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Biomedical subjects

C M Payne

Publications and source records attributed to C M Payne.

At least 73 records · Page 4Linked to original sources

Eccrine and squamous differentiation in Merkel cell carcinoma. An immunohistochemical study.

Of the 42 Merkel cell carcinomas that we studied, two showed numerous tubular structures within sheets and nests of small cells. The small cells stained for both neuron-specific enolase and keratin. The keratin decorated a dot-like paranuclear structure. The ducts stained positively for carcinoembryonic antigen (CEA) and CF-1 (cystic fibrosis-1, a monoclonal antibody that only stains eccrine duct and acrosyringium). Electron microscopy performed on one case showed cytoplasmic dense-core neurosecretory granules and intercellular lumina lined by cells containing microvilli. These ultrastructural and immunohistochemical features support the concept of eccrine differentiation in these tumors. A third case contained foci of typical keratinizing squamous cell carcinoma admixed with sheets of small cells. The immunohistochemical and ultrastructural characteristics of this tumor were essentially similar to those of a conventional Merkel cell carcinoma. Our findings suggest that Merkel cell carcinomas, similar to neuroendocrine tumors from other anatomic sites arise from a primitive totipotential stem cell that has the capacity to differentiate along different cell lines.

Adenocarcinoma↗

Blepharopigmentation: histopathologic observations and X-ray microanalysis.

Blepharopigmentation or permanent eyeliner is a popular cosmetic procedure currently performed by a variety of methods. All methods attempt to implant ferrous oxide pigment into the dermis. We performed histopathologic studies on a series of three eyelid specimens, including two by a previously undescribed multi-needle pigment delivery system. Light microscopy revealed the epidermis to be pigment-free and the dermis to contain pigment in clumps. Transmission electron microscopy (EM) demonstrated that the pigment was largely in macrophages. Energy-dispersive x-ray micro-analysis showed that in addition to iron and talc, titanium particles were also present. These findings suggest that the pigment is tolerated by the eyelid despite the fact that current pigments are contaminated.

Adult↗

Nuclear contour irregularity correlates with Leu-9-, Leu-8- cells in benign lymphoid infiltrates of skin. An ultrastructural morphometric and quantitative immunophenotypic analysis suggesting the normal T-cell counterpart to the malignant mycosis fungoides/Sézary cell.

The purpose of the present study was to determine if a nonmalignant skin-associated T-cell might exhibit nuclear irregularity and represent the normal counterpart to the malignant Sézary T-cell found in mycosis fungoides (MF) and the Sézary syndrome (SS). Punch skin biopsies from ten benign lymphoid infiltrates of skin were subjected to ultrastructural morphometric analysis and quantitative immunohistochemistry (on serial frozen sections) using a battery of monoclonal antibodies. Form factor (FF) (4 pi A/p2) was used to assess nuclear contour irregularity. The lymphoid infiltrates were morphometrically heterogeneous (range of FF values: 0.482-0.704). Immunophenotypically, there was marked variation in host response to the variety of antigens presented. Linear regression analysis was used to determine if nuclear contour irregularity showed any statistical relationship to immunophenotypically defined lymphocyte subpopulations. It was determined that nuclear contour irregularity (mean FF values) did not correlate with the presence of any surface antigen tested. This included the antigens Leu-2a, Leu-3a + b, Leu-4, Leu-6, Leu-7, Leu-8, Leu-9, Leu-14, and Ia. There was, however, significant correlation of increased nuclear contour irregularity with the presence of Leu-9- and Leu-8- cells (r = 0.7 and 0.6, respectively), lymphocyte subsets reportedly deficient in MF and the SS. This finding leads to the speculation that the Leu-9-, Leu-8- reactive T-cell with an irregular nucleus might represent the normal counterpart to the malignant clonally expanded T-cell found in MF and the SS. It was also determined that helper to suppressor ratios varied 68-fold from 0.2 to 13.5 among these ten benign lymphoid infiltrates of skin. This finding underscores the futility of using helper to suppressor ratios as a diagnostic tool in defining T-cell malignancies.

Adult↗

Burkitt's-like lymphoma of T-cell type.

Over an 8-yr period, we studied 29 cases of Burkitt's/Burkitt's-like lymphoma and unexpectedly found 2 Burkitt's-like cases of the T-cell type. One case presented as diffuse adenopathy in a 35-yr-old male. A second case presented as a jaw mass in a 2-yr-old girl with Down's syndrome. Histologically, each case demonstrated usual Burkitt's-like morphology (intermediate-size cells with high nuclear/cytoplasmic ratio, 1 to 3 prominent nucleoli, high mitotic rate, basophilic cytoplasm, and cytoplasmic vacuolation). Ultrastructural morphometric data corroborated the Burkitt's-like nature of these neoplasms. Immunologically, the neoplasms were of "novel" T-cell phenotype, as seen in peripheral T-cell lymphoma (PTL). The cases showed variable expression of activation antigens (e.g., Ia) and weak to moderate expression of proliferation antigens as measured by Ki-67. This modest proliferative activity (less than 25% Ki-67 expression) contrasts with Burkitt's-like lymphomas of the B-cell type which usually show greater than 80% Ki-67 expression. The jaw tumor also demonstrated positivity for human progenitor cell antigen (HPCA) as commonly found in leukemia. Both cases mimic granulocytic sarcoma by virtue of their eosinophilic/myelocytic recruitment--a phenomenon previously reported in association with PTL. The patients have survived 62 wk and 20 wk, respectively, surpassing the survival rates seen in our concurrent B-cell Burkitt's-like lymphomas (12 wk). Burkitt's-like lymphoma of the T-cell type appears to be a distinctive immunological subset of potential clinical and prognostic relevance.

Adult↗

The role of immunohistochemistry, electron microscopy, and ultrastructural cytochemistry in the diagnosis of mixed carcinoma-neuroendocrine neoplasms.

We studied four mixed carcinoma-neuroendocrine neoplasms from gastrointestinal tract and pancreas by routine light microscopy (LM), immunohistochemistry (IH), electron microscopy (EM), and ultrastructural cytochemistry (UC). By LM, the individual tumors showed fairly pure neuroendocrine (carcinoid) or epithelial (papillary) patterns, mixed neuroendocrine-carcinoma features and poorly-differentiated tumor in sheets and nests which did not lend itself to morphologic characterization. IH demonstrated mixed expression, within different areas of the same neoplasm, of epithelial antigens (keratins and carcinoembryonic antigen [CEA]) and neuroendocrine markers (neuron-specific enolase [NSE], bombesin and neurohormonal peptides). By EM, each tumor showed ultrastructural features of epithelial and neuroendocrine differentiation which varied substantially in terms of number of cells involved and their distribution; two of the neoplasms showed biphasic differentiation within single cells. The nature of the neurosecretory granules was verified with the uranaffin reaction (UR). This study illustrates the value of combining LM, IH, EM and UC for the identification of mixed carcinoma-neuroendocrine lesions.

Aged↗

Cytogenetics of bone marrow fibroblastic cells in idiopathic chronic myelofibrosis.

To determine the nature of the fibroblastic proliferation in myelofibrosis, we studied the cytogenetic composition of a pure population of in-vitro bone marrow fibroblastic cells (FC) from a patient with idiopathic chronic myelofibrosis who had trisomy 8 in her unstimulated peripheral blood cells. This cytogenetic abnormality was absent in all the FC studied supporting the premise that in the myeloproliferative disorders the myelofibrosis represents a secondary or non-neoplastic reaction to the clonal proliferation of haematopoietic stem cells.

Aged↗

Ultrastructural similarities between Chlorohydra viridissima and human neurosecretory granules: a cytochemical study using the uranaffin reaction.

The uranaffin reaction is an ultrastructural cytochemical procedure which, in humans, stains the cores of true neurosecretory granules of all morphological types, and will not stain the granules of exocrine-type glands or lysosomes found in a variety of cell types. Positively-charged uranyl ions appear to react with concentrated polyphosphate groups and stain the nucleotides known to be present in the neurosecretory granules of higher organisms. In Chlorohydra viridissima, two morphological types of neurosecretory granules were identified within the epidermis and gastrodermis by routine electron microscopy; one granule type was small and displayed a central dense core with a surrounding clear halo, whereas, the other was larger and displayed an eccentric core with a loosely-associated granule membrane. Both types stained with the uranaffin reaction, but the characteristic granules of the exocrine-type digestive glandular cells and the mucous cells of the gastrodermis were uniformly uranaffin-negative. In the gastrodermis, a third granule type was identified which showed a larger uranaffin-positive core. The discovery of uranaffin-positive neurosecretory granules in Hydra suggests that formation of nucleotide-neurohormone complexes as a means for packaging and storage of neurohormones within the granule matrix, may have existed in primitive nervous systems.

Animals↗

Morphological evidence of an altered bone marrow microenvironment in patients with acute nonlymphoblastic leukemia and myelodysplastic disorders.

Type IV nuclear bodies are classified as true intranuclear inclusions that ultrastructurally contain numerous densely packed 20- to 30-nm osmiophilic granules surrounded by a microfibrillar cortex. In the present study, we have found statistically significant ultrastructural differences in the frequency and size of type IV nuclear bodies in the in vitro bone marrow fibroblastic cells (FC) derived from eight nonleukemic subjects and 13 patients with acute nonlymphoblastic leukemia (ANLL) and myelodysplastic disorders (MDD). Patients with ANLL, MDD, and myelofibrosis, as a group, had four times as many type IV nuclear bodies as nonleukemic subjects. The mean frequency of type IV nuclear bodies for patients with ANLL and MDD was 2.68% +/- 3.27% as compared with 0.63% +/- 1.06% for the nonleukemic subjects (p less than 0.05). The mean maximum type IV nuclear body area of the ANLL and chronic myelomonocytic leukemia (CMML) patients as a group was 2.08 +/- 1.10 micron2, compared with a mean maximum area of 0.93 +/- 0.10 micron2 from nonleukemic subjects (p less than 0.05). The FC were otherwise morphologically indistinguishable and displayed the typical ultrastructural features of fibroblasts. These findings have provided the first morphologic evidence that supports the concept of an altered bone marrow microenvironment in patients with ANLL and MDD. Since type IV nuclear bodies are found in high frequency in virally infected tissues, our quantitative ultrastructural findings raise the possibility of a local viral infection that affects the bone marrow microenvironment of patients with ANLL and some MDD disorders.

Acute Disease↗

An ultrastructural morphometric and immunophenotypic evaluation of Burkitt's and Burkitt's-like lymphomas.

Six cases of Burkitt's lymphoma (BL) and 12 cases of Burkitt's-like lymphoma (BLL) were classified by using strict histologic and cytologic criteria. These cases were processed for electron microscopy and analyzed by using computerized image analysis techniques. Form factor (4 pi A/P2) was used to measure nuclear contour irregularity. The mean of the standard deviation (SD) of nuclear area and form factor was used to assess pleomorphism. Overall, there were 8 similarities and 10 statistically significant dissimilarities out of 18 parameters analyzed. The similarities (p greater than 0.05) between the BL and BLL groups included the means of form factor, nuclear area/cytoplasmic area, SD of nuclear area/cytoplasmic area, number of nuclear pockets/100 nuclei, percentage of cells with nuclear pockets, number of lipid droplets/micron 2 of cytoplasm, percentage of cells with lipid droplets and number of mitochondria/micron 2 of cytoplasm. The dissimilarities (p less than 0.05) included the means of nuclear perimeter, SD of nuclear perimeter, nuclear area, SD of nuclear area, cellular area, SD of cellular area, cytoplasmic area, SD of cytoplasmic area, SD of form factor, and nucleolar frequency. Multiparameter analysis clearly separated these 18 patients into two distinct groups and confirms that the subtleties used in the histologic classification of these lymphoma subtypes are meaningful. Sixteen cases of BL and BLL were snap-frozen in isopentane and analyzed by using 16 lymphoid surface markers. All of the immunoglobulin-positive BL were of the mu isotype, whereas the BLL cases were divided between mu (6 cases) and gamma expression (4 cases). All 4 of the BL evaluated manifested CALLA expression, whereas 3 of the 11 BLL evaluated coexpressed CALLA. One BL case was of a pre-pre-B phenotype and one BLL case was of pre-B phenotype. The BL and BLL were compared to 49 cases of SIg (+) large cell lymphomas. The high incidence of coexpression of lambda, CALLA, and Ki-67 in BL and BLL separates these lymphomas, as a group, from the large cell lymphomas. We have also determined from this study that the separation of patients into distinct BL and BLL subtypes is clinically relevant. The BL group were all children (median of 6.5 years) compared with the BLL group who were all adults (median of 63 years). The complete remission rate was higher in the BL (67%) than in the BLL group (25%).4off

Adult↗

Cutaneous myiasis. Immunohistologic and ultrastructural morphometric features of a human botfly lesion.

This study documents the immunohistologic and ultrastructural morphometric features of a case of cutaneous myiasis due to Dermatobia hominis. The mixed host inflammatory response surrounding the larvae included lymphoblasts, eosinophils, activated fibroblasts, mature histiocytes, mast cells, plasma cells, and Langerhans cells, indicating a complex interactive immunologic response to the botfly parasite. Immunotyping revealed that the dominant dermal cells were activated (Ia+) T-helper cells. Although the strikingly elevated T-helper/T-suppressor cell ratio might suggest a monoclonal infiltrate, a mixture of Leu 8+ and Leu 8- T-cells indicates both immunoregulatory subsets of T-helper cells as found in a reactive process. Furthermore, our ultrastructural histogram found the lymphoid nuclear shapes were oval with few nuclear invaginations as found in inflammatory infiltrates. As indicated by electron microscopy, there were abundant activated fibroblasts elaborating collagen which may relate to larval containment.

Central America↗

Ultrastructural morphometric analysis of nuclear contour irregularity in normal cord and adult blood: correlation with distinct lymphocyte subpopulations.

Cord blood lymphocytes obtained from ten healthy newborns and peripheral blood obtained from ten healthy adults were compared by using ultrastructural morphometric methods. Cord blood lymphocytes could be distinguished from adult lymphocytes on the basis of nuclear contour irregularity (form factor) and perimeter (P less than .001). The mean nuclear form factor (FF) value of the cord lymphocytes, as a group, was 0.603 +/- 0.034; the mean nuclear FF value of adult lymphocytes was 0.755 +/- 0.032. Lymphocyte subpopulations were quantitated by flow cytometric and immunofluorescence techniques and correlated with nuclear contour irregularity (mean FF values) by using linear regression analysis. Overall, the correlations between nuclear contour irregularity and the proportions of distinct lymphocyte subpopulations were opposite for cord and adult blood. Increased nuclear contour irregularity was associated with increased proportions of immature lymphocytes (non-T, non-B lymphocyte population) in the neonate and with increased proportions of T cells in the adult. Of the T cells, increased nuclear contour irregularity showed a better correlation with increased proportions of T helper cells compared with T suppressor cells. A plot of the distribution of FF values indicated two populations of lymphocytes having convoluted and nonconvoluted nuclei, respectively. No true Sézary cells could be identified in cord blood with ultrastructural morphometric criteria, despite the abundance of cerebriform mononuclear cells identified by visual inspection. The lymphocyte with the most irregular nuclear contour was found in an adult and had an FF value of 0.132 (13% of a circle). The contribution of this study to the diagnosis of cutaneous T cell lymphomas and the Sézary syndrome is discussed.

Adult↗

An eight-year study of the viral agents of acute gastroenteritis in humans: ultrastructural observations and seasonal distribution with a major emphasis on coronavirus-like particles.

During an 8-yr period, 862 stool specimens from patients with gastroenteritis were examined by electron microscopy after negative staining with 2% phosphotungstic acid (pH 6.5). Forty-one percent of the specimens submitted over an 8-yr period were determined to be positive for virus or viruslike particles belonging to one or more of seven morphologically distinct viral groups. Coronavirus-like particles (CVLPs) were present in 69.8% of the positive stool specimens. Membranous profiles containing "complement-type" holes (10 nm in diameter) were identified in some preparations containing CVLPs. The second most prevalent viral agent found in stool specimens was the rotavirus (17% of all positive stools). The incidence of other viruses identified in the survey were as follows: adenovirus 4.5%, picorna/parvovirus agents 2.9%, Norwalk-like agent 2.9%, astrovirus 1.9%, and calicivirus 0.5%. Unclassified small round viruses (approximately 25-30 nm in diameter) represented 0.5%. It was also determined that there was a seasonal distribution in excretion of all viruses except for CVLPs. A greater number of viruses were identified in the cooler, drier months of the year.

Adenoviruses, Human↗

Comparison of the usefulness of histochemistry and ultrastructural cytochemistry in the identification of neuroendocrine neoplasms.

Neuroendocrine (NE) neoplasms range from well to poorly differentiated types. These neoplasms usually contain neurosecretory (NS) granules demonstrated by either transmission electron microscopy (TEM) or silver reduction methods. By using the uranaffin reaction, one can differentiate NSG from other membrane-bound organelles. Recently, a variety of antibodies reactive against specific peptides or neurotransmitter substances have been advocated as being diagnostically useful. Using the peroxidase-anti-peroxidase (PAP) or Avidin-Biotin technics, we studied 41 NE neoplasms using anti-sera specific for neurospecific enolase (NSE), bombesin, adrenocorticotropic hormone (ACTH), calcitonin, and serotonin. All cases were shown to contain NS granules with a positive uranaffin reaction. In all 25 well-differentiated cases, at least one anti-serum gave a positive reaction. NSE was positive in 22 of the 25. In the poorly differentiated group, 7 (43.2%) of 16 were negative for all anti-sera tested. In these negative cases TEM using the uranaffin reaction remains an important diagnostic test.

Cytoplasmic Granules↗

Fibrolamellar carcinoma of liver: a primary malignant oncocytic carcinoid?

Immunohistochemical and ultrastructural findings in two cases of fibrolamellar carcinoma of the liver and two cases of hepatocellular carcinoma of the common histologic type are described. Ultrastructural examination of both cases of fibrolamellar carcinoma revealed the presence of neurosecretory (NS) granules which were sparse in some cells and abundant in others. Many of the tumor cells had a distinct oncocytic appearance with abundant mitochondria. A portion of the glutaraldehyde-fixed neoplasm was processed for the uranaffin reaction (an ultrastructural cytochemical stain specific for the NS granules of neuroendocrine tissue). Abundant uranaffin-positive granules were found in the neoplastic cells of both cases of fibrolamellar carcinoma, whereas no uranaffin-positive granules were found in hepatocellular carcinoma of the common histologic type. There was no statistical difference in the mean diameter of the uranaffin-positive granules measured from both cases. Immunohistochemistry revealed the presence of neuron-specific enolase (NSE) and serotonin in one of the two cases of fibrolamellar carcinoma and no NSE staining in two cases of hepatocellular carcinoma of the common histologic type. These findings suggest that some liver tumors presenting histologically as fibrolamellar carcinoma may be neuroendocrine in nature.

Adult↗

An ultrastructural morphometric and immunohistochemical analysis of cutaneous lymphomas and benign lymphocytic infiltrates of skin. Useful criteria for diagnosis.

Our combined ultrastructural, immunohistochemical, histologic, and clinical studies over the past five years have allowed us to compile diagnostic criteria useful in the evaluation of cutaneous lymphomas. As a group, mycosis fungoides (MF) patients could be distinguished from those with benign disorders of skin using ultrastructural morphometry (mean form factor and perimeter values), but with some overlap between groups. Another approach, the ultrastructural histogram method, however, clearly separated MF patients from patients with chronic dermatitis. Immunohistochemistry was useful in distinguishing cases of cutaneous peripheral T-cell lymphoma from MF cases on the basis of the occurrence of "novel phenotypes." Neoplastic T-cell infiltrates of skin can usually be distinguished from benign polyclonal T-cell infiltrates by the presence of one T-cell subset to the exclusion of others. Patients with convoluted B-cell lymphomas could also be distinguished from MF patients using ultrastructural morphometric dual parameter analysis. The diagnostic complexity of several cutaneous T-cell lymphoma cases is illustrated. We have emphasized in this study the strength of combining quantitative electron microscopy, immunohistochemistry, and histology in the diagnostic workup of cutaneous lymphomas. This integrative approach may be necessary to assure a definitive diagnosis in difficult cases.

Adult↗