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H Galera-Davidson

Publications and source records attributed to H Galera-Davidson.

At least 37 records · Page 2Linked to original sources

Blue nevus: classical types and new related entities. A differential diagnostic review.

Blue nevus is an uncommon pigmented lesion of dermal melanocytes. By convention, two well defined histologic variants, designated as "common" and "cellular", have been recognised. In the last few years, these lesions have attracted much attention due to the recognition of news entities and to its confusion with malignant melanoma. In the present review, we point out the more striking features of new related entities (combined nevus, deep penetrating nevus, compound blue nevus) and establish the differential diagnosis with conflictive lesions such as atypical blue nevus, locally aggressive blue nevus, congenital giant melanocytic nevus with nodular growth and melanocytic dermal tumor of unpredictable outcome. We also review the concept of malignant blue nevus and the significance of lymph node metastases. The blue nevus is an uncommon pigmented lesion consisting of dermal melanocytes that can appear in diverse forms: dendritic, spindle-shaped, oval-shaped, or polyhedral. Although it usually occurs in skin, it has been reported in other locations, such as oral mucosa, sclera, uterine cervix, vagina, prostate, spermatic cord, pulmonary hilus, orbit, conjunctiva, maxillary sinus, breast, and lymph nodes 3,8,42,49. Generally, it occurs in adults as a single, acquired, intensely pigmented lesion, although familial and multiple nevi have been reported 7,39. By convention, there are two well-defined histologic variants, designated as "common" and "cellular", but lesions often manifest intermediate features. In the last few years, blue nevus has attracted much attention due to the recognition of new (clinical and histologic) entities and to its confusion with malignant melanoma.(ABSTRACT TRUNCATED AT 250 WORDS)

Diagnosis, Differential↗

Use of computer graphic filters for the nuclear grading of hematoxylin and eosin-stained specimens from prostatic lesions.

An inexpensive workstation is being developed to assist pathologists in diagnosing routine hematoxylin and eosin-stained slides. A linear discriminant model was applied to karyometric features of prostate lesions, and a grade according to Mostofi was determined from the discriminant values. Twenty cases, five of hyperplasia and five each of carcinoma Mostofi grades I, II and III, for a total of 600 nuclei, were selected to train the model. Computer graphic filters were constructed from the discriminant values. Each segmented nucleus has a colored frame (the graphic filter) displayed around it. The color, determined from discriminant values and correlated with the grades, ranges from green for hyperplasia, yellow for low grade, orange for medium grade and red for high grade. An additional 20 cases, 5 of hyperplasia and 5 each of the Mostofi grades, for a total of 538 nuclei, were selected to test the graphic filter. Ninety-six percent of the hyperplasia nuclei were framed in green, 84% of low grade nuclei were framed in yellow, 90% of medium grade nuclei were framed in orange, and 89% of high grade nuclei were framed in red. These results indicate the potential of the color graphic filter to show the pathologist immediate and accurate visual information about the grade of a nucleus. This method may help with the difficult diagnosis of borderline lesions and may help in making the diagnosis from scanty biopsy material.

Cell Nucleus↗

Importance of different nuclear morphologic patterns in grading prostatic adenocarcinoma. An expanded model for computer graphic filters.

The aim of this work was to continue the development of an interactive workstation for the nuclear grading of prostatic lesions by including a large range of nuclear patterns. A previous model was based on four groups: hyperplasia, Mostofi grade 1, Mostofi grade 2 and Mostofi grade 3. Each group included the most common nuclear patterns of the lesions. One set used to test the model included cases showing patterns different from the typical ones of the model. Poor results were obtained for low and medium grades. A review of all the cases in our database led to the conclusion that different nuclear patterns can belong to the same "nuclear grade." Thus, in this work the model was expanded to include six groups: hyperplasia, two subgroups for Mostofi grade 1, two subgroups for Mostofi grade 2 and Mostofi grade 3. A set of 900 nuclei, 150 in each group, was selected to test the model. An additional 300 nuclei, 50 in each group, were used for a test set. The overall success rate for classifying the nuclei in the test set using the new model was 93% as compared to a rate of 71% obtained for the similar test set, described above, using the previous model. Moreover, correlating karyometric features with nuclear morphology indicated a role for nucleoli in nuclear grading. The good results obtained with large and heterogeneous sets of cases indicate that the procedures used to develop this model may be adapted for the development of models for the nuclear grading of other tumors.

Adenocarcinoma↗

Nuclear DNA patterns in adrenal cortex proliferative lesions.

In cortical adrenal gland tumours there are discrepancies between morphological criteria for malignancy and biological behaviour. This makes it difficult to select the appropriate treatment. We have studied morphometric and DNA densitometric features of 24 adrenal proliferative lesions (hyperplasia, adenoma, and carcinoma) by means of slide cytometry. All variables have been correlated with pathological diagnosis. The samples were selected from paraffin-embedded tissue, and representative lesions were Feulgen stained. Densitometric study showed aneuploid cell lines in every carcinoma, 5 of 8 adenomas, and 5 of 10 hyperplastic lesions. Both DNA nuclear content (mean ploidy of 2.11 c, 2.41 c, and 3.05 c) mean nuclear area (average of 31.26 microns 2, 35.92 microns 2, and 42.39 microns 2) showed progressive increase from hyperplasia to adenoma, and carcinoma. Mean shape factors were lowest in adenomas (1.69) and highest in carcinomas (1.82). Those karyometric variables which showed statistically significant differences (p < 0.05) among diagnostic groups were included in a stepwise three-way discriminant analysis. Only three parameters, shape factor (p = 0.0008), mean ploidy (p = 0.0012), and adrenal weight (p = 0.0055) persisted as independent predictive factors. Using the three variables selected by discriminant analysis on our cases, 100% of the adenomas were correctly classified, 83% of the carcinomas, and 80% of the hyperplasias. Tumour weight and nuclear shape factor differentiated adrenal cortex adenoma from carcinoma, while mean ploidy distinguished adrenal cortical hyperplasia from carcinoma. Nuclear pleomorphism (shape factor) and DNA-ploidy are the most important nuclear features in predicting the biological course of proliferative adrenal cortex lesions, although by themselves they are not bona-fide discriminators.

Adenoma↗

Chromatin texture features in hematoxylin and eosin-stained prostate tissue.

A pilot study was undertaken to determine the expression of certain nuclear features in prostatic lesions. Twenty cases, 5 of hyperplasia and 5 each of carcinoma, Mostofi grades I-III, were selected as a training set, and an additional 20 cases were used as a test set, including 5 cases of hyperplasia and 5 cases each in Mostofi grades I-III. Images of hematoxylin and eosin-stained, 4-microns paraffin sections were obtained with a JVC BY-110 three-color camera and digitized by an IBM personal computer with a Matrox MVP-AT/NP imaging board. Thirty nuclei for each case from the training set, for a total of 600 nuclei, and 10 nuclei for each case from the test set, for a total of 200 nuclei, were analyzed by quantitative cytometric software on a SUN 3/60 workstation. A linear discriminant model was used for statistical analysis. One hundred percent of the hyperplasia group, 98% of the low grade group, 92% of the medium grade group and 82% of the high grade group were classified correctly in the test set with an overall success rate of 93%. Statistically significant chromatin texture features included heterogeneity, condensation, margination, run length nonuniformity, long run emphasis, gray level nonuniformity and inertia. Area, roundness and staining intensity (total extinction) were also significant. The results with standard hematoxylin and eosin-stained tissue sections were similar to those previously obtained with Feulgen-stained material. These results indicate that routine hematoxylin and eosin-stained material offers consistent diagnostic clues.

Chromatin↗

Quantitative changes in the frequency and distribution of the C-cell population in the rat thyroid gland with age.

The development of calcitonin cells (C-cells) was investigated in rat thyroid glands from birth to 120 days, using an immunoperoxidase technique and a point-counting method. The proportion of C-cells to follicular cells was 4.5% on the day of birth and increased progressively to 10.4% by 120 days. The highest density of C-cells was noted in the mid-region of the lobes along a longitudinal axis. The caudal and cephalic regions of the lobes contained smaller numbers of C-cells. The C-cells tended to be more numerous in the posterior aspects of the lobes. Although the numbers of C-cells in 120-day-old animal were markedly increased as compared to animals at the time of birth, the cell distributions within the glands were similar at all ages.

Aging↗

Evidence of the occurrence of calcitonin cells in the ultimobranchial follicle of the rat postnatal thyroid.

A study on thyroid glands of Wistar rats of ages ranging from 1 to 120 days was carried out. The glands were serially sectioned and stained for calcitonin using the peroxidase antiperoxidase method. All the thyroids contained ultimobranchial follicles (UBF) located partially embedded among the usual follicles but in a 5-day-old rat this structure showed an unusual position in the interstitium of connective tissue between the cartilage of the trachea and the thyroid gland. We have observed in the wall of that UBF the presence not only of resting C cells but also mitotic figures of C cells. Furthermore, on the opposite side of the same UBF an active area of formation of thyroid follicles was found. These observations provided the first evidence of the contribution of the UBF in the formation of C cells during the postnatal life of the rat. Furthermore, it is suggested that some C cells may share a common origin with ultimobranchially derived follicular cells.

Aging↗

Mitotic activity of the endocrine cells in rat thyroid glands during postnatal life.

This paper presents the results of investigations into the mitotic rates of thyroid endocrine cells in normal postnatal rats, aged 1-120 days. Our study revealed considerable age-dependent shifts in the mean mitotic activity of follicular cells and C-cells. The maximum indices of endocrine cell renewal were reached during the first 10 days of life, decreasing gradually and significantly until 25 days. At 1 month, there was a significant recuperation of the division rate for both cell types, which declined in the adult rat. These results mean that the proliferation of C-cells and follicular cells is inversely proportional to age. The preferential zone of localization of mitoses of both cell types is the central region of the thyroid lobe. The present paper provides new evidence for the postnatal origin of C-cells and follicular cells from the preexisting endocrine cells.

Aging↗

Histometry of normal thyroid glands in neonatal and adult rats.

The present histometric study is on thyroid glands of Wistar rats ranging in age from 0 to 120 days. The mean volume of one lobe of the thyroid in 4-month-old animals was some 22-, 10-, 5-, and 3-fold greater, respectively, than the volumes in the newborn, 5-, 10-, and 30-day-old rats. At 4 months of age the mean length of the lobe was 3 times greater than at birth. The volumetric fractions (Vv) of the different histological components (follicular cells, C-cells, colloid, and interstitial tissue) changed considerably in the course of development. The Vv of follicular cells diminished from 61.4% at birth to 37.2% at 4 months. C-cells increased from 2.9% in the newborn to 4% at 15 days, with no further significant change at 4 months. Colloid and stroma together represented 35.7% at birth, increasing to 58.5% at 120 days. In the course of the first 4 months of life, the absolute volumes occupied by follicular cells, C-cells, colloid, and stroma increased 13.25, 30.75, 38.6, and 33.7 times, respectively; these changes reflect the variations that occur in the volume of the gland and the Vv throughout postnatal development.

Animals↗

Correlation between visual clues, objective architectural features, and interobserver agreement in prostate cancer.

Three pathologists evaluated a number of designated architectural features to assign grades to 41 cases of well- to moderately differentiated adenocarcinoma, and their opinions were compared. The consensus opinion was obtained and evaluated against objective measurements of glandular architecture that were obtained by morphometric techniques. The observers agreed on gland size, gland uniformity, and the number of glands per field in only 49%, 31%, and 39% of cases, respectively. There were significant differences in the Gleason grades assigned by observers. Paired matching of individual Gleason grades showed agreement among observers in 44% (18 of 41), 56% (23 of 41), and 75% (31 of 41) of cases, respectively. This level of interobserver disagreement occurred even though cases with predominant patterns were selected carefully and those with variable patterns were excluded. A direct relationship appears to exist between increasing Gleason grade and increasing glandular variability, and there is an inverse relationship between Gleason grade, gland lumen area, and the number of glandular nuclei, as assessed by a group of pathologists.

Humans↗

Value of the cribriformity factor in grading prostatic carcinoma.

Architectural and histometric features for the objective grading of prostate adenocarcinoma in histologic specimens were analyzed in five cases each of Gleason primary grades 2, 3A, 3B, 3C, 4A and 4B, selected as "typical" for the histopathologic images. Tissue sections from the selected cases were stained by the Feulgen method. Fifteen fields for each grade, for a total of 4,430 glands, were digitized by a video-based microphotometer at low resolution (pixel spacing of 2 microns). Outer and inner outlines of the glandular epithelium were traced manually using a mouse. For each field the number of glands, the gland area, the lumen area, the area of the glandular epithelium and the cribriformity factor were computed. The gland area and its variance proved to be useful indicators for lower-grade lesions, whereas the variance of cribriformity resulted in an excellent grading indicator in the Gleason 3-4 range when cribriform glands were present.

Adenocarcinoma↗

Nucleolar organizer regions in pigmented skin lesions. Value in the differential diagnosis of Spitz nevi.

Forty-one cases of typical melanocytic skin lesions (15 intradermal nevi, 14 Spitz nevi and 12 malignant melanomas) were used to investigate the value of staining of nucleolar organizer regions (NORs) in the differential diagnosis of such pigmented lesions. Histologic sections were stained by the silver colloid (Ag) method, with and without the prior use of a melanin blocking agent. There were statistically significant differences in the mean numbers of AgNORs per nucleus between the groups of lesions studied (1.658 for intradermal nevi, 3.0042 for Spitz nevi and 6.669 for malignant melanomas). Sections treated with potassium permanganate (melanin blocking agent) prior to staining showed an obvious increase in the AgNOR scores in all groups; this increase was highest for Spitz nevi. Although AgNOR staining allows a distinction to be made between intradermal nevi and malignant melanomas, the striking overlap between the counts for Spitz nevi and malignant melanomas precludes the use of this technique as the sole method for establishing the diagnosis of malignancy. Other clinical and morphologic data are especially required to make the diagnosis of Spitz nevi.

Analysis of Variance↗

Nuclear planimetry in renal-cell tumors.

A morphometric study using conventional planimetry was carried out in 73 renal-cell tumors (64 adenocarcinomas and 9 adenomas) in order to correlate the objective nuclear measurements with some histologic and clinical data believed to have prognostic value. The use of a discriminant function to correctly separate adenomas and low-grade adenocarcinomas was also investigated. There was a strong association between the nuclear grade and the following parameters: nuclear area, nuclear major diameter and nuclear elongation. There was also a relationship between an adverse outcome and the major nuclear diameter and nuclear elongation. In a univariate survival analysis, only the clinicopathologic stage, the nuclear grade and the histologic presence of a pseudosarcomatous cell population had predictive value. Multivariate survival analysis using Cox models showed that the clinicopathologic stage, major nuclear diameter, presence of anaplastic cells and nuclear area had predictive value. Although the minor nuclear diameter reached a significant level, a discriminant function that would correctly separate adenomas and low-grade renal-cell carcinomas could not be formulated.

Adenoma↗

Histometric features for the grading of prostatic carcinoma.

Histometric features for the objective grading of prostatic adenocarcinoma in histologic specimens were analyzed in five cases each of well, moderately and poorly differentiated lesions. Tissue sections from the selected cases were stained by the Feulgen method and digitized by a video-based microphotometer. Twenty total fields were recorded for each grade: ten at high resolution (an image sampling of 0.5 micron per pixel) and ten at low resolution (0.8 micron per pixel), with two fields per case recorded at each resolution. The images were segmented by an automated expert system-guided scene segmentation procedure. The performance of that procedure was measured by comparing the automated counts of nuclei in the segmented fields to the visual counts made by a pathologist in the same fields. For well, moderately and poorly differentiated cases, respectively, the nuclear counts made by the expert system at high resolution were 2.7%, 4.2% and 4.7% higher than the visual counts (as estimated from a total of 6,628 nuclei), but 1.2%, 2.5% and 1.1% lower at low resolution (10,329 nuclei). High-resolution features and tissue textural features were computed for each case. The high-resolution features showed good separation between the three groups of cases. The tissue textural features showed consistent separation between well and moderately differentiated cases. The relaxation of the spatial resolution (to 0.8 micron/pixel spacing) did not affect the selection of features, but led to less separation between the data from different grades. In conclusion, the automated system performed satisfactorily in distinguishing sections of prostatic tumors of varying degrees of differentiation.

Adenocarcinoma↗

Cytophotometric DNA measurements in medullary thyroid carcinoma.

The prognostic significance of objectively measured karyometric variables (ploidy pattern, nuclear roundness, area, elongation, chromatin texture, and nearest nucleus distance) was investigated in relation to clinical (stage and type of disease) and morphologic (histologic patterns) variables in 27 patients with the diagnosis of medullary thyroid carcinoma (MTC). The DNA and karyometric measurements of Feulgen-stained nuclei were made with a video cytometry system. The five-year and ten-year adjusted survival rates were 74.4 +/- 10.1% and 59.5 +/- 15.6%, respectively. Cox's survival analysis for mortality showed that only stage, age, sex, and 5N exceeding rate had predictive value (overall P = 0.0012) in decreasing order. Patients with the best prognosis were young females with clinical Stage I disease and low 5N exceeding rate tumors. When karyometric and histometric variables were considered by themselves survival correlates with the standard deviation (SD) of the nearest nuclear distance and nuclear elongation; that is, patients with crowded, high cellularity tumors and elongated cells had the worst prognosis. In univariate analyses only clinical stage correlated with adjusted survival rate. Multivariate survival analysis for morbidity showed that patients in Stages greater than or equal to II and high SD of ploidy values were free of symptoms for short intervals. When morphometric data were considered alone, patients with high variance in the chromatin texture and highly variable nuclear areas had shorter asymptomatic intervals.

Adolescent↗

Karyometric marker features in fine needle aspirates of invasive follicular carcinoma of the thyroid.

Karyometric measurements were performed on fine needle aspirates of clearly identifiable tumor areas and adjacent normal-appearing areas in the surgical specimens from ten patients with invasive follicular carcinoma of the thyroid. Similar measurements were performed on aspirates from nine patients free of thyroid disease (controls). A total of 95 karyometric features were evaluated for each nucleus. Analysis of variance of optical density values indicated (1) a similarity between tumor and normal-appearing nuclei from carcinoma cases, (2) a significant difference between those nuclei and control nuclei and (3) that most of the differences were due to the differences of tissue origin. Stepwise linear discriminant analysis selected ten features that produced a statistically highly significant separation of tumor nuclei from control nuclei. A similar analysis selected six features that produced a statistically highly significant discrimination of normal-appearing nuclei from control nuclei; the validity of those karyometric features as markers of malignancy in normal-appearing nuclei from tissues adjacent to invasive follicular carcinomas of the thyroid was demonstrated by analysis in further training and control sets of nuclei. This analysis in thyroid aspirates identified more marker features than did a previous similar analysis using tissue sections.

Adenocarcinoma↗

Karyometric marker features in fine needle aspirates of microinvasive follicular carcinoma of the thyroid.

Karyometric measurements were performed on fine needle aspirates of clearly identifiable tumor areas and adjacent normal-appearing areas in the surgical specimens from ten patients with microinvasive follicular carcinoma of the thyroid. Similar measurements were performed on aspirates from nine patients free of thyroid disease (controls). A total of 95 karyometric features were evaluated for each nucleus. As compared with the control nuclei, the normal-appearing nuclei showed a 6% increase in total nuclear optical density (OD) while the tumor nuclei showed a 14% increase. Analysis of variance indicated a significant difference between the normal-appearing nuclei and the control nuclei, with most of the difference due to the differences of tissue origin. Discriminant analysis selected nine features that produced a statistically highly significant separation of tumor nuclei from control nuclei. A similar analysis selected five features that produced a statistically highly significant discrimination of normal-appearing nuclei from control nuclei; the validity of those karyometric features as markers of malignancy in normal-appearing nuclei from tissues adjacent to microinvasive follicular carcinomas of the thyroid was demonstrated by analysis in further training and test sets of nuclei.

Adenocarcinoma↗