short period. Sampling errors in flow cytometry may result from the preparation of single cell suspensions which in certain tumor entities may suppress a varying amount of particularly fragile cells or nuclei. The prognostic significance of DNA ploidy, stem line heterogeneity and S-phase fraction is clearly described in quite a number of tumor entities. Independent of its prognostic value, the cytometric identification of stem lines might be particularly useful in the follow-up of tumor patients, where it may indicate the effectivity of systemic therapy. The development of therapeutic concepts is aptly supported by flow cytometric cell cycle analysis which helps to assess the in vitro effect of combined cytostatics on the proliferative process. Moreover, multiparameter analysis of biopsy samples may provide greater accuracy in characterising individual tumor stem lines and may furthermore help to develop improved protocols for the therapy of solid tumors.

Immunohistochemical staining of infiltrates in oral lichen planus.

Abstract: Summary Immunohistochemical examination of lymphocyte and accessory cell infiltrates was performed in 24 cases of oral lichen planus using a double staining technique. The major population of the superficial stromal lymphocytes was T cells which were mostly composed of dominant CD 4 + Leu8 − (helper T cells) and lesser numbers of CD 8 + 11b − cells (cytotoxic T cells). Contrarily, many more CD 8 + 11b − cells than CD 4 + Leu8 − cells had infiltrated the epithelium. Some infiltrated T cells expressed interleukin-2 receptor and about half of cytotoxic T cells expressed class II antigen. HLA-DR-positive monocytes were also observed in both the superficial stroma and the epithelium. A number of HLA-DR-bearing CD 1 + cells (Langerhans/dendritic cells) and CD l1c + cells (macrophages) were observed in the lower layers of the epithelium which were sometimes degenerative. Having significant correlation with the infiltration intensities of subepithelial macrophages and epithelial CD 8 + cells (cytotoxic/suppressor T cells), epithelial Langerhans cells variably infiltrated. Superficial stromal CD 8 + cells correlated with epidermal CD 8 + and CD 4 + cell (helper/inducer T cells) infiltrates. These findings are consistent with the notion that Langerhans cells and macrophages play an important role in antigen presentation, and suggest that cellular immunity, mediated by cytotoxic T cells with helper T cells, may be related to the pathogenesis of oral lichen planus.

Bronchial carcinoids with S-100 positive sustentacular cells. A comparative study with gastrointestinal carcinoids, pheochromocytomas and paragangliomas.

Abstract: Fourty-six bronchial carcinoids, twelve tumourlets and twenty areas of neuroendocrine cell dysplasia (NED) were immunohistochemically evaluated for various neuroendocrine markers, S-100 protein (S-100), myelin basic protein, intermediate filaments, actin, Leu-7 and several neurohormonal polypeptides Eighteen of the bronchial carcinoids (391%) showed a biphasic cell pattern, with abundant stellate-shaped S-100 positive cells (SC) SC were not reactive for chromogranin A, myelin basic protein, cytokeratins, neurofilaments, glial fibrillary acidic protein or actin, and were only occasionally weakly positive for vimentin SC were not detected in the tumourlets nor in the NED observed For comparison a group of other neuroendocrine tumours (11 gastrointestinal carcinoids, 4 pheochromocytomas and 4 paragangliomas) were immunostained for S-100, chromogranin A and actin SC similar to the ones detected in the bronchial carcinoids could be detected in appendiceal carcinoids, paragangliomas and in two out of four pheochromocytomas Our present data are in keeping with a Schwannian/sustentacular nature of SC rather than that of a histiocytic or myoepithelial nature We suggest that SC-rich bronchial carcinoids are biphasic tumours, which could be designed "paraganglioid" bronchial carcinoids The relationship between SC-rich bronchial carcinoids and tumourlets/NED is a matter of further investigation: SC-rich bronchial carcinoids may either differentiate in a biphasic pattern during tumoural growth or may not be histogenetically related to tumourlets

Comparative investigations of regional lymph nodes and pseudocapsules after implantation of joint endoprostheses.

Abstract: Summary Morphological alterations of pseudocapsules and regional lymph nodes were studied by light and electron microscopy and by Laser Microprobe Mass Analysis (LAMMA). The tissue specimens originated from 32 autopsies of patients with hip joint endoprostheses (time in situ: 3 weeks — 15 years, average: 6 years) and two cases with knee joint endoprostheses. Characteristic changes of the lymph nodes as well as of the pseudocapsules consisted in an infiltration by monocytic histiocytes with various intracytoplasmatic wear particles. The foreign material consisted mainly of the components of bone cement: polymethylmethacrylate (PMMA) and zirconium oxide, to a lesser degree of polyethylene from the articulating surfaces. In two cases with special types of prostheses ceramic or metallic wear particles could be detected too. Most of the wear particles were found in the ipsilateral parailiac lymph nodes and in the paraaortic lymph nodes bilaterally. In the cases with mostly stable prostheses small amounts of wear particles were found in the lymph nodes as soon as 1.5 years after insertion and their number increased in all groups of lymph nodes after longer duration of the implant. The phagocytosing histiocytes showed degenerative changes. At present it is not clear, if the cell damage is caused by the amount of phagocytosed wear particles alone or if specific toxic effects of certain substances are of importance.

Are there Characteristic Alterations of Lung Tissue Associated with Crohn's Disease?

Abstract: Two male patients aged 12 and 31 years suffered from Crohn's disease for more than six years and were treated with Cortison for more than four years. Surgical excision of parts of the terminal ileum was performed in both patients. They suffered from pulmonary symptoms as dyspnoea, shortness of breath and ventilation disturbances two years after operation. Wedge biopsies of the lungs revealed the following histomorphological findings: 1. Granulomatous interstitial lymphocyte infiltrates 2. Acute alveolitis with severe dysplasia of pneumocytes 3. Moderate interstitial fibrosis. Immunohistology performed in one case showed predominantly lambda chains expressed by lymphocytes associated with IgA and IgM. IgG was missing, furthermore kappa chains could not be detected. Macrophages contained endogenous lectins (sugar receptors) for fucose, maltose, and N-acetyl-D-glucosamine (glcNAc). No receptors specific for mannose, lactose, and heparin could be found. Pneumocytes did not bind the neoglycoproteins but were found to express HLA-DR receptors detectable by the monoclonal antibody LN 3 in dysplastic pneumocytes only. The histomorphological and immunohistochemical findings suggest that the analyzed alterations of lung tissue are related to the underlying disease of enteritis regionalis.

Xanthogranulomatous Cholecystitis: Histopathological Study and Classification

Abstract: Summary Xanthogranulomatous cholecystitis (XC) is a chronic inflammatory lesion of the gallbladder histologically characterized by the presence of varying amounts of foamy histiocytes in the inflammatory infiltrate. In this study a review of 63 cases selected from 1207 surgically removed gallbladders is presented; the percentage found (5.2%) is slightly higher than that of previous reports showing that XC is less uncommon than generally believed. A detailed microscopic study is performed: the authors observed according to the histological features particularly the different patterns of distribution of the inflammatory infiltrate and postulate the existence of three subtypes of XC: multinodular, focal and diffuse XC. Finally, the main etiopathogenetic hypotheses are briefly discussed.

Malignant pleural mesothelioma: some aspects of epidemiology, differential diagnosis and prognosis. Histological and immunohistochemical evaluation and follow-up of mesotheliomas diagnosed from 1964 to January 1985.

Abstract: Summary 64 diffuse pleural mesotheliomas diagnosed between 1964 and January 1985 at the Institute of Pathology of the University of Freiburg were analyzed. Since 1980 an increase from one case to 10 cases per year has been observed. The tumor was 3 to 4 times more frequent in men than in women. The age distribution showed a peak between the age of 50 and 60. In 26 cases evidence of exposure to asbestos was detected. In one patient radiotherapy of Hodgkin's disease may have been of etiological significance. The median survival time was 13 months. The five-year survival rate was only 4%. Histologic reevaluation was only possible in cases diagnosed after 1975. Of 43 cases thus evaluated 26 were pure mesothelial, 15 biphasic and 2 of the spindle-cell subtype. A median survival time of 23 months for pure mesothelial mesothelioma in comparison to 13 months for the biphasic mesothelioma indicated a better prognosis for pure mesothelial mesothelioma. Although no other primary tumors were detected, in 10 cases the differential diagnosis of adenocarcinoma had to be considered, and in 3 cases tumors of non-epithelial origin had to be excluded. 35 of 43 mesothelioma were CEA-negative, 38 out of 43 cytokeratin-positive, and 33 out of 43 were EMA-positive. Factor- VIII-related antigen was not demonstrated. 12 of 43 mesotheliomas showed PAS-positive staining, 29 of 43 were stained with Alcian blue. 7 of these 29 showed a positive digestion with hyaluronidase. Although CEA may not be negative in every mesothelioma, this marker seems to be a valid tool for the differential diagnosis of adenocarcinoma. In order to safeguard against a mistaken diagnosis of pleural mesothelioma, the exclusion of other tumors is always indispensable.

Vacuolar Myelopathy in AIDS: A Morphological Analysis

Abstract: Between 1986 and 1988 we studied the spinal cord of 40 patients dying of AIDS. Transverse and longitudinal sections from a minimum of four levels of the spinal cord were examined by means of conventional histology, immunohistochemistry and electron microscopy. Out of 22 cases there were 6 showing a mild, 11 a moderate and 5 a severe myelopathy. Among these cases with severe myelopathy, vacuolar degeneration of the posterior, lateral, and anterior columns of the white matter, which are typical findings of vacuolar myelopathy (VM), were present. Cervical and thoracic cords were affected in all cases, the lumbal cord, however, in only two. Fusiform vacuoles, 30 to 180 microns in diameter and 200 to 500 microns in length, could be seen rising between the axolemma and the myelin sheath. Most of them were still containing an axon cylinder. Foamy phagocytic cells, phagocytosing axons of apparently preserved structure were found within the vacuoles. These foamy macrophages contained rests of axons in their cytoplasm. However, only one case with severe tissue disruption exhibited myelin debris as well. Our morphological findings suggest that in VM of AIDS a process of phagocytosis directed against the axon cylinders occurs simultaneously with vacuolar degeneration of the white matter of the spinal cord. The results suggest furthermore that VM, especially its moderate form, appears to be a more frequent condition than previously assumed.

Histopathological Changes in the Skin and Subcutaneous Tissues of Mouse Legs after Treatment with Hyperthermia

Abstract: The right hind legs of mice wee heated in a waterbath at 44 degrees C. The animals were killed at various time intervals after exposure. Tissue damage was studied histologically. After 15 min exposure light and reversible changes were seen including oedema and some neutrophilic inflammatory infiltration immediately after treatment. After 30 min exposure an extensive inflammatory infiltrate and strong oedema were seen during the first days after treatment. Adjacent to areas in the skin with strong oedema extensive muscular necrosis was observed. The muscular tissue regenerated almost completely in three weeks. After 60 min heating the histological picture was dominated by massive necrosis of muscle, subcutaneous fat tissue and skin during the first week after treatment followed by local ulceration. From about the 7th day after treatment regeneration of the epithelium started and granulation tissue could be observed in the margin of the ulceration. Healing of the skin was completed at about day 21 after treatment. Our results indicate that heat induced tissue damage in some tissues is due to a direct effect on the cells composing the tissue (e.g., fat cells in subcutaneous fat) but that, in most other tissues (e.g., muscle and skin) it is a consequence of damage to the vasculature.

Antigenic profile of mammary fibroadenoma and cystosarcoma phyllodes. A study using antibodies to estrogen- and progesterone receptors and to a panel of cell surface molecules.

Abstract: Summary Using serial frozen sections, monoclonal antibodies and an indirect immunoperoxidase method, 13 fibroadenomas (FA) and 3 cystosarcomas phyllodes (CSP) were analyzed for the expression of Egp34, HEA319-antigen, leucocyte differentiation antigens CD10, CD30, CD57, CD72, CDw75, and CD77, epidermal growth factor receptor (EGFR), estrogen (ER) and progesterone receptor (PR), and transferrin receptor (CD71). Egp34, CDw7S, HEA319 antigen, CDlO, and CD30 turned out to be consistently expressed in different cell types constituting FA and CSP and revealed that in malignant CSP the myoepithelial compartment acquires the ability to invade the stroma. Phenomenologically, the variable mode of expression of CDS7 in myoepithelial cells, of CD77 in ductal epithelium, and of CD72 in both epithelial and stromal cells is suggestive for reflecting differences in their functional state but cannot be further interpreted at present. Expression of PR and ER was restricted to duct cells and was relatively independent, non-systematical. However, expression of ER and EGFR was inverse. This was also true for EGFR and CD71 in both duct cells and myoepithelial cells of FA. In contrast, stromal cells of FA were able to co-express EGFR and CD71 in the absence of PR and ER. This suggests a hormone-independent stimulation of the stromal cell compartment, possibly leading to local proliferation as the primary event in tumorigenesis of FA. In malignant CSP, however, the main proliferating cell is an abnormally mobile, HEA319 antigen-, CDl0- and CD30-positive myoepithelial cell found to co-express ERFR and CD71 which is abnormal for this cell type but encountered in (myo-)fibroblasts of FA.

Stem cell origin of human myeloid blood cell neoplasms.

Abstract: Studies with G6PD and molecular probes indicate that the myeloid leukemias and the chronic myeloproliferative disorders are clonal diseases. The G6PD data indicate that chronic myelogenous leukemia, polycythemia vera and essential thrombocythemia involve stem cells pluripotent for granulocytes, erythrocytes, megakaryocytes and lymphocytes. Agnogenic myeloid metaplasia is also a clonal disease that involves multipotent hematopoietic stem cells. However, myelofibrosis, the predominant clinical manifestation, occurs secondarily and is not a component of the abnormal clonal proliferation. Acute nonlymphocytic leukemia is a clonal disease, but G6PD studies suggest that there are at least two forms of this leukemia. In one type of ANL, the involved stem cells exhibit pluripotent differentiative expression. In another type of ANL, differentiative expression is largely restricted to the granulocytic pathway. The heterogeneity of ANL has both clinical and pathogenetic implications.

What's New in the Mechanisms of Host Resistance to Candida Albicans Infection?

Abstract: Summary Despite extensive investigation, the mechanisms of host resistance against C. albicans infection remain poorly understood. Granulocytes and macrophages are the major effector cell types; however, their intrinsic candidacidal activity is rather limited, and its full expression requires augmentation by components of the T cell-initiated lymphokine cascade. Consequently, susceptibility to recurrent mucocutaneous infections may be associated with aberrant T cell function. In contrast, protection from systemic infection appears to be mediated by candida-specific antibodies.

Variations in microscopic anatomy and ultrastructure of human embryonic hearts subjected to three different modes of fixation.

Abstract: Summary The external form and the internal contour of the ventricular surfaces were studied in human embryonic hearts following three modes of fixation: A) simple immersion fixation, B) indirect ventricular perfusion through the umbilical vein and C) high flow-low pressure ventricular perfusion-inflation. Fixation artifacts, resulting in distortion of the external form of the heart together with distortion of the internal contour of the ventricular cavities, were observed in specimens submitted to modes A and B of fixation. By contrast, hearts fixed by direct ventricular perfusion-inflation (C), showed less distortion in their external form, and the various intraventricular components maintained their spatial relationship among themselves and with the great arteries. Thus, reproducible developmental anatomical features at organ and tissue levels were readily available for study. The relevance of a direct ventricular perfusion-fixation method is discussed in relation to the value of human cardiac developmental data obtained in the past, after using simple immersion, or other modes of fixation.

Left and right sided breast cancer.

Abstract: Many studies have shown that unilateral breast cancer is more frequent in the left breast than in the right. This has been investigated in the Icelandic Cancer Registry. Information on all but 18 female breast cancer cases diagnosed in the forty-year-period from 1948 to 1987, a total of 2139 cases, was used. Of these 2011 were unilateral, 1069 were in the left breast, an excess of 13%. Primary breast cancer in both breasts was diagnosed in 81 women, 35 in the left breast first, and 46 in the right breast first. The excess risk of developing cancer remains for the left breast also for women who have already lost one breast because of cancer. Information on whether their relatives had developed breast cancer existed for 1197 of these women. Patients with an affected first degree relative were of 2.54 fold risk of developing contralateral primary breast cancer, but women with no affected relative were at a reduced risk (not significant). Patients with right sided breast cancer are more likely to have a relative with breast cancer. The breast cancer status of the relatives did not influence the risk of death, so a better survival of familial cases could not be shown.

Unusual Prostatic Carcinomas

Abstract: Summary Over 90% of malignant epithelial tumors of the prostate are common carcinomas. Uncommon or rare prostate carcinomas can histogenetically be related to 4 epithelial types of the prostate: the secretory epithelium, the basal cells, the endocrine cells and the transitional epithelium. The rare, purely mucinous carcinoma and the ductal papillary carcinoma belong to the type of secretory epithelium. The latter is rarely seen in the large central prostatic ducts, it develops more frequently in peripheral ducts and is combined with common prostate carcinoma. The so-called endometrioid carcinomas of the utriculus described in the literature are probably ductal prostate carcinomas. To date no carcinoma has been found in the utriculus. The adenoid cystic carcinoma of the prostate is a basal cell tumor with preponderantly good prognosis. Endocrine cells are disseminated in most common prostate carcinomas. Thereby mixed forms showing both portions of a common adenocarcinoma and of a carcinoid may occur. Pure carcinoids of prostate are rare findings. The small cell carcinoma of the prostate is the highly malignant variant of the endocrine cell type. Immunohistochemiocally, a multitude of proteohormones are demonstrable in endocrine tumor cells. The ectopic ACTH prodcution with Cushing's syndrome is of particular clinical significance.

Histology of the lower intestinal tract in Crohn's disease of children and adolescents. Multicentric Paediatric Crohn's Disease Study.

Abstract: Summary Serial sections of 1047 colonic and rectal biopsies from 385 children and adolescents suffering from Crohn's disease were studied histologically. Inflammatory alterations were seen in 76% of the biopsies and 84% of the patients. Incidence of inflammatory infiltration, of crypt abscesses, of erosions, and of ulcers decrease from caecum to rectum were studied. The incidence of granulomas falls along the colon but rises in the rectum. The occurrence of granuloma depends rather on the severity of the inflammation than on the biopsy site. Granulomas are present in 26% of the biopsies and 42% of the patients. Compared to adults, the incidence was twofold in children. Discontinuous type of infiltration, density of infiltration, crypt abscesses, rectal erosions prevail in children, diffuse type of infiltration, and colonic ulcers in adults. Incidence of granulomas is reduced after the second year of illness and after the 16th year of life. The number of granulomas per mm3 biopsy is increased in children, their average size in adults.

Stereotactic biopsy diagnosis of primary non-Hodgkin's lymphoma of the central nervous system. A histological and immunohistochemical study.

Abstract: We report 29 cases of primary non-Hodgkin lymphomas (NHL) of the Central Nervous System (CNS), 26 of which were diagnosed by stereotactic biopsy and 3 by autopsy. In seven cases the patients were affected by AIDS. Histological examination of this series revealed 15 cases of immunoblastic lymphoma, 12 cases of centroblastic lymphoma, 1 case of lymphoplasmacytic immunocytoma and 1 case of unclassified high grade lymphoma. By immunohistochemistry the B-cell origin of lymphoma cells was demonstrated in 28/29 cases. Eight cases were assigned to the B-cell lineage by demonstration of monotypic surface or cytoplasmic immunoglobulin or of the B-cell phenotype CD22+, CD2-, CD3-, CD5-. In twenty cases the B-cell nature of lymphoma was identified by positivity with two or more anti-B monoclonal antibodies (LN1LN2MB2) and negativity by the anti-T monoclonal antibody UCHL1. The histologically unclassified case was a peripheral T-NHL (CD1-, CD2+, CD3-, CD5+, CD22-). We conclude that histological and immunohistological evaluation of stereotactic biopsy specimens provides sufficient information for diagnosis and phenotypic characterization of primary NHL of the CNS. These lymphomas exhibit important predominance of high-grade malignancy histological types and are nearly always B-cell derived. In addition, we provide further evidence that the panel of monoclonal antibodies LN1, LN2, MB2, and UCHL1 is useful for immunophenotypic characterization of brain lymphomas when only paraffin embedded stereotactic biopsy tissue is available.

Clinical and pathological changes of the heart in brain death maintained with vasopressin and epinephrine.

Abstract: In ten brain death patients circulatory stability was attained with both vasopressin and a minimum dose of epinephrine for more than a week. Clinical and pathological changes of the heart after brain death were examined in this model. ST-T wave changes of ECG were initially observed in 57%. The required dose of epinephrine to maintain the systemic blood pressure was rather high in the first two days after brain death and could be reduced below 0.1 kg/min in a steady state. Normal level of CPK-MB in this study indicated that the damage of the heart was reversible. The cardiac biopsy specimens from the right ventricular septum were obtained serially and they showed normal or slightly swollen mitochondria. The mitochondrial scores were below 1.0 in seven patients, and they were elevated to more than 1.0 in three patients with prolonged shock. The heart of brain death was suppressed by the shock at brain death, but it could be preserved in good condition for several days with our circulatory support which uses both arginine vasopressin and epinephrine.

Localized fibrous tumors of the pleura: correlation of histopathological, immunohistochemical and ultrastructural features.

Abstract: Summary The histogenesis of localized fibrous tumor of the pleura (LFTP) is controversial. We studied 12 LFTP's by light microscopy; by immunohistochemical staining for cytokeratin (CK), vimentin, muscle-specific actin, desmin, S-100 protein, epithelial membrane antigen (EMA) and factor VIII; by electron microscopy in 6 tumors; and by lung digestion for asbestos bodies in 4 cases. Three histologic patterns occurred in combination: 1) collagenous, 2) cellular and 3) hypocellular/myxoid. Hemangiopericytoma-like foci were prominent in the cellular areas of 9 tumors. Unusual features included diffuse small cells in 3 tumors, microcystic foci in 2, macrocystic areas in 5 and tumor giant cells in 4 tumors. Neoplastic cells in all patterns stained positively for vimentin and actin in 9 and 4 tumors, respectively, and were negative for all other markers. CK and EMA were identified in mesothelial and epithelial invaginations only. Ultrastructurally, neoplastic cells demonstrated intercellular junctions, intermediate or thin filaments, dense bodies and rough endoplasmic reticulum. Basal lamina was focally present in 5 tumors, while tonofilaments, desmosomes and short microvilli were observed in one case. Our results support the conclusion that LFTP is a neoplasm of the multipotential subserosal cell, and usually expresses mesenchymal (fibroblastic/myofibroblastic) differentiation. Coexpression of mesothelial features is rare. Lung asbestos body quantitation in 4 patients suggests that there is no association between LFTP and asbestos exposure.

Papillary tumour of the vagina resembling transitional cell carcinoma.

Abstract: A case of a peculiar papillary neoplasia of the vagina resembling a urothelial tumour is presented. Four vaginal tumours were excised from a 76-year-old woman. Five years before this patient had undergone a uretero-nephrectomy for a non-invasive papillary transitional cell carcinoma of the renal pelvis. The four vaginal tumours demonstrated gross and microscopic similarities to low-grade papillary transitional cell carcinoma of the urinary tract. This observation indicates that multicentric, non-invasive, papillary tumours may affect the whole uro-genital area. The vaginal wall was not overlaid by a normal squamous epithelium, but by a peculiar "transitional-like" epithelium. Variegated endocrine cells were documented within this lining, using immunohistochemical and ultrastructural techniques. The eventuality of a histogenetic link between the tumour and the adjacent epithelial lining remains unresolved.

Mesothelial proliferation due to asbestos and man-made fibres. Experimental studies on rat omentum.

Abstract: Summary The intraperitoneal test in rats has proven to be an appropriate method controlling fibrogenicity and carcinogenicity of asbestos fibres and other fibrous dusts. We analyzed the reaction patterns of mesothelial cover layer to different natural mineral fibres (crocidolite, chrysotile, actinolite, erionite, wollastonite) and man-made mineral and synthetic fibres (glass fibres 104/475, polypropylene, aramide fibres). The injection of doses between 0.01 and 100 mg dust suspended in saline solution led to a continued repairing proliferation of submesothelial connective tissue cells and focal submesothelial fibrosis. These changes were never observed after application of granular dusts as mine dust and quartz. After 15 to 28 months we often found an association of fibrosis and local reactive hyperplasia of partly atypical proliferation of rat omentum mesothelium. These changes were also demonstrated in cases without macroscopically visible tumors. In later stages the underlying fibrosis was often infiltrated and dissolved by mesotheliomas.

The Enterochromaffin Cells in the Mouse Gastrointestinal Tract after Streptozotocin Treatment

Abstract: Summary Effects of 5 weeks streptozotocin treatment on the mouse gastrointestinal tract were studied with special emphasis on enterochromaffin (EC) cells. In the streptozotocintreated animals the frequency of EC cells was reduced in the antral area and in the small intestine, but increased in the colon. The length of the intestinal tract and the mucosal thickness were increased in these animals. Possible mechanisms underlying these abnormalities of the EC cell system are discussed.

Immunohistochemical assessment of growth fractions in colorectal adenocarcinomas with monoclonal antibody Ki-67. Relation to clinical and pathological variables.

Abstract: Immunostaining with monoclonal antibody Ki-67 (MAb Ki-67) has been employed to determine the growth fractions in a series of 139 primary adenocarcinomas of the large bowel. A wide range (18.9-71.4%; mean 39.4%; median 37.2%) in the percentage of Ki-67 reacting cells (Ki-67 index) was observed. The Ki-67 index was found to be unrelated to tumour stage, lymph node involvement, and presence of synchronous distant metastases. Mucinous carcinomas showed higher levels of Ki-67 reactivity than non-mucinous adenocarcinomas (P = 0.0003). Among non-mucinous adenocarcinomas a significant inverse correlation was demonstrated between the percentage of Ki-67 stained cells and the degree of differentiation (P = 0.002), and preservation of nuclear polarity (P less than 0.001). Moreover, tumours of patients younger than 45 years were generally characterized by high numbers of proliferating cells. There was no correlation between Ki-67 index and the other clinical and pathological variables examined. In most cases small differences in Ki-67 reactivity were observed in different samples from the same tumour. These results demonstrate that immunohistochemical assay with MAb Ki-67 represents a simple and reliable method for the assessment of proliferative activity in colorectal adenocarcinomas and suggest that Ki-67 labeling may provide information of clinical relevance in the management of patients with large bowel cancer.

Extracellular matrix in preneoplastic lesions and early cancer of the lung.

Abstract: Summary Characterization of preneoplastic lesions mainly concentrated on cellular, nuclear and epithelial atypias. The extracellular matrix was almost neglected, although malignant tumour cells interact with extracellular matrix molecules during tumour invasion. Until now systematic investigations of extracellular matrix components in preneoplastic lesions and early stages of lung cancer are lacking. 150 preneoplastic lesions, 10 specimens of early cancer and 30 specimens of normal bronchial mucosa were examined by means of immunofluorescence microscopy. The distribution of collagen type I and III and the non-collagenous glycoproteins laminin and fibronectin have been investigated by an indirect immunohistochemical method. With an increasing degree of preneoplasia an increased matrix disarrangement of the basement membrane zone could be observed. In severe dysplasia and carcinoma in situ neosynthesis of collagen type III and especially laminin in close association to neoangiogenesis could be demonstrated besides a disintegration of extracellular matrix components. In early lung cancer numerous laminin positive basement membrane like structures are situated around tumour cells. An enhanced deposition of collagen type I and III fibres could be demonstrated around tumour cell islets. The results indicate a partial loss of function in preneoplastic basal cells in cases of dysplasia and carcinoma in situ. In early stages of invasive squamous cell carcinoma of the bronchus, extracellular matrix components obviously could be produced by tumour cells.

Metastasizing Pleomorphic Adenoma with Myoepithelial Cell Predominance

Abstract: The biological behavior of pleomorphic adenomas (mixed tumors) of salivary gland origin is complex Tumors with benign histologic features may exhibit recurrence and locally aggressive behavior especially after incomplete excision A small percentage of pleomorphic adenomas have obvious malignant components in epithelial or in both epithelial and mesenchymal components and can metastasize There are also rare case reports which appear to document typical pleomorphic adenomas of salivary gland with histologically identical visceral and lymph node metastases Recently myoepithelial cell proliferation has been identified as a possible predictor of aggressive clinical behavior in otherwise histologically benign pleomorphic adenomas We report such a parotid gland lesion with local recurrence and retroperitoneal spread DNA-flow cytometry of cells from the paraffin-embedded primary and metastasis showed similar aneuploid populations Aneuploidy appeared to reflect the malignant potential of this particular pleomorphic adenoma and suggests that DNA-flow cytometry of salivary gland tumors may yield important prognostic information