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Nuclear grading of renal cell carcinomas--is morphometry necessary?

Comparative investigations of subjective with objective nuclear grading methods of renal cell carcinomas are almost completely lacking. Therefore, we graded 94 cases of this carcinomas by a simple, subjective microscopical estimation as well as by a morphogenetic measurement of nuclear area. Both procedures proved prognostically useful, but the best results were achieved by morphometry. By this method three prognostic groups of renal cell carcinoma were found, provided that the borderlines were drawn at 28 microns 2 and 60 microns 2, respectively. Particularly favourable and unfavourable cases could be separated from average ones, if the means and standard deviations of both the nuclear areas and the diameters were evaluated. Overall, morphometric nuclear analyses are highly desirable, if, for example, morphological data are to be used in the context of prognostic or therapeutic studies on renal cell carcinoma. However, there is a broad distribution of the values for individual cases so that, tumour-biologically, no exact demarcation of prognostically different groups can be expected.

Adult

Papillary cystic tumours of the pancreas: an analysis by nuclear morphometry.

Papillary cystic tumour (PCT) is a rare, low-grade malignant pancreatic neoplasm, in which the histological criteria for malignancy are still uncertain. We performed a histological examination of 3 metastasizing PCTs, while comparing them with 18 non-metastasizing PCTs, using a computed image analyser. The mean maximum nuclear diameter, the mean standard deviation (SD) of the nuclear diameter, the mean nuclear area and the nuclear-nonnuclear (N/NN) ratio obtained by the image analyser of the metastasizing PCTs (7.23 microns, 2.21 microns, 30.45 microns2, 36.41%) were all significantly larger than those of the non-metastasizing PCT (6.34 microns, 1.59 microns, 23.66 microns2, 23.74%; P < 0.005, P < 0.005, P < 0.005, P < 0.001 respectively). However, there were no statistical differences in either the nuclear ellipsoidity or nuclear regularity. These results suggested that nuclear morphometry might be a useful parameter to define metastatic potential, in addition to histological variables such as venous invasion, nuclear grade and mitotic rate.

Adolescent

A computerised technique for morphometry and 3D reconstruction of embryological structures.

In the last decade we have witnessed the development of software technology capable of image analysis and morphometry [1, 8-12]. Although these methods are sometimes difficult to master in a practical sense, they are tremendously efficient and precise when applied to the study and measurement of developing biological structures, particularly in the field of embryology. In this study we describe the application on human embryos of an image analyzing system that enables one to perform quantitative analyses of the morphology and size of developing organs and structures as well as their ultimate three-dimensional reconstruction (3DR).

Analysis of Variance

Influence of splenectomy on platelet morphometry and function.

Functional and morphometric platelet abnormalities may be influenced by splenectomy and thus contribute to postoperative thrombohaemorrhagic complications, especially in patients with splenomegaly and/or platelet defects. We investigated platelet function, platelet secretion, and platelet morphometry before and one week after splenectomy in seven patients with normal platelet production and normal spleen size (Hodgkin's disease) and five patients with splenomegaly and platelet abnormalities (4 with myeloproliferative disorders and 1 with chronic myelomonocytic leukemia). Severe postoperative thrombohaemorrhagic complications occurred only in patients with myeloproliferative disorders, although platelet count and mean platelet volume increased in almost all patients after splenectomy. Four patients with myeloproliferative disorders had impaired platelet aggregation before splenectomy that improved in only one patient after surgery. Platelet buoyant density in this patient group was decreased before splenectomy and normalised thereafter. Concomitantly, intraplatelet concentrations of alpha-granular proteins increased. Before splenectomy, there was a positive correlation between platelet density and platelet volume in patients with Hodgkin's disease (r = 0.59, p less than 0.001), but not in patients with myeloproliferative disorders. There was no correlation between platelet density and platelet volume after splenectomy in either patient group. In conclusion, morphometric platelet abnormalities were found in all patients after splenectomy. In patients with myeloproliferative/myelodysplastic disorders, decreased platelet buoyant density normalised and intraplatelet concentrations of alpha-granule proteins were elevated after splenectomy. However, platelet function defects in this patient group were not corrected and may have been a major cause of thrombohaemorrhagic complications in the postoperative period.

Adult

Metacarpal morphometry in monozygotic dizygotic elderly twins.

The relative importance of genetic factors in the pathogenesis of age related bone loss has been investigated in a study involving 17 monozygotic (MZ) and 8 dizygotic (DZ) pairs of twins aged 64 to 75 years. Radiographic morphometry was performed at the midpoints of the 2nd, 3rd and 4th metacarpals of both hands and the mean total and cortical widths were evaluated. The heritability, h2, was calculated as the difference between the intrapair variances in same sexed DZ and MZ pairs divided by the intrapair variance in DZ pairs. The mean intrapair variance of both total and cortical width was found to be four to five times higher in DZ than in MZ pairs. The differences are highly significant with an h2 value between 0.7 and 0.8, indicating a predominant genetic influence. It is stressed that this result applies only to the population from which the twin sample was drawn.

Aged

Correlative ultrastructural morphometry of human prolactin-producing adenomas.

Ultrastructural morphometry was applied to 24 surgically removed human sparsely granulated prolactin cell adenomas in an attempt to correlate the measurements with blood prolactin levels, size of tumour, and age and sex of patient. No correlation was apparent. However, further evaluation revealed that correlation existed between size of tumour and blood prolactin levels, indicating that tumour mass, and not subcellular morphology, was related to the amount of prolactin released.

Adenoma

Optic disc morphometry in chronic primary open-angle glaucoma. II. Correlation of the intrapapillary morphometric data to visual field indices.

The intrapapillary morphometric data of 290 optic nerve heads of 158 patients with chronic primary open-angle glaucoma and of 253 unselected normal subjects were correlated with the visual field indices of Octopus program 32,34-Delta. Only one eye per patient was considered. Significant correlations (P less than 0.001) were revealed for the neuroretinal rim (NRR) area as a whole and in four defined disc sectors, the ratio of lower temporal to upper temporal rim area, the rim width, the optic cup area and diameters, the horizontal and vertical cup/disc (c/d) ratios, and the quotient of horizontal to vertical c/d ratio. Correlation coefficients ranged between 0.30 and 0.77. They were highest for the rim area of the inferior temporal disc sector, followed by the superior temporal, nasal, and temporal sectors. There were no correlations for the optic disc size and form. The topographic morphometry of the intrapapillary optic disc structures was unremarkable in four glaucomatous eyes with small discs.

Adolescent

Optic disk morphometry in high myopia.

The optic nerve head in highly myopic eyes is distinctly different from normal optic disks. We performed magnification-corrected morphometry of photographs of 51 optic nerve heads in highly myopic eyes (myopic refraction of more than -8.00 diopters). Mean refraction was -15.49 +/- 5.76 diopters (range, -8.00 to 28.00 diopters), mean age 63.0 +/- 12.1 years (range, 27-87 years). The disks were significantly (P less than 0.000001; Wilcoxon-Mann-Whitney test) larger and more ovally configurated than 457 unselected normal optic nerve heads with a myopic refraction of less than -8.00 diopters. Refraction, size of the disk, and area of the parapapillary region with chorioretinal atrophy were significantly (P less than 0.00001) correlated with each other. The parapapillary vessel diameter was independent from the disk size. Highly myopic disks can be regarded as secondary acquired macrodisks, the size of which is correlated with refraction and possibly age. They should be differentiated from secondary, acquired macrodisks in congenital glaucoma and from primary macrodisks. As in normal eyes, the parapapillary vessel caliber can be used to estimate the optic disk size in relative and approximately absolute units.

Aged

Triple approach for diagnosis and grading of meningiomas: histology, morphometry of Ki-67/Feulgen stainings, and cytogenetics.

With regard to meningioma grading and the recently introduced "atypical" meningioma, we evaluated 160 cases retrospectively by conventional histology and image analysis. For that, the cell nuclei were stained with a Ki-67 (MIB1)/Feulgen-method on paraffin sections, thus enabling the assessment of both the Ki-67 proliferation index and nuclear morphometric features, such as tumour cell arrangement, nuclear pleomorphism, and cellularity. It could be demonstrated that the Ki-67 proliferation index is the most important criterion for distinguishing anaplastic meningiomas (WHO "grade" III) (mean Ki-67 index: 11%) from those of common type (WHO "grade" I) (mean Ki-67 index: 0.7%). The parameter for the "relative volume weighted mean nuclear volume" is another valuable morphometric feature. The "atypical" meningioma (WHO "grade" II) which should represent an intermediate category between common type and anaplastic meningiomas is characterized by a mean Ki-67 proliferation index of 2.1%. Common type meningiomas which comprise almost 50% of the cases of this series have a relapse rate of 9%. "Atypical" and anaplastic meningiomas recurred in 29% and 50%, respectively. Since the term "atypical" meningioma is confusing in the context of tumour grading, the term "intermediate type meningioma" is proposed. Furthermore, the results of cytogenetic analyses of 142 cases of this series were evaluated and compared with the meningioma grades. Thereby, 25 cases disclosed, independent of the typical loss of one chromosome 22, cytogenetic features assumed to be progression-associated, e.g., the gain or loss of different chromosomes and the deletion of the short arm of one chromosome 1 (hyperdiploidy, increased hypodiploidy, 1p-), when correlated to the histological and morphometric findings or the high relapse rate. For meningioma diagnosis and grading, a practical guideline is proposed based upon histology, morphometry (Ki-67), and cytogenetics.

Biomarkers, Tumor

Vertebral and metacarpal morphometry as indicators of nutritional improvement.

Because of the importance of nutrition in the development of bone mass, we studied the nutritional state, and bone state by means of metacarpal radiogrammetric measurements and vertebral morphometry in a group of 40 premenopausal women born between 1960 and 1970, mean age 29 +/- 5 years, and in another group of 40 postmenopausal women born between 1934 and 1944, mean age 55 +/- 4 years. Both groups were considered normal, the main characteristic distinguishing them being that the women born between 1934 and 1944 grew up in a period of widespread malnutrition in Spain and the women born between 1960 and 1970 grew up in a period of normal nutrition. Protein, carbohydrate and fat intake in these two periods differed significantly (p < 0.0001 in the three cases by Fischer's exact test). The values of the metacarpal measurements, anterior height of the dorsal vertebrae from T-4 to T-12, and posterior height from L-1 to L-4 between the premenopausal and postmenopausal groups of women were significantly different (p < 0.001) (Anova test). These findings show the importance of nutrition in the development of bone mass during childhood.

Absorptiometry, Photon

[Roentgen morphometry of the shoulder in diseased rotator cuff. Value of plain roentgen examination in comparison with arthroscopy].

A comparison between the pathomorphological substrate and the X-ray morphometry of the shoulder joint was made with 482 arthroscopically treated patients. Radiological parameters and indices for the prediction of the development of the impingement-syndrome were developed from this comparison. With these parameters and indices is it possible to predict the pathomorphological substrate and to differentiate between subacromial and coracoidal impingement.

Acromioclavicular Joint

Combined use of nuclear morphometry and DNA ploidy as prognostic indicators in nonresectable adenocarcinoma of the pancreas.

The introduction of combined modality treatment has only marginally affected the prognosis in nonresectable pancreatic carcinoma. Evaluation of easily accessible prognostic variables could be of clinical importance when selecting patients for proper therapy. DNA ploidy and morphometric variables were chosen as prognostic markers and assessed on cytologic material obtained by fine-needle aspiration biopsy (FNAB) from 128 patients with pancreatic carcinoma. The nuclear DNA content was measured by image cytometry. Patients were categorized as short-term (< or = 6 mo) and long-term survivors (> 6 mo). Ninety-eight of 116 nonresectable patients were possible to evaluate. There were significant differences between short- and long-term survivors with regard to DNA ploidy (p < 0.01) and the morphonuclear variable anisokaryosis (p < 0.001). In patients with either DNA aneuploid tumors or anisokaryosis > or = 0.6, the survival time was 6 mo or less in 85 and 93%, respectively. When both these criteria were fulfilled, only 5% survived for more than 6 mo. Thus, DNA ploidy and morphometry, separately or in combination, may provide prognostic information in nonresectable pancreatic carcinoma.

Adenocarcinoma

Comparative aspects of cardiac ultrastructure, morphometry, and electrocardiography of hearts from rats fed restricted dietary copper and selenium.

Comparative cardiac ultrastructure, morphometry, and electrocardiography after dietary copper and selenium restriction were examined. Male weanling Long-Evans rats were fed diets that were either adequate in both copper and selenium (Cu+/Se+) or restricted in either Cu (Cu-) or Se (Se-) for 8 wk. At wk 8, electrocardiograms (ECG) and dP/dts were obtained and heart tissue was utilized for electron microscopy. Upon examination, Cu- rats were anemic, exhibited a greater heart: body weight ratio, and developed concentric hypertrophy characterized by an enhanced thickening of the left and right ventricular free walls, and interventricular septum. ECG recordings from lead aVF in the Cu- group showed a greater R wave amplitude in comparison to the Cu+/Se+ group. Se- rats recorded a greater left ventricular +dP/dtmax than both the Cu+/Se+ and Cu- groups. Cardiac myofibril volume densities were decreased in both Cu- and Se- rats in comparison to the Cu+/Se+ rats. In addition Cu- rats showed a greater mitochondria:myofibril ratio. Sarcomere contractile protein disarray was present in both the Cu- and Se- groups. Se- myocytes also showed evidence of edema and mitochondrial fragmentation. The subcellular alterations suggest that similarities exist in the cardiac remodeling processes associated with copper and selenium restrictions.

Animals

Diagnostic morphometry of isolated lymph node cells from patients with mycosis fungoides and Sézary's syndrome.

Mycosis fungoides (MF) and Sézary's syndrome are cutaneous T cell lymphomas, characterized by the presence of lymphoid cells with deeply indented nuclei (CMC) in the infiltrate. In order to find objective criteria for the diagnosis of early MF involvement of lymph nodes from patients with MF, we performed morphometric analysis of lymphoid cells in lymph node cell suspensions measuring the degree of nuclear indentation as expressed by the nuclear contour index (NCI). Statistical discriminant analysis was used to analyze the differences in the NCI histograms between lymph nodes without and with MF involvement and to select the most discriminating parameters for diagnostic classification. Using a training set of 6 lymph nodes from patients with unrelated diseases and 8 lymph nodes from patients involved by cutaneous T cell lymphomas, the mean and standard deviation of the NCI histograms were selected as the most discriminating parameters. All lymph nodes from the training set were assigned to the correct diagnostic classification group with a probability over 90%. The predictive value of the morphometric classification was tested on a set of 12 enlarged lymph nodes from patients with MF. The histological diagnosis was used as a reference. In 10 cases the morphometric classification was identical to the histological classification, whereas in two cases (1 classified as positive, 1 as negative) a disagreement was found. It is concluded that morphometry of lymphoid cells can contribute substantially to the diagnosis of early MF involvement in lymph nodes.

Adult

Morphometry of nucleoli as an indicator for grade of malignancy of bladder tumors.

To establish a new indicator for the classification of human urinary bladder cancers, the nucleoli of normal epithelial and neoplastic cells were analyzed, using morphometric techniques. By electron microscopy, the nucleolar profiles of cells from grade 2 and 3 transitional cell carcinomas were often small and irregular. Morphometry showed that the nucleolar volumes, nucleolar/nuclear volume ratios, volume densities of various nucleolar components, and the numbers of fibrillar centers (FCs) altered significantly with an increase in tumor grade. In particular, an increase in FC numbers in the nuclei of higher grade tumors was associated with a decrease in individual volume. The number of FCs in intact urothelial cells obtained from patients with bladder tumors is significantly larger than in the normal urothelial cells. This may be related to the multicentric origin of bladder cancers. These results suggest that morphometric analysis of nucleoli is useful in evaluating the degree of differentiation and invasive capacity of human bladder tumor cells. In particular, the number and individual volume of FCs may be an indicator of tumor malignancy.

Adult

Computer-assisted morphometry of the intracapillary leukocyte pool in the rabbit lung.

Computer-assisted morphometry was performed to evaluate the number and cell characteristics of capillary and alveolar leukocytes in rabbit lungs. An image-processing system and a programmable spread-sheet program were used, which allowed morphometric analysis of a large reference area. Neutrophils represented the largest intracapillary leukocyte population (2.2 x 10(7)/ml parenchyma, which corresponds to an approximately 104-fold microvascular enrichment of this cell type related to cell counts calculated for the capillary blood volume). In addition, large numbers of intracapillary lymphocytes (1.7 x 10(7)/ml parenchyma; 47-fold enrichment) and monocytes (0.3 x 10(7)/ml parenchyma; 86-fold enrichment) were detected. The total count of pulmonary leukocytes thus approximated the total number of pulmonary endothelial cells; and the total circulating pools of the different leukocytes were surpassed by the corresponding lung capillary pools, 3.2-fold for neutrophils, 1.2-fold for lymphocytes and 4.8-fold for monocytes. In contrast, alveolar cell numbers ranged from 1-2% of the capillary counts for all types of leukocytes. We conclude that the rabbit lung microvasculature harbours large pools of immunocompetent cells, which may contribute to host-defense mechanisms at the gas-exchange area.

Animals

Measurements of vertebral shape by radiographic morphometry: sex differences and relationships with vertebral level and lumbar lordosis.

OBJECTIVE: To examine sex-related and vertebral-level-specific differences in vertebral shape and to investigate the relationships between the lumbar lordosis angle and vertebral morphology. DESIGN AND PATIENTS: Lateral thoracic and lumbar spine radiographs were obtained with a standardized protocol in 142 healthy men and 198 healthy women over 50 years old. Anterior (Ha), central (Hc) and posterior (Hp) heights of each vertebra from T4 to L4 were measured using a digitizing technique, and the Ha/Hp and Hc/Hp ratios were calculated. The lumbar lordosis angle was measured on the lateral lumbar spine radiographs. RESULTS: Ha/Hp and Hc/Hp ratios were smaller in men than women by 1.8% and 0.7%, respectively, and these ratios varied with vertebral level. Significant correlations were found between vertebral shape and the lumbar lordosis angle. CONCLUSIONS: These results demonstrate that vertebral shape varies significantly with sex, vertebral level and lumbar lordosis angle. Awareness of these relationships may help prevent misdiagnosis in clinical vertebral morphometry.

Aged

Electron microscopy and morphometry enhances differentiation of epidermolysis bullosa subtypes. With normal values for 24 parameters in skin.

Electron microscopy combined with morphometry was used to establish values for 24 parameters in normal skin. These results were compared with those similarly obtained from samples of epidermolysis bullosa with a view to facilitating classification of the disease. Six of the eight subtypes of epidermolysis bullosa investigated could be differentiated. Four subtypes showed values for structural components in intact skin which were outside the normal range: (1) epidermolysis bullosa simplex generalisata gravis (hemidesmosomes); (2) epidermolysis bullosa dystrophica Pasini and (3) Cockayne-Touraine (anchoring fibrils); and (4) epidermolysis bullosa acquisita (anchoring fibrils, hemidesmosomes, and lamina lucida and lamina densa aspects of the dermoepidermal junction). Two subtypes revealed specific features which could be assessed qualitatively: distinctive, circumscribed, clumped tonofilament bodies were present in basal keratinocytes from epidermolysis bullosa herpetiformis Dowling-Meara and thick (30 nm diameter) cross-striated anchoring fibrils were absent in epidermolysis bullosa dystrophica generalisata gravis. Epidermolysis bullosa simplex Köbner and Weber-Cockayne forms could not be distinguished.

Adolescent