- Metastatic Medullary Carcinoma of Thyroid to Breast; A Case Initially Diagnosed as Primary Invasive Lobular Carcinoma: A Case Report.
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Youngseok Lee, Jungsuk An, Chul Hwan Kim, Bom Woo Yeom, Jong Sang Choi, Yang Seok Chae
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Korean J Pathol. 2007;41(6):412-415.
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- Metastasis to the breast from medullary carcinoma of the thyroid is extremely rare. We report a case of metastatic medullary carcinoma of the thyroid which presented as multiple breast masses with ipsilateral axillary lymphadenopathy in a 48-year-old woman. Six years ago, she underwent total thyroidectomy and neck dissection because of palpable neck masses, with a diagnosis of medullary thyroid carcinoma. Histological features of breast masses showed single- file or linear-cord arrangements, with plasmacytoid appearance, and the initial diagnosis was invasive lobular carcinoma. She underwent modified radical mastectomy. The tumor cells were diffusely positive for E-cadherin, calcitonin and thyroid transcription factor-1 (TTF-1) and were metastatic medullary carcinoma of thyroid. In the patients with a history of medullary carcinoma of the thyroid, a careful examination is necessary for a breast mass composed of solid and cord-like clusters of small round to ovoid cells with plasmacytoid appearance.
Immunohistochemical staining for E-cadherin, calcitonin and TTF-1 could be helpful for differential diagnosis.
- Genetic and Epigenetic Alterations of the Wnt/beta-catenin Signaling Pathway in Cancer of the Ampulla of Vater.
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Gwang Il Kim, Jeong Boon Kim, Sang Bum Park, Young Sik Kim, Han Kyeom Kim, Bom Woo Yeom, Yang Seok Chae
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Korean J Pathol. 2007;41(4):224-231.
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- BACKGROUND
Carcinoma of the ampulla of Vater is rare and its pathogenesis is unclear. The role of epigenetic changes in the APC or CDH1, in the Wnt pathway, has not been reported in ampullary carcinomas.
METHODS
We performed immunohistochemistry on 73 sporadic ampullary carcinomas to identify Wnt-related molecules (APC, beta-catenin, E-cadherin, c-erbB2, cyclin D1) and examined mutations in the CTNNB1, loss of heterozygosity of 5q21, and the methylation status of the CpG island of APC and CDH1.
RESULTS
Thirteen tumors (17.8%) showed abnormal nuclear localization of beta-catenin; this was more prominent in the intestinal type than in the pancreaticobiliary type (p=0.01). The loss of APC correlated with the loss of beta-catenin or c-erb B2 (p<0.01). The prognosis was worse in the group with APC loss than when APC was maintained (p<0.05). There was no mutation identified in CTNNB1. Six (24%) out of 25 informative cases had 5q21 allelic loss. CpG island methylation in APC and CDH1 was detected in 33 (45.2%) and 29 (31.5%) cases, respectively.
CONCLUSIONS
The absence of mutations in CTNNB1 and the epigenetic alteration of APC and CDH1, might be characteristic changes in the Wnt/beta-catenin signaling pathway during the carcinogenesis of ampullary carcinomas.
- Fine Needle Aspiration Cytology of Extranodal Marginal Zone B cell Lymphoma with Abundant Plasma Cells and Eosinophilic Histiocytes in Parotid Gland.
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Youngseok Lee, Jungsuk An, Yang Seok Chae, Bom Woo Yeom, Jong Sang Choi, Chul Hwan Kim
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Korean J Cytopathol. 2007;18(2):165-169.
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- The authors present the fine needle aspiration cytology (FNAC) cytologic findings of a case of extranodal marginal zone B cell lymphoma (MZBCL), which featured abundant plasma cells and eosinophilic histiocytes arising in both parotid glands. A 49-year-old female presented with palpable masses in both parotid glands. She had been suffering from systemic lupus erythematosus and rheumatoid arthritis. The lesions were evaluated by FNAC and smears showed a small number of clusters of oncocytic cells with abundant eosinophilic granular cytoplasm and small nuclei, intermixed with small to medium-sized lymphoid cells containing round to lobulated nuclei, which suggested Warthin's tumor. Some of lymphoid cells had a plasmacytoid appearance, and some scattered large cells contained a large amount of eosinophilic cytoplasm. Bilateral superficial parotidectomy was performed and a histopathologic study indicated MZBCL with abundant plasma cells, intermixed with eosinophilic histiocytes. The presence of oncocytic cells and a mixture of lymphoid and plasma cells indicates Warthin's tumor, but the cytologic features of a relatively monotonous small to medium-sized lymphoid infiltrate suggest the possibility of MZBCL in the clinical setting of an FNAC study performed on a patient suffering from a connective tissue disease.
- Follicular Lymphoma with Monoclonal Plasma Cell Differentiation: A Case Report.
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Hyun chul Kim, Young Seok Lee, Jung woo Choi, Ae ree Kim, Bom Woo Yeom, Han kyeom Kim, In sun Kim
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Korean J Pathol. 2006;40(2):151-155.
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- We present a case of recurrent follicular lymphoma with an extensive plasma cell component involving infra-auricular lymph nodes in a 64 year-old woman. Immunohistochemical staining showed a strongly positive reaction of the follicles with CD20, bcl-2, bcl-6, CD10 and CD21 on the first biopsy specimen. The intrafollicular and interfollicular plasma cells showed monoclonality for IgG heavy chain and lambda light chain. The histological and immunohistochemical findings in the recurrent tumor were identical with those of the original. Discussion is focused on the importance of the differential diagnosis between reactive lymphoid hyperplasia and other lymphomas having plasmacytic differentiation.
- Liposclerosing Myxofibrous Tumor in Tibia: A Case Report and Review of the Literature.
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Jung Woo Choi, Young Seok Lee, Ju Han Lee, Han Kyeom Kim, Bom Woo Yeom, Jong Sang Choi, Hong Chul Lim, Chul Hwan Kim
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Korean J Pathol. 2005;39(3):207-210.
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- Liposclerosing myxofibrous tumor (LSMFT) is a benign fibro-osseous lesion that is characterized by a complex mixture of histologic elements, including its fibrous dysplasia-like features and its lipoma, myxofibroma, xanthoma and pseudo-Paget's bone patterns. However, this lesion is considered by some researchers as a variant of fibrous dysplasia or as the non-specific end result of degenerative change, while it is considered by others as a definite clinicopathologic entity. Here, we report on a case of LSMFT occurring in tibia, which is a very uncommon location for this tumor, and we review the related literatures. The case presented here shares features with those described for LSMFT, except for the location of this tumor. We believe that more studies on a larger scale that compare LSMFT with other benign bone lesions, including fibrous dysplasia, are required to clarify the origin and behavior of this lesion.
- The Expressions of Tyrosine Kinase Receptors, EphA2, c-met and c-erbB-2 in the Human Breast.
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Soo Kee Min, Hyun Deuk Cho, Seong Jin Cho, Hye Rim Park, Hyung Sik Shin, Young Euy Park, Bom Woo Yeom
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Korean J Pathol. 2005;39(1):15-22.
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- BACKGROUND
Tyrosine kinase receptor (TKR) is an important protein for normal-development, growth and tumorigenesis in human tissues. The purpose of this study was to evaluate the effect of TKR in the progression of breast cancer.
METHODS
The expressions of EphA2, c-met and c-erbB-2 were examined, by using immunohistochemical methods and RT-PCR, in samples of breast tissue that included 111 samples of normal epithelium, 34 samples of ductal carcinoma in situ (DCIS), and 109 samples of invasive ductal carcinomas (IDC).
The results were compared with the prognostic parameters of breast cancer including the tumor grade, growth pattern, lymph node metastasis and the expressions of ER, PR, p53 and Ki-67.
RESULTS
The protein expressions of the three TKRs were higher in DCIS and IDC than in normal epithelium. The protein expression of EphA2 was correlated with a tumor grade, a labeling index of Ki-67, and the protein expression of c-met. Overexpression of c-erbB-2 was correlated with lymph node metastasis. The mRNA levels of the three TKRs were correlated with each other in normal tissue and IDC.
The level of c-met mRNA was higher in the low grade tumors.
CONCLUSIONS
The three TKRs may play roles in the tumorigenesis of human breast cancer. The overexpressions of EphA2 and c-erbB-2 may be a poor prognostic parameter in breast cancers.
- Comparative Analysis of Serum Mannose-Binding Lectin in Normal Population and Patients with Different Types of Cancer.
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Bum Joon Kim, Young Sik Kim, Eun Mee Han, Eung Seok Lee, Nam Hee Won, Geung Hwan Ahn, Dale Lee, Bom Woo Yeom
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Korean J Pathol. 2004;38(5):306-310.
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Abstract
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- BACKGROUND
Mannose-binding lectin (MBL) is a serum protein of innate immunity. Its genetic mutations lead to deficiency of serum MBL and recurrent pyogenic infection in childhood.
However, little is known about the frequency of its gene mutations or serum levels in Korean population and patients with cancers.
METHODS
We studied the mutational genotypes of MBL exon 1 codon 52, 54, and 57 or serum MBL levels from 102 normal adults and 228 cases of breast, stomach, colon, uterine cervical, and lung cancers by allele-specific PCR and enzyme-linked immunosorbent assay.
RESULTS
MBL gene mutations were found in 32 of 102 normal adults (31.4%), and were restricted only to exon 1 codon 54 showing homozygous (n=5, 4.9%) or heterozygous mutations (n=27, 26.5%). Mean and median serum MBL in the patients with cancers were increased (2,647+/-1,742 and 2,915 ng/mL, mean+/-S.D. and median) than those of normal adults (1,906+/-1,359 and 1,758 ng/mL). Serum MBL level was significantly increased in the patients with stomach, uterine cervical, colon, and lung cancers.
CONCLUSION
Our results indicate that the frequency and pattern of MBL gene mutations and its serum level is very similar among northeastern Asian populations. In addition, MBL might be involved in an immunologic response against common cancers, although further studies are needed.
- K-ras Gene Mutations and Expression of K-ras, p16, Cyclin D1 and p53 in Synchronous Lesions of The Colon Adenoma-Carcinoma Sequences.
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Hwa Eun Oh, Seong Jin Cho, Nam Hee Won, Dale Lee, Insun Kim, Bom Woo Yeom
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Korean J Pathol. 2001;35(4):291-298.
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- BACKGROUND
The colorectal adenoma-carcinoma sequence represents a well-known para-digm for the sequential development of cancer driven by the accumulation of genomic defects. Although the colorectal adenoma-carcinoma sequence has been well investigated, the studies about tumors of different dignity co-existent in the same patient are rare.
K-ras mutation is an early genetic change in colon cancer.
The genes involved in the cell cycle such as cyclin D1, p16, and p53 are important in the tumorigenesis of the colon. The aims of this study were to determine K-ras gene mutation and expression of K-ras, p16, cyclin D1 and p53 in synchronous lesions of the colon adenoma-carcinoma sequences and their possible relationship with K-ras mutation.
METHODS
The materials included 45 colonic adenocarcinomas which were accompanied by adenoma (22 low grade and 26 high grade). By using polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP), we detected K-ras mutation of codon 12. An aberrant K-ras, p16, cyclin D1 and p53 expressions were stained using an immunohistochemical method. RESULTS: K-ras mutation was 52.4% (11/21) of high grade adenomas. K-ras expression was 65.4% (17/26) of high grade adenomas. p16 and cyclin D1 expressions were 50% (11/22) and 90.9% (20/22) of low grade adenomas, respectively. p53 expression was 75.6% (34/45) of adenocarcinomas. There were statistical correlations among K-ras, p16 and cyclin D1.
CONCLUSIONS
These results indicate that the ras gene mutation is an early event and the overexpressions of p16, cyclin D1 and p53 are associated with K-ras mutation and expression in adenoma-carcinoma sequences.
- Association between the Expresson of MMP-2 and TIMP-2, and Growth Pattern of Tumor Border, Lymph Node Metastasis, and Estrogen Receptor in the Invasive Ductal Carcinoma of the Breast.
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Soo Kee Min, Joon Mee Kim, Young Chae Chu, Young Up Cho, Bom Woo Yeom
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Korean J Pathol. 2000;34(5):366-373.
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- The most important prognostic factor of breast cancer is the status of lymph node or distant metastasis, which is resisted by basement membrane and stromal matrix. MMP (matrix metalloproteinase)-2 is a 72-kilodalton type IV collagenase/ gelatinase and degrades the type IV collagen which is a main component of the basement membrane.
Therefore, MMP-2 is believed to be one of the key molecule for cancer invasion and metastasis. Enzymatic activity of MMP is inhibited by TIMPs (tissue inhibitors of metalloproteinase).
TIMP-2 forms a complex with latent pro-MMP-2 and inhibits the active forms of MMP-2. The balance of MMPs and TIMPs is suspected as the important factor of invasion and metastasis of the tumor cells. We studied the association between the expression of MMP-2/TIMP-2 and growth pattern of tumor border, lymph node metastasis, and estrogen receptor expression in the 57 cases of invasive ductal carcinoma of the breast using immunohistochemical staining methods. The results revealed increased expression of MMP-2 in the infiltrating tumor border and tumors with positive lymph node metastasis and negative estrogen receptor with no statistical significance (p>0.05). But the expression of TIMP-2 was increased in expanding tumor border and tumors with positive lymph node metastasis and negative estrogen receptor without statistical significance (p>0.05).
- p53 Mutation and Expression of Rb Protein in Germ Cell Tumors.
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Ju Han Lee, Mee Yon Cho, Hae Hyeog Lee, Bom Woo Yeom, Nam Hee Won
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Korean J Pathol. 1998;32(12):1074-1080.
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Abstract
- We investigated the role of the tumor suppressor genes in the germ cell tumor. Immunohistochemistry (IHC) and polymerase chain reaction-single strand conformational polymorphism (PCR-SSCP) for p53 mutation were done in 46 cases of the germ cell tumor with paraffin embedded tissue.
The immunohistochemical staining for Rb protein was also performed in the same specimens. The following results were obtained. The overexpression of the p53 protein was detected in 7 of 46 cases (15%). p53 mutation by PCR-SSCP was detected in 1 of 46 cases (2.2%). Expression of Rb protein was negative in 19 cases (41%). These results suggest that p53 mutation does not play an important role in the initiation and progression of germ cell tumors.
- A Comparative Study of Immunohistochemical Expression of p53, bcl-2, c-erbB-2, and MIB-1 in Polypoid and Infiltrative Colorectal Carcinomas.
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Jeong Seok Moon, Seong Hwan Park, Bong Kyong Shin, Ju Han Lee, Joon Ho Shin, Bom Woo Yeom
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Korean J Pathol. 1998;32(8):581-589.
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Abstract
- Almost all colorectal carcinomas have been thought to develop from pre-existing adenomas. However, some colorectal carcinomas can arise directly from normal flat mucosa, and usually form infiltrative mass at the early stage. The carcinogenesis of this infiltrative carcinoma may be different from the well-known adenoma-carcinoma sequence, which usually forms a polypoid mass. The purpose of this study is to investigate the different expression of various oncogenes in polypoid carcinoma and infiltrative carcinoma.
We performed immunohistochemical staining on p53, bcl-2, c-erbB-2 and MIB-1 in 29 polypoid carcinomas arised from adenomas, and 21 infiltrative carcinomas. The average tumor size of infiltrative carcinomas (5.5 cm) was larger than that of polypoid carcinomas (3.1 cm), and the polypoid carcinomas were differentiated more than the infiltrative carcinomas. The results of p53, bcl-2, c-erbB-2, and MIB-1 antisera immunoreactivity in the polypoid carcinoma were 79%, 17%, 21%, and 100%, and those in the infiltrative carcinoma were 71%, 29%, 29%, and 100%, respectively.
However the diffuse positivities of p53 and MIB-1 antisera were slightly higher in the infiltraive carcinomas (62%, 76%) than in the polypoid carcinomas (55%, 41%) (p=0.63, 0.01). And the results of p53 and c-erbB-2 immunoreactivity in the adenomas were 52% and 17%, respectively, which is significantly lower than that in the polypoid carcinoma(p=0.03, 0.74). The immunoreactivty of bcl-2 in the adenoma was 72%, which was significantly higher than that in the polypoid carcinoma (17%) (p<0.01). In summary, we did not show the significant difference in expression of p53, bcl-2, c-erbB-2, and MIB-1 proteins between polypoid and infiltrative carcinomas. However, the tendency of infiltrative carcinomas having a more aggressive nature suggests another carcinogenetic mechanism is involved in the colorectal carcinogenesis.
- Cytologic Features of Medullary Carcinoma of the Thyroid Occurring in a Child: A Case Report.
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Jeong Seok Moon, Hye Sun Kim, Seong Jin Cho, Yang Seok Chae, Bom Woo Yeom
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Korean J Cytopathol. 1996;7(2):213-217.
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- Medullary carcinoma of the thyroid gland is a malignant neuroendocrine tumor arising from calcitonin producing-parafollicular cells. The tumor is clinically divided into sporadic and familial form, constituting about 80% and 20%, respectively. Recently, we experienced a case of unilateral and solitary sporadic medullary carcinoma of the left thyroid gland. The patient was a 9 year-old female, who presented with a palpable mass on the anterior lateral neck of 8 months duration without any familial and personal history of neuroendocrine disease. The cytopathologic findings showed spindle cells and plasmacytoid cells in the background of colloid-like materal. The nuclei were eccentrically located, mildly hyperchromatic and pleomorphic, showing speckled chromatin pattern without nuclear inclusion or prominent nucleoli. The cytoplasm was abundant and had a pale granular cyanophilic appearance. No amyloid materal could be identified.
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