Journal of Pathology and Translational Medicine

Original Articles

Morphometric Analysis of Preeciamptic Nephropathy with Focal Segmental Glomerulosclerosis.: Tae Sook Kim, Hyun Soon Lee; Korean J Pathol. 1995;29(5):624-633.

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Abstract: To evaluate the structural characteristics that might be related to the clinical features noted in preeclamptic patients with focal segmental glomerulosclerosis(FSGS), we analyzed post-partum renal biopsies of 8 preeclamptic patients with FSGS (group 1) by morphometry and glomerular studied the structural-functional relationships. These findings were also compared with those from three postpartum cases with minimal change lesion(group 2) and normal age-matched women(group 3). Mean glomerular volume (MGV) in group 1 and group 2 was (2.64 +/- 0.49) x 10(6) micrometer3 and (2.56+/-0.25)x 10(6) micrometer3, respectively. MGV in both groups was significantly increased compared with that of the control group [(1.11+/-0.22)x10(6) micrometer3](p<0.0005). The volume density of the mesangium/glomerulus [Vv(mes/glom)] in the group 1 patients was significantly increased (p<0.0001) when compared with that of the group 2 and the control group patients. The increment of Vv(mes/glom) was related to both the mesangial cell proliferation and expansion of mesangial matrix. The volume density of the capillary lumen/glomerulus [Vv(cap/glom)] in group I was significantly decreased(p<0.0001) when compared with that of group 2 and the control group. Vv(cap/glom) was directly related to Ccr in group l(r=0.70, p=0.05). These results suggest that reduced capillary luminal area caused by mesangial interposition is related to the decreased glomerular filtration rate in preeclamptic FSGS.

A Morphometric Study of Glomerular Dimensions in Relation to Glomerular Location, Age and Sex in Koreans.: Hyun Hee Lee, Hyeon Joo Lee, In Joon Choi; Korean J Pathol. 1996;30(4):328-339.

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Abstract PDF: As measurement of glomerular size in the assessment of several renal diseases becomes increasingly important, it has become necessary to devise rapid simple methods for the assessment of glomerular size and to have on hand reference ranges. A few reports on glomerular size have been published in Western literature, but their body builds are different from Koreans. In this study, 100 glomeruli(50 glomeruli each from the outer cortical and the juxtamedullary area) were measured in sections taken from 74 kidneys(ages 3 days~73 years) obtained from autopsy utilizing the semi-automatic image analyser. The percentage of glomerular sclerosis was measured based on its location. The sphere diameter, maximum diameter, area and sphere volume of non-sclerotic glomeruli were measured and evaluated with respect to age, sex and the location of the glomeruli. The results were as follows; 1) Mean glomerular dimensions including sphere and maximum diameter, area and sphere volume increased until 40 years of age, then reached a plateau. The percentage of sclerotic glomeruli then increased slowly with age but without statistical significance. 2) The glomerular dimensions and sclerosis showed no significant differences according to sex. 3) Juxtamedullary glomeruli were larger than the outer cortical ones which was statistically significant in age groups of 0~10, 11~20 and 41~50 years. The percentage of sclerotic glomeruli was generally greater in the outer cortex. 4) Differences in the values of glomerular dimensions between outer cortical and juxtamedullary area were similar in all age groups. 5) All parameters of measurement showed consistent and similar trends between the different groups. 6) The measurements of the largest 12 glomeruli out of randomly-selected 50 glomeruli gave similar results when compared with those of 50 glomeruli. It was evident from our results that glomerular size is influenced by age and glomerular location, but not by sex. The method of assessing glomerular size used in this study will not necessarily give the true, absolute value of size but it may be a simple, practical and useful method of comparing glomerular size in different groups of patients.

Comparison of Glomerular Size between Focal Segmental Glomerulosclerosis and Minimal Lesion in Children.: Jung Yeon Kim, Hyun Soon Lee; Korean J Pathol. 1996;30(10):903-911.

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Abstract PDF: The pathogenetic mechanism of focal segmental glomerulosclerosis (FSGS) is not known. Some authors suggest glomerular hypertrophy may precede the development of FSGS in patients with minimal lesion. It was recently reported that the size of nonsclerotic glomeruli in adults with FSGS is significantly larger than that of cases with minimal lesion. It is not clear whether glomerular hypertrophy observed in adults with FSGS is also seen in children with FSGS. Thus, we have analyzed 37 renal biopsies from children with FSGS by morphometry and the data were compared with 37 renal biopsies from age- and sex-matched patients with minimal lesion. The number of glomeruli submitted for morphometric analysis was 22.6+/-14.2 in cases with FSGS and 30.9+/-11.4 in cases with minimal lesion. Mean glomerular volume (MGV) in FSGS group was significantly larger than that of minimal lesion [(13.1+/-3.9) x10(5) microm3 vs. (10.1+/-1.9) x10(5) microm3, p<0.001]. The relative interstitial volume of renal cortex in patients with FSGS was significantly larger than that of minimal lesion [(0.106+/-0.051) microm3/microm3 vs. (0.029+/-0.012) microm3/microm3, p<0.0001]. In FSGS, the percentage of glomeruli with FSGS was significantly correlated with relative interstitial volume of renal cortex (r=0.79, p<0.0001). As is the case for adult FSGS, MGV of children with FSGS is significantly larger than that of minimal lesion. Thus, the presence of glomerular hypertrophy observed in biopsies with minimal lesion nephropathy seems to be an indication that the coexistent FSGS lesions are undetected due to sampling problems.

Prenatal Development of Eccrine Sweat Gland: Morphologic and Morphometric Analysis.: Nam Bok Cho, Tae Jin Lee, Je G Chi, Kye Yong Song; Korean J Pathol. 1997;31(2):121-134.

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Abstract PDF: To elucidate the developmental sequence of the eccrine sweat gland, a morphologic and a morphometric observation were done using developing human embryos and fetuses. Five embryos and sixty four fetuses from the 9th to the 38th week of the gestational age were studied. The skin was sampled in eight different areas, i.e., scalp, forehead, face, chest, abdomen, back, palm and sole. Routine histological sections were made for histological evaluation and morphometric analysis. The results obtained were as follows : The primordia of the eccrine sweat glands appeared first as regular undulation of the basal cells in the palm and the sole in the 13th week of getation. Subsequently, elongation and coiling of the cell cords were noted from the 16th to the 18th weeks. Intraductal lumen formation was first noted in the 20th week. Secretory segment of the eccrine sweat glands were noted from the distal part of the coiling intradermal sweat duct in the 22nd week of the gestational age. The eccrine sweat glands became fully developed by the 28th week of gestation and this included the clear cell, the dark cell and the myoepithelial cell. In the morphometric analysis, the number of eccrine epithelial buddings were decreased with aging and the highest were in the palm and the sole. The diameter of the eccrine sweat duct showed no significant change by gestational age or in the different sites observed. Straight and coiled eccrine sweat ducts or glands were lengthened into the deep reticular dermis and upper portion of the subcutaneous adipose tissue with an increase of the gestational age. The above results suggest that developmental stage and the number of eccrine glands of the skin in the fetal stage is different from other areas of the body, especially in the palm and the sole.

Prenatal Development of Sebaceous Gland: Morphologic and Morphometric Observation.: Im Joong Yoon, Je Geun Chi, Kye Yong Song; Korean J Pathol. 1998;32(4):273-282.

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Abstract PDF: This study was conducted to illustrate the histological and morphometric features of the sebaceous gland of human fetal skin. For this purpose, we studied 12 human embryos and 60 fetuses from the 4 th to 38 th week of gestation. In each case, we sampled eight different areas of skin, i.e., scalp, forehead, face, chest, abdomen, back, extremity, and palm and sole. Through routine tissue processing, hematoxylin and eosin preparations were made for morphology and morphometric analysis. The sebaceous gland anlagen is noted in the face and scalp by the 14th week of gestation, being subsequently generalized in other parts of the body, namely by 16th week of gestation. The lobation of the sebaceous gland subsequently differentiated into multilobular appearance in the face and scalp by the 17th week of gestation and in the chest and abdomen by the 26th week of gestation. The sebaceous ducts were seen by the 21th week of gestation in face and scalp, and in the chest and abdomen by the 27th week of gestation. In morphometric observation, the number and diameter of sebaceous gland were reached its peak during the 21st to 24th week of gestation, and then decreased gradually until it became constant in later days of the gestational period. In general, cephalic portion of the body had more sebaceous glands and also was larger in diameter. This difference became negligible as fetuses reached the term.

Morphohistometric Investigation and bcl-2 Expression in the Placenta of Chromosomally Abnormal Pregnancy.: Joung ho Han, Kyu Rae Kim, Yeon Lim Suh, Mi Kyung Kim, Young Hyeh Ko, Dae Shick Kim, Howe Jung Ree; Korean J Pathol. 1999;33(5):353-360.

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Abstract PDF: To evaluate the significance of placental histology, a collaborative histological and cytogenetic study was performed on the products of 88 spontaneous abortions, and subsequently bcl-2 immunostaining was performed on 62 cases. The morphometric parameters included were DCIRCLE, FORMSHAPE, CPRATIO, and the expression of bcl-2 immunostainig was graded in four categories (I to IV). The results were as follows: 1) 40% (n=35) were chromosomally abnormal: trisomies predominated (57%, n=20) and was followed by triploidy (14%, n=5), double trisomy (6%, n=2), monosomy X (6%, n=2), inversion (9) (6%, n=2). 2) mean of DCIRCLE in chromosomally abnormal pregnancy was 40 micrometer larger than that in chromosomally normal pregnancy (p=0.012, one side t-test), while no difference was found in FORMSHAPE and CPRATIO between chromosomally abnormal and normal pregnancy. 3) bcl-2 expression was found in syncytiotrophoblast and cytotrophoblast. bcl-2 expression was weaker in chromosomally abnormal pregnancy with intensity I and II of 59% than chromosomally normal pregnancy with intensity I and II of 24%. 4) In comparison bcl-2 expression with DCIRCLE, in chromosomally normal abortion one (10%) in I & II and one (3%) in III & IV showed large DCIRCLE (above 360 micrometer), while 11 (85%) in I & II and 3 (33%) in III & IV in chromosomally abnormal pregnancy. It would mean that bcl-2 protein is necessary in preservation of pregnancy and placental morphology. Abnormal villous diameter and weak bcl-2 expression may be suggestive of chromosomal anomaly. Besides other histologic parameters, application of bcl-2 immunostaining and morphometric analysis probably give more sensitive and specific results in identifying chromosomally abnormal abortion.

Glomerular Basement Membrane Thickness in Minimal Change Disease.: Yoon Mee Kim, Soon Hee Jung, Hyeon Joo Jeong; Korean J Pathol. 2000;34(12):994-1000.

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Abstract PDF: The thickness of the glomerular basement membrane may vary not only in glomerular disease, but also in normal persons according to age and sex. But there has been no data on the normal thickness of the basement membrane in Korea. This study was designed to determine the glomerular basement membrane thickness as a reference value according to age and sex, in 50 cases of minimal change disease obtained from patients aged 2~67 years. Measurement of glomerular basement membrane was made on electron micrograph using an image analyzer. The thickness of each case was estimated by the arithmetic and harmonic mean methods. The mean thickness of the glomerular basement membrane was 291.9 47.9 nm by harmonic mean method and 284.2 43.7 nm by arithmetic mean method. And the harmonic mean thickness of the glomerular basement membrane according to age was 249.1 32.5 nm (1~5 years), 256.6 45.3 nm (6~10 years), 279.2 57.9 nm (11~15 years), 303.2 43.8 nm (16~20 years), 335.3 37.5 nm (21~30 years), and 291.1 22.5 nm (over 30 years), respectively. There was a trend that the thickness of glomerular basement membranes increased with the age till 30 years of age. There was no significant sex-related difference. In conclusion, the mean glomerular basement membrane thickness is comparable to the data from western people and shows a trend of increasing thickness according to the age.

Expression of Glomerular-Smooth Muscle Actin and Vimentin in Idiopathic Membranous Nephropathy as Prognostic Indicators.: Min Jin Lee, Ok Kyung Kim; Korean J Pathol. 2001;35(1):26-34.

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Abstract PDF: BACKGROUND
The natural history of idiopathic membranous nephropathy (IMN) is heterogeneous with some patients showing spontaneous remission while others show a progressive course leading to end-stage renal failure. We tried to assess quantitatively alpha-smooth muscle actin (alpha-SMA) and vimentin expression as markers to predict the outcome of membranous nephropathy.
METHODS
This study included 24 patients with biopsy proven IMN. We measured the volume of the positive area for alpha-SMA and vimentin within the glomeruli and compared the results with 5 patients in the normal control group. We evaluated glomerular alpha-SMA and vimentin expression in correlation with BUN and serum creatinine level at the time of diagnosis and after treatment.
RESULTS
Glomerular alpha-SMA and vimentin in IMN were higher than in the control group. Glomerular alpha-SMA was significantly higher in progressive IMN than in non-progressive IMN. The glomerular alpha-SMA was sifnificantly correlated with BUN and serum creatinine at last follow-up (p<0.05), but there was no statistically significant correlation at diagnosis. The glomerular vimentin was not different between progressive and non-progressive groups.
CONCLUSION
These data suggest that the expression of glomerular alpha-SMA may be a useful prognostic indicator and may be able to differentiate between patients with membranous nephropathy who respond well to treatment and those who continue to progress.

Morphometry of Nuclei in Adenocarcinoma of Prostate.: Hye Rim Park, Seung Wan Char, Jin Hee Sohn, Young Euy Park; Korean J Cytopathol. 1995;6(2):99-105.

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Abstract PDF: Morphometry of nuclei of the benign and malignant prostatic lesions was performed to study the relationship between nuclear size and shape and the prognosis of prostatic adenocarcinoma. Fifty one cases of prostatic adenocarcinoma and 13 cases of benign prostatic hyperplasia were included to evaluate area, perimeter, Dmax, Dmin, and 5 form factors of the nuclei by image analyzer(Zeiss Ibas 2000) using hematoxylineosin stained slides. All analytic factors of nuclear size and shape were significantly different between benign lesions and adenocarcinomas. Increased nuclear size was associated with nuclear irregularity, presence of metastasis, advanced clinical stage, and high Gleason's grade and score of prostatic adenocarcinoma. On Kaplan-Meier method, survival was decreased with older age, no hormonal treatment, stage D, high Gleason}s grade and stage as well as with larger size and irregular shape of the nuclei. In conclusion, morphometry of nuclei of the prostate can be a helpful tool to differentiate between benign and malignant lesions. Nuclear morphology is thought to be associated with prognosis of prostatic adenocarcinoma.

Nuclear Morphometry of Fibroadenoma and Carcinoma of Breast: Comparison between fine needle aspiration cytology and biopsy.: Jin Hee Sohn, Young Hee Choi, Young Eui Park; Korean J Cytopathol. 1998;9(2):161-168.

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Abstract PDF: Primary breast lesions diagnosed by fine needle aspiration cytology, confirmed by histologic examination were analyzed by morphometry to evaluate the difference between benign and malignant lesions, and the methods obtaining the sample. Four size factors and 5 form factors were evaluated in 22 fibroadenomas and 20 carcinomas by image analyzer(Zeiss Ibas 2000) using the H-E stained slides. Nuclear size was significantly larger in the carcinoma cells than fibroadenoma cells both in the cytology and biopsy specimens, but the form factors were not significantly different. Both fibroadenoma and carcinoma cells were significantly larger in cytologic smear than histologic section. The cells in the cytology were more regular and round than those in histology, but not statistically significant. Fibroadenomas having cellular proliferation and atypism exhibited larger size and more irregular nuclei than non-proliferative fibroadenoma, but not statistically significant. Therefore nuclear morphometric analysis can be a helpful method to diagnose the questionable breast lesions and is a method appropriate for use as a quality control procedure in the fine needle aspiration cytology.

Morphometric Analysis for Cytological Diagnosis of Thyroid Papillary Carcinoma.: Jong Ok Kim, Bo Seong Yang, Hye Soo Kim, Jong Min Lee, Dong Ho Lee, So Young Shin, Chang Suk Kang, Hye Kyung Lee; Korean J Cytopathol. 2006;17(2):116-119.

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Abstract PDF: The diagnosis of papillary thyroid cancer is generally based on the findings of intranuclear cytoplasmic inclusions and nuclear grooves. Although anisokaryosis and poikilokaryosis, in papillary thyroid cancer, are not distinct when compared to other cancers, cytological examination can provide useful preoperative information. Our study evaluated the diagnostic role of computer-assisted image analysis for the pre-surgical assessment of papillary thyroid carcinoma. Thyroid aspirates from twenty female patients who were histologically confirmed to have both papillary carcinoma and benign nodules were studied. Different populations of 50 benign cells and 50 malignant cells were analyzed. Five morphometric parameters were selected for analysis: nuclear area, perimeter, maximum length, maximum width and intensity standard variation. The values obtained for papillary carcinomas were higher than the surrounding benign nodules as follows: nuclear area 63.5 vs. 36.1 (p=0.000), nuclear perimeter were 29.4 vs. 22.0 (p=0.000), maximum length 9.6 vs. 7.1 (p=0.000), maximum width 8.2 vs. 6.3 (p=0.000), the ratio between maximal length and maximal width 1.16 vs. 1.13 (p=0.000), the standard variation of intensity 14.9 vs. 15.9 (p=0.101) respectively. Therefore, morphometric information can be helpful for the differential cytological diagnosis of papillary thyroid carcinoma.

Analysis of DNA Ploidy Patterns and Nuclear Morphometry in Diethylnitrosamine Induced Hepatocyte Nodules and Hepatocellular Carcinoma of Rats.: Chan Choi, Myung Kwan Kim, Kwan Mook Chae, Eun Cheol Kim, Hyung Bae Moon; Korean J Pathol. 1993;27(3):226-234.

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Abstract PDF: This study was designed to answer the question; (1) How does the DNA ploidy pattern change in hepatocarcinogenesis? (2) How does the nuclear morphology change in hepatocarcinogenesis? Diethylnitrosamine(DEN) (16.5 mg per kg) was subcutaneously injected to female Sprague-Dawley rats(150~200g) by weekly interval for 30 weeks. DNA ploidy and parameters of nuclear morphology were measured by image analyser(IBAS 200, Kontron, FRG). The DNA ploidy pattern was divided into three basic patterns(diploid, polyploid, and aneuploid modes). In 8 cases of saline-injected control rats, the DNA histograms showed all polyploid pattern. Inhepatocyte nodules(hyperplastic nodules), DNA diploidy was the most frequent pattern, being followed by polyploid and aneuploid DNA patterns, contrast to hepatocelular carcinomas in which polyploid DNA pattern was most frequently noted being followed by diploid and aneuploid DNA pattern. Although the nuclei of hepatocytes in hepatocyte nodules and hepatocellular carcinomas were larger and more pleomorphic than those of normal hepatocytes, they were as same as those of normal hepatocytes in regard to nuclear hyperchromasia. DNA content, which was increased in hepatocarcinogenesis, was significantly related to the nuclear area.

Discriminant Analysis of Tumor Cell Subpopulation Based on Morphometric and Photometric Features: Observations on tumor cells of the uterine cervix carcinoma.: Chang Soo Park, Dae Yong Choi, Min Cheol Lee, Sang Woo Juhng; Korean J Pathol. 1993;27(2):108-114.

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Abstract PDF: DNA aneuploid cells are poorly characterized in both biochemical and morphological terms. This study was performed to see the relationship between DNA ploidy and morphometric and photometric nuclear features. DNA contents of tumor cells were measured by image cytometry in 46 cases of micro- or early invasive squamous cell carcinoma of the uterine cervix. Also measured were nuclear area, perimeter, maximum diameter, chromatin pattern index, and staining intensity. Among the 46 cases, 20 cases which had both DNA diploid and aneuploid cell subpopulations were selected, and the two subpopulations were discriminated statistically. Multivariate discriminant analysis seperated clearly the two subpopulations, whereas univariate analysis failed. For canonical discriminant function, nuclear area was selected first, followed by staining intensity in each case. Other variables selected afterwards were nuclear perimeter, maximum diameter, and/or chromatin pattern index in random fashion. Correlation coefficient between the canoncial discriminant function and the variables were 0.20~0.40 for nuclear area and 0.25 or less for the others. The above results suggest that DNA ploidy is a parameter more or less independent on individual morphometric and photometric parameters.

Morphometric Analysis of Cirrhotic Nodules in Hepatocellular Carcinoma-bearing Livers.: Gyeong Hoon Kang, Yong Il Kim; Korean J Pathol. 1991;25(4):338-345.

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Abstract PDF: It has been well known that liver cirrhosis, regardless of its etiology, is an important predisposing factor in hepatocarcinogenesis. However, the type of cirrhosis in hepatocellular carcinoma(HCC)-bearing liver varies not only by geographic areas but also with the cirteria applied for morphological classification of cirrhosis. To elucidate the relationship between the nodule size of HCC-bearing cirrhotic liver and clinicopathologic features, we measured cirrhotic nodule areas of 49 surgically resected HCC cases using image analyzer. The morphological type of cirrhosis was predominantly macronodular(49%), and followed by mixed(37%) and micronodular(14%). Seventy percent of the cases showed seropositivity for HBsAg. The average area of cirrhotic nodules was significantly larger in HBsAg-positive cases(mean: 6.14 mm2) than that of HBsAg-negative cases(mean: 2.5 mm2)(p<0.05), and their size was bigger in cases with grossly expansile pattern of HCC than those cases with infiltrative ones(p<0.05). Based on the above findings, we assume that seropositivity of HBsAg may influence on the regenerative activity of cirrhotic nodules and also subsequent increase of risk for further development of HCC. The presence of cirrhohsis and nodule size seem to be the important contributing factors to determine the growing patterns of HCC.

Morphometric Study on Mucinous Tumors of the Ovary.: Joo Seub Keum, Jung Dal Lee; Korean J Pathol. 1991;25(4):305-317.

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Abstract PDF: Mucinous tumors of the ovary are the most common tumors arising from the common epithelium of the ovary in Korean. Distinguishing the tumor with borderline malignancy from mucinous cystadenocarcinoma is very important in determining proper therapeutic modalities and prognosis. Authors have undertaken morphometric analysis of various parameters from both borderline lesions and carcinomas of mucinous nature of the ovary. In each, five cases of the borderline and malignant tumors were subjected to be evaluated. Various cytologic and histologic parameters were analyzed using Kontron IBAS-I. 1) The most helpful parameter-for differentiation between borderline and malignant mucinous tumors is cell concentration (sensitivity 80%, specificity 80%). The discrimination value is more than 35 cells per 100 micrometer of the basement membrane length. If the cellular concentration is higher than the discriminating value, that indicates malignancy. 2) Tumor cell height, though it is other parameter of stratification, is not helpful for differentiation of the two lesions. 3) Cytologic atypia, either in size or in form, can not be a criterion distinguishing the borderline from malignancy. 4) Papillary growths can not be a criterion of either borderline and malignant lesions. 5) The degree of irregularity at tumor-stroma interface is not helpful for differentiation between borderline and malignancy.

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