Reproducibility of morphometric image analysis.
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Cell Nucleus↗
Biomedical subjects
I Dardick
Publications and source records attributed to I Dardick.
Non-Hodgkin's lymphoma classification: ultrastructural morphometric studies for the quantification of nuclear compartments in situ.
The condensed chromatin distribution in the nuclei of lymphocytes in non-Hodgkin's lymphoma (NHL) is a key element, along with nuclear size and shape, in the classification of this disease for therapeutic and prognostic purposes. This report describes the ultrastructural comparative quantification of the condensed chromatin and the interchromatinic (nuclear matrix or euchromatin) region in the nuclei of mitogen-stimulated human peripheral T lymphocytes and mouse spleen B lymphocytes, human germinal center lymphocytes, and lymphocytes in ten cases of NHL of a variety of subtypes. The sequential morphologic nuclear changes induced in lymphocytes by mitogens are reflected in human germinal center lymphocyte populations. The common features include the changes in the distribution and volume of condensed chromatin aggregates, as well as the fact that the major increments in nuclear volume during lymphocyte transformation result from increases in the volume of the interchromatinic region. In all subtypes of NHL analyzed morphometrically, subpopulations of lymphocytes were identified in which mean nuclear, condensed chromatin, and interchromatinic volumes were more or less equivalent to those of normal lymphocyte subsets in germinal centers in reactive hyperplasia. However, in NHL the abnormal cytologic characteristics of the nucleus result, at least in part, from a complex interplay of condensed chromatin distribution and amount, and the size of the interchromatinic region. Further complexity is introduced by the fact that in NHL these two nuclear compartments can independently be normal, increased, or reduced in size. Morphometric quantification of lymphocytes in NHL indicates that the interchromatinic (matrix) region of the nucleus is the key element in establishing the nuclear volume of neoplastic lymphocytes. The structural and functional, ribonucleoprotein interchromatinic region of the nucleus was visualized in normal and neoplastic lymphocytes by regressive uranyl-EDTA staining. Quantitative morphometric analysis indicates that the cytologic appearance of neoplastic lymphocytes, even within subtypes of NHL, is heterogeneous and that condensed chromatin quantity and distribution may be more critical than nuclear size in distinguishing between certain subtypes of NHL. Improvements in the classification of NHL will occur only with understanding of the alterations in the biologic mechanisms controlling gross nuclear organization and the morphologic events of the various differentiation pathways available to antigen-stimulated lymphocytes.
Animals↗
Ultrastructural similarities of adenoid cystic carcinoma and pleomorphic adenoma.
Ultrastructural examination of five adenoid cystic carcinomas, three breast and two salivary gland, reveals identical patterns of tumour cell differentiation, organization and distribution of cellular products (Zaloudek, Oertel & Orenstein 1984). In both sites, there is proliferation of two populations of cells, one with characteristics and organization of duct-type luminal epithelial cells and a second that forms the principal proliferating component and has the overall organization and appearance that would suggest that they represent modified myoepithelial cells. Recent ultrastructural studies also indicate that tumour cell types and histological organization similar to those described for adenoid cystic carcinoma occur during histodifferentiation of salivary gland pleomorphic adenoma (Dardick et al. 1983a, b). The characteristic histological pattern of adenoid cystic carcinoma is dependent on the formation of pseudolumina containing proteoglycans and reduplicated basal lamina. Similar, but smaller, lumina of like organization and contents are evident in some cases of pleomorphic adenoma. Both the ultrastructural similarities of the tumour cell types and their organization, in adenoid cystic carcinoma and pleomorphic adenoma, suggest that these tumours have a similar histogenetic basis. The fact that one lesion is malignant and the other benign does not preclude common types of tumour cells and developmental processes.
Adenoma, Pleomorphic↗
A role for electron microscopy in salivary gland neoplasms.
Undoubtedly, electron microscopy has a specific role to play in the diagnosis of a select group of salivary gland neoplasms. However, this tool has a current central role, along with immunohistochemical techniques, in elucidating morphogenetic processes in salivary gland tumors. New information gained from ultrastructural surveys of these tumors can be applied to improving classification and the diagnostic problems that are not infrequent for the surgical pathologist with salivary gland lesions.
Adenoma↗
Malignant myoepithelioma of parotid salivary gland.
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Aged↗
Intracranial metastasis from a malignant mixed tumor of parotid salivary gland.
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Brain Neoplasms↗
Electron microscopic analysis of lymphocyte nuclei in non-Hodgkin's lymphoma.
Ultrastructural studies of normal and neoplastic lymphocytes are presented that qualitatively and quantitatively assess the central cell organelle currently used by surgical pathologists in the classification of non-Hodgkin's lymphoma, the nucleus. Events occurring during normal lymphocyte transformation can be used to appreciate essential mechanisms involved in producing the appearance of the nucleus as seen by microscopy. Quantitation of nuclear subcompartments by morphometric image analysis reveals that determination of nuclear size is primarily due to the ribonucleoprotein materials distributed between condensed chromatin masses, the interchromatinic (euchromatin or nuclear matrix) region. Furthermore, such investigations show that amounts and distribution of condensed chromatin in lymphocyte nuclei cannot be adequately assessed from routine histologic sections. Ultrastructural morphometric analysis of representative cases of the principal subtypes of NHL indicates that the atypical morphologic appearance of neoplastic lymphocytes results from a complex interplay between total amounts of condensed chromatin in nuclei and the size of individual aggregates of condensed chromatin, one or both of which may be abnormal in NHL. Abnormalities of interchromatinic materials are also likely involved in ordering the gross appearance of the nucleus. Understanding of both the dynamic capabilities of the nucleus, and the organization of and interplay between the various subcompartments of this organelle will be helpful in improving the classification of NHL by surgical pathologists.
Animals↗
Myoepithelial cells in salivary gland tumors. An immunohistochemical study.
Normal salivary glands and 55 salivary gland tumors were examined by immunostaining (immunoperoxidase [IMP] and immunofluorescence [IMF]) to identify myoepithelial cells (MCs) and speculate on their role in the histogenesis of the tumors. The classic (C) MCs of normal salivary glands stained by IMP with antibodies to cytokeratin and S100 protein and stained by IMF with the same antibodies and with antibodies to vimentin and actin. Modified (M) MCs of pleomorphic adenomas stained positively by IMP and IMF with all of the preceding antibodies. In many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas, variable numbers of CMCs and MMCs stained positively by IMP with anti-cytokeratin and anti-S100 protein antibodies. No MCs were detected in adenolymphomas or acinic cell carcinomas. We believe that MCs play a major role in the histogenesis of pleomorphic adenomas and may also be important in many mucoepidermoid carcinomas, adenoid cystic carcinomas, and basal cell adenomas.
Actins↗
Salivary gland components involved in the formation of squamous metaplasia.
Squamous metaplasia is not an uncommon feature of a number of salivary gland lesions. Arterial ligation of rat submandibular and sublingual salivary glands was used for study of the processes and cell types involved in the development of the squamous metaplasia that occurs in ischemic and infarcted portions of gland parenchyma 6 to 8 days following vessel ligation. Light and electron micrographs show that the principal portion of salivary gland tissue undergoing squamous metaplasia is the acinar-intercalated duct cell complex. Early stages of this process involve a gradual dedifferentiation of acinar cells and hyperplasia of acinar, duct luminal cells, and myoepithelium. Subsequently, both luminal and myoepithelial cells have increasing accumulation of tonofilaments and formation of desmosomes, and centrally located cells may undergo keratinization. Immunohistochemical staining of ischemic salivary gland tissue with developing squamous metaplasia was performed with the use of rabbit antisera to human epidermal and Mallory body cytokeratins. The two antisera gave complementary patterns in normal acini and ducts, with antibody to epidermal cytokeratin (ECK) staining only myoepithelial cells and antibody to Mallory body cytokeratin (MBCK) staining mainly luminal epithelial cells. In early phases of squamous metaplasia (6 days after ligation), antibody to ECK stained central and peripheral (myoepithelial) cells, but by 8 days after ligation only central cells were stained. At 6 days after ligation, a proportion of central cells in squamoid clusters stained with antibody to MBCK, and myoepithelial cells were unstained. By 8 days after arterial ligation, cell clusters exhibiting squamous metaplasia were completely unstained with antibody to MBCK, despite the presence ultrastructurally of numerous tonofilament bundles in both types of cells forming these clusters. The propensity for squamous alteration of acinar-intercalated duct complexes has important connotations for salivary gland tumors such as pleomorphic adenoma and mucoepidermoid carcinoma.
Animals↗
Ultrastructural aspects of the histogenesis of diffuse and localized mesothelioma.
During an ultrastructural review of 30 diffuse and 10 localized mesotheliomas, it was apparent that some micrographs showed various stages in the developmental processes involved in the formation of histological patterns in diffuse mesotheliomas and a histogenetic link between diffuse and localized mesotheliomas. Cells in the stromal or sarcomatous regions of diffuse mesothelioma often show varying degrees of mesothelial differentiation and a gradual transition to cells with typical mesothelial characteristics that organize into structures recapitulating the surface layer of serosal membranes. Tumor cells in localized mesotheliomas had many similarities to the "stromal" cells in the diffuse counterpart including intercellular junctions, rare microvilli and occasional foci of basal lamina. It is postulated that diffuse and localized mesotheliomas share a common histogenetic origin as a result of neoplastic induction of specialized submesothelial cells. In this concept, tumor cells in diffuse mesotheliomas reflect stages in the differentiation and organization of normal serosal membranes and localized mesotheliomas mirror the earliest phases of this process.
Humans↗
Nuclear morphologic and morphometric analyses of large noncleaved cell and immunoblastic non-Hodgkin's lymphomas.
Both morphologically and immunologically, non-Hodgkin's lymphoma (NHL) of the large cell type has been shown to be a heterogeneous category. However, the homogeneity of the nuclear parameters, particularly size and condensed chromatin organization, used to classify this subtype of NHL has not been investigated. In fact, objective morphologic techniques have not been systematically applied to verify the segregation of NHL on the basis of nuclear parameters, a concept common to all current classification systems. In this study morphometric image analysis was used to compare the nuclei in 20 specimens from NHLs of the large cell type with those in mantle zone and germinal center lymphocytes from lymph nodes with reactive hyperplasia. Results of the assessment of mean nuclear area in large cell lymphomas revealed that this class is also heterogeneous, with some of the specimens having a nuclear size in the upper range of that for normal small lymphocytes. In addition, in only a few of these specimens was the mean nuclear area within the range of that for fully transformed germinal center lymphocytes. The majority of large cell lymphomas have a nuclear size more characteristic of partially transformed lymphocytes in germinal centers. In addition to indicating inconsistencies in the current diagnostic criteria used in NHL classifications, the results indicate reasons for interobserver variations in clinicopathologic trials; the validity of nuclear size as a prognostic indicator and the biologic basis for classifying NHL as a reflection of normal lymphocyte transformation are also questioned. In terms of patient management, the classifications of NHL currently used require objective reappraisal.
Cell Nucleus↗
Peritoneal epithelial lesions associated with proliferative serous tumours of ovary.
The peritoneal epithelial lesions in 40 cases of proliferating ovarian serous tumour are described. The lesions were varied and of both neoplastic and non-neoplastic form. The most common was serous tumour similar to that in the associated ovarian neoplasm. Tumour of this type was present in some or all of the peritoneal lesions in 77.5% of cases. In nearly two-thirds, the tumour was superficial; in the rest it invaded omentum. Occasionally, the infiltrating tumour was poorly differentiated. Benign tubular lesions resembling endosalpingiosis occurred in 16 (40%) of the 40 cases, but in seven it was associated with serous tumour. Psammoma bodies frequently accompanied serous tumour and endosalpingiosis and in occasional cases the majority of lesions consisted of psammomatous foci. The duration of follow up is too short to adequately assess the biological significance of these findings but it is clear that the peritoneal tumour occasionally may kill the patient within a few years. 'Serous tumour of low malignant potential' is the most appropriate term to describe the general group of ovarian serous tumours of so-called 'borderline malignant' type.
Adolescent↗
Mucoepidermoid carcinoma: ultrastructural and histogenetic aspects.
Ultrastructural examination of 6 mucoepidermoid carcinomas (4 from parotid salivary gland and 2 from lung) was used to investigate tumor cell types, their interrelationship, histogenetic aspects and factors involved in the multiplicity of histological patterns in this tumor. On the basis of light-microscopic cellular features, mucoepidermoid carcinomas are generally thought to be formed by 3 principal cell types, mucinous, squamous and intermediate. However, low-magnification electron micrographs reveal that there are 2 basic tumor-cell types interpreted as modified luminal epithelial and myoepithelial cells. Both cell types may independently show a range of fine structural modification and organizational arrangement. Luminal epithelial cells have varying degrees of mucin production and lumen formation in some regions, while modification of these cells is one mechanism for squamoid and frankly squamous appearances in other areas. Preferential proliferation of the second type of tumor cell aligned on the outer aspect of luminal epithelial cells is responsible for the development of isomorphic regions composed of intermediate cells. Squamous metaplasia can also occur in relationship to these latter cells. Based on these observations and recent ultrastructural and histochemical studies of salivary gland tumors, it is suggested that, in addition to the excretory duct, neoplastically altered cells in the acinar-intercalated duct region must be considered as a potential source for the development of mucoepidermoid carcinomas.
Adult↗
Ultrastructure of poorly differentiated diffuse epithelial mesotheliomas.
In differentiating diffuse epithelial mesothelioma from metastatic adenocarcinoma in pleural and peritoneal biopsies, the number and form of microvilli and the amount and distribution of tonofilaments are thought to be the most useful criteria. This report details 5 cases of diffuse epithelial mesothelioma in which the characteristic fine structural features of neoplastic mesothelial cells were markedly modified. The majority or all tumor cells were poorly differentiated in electron micrographs, particularly with reduced prominence or absence of intermediate filaments, desmosomes, intracytoplasmic lumina, and microvilli. Immunohistochemistry revealed the absence of carcinoembryonic antigen and the presence of cytokeratin in all cases. Comparison with a better differentiated case suggests cytologic details that are useful in distinguishing the poorly differentiated type of epithelial mesotheliomas from adenocarcinoma. These include a mosaic pattern of closely associated tumor cells with a few long, narrow cytoplasmic processes lying parallel to adjacent plasma membranes, abundant cytoplasm with limited organelles usually having a polar arrangement, and nuclei with markedly disaggregated chromatin and prominent nucleolonemal-type nuclei.
Biopsy↗
Salivary gland monomorphic adenoma. Ultrastructural, immunoperoxidase, and histogenetic aspects.
Monomorphic adenoma of basal cell type is a salivary gland tumor believed to result from a proliferation of a single type of cell. However, ultrastructural and immunocytochemical investigations of 6 monomorphic adenomas (5 from parotid and 1 from intraoral minor salivary gland) indicate that there are two classes of these lesions, one composed of two types of tumor cells and the other wholly or predominantly made up of one type of cell (isomorphic). In the former group, the organization of the tumor cells closely mimicked that of normal and hyperplastic salivary gland intercalated ducts. Aggregates of tumor cells were arranged as an inner layer of luminal epithelial cells which were surrounded by an outer layer of cells that, in some cases, had ultrastructural and immunohistochemical features indicating myoepithelial cell differentiation. In some adenomas formed by two types of tumor cells, basal-lamina-lined extracellular spaces were identified ultrastructurally in relation to modified myoepithelial cells; such spaces had the same fine-structural features as those reported in pleomorphic adenoma and adenoid cystic carcinoma. Predominantly isomorphic adenomas were composed exclusively of luminal epithelial cells. These results indicate that despite the varied histologic patterns in the numerous subtypes of monomorphic adenoma, there is a central theme of differentiation and organization in this type of neoplasm which recapitulates the ductoacinar unit of normal salivary gland parenchyma.
Adenoma↗
Morphometry of normal human lymphoid tissues. Nuclear parameters for comparative studies of lymphoma.
Prior to performing morphometric studies of non-Hodgkin's lymphoma, baseline nuclear parameters of the various compartments of normal human lymphoid tissue are needed. Such information was obtained from traced nuclear profiles from a series of human lymph node biopsy specimens and samples of tonsil and spleen. All tissues showed reactive hyperplasia. In combined samples of adult lymph node specimens, nuclear parameters of mantle and paracortical lymphocytes were similar, but were smaller and more regular than small, unstimulated germinal center lymphocytes. Despite variation in mean nuclear size between various lymph node samples, transformed lymphocytes in germinal centers had a constant relationship to the nuclei of small untransformed lymphocytes in these regions. Our results indicate that there is considerable variation in the nuclear parameters of lymphocytes within a specific region of the normal lymph node of each case, but that such differences are difficult to appreciate in histologic preparations.
Adolescent↗
Morphometry of normal human lymphoid tissues. Nuclear invaginations and clefts.
We performed morphometric analysis on samples of human lymphoid tissue involved by reactive hyperplasia to assess the basis for the concept of cleaved lymphocyte nuclei in current non-Hodgkin's lymphoma classification. Histologic sections from all regions of lymph node showed considerable variation (usually 9% to 16%) in the proportion of nuclear profiles, with invaginations of at least 0.4 micron. Invaginations sufficiently deep to label nuclear profiles as "cleaved" occurred in 2% or less of lymphocytes of all regions seen on 1-micron plastic-embedded sections. The majority of nuclear invaginations were less than 1.6 micron deep. Analysis of the morphometric data suggests that the nuclei of germinal center lymphocytes undergoing antigen-induced transformation do not progress through a specific phase in which they become increasingly cleft. With the increased angularity and irregularity of lymphocyte nuclear profiles in germinal centers, the "cleaved" appearance of these nuclei in paraffin-embedded sections seems to be due to linear creases and overlapping segments of the nucleus.
Adolescent↗
Chordoid sarcoma (extraskeletal myxoid chondrosarcoma).
Evaluation of a series of 12 chordoid sarcomas suggests that there is a wider range of histological features in this entity then previously appreciated. Six of the lesions had a typical tumor cell organization and a mixture of cellular and myxoid stromal components, while the remaining cases were atypical because of a more solid growth pattern. Four of the 12 cases, that included both typically myxoid and more cellular examples, had small foci with hyalinized stroma segragating individual or small groups of tumor cells with and without lacunar spaces. Two atypical cases revealed more extensive and obvious chondrocytic differentiation in recurrent or metastatic lesions and in one of these, the histological pattern was that of mesenchymal chondrosarcoma. Ultrastructural examination of three cases revealed fine structural features of both the tumor cell population and extracellular matrix compatible with chondrocytic differentiation. Results of light and electron microscopy of this series of chordoid sarcoma add further support for categorizing this tumor with other malignant chondrocytic neoplasms. It is probable that chordoid sarcoma and extraskeletal myxoid chondrosarcoma represent the same entity and that this lesion has a close histogenetic relationship to mesenchymal chondrosarcoma.
Adult↗