Journal of Pathology and Translational Medicine

Volume 35(6); December 2001

Original Articles

Diagnostic Utility of Polymerase Chain Reaction-Based Clonality Analysis for Immunoglobulin Heavy Chain Gene and T-cell Receptor Gamma Chain Gene Rearrangement in Lymphoid Neoplasms.: Eun Yoon Cho, Young Hyeh Ko, Dae Shick Kim, Jae Joon Han, Howe J Ree; Korean J Pathol. 2001;35(6):461-469.

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Abstract: BACKGROUND
The clonality of lymphoid infiltrates determined by polymerase chain reaction (PCR) for immunoglobulin heavy chain (IgH) or T cell receptor (TCR) genes is not only useful in confirming the diagnosis of malignant lymphoma but also in establishing the lineage of a clonal lymphoid proliferation. We analyzed the efficiency of PCR analyses for IgH and TCRgenes that have been routinely applied for the diagnosis of malignant lymphoma in our laboratory.
METHODS
Paraffin sections of 200 cases were analyzed by seminested PCR. Primers were FRIIIA-LJH/VLJH consensus primer for IgH gene and V-J consensus primer for TCR gene. The cases showing negative results by PCR for TCR gene were further analyzed by multiplex V family primers with heteroduplex analysis.
RESULTS
PCR approach for IgH gene allowed detection of clonality in 100% of cases with false positive rate of 0.3% and false negative rate of 0%. The combination of PCR for TCR consensus primers with multiplex V family primers allowed detection of clonality in 91% of cases with false positive rate of 0.6% and false negative rate of 10.3%.
CONCLUSIONS
Combined analysis of IgH and TCR gene rearragnements by the PCR technique followed by heteroduplex analysis can be a useful diagnostic adjunct to determine the clonality of various lymphoproliferative diseases with high sensitivity. But clinical, morphological and immunophenotypical correlation should be considered to reach the final diagnosis due to a few false positive cases.

Primary Nodal Marginal Zone B-cell Lymphoma: Clincopathologic Analysis of Splenic and Mucosa-Associated Lymphoid Tissue Type.: Jae Joon Han, Young Hyeh Ko, Eun Yoon Cho, Mi Kyung Kim, Nam Hun Kim, Howe J Ree; Korean J Pathol. 2001;35(6):470-476.

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Abstract: BACKGROUND
Primary nodal marginal zone B-cell lymphoma (MZBL) is recently divided into mucosa-associated lymphoid tissue (MALT) type and splenic type. Herein, we analyzed clinicopathologic differences of those two types of nodal MZBL.
METHODS
Histologic and clinical findings of eleven cases of primary nodal MZBL lymphoma were reviewed. Immunohistochemical stains for IgD, Ki-67, CD3, and CD20 were performed.
RESULTS
The cases were classified as splenic type in four, MALT type in five, and unclassified in two. The age at presentation was 36.7 years old (range: 16-73) in splenic type and 48 years old (range: 31-68) in MALT type. Two patients with splenic type and one with MALT type had a long history of lymphadenopathy up to 9 years. Whereas tumors of splenic type showed nodular infiltration of tumor cells with follicular colonization and hyperplastic germinal center, tumors of MALT type showed mainly sinusoidal or parafollicular infiltration and atrophic germinal centers. All the patients with splenic type were alive at last follow-up and one patient with MALT type died of disease at 5 months after diagnosis.
CONCLUSIONS
Although the number of cases we analyzed was small, splenic type seems to be distinct from MALT type and lower grade neoplasm.

The Expression of DNA Dependent Protein Kinase Protein in Malignant Lymphoma.: Tae Woong Noh, Nam Hoon Cho, Woo Ick Yang; Korean J Pathol. 2001;35(6):477-485.

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Abstract: BACKGROUND
DNA dependent protein kinase (DNA-PK) composed of Ku70, Ku80 and DNA-PK catalytic subunit (DNA-PKcs), plays an important role in the primary repair of break points of damaged DNA and is involved in the recombination of the V, D, and J genes. Loss of DNA-PK may lead to immunodeficiency and malignant lymphomas. This hypothesis has been supported by animal study in a Ku70 knock-out mouse model. The relationship between DNA-PK and human malignant lymphoma has not yet been studied.
METHODS
We examined the loss of DNA-PK proteins in 85 representative cases of different subtypes of malignant lymphoma. Immunohistochemical stains for DNA-PK subunits were performed on formalin-fixed and paraffin-embedded tissue sections.
RESULTS
Lymphomas demonstrated statistically significant loss of Ku70, Ku80 and DNA-PKcs. T cell lymphomas showed more loss of DNA-PK proteins in comparison with B cell lymphomas. According to the World Health Organization (WHO) classification system, both T cell lymphomas and high-grade subtypes of B cell lymphomas demonstrated similar degree of loss of DNA-PK proteins.
CONCLUSIONS
We confirmed the loss of DNA-PK proteins in malignant lymphomas through the results of our study, and the loss of these proteins seems to be more significant in high-grade lymphomas. These findings support the role of DNA-PK as a tumor suppressor gene.

Expression of beta-Catenin, c-Myc, and Cyclin D1 in Pulmonary Adenocarcinomas.: Bong Kwon Chun, Hye Kyoung Yoon; Korean J Pathol. 2001;35(6):486-495.

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Abstract: BACKGROUND
beta-Catenin has dual functions: adhesive molucule and transcriptional activator. Subcellular accumulation of beta-catenin and subsequent formation of beta-catenin- Tcf/Lef-1 complexes, as well as c-myc and cyclin D1 genes which were recently defined as target genes of beta-catenin- Tcf/Lef-1, has been shown to be important in the development of colorectal and breast carcinomas. The author investigated the rate of subcellular accumulation of beta-catenin and overexpression of c-myc and cyclin D1, and also investigated the association between them in the pulmonary adenocarcinomas.
METHODS
Fifty-one surgically resected primary adenocarcinomas of the lung, including 11 bronchioloalveolar carcinomas, were investigated by immunohistochemical analysis with monoclonal antibodies specific for beta-catenin, c-myc and cyclin D1. Clinico-pathological information were collected from the patient charts and surgical pathology reports.
RESULTS
Accumulation of beta-catenin in the nucleus and/or cytoplasm and overexpression of c-myc and cyclin D1 were observed to be 20%, 37%, 16%, respectively. Ten cases showing accumulated patterns of beta-catenin revealed alternative overexpressions of c-myc (7 cases) and cyclin D1 (3 cases). In nonmucinous tumors, 9 cases showing overexpression of c-myc or cyclin D1 revealed accumulations of beta-catenin. The accumulation of beta-catenin was not statistically related to clinico-pathological parameters. The association between c-myc overexpression and histological subtype of tumors was observed.
CONCLUSIONS
It is suggested that the accumulation of beta-catenin is closely associated with tumorigenesis in a minor subset (20%) of peripheral adenocarcinomas of the lung. It is also suggested that transactivation of beta-catenin may closely be associated with the overexpression of c-myc or cyclin D1 in the nonmucinous adenocarcinoma.

Apoptosis of Alveolar Cells in Pneumocystis Carinii Pneumonia: Application of Electron Microscopic Terminal Deoxynucleotidyl Transferase-Mediated dUTP-Biotin Nick End Labeling Method.: Kyu Hun Kang, Sang Pyo Kim, Kun Young Kwon; Korean J Pathol. 2001;35(6):496-505.

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Abstract: BACKGROUND
Pneumocystis carinii (P. carinii) attaches to alveolar cells and causes injury to the epithelial cells by direct toxic effects or inhibition of epithelial growth and replication. Although respiratory cell damage or death is a common feature in P. carinii pneumonia, there has been little reports about expression of apoptosis of the lung tissue in the literatures.
METHODS
We examined expression of fibronectin and vitronectin in the interaction between P. carinii and alveolar cells, and in situ terminal deoxynucleotidyl transferase-mediated dUTP biotin nick end-labeling (TUNEL) expression of apoptosis in the respiratory cells by immunohistochemistry and pre-embedding immunoelectron microscopy.
RESULTS
Light microscopic (LM) and electron microscopic (EM) immunohistochemical stains for the fibronectin and vitronectin showed strong expressions on the pellicles and tubular extensions of P. carinii and weak expression along the surfaces of type I alveolar cells. LM and EM TUNEL stains showed positive expression in the nuclei of alveolar cells, apoptotic bodies in the cytoplasm of alveolar macrophages and cellular debris in alveolar spaces.
CONCLUSIONS
P. carinii induces injury and apoptosis of alveolar cells after attachment of the organisms to host cells, and alveolar macrophages enhance the clearance of apoptotic bodies of alveolar cells as well as phagocytosis and degradation of P. carinii.

Immunohistochemical Expression of CD117, CD34, Vimentin and alpha-Smooth Muscle Actin in Gastrointestinal Stromal Tumors.: Jong Kuk Kim, O Jun Kwon, Byung Heon Kim; Korean J Pathol. 2001;35(6):506-512.

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Abstract: BACKGROUND
The interstitial cell of Cajal (ICC), the cell of origin for gastrointestinal stromal tumor (GIST), expresses CD117 (c-kit) which is a receptor for KIT ligand in cell membranes. It is immunohistochemically positive for CD117, CD34 and vimentin, but not for alpha-smooth muscle actin (SMA).
METHODS
We performed the immunohistochmical study with anti-CD117, anti-CD34, anti-VMT and anti-alpha-SMA in paraffin-embedded tissue of 28 GISTs and 19 smooth muscle tumors arising in the gastrointestinal tract, mesentery, omentum and retroperitoneum (GISMT) to determine the precise nature of GIST cells.
RESULTS
The positive rates of CD117, CD34 and vimentin in extraGISTs were significantly higher than in GISMTs. The positive rate of alpha-SMA in GIST was not significantly different than in GISMTs.
CONCLUSIONS
A subset of GISTs may express alpha-SMA as well as CD117 and the cell of their origin may be a ICC precursor cell which is capable of differentiating bidirectionally into ICC and smooth muscle cell. This explains why GISTs may arise out of gut where ICC is not present and that they may represent the tumors arising from ICC precursor cell present around the gastrointestinal tract.

Apoptosis in Renal Hypertrophy after Uninephrectomy in the Rats.: Chan Pil Park, Jung Woo Noh, Joo Seob keum, Myung Sook Kim, Moon Hyang Park; Korean J Pathol. 2001;35(6):513-523.

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Abstract: BACKGROUND
Glomerular compensatory hypertrophy maintains decreased renal function after uninephrectomy (UNX). Proliferation and apoptosis of renal cells may be involved in hypertrophy.
METHODS
In small and large male Sprague-Dawley rats, contralateral kidneys were harvested 1, 7, 14 and 30 days after UNX. Apoptosis was assessed by the Tdt-mediated dUTP-digoxigenin nick end labelling method. Proliferating cell nuclear antigen and Fas ligand (FasL) expression was determined by immunohistochemically.
RESULTS
Morphometrically, glomerular hypertrophy was observed in both small and large rats after UNX, and it was more significant in the small rats. The glomerular proliferation index (PI) was gradually increased from day 7 but decreased on day 30 in the small rats. Glomerular PI was significantly increased from day 7 in large rats and peaked at day 14. Apoptotic cells in the glomeruli were slightly increased on day 1 and on day 7 in both groups of rats. The expression of FasL was gradually increased in the distal tubular epithelium in both groups.
CONCLUSIONS
These results demonstrate different profiles regarding the compensatory growth of the kidney, cell proliferation, and apoptosis during the period of compensatory hypertrophy in uninephrectomized rats of different weight and age. Apoptosis may play a role in regressing a number of proliferated cells during renal compensatory hypertrophy.

Expressions and Diagnostic Usefulness of MIB-1 and p53 in Uterine Smooth Muscle Tumors.: Mi Jin Kim, Yong Jin Kim, Seung Ho LeeSeungHo; Korean J Pathol. 2001;35(6):524-530.

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Abstract: BACKGROUND
Controversy still remains concerning the criteria for the categorization of uterine smooth muscle tumors by conventional histologic examination. Various ancillary techniques have been used to improve diagnostic accuracy.
METHODS
Immunohistochemical study of MIB-1 and p53 was performed on 10 usual leiomyomas (UL), 13 cellular leiomyomas (CL), 5 bizarre leiomyomas (BL), 2 cases of intravenous leiomyomatosis (IL), 5 smooth muscle tumors of uncertain malignant potential (STUMP) and 8 leiomyosarcomas (LMS), to investigate the diagnostic value of MIB-1 and p53 in uterine smooth muscle tumors.
RESULTS
The MIB-1 labelling index was low in ULs and their variants (mean 5.67+/-5.53), but it was increased in STUMPs (17.67+/-6.51) and markedly increased in LMSs (35.71+/-11.35). In ULs and their variants, no immunostaining for p53 was noted except in one case of BL, while 2 (40%) of 5 STUMPs and 3 (38%) of 8 LMSs showed positive reactions for p53. There were significant differences among leiomyoma, STUMP and LMS in the MIB-1 labelling index and p53 expression.
CONCLUSIONS
These results suggest that both abnormal expressions of p53 and a high MIB-1 labelling index are frequently associated with leiomyosarcoma. Our data also indicate that the classification system of Kempson and Hendrickson is well correlated with the MIB-1 labelling index.

Ki-67 Labelling Index and Bax Expression According to the Capsular Invasion in the Follicular Neoplasms of the Thyroid.: Hee Kyung Kim, Dong Wha Lee, So Young Jin, Dong Won Kim; Korean J Pathol. 2001;35(6):531-535.

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Abstract: BACKGROUND
There have been a few studies concerning the differential diagnosis between follicular adenomas and minimally invasive follicular carcinomas, but it is difficult to exclude the possibility of minute capsular and/or vascular invasion throughout the capsular areas as a whole.
METHODS
We examined the diagnostic usefulness of Ki-67 labelling index and bax expression for the differential diagnosis of follicular adenomas and minimally invasive follicular carcinomas.
RESULTS
The result of immunohistochemical staining with Ki-67 and bax antibodies were analyzed in 58 cases of follicular neoplasms from 1996 to 1999. Of 58 cases, 35 were follicular adenomas and 23 were minimally invasive follicular carcinomas. The Ki-67 labelling index was significantly higher in minimally invasive follicular carcinoma of the thyroid (Ki-67 labelling index, 1.62+/-0.35%) than follicular adenoma (0.46+/-0.21%) (P<0.05). Of the follicular adenomas, Ki-67 labelling index of the tumor with 5 cm or more in diameter was 0.38+/-0.13%, while that of the tumor with less than 5 cm was 0.51+/-0.24%. Of the minimally invasive follicular carcinoma, Ki-67 labelling index of the tumor with 5 cm more was 1.30+/-0.07%, while that of the tumor with less than 5 cm was 1.65+/-0.37%. Diffuse bax expression was seen in 27 of 35 cases of follicular adenomas and 2 of 23 cases of minimally invasive follicular carcinoma (P<0.05).
CONCLUSIONS
Our findings suggest Ki-67 labelling index and the degree of bax expression are useful markers for the differential diagnosis between the follicular adenoma and the minimally invasive follicular carcinoma of the thyroid.

Differentiation, Proliferative Index, and Caspase 3 Expression Rate in the Immunohistochemical Stains of Medulloblastoma as Prognostic Factors.: Sung Eun Kim, Woo Ick Yang, Tai Seung Kim; Korean J Pathol. 2001;35(6):536-543.

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Abstract: BACKGROUND
Medulloblastoma is a highly malignant neuroepithelial tumor of the childhood, less frequently, of adults, located in the posterior cranial fossa. It shows multiple lines of differentiation, expressing neuronal, glial, mesenchymal and ectodermal markers. The prognostic significance of cell differentiation has been studied, but received little agreement. In highly malignant tumors, very high proliferative index has been demonstrated. A major contributor to cell loss in medulloblastoma is reported to be apoptosis. In medulloblstoma, a linear relation between apoptotic index and proliferative index has not been convincingly demonstrated.
METHODS
We analyzed the immunohistochemical features, proliferative indices and apoptotic indices in medulloblastoma patients with regard to their clinical courses. Clinical features of 58 patients with medulloblastoma were reviewed. The presence of glial fibrillary acidic protein, synaptophysin, vimentin, and epithelial membrane antigen were examined with immunohistochemical method. The proliferative index (Ki-67) and caspase 3 expressing rate were calculated.
RESULTS
There was no significant correlation between the prognosis and the degree of cell differentiation. The positive correlation was noted between proliferative index and apoptotic index in a tumor mass.
CONCLUSIONS
Only proliferative index could be used as a prognostic factor.

Case Reports

Emphysematous Cystic Pulmonary Metastasis of Angiosarcoma.: Tae Heon Kim, Ji Sun Song, Soon Hee Jung, Ki Jun Sung, Eun Gi Kim; Korean J Pathol. 2001;35(6):544-546.

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Abstract: Pulmonary metastatic angiosarcoma usually reveals multiple nodular lesions associated with parenchymal hemorrhage. It is presented, in rare cases, as multiple emphysematous cystic lesions, complicated by pneumothorax. We experienced a case of pulmonary metastastasis from angiosarcoma of the scalp in a 58-year-old male showing multiple thin-walled emphysematous cystic lesions. The tumor cells spread along the subpleural and interlobular septa, focally surrounding the cystic lesions. This case suggests that a rare metastatic pattern seen in angiosarcoma of the scalp should be considered as a differential diagnosis of bullous emphysematous lesion.

Triple Synchronous Cancers of Stomach, Pancreas, and Kidney.: Seung Koo Lee, Byung Ha Choi, Shin Kwang Khang, Byung Sik Kim, Jooryung Huh; Korean J Pathol. 2001;35(6):547-550.

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Abstract: Synchronous occurrence of triple distinct malignant tumors in the same patient is very rare. We report a unique case of a triple cancer occurring in a 70-year-old Korean woman with synchronous signet ring cell carcinoma of the stomach, renal cell carcinoma of the conventional type of the left kidney, and invasive ductal adenocarcinoma and intraductal papillary carcinoma of the pancreas. All three cancers were successfully resected simultaneously by total gastrectomy, nephrectomy, and partial pancreatectomy with corresponding lymphadenectomies. This patient tolerated these surgical procedures well and led a normal healthy life during the 18 months of follow-up. In summary, a successful resection of synchronous triple cancers which has never been previously reported in such combination, is described.

Mesoblastic Nephroma of Adulthood.: Jae Woo Park, Jae Hun Chung, Jae Hyuk Lee, Jong Hee Nam, Chan Choi, Min Cheol Lee, Chang Soo Park, Sang Woo Juhng; Korean J Pathol. 2001;35(6):551-554.

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Abstract: Mesoblastic nephroma is a benign neoplasm of the kidney, which is usually diagnosed during the first six months of life. Incidence in adults is exceedingly rare. We report herein a case of mesoblastic nephroma that occurred in the upper pole of the right kidney of a 39-year-old woman. It was a round mass measuring 3X3X2 cm in dimension. Microscopically, it consisted of uniform spindle cells with foci of hyalinization and dystrophic calcification. Tubular structures were entrapped in the tumor. Upon immunohistochemical staining, the spindle cells were found to be positive for smooth muscle actin, desmin, and vimentin. The epithelial cells of the entrapped tubules were positive for cytokeratin. On electron microscopic examination, the spindle cells demonstrated smooth muscle differentiation identified by indented nuclei, microfilaments beneath the cell membrane, dense bodies, and basal lamina-like materials.

Cystadenoma of the Rete Ovarii.: Eungseok Lee, Dae Su Kim, Insun Kim; Korean J Pathol. 2001;35(6):555-557.

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Abstract: The rete ovarii is a rare site for tumor development. We present a case of cystadenoma originating from the rete ovarii of a 58-year-old woman. It was a unilocular cyst of 7.0 cm in size, lined by flat, cuboidal, or columnar epithelial cells supported by fibromuscular tissue. Papillary growth and crevice formation of the inner surface were characteristic. The presence of a normal rete ovarii was helpful in correct diagnosis.

Recurrent Malignant Phyllodes Tumor with Liposarcoma.: Ji Shin Lee, Hyung Seok Kim, Jong Jae Jung, Chong Dug Cho; Korean J Pathol. 2001;35(6):558-560.

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Abstract: Phyllodes tumors are an uncommon mammary tumors composed of benign epithelial elements and cellular, spindle cell stroma. Adipose differentiation is an uncommon stromal alteration in phyllodes tumors. Herein, a case of recurrent phyllodes tumors with liposarcomatous stroma is described. A 30-year-old female presented with a left breast mass. Histologic examination showed a phyllodes tumor with low-grade malignant potential exhibiting a few mitoses and moderate cellularity. It also contained mature adipose tissue as well as a well-differentiated liposarcomatous area. This tumor recurred 43 months later. The recurrent tumor had a higher cellular density and more mitoses than the primary tumor.

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