Journal of Pathology and Translational Medicine

Volume 31(2); February 1997

Original Articles

Congenital Anomalies Observed by Autopsies at the Seoul National University Children's Hospital.: Jin Haeng Chung, Jeong Wook Seo, Chong Jai Kim, Chul Woo Kim, Je G Chi; Korean J Pathol. 1997;31(2):93-99.

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Abstract PDF: A retrospective analysis was performed on the 968 cases of fetal or pediatric autopsies over five year period (1990-1994), at the Seoul National University Children's Hospital. Age/mode distribution of cases were artificial abortus(30.6%), spontaneous abortus(12.0%), stillbirth(21.9%), neonates(29%), infants(2.8%) and children(0.9%). Male/female ratio was 1.21. Overall incidence of congenital anomalies was 60.8% and 34.0% of all cases had anomalies involving multiple organ systems. Percentage of cases with any anomaly was 71.6% in artificial abortus, 35.3% in spontaneous abortus, 59% in still births, 65.5% in neonates and 38.9% in infant and children. Common organ systems involved were the cardiovascular system (39.0%), musculoskeletal system (23.6%), nervous system (22.6%), gastrointestinal system (19.9%), and urinary system (14.6%). From these results, we found that the congenital anomalies were most significant diseases of the perinatal period and the cardiovascular anomalies were the most common anomalies of them.

Morphologic Comparisons of Focal Segmental Glomerulo-sclerosis between Human and 5/6 Nephrectomy Rat Model.: Yong Jin Kim, Yong Sun Kim, Chae Hong Suh; Korean J Pathol. 1997;31(2):100-111.

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Abstract PDF: This study was conducted to set up a common mechanism for varying phases of focal segmental glomerulosclerosis(FSGS) by comparing the morphological differences between human FSGS and changes in 5/6 renal ablation animal model, which has been accepted as experimental prototype for hyperfiltration theory as pathogenesis of FSGS. Both the human and the experimental rats showed very similar changes such as segmental glomerulosclerosis, vacuole formations or inclusion of small granules of podocytes, appearance of foamy cells in the capillary lumina, eosinophilic deposits along the mesangial area, and focal atrophy of tubules with associated interstitial fibrosis. The halo, frequently seen in human FSGS, is due to detachment of visceral epithelium from basement membrane, however, did not appear in the experimental rat specimen. On the other hand, the foamy cells and hyalinization were more frequently noted in the rat series and even involved the arterioles. The mesangial proliferation never appeared in the rat series occasionally found in human FSGS. In conclusion, the pathogenesis of FSGS cannot depend solely on the hyperfiltration theory of hemodynamic derangement, but has complex impairment of visceral epithelium and cells forming the constituents of basement membrane.

Immunohistochemical Study on the Expression of Mutated p53 Protein and Bcl-2 Protein in Melanocytic Lesions of Skin.: Wha Jin Lee, Joon Hyuk Choi, Won Hee Choi; Korean J Pathol. 1997;31(2):112-120.

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Abstract PDF: To investigate the immunohistochemical expression of mutated p53 protein and bcl-2 protein in the cutaneous melanocytic lesion, 15 cases of compound nevus, 10 cases of congenital melanocytic nevus, 15 cases of primary malignant melanoma(4 cases less than 1.5 mm thick and 11 cases more than 1.5 mm thick), and 10 cases of metastatic malignant melanoma(7 cases in lymph node and 3 cases in soft tissue) were examined. All cases of compound nevi and of congenital melanocytic nevi showed no immunoreactivity for p53 protein. p53 protein overexpression was observed in 75%(3/4) wth primary malignant melanoma less than 1.5 mm thick, 81%(9/11) with primary malignant melanoma more than 1.5 mm thick, and 100%(10/10) with metastatic malignant melanoma. The difference in p53 protein overexpression was statistically significant between benign nevi and malignant melanoma(p<0.01). Bcl-2 protein expression was observed in 73%(11/15) with compound nevus, 70%(7/10) with congenital melanocytic nevus, 75% (3/4) in primary malignant melanoma less than 1.5 mm thick, 54%(6/11) with primary malignant melanoma more than 1.5 mm thick, and 40%(4/10) with metastatic malignant melanoma. These findings suggested that mutation of p53 gene may be an important mechanism in the development of malignant melanoma. Although bcl-2 protein was expressed in cutaneous melanocytic lesion, no correlation was found between p53 protein and bcl-2 protein expression in malignant melanoma.

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.

The p53 Mutation and DNA Ploidy in Human Metastatic Breast Cancer.: Seong Jin Cho, Ae Ree Kim, Nam Hee Won; Korean J Pathol. 1997;31(2):135-144.

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Abstract PDF: The p53 gene, one of the tumor suppressor genes, is believed to play an important role through mutation and overexpression in the progression of various human malignant tumors. To compare the p53 mutation status between the primary and metastatic lesions of breast cancers and to investigate the mutational pattern of p53, immunohistochemistry (IHC) and polymerase chain reaction and single strand conformational polymorphism (PCR-SSCP) were performed in 25 cases of breast cancers with paraffin embedded tissue. Mutant protein products or point mutation were detected through IHC or PCR-SSCP method. And flow cytometrical (FCM) analysis were performed in the same paraffin blocks to correlate the DNA ploidy and p53 mutation. The following results are summarized. 1. The detection of the p53 gene mutation and overexpression of the p53 protein were measured in 40% and 48%, respectively, in 25 primary tumors, either or both methods was detected in 64%. 2. A concordance rate of the p53 protein expression between the primary and metastatic lesions of 25 breast cancers was 100%, but the concordance rate of the p53 gene mutation was 72%. 3. The correlation between the p53 mutation and the DNA aneuploidy was not statistically significant (p=0.38) 4. A p53 mutation by IHC or PCR-SSCP was more frequently detected in grade III breast cancers than in grade I or II. 5. Among 5 to 9 exons of the p53 gene, exon 7 was the most frequent mutation spot in this study. 6. Additional mutation of the p53 gene was developed in the three metastatic lesions. With the above results it is suggested that the p53 protein overexpression by immunohistochemistry is not correlated with the p53 mutation by PCR-SSCP. The p53 mutation pattern between the primary and metastatic lesions are not idenitical and an additional point mutation can occur in the metastatic lesion. The DNA aneuploidy is more frequently detected in the cases with the p53 protein overexpression than in the p53 protein negative, but it is not statistically significant.

Immunohistochemical Analysis of nm23 Protein in Infiltrating Ductal Carcinoma of the Breast.: Min Hee Jung, Seung Cheol Lee, Yoon Kyung Sohn, In Soo Suh; Korean J Pathol. 1997;31(2):145-151.

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Abstract PDF: The nm23 gene was originally identified from murine melanoma cell lines of varying metastatic potential. A strong association has been observed between reduced expression of nm23 gene and acquisition of metastatic behavior in some tumor cells including breast cancer and melanoma, but not in others such as colon cancer, neuroblastoma, and cervical cancer. It was proposed that nm23 may function as a suppressor gene for tumor metastasis. It has recently been found that the sequence of nm23 and NDP-kinase(NDP-K) was identical. Mortality associated with human breast carcinoma is almost entirely due to subsequent metastasis, but the molecular basis of this metastasis is not understood. Elucidation of the genetic control of metastatic propensity of a tumor is important in determining prognosis and choice of therapy. The purpose of this study was to investigate the relationship of nm23 protein expression with axillary lymph node metastasis and other prognostic factors. Using an immunohistochemical technique and employing a polyclonal antibody to nm23 protein, we have determined nm23 expression in a series of 72 infiltrating ductal carcinomas of the breast. Immunostaining for the nm23 gene product have heterogenous cytoplasmic and nuclear staining in 61 patients(84.7%). Sections were scored according to relative abundance(1 = less than 25% of the cells, 2 = 26-75%, 3 = 76-100%). In 61 patients with positive immunostaining, the staining was scored as 1 in 41.6%, 2 in 18.0%, and 3 in 40.2%. The staining of tumor cells was greater than that in normal epithelial cells and stromal cells. No relationship was found between nm23 expression and lymph node metastasis, histologic grade, tumor size, estrogen receptors or progesterone receptors. Therefore, nm23 protein is increased in neoplastic tissues but no correlation with metastatic potential could be demonstrated. The biological mechanism of over-expression of nm23 in malignant cells and its role in tumor progression remain to be determined.

Expression Pattern of the Rb Protein and its Correlation with Prognosis in Primary Lung Cancer.: Hea Kyoung Hur, Seo Hee Rha, Sook Hee Hong; Korean J Pathol. 1997;31(2):152-161.

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Abstract PDF: An immunohistochemical stain for the Rb tumor suppressor gene product was performed in pathologic specimens from 72 primary lung cancer patients to study the correlation between its expression and histologic type, cancer differentiation, clinical stage and survival rate. The expression of the Rb protein was positive in 34 cases(47.2%) and negative in 38 cases(52.8%). The Rb protein was not expressed in 16 of 42 cases(38.1%) in squamous cell carcinoma, in 17 of 23 cases(73.9%) in adenocarcinoma, in one of three cases(33.3%) in undifferentiated large cell carcinoma, in two of two cases(100%) in small cell carcinoma, in one of one case(100%) in an adenosquamous carcinoma and in one of one case(100%) in an atypical carcinoid. There were significant difference of the Rb protein expression between squamous cell carcinoma and adenocarcinoma(p<0.05). The expression of Rb protein was not correlated with degree of cancer cell differentiation and clinical stage of the lung cancer(p>0.05). The two year survival rate for patients with the Rb positive was 65% compared with 37% for those with the Rb negative which was significant(p<0.05). This result suggests that an altered or the absence of the Rb protein in cancer cells can be a valuable prognostic factor in the lung cancer.

Clear Cell Islet Cell Tumor of the Pancreas: An Immunohistochemical and Ultrastructural study.: Seung Sam Paik, Young Ha Oh, Eun Kyung Hong, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1997;31(2):162-166.

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Abstract PDF: A clear cell islet cell tumor of the pancreas is extremely rare and characterized by extensive clear cell components. Electron microscopic and immunohistochemical findings are essential to prove that the mass with clear cells is an unusual manifestation of an islet cell tumor. Herein, we report a case of clear cell islet cell tumor of a 54-year-old woman with abdominal pain. The tumor was composed of polygonal clear cells arranged in nests, trabeculae, and ribbon pattern with the extensively fibrous stroma. These tumor cells showed strong reactivity for chromogranin and weak reactivity for somatostatin and glucagon. An electron microscope revealed that the important contributing factor of the clear cytoplasmic change was mainly due to an accumulation of lipid droplets, coupled with cytoplasmic swelling in some areas. Some tumor cells showed many endosecretory granules ranging from 111 to 297nm in diameter. In the clinical and immunohistochemical findings these granules were consistent with somatostatin granules in morphology and size.

Case Reports

Alzheimer's Disease: Report of two cases.: Hee Sung Kim, Yeon Lim Suh, Kyung Sue Hong, Duk Lyul Na; Korean J Pathol. 1997;31(2):167-173.

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Abstract PDF: Alzheimer's disease (AD) is the most common etiology of dementia, that has not been previously reported in Korea. We have experienced two cases of Alzheimer's disease, one occurred in a 53-year-old man with dementia and the other occurred in a 36-year-old woman with a family history of early onset dementia. A neocortical biopsy was done to rule out the cause of dementia and showed diffusely scattered numerous senile plaques and neurofibrillary tangles in cortex of both cases. Interestingly, GFAP, an immunohistochemical stain showed strong positivity in neuritic plaques and the surrounding fibrillary gathering.

Ossifying Fibromyxoid Tumor of Soft Parts.: Seok Hoon Jeon, Seung Sam Paik, Eun Kyung Hong, Moon Hyang Park, Jung Dal Lee; Korean J Pathol. 1997;31(2):174-178.

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Abstract PDF: An ossifying fibromyxoid tumor of soft parts is a rare, recently described, fibro-osseous neoplasm of uncertain histogenesis. It occurs most frequently within the subcutis or skeletal muscle of the extremities. Its biologic behavior is generally regarded as benign with at worst a locally aggressive clinical course. But, atypical and malignant variants have been recently reported. Herein we report a case of a benign ossifying fibromyxoid tumor which occurred in the left upper back of 41-year-old man. The tumor is composed of uniformly round or polygonal cells arranged in cords or nests which are separated by myxoid and hyalinzed fibrous matrix and associated with irregular bony trabeculae. The tumor cells are strong positive for vimentin. Ultrastructural findings and a review of literatures are added.

Original Article

Signet Ring Cell Variant of Invasive Lobular Carcinoma of Male Breast.: Seung Sam Paik, Seok Hoon Jeon, Moon Hyang Park, Pa Jong Jung, Jung Dal Lee; Korean J Pathol. 1997;31(2):179-181.

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Abstract PDF: Lobular carcinoma of the male breast is very rare, because of the absence of lobules in the normal male breast. Herein, a case of lobular carcinoma of the male breast with cellular features of signet ring cells is described. A 57-year-old man presented with a left breast mass. Histologic examination showed classic invasive lobular carcinoma with in situ component. Most infiltrating tumor cells had a prominent signet ring cell appearance. The patient was phenotypically male and had fathered children. There was no history of predisposing factors to breast lesion, such as hormone use or gynecomastia.

Case Reports

Primary Adenosquamous Carcinoma of Jejunum.: Soon Ran Kim, Jung Weon Shim, Hye Kyung Ahn, Young Euy Park, Dae Gi Song, Young Cheol Lee, Myung Seuk Lee; Korean J Pathol. 1997;31(2):182-184.

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Abstract PDF: Adenosquamous carcinomas of the intestine are rare tumors, especially when they occur in the small bowel. We report a case of primary adenosquamous carcinoma of the proximal jejunum in a 66 year old woman with no underlying pathologic condition. The tumor mainly consisted of well differentiated squamous cell carcinoma showing keratin pearl and conspicuous intercellular bridges, and minor portion revealed well differentiated adenocarcinoma. The tumor seemed to have originated from the mucosal epithelium, invading the entire wall and metastasizing to the regional lymph nodes. Previous reports of adenosquamous carcinoma of the small intestine have been associated with metastatic disease from distant sites or intestinal duplication. In the colon, squamous cell differentiation have been seen in about 0.05% of adenocarcinomas and in 0.4% of adenomata. The pathogenesis of squamous cell carcinoma of the intestine is unknown, but some possible mechanisms are proposed. :1)malignant transformation of squamous cell epithelium in the submucosa, 2)aberrant differentiation of stem cells to squamous cell with subsequent malignant change, 3)squamous metaplasia of glandular cells with subsequent malignant change, 4)transformation of an adenosquamous into an epidermoid carcinoma.

Familial Juvenile Polyposis.: Sun Hee Chang, Shi Nae Lee, Hea Soo Koo, Ok Kyung Kim, Sun Sub Jung, Eung Bum Park; Korean J Pathol. 1997;31(2):185-188.

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Abstract PDF: Familial juvenile polyposis is a rare intestinal polyposis characterized by the occurrence of multiple juvenile polyps in the gastrointestinal tract. We report a case of familial juvenile polyposis in a 17-year-old man with a review of the literature. This patient underwent total colectomy due to a 6 years history of rectal bleeding. Grossly, the colon showed 36 variable sized pedunculated polyps, measuring 2.5cm x 2cm from the largest size and 0.2cm x 0.2cm to the smallest size. Histologically, the polyps consisted of cystically dilated glands, lined by normal colonic epithelial cells, scattered in loose, edematous stroma containing inflammatory cell infiltration. There were no areas of tubular adenoma or malignancy in any of the polyp.

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