Rationale and potential for image analysis in histopathology: an overview.
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Diagnosis↗
Biomedical subjects
I Dardick
Publications and source records attributed to I Dardick.
Ultrastructural morphometry and the control of lymphocyte nuclear size in non-Hodgkin lymphoma: a review.
Morphologic features, particularly nuclear characteristics, continue to be a major factor in the classification of the subtypes of non-Hodgkin lymphoma (NHL). Information is limited or nonexistent, however, concerning the mechanisms responsible for nuclear appearance. This is particularly true for nuclear size. In determining which of the nuclear compartments--condensed chromatin or the interchromatinic (euchromatin or nuclear matrix) region--is responsible for nuclear size, ultrastructural morphometric analysis has been a useful tool. Linear regression analysis has been used to compare, in turn, condensed chromatin area (CCA) and interchromatinic area (ICA) against nuclear area (NA). Whether in normal or neoplastic lymphocytes, correlation coefficients are moderately good when CCA is matched against NA, but CCA is only a weak predictor of NA. In contrast, correlation coefficients are remarkably high for ICA compared to NA, and ICA predicts NA to the degree of 94% to 97%. This holds true for all NHLs tested and for reactive hyperplasias. Despite abnormalities in lymphocyte nuclear size in NHL, the size of any nucleus is controlled by the amount of interchromatinic material to an exceptional degree. Even so, the mechanisms responsible for major changes in nuclear volume during transformation of normal lymphocytes are apparently altered in NHL. Morphometric analysis, ultrastructurally, can assist in understanding, testing, and defining diagnostic morphologic criteria in this disease.
Cell Nucleus↗
The role of electron microscopy in evaluating ciliary dysfunction: report of a workshop.
This report summarizes the proceedings of a workshop organized with the purpose of bringing together many of those with substantial experience in this troublesome area of pathology for an active interchange of ideas, opinions, problems, and solutions. Recognition was given the fact that current knowledge and technical capabilities are woefully inadequate for dealing with the diagnostic questions now being asked. Until such time as these inadequacies can be remedied, a very conservative approach to the interpretation of ultrastructural studies is advocated.
Adolescent↗
Reliability of criteria for ultrastructural identification of neuroendocrine granules.
For full diagnostic use to be made of the neurosecretory granule, the range of sizes, forms, and staining qualities for this cytoplasmic organelle, along with the extent of its expression in various neoplasms, must be established. Neurosecretory type granules occasionally occur in nonneuroendocrine tumors. A series of carcinoids of the lung provides a model for assessing the morphologic types of cytoplasmic granules identified by antibodies to chromogranin A and immunogold labeling. The results show that granule structure in tumors is pleomorphic. Despite having sizes within the expected range, many labeled and, indeed, unlabeled secretory granules are atypical, particularly in structural form. Cell-to-cell variation in the proportion of even typical neurosecretory granules labeling for chromogranin A is the rule. Studies correlating biochemical, immunohistochemical, electron microscopic, and perhaps in situ hybridization characteristics are required to define better the criteria for unequivocal identification of neurosecretory granules in tumors.
Adenocarcinoma↗
Role of electron microscopy in head and neck pathology in adults and children.
Diagnostic electron microscopic studies specific to the head and neck region are limited in both children and adults. Even information about the workload created by specimen acquisition from this region in the electron microscopy laboratory is lacking. To address these deficiencies, various specimens gathered from adults (N = 6607) and children (N = 1556), over a 5- and 10-year period, respectively, and blocked in plastic resin were surveyed. Head and neck samples accounted for 16.4% of these samples from adults and 13.5% from children, representing sizable contributions to workload from an anatomic region amounting to less than 10% of body mass. In adults, diagnostic problems posed by metastatic neoplasms account for a considerable proportion of the cases submitted for electron microscopy; in the pediatric age group, undifferentiated primary tumors of the head and neck region frequently require ultrastructural study. In both circumstances, spindle cell, look-alike, neuroendocrine, and small cell tumors can frequently be rapidly assessed and differentiated by ultrastructural details. Problem cases are inevitable given the complexity of this region and the number of different tissues and organs in close proximity. It is advantageous to anticipate the possibility of encountering difficult differential diagnostic problems by sampling lesions of the head and neck for glutaraldehyde fixation more frequently.
Adult↗
Extraskeletal myxoid chondrosarcoma with intracisternal microtubules.
A case of extraskeletal myxoid chondrosarcoma with intracisternal microtubules is presented. The microtubules were generally straight, parallel, closely packed, and evenly spaced, but they did not form geometric arrays. Aggregates of stromalike myxoid material were present in the cisternae and the adjacent cytoplasm. Microtubules were never found within the cytoplasm. A similar ultrastructural appearance was seen in 4 of 10 other examples of extraskeletal myxoid chondrosarcoma.
Aged↗
Myofilament localization and immunoelectron microscopic detection of muscle-specific actin in neoplastic myoepithelial cells in pleomorphic adenomas and myoepitheliomas.
Elucidating the cellular characteristics of the nonluminal or myoepithelial cells of pleomorphic adenomas is one approach to establishing the diagnostic criteria for myoepitheliomas. Ultrastructural features of nonluminal tumor cells in 22 pleomorphic adenomas and of tumor cells in 9 myoepitheliomas were assessed from micrographs of routinely fixed and epoxy resin-embedded samples. Recognizable myofilaments were only moderately prominent in 1 myoepithelioma. In the rest of the cases, irrespective of whether nonluminal cells of pleomorphic adenomas or tumor cells of myoepitheliomas were spindle, angular, round, or plasmacytoid in form, myofilaments were noted only in one third of the cases and were present even in these in a small proportion of the tumor cells. Intermediate filament accumulations and basal lamina were more frequent findings associated with nonluminal tumor cells. Six pleomorphic adenomas and 2 myoepitheliomas had been fixed in half-strength glutaraldehyde and embedded in LR White resin for immunoelectron microscopic detection of muscle-specific actin. In 3 (2 pleomorphic adenomas and myoepitheliomas) of these 8 cases, readily visualized bands of filaments in many tumor cells were strongly labeled by the colloidal gold probe detecting muscle-specific actin even when myofilaments were minimal and infrequent in 2 cases and undetectable in the third by routine transmission electron microscopy. Lack of myofilament detection by immunocytochemistry or routine electron microscopy does not exclude a diagnosis of pleomorphic adenoma or myoepithelioma when growth patterns and cytology indicate such diagnoses. Immunoelectron microscopy, in fact, shows that muscle-specific actin can be detected even when myofilaments or muscle actin are apparently absent or minimal by routine electron microscopy or immunohistochemistry, respectively. Because examples of pleomorphic adenoma and myoepithelioma each with similar histologic and cytologic features of the myoepitheliomatous cells can have variable degrees or complete absence of expression of myofilaments or muscle-specific actin, the time-honored term myoepithelial for the nonluminal cells of pleomorphic adenomas and the term myoepithelioma are legitimate even in the absence of those markers that are specific for normal myoepithelial cells.
Actins↗
Myoepithelioma: definitions and diagnostic criteria.
Due to their infrequency and multiplicity of histopathology, myoepitheliomas present difficulties in diagnosis and classification. Cellular varieties can be misdiagnosed as malignancies. Improvements in and clarification of diagnostic criteria are, therefore, required. A key to determining diagnostic criteria for myoepitheliomas is to study cellular morphology, cytoplasmic filament expression, and ultrastructural features of the nonluminal, i.e., neoplastic myoepithelial/basal, tumor cells of pleomorphic adenomas, and apply this information to defining myoepitheliomas. Cytologic and growth patterns of nonluminal cells in pleomorphic adenomas, including plasma-cytoid cells, are reflected in myoepitheliomas. Results also indicate that muscle-specific actin and myofilaments are expressed only in a proportion of cases, and generally in not more than 60-70% of nonluminal cells in pleomorphic adenoma; this also applies to benign and malignant myoepitheliomas. The absence of these markers does not exclude a diagnosis of myoepithelioma. Vimentin and glial acidic fibrillary protein, however, are strongly and diffusely expressed in the majority of pleomorphic adenomas and myoepitheliomas and are more reliable markers for these tumors than muscle-specific actin. Like so many other salivary gland tumors, myoepitheliomas present an equally complex histomorphology and variable expression of antigenic markers, only some of which are associated with myoepithelial and basal cells of the acini and ducts of the normal salivary gland.
Actins↗
Ultrastructural distinction of basaloid-squamous carcinoma and adenoid cystic carcinoma.
Basaloid-squamous carcinoma is a unique and infrequent variant of squamous cell carcinoma with a predilection for occurring in the upper aerodigestive tract. The cardinal diagnostic criteria are the presence of basaloid cells arranged in lobules or cords and a squamous component. Another feature that distinguishes basaloid-squamous carcinoma from conventional squamous cell carcinoma is the development of multiple foci of amorphous, eosinophilic, or mucinous materials among the basaloid tumor cells. It is this feature in basaloid-squamous carcinoma that causes confusion with adenoid cystic carcinoma, especially the solid variant of adenoid cystic carcinoma. To clarify the distinctive features of these two types of tumors, the ultrastructural findings in three basaloid-squamous carcinomas from the head and neck region were compared with three adenoid cystic carcinomas, one from the head and neck region and one each from trachea and bronchus. Widened intercellular spaces, tonofilaments, and replicated basal lamina were present in both types of tumor. However, the ultrastructural features of glandular differentiation were present only in adenoid cystic carcinoma, whereas the ultrastructural features of squamous cell differentiation were present only in basaloid-squamous carcinoma. The distinction between basaloid-squamous carcinoma and adenoid cystic carcinoma is important since basaloid-squamous carcinoma is a clinically aggressive, high-grade form of squamous cell carcinoma, generally with a worse prognosis than adenoid cystic carcinoma.
Adult↗
Cytopathology and ultrastructure of primary rhabdoid tumor of lung.
This case report presents the light microscopy, immunocytochemistry, and ultrastructure of the first unequivocal extrarenal rhabdoid tumor occurring in lung. Smears and cell blocks prepared from a fine-needle aspiration biopsy show the cytopathological features of this unusual neoplasm, in this case presenting in a 74-year-old male. Electron microscopy of the surgically resected circumscribed pulmonary mass assisted in establishing the diagnosis by demonstrating the considerable accumulation of cytoplasmic intermediate filaments that characterize cells in extrarenal rhabdoid tumor and account for the hyaline "inclusion" in this particular lesion.
Aged↗
Immunoelectron microscopy for chromogranin A in small cell neuroendocrine carcinoma of lung.
To see if immunoelectron microscopy can improve localization of neurosecretory granules, postembedding immunolabelling for chromogranin A was performed on 15 examples of small cell anaplastic (neuroendocrine) carcinomas primary in lung, five cases of bronchopulmonary carcinoids, and two cases of pheochromcytoma; both the carcinoids and pheochromocytomas had neurosecretory granule-rich cytoplasm by routine electron microscopy and some neurosecretory granules were identified in each of the small cell carcinomas. Immunolabeling for chromogranin A resulted in many colloidal gold particles over cytoplasmic secretory granules in both pheochromcytomas and four of the carcinoids. One carcinoid that was focally positive by immunoperoxidase staining was negative by immunoelectron microscopy. None of the 15 cases of small cell carcinoma stained for chromogranin A using immunoperoxidase techniques, but three had a small number of secretory granules weakly labeled by the anti-chromogranin A/colloidal gold complex. Immunoelectron microscopy, at least using standard glutaraldehyde fixation and epoxy resin embedding, does not increase the sensitivity of neurosecretory granule identification in small cell neuroendocrine carcinomas of the lung. Results of other studies of this neoplasm suggest that despite transcription of chromogranin genes, synthesis of the specific protein may occur to a limited extent or not at all.
Carcinoid Tumor↗
Quantitative ultrastructural study of nuclei from exfoliated benign and malignant mesothelial cells and metastatic adenocarcinoma cells.
Various approaches, including morphometric image analysis, are currently being used to improve the distinction between diffuse mesothelioma and metastatic adenocarcinoma of the serous membranes. Since exfoliated cells of malignant mesotheliomas were thought to have nuclear profile contours with greater irregularity than the similar profiles in metastatic adenocarcinoma cells in pleural effusions, this and other nuclear parameters were measured in ultrastructurally examined preparations from three cases of reactive mesothelial hyperplasia, seven examples of diffuse mesothelioma and three cases of metastatic adenocarcinoma (with primaries in the ovary, esophagus and prostate). Contrary to the subjective impression, the nuclei in metastatic adenocarcinomas actually had a mean nuclear contour index greater than that found in diffuse mesotheliomas; statistically, the difference was not significant. Likewise, such other nuclear parameters as nuclear area, condensed chromatin area and contour index, percentage of condensed chromatin and number of condensed chromatin clumps per nuclear profile did not discriminate between malignant mesotheliomas and adenocarcinomas metastatic to pleural surfaces. These morphometric results quantitate the similarities in nuclear size, nuclear shape and condensed chromatin arrangement in these two types of tumor and explain why the cytopathologist has such great difficulty in distinguishing between exfoliated mesothelioma and adenocarcinoma cells in most cases.
Adenocarcinoma↗